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I I I I CHARGE NUMBER: PROJECT TITLE; PROJECT'LEADERr, WRITTEN BY; PERIOD COVERED: DATE OF REPORT; 2520 Synthesis of Flavorants William B. Edwards, III William B. Edwards, III, Dick Howe and David L. Williams July, 1981 August 2, 1981 I. Terpenoid Flavorants 1,2 The methylation of a mixture of cis- and trans-3-isopropyl-6-oxo-2- heptenoic acid gave a mixture of the corresponding methyl esters (I). I Separation of the esters by GLC gave the trans ester which will be hydro- lysed to the acid, a tobacco constituent. Ad'd'itional crude cis- and trans-2-methyl-5-isopropyl-7-cyano-l,3- heptadiene was prepared. Distillation of the mixture.(70% trans) gave fractions ranging from 59% to 90% trans. HPLC studies showed that the mixture could be separated on a semi-preparative basis. The reaction of 2-methyl-5-isopropyl-7-cyano-1,3-heptadiene (90% trans) with isobutyl- magnesium bromide afforded the tobacco constituent 2,10-dimethyl-7- isopropy?-8E,10-undecadiene-4-one (II). II was contaminated with about 10% of the cis isomer which was removed by HPLC to give the pure trans product. 11

-2- The alkylation of the pyrrolidine enamine of isovaleraldehyde with methyl acrylate followed by hydrolysis afforde&the desired methyl 4- isopropyl-5-oxopentanoate (III'). Oxidation via "Jones" reagent gave 4- carbomethoxy-2-isopropylbutanoic acid (,IV). Saponification to the tobacco identical diacid (V) will be carried out. CO2H COZH' Lx, C02H To help complete work for a patent disclosure the following long chain esters were prepared [VI (a-d)]: R=a) -CH2(CH2)8CH3 n-Decyl 3-methyl-5-oxohexanoate b) -CH(CH2)SCH3 4-Decyl 3-methyl-5-oxohexanoate C02R I CH2CHzCH3 VI c) -CHCH3 2-Hexadecyl 3-methyl-5-oxohexanoate I 6H2t1,H2)12CH3 -CH2 (CH2 ) a oCH3 n-Docosyl 3'-methyl-5-oxohexanoate Purification of these compounds by column chromatography and distill- atton will be carried out, - The following compounds were placed in the CR file: CR-2020 lS,5C,6S-C+)-5-methyl-l-(1-methylethyl)-4-oxobicyclo (3.1,0)heptan-3-one (one isomer) CR-2021 1S,5~,6S-(-)-5-methyl-l-(1-methylethyl)-4-oxobicyclo (3.1'.0)heptan-3-one (one isomer) CR-2030 n-Hexadecyl 5-oxohexanoate CR-2031 n-Hexadecyl 3-methyl-5-oxohexanoate 02CH3

-3- CR.-2032 n-Hexadecyl, 3,3-dimethyl-5-oxohexanoate CR-2033 n-Hexadecyl 2-isopropyl-5-oxohexanoate I r C [ II. The Cigarette Beetle Pheromone' Laboratory testing3has established the crude pheromone from the second synthesi.s4is of similar activity to that from the first synthesis.' Hexane solutions of samples of the crude pheromone from both syntheses have been submitted to Steve Long of Project 1101 for field trials. III. Heteroaromatic Flavorants2 In order to expand our process patent coverage on the free radical induced acylation of azaaromatics, propionaldehyde was -eacted with 2-t-butyl- pyrjdi;ne to give a mtxture of 6-and 4-propionyl-2-t-butylpyridine. The isomers have been separated and.characterized. The reaction of propionaldehyde with 5H-5-methyl-6,7-dihydrocyclopenta- pyrazine has been run to afford a mixture of 2-propionyl-and 3-propionyl-5H- 5-neth,yl-6,7-dihydrocyclopentapyrazine. These compounds will be part of a composition patent. ZY. Development Support2 The optical rotation and melting point values for a number of samples of WS-14 were determined for Howard Maxwell. REFERENCES: 1),. W. B. Edwards, III: NB 7600 2) _ D. L. Williams: NB 7618 3) Steve Long; Project 1101 41 Monthly Reports, Project 2520, March and Apri~l, 1981 5) Third Quarter Report, Chemical Research Division, Sept., 1980 ;:~