Description:Technical Field of the Invention
The present invention relates to an improved process for the preparation of female sex pheromone (11E)-hexadecenyl acetate, the major component of Brinjal moth Leucinodes orbonalis particularly Brinjal fruit and shoot Borer (BFSB).

Background of the Invention
Brinjal belongs to Solanaceae family and is popular and economically important vegetable crop among small scale farmers. In India, brinjal is grown throughout the year with an area of 7.05 thousand hectare. Among the insect pests infesting brinjal, the major ones are shoot and fruit borer, Leucinodes orbonalis Guenee; whitefly, Bemicia tabaci; leafhopper, Amrasca biguttula biguttula; Epilachna or hadda beetle, Henosepilachna vigintiocto punctata and non-insect pest, red spider mite, Tetranychus macfarlanei and Tetranychus urticae Koch. Out of all these Brinjal Shoot and Fruit Borer (BSFB), L. orbonalis is the key brinjal moth found throughout Asia.

A blend of (E)-11-hexadecenyl acetate and (E)-11-hexadecenol respectively in 100:1 blend ratio, constitute the female released sex pheromone system of brinjal shoot and fruit borer (Leucinodes orbonalis) insect pest. Sex pheromone mediated mass trapping of brinjal shoot and fruit borer is one of the latest Integrated Pest Management (IPM) tools developed to protect the brinjal crop from economic losses caused by brinjal shoot and fruit borer insect pest. Improved process technology for large scale production of (E)-11-hexadecenyl acetate is of commercial significance.

D Michael Jackson et al., J Economic Entomology, 91(4), 950-963, 1998 & convenient synthesis of (E)-l 1-hexadecenyl acetate discloses the female sex pheromone of the brinjal moth Leucinodes orbonalis Guenee (Neelakanthi E Gunawardena, J. Natn. Sci. Coun. Sri Lanka, 1992, 20(1): 71-80), the draw backs are percentage yield very low i.e., 27% and are highly sensitive and expensive reagents and solvents.
Another art of Synthesis of insect sex pheromones Clive A. Henrick, Tetrahedron, 1977, 33: 1845-1889, where in synthesis of long chain trans- alkenes (C10-C16) alcohols, acetates and aldehydes were reported using excess of lithium amide in tetrahydrofuran or n-butyl lithium in hexane for alkylation reactions and sodium in large quantities of liquid ammonia and ether or lithium aluminium hydride in diglyme for selective trans reduction of triple bonds. The drawbacks are less yields & purities, and are highly expensive and sensitive that are not suitable for large scale production of (E)-11-hexadecenyl acetate.

CSIR in 659/DEL/2006 application discloses an improved process for the preparation of (E)-ll-hexadecen-1-ol (STR-I) and (E)-ll-hexadecenyl acetate (STR-II). More particularly, the present invention relates to a process for the preparation of (E)-ll-hexadecen-l-ol (STR-I) and (E)-l 1-hexadecenyl acetate (STR-II) in multi-gram batch scale against the reported milligram batch size.
Barrix Agro Sciences Private Limited in 4860/CHE/2015 discloses Z-11-hexadecenyl acetate using phosphonium salt.

Therefore, there is a need to develop a novel method for synthesizing the sex pheromone of the Brinjal moth that has fast and mild reaction conditions with good environmental compatibility that have economic significance with high yields.

Brief Summary of the Invention
An object of the invention is to provide an improved process for the preparation of female sex pheromone of 11E-hexadecenyl acetate, the major component of brinjal moth Leucinodes orbonalis.

Another object of the invention is to aim at a kind of raw material of offer is cheap and easy to obtain, simple synthetic route & reaction conditions. The sex pheromone 11E-hexadecenyl acetate of Leucinodes orbonalis which is synthesized is economic with high purity & stereoselectivity.
Detailed Description of the invention
Main object of the present invention is to provide a novel synthetic route of a sex attractant the PTB pheromone, namely 11E-Hexadecenyl acetate using n-hexanal and Malonic acid.

The invention aims to provide a novel method for synthesizing sex pheromone of Brinjal moths particularly Brinjal fruit and shoot Borer (BFSB).

The present invention provides a kind of synthetic method of namely 11E-Hexadecenyl acetate, which comprises the stepsof：

a. Condensation of n-hexanal and Malonic acid in presence of base triethyl amine or DMF (N,N di-methyl formamide) to generate 3E-Octenoic acid, more preferably triethylamine;
b. Reducing 3E-Octenoic acid in presence of Vitride or sodium borohydride or Lithium aluminium hydride to obtain 3E-octen-1-ol, more preferably vitride;
c. Chlorination of 3E-octen-1-ol using Thionyl chloride, or PCl3/POCl3, to more preferably thionyl chloride, to obtain 1-chloro-3E-octene;
d. Carrying out coupling of 1-chloro-3E-octene and 1-tertiary butoxy 8-Bromo octane with Grignard reagents to obtain 1-Tertiary butoxy-11E-hexadecene; and
e. Acetylation of 1-Tertiary butoxy-11E-hexadecene using acetyl chloride or acetic anhydride to obtain 11E-Hexadecenyl acetate.

The resultant sex pheromone 11E-Hexadecenyl acetate is utilized for manipulating behavior of female brinjal fruit and shoot borer.

The method for synthesizing the sex pheromone of the brinjal moth is detailed herein below:.

1. Synthesis of 3E-Octenoic acid (5):
Condensation of n-Hexanal & Malonic acid was carried out under nitrogen atmosphere at room temperature, in presence of base Triethyl amine at high temperature of about 80°C, continued the stirring of mixture then cooled, separated organic and aqueous layer by addition of HCl & MTBE to obtain 3E-Octenoic acid.

2. Synthesis of 3E-octen-1-ol (4):
Reducing 3E-Octenoic acid with a reducing agent Vitride (Red-Al® sodium bis(2-methoxyethoxy)aluminum hydride)or Sodium borohydride or Lithium aluminium hydride to obtain 3E-octen-1-ol , most preferably Vitride is used.

3. Synthesis of 1-Chloro-3E-Octene (3):
Simple chlorination of 3E octane-1-ol was carried out using chlorinating reagents Thionyl chloride or PCl3 or POCl3 or PCl5, in the presence of base media triethylamine, under reflux temperatures to obtain 1-Chloro-3E-Octene, most preferably thionyl chloride is used.

4. Synthesis of 1-Tertiary butoxy-11E-hexadecene (2):
Grignard coupling reaction was carried out using magnesium turnings & Iodine to 1-chloro-3E-octene 1-tertiary butoxy 8-Bromo octane under nitrogen atmosphere, at reflux temperatures to obtain 1-Tertiary butoxy-11E-hexadecene. These coupling reactions are carried out to extend carbon chain without disturbing the position of E-type double bond, that have the advantages of simple synthetic route, mild reaction condition, good environmental compatibility and the like.

5. Synthesis of 11E-Hexadecenyl acetate (1):
Simple acetylation reaction of 1-Tertiary butoxy-11E-hexadecene wascarried out using acetylating reagent like acetyl chloride or acetic anhydride, more preferably acetyl chloride is used to obtain 11E-Hexadecenyl acetate.

The present synthesis route of sex pheromone of brinjal moth Leucinodes orbonalis particularly Brinjal fruit and shoot Borer (BFSB) resulted under mild reaction conditions, simple reaction route, and low reagent toxicity and good environmental compatibility, has important theoretical significance and application value.

Scheme 1: Illustrates the synthesis of 11E-Hexadecenyl acetate

Characterization of 11E-Hexadecenyl acetate:
1H NMR (CDCl3, 400 MHz, δ ppm): 5.43-5.33 (m, 2H), 4.02 (t, 2H), 2.08 (s, 3H), 1.98 (m, 4H), 1.64 (m, 2H), 1.4 (m, 2H), 1.3 (m, 4H), 0.88 (t, 3H).

Experimental details:

Example 1. Synthesis of 3E-Octenoic acid (5):
Triethyl amine (151g) & Malonic acid (103.8g) were charged in RBF under nitrogen atmosphere at RT, followed by addition of n-Hexanal (100 g) and stirred at 80°C, continued stirring the mixture for 4 hrs, cooled the mixture and added 800ml of 1N HCl and 500 ml of MTBE, stirred and separated both organic and aqueous layers, aqueous layer is extracted with MTBE (200ml), dried and distilled off the organic layer under vacuum to obtain 3E-Octenoic acid (130 g) with yield >95% and analyzed by GC with purity >90% .

Example 2. Synthesis of 3E-Octen-1-ol (4):
Charged Red-AL (405 g) in RBF under nitrogen atmosphere at RT along with Toluene (400 ml), stirred and cooled to 10 °C, slowly added 3E-Octenoic acid (100 g) at 10°-15°C, stirred followed by addition of HCl solution (1.0Lt) and MTBE (200 ml), separated the MTBE layer and dried with sodium sulphate (20gr) and distilled off the MTBE layer under vacuum to obtain 3E-octen-1-ol (45 g) with yield >50% and analyzed by GC with purity >94.0%.

Example 3. Synthesis of 1-Chloro-3E-Octene (3):
Charged MDC(400ml) and 3E-Octene-1-ol(100g) in RBF and cooled 10 °C, added TEA(94.7g), and stirred, followed by addition of Thionyl chloride (120.8g), heated to reflux, and stirred for 4 hrs, then cooled to RT, quenched the mass in to water (400ml) and separated aqueous and organic layers, and extracted the aqueous layer with MDC (200ml), neutralized the MDC layer with 10% sodium bicarbonate solution 200ml, dried and distilled of MDC under vacuum to obtain 1-Chloro-3E-Octene (80gr) with Yield >70 % and analyzed by GC with Purity of >95.0 %.

Example 4. Synthesis of 1-Tertiary butoxy-11E-hexadecene (2):
Charged Magnesium turnings (17.2g) under nitrogen atmosphere and added THF(50ml) slowly into the reactor at 65°C under nitrogen atmosphere, and charged Iodine (0.5gr), 1,2-dibromoethane (1ml) and 1-chloro-3E-octene (100gr) in THF(100ml), stirred under reflux, and cooled the Grignard reagent to 30°C & charged THF(145gr) in another RBF add 1-tertiary butoxy 8-Bromo octene (145 gr) and add copper iodide to THF. Add above prepared Grignard reagent to the mass at 10°C , stir and quench the mass with 10% Sulphuric acid solution, then separated both aqueous and organic layers, charged MTBE(200ml) to the aqueous layer for extraction, washed the combined MTBE and THF layers with brine solution(200ml), distilled off organic layer under vacuum to obtain 1-Tertiary butoxy-11E-hexadecene (80g) with yield >49.5% and analysed by GC with Purity of >94.0 %.

Example 5. Synthesis of 11E-Hexadecenyl acetate (1):
Charge Acetic acid (300 ml) and 1-Tertiary butoxy-11E-hexadecene(100g) in RBF, add acetyl chloride (39.7g) at RT and stir the mass for 5hrs at 50-55°C and add water(500ml) and MTBE (200ml), stir and separate both organic and aqueous layer, extract MTBE distil off organic layer under vacuum to get 11E-Hexadecenyl acetate (85 g) yield >90.0% and analysed by GC with purity >94.0%
, Claims:
1. A novel method for synthesizing sex pheromone of Brinjal moth 11E-Hexadecenyl acetate is characterized by comprising the following steps: condensation of n-hexanal and Malonic acid in presence of base triethyl amine or DMF (N,N di-methyl formamide) to generate 3E-Octenoic acid; then reducing 3E-Octenoic acid in presence of Vitride or Sodium borohydride or Lithium aluminium hydride to obtain 3E-octen-1-ol; followed by chlorination using Thionyl chloride, or PCl3/POCl3; and then carrying out coupling of 1-chloro-3E-octene and 1-tertiary butoxy 8-Bromo octane with Grignard reagents; finally carrying out acetylation of and 1-Tertiary butoxy-11E-hexadecene using acetyl chloride or acetic anhydride to obtain 11E-Hexadecenyl acetate.

2. The method of synthesis as claimed in claim 1, wherein the condensation is carried out in presence of triethylamine preferably.

3. The method of synthesis as claimed in claim 1, wherein the reducing agent utilized is Vitride.

4. The method of synthesis as claimed in claim 1, wherein the chlorination is carried out by Thionyl chloride preferably.

5. The method of synthesis as claimed in claim 1, wherein the acetylation is carried out by acetyl chloride preferably.

6. The method of synthesis as claimed in claim 1, wherein the coupling is carried out by known Grignard reagents.