1H‐4,5,6,7‐Tetrahydro‐1,3‐diazepines. part II: basicity and hydrolysis of 1, 2‐diaryl derivatives

Abstract

Basicity and alkaline hydrolysis of 1,2-diaryl-1H-4,5,6,7-tetrahydro-1,3-diazepines 1 are studied. Results are analyzed on the basis of Hammett and Swain-Lupton constants, finding good structure-basicity correlation when both, inductive and mesomeric effects, are considered together. Regioselectivity is observed in the alkaline hydrolysis of compounds 1, and it is analyzed in light of the stereoelectronic control theory. Results are compared with those previously obtained for five and six membered ring homologues: 1H-4,5-dihydroimidazoles and 1,4,5,6-tetrahydropyirimidines respectively.

Synthesis and properties of seven- to nine-membered ring nitrogen heterocycles. Cyclic amidines and cyclic amidinium salts

“…Cyclic amidines are monobases which, upon protonation on N-3, become cyclic amidiniums salts that are strongly stabilized by mesomeric effect (Scheme 24). 35,36,74…”

“…Upon comparing the basicity of the seven and eight-membered 1,2-diaryl substituted cyclic amidines (n=2,3) with that of the lower amidine (n=0,1), it was observed that basicity decreases in the order tetrahydropyrimidines (n=1) > tetrahydrodiazepines (n=2) > hexahydrodiazocines (n=3) > imidazolines. 35,36,74 This phenomenon was attributed to the possible torsion of the seven and eight-membered rings that may result in a less favored delocalization of the amidinium charge, and consequently in a decrease in basicity.…”

“…The effects of the sustituents on the N-1 aryl, were analyzed in a series of 1-aryl-2-phenyltetrahydrodiazepines. 35,36…”

“…1,2-Diaryltetrahydrodiazepines and hexahydrodiazocines are resistant to acid hydrolysis due to the high stability of the amidinium ion. 36 However, due to their amidinic nature, they are hydrolyzed in alkaline solutions affording N-acyl derivatives of the corresponding tetra-and pentamethylenediamines. The observed regioselectivity was analyzed in the light of the stereoelectronic control theory (Scheme 26).…”

“…30 Seven-and eight-membered substituted cyclic amidines are also useful precursors for the synthesis of heterocyclic ring systems as amidinium salts by alkylation, [31][32][33] and selectively substituted alkylenediamines by either reduction or alkaline hydrolysis. [34][35][36] In recent years, cyclic amidinium salts (CAS) with a fully saturated backbone (II) have attracted a great deal of attention. 1H-Dihydroimidazolium and tetrahydropyrimidinium salts (II, n = 0, 1) have been the most investigated CASs.…”