Study on 1,3,5-triazine chemistry in dehydrocondensation: gauche effect on the generation of active triazinylammonium species.
The reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with various nitrogen-containing compounds, particularly tertiary amines (tert-amines), has been studied for the preparation of 2-(4,6-dimethoxy-1,3,5-triazinyl)trialkylammonium salts [DMT-Am(s)]. DMT-Ams derived from aliphatic tert-amines exhibited activity for the dehydrocondensation between a carboxylic acid and an amine to form an amide in a model reaction. Based on a conformational analysis of DMT-Ams and tert-amines by NMR and X-ray diffraction methods, we concluded that a β-alkyl group maintained in a gauche relationship with the nitrogen lone pair of tert-amines significantly hinders the approach of CDMT to the nitrogen. Thus, trimethylamine and quinuclidine without such alkyl groups readily react with CDMT whereas triethylamine, possessing two or three such gauche β-alkyl groups in the stable conformations, does not react at all. The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of DMT-Ams possessing various tertiary amine moieties. An investigation of the dehydrocondensation activity of tert-amines in a CDMT/tert-amine system that involves in situ generation of DMT-Am, showed that the gauche effect of the β-alkyl group becomes quite pronounced; the yield of the amide decreases significantly with tert-amines possessing an unavoidable gauche β-alkyl group. Thus, the tert-amine/CDMT systems are useful for judging whether tert-amines can readily react with CDMT without isolation of DMT-Ams.
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Japan. kunisima@p.kanazawa-u.ac.jp
Munetaka
M
Kunishima
Takae
T
Ujigawa
Yoshie
Y
Nagaoka
Chiho
C
Kawachi
Kazuhito
K
Hioki
Motoo
M
Shiro
D000588:Amines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012492:Salts; D014227:Triazines / Q000737:chemistry*; D014961:X-Ray Diffraction
D000588:Amines; D000644:Quaternary Ammonium Compounds; D012492:Salts; D014227:Triazines