IE43363B1 - Cyclopropane derivatives - Google Patents
Cyclopropane derivativesInfo
- Publication number
- IE43363B1 IE43363B1 IE71976A IE71976A IE43363B1 IE 43363 B1 IE43363 B1 IE 43363B1 IE 71976 A IE71976 A IE 71976A IE 71976 A IE71976 A IE 71976A IE 43363 B1 IE43363 B1 IE 43363B1
- Authority
- IE
- Ireland
- Prior art keywords
- methyl
- cyclopropane
- compounds
- dimethyl
- compound
- Prior art date
Links
- 125000001559 cyclopropyl group Chemical class [H]C1([H])C([H])([H])C1([H])* 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 34
- -1 triphenyl isopropyl phosphonium halide Chemical class 0.000 claims abstract description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 17
- 150000001241 acetals Chemical class 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 7
- 230000002378 acidificating effect Effects 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 150000007942 carboxylates Chemical class 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- HHBXWXJLQYJJBW-UHFFFAOYSA-M triphenyl(propan-2-yl)phosphanium;iodide Chemical group [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C)C)C1=CC=CC=C1 HHBXWXJLQYJJBW-UHFFFAOYSA-M 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 2
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 1
- 150000001942 cyclopropanes Chemical class 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 5
- 229910052753 mercury Inorganic materials 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000749 insecticidal effect Effects 0.000 description 4
- 239000011369 resultant mixture Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLOPRKKSAJMMEW-SFYZADRCSA-N (+)-trans-chrysanthemic acid Chemical compound CC(C)=C[C@@H]1[C@@H](C(O)=O)C1(C)C XLOPRKKSAJMMEW-SFYZADRCSA-N 0.000 description 1
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- PXIMQGSMXJFQOF-UHFFFAOYSA-N triphenyl(propan-2-yl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C)C)C1=CC=CC=C1 PXIMQGSMXJFQOF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
1502527 Cyclopropane derivatives ROUSSEL UCLAF 6 April 1976 [7 April 1975] 13941/76 Heading C2C The invention comprises a process for the preparation of compounds of the formula where R is C 1- C 6 alkyl, each R 1 is C 1 -C 4 alkyl or the two R 1 radicals together represent -(CH 2 ) n - in which n is 2 or 3 and X is O or S by reacting a compound of the formula in the presence of a strong base with a triphenyl isopropyl phosphonium halide. The invention further comprises methyl 2,2-dimethyl-3RS- formyl - cyclopropane - 1RS - carboxylate diethyl acetal and methyl 2,2-dimethyl-3RS- formyl-cyclopropane-1RS-carboxylate diethylene acetal. Compounds of Formula III may be hydrolysed under acidic conditions to yield a compound of the formula which may subsequently be saponified to yield the free acid.
Description
This invention relates to a process for preparing acetal derivatives of alkyl 2,2-dimethyl-3RS-formylcyclopropane-lRS-carhoxylates (dl-trans- heini carbonic aldehyde) and to the acetal derivatives prepared thereby as well as to their conversion into the corresponding aldehydes ahd to 2,2-dimethyl-3RS-formyl-cyclopropane-; IRS-carboxylic acid.
According to the present invention there is provided a process for the preparation of compounds of general
(wherein R represents an alkyl radical containing from 1 to 6 carbon atoms, each R^ radical represents an alkyl radical containing from 1 to 4 carbon atoms or the two R^ radicals together represent a -(Cf^^-group in which n is or 3, and X represents an oxygen or a sulphur atom) which comprises reacting a compound of formula II,
-. 2
RjX kJ / \
CH = CH (II)
C- OR 0 (wherein R, R^ and X are as defined above), in the presence of a strong base, with a triphenyl isopropyl phosphonium halide.
The reaction may, for example, be carried out using triphenyl isopropyl phosphonium iodide,bromide or chloride,use of the iodide being preferred. The amount of halide used is not critical since reaction may only take place at the double bond, the aldehyde group being blocked in the acetal form.
The use of at least one molar equivalent of the halide, based on the compound of formula II, is however, conveniently used to ensure completion of the reaction.
Amongst the strong bases which may be used in the process according to the invention, particularly useful are, for example alkali metal hydrides, alkali metal amides, alkali metal alcoholates and alkyl lithium compounds. Most preferred is the use of n-butyl lithium.
The reaction is conveniently carried out in an organic
- 3 43363 solvent such as for example, tetrahydrofuran, dimethy1sulphoxide, 1,2-dimethoxyethane, diethylene glycol monoethyl ether, diethylene glycol diethyl ether or diethyl ether.
In the compounds of formulae II and III R preferably represents a methyl group. Also preferred is the use of> compounds of formulae II and III wherein X represents an oxygen atom.
In a particularly preferred embodiment of the inven10 tion , methyl E-4,4-dimethoxy-but-2-enoate, methyl E-4,4diethoxy-but-2-enoate or methyl 4,4- ethylenedioxy-Ebut-2-enoafce^ is reacted with a triphenyl isopropyl phosphonium halide, preferably the iodide and preferably in the presence of n-butyl lithium.
The compound of formula III obtained according to the process of the present invention may, if desired, be subsequently hydrolysed, under acidic conditions, to a
H (I) (wherein R is as hereinbefore defined).
The hydrolysis may be carried out in the presence of an acid such as, for example acetic acid, sulphuric acid, perchloric acid, £-toluenesulphonic acid or hydrochloric acid, the use of perchloric acid being preferred. The hydrolysis is conveniently carried out in an organic solvent which renders the starting compound soluble such as for example, tetrahydrofuran.
The use of the process according to the invention and the subsequent hydrolysis of the product thus obtained is of great industrial interest in that it permits, in two stages , the- preparation of alkyl 2,2-dimethyl-3RS-formylcyclopropane-lRS-carboxylates starting from compounds which are easily obtained. These esters may then be converted, by saponification, into 2,2~dimethyl-3RS-formyl-cyclopropanelRS-carboxylic acid, which is a very useful compound for the synthesis of compounds of the pyrethrinoid type, that is to say, acid esters having the cyclopropane structure and possessing insecticidal activity. A number of extremely
2θ varied and active pyrethrinoid esters with insecticidal activity have recently been discovered which may be prepared by use of the Wittig reaction on the free aldehyde function
- 5 of 2,2-dimethyl-3RS-formyl-cyclopropane-IRS-carboxylic acid. (See, for example, French Patent Specifications Nos. 1,595,780; 2,045,177; 2,140,794 and 2,185,612). A simple synthetic route to the acid is therefore of considerable use in the formation of these esters.
2,2-dimethyl-3RS-formyl-cyclopropane-lRS-carboxylic acid was for a long time industrially inaccessible until it was discovered that it could be obtained by ozonolysis of dl-trans-chrysanthemic acid. dl-trans-Chrysanthemic
JO acid, however, is itself not easily obtainable and therefore the synthesis of these new insecticidal pyrethrinoid esters was an expensive procedure.
a
The process of the invention thus provides/new route to the production of insecticidal pyrethrinoid derivatives.
2o Methyl E-4,4-dimethoxy-but-2-enoate may be prepared by the process described by C. Escobar, An. Quim. 67, 43-57 (1971).
. 6 _
The other compounds of formula II may he prepared by analagous methods or by formation of the acetal from the corresponding alkyl E-4-oxo-but-2-enoates according to standard methods e.g. by reaction with the appropriate alcohol or glycol in an acid medium.
Alkyl E-4-oxo-but-2-enoates may be obtained according to the process described in Bull. Soc. Chim. 1567 (1961).
Of the compounds of formula III which may be prepared according to the process of the present invention methyl 2,2-dimethyl-3RS-formyl-cyclopropane-lRS-carboxylate diethyl acetal and methyl 2,2-dimethyl-3RS-formylcyclopropane-lRS-carboxylate diethylene acetal are also novel compounds and constitute still further features of the present invention.
The following non-limiting Examples serve to illustrate the present invention.
- 7 Example 1; Methyl 2,2-dimethy1-3RS-formyl-cyclopropane-IR carboxyiate
a) methyl 2,2-dimethyl-3RS-formy1-cyclopropane1RS-carboxyiate_dimethyl acetal:
11.23 g of triphenyl isopropyl phosphonium iodide are introduced into 200 cm of tetrahydrofuran. The solut. 3 ion obtained is cooled to 0°C and 15.5 cm of a 1.75 N solution of n-butyl lithium in hexane are added thereto.
The mixture thus formed is brought to 20°C and agitated for 15 minutes at this temperature. 3.52 g of methyl , 3
E-A,A-dimethoxybut-2-enoate, dissolved in 10 cm of tetrahydrofuran,are added thereto and the resultant mixture is agitated for 2 hours. A portion of water is added and the solution obtained is extracted with ether.
The ether extracts are washed with a saturated solution of sodium chloride, dried, concentrated to dryness and then rectified. 3.57 g ot methyl 2,2-aimethyl-3RS-formylcyclopropane-lRS-carboxylate dimethyl acetal are obtained. B.Pt. = I00-102°C under 25 mm of mercury.
2o b) mathyl 2,2-dimethyl-3RS-formyl-cyclopropane1RS-carboxyl ate;
To 2.02 g of the dimethyl acetal obtained in stage (a) 3 are added, at 0°G, 110 cm of a 3N aqueous solution of _ 8 perchloric acid and 25 cm of tetrahydrofuran. The solution obtained is agitated for 1 hour and then a portion of ice is added. The resultant mixture is extracted with ether.
The ether extracts are washed with an aqueous solution of sodium bicarbonate,then with water, dried and finally concentrated to dryness. 1.46 g of methyl 2,2 -dimethyl3RS-formyl-cyclopropane-lRS-carboxylate ' are obtained.
The methyl E-4,4-dimethoxy-but-2-enoate used as a starting material in stage (a), may be prepared in the following manner:
To 5.70 g of methyl E-4-oxo-but-2-enoate are added 3 cm of methanol, 0.25 g of p-toluenesulphonic acid,
100 cm of benzene and 5 g of molecular sieve. The mixture obtained is refluxed for 18 hours and then left for 48 hours at ambient temperatures. The mixture is diluted with ether then washed with water and with a saturated solution of sodium chloride. It is subsequently dried and the solvents are removed by distillation under reduced pressure. The residue is rectified under 25 mm of mercury. 5.22 g of crude methyl E-4,4-dimethoxy-but-2-enoate are obtained (B.Pt. = 92°G under 25 mm of mercury).
The product, which contains a small quantity of the starting aldehyde, is again reacted for 4 hours under - 9. 43383 similar conditions to those described previously and, afte rectification, 4.3 g of pure methyl E-4,4-dimethoxy-but-2enoate are obtained. This compound is described in the literature [ C. Escobar, An. Quim. _&7, 43-57 (1971)j
Example 2; Methyl 2,2-dimethyl-3RS-formyl-cyclopropane1RS- carboxylate .
a) methyl 2,2-dimethyl-3RS-formyl-cyclopropanelRS-carboxylate_diethyl acetal;
At 0°C, 0.495 g of triphenyl isopropyl phosphonium 3 iodide are introduced into 10 cm of tetrahydrofuran.
0.7 cm of a 1.5 N solution of n-butyl lithium in hexane are added thereto and the temperature is allowed to rise to 20°C. 0.188 g of methyl E-4,4-diethoxy-but-2-enoate, dissolved in 2 cm of tetrahydrofuran, are added to the solution thus obtained and the resultant mixture is agitated for 30 minutes. A portion ot water is added and the mixture thus formed is extracted with ether. The organic extracts are dried'and then concentrated to dryness.
The residue is chromatographed on silica gel by elution with a 3:7 mixture of ether and petroleum ether. 0.114 g of methyl 2,2-dimethyl-3RS-formyl-cyclopropane-].RS-carboxylate diethyl acetal are obtained.
433
b) methyl 2, Σ-όίιτίΕΙΑνΙ-ΒΚε-ίοπηγΙ-ογοΙορΓορΗΓΗί-ΙΚε carboxylate:
By hydrolysing the diethyl acetal obtained in stage (a) above, in a manner similar to that used in stage (b) of Example 1, methyl 2,2-dimethyl-3RS-formyl-cyclopropane lRS-carboxylate is obtained.
Methyl E-4,4-diethoxy-but-2-enoate can be prepared, in the following manner:
1.14 g of methyl E-4-oxo-but-2-enoate, 2.22 g of 10 ethyl orthoformate, 0.025 g of ammonium chloride and 2 cm of ethanol are admixed and the mixture thus obtained is refluxed for 30 minutes. A portion of ether is added to the mixture which is then washed with water and with a saturated solution of sodium chloride. The mixture is 15 dried, then concentrated to dryness by distillation under reduced pressure and rectified. 1.52 g of methyl E-4,4diethoxy-but-2-enoate are obtained. B.Pt. = 110°C under 25 mm of mercury.
Example 3: Methyl 2,2-dimethyl-3RS-formyl-cyclopropane2o lRS-carboxylate
a) methyl 2,2-dimethyl-3R5-formyl-cyclopropane1RS-carboxylate_diethylene acetal:
At 0°C, 0.7 cn7 of a 1.75 N solution of n-butyl lith in hexane are introduced into a solution of 0.475 g of 3 triphenyl isopropyl phosphonium iodide in 10 cm of tetrahydrofuran. The solution obtained is agitated for
minutes at 25° and then 0.15 g of methyl E-4,4-ethylene dioxy-hut-2-enoate, dissolved in 2 cm of tetrahydrofuran, are added thereto. The resultant mixture is agitated for hours and then extracted with ether. The ether extracts are dried and concentrated to dryness. The residue is chromatographed on silica gel by elution with a
3:7 mixture of ether and petroleum ether. 0.150 g of methyl 2,2-dimethyl-3RS-formyl-cyclopropane-IRS-carboxyl·· ate diethylene acetal are obtained.
b) Methyl 2,2-dimethyl-3RS-formyl-cyclopropane-1RS15 carboxylate;
By hydrolysing the diethylene acetal obtained in stage (a) above, in a manner similar to that used in stage (b) of Example 1, methyl 2,2-dimethyl-3RS-formyl-cyclopropanelRS-carboxylate is obtained.
Methyl E-4,4-ethylenedioxy-but-2-enoate can be prepared in the following manner:
«3363
3.1 g of ethylene glycol, 0.050 g of £-toluene3 sulphonic acid, 20 cm of benzene and 1 g of molecular sieve are added to 1.14 g of methyl E-4-oxo-but-2-enoate.
The mixture obtained is refluxed for 7 hours and then cooled. A portion of ether is added to the mixture and the resultant solution is washed with water and then with a saturated aqueous solution of sodium chloride. The solution is subsequently dried, concentrated to dryness and then rectified. 0.96 g of methyl E-4,4-ethylenedioxybut-2-enoate are obtained. B.Pt. = 122°C under 25 mm of mercury.
Claims (26)
1. A process for the preparation of compounds of general formula III, o 1« (III) ) 5 (wherein R represents an alkyl radical containing from 1 to 6 carbon atoms, each R^ radical represents an alkyl radical containing from 1 to h carbon atoms or the two R^ .radicals together represent a “( CH 2^n“ S rou P which n is 2 or 3, and X represents an oxygen or a 10 sulphur atom) which comprises reacting a compound of formula II, (wherein R, R^ and X are as defined above), in the presence of a strong base, with a triphenyl isopropyl 15 phosphonium halide. 43383
2. A process as claimed in claim 1 wherein the triphenyl isopropyl phosphonium halide is triphenyl isopropyl phosphonium iodide.
3. A process as claimed in claim 1 or claim 2 wherein 5 the strong base comprises an alkali metal hydride, amide or alcoholate or an alkyl lithium compound. J’
4. A process as claimed in claim 3 wherein the strong base comprises n-butyl lithium.
5. A process as claimed in any of the preceding claims 10 wherein the reaction is effected in the presence of an organic solvent.
6. A process as claimed in claim 5 wherein the solvent comprises tetrahydrofuran, dimethylsulphoxide, 1,2-dimethoxyethane, diethylene glycol monoethyl ether, diethylene 15 glycol diethyl ether or diethyl ether.
7. A process as claimed in any of the preceding claims wherein R represents a methyl group.
8. A process as claimed in any of the preceding claims wherein X represents an oxygen atom. 20
9. A process as claimed in any of claims 1 to 6 wherein the compound of formula II is methyl E-4,4-diethoxy-but-2enoate. 4 3 3 6 3
10. A process as claimed in any of claims 1 to 6 wherein the compound of formula II is methyl E-4,4ethylenedioxy-but-2-enoate.
11. A process for the preparation of compounds of general formula III as defined in claim 1, as claimed in claim 1 substantially as herein described.
12. A process for the preparation of compounds of general formula III as defined in claim 1, substantially as herein described in any one of Examples 1 to 3.
13. Compounds of general formula III as defined in claim 1 whenever prepared by a process as claimed in any of claims 1 to 12.
14. Methyl 2,2-dimethyl-3RS-formyl-cyclopropane-lRS carboxylate . diethyl acetal whenever prepared by a proces as claimed in any of claims 9, 11 and 12.
15. Methyl 2,2-dimeth.yl-3RS-f£>rmyl-cyclopropane-lRScarboxylate . diethylene acetal whenever prepared by a process as claimed in any of claims 10, 11 and 12.
16. A process as claimed in any of claims 1 to 12 wherein the compound of formula III obtained is subsequently hydrolysed under acidic conditions to yield a compound of formula I, II C-OR Η (I) (wherein R is as defined in claim 1). >
17. A process as claimed in claim 16 wherein the hydrolysis is carried out in the presence of perchloric acid.
18. A process as claimed in claim 16 or claim 17 wherein the hydrolysis is carried out in the presence of an organic solvent.
19. A process as claimed in claim 18 wherein the solvent comprises tetrahydrofuran.
20. A process for the preparation of compounds of general formula I as defined in claim 16, as claimed in claim 16, substantially as herein described.
21. A process for the preparation of compounds of 15 general formula I as defined in claim 16 substantially as herein described in any one of Examples 1 to 3.
22. Compounds of general formula I as defined in claim 16 whenever prepared by a process as claimed in any of claims 16 to 21.
23. A process as claimed in any of claims 16 to 21 where the compound of formula I obtained is subsequently saponified to 2,2-dimethyl-3R.S-formyl-cyclopropane-IRScarboxylic acid. 5
24. 2,2-Dimethyl-3RS-formyl-cyclopropane-IRS-carboxylic acid whenever prepared by a process as claimed in claim 23 i
25. Methyl 2,2-dimethyl-3RS-formyl-cyclopropane-lRScarboxylate diethyl acetal.
26. Methyl 2,2-dimethyl-3RS-formyl-cyclopropane-lRS10 carboxylate diethylene acetal.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE155169A BE827652A (en) | 1975-04-07 | 1975-04-07 | NEW PROCESS FOR THE PREPARATION OF LOWER ALCOYL ESTERS OF HEMICARONIC ALDEHYDE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE43363L IE43363L (en) | 1976-10-07 |
| IE43363B1 true IE43363B1 (en) | 1981-02-11 |
Family
ID=3842757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE71976A IE43363B1 (en) | 1975-04-07 | 1976-04-06 | Cyclopropane derivatives |
Country Status (11)
| Country | Link |
|---|---|
| JP (2) | JPS5929058B2 (en) |
| BE (1) | BE827652A (en) |
| CA (1) | CA1091250A (en) |
| CH (1) | CH609027A5 (en) |
| DE (1) | DE2615160A1 (en) |
| DK (1) | DK134176A (en) |
| FR (1) | FR2306970A1 (en) |
| GB (1) | GB1502527A (en) |
| IE (1) | IE43363B1 (en) |
| IT (1) | IT1065993B (en) |
| NL (1) | NL7603678A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE827652A (en) * | 1975-04-07 | 1975-10-07 | NEW PROCESS FOR THE PREPARATION OF LOWER ALCOYL ESTERS OF HEMICARONIC ALDEHYDE | |
| DE2923774A1 (en) * | 1979-06-12 | 1980-12-18 | Bayer Ag | METHOD FOR PRODUCING 3,3-DIMETHYL-CYCLOPROPAN-1,2-DICARBONIC ACID ESTERS |
| DE2927133A1 (en) * | 1979-07-05 | 1981-01-08 | Bayer Ag | METHOD FOR PRODUCING 2-FORMYL-3,3-DIMETHYL-CYCLOPROPAN1-CARBONIC ACID ESTERS |
| FR2490633A1 (en) * | 1980-09-24 | 1982-03-26 | Roussel Uclaf | PROCESS FOR THE PREPARATION OF CYCLOPROPANE CARBOXYLIC ACID DERIVATIVES WITH ALDEHYDE FUNCTION |
| FR2624511B1 (en) * | 1987-12-11 | 1990-09-21 | Roussel Uclaf | ENANTIOSELECTIVE PROCESS FOR PREPARING HEMICARONIC ALDEHYDE DERIVATIVES WITH TRANS OR CIS STRUCTURE |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE827652A (en) * | 1975-04-07 | 1975-10-07 | NEW PROCESS FOR THE PREPARATION OF LOWER ALCOYL ESTERS OF HEMICARONIC ALDEHYDE |
-
1975
- 1975-04-07 BE BE155169A patent/BE827652A/en not_active IP Right Cessation
-
1976
- 1976-03-26 DK DK134176A patent/DK134176A/en not_active IP Right Cessation
- 1976-03-31 FR FR7609336A patent/FR2306970A1/en active Granted
- 1976-04-05 CA CA249,575A patent/CA1091250A/en not_active Expired
- 1976-04-06 IT IT4888476A patent/IT1065993B/en active
- 1976-04-06 GB GB1394176A patent/GB1502527A/en not_active Expired
- 1976-04-06 IE IE71976A patent/IE43363B1/en unknown
- 1976-04-07 CH CH438276A patent/CH609027A5/en not_active IP Right Cessation
- 1976-04-07 NL NL7603678A patent/NL7603678A/en not_active Application Discontinuation
- 1976-04-07 DE DE19762615160 patent/DE2615160A1/en not_active Withdrawn
- 1976-04-07 JP JP3830476A patent/JPS5929058B2/en not_active Expired
- 1976-04-07 JP JP3830576A patent/JPS51127050A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK134176A (en) | 1976-10-08 |
| IT1065993B (en) | 1985-03-04 |
| DE2615160A1 (en) | 1976-10-21 |
| CA1091250A (en) | 1980-12-09 |
| NL7603678A (en) | 1976-10-11 |
| FR2306970B1 (en) | 1979-10-05 |
| FR2306970A1 (en) | 1976-11-05 |
| JPS51127049A (en) | 1976-11-05 |
| CH609027A5 (en) | 1979-02-15 |
| JPS5929058B2 (en) | 1984-07-18 |
| JPS51127050A (en) | 1976-11-05 |
| GB1502527A (en) | 1978-03-01 |
| BE827652A (en) | 1975-10-07 |
| IE43363L (en) | 1976-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU198437B (en) | Process for producing mono- or bis-carbonyl-compounds | |
| SU995705A3 (en) | Process for preparing 5-fluoro-2-methyl-1-(methylsulfinyl-benzyledene)indenyl-3-acetic acid | |
| US3009946A (en) | Process for preparing chrysanthemumdicarboxylic acid and esters thereof | |
| IE43363B1 (en) | Cyclopropane derivatives | |
| US3527789A (en) | Production of poly(lower)alkyl alkenepolycarboxylates | |
| IE43461B1 (en) | Cyclopropane derivatives | |
| US3576880A (en) | 5(2,6,6-trimethyl - 1 - hydroxy-cyclohex-2-enyl) -3 methyl-penta-2,4-dien-1-al derivatives | |
| EP0007652B1 (en) | Derivatives of 3-azabicyclo(3.1.0)hexane and a process for their preparation | |
| US3910958A (en) | Process for preparing arylacetic acids and esters thereof | |
| US4453013A (en) | Process for preparing novel acetylenic compounds useful as starting materials for preparing an alicyclic ketone | |
| US3287372A (en) | Process and intermediates for manufacture of 2-(dialkylmethyl)-5-alkyl-2-cyclohexen-1-ones | |
| US4307244A (en) | Process for the preparation of methyl 2,2-dimethyl, -3-(2'methyl-propenyl)-cyclopropane-1,1-dicarboxylate | |
| US4009172A (en) | 2,3,3A,6,7,7A-Hexahydro-thieno[3,2-b]pyridin-(4H)5-ones | |
| US4233464A (en) | Cyclohexene carotinoid intermediates | |
| JP3254746B2 (en) | Terminal acetylene compound and method for producing the same | |
| US2768967A (en) | Process for manufacture of 2, 5 diketo-8-nonen-3-ol | |
| US4272456A (en) | Derivatives of 8-dehydro-vitamin A and their preparation | |
| US3892814A (en) | Cyclopropane derivatives | |
| US5171867A (en) | Method of preparing 2,5-dimethyl-4-hydroxy-2h-furan-3-one | |
| US4173707A (en) | Cyclopentanol derivatives | |
| JPH06166680A (en) | Production of alkyl 3-oxo-2-pentyl-1-cyclopenteneacetate, and epoxy ester as starting material | |
| US4390718A (en) | Prostaglandin intermediates | |
| EP0281661B1 (en) | 2-alkoxycarbonyl-4-(4-pyridyl)cyclohexanones and process for preparing them | |
| US4424362A (en) | Process for preparing a trans-6-propenyl benzimidazole | |
| JP2581186B2 (en) | Method for producing 4-substituted-2-cyclopentenone ester derivative |