Hexahydropyrimidines, conformational

There is an admirable summary of the stereochemistry of barbiturates and di- to hexahydropyrimidines Further information on reduced pyrimidines is collected <70HC 16-81)322) and some examples of the use of proton NMR spectra in elucidating the conformations of hydropyrimidines is given elsewhere (Section 2.13.1.3.1), based on the general principles of such work <65QR426). 

Emphasis is placed on simply substituted free bases. The problems of conformational equilibria in /V-alkylpiperidinium salts and N-quaternization reactions and the relationships of these to conformational equilibria in the free bases are not covered, since this area is a large one requiring separate treatment. In other relevant previous reviews, the topics include heterocyclic conformational analysis,3-7 interactions in azacyclic systems,8 the conformational analysis of piperidine,9 hexahydropyrimidines,10,11 hexahydropyri-dazines,12 quinolizidines,13 the conformational analysis of bi- and polycyclic... 

For l,3-diethyl-2-methyl-l,3-hexahydropyrimidine, the ring inversion equilibrium favors the 2(ax)-Me conformer, and the data for the N-inversion equilibria (Table XXVII) refer to the set with 2(ax)-Me.287... 

It can no longer be claimed that dipole moments give reliable quantitative measures of conformational equilibria, and therefore the precise conformation of the perhydroquinazolines awaits low-temperature 13C-NMR measurements. However, for the di-H-axial conformation 332 to be predominant would be unique there is no evidence for any other hexahydropyrimidine existing even partially in such a conformation. 

Kappe, C. O., Falsone, S. F., Fabian, W. M. F., Belaj, F. Synthesis and reactions of Biginelli compounds. 13. Isolation, conformational analysis and x-ray structure determination of a trifluoromethyl-stabilized hexahydropyrimidine - an intermediate in the Biginelli reaction. Heterocycles 1999, 51, 77-84. 

Tricyclic bis-aminals, the bispyrimidine derivatives (36) and (38), having 10- and 12-membered rings adopt [2323] (37) and [3333] (39) conformations, respectively, each having out-in bridged hexahydropyrimidine rings <93JA6580). 

NMR studies have been used to investigate the conformational preferences of a number of fused 1,3-diazepine systems. The preferred conformation of Ar,AT -dimethyl-2,3,4,6-tetrahydro-2,4(l//)-diazepine is reported to be the chair-axial-equitorial conformer (4) <85TL13> whereas the perhydro-system (5) is predominantly the rranj-fused conformer <90MRC426>. An extensive NMR study of a number of hexahydropyrimidines Ar,AT -bridged by methylene groups has been undertaken in support... 

Theoretical conformational analyses of 2-hydroxypiperidine and 2-hydroxy-hexahydropyrimidine indicated that the anomeric effect is due to charge back donation from lone pairs rather than to dipolar repulsion. A molecular orbital study of the reverse anomeric effect in AT-pyranosylimidazoles suggested that the effect is not a general phenomenon even for glycosylated quartemary ammonium compounds. The proportions of axial anomers of various glucosylamines and their conjugate acids have been determined by H-NMR spectroscopy. The changes upon iV-protonation were small and were accounted for by steric reasons rather than reverse anomeric effect. ... 

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