Claims:1. A process for preparation of a sex attractant pheromone, (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate and its intermediate using 1-hexyne as starting material which is characterized by:
a. reacting 1-hexyne with ethylene oxide in presence of THF solvent to obtain 3-octyn-1-ol,
b. converting the 3-octyn-1-ol into 7-octyn-1-ol in presence of EDA and sodium hydride,
c. halogenating the 7-octyn-1-ol in presence of a halogenating agent, toluene and KOH to yield 8-halo-oct-7-yn-1-ol, ,
d. acetylating the 8-halo-oct-7-yn-1-ol in presence of acetylating agent and a base in toluene to give 8-halo-7-octyn-1-yl acetate, ,
e. reacting the 8-halo-oct-7-yn-1-yl acetate with 1-chloro-3Z-octene in presence of Mg, CuI, and THF to give (Z)-11-Hexadecen-7-yn-1-yl acetate, ,
f. reducingthe (Z)-11-Hexadecen-7-yn-1-yl acetate into 7Z, 11Z-Hexadecadien-1-yl acetate in the presence of Nickle acetate, sodium borohydride, methanol and EDA,
g. isomerizing the (Z)-11-Hexadecen-7-yn-1-yl acetate into (E)-11-Hexadecen-7-yn-1-yl acetate in the presence of Sodium nitrite and Nitric acid,
h. reducing the (E)-11-Hexadecen-7-yn-1-yl acetate to 7Z, 11E-Hexadecadien-1-yl acetate in the presence of Nickle acetate, sodium borohydride, and EDA.

2. The process for preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate as claimed in claim 1, wherein the preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate comprise the preparation of 3-octyn-1-ol by reacting 1-hexyne with ethylene oxide in presence of THF solvent.
3. The process for preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate as claimed in claim 1, wherein the preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate comprise the conversion of 3-octyn-1-ol into 7-octyn-1-ol intermediate is carried out in presence of EDA, Sodium hydride.

4. The process for preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate as claimed in claim 1, wherein the halogenating agent is selected from bromine, chlorine, most preferably liquid bromine.

5. The process for preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate as claimed in claim 1, wherein the acetylating agent is acetic anhydride and base sodium bicarbonate.

6. The process for preparation of (Z, Z/Z, E) 7, 11- Hexadecadien-1-yl acetate as claimed in claim 1, wherein the (Z, Z/Z, E) 7, 11- Hexadcadien-1-yl acetate is sex attractant insect pheromone more specifically ofpink bollworm.
, Description:Technical Field of the Invention
The present invention relates to a process for the preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate using 1-hexyne as starting material through its intermediates, viz., 3-octyn-1-ol and/or 7-octyn-1-ol.

Background of the Invention
Gossyplure, a mixture of 7,11-hexadecadienyl acetate stereoisomers, is a known pheromone for several insect species. In order to make this compound widely available for use in insect control, economic large-scale synthetic conversion processes must be developed. While synthetic routes for the preparation of gossyplure have been disclosed in the prior art, the known routes suffer from the disadvantages of requiring multiple reaction steps with consequent low over all product yield, consumption of large quantities of reagents which do not contribute to the process economics and final product structure.

A multistep synthetic route for the preparation of gossyplure has been proposed by Muchowski and Venuti, as disclosed in U.S. 4,296,042 (1981). According to this synthetic method, (1) an omega-hydroxyalkyl diphenyl phosphine is converted into a cyclic polymethylene 1,1-diphenyl phosphonium bromide, - (2); the cyclic phosphonium bromide is then converted into a cyclic phosphonium ylid by treatment with an alkali metal alkoxide(3), then (3) is coupled with a protected aldehyde or ketone to produce a phosphine oxide. The phosphine oxide is (4) treated with an organolithium compound to obtain (5), then (5) is coupled with a second aldehyde (6) and finally (6) the resulting lithium salt is decomposed, producing a crude, protected diene-ol(7). The protected diene-ol is (7) hydrolyzed and esterified by treatment with acetic acid/acetyl chloride. Again, numerous reaction steps are required as the desired chain length and stereochemistry are achieved in a piecemeal fashion. In summary, due to the large number of reaction steps required, the relative unavailability of many required reagents and the step-wise fashion in which the desired carbon backbone is constructed, the known synthetic routes for the production of gossyplure are not amenable to carry out economically on a large scale.
While synthetic routes for the preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate pheromone have been disclosed in the prior art, the known routes suffer from the disadvantages of requiring multiple reaction steps with consequent low over all product yield, consumption of large quantities of reagents which do not contribute to the process economics and final product structure.

Therefore, it is an objective of the present invention to provide an efficient process for the preparation of (Z,Z/Z,E) 7,11- Hexadecadien-1-yl acetate pheromone using cheaper and readily available raw materials.

Brief Summary of the Invention
Accordingly, the exemplary embodiments of the invention provide a process for the preparation of (Z,Z/Z,E) 7,11- Hexadecadien-1-yl acetate pheromone and its intermediate using 1-hexyne as the starting material through the intermediates viz., 3-octyn-1-ol and 7-octyn-1-ol.

The (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate pheromone stereoisomers, is a known pheromone for several insect species. In order to make this compound widely available for use in insect control, economic largescale synthetic conversion processes must be developed.

Briefly, the present invention provides a simple three-step process for preparing functional group-containing olefinic compounds such as, for example, flavors, fragrances, and Semio-chemicals. As used herein, “Semio-chemical” means a chemical that conveys a signal from one organism to another, for example, in such a way as to modify the behavior of the recipient organism (including, for example, allomones, kairomones, synomones, and pheromones, which can have, for example, arrestant, attractant, repellent, deterrent, or stimulant properties).
The starting material, 1-hexyne employed for the preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate pheromone which makes use of readily available and inexpensive raw materials, and hence is easily scalable for industrial production. Furthermore, the inventors have recognized that it would be advantageous to have increased control over the stereoselectivity of the intermediate compounds in the preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate.

Brief Description of the Drawings
The present invention will be more readily understood from the detailed description of embodiments thereof made in conjunction with the accompanying drawings of which:

Fig. 1 – synthetic scheme of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate.

Detailed Description of the invention
The present invention to provide a novel process for preparation of a sex attractant, the pink bollworm pheromone, namely (Z,Z/Z,E) 7,11- Hexadecadien-1-yl acetate pheromone and its intermediates 3-octyn-1-ol, 7-octyn-1-ol using 1-hexyne as the starting material .

An embodiment of invention provides an efficient and economic process for the synthesis of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate sex pheromone and intermediates thereof, for attracting the pink bollworm moth.

Another embodiment of invention provides a process for preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate, sex pheromone, encompasses preparation of gossyplure intermediates, viz., 3-octyn-1-ol, 7-octyn-1-ol using 1-hexyne as starting material , which comprises the following steps:
A. reacting 1-hexyne with ethylene oxide in presence of THF solvent to obtain 3-octyn-1-ol,
B. converting the 3-octyn-1-ol into 7-octyn-1-ol in presence of EDA and sodium hydride.
The above process is shown in below schemes1 and 2. Scheme 1 illustrates the synthetic scheme of 3-Octyn-1-ol.
Scheme 1:

Scheme 2 illustrates the synthetic scheme of 7-Octyn-1-ol.
Scheme 2:

Accordingly, the invention provide method of preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate using 7-octyn-1-ol intermediate which process comprising the steps;

A. halogenating 7-octyn-1-ol in presence of halogenating agent to yield 8-halo oct-7-yn-1-ol, ,
B. acetylationg the 8-halo-oct-7-yn-1-ol in presence of acetylating agent and base to give 8-halo-7-octyn-1-yl acetate,
C. reacting the 8-halo-oct-7-yn-1-yl acetate with 1-chloro-3Z-octene Grignard reagent in presence of CuI, and THF as a solvent media to give (Z)-11-Hexadecen-7-yn-1-yl acetate,
D. reducing the (Z)-11-Hexadecen-7-yn-1-yl acetate in the presence of Nickle acetate, sodium borohydride, methanol and EDA to obtain 7Z, 11Z-Hexadecadien-1-yl acetate;
E. isomerizing the (Z)-11-Hexadecen-7-yn-1-yl acetate in the presence of Sodium nitrite and Nitric acid to obtain (E)-11-Hexadecen-7-yn-1-yl acetate ,
F. reducing the (E)-11-Hexadecen-7-yn-1-yl acetate in the presence of Nickle acetate, sodium borohydride, and EDA to obtain 7Z, 11E-Hexadecadien-1-yl acetate.
According to the present invention, the halogenating agent is selected from bromine, chlorine, iodine, most preferably liquid bromine.
According to the present invention, the acetylating agent is acetic anhydride and the base sodium bicarbonate.
The synthetic method for the preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate, is provided in scheme 3.
Scheme 3:

Accordingly, the exemplary embodiments of the invention provide method of preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate, sex attractant insect pheromone more specifically of pink bollworm.

Another embodiment of the invention provides method of preparation of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate that includes the conversion of 3-octyn-1-ol into 7-octyn-1-ol, which is carried out in presence of EDA, NaH, and solvent MTBE, wherein 3-octyn-1-ol is initially converted to (Z)-oct-3-en-1-ol in presence of EDA and methanol.

The present invention provides means for the synthesis of isomers of (Z,Z/Z,E) 7, 11- Hexadecadie-1-yl acetate, the preparation of isomeric mixtures thereof, and intermediates therefor.

Furthermore, in preferred embodiments, it has been identified by the present inventors that the stereoselectivity of the double bond forming step can be controlled by carefully choosing the starting compound. Surprisingly, when the substituents (that is, the three moieties other than the alkylidene moiety) are aryl groups or hetaryl groups, the process of the invention can provide a high yield of Z-configured functional group-containing olefins; when the substituents are alkyl groups or cycloalkyl groups, the process of the invention can provide a high yield of E-configured functional group-containing olefins. Thus, the invention provides processes for preparing pheromone compounds that can provide a high yield of a desired isomer.

The sex pheromone of the pink bollworm, Pectinophora gossypiella, is an approximate 1:1 mixture of (Z,Z)- and (Z,E)-7,11-hexadecadienyl acetate. This sex pheromone, the above-identified mixture of isomers, is known as Gossyplure. A component of Gossyplure, (Z,E)-7,11-hexadecadienyl acetate, is the sex pheromone of the Angoumois grain moth, Sitotroga cerealella, and is known as Angoulure. An isomeric component of Gossyplure, the Z,Z isomer, elicits no response from the male Angoumois grain moth and it appears that the relatively large amount of the Z,Z isomer in Gossyplure interferes with the Z,E isomer such that Gossyplure cannot be used as a substitute for Angoulure.

The isomeric components making up Gossyplure, i.e. (Z,Z)- and (Z,E)-7,11-hexadecadienyl acetate, are important materials. However, the isolation or recovery of (Z,Z/Z,E) 7, 11- Hexadecadien-1-yl acetate, is essentially not economical.

The following examples are presented to further explain the invention with experimental conditions, which are purely illustrative and are not intended to limit the scope of the invention.

EXAMPLES:
Example 1. Synthesis of 3-Octyn-1-ol:
Charged CH3MgCl (460 g) in 3M THF under nitrogen atmosphere to the flask, added 1-Hexyne (100 g) drop wise while stirring, cooled the reaction mixture to 0-5oC using an ice-salt bath and added ethylene oxide (80.5 g) dropwise, maintained temperature below 30oC, separated the organic layer, washed the organic layer with brine, extracted the aqueous layer with hexanes(400ml) to yield 3-Octyn-1-ol (117 g).
Yield: 76% with >98% purity (GC).

Example 2. Synthesis of 7-Octyn-1-ol from 3-Octyn-1-ol:
Charged Sodium hydride (95 g) under nitrogen, slowly added EDA (500 ml), raised the temperature of the reaction mixture to 60-65°C, cooled the mixture to 45°C and slowly added 3-octyn-1-ol (100 g) at 45-75°C, added MTBE (200 ml), stirred, separated both MTBE and aqueous layers, recovered the crude material under high vacuum distillation to yield 7-Octyn-1-ol (70 g).
Yield: 71%, with purity: 98.0 %

Example 3. Synthesis of (Z)-11-Hexadecen-7-yn-1-yl acetate:
Charged water at 25-30 °C and KOH flakes (222 g), added drop wise cooled liquid bromine (194 g) followed by slow addition of 7-octyn-1-ol (100 g), toluene (500 ml). After completion of the reaction by TLC, washed the toluene layer to yield 8-bromo oct-7-yn-1-ol, further Charged NaHCO3(98 g) to 8-bromo-7-octynol toluene layer added acetic anhydride (119 g), maintained the temperature at 70-75 °C for --hrs, filtered, washed with water, distilled off toluene to yield 8-bromo oct-7-yn-1-yl acetate (170 g). Dissolved 1-Chloro-3Z-Octene (100 g) in THF (400 ml) and charged Mg turnings (18 g), added Iodine (0.1 g), 1,2-dibromoethane (0.2 ml), stirred the reaction mixture under nitrogen atmosphere, cooled, and charged Copper iodide (4.1 g) and 8-bromo oct-7-yn-1-yl acetate (135 g), stirred to complete the coupling reaction, quenched the mass and extracted with MTBE (200 ml), separated the organic layer, washed with brine solution, evaporated the solvent to yield (Z)-11-Hexadecen-7-yn-1-yl acetate (74 g). Yield: 48%; with >92% purity.

Example 4. Synthesis of (Z, Z)-7, 11- Hexadecadien-1-yl acetate:
Reduction of (Z)-11-Hexadecen-7-yn-1-yl acetate (100 g), in presence of Nickle acetate (35 g), sodium borohydride (6.3 g), EDA (21 g) and methanol (500 ml), distill off methanol, extracted the product using toluene, distill of toluene under vacuum to yield (Z, Z)-7, 11- Hexadecadien-1-yl acetate (80 g). Yield: 80%; with >92% purity.

Example 5. Synthesis of (Z, E)-7, 11- Hexadecadien-1-yl acetate:
Charged (Z)-11-Hexadecen-7-yn-1-yl acetate (100 g), sodium nitrite (5 g) and nitric acid (15 g), in water (200 ml) and reacted at a temperature of 45 to 50°C for 1 hr to yield (E)-11-Hexadecen-7-yn-1-yl acetate (100 g).
Similarly, reduction of (E)-11-Hexadecen-7-yn-1-yl acetate (100 g), in presence of Nickle acetate (35 g), sodium borohydride (6.3 g), EDA (21 g) and methanol (500 ml), was carried out at a temperature of 25 to 30°C for 3 to4 hrs; distilled off methanol, extracted the product using toluene, distilled of toluene under vacuum to yield (Z, E)-7, 11- Hexadecadien-1-yl acetate (80 g). Yield: 80%; with >92% purity.