FIELD OF INVENTION:

This invention relates to an improved synthesis of Tetradecatrienyl acetate, a component of moth attractants used in the management of Tomato pest,Serobipalpuloidesabsoluta.

BACKGROUND OF THE INVENTION:

All crops are susceptible to attack of pests and insects. It is important to control these pests in the interest of the agricultural economy. Broad based pesticides & insecticides are often used for spraying. This method targets all insects and exposes the farmers to hazards of exposure. It imposes the burden of costs on the farmer and the danger of carryover residues on the consumer. Another significant downside is the danger of the insects developing immunity & pesticide resistant strains, which are difficult to control.

S. absoluta is a scourge for tomatoes farmers in general but outbreaks are known to be particularly virulent in Latin America. Loss of crops up to 100% has been described.

The major sex attractant emitted by Scrobipalpuloidesabsoluta females is shown to be (3E,8Z,llZ)-3,8,ll-tetradecatrien-l-yl acetate. In field tests and wind tunnel bioassays, the synthetic ester was found to be highly attractive to conspecific males. The male response to this pheromone, however, is restricted to the early-morning time window during which females exhibit calling behavior. Each female sex gland contains ca. 1-5 ng of this pheromone.

Attractants for many species of moths have been identified in the literature for preservation of the crops and thus to maintain the produce.

US 5,728,376 reports that a mixture of 3,8,11 tetradecatrienyl acetate and 3,8tetadecadienyl acetate can be used as a moth attractant for S. absoluta. It also reports a synthesis for both the components.

J. of chemical Sc. Perkin tran. I) 1998, 1839-1858 reports the reduction of 2-((8Z,l 1Z)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyranto the corresponding 8Z,11Z, 3E trienylderivative using sodium in liquid ammonia.

Synthesis of 3E,8Z,11Z tetra decatrienylacetate in prior art starts with(tetra hydro pyran 2-yloxy) 4 pentyne and involves several stages to obtain 3E,8Z, 11Z tetradecatriene-1-ol (Scheme 1).

Scheme 1

Therefore, there is a need in the art to provide an effective and robust synthesis for preparation of 3E 8Z, 11Z tetra decatrienyl acetate.

Accordingly, the object of the present invention is to provide an improved synthesis for preparation of 3E 8Z, HZ tetra decatrienyl acetate, which is easier to scale up on industrial level.

SUMMARY OF THE INVENTION:

Thus, the present invention provides a synthesis for preparation of 3E 8Z, HZ tetra decatrienyl acetate starting from 4 pentyne 1 ol (1). The synthesis of the present invention involves conversion of 4 pentyne 1 ol to the corresponding Bromo derivative (2) using phosphorus tribromide, which is then coupled with 2- ynylpentyl Bromide (4) in presence of CuX (X=I,Br,Cl and CN),to yield a CIO component (5). The triple bonds of the CIO component are reduced using Ni acetate to obtain compound (6), which is further treated with homo propargyl alcohol (3 butyne l-ol) to increase the chain length by four carbon atoms, to obtain compound (8). The resultant product (8) is then reduced with sodium/liq. NH3 followed by treatment with pTSA to obtain tetradeca 3,8,11 trenyl l-ol(10), which is
The brominating agent used in step A is selected from phosphorus tribromide, bromine etc and the reaction is conveniently carried at 0 to 10°C in presence of an aromatic hydrocarbon solvent.

The copper source as mentioned above may be selected from CuX, wherein, X=I,Br,Cl and CN. The coupling reaction is carried in presence of copper source and an iodine source and in presence of base, potassium carbonate at room temperature. The coupling reaction is carried out in polar aprotic solvent such as DMF, DMSO etc. The typical iodine source for the purpose of the current invention is selected from sodium iodide/potassium iodide.

The reduction of 10-iododeca-3,6-diyne is conducted in presence of Nickel diacetatetetrahydrate and sodium borohydride solution in suitable alcohol such as ethanol and isopropanol.

The reduction of 2-((8Z,llZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran is conducted in presence of sodium/liq. Ammonia.

The reduction of 2-((3E,8Z,llZ)-tetradeca-3,8,ll-trienyloxy)-tetrahydro-2H-pyran is carried with pTSA in methanol at room temperature to obtain 3E 8Z, HZ tetra decatrienyl l-ol.

The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

Examples Example 1

Preparation of l-bromopent-2-yne2:

To a stirred solution of 2 pentyll-ol 1 (200g, 2.37 mol) in hexane (2 lit) was added Phosphorous tribromide (32lg, 1.19 mol) at 0°C drop wise. Reaction mixture was allowed to stir at RT for 4h. After completion of the starting material (by TLC), reaction finally converted into tetradeca 3,8,11 trenyl l-ol acetate(ll). The synthesis of the present invention is depicted in scheme 2 below:

Scheme 2

DETAILED DESCRIPTION OF THE INVENTION:

In accordance with the above, the present invention is directed to an improved cost effective synthesis of 3E, 8Z, 11Z Tetradecatrienyl -1-acetate, a component of moth attractant.

Accordingly, an improved synthesis for preparation of 3E 8Z, 11Z tetra decatrieny lacetatecomprising;

a) Reacting 4pentyne 1 ol with brominating agent to obtain bromo derivative;

b) Coupling the bromo derivative with 2- ynylpentyl Bromide in presence of copper source/iodine source to yield 10-iododeca-3,6-diyne;

c) Reducing 10-iododeca-3,6-diyne to obtain (3Z,6Z)-lO-iododeca-3,6-diene;

d) Treating (3Z,6Z)-10-iododeca-3,6-diene with 2-(but-3-ynyloxy)-tetrahydro-2H-pyran to obtain 2-((8Z,l lZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran; And

e) Reducing 2-((8Z,llZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran to obtain (3E,8Z,llZ)-tetradeca-3,8,ll-trien-l-ol, which on subsequent conversion to 3E,8Z, 1 lZ)-tetradeca 3,8,11 trienyl 1 -ol acetate.

mixture was quenched with ice water (1 lit). The organic layer was separated and washed with water (1 lit) followed by 10% sodium bicarbonate solution (500 ml). Hexane was removed under reduced pressure and purified the product by column chromatography to give l-bromopent-2-yne 2 (250g, yield 71.5%).

Example 2

Preparation of 5-bromopent-l-yne 4:

To a stirred solution of 4 pentyl l-ol 3 (300g, 3.56 mol) in diethyl ether (3 lit) was added Phosphorous tribromide (481.5g, 1.78mol) at 0°C drop wise. Reaction mixture was stirred at RT for 12h. After completion of the starting material (by TLC), reaction mixture was quenched with ice water (1.5 lit). The organic layer was separated and washed with water (1 lit) followed by 10% sodium bicarbonate solution (750 ml). Ether was removed under reduced pressure and purified the product by column chromatography to give 5-bromopent-1 -yne 4 (220g, yield 41.9%).

Example 3

Preparation of 10-iododeca-3,6-diyne5:

The mixture of 5-bromopent-l-yne 4 (250g, 1.7 mol),l-bromopent-2-yne 2 (307g, 2.1 mol), sodium iodide (452g, 3 mol), copper iodide (226g, 1.18 mol), potassium carbonate (262g, 2 mol) in DMF (2 lit) was stirred under nitrogen atmosphere at RT for 36h. Completion of the starting material was monitored by TLC. The reaction mixture was poured into saturated ammonium chloride solution (3 lit) and extracted with diethyl ether (3x1 lit). The combined organic layers was washed with water (3x1 lit), dried over sodium sulfate and concentrated under reduced pressure to give the crude product. Crude product was purified on silica gel column chromatography to give pure 190g of 10-iododeca-3,6-diyne 5 (yield 24.5%)

Example 4

Preparation of (3Z,6Z)-10-iododeca-3,6-diene 6:

To the solid Nickel diacetate tetrahydrate (40g, 0.16mol) was added sodium borohydride solution (15g in 400ml of ethanol, 0.394 mol) slowly drop wise. Then the mixture was stirred for 15min at RT. Ethylene diamine (12 ml, 0.18 mol) was added and stirred for 20 min. 10-iododeca-3,6-diyne 5 (190g, 0.730mol) in 1.45 lit of ethanol was added to the reaction mixture and hydrogen gas was purged into the reaction mixture. Completion of the starting material was monitored by TLC. Solids were filtered off and the ethanol was removed under reduced pressure. Crude material was diluted with water (750 ml) and extracted with DCM (2xllit). The combined organic layers was dried over sodium sulfate and concentrated under reduced pressure to afford crude product. The crude product was purified by silica gel column chromatography to give (3Z,6Z)-10-iododeca-3,6-diene 6 (120g, yield 51%)

Example 5

Preparation of 2-((8Z,l lZ)-tetradeca-8,l l-dien-3-ynyloxy)-tetrahydro-2H-pyran 8:

To the solution of 2-(but-3-ynyloxy)-tetrahydro-2H-pyran 7 (12.65g, 82 mmol) in THF (110ml) at -78°C was added BuLi (32.6 ml, 2.5M solution in hexane). Then the reaction mixture was warmed to -40°C slowly over a period of 30 min and stirred at -40°C for 15min.Reaction mixture was re-cooled to -78°C and the mixture of (3Z,6Z)-10-iododeca-3,6-diene 6 (9g, 34 mmol), HMPA (22 ml) was added slowly. Then the reaction mixture was allowed to RT and stirring was continued for 12h. Saturated ammonium chloride solution (200ml) was added and extracted with ether (2x200 ml). The combined organic layers was concentrated under reduced pressure and purified by column chromatography to yield 2-((8Z,llZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran 8 (5g, 40%)
Example 6

Preparation of 2-((3E,8Z,l lZ)-tetradeca-3,8,l l-trienyloxy)-tetrahydro-2H-pyran 9:

Sodium (5g, 217mmol) was added to liquid ammonia (480 ml) in a two necked round bottom flask (equipped with ammonia condenser) at -78°C. A deep blue solution was observed. Then 2-((8Z,llZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran 8 (9g, 30.8 mmol) in 80 ml of dry ether was added drop wise to the reaction mixture. The reaction mixture was stirred at -78°C for 2h. Solid ammonium chloride (46g, 867 mmol) was added to the reaction mixture. Evaporated the ammonia, and the mass was extracted with ether (2x100ml). Organic layer was concentrated under reduced pressure and purified by column chromatography to give 2-((3E,8Z,llZ)-tetradeca-3,8,l 1-trienyloxy)-tetrahydro-2H-pyran 9 (5g, 55%)

Example 7

Preparation of (3E,8Z,1 lZ)-tetradeca-3,8,l 1-trien-l-ol 10:

The solution of 2-((3E,8Z,llZ)-tetradeca-3,8,l l-trienyloxy)-tetrahydro-2H-pyran 9 (5g,17.1 mmol) and pTSA (500 mg) in methanol was stirred at RT for 2h. After completion of the starting material by TLC, methanol was removed under reduced pressure and extracted with DCM (200ml). Organic layer was concentrated under reduced pressure and purified by column chromatography to yield (3E,8Z,1 lZ)-tetradeca-3,8,l 1-trien-1-ol 10 (3g,84%).

Example 8

Preparation of (3E,8Z,1 lZ)-tetradeca-3,8,l 1-trien-l-ol acetate 11
3E,8Z,llZ)-tetradeca-3,8,l 1-trien-l-ol 10 was converted into 3E,8Z,11Z)-tetradeca-3,8,11-trien-l-ol acetate 11 in a conventional manner by treatment with acetic anhydride in presence of a suitable base.

We claim,

1. An improved synthesis for preparation of 3E 8Z, 11Z tetra decatrienylacetatecomprising;

a) Reacting 4-pentyne 1 ol with brominating agent to obtain bromo derivative;

b) Coupling the bromo derivative with 2- ynylpentyl Bromide in presence of copper source and iodine source to yield 10-iododeca-3,6-diyne;

c) Reducing 10-iododeca-3,6-diyne to obtain (3Z,6Z)-10-iododeca-3,6-diene;

d) Treating (3Z,6Z)-10-iododeca-3,6-diene with 2-(but-3-ynyloxy)-tetrahydro-2H-pyran to obtain 2-((8Z,l 1 Z)-tetradeca-8,1 l-dien-3-ynyloxy)-tetrahydro-2H-pyran; and

e) Reducing 2-((8Z,l lZ)-tetradeca-8,ll-dien-3-ynyloxy)-tetrahydro-2H-pyran to obtain (3E,8Z,llZ)-tetradeca-3,8,ll-trien-l-ol, which on subsequent conversion to 3E,8Z,1 lZ)-tetradeca 3,8,11 trenyl l-ol acetate.

2. The process according to claim 1, wherein, the brominating agent used is selected from phosphorus tribromide, bromine etc.

3. 3.The process according to claim 1, wherein, the bromination reaction is conveniently carried at 0 to 10°C in presence of an aromatic/aliphatic hydrocarbon solvent.

4. The process according to claim 1, wherein, the copper source is selected from CuX, wherein X=I,Br,Cl and CN.

5. The process according to claim 1, wherein, the iodine source is selected from soium iodide or potassium iodide.

6. The process according to claim 1, wherein, the coupling reaction is carried in presence of sodium iodide and copper iodide and in presence of base, potassium carbonate.

7. The process according to claim 6, wherein, the coupling reaction is carried at room temperature in polar aprotic solvent selected from DMF or DMSO.

8. The process according to claim 1, wherein, the reduction of 10-iododeca-3,6-diyne is conducted in presence of Nickel diacetatetetrahydrate and sodium borohydride solutionin suitable alcoholic solvent.

9. The process according to claim 8, wherein, the alcoholic solvent is selected from ethanol and isopropanol.

10. The process according to claim 1, wherein, the reduction of 2-((8Z,llZ)-tetradeca-8,1 l-dien-3-ynyloxy)-tetrahydro-2H-pyran is conducted in presence of sodium/liq. Ammonia.

11. The process according to claim 1, wherein, the reduction of 2-((3E,8Z,llZ)-tetradeca-3,8,ll-trienyloxy)-tetrahydro-2H-pyran is carried with pTSA in methanol at room temperature to obtain 3E 8Z, 11Z tetra decatrienyl l-ol.