The chemistry of 2‐aminobenzoyl hydrazides. 1. Effects of orthoester substituents on the mode of cyclization

Abstract

Treatment of substituted 2‐aminobenzoyl hydrazides with orthoesters has been found to yield different products depending upon the type of orthoester employed. Equimolar quantities of orthoester and hydrazide yield 3‐amino‐4(3H)‐quinazolinones, whereas utilization of a two‐fold excess (or greater) of orthoester yields, in some cases, 3,4‐dihydro‐5H‐1,3,4‐benzotriazepin‐5‐ones as minor products in addition to N‐[4(3H)‐quinaz‐olinon‐3‐yl]imidate esters as major products. Treatment of hydrazides with trimethyl orthobenzoate yields substituted 5‐(2‐aminophenyl)‐1,3,4‐oxadiazoles and 3,4‐dihydro‐5H‐1,3,4‐benzotriazepin‐5‐ones. The steric bulk of the phenyl group in trimethyl orthobenzoate effects the formation of adduct at the β‐nitrogen of the hydrazide which cyclized to the oxadiazole and benzotriazepinone products. In the aliphatic orthoester series, the formation of adduct to the aromatic amino group appears to be favored which gives rise to quinazolinone and benzotriazepinone products.

1-[(1-Ethoxypropylidene)amino]-2-ethyl-4-(4-hydroxybenzyl)imidazol-5(4H)-one

“…Numerous transformations of this class of compounds are known to lead to four-membered azetidines (Amr et al, 2008), five-membered pyrroles (Alawandi & Kulkarni, 2006), 1,3,4-oxadiazoles (Dabiri et al, 2006;Leiby, 1984) or 1,2,4-triazoles (Francis et al, 1991;Taha & El-Badry, 2007) and to six-membered systems such as substituted pyrimidines (Elgemeie et al, 2001), oxadiazines (Dubey et al, 2005) or triazines (Neunhoeffer & Klein-Cullmann, 1992;Lobanov et al, 1991). Numerous transformations of this class of compounds are known to lead to four-membered azetidines (Amr et al, 2008), five-membered pyrroles (Alawandi & Kulkarni, 2006), 1,3,4-oxadiazoles (Dabiri et al, 2006;Leiby, 1984) or 1,2,4-triazoles (Francis et al, 1991;Taha & El-Badry, 2007) and to six-membered systems such as substituted pyrimidines (Elgemeie et al, 2001), oxadiazines (Dubey et al, 2005) or triazines (Neunhoeffer & Klein-Cullmann, 1992;Lobanov et al, 1991).…”

“…Carboxylic acid hydrazides constitute useful precursors for the synthesis of nitrogen-and nitrogen/oxygen-containing heterocycles. Numerous transformations of this class of compounds are known to lead to four-membered azetidines (Amr et al, 2008), five-membered pyrroles (Alawandi & Kulkarni, 2006), 1,3,4-oxadiazoles (Dabiri et al, 2006;Leiby, 1984) or 1,2,4-triazoles (Francis et al, 1991;Taha & El-Badry, 2007) and to six-membered systems such as substituted pyrimidines (Elgemeie et al, 2001), oxadiazines (Dubey et al, 2005) or triazines (Neunhoeffer & Klein-Cullmann, 1992;Lobanov et al, 1991). One subgroup of the hydrazide family is the class of -aminocarboxylic acid hydrazides, which are compounds containing at least two potential reaction sites.…”

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

“…Alternative methods using ethyl chloroformate instead of the rather unpleasant triphosgene gave unsatisfactory results. 54 Subsequent heating of the isatoic anhydride derivative 64 with L-proline in DMSO gave the desired PBD 50.…”

A Simple Green Protocol for the Condensation of Anthranilic Hydrazide with Cyclohexanone and N‐Benzylpiperidinone in Water

“…Treatment of 2‐aminobenzoyl hydrazides with orthoesters has been found to yield 3,4‐dihydro‐5 H ‐1,3,4‐benzotriazepin‐5‐ones, 3‐amino‐3,4‐dihydroquinazolin‐4‐ones and 2‐(2‐aminophenyl)‐1,3,4‐oxadiazoles (Fig. , e.g., V ) .…”