Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H-pyrroles via ring expansion and ring expansion/ring contraction of tetrahydropyrimidinesElectronic supplementary information (ESI) available: IR and NMR (1H and 13C) spectra of all obtained compounds, detailed procedure for multi-gram scale syntheses of 2-benzoyloxyethanal (8) and N-[(2-benzoyloxy-1-tosyl)ethyl]urea (9). See DOI: 10.1039/c1ob06284k

• Main Authors: Fesenko, Anastasia A, Trafimova, Ludmila A, Shutalev, Anatoly D
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c1ob06284k

A general approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-1 H -1,3-diazepin-2-ones based on the ring expansion reaction of 1,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been developed. The first step of the synthesis was preparation of N -[(2-benzoyloxy-1-tosyl)ethyl]urea by three-component condensation of 2-benzoyloxyethanal, urea and p -toluenesulfinic acid. Nucleophilic substitution of the tosyl group in the obtained sulfone with sodium enolates of -phenylthioketones followed by cyclizationdehydration, and debenzoylation gave 4-hydroxymethyl-5-phenylthio-1,2,3,4-tetrahydropyrimidin-2-ones which were transformed into the 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as NaCN, sodium diethyl malonate, PhSNa, MeONa, NaBH 4 , sodium succinimide, or potassium phthalimide, afforded the target multi-functionalized diazepinones. The obtained 6-phenylthio-diazepinones and their 6-tosyl-substituted analogues were converted into 3-substituted 1-carbamoyl-1 H -pyrroles under acidic conditions as a result of ring contraction. Effective one-pot synthesis of the latter from 4-mesyloxymethyl-pyrimidines was realized using a ring expansion/ring contraction sequence. Nucleophile-promoted ring expansion of 4-mesyloxymethyl- and 4-chloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones gave functionalized 2,3,4,5-tetrahydro-1 H -1,3-diazepin-2-ones which were converted into 3-substituted 1-carbamoyl-1 H -pyrroles under acidic conditions.