IL30905A - Process for preparing a cyclopropanecarboxylic acid - Google Patents

Description

The present invention has as object a process for ■' preparing a cyclopropanecarboxylic acid.

The invention has more specifically as object. a . process for preparing d-trans -pyrethric acid, also called 1-(R) ,2-(R) seq. trans-chrysanthemum dicarboxylic acid mono- methyl ester or ¾ 3-dimethyl-2-(R)-(2 ' -methoxycarbonyl -trans- f formula I: . The preparation of natural d-tr'ans-pyrethric acid, by hemisynthesis, presents a great industrial interest since this acid is a constituent of the natural pyrethrins and of pyrethric esters, very active synthetic insecticides, such as the ester of d -trans-pyrethric acid and of (5-benzyl) 3-furyl-methyl alcohol, an ester for. which' the "knock-down" effect is articularl outstandin . in which R represents, a lower alkyl radical, and obtains, .. after purification, the desired d-trans-pyrethric acid.

The invention can "be further characterized by the points enumerated below: - the anhydrous organic solvent in which is effected the condensation of the phosphonopropionic ester with the '.hemicaronic aldehyde is, for example, an ether such as*' tetrahydrofuran, diethyl ether, dioxan or dimethoxyethane , an aliphatic alcohol such as methanol or t-butanol, · dimethylsulphoxide or else a disubstituted amide such as dimethylformamide ; ' . .j rent/ : - the strong basic/in the presence of which is effected the condensation of the hemicaronic aldehyde "wit ' the-, phosphonopropionic ester is, for example, an alkali amide '·· . such as sodium amide, an alkali hydride, an alkali. · alcoholate, an alkali-metal; - the condensation of the hemicaronic aldehyde ..with..' the ■ phosphonopropionic ester is effected under inert" atmosphere •to avoid as far as possible the oxidation of the aldehyde. In a method of operation actually preferred, the purification of the crude condensation product is achieved by formation of an alkali-metal ' salt , such as the sodium or potassium salt, of the salt of L(+)- or ' D(-)-threo-l~2-. ' nitrophe'nyl-2-N,N-dimethylaminopropane-l,3-diol , or else of the s'alt of 1-quinine, which allows of the elimination of undesirable isomers. ■. _ ; : The 0,0-dialkyl 1-methoxycarbpnylethylphosphonate . - - - - - Ό,Ο-d.imethyl 1-methoxycarbonylethylphosphonate is not, as' far as is known, described in the literature. By analogy with' the preparation of the alkyl phosphonoacetates cf. ARBUSOV, ,'J.of General Chem.of U.S.S.R., 46, 297 and 61, 620] . y . 0,0-dimethyl 1-methoxycarbonylethylphosphonate is obtained by . condensation of trimethyl phosphite (CH^O) ^P with a methyl o-halogenopropipnate , by condensation of trimethyl phosphono- iodide in the presence of an alkali-metal or by the action of an alkali salt of a dimethyl phosphite on a methyl a-halogeno.propionat.e .

An example of preparing 0,0-dimethyl 1-methoxycarbonylethyl- phosphonate is given- in the experimental part. 0,0-diethyl 1-methoxycarbonylethylphosphonate is , prepared by the application of the method, of H.W.COOVER ■. et al. [Am.Soc. 2 » P.1963. (1957)3.

. L(+)-threo-l-£-nitrophenyl-2-N,N-dimethylaminopropane- 1, 3-diol and the corresponding J(-) derivative are described in French Patent No. 1,481,978.

Instead of the phosphonates of formula III, it is possible to- use^ other reactants among which may be cited the triarylalkyl phosphonium salts, specifically the tri- phenylalkyl phosphonium salts, which, under the action of a strong base, give rise to an alkylidene-phosphorane , the salts of (tris-dialkylamino).-alkylphosphonium, of [ (bis-dialkylamino) aryl] -alkylphosphonium and of (dialkylaminodiaryl) -alkylphos - _ phonium. which, under the action of a strong base, give rise likewise to an alkylidene-phosphorane' as .well as certain activated derivatives of oxygen phosphorus compounds, such as j phosphine oxides and phosphinic esters which, in the ' f a . Preparation: 0,0-dimethyl 1-methoxycarbonylethylphosphonate Under an atmosphere of nitrogen, one carries to 115°C a mixture of 124.1 g. of trimethyl phosphite .and 183.7 g. of •methyl a-bromopropionate. One maintains the reaction mixture at this temperature for forty-eight hours. After cooling, the reaction mixture is rectified under reduced pressure and one t obtains 76.9 g. of.0,0-dimethyl l-methoxycarbonylethyl' phosphonate .. ^· *ΐ8 mm = ^®°c> used as is ror condensation with the hemicaronic aldehyde, ; · ■The saponification index of this product is 285 ^ . of caustic potash per 1 g.

As far as is known, this compound is hot described in the literature.

Example : d-trans -p rethric acid or 3-, 5-dimethyl -2-(R) -(21 - · me hox carbony -trans-1 ' -propenyl) -1-(R) -cyclo- · propanecarboxylic acid Into 40 c.c. of tetrahydrofuran one introduces 3.84 g. of sodium amide (content: 92%), one cools the mixture to -5°C · and introduces thereto drop by drop a solution of 17.7 g. of 0,0-dimethyl 1-methoxyearbonylethylphosphohate 1 , · in solution in 40 c.c. of tetrahydrofuran. One brings the reaction mixture to 20°C, agitates it for three hours at this temperature and introduces thereto 1.92 g. of' sodium amide (content : 93 ·. One. cools the reaction mixture to -5°C, introduces thereto drop by; drop a solution of 6.4 g. of 1-(R) ,2-(R) -hemicaronic aldehyde (or 3,3-dimethyl-2-(R)-formyl-l-(R)-cyclopropane- ' carboxylic acid) in 40 c.c. of tetrahydrofuran. One brings _ .the reaction mixture to 20°C, maintains it' for three hours^and thirty minutes at this temperature ' then concentrates to ■ ( .>". _ combined ethereal' extracts -with..water, mixes the aqueous . phases and acidifies them to pH = 1 by adding a concentrated ■·., "..·, aqueous solution of hydrochloric acid. The aqueous acid.' phases are extracted with methylene chloride, the combined • .... methylene chloride extracts are washed with water, dried ' then concentrated to dryness under reduced pressure. :·. a) Purification by formation of the 1 -Quinine salt The residue (9.48 g.) is dissolved in 100 c.c. of acetone containing 16% water, one adds to the solution 12 g. ■ - of laevo-rotatory basic quinine, heats the reaction mixture - on a vapour-bath until . total, ^dissolution and cools the mixture slowly. The crystals thus formed are isolated by '".. suction-filtering and one obtains 9.19 g. of crude 1-quinine ..: '··' salt . '' . '■'· ''' ' ■ .

.·'' '', ' From the mother-liquors one extracts a' second-yield. "of "the same quality (weight: 2. ]A g.').

The first and the second yields -; are combined and <:' crystallized fim acetone containing 16% water and one obtains .' •'7.5 g. of 1-quinine salt of 1-(R) ¾2-(R) seq . -trans -chrysanthemum dicarboxylic acid monomethyl ester, m.pi = 169°C, [a]^° = -101,5° (c' = 1%, methanol). ■ ;■: From the mo her-l quor3. of purification, one extracts a second yield-' . of the same quality.

■■ . Into a mixture of 60 c.c. of ethyl ether and 60 c.c. ■-..· ;.·. of aqueous 2N solution of hydrochloric acid, one introduces , the.7.5 g«-of quinine salt" obtained above, agitates,' separates the ethereal phase b decanting, ' washes it. ith' ■ '. water, extracts the washings with ether, combines the' ethereal phases', dries them and concentrates them to dryness under reduced pressure. The residue is rectifi'ed in vacuo and one obtains.2.61 of' d -trans -pyrethric acid or .3, 3rdimethyl- r- (c · = 1·.2 , carbon tetrachloride). ·■ -•Analysis: ' C1;L%6¾. = 212.24 ..

Calculated: 0% 62.25 . 7.60. , , , Found:. 62.5 ' 7.8 ■ .' ■■ ·.'·' * ■ [ . ..' ' . ·'. ■ U. V. Spectrum (ethanol) : · Max. at 238-239 mu (ε = 15 , 100) ■·■ I.R. Spectrum (chloroform): The I.R. spectrum is identical to that published by MATSUI et al. [Agr .Biol. Chem. Japan, 22, p.37^ (1963)3 · ' .'N.M.R. Spectrum (deutero chloroform) (reference: 60 Mhz) ÷The N.M.R* spectrum is in accordance with the "trans" configuration of. the ring and the "trans " /configuratio -.:'.'.· of the oleifinic chain.

It is broken down thus: - 7 and 83 Mhz · · "to" "the hydrogens of. the . methyls at. \ positio . ' position 101.5-107 Mhz ■ ' corresponding to the hydrogen at l/(doublet); - 117. -119. Mhz corresponding to the hydrogens of the methyl • of the lateral chain; ..- 128-138-143 Mhz corresponding to the hydrogen at 2 (triplet); -. 227. Mhz , corresponding to. the hydrogens of the methyl of the ester function; - 387-397 Mhz corresponding to the hydrogens >of the double ·■■■' bond of the lateral chain {doublet); - 664 Mhz corresponding to the hydrogen of the C-OH at 1. · ; · . ■ ' . . .. · Circular dichroism (dioxan): ' ·_' *··. ' . "■··.. · Max. at 232 ιημ: Δε = +7.98 ■ By replacing 0, 0-dimethyl ;l-methoxycarbonylethyl- phosphonate by the corresponding 0 , 0-diethyl .derivative.,'· ■-: the-result obtained is identical. b) Purification by formation of the sodium salt ■> The residue (9.48 g. ) ,is dissolved in 60 c.c. of acetone. acetone. One obtains the sodium salt of d -trans -p.yrethric acid, [a]^° = +56° + 2° (c. = 1%, water). The product is soluble in water and insoluble in acetone and ether.

By continuing as indicated under (a) , "one obtains d-t. pyrethric acid identical to that described above, c) Purification -by formation of the salt of L(+) -threo-l-p- " nitrophenyl-2-N,N^imethylaminopropane-l , 3-diol . The residue (9.48 .) is dissolved in $0 c.c. of ethyl acetate. One adds 11.1 g. of L(+)-threo-l-p_-nitro-phenyi-2-N,N-dimethylaminopropane-l ,3-diol and heats the mixture at reflux until ·· total dissolution. One cools to a temperature lying between 0°C and +5°C; " the salt crystallizes; one. suction-dries it and washes with ethyl acetate. One obtains 11.4 g. of salt of L(+)-threo-l-£- . nitrophenyl-2-N,N-dimethylaminopropane-l,3-diol of d-trans-pyrethric acid.

The product isi of a pale, yellow colour;- it melts at about 125°C; [oc] ° = +52° + 2° (c = 1%> ethanol). V .

It is soluble. in methanol and acetone, little soluble in water, ether and ethyl acetate.

V' As far as is known, this product is not described in the literature. ■ ■ . · ... By continuing.as indicated unde -(a), one obtains . d-trans-pyrethric acid identical to that' described above.

Claims (4)

1. •QLAIMS WHAT IS CLAIMED ISi A process for preparing d-trans-pyrethric acid, also called 1-(R) ,2-(R)seq. trans-chrysanthemum dicarboxylic acid mono- methyl ester or 3» 3-dimethy1- -(E) -(2 ' -methoxycarbonyl-trans l.' : ch ph .the 1-(R) ,2-(R) -hemicaronic aldehyde, in the presence of agent/ a strong basic/and i an. anhydrous organic solvent, 0,0- dialkyl.1-methoxycarbonylethylphosphonate, of formula:. '■.·:' in which R represents a lower alkyl radical, . 1 ■:- and obtains, after purification, the desired d-trans-' : pyrethric acid.
2. 2. A process according to claim 1, characterized, in that R ' '. represents the methyl radical.' .'
3. 3. A process according to claim 1, characterized in that the . anhydrous organic solvent is selected from the group · consisting. of tetrahydrofuran, diethyl ether, dioxan, dimethoxyethane, .methanol, t-butanol, dimethylsulphoxide . and dimethylformamide. · '. ' ¾ . _ ■;
4. 4. A process according to claim 3» characterized ' in- that the the strong "basic agent is selected from the group consisting of _,_ an alkali-metal amide, an alkali-metal hydride, an alkali-metal . alcoholate and an alkali -metal . " ' .

   6. A process according to claims 1 to 5» characterized in that .. ; the condensation of the hemicaro ic aldehyde ,..;wi.t the ' ' phosphonopropionic ester is effected under an inert ·. atmosphere. ' 7· A process according to claims 1 to 6, characterized in that r. the purification of. the crude condensation product is ' '■■ achieved by formation of a salt seected from' the group '.consisting of an alkali-metal salt, the L(+)- or D(-)-threo- ' l_ -nitrophenyl-2-N,N-dimethylaminopropane-l , 3-diol and the 1-quinihe salt.

   8. A process according to claim 7» characterized in that the purification is effected by formation of the 1 -quinine salt.

   9. ^ The salt of L(+)-threo-l-2-nitrophenyl-2-N,N-dimethylamino- propane-l,3-diol of d - rans-py ethric acid . ; ' - ' ■:' . .. ; COHEN ZEDE TSPISBAJEH · ··· ■.. ' . ■,·■■ ' ./"'' . ,' '■ ' P. Q. Box ' 1169, Tel-/ viv . Attorneys for Applicant .-,·