Regiospecific Synthesis and Structural Studies of 3,5-Dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones and Comparison with 1,3-Dihydro-2H-benzo[b][1,4]diazepin-2-ones

Nine 3,5-dihydro-4 H -pyrido[2,3- b ][1,4]diazepin-4-ones ( 17 - 25 ), some of which contain fluoro-substituents, have been regiospecifically prepared by reaction of 2,3-diaminopyridines with ethyl aroylacetates. In two cases, open intermediates have been isolated and these are related to the reaction pathway. The X-ray crystal structure of 1-methyl-4-phenyl-3,5-dihydro-4 H -pyrido[2,3- b ][1,4]diazepin-4-one ( 23 ) has been solved (formula, C 15 H 13 N 3 O; crystal system, monoclinic; space group, C 2/ c ). This is an asymmetric unit constituted by a single nonplanar molecule and its conformational enantiomer due to the presence of the seven-membered diazepin-2-one moiety, which introduces a certain degree of torsion in the adjacent pyridine ring. The 1 H, 13 C, 15 N, and 19 F NMR spectra were obtained and the chemical shifts, together with those of the previously published 1,3-dihydro-2 H -benzo[ b ][1,4]diazepin-2-ones ( 1 - 16 ), i.e., a total of 544 values, were successfully compared with the chemical shifts calculated at the gauge invariant atomic orbital (GIAO)/Becke, three-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,p) level. The seven-membered ring inversion barrier in 5-benzyl-2-phenyl-3,5-dihydro-4 H -pyrido[2,3- b ][1,4]diazepin-4-one ( 25 ) was determined and, in conjunction with the data from the literature, compared with the B3LYP/6-311++G(d,p) computed values. This allowed the determination of several structural effects. The rotation about the exocyclic N1-CR bond was also calculated and its dynamic properties were discussed.