Method for producing (E,Z)-7,9-dodecadienyl-1-acetate

Abstract

The present invention concerns a method to access (E,Z)-7,9-dodecadienyl-1-acetate in two synthesis steps with excellent yields and selectivity greater than 70% by transformation of 2-hexenal into a novel intermediate, which is itself then transformed into (E,Z)-7,9-dodecandienyl-1-acetate.

Claims

1. A compound of formula 1 ##STR00011## where R1 and R1, identical or different, designate an alkyl or aryl group, wherein the compound of formula 1 is an (E,Z) isomer.

2. The compound according to claim 1, wherein the alkyl group is chosen from linear or branched C1-C6 alkyls and the aryl group is chosen from among phenyl, benzyl, mesityl or tolyl.

3. A method for synthesis of (E,Z)-7,9-dodecadienyl-1-acetate, said method comprising: providing, as an intermediate, a compound 1 according to claim 1 in a solvent; adding a catalytic system containing at least one iron atom at oxidation degree III; adding, at a temperature T3 comprised between 20 C. and 60 C., a compound of the formula XMg(CH.sub.2).sub.6OMgX where X and X are identical or different and designate a halogen atom; adding an acetylation agent; and recovering (E,Z)-7,9-dodecadienyl-1-acetate after washing and evaporation.

4. The method according to claim 3, wherein the solvent includes at least THF, MeTHF, methylcyclohexane (MeCy), diethyl ether, methyl tert-butyl ether, 1,2-dimethoxyethane or mixtures thereof.

5. The method according to claim 3, wherein the temperature T3 is comprised between 0 C. and 30 C.

6. The method according to claim 3, wherein the catalytic system includes iron trihalides, iron triacetate, iron tris-aceytlacetonate, iron (III) nitrate, or iron (III) phosphate.

7. The method according to claim 6, wherein the iron trihalides, iron triacetate, iron tris-aceytlacetonate, iron (III) nitrate, or iron (III) phosphate is in the presence of ligands chosen from phosphorus or nitrogen ligands.

8. The method according to claim 6, wherein the catalytic system is present at 0.5 mol % to 2 mol % with respect to the solvent and compound of formula 1, wherein the temperature T3 is between 5 C. and 25 C., wherein X and X are each a chlorine or bromine atom, wherein the acetylation agent is acetoyl halides, acetic anhydride or alkyl acetate, and wherein the washing is performed with an aqueous acid solution at a pH between 2 and 6 then with a solution at a pH between 7 and 9.

9. A composition including at least 70% of the E,Z isomer of the compound of claim 1.

Description

EXAMPLES

(1) The raw materials and solvents are raw materials available commercially from Sigma Aldrich.

(2) 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 an Innowax 30 m, 0.25 mm, 0.25 m column with helium as the vector gas.

(3) The furnace follows the following temperature profile: T0=150 C., Initial time 10 min. Gradient 20/min; Final temperature: 200 C. Duration 7 min.

(4) The injector is at 250 C., the detector at 300 C.

(5) The volume injected is 1 L. The concentration of the sample is 4 g/L in ethyl acetate (EtOAc).

(6) The reactions are performed in a 2 L double-walled glass reactor provided with a low-temperature cooling system and the distillations are performed by means of a 10 theoretical-plate glass column.

Example 1: Preparation of the Key Intermediate with R1 and R1=Ethyl

(7) In a reactor provided with stirring, 50 g (0.51 moles) of 2-hexenal diluted in 10 volumes of a 3-2 mixture of THF and NMP (S1) are prepared, the reaction medium temperature is lowered to a temperature T1 of 15 C., and then 69 g (0.61 moles) of potassium tert-butoxide are added. At the end of one hour, at temperature T2, still 15 C., 97 g (0.56 moles) of diethyl chlorophosphate are added. The reaction is stirred for one hour and then the product formed is isolated by washing with a sodium hydroxide solution that permits obtaining 500 g of a solution of enol phosphate in THF. The solution is dried on MgSO.sub.4 until the residual water content is less than 0.1%, the content in enol phosphate is assayed by gas chromatography. This solution may be used as such in the following examples.

(8) Compound 1 is isolated by evaporation of the solvents under partial vacuum. 105 g of diethyl-hexa-1,3-dien-1-yl phosphate are recovered in the form of a mixture of two isomers in the following ratio:

(9) Z,Z-diethyl-hexa-1,3-dien-1-yl phosphate: <1%

(10) Z,E-diethyl-hexa-1,3-dien-1-yl phosphate: <1%

(11) E,Z-diethyl-hexa-1,3-dien-1-yl phosphate: 72%

(12) E,E-diethyl-hexa-1,3-dien-1-yl phosphate: 27%

(13) Characterization:

(14) Retention time by gas chromatography: Z,Z-diethyl-hexa-1,3-dien-1-yl phosphate: 13.96 min; Z,E-diethyl-hexa-1,3-dien-1-yl phosphate: 14.27 min; E,Z-diethyl-hexa-1,3-dien-1-yl phosphate: 14.43 min; E,E-diethyl-hexa-1,3-dien-1-yl phosphate: 15.27 min.

(15) RMN .sup.1H ( ppm, CDCl.sub.3): 6.65 (1H, doublet of doublet, CH); 6.26 (1H, triplet, CH); 5.79 (1H, triplet, CH); 5.4 (1H, doublet of triplets), 4.15 (4H, triplet, OCH.sub.2), 2.11 (2H, multiplet, CH.sub.3CH.sub.2), 1.33 (6H, triplet, CH.sub.3CH.sub.2O), 0.97 (3H, triplet, CH.sub.3CH.sub.2CH).

Example 2: Synthesis of (E,Z) 7,9-Dodecadienyl-1-Acetate

(16) 1.8 g (5.1) mmol of iron tri(acetylacetonate) are added to the intermediate solution of Example 1 and then 0.61 moles of BrMg(CH.sub.2).sub.6OMgBr in solution at 1.6 mol/L in MeTHF are poured gently into the reactor. During this addition, the reaction medium is kept at temperature T3 of 25 C. After two hours, 260 g of acetic anhydride are added to the reaction medium, which is now kept stirred at room temperature, until total conversion of the alkoxide formed during iron coupling.

(17) The reaction medium is then washed with a 0.01 molar hydrochloric acid solution, and then with a sodium carbonate solution at a pH of 8. The organic phase is recovered and then concentrated under vacuum to recover crude 7,9-dodecadienyl-1-acetate (88 g assayed at 90% chemical purity and in an E,Z/Z,Z isomer ratio of 76%). I.e., a crude yield of 69% relative to hexenal.

(18) The crude is distilled under high vacuum to give 75 g of 7,9-dodecadienyl-1-acetate with 98% chemical purity and an E,Z isomer content of 76%. I.e., a yield of 66% relative to hexenal.

(19) Enrichment in E,Z Isomer:

(20) The 75 g obtained are mixed with 130 g of urea in 800 ml of methanol. The mixture is left to rest for 3 hours. The suspension is filtered and the residue is washed twice with 100 ml of diethyl ether. The washing fractions are collected with the filtrate and then evaporated under low pressure until complete evaporation of the solvents. 61 g of 7,9-dodecadienyl-1-acetate are obtained, of a chemical purity of 98% and with a content of 90% E,Z isomer.

Examples 3 to 20

(21) In all of the following examples, the experimental protocol of Examples 1 and 2 is used, varying the following parameters: S1: hexenal dilution solvent. S2: diethyl-hexa-1,3-dien-1-yl-phosphate dilution solvent. S3: magnesium compound dilution solvent X: halide of compound XMg(CH.sub.2).sub.6OMgX T1: hexenal deprotonation temperature T2: diethyl-hexa-1,3-dien-1-yl-phosphate synthesis temperature T3: organomagnesium coupling temperature N1=number of moles of potassium terbutanolate/number of moles hexenal N2=number of moles of diethyl chlorophosphate/number of moles of hexenal N3=number of moles of magnesium/number of moles of hexenal

(22) The parameters varying in the examples are summarized in Table 1

(23) TABLE-US-00002 N2 N4 N4 Example S1* S2 S3 X T1 T2 T3 (mol) (mol) (mol) 3 THF/NMP THF THF Br 78 78 0 1.2 1.1 1.2 (17/12) 4 THF/NMP THF MeTHF Br 70 78 0 1.2 1.2 1.2 (36/12) 5 THF/NMP THF MeTHF Br 55 78 0 1.1 1.1 1.2 (36/17) 6 THF/DMPU THF MeTHF Br 35 78 0 1.2 1.1 1.2 (36/17) 7 THF/NMP THF MeTHF Br 25 0 25 1.2 1.1 1.2 (36/17) 8 THF/NMP THF MeTHF Br 15 0 0 1.2 1.1 1.2 (36/17) 9 THF/NMP THF MeTHF Br 15 15 0 1.2 1.1 1.2 (36/17) 10 THF/DMPU THF MeTHF Br 15 15 0 1.2 1.1 1.2 (36/17) 11 THF/TMEDA THF MeTHF Br 15 15 0 1.2 1.1 1.2 (36/17) 12 THF/NMP THF MeTHF Br 15 10 0 1.2 1.1 1.2 (36/17) 13 THF/NMP THF MeTHF Br 15 0 0 1.2 1.1 1.2 (36/17) 14 MTBE/NMP MTBE MeTHF Br 15 15 25 1.2 1.1 1.2 (36/17) 15 MeCy/NMP MeCy MeTHF Br 15 15 0 1.2 1.1 1.2 (36/17) 16 MeCy/NMP MeCy MeTHF Br 15 15 25 1.2 1.1 1.2 (10/2) 17 THF/DMF THF MeTHF Br 15 15 25 1.2 1.1 1.2 (36/12) 18 DMF/NMP THF MeTHF Br 15 15 30 1.2 1.1 1.2 (14/2) 19 DMF/NMP THF THF Br 15 15 25 1.2 1.1 1.2 (14/2) 20 DMPU/NMP THF THF Br 10 10 20 1.2 1.1 1.2 (14/2) 21 DMPU/NMP THF THF Br 10 10 25 1.2 1.1 1.2 (2/2) 22 NMP 5V THF THF 5 5 25 1.2 1.1 1.2 23 NMP 5V THF THF 5 0 25 1.2 1.1 1.2 *the solvent mixture is indicated: the figures in parentheses designate the respective volumes of solvent components relative to hexenal.

(24) The crude yield (C.sub.Y) of each example reflects the crude molar yield before distillation.

(25) The C.sub.Y(E,Z) ratio designates the proportion of E,Z isomer relative to E,E isomer.

(26) The C.sub.Y and C.sub.Y(E,Z) data respectively designate the molar yield and the proportion of E,Z isomer relative to E,E isomer after the purification step.

(27) These results for each example are summarized in Table 2:

(28) TABLE-US-00003 Example Yc (%) Yc.sub.(E,Z) (%) Yield (%) Yield.sub.(E,Z) (%) 3 63 80 61 85 4 62 80 60 85 5 59 79 50 86 6 61 74 51 86 7 59 77 51 82 8 61 74 52 81 9 59 74 49 81 10 49 57 ** ** 11 42 66 ** ** 12 59 74 24 91 13 44 63 ** ** 14 51 74 ** ** 15 62 74 49 81 16 44 65 ** ** 17 65 74 52 80 18 14 72 ** ** 19 14 72 ** ** 20 38 66 ** ** 21 38 66 ** ** 22 25 57 ** ** 23 25 57 ** ** ** the experiments have not been purified