碱性条件下顺(2-乙酰胺基-1-溴-2-(对-甲氧基苯基)乙基)膦酸二乙酯的1,2消除反应

1,2 Elimination of syn Diethyl (2-acetylamino-1-bromo-2-(p-methoxyphenyl)ethyl) phosphonate under Basic Condition

报道了在碱性条件下,顺(2 -乙酰胺基- 1 -溴 -2- (对- 甲氧基苯基)乙基)膦酸二乙酯进行的是-1,2-消除 反应而不是所期望的亲核取代反应。产物结构用红外光谱、高分辨质谱和核磁共振等分析方法确证。与文献 报道的甲基磺酸酯离去基团相比,在碳酸钾存在下,反应原料中的α- 溴原子作为相对较弱的离去基团导致很 低的转化率;而在1,8 -二氮杂双环[5,4,0] -十一碳 -7 -烯(DBU)存在下,由于α- 溴原子较强的电负性,其诱导 作用使得邻位β- 氢原子较易与碱作用,因而导致1,2消除反应。在无碱条件下α- 溴原子较弱的离去性和膦酸 酯较大的空间阻碍应是苯并三唑不能取代溴原子的原因。

A preferential 1,2 elimination reaction of syn diethyl (2-acetylamino-1-bromo-2-(p-methoxy- phenyl)ethyl)phosphonate 1 rather than the anticipated nucleophilic substitution reaction under basic conditions is described in the present paper. The product was characterized by IR, HRMS and NMR spectra. The relatively low ability of the α bromine as a leaving group compared to that of the mesylate group reported in the literature should be attributed to the low degree of conversion when K_2CO_3 was used. And when 1,8-diazabicyclo\-undec-7-ene(DBU) was used, the more sensitivity towards the base of the β proton caused by the induction effect from the higher electronegative α bromine atom should account for the elimination reaction. Without the base, the failure of the displacement of the bromine atom by benzotriazole should be due to the poor leaving ability of bromine as well as the steric hindrance from the bulky phosphonate group.