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Chapter 6
Synthesis of benzodiazepines
6.8 Experimental section
Thin-layer chromatography was accomplished on 0.2-mm precoated plates of
silica gel G60 F 254 (Merck). Visualization was made with UV light (254 and 365nm)
or with an iodine vapor. IR spectra were recorded on a FTIR-8400 spectrophotometer
using DRS prob. 1 H (300 MHz), 1 H (400 MHz), 13 C (75 MHz) and 13 C (100 MHz)
NMR spectra were recorded on a Bruker AVANCE II spectrometer in CDCl 3 and
DMSO. Chemical shifts are expressed in δ ppm downfield from TMS as an internal
standard. Mass spectra were determined using direct inlet probe on a GCMS-QP 2010
mass spectrometer (Shimadzu). Solvents were evaporated with a BUCHI rotary
evaporator. Melting points were measured in open capillaries and are uncorrected.
General procedure for the synthesis of 2-chloro-N-(2-(4-
fluorobenzoyl)phenyl) acetamide (ADZ-02).
To a solution of 2-amino-4’-fluorobenzophenone (0.0046 mol) in toluene
(10mL), a solution of chloroacetyl chloride (0.0049 mol) in toluene (2 mL) was added
drop wise at 0 °C within 0.5 h. The reaction mixture was further stirred at room
temperature for 5 h. The resulting reaction mixture was evaporated to dryness. The
crude product was triturated with ethanol (10 mL) and the crystalline solid separated
was collected by filtration to give desired product ADZ-02 in 87-90% yield.
General procedure for the synthesis of 5-(4-fluorophenyl)-1H-beno[e]
[1,4]diazepin-2(3H)-one (ADZ-03).
To a solution of 2-chloro-N-(2-(4-fluorobenzoyl)phenyl)acetamide (0.0068
mol) in ethanol (40 mL), hexamethylenetetramine (HMTM; 0.015 mol) and
ammonium acetate (0.015 mol) were added. The reaction mixture was stirred at reflux
temperature for 3 h. Then the reaction mixture was evaporated to dryness. Distilled
water (30mL) was added, and the resulting suspension was stirred at 60 °C for 0.5 h.
The suspension was cooled to 20 °C and filtered. The crude product was crystallized
from toluene to obtained ADZ-03 in 80-85% yield.
Department of Chemistry, Saurashtra University, Rajkot-360005 216