Study on 1,3,5‐Triazine Chemistry in Dehydrocondensation: Gauche Effect on the Generation of Active Triazinylammonium Species

Abstract

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.

Study of 1,3,5-Triazine-Based Catalytic Amide-Forming Reactions: Effect of Solvents and Basicity of Reactants

“…Since we were concerned with the side reaction between 2a and CDMT (Chart 1), we determined yields of the resulting amine-substituted product (4a) in addition to the desired amide (3a). On the basis of the reactivity of tert-amines toward CDMT caused by the gauche β-alkyl group, 12) we employed NMM, N,Ndimethylglycine ethyl ester (DMGE), and N,N-dimethylbutylamine (Me 2 NBu) as catalysts, and triethylamine (Et 3 N), N,Ndiisopropylethylamine (i-Pr 2 NEt), N-cyclohexylmorpholine (NCHM), N,N-diethylaniline (PhNEt 2 ), and sodium bicarbonate (NaHCO 3 ) as PCAs. DMGE and Me 2 NBu would be suitable catalysts for investigation of the effect of their basicity, because they have different basicities and have similar steric Note * To whom correspondence should be addressed.…”

“…[9][10][11][12] We found catalytic dehydrocondensation involving the in situ generation of DMT-Am from a stoichiometric amount of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and a catalytic amount of a tert-amine, as summarized in Chart 1. 13) In this system, the addition of a base, proton capture agent (PCA), 14) which is inert toward CDMT, is essential for the regeneration of the tert-amine from its hydrochloride.…”

“…[6][7][8] Related triazine-based compounds, N- (4,6-dimethoxy-1,3,5-triazin-2-yl)-N,N,N-trialkylammonium chloride (DMT-Ams), which consist of tertiary amines (tertamine) instead of N-methylmorpholine (NMM), have a similar reactivity for dehydrocondensation. [9][10][11][12] We found catalytic dehydrocondensation involving the in situ generation of DMT-Am from a stoichiometric amount of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and a catalytic amount of a tert-amine, as summarized in Chart 1. 13) In this system, the addition of a base, proton capture agent (PCA), 14) which is inert toward CDMT, is essential for the regeneration of the tert-amine from its hydrochloride.…”

“…12) This effect indicates that a steric environment around the nitrogen atom rather than the basicity of the tert-amines is predominantly correlated with their reactivity. However, we have not investigated the effect of the basicity of tert-amines in a similar steric environment.…”

Catalytic role of PPh3 and its polymer bound analog in the amidation of carboxylic acids mediated by 2,4,6-trichloro-1,3,5-triazine

“…Systems such as TCT/Et 3 N 7,12 or N-methylmorpholine (NMM), 5,6,9 oligomeric dichlorotriazine/NMM, 13 CDMT/NMM, [14][15][16]10,17,18 CDMT/N,N-dimethylglycine esters, 19,20 and CDMT/chiral tertiary amines 21 have all been successfully applied to the amidation of various carboxylic acids. While the mechanism for the TCT-mediated reactions remains unclear, 1 the added tertiary amine is believed to play an important role (apart from acting as a base) in functioning as a catalyst for preactivation of the triazine ring toward nucleophilic substitution.…”