1-Cyclohexeneacetic acid

Fused ring 7-lactones may also be formed by cyclizations of l-cycloalkeneacetic acids under equilibrating conditions. Nicolaou obtained evidence for the presence of an unstable -lactone in the phenyl-selenolactonization of 1-cyclohexeneacetic acid, but rearrangement occured readily at room temperature to the more stable 7-lactone (equation 12).32 An example of a one-step conversion of a 2-methyl-1-cyclohexeneacetic acid to a fused butenolide by use of diphenyldiselenide and electrochemical oxidation has been reported.47 Recent studies by Rutledge showed that simultaneous addition of bromine and thallium carbonate to 1-cyclohexeneacetic acid gave the 7-lactone as the exclusive product (compare to Table 2) however, the mechanism of this reaction may differ from other cyclofunctionalizations.21... 

The cyclization of 1-cyclohexeneacetic acid (1) has been studied under a variety of conditions. Treatment of the thallium salt with iodine affords a mixture of the y-iodo-/ -lactone 3 and a /J-iodo-y-lactone 29. (47 , 55 )-5-Iodo-l-oxaspiro[3.5]nonan-2-one (3), which predominates in the mixture, rearranges to the thermodynamically more stable /i-iodo-y-lactone. nV-hexahydro-3a-iodobenzofuran-2(3/7)-one (2). 

To a stirred solution of 0.14 g (1 mmol) of 1-cyclohexeneacetic acid (1) in 15 mL of dry benzene or Et20 is added 0.249 g (1 mmol) of thallium(I) cthoxidc and the resulting precipitate is washed with pentane and dried to give the corresponding salt yield 96% mp 119.5-120 C. 

If the bromolactonization of 1-cyclohexeneacetic acid is carried out under mild conditions employing commercially available jV-bromosuccinimide in dimethylformamide, the /1-lactone is obtained in 88 % yield,0a. Employing 3-broino-5,5-dimethylhydantoin as electrophile results in the /1-lactone in 91 % yield10b,... 

Cyclization of tetrahydropyranyl ether (245) with BF3-Et20 in trichloroethanol gives (246) in 61% yield. Similar cyclizations can be carried out on acylal derivatives. Acid-catalyzed cyclization of 1-cyclohexeneacetic acid (247) with formaldehyde gives (249) via the presumed intermediacy of (248). If the terminal end of the double bond is more highly substituted, cyclization occurs in an exocyclic mode to give (83). Treatment of (250) with methanesulfonic acid gives (251), which cyclizes to give (252) after loss of a proton (Scheme 36). ... 

As an example, methylenecyclohexane is obtained as decarboxylation product on distillation of 1-cyclohexeneacetic acid 34... 

An intimate mixture of 2-carboxy-l-cyclohexeneacetic acid and NH4-carbonate gradually heated to 230° in an oil bath —1,3-dihydroxy-5,6,7,8-tetrahydroisoquinoline. Y 92%. (R. Grewe and A. Mondon, Chem. B. 82, 279 (1948).)... 

Moreover, it is quite certain that the double bond does not migrate before the decarboxylation by three-carbon tautomerism —CH=CH—CH2— —CH2—CH CH— (this usually requires base catalysis but can also occur without a catalyst at temperatures above 200°) the migration occurs only when allied to elimination of carbon dioxide, as is shown by the fact that it takes place also when a9 -dimethyl- 1-cyclohexeneacetic and 2,2-dimethyl-3-butenoic acid are decarboxylated although neither of these acids possesses a vinylic hydrogen atom ... 

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