Regioselectivity of the hydrolysis of 2-(1-alkoxyvinyl)-substituted imidazolidines, 1,3-thiazolidines, and 1,3-oxazolidines

Abstract

2-(1-Alkoxyvinyl)-1,3-thiazolidines reacted with H 2 O or D 2 O in the presence of 105 mol % of p-toluenesulfonic acid or trifluoroacetic acid (20°C, 1 h) to give 2-acetyl-1,3-thiazolidine in quantitative yield. 2-(1-Alkoxyvinyl)-3,5-diphenylimidazolidines underwent hydrolysis in the presence of 20 mol % of an acid (20°C, 24 h) at the vinyloxy group with high regioselectivity yielding 2-acetylimidazolidines. Hydrolysis of 2-(1-alkoxyvinyl)-3-phenyl-1,3-oxazolidines in the presence of 10 mol % of p-toluenesulfonic acid (20°C, 5 days) takes two pathways, one of which involves the endocyclic C-O bond with ring opening and the other involves the vinyloxy group to produce 2-acetyl-3-phenyl-1,3-oxazolidine. Unlike phenyl-substituted 1,3-thiazolidines and imidazolidines, hydrolysis of their 3-methyl-and 3,5-dimethyl-substituted analogs in acid medium occurs mainly via ring opening. The observed hydrolysis pathways were interpreted in terms of B3PW91/6-311G(d,p) quantum-chemical calculations.Interest in the chemistry of 2-alkyl-[1] and 2-acyl-1,3-oxazolidines [2], 2-alkyl-[3] and 2-acetyl-1,3-thiazolidines [4], 2-alkylimidazolidines [5], and 2-acetylimidazolidines [6] is related to the presence of the corresponding fragments as structural units of many medical agents and natural compounds, as well as to their use as starting compounds for the synthesis of pharmaceuticals and fragrant substances. In particular, some 2-acyloxazolidines are convenient precursors in the synthesis of alkaloids [7]. 2-Alkylthiazolidines exhibit radioprotective, antimutagenic, antibacterial, and antiviral activity [3,8]. Compounds of the thiazolidine series are important as models for studying biochemical transformations of their complex analogs involved in natural processes [9].Hydrolytic stability of the above listed heterocyclic compounds is an important factor determining their application as therapeutic agents which undergo cleavage of the heteroring in vivo [10,11]. It is known that L-cysteine responsible for intracellular level of glutathione could be introduced at a required dose as appropriate prodrugs, 2-alkylthiazolidines [10,11]. The nitrogen-containing heteroring in vivo undergoes nonenzymatic hydrolysis to release amino acid and the corresponding aldehyde. The mechanism of acid hydrolysis of some 1,3-thiazolidines was studied in vitro [12]. The results of kinetic studies on hydrolytic ring opening in 2-aryl-N-methyl(phenyl)oxazolidines showed that the rate of hydrolysis and optimal pH value often strongly depend on the nature and/or stereochemistry of substituents in the oxazolidine ring [13].We previously found that 2-alkoxypropenals readily react with 2-aminoalkanols [14], 2-aminoethanethiol [15], and ethane-1,2-diamines [16] to give the corresponding 2-(1-alkoxyvinyl)-1,3-oxazolidines, -1,3-thiazolidines, and -imidazolidines as mixtures with their open-chain tautomers. The fraction of the cyclic structure decreases as the solvent polarity rises [15,16],

Synthesis of Diheteroatomic Five‐Membered Heterocyclic Compounds from α,β‐Unsaturated Aldehydes

“…The authors found that the introduction of substituents into the oxazolidine ring enhanced the stability of the cyclic form (Scheme ) . Regioselective MWI‐promoted hydrolysis of 2‐(1′‐ethoxyvinyl)‐3‐phenyl‐1,3‐oxazolidine across the vinyloxy group allowed 2‐acetylsubstituted analogues 180 a to be synthesized in up to 70 % yield . Notably, these compounds could not be prepared from glyoxals …”

“…The interaction of thiazolidine 216 a with excess (105–107 %) p TsOH or CF 3 COOH (TFA) in water or D 2 O proceeded through easy regiospecific hydrolysis of the alkoxyvinyl group to furnish 2‐acetyl‐1,3‐thiazolidine 218 , which was readily isolated as the tosilate, in up to 100 % yield (by 1 H NMR spectroscopy) . This reaction opened an access to cyclic thioaminals of methylglyoxal, which were previously obtained as a mixture of three products from the scarcely available and easily polymerizable methylglyoxal …”