Claims:
1. A method of synthesizing methyl 2,6,10-trimethyltridecanoate (I), a sex attractant pheromone, comprising the steps of:
a) brominating citronellol (VIII) with bromine in presence of pyridine and MDC and triphenyl phosphine to yield 8-bromo-2,6-dimethyloct-2-ene (VII);
b) protecting 8-bromo-2,6-dimethyloct-2-ene (VII) with triphenyl phosphine in presence of acetonitrile and MTBE, followed by addition of 2-methyl pentanal (VI) in presence of THF to yield (Z)-2,6,10-trimethyl trideca-2,8-diene (V);
c) oxidation of (Z)-2,6,10- trimethyl trideca-2,8-diene (V) with SeO2 and tert-Butyl hydroperoxide (TBHP) in presence of MDC to yield (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (IV);
d) hydrogenation of (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (IV) in presence of Raney Nickel in methanol to yield 2,6,10-trimethyl tri deca-1-ol (III);
e) oxidation of 2,6,10-trimethyl tri deca-1-ol (III) with Tempo and sodium hypo chloride in presence of KBr, MDC to yield 2,6,10-trimethyl tri decanal (II); and
f) oxidation of 2,6,10-trimethyl tri decanal (II) with Oxone in presence of methanol to yield methyl 2,6,10-trimethyltridecanoate (I).

2. The method of synthesis as claimed in claim 1, wherein the extraction of stage wise compounds of step a) to f) are carried out in presence of Hexane.

3. The method of synthesis as claimed in claim 1, wherein the preparation of 8-bromo-2,6-dimethyloct-2-ene in step a) is carried out in presence of MDC at 0 to 5oC.

4. The method of synthesis as claimed in claim 1, wherein the methyl 2,6,10-trimethyltridecanoate (I) is sex attractant insect pheromone for Stink bug.
, Description:Technical Field of the Invention
The present invention relates to a method for synthesizing methyl 2,6,10-trimethyltridecanoate (I) which is a sex attractant, insect pheromone preferably of Stink bug.

Background of the Invention
In Insect Pheromone Synthesis in Brazil: An Overview J. Braz. Chem. Soc., Vol. 18, No. 6, 1100-1124, 2007 by Paulo H. G. Zarbin discloses the syntheses of insect pheromones developed and published by Brazilian research groups and aims to present the state of the art of this area in the country, and also to serves as a quick view of the already synthesized molecules and employed methodology. The syntheses are presented in chronological order, except when they refer to different approaches for the same molecule, after an allylic oxidation and two Wittig reactions, the pheromone 15 (12% overall yield) was obtained in good yields in scheme 17.

In J. Braz. Chem. Soc., Vol. 11, No. 6, 572-577, 2000 Synthesis of the Minor Sex Pheromone Component of Two Brazilian Soybean Stink Bugs (Het.: Pentatomidae), and an Analogue Compound by Paulo H. G. Zarbin discloses The stink bugs Euschistus heros and Piezodorus guildinii (Heteroptera: Pentatomidae) are economically important soybean pests in Brazil. An intriguing characteristic of these species is the fact that they use the same chemical compounds as sex pheromone, e.g., methyl 2,6,10- trimethyl dodecanoate (1) (minor) and methyl 2,6,10-trimethyltridecanoate (2). In order to investigate the specific biological function of these molecules and to increase the knowledge of the communication system of each species, we have synthesized the minor component 1 and an analogue compound, methyl 2,6,10-trimethyltetradecanoate (3). These compounds will be tested on indoor bioassay, in addition with the previously synthesized major component 2.

In the Liebigs Ann. Chem. 1994,1153-1160 discloses all of the eight possible stereoisomers of methyl 2,6,10-trimethyltridecanoate (l),the male-produced attractant pheromone of the South American soybean pest, Euschistus heros, and that of E. obscurus, are synthesized by starting from the enantiomers of citronellol (2) and methyl 3-hydroxy-2-methylpropanoate.

The first attractant pheromone identified for a member of this complex was that of the southern green stink bug, N. viridula (Baker et al., 1987). The chemical communication system of E. heros was elucidated by Aldrich et al. (1994), and evidence was presented that methyl 2,6,10-trimethyltridecanoate (1) is a component of the male-produced pheromone of the species (Borges et al., 1998a). Recently, we identified methyl 2,6,10-trimethyltridecanoate (1) and methyl 2,6,10-trimethyldodecanoate (2) as two male-specific compounds of P. guildinii, and reported the sharing of pheromone components between P. guildinii and E. heros (Borges et al., 1999).

To date, no bioassays have been conducted to check the biological activity of mixtures of stereoisomers of methyl 2,6,10-trimethyldodecanoate (2), nor has the reaction of the stink bugs to different blends of compounds 1 and 2 been described. It was previously observed that the activity of pure isomers of 1 in E. heros does not significantly differ from that of the racemic mixture (Costa et al., 1999). Here we describe a straightforward synthesis of compounds 1 and 2 as mixtures of stereoisomers and the biological activity of the synthetic compounds against females of E. heros. The material will also be used to monitor the response of P. guildinii for the first time in the field.

To the best of knowledge known at the time of this patent application, there is a need for improved methods for stink bug pheromones that are develop less expensive.

Brief Summary of the Invention
Main object of the present invention is a method of synthesizing methyl 2,6,10-trimethyltridecanoate (I), a sex attractant pheromone using citronellol.

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 shows step wise synthetic scheme 1 of methyl 2,6,10-trimethyltridecanoate (I).

Detailed Description of the invention
An embodiment of the present invention is to provide a method of synthesizing methyl 2,6,10-trimethyltridecanoate (I), a sex attractant pheromone, comprising the steps of:
a) brominating citronellol (VIII) with bromine in presence of pyridine and MDC and triphenyl phosphine to yield 8-bromo-2,6-dimethyloct-2-ene (VII);
b) protecting 8-bromo-2,6-dimethyloct-2-ene (VII) with triphenyl phosphine in presence of acetonitrile and MTBE, followed by addition of 2-methyl pentanal (VI) in presence of THF to yield (Z)-2,6,10-trimethyl trideca-2,8-diene (V);
c) oxidation of (Z)-2,6,10- trimethyl trideca-2,8-diene (V) with SeO2 and tert-Butyl hydroperoxide (TBHP) in presence of MDC to yield (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (IV);
d) hydrogenation of (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (IV) in presence of Raney Nickel in methanol to yield 2,6,10-trimethyl tri deca-1-ol (III);
e) oxidation of 2,6,10-trimethyl tri deca-1-ol (III) with Tempo and sodium hypo chloride in presence of KBr, MDC to yield 2,6,10-trimethyl tri decanal (II); and
f) oxidation of 2,6,10-trimethyl tri decanal (II) with Oxone in presence of methanol to yield methyl 2,6,10-trimethyltridecanoate (I).

Another embodiment of the invention is a method of synthesis wherein the extraction of stage wise compounds of step a) to f) are carried out in presence of Hexane and the preparation of 8-bromo-2,6-dimethyloct-2-ene in step a) is carried out in presence of MDC at 0 to 5oC.

The method of synthesis of methyl 2,6,10-trimethyltridecanoate (I) is sex attractant insect pheromone for Stink bug.

The attractiveness of Euschistus heros (F.) (Hemiptera: Pentatomidae) females to the eight stereoisomers of the methyl 2,6,10-trimethyltridecanoate, major component of the sex pheromone produced by the males of this species, was studied in a double choice olfactometer. Bioassays showed that the (2R, 6R, 10S) stereoisomer was necessary for the attractiveness of females, presenting better results in relation to the others. Although the stereoisomeric mixture of methyl 2,6,10-trimethyltridecanoate evoked significant attraction to the females (Borges et al. 1998a, 1998b), it was less attractive than the (2R, 6R, 10S) stereoisomer alone.
The use of the correct stereoisomer may be very important when regarding biological systems, since the presence of a lower quantity of another stereoisomer may evoke an acute inhibitory effect. The existence of other stereoisomers may disguise the behavioral responses of the E. heros females to the synthetic pheromone, diminishing its attractiveness, as appears to occur with the (2R, 6S, 10S) stereoisomer. However, the reason of why this happens is unknown.

Methyl (2R, 6R, 10S) – trimethyl tridecanoate was the most attractive stereoisomer of all. It was tested against the stereoisomeric mixture, considered initially to be the source of greater attractiveness to the E. heros females.

Experimental details:
Example 1. Synthesis of 8-bromo-2,6-dimethyloct-2-ene (VII):
In RBF charge MDC (800ml) and TPP (201gr) at room temperature, then cool the reaction mass to 0°C, and slowly added bromine (112g) at 0 to 5oC. Stir the reaction mass for 1 hour, followed by the slow addition of citronellol (100g) and pyridine (56.6g) under stirring. Filter and distil off the MDC layer under reduced pressure, and then cool to 10°C, charge Hexane (400ml) to the filtrate, and wash with hexane (200ml), distill off the hexane layer under reduced pressure at below 50°C to yield 8-bromo-2,6-dimethyloct-2-ene, analyzed by GC.
Yield: 1.3 Kg (92.8%) and purity: 96%

Example 2. Synthesis of (Z)-2,6,10-trimethyl trideca-2,8-diene (V):
Charge acetonitrile (400ml) into the RBF at room temperature, added triphenyl phosphine (TPP) (130g) to the reaction mixture, further added 8-bromo-2,6-dimethyloct-2-ene (100gr) and raise the temperature to reflux at 80-85°C under stirring for about 65 hours. Reaction completion is confirmed by TLC method, followed by distillation of acetonitrile completely under reduced pressure at 50-55°C. Cool the reaction mixture to room temperature. Charge MTBE (200ml) to the residue, stir for 10 mins and decant the MTBE layer to yield a protected compound (214g), to which further charge THF (600ml) and slowly added potassium tertiary butoxide (54.1g), Stir for 1 hour at room temperature and cool the temperature to 10-15°C. Slowly added 2-methyl pentanal (35.6g) to the reaction mixture at 0-5°, stir for 1hour, check for the completion of reaction by GC, and add water, stir for 10 mins then separate THF layer and distill off THF completely. Add hexane (300ml) to the reaction mixture at room temperature, stir, filter off salt and washed with hexane, excess hexane is distilled off under reduced pressure at 50°C, to yield (Z)-2,6,10-trimethyl trideca-2,8-diene crude compound by high vacuum distillation, followed by purification, analyzed by GC.
Yield: 54.1g (53.5%) and purity: 92%

Example 3. Synthesis of (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (IV):
Charge MDC (500ml) into the RBF at room temperature, added SeO2 (25g) and cool to 0°C. then added tert-Butyl hydroperoxide (TBHP) (173.7g) at 0-5°C and stir the reaction mixture for 30 mins. Added (Z)-2,6,10-trimethyl trideca-2,8-diene (100 g) to the reaction, stir for 30 mins and allow the mixture to settle to room temperature. Completion of reaction is confirmed by TLC & GC and distill off the MDC completely under reduced pressure at below 35°C, then charge hexane, wash the hexane layer twice with 2.5% caustic soda solution (200ml +200ml), and with brine solution. Dry the hexane layer over Na2SO4 and distill the hexane layer under reduced pressure at below 60°C, analyze by GC, purified to yield (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal.
Yield: 100g (94.3%) and purity: 70%

Example 4. Synthesis of 2,6,10-trimethyl tri deca-1-ol (III):
Charge Raney Nickel (30gr) to the RBF at room temperature with methanol under nitrogen atmosphere, and added (2E,8Z)-2,6,10-trimethyl trideca-2,8-dienal (100gr) to the reaction mixture, stir the mixture for 10 mins and flush out the reaction mixture with nitrogen (0.2kg) and hydrogen (0.3kg), maintain hydrogen atmosphere at 4kg/cm2 at room temperature for 5 hours. completion of the reaction is confirmed by GC, filter the reaction mixture through celite bed with methanol. Distill off methanol under vacuum, add water (200ml) and Hexane (200ml). Extract the aqueous layer with hexane, and wash with Brine solution and dry over Na2SO4, distill off hexane under reduced pressure at below 50°C to yield 2,6,10-trimethyl tri deca-1-ol analyzed by GC.
Yield: 80g (78.4%) and purity: 70%

Example 5. Synthesis of 2,6,10-trimethyl tri decanal (II):
Charge water (500 ml) and sodium bicarbonate (69.4g) into the RBF and added 2,6,10-trimethyl tri deca-1-ol (100 g), and MDC (500 ml), followed by addition of KBr (9.8 g), stir for 10 minutes and cool the reaction mixture to 00C, added Tempo (6.4 g), by slow addition of sodium hypochlorite solution (684 g), stir for 1 to 2 hours, filter the reaction mixture and wash with MDC (200ml). separate both the layers, extract the aqueous layer with MDC, further wash with sodium thiosulphate and distil off the MDC under vacuum to yield 2,6,10-trimethyl tri decanal analyzed by GC.
Yield: 70g (70.7%) and purity: 75%

Example 6. Synthesis of methyl 2,6,10-trimethyltridecanoate (I):
Charge 2,6,10-trimethyl tri decanal (100g) and methanol (500ml) to the RBF at room temperature, added Oxone (500g) to the reaction mixture, stir for 60 hours, filter, distill off 80% of methanol under vacuum, added water (200ml) and hexane (200ml) to the reaction mixture. Extract the aqueous layer with hexane, wash the hexane layer with brine solution and dry over Na2SO4, distill off hexane under reduced pressure at below 50°C to yield methyl 2,6,10-trimethyltridecanoate analyzed by GC.
Yield: 70g (62.2%) and purity: 85%