The selective basic hydrolysis of 3-acetoxy-?-bromoJ-(o-chlorophenyl)-l-ethoxycarbonylmethyl-l,2dihydro-3H-1,4-bep,~,epin-2-one has been carried out, resulting in the sequential formation of 3-hydroxy-]-ethoxycarbonylmethyl-, 3-hydroxy-l-methoxycarbonylmethyl-, and 3-hydroxy-l-carboxymethyl derivatives. The structure of the 1-methoxycarbonylmethyl derivatives has been established by x-ray structural analysis.
The search for new psychotropic drugs has stimulated the introduction of a variety of different substiments into different positions in both the heterocyelic and aromatic rings of 1,4-benzdiazepines. During the course of these studies a series of interesting chemical reactions in this class of compounds was discovew.d.
The inlroduction of bulky substituents in the 1-and 3-positions of 5-aryl-l,2-dihydro-3H-1,4-benzdiazepin-2-ones reduces, as expected, their psychotropic activity [1]. This probably explains why the chemical behavior of 1alkoxycarbonylmethyl-3-acyloxy-1,2-dihydro-3H-1,4-benzalaTepin-2-ones has not been studied.
We have investigated the basic hydrolysis of 3-acetoxy-7-bromo-5-(o-chlorophenyl)-1 -ethoxyearbonylmethyl-1,2-dihydro-3H-1,4-bew,~i-7~'-pin-2-one (I), which is obtained via alkylation of the corresponding N-oxide (II) [2] with ethyl bromoacetate followed by treatment of the resulting compound (m') with hot acetic anhydride.
Hydrolysis of the este~ group in 3-acetoxy-1,4-bevTdl.Tepin-2-ones is generally carded out with excess base in an aqueous organic solution [3]. Upon treatment of compound (I) with one equivalent of base at room temperature the acetoxy group is selectively removed and it is possible to isolate 1-ethoxyearbonylmethyl-l,4-benzdiazepin-2.one. The ease of this hydrolysis reaction under such mild conditions can be explained in terms of "anchimeric assistance" by the ethoxycarbonyl group, which can be oriented in space directly at the CO) atom in the hewacx:ycle and thus facifitate departure of the leaving group because of its electron donating effect.