Cyclohexylidene acetic acid

The 5,6-O-isopropylidene acetal (152) of L-ascorbic acid has been prepared,340 and von Schuching and Frye341 prepared the corresponding cyclohexylidene acetal. These compounds were found to be more resistant than L-ascorbic acid toward oxidation, and the parent acid can be readily regenerated by acid hydrolysis. The derivative was used in the synthesis of 14C-labeled vitamin C. The C-2 and C-3 enols of L-ascorbic acid or its acetone derivative (152) can be readily methylated with diazomethane, yielding the corresponding dimethoxy analogues. 

The relative ease of acid-catalysed hydrolysis (0.53 M sulfuric acid in 2 1 aqueous 2-propanol at room temperature) follows the order cyclopentylidene > isopropylidene > cyclohexylidene. For example, the half life for the hydrolysis of 1,2-0-alkylidene-cx-D-glucopyranoses followed the order cyclopentylidene (8h), isopropylidene (20 h), cyclohexylidene (124 h).57 The higher acid lability of cyclopentylidene acetals has been frequently exploited in synthesis. Thus, aqueous or ethanolic acetic acid at room temperature is able to liberate a 1,2-diol in the presence of an isopropylidene group [Scheme 3.37],5R an 0-trityl group [Scheme 3.38]59 and a p-methoxybenzyl ether but not a tetrahydropyra-nyl group [Scheme 3.39],60... 

Diorgano 4,4-dimethyl-2,6-dioxo-cyclohexylidene tellurium compounds were also converted to diorgano tellurium dihalides by hydrogen halides in boiling ethanol and to diorgano tellurium diacetates by acetic acid. ... 

Oxidation of cyclohexane with cobalt(III) acetate in acetic acid under nitrogen at 343 K gives mainly cyclohexyl acetate, 2-acetoxycyclohexanone and cyclohexylidene diacetate and traces of cyclohexanone, cyclohexanol, and bicyclohexyl. In the presence of O2, adipic acid is the main product. Reactivities of cyclohexane and cyclohexane-tfi2 are equal within experimental error, and loss of a proton does not occur in the ratecontrolling step. The mechanism for this oxidation has been rationalized in terms of an initial electron transfer, in which the species are in equilibrium, followed by loss of a proton from the radical cation ... 

The lessons learned from the abortive experiments in Scheme 12 were invaluable to Kozikowski and co-workers in developing a slate of do s and dont s for the final strategy (Scheme 13). Most notably, it transpired that the a,P-epoxy lactone C16 (c.f. C9, Scheme 12) underwent classical reductive elimination with zinc in acetic acid to give the P-hydroxy lactone C17, and cyclohexylidenation, followed by oxidation then led to the actinobolin skeleton in CIS. Final processing to give actinobolin hydrochloride now proved to be uneventful. 

Sugar isopropylidene acetals have been prepared by ultrasonic irradiation of a suspension of the sugar in propanone in the presence of 98% sulphuric acid or 70% perchloric acid. The sugar dissolves within 30 minutes and the acetals are isolated after neutralization with sodium or potassium carbonate. Cyclohexylidene acetals were prepared in a similar manner. 

The n.m.r. spectroscopic investigation of the reactions of pentonolactones with acetone and benzaldehyde in acidic media is covered in Chapter 21, as are conformational studies on 2,3-G-isopropylidene-a-L-sorbopyranose derivatives. l,2-0-Isopropylidene-a-D-t /o-pentodialdo-l,4-furanose dimers are referred to in Ch er 22, and some 7-carbon sugar lactones which were characterized as their isopropylidene-and cyclohexylidene-acetals are noted in Chtytters 2 and 16. 

Kaneko, H., and K. Ijichi Aroma of Cigar Tobacco. I. Isolation of 2-Hydroxy-2,6,6-trimethyl-cyclohexylidene-l-acetic Acid Lactone (Dihydroactinidiolide) from Ether Extract of Cigar Leaves. Agric. Biol. Chem. 32, 1337 (1968). 

H]cyclohexylidene acetate, which served as precursor to 2-(S-(p-methyl)benzylmercap-to)-2,2-[ H]cyclopentamethylene propionic acid (62). 

By adding l4C-labelled sodium cyanide to L-threo-pentos-2-ulose (9), L-[l-14C]ascorbic acid was prepared (see Scheme 2) having an activity592-596 of 2.1 x 108 counts, min-1, mg-1. L-Xylose was prepared by the sequence shown in Scheme 21. The resulting L-xylose was oxidized with cupric acetate to 9 in 40-50% yield. In the second procedure, [1-14C]1 (specific activity 0.1 /iCi. mg-1) was purified by way of 5,6-O-cyclohexylidene-L-ascorbic acid.596... 

Concentrated hydrofluoric and trifluoroacetic acid cleave 7e-(4,4-dimethyl-2,6-dioxo-cyclohexylidene)-telluraxanthene forming telluraxanthene difluoride and bis[trifluoro-acetate]3, respectively. 

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