Synthesis and Pharmacological Activity of N- and O-Acyl Derivatives OF 2,6-Diphenyl-4-hydroxypiperidines and Tetrahydropyridines

Synthesis and Molecular Structure of 9-(Arylidene)amino- 11-(2-hydroxyphenyl)-8-oxa-12-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trienes Formed by Cascade Reaction of 2,6-Di(2-hydroxy-phenyl)-4-oxopiperidines with Arylaldehydes and Ammonia

“…Synthesis and Molecular Structure of New 8-Oxa-12-azatricyclotridecanes Multicomponent reactions of aromatic aldehydes with aliphatic ketones in the presence of ammonium acetate form a class of general Petrenko-Kritchenko domino reactions [1] and are widely used for the preparation of 2,6-diaryl substituted γ-piperidones, [2,3] which are important initial compounds in synthesis of biologically active agents. [4][5][6][7] However, in the case of salicylic aldehyde (SA) this method does not result in corresponding piperidones. For example, when acetone or its homologues are used as a dialkylketone component, the main product of the cascade condensation would have structure of ortho-hydroxyphenylimino substituted benzopyranes.…”

“…For example, when acetone or its homologues are used as a dialkylketone component, the main product of the cascade condensation would have structure of ortho-hydroxyphenylimino substituted benzopyranes. [8] Moreover, the derivatives of oxaazatricycloalkanes [9,10] particularly, benzopyranyl substituted 8-oxa-10-azatricyclo[7.3.1.0 2,7 ]tridecane [11,12] are formed in the multicomponent reaction of SA with a classic ethyl 3-oxobutanoate component and ammonium or methylammonium acetate.…”

“…The mixtures of SA with monophenylacetone [13] or with 1,3-diphenyl acetone [14] and ammonium acetate (taken in 2:1:2 proportion) did produce 2,6-di(2-hydroxyphenyl) substituted 3-phenylpiperidone [13] or 3,5-diphenylpiperidone, [14] though the reaction mixture also contained in the latter case 2-hydroxybenzylidenoamino substituted 8-oxa-12-azatricyclo[7.3.1.0 2,7 ]tridecane, separated later [15] individually and characterized by X-ray analyses in the free form [15] or as acetate ethanol disolvate [16] (Figure 1).…”

“…In this work, we continue our investigation to broaden the boundaries of the cascade method application for the preparation of 8-oxa-12-azatricyclo[7.3.1.0 2,7 ]tridecanes. First, in the one-step triple component condensation we used the mixtures of SA with monophenylacetone 1a or 1-phenyl-4-(4-hydroxy)butan-2-one 1b and ammonia in a considerable excess (in 3:1:5 proportion).…”

“…Indeed, the aminallike structure showed sterically preferable O-nucleophilic heterocyclization by oxyphenyl substituent at C-6 of the piperidine cycle. The X-ray data of the known diphenyl substituted 8-oxa-12-azatricyclo[7.3.1.0 2,7 ]tridecane 2c in the free form [15] or in acetate ethanol disolvate [16] both demonstrated that one benzoxy group connected with α-position of the piperidine cycle was condensed 1,3-diaxially with it, thus forming dihydropyranic nucleus, while another analogous 2-hydroxyphenyl group together with two phenyl groups at β-, β'-positions of the piperidine moiety were all equatorial. It witnessed for the Petrenko-Kritchenko reaction reversibility to produce sufficient quantity of the axially oriented α-2-hydroxyphenyl group in the synthesized intermediate piperidones.…”