Synlett 2012; 23(16): 2426-2427
DOI: 10.1055/s-0032-1317182
© Georg Thieme Verlag Stuttgart · New York

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride

Ana Zivanovic
School of Chemistry, University of Wollongong, Wollongong 2522, NSW, Australia   Email:
› Author Affiliations
Further Information

Publication History

Publication Date:
13 September 2012 (online)


4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholi­nium chloride (DMTMM) is a highly effective coupling reagent used for both amide synthesis and for the preparation of esters.[1] [2] The advantages of using DMTMM as a coupling reagent include excellent product yields and the possibility that reactions can be performed in one step at room temperature and under atmospheric conditions.[ 1 ] Readily removed and solubilising solvents (e.g. MeOH, EtOH, i-PrOH) including water, can be used in reactions with DMTMM and no drying requirements are needed for the reaction solvents.[ 3 ] Furthermore, no additives are required and acids can be activated in situ.[ 2 ]

The by-product of the reaction with DMTMM (2-hydroxy-4,6-dimethoxy-1,3,5-triazine, HO-MDT) is highly water soluble and can be easily removed from the main reaction product.[2] [4] The recovered by-product can also be converted back into the starting material via 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT).

DMTMM is commercially available, but can also be prepared in a straightforward manner by reaction between CDMT and n-methylmorpholine (NMM) or from cyanuric chloride.[3] [5] The reagents for the preparation of ­DMTMM are inexpensive, providing an economical benefit when using this reagent.

Zoom Image
Scheme 1 Preparation of DMTMM from CDMT
  • References

  • 1 Kunishima M, Morita J, Kawachi C, Iwasaki F, Terao K, Tani S. Synlett 1999; 1255
  • 2 Kunishima M, Kawachi C, Hioki K, Terao R, Tani S. Tetrahedron 2001; 57: 1551
  • 3 Kunishima M, Kawachi C, Morita J, Terao K, Iwasaki F, Tani S. Tetrahedron 1999; 55: 13159
  • 4 Kunishima M, Hioki K, Wada A, Kobayashi H, Tani S. Tetrahedron Lett. 2002; 43: 3323
  • 5 Falchi A, Giacomelli G, Porcheddu A, Taddei M. Synlett 2000; 275
  • 6 Hojo K, Maeda M, Tanakamaru N, Mochida K, Kawasaki K. Protein Pept. Lett. 2006; 13: 189
  • 7 Pradidphol N, Kongkathip N, Sittikul P, Boonyalai N, Kongkathip B. Eur. J. Med. Chem. 2012; 49: 253
  • 8 Hyun H, Yui N. Macromol. Rapid Commun. 2011; 32: 326
  • 9 Tanaka T, Noguchi M, Watanabe K, Misawa T, Ishihara M, Kobayashi A, Shoda S.. Org. Biomol. Chem. 2010; 8: 5126
  • 10 Pudlo M, Allart-Simon I, Tinant B, Gerard S, Sapi J. Chem. Commun. 2012; 48: 2442
  • 11 Mizuhara T, Hioki K, Yamada M, Sasaki H, Morisaki D, Kunishima M. Chem. Lett. 2008; 37: 1190
  • 12 Shieh WC, Chen ZL, Xue S, McKenna J, Wang RM, Prasad K, Repic J. Tetrahedron Lett. 2008; 49: 5359
  • 13 Wu CL, Huang ZX, Shang ZP, Zhou MQ, Deng Y. Chin. J. Org. Chem. 2011; 31: 1262