PL122152B1 - Process for preparing derivatives of 3-/thiomethyl/ cephalosporinsnov - Google Patents

Description

The invention relates to a method for preparing 3-(thiomethyl)cephalosporin derivatives by substituting the acetoxy group in cephalosporanic acid with a sulfur nucleophile. The substitution of the acetoxy group of cephalosporins with a sulfur nucleophile is a reaction known from U.S. Patent No. 3,278,531. In the above patent specification and other publications, for example J.D. Cocker J. Chem. Soc., 1965, 5015, states that the reaction takes place only in an aqueous medium. Practically, in the substitution reactions, a cephalosporanic acid salt in water and a nucleophilic sulfur compound or its salt are used, at a pH of 5-8. The combination of an aqueous medium, elevated temperature (35-70°C) and an almost neutral to alkaline pH, usually has a destructive effect on many cephalosporin rings, and the products obtained in this way often require lengthy purification. Attempts to carry out the substitution reaction of cephalosporanic acids in water at a lower pH of 2-3 lead to the formation of significant amounts of 1-actone in a side reaction, which greatly reduces the yield of the desired product. From the German patent description No. No. 2,344,451 and British Patent No. 1,368,716 disclose the substitution of the acetoxy group of cephalosporins with a sulfur nucleophile in an organic solvent in a reaction system containing water. It has now been found that the substitution of the acetoxy group, as well as other 3-acyloxy groups in cephalosporin acids, with a sulfur nucleophile can be carried out very advantageously in organic solvents but under anhydrous conditions. The reaction under such conditions is not complicated by lactone formation, the yields are generally higher, and the product is easier to isolate. Some products even precipitate spontaneously from the reaction mixture. It is assumed that this process is general in nature and can be applied to practically any sulfur nucleophilic compound and any cephalosporanic acid. The process according to the invention is a new process in which 3-(thiomethyl)cephalosporin derivatives of the general formula I are prepared, wherein R 13 represents a group of the formula II, wherein each R 4 represents, independently, a hydrogen atom, an alkyl group of 1-4 carbon atoms, an alkenyl group of 2-3 carbon atoms, a cyclohexyl or phenyl group, or R 13 represents a group of the formula III, an alkyl group of 1-4 carbon atoms, a group of the formula IV or a group of the formula V, wherein each R 3 represents, independently, an alkyl group of 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, methanesulfonamide or trifluoromethyl group, q is 0, 1 or 2 and R6 is a group which together with the group of formula 14 forms an optionally substituted five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in the following combinations: 1 nitrogen atom and 0 or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen or 4 nitrogen atoms, where all the other atoms in the ring are carbon atoms, or R6 is a group which together with the group of formula 14 forms an optionally substituted five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in the following combinations: 1 nitrogen atom and 0 or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen or 4 nitrogen atoms, where all the other atoms in the ring are carbon atoms, or R6 is a group which together with the group of formula 14 forms a 2-ben'unridazotillorva, 2-benzothiazolyl, 2-benzoxazolyl radical or a radical of formula 15, R1 is a hydrogen atom or a methoxy group, R2 is a phthalimide, succinimide group, a group of formula 6, in which L is a hydrogen atom or a group nitroso, or R2 is a group of the formula R3 -C(=0)-NH-, in which R3 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, a -CEL-chloroalkyl group with 1-3 carbon atoms in the alkyl part, a -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part. cyanoaflulu with 1-4 carbon atoms, grape hydroxyalkyl with 1-4 carbon atoms R3 is a 4-keto-4-carboxybutyl group, a 3-carboxypropyl group, a group of the formula (7), wherein each a and ar is independently a hydrogen atom, a alkyl group with 1-4 carbon atoms, an alkyl group with 1-4 carbon atoms, a halogen atom or a hydroxyl group. Z is an oxygen or sulfur atom and m is the number 0 or 1, or R5 is a group of the formula P-C3i(Q)-, in which P is a 2-thienyl, 3-thienyl or phenyl group, a phenyl group of the formula (8), wherein a and a1 are as defined above and Q is a hydroxyl, formyloxy, acetoxy, carboxyl of the formula —C(=O)—O—A2, in which A2 is a diphenylmethyl, p-nitrobenzyl, benzyl, 2,2,2-trichlorocetyl, tert.-butyl or p-methylbenzyl group, or Q is a grape sulfonate group or a group of the formula Me-O-SO2-, in which Me is an alkali metal atom, or Q is an acylamino group of the formula —NH—C(=O)—T, in which T is an amino group, a group of the formula —NH—C(= «NH)—NHi, ^-N =O)—CH=CHR», a group of the formula 9, 10, 11 or 12, in which R7 is a hydrogen atom, or an alkyl group with 1—3 carbon atoms, R' is a phenyl group, halophenyl, furyl, methylamino, dimethylquinine, ethylamino, diethylamino, methylethylamino, propylamino, dimethylamino, diisopropylamino, phenylamino or diphenylamino, R* is a hydrogen atom, an alkyl group with 1-4 carbon atoms or a phenyl group, R* is a hydrogen atom, an alkyl group with 1-3 carbon atoms or a methylsulfonyl group, R* is an ethylene, trimethyl or vinylene group and p is 2 or 3, or R* is a group of formula 13 or a group of formula 13 in which the OH group is replaced by a —OCH1 or —O—C(=O)CH1 group, wherein P* in formula 13 has the meaning given above for P or denotes the 2-furyl group; or R3 is a group of the formula V-S(0)-CHa-, in which V is a group of the formula -CFj or of the formula -CHi-X, in which X is a hydrogen atom, a methyl group, a group of the formula -CHa, a group -CN or 2-thieoyl, 3-thienyl, 2-furyl, 2-oxazoliqua, 2-thiazolyl, 1-tetrazolyl, 1-benzotfrazolyl, 2-oxazolyl), 2-thiazclLIot o, 1,2,3-tnazclyl-5-thio-# lr3,4-triazol)-2-yl, 1,3,4-thiadiazolyl-2-tic-, group 5-methyl-1J394-dadiazoyl-2-thio, 1r2,4-thiadiazoyl-5-thio, 3-methyl-1A4-thiadiazolyl-5-thio, 1,2,5-nadiazolyl-3-thio, 1,3A-oxadiazolyl-2-thio, 5-methyl-1,3,4-oxadiazolyl-2-4-thio, 1-methyl-5-tetrazolyl thio, pyridylthio, 4-cyano-1,2,3-triazolyl-1 or 3-cyano-1,2,4-triazolyl-1. The method according to the invention consists in that the compound of formula 16 in which R1 and R2 have the meanings given above and R is an alkyl group with 1-3 carbon atoms, cycloalkyl with 4-6 carbon atoms, amino, mono- or di(alkyl)amino with 1-3 carbon atoms in the alkyl radical, a group of formula 17, 18 or 19, is reacted in the presence of an organic solvent with a sulfur nucleophile having the elevation V&*—S—R14, wherein R" has the above-mentioned meaning and R" is a hydrogen atom, or in the case where R13 is a methyleneamine group, and only then, R14 together with R13 forms a thiourea, and a feature of the process according to the invention is that the reactions are carried out under anhydrous conditions. The products of the process according to the invention exhibit antibacterial activity, and moreover, many of them are intermediates for the production of other cephalosporins having also antibacterial activity, as shown, for example, in U.S. Patent No. 3,932,393. In the above definitions, the term "alkyl" refers to various straight-chain and branched-chain alkyl groups. The term R3 as an alkyl group having 1-3 carbon atoms refers to groups such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, amyl, isoamyl, hexyl, 2,3-dimethylbutyl and the like. The term —CH2-chloroalkyl group having 1-3 carbon atoms in the alkyl portion and —CH2-fluoroalkyl group having 1-3 carbon atoms in the alkyl portion refer to groups such as chloroethyl, fluoroethyl, 2-chlorocetyl, 2-chloropropyl, 3-fluoropropyl and 4-chlorobutyl. The term —cyanoalkyl group having 1-4 carbon atoms refers to groups such as cyanomethyl, 2-cyanacetyl, 3-Cyaropropyl and 2-Cyanopropyl. The term hydroxyalkyl with 1-4 carbon atoms denotes groups such as hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl and 2-hydroxypropyl. It is desirable that the amino groups in the 3-(acyloxymethyl)cephalosporinic acid formula (XXI) as well as in the sulfur nucleophile are protected. Methods for protecting amino groups are known, for example, from "Protective Groups in Organic Chemistry," published by J.T.W. McOmie, Puknum Press, London and New York, 1973. In general, the amino protecting group should be removable, but this is not essential. The term "halogen" refers to fluorine, chlorine, bromine, or carbon dioxide. The term "alkoxy" refers to methoxy, ethoxy, isopropoxy, n-butoxy, and propoxy. The term "alkali metal" refers preferably to 35 Examples of groups with the formula R3—C(=0)—NH— are the following groups: formcmidewa, aoetamidewa, prepicnemidewa, butyranudowa, «-methylcprcp:onfmidewa, walcramidewa, o-methyl butyamidewa, trimethylcacctE midcwa, pentanccarbenamidew*, htksLnckarbcn*' midcwa, 3-chloroprc- 40 pionamideva, 3-chlorobutyramideva, 4-fluorobutyramide, 5-chloropropionaimdcwa, cyjaBcace(amidcwa, 2-cyanoprop:anamidcwa, 3-cypnopropionaimdcwa, 4-cyaao- butyramtdowa, hydraxycetamideva, 2-hydroxyiró* pionamideva, 3-hydrcksybuCyramidcwa, p-nh*afr» 45 zylcksykaibcnylc^mincwa, lII-is.-butcksykaibcnyl£«H» 122 152 5 new, (2,2,2-trichloroethoxy (carbonylamino, 5- (2,5- -dichlorobenzamido) -5- carboxyval eramide, 5- -acetamido -5- carboxyvaleramide, 5-carbomethoxy- -5- (2,4-dichlorobenzamido)valeramide, 5-carbo-n- -butoxy-5- (2,4-dichlorobenzamido)valeramide, 5- -carboxy -5- (2,4-dichlorobenzamido)valeramide, 5-(p-propionamido-5-carboxyvaleramide, 5-(3-chloropropionamido)-5-carboxyvaleramide, 5-benzamido-5-carboxyvaleramide, 5-keto-5-carbexvaleramide and 4-carboxybutyramido. PF with groups of the formula R*—C(=0)—NH—, in which R3 is a group of formula 7 and may represent the number 0 * and groups such as phenylacetamido, 2-(p-methylphenylq)acetamido, 2-(m-ethylphenylAcetamido, 2-(p-iso- propylphenyl)acetamido, 2-(o-methylphenyl)acetamido- 2-(p-chlorophenyl)acetamide, 2-(p-bromophenyl)acetamide, 2-(2,4-dichlorophenyl)acetamide, 2-(m-bromophenyl)acetamide, 2-(p-fluorophenylacetamide, 2-(o-fluorophenyl)acetamide, 2-(3,4-dihydroxyphenyl)acetamide, 2-(p-hydroxyphenyl)acetamide, 2-(m-hydroxyphenyl)acetamide, 2-(2,6-dimethyloxyphenyl)acetamide, 2-(m-methoxyphenyl)acetamide, 2-(p-isopropoxyphenyl))acetamide, 2-(p-isopropoxyphenyl) ... (m-ethoxyphenylacetamide, 2-(p-meth)phenyl)acetamide, 2-(3,4-dimethoxyphenyl)acetamide, 2-(p-tert.butoxyphenyl)acetamidate, 2-[p-(acetamidomethyl)phenyl]acetamide, 2-[p-(tert.-butoxycarbonylaminomethyl)phenyl]acetamide, 2-[o-(tert.-butoxycarbonylaminomethyl)phenyl]acetamide, 2-(m-butoxyphenylacetamide and 2-(3-chloro-4-methylphenyl)acetamide. If in the above formula m^la Z represents an oxygen atom —O— an example of such a group is the phenoxyacetamide group, 2-(p-methylphenoxyacetamide), 2-(m-ethylphenoxyacetamide), 2-(p-isopropylphenoxyacetamide), 2-(o-methylphenoxyacetamide), 2-(p-chlorophenoxy)acetamide, 2-(p-bromophenoxyacetamide, 2-(2,4-dichlorophenoxyacetamide), 2-(m-bromephenoxyacetamide, 2-(p-fluorophenoxyacetamide, 2-(o-fluorophenoxyacetamide, 2-(2,6-dimethoxyphenoxyacetamide), 2-(m-ethoxyphenoxy)acetamide, 2-(p-MethoxyphenoxyAcetamide, 2-(3,4-Dimethoxyphenoxy)acetamide, 2-(p-tert.-butoxyphenoxyacetamide, 2-(o-butoxyphenoxyacetamide, 2-(3-chloro-4-methylphenoxyacetamide, 2-(3-hydroxy-4-methylphenoxyacetamide, 2-(o-chlorophenoxy)acetamide, 2-(3-hydroxy-4-methylphenoxyacetamide, 2-(o-chlorophenoxy)acetamide, 2-(p-isopropoxyphenoxy)acetamide, 2-[o-(acetamidomethyl)phenoxyacetamide and 2-[p- (tert.-alpha-oxycarboxymethylaminomethyl)phenoxy]acetamide. In the case where in the above formula m=1 and Z- denotes a sulfur atom —S—, examples of such groups are 2-(phenylthioacetamide), 2-(p-methylphenylthio)acetamide, 2-(m-ethylphenylthioacetamide, 2-(p-isopropylphenylthioacetamide, 2-(c-methylphenylthio)acetamide, 2-(p-chlorophenylthio)acetamide, 2-(p-bromophenylthio)acetamide, 2-(2,4-dichlorophenylthio)acetamide, 2-(m-bromophenylthio)acetamide, 2-(p- -fluorophenylthioAcetamide, 2-(o-fluorophenylthio)acetamide, 2-(3,4-dihydroxyphenylthio)acetamide, 2-(p-hydroxyphenylthioAcetamide, 2-(m-hydroxyphenylthio)acetamide, 2-(2,6-dimethoxyphenylthioAcetamide, 2-(m-ethoxyphenylthioAcetamide, 2-(p-methoxyphenylthioAcetamide, 6-phenylthioAcetamide, 2-(3,4-dimethylphenylthioAcetamide, 2-(p-t-butoxyphenylthioAcetamide, 2-(m-butoxyphenylthioAcetamide, 2-(3-chloro-4-methyl- 2-(3,4-dimethylphenylthio)acetamide, 2-(3,4-dichlorophenylthio)acetamide, 2-(2,5-dichlorophenylthio)acetamide, 2-(3-fluoro-4-chlorophenylthio)acetamide, 2-(3-chloro-4-fluorophenylthio)acetamide, 2-(2,6-difluorophenylthio)acetamide, 2-(m-fluorophenylthio)acetamide, 2-[o-(acetamido-methyl)phenylthio]acetamide and 2-[p-(tert-butoxycarbonylaminomethyl)phenylthio]acetamide. In case R3 means a group of the formula P— —CH(Q)—, an example of a group of the formula R3—C(—O)— —NH— is the mandelamido group (phenylhydroxyacetamido), its O-formyl and O-acetyl derivatives, the 2-carboxy-2-phenylacetamido group, the 2-sulfo-2-phenylacetamido group, the protected 2-amino-2-phenylacetamido group, in which the protected amino group is, for example, carbonylamino, tert.-butoxycarbonylamino, trichlorobenzyloxycarbonylamino or p-nitrobenzyloxycarbonylamino, and the 2-acylamino-2-phenylacetamido group. These groups also include groups substituted in the 2-position 2-thienylacetamido and 3-thienylacetamido, i.e. the above groups in which the phenyl group is replaced by a 2-thienyl or 3-thienyl group. ; Examples of the above acetamido groups are the mandeamido group (2-hydroxy-2-phenylacetamido), 2-hydroxy-2-(p-methylphenyl)acetamido, 2-hydroxy-2-(p-hydroxyphenylacetamido), 2-hydroxy-2-(m-hydroxphenylacetamido, 2-hydroxy-2-(p-methoxyphenylacetamido), 2-hydroxy-2-(m-bromophenyl)acetamido, 2-hydroxy-2-(p-chlorophenylAcetamide, 2- -hydrokayl-2-(3-methyl-4-fluorophenyl)acetamide, 2-hydroxy-2-(o-fluorophenyl)acetamide, 2-hydroxy-2-(p-fluorophenyl)acetamide, 2-hydroxy-2-(p-isopropylphenylAcetamide, 2-O-formyl-2-(3,4-dimethylphenylAcetamide, 2-O-formyl-2-(p-chlorophenyl)acetamide, 2-O-formyl-2-(m-isopropoxyphenyl)acetamide, 2-O-formyl-2-(m-bromophenylAcetamide, 2-O- -formyl-2-phenylacetamide, 2-O-formyl-2-(3,4-dimethoxyphenyl)acetamide, 2-O-acetyl-2-phenylacetamide, 2-O-acetyl-2-(p-hydroxyphenylacetamide, 2-hydroxy-2-[(p-acetamidomethyl)phenyl[acetamide, 2,-O-formyl-2-(p-hydroxyphenyl)acetamide, 2-hydroxy-2-(thienyl-2-acetamide, 2-hydroxy-2-(thienyl-3-acetamide, 2-formyloxy-2-(thienyl-3-acetamide, 2-acetoxy-2-(thienyl-2-acetamide, 2-acetoxy-2-(thienyl-2-acetamide, 2-formyloxy- -2-(thienyl-3-acetamido, 2-acetoxy-2-(thienyl-3-acetamido, 2-(tert.-butoxycarbonyl)-2-phenylacetamido, 2-(2,2-trichloroethoxycarbonyl)-2-(p-methylphenylAcetamido, 2-(benzyloxycarbonyl)-2-(p-hydroxyphenylAcetamido, 2-(tert.-butoxycarbonyl)-2-(p-hydroxyphenylAcetamido, 2-(p-nitrobenzyloxycarbonyl)-2-(m-hydroxyphenylAcetamido, 2-(p- -methoxybenzyloxycarbonyl)-2-(p-methoxyphenyl)acetamide, 2-(diphenylmethoxycarboxylic)-2-(m- -bromophenylAcetamide, 2-(tert.-butoxycarbonyl)-2-(p-chlorophenylAcetamide, 2-(2,2,2-trichloroethoxycarbonyl)-2-(3-methyl-4-fluorophenyl)acetamide, 2-(benzyloxycarbonyl)-2-(o-fluorophenylAcetamide, 2-(p-nitrobenzyloxycarbonyl)-2-(p-fluorophenylAcetamide, 2-(p-methoxybenzyloxycarbonyl)-2-(p-methylphenyl)acetamide, (p-isopropylphenylAcetamide, 2-(tert-butoxycarbonyl)-2-(3,4-dimethylphenyl)acetamide, 2-(tert-butoxycarbonyl)-2-(m-isopropoxyphenyl)acetamide, 2-(diphenylmethoxycarbonyl)-2-(3,4-dimethoxyphenyl)acetamide, 2-(tert-butoxycarbonyl))-2-[p-(2,5-dichlorobenzamidomethyl)phenyl]acetamide, 2-(tert-butoxycarbonyl)-2-(thienyl-2)acetamide, 2-(tert-butoxycarbonyl)-2- (thien-3-yl)acetamide, 2-(sodiumoxysulfonyl)-2-phenylacetamide, 2-(sodiumoxysulfonyl)-2-(p-methylphenyl)acetamide, 2-(potassiumoxysulfonyl)-2-(p-hydroxyphenyl)acetamide, 2-(lithoxysulfonyl)-2-(m-hydroxyphenyl)acetamide, 2-(sodiumoxysulfonyl)-2-(p-methoxyphenyl)acetamide, 2-(sodiumoxysulfonyl)-2-(m-bromophenyl)acetamide, 2-(sodiumoxysulfonyl)-2-(p-chlorophenyl)acetamide, 2-(sodiumoxysulfonyl)-2- (3-methyl-4-fluorophenyl)acetamido, 2-sodooxysulfonyl)-2-(o-fluorophenyl)acetamido, 2-(sodooxysulfonyl)-2-(p-fluorophenyo)acetamido, 2-(sodooxysulfonyl)-2-(p-aceta- midomethylphenyl)acetamide, 2-(sodooxysuTfcnylc)-2-(p-isopropylphenyl)acetamide, 2-(sodcoxysulfonyl)-2-{3,4-dimethylphenyllp)acetamide, 2-(sodooxysulfonyl)-2- (m- isopropoxyphenyl)acetainide, 2- (-sodooxysulfonyl)-2- (3,4- dimethoxyphenyl)acetamide, 2-(sodooxysulfonyl)-2-(thienyl-2)acetamide, 2-(potassiumoxysulfonyl-2-(thieny]o-3)acetamide, 2-(p-nitrobenzyloxycarbonylamino)-2-phenylacetamide, 2-(tert.-butoxycarboxycarbonylamino)-2- (thienyIo-2)acetamido, 2- (benzyloxycarbonylamino)- -2-(m-hydroxyphenyl)acetamido, 2-CH-tz.-butoxycarbonylamino)-2- (p-hydroxyphenyl)acetamido, 2- -ureido -2- phenylacetamide, 2-ureido -2-(thienyl-2)acetamide, 2-(3-amidino-1-ureido)-2-phenylacetamide, 2-(3-methylaminocarbonyl-1-ureido)-2-phenylacetamide, 2-(3-dimethylaminocarbonyl-3-methyl-1-ureido)-2-phenylacetamide, 2-[N-(imidazolidinone -2- yl -1- carbonyl)amino] -2-phenylacetamide, 2- [N-(3-methylimidazolidinone -2- yl -2-carbc-nyl)amino] -2-phenylacetamido, 2- [N-(hexahydrocpyrimidinon -2-yl -1-carbonyl)amino [-2-phenylacetamido, 2-[N-(3-methylhexahydropyrimidinon-2-yl-1-carbonyl)amino[-2-phenylacetamido, 2-[N-(3-methanesulfonylhexahydropyrimidinon-2-yl-1-carbonyl)amino[-2-phenylacetamido, 2-(3-di-n-propylaminocarbonyl-1-ureido)-2-phenylacetamido, 2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino[-2-phenylacetamido, 2-[(3-methylsulfonyl-2-ketoimidazolidin-1-yl)carbonylamino]-2-phenylacetamido, thamido, 2-[(2-keto -4-imidazolinyl-1)carbonylcamino]-2-phenylacetamido, 2-[(4-keto 4H - thiopyranyl - 3)carbonylamino[-2-phenylacetamido, 2-(3-methyl-3- -(methylcarbonyl)ureido)-2-phenylacetamido, 2-(3- -methyl-3- (cinnamoylureido))-2-phenylacetamido, 2-(3-methyl-3- (acryloylureido))-2-phenylacetamido, 2-[(4-ethyl-2,3- diketopiperazinyl-1)carbonylami-[-2-thienylacetamido, 2-[(4-ethyl-2,3- diketopiperazin-1-yl)carbonylamino[-2-(p-hydroxyphenylacetamide], 2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino[-2-phenylacetamide], 2-[(2-ketoimidazolidinyl-1-(carbonylamino]-3-thienylacetamide and 2-[(2-keto-3-(methylsulfonyl)-4-imidazolinyl-1-yl)carbonylamino[-2-(p-hydroxyphenyl)acetamide. An example of groups of formula R3—C(=O)—NH—, where R3 is a group of formula 13 is the 2-(hydroxyimino)-2-phenylacetamide group, 2- (methoxyimino)-2-phenylacetamide, 2-(acetoxyimino)-2-phenylacetamide, 2- (hydroxyimino)-2-(thienyl-2)acetamido, 2-(hydroxyimino)-2- (furyl 2-)acetamido, 2- (methoxyimino)- -2- (thienyl -3)acetamido, 2-(methoxyimino)^-(furyl -2)acetamido, 2-(methoxyimino)-2-(p-hydroxy-phenyl)acetamido, 2-(hydroxyimino)-2-[2-(2,2,2 - 5 tricMorc*toxycarbonyl Ioainino)-4-thiazolyl]-acetamido (tautomeric with group 2- (hydroxyimino) -2- [2-(2,2,2- -trichloroethoxycarbonylimino) -4- thiazolinyl -4 [acetamide], 2- (methoxyimino) -2- [2 - (p- nitrobenzyloxycarbonylamino) -4- thiazolyl]acetamide (tautomeric 2-(methoxyimino)-2- [2-(p-nitrobenzyloxycarbonylimino)-4-thiazolinyl-4]acetamido) and 2* -(methoxyimino)-2- (4- chlorophenyl)acetamido. Examples of groups with the formula R3—G(=0)—NH—, in which R* is a group with the formula V—S(0)n—CH2— is the 15th group 2- (trifluoromethylthio)acetamide, 2-(methylsulfonyl)acetamide, 2-(cyanomethylthio)acetamide, 2-(azidomethylthio)acetamide, 2-(ethylsulfonyl)acetamide, 2-(2,2,2-trifluoroethylthio)acetamide, 2-(methylsulfinyl)acetamide and 2-(cyanomethylsulfonyl)acetamide. An example of a group of the formula R3—C(=O)—NH-, in which R* is a group of the formula Y—CH2—, is the 2-(thienyl-2)acetamide, 2-(thienyl-3)acetamide, 2-(furyl-2)acetamide, 2-(oxazolyl-2)acetamide, 2-(tJazc- & lilo-2)acetamide, 2-(tetrazolylIo-l)acetamide, 2- - (benzotriazolyl-l)acetamide, 2-(cksazolio-2-thio)acetamide, 2-(thiazolyl-2-thio)acetamide, 2-(1,2,3- -triazolyl -5-thio)acetamide, 2-(1,3,4 - triazolyl -2- -thio)acetamide, (1,3,4-thiadiazolyl -2-thio)acetamide, 30 2-(5-protected amino-1,3,4-thiadiazolyl -2-thio)acetamide, 2- (5- methyl-1,3,4-thiadiazolyl-2-thio)acetamide, 2-(1,2,4-thiadiazolyl-5-thio)acetamide, 2-(3-methyl- -1,2,4- thiadiazolyl -5-thio)acetamide, 2-(1,2,5 -thiadiazolyl -3- thio)acetamide, 2-(1,3,4 - oxadiazolyl -2-thio)acetamide, 2-(5-methyl- 1,3,4-oxadiazolylIo -2-thioacetamide, 2-(l-methyltetrazolyl-5-thio)acelamide, 2-(pyridylthio)acetamide, 2- (4-cyano-l,2,3-triazolyl-l)acetamide, 2-(3-cyano-l,2,4-triazolyl-l)acetamide and 2-(2-protected amino-4-thiazolyl)acetamide 40 tautomeric with 2-(2-imino-4-thiazolinyl-4)acetamide. Many of cephalosporanic acids used as starting compounds in the process of the invention are known compounds and all are obtained by known methods, attention should be paid to "Cephalosporins and Penicillins, Chemistry and Biology", publisher Edwin H. Flynn, Academic Press, New York, 1972, especially the chapter 3,4 and 15 and the references and descriptions quoted there U.S. Patent No. 3,914,157 and South African Patent No. 71/3229. Preferred sulfur nucleophiles are those of the formula R13—S—R14, wherein R13 is a group of formula 5. Suitable five-membered heteroaromatic rings of formula 5 include pyrrole, oxazole, isoxazole, thiazole, isofazole, pyrazole, imidazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, oxatriazole, tetrazolium. Suitable six-membered rings include pyridine, pyridazine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrazine, and 1,2,4,5-tetrazine. Some of the heteroaryl thiols, alkyl thiols, and phenyl thiols of formula R1—S—R14 exist as thiones or tautomeric mixtures of thiols and thiols. An example is 2-methyl-1,3,4-thiadiazole-5-thiol, which exists as tautomers of formulae 20 and 21. The reaction carried out by the method of the invention occurs with the mentioned sulfur nucleophilic groups, regardless of whether they are present as thiols or thiols. Thus, the invention encompasses processes carried out using thiols or thiol-thion tautomers of the mentioned compounds. Heteroaryl thiols may be unsubstituted or substituted with one or more substituents. In general, the nature of the substituent is not critical. For best results, the primary or secondary amino group should be protected. If the heteroaryl thiol contains more than one thiol group, then the one that does not react should be protected. Methods for protecting thiols are known from the above-cited McOmie publication. If these groups are protected, the reaction proceeds regardless of the nature of the substituent. It is preferable to avoid excessively large substituents. In general, those substituents having a total molecular weight of not more than about 500. Most substituted heteroaromatic rings contain substituents having a total molecular weight of less than about 250. Suitable substituents include an alkyl group of 1-4 carbon atoms, an alkenyl group of 2-4 carbon atoms, an alkynyl group of 2-4 carbon atoms, a cycloalkyl group of 5-6 carbon atoms, a benzyl group, a phenylethyl group, an aryl group such as phenyl, a specified substituted phenyl group, a halogen atom, a —CF 1 , ═O group, an —OH group, a protected amino or alkylamino group of 1-4 carbon atoms, a —COOH group, a —COOA 2 group, a —CONH 2 group, a protected aminomethyl or alkylaminomethyl group of 1-4 carbon atoms. carbon in the alkyl part, group —CH2SO3 — alkali metal atom, group — —CH2C OOH, —CH2COOA* or —(CH2)2N (CHj)2. Examples of sulfur nucleophilic compounds of formula R13 —S-R14 are thioureas such as allylthiourea, N,N'-di-n-butylthiourea, N,N'-di-tert.-butylthiourea, N,N'-dicyclohexylthiourea, N,N1-diisopropylthiourea, N^-dimethylthiourea, N-methylthiourea, N,N,N',N'-tetraethylthiourea, N,N,N',N'-tetramethylthiourea, thiourea, N-phenylthiourea, N,N'-diphenylthiourea and N,N'-dimethylthiourea. Sulfur nucleophiles also include thiobenzoic acid and alkyne thiols such as methanethiol, ethanethiol, 1- or 2-propanethiol, 1- or 2-butanethiol and 2-methylpropanethiol. Representative benzene thiols of the above formula are benzene thiol, 4-b-omo-3-methylbenzenethiol, p-bromobenzenethiol, p-chlorobenzenethiol, 2,5-dichlorobenzenethiol, 2,4-dichlorobenzenethiol, 4-fluorobenzenethiol, m-methoxybenzenethiol, p-methoxybenzenethiol, p-nitrobenzenethiol and p-methylbenzenethiol. Further examples of sulfur nucleophiles are heteroaryl thiols such as pyrrol-2-thiol, pyrazole-3-thiol, 2-methylpyrazole-3-thiol, 2-methylimidazolole-4-thiol, imidazolole-2-thiol, oxazolole-4-thiol, isoxazolole-3-thiol, thiazolole-2-thiol, isothiazolole-3-thiol, 1-methyl-1,2,3-triazolole-5-thiol, 1-benzyl-1,2,3-triazolole-4-thiol, 2-methyl-1,2,3-triazolole-4-thiol, 3,5-dimethyl-1,2,3-triazolole-4-thiol, 1,2,4-triazolole-3-thiol, 4-methyl-1,2,4-triazolole-5-thiol, 3-methyl-1,2,4-triazolethiol-5, 3,4-dimethyl-1,2,4-triazolethiol-5, 2-methyl-1,2,4-triazolethiol-5, 2-benzyl-1,2,4-triazolethiol-5, 2,3-dimethyl-1,2,4-triazolethiol-5, 4-methyl-3-(trifluoromethyl)-1,2,4-triazolethiol-5, 3-carbamyl-4-methyl-1,2,4-triazolethiol-5, 3-(carboxymethyl)4-methyl-1,2,3-triazolethiol-5, 3-(carboethoxymethyl)-4-methyl-1,2,4-triazolethiol-5, 3-amino-4- methyl-1,2,4-triazolethiol-5 with protected amino group, 3-hydroxy-4-methyl-1,2,4-triazolethiol-5, 5-methyl-1,2,3-oxadiazolethiol-4, 1,2,4-oxadioazolethiol-3, 3-methyl-1,2,4-oxadazolethiol-5, 3-methyl-1,2,5-oxadazolethiol-4, 2-methyl-1,3,4-oxadiazolethiol-5, 3-methyl-1,2,4-thiadiazolethiol-5, 1,3,4-thiadiazolethiol-5, 2-methyl-1,3,4-thiadiazolethiol-5, 2-(N-methylacetamido)- -1,3,4-thiadiazole-5-thiol, 5-terrazole-5-thiol, 1-methyltetrazole-5-thiol, 1-benzyltetrazole-5-thiol, 1-(carboxymethyl)tetrazole-5-thiol, 1-[(sodiumoxysulfonyl)methyl]tetrazole-5-thiol, 1-[(2-dimethylaminoethyl)tetrazole-5-thiol, 1,2,3,4-oxatriazole-5-thiol, pyridinethiol-2, pyridinethiol-2-1-oxide, pyridizinethiol-3, pyrimidinethiol-2, pyrazinethiol-2, 1,2,3-triazinethiol-4, 1,2,4-triazinethiol-3, 4,5-dihydro-6- -hydroxy-4-methyl-5-keto-1,2,4-triazonothiol-3, 1,3,5-triazinethiol-2, 1,2,4,5-tetrazinethiol-3, benzimidazolethiol-2, benzothiazolethiol-2, benzoxazolethiol-2 and tetrazolo (1,5-b)pyridazinethiol-6. Most of the sulfur nucleophiles which are used in the process according to the invention are known compounds and all can be obtained by known methods. In the case of heteroarylthiols, the numerous volumes of "Heterocyclic Gompounds", editor Robert C. Elderfield, John Wiley and Sons, Inc., N.Y., are worthy of note. and various volumes on individual heterocyclic systems in the series "The Ministry of Heterocyclic Compounds," published by Weissberger et al., John Wiley and Sons, N.Y. An essential condition of the process according to the invention is that the reactions are carried out in an organic solvent. However, the type of solvent is not essential, since a large number of organic solvents have given satisfactory results. It has been found that generally such groups of solvents as aliphatic and aromatic hydrocarbons, alcohols, amides, ethers, ketones, carboxylic acids, carboxylic acid esters, halogenated hydrocarbons, nitro compounds, nitriles and thioethers are suitable. Since some nucleophiles are liquids, an excess of such a reagent can serve as a solvent. The solvent should be inert in the sense that it cannot react with any of the reagents. Particular solvents suitable for carrying out the reaction include pentane, cyclopentane, hexane, heptane, octane, benzene, toluene, o-, m-, or p-xylene, cumene, methylene, p-cymer, pentene-1, diethyl ether, butyl ethyl ether, diamyl ether, benzyl ethyl ether, acetone, methyl ethyl ketone, 2-butanone, 3-pentanone, methyl isobutyl ketone, cyclohexanone, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, ethyl propionate, butyl acetate, isobutyl acetate, t-butyl acetate, amyl acetate, isoamyl acetate, ethyl isovalerate, methyl benzoate, benzyl acetate, methyl butyrate, diethyl carbonate, dimethyl maleate, diethyl oxalate, ethylene glycol diacetate, diethyl malonate, fluorobenzene, chlorobenzene, bromobenzene, o-, m- or p-fluorotoluene, o-, m- or p-chlorotoluene, o-, m- or p-bromotoluene, 2-chloroethane, 1- or 2-chloropropane, 1- or 2-chlorobutane, 1-chloro-2-methylpropane, 1,2- or 65 3-chloropentane, 1-chloronaphthalene, methylene chloride, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, o-, m- or p-dichlorobenzene, nitromethane, nitroethane, 1- or 2-nitropropane, nitrobenzene, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, valeronitrile, benzonitrile, and phenylacetonitrile. Preferred solvents are hydrocarbons such as benzene, toluene, o-, m-, or p-xylene, cumerin, and mesitylene. Preferred solvents also include halogenated hydrocarbons such as chloroethane, 1- or 2-chloropropane, 1- or 2-chlorobutane, isobutyl chloride, 1-, 2- or 3-chloropentane, methylene chloride, chloroform, 1,2-dichloroethane, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2- trichloroethane, 1,11,2,2-tetrachloroethane, fluorobenzene, chlorobenzene, bromobenzene, o-, m- or p-fluorotoluene, O", m- or p-chlorotoluene, o-, m- or p-bromotoluene, o-, m- or p-dichlorobenzene. Also preferred solvents are acids such as oetic acid, propionic acid, butyric acid, isobutyric acid and acid Preferred ester solvents include methyl acetate, ethylene glycol diacetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, perethyl acetate, ethyl propionate, methyl butyrate, n-butyl metabisulfite, propylene carbonate, and ethylene carbonate. Preferred solvents also include nitro compounds such as nitrobenzene, nitromethane, nitroethane, and nitropropane; nitriles such as acetonitrile, propionitrile, butyrylonitrile, isobutyronitrile, valeronitrile, benzonitrile, and phenylacetonitrile; and ketones such as methyl ethyl ketone and methyl ethyl ketone. methyl isobutyl ketone. Particularly preferred solvents are acetonitrile, 1,2-dichloroethane, methylene chloride, propionitrile, methylbenzene, nitroethane, acetic acid, isopropyl acetate, butyl acetate, and methyl isobutyl ketone. The 3-(acyloxymethyl)cephalosporins of general formula (XVI) used are designated as acids. It is assumed that the acid undergoes the reaction because cephalosporin salts are generally insoluble in organic solvents. An exception is the solubility of cephalosporin salts in carboxylic acids such as acetic acid. The reaction can therefore be carried out by dissolving a 3-(acyloxymethyl)cephalosporin salt, such as an alkali metal salt, in the carboxylic acid. Regardless of the Depending on the nature of the solvent, it is necessary to conduct the process under substantially anhydrous conditions. The reaction mixture should generally contain less than 5% water, preferably less than 1% water, with less than 0.5% water being more preferred. If the commercial starting materials and solvents are not sufficiently anhydrous, water can be removed by known methods such as azeotropic distillation and by using drying agents such as alumina, silica gel, anhydrous calcium sulfate, and the like. The reaction takes place over a wide temperature range. It is generally carried out at 50°C to 140°C, but better results are usually obtained at 70°C to 120°C. The reaction can be carried out at elevated pressures, but no advantage is observed. Therefore, for reasons of simplicity, atmospheric pressure is usually used. process. The amounts of reagents are not critical. In general, an excess of 1.0-5.0 molar equivalents of the sulfur nucleophilic compound per molar equivalent of 3-(acyloxymethyl)cephalosporin is preferred. The process according to the invention is particularly applicable to the introduction of the following heteroarylthio groups into the 3-position of the cephalosporin: 5-methyl-1,3,4-thiadiazolyl-2-thio, 1-methyl-1H-tetrazolyl-5-thio, 1-carboxymethyl-1H-tetrazolyl-5-thio, 4-methyl-6-hydroxy-5-keto-1,2,4-triazinyl-3-thio, 1-methyl-1,3,4-triazolyl-2-thio, 2-methyl- -1,3,4-triazolyl-5-thio, 1,2-dimethyl-1,3,4-triazolyl-5-thio, 3-methyl-1,3,4-triazolyl-5-thio, 2,3-dimethyl-1,3,4-triazolyl-5-thio, 1-methyl-2-trifluoromethyl-1,3,4-triazolyl-5-thio, 1-methyl-2-carboxymethyl-1,3,4-triazolyl-5-thio, 1-methyl-2-carboxymethyl-1,3,4-triazolyl-5-thio, 1-methyl-2-(protected aminomethyl)-1,3,4-triazolyl-5-thio, 1-methyl- methyl-2-(protected amino)-1,3,4-triazolyl-5-thio, 1-methyl-2-hydroxy-1,3,4-triazolyl-5-thio, 1H-tetrazolylc-5-thio, 1-(2-dimethylaininoethyl)-1H-tetrazolyl*5-thio, 1-(sulfomethyl)-1H-tetrazolyl-5-thio, its alkali metal salt, 5-methyl-1,3,4-oxadiazolyl-2-thio, 1,3,4-20-thiadiazolyl-2-thio, 3-methyl-1,2,4-tiad:azolyl-5-thio and 2- - (protected aminomethyl)-1,3,4-thiadiazolyl-5-thio. To the important known cephalosporins of formula I which can be The products to be synthesized by the method according to the invention include cefamandole of formula 22, formylcefamandole and celazafluT of formula 26, SCE-963 of formula 27, BLS-786 of formula 28, CS-1170 of formula 29, SQ-67590 of formula 30, SKF-75073 of formula 31, BBS-226 of formula 32 and SQ-14359 of formula 33. The products of the process according to the invention, their deblocked derivatives and pharmacologically acceptable salts are used in the treatment of infections in warm-blooded mammals when administered parenterally in a non-toxic dose of 10-500 mg/kg of body weight. Preparations containing active The compounds are prepared in a known manner. The examples given illustrate the process of the invention. Example 1. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thienyl-2(acetamido)-3-cephem-4-carboxylic acid in acetonitrile. To 25 ml of acetonitrile placed in a flask equipped with a condenser with a tube containing anhydrous calcium sulfate sold under the brand name Drierite as a drying agent, 2.2 g (5.5 mmol) of 7-[2-(thienyl-2)acetamido-[cephalosporanic acid] and 1.0 g (8.6 mmol) of 1-methyl-1H-tetrazole-5-thiol are added. Calcium The mixture was stirred and heated to boiling, monitoring the reaction by thin-layer chromatography. After 90 minutes of heating, the chromatography showed the presence of about 2/3 of the starting cephalosporanic acid and 1/3 of the desired product. After three hours, the chromatography showed the presence of about 1/3 of the starting cephalosporanic acid and 2/3 of the desired product. After 6 hours, according to the chromatography, the reaction was practically complete, and then the mixture was cooled to room temperature and allowed to stand overnight. The solvent was evaporated on a rotary evaporator, and the residual foam was dissolved in 10 ml of ethanol. After dropwise addition of 1 ml of dicyclohexylamine solution in 10 ml of ethanol precipitated the dicyclohexylammonium salt of the product, which was filtered off after 15 minutes of stirring. This product was washed with 15 ml of ethanol and dried under reduced pressure at 40°C for 2 hours. 2.50 g (76.1%) of product 65 was obtained, melting at 183-184°C (with decomposition).122 152 13 The PMR and IR spectra and thin-layer chromatography give results identical to those for the original sample of the product obtained by the previous method by substitution in an aqueous medium. The PMR spectrum (DMSO-cUM): 3.52 (mA2-CHO, 3.76 (s,2,CH2CONH-), 3.92 (s,3, —CH1 in tetrazole), 4.35 (s,2,3—CH2S), 5.00 (d, 1, Q—Hf J=5Hz), 5.55)q, 1, C—H, J=5Hz, J=9Hz), 6.95 (d, 2, 3 and 4-^1 from thiophene, J=3Hz), 7.35 (t, 1.5—H from thiophene, J-3Hz) and 8.75 (d, 1,—CH2CONH—, J=9Hz). Example 2. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thienyl-2-acetamido]-cephem-3-carboxylic acid in acetonitrile. 4.0 g (10 mmol) of 7-[2-(enyl-2-acetamido]-cephalosporanic acid and 5.8 g (50 mmol) of 1-methyl-1H-tetrazol-5-thiol was heated to reflux in 50 ml of anhydrous acetonitrile (stored over anhydrous sulfonic acid resin, sold under the trade name Amberlit 15) and reacted in an anhydrous atmosphere for 8 3/4 hours. Thin-layer chromatography showed that the reaction was almost complete after 8 3/4 hours. The solvent was evaporated and the residue added to 125 ml of chlorol. After addition of a solution of 6 ml of dicyclohexylamine in 75 ml of ethanol, the product precipitated as the dicyclohexylamine salt. After washing and drying, 4.50 g of product was obtained; yield: 71.0%. IR and PMR spectra and thin-layer chromitography show that the product is identical to an authentic sample of the product obtained by the aqueous substitution method. The CMR spectrum is the same as for product X in Example I. Example III. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)methyl]-7-[2-(thienyl-2)acetamido]cephem-3-carboxylic acid in 1,2-dichloroethane. 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol in 25 ml of 1,2-dichloroethane are heated at reflux in an anhydrous atmosphere for 5.5 hours. The solvent was removed using a rotary evaporator, and a solution of 2 ml of dicyclohexylamine in 25 ml of ethanol was added dropwise to the residue dissolved in 25 ml of ethanol. The product crystallized as the dicyclohexylamine salt. The mixture was stirred for 20 minutes at room temperature, then filtered, washed with 25 ml of ethanol, and dried at 40°C under vacuum. 2.34 g (73.8%) of a cream-colored solid was obtained. The IR and PMR spectra were the same as for the sample obtained by substitution in an aqueous medium. The PMR spectrum was the same as for the product of Example 1. Example IV. Preparation of 3-[1-Methyl-1H-tetrazolyl-5)thiomethyl]-7-aminocephemo-3-carboxylic acid in 1,2-dichloroethane. 3.0 g (10 mmol) of 7-formamidocephalosporanic acid and 2.4 g (20 mmol) of 1-methyl-1H-tetrazol-5-thiol are stirred and heated to reflux for 7 hours in 50 ml of 1,2-dichloroethane. The mixture is cooled to room temperature and left at this temperature overnight. A red gummy precipitate forms. The 7-formyl group is removed from the product as follows. The solvent was removed using a rotary evaporator, and the residue was dissolved in 25 ml of methanol and 2.8 ml of concentrated hydrochloric acid and left at room temperature overnight. The solution was diluted to 50 ml with water, and the pH, initially 0.9, was raised to 3.6 by the dropwise addition of triethylamine. The resulting light yellow crystals were filtered off, washed with water, and dried. 2.10 g (64%) of product was obtained. The PMR spectrum was identical to that of the product obtained by aqueous substitution. PMR spectrum (D2O, NaHCO3) <5: 3.65 (q, 2.2—CH2, Jab=16.5Hz), 4.08) (s, 3,—CH3 in tetrazole), 4.16 (q, 2.3—CH2S—, Jab=12.5Hz), 5.05 (d, 1, C1—H, J=5Hz) and 5.45 (d, 1, 10 C1—H, J=5Hz). Example 5. Preparation of 3-[(1-methyl-1H-tetraiohlo-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid-4 in isopropyl acetate. 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamido]-15-cephalosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol were heated to reflux in 25 ml of isopropyl acetate with stirring for 23 hours. The reaction mixture was cooled to room temperature. Thin-layer chromatography showed that some starting cephalosporanic acid remained. The light cream precipitate was filtered off, washed with isopropyl acetate, and dried. 1.60 g (70.8%) of product was obtained. The CMR spectrum confirmed the identity of the product and showed that it was obtained from 1% of the starting cephalosporin. FMR spectrum (DMSO-d*): 3.72 (s, 2, 2- ~ CHaX 3*O(* 2, -^OLCONH-), 3.99 & 3* -CH, from tetrazole), 4.30 2,3-^Clk-S~), 5.10 (d, 1, C^H, J-5Hz), 5.70 (q, 1, Cr-, J-5Hz, J=8Hz), 6.92 (d, 2, 30 3- and 4-^H from thiophene, J-3Hz), 735 (t, 1, 5—H of thiophene, J ~3 Hz) and 8.78 (d, 1, —CHiCONH—, J-8 Hz). Example VI. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)methyl]-7-[2-(thienyl-2(aortamido)-3-cephem-4-carboxylic acid in propionitrile. 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamidol-cephalosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol in 25 ml of anhydrous propionitrile are heated at reflux (97°C) until complete disappearance of the starting cephalosporanic acid is detected by thin layer chromatography, which takes 4.5 hours. The reaction mixture is cooled to room temperature and the solvent is evaporated using a The residue was dissolved in 35 ml of warm ethanol and a solution of 2 ml of dicyclohexylamine in 10 ml of ethanol was added. The dicyclohexyl ammonium salt precipitated. The mixture was stirred for 10 minutes at room temperature, filtered, washed with ethanol, and dried. 1.24 g (39.0%) of product was obtained, without the product lost in the rotary evaporator. The CMR spectrum was identical to that of the product of Example 1. Example 7. Preparation of 3-[1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid 4 in acetonitrile with the addition of dihydrogen phosphate. 3,5-Dichlorophenyl. 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid, 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazol-5-thiol and 3,5-dichlorophenyl dihydrogen phosphate (0.122 g, 0.5 mmol) are heated overnight (0.01 in 25 ml of anhydrous acetonitrile at a temperature of about 70°C. The solvent is evaporated on a rotary evaporator to a volume of about 8-10 ml, at which time the product begins to crystallize. The mixture is stirred for half an hour and then 25 ml of isopropyl acetate are added dropwise over the course of half an hour, which causes further crystallization. Crystallization. After half an hour of additional stirring, the precipitate was filtered off, washed with isopropyl acetate, and dried. 0.98 g (43.4%) of product was obtained, the PMR spectrum of which was identical to that of the product of Example 5. Example VIII. Preparation of 3-[(1H-tetrazol-5-yl)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid in acetic acid. To 25 ml of glacial acetic acid were added 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazol-5-thiol. The mixture was heated to 60°C and left at this temperature for one hour. Thin-layer chromatography showed only traces of the product. The reaction mixture was heated for 5 hours at 80°C, then left overnight, and the product was filtered off, washed with acetic acid, and dried. 0.71 g (31%) of product was obtained, the PMR spectrum of which was identical to that of the product of Example 5. Example 9. Preparation of 3-[(4,5-dihydro-c% hydroxy-4-methyl-5-keto-1,2,4-triazinyl-3)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid- in acetonitrile. To 25 ml of anhydrous acetonitrile placed in a reaction flask immersed in an oil bath at a temperature of 4-85°C, 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 1.2 g (7.5 mmol) of 4,5-dihydro-6-hydroxy-4-methyl-5-oxo-1,2,4-triazine-3-thiol are added. The flask is equipped with a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierit, as a drying agent. The mixture is stirred gently with a magnetic stirrer for 16 hours under the above conditions. The product crystallizes from the hot solution. The mixture is cooled to room temperature, filtered, the precipitate is washed with acetonitrile and acetone and dried under reduced pressure. 1.81 g (72.6%) of product are obtained in the form of whitish crystals, melting at 161°C (with decomposition). After standing, a second batch of crystals falls out from the filtrate. After filtration, washing with acetonitrile and drying, 0.26 g (10.5%) of product is obtained, also melting at 161°C (with decomposition). The total yield is therefore 83.1%. Example 10. Preparation of 3-[(5-methyl-1-3,4-oxadiazol-2-yl)thiomethyl]-7-[2-(thien-2-yl)acetamido]-cephem-3-carboxylic acid in 1,2-dichloroethane. A mixture 2.0 g (6 mmol) of 7-[2-(thien-2-yl)acetamido[-cephalosporanic acid] and 0.87 g (7.5 mmol) of 5-methyl-1,3,4-octadiazoletholyl-2-ol in 25 ml of 1,2-dichloroethane are placed in a flask equipped with a magnetic stirrer and a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierit, as a drying agent. The flask is immersed in an oil bath at 84-85°C for 8 hours and cooled for two days. Some of the product crystallizes and is filtered off, washed with 1,2-dichloroethane and dried, yielding 1.10 g (48.7%) of the product. The product dissolves in 15 The mixture is then removed by evaporation and filtered to remove insoluble matter. 75 ml of demineralized water are then added dropwise, and the precipitated product is filtered off and dried. 0.61 g of product is obtained, melting at >114°C (with decomposition). After evaporation of the filtrate, 0.23 g of a mixture of the product and both starting compounds is obtained. Example 11. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2-acetamido]-3-cephem-4-carboxylic acid in nitromethane. To 25 ml of anhydrous nitromethane is added 2.0 g (5 mmol) of 7-[2-(thienyl-2-acetamido]-cephalosporin and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazolium-5-thiol. The flask was immersed in an oil bath at 100-101°C for 4.5 hours and then cooled to room temperature. Thin-layer chromatography showed that the reaction was complete. The solvent was evaporated on a rotary evaporator and the residue was dissolved in 75 ml of warm ethyl acetate. The solution was filtered to remove a small amount of insoluble material and then extracted with two 25 ml portions of 5% aqueous sodium bicarbonate solution. To the combined extracts was added 50 ml of ethyl acetate and the pH was adjusted to approximately 1.0 with 70% aqueous sodium bicarbonate solution. The acetate layer was separated and the aqueous layer was extracted with 25 ml of ethyl acetate. The combined acetate layers were dried over anhydrous sodium sulfate and concentrated to 25 ml using a rotary evaporator. After the dropwise addition of 50 ml of diethyl ether, the product crystallized and was filtered off, washed with diethyl ether, and dried. 1.27 g (56.2%) of cream-colored crystalline product was obtained, melting at 156-159 °C (with decomposition). The identity of the product was confirmed by CMR. Example XII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2-acetamido]-30 acid 3-Cephem-4-carboxylic acid in methylene chloride. A mixture of 11.9 g (30 mmol) of 7-[2-2-(thienyl-2)acetamido]-cephalosporanic acid and 7.0 g (60 mmol) of 1-methyl-1H-tetrazole-5-thiol in 300 ml of cyclohexane-stabilized methylene chloride is placed in a 1 liter acid-resistant autoclave equipped with a heater. The mixture is stirred and heated at 83-86°C for 16 hours under a pressure of 2.952-102 kPa. The mixture is then cooled to room temperature. Thin layer chromatography shows conversion to the product, with only traces of the starting acid remaining. The mixture was allowed to stand at room temperature until crystallization occurred. After concentration to approximately 200 ml, the precipitate was filtered off and washed with methylene chloride. 7.37 g (54.3%) of a white crystalline solid was obtained, melting at 163.5-164°C (with decomposition). The filtrate was diluted with 100 ml of diethyl ether, the precipitate was filtered off, washed with diethyl ether, and dried. A second portion of 1.40 g (10.3%) of product was obtained as light yellow crystals. A third portion of 1.18 g (8.7%) was obtained by diluting the filtrate with isopropyl acetate. The total yield was therefore 73.3%. Example XIII: Preparation of cephalosporin 3-[(1-Methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thienyl-2-acetamido]-cephem-3-carboxylic acid-4-in fluorobenzene. A mixture of 2.0 g (5.04 mmol) of 7-[2-(thienyl-2)acetamido]cephalosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol-5-in 75 ml of fluorobenzene (boiling point 85.1°C) is stirred in a flask fitted with a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierite, as a drying agent. The whole is heated to boiling point and the course of the reaction is monitored by means of a Thin-layer chromatography using ethyl acetate-acetic acid 65 7:1. The mixture remains heterogeneous and the reaction is practically complete after 72 hours. The reaction mixture is cooled to room temperature, the precipitated product is filtered off, washed with fluorobenzene, and dried at 40°C under vacuum for five hours. 2.13 g (93.4%) of product are obtained as cream crystals, melting at 161-162°C (with decomposition). The identity of the product is confirmed by PMR. Example 14. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-acid [2-(2-thienyl)acetamido]-10-cephem-3-carboxylic acid in thiophene. A mixture of 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamido]-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazole-5-thiol was heated at reflux in 25 ml of thiophene for 7 hours. During this time, the product crystallized. The reaction mixture was cooled to room temperature, stirred for 30 minutes to complete crystallization, then the precipitate was filtered off, washed with 0.5 ml of thiophene, and dried under vacuum for 2 hours. 1.82 g (80.2%) of the product was obtained as 20 White crystals, melting at 162-163°C (with decomposition). Thin-layer chromatography shows the presence of additional product in the filtrate. Example 15. Preparation of 3-[(5-methyl-1,3,4-thiadiazoyl-2-methyl]-7-[1H-tetrazoliyl-1)acetamido]-cephalosporanic acid in acetonitrile. A mixture of 0.76 g (2.0 mmol) of 7-[2-(1H-tetrazoliyl)acetamido]-cephalosporanic acid and 0.33 g (2.5 mmol) of 5-methyl-1,3,4-thiadiazole-2-thiol is heated to boiling in 10 ml of pure acetonitrile for 30 two hours and forty minutes. The product crystallizes during this time. The reaction mixture is cooled in an ice bath and the product is filtered off, washed with 3 ml of acetonitrile and dried under vacuum at 40°C. 0.61 g (67%) of product is obtained, the identity of which was confirmed by CMR. CMR spectrum: 2.68 (s, 3, —CH3 from tetrazole), 3.72 (s, 2, 2 — CH2), 4.40 (q, 2, 3 — CH2S—, Jab= 13 Hz), 5.12 (d, 1, C6 — H, J=5 Hz), 5.38 (s, 2, — CH2CONH—), 5.72 (q, 1, C7—H,J=5Hz,J=9Hz), 9.00(s,l,5—H from thiophene) 40 4 9.17 (d, 1, —CH2CONH—).Example XVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-formyloxy-2-phenyl-acetamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 45 To 25 ml of 1,2-dichloroethane are added 2.17 g (5 mmol) of 7-(2-formyloxy-2-phenylacetamido)-cephalosporic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazolethiol-5. The whole is heated to boiling point for six hours, taking samples by thin-layer chromography at 3 and 6 hours. The mixture was heated for an additional hour and allowed to cool overnight. The solvent was evaporated, and diethyl ether was added to the residue, forming a gummy precipitate that subsequently solidified. After filtration, washing with diethyl ether, and drying, 1.90 g (77.0%) of product was obtained. PMR spectrum (DMSO-d6) <$: 3.52(s, 2.2—CH2) 3.88 (s, 3, —CH3 from tetrazole), 4.10(s, 2.3—CH2S—), 4.92(d, 1, C6—H), 5.62(q, 1, C7—H, J=5Hz, J=9Hz), 6.06(s, 1, eo —CHCONH—), 7.26(s, 5, phenyl protons) and 8.28 (s, 1, —OC( =O)H). Example XVII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[5-carboxy-5-(2,5-dichlorobenzamido)-valeramido]-cephem-3-carboxylic acid-4 in acetonitrile (A) and 1,2-dichloroethane{B).A) Mixture 2.9 g (5 millimoles) of 7-[5-carboxy-5-(2,4-dichlorobenzamido)valeramido]-cephalosporanic acid and 1.2 g (10 millimoles) 1-methylIo-1H-tetrazolothioIu-5 in 50 ml of acetonitrile, heated at reflux overnight (about 18 hours). Thin layer chromatography shows that the reaction is approximately 90% complete. The reaction mixture was evaporated and the residue suspended in ethyl acetate and filtered, yielding 1.51 g (48.3%) of product. B) A mixture of 2.9 g (5 mmol) of 7-[5-(carboxy-5-(2,4-dichlorobenzamido)valeramido]-cephalosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol in 50 ml of 1,2-dichloroethane was heated at reflux for 5.5 hours. Thin-layer chromatography showed a reaction completion of about 90%. The solvent was decapitated and the remaining plastic precipitate was triturated in boiling ether and filtered off, yielding 2.83 g (89.3%) of product as a dark yellow solid. crystalline precipitate. CSF spectrum (DMSO-d65: 1.78 and 2.26(dvam,adipoyl side chain), 3.66(m, 2.2—CH2), 3.95/s, 3, —CHi from tetrazole), 4.30(m,2.3—CH2S—), 5.08(d, 1, O—H, J=5Hz), 5.68(q,l,C7—H,J=5Hz), 7.50 and 7.62(divas, 2,4-dichlorophenyl) and 9.00(m, 2, two groups —CONH—).Examples XVIII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2(acetamido] acid) -phenyl-3-carboxylic acid-4-dichloroethane. A mixture of 99 g (2.5 mmol) of 7-[2-(2-thienyl-2)acetamido]-oephalosporalic acid and methyl-1H-tetrazolium-5-thiol in 12.5 ml of 1,2-dichloroethane was heated to reflux, removing the acetic acid formed as a by-product by passing the recycled 1,2-dichloroethane through calcium oxide. After 5 3/4 hours of heating, the reaction mixture was cooled to room temperature and filtered. The flocculent needle-shaped precipitate was washed with 10 ml of 1,2-dichloroethane and dried, yielding 0.77 g (68.1%) of the product. After evaporation of the filtrate, An additional 0.04 g (3.5 %) of product is obtained. The identity of the product is confirmed by thin-layer chromatography and, in the case of the main product, by CMR analysis. The CMR spectrum is identical to that of the product of Example 5. Example 19. Preparation of 3-[(-5-methyl-1,3,4-thiadiazolyl)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid in acetonitrile. A mixture of 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 2.64 g (20 mmol) of 5-methyl-1,3,4-thiadiazolethiol-2 in 25 ml of acetonitrile is heated at 79 °C overnight. Thin layer chromatography showed only traces of the starting cephalosporanic acid. The reaction mixture was filtered to remove an oily residue and the solvent was removed on a rotary evaporator. The residue was crystallized from a 1:1 mixture of acetonitrile and isopropyl acetate, filtered off, washed and dried under vacuum. 1.59 g (33.9%) of product was obtained, melting at 166 °C. The identity of the product was confirmed by IR, UV, mass spectrum and elemental analysis. PMR ((DMSO-d e )S: 2.68 (s, 3, -CH 3 from tetrazole), 3.68 (s, 2,2 -CH 2 ), 3.76 (s, 2, —CH2CONH—), 4.38 (q, 2, 3—CH2S), J = =13Hz),5.10(d, 1, C6—H, J=5Hz), 5.70(q, 1, C7—H, J=5Hz, J=9Hz), 6.92(d, 2.3— and 4—H from thiophene), 7.37 (t, 1,5—H from thiophene) and 9,10(d, lt—CH2CONH-., J=9Hz).122 152 19 Example XX. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in 1,1,2-trichloroethane. Mixture 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido[-cephalosporanic acid] and 1.2 g (10 mmol) of 1-methyl-1H-tetrazolethiol in 25 ml of 1,1,2-trichloroethane are heated to 100-101°C. The reaction is monitored by thin-layer chromatography. After stirring at 100-101°C for 4 hours, thin-layer chromatography shows no trace of starting cephalosporanic acid. The mixture is stirred and cooled to room temperature. The reaction mixture is seeded and stirred overnight, during which time the product crystallizes. The solvent is evaporated and 25 ml of 1,2-dichloroethane is added. The product is filtered off, washed with water and dried. 1 is dried under reduced pressure. 0.98 g (43.4%) of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid is obtained, melting at 158°C (with decomposition). Example XXI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid in nonmethylethyl ketone (A) and 1,1,2-trichloroethene (B). A) A mixture of 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamdo]-acetosporanic acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazol-5-thiol in 25 ml of methyl ethyl ketone was heated at reflux for 48 hours. Thin-layer chromatography showed only traces of the starting cephalosporanic acid. The reaction mixture was washed with a solution of 2.5 g of sodium bicarbonate in 50 ml of water. To the aqueous layer was added 1 g of charcoal and 50 ml of ethyl acetate, and the pH was then lowered to 1.6 by adding 4 ml of methanesulfonic acid in 30 ml of water. The ethyl acetate layer was dried over sodium sulfate and evaporated on a rotary evaporator to an oily residue. The product crystallized after the addition of 50 ml of ether. The mixture is filtered off, washed, and dried under reduced pressure. 0.94 g (41.6%) of product is obtained, the PMR spectrum of which is identical to that of the product of Example V. B) The procedure is repeated, using the same amounts of starting compounds as in (A), but using 50 ml of 1,1,2-trichloroethylene as the solvent. The reaction mixture is heated at reflux for 16 hours. Thin-layer chromatography shows the disappearance of the starting cephalosporanic acid. The product is isolated as described in (A). 0.47 g (20.8%) of product is obtained, the PMR spectrum of which is identical to that of the product of Example V. Example XXII. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-acid [2-phenylacetamido)-7-methoxy-cephem-3-carboxylic acid in 1,2-dichloroethane. A mixture of 210 mg (0.5 mmol) of 7-(2-phenylacetamido)-7-methoxycephalosporanic acid and 87 mg (0.75 mmol) of 1-methyl-1H-tetrazolium-5-thiol in 15 ml of 1,2-dichloroethane was stirred and heated to reflux under nitrogen for 6 hours. Thin layer chromatography showed only traces of the starting cephalosporanic acid. An additional 29 mg (0.25 mmol) of 1-methyl-1H-tetrazolium-5-thiol was added and the mixture was heated to reflux for 6 hours. The reaction mixture was stirred for another three hours. Thin-layer chromatography showed no noticeable changes. The reaction mixture was washed four times with saturated sodium bicarbonate solution. The carbonate layer was washed three times with ethyl acetate, then a fresh portion of ethyl acetate was added, cooled to 0°C, and the pH was adjusted to 2.2.5 with 20% HCl. The layers were separated, and the aqueous layer was washed with ethyl acetate. The combined ethyl acetate layers were washed with saturated NaCl solution, dried over magnesium sulfate, filtered, and evaporated. 199 mg (83.6%) of a light green foamy precipitate was obtained, the identity of which was confirmed by the CMR spectrum and thin-layer chromatography. The CMR spectrum (CDCb+ Id acetone-dtf5: 3.45(s, 3,—OCHs), 3.55(s, 2, 2—CH2), 3.75 (s, 2, CoHsCHzCO—), 3.9(s,3,CH3from tetrazolium), 4.4(s,2, 3—CH2S—), 5.15(s, 1, C6—H), 7.35(s, 5, C6H5-), 8.0(8, 1, -CH2CONH-) in and about 11.2(s,1,J«OHz,-COOH). Example XXIII. Preparation of 3-[(2-benzothiazolyl)thiomethyl]-7-[2-(thienyIo-2)aoethamido]-cephem-3-carboxylic acid-4 in 1,2-dichloroethane. 1.0 g (2.5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.625 g (3.75 mmol) of 2-mercaptobenzothiazole were placed in a flask, the air was removed with a stream of nitrogen, 25 ml of 1,2-dichloroethane was added, and the mixture was heated at reflux for 24 hours. The mixture was cooled and filtered, yielding 1.1 g (88%) of a cream-colored product, melting at 190.5°C-191°C. This product was dried overnight under vacuum at 40°C and analyzed. The identity of the product was confirmed by spectral analysis. It included PMR, DV, IR, mass spectra, and elemental analysis. The PMR spectrum (DMSO-d«V: 3.74(s, 2.2—CH2), 3.80(s, 2, —CH2COKH—), 4.58(q, 2.3—CH2S—, J=13Hz), 5.14(d, 1.0-H, J=5Hz), 5.73(q, 1, C7—H, J«5Hz J—8Hz), 6.96, 7.43 and 7.96 (three m, phenyl ring 85 and thienyl), 9.10(d, 1,—CH2COKH—, J=8Hz). Example XXIV. Preparation of 3-[(N-methylacetamido)-1,3,4-thiadiazcl;lc-2)t'methyl] -7- [2- (tie- 41. A mixture of 2.0 g (5 mmol) of 7-[2-(thienyl-2-(acetamido)-cephem-3-carboxylic acid] and 1.42 g (7.5 mmol) of 5-(N-methylacetamide)-1-(thiadiazole)-acetamide in 50 ml of 1,2-dichloroethane was heated at reflux for 10 hours. The reaction mixture was cooled, filtered, washed with 1,2-dichloroethane and dried under reduced pressure. 2.06 g (78.3%) of product was obtained, melting at 178-179 CC. The identity of the product was confirmed by IR, TJV, PMR and mass spectrum analyses and elemental analysis. PMR spectrum (DMSO-dtf5: 2.42(s, 3, —COCHa), 3.74(m, 7, 2—CH2, —CH3 from tetrazole and CH2CONH—), 4.35(q, 2, 3—CH2, J=13Hz), 5.10(d, 1, C«—H, J=5Hz), 5.70(q, 1, Ct—H, J-5Hz, J=9Hz), 6.96 and 7.36(two m, 3, H from thiophene) and 9.10(d, 1, —CH2 65 CONH—, J=9Hz). Example XXV. Preparation of 3-[(1-methyl- 1H-tetrazoyl-5)tphomethyl]-7-(N-tert-butoxycarboxyl)-2-phenylglycylamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 45 ml of 1,2-dichloroethylene are heated at boiling point to remove the azeotreceptive mixture with water, and then the solvent is distilled to a volume of 30 ml and cooled. 253 mg (0.5 mmol) of 7-(N-tert-butoxycarboxyl-2-phenylglycylmide)cephalic sporane acid are added and distilled and piped to a volume of 122 1/2 21 15 ml and cooled again. Add 87 mg (0.75 millimol) of 1-methyl-1H-tetrasol-5-thiol and reflux under nitrogen, monitoring the reaction by thin-layer chromatography. After 16 hours, chromatography showed only traces of the starting material. The reaction mixture was washed four times with saturated sodium bicarbonate solution, the carbonate layers were combined and washed twice with ethyl acetate. Add fresh ethyl acetate to the washed carbonate solution, cool to 0°C, and adjust the pH to 2.4 with 20% HCl. The layers were separated, and the aqueous layer was washed with ethyl acetate. The acetate layers were combined, washed with saturated NaCl solution, and dried over magnesium sulfate, filtered, and evaporated. 224 mg (80%) of a white foamy product is obtained, the identity of which is confirmed by thin-layer chromatography (TPMC). CSF analysis shows the presence of a small amount (< 0.10%) of the starting cephalosporanic acid. The product is suspended in 10 ml of diethyl ether and triturated for 1 hour. The ether is decanted, 10 ml of diethyl ether is added, and triturated for another hour. The ether is decanted and evaporated to dryness, leaving the product as a white powder. The identity of the product is confirmed by thin-layer chromatography and CSF. CSF spectrum (CDQ, M: 140(i»^) —COO-m-rz. -C*H»), 3.6 (s, 2.2—CHa), 3.95(s3, CHi from tetrazolium)* 4.3(s, 2.3—CILS—), 4.9(d, 1, J-6H* Q—H), 5.4(d, 1, J-8H* C6H3CH—), 5.75(q, 1, J- 30 -4Hz, Cr-H), 6.2(d, 1, J*=8Hz, OHsCH)—NH)—), 7.4 (s,5,C6Hs—), 7.65(d,l,J=*8Hz,CONH) and about *.3(s,l,COOH). Example XXVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)t omethyl]-7-[N- (III-butoxycarbonyl)-2-(p-hyd:ocylphenyl)glycylamido]-cephemo-3-carboxyl-4 in 1,2-dichloroethane. 45 ml of 1,2-dishlorootate are heated at reflux using an asotropic solution and 15 ml of the solvent are removed. After 30 ml, 30 ml are cooled, 260.5 mg of 40 (0.5 millimohm) 7-[N-(tert-butoxycarbonyl)-2-(p-hydroxy)glycylamido]-cephalosporan acid are added, the solvent is distilled to a volume of 15 ml and cooled again, and then added 87 mg (0.75 millimoles) of 1-methyl-1H-tetrazobthiol-5 and heated at 65-70°C, monitoring the reaction by thin-layer chromatography. After 3 hours, chromatography showed almost complete disappearance of the starting compound. After 4 hours, the mixture was worked up and purified in practically the same manner as in the previous examples. 189 mg (65.5%) of crude product and 46 mg (approximately 16%) of purified product were obtained. PMR spectrum (CDCb+2d acetone-d6) <5: 1.45 (s, 9,— —COO—tert.—C4H9), 3.35 (s, 2, 2—CH2), 3.85 (s, CH3 from tetrazole), 4.3 (s, 2, 3~CH2S—) 4.9 (d, 1, J=*6Hz, 55 C6—H), 5.3 (q, 1, J=3Hz, Ci—H), 5.4 (s, 1, HO— —CeHsCH—), 5.75 (d, 1, J=6Hz, HO—CaHsCH— —(—NH)—), 6.4 (s, 1, COOH), 6.8 (d, 2, J=8Hz, group of formula 34) and 7.9 (d, 1, —CONH—). Example XXVII. Preparation of 3-[(1-(2-phenoxyacetamido)-3-cephem-4-carboxylic acid in 1,2-dichloroethane. 60 ml of 1,2-dichloroethane are heated to reflux using an azeotropic adapter and 15 ml of solvent are removed. The remaining 45 ml are cooled, 406 ml (1 mmol) of 7-(2-phenoxyacetamido)-5-phalosporaic acid are added, the solvent is distilled to 30 ml and the mixture is cooled again. 174 mg (1.5 mmol) of 1-methyl-1H-tetrazole-5-thiol are added and the mixture is heated to reflux under nitrogen for 12 hours. Thin layer chromatography, developed with 10 parts ethyl ether and 3 parts 3:1 acetic acid:water, shows the presence of product, excess thiol, a small amount of starting cephalosporanic acid and an unknown compound. The reaction mixture is worked up in practically the same manner as described in the two preceding examples. Chromatography of the final product shows that it is identical with the product obtained in the previously known manner. PMR spectrum (CDCb)*: 3.65 (s, 2, 2—CHz), 3.*(s, 3 CH3 from tetrazole), 4.35 (s, 2, 3—CH2S—), 4.65 (s, 2, C*H, CH2—), 5.1 (d, 1, J—4H*, C6^H), 5.9 (q, 1, J—4Hz C7—H), 7.1 (m, 5, C6Hs—), 7.6 (d, 1, J=*10Hz, —CONH—) and about 9 (s, 1, —COOH). Examples XXVIII-XXXI. Preparation* of 3-[(l-methyl-jlH-tetrazolyl-5)thiomethylJ-7*{2-(thienylT 2)Lcetamido]-cefemo-3* carboxylic acid-4 in fluorobenzone* Acid - 3Kl(l*iftstyb-lH-t«tra3KliJo-5)ttoinetylJ' 1* K-a)acetamideQ1-cifemo-3-carboxylic acid-4 is prepared in four different reactions using different cephalosporasic acids; XXVIII — 41 mg (0.1 mmol) 3-(propionyl-oxymethyl)-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid, XXIX — 42 mg (0.1 mmol) 3-(2-methylpropionylpoxymethyl)-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid, XXX — 42 mg (0.1 mmol) 3-(n-butyryloxymethyl)-7-[2-(enyl-2)acetamido]-cephem-3-carboxylic acid, XXXI — 43 mg (0.1 mmol) 3-(cyclobutylcarbonyloxymethyl)-7- [2-(2-thienyl-2)acetamide]-3-carboxylic acid. In each case, the compound is suspended in 10 ml of fluorobenzene (dried over an aluminosilicate drying agent, sold under the name Linde 4-A molecular sieves). In each case, 18 mg (0.15 mmol) of 1-methyl-1H-tetraazole-5-thiol is added, and the reaction mixture is heated at reflux for about 24 hours. The precipitated product is filtered off and dried. Thin-layer chromatography in a mixture of ethyl acetate and acetic acid shows that the substitution is quantitative in each case. The CMR spectra of each product are identical to those of the sample obtained by substitution in an aqueous medium. Example XXXII. Preparation of 3-[(3-methyl-1,2,4-oxad4azol-5-yl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid in 1,1,2-trichloroethane. 396 mg (1 mmol) of 7-[2-(2-thienyl)acetamido]-cephalosporanic acid are suspended in 40 ml of 1,1,2-trichloroethane and 116 mg (1 mmol) of 3-methyl-1,2,4-oxadiazol-5-thiol are added. The reaction mixture is heated for about 3 hours at 113°C in an oil bath, then allowed to cool overnight and evaporated to an oil. To this residue is added ethyl acetate and saturated sodium bicarbonate solution. 122 152 23 The acetate extract was washed with sodium bicarbonate solution. The carbonate layers were combined and washed with ethyl acetate. The aqueous layer was covered with a new portion of ethyl acetate, cooled in an ice bath, and the pH adjusted to 2.5 with 20% HCl. The layers were separated, and the aqueous layer was extracted again. The acetate solution was washed, stirred with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated. 1,1,2-Trichloroethane was added to the residue, and the product solidified. 220 mg (48%) was obtained. The identity of the product was confirmed by PMR, IR, and UV spectra, as well as a bioautogram. PMR spectrum (DMSO- 6, 6, 1, 2, 3, CHr from oxadiazole), 3,7 (q, 2, J=18Hz, 2—CHiK 3,8fe,2,—dfeCONH—), 4,4 (q, 2, J=14Hz, 3—CH2S—), 5,1 (d,1, J=5Hz, Ctf—H), 5,6 (q, 1, J=4Hz, Ct—Hft 69,7,3 (t,d, 39 Hz of thiophene), 9,1 (d* 1, J-8Hz, —CHaGONH—). In class XXXIII. Preparation of 3-[(1H- 1,3,4-triazotyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido] acid Cephem-3-carboxylic acid-4 in 1,1,2-trichloroethane. 396 mg <1 mmol) of 7-[2-(thienyl-2)acetamido]cephalosporanic acid is suspended in 30 ml of 1,1,2-trichloroethane and 100 mg (approximately 1 mmol) of 1H-1A4-triazol-5-thiol is added. The mixture is heated to 105°C. After 30 minutes, the product precipitates. The mixture is heated at about 100°C for about 6 hours and then cooled to room temperature. The product is filtered off and washed with 1,1,2-trichloroethane. Yield: 388 ml (87%). *¦ The identity of the product is confirmed by IR, CSF and UV and bioautogram. The bioautogram also indicates the presence of the starting cephalosporanic acid, the amount of which according to high-pressure chromatography is 6.8%. The CSF spectrum (DMSO-KfcJS: 3.7 (s,2, 2^CHi), S,8(«,2,—CHiCONH—), 4.2 (q, 2, J=5Hz, 3^GH2^S—), 5.1 (d,1, J~5Hz, Ctf—H), 5.7 (q, 1, J=4Hz, C7—H), 7.0 ( and 7.4 (t,d,3,H of thiophene), 8.45 (s,3, NHztriazole) and 9.13 (d, 1, J=8Hz,— —CHiCONH—). Example XXXIV. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(2-phenylacetamido)cephem-3-cyboxylic acid in chloroform. 195 mg (0.5 mmol) of 7-(2-phenylacetamido)-cephalosporanic acid were suspended in 75 ml of chloroform and 75 mg (0.65 mmol) of 1-methyl-1H-tetrazol-5-thiol were added. The reaction mixture was heated in a water bath at 0°-85°C for 3 hours and 60 ml of the solvent was distilled off. Thin layer chromatography showed the presence of a very small amount of product. 20 ml of 1,2-dichloroethane and heating continued overnight. Chromatography showed the presence of a small amount of the starting cephalosporin. After a total of 26 hours, the reaction mixture was cooled to room temperature. The product was worked up as described in Example 32, yielding 80 mg of purified compound (35%). The product identity was confirmed by IR, UV, and bioautograph, PMR (DMSO-d). <5: 3.6(s,2,2—CH2), 3.7(s, 2,—CH2CONH—), 4.0(s,3,CH3 from tetrazolium), 4.3(s, 2, 3-CH2S—), 5.1 (d, 1, J=5Hz, C6—H), 5.7(q, 1, J=4Hz,C7—H), 24 314 mg (1 millimole) acid 7-acetamidocephalosporanic acid and 98 mg (0.65 mmol) of 1-methyl-1H-tetrazolium-5-thiol are stirred in 70 ml of 1,2-dichloroethane and then 50 ml of solvent are distilled off, then heated and boiled for about 24 hours. The reaction mixture is worked up as in Example XXXII, obtaining 120 mg (32 %) of the product, the identity of which is confirmed by analysis of the CMR, IR, UV spectra and bioautogram. CMR (DMSO-d65: 1.97 (s, 3, in CHsCONH—), 3.7 (s, 2—CH2), 4.0 (s, 3, CHjtetrazole)* 4.35 (s, 2.3—CH2S—), 5.1 (d, 1, J-5Hz, O—H), 5.7(0^ 1, J=4Hz, C7—H) and 8.8(d, 1, J=8Hz, —CH2CONH—). Example XXXVI. Preparation of 3-[(3-methyl-1,2,4-thiadiazolyl-5)thiomethyl[-»7-[2-thienyl-2)acetami-15 to]cephemo-3-carboxylic acid-4 in 1,1-dichlorcetane. Mixture of 200 mg (0.5 mmol) of 7-[2-(thienyl- 2)acetamido]-cephalosporan acid and 85 mg (0.65 mmol) of 3-methyl-1,2,4-thiad:azolothiol-5 in 50 ml of 1,2-dichloroethane, heated at 95°C, in an oil bath. The bath temperature was then maintained at approximately 90°C for approximately 19 hours. The reaction mixture was removed from the bath, cooled, and refrigerated for one day. Three volumes of ethyl acetate were added and digested with two 50 ml portions of saturated sodium bicarbonate solution. The combined carbonate extracts were extracted with ethyl acetate, covered with a fresh layer of ethyl acetate, and cooled in an ice bath. The pH was then adjusted to 2.0, the layers were separated, and the aqueous layer was extracted again with ethyl acetate. The combined ethyl acetate extracts were washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated to give 252 mg of foamy precipitate. This precipitate was crystallized from acetone and diethyl ether, giving 153 mg (65%) of product, the identity of which was confirmed by CMR, UV, and IRibioautogram. CMR spectrum (DMSO-d65: 3.7 (s, 2.2—CH2), 3.8 (s, 2^—CH2CONH—), 4.5 (q, 2, J = 15 Hz, 3—CH2S—), 5.1 (d, 1, J = 5 Hz, C1—H), 5.7 (q, 1, J = 4 Hz, C7—H), 6.96 and 7.38 (t, d, 3, H of thiophene) and 9.13 (d, 1, J = 8 Hz, —CH2CONH—). Example XXXVII. Preparation of 3-[(2-pyrimidinyl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid in acetonitrile. A mixture of 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamido]-cephalosporanic acid and 0.62 g (5.5 mmol) of 2-mercaptopyrimidine in 25 ml of anhydrous acetonitrile was heated at reflux for about 16 hours with stirring. Thin-layer chromatography showed complete conversion to the product. The reaction mixture was cooled to room temperature and the product was separated, washed with about 50 ml of acetonitrile and dried at 50°C for 4 hours. under reduced pressure. 1.86 g (83 %) of cream crystals are obtained, melting at 217°C (with decomposition). The CMR spectrum in DMSO-d6S does not show the presence of the starting compound. The identity of the product is confirmed by IR, UV and CMR. CMR spectrum (DMSO-d6S: 3.55(q, 2, 2-CH)2, J=18Hz), 3.74(s, 2, -CH2CONH-), 4.28 (q, 2, 3-CH2S^, J=13Hz), 5.00(d, 1, C6-H, J=5Hz), 5.64(q, 1, C7-H, J+5Hz, J=9Hz), 7.08 and 8.52 (m, d, 6, H z thiophene and pyrimidine) and 9.00(d, 1, —CH2CONH—, J=9Hz). Example XXXVIII. Preparation of 3-[(pyrimidin-2-yl)thiomethyl]-7-[2-(thien-2-yl)acetamido]-6S-cephem-3-carboxylic acid in acetic acid. A mixture of 2.0 g (5 mmol) of 7-[2-(thien-2-yl)acetamido]-cephalosporanic acid, 0.6 g (5.4 mmol) of 2-mercaptopyrimidine and 0.41 g (5 mmol) of sodium acetate in 25 ml of glacial acetic acid is heated at 85°C for 4 hours. During heating, The product crystallizes. The mixture is cooled to room temperature, filtered off, washed with acetic acid, and dried, yielding 1.58 g (70.5%) of a cream-colored, crystalline product, melting at 218°C (with decomposition). The identity of the product is confirmed by IR, UV, CMR, and elemental analysis. The CMR spectrum is identical to that of the product of Example XXXVII. Example XXXIX. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thienyl-2-acetamido]-cephem-3-carboxylic acid in acetic acid. A mixture of 2.0 g (5 mmol) of 7-[2-(2-thienyl-2-acetamido]-cephem-3-carboxylic acid in acetic acid A mixture of acetamido-cephalosporanic acid, 0.81 mg (7 mmol) of 1-methyl-1H-tetrazole-5-thiol and 0.41 mg (5 mmol) of sodium acetate in 25 ml of glacial acetic acid was heated at 75-77°C for 8 hours. The reaction was monitored hourly by thin-layer chromatography, and completion was observed after 8 hours. The reaction mixture was cooled to 40-45°C and the acetic acid was removed under reduced pressure. To the residue was added 50 ml of ethyl acetate and 50 ml of water. The aqueous layer was acidified to pH 1.5 with 1N H2SO4. The ethyl acetate layer was separated, dried over anhydrous sodium sulfate, and the solvent was evaporated. in a rotary evaporator. The remaining light oil was dissolved in 50 ml of ethanol and a solution of 2 ml (10.2 mmol) of dicyclohexylamine in 10 ml of ethanol was added. The dicyclohexyl ammonium salt precipitated almost immediately. The mixture was stirred for 15 minutes, the precipitate was filtered off, washed with ethanol, and dried. A total of 1.2 g (37.8%) of product was obtained, melting at 185-186°C, identical, according to IR, PMR, and UV, to the product obtained previously. Example 40. Preparation of 3-[(1-benzyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thien-2-yl)acetamido]-cephem-3-carboxylic acid in 1,2-dichloroethane. A mixture 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamido]cephalosporanic acid and 1.44 g (7.5 mmol) of 1-benzyl-1H-tetrazole-5-thiol in 25 ml of 1,2-dichloroethane were heated and stirred at 85°C overnight in an oil bath. Thin-layer chromatography showed no trace of starting cephalosporanic acid. The solvent was removed by rotary evaporation. The remaining foamy precipitate was dissolved in 25 ml of methanol and the mixture was heated in a steam bath until complete dissolution. The solvent was removed by rotary evaporation. The product crystallized. The mixture was stirred for 15 minutes, the precipitate was filtered off, and washed with water. methanol and dried under reduced pressure. 1.6 g (60.6%) of product is obtained, melting at 171-171.5°C. Example 41. Preparation of 3-amidinothiomethyl-7-[2-(2-thienyl)acetamido]cephem-3-carboxylic acid in acetonitrile. A mixture of 3.12 g (8 mmol) of 7-[2-(2-thienyl)acetamido]cephalosporanic acid and 912 mg (12 mmol) of thiourea in 15 ml of acetonitrile (dried over an aluminosilicate drying agent, sold under the name Linde 4-A molecular sieve) is stirred and heated at 87°C for 24 hours. hours. After one hour, a precipitate began to form from the mixture. After 24 hours, the product was filtered from the hot reaction mixture and dried. 2.5 g (76%) of product were obtained. Elemental analysis: calculated: C 43.68, H 3.91, N 13.58, found: C 43.50, H 4.03, N 13.29. The CMR spectrum confirmed the identity of the product. Example 42. Preparation of 3-benzoyl-10-thiomethyl-7-[(2-(thienyl-2)acetamido]-cephem-3-carboxylic acid in isopropyl acetate. 1.0 g (2.5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 510 mg (3.7 mmol) of thiobenzoic acid were suspended in 20 ml of anhydrous isopropyl acetate and the mixture was heated at reflux for 31 hours. During this time, the reagents were completely dissolved. The solvent was evaporated under reduced pressure. Thin-layer chromatography showed that the residue was a 60:40 mixture of product and unreacted starting material. A sample of the product was purified by preparative thin-layer chromatography on silica gel, developed with a 16:1 mixture of acetone and acetic acid. PMR spectrum (DMSO-d₂: 3.50 (ABq, 2H, 2-CH₂, 23 J₂H₂ J₂f₀9 Hz), 3.82(g2H,^CH2CONH—), 4.20(d, 2H, 3—GH*S—J-5Hz), 5.03 J-5Hz), 5.69 (d, 1H, Ct—H, J-5Hz), 6.89—8.0 (m. 8H, aromatic H). -?.* Example 43. Preparation of 3-(phenylthio)methyl-7-[2-(2-thienyl)acetamido]cephem-3-carboxylic acid in 1,2-dichloroethane. A mixture of 2.0 g (5 mmol) of 7-[2-(2-thienyl)acetamido]cephalosporanic acid and 0.75 ml (7.5 mmol) of benzenethiol in 25 ml of 1,2-dichloroethane was heated overnight at reflux. Thin-layer chromatography showed no starting cephalosporanic acid. The solvent was evaporated on a rotary evaporator and 25 ml of ethanol was added to the residue and heated, partially dissolving the precipitate. To completely dissolve the residue, 25 ml of methanol was added and the mixture was heated. The resulting solution was filtered through cotton wool, 2.0 g of charcoal was added, stirred for 5 minutes, and filtered through filter aid. The solvent was evaporated on a rotary evaporator. The CMR spectrum of the residue showed the presence of some starting thiol. The residue was suspended in 125 ml of isopropyl acetate, filtered, and refrigerated overnight. The filtrate was then diluted with 25 ml of ethyl acetate and washed with 25 ml of dilute sodium bicarbonate solution to remove the thiol. The acetate layer was added to 25 ml of water and the pH was adjusted from 8.5 to 1.4 with sulfuric acid. The acetate layer was dried over magnesium sulfate, filtered, and evaporated on a rotary evaporator. 0.92 g (19.4%) of a foamy solid was obtained. 55 CSF spectrum (DMSO-d65: 3.58 (m, 2, 2—CH2), 3.75 (s, 2, —CH2CONH—), 4.12(q, 2, 3—CH2S—, J = 13Hz), 5.08(d, 1,C6—H,J=5Hz), 5.66(q, 1, C7—H, J=5Hz, J=9Hz), 7.15(m, 8, H from thiophene and benzene), 9.10(d, 1, -CH2CONH-, J=Hz). 60 Example -cefemo-3-carboxylic acid-4 w 1,2-Dichloroethane. A mixture of 1.95 g (5 mmol) of 7-(2-phenylacetamido)cephalosporanic acid and 0.99 g (7.5 mmol) of 5-methyl-6-1,3,4-thiadiazol-2-thiol in 25 ml of 1,2-dichloroethane was heated at reflux for 16 hours. Thin-layer chromatography showed traces of the starting cephalosporanic acid. The product crystallized during the reaction. The reaction mixture was cooled to 0-5°C, filtered, washed with cold 1,2-dichloroethane and dried in vacuo. 1.82 g (78.8%) of product was obtained, m.p. melting point 171-172°C. CSF spectrum (DMSOd*)*: 2.70(s, —CH3 from thiadiazole), S.58(^.2,—ClLCONH—), 3.70fwide s,2.2—CH2), 4.40(q, 2.3—CH2S—, l*13Hz, 5.12 (d, 1, C6—Hf J- 5H*X S,72(ash Ci~to, J^5Hz,J-9Hz), 7.28 (s, 5, phenytic H), M&(dyi;--CteCONH—, J^9Hz. Example cefemo -3- carboxylic acid-l w methylene chloride. A mixture of 24 g (60 ml) of 7-[2-(thien-2-yl)acetonidol-cephalosporanic acid, 7.0 ml of methylene chloride, and 600 ml of methylene chloride was stirred and heated in an autoclave at 84-86°C for 18 hours. The reaction mixture was cooled to room temperature. A small amount of insoluble matter was filtered off, and the filtrate was evaporated. Ethyl acetate was added to the residue and filtered. About 150 ml of water was added to the filtrate, stirred, and 1N NaOH solution was gradually added to pH 5.5. The aqueous layer was evaporated and concentrated to about 75 ml, then reduced to 700 ml with water and acetic acid was added. Ice-cold water to pH 3.8. An amorphous precipitate formed and the mixture was stirred in an ice bath for 3 hours and then cooled overnight. The precipitate was filtered off, 100 ml of ethyl acetate was added to the filtrate and the pH was adjusted to 2.0 with concentrated hydrochloric acid. The organic layer was separated and extracted with 100 ml and then 159 ml of ethyl acetate. The combined organic layers were dried over magnesium sulfate and the solvent was evaporated. The amber pan-like precipitate was dissolved in 5 ml of ethyl acetate, seeded with the product and allowed to stand in the refrigerator overnight. The precipitated crystalline solid was filtered off, washed with cold isopropyl acetate and dried under vacuum at about 50pcs. 32 g (14%) of the product are obtained, the identity of which is confirmed by the PMR spectrum. PMRJ spectrum: 2*00(s,3, 3^CH2SGH3, 3.74 (m, 3—CH2S^,!2—CH2i—CH2CONH—, 5.14 (d, 1, O—H, J-5Hz), 6.64(q,1,C7-H, J=5Hz, J=9Hz), 7.15(m,3, Hz of thiophene) and 9.12(d, 1, ^CHjCONH-, J=9Hz). Example XLVI. -3-(1-methyl-1H-tetrazolyl-5)thiomethyl-cefemo-3-carbexyl-4, as salt sodium hydroxide in benzene. A mixture of 2.17 g (4.65 mmol) of 7-(2-formyl-oxy-2-phenytoacetamido)-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazol-5-thiol in 25 ml of benzene was heated at reflux (approximately 0°C) for 12 hours. During heating, a soft precipitate formed on the walls of the vessel, which formed a glassy precipitate on cooling. Thin-layer chromatography showed that the filtrate contained only traces of product, while the precipitate on the walls contained mainly the product and some deformyl compound. The reaction mixture with The mixture was evaporated with acetone. The resulting sandy residue was dissolved in 35 ml of anhydrous acetone and 10 ml of a solution containing 1.25 g of sodium 2-ethylhexanoate in acetone was added. The sodium salt of the product precipitated. After one hour, the product was filtered off, washed with 20 ml of acetone and dried. 1.38 g (58%) of the product* was obtained, the identity of which was confirmed by thin-layer chromatography and analysis of the CSF spectrum. CSF spectrum (D2O)*: 3.48 (q,2.2—CH* J~18Ha,) 4.00 (s,3, —-CHr % tetrazolium), 410 (m, 2; 3—CH2S—), 5.05 (d, 1, C6—H J«5Hz), 57©(d, U C7—H, J-5Hz), 6.24(s, 1, —CHCONH—, 7»5a(», 5, phenytic H) and 8.33 (s, 1, —O—CH)»0). 10 Example XLVII. Preparation of 7*(2-(bmy- looksy -2- phenyioacetamido)-3- [(I-methyl-1H- tetrazo-yl-1)thiomethyl]-cefcmo-3-carboxylic acid in carbon tetrachloride. Mixture of 2.17 g (4.65 mmol) of 7-(2-formyl-oxy-2- phenyioacetamido)-cefek) SporaiKwę and 0.87 g (7.5 mmol) I-methyl -1H- Tetrazolium thioate-5 in 25 ml of carbon tetrachloride was heated to boiling point (approximately 77°C). Cooled to room temperature over 12 hours, and the supernatant from the hardening semi-solid precipitate was decanted. 25 ml of 1,2-dichloroacetate was added to the precipitate and heated. The product crystallized. Cooled to room temperature and stirred for approximately one hour, then filtered, washed with 10 ml of 1,2-dichloroethane, and dried under vacuum at 45°C overnight. 1.54 g (65%) of a white crystalline precipitate was obtained. The product's identity was confirmed by PMR spectral analysis and chromatography. Thin-layer, which shows the presence of trace amounts of the deformyl compound. The PMR spectrum is identical to that of the product of Example XVI. Example XLVHI. Preparation of 3-methyl-1,2,4-oxadiazolethiol-5. 30 g (0.4 mol) of acetamide oxime, 100 ml (1.6 mol) of carbon disulfide, and 56 ml (1 mol) of triethylamine are stirred in 1 liter of pyridine. Nitrogen is bubbled through the carbon disulfide solution. The mixture is heated in an oil bath at 70°C for three days and then evaporated. Ethyl acetate and saturated sodium carbonate solution are added to the oily residue. The layers are separated, and the organic layer is washed with saturated sodium bicarbonate solution. The combined carbonate solutions are extracted with ethyl acetate, and the ethyl acetate extract is discarded. The aqueous extract is covered with a layer of fresh ethyl acetate and cooled in an ice bath. The pH is adjusted to 2.5 with 20% hydrochloric acid, then sodium chloride is added until the solution is saturated. The solution is extracted with ethyl acetate, washed with saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solution is filtered, and the filtrate is evaporated to 1/2 of the original volume, then an equal volume of carbon tetrachloride is added and evaporated until crystallization begins. 24.8 g (52%) of product is obtained. Example 49: Preparation of acid 3-[(^methyl-1,2,4-cksadazolylc-5)thiomethyl]-7-[2-(thienyl^2)cetamido]-cefemo-3-carboxyl-4 in 1,2-dichloroethane. 100 mg (0.25 mmol) of 7-[2-(thienyl-2)-cetami-do]-3-(carbamylooxymely:o)-cefcmo -3- carbexyl- 60 wegc-4 acid are suspended in 25 ml of 1,2-dichloroethane and 35 mg (0.30 mmol) are added while stirring 3-Methyl-1,2,4-oxadiazolothiol-5. The reaction mixture is heated in an oil bath at 110°C and 5 ml are distilled off. solvent containing traces of water. The temperature of the oil bath was reduced to 90-95°C and held for 122-152-29 hours. The mixture was then cooled to room temperature, the insolubles were filtered off, and washed with 1-dichloroethane and diethyl ether. Thin-layer chromatography showed that this was unreacted starting material, containing only traces of product. The filtrate was evaporated, and sodium bicarbonate solution and ethyl acetate were added to the oily residue. The layers were separated, and a new portion of ethyl acetate was added to the aqueous layer, cooled in an ice bath, and the pH was adjusted to 2.5 with 20% hydrochloric acid. The organic layer The aqueous phase is separated and the aqueous phase is extracted with a fresh portion of ethyl acetate. The combined ethyl acetate extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated. The oily residue is crystallized from a 1:1 mixture of hexane and ethyl ether. 13 mg (11.5%) of product are obtained, the identity of which is confirmed by the CMR and IR spectra, identical to those of the compound obtained according to Example XXXII. Example L. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(2-tert-butoxycarbonyl-2-phenylacetamido)-cephem-3-carboxylic acid in nitromethane. A mixture of 490 mg (1 mmol) of acid 7-(2-Hydrobutoxycarboxylate) and 145 mg (1.25 mol) 1-methyl-H-tetrazolium-5-thiol in 15 ml of anhydrous nitromethylbenzene. Heat the mixture with nitrogen at 90°C for 8 hours. Thin-layer chromatography shows the presence of product, excess thiol, decarboxylated product, and no starting cephalosporanic acid. The nitromethylbenzene is evaporated and the remaining orange foamy precipitate is dissolved in 10 ml of saturated sodium bicarbonate solution. Add 20 ml of water and wash with methyl acetate until a clear solution is obtained. The acetate solutions were combined, 20 ml of water was added, the mixture was cooled to 0°C, and the pH adjusted to 2.2 with 20% hydrochloric acid. The layers were separated, and the aqueous layer was washed with ethyl acetate. The combined acetate extracts were washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated. 455 mg (83%) of a brown foamy precipitate was obtained. Thin-layer chromatography showed the presence of product, traces of thiol, and traces of decarboxylated product. 455 mg (0.833 mmol) of product was dissolved in 7 ml of ethyl acetate, and 0.833 ml of lithium acetate was added dropwise with stirring. A brown precipitate of the salt was obtained. lithium, which was filtered off, washed with ethyl acetate, and dried overnight under vacuum at room temperature. 368 mg (80%) of product was obtained, the identity of which was confirmed by thin-layer chromatography, CMR spectrum, bioautogram, elemental analysis, and IR and UV spectra. Chromatography showed traces of the decarboxylated compound. CMR spectrum (CDC1b)$: 1.4(s, 9, —COCMII- er.-COfc)* 3^(8, 2, 2^0%), 385 4.3(s, 2, 3—CHaS—), 4.44 and 4.45(2s, 1, C«H*--CH), 4fitór U J«=6 Hz, C«^-H)v 5.8(fl, 1, J=6Hz, Ct—H), 7^5(sl5,C6H5—), 8.2 and 7,&(2d, Ir, J~9Hz, —CONH—) and 9.3 (s 1, —COOH). UL Example Preparation of 3-[(1-methyl- 1H-tetrazolium-5)thiomethyl]-7- [N- (1,3-dimethylureidocarbonyl)-2-phthyrifogylcylamido]-eephemo-3-carboxylic acid-4 in nucometanife. 30 130 mg (0.25 mmol) of 7-[N-(1,3-dimethyl-ureidocarbonyl)-2-phenylglycylamido]-cephalcsporanic acid is suspended in 5 ml of mtromethane and added 43.5 mg (0.375 mmol) of 1-methyl-1H-tetrazocthiol-5. Calcsc 5 was heated under nitrogen at 85°C for 12 hours and then left at room temperature over the weekend. The reaction mixture was filtered and the precipitate was washed with a small amount of nitromethane and then dried in a vacuum oven at 35°C. 1083 mg (58%) of product was obtained, the identity of which was confirmed by thin-layer chromatography, CMR, IR, TJV spectra, elemental analysis, and bioautogram. CMR spectrum (DMSO-d*)*: 2.65 (d, 3, J-4 Hz, —CON HCHj), 3.15 (s, 3, CONCHaCO—), 3.6 (s, 2, 2—CH2), *5 3.9 (s, 3, CHj from tetrazole), 4.3(s, 2, 3—CHaS—\ 5.0(d, 1, J=5Hz, Ce—H), 5.5(d, 1, J-=7Hz, CeH^CH^N- (HCOX 5.7 (q, 1, C7—H)„ 5.8 (q, 1, —CONHCH3, 7.4(s, 5, Ott —), 9.3(d, 1, J=8Hz, C6H5CHCONH—). 10(o\M=8Hz, C«H5 -CH(NH-)—CO—). 20 Example LU. Preparation of 3-[(1-methyl- 1H-tetrazol-5)thiomethyl]-7-[2-thienyl-2(acetamol)-cephem-3-acid 4-carboxylic acid in acetonitrile with added tetrabutylammonium iodide. A mixture of 2.0 (5 mmol) 7-[2-(thienyl-2)acetone-3-carboxylic acid, 1.2 g (10 mmol) 1-methyl-1H-tetrazolium-5-trimethyl]-, 0.2 g tetrabutylammonium iodide and 25 ml anhydrous acetonitrile was heated at reflux for 8 hours. The reaction mixture was cooled to room temperature and the solvent was removed by rotary evaporation. A hot mixture of 25 ml isopropyl acetate and 5 ml acetonitrile was added to the residue, then filtered and allowed to evaporate slowly. Cooling. The product that crystallized in the form of cream crystals was filtered off, washed with isopropyl acetate, and dried. 1.30 g (57.5%) of product was obtained, the CMR spectrum of which was identical to that of the product from Example V. Example LHL Preparation of 3-[1-methyl-40 LH-tetrazoryl-5-thiomethyl]-7-[2-(2-thienyl)acetamidol-3-cephem-4-carboxylic acid in 1,2-dichloroethane with the addition of tetrabutylammonium iodide. The procedure of Example LU was repeated, except that 1,2-dichloroethane was used as the solvent. After adding 2 ml of dicyclohexylamine, the following was obtained: 1.55 g (48.9%) of the dicyclohexylammonium salt of the product, the PMR spectrum of which is identical to that of the product of Example 1. Example 74. Preparation of 3-(phenylthio)methyl-7-[2-(thienyl-2)acetamido]-ephem-3-carboxylic acid in 1,2-dichloroethane with the addition of 1-methyl-5-(methylthio)-1H-tetrazole. A mixture of 2.0 g (5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid, 0.75 ml (7.5 moles) of benzenethiol and 0.65 g of 1-methyl-1S-methylthio-1H-tetrazole in 25 ml of 1,2-dichloroethane is heated to boiling point. Thin-layer chromatography after about 14 hours of heating shows that the reaction is complete. The solvent is evaporated on a rotary evaporator and the residue is extracted several times with diethyl ether. After removal of the solvent, 1.66 g of a yellowish-brown precipitate (74 %) remains. The IR and PMR spectra are identical to those of the product prepared according to the previous examples. Example LV. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thien-2-yl)acetamido]-cephem-3-carboxylic acid in isopropanol. A mixture of 2.0 g (5 mmol) of acid 7-[2-(2-thienyl)acetamido]-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazol-5-thiol in 25 ml of isopropanol are placed in a flask fitted with a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierite. The flask is immersed in an oil bath at 84-85°C. The course of the reaction is monitored by thin-layer chromatography. After 40 hours of heating at 82-83°C, only half of the cephalosporanic acid has reacted. Example 66. Preparation of 3-(2-oxazolylthiomethyl)-7-[2-(1H-tetrazol-1-yl)acetamido]-3-cepheme 4-carboxylic acid in nitromethane. A suspension of 0.38 g (1 millimole) of 7-[2-(1H-tetrazol-1-yl)acetamido]-cephalosporanic acid and 0.11 g (1.1 millimole) of 2-oxazolethiol in 5 ml of nitromethane is placed in an oil bath at 90-91°C. The reaction is carried out in a dry nitrogen atmosphere. After 20 minutes, all the reagents dissolve, and after 35 minutes the product begins to crystallize. After 6 hours, the reaction mixture is cooled to room temperature, the product is filtered off, washed with 7 ml of nitromethane, dried in air and then dried under reduced pressure for 3 hours at 90-91°C. 40°C. 0.36 g (85.7%) of a cream-colored crystalline product is obtained, melting at 196°C (with decomposition). The CMR spectrum shows that the product contains 70% of the desired compound and 30% of the starting cephalosporanic acid. The product is recrystallized from 5 ml of DMSO-d6 and 10 ml of water, filtered, washed with 5 ml of a 2:1 mixture of water and DMSO-d6, air-dried and then dried under vacuum at 50°C for 6 hours. 0.26 g of product is obtained, the CMR spectrum of which shows 87% of the desired compound and 13% of the starting cephalosporanic acid. The recrystallization is repeated using 3 ml of DMSO-d6 and 6 ml of water and stirring for 1 hour. 0.21 g of product is obtained, the CMR spectrum of which (DMSO-d6) shows that the cephalosporanic acid content has decreased to 5% and confirms the identity of the desired compound. CMR 6: 3.75 (s, 2, 2-CH2), 4.34 (q, 2, 3-CH2-S, J=14Hz), 5.16 (d, 1, Gs-H, J=5Hz), 5.76 (q, 1, C7-H, J=5Hz, J=9Hz), 5.44 (s, 2, —CH2CONH-), 7.28 (s, 1, C4-^-H of the oxazole), 8.14 (s, 1, C3-H of the oxazole), 9.37 (s, 1, H from tetrazole) and 9.53 (d, 1, _CONH—, J=9Hz).Example LVII. Preparation of 3-(2-oxazolylmethyl)-7-(2-formyloxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 0.52 g (1 mmol) of 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid solvate with methylene chloride and 0.12 g (1.1 mmol) oxazolothiol-2 in 20 ml of 1,2-dichloroethane are heated at reflux temperature for about 16 hours and then cooled to room temperature. Thin layer chromatography shows a clear conversion The desired compound was obtained. The reaction mixture was concentrated on a rotary evaporator to about 10 ml. After some time, some crystalline, gelatinous precipitate precipitated out. This was filtered off, washed with 1,2-dichloroethane, and dried, yielding 0.12 g of a gray solid. After complete removal of the solvent from the filtrate, 0.45 g of a light yellow foamy solid was obtained. This solid was triturated with 25 ml of diethyl ether and dried, yielding 0.21 g of a light yellow powder, the identity of which was confirmed by the PMR spectrum: 3.56 (m, 2, 2-CH2), 4.24 (q, 2, 3-CH2S-, J = 13 Hz), 5.00 (d, 1, C6-H, J = 5 H2). 5.70 (q, 1, C7—H.J=5Hz, J=9Hz), 6.14(s, 1, C6H5—CH—), 7.25 (s, 1.5 C4—H from oxazole), 7.45 (m, 5, H from phenyl), 8.12 (s, 1, Cs—H from oxazole), 8.35 (s, 1, —CHO) and 9.40 (d, 1, —CONH—, J=9Hz).Example LVIII. Preparation of 3-[(4-phenylthiazolIo-2)thiometyIo]-7-[2-(thienyIo-2)acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. Mixture of 2.0 g (5 mmol) of 7-[2- (2-thienyl-acetamido[-cephalosporanic acid) and 1.44 g (7.5 ml)-4-phenylthiazol-2-thiol in 35 ml of acetonitrile were heated at reflux for 16 hours, protected from atmospheric moisture by a tube containing anhydrous calcium sulfate, sold under the trade name Drierite, as a drying agent. Thin-layer chromatography showed pure conversion to the new product. After cooling the reaction mixture to room temperature and stirring for 2 hours, the product crystallized, was filtered off, washed with acetonitrile and dried. 2.25 g (85.6%) of the product were obtained, melting at 180°C (with decomposition). The CMR spectrum confirmed the identity of the product. Example LIX. Preparation of 3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-(1H-tetrazol-1-yl)acetamido]-3-cephem-4-carboxylic acid in nitromethane. To 25 ml of nitromethane with alumina were added 1.92 g (5 mmol) of 7-[2-(1H-tetrazol-1-yl)acetamido]-cephalosporanic acid and 0.79 g (6 mmol) of 5-methyl-1,3,4-thiadiazol-2-thiol and the mixture was stirred and heated at 95°C in an oil bath for 4 hours. Thin-layer chromatography showed that only traces of the starting cephalosporanic acid remained. (less than 352%). The reaction mixture was cooled to room temperature, filtered, washed with nitromethane, and dried under vacuum. 2.11 g (92.5%) of product was obtained, melting at 183.5°C (with decomposition), the identity of which was confirmed by the CMR spectrum. Example 69. Preparation of 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-1-acetamido]-cephem-3-carboxylic acid in propionitrile. To 25 ml of propionitrile from perneutral alumina, 1.92 g (5 mmol) of 7-[2-(1H-tetrazolyl-1-acetamido] acid was added. -cephalosporanic acid and 0.99 g (7.5 mmol) of 5-methyl-1,3,4-thiadiazol-2-thiol. The mixture was heated and stirred at reflux (97°C) for 9 hours. Thin-layer chromatography showed only traces of the starting cephalosporanic acid. The reaction mixture was cooled to room temperature, filtered, washed with propionitrile, and dried in vacuo. 2.04 g (89.5%) of product was obtained, melting at 186.5°C (with decomposition). The identity of the product was confirmed by the CMR spectrum. Example 61. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-acid (2-Formyloxy-2-phenylacetamido)-cephem-3-carboxylic acid from 7-aminocephalosporanic acid in 1,2-dichloroethane. To a suspension of 13.62 g of 7-aminocephalosporanic acid 60 (0.05 mole) in 100 ml of 1,2-dichloroethane is added 26.25 g of trimethylsilylacetamide (0.200 mole). The reaction mixture is heated to 40°C, the reagents dissolve to form a cloudy solution, which is then cooled to 20°C. A solution of 10.92 g (0.055 mol) of 2-formyloxy-2-phenylacetyl chloride in 25 ml of 1,2-dichloroethane is added dropwise over 20 minutes, raising the temperature to 30°C. The mixture is stirred for 2 hours, 100 ml of 1,2-dichloroethane is added, and the mixture is washed with three 100 ml portions of water. The aqueous layers are combined and extracted with 2 x 50 ml of 1,2-dichloroethane, which is then washed with 40 ml of water. The organic extracts are combined and stirred for 20 minutes with 2.0 g of activated carbon, sold under the brand name Darco G-60, and then with diatomaceous earth, sold under the brand name Hyflo Super-Cel. The total volume of the solution is 375 ml, and it contains the desired 7-(2-formyloxy-2-phenylpacetamido)-cephalosporinic acid. This solution is evaporated at approximately 30°C to a weight of 336 g, which is determined to be equivalent to 250 ml of 1,2-dichloroethane and 22 g of 7-(2-formyloxy-2-phenylacetamido)-cephalosporinic acid. To this solution was added a solution of 6.39 g (55 mmol) of 1-methyl-1H-tetrazol-5-thiol in 250 ml of 1,2-dichloroethane and the mixture was heated to boiling. The water from the previous washes was distilled azeotropically using an azeotropic adapter. Thin-layer chromatography after 12 hours at reflux showed an almost normal reaction. The reaction mixture was cooled to room temperature and seeded to precipitate the product, 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(2-formyloxy-2-phenylacetamido)-3-cephem-4-carboxylic acid. After approximately 2 hours, the product was filtered off and washed with 63 ml of 1,2-dichloroethane. 13.90 g (56.7% based on 7-AC acid) of product was obtained. Thin-layer chromatography showed the purity of the product and the CMR spectrum confirmed that it was identical to the product prepared according to Example XVI. Example LXII. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(formyloxy-2-phenylacetamido)-3-cephem-4-carboxylic acid in 1,2-dichloroethane. To 25 ml of 1,2-dichloroethane are added 2.33 g (5 mmol) of 7-(2-formyloxy-2-phenylacetamido)cephalosporanic acid and 0.64 g (5.5 mmol) of 1-methyl-1H-tetrazol-5-thiol, and the mixture is heated at reflux for 12 hours. The reaction mixture was cooled to room temperature, then heated again to boiling point and 10 ml of solvent was distilled off. Then 10 ml of carbon tetrachloride was added dropwise at a temperature close to boiling point (77°C). The mixture was cooled to room temperature and stirred for one hour, the product was filtered off, washed with 14 ml of a 40% solution of carbon tetrachloride in 1,2-dichloroethane and dried in vacuo at 50°C. 2.12 g (86.5%) of product was obtained, the spectrum of which was identical to the PMR spectrum of the product prepared according to Example XVI. Example LXIII. Preparation of 3-[(3-(benzyloxycarbonylamino)methyl)-1,2,4-triazol-5-yl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid in nitromethane. A mixture of 2 g (5 mmol) of 7-[2-(2-thienyl)acetamido]-cephalosporanic acid and 2 g (7.6 mmol) of 3-(benzyloxycarbonylaminomethyl)-1,2,4-triazol-5-thiol in 35 ml of nitromethane is heated at 80-90°C, with stirring, for 6 hours. The reaction mixture is cooled and the product is filtered off. After two recrystallizations from aqueous acetone, 1.2 g (40%) of a cream-colored crystalline solid was obtained, melting at 174-178°C. Elemental analysis for the formula CasH^NeOeSs: calculated: C-49.99, H-4.03, N-13.99, S-16.01 and found: C-50.20, H-4.03, N-13.76, S-15.68. Example 64. Preparation of 3-[(1-(carboxymethyl)-1H-tetrazol-5-yl)thiomethyl-7-[2-(thienyl-2)acetamido-3-cephem-4-carboxylic acid in acetonitrile. 1.0 g (2.5 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.61 g (3.8 mmol) of 1-(carboxymethyl)-1H-tetrazole-5-thiol in 75 ml of acetonitrile was heated to boiling, and 35 ml of solvent was distilled off. The mixture was then heated at reflux for 13 hours, cooled, filtered, and the filtrate concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with 1N hydrochloric acid and brine, and dried over sodium persulfate, and hexane was added. The precipitate was filtered off and triturated with ether, yielding 0.475 g (38%) of a brownish-yellow solid. The identity of the product was confirmed by comparison with a sample obtained by a different synthetic route. Example LXV. Preparation of 3-[(5-methyl-13,4-thiadiazol-2-yl)thiomethyl]-7-(3-chloropropionamido)-cephem-3-carboxylic acid in nitromethane. A suspension of 1.0 g (2.5 mmol) of 7-(3-chloropropionamido)-cephalosporanic acid and 0.4 g (3 mmol) of 5-methyl-1,3,4-thiadiazol-2-thiol in 20 ml of nitromethane was immersed in an oil bath at 95-96°C. Thin-layer chromatography showed the reaction to be complete after 3 hours. The reaction mixture was cooled to room temperature, filtered, and evaporated under reduced pressure. The remaining light red oil crystallized after standing at room temperature for two hours. It was triturated with 15 ml of ethyl acetate, filtered, washed with ethyl acetate, and dried. 0.64 g (55.2%) of product was obtained, the identity of which was confirmed by IR, UV, titration, microanalysis, and CSF. Elemental analysis for formula C16H19ClN4O4S3: calculated: C 41.51, H 4.14, N 12.10, S 20.78, Cl 7.66; found: C 41.70, H 4.23, N 11.84, S 20.51, Cl 7.88. Example LXVI. Preparation of 3-[(1-benzyl-1H-1,2,3-triazol-5-yl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid in 1,2-dichloroethane. 200 mg (0.5 mmol) of 7-[2-thienyl-2)acetamido]-cephem-3-carboxylic acid and 140 mg (0.7 mmol) of 1-benzyl-1H-1,2,3-triazol-5-thiol in 15 ml of 1,2-dichloroethane are stirred and heated at 65°-70°C for 21 hours. The solvent is removed under reduced pressure, 25 ml of saturated hydrogen carbonate solution are added. Sodium hydroxide was added and the mixture was extracted with two portions of ethyl acetate. A further portion of ethyl acetate was added to the aqueous phase, the mixture was cooled in an ice bath, and the pH was adjusted to 2.5 with 20% hydrochloric acid. The acidic product was extracted with two portions of ethyl acetate, and the combined ethyl acetate extracts were washed with saturated aqueous NaCl solution and dried over anhydrous magnesium sulfate. The magnesium sulfate was filtered off, and the ethyl acetate was evaporated under reduced pressure. 76 mg of product was obtained, which, as determined by thin-layer chromatography, was a mixture of the starting material and the product. Standards of the product and the reference compounds were used for comparison. Examples LXVII—LXXII. Substitution of 7-methoxy-7-[2-(1H-tetrazol-1-yl)acetamido]-cephalosporanic acid with various thiols in nitromethane. 7-methoxy-7-[2-(1H-tetrazol-1-yl)acetamido]-cephalosporanic acid is reacted with various thiols in nitromethane. The procedure is practically the same as that described above, except that high-pressure liquid chromatography is used to isolate the products from mixtures with unreacted starting compounds. The following compounds are obtained: 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-methoxy-7-[2-(1H-tetrazol-1-yl)acetamido] acid -cefemo -3- carboxyl-4, UV max (ethanol) 273 mu (e=9.082), qua«3- [(5-methyl-13,4-thiadiazolyl-2)thiomethyl] -7- mephoxy -7- [2-(lH-terazolyl-l)acetamido]-cefemo -3- carboxyl-4, UV max (ethanol) 273 m# (Elemental analysis for GsHmNsOsS*: calculated: C - 37.18, H - 3.33, N - 23.13 found: C-36.99, H-3.31, N-22.86 acid 3-[(5-methyl-1,3,4-oxadiazolyl-2)thiomethyl] -7- methoxy -7- [2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4. UV max (ethanol) 269 nv* (€=8.910). Elemental analysis for G5H16N1O6S2: calculated: C - 38.46, H - 3.44, N - 23.92. found: C - 38.58, H - 3.69, N - 23.91 3-acid [(1-carboxymethyl1H-tetrazolyl-5)thiomethyl]-7- methoxy -7- [2-(1H-tetrazolyl-o-1)acetamido]-ce¬ femo -3-carbpoxy-4, UV max (ethanol) 269 m/i (c= 7669). Elemental analysis for G5H16N10O7S2: calculated: C - 35.16 H - 3.15, N - 27.33 found: C-35.42, H-3.38, N-27.39 acid 3-[(4,5-dihydro-6- hydroxy-4-mctyl-5- keto- 1,2,4-tirazinyl-3)thiomethyl]-7- methoxy -7-[2-(lH- tetrazolyl-l)acetamido] -cefemo -3- carboxyl-4, UV max (ethanol) 274 (c=11967). Elemental analysis for C16H17N9O7S2: calculated: C-37.57^ H-3.35, N-24.65 found: C-36.96, H-3.80, N-27.63 acid 3- [(1A4-triazoliIo-5)thiomethyl] -7- methoxy -7- [2- (lH-tetrazolyl-l)acetamido] -cefemo -3- carboxylic acid -4. Elemental analysis for G4H15N9O5S2: calculated: C - 37.08, H - 3.33, N - 27.80 found: C-36.98, H-3.43, N-27.79 Example LXXIII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl[-7-[2-(4-ethyl-2,3-di-ketopiperazinyl-1-carbonylamino)-2-phenylacetamido]-cefemo-3-carboxylic acid-4nitromethane. To 6 m of dried nitromethane 0.3 g (0.5 mmol) of 7-[2-(4-ethyl-2,3-dioxopiperazinylcarbonylamino)-2-phenylacetamido]-cephalosporanic acid hydrate and 0.0725 g (0.625 mmol) of 1-methyl-1H-tetrazol-5-thiol are added over alumina. The reaction mixture is heated at 85°C under nitrogen for 12 hours. The nitromethane is evaporated and the remaining brown foam is redissolved in sodium bicarbonate solution and washed twice with ethyl acetate. Fresh ethyl acetate is added, the mixture is cooled to 0°C and the pH is adjusted to 2.3. The layers are separated and the aqueous layer is washed with ethyl acetate. The ethyl acetate solutions were combined, washed with saturated NaO solution, dried over anhydrous magnesium sulfate, filtered, and evaporated. 130 mg (40% of theory) of a light yellow powder was obtained. The product's identity was confirmed by the CSF spectrum. <5: 1.2 (t, 3, —NCHzCHj, J-7Hz), 3.65(m, 6, N^CH2CH3 and H 5 piperazine), 4.0 (s, 3, —CHs from tetrazole), 4.4 (s, 2, 3—CH2S—), 5.1 (d, 1,C6—H,J-6Hz) and 5.8(d, 1, C7—H, J-8Hz), 6.0(d, 1, GsHs—CH)—N)—, J=*6Hz), 7.4 (m., 5, phenyl H), 8.4(d, 1, -^CHCONH—, J=8Hz) and 10.0(d, 1, —CH)—NH(CONH—, J-6Hz). 10 Example LXXIV. Preparation of 3-[(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(4-ethyl-2,3-dioxopiperazinyl-1-carbonylamino)-2-phenylacetamido]-cephem-3-carboxylic acid in 1,2-dichloroethane. 0.3 g (0.5 mmol) of 7-[2-(4-ethyl-2,3-dioxopiperazinylcarbonylamino)-2-phenylacetamido]-cephem-3-carboxylic acid hydrate is dissolved in 45 ml of 1,2-dichloroethane dried over alumina and the solution is heated to 95°C to remove water azeotropically. After collecting 40 ml of solvent, 10 ml of nitromethane and 0.160 g (1 mil) of 1-(carboxymethyl)-1H-tetrazol-5-thiol are added. The reaction mixture is heated at 90°C under nitrogen for 12 hours. The mixture is then filtered and the solvent is removed by evaporation. A gummy residue is obtained, to which ethyl acetate and saturated sodium bicarbonate solution are added. The mixture is washed twice with ethyl acetate, fresh ethyl acetate is added, cooled to 0°C and the pH is adjusted to 2.3 with 20% HCl. The layers are separated and the aqueous layer is washed with ethyl acetate. The acetate solutions were combined and washed with saturated HCl, dried over anhydrous magnesium sulfate, filtered, evaporated, and dried at room temperature. 123 mg of product was obtained. The identity of the product was confirmed by the PMR spectrum. <5: 1.2 (t,3,—NCH2CH3, J=7Hz), 3.6 (m,4,N—CH2CH3 and 5—H of piperazine), 4.1 (m, 2, 4—H of piperazine), 4.4 (s, 2, 3^CH2S—), 5.1 (d, 1, C8—H, J=5Hz), 5.3 (s, 2, 1—CH2COOH of tetrazole), 5.75 (d, 1, C7—H, J=6Hz), 5.9 (d, 1, CjHs—CH)N C(—), 7.4 (m, 5, H of phenyl) and 9.9 (d, 1, C6H5—CH(NH)—, J=7Hz). Example LXXV. Preparation of 3-[(4,5-dihydro-4-methyl-6-hydroxy-5-keto-1,2,4-triazin-3-yl)thiomethyl]-7-[2-(4-ethyl-2,3-dioxopiperazinyl-1-carbonylamino)-2-phenylacetamido]-cephem-3-carboxylic acid in nitromethane. 0.3 g (0.5 mmol) of 7-[2-(4-ethyl-2,3-dioxopiperazinyl-1-carbonylamino)-2-phenylacetamido]-cephalosporanic acid hydrate and 0.111 g (0.625 mmol) of 5-keto-1,2,4-triazine-3-thiol were dissolved in 10 ml of nitromethane under nitrogen at room temperature and the reaction mixture was heated at 85°C for 12 hours. The brown gummy precipitate formed was discarded. The solvent was evaporated slowly, and a yellow precipitate formed. The residue was cooled, filtered, and washed with diethyl ether, giving two cream-colored solids, identical after thin-layer chromatography. Total yield is 80 mg (24%). The identity of the product was confirmed by the CMR£ spectrum: 1.1 (t, ^ 3, —NCH2CH3, J=6Hz), 3.3 (s, 3, CH3 from triazine), 3.65 (m, 4, N-CH2CH3 and 5H from piperazine), 4.0 (m, 2,6—H of piperazine), 4.6 (s, 2, 3—CH2—S—), 5.1 (d, 1, Gj—H, J«5Hz), 5.75 (m, 2, GsH, —CH(N)—i C7—H), 7.45 (m, 5, H of phenyl), 9.5 (d, 1, —CHCONH—, J=8Hz) and 10.0 (d, 65 1, OH,—CH(NH)-, J=Hz).122 152 37 Example LXXVI. Preparation of 3-[(5-methylthio-1,3-4-thiadiazol-2-yl)thiomethyl]-7-[2-(1H-tetrazol-1-yl)acetamido]-cefme-3-carboxylic acid in nitromethane. 15.0 g (39.2 mmol) of 7-[2-(1H-tetrazolyl-1)-acetamido]-cephalosporanic acid and 6.43 g (39.2 mmol) of 5-(methylthio-1A4-thiadiazol-2-thiol) were suspended in 500 ml of nitromethane passed through a column of neutral alumina. The mixture was heated to 95°C and kept at this temperature for 6 hours. It was then cooled overnight, filtered, washed with 250 ml of nitromethane and dried at 45°C for 4 hours, to obtain 18.08 g of product (94.9%). This product was added to 150 ml of water and 4.0 ml of acetic acid. The pH was adjusted to 100. 6.3 with 1N NaOH (107 ml) and stirred for one hour. A solution of 257 ml of 60% sodium lactate and 65 ml of ethanol was added and the mixture was allowed to stand for 45 minutes. It was then stirred for 45 minutes, filtered, washed three times with ethanol and dried. 18.1 g was obtained. The product was resuspended in 300 ml of ethanol for 3 hours, filtered, washed with ethanol and dried. 14.85 g was obtained. The identity of the product was confirmed by high-pressure liquid chromatography. Example LXXVII-LXXXVII. Preparation of 3-[(5-methyl-1,4-thiadia2,2-2-methyl-1,7-[2-(1,4-tetrazolyl-1,7-acetamido]-cephemic acid. 3-carboxylic acid in various solvents. 7-[2-(1H-tetrazolyl-1)acetamidol-cefalexolic acid is reacted with 5-methyl-1,3,4-thiadiazolethiol-2-ol in various solvents. The basic reaction conditions are given in the table. Other reaction data are similar to those in the previous examples. 38 of iodine at 84-86°C for 8 hours. The reaction mixture is cooled to room temperature and 0.4 g (1.6 mmol) of iodine is added to convert the unreacted thiol to the disulfide. The mixture is stirred for 20 minutes at room temperature, poured into 100 ml of ethyl acetate in 50 ml of water and the excess I2 is removed by adding sodium sulfite. The layers are separated and The ethyl acetate layer was washed with two 100 ml portions of water and once with 50 ml of 20% NaCl solution, and then dried over anhydrous sodium sulfate. The ethyl acetate was removed in a rotary evaporator, and the residue was dissolved in 10 ml of methanol. 0.21 g (2 mmol) of lithium acetate dihydrate was added and stirred for 20 minutes at room temperature. The crystallized product was filtered off, washed with 5 ml of methanol, and dried. 0.34 g (69.4%) of white crystals were obtained. The identity of the product was confirmed by the CMR spectrum: 3.50 (ABq, J=17 Hz), 3.92 (s, —CH3 from tetrazole), 4.20 (s, 3—CH2S—), 5.04 (d, C«—H, J=5Hz), 5.24(s, GJL CHCONH—), 5.64 (d, C7—H, J=5Hz) and 7.44(s, C6H5— —H). The CMR spectrum is identical to the spectrum of the original sample of the product obtained by substitution in an aqueous medium. Example LXXXVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-{2-[o-(tertiary-butoxycarbonylaminoinethyl)phenoyl]arc-3-carboxylic acid-4-vitimethylmethane. 0.2 g (0.386 mmol) 7-{2-[o-(Ul-butoxycarbonylaminomethyl)phenyl]acetamido}-cephalosporanic acid and 0.047 g (0.405 mmol) of 1-methyl-1H-tetrazol-5-thiol is reacted in 5 ml of nitromethane at 85°C under nitrogen for 12 hours. Table Amount of cephalosporanic acid 1.91 g 0.96 g 1.96 g 1.26 g | 3.82 1.91 g 2.02 g* 1.928 Amount of thiol 0.86 g 0.363 g 0.5 g 0.5 g 1.98 g 0.99 g 1.0 g 0.79 g Solvent acetonitrile (dried over a sieve) nitrobenzene 1:1 mixture of 1,2-dichloroethane and nitromethane nitroethane propylene carbonate ethylene carbonate acetic acid mixture of 52.5% nitromethane and 47.5% 2-nitropropane Temperature boiling point 85°C 100°C 85°C 90°C 95 °C 95°C 85°C 95 °C Time 24 hours 16 hours 72 hours 14 hours 16 hours 8 hours 6 hours 5 hours 3 hours 50 minutes Yield % 87 83 88 84 68 22 55 | 89 Analysis I 190°C | 181 °C (with decomposition) | 182-183°C [ (with decomposition) I 177 °C 1 (with decomposition) [ — | — | — ( — [ * in sodium salt form Example LXXXV. Preparation of 3-[(1-methyl-1H-tetrazole] acid lithium salt 0.48 g (1 mmol) of 7-(2-hydroxy-2-phenylacetamido)-cephem-3-carboxylic acid and 0.5 g (4.3 mmol) of 1-methyl-1H-tetrazol-5-yl)-3-(2-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-{2-[o-(tert.-butoxycarbonylaminomethyl)phenyl]acetamido}-cephem-3-carboxylic acid are reacted in 15 ml of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-{2-[o-(tert.-butoxycarbonylaminomethyl)phenyl]acetamido}-cephem-3-carboxylic acid. The identity of the product is confirmed by the PMRS spectrum: 1.45 (s, 9, —C(CH3)O, 3.65(s, 4, 2—CH* and —CHiCONH—), 3.85(s, 3, —CH3 from tetrazolium), 4^3 (m, 4, 3—CHaS— a and —CH2NHCOO—DJ-rz.—C4Hf), 5.0 (d, 2, C«—H,122 152 39 J=4Hz), 5.7(q, 1, Ci—H), 7.25(s, 5, Hphenyl and —CONH) and 8.9 (s, 1, —COOH). Example LXXXVII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethi]-7-(2-ureido-2-phenylacetamido)-cefemo-3-carboxylic acid in nitromethane. 0.224 g (0.5 mmol) of 7-(2-ureido-2-phenylacetamido)-cephalosporanic acid and 0.061 g (0.525 mmol) of 1-methyl-1H-tetrazolethiol-5 are reacted in 8 ml of nithiomethane at 85°C for 12 hours. 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-ureido-3-phenylacetamido)-cephem-3-carboxylic acid is obtained. The identity of the product is confirmed by the CMR spectrum. <5: 3.5 (d, 2, 2-CHz, J=3Hz), 3.83 (s, 3, —CH3 from tetrazole), 4.17(d, 2, 3—CH2S—, J=3Hz), 4.9(d, 1, C6—H, J=5Hz) 5.4(d, 1, —CH2CONH—, J=8Hz), 5.6(m, 3, C7—H and —NH2), 6.7(d, 1, C6H5CH(NH)—, J-8Hz), 7.25)(m, 5, Hz of phenyl and 9.2(d, 1, —CH2CONH^, J=8Hz). Example LXXXVIII. Preparation of 3-[(1- 2-methyl-1H-tetrazolyl-5)thiomethyl] acid (2-cyanoacetami- to)-cephemo-3-carboxylic acid-4 in nitromethane. 0.339 g (1 mmol) of 7-(2-cyanoacetamido)-cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazolothiol-5 are reacted in 10 ml of nitromethane 2 at 85 °C, under nitrogen, for 12 hours. 3-[(l-methyl) acid is obtained -1H-tetrazolyl-5)thio- methyl [-7- (2- cyanoacetamido)-cefemo -3- carboxylic-4. The identity of the product is confirmed by the CSF spectrum <5: 3( 3.5 (s, 2, 2—CH2), 3.65 (s, 2, CNCH2CONH—), 3.95 (s, 3, —CH3 from tetrazolium), 5.35 (s, 2, 3—CHiS—), 5.1 (d, 1, C6—H, J=6Hz), 5.75(q, 1, C7—H, J=4Hz), 7.8 (s, 1, -COOH) and 8.7 (d, 1, -CH2CONH-, J=9Hz). carboxylic acid-4 in nitromethane. 0.390 g (0.855 mmol) of 7-[2-(m-chlorophenylthio)acetamido]cephalosporanic acid and 0.104 g (0.9 mmol) of 1-methyl-1H-tetrazol-5-thiol are reacted in 10 ml of nitromethane under nitrogen at 85°C for 12 hours to give 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(m-chlorophenylthio)acetamido]-cephem-3-carboxylic acid. The identity of the product is confirmed by the CMR spectrum. <5 3.6(s, 2, 2—CH2) 3.75 (s, 2, —CH2CONH—), 3.9 (s, 3, —CH3 from tetrazole), 4.4(s, 2, 3—CH2S—), 5.0(d, 1, C6—H, J=5Hz), 5.8(q 1, C7—H, J=4Hz), 7.15(m, 4, ^ phenyl protons), 7.7 (d, 2—CH2CONH—, J=8Hz) and 8.5(s, 1, COOH). Example XC. Preparation of [(1-methyl- -1H-tetrazol-5-yl)thiomethyl]-7-[2-(phenylthio)acetamido]-cephem-3-carboxylic acid in nitromethane. 55 0.422 g (1 mmol) of 7-[2-(phenylthio)acetamido]-cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazol-5-thiol are reacted in 10 ml of nitromethane at 85°C under nitrogen for 12 hours. [(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(phenylthio)acetamido]-cephem-5-carboxylic acid is obtained. The identity of the product is confirmed by the CMR spectrum. <$: 3.7 sol), 4.35 (s, 2.3—CH2S—), 4.9 (d, 1, C« —H, J=6Hz), 85 40 5.8 (q, 1, C7—H, J*=4Hz), 7.25 (s, 5, H phenyl), 7.7 (d, 1, —CH2CONH—, J=8Hz) and 9.4 (s, 1, —COOH). Example 101. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(thien-2-yl)acetamido]-cephem-3-carboxylic acid in n-butyl formate. 3.96 g (10 mmol) of 7-[2-(2-thienyl)acetamido]-cephalosporanic acid and 1.28 g (11 mmol) of 1-methyl-1H-tetrazol-5-thiol are reacted in 98 ml of n-butyl formate at 84-86°C for 43 hours. 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid is obtained, melting at 167.5-168°C. The yield is 79.5%. The PMR spectrum is identical to that of Example 5. Example 102 Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid-4-in toluene. The reaction is carried out on the same scale as in Example 101, except that 150 ml of toluene is used, the temperature is 84-86°C, and the reaction time is 136 hours. The melting point of the product is 163-183.5°C, and the yield is 88.5%. The PMR spectrum of the product is identical to that of Example 5. Example 103. Preparation of 3-[(1-methyl-1H-tetrazol-5-yl)t'omethyl]-7-(tert.-butoxycarbonylamino)-cephem-3-carboxylic acid-4-in nitromethane. 0.372 g (1 mmol) of 7-(tert.-butoxycarbonylamino)cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazol-5-thiol are reacted in 10 ml of nitromethane at 80 °C for 12 hours. 3-((1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(tert.-butoxycarbonylamino)cephem-3-carboxylic acid is obtained. The identity of the product is confirmed by the CMR spectrum. <5: 1.45) (s, 9, —C(CH3)3), 3.7(s, 2, 2—CH2), 3 95(s, 3, —CH, from tetrazole), 4.4(s, 2, 3—CH2S—), 5.0(s, 1, Cs—H). 5.6 (s, 2, C7—H and CH2CO—NH) and 13(s, 1, —COOH). Example XCIV. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(4-ethyl-2,3-di- ketopiperazinylcarbonylamino)-2-(p-hydroxyphenyl)acetamido]-cefemo-3-carboxylic acid. 0.180 g (0.306 mmol) of 7-[2-[4-ethyl-2,3-dioxopiperazinylcarbonylamino-2-(p-hydroxyphenyl)acetamido]-cephalosporanic acid and 0.0374 g (0.322 mmol) of 1-methyl-1H-tetrazole-5-thiol are reacted in 6 ml of nitromethane at 80°C for 12 hours to give 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-[2-(4-ethyl-2,3-dioxopiperazinylcarbonylamino)-2-(p-hydroxyphenyl)acetamido]-cephem-3-carboxylic acid. The identity of the product is confirmed by the CMR spectrum. <5: 1.2 (t, 3, N—CH2CH3), 3.6(m, 6, 2-CH2, 6—H and N—CH2 CH3 piperazine), 3.9 (m, 2, 5—H piperazine), 3.95(s, 3, —CH3 tetrazolium), 4.4(s, 2.3—CH2S—), 5.0 (d, 1, G*—H, J=6Hz), 5.6(d,l,C7—H,J=6Hz), 5.8 (d, 1, CHCONH— —, J=8Hz), 6.8 (d, 2, phenyl H, J=8Hz), 7.3 (d, 2, phenyl H, J=8Hz), 8.3(d, 1, —CHCONH, J=8Hz) and 9.9(d, 1, —CH(NH)CONH—, J=6Hz).Example XCV. Preparation of 3-[(1,3,4- thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-1)acetami- to]-cefemo-3-carboxylic acid-4 in acetonitrile. 0.38 g (1 mmol) of 7-[2-(1H-tetrazolyl-1(acetamido]-cephalosporanic acid and 0.15 g (1.27 mmol) of 1,3,4-thiadiazolothiol-2 are reacted in 15 ml of acetonitrile, at reflux temperature, under nitrogen, 24122 152 41 hours. 3-[(1,3,4-thiadiazolyl-2)thiomethyl]-7-[2- (1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4 is obtained. The identity of the product is confirmed by the CSF spectrum. <$: 3.74(m, 2, 2—CH2—), 4.48 (q, 2, 3—CH2—S, Jab=14), 5.16 (d, 1, C6—H, J=5), 5.42 (s, 2, —CH3 from tetrazole), 5.76(q, 1, C7—H, J6.7=5, J7NH=8), 8.87 (s, 1, tetrazole ring), 9.40 (s, 1, starting thiadiazole thiol), 9.53 (d, 1 -CH2CONH -, J=8Hz) and 9.57 (s, 1, thiadiazole ring). Example XCVI. Preparation of 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl]-7-[5-carbomethoxy-5-(2,4-dichlorobenzamidovaleramido]-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 0.3 g (0.5 mmol) 7- acid [5-carbomettics -5- (2,4- dichlorobenzamido/valeramido] - cephalosporan acid and 0.1 g (0.75 mmol) 5-methyl-1,3,4-thiadiazolothiol-2 are reacted in 1,2-dichloroethane at reflux temperature for 16.5 hours to obtain 3-[(5-me- tyl-1,3,4-thiadiazolyl-2)thiomethyl] -7- [5- carbometcksy- 5-(2,4-dichlorobenzamido/valeramido] -cefemo -3-carboxylic acid-4. Example -3-carboxylic acid-4 in acetonitrile. 1.91 g (5 millimoles) of 7-[2-(1H - tetrazolUo-1) acetamido]-cephalosporanic acid and 0.7 g (6 millimoles) 1-methyl-1H- tetrazolothiol-5 in 50 ml of acetonitrile are heated at reflux temperature for 24 hours and cooled to this temperature The solvent is removed in a rotary evaporator to about 10 ml. 40 ml of ethanol are added, followed by 0.3 g of lithium hydroxide in 10 ml of methanol. This product, the lithium salt of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl-7-[2-(1H-tetrazolyl-1)acetamido]-cephem-3-carboxylic acid, crystallizes. After the reaction, the mixture is stirred for 45 minutes at room temperature, the product is filtered off, washed with ethanol and dried under vacuum at 40°C. 1.60 g (72%) of product is obtained, the identity of which is confirmed by analysis of the CSF spectrum. Example XCVIII. Preparation of 3-[(5- methyl-1,3,4-thiadiazol-2-ylmethyl]-7-(2-formyloxy-2-phenylacetamido)-cephem-3-carboxylic acid in 1,1-dichloroethane. 4.6 g (8.8 mmol) of 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid and 1.52 g (11.5 mmol) of 5-methyl-1,3,4-thiadiazol-2-thiol in 50 ml of 1,2-dichloroethane are heated at reflux for 12 hours and cooled to room temperature. This product is 3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid. 3-(phenylacetamido)-cephem-3-carboxylic acid precipitated as a thick paste. The mixture was diluted with an additional 50 ml of 1,2-dichloroethane and stirred for 4 hours at room temperature. The product was filtered off, washed with 1,2-dichloroethane until the filtrate became clear, and dried under vacuum at 40-45°C. 2.8 g (63%) of product was obtained, the identity of which was confirmed by CSF analysis. Example XCIX. Preparation of 3-[(4,5-dihydro-6-hydroxy-4-methyl-5-keto-1,2,4-triazin-3-yl)thiomethyl-7-[2-(1H-tetrazol-1-yl)acetamido]-cephem-3-carboxylic acid in acetonitrile. 8.9 g (23.2 mmol) of 7-[2-(1H-tetrazolyl-1)acetamido]cephalosporanic acid and 4.1 g (25.8 mmol) of 4,5-dihydro-6-hydroxy-4-methyl-5-oxo-1,2,4-triazine-3-thiol in 200 ml of acetonitrile were heated at reflux for 23 hours and then cooled to room temperature. During the reduction, the product crystallized, was filtered off, washed with 50 ml of acetonitrile and dried under reduced pressure at 40-50°C. 9.70 g were obtained. (86.6%) of 3-[(4,5-dihydro-6-hydroxy-4-methyl-5-keto-1,2,4-triazin-3-yl)thiomethyl]-7-[2-(1H-tetrazol-1-yl)acetamido]-cephem-3-carboxylic acid-4, the identity of which is confirmed by analysis of the CMR spectrum. Example C-CXLIV. In the process according to the invention, the following reactions are also carried out: the sodium salt of 7-(2-sulfo-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazol-5-thiol to obtain the sodium salt of 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7-(2-sulfo-2-phenyl- acetamido)-cefemo -3- carboxylic acid-4, 7-[2-(4- pyridylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl -1H- tetrazolothiol-5 20 to obtain 3-[(1-methyl -1H-tstrazolyl-5)thiomethyl[-7- [2-(4-pyridylthio)acetamido [-cefemo -3-carboxylic-4, 7-[5-carbo-n- butoxy -5- (2,4-dichlorobenzamido)valeramido]-cephalcsporanic acid is reacted with 5-methyl-1,3.4-thiadiazellothiolein-2 and obtains 3-[(5- methyl - l3»^thia*a^iyló-2)thiomethyl] -7-15-carbo-n-butoxy-5-(2,4-dichlorobenzamido)valeramido]-cephemo-3-carboxylic acid-4, 7-[5-carbo-n-butoxy-5-(2,4-dichlorobenzamido)valeramido]-cephalosporans are reacted with 1-methyl-1H- tetrazolothiol-5 and are obtained 3- [(1-methyl -1H- tetrazolyl -5)thiomethyl] -7- [5-carbo-n- butoxy -5- (2,4-dichlorobeDzamido)valeramidc] - cephemo -3-carboxylic-4, 35 acid 7-{2-[2-(p-nitrobenzyloxycarbonylamino)thiazcyl-4] -2- (methoxyimino)acetamido}-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolothiol-5 to obtain 3-[(1-methyl -1H-tetrazolyl-5)ticmethyl]-7-{2-[2-(p-nitrobenzyloxycarbonylamino)thiazolyl-4]-2- (methoxyimino)acetamido}-cefemo-3- carb- xyl-4, 7-{2- [2- (p- nitrobenzyloxycarbonylamino)thiazo- HIo-4] acetamido} cephalosporanic acid is reacted with 1-methyl-1H-tretrazolothiol-5 to obtain 3-[(1- methyl -1H- tetrazolyl-5)thiomethyl[-7- {2-[2-(p-nitrobenzyloxycarbonylcamino)thiazolyl-4]acelamidol-ce-femo-3-carboxylic-4, 7-[(2,2,2 - trichlorcetoxy)carbonylamino]-ce- phalosporanic acid is reacted with 6-hydroxypyridazinethiol-3 and the acid is obtained 3-[(6-hydroxypyridazinyl-3)thiomellyl]-7-[(2,2,2-trichloroethoxy)carbomyTylamino]-cephemo-3-carboxylic acid-4, 7-[2-(tieryl-2)acetamido]-cephalosporan acid is reacted with 6-hydroxypyridazinethiol-3 and the acid is obtained 3-[(6-hydroxypyridazinyl-3)ticmethyl]-7-[2-(thienyl-2)acetamido]-cephemo-3-carbylic acid-4, 7-[(2,2,2-trichloroethcksy)carbonylamino]-cephalosporanic acid is reacted with tetrazolo[1,5-b]pi- rydazinethiol-6 and 3-] (tetrazolo [1,5-b] pyridazinyl-6) thiomethyl] -7- [(2,2,2-trichloroethoxy)carbomylaminc] -cefemo -3-carbphyllyl-4 acid is obtained, 7- [2- (thienyl-2 (acetamido] -cephalcsporate acid is reacted with tetrazolium [1,5-b] 3-[(tetrazolo]1,5-b[pyridazin-6-yl)122 152 43 thiomethyl[-7-[2-(thienyl-2(acetamido]-cephem-3-carboxylic acid-4, 7-[(2,2,2-trichloroethoxy)carbonylamino]-cephalosporanic acid is reacted with 1-(sulfomethyl)-1H-tetrazol-5-thiol-sodium salt to obtain 3-{[1-(sulfomethyl)-1H-tetrazol-5-yl]thiomethyl}-7-[(2,2,2-trichloroethoxy)carbonylamino[-cephem-3-carboxylic acid-4, 7-[2- 3-{[1-sulfomethyl)-1H-tetrazol-5-yl]thiomethyl}-7-[2-(2-thienyl-2)acetamido]-cephalosporanic acid is reacted with 1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-thiol to give 3-{[(1-(2-dimethylamino)ethyl)-1H-tetrazol-5-yl]thiomethyl}-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid sodium salt. 7-1-(2,2-trichloroethoxy)carbonylamino]-cephalosporanic acid is reacted with 1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-thiol to give 3-{[(1-(2-dimethylamino)ethyl)-1H-tetrazol-5-yl]thiomethyl}-7-[2-(thienyl-2)acetamido]-cephem-3-carboxylic acid. [(2,2,2-tricMoroethoxy)carbonylcamino] -ce¬ -2-carboxylic acid-4, 7- [2- (thienyl-2)acetamido [-cephalosporanic acid is reacted with 1-[2-(dimethylamino)ethyl]- -IH- tetrazolothiol-5 to obtain 3-{ [1 - (2-dimethylamino(ethyl)-IH-tetrazolyl-5]thiomethyl}-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic-4, 7-[2-(thienyl-2)acetamido]-cephalosporanic acid 25 is reacted with p-methoxybenzenethiol to obtain the acid 3-[(p-methoxyphenayl)thiomethyl] -7-[2-(thienyl-2 acetamido]-cefemo-3-carboxylic-4, 7-[2-(thienyl-2)acetamido]-cephalosporanic acid is reacted with p-chlorobenzenethiol to obtain 3-[(p-chlorophaiyio)thiomethyl]-7-[2-(thienyl-2) acid acetamido]-cefemo -3-carboxylic acid-4, 7-[2-(thienyl-2(acetamido]-cephalesporanic acid is reacted with o-toluenethiol to obtain 3-[(o-tolyl)thiomethyl)-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4, acid 7- [2-(1H-tetrazolyl-l)acetamido]-cephalosporan acid is reacted with 1,3,4-t-diazolyl-2-thiol to obtain 3-[(1,3,4-thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-l)acetamido] acid -cefemo-3-carboxylic-4, 40 7-phthalimide-cefemosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolothiol-2 to obtain 3-[(5-methyl-1,3,4-tadiazolyl-2)thiomethyl]-7-phthalimidocefemo-3-carboxylic acid 7 - (2-hydroxy -3-phenylacetamido) - cephalospora- 45 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl]-7-(2-hydroxy-2-phenylacetamido)-cephem-3-carboxylic acid, 7-(2-acetoxy-2-phenylacetamido)-cephalosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolyl-2-thiomethyl]-7-(2-acetoxy-2-phenylacetamido)-cephem-3-carboxylic acid, 3-[(5-methyl-1,2,4-thiadiazolyl-2)thiomethyl]-7-(2-acetoxy-2-phenylacetamido)-cephem-3-carboxylic acid, 7-[2-(trifluoromethylthio)acetamido]-cephem-3-carboxylic acid, 55 sporanic acid is reacted with 1-methyl-1H-tetrazol-thiol-5 to obtain 3-[(1-mctyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(trifluoronethylthio)acetamido]-ce¬femo-3-carboxylic acid-4, 7-{2- [2-(p-nitrobenzyloxycarbonylamino)thia- 60 zoliio-4]-2-(methoxyimino)acetamido}-cephalosporanic acid is reacted with 4,5-dihydro-6-hydroxy-4-methyl-5-ketol-1,2,4-triazinethiol-3 to give 3* acid [(4,5-dihydro) -6- hydroxy -4- methyl -5-keto-1,2,4- triazinyl-3)thiomethyl] -7- {2- [2- (p-nitrobenzyloxycarbonylamino)thiazolyl-4] -2-(methoxyimino)acetamido}-ce- femo -3-carboxylic acid-4, 7-{2- [2- (p-nitrobenzyloxycarbonylamino)thiazolyl-4] acetamido}-cephalosporanic acid is reacted with 1-[2-(dimethylamino)ethyl]-IH-tetrazolothiol-5 to obtain 3-{[l-(2-)dimethylamino(ethyl)-1H-tetrazolyl-5]thiomethyl}-7-{2-[2-(p-nontrobenzyloxy- carbonylamino)thiazolyl-4]acetamido}-cefemo 7-{2-[o-(tert.-butoxycarbonylaminomethyl)phenyl]acetamido}-cephalosporanic acid is reacted with tetrazolo[1,5-b]pyridazine-6-thiol to give 3-[(tetrazolo]1,5-b[pyridazine-6-yl)thiomethyl]-7-{2-[o-tert.-butoxycarbonylaminomethyl)phenyl[acetamido}-cephem-3-carboxylic acid, 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-(sulfomethyl)-1K-tetrazole-5-thiol sodium salt to give 3-{[1-(sulfomethyl)- 1H-tetrazol-5-[thiomethyl]}-7-(2-formyloxy-2-phenylacetamido)-cephem-3-carboxylic acid, 7-(2-hydroxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-(sulfomethyl)-1H-tetrazol-5-thiol sodium salt to give 3-{[1-(sulfomethyl)-1H-tetrazol-5-yl]thiomethyl}-7-(2-hydroxy-2-phenylacetamido)-cephem-3-carboxylic acid, 7-[2-(thienyl-2)acetamido]-cephalosporanic acid is reacted with 2-oxazole-thiol to give 3-[(oxazolyl-2)thiomethyl] 7-[2-(2-thienyl)acetamido]-cephem-3-carboxylic acid, 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-(carbeximethyl)-1H-tetrazol-5-thiol to give 3-{[1-(carboxymethyl)-1H-tetrazol-5-yl]thiomethyl}-7-(2-formyloxy-2-phenylacetamido)-cephem-3-carboxylic acid, 7-[2-(trifluoromethylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl-1H-tetrazol-5-thiol to give 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-7- [2-(trifluoromethylthio)acetamido]-cefemo-3-carboxylic acid-4. 7-[2-(cyanomethylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl-IH-tetrazolothiol-5 to obtain 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2r(cyanomethylthio)acetamido]-cefemo-carboxylic acid-, acid 7-methoxy -7- [2- (cyanomethylthio)acetamido] - cephalosporan acid is reacted with 1-methyl -1H-tetrazolothiol-5 to give 3- [(1-methyl -1H-tetrazolyl-5)thiomethyl] -7-methoxy -7- [2- (cyanomethylthio)acetamido]-cefemo-3-carboxylic acid-4, 7-[2-(o-benzoylaminomethylphenyl)acetamido]-cephalosporanic acid is reacted with 1-(carboxymethyl)-1H-tetrazolylthiol-5 and 3-[(l-carbo- ximethyl-1H-tetrazolyl-5)thiometyIo]-7-[2-(o-benzoyl-aminomethylphenyl)acetamido]-cefemo-3-carboxylic-4, 7-(2-ureido-2-thienylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolylthiol-5 to obtain 3- [(1-methyl -IH-tetrazolyl-5)thio-methyl] -7-(2-ureido -2- thienylacetamido)-cefemo -3- carboxylic-4, 7-[2-(2-aminotiazolyl-4)acetamide o]-cephalosporic acid is reacted with 1-[2-(dimethylamino)ethyl]-1H-tetrazolothiol-5 and 3-{ acid is obtained [l-(2-dimethylaminoethyl)-IH-tetrazolyl-5]thiomethyl}-7-[2-(2-aminotiazolyl-4)acetamido]-cephalosporanic acid, 7-(5-benzoylamino-5-carboxyvaleramido)-ce-122 152 45 phalosporanic acid is reacted with 4,5-dihydrogen -6- hydroxy -4- methyl -5-keto-1,2,4-triazinethiol-3 and [(4,5-dihydro -6-hydroxy -4-methyl -5-keto-1,2,4-triazinyl-3)thiomethyl] -7-5-benzoyl- amino -5-carboxyvaleramido)-cefemo -3- carboxylic acid, 7- (5-benzoylamino -5-carboxyvaleramido)-ce-phalosporanic acid is reacted with 1-methyl- 1H- 1,2,3-triazolothiokm-5 to obtain 3-[(1-methyl -1H- 1,2,3-triazolyl-5)u'omethyl] -7-(5-benzoylamino -5-car- boxyIeramido)-cephemo-3-carboxylic acid-4, acid 7-(5-benzotlamino-5-carboxyvaleramido)-cephalosporanic acid is reacted with 1-(carboxymethyl)-1H-tetrazolothiol-5 to obtain 3-[(1-carboxymethyl-1H-tetrazolyl-5)thiomethyl]-7-(5-benzoylcamino-5-carboxyvaleramido)-cefemo acid -3- carboxylic-4, 7- (5-benzoylamino -5-carboxyvaleramido)-cephalosporanic acid is reacted with 5-methyl-1,3,4-oxa-diazolothiol-2 to obtain 3- [(5-methyl-1,3,4- bxadiazolllo-2)tiomttlcl -7-(5-benzoylamino) -5-carbo- xivaleramidbcefemb *3-carboxylic acid-4, 7-(5-benzofloamino *5* carboxyvaleramido)-cephalosporan acid is reacted with 1-benzyl -1H-tetra- zolothiol-5 and you get 3^[(£berizoiib -1H- tetrazolyl-5)ticmethyl] -7- (5-benzoylamino-5-carbclrey-walefaniido)-cephalosporanic acid, °5 7-(5-benzoylamino-5-carboxyvaleramidb)-cephalosporanic acid is reacted with thiourea and 3-amidinothiomethyl -7-(5-benzoylamino-5-) acid is obtained carboxyvaleramido^cefcmo -3-carboxylic acid-4, 7-methoxy-7-(5-benzoylamino-5-carboxyvaleramido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolothio-5 to obtain 3-[(l-methyl-1H-tetrazolium-5)thiomethyl]-7-methoxy-7-(5-benzoyl-amino acid -5-carboxyvaleramido)-ceremo -3- carboxylic-4, 7-methoxy -7- (5- benzoylamino -5-carboxyvaleramido)-cephalosporanic acid is reacted with 5-methylIol- 1,3,4-thiadiazolothiol-2 to obtain 3-[(5-me- tyl-1,3,4-thiadiazolyl-2)thiomethylt-7-methoxy -7-(5-benzoylamino-5-carboxyvaleramido)-cephemo-3-carboxylic-4, 7-methoxy-7-(5-benzoylamino-5-carboxyvaleramido)-cephalcsporanic acid is reacted with 4,5-dihydrogen -6-hydroxy -4-methyl-5-keto -1,2,4- triazine-thiol-3 and 3- [(4,5-dihydro-6- hydroxy -4- methyl -5-keto-1,2,4-triazinyl-3)trcmethyc] -7- methoxy -7-(5-benzoylamino -5-carboxyvaleramido) - cefemo -3-carboxylic-4 acid is obtained 7-methoxy -7- (5-benzoylamino-5-carboxyvaleramido)-cephalosporanic acid is reacted with thiourea to obtain 3-amidinothiomethyl-7-methoxy-7-(5-benzoylamino-5-carboxyvaleramido)-cefemc-3-carboxylic acid, 7-(5-butoxycarbcnylcsmino-5-kaibcksywaIeramido)-3-carbamyloxymethylcephem-3-carbcksyl-4 is reacted with thiourea to obtain 3-amidinothiomethyl-7-(5-butoxycarbonylamino-5-carboxyvaleramido)-cephemo-3-carbcksyl-4 acid, acid 7-(5-butoxycarbonylamino -5-carboxyvaleramido) -3-carbamyloxymethylcefemo -3- carboxylic acid-4 is reacted with 1-methyl -1H-tetrazolothiol-5 to obtain 3-[(1-methyl -1H- tetrazolyl -5)ticmethylol -7-(5-butoxycarbonylamino -5- carboxyvalera- mido)-cefemo-3-carboxylic acid, 7-(5-butoxycarbonylamino-5- carboxyvaleramido)-3- carbamyloxymethylcefemo-3-carboxylic acid is reacted with 5-methyl-1,3,4-thiadiazciothiol-2 and the acid is obtained 3-[(5-methyl-1,3,4-thiadiazolyl«2)thiomethyl] -7-(5- butoxycarbonylamino -5-carboxy- valeramidocefemo-3-carboxylic acid-4, 5 7-(5-butoxycarbonylamino -5- carboxyvaleramido) -3- carbamyloxymethylcefemo -34carboxylic acid, reacts with 1-(carboxymethylIo) -1H- tetrazole thiol-5 and 3-[(1-carboxymethyl-1H-tetrazolyl-5)thiomethyl]-7-(5-butoxycarbonylamino~5-10 carboxyvaleramido)-cephemo-3-carboxylic acid-4 is obtained. Patent claims 1. Method for preparing derivatives of 3-(thiomethyl)cephalosporins with general formula 1, in which R is a group of formula 2, in which each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkenyl group with 2-3 carbon atoms, a cyclohexyl or a phenyl group, or R13 is a group of formula 3, an alkyl group with 1-4 carbon atoms, a group of formula 4 or a group of formula 5, in which each R5 is independently an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, trimethylsulfonamide or trifluoromethyl group, a denotes a number 0, 1 or 2, and R1 denotes a group, forming a group of formula 14, optionally substituted, tri- or a tetra-membered heteroaromatic ring containing a total of 1—4 heteroatoms in combinations of 1 nitrogen atom and 0 or 1 oxygen or 0 or 4 nitrogen atoms, 2 nitrogen atoms and 1 oxygen or 0 or 1 oxygen or 0 or 4 nitrogen atoms, all other ring atoms being carbon atoms, or R < denotes a moiety forming together with the moiety of formula 14 a 2-benzoxazolyl, 2-benzimidazolyl, 2-benzothiazolyl radical or a radical of formula 15, Rl denotes a hydrogen atom or a methoxy group, and R* denotes a phthalmide, succinimide, group of formula 6, in where L is a hydrogen atom or a nitroso group or R2 is a group of the formula R3-.C(=*0)-^NH-, in which R3 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, a CH-chloroalkyl group with 1-3 carbon atoms in the alkyl part, a -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part, cyanoalkyl group o R3 denotes a 4-keto-4-carboxybutyl group, a 3-carboxypropyl group, a group of formula VII, in which a and a1 are the same or different and denote a hydrogen atom, an alkyl group of 1-4 carbon atoms, an alkoxy group of 1-4 carbon atoms, a halogen atom or a hydroxyl group, Z denotes an oxygen or sulfur atom and m denotes 0 or 1, or R3 denotes a group of the formula P-CH(Q)-^, in which P denotes a 2-thienyl, 3-thienyl or phenyl group of formula VIII, in which a and a1 have the meaning given above, and Q denotes a hydroxyl, formyloxy, acetoxy, carboxyl group of the formula —C(—O)~-O—A2, in which A2 denotes a diphenylmethyl, p-nitrobenzyl, benzyl, 2,2,2-trichloroethyl, tert.-butyl or p-methoxybenzyl group, or Q denotes a sulfonate, acylamino group of the formula —NH—C(=O)~T, in which T denotes a group of the formula —NH—C(=* N)—NH2, N(R?)—C(=O)—R», ~N(R*)—C)—CH= =CHR9, or T denotes a group of the formula 9, 10, 11 or 12, in which R7 denotes a hydrogen atom or an alkyl group with 1-3 carbon atoms, R8 is a phenyl, chlorine-122,152,47,cophenyl, furyl, methylamino, dimethylamino, ethylamino, diethylamino, methylethylamino, propylamino, dipropylamino, diisopropylamino, phenylamino or diphenylamino group, R* is a hydrogen atom, an alkyl group with 1-4 carbon atoms or a phenyl group, R10 is a hydrogen atom, an alkyl group with 1-3 carbon atoms or a methylsulfonyl group, R" is an ethylene, trimethylene, or vinylene group and p is 2 or 3, or R3 is a group of formula 13 or a group of formula 13, in which the group OH is replaced by a group —OCHj or a group —OC (=O)CH3, wherein P' in formula 13 has the meaning given above for P or represents a 2-furyl group, or R3 represents a group of the formula V—S(O)n—CH2—, in which V represents a group of the formula —CFs or —CH2—X, in which X represents a hydrogen atom, a methyl group, a —CF3 group, CN or —Nj and n represents the number 0, 1 or 2, or R3 represents a group of the formula Y—CH2, in which Y represents a 2-thienyl, 3-thienyl, 2-furyl, 2-oxazolyl, 2-thiazolyl, 1-tetrazolyl, 1-benzotriazolyl, 2-oxazolylthio, 2-thiazolylthio, 1,2,3-triazolyl-5-thio, 1,3,4-triazolyl-2-thio, 1,3,4-thiadiazolyl-2-thio, 5-methyl-1,3,4-thiadiazolyl-2-thio, 1,2,4-thiadiazolyl-5-thio, 3-methyl-1,2,4-thiadiazolyl- 5-thio, 1,2,5-thiadtazolyl-3-thio, 1,3,4-oxadiazolyl-2-thio, 5-methylIo-1,3,4-oxadiazolyl-2-thio, 1-methyl-tetrazolyl-5-thio, pyridiothio, 4-cyano-1,2,3-triazolyl-1 or 3-cy- jano-l,2,4-triazolyl-l according to which the compound has the formula 16, wherein R1 and R2 have the above-mentioned meaning and R denotes an alkyl group with 1-3 carbon atoms, a cycloalkyl group with 4-5 carbon atoms, an amino group, a mono- or di(alkyl)amino group with 1-3 carbon atoms in the alkyl radical - the group of formula 17, 18 or 19 is reacted in the presence of an organic solvent with a sulfur nucleophile of the formula R"-S-R14, wherein R13 has the above-mentioned meaning and R" denotes a hydrogen atom, or if R13 denotes a methyleneamine group, and only then, R" together with R13 forms a thiourea, with the exception that the reaction is carried out under anhydrous conditions. 2. A method according to claim 2, characterized in that the reaction is carried out at a temperature of 50-140°C. 3. A process according to claim 2, characterized in that the reaction is carried out at a temperature of 70-120°C. 4. A process according to claim 1, 2 or 3, characterized in that the solvent is a hydrocarbon, an alcohol, an amide, a ketone, a carboxylic acid, a carboxylic acid ester, a halogenated hydrocarbon, a nitro compound, a nitrile or a tic ether. 5. A method according to claim 4, characterized in that the solvent used is acstonitrile, 1,2-dichloroethane, methylene chloride, propionitrile, nitromethane, nitroethane, acetic acid, isopropyl acetate, butyl acetate, methyl isobutyl ketone, fluorobenzene, methyl ethyl ketone, 1,1,2-trichloroethane, chloroform, benzene, carbon tetrachloride, isopropanol, nitrobenzene, propylene carbonate, ethylene carbonate, 2-nitropropene, or n-butyl formate. 1, characterized in that 7-[2-(1H-tetrazolyl-1)-acetamido]-cephalosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolyl-2-thiol to obtain 3-[(5-methyl-1,3,4-thiadiazolyl-2)-thiomethyl]-7- acid [2-(1H-tetrazolyl-1)acetamido]-cefemo-carboxyl acid. 48 7. The method according to claim 48. 7. A process according to claim 1, characterized in that 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazol-5-thiol to obtain 3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-7-(2-formyloxy-2-phenylacetamido)-cephem-3-carboxy-4-oic acid. 1, characterized in that 7-[2-1H-tetrazolyl-1)acetamido]-cephalosporanic acid is reacted with 1,3,4-thiadiazolyl-2-thiol to obtain 3-[(1,3,4-thiadiazolyl-2)thiomethyl]-7-[2-(1-tetrazolyl-1)acetamido] acid -cefemo-3-carboxylic acid-4. 9. The method according to claim 2. The process of claim 1, wherein 7-(2-hydroxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazol-5-thiol to obtain 3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-7-(2-hydroxy-2-phenylacetamido)-cephem-3-carboxylic acid. 10. A method for the preparation of 3-(thiomethyl)-cephalosporin derivatives of the general formula I, wherein R" is a group of the formula II, wherein each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkenyl group with 2-3 carbon atoms, a cyclohexyl or phenyl group, or R13 is a group of the formula III, an alkyl group with 1-4 carbon atoms, a group of the formula IV or a group of the formula V, wherein each R5 is independently an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, methanesulfonamide or trifluoromethyl group, q is 0, 1 or 2, and R6 denotes a group forming, together with the group of formula 14, an optionally substituted five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in combinations of 1 nitrogen atom and 0 or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen atom or 4 nitrogen atoms, wherein all the remaining ring atoms are carbon atoms, or R6 denotes a group forming, together with the group of formula 14, a 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl radical or a radical of formula 15, R1 denotes a hydrogen atom or a methoxy group, and R2 denotes a group of formula R3—C(=O)——NH—, in which R3 denotes a group of formula P—CH(Q)— wherein a and a1 are the same or different and represent a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom or a hydroxyl group, and Q represents a group of the formula Me—O—SO2— wherein Me represents an alkali metal atom or an acylamino group of the formula —NH—C(=O)—T, wherein T represents an amino group according to the formula 16 wherein R1 and R2 have the meanings given above, and R represents an alkyl group with 1-3 carbon atoms, an amino group, a mono- or di(alkyl)amino group with 1-3 carbon atoms in the alkyl radical or a group of the formula 17, 18 or 19, is reacted in the presence of an organic solvent with a nucleophilic sulfur compound of formula R13 —S—R14, wherein R1J has the meaning given above and R" is a hydrogen atom or if R13 is a methyleneamine group and only then, R14 together with R13 forms thiourea, characterized in that the reaction is carried out under anhydrous conditions.122 152 R1 COOH \^& formula1 +\, q formula2 formula4 formula5 OCh-? ^ CHb tH3 W20r 7 formula6 ° s^. f(, o °1 JLf formula8 V*0 tfi^A n D10 \ kl/~u formula10 formula9 plO122 152 (OH), O formula11 1)I-0H P- C-C- II o formula 13 W*? -c oR1 k/S formula 12 formula 14 f-r5 ^Ny-CHjOCOR formula 15 COOH formula 16 -C"CHOOH -OCH OCH, ÓCH3 formula 17 -C-CH^yOSOsH OCH3 formula 19 OH OH formula 18122 152 ^CH3 -— S^k^CHs HS- formula 20 formula 21 0 (^-CH-C-NH -rf^ N—N formula 22 C00H U ^CH-C-NH-r^^ N-i^J OCHO 0^Nr CH2_S^N^ COOH X, formula 23 un3 r^=y o formula 24 COOH122 152 l)Ms| O N^N-CH^C-NHrT^ N-N COOH formula 25 ' O CF3SCH2CNH J^^K^ formula 26 o r^T-CH^CNHw-S.NH, COOH formula 27 CH2-CH2-N(CH3)2122 152 O {^CH2CNH-pTS 000,4 CH2COOH -i—(^ U—H -. My-cH2-sX^ formula 28 O OCI-fa NCCH^Cr^CNHffs^, N-N nM^CH2-S"VN &'y ^2 o-y. formula 29 o COOH CH3 NCCHSC^CNH-r^ S N-M COOH CH, formula 30122 152 _ O ( VcH-CNH^h rHf OH O' CH2-S^ tf**1 cksoh formula 31 COOH formula 32 o if^CH-CNH-rY^ *t~y ^ 0^CH2-SY c=0 ^ CH3 ^IH2 formula 33 H HO^iCH- formula 3^ LDD Z-d 2, «. U68/I400y«3, n. 85+20 copies. Price 100 PLN PL PL PL PL PL PL PL PL PL PL PL PL PL

Claims (1)

1.