An Expedient Synthesis of the Sugarcane Borer Pheromone Components

A practical synthesis of the title compounds has been developed. The salient features of the synthesis were i) use of easily accessible starting materials viz. aleuritic acid, 10-undecenoic acid, cyclohexanone etc. and ii) fixation of the required olefinic geometry via Wittig and acetylenic routes.


Introduction
Sugarcane is one of the important commercial crop cultivated in various parts of India.However, the productivity of sugarcane is drastically lowered due to the damage caused by several pests [1][2][3][4].The most important amongst the pests are the stem and top shoot, as well as the internode borers, Chilo auricilius, C. sacchariphagus and C. indicus and pyrilla which are of regularly occurr.The stem borers especially are cosmopolitan in nature and are widespread in Java, Formosa, Philippines, Japan, India etc.
Due to the concealing habit of the pests, they are not exposed to parasitation or predation by natural enemies or to contact with insecticides.Hence, effective control of these seems only possible by reducing the fertility of wild females via their pheromone which has been isolated [5] as a four component mixture composed of (7Z)-dodecenyl acetate 1, (8Z)-tridecenyl acetate 2, (9Z)-tetradecenyl acetate 3 and (10Z)-pentadecenyl acetate 4. The best formulation for mass trapping was found to be a 8:16:1 ratio of 1: 2: 4, while for communication disruption a mixture of 1, 2, 3 and 4 in a combination of 4:8:4:1 [5] cocktail was the most efficient.
Although an efficient pheromone-based strategy for the protection of sugar cane requires a multiple blend system of all the pheromone components, little effort has so far been directed towards their syntheses.To the best of our knowledge, only the syntheses of 1 [6][7][8][9] and 3 [10][11][12] have so far been reported.Earlier, we synthesised [6] the pheromone component 1.The syntheses of the other components are reported herein.

Synthesis of 2
For the synthesis, 1-hexyne (5) was first prepared [13] by alkylation of acetylene with 1-bromobutane.For the preparation of the required C 7 -synthon 7, cycloheptanone was subjected to the Bayer-Villager reaction with HCO 3 H [14] to give the hydroxy acid 6 which on bromination with HBr furnished 7. Alkylation of 5 with 7 using LiNH 2 as the base gave the acid 8 which after esterification to 9 was reduced with LAH to give the alcohol 10.Its semi-hydrogenation over the P-2 Ni [15] catalyst gave the cisalcohol 11 which was converted to the pheromone 2 by acetylation (Scheme).

Synthesis of 3
Aleuritic acid (12), available from shellac was converted to the known ester 13 [16] and subjected to NaIO 4 cleavage to give the desired C 9 -and C 7 -components [16], 14 and 15 respectively.Although, the individual components could be separated by column chromatography, the protocol did not seem suitable for a large-scale synthesis.Hence, we attempted their separation by distillation under reduced pressure which gave the aldehyde 14 in excellent yield.However, the high temperature required for the distillation of 15 led to substantial polymerization.Consequently, the product mixture containing 14 and 15 was directly treated with dihydropyran (DHP) in the presence of pyridinium paratoluenesulphonate (PPTS) to afford the pyranylated aldehyde 16 along with 14 which could be easily separated by distillation.The Z-selective Wittig reaction between the C 5 -phosphonium salt 17 [17] with 14 in the presence of dimsyl anion as the base gave the ester 18.Its LAH reduction to the alcohol 19 followed by acetylation furnished the pheromone 3 which was characterized by comparing its physicochemical data with those reported in the literature [12].

Synthesis of 4
For this synthesis, 10-undecenoic acid (20), easily available by cracking castor oil [18] was chosen as the starting material.Its dihydroxylation with HCO 3 H [14] furnished the known [19] diol acid 21, which was esterified to the ester 22.After its NaIO 4 cleavage, the resultant aldehyde 23 was subjected to the Z-selective Wittig reaction with 17 to furnish the ester 24.Its LAH reduction and subsequent acetylation furnished the pheromone 4.

General
All bp's and mp's were uncorrected.The IR spectra were scanned with a Perkin-Elmer 783 spectrophotometer and only the pertinent values are expressed, in cm -1 .The 1 H-NMR spectra were recorded, either with a Varian EM 360L (60 MHz) or a Bruker AC-200 (200 MHz) spectrometer, using CDCl 3 as the solvent.The chemical shift ( δ) and coupling constant (J) values are expressed in ppm and Hz only.The GLC analyses were carried out on a Shimadzu GC-7A chromatograph fitted with a flame ionization detector and glass packed column for routine analysis and a capillary column for the determination of isomeric compositions.The mass spectra (EI) were recorded at 70 eV with a Shimadzu GC-MS QP-1000A spectrometer.Unless otherwise mentioned, the organic extracts were dried over anhydrous Na 2 SO 4 .

Methyl tridec-8-ynoate (9)
To a stirred solution of LiNH 2 [prepared from Li (3.2 g, 0.45 mol) using Fe(NO 3 ) 3 (0.1 g) as the catalyst] in liquid ammonia (300 mL) was added the alkyne 5 (24.6 g, 0.3 mol) and the mixture stirred for 1 h.A solution of the acid 7 (20.9g, 0.1 mol) in THF (150 mL) was then added dropwise over the course of 1 h.The reaction mixture was stirred for 4 h at the same temperature and left overnight.The residue was treated with dil.HCl (10:1) and extracted with ether.The ether layer was extracted thoroughly with 5% aqueous NaOH, then the ether layer separated and the aqueous layer acidified with dil.HCl.This was then reextracted with ether, the new organic extract was washed with water, brine and dried.Concentration of the extract gave the crude acid 8 which was used for the next step without any purification .

(Z)-9-Tetradecenyl acetate (3)
A mixture of 19 (4.24 g, 0.02 mol) and Ac 2 O (15 mL) in pyridine (10 mL) was stirred for 12 h at room temperature.Water was added to the mixture which was stirred for another 1 h and extracted with ether.The ether layer was washed with 5% aqueous HCl, water, 10% aqueous NaHCO 3 , water and brine.After drying, the extract was concentrated in vacuo and the residue distilled to obtain pure

Methyl 10,11-dihydroxyundecanoate (22)
A solution of HCO 3 H [prepared from 30% H 2 O 2 (25 mL) and HCO 2 H (15 mL) at 0 o C] was slowly added to 10-undecenoic acid (20) (18.4 g, 0.1 mol).The reaction mixture was stirred for 8 h at 40 o C and subsequently at room temperature overnight.The mixture was distilled in vacuo (10 mm), the residue diluted with water and extracted with ether.The ether layer was washed with water, dried (MgSO 4 ) and concentrated.
The residue was treated with 5% aqueous KOH (100 mL) and heated on a steam bath for 1 h, cooled and poured into excess cold dil.HCl (1N) under vigorous stirring (maintaining the temperature ~20 o C).The mixture was extracted with ether which was washed with water, dried and concentrated to give the crude diol acid 21 which was recrystallized from EtOH/H 2 O. Yield: 13.2 g (55%); mp: 86-87 o C, (lit.[19]