2-Chloro-4,6-dimethoxy-1,3,5-triazine

February 2026 2-Chloro-4,6-dimethoxy-1,3,5-triazine.svg 125px 2-chloro-4,6-dimethoxy-1,3,5-triazine CDMT 3140-73-6 correct CAS 1631172 correct FDA 6KB2H8FE5Q 17426 221-541-0 18450 COc1nc(Cl)nc(OC)n1 1S/C5H6ClN3O2/c1-10-4-7-3(6)8-5(9-4)11-2/h1-2H3 GPIQOFWTZXXOOV-UHFFFAOYSA-N 5 6 3 2 1 White crystalline solid 71-74 Weber A. J. M. Huysmans W. G. B. Mijs W. J. Bovée W. M. M. J. Smidt J. Vriend J. The structure of the condensation product of methyl cyanoacetate and 2,4-dimethoxy-6-chloro-l,3,5-triazine Recueil des Travaux Chimiques des Pays-Bas 1978 97 4 107–110 10.1002/recl.19780970406 Sigma-Aldrich corrosion exclamation mark environment Danger 302 315 317 318 319 335 411 261 264 264+265 270 271 272 273 280 301+317 302+352 304+340 305+351+338 305+354+338 317 319 321 330 332+317 337+317 362+364 391 403+233 405 501 2-Chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) is a triazine derivative commonly used in acylation reactions for the synthesis of amides and esters as well as for activation of alcohols in a diverse range of other reactions. Almost exclusively used with N-methylmorpholine (NMM) as a Brønsted base, its reactivity is closely related to DMTMM. Preparation alt=CDMT synthesis|center|400x400px CDMT can be prepared from cyanuric chloride in a mixture of methanol, water and sodium bicarbonate.Dudley James R. Thurston Jack T. Schaefer Frederic C. Holm-Hansen Dagfrid Hull Clarence J. Adams Pierrepont 1951 Cyanuric Chloride Derivatives. III. Alkoxy-s-triazines Journal of the American Chemical Society 73 7 2986–2990 10.1021/ja01151a003 0002-7863 CDMT directly precipitates from this aqueous reaction mixture, but careful control of base stoichiometry and temperature is required to obtain high selectivity between the mono-, di- and trimethoxy-triazines and prepare CDMT in high yield.Cronin Jason S. Ginah Francis O. Murray Angela R. Copp James D. 1996 An Improved Procedure for the Large Scale Preparation of 2-Chloro-4,6-dimethoxy-1,3,5-triazine Synthetic Communications en 26 18 3491–3494 10.1080/00397919608003754 0039-7911 WO2016103185A2 Method for the industrial production of 2-halo -4,6-dialkoxy-1,3,5-triazines and their use in the presence of amines 2016-06-30 Beghetto Valentina https://patents.google.com/patent/WO2016103185A2/en?oq=WO2016/103185 DMTMM is prepared in a nucleophilic aromatic substitution between CDMT and NMM.Kunishima Munetaka Kawachi Chiho Monta Jun Terao Keiji Iwasaki Fumiaki Tani Shohei 12 November 1999 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride: an efficient condensing agent leading to the formation of amides and esters Tetrahedron 55 46 13159–13170 10.1016/S0040-4020(99)00809-1 0040-4020 Uses CDMT is a general reagent for acylation of carboxylic acids, providing access to amides and esters in high yields under mild conditions.Kamiński Zbigniew J. 1 January 1985 2-chloro-4,6-disubstituted-1,3,5-triazines a novel group of condensing reagents Tetrahedron Letters 26 24 2901–2904 10.1016/S0040-4039(00)98867-1 0040-4039 NMM is almost exclusively used as the Brønsted base in acylation and the reactivity of CDMT is hard to distinguish from DMTMM in the context of acylations.Sole Roberto Gatto Vanessa Conca Silvia Bardella Noemi Morandini Andrea Beghetto Valentina 2 January 2021 Sustainable Triazine-Based Dehydro-Condensation Agents for Amide Synthesis Molecules en 26 1 191 10.3390/molecules26010191 free 1420-3049 7795458 33401732 The activated ester intermediate in these reactions is the 2-acyloxy-4,6-dimethoxy-1,3,5-triazine which has been characterized using IR and NMR spectroscopy. CDMT has been shown to form a wide variety of amidations, including peptides, with low risk of epimerization.Kamiński Zbigniew J. 1987 2-Chloro-4,6-dimethoxy-1,3,5-triazine. A New Coupling Reagent for Peptide Synthesis Synthesis en 1987 10 917–920 10.1055/s-1987-28122 0039-7881 CMDT has been successfully used at multikilogram scales to prepare the secondary amide in the antitumor agent Pemetrexed.Organic Process Research & Development 10.1021/op9802172 A Practical Synthesis of Multitargeted Antifolate LY231514 1999 Barnett Charles J. Wilson Thomas M. Kobierski Michael E. In the case of esterification, broad reactivity is observed but the addition of magnesium chloride is often required.Kamińska Janina E. Kamiński Zbigniew J. Góra Józef 1999 2-Acyloxy-4,6-dimethoxy-1,3,5-triazine - A New Reagent for Ester Synthesis Synthesis 1999 04 593–596 10.1055/s-1999-3448 alt=CDMT reaction|center|400x400px CDMT has been used to activate alcohols, transforming them into electrophiles for a variety of transformations. It has been used in glycosylations.Tanaka Tomonari Kikuta Naoya Kimura Yoshiharu Shoda Shin-ichiro 5 June 2015 Metal-catalyzed Stereoselective and Protecting-group-free Synthesis of 1,2- cis -Glycosides Using 4,6-Dimethoxy-1,3,5-triazin-2-yl Glycosides as Glycosyl Donors Chemistry Letters en 44 6 846–848 10.1246/cl.150201 0366-7022 The anomeric position can be activated selectively without protecting the other hydroxy groups. The isolated CDMT-adduct undergoes stereoselective reaction with alcohols when used as solvent in the presence of catalytic [CuI(CH3CN)4]PF6. Isolated CDMT-adducts have also been used as electrophiles in nickel-catalyzed Suzuki-Miyaura cross couplings.Journal of Organic Chemistry 10.1021/jo4005537 Nickel-Catalyzed Suzuki–Miyaura Coupling of Heteroaryl Ethers with Arylboronic Acids 2013 Li Xiao-Jian Zhang Jin-Ling Geng Yu Jin Zhong alt=CDMT reaction|center|400x400px alt=CDMT reaction|center|400x400px Safety In vivo dermal sensitization studies according to OECD 429OECD https://www.oecd-ilibrary.org/environment/test-no-429-skin-sensitisation_9789264071100-en Test No. 429: Skin Sensitisation: Local Lymph Node Assay 2010 Organisation for Economic Co-operation and Development Paris en confirmed CMDT is a strong skin sensitizer, showing a response at 0.03 wt% in the local lymph node assay (LLNA) placing it in Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Dermal Sensitization Category 1A.Graham Jessica C. Trejo-Martin Alejandra Chilton Martyn L. Kostal Jakub Bercu Joel Beutner Gregory L. Bruen Uma S. Dolan David G. Gomez Stephen Hillegass Jedd Nicolette John Schmitz Matthew 20 June 2022 An Evaluation of the Occupational Health Hazards of Peptide Couplers Chemical Research in Toxicology en 35 6 1011–1022 10.1021/acs.chemrestox.2c00031 0893-228X 9214767 35532537 These studies confirm that DMTMM is a less sensitizing alternative to CDMT, as suggested by anecdotal observations in the literature.Kunishima Munetaka Kawachi Chiho Monta Jun Terao Keiji Iwasaki Fumiaki Tani Shohei 12 November 1999 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride: an efficient condensing agent leading to the formation of amides and esters Tetrahedron 55 46 13159–13170 10.1016/S0040-4020(99)00809-1 0040-4020 References Category:Triazines Category:Peptide coupling reagents Category:Methoxy compounds Category:Chloroarenes