Dabholkar Vijay V, Gavande Rahul P
Organic Research Laboratory, Department of Chemistry, KC College, Churchgate, Mumbai-400 020, India.
Acta Pol Pharm. 2012 Mar-Apr;69(2):247-52.
Diethyl bromomalonate (2) with an equimolar amount of 2-aminophenol (1) in the presence of sodium fluoride undergoes a cyclization reaction to form 2H,4H-2-ethoxycarbonyl-3,4-dihydro-3-oxo-1,4-benzoxazine (3). Furthermore, compound 3 undergoes a condensation reaction with hydrazine hydrate in the presence of methanol to yield 2H,4H-2-hydrazinocarbonyl-3,4-dihydro-3-oxo-1,4-benzoxazine (4), which on further reaction with aryl isothiocyanates gave 2H,4H-2-[ (4'-substituted)-phenylthiosemicarbazino]-carbonyl-3,4-dihydro-3-oxo-1,4-benzoxazine (5). Compound 5 on treatment with NaOH, cone. H2SO4 and diethylmalonate (6). afforded 2H,4H-2-[2'H-3'-thioxo-4'-substituted phenyl-1',2',4'-triazole-5-yl]- 3,4-dihydro-3-oxo-1,4benzoxazine (7). 2H,4H-2-[2'-amino-(substituted)-phenyl-1,3',4'-thiadiazol-5-yl]-3,4-dihydro-3-oxo-1,4-benzoxazine (8) and 2H,4H-2-[5'H-5'-dihydro-2'-thioxo-3'-phenyl-4',6'-dioxo-1,3-diazine]-aminocarbonyl-3,4-dihydro-3-oxo-1,4-benzoxazine (9), respectively. The synthesized compounds were investigated for their antibacterial activities against Gram positive as well as Gram negative bacteria with ampicillin trihydrate as standard drug. Structures have been elucidated on the basis of spectral and chemical analyses.
丙二酸二乙酯（2）与等摩尔量的2-氨基苯酚（1）在氟化钠存在下发生环化反应，生成2H,4H-2-乙氧羰基-3,4-二氢-3-氧代-1,4-苯并恶嗪（3）。此外，化合物3在甲醇存在下与水合肼发生缩合反应，生成2H,4H-2-肼羰基-3,4-二氢-3-氧代-1,4-苯并恶嗪（4），其与芳基异硫氰酸酯进一步反应得到2H,4H-2-[（4'-取代）-苯基硫代氨基脲基]-羰基-3,4-二氢-3-氧代-1,4-苯并恶嗪（5）。化合物5用氢氧化钠、浓硫酸和丙二酸二乙酯（6）处理，分别得到2H,4H-2-[2'H-3'-硫代-4'-取代苯基-1',2',4'-三唑-5-基]-3,4-二氢-3-氧代-1,4-苯并恶嗪（7）、2H,4H-2-[2'-氨基-（取代）-苯基-1,3',4'-噻二唑-5-基]-3,4-二氢-3-氧代-1,4-苯并恶嗪（8）和2H,4H-2-[5'H-5'-二氢-2'-硫代-3'-苯基-4',6'-二氧代-1,3-二嗪]-氨基羰基-3,4-二氢-3-氧代-1,4-苯并恶嗪（9）。以三水合氨苄西林为标准药物，对合成的化合物进行了抗革兰氏阳性菌和革兰氏阴性菌的抗菌活性研究。结构已通过光谱和化学分析得以阐明。
