Acetaldehyde, amino-, diethyl acetal

Numerous variations of this reaction have been studied, principally those involving a prior inclusion of the nuclear sulfur atom in a thioacylamino compound. Thus, thiobenz-amido acetaldehyde diethyl acetal (8) underwent ring closure to 2-phenylthiazole (9) on gentle heating (57JCS1556). Similarly, iV-thioacyl a-amino acids also undergo ready ring closure to thiazoles. 

Thus, in a novel synthesis of hypoglycine A (96), hydroxycyclopropanation of ethenyl-acetaldehyde diethyl acetal (93) followed by formal dehydration of the cyclopropanol 94 via its tosylate intermediate gave the methylenecyclopropane species 95, a key precursor to the target amino acid (Scheme 11.26) [92]. 

Phthalimidoacetaldehyde diethyl acetal boiled 20 hrs. with 25%-KOH amino-acetaldehyde diethyl acetal. Y 85%.—At room temp., the corresponding phthal-amic acid is obtained in 80% yield (cf. Synth. Meth. 13, 50). F. Fischer and H. Riese, J. pr. 12, 177 (1961). 

Frutos prepared 2-fluoromethylimidazoles via the cyclization of the amidines formed by the Cu(I)-piomoted addition of a-amino acetals to fluoroacetonitrile (Scheme 19) [29]. The reactions were performed either stepwise or in a one-pot fashion (depending upon the removal of Cu salts before or after the cycUzation) in which the amidine formation was carried out in the absence of any solvent followed by the cyclization using TFA or HQ-MeOH. Thus, the addition of (methylamino) acetaldehyde dimethyl acetal and (benzylamino)acetaldehyde diethyl acetal with fluoroacetonitrile followed by cyclization afforded the corresponding 2-(fluoro-methyl)imidazoles in 96 % and 53 % yields, respectively. 

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