Kinetics of Cyclization of 2-(N-B-Bromoethyl)-amino-5-substituted Benzophenones into 1,4-Benzodiazepines

Sa？etak The overall pseudo-first order cyclization rates of 2-N-/J-bro moethylamino-5-substituted benzophenones 1-3 into 1,4-benzodiazepines 7-9, determined in 60/o ethanolic ammonia at 100 °c, 115 °c, and 125 °c respectively, were found to range between 1.0 X 10-？ and 8.33 X 10-？ s-1 for 1, between 1.6 X 10-4 and 5.83 X 10-？ s·1 for 2 and between 6.66 X 10-5 and 3.16 X 10-？ s-1 for 3. Rate values calculated from the rising concentrations of cyclization products 7-9 were lower indicating the formation of stable intermediates. It is assumed that these are protonated aziridine derivatives 4-6, since compounds 4 and 5 were identified as intermediates by TLC and GLC. The formation rate for the model compound 2-amino-5-chlorobenzophenone imine was found to be only 5.8 x 10-7 s-1 at 125 °C, which eliminates imine (C=NH) derivatives of 1-3 as possible intermediates. The ammonolysis rates of 3-phenylpropylbromide between 110 °c and 125 °c, were found to range from 1.5 X 10-4 to 4.16 X 10-？ s·1？ These values revealed that the ~-participation of the N(2)-atom, being a relatively rapid equilibrium, does not enhance the overall cyclization rate. The following parameters characterize the overall cyclization process; l'i H=I= = 50.0 ± 4.0 kJ mo1-1 and l'i S=I= = -156 ± 5 J mo1-1 K-1 for 1, /'i H=I= = 89.9 ±.4.0 kJ moP K 1 for 2, l'i H=I= = = 75.3 ± 4.0 kJ moi-1 and l'i S=I= = -89 ± 4 J moi-1 K' for 3