Chloro-4,6-dimethoxy-l ,3,5-triazine

Chloro-4,6-dimethoxy-l,3,5-triazine (100) reacts with iV-methylmorpholine at 20 °C to yield an isolable quaternary triazinylammonium salt (101 R = Me, R, R = C4H8O). This salt can then be reacted with a carboxylic acid to yield a 2-acyloxy-4,6-dimethoxy-l,3,5-triazine (102), which, in turn, can be reacted with an amine to yield an amide (103). This sequence of reactions provides an explanation for the activation (formation of reactive ester) of the carboxylic acid function by 2-chloro-4,6-disubstituted-l,3,5-triazines (100) in the presence of hindered amines. Several other hindered amines may replace iV-methylmorpholine in the process, but unhindered amines such as triethylamine and tributylamine were inactive. ... 

Rather surprisingly the only polycyclic ring system to have found significant commercial application in FBAs is pyrene. The triazinyl derivative (3.64), which is synthesised by a Friedel-Crafts reaction between pyrene and 2-chloro-4,6-dimethoxy-l,3,5-triazine, is an important brightener for polyester and cellulose acetate. 

An inexpensive substitute to DMTMM is 2-chloro-4, 6-dimethoxy-l,3,5-triazine in the presence of an additional organic base (103). 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

Scheme 5 Reaction of 2-Chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) with 4-Methylmorpholine To Form 4-(4,6-Dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium Chloride (DMTMM, 7)...

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-28). For an indirect way to convert carboxylic esters to ketones, see 16-82. A similar reaction with hindered aryl carboxylic acids has been reported. " Treatment of a p-amido acid with two equivalents of M-butyllithium, followed by reaction with an acid chloride leads to a p-keto amide.Carboxylic acids can be treated with 2-chloro-4,6-dimethoxy[l,3,5]-triazine and the RMgX/Cul to give ketones. " ... 

In 1995 Nicolaou and coworkers initiated a renaissance in the construction of sugar amino acid conjugates with their synthesis of carbonucleotoids [49]. Although they did not prepare amide-linked carbohydrates, they did introduce the term carbopep-toid to designate such materials. Shortly thereafter, a number of papers directed toward the synthesis of carbopeptoids appeared. One of the earliest was reported by Wessel et al., who used nor-muramic acid derivatives and condensed them in solution by means of 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT) in DMF to construct a tetramer (Fig. 27). 

Chloro-4,6-dimethoxy-l,3,5-triazines have been employed as reagents for the synthesis of 4,4-dimethyloxazolines from carboxylic acids and 2-amino-2-methyl-l-propanol... 

Triazines, such as 2,4,6-trichloro[l,3,5]triazine and 2-chloro-4,6-dimethoxy [l,3,5]triazine are known selective coupling reagents for amide synthesis [73]. 

An improved procedure for the large-scale preparation of 2-chloro-4,6-dimethoxy-l,3,5-triazine (5) is described by J. D. Copp et al.74 The application of three equivalents of sodium hydrogen carbonate as base results in less conversion to the 2,4,6-trimethoxy-l,3,5-triazine. 

Esters. Prepared from 2-chloro-4,6-dimethoxy-l,3,5-triazine and RCOOH these compounds undergo transacylation to alcohols in the presence of MgBrj. 

Numerous syntheses have been reported of the AT i receptor antagonist telmisartan, which contains two benzimidazoles/ Although typical reductive cyclization conditions are used in most of the reported syntheses, one patent describes unique cyclization conditions for formation of the second benzimidazole ring system/ In this one-pot protocol, the 2-propyl-4-methyl-l//-benzimidazole-6-carboxylic acid is first activated with 2-chloro-4,6-dimethoxy-l,3,5-triazine in A-methyl morpholine (NMM) and methanol, then treated with A-methyl-o-phenylenediamine and heated to reflux to provide the cyclized product. This protocol allow for synthesis of the benzimidazole system under nonacidic conditions and moderate temperatures. 

Due to high reactivity toward nucleophiles, 1,3,5-triazines are used for activation of reactions where elimination of water or amine is required. 2-Chloro-4,6-dimethoxy-l,3,5-triazine 30 significantly facilitates elimination of dimethylamine in the synthesis of a,P-unsaturated esters 31 via Eschenmoser s methylenation (13TL1758). 

Abbreviations CDMT = 2-chloro-4,6-dimethoxy-l,3,5-triazine EDCI = l-ethyl-3-(3-dimethyla-minopropyl)carbodiimide BOP = benzotriazol-l-yloxy-tris-(dimethylamino)phosphonium hexa-fluorophosphate DIPEA = diisopropylethylamine DEPC = diethylphosphoryl cyanide CBM IT = l,l-carbonylbis(3-methylimidazolium triflate HOBt = 1-hydroxybenzotriazole hydrate HBPyU = 0-(benzotriazole-l-yl)-iV,Af,A,Af-bis(tetramethylene)uronium hexafluorophosphate. 

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