DE2414794C3 - Process for the preparation of optically active allethrolone - Google Patents

Description

COOH

COOH

in a known manner with α-phenylethylamine in a known manner with α-phenylethylamine the formula formula

CH-CH ₃
NH ₂

(Π)

20 CH - CH ₃
NH ₂

u-Phenyl - /? - p-tolylethylamine of the formula

u-Phenyl-zi-p-toylethylamine of the formula

CH ₃

NH ₂ (HI)

CH ₃ (III)

NH,

threo - 2 - dimethylamino - 1 - (p - nitrophenyl) -

1,3-propanediol of the formula threo-2-dimethylamino-l- (p-nitrophenyl) -l, 3-pro-

35 pandiol of the formula
CH ₃ CH ₃

HN
-CC-CH ₂ (IV)

OH

OH

or a naphthylethylamine of the formula
NH ₂

CH - CH,

(V)

reacted in a molar ratio of 0.5 to 1.5 moles of amine per mole of the allethrolonyl phthalate in the presence of an inert solvent, separating the amine salt obtained, if desired after purification, decomposing it in the usual manner with acid and the resulting optically active acidic allethrolonyl phthalate in a known manner Hydrolyzed at room temperature up to 250 ^° C. but with water or in an aqueous solvent, optionally in the presence of a base which is used in a molar ratio of 0 to 1.2, preferably 1 to 1.0 mol per mol of acidic allethrolonyl phthalate.

CH ₃ CH ₃
HN
O ₁ N- <f ^ CC-CH ₂ (IV)

OH

OH

45

or a naphthylethylamine of the formula

NH,

CH - CH ₁

55 in a molar ratio of 0.5 to 1.5 moles of amine per mole of the allethrolonyl phthalate converts in the presence of an inert solvent, separates the amine salt obtained, if desired after purification, decomposes it in the usual way with acid and the resulting optically active acidic allethrolonyl phthalate in itself hydrolyzed in a known manner at room temperature up to 250 ° C with water or in an aqueous solvent, optionally in the presence of a base which is used in a molar ratio of 0 to 1.2, preferably 1 to 1.0 mol per mol of acidic allethrolonyl phthalate.

The method according to the invention can be represented by the following scheme:

O
/ C
11th COOH
ι a) optically K O
' \ /1
C.
Il COOAm
I. 1 Il
O optically active lawn Il
O 11th
O r) V active Amine salt Il
O race mi shear Phlhal acid half ester

b) acid or base

COOH

OH

c)

Hydrolysis with water, if necessary in the presence of a base

optically active allethrolone

Il ο ο

optically active phthalic acid half-ester

Allethrin (allethrolonyl chrysanthemate) was previously used Widely used as being less toxic to mammals and more quickly effective. It has a similar chemical structure and insecticidal activity to natural pyrethrins. Since Allethrolon, the alcohol portion of the allethrin, has an asymmetric carbon atom in the 4-position, this compound exists in two optically isomeric forms. From the chrysanthemum monocarboxylic acid esters of Allethrolone, the (+) -Allethrolone ester is known for being many times larger has an insecticidal effect than the (- (-Allethroloneester. It is therefore very important to use a method for Production of optically active allethrolone available on an industrial scale is feasible.

The only known method for the production of optically active allethrolone is based on the optical Splitting of the semicarbazones of the diastereoisomers (iJ-AllethronlonyH + Hrans-chrysanthemate under Application of a fractional crystallization and splitting of the separated semicarbazone in the optically active allethrolone (F.B. La Farge et al., J. Org. Chem., Vol. 19,457, 1954). However, this method cannot be carried out industrially as there are many Reaction steps have to be carried out, the process implementation is complicated and the overall yield is low is achieved.

From La Forge et al. the hydrolysis of the acidic allethrolonyl phthalates was examined in detail (F.B. La Forge et al., J. Am. Chem. Soc, 74,5392, 1952). It could be shown that even with Room temperature said phthalate with an excess of sodium hydroxide, d. H. 2.2 equivalents, could be hydrolyzed, but not the allethrolone, but only a dimeric product obtained from the condensation of 2 allethrolone molecules. Already on the ground Due to this fact, the optical splitting of the allethrolone via salts of the acid phthalate had to be considered impossible to be considered. Furthermore, the authors mentioned at the beginning of their report stated that that allethrolone cannot generally be obtained by hydrolysis of allethrin.

The above problem can also be understood from the fact that pyrethrolone (2- (2'-4'-pentadienyl) -4-hydroxy-3-methyl-2-cyclopentenone not obtained by hydrolysis of pyrethrin ((+) -pyrethrolonyl (+) -trans-chrysanthemate) which has a chemical structure very similar to that of allethrin. Therefore, to make pyrethrolone, Standinger and Ruzicka used a very laborious one Process used in the manufacture of pyrethrin semicarbazone. Cleavage of the ester bond through a base-catalyzed ester interchange reaction and decomposition of pyrethrolone-semicarbazons to pyrethrolone with aqueous sodium bisulfate (cf. H. S t andinger and L. Ruzicka, HeIv. Chem. Acta., Vol. 7,177,1924).

It has therefore hitherto been considered practically impossible to use optically active allethrolone industrially to manufacture.

The invention is based on the finding that the production of an optically active acidic Allethrolonyl phthalate and its hydrolysis to allethrolone is possible if one according to the invention namely initially the acidic allethrolonyl phthalate reacts with certain optically active amines, the amine salt obtained hydrolyzed with acid and the optically active acidic allethrolonyl phthalate obtained in a simple manner with water or a solvent contained in water, if appropriate in the presence of a base, the amount of which is from 0 to 1.2 and preferably from 0 to 1.0 mol per mole of acidic AlIethrolonylphthalat is hydrolyzed.

The inert solvent used in the first stage consists of hydrocarbons, for example Benzene, toluene or hexane, chlorinated hydrocarbons, for example chloroform, carbon tetrachloride, Chlorobenzene, dichloroethane or tetrachlorethylene. Ethers, for example ethyl ether or isopropyl ether,

Ketones, ζ. B. acetone, methyl ethyl ketone, methyl isobutyl ketone or diisobutyl ketone, esters, for example ethyl acetate, or lower alkanols, for example Methanol, ethanol, propanol or isopropyl alcohol, Mixtures thereof or mixtures thereof with water.

The racemic acid (+ HAllethrolonyl phthalate used as starting material can be obtained according to the in J. Am. Chem. Soc, Vol. 74, 5392, 1952 or by reacting allethroion with ° hthalsäureanhydrid in the presence of a tertiary Amines, such as triethylamine, can be produced.

The hydrolysis of the acidic allethrolonyl phthalate in the third stage proceeds in an unexpected manner very smoothly by simply heating in water or in an aqueous solvent, with the allethrolone can be obtained in a good yield. If necessary, the hydrolysis can be carried out by the addition a base in an amount up to 1.2 moles per mole of acidic allethrolonyl phthalate. This amount is below that of the known method and therefore possibly causes the gulen Exploit.

Although can be seen from the examples. that the presence of a base is not essential to the implementation of the invention, the addition of a base is preferred in order to accelerate the rate of hydrolysis. It is very important that the amount of a base added is preferably not more than 1 equivalent of the acidic allethrolonyl phthalate. The use of a base in a large excess of more than 1.2 equivalents results in rapid formation of the dimeric allethrolone, which from La Forge et al. has been described so that no alletrolon can be obtained.

According to the invention the hydrolysis of the acidic Allethrolonylphthalats is carried out in a solvent at a temperature varying between room temperature and 250 ^c C, wherein the reaction time is several minutes to 100 hours. If necessary, the hydrolysis can be carried out under increased pressure in order to accelerate the reaction, it being possible to add a base in the specified small excess to acidic alletholonyl phthalate and to admix a surface-active agent. The solvents that can be used are, for example, water or water-miscible solvents, e.g. B. methanol. Ethanol. Glycerin, ethylene glycol. Diethylene glycol. Triethylene glycol, acetone. Tetrahydrofuran. Dioxane, Dimethylsulfoxidund Dimethylformamide To protect the allethrolone against undesired side reactions, the reaction can be carried out in an aqueous solvent with water immiscible solvents, for example ether. Benzene, toluene. Xylene. Dichloromethane, chloroform. Carbon tetrachloride. Dichloroethane, petroleum ether, petroleum benzine. Ligroin. η-hexane, 1-butanol, 2-butanol. tert-butanol and methyl ethyl ketone. be performed. For the same reason, the reaction can be carried out in a (κ> buffer, which enables the reaction system to be kept almost neutral.

The base which is used according to the invention preferably consists of an alkali or alkaline earth metal hydroxide, oxide, carbonate, bicarbonate. phosphate, cyanide. -sulfide. -boiat, -formate, -acctate, -propional or benzoal. Amines (including ammonia) such as methylamine. Dimethylamine. Trimethylamine, Ethylamine, diethylamine, triethylamine, cyclohexylamine, Dicyclohexylamine N-methylcyclohexylasiun, N.N-dimethylcyclohexylamine, pyrrolidine, N-methylpyrrolidine. Piperidine, N-methylpiperidine, foorpholine, N-methylmorpholine, aniline, N-methy]. aniline, N-ethylaniline, N, N-dimethylaniline N, N-diethylaniline, Benzylamine, N-methylbenzylamine, N, N-dimethylbenzylamine, Pyridine, quinoline, isoquinoline, and-, //- and γ-picoline can also be used will. These bases can also be used in the form of a mixture.

The optically active salt of the second stage can be hydrolyzed without being optically active acid allethrolonyl phthalate is isolated.

After the hydrolysis, the reaction mixture is made basic, if necessary, and treated with sodium chloride, Saturated urea and sodium sulfate and then with an organic solvent such as Benzene, toluene or ether extracted.

The separated organic layer becomes after washing with a saturated aqueous sodium chloride solution dried and concentrated under reduced pressure to give pure alletrolon. If the hydrolyzed mixture is acidified first, then allcihrolone becomes oily and crystalline Phthalic acid deposited at the same time. In this case, the mixture is made with an organic solvent triturated and filtered, whereupon the separated organic layer in the same manner as above has been described.

The following examples illustrate the invention.

example 1

18 g η-hexane are added to a solution of 16.0 g of acidic (±) -alleihrolomlphthalate and 6.4 g of (+ hi-phenylethylamine, dissolved in 55 g of benzene. After standing at room temperature, the precipitated crystals are filtered off. This gives 8.0 g of a crude Sal / es F. 111 113 C. the SaI / is recrystallized from the same mixture of benzene and n-hexane to give 6.0 g of white crystals are obtained F. 115 116 C;.. [.] ; ■ '-17.8 (in ethanol) the purified Sal / is a cold 2% sodium bicarbonate / for separation of free (+) -N- Phenylälh% lamin added, which is extracted with benzene..

b) The aqueous layer is acidified with concentrated hydrochloric acid, whereupon the separated oily material is extracted with ether. The etching layer is washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. 4.1 g of acid (-) -allelhrolonyl phthalate are obtained in the form of a very viscous oily material \ <i]% -45.9 "(in ethanol).

c) 12.8Og acid (- l-allethrolonyl phthalate ([«]? -" -45.9 [in ethanol]), 50.0 g of water and 3.23 g of sodium bicarbonate are heated to 100.degree. the Reaction mixture is then cooled to room temperature, saturated with sodium chloride and then extracted twice with ether. The ethereal solution is mixed with a saturated aqueous sodium chloride solution washed, dried over anhydrous magnesium sulfate and under reduced pressure concentrated to give 5.40 g of a light yellow oil. If crystals have separated out in the oil, then the mixture is triturated with chloroform, filtered and concentrated. The oil is made by vacuum distillation cleaned. Bp. 109 ■ -110 C / 0.3 mm Hg. Es

then there is practically pure (-) - AI! ethrolone, like it on the basis of the NMR, the IR and the gaschromatographischcn Values results in [«] £ 6.5 ° (in ethanol).

If instead of sodium bicarbonate in stage c) 70 g of water and 7.90 g of a 40% strength are used aqueous dimethylamine and is based on 21.0 g of acid (-) - allethrolonyl phthalate, [«]? -44.58 ° (in ethanol) off, after 7 hours of heating at 100 ° C, 9.15 g of optically active allethrolone [«]! ' -6.57 ° (in ethanol).

If 17.1 g of acidic (-) - AlIethrolonylphthalat, [«] £ '-44.58 ° (in ethanol), 57 g of water are heated and 3.5 g of a 28% strength aqueous ammonia solution at 100 ° C. for 8 hours, 8.0 g of one are obtained optically active allethrolons, [«] £ - 6.52 ° (in ethanol).

Example 2

a) 18.0 g of acid (±) -Allethrolonylphthalat and 12.6 g (-) - «- Phenyl - // - p-tolyIäthylamin are in 60 ml of toluene dissolved, whereupon the solution is left to stand overnight at room temperature. The precipitated Crystals are filtered and washed with toluene, with 8.0 g of white prisms. can be obtained.

b) The salt is treated with a 1% hydrochloric acid to separate free acidic (-) - allethrolonyl phthalate split, which is then extracted with ether. The aqueous layer is with a Made basic 5% aqueous sodium hydroxide solution, whereupon oily (-) -a-phenyl- / i-p-tolylethylamine is recovered. The ether layer is washed with water, dried and reduced under reduced pressure Pressure restricted. This gives 4.60 g of acidic (-) -Allethrolonylphthalat in the form of a very viscose oil, [«]? -49.6 ° (in ethanol).

c) This step is carried out as in Example 1 and leads to the same result.

Example 3

a) 18.0 g of acid (±) -allethrolonyl phthalate and 12.6 g of (-) - a-phenyl - /? - p-tolylethylamine are in 80 ml of benzene dissolved. The solution is left to stand at room temperature overnight. The rainfall are filtered and washed with benzene. This gives 8.7 g of colorless crystals, F. 128- 129 ° C.

b) The salt is treated in the same way as in Example 1, with 5.0 g of acid (-) - allethrolonyl phthalate can be obtained in the form of a very viscous oil, [α]? -50.2 ° (in ethanol).

c) This step is carried out in Example 1 and gives the same result.

Example 4

a) 18, Og acid (±> -Allethrolonylphthalat and 12.6 g (-) - o-Pheiryl - ^ - p-tolyläihylamm are dissolved in 80 ml of a mixture of benzene and n-hexane (4: 1), whereupon the The precipitated salt is filtered, washed and recrystallized from 80 ml of the above solvent to give 10.6 g of the pure salt, mp 126.5-128 ° C.

b) The salt is treated in the same way as in Example 1. This gives 6.1 g of acid (-) - Allethrolonyl phthalate in the form of a very viscous oil, [«]? -47.2 ° (in ethanol).

ι ο c) This stage is done in the same way as in the example 1 and gives the same result.

Example 5

a) 18.0 g of acid (±) -AllethrolonyIphthalat and 14.4 g - d (-) -threo-1 - (p-nitrophenyl) -2-N, N-dimethylaminopropane-1,3-diol are in a hot mixture of 60.0 g of isopropyl ether and 80.0 g of methanol, whereupon the solution is cooled to room temperature. The precipitates are filtered and twice recrystallized from the same solvent to give 10.10 g of the pure salt, mp 98-101 ° C; [α] ί? -33.51 ° (in methanol).

b) The salt is mixed with 1% hydrochloric acid to release acidic (-) -Allethrolonyl-

split phthalate, which is extracted with ether. The ether layer is washed with water and dried over anhydrous magnesium sulfate and concentrated. 5.50 g of acid (-) -Allethrolonylphthalat are obtained in the form of a very viscous oil [a]% -47.3 (in ethanol).

c) This stage is carried out as in Example 1 and gives the same result.

Example 6

a) To a hot mixture of 80 g of toluene and 30 g of η-hexane, 18.0 g of acidic (±) -allethrolonyI-phthalate and 10.3 g of (-) - a- (2-naphthyl) ethylamine are added, whereupon the mixture is cooled to room temperature. The precipitated salt filtered vrird, washed and dried in a desiccator to obtain 6.50 g of colorless crystals are obtained, mp 113- 115 ⁰ C; {avi + 9.93 ° (in ethanol).

b) The salt is treated with 1% hydrochloric acid to separate acidic (+) -allethroionyl phthalate split, which is then extracted with ether. The ether layer is washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give 4.10 g acid (+) -allethrolonylphthalate in the form of a very

viscous oil are obtained; [a] F + 41.7 ° (in ethanol).

c) 9.7 g of acid (+) -Allethrolonylphthalat, [α]? + 48.7 ° (in ethanol), 50.0 g of water and 1.37 g of sodium bicarbonate are heated to 100 ° C for 10 hours and then treated in practically the same way as in Example 1, with 4.5 g of an optically active Allethrolons are obtained; {ä $ g + 6.8 ° (in ethanol).

7096T4 / 353

Claims (1)

Claim: The invention relates to a process for the production of optically active allethrolone (2-allyl-4-hydroxy-S-methyW-cyclopentenone), the process for the production of optically active net is characterized by the fact that the phthalic acid ester of 2-AlIyI-Aliethrolon, characterized, 5 4-hydroxy-3-methyl-2-cyclopentenons (allethrolons) that the phthalic acid ester of 2-allyl-4-hy- the formula droxyO-methyW-cyclopentenons (Allethrolons) the formula