Latent Brønsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides

Abstract

Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N,N-dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Brønsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.

Key words

amide - N,N-dimethylacetamide - urea - Brønsted base - amine - acid chloride

• References

• 1a Schneider N. Lowe DM. Sayle RA. Tarselli MA. Landrum GA. J. Med. Chem. 2016; 59: 4385
• 1b Brown DG. Boström JJ. Med. Chem. 2016; 59: 4443
• 2a Valeur E. Bradley M. Chem. Soc. Rev. 2009; 38: 606
• 2b Pattabiraman VR. Bode JW. Nature 2011; 480 (7378): 471
• 2c Saxon E. Armstrong JI. Bertozzi CR. Org. Lett. 2000; 2: 2141
• 2d Wilson RM. Stockdill JL. Wu X. Li X. Vadola PA. Park PK. Wang P. Danishefsky SJ. Angew. Chem. Int. Ed. 2012; 51: 2834

Selected examples:
• 3a Frederick W. Raymond K. J. Am. Chem. Soc. 1980; 102: 2289
• 3b Belser P. Von Zelewsky A. Frank M. Seel C. Voegtle F. De Cola L. Barigelletti F. Balzani V. J. Am. Chem. Soc. 1993; 115: 4076
• 3c Belser P. Dux R. Baak M. Cola L. De Balzani V. Angew. Chem., Int. Ed. Engl. 1995; 34: 595
• 3d Watanabe S. Ikishima S. Matsuo T. Yoshida K. J. Am. Chem. Soc. 2001; 123: 8402
• 3e Ferraris D. Ko Y.-S. Pahutski T. Ficco RP. Serdyuk L. Alemu C. Bradford C. Chiou T. Hoover R. Huang S. Lautar S. Liang S. Lin Q. Lu MX.-C. Mooney M. Morgan L. Qian Y. Tran S. Williams LR. Wu QY. Zhang J. Zou Y. Kalish V. J. Med. Chem. 2003; 46: 3138
• 3f Ben-Haida A. Hodge P. Colquhoun HM. Macromolecules 2005; 38: 722
• 3g Kazuhisa Ishimoto K. Fukuda N. Nagata T. Sawai Y. Ikemoto T. Org. Process Res. Dev. 2014; 18: 122
• 3h Xin P. Zhu P. Su P. Hou J.-L. Li Z.-T. J. Am. Chem. Soc. 2014; 136: 13078

Selected examples:
• 4a Kuz’min NI. Kabanova NI. Zhizdyuk BI. Chegolya AS. J. Org. Chem. USSR (English Translation) 1981; 17: 2139
• 4b Temple C. Bennett L. Rose J. Elliott R. Montgomery J. Mangum J. J. Med. Chem. 1982; 25: 161
• 4c Yoshida K. Okugawa T. Nagamtsu E. Yamashita Y. Matsuoka M. J. Chem. Soc., Perkin Trans. 1 1984; 529
• 4d Caperelli CA. Conigliaro J. J. Med. Chem. 1986; 29: 2117
• 4e Tamura N. Matsushita Y. Yoshioka K. Ochiai M. Tetrahedron 1988; 44: 3231
• 4f Hulinská H. Polívka Z. Jílek J. Šindelář K. Holubek J. Svátek E. Matoušová O. Buděšínský M. Frycová H. Protiva M. Coll. Czech. Chem. Commun. 1988; 53: 1820
• 4g Tamura M. Kawano Y. Chem. Pharm. Bull. 1990; 38: 116
• 4h Yakovlev YuYu. Nurmukhametov RN. Barashkov NN. Klimenko VG. Russ. J. Phys. Chem. 1991; 65: 110
• 4i Bigham EC. Mallory WR. Hodson SJ. Duch DS. Ferone R. Smith GK. Heterocycles 1993; 35: 1289
• 4j Pillai KM. R. Diamantidis G. Duncan L. Ranganathan RS. J. Org. Chem. 1994; 59: 1344
• 4k Raymond J. Cvetovich RJ. DiMichele L. Org. Process Res. Dev. 2006; 10: 944
• 4l Yamaoka N. Kodama H. Izuhara Y. Miyata T. Meguro K. Chem. Pharm. Bull. 2011; 59: 215
• 4m Mori Y. Iwamoto M. Mori K. Yoshida M. Honda T. Nagayama T. Nishi T. Heterocycles 2014; 89: 1413
• 4n Sato K. Takahagi H. Yoshikawa T. Morimoto S. Takai T. Hidaka K. Kamaura M. Kubo O. Adachi R. Ishii T. Maki T. Mochida T. Takekawa S. Nakakariya M. Amano N. Kitazaki T. J. Med. Chem. 2015; 58: 3892
• 5a Tso W.-W. Snyder CH. Powell HB. J. Org. Chem. 1970; 35: 849
• 5b Benedetti IE. Di Blasio B. Baine P. J. Chem. Soc., Perkin Trans. 2 1980; 500
• 5c Arnett EM. Quantitative Comparisons of Weak Organic Bases . In Progress in Physical Organic Chemistry . Vol. 1. Cohen SG. Streitwieser A. Taft RW. Wiley-Interscience Publishers; New York: 1963: 223
• 6 Brady WT. Lloyd RM. J. Org. Chem. 1980; 45: 2025
• 7a Dean JA. Lange’s Handbook of Chemistry . 15th ed. McGraw-Hill; New York: 1999
• 7b Cox BG. Acids and Bases, Solvent Effects on Acid-Base Strength . Oxford University Press; Oxford: 2013
• 8 Perron V. Abbott S. Moreau N. Lee D. Penney C. Zacharie B. Synthesis 2009; 283