The Reactivity of 1-Methyl Group of Guaiazulenes for Oxidation by Quinones

Toshiya OKAJIMA*, Yuuko KONOMI and Shinji KUROKAWA

Department of Chemistry, Faculty of Culture and Education, Saga University;
1 Honjo-machi, Saga-shi840-8502Japan

Previously, we have reported the methodology for chemical conversion of guaiazulene (7-isopropyl-1,4-dimethylazulene, 1) to 7-isopropyl-4-methylazulene-1-carbaldehyde (4) by protecting-deprotecting technique of reactive 3-position. In the synthetic scheme, DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone, 5c) was used to convert unreactive 1-methyl group into formyl one. Computational calculation (RHF/3-21G//AM1) suggested that (1) o-chloranil (6b) is also effective as the oxidant instead of DDQ, which decomposes to highly toxic hydrogen cyanide (HCN), and (2) three weaker oxidants (p-benzoquinone (5a), and p-chloranil (5b), and o-benzoquinone (6a)) do not oxidize the desired reactants. In accordance with these prediction, 3-trichloroacetyl derivative (2d, Z=-COCCl3) was successfully converted to the corresponding 1-formyl derivative (3, Z=-COCCl3) in 90% yield, when treated with 3-equimolar o-chloranil. Moreover, the treatment of 2d with the latter three oxidants gave no 1-formyl derivative. The oxidation of 1-methyl group of azulene derivatives by quinones is considered to be thermodynamically controlled, according to the same tendency between the theoretical predictions and the experimental results.
This study provided a good example of successful prediction of experimental results by simple application of computational technique in organic synthesis.

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