Novel Composition Of 7,9-Dodecadienyl-1-Acetate Isomers And Process For Production Thereof

Abstract

The present invention relates to a process for preparing a mixture M1 of enol phosphate isomers devoid of (E,E) isomer and comprising at least 98% of (E,Z) isomer, at least 0.1% of (Z,Z) isomer and at least 0.1% of (Z,E) isomer, comprising bringing a mixture of isomers of said enol phosphate comprising a detectable amount of (E,E) isomer into contact with a hydrolysable dienophile in an organic solvent, followed by base hydrolysis of the medium obtained and elimination of the adduct formed, in order to obtain the mixture M1 devoid of (E,E) isomer.

Claims

1. A process to obtain an isomer mixture M2 of a compound of formula 3. ##STR00014## wherein R.sub.2 is a linear alkyl group comprising 1 to 8 carbon atoms, R.sub.3, R.sub.4 and R.sub.5 are independently chosen from among H and CH.sub.3, R.sub.6 represents a linear or branched C.sub.1-C.sub.6 alkyl group, wherein its isomeric purity is greater than or equal to 98% in (E,Z) isomer and wherein it contains at least 0.1% of (Z,E) and (Z,Z) isomers and less than 1% of (E,E) isomer, comprising the steps of: a) Contacting a mixture of enol phosphate isomers of formula 1 ##STR00015## wherein R.sub.1 and R′.sub.1 independently designate an alkyl group comprising 1 to 6 carbon atoms or an aryl group, and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as defined above, with a hydrolysable dienophile D, wherein the mixture of enol phosphate isomers of formula 1 comprises a detectable quantity of (E,E) isomer, and wherein the detectable quantity is a quantity above 0.1%, b) Basic hydrolysis of the medium obtained in step a) and elimination of the adduct formed to obtain a mixture M1 of enol phosphate isomers of formula 1, free of (E,E) isomer and comprising at least 98% of (E,Z) isomer, at least 0.1% of (Z,Z) isomer and at least 0.1% of (Z,E) isomer, and c) Contacting the mixture M1 of enol phosphate isomers of formula 1 free of (E,E) isomer and comprising at least 98% of isomer (E,Z), at least 0.1% of (Z,Z) isomer and at least 0.1% of (Z,E) isomer obtained at step b) with a compound XMg-R.sub.6-OMgX, wherein each X independently represents a halogen atom, and RB represents a linear or branched C.sub.1-C.sub.6 alkyl group, and then contacting the mixture obtained with an acylation agent.

2. The process according to claim 1, wherein enol phosphate of formula 1 is a compound of formula 2. ##STR00016## R.sub.1 and R′.sub.1 having the same meaning as in claim 1.

3. The process according to claim 1, wherein the step a) is performed at a temperature T equal to 70° C.

4. The process according to claim 1, wherein the hydrolysable dienophile D is maleic anhydride.

5. The process according to claim 1, wherein the step a) is performed in an organic solvent S which is methylcyclohexane.

6. A mixture M1 of (E,Z), (Z,E), and (Z,Z) enol phosphate isomers of formula 1 as defined in claim 1, having an isomeric purity greater than or equal to 98% in (E,Z) isomer and containing at least 0.1% of (Z,E) and (Z,Z) isomers.

7. The mixture M1 according to claim 6, wherein the enol phosphate of formula 1 is diethyl-hexa-1,3-dien-1-yl phosphate.

8. An isomer mixture M2 of a compound of formula 3 ##STR00017## wherein R.sub.2 is a linear alkyl group comprising 1 to 8 carbon atoms, R.sub.3, R.sub.4 and R.sub.5 are chosen independently from H and CH.sub.3, R.sub.6 represents a linear or branched C.sub.1-C.sub.6 alkyl group, having an isomeric purity greater than or equal to 98% in (E,Z) isomer and containing at least 0.1% of (Z,E) and (Z,Z) isomers and less than 1% of (E,E) isomer.

9. The mixture M2 according to claim 8, wherein the compound of formula 3 is 7,9-dodecadienyl.

10. The process according to claim 1, wherein the enol phosphate isomer mixture comprising a detectable quantity of (E,E) isomer of step a) is obtained from (E) hex-2-enal.

11. The process according to claim 1, wherein the dienophile D is selected from the group consisting of maleic acid, acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, n-propyl acrylate, n-butyl acrylate, methyl methacrylate, ethyl methacrylate, n-propyl methacrylate, n-butyl methacrylate, dimethyl maleate, diethyl maleate, and maleic anhydride.

12. The process according to claim 1, wherein the acylation agent is chosen in the group comprising acetoyl halides, acetic anhydride and alkyl acetates.

Description

EXAMPLES

[0075] The raw materials and solvents are raw materials available commercially from Sigma Aldrich.

[0076] The enol phosphate (diethyl-hexa-1,3-dienyl phosphate) is synthesized by applying the process described in WO2016001383.

[0077] The Grignard reagent is prepared from 6-chloro-hexan-1-0l, n-butyl magnesium chloride and magnesium.

[0078] The analytical method consists of gas chromatography (GC) analysis on a HP 5890 Series II device equipped with a FID detector. The chromatographic column is a Innowax 30 m, 0.25 mm, 0.25 μm column, the carrier gas is helium and the pressure is 11 psi.

[0079] The furnace follows the following temperature profile: T0=150° C., Initial time 10 min.

[0080] Gradient 20°/min; Final temperature: 200° C. Duration 7 min.

[0081] The injector is at 250° C., the detector at 300° C.

[0082] The volume injected is 1 μl. The concentration of the sample is 4 g/L in ethyl acetate (ETAC).

[0083] The reactions are conducted in a 20-L reactor with mechanical stirring (400 rpm), equipped with a thermometer and a nitrogen inlet. The system is cooled with a cryostat as necessary.

Example 1 (Non-Invention): Improvement of the Isomeric Purity of a Mixture of 7,9-dodecadienyl acetate Isomers by Treatment with Urea

[0084] A 20-L glass reactor is loaded with 2.94 kg (8.92 equiv.) of urea and 11.8 L (5.9 vol) of methanol then stirring is started while maintaining the temperature at 55±5° C. until complete dissolution of the solids.

[0085] 2065 g (1 equiv.) of a mixture of 7,9-dodecandienyl acetate isomers is added so that the internal temperature of the reactor does not go below 40° C. The temperature is maintained at 40±5° C. for one hour, then lowered to 20±5° C. in 3 hours. Crystallization starts during this cooling. The reaction mixture is then stirred at 20±5° C. for more than 12 h, then the temperature is lowered by 5° C. per hour until a temperature of 5° C. is obtained that is maintained for 2.5 h while continuing to stir. The solids are then removed by vacuum filtration of the reaction mixture. The products are then washed with methanol (500 ml) and concentrated by vacuum filtration, then washed with stirring with a mixture of water (2 vol) and MTBE (1.15 vol). After phase separation, the aqueous phase is removed and the organic phase is concentrated. 1334 g of a new mixture of 7,9-dodecadienyl acetate isomers is obtained, or a yield of 65%.

[0086] After this first inclusion in urea of 2065 g of a mixture of pheromone isomers, which leads to 1334 g of enriched pheromone, a second inclusion in urea is done in a 1-L reactor, with 100 g of the enriched batch (same protocol as the one described previously while keeping the proportionality of reaction agents). A third inclusion is then conducted with 62.6 g of doubly enriched pheromone isomer mixture still with the same protocol.

[0087] The isomeric purity of the products after one, two or three inclusions of urea is characterized by gas chromatography and the result presented in the table below is obtained.

TABLE-US-00002 Isomer Isomer Isomer Isomer (7Z, 9Z) (7Z, 9Z) (7Z, 9Z) (7Z, 9Z) Initial mixture of 0.86% 80.23% 1.13% 17.78% 7,9-dodecadienyl acetate isomers after first 1.33% 91.85% 1.35%  5.47% purification with urea after second 1.88% 92.78% 0.66%  4.68% purification with urea after third 2.75% 91.57% 0.35%  5.33% purification with urea

[0088] It is observed that such a treatment with urea is time-consuming and tedious and does not allow reaching very high purities, even by doing several successive purifications with urea Thus, after three successive treatments with urea following the protocol described previously, a ceiling is attained with around 5% of (E,E) isomer, furthermore, a part of the pheromone is degraded.

Example 2 (Non-Invention): Improvement of the Isomeric Purity of a Mixture of

7,9-dodecadienyl acetate Isomers by Direct Action of a Hydrolyzable Dienophile

[0089] Into a 250-mL four-necked flask are introduced 10 g of a mixture of 7,9-dodecandienyl acetate isomers (44.6 mmol) (isomeric purity given in the table below), 40 ml of methylcyclohexane and 4.37 g of maleic anhydride (hydrolyzable dienophile D) (44.6 mmol; 1.0 equiv.).

[0090] The reaction mixture is heated at T=70° C. for 3 hours and then cooled to 30° C., and a saturated NaHCO.sub.3 is added (1.14 M, 50 ml).

[0091] After 30 minutes with stirring, the aqueous phase is extracted with heptane (2×20 ml), washed with a saturated aqueous solution of NaCl (5.92 M, 20 ml) and then with water (20 mL), and concentrated under vacuum.

[0092] 7.5 of the purified pheromone mixture are obtained of isomeric composition:

TABLE-US-00003 Isomeric purity in % Isomers (7Z, 9Z) (7E, 9Z) (7Z, 9E) (7E, 9E) 7,9-dodecadienyl acetate 5.59 67.47 2.82 24.10 before treatment 7,9-dodecadienyl acetate 7.78 85.60 1.86 4.76 after treatment

[0093] This non-invention example illustrates two facts: [0094] 1) The Diels-Alder reaction does not lead to a total elimination of (E,E) isomer. [0095] 2) The mass yield of this step is 75%, which means that the previous costly step (coupling reaction of enol phosphate with the magnesium compound) has its real productivity reduced by 25%.

Example 3: Improvement of the Isomeric Purity of a Mixture of diethyl-hexa-1,3-dien-1-yl Phosphate Isomers by the Process According to the Invention Leading to Mixture M1

[0096] A mixture of diethyl-hexa-1,3-dienyl phosphate isomers is obtained from trans-hexen-1-al by following the process described in patent WO2016001383.

[0097] Into the 20-L reactor are introduced 2085 g of this crude mixture of diethyl-hexa-1,3-dienyl phosphate (8.90 mol) (isomeric purity given in the table below), 8.34 L of methylcyclohexane and 523.0 g of maleic anhydride (5.33 mol, or 0.6 equiv.).

[0098] The reaction mixture is heated at T=70° C. for 3 hours and then cooled to 10° C., and an aqueous sodium hydroxide solution is added (3 M, 4.17 L).

[0099] After 30 minutes with stirring, the aqueous phase is extracted with heptane (2×3.13 L), washed with a saturated aqueous solution of NaCl (10% w/w; 1×2.09 L) and concentrated under vacuum.

[0100] 1566 g of mixture M1 of diethyl-hexa-1.3-dienyl phosphate are obtained of isomeric composition:

TABLE-US-00004 Isomeric purity in % Isomers (1Z, 3E) (1Z, 3Z) (1E, 3Z) (1E, 3E) mixture before 1.03 1.07 73.60 24.30 treatment mixture after 0.74 0.81 98.45 0 treatment M1

Example 4: Obtaining Pheromone Mixture M2 from a Purified Mixture of diethyl-hexa-1,3-dien-1-yl Phosphate Isomers

[0101] From the enol phosphate mixture M1 of Example 3, the process described in WO2016001383A1 is applied to obtain pheromone mixture M2.

[0102] The following are introduced into the four-neck reactor, under nitrogen: the Grignard alcoholate reagent, prepared from 67.1 of de 6-chloro-hexan-1-ol (491.7 mmol), 474 ml of THF and magnesium (983.5 mmol).

[0103] The mixture is then cooled to 5° C. then the iron (111) acetylacetonate catalyst is added (158 mg, 0.1% mol). To this black mixture are added 97.5 g of preceding mixture M1 (416.3 mmol) in 20 minutes while keeping the temperature below 5° C.

[0104] After 2 h of stirring at 25° C., the mixture is cooled to −5° C. and 85 mL of acetic anhydride are added dropwise in 20 minutes. After one hour of stirring at room temperature, the reaction mixture is acidified by an aqueous HCl solution (1 N, 680 ml). The aqueous phase is extracted three times with methyl tert-butyl ether (3×120 ml). The three organic phases are recombined, then washed with water and concentrated under vacuum.

[0105] 7,9-dodecandienyl acetate mixture M2 is then obtained (m=65.7 g). The initial overall yield of purified enol phosphate is 70% (mass purity=95%; isomeric purity=98%)

TABLE-US-00005 Isomeric purity in % Isomers (1Z, 3E) (1Z, 3Z) (1E, 3Z) (1E, 3E) Mixture M1 0.74 0.81 98.45 0 Isomers (7Z, 9Z) (7E, 9Z) (7Z, 9E) (7E, 9E) Mixture M2 98.0 0.9