DE1807091B2 - METHOD FOR MANUFACTURING DTRANS-PYRETHRIC ACID - Google Patents

Description

Il

RO OC-O-CH ₃

P — C — H

R-O

CH,

in which R is a lower alkyl radical, allows the impure d-trans-pyrethric acid obtained to act in the usual way for cleaning, especially in an alkali or l (+) - or d (-) - threo-l-p-nitrophenyl - 2 - N, N - dimethylaminopropane -1,3-diol salt transferred and from this the free acid in a known manner by treatment with releases aqueous hydrochloric acid.

2. The method according to claim 1, characterized in that that one uses a phosphonate of the above general formula in which the R represents a methyl radical.

3. The method according to claim 1, characterized in that the anhydrous organic Solvent tetrahydrofuran used.

The present invention relates to a process for the preparation of d-trans-pyrethric acid, too 1 - (R), 2 - (R) seq. - trans - Chrysanthemum - dicarboxylic acid - monomethyl ester or 3,3 - dimethyl - 2 - (R) - (2 ' - methoxy carbonyl-trans -Γ - propenyl) -1 - (R) - cyclopropane-carboxylic acid called, the formula I.

CH,

COOCH,

CH

40

45

CH

COOH

(D

The semi-synthetic production of the natural d-trans-pyrethric acid is highly technical Interest as this acid one. Part of the natural pyrethrins and the synthetic, very active ones Insecticidal pyrethrin ester is e.g. B. the ester of d-trans-pyrethric acid with (5-benzyl) -3-furylmethyl alcohol, for whom the so-called "knockdown" effect is particularly remarkable.

The hemisynthesis of d-trans-pyrethric acid is extremely difficult to carry out and, as far as is known, apart from that in the work of M a t s u i and co-workers (Agr. Biol. Chem. Jap., Vol. 27, 373 [1963]) no other manufacturing process has been described to this day, whereby these aforementioned works render the earlier investigations by S t a u d i η ge invalid r and co-workers (HeIv. Chim. Acta, Vol. 7, 201 [1924]) and by C r ο m b i e and colleagues. (J. Chem. Soc, Vol. 2, 743 [1957]) seem to show. The hemisynthesis of M a t s u i et al. Starts from the d-trans-chrysanthemum monocarboxylic acid and requires 5 steps to produce d-trans-pyrethric acid.

The production process according to the invention is carried out in such a way that 1- (R), 2- (R) -hemicaronaldehyde or 3,3-dimethyl-2- (R) -formyl-1 - (R) - cyclopropane - carboxylic acid ( _Bp . O9 115 ⁰ C, [ _a ] f = + 36 ° ± 1 [c = 1%, benzene]) of the formula II

C = O

COOH

(H)

starts out, a compound obtained by oxidation of the d-trans-chrysanthemum monocarboxylic acid with Ozone according to that for the racemate by Ryo Yamamoto (Scient. Papers Inst. Phys. Chem. Res., Vol. 3, 193 to 222 [1925]) described processes, and where, starting from the aldehyde, only a single stage is required for the production of d-trans-pyrethric acid.

The inventive method for the preparation of d-trans-pyrethric acid is characterized in that on the 1- (R), 2- (R) -hemicaronaldehyde in the presence of an alkali amide, hydride, alcoholate or metal in an inert gas atmosphere and in an anhydrous organic solvent, especially at -5 to +20 ⁰ C, a 1-Methoxycarbonyläthyl-

Ο, Ο-dialkyl phosphonate of the general formula III

R-O O

\ T /

P — C — H

CO-CH ₁

(III)

R-O

CH,

IO

in which R is a lower alkyl radical, allows the impure d-trans-pyrethric acid obtained to act in Usually for cleaning, especially in an alkali or i. (+) ~ or d (-) -threo-1-p-nitrophenyl-2 - N, N - dimethylaminopropane -1,3 - diol - salt transferred and from this the free acid in a manner known per se by treatment with aqueous hydrochloric acid releases.

The present invention can be further characterized by the points listed below be: The anhydrous organic solvent, in whose environment the condensation of the phosphonopropionic acid ester with which hemicaronaldehyde is carried out is, for example, an ether such as tetrahydrofuran, Diethyl ether, dioxane or dimethoxyethane, an aliphatic alcohol such as methanol or tert-butanol, dimethyl sulfoxide or a disubstituted one Amide, such as dimethylformamide.

The alkali amide used as a strongly basic agent is z. B. sodium amide.

The condensation of the hemicaronic aldehyde with the phosphonopropionic acid ester is carried out in an inert Atmosphere to avoid oxidation of the aldehyde.

In a particularly preferred embodiment, the crude condensation product is purified by forming an alkali salt such as the sodium or potassium salt, or the salt of l (+) - or d (-) -threo-l-p-nitrophenyl-2-N, N-dimethylaminopropane-l, 3-diol, which allows removal of the undesired isomers.

As 1 - methoxycarbonyl - ethyl - O, O - dialkyl - phosphonate is preferred the 1 - methoxycarbonylethyl-O, O-dimethyl- or the -Ο, Ο-diethyl phosphonate used.

Analogously to the preparation of the alkyl phosphonoacetates (cf. Arbusov and Razumov, J. Russ. Phys. Chem. Soc, Vol. 61, 623 [1929]), the 1-methoxycarbonyl-ethyl-O ^ -dimethyl-phosphonate is obtained by condensation of the Trimethylphosphite (CH ₃ O) ₃ P with a «-halogen-methyl-propionate, by condensation of the trimethyl-phosphonacetats

(CH ₃ O) ₂ P-CH ₂ -CO ₂ CH ₃

55

with methyl iodide in the presence of an alkali metal or by the action of an alkali metal salt of a Dimethyl phosphite on an α-halomethyl propionate obtain. An example of the production of 1 - methoxycarbonyl - ethyl - O, O - dimethyl - phosphonate is described in the experimental section below.

The l-methoxycarbonyl-ethyl-O ^ -diethyl-phosphonate is z. B. using the method of H. W. C ο ο ν e r and co-workers. (J. Am. Chem. Soc, Vol. 79, p. 1963 [1957]).

The L (+) - threo -1 - ρ - nitrophenyl - 2 - N, N - dimethylaminopropane-1,3-diol and the corresponding d (-) - derivative are in the French patent 1 481 978.

Instead of the phosphonates of the general formula III, certain activated derivatives can also be used of oxygen-containing compounds of phosphorus, for example the phosphine oxides and phosphine esters, may be used in the presence of a strongly basic agent in the form of a carbanion of the type

can react. The following example is intended to illustrate the invention.

To prepare the starting material, a mixture of 124.1 g of trimethyl phosphite and 183.7 g of α-bromo-methyl propionate is heated to 115 ° C. under a nitrogen atmosphere. The reaction mixture is kept at this temperature for 48 hours. After cooling, the reaction mixture is rectified under reduced pressure, obtaining 76.9 g of l-methoxycarbonylethyl-OjO-dimethyl phosphonate, Kp. _Ls = 140 ⁰ C. which is used as such for the condensation with the Hemicaronaldehyd. The saponification index of this product is 285 mg potassium hydroxide per 1 g.

example

3.84 g of sodium amide (92% content) are added to 40 ecm of tetrahydrofuran under a nitrogen atmosphere, the mixture is cooled to -5 ° C. and a solution of 17.7 g of 1-methoxycarbonyl-ethyl-O ^ -dimethyl- is added dropwise. phosphonate in 40 ecm tetrahydrofuran too. The reaction mixture is brought to 20 ° C., stirred for 3 hours at this temperature and 1.92 g of sodium amide (content 92%) are added. The reaction mixture is cooled to -5 ° C., a solution of 6.4 g of 1- (R), 2- (R) -hemicaronic aldehyde (or 3,3-dimethyl-2 - (R) - formyl -1 - (R) - cyclopropane - carboxylic acid) in 40 ecm tetrahydrofuran. The reaction mixture is brought to 20 ° C., kept _{at this temperature for 3V for 2} hours and then concentrated to dryness under reduced pressure. 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 a pH of 1 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 pressure.

a) The residue (9.48 g) is dissolved in 60 ecm of acetone. 4.5 ecm of 10 n sodium hydroxide are added.

The sodium salt crystallizes out; it is suctioned off at a temperature between 0 and +5 ⁰ C and washed with acetone. The sodium salt of d-trans-pyrethric acid is obtained, Ia] I ⁰ = + 56 ° ± 2 (c = 1%, water). The product is soluble in water and insoluble in acetone and ether.

In a mixture of 60 ecm of ethyl ether and 60 ecm of an aqueous 2 N hydrochloric acid solution

7.5 g of the salt obtained above are added to the solution, the mixture is stirred, the ethereal phase is separated off by decantation, washed with water, the washing water is extracted with ether, the ethereal phases are combined, dried and concentrated to dryness under reduced pressure. The residue is rectified in vacuo. 2.61 g of d-trans-pyrethric acid are obtained. Kp. ₀ . ₂ = 130 ° C, [a] S ⁰ = + 81.5 ° (c = 1.2%, carbon tetrachloride).

IO

Analysis for C ₁₁ H ₁₆ O ₄ (molecular weight 212.24): Calculated ... C 62.25, H 7.60%; found .... C 62.5, H 7.8%.

UV spectrum (ethanol) maximum at 238 to 239 ΐαμ (ε = 15 100).

IR spectrum (chloroform)

The IR spectrum is identical to that of M a t s u i and colleagues. (Agr. Biol. Chem. Jap., Vol. 27, 374 [1963]) published.

25th

NMR spectrum (deuterochloroform, based on MHz)

The NMR spectrum agrees with the "trans" configuration of the ring and the "trans" configuration of the olefin chain.

It is made up of:

76 and 83 MHz, corresponding to the hydrogen atoms of the methyl groups in the 3-position, 101.5-107 MHz, corresponding to the hydrogen atom in position 1 (doublet);

117.5-119MHz, corresponding to the hydrogen atoms the methyl group of the side chain, 128-138-143 MHz, corresponding to the hydrogen atom in the 2-position (triplet), 227.5 MHz, corresponding to the hydrogen atoms the methyl group of the ester function,

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

664 MHz, corresponding to the hydrogen atom of

C-OH group
O

in 1 position.

Circular dichroism (dioxane)

Maximum at 232 ηΐμ: Ae = +7.98.

When replacing the l-methoxycarbonyl-ethyl-O ^ -dimethyl-phosphonate the same result is obtained with the corresponding Ο, Ο-diethyl derivative.

b) The same residue (9.48 g) as used in a) is dissolved in 30 ecm of ethyl acetate. 11.1 g of L (+) -threo-lp-nitrophenyl-2-N, 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 0 and +5 ⁰ C; the salt crystallizes out, it is filtered off with suction and washed with ethyl acetate. 11.4 g of the L (+) -threo-1 - ρ - nitrophenyl - 2 - N, N - dimethylaminopropane-1,3-diol salt of d-trans-pyrethric acid are obtained.

The product has a pale yellow color, it melts at about 125 ° C, [α] f = + 52 ° ± 2 (c = 1%, ethanol). It is soluble in methanol and acetone, but not very 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-pyrethric acid, which with the above described is identical.

Similar results are obtained if, instead of sodium amide, sodium hydride or Sodium alcoholates used.

Claims (1)

Patent claims: 1. Process for the preparation of d-trans-pyrethric acid the formula characterized in that the l- (R), 2- (R) -hemicaronaldehyde in the presence of an alkali amide, hydride, alcoholate or metal in an inert gas atmosphere and in an anhydrous organic solvent, in particular at -5 to +20 ⁰ C, a 1-methoxycarbonylethyl Ο, Ο-dialkyl phosphonate of the general formula