Acetic formic anhydride methyl group reactions

Reaction with Grignard reagents. Edwards and Kammann7 studied the reaction of phenylmagnesium bromide in ether at —70° with one equivalent of formic-acetic anhydride and found that the less hindered carbonyl group of the mixed anhydride reacts preferentially, with the result that the aldehydic product (5) predominates strongly over the methyl ketone (6). With ether as solvent, the ratio... 

For the synthesis of the AMT ester (VIII.151), bromide (VIII. 156)-HBr was condensed in situ with 4-aminobenzoic acid and the product, 4-amino-4-deoxypteroic acid (APA), was treated directly with a mixture of formic and acetic acid to obtain the W °-formyl derivative (FmAPA, 65% yield) [292]. Condensation of FmAPA with y-r-butyl a-methyl L-glutamate to form the diester (VIII. 155) was accomplished in 82% yield by a modified mixed anhydride procedure involving four cycles of in situ carboxyl group reactivation. Hydrolysis of the methyl ester and W -formyl group at the same time with NaOH proved impossible as a result of an unforeseen loss of the y-t-butyl ester. When the a-methyl ester was first removed under mild conditions with Ba(0H)2, however, the relatively stable V -formyl derivative (VIII.154) was isolated satisfactorily in 79% yield. Subsequent cleavage of the W -formyl group was then accomplished by carefully controlled hydrolysis in 0.25 M NaOH (1.75 h at 25 °C). In an alternative synthesis, FmAPA was activated by reaction with bis(4-nitrophenyl) carbonate to obtain the corresponding... 

The lifetime of methyl oxirane with respect to reaction with OH will be about 25 days, assuming that the lower rate coefficients noted above are correct. No studies of the mechanism of the oxidation have been conducted. By analogy to chemistry of oxirane presented in section III-E-1.4, OH attack at the CH group (likely the dominant site) will result in the formation of acetic acid and CO, via a-ester rearrangement of the CH3C(0)0CH20 radical, and formic acetic anhydride [CH3C(0)0C(0)H] via reaction of this radical with O2. 

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