DK155008B - Fremgangsmaade til fremstilling af 3-methylencepham-forbindelser - Google Patents
Fremgangsmaade til fremstilling af 3-methylencepham-forbindelser Download PDFInfo
- Publication number
- DK155008B DK155008B DK106677AA DK106677A DK155008B DK 155008 B DK155008 B DK 155008B DK 106677A A DK106677A A DK 106677AA DK 106677 A DK106677 A DK 106677A DK 155008 B DK155008 B DK 155008B
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- Denmark
- Prior art keywords
- group
- general formula
- compounds
- methylencepham
- preparation
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 9
- HTFTURZHXAWZPC-SSDOTTSWSA-N (6r)-3-methylidene-5-thia-1-azabicyclo[4.2.0]octan-8-one Chemical class C1C(=C)CS[C@@H]2CC(=O)N21 HTFTURZHXAWZPC-SSDOTTSWSA-N 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims description 6
- -1 2-benzothiazolyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000006303 photolysis reaction Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 230000015843 photosynthesis, light reaction Effects 0.000 claims description 4
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 238000006552 photochemical reaction Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 241000219470 Mirabilis Species 0.000 description 1
- 241000588772 Morganella morganii Species 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000001485 cycloalkadienyl group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- VLAPMBHFAWRUQP-UHFFFAOYSA-L molybdic acid Chemical compound O[Mo](O)(=O)=O VLAPMBHFAWRUQP-UHFFFAOYSA-L 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical class OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/08—Preparation by forming the ring or condensed ring systems
- C07D501/10—Preparation by forming the ring or condensed ring systems from compounds containing the penicillin ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Cephalosporin Compounds (AREA)
Description
i
DK 155008 B
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af 3-methylencepham-forbindelser med den almene formel R2 ^’νηϊ—rs- oX_N\Ic„2 (i) C-OR3
II
io o 1 2 i hvilken R er en acylgruppe, R er et hydrogenatom eller 3 en α-methoxygruppe, og R er et hydrogenatom, en c^-C^-al-kylgruppe, en 2,2,2-trichlorethyl-, trimethylsilyl-, diphe-15 nylmethyl-, benzyl-, 4-methoxybenzyl- eller 4-nitrobenzyl-gruppe.
3-Methylencepham-forbindelser med den almene formel I er kendt som værdifulde organiske mellemprodukter til fremstillingen af cephalosporin-antibiotika, der er effektive 20 over for gram-negative bakterier, såsom Escherichia coli, Proteus vulgaris, Proetus mirabilis, Proteus morganii, Salmonella schottmuelleri, Klebsiella pneumoniae AD, Klebsiella pneumoniae B og Paracolobactrum arizoniae, og gram-positive bakterier, f.eks. Staphylococcus aureus, Streptococcus ργο-25 genes og Diplococcus pneumoniae, jfr. USA patentskrift nr. 3.883.518.
Ved omsætningen af 3-methylencepham-forbindelser med den almene formel I med en organisk base sker der en isome-risering til de tilsvarende desacetoxycephalosporiner, jfr.
30 f.eks. Chauvette et al., J. Org. Chem. 3jJ, 2994 (1973). Den oxidative spaltning af 3-methylencepham-forbindelserne med den almene formel I giver de tilsvarende 3-hydroxycephera-forbindelser, jfr. f.eks. hollandsk patentansøgning nr. 73.09136.
35 Formålet med opfindelsen er at tilvejebringe en ny metode til fremstilling af 3-methylencepham-forbindelser 2
DK 155008 B
med den almene formel I ud fra penicillin-precursorer, og dette formål opnås ved fremgangsmåden ifølge opfindelsen, der er ejendommelig ved, at et azetidin-2-on-derivat med den almene formel 5 R2 1 = 4
R -NH -y S-S-R
J—n-ch-c=ch2 <ii) 3 '
R -O-C CH
10 II 3 o 12 3 i hvilken R , R og R har de ovenfor angivne betydninger, og R^ betyder en 2-benzothiazolylgruppe eller en aromatisk, 15 heterocyclisk gruppe med mindst 5 ringled, der indeholder _3 et nitrogenatom, i en koncentration på fra 3 x 10 til 3 x _2 10 mol pr. liter halogeneret carbonhydnd, methanol eller acetonitril som opløsningsmiddel underkastes fotolyse.
Fremgangsmåden ifølge opfindelsen gennemføres som 20 nævnt i et organisk opløsningsmiddel og fortrinsvis under en beskyttelsesgas, f.eks. argon eller nitrogen. Egnede opløsningsmidler er halogenerede carbonhydrider, f.eks. methylenchlorid og chloroform, samt methanol og acetonitril.
Til fotolysen anvendes der en lyskilde, der udsender 25 lys, som absorberes af azetidin-2-on-udgangsforbindelserne.
Disse forbindelser absorberer lys med en bølgelængde på fra ca. 230 nanometer til ca. 500 nanometer. Som lyskilde anvendes der fortrinsvis en kviksølvdamplampe. En hensigtsmæssig lyskilde er en kviksølv-middeltryklampe med et glasfilter 30 til laboratorieformål (Pyrex-glas)
Bestrålingstiden og reaktionstemperaturen kan ligge i et forholdsvis bredt område. Reaktionen gennemføres fortrinsvis ved stuetemperatur i et tidsrum, der afhænger af det udsendte lys* intensitet.
35 Azetidin-2-on-derivaterne med den alemene formel II
kan fremstilles ved anvendelse af en i de britiske patent- 3
DK 155008 B
skrifter nr. 1.403.002 og 1.403.003 beskrevne fremgangsmåder ud fra de tilsvarende penicillansyrederivater med den almene formel 2 R' 5 i = .c. CH3 I CHo 0J_N-k c_oR3 ^
II
o 10 12 3 i hvilken R , R og R har de ovenfor angivne betydninger.
Oxidation af disse derivater med et oxidationsmiddel, enten alene eller i nærværelse af en katalytisk mængde af en forbindelse af et metal fra gruppe Vb eller VIb i det 15 periodiske system, giver de tilsvarende sulfoxider med den almene formel R2 ° 20 I 3 (IV) CF?-N-k 3
C-OR
II
O
’ 12 3 i hvilken R , R og R har de ovenfor angivne betydninger.
25 Eksempler på de oxidationsmidler, der kan anvendes, er hydrogenperoxid og per syrer, f.eks. perbenzoesyre, m--chlorperbenzoesyre, percarbonsyre eller periodsyre. Eksempler på de katalysatorer, der kan anvendes, er wolframsyre, molybdensyre eller vanadiumsyre og deres alkalimetal-30 og jordalkalimetalsalte.
Sulfoxiderne med den almene formel IV kan omsættes med en mercaptan med den almene formel R4-SH (V) 35 4 4
DK 155008 B
i hvilken R har den ovenfor angivne betydning, hvilket giver de tilsvarende azetidin-2-on-derivater med den almene formel II. Omsætningen kan foretages i et organisk opløsningsmiddel, fortrinsvis under tilbagesvalingsbetingelser.
4 5 Den aromatiske, heterocycliske gruppe R indeholder et nitrogenatom og mindst fem ringled. Den heterocycliske · gruppe kan være en gruppe med en enkelt eller flere ringe.
Den er knyttet til svovlatomet i forbindelserne med de almene formler II og V via et carbonatom i den heterocycliske ring.
10 Acylaminogruppen R^-NH i 4-stillingen i azetidin-2- -on-derivatet med den almene formel II påvirker ikke fotolysereaktionen ifølge opfindelsen. Som eksempler på denne acylaminogruppe kan nævnes de gængse grupper i 7-stillingen i cephalosporiner. Foretrukne acylaminogrupper R^-NH- har 15 den almene formel
O
5 II
R-CH-C-NH- (VI) 20 i* 5 i hvilken R er eventuelt med en eller to hydroxygrupper, halogenatomer, alkyl- eller alkoxygrupper med 1-4 C-atomer 25 substitueret phenyl- eller phenoxygruppe, en eventuelt med en alkylgruppe med 1-4 C-atomer eller et halogenatom substitueret thionyl-, furyl- eller pyridylgruppe, en cycloal-kyl- eller cycloalkenylgruppe med 3-7 C-atomer eller en cycloalkadienylgruppe med 6 eller 7 C-atomer, og R^ er et 30 hydrogenatom, en hydroxy-, amino-, carboxy- eller ureido-gruppe.
De følgende eksempler tjener til nærmere belysning af fremgangsmåden ifølge opfindelsen.
5
DK 155008 B
Eksempel 1 N-Phenylacetyl-7-amino-3-methylencepham-4-carb-oxylsyre-trichlorethylester En opløsning af 1 mmol 2,2,2-trichlorethyl-4-(benzo-5 thiazol-2-yl)-dithio-3-(2-phenylacetamido)-a-isopropenylaze-tidin-2“On-1-acetat i 300 ml methylenchlorid anbringes i en gængs beholder til udførelse af fotokemiske reaktioner og bestråles under anvendelse af en 450 Watt kviksølvmiddel-tryklampe, medens der bobles argon gennem opløsningen. Efter 10 2 timers bestråling fortsættes gennemboblingen med argon i 10 minutter. Reaktionsblandingen inddampes til tørhed under formindsket tryk, hvilket giver en orange olie. Chromatografi på silicagel og inddampning af eluatet giver produktet som et hvidt krystallinsk fast stof. Omkrystallisation fra me-15 thylenchlorid/ether/hexan giver en analyseren prøve med smeltepunkt 149-150°C (sønderdel.).
Massespektrum m/e 464 (M+); NMR: δ (CHCl^): 3,42 (d af d, 2H, J = 7,14), 363 (s, 2H), 4,68 (d af d), 2H, J = 1), 5,17 (s, IH), 5,23 (d, 2H, J = 4), 5,38 (d, IH, J = 4), 20 5,68 (d af d, IH, J = 5,8), 6,15 (d, IH, J = 10), 7,40 (s, 5H); IR (KBr) 3300, 1765, 1760, 1660 cm"1.
Analyse, beregnet for C^gH^y^O^Cl^S: C 46,61, H 3,69, N 6,04, S 6,91, Cl 22,93 Fundet: C 46,84, H 3,80, N 5,89, S, 8,02, Cl 22,89.
25
Eksempel 2 N-Phenoxyacety1-7-amino-3-methylencepham--4-carboxylsyre-trichlorethylester En opløsning af 0,64 mmol 2,2,2-trichlorethyl-4-(ben-30 zothiazol-2-yl)-dithio-3-(3-phenoxyacetamido)-a-isopropenyl-azetidin-2-on-l-acetat i 750 ml methylenchlorid anbringes i en gængs beholder til udførelse af fotokemiske reaktioner og bestråles ifølge eksempel 1 i 2 timer. Derefter fortsættes gennemboblingen med argon i 10 minutter. Reaktionsblandingen 35 inddampes til tørhed under formindsket tryk, hvilket giver en brun olie. Chromatografi på silicagel (cyclohexan: ethyl- 9 6
DK 155008 B
acetat = 3:1) giver efter inddampning af eluatet en olie.
NMR: δ (CDC13): 3,58 (d af d, J = 7,14), 4,60 (s), 4,85 (s), 5,18 (m), 5,55 d, J = 4), 5,82 (d af d, J = 4,8), 7,2 (m) ; IR (CHCl^) 1780, 1765, 1695 cm massespektrum m/e 5 478 (M+).
Claims (3)
1. Fremgangsmåde til fremstilling af 3-methylencepham--forbindelser med den almene formel 5 R1 1. c R -NH =- 0<1-(I) C-OR2 10 g 1 2 i hvilken R er en acylgruppe, R er et hydrogenatom eller 3 en a-methoxygruppe, og R er et hydrogenatom, en C^-C^-al-kylgruppe, en 2,2,2-trichlorethyl-, trimethylsilyl-, diphe-15 nylmethyl-, benzyl-, 4-methoxybenzyl- eller 4-nitrobenzyl-gruppe, kendetegnet ved, at et azetidin-2-on-de-rivat med den almene formel
2 P r1_nh -ψ-r-S-S-R3 20 0J-n-ch-c=ch2 (ii) 3 ' · R -O-C CH0 II
3 O 123 25. hvilken R , R og R har de ovenfor angivne betydninger, og R3 betyder en 2-benzothiazolylgruppe eller en aromatisk, heterocyclisk gruppe med mindst 5 ringled, der indeholder -3 et nitrogenatom, i en koncentration på fra 3 x 10 til 3 x -2 10 mol pr. liter halogeneret carbonhydrid, methanol eller 30 acetonitril som opløsningsmiddel underkastes fotolyse. 35 Fremgangsmåde ifølge krav 1,kendetegnet 2 ved, at fotolysen gennemføres med lys med en bølgelængde på 3 230-500 nanometer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66698976 | 1976-03-15 | ||
| US05/666,989 US4375397A (en) | 1976-03-15 | 1976-03-15 | Process for preparing 3-methylene cephalosporins |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK106677A DK106677A (da) | 1977-09-16 |
| DK155008B true DK155008B (da) | 1989-01-23 |
| DK155008C DK155008C (da) | 1989-06-12 |
Family
ID=24676364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK106677A DK155008C (da) | 1976-03-15 | 1977-03-11 | Fremgangsmaade til fremstilling af 3-methylencepham-forbindelser |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4375397A (da) |
| JP (1) | JPS52111592A (da) |
| BE (1) | BE852469A (da) |
| CA (1) | CA1062654A (da) |
| CH (1) | CH597239A5 (da) |
| DE (1) | DE2709529C2 (da) |
| DK (1) | DK155008C (da) |
| FR (1) | FR2344561A1 (da) |
| GB (1) | GB1579296A (da) |
| HU (1) | HU172544B (da) |
| IE (1) | IE45116B1 (da) |
| NL (1) | NL7702342A (da) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4190724A (en) * | 1978-11-13 | 1980-02-26 | Eli Lilly And Company | Process for 3-exomethylenecepham sulfoxides |
| US4966443A (en) * | 1988-02-22 | 1990-10-30 | Fuji Photo Film Co., Ltd. | Light beam scanner |
| JPH023451U (da) * | 1988-06-16 | 1990-01-10 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2265798C2 (de) * | 1971-06-24 | 1985-09-26 | Fujisawa Pharmaceutical Co., Ltd., Osaka | Verfahren zur Herstellung von Oxoazetidin-Derivaten |
| US3898142A (en) * | 1972-03-24 | 1975-08-05 | Schering Corp | Photolytic cyclization of an amino-keto acylate |
-
1976
- 1976-03-15 US US05/666,989 patent/US4375397A/en not_active Expired - Lifetime
-
1977
- 1977-02-14 CA CA271,660A patent/CA1062654A/en not_active Expired
- 1977-02-18 IE IE362/77A patent/IE45116B1/en not_active IP Right Cessation
- 1977-03-04 NL NL7702342A patent/NL7702342A/xx not_active Application Discontinuation
- 1977-03-04 DE DE2709529A patent/DE2709529C2/de not_active Expired
- 1977-03-04 GB GB9266/77A patent/GB1579296A/en not_active Expired
- 1977-03-08 FR FR7706779A patent/FR2344561A1/fr active Pending
- 1977-03-10 CH CH303577A patent/CH597239A5/xx not_active IP Right Cessation
- 1977-03-11 DK DK106677A patent/DK155008C/da not_active IP Right Cessation
- 1977-03-14 HU HU77SU00000942A patent/HU172544B/hu unknown
- 1977-03-15 JP JP2911877A patent/JPS52111592A/ja active Granted
- 1977-03-15 BE BE175798A patent/BE852469A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IE45116B1 (en) | 1982-06-30 |
| IE45116L (en) | 1977-09-15 |
| US4375397A (en) | 1983-03-01 |
| JPS52111592A (en) | 1977-09-19 |
| JPS6120554B2 (da) | 1986-05-22 |
| DK106677A (da) | 1977-09-16 |
| NL7702342A (nl) | 1977-09-19 |
| DE2709529A1 (de) | 1977-09-22 |
| HU172544B (hu) | 1978-09-28 |
| GB1579296A (en) | 1980-11-19 |
| CH597239A5 (da) | 1978-03-31 |
| DK155008C (da) | 1989-06-12 |
| FR2344561A1 (fr) | 1977-10-14 |
| DE2709529C2 (de) | 1986-01-02 |
| BE852469A (fr) | 1977-09-15 |
| CA1062654A (en) | 1979-09-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |