Modified Purines. Rearrangement Through 5-Substituted Purine Intermediates
type: CreativeWork
description: A novel rearrangement has been utilized for the synthesis of imidazo{1,5-a}-1,3,5-triazinones (1) which are analogues of N(9)-substituted guanines, hypoxanthines, and xanthines. Structures were established in this series (1) on the basis of precursors and routes of synthesis, infrared spectra, mass spectra, ('1)H and ('13)C nuclear magnetic resonance spectra, and X-ray crystallographic analysis of one member among the interrelated compounds in the series. Condensation of various (alpha)-cyanoesters with urea, thiourea, guanidine, and N('1),N('1)-dimethylguanidine yielded substituted 4,5-dihydropyrimidin-4-ones (2). Treatment of the 4,5-dihydropyrimidin-4-ones 2 with chlorotrimethylsilane and hexamethyldisilazane in pyridine gave the correspondingly substituted imidazo{1,5-a}-1,3,5-triazinones 1. The syntheses of compounds of type 1 by cyclization-rearrangement of the monocyclic derivatives 2 indicated the generality of this synthetic approach to imidazo{1,5-a}-1,3,5-triazines with variation in substitution at C(2), C(5), and the C(5)-amide group of the 4,5-dihydropyrimidin-4-one precursors 2 (see numbering system in 2). The possibility of successful preparation of imidazo{1,5-a}-1,3,5-triazine products with variation in substitution at C(5) is of particular interest in view of (a) the analogy between C(8) substitution in the imidazo{1,5-a}-1,3,5-triazines 1 and N(9) substitution on guanine, hypoxanthine, and xanthine; and (b) since substitution at C(5) of the monocyclic heterocycle results in substitution on C(8) in the corresponding imidazo{1,5-a}-1,3,5-triazine. Incorporation of a ribosyl unit or analogous moiety at the C(5) position of the monocyclic heterocycle could give, after cyclization-rearrangement, imidazo{1,5-a}-1,3,5-triazine analogues of naturally occurring nucleic acid bases. Additional modifications could then provide analogues of naturally occurring nucleosides, nucleotides, and coenzymes.
abstract: A novel rearrangement has been utilized for the synthesis of imidazo{1,5-a}-1,3,5-triazinones (1) which are analogues of N(9)-substituted guanines, hypoxanthines, and xanthines. Structures were established in this series (1) on the basis of precursors and routes of synthesis, infrared spectra, mass spectra, ('1)H and ('13)C nuclear magnetic resonance spectra, and X-ray crystallographic analysis of one member among the interrelated compounds in the series. Condensation of various (alpha)-cyanoesters with urea, thiourea, guanidine, and N('1),N('1)-dimethylguanidine yielded substituted 4,5-dihydropyrimidin-4-ones (2). Treatment of the 4,5-dihydropyrimidin-4-ones 2 with chlorotrimethylsilane and hexamethyldisilazane in pyridine gave the correspondingly substituted imidazo{1,5-a}-1,3,5-triazinones 1. The syntheses of compounds of type 1 by cyclization-rearrangement of the monocyclic derivatives 2 indicated the generality of this synthetic approach to imidazo{1,5-a}-1,3,5-triazines with variation in substitution at C(2), C(5), and the C(5)-amide group of the 4,5-dihydropyrimidin-4-one precursors 2 (see numbering system in 2). The possibility of successful preparation of imidazo{1,5-a}-1,3,5-triazine products with variation in substitution at C(5) is of particular interest in view of (a) the analogy between C(8) substitution in the imidazo{1,5-a}-1,3,5-triazines 1 and N(9) substitution on guanine, hypoxanthine, and xanthine; and (b) since substitution at C(5) of the monocyclic heterocycle results in substitution on C(8) in the corresponding imidazo{1,5-a}-1,3,5-triazine. Incorporation of a ribosyl unit or analogous moiety at the C(5) position of the monocyclic heterocycle could give, after cyclization-rearrangement, imidazo{1,5-a}-1,3,5-triazine analogues of naturally occurring nucleic acid bases. Additional modifications could then provide analogues of naturally occurring nucleosides, nucleotides, and coenzymes.
author: Holtwick, Joseph Bernard
language: eng
keywords: Chemistry, Organic
date published: 2014-12-13T20:11:18Z
date modified: 2026-07-22T22:25:57Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/67278