DE1807091A1 - Process for the preparation of a cyclopropane carboxylic acid and the products obtained thereby - Google Patents

Description

PATENT LAWYERS DR. F. ZUM8TEIN - DR. E. ASSMANN DR. R. KOENIQSBERQER - DIPL-PHYS. R. HOLZBAUER TILBFONl M »4 7« UO * Ml · 11

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BANK ACCOUNT

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% 5/30 / Si Oasis 1217

BOTJSSEI, - WLAF _% Paris, Frankreioh

▼ learn EUR producing a OjrclopropÄn-carboneäure and ^ thereby resulting products.

The present invention relates to a process for the preparation of a cyclopropane carbonate.

The Epfin tune relates in particular to a process for the production of d-trans-pifrethric acid, also 1- (R), 2- (R) seq.-trans-Ohryaotheaum-dicarbonaäureHtoxioeathyleeter or 3,5-diaethyl-2- (B) - (2 · - »ethoaiyoerbonyl-to» »» - ^ '-propenyl) -1 -. (H) -cyolopropejioarbons & ure called, the Toxvel I ■ -

(D

The semisynthetic production of the natural d-trane-pyrethric acid is of great technical interest, since this acid is a component of the natural pyrethrins and the synthetic, more active insecticidal pyrethric acid, such as the ester of d-trans-pyrethric acid eit de »(5-Eeneyl) -5-ftixyl-ethyl alcohol, an ester for which the aforementioned" Knock-dovm ^l '-Iffek: fe

909840 / I7SS

particularly noteworthy is ο

The hemi-synthesis of d ~ trans ~ pyrethric acid is extremely difficult to carry out and, as far as is known, is beyond that in the. Work by MATSUI et should »CAgr _o Biol = Chemo Japo 2 £, 375 (1963) 3 no other manufacturing process has been described up to the present day, whereby these aforementioned works render the earlier investigations by STAUDINGER et coll * CHeIv ^ 2 invalid * ^2Oi (1924) 3 and von OROMBIE et coll. CJ ₀ Chemo Soc 2 7 ^ 3 0957) 3 au seem to show * The synthesis of MATSUI et coil starts from the d-trans-chrysanthemum acid and requires deac d- trans-pyrethric acid 5 stages «,

The manufacturing method according to the invention is carried out in this way that from 1 ~ (R), 2- (R) -hemicaronic aldehyde or from the 3i3-di » thl2 (R) fl1 (R) lBACK

115 ° 0, Ca] ß ° « + 36 ° ψ 1 (c« 1 % "Benssol)! of the general formula II

emanates from a compound «which can be obtained by oxidation of the d-trans ·» Chrysanthemum acid m.ifc oboe after the for that

Ralcemat by RYO YAMAMOTO CScient «Papers Inst« Phys » GhQm, Hes. Ί * 193-222 (1925) 3 described processes, and where one, starting from the aldehyde dei? Lvate, for herat el ment of d-trane-pyrethric acid only a single step θ "required»

This method according to the invention is thereby in the weeentHoben marked * that the variant with Pboaphonat the Wittig-Beaktion carries out »iEdeo nan on the 1- (R), 2- (R) -Hemi-

909840/176 8 -

BATH ORIGINAL

oaroa ~ aldehyde la (present “In ·· strongly basic agent and in • Inm anhydrous organic solventm ± lieu da · 1-Hethoxycaxbonyläthyl ^ .O-dialkyl-phosphonet der Fon”! III

In the lower alkyl radical means

• Imrlrkta, according to Λτ H «lniguiig, leaves the usual d-trene-pyrethrinic acid.

The present invention can also be identified by the following items:

- The anhydrous organic solvent, in the environment of which the Eondessation of the Phoaphonpropionsäureeetere is carried out with the Hesdcaron aldehyde, is' for example an Xthar, such as, for example, tetrehydrofuran, diethyl ether, Sioxane or Binethoxyethane, an aliphatic alcohol, such as B. Methanol or tert-butanol, Diaethylsulfox ^ or a disubstituted amide "like β · Β" SiBethylfornaaidf

- the strongly basic agent is _Y durchgeftlhrt in its Oegenwmrt the Kondea- _(sation of Heeicaron-aldehyde with de "Phoephenpropioneaareester, for example, a Alkallastallaiiid such as Katriuaaaid, an alkaline tallhydrid, a Alkaliaetallalkoholat, an alkali metal;

- The condensation of the hemioaronic aldehyde with the Phoa phonpropioneäureeater is carried out in an inert atmosphere in order to avoid as much as possible the oxidation of the aldehyde bu.

In a particularly preferred form, the crude Kondeneationeprodukta is broken down by the formation of a total alkali salt, such as B, of the Natriuia or KaliumsalaeB »of the salt of L (+) - or D (-) - threo-1-p -]? Itrophenyl-2-K _t N-

909840/1765

dimetiiyla * inopropane «> 1,2 ~ 4iol or also des l ~ Cbinio ~ Sal & e8 _t which allows the removal of the undesired isomers»

Ale i-methoxycarbonyl-ethyl-O ^ O-dialkyl-phosphonai; i-methoxycarbouyl-ethyl-OjO-dimöthyl- or -O ₁ O-diethyl-phosphonate is used as a precaution.

As far as is known, the i ^ ethoxycarbonyl-ethyl- ^ O-diaetaylphosphonate is not described in the literature. Analogous to the production of the alkyl phoaphonacetates Cvergl * ARBUSCV, Jo of General Che «. the U.S.SoR », ££, 29? and § £, 6203 is the methoxy-carbonyl-ethbjl-O _f CMlinethyl-pnoaphonat by condensation of the trixothylphosphite (CBLO) JP »with an α-halomethylpropionate, by condensation of the triuothylphophonacetate

with methyl iodide in the presence of an alkali " metals or by the action of an alkali metal salt Bimethy! Phosphite obtained on a w-halomethyl propionate, An example of the preparation of 1-methoxycarbonyl-ethyl- · 0.0 ~ disiethyl ~ phophonate is in the experimental below Part described.

The 1-methoxycarbonyl-ethyl-0,0 »diethyl-phosphonate is under Use of the procedure woa H.W, COOVSi et coil · CAa »Soc * 22 * Page 1963 (1957) 3 produced.

The L (*) -. Threo-1 ~ p-Kitrophenyl - 2- «N _t ! R» diaethylaHiinopropan-1 ₄ 3 · -diol and the corresponding U (~) -D © riTat are in the French patent 1,481 978 described.

Instead of the phosphonate © of the formula III, other reagents can also be used ien are used, of which the triarylalkyl phosphboni » umealze, in particular the triphanylalkyl-phosphonitoisalBe «u are to be called, dio under the action of an etarkea base lead an alkylidene phosphorane, the (frie ~ dial & yla.! aino) ~

and (dialkylamino-diaryl) -alkyl-phoophoniuiuiBsal2! e _i die uD.ter d «r

909Θ40 / 176S

BATH ORIGINAL

¹¹ IP- Γ ν - / - '»' lawn

Action of a strong base ", also below an" alkylidene phosphorane lead as well as certain activated derivatives of oxygen-containing compounds of phosphorus, for example dio Phosphine oxides and phosphine ethers, which in the presence of a strongly ba ailing agent in the 7oxn of a carbanion of type

^^ react.

The following example is intended to illustrate the invention without it however, restrict it to this.

Production of 1 ~ methoxrcarboixyl ~ ethyl ~ Q _t O - <l ± BethyX-T) hoBT) honat. A mixture of 134.1 grams of trimethylphosphite; and Ί83,7 g a-Broamethyl propionate HEAT & nan t under a Sticketoffatmoephäre to 115 ⁰ C. It is the Reaktionsmiechung holding for 48 hours at this temperature. BaOH de 'cooling is rectified the Beaktionsaischung under vermindertea pressure and "to receive 76τ9 β 1 ~ ^ Meth03C arbonyl-Sthyl-0,0-di" ethylpiioflphoixat _r Kp _{18 ΚΛ} - 140 ⁰ C, the sow as such old for condensing the Hemicaronaldehyde used

The saponification index of this product is £ 285 potassium hydroxide per 1g,

As far as is known, this compound is not described in the literature.

Example .

d ^ trans-Rrrethrinsänre or 3 «3-DiBethyl« 2 * - (R) »(g ^> -MethO3qrc8rbo «

under a ticketoffat official

In 40 cca tetrahydrofuran are aanfSTsA- g & Hatrium aid (content 92%), the mixture cooled to -5 ⁰ C., and added dropwise a solution of 17.7 g i-Methoxycarbonyl-ethyl-O ^ O-dJjiethylphosphonat in 40 cc «tetrahydrofuran bu · It brings the Beaktionsaisohung to 20 ⁰ C ₉ is stirred for 5 hours at this temperature and 1 * 92 g Hatriuoaiiid (content <&%) su cool the Reaktionsmiechung in. - 5 ⁰ C., add dropwise a solution of 6 , 4 g 1- (R), 2 ~ ('Jl) -Heaicaron-aldehyde (or 3i3-dimethyl-2- (R) -fori ^ rl-1- (R) -cyclopropane-oarboic acid) in 40 cc *

80984Q / 17IS

Tetrahydrofuran au * bringing the Heaktionsmischung to 2O ⁰ C, holding for 3 1/2 hours at this temperature and then concentrated by evaporation under reduced pressure to dryness. Water is added to the residue, the aqueous phase is washed with ether, the combined ether extracts are washed with water, the aqueous phases are mixed and acidified to pH by adding an aqueous concentrated hydrochloric acid solution, the acidic aqueous phases are extracted with methylene chloride * the combined methylene chloride extracts are washed with water, dried and then concentrated to dryness under reduced bridge.

"a) Reinifpn ^ by the formation of the I-quinine salt a Per Bücketand (9-AQ g) is dissolved in 100 ecm acetone with 16% water, to the solution is added 12 g linkedr@heii.der OMninb & e® su, warms the Reaction mixture in a steam bath until completely dissolved and the mixture slowly cools. « The crystals formed are isolated by suction and 9t19g of the crude I-quinine salt are obtained»

A second PrafeMon of the same quality (2.14 g) _{or similar is obtained from the mother liquors}

The first and second fractions are combined and crystallized from acetone with 16% water, and 7.5 g of the quinine salt of 1 ^ (H), 2- (H) »seq,« »tran8-0lirysanthemiim- are obtained. -di «arbonic acid monomethyl ester, E - 169 ⁰ C, IaI ²⁰ J« -101.5 ° (c »1% _v methanol) ο

A second fraction is obtained from the purification mother liquors the same quality ..

• 7 »5 g of the quinine salt obtained above are added to a mixture of 60 ecm of ethyl ether and 60 ecm of an aqueous 2 η hydrochloric acid solution, and the mixture is stirred _? separating the ether phase by decantation, washed they take -with * _t esctrabiert; the washing water with ether, the etheric bases, dry them and concentrate them to the irermiiiderteia Brack sup frockne. The residue is rectified under Yakiraa and you get 2.61 g of d-trans-rethric acid or 3,3-dimethyl-2 "(H)-

909840/1765

BATH ORIGINAL

(2 '~ aethoxycarbonyl ~ trane-i' -propenyl) -1- (fi) -cyclopropaii-oeup-

bona acid, b.p. _{0 2 M} - 130 ° C, CaJ Jj ⁰ - ♦ 81 _? 5 ° (c - 1.2 9ft, »etr * -

chlorocarbon) «

Analje · for O ₁₁ H ₁₆ O ₄ (212.2 *) calc . : 0 62.25 H 7.60

found: 62.5 7 »8 %

Uy spectrua. Ethanol) "Max. At 238-239 ep (£." 15 100) IB spectrum (chloroform): The IB spectrum is identical to that of MATSUI et coll, CAgr _e Biol, Ohem. Yep 22, page 37 * (1963) 3 published.

BMR spectrum (deuterochloroform; based on 60 MH *) ί the BMR spectrum agrees with the dex · "trans" configuration of the ring and the Hrans "configuration of the olefin chain. It is composed of:

76 and 83 MHz _? corresponding to the hydrogens of the methyl groups in the 3-position;

101 * 5-107 MH » _t corresponds to the hydrogen in the 1-position

(Doublet);

i17 _t 5-119 MHj5 _Y corresponding to the hydrogen of the methyl group of the side chain;

128-138-143 MHz »corresponding to the hydrogen in the 2-position (Triplet) j

227 * 5 MHz, corresponding to the hydrogen of the methyl group the ester function {

387 - 397 MHe, corresponding to the hydrogen of the double bond the side chain (doublet);

664 MHz, corresponding to the hydrogen of the C-OH group in the 1-position β 0

Circular dichroism (dioxane); Max. At 232 mui A £ - + 7 »98.

When replacing the i-methoxycarbonyl-ethyl-OyO-dimethyl-phosphouatβ the corresponding 0,0-diethyl derivative is obtained. the same result

b) Purification by forming the sodium salt. The residue (9.48 g) is dissolved in 60 ecm of acetone. One gives 4.5 ecm 10 η sodium hydroxide zn.
The sodium salt crystallizes out; it is suctioned off at a temperature between 0 and> 5 ⁰ G and washed with acetone.

The sodium salt of d-trans-pyrethric acid "Ca] ξ" is obtained

♦ 56 ° + 2 (c- 1 % _r water) · The product is soluble in water

909840/1765

and insoluble in acetone and ether.

If one continues as indicated under (a), one obtains the d ~ tr8Jk0 «-pyrethric acid, which is identical to that described above.

c) Purification by the formation of the L (+) - threo-iH> -Sitrophenyl · - » 2 ~ N, N« -dimethylaminopropane-1,3-diol salt a.

The residue (9 «48 g) is dissolved in 30 ecm of ethyl acetate. 11.1 g of L (+) - threo-1 ~ p-nitrophenyl-2-! T, N-dimethylaminopropane-1,3-diol are added and the mixture is heated under reflux until it is completely dissolved. It is cooled to a temperature between O ⁰ C and +5 ⁰ C from; the salt crystallizes from _i it is filtered off with suction and washed with ethyl acetate. 11.4 g of the L (+) - threoi-p-nitrophenyl-2-NTN-dimethylaminopropane-1,3-diol salt of d-trans-pyrethric acid are obtained.

The product has a pale yellow color "it melts at about 125 ⁰ C, CaI ² Jq - * 52 ° + 2 (c« 1%, ethanol) "Ee is soluble in methanol and acetone, a little soluble in water, ether and ethyl acetate.

As far as is known, this product is not described in the literature.

If one continues as indicated under (a), one obtains the d-trans-fyrethric acid, which is identical to the one described above »

9098AO / 1765

BATH

Claims (1)

Claims Λ ο method EUR preparation of the d-Transs-Pyrethrinsäure also ester or 3,3-dimethyl-2- (R) - (2 ^f - «ethoiyaarbonyl-trane-i · -propenyl) -1- (R) -cycloproptn-carboxylic acid called, the JOrael ³ V CO ₂ H characterized in that the 1- (R), 2- (R) -He »ici aldehyde in the presence of a strongly baeiechen Surfagene and a "organieohen Lösungemittelailieu waeserfreien as"one-Kethoxyoart> onyl-öthyl-0 _f 0 dialkyl pho8phonat the Pornel -4 - in which R is a lower alkyl, allows to act and the desired d-trana-pyrethrinic acid is obtained after purification. 2. Process according to claim 1, characterized in that the radical R denotes a methyl radical. 3 «The method according to claim 1, characterized in that one as an anhydrous organic solvent, a solvent from the group consisting of tetrahydrofuran, diethyl ether, dioxane, diaethoxyethane, methanol, tert-butanol, dimethyl sulfoxide and 909840/1765 Dimethylfornamide is used. 4. The method according to claim 3, characterized in that AaS one Any anhydrous organic solvent tetrahydrofuran or ether is used. 5, method according to one of the preceding claims, characterized It is possible to use strong baaiachee agents to oil a baee of the group Alkalimetallanld, Alkalinetallhydrid »Alk & linetallalkoholat und Alkaline tallj / ervendet · A 6. Method according to one of the preceding approaches »thereby characterized that nan the condensation dea Heaioaroft aldehydes with the Phoephonpropionaureeeter in an 'inert Ataoephar performs. 7. A method according to one of the preceding claims, characterized in that the purification of the crude _t Kondensationepro «-products via the formation of a Salses from the group Alkalinetall" sals, L (+) - or D (-) - threo--ip Hitrophenyl-SN .N-dinethylaninopropane-1,3-diol-Sal »and 1-quinine-Sal» takes place, 8. The method according to claim 7, characterized in that the Purification takes place via the formation of the l-Chlnln-Saleea. 9 · i-Kethoxycarbonyl-ethyl-O ^ -diaethyl-phosphonate. 10 "Daa L (4) -threo-1-> p-nitrophenyl-> 2 <-N, N" -dinethylaaiiiopropane-1,3-diol salt of d-trans-pyrethric acid. 909840/1766