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Z. Naturforsch. 2013, 68b, 397 – 402
doi:10.5560/ZNB.2013-2338
Synthesis of N-Acylated 1,5-Benzodiazepines: Differentiation between Two Possible Acylation Sites via Hydrogen Bonding
Carlos A. Escobar1, Odette A. Alvarado1, Judith A. K. Howard2, and Mauricio Fuentealba2,3
1 Universidad Andres Bello, Facultad de Ciencias Exactas, Departamento de Ciencias Químicas, Laboratorio de Síntesis Orgánica, Av. República 275, Santiago, Chile
2 Department of Chemistry, Durham University, Durham DH1 3LE, United Kingdom
3 Pontificia Universidad Católica de Valparaíso, Facultad de Ciencias, Instituto de Química, Av. Universidad N. 330, Curauma, Valparaíso, Chile
Reprint requests to Dr. Carlos A. Escobar. Fax: (+56 2) 661 82 69. E-mail: cescobar@unab.cl
Received December 26, 2012 / published online April 19, 2013
Temperature-dependent regioselectivity between amino and hydroxyl groups mediated by hydrogen bonding was observed in the reaction of acetic anhydride with 2-(2,3-dimethoxyphenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine (1), obtaining 1-acetyl-2-(2,3-dimethoxyphenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine (1a), when these were reacted at room temperature, and 4-(2-acetoxyphenyl)-1-acetyl-2-(2,3-dimethoxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine (1b), when they were refluxed (148–150 °C). Acylation of the less hindered analog 4-(2-hydroxyphenyl)-2-phenyl-2,3-dihydro-1H-1,5-benzodiazepine (2) via crotonyl chloride (a bulky acylating agent compared with acetic anhydride) afforded by refluxing only 1-crotonyl-4-(2-hydroxyphenyl)-2-phenyl-2,3-dihydro-1H-1,5-benzodiazepine (2a). All compounds were characterized spectroscopically, and the molecular structures of compounds 1a and 2a were determined by X-ray diffraction analysis.
Key words: 1,5-Benzodiazepine, Intramolecular Hydrogen Bond, N-Acylation, Regioselectivity
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