Synthesis of N-Trifluoromethyl Thiocarbamates and Ureas from 3-Aminopyridine-Derived Carbamates

Abstract

The synthesis of N-trifluoromethyl thiocarbamates and ureas from 3-pyridyl isothiocyanates via the nucleophilic substitution reaction of perfluorophenyl pyridin-3-yl(trifluoromethyl)carbamate is described. Recently, Schoenebeck’s group reported a straightforward method to access N-trifluoromethyl analogues of amides and related carbonyl compounds. However, N-trifluoromethyl thiocarbamates and ureas derived from pyridine-containing amines remain a synthetic challenge. In this paper, the strategy relies on the operationally simple preparation of perfluorophenyl pyridin-3-yl(trifluoromethyl)carbamates, which can smoothly undergo nucleophilic substitution reactions with thiophenol, sodium mercaptide, and amine. Various functional groups such as amide, halogen, ether, and ester were tolerated under these reaction conditions. Notably, alkylamine structures containing pyridine heterocyclic rings are also compatible to access N-trifluoromethyl thiocarbamates.

Key words

N-trifluoromethyl thiocarbamate - N-trifluoromethyl urea - pyridine-containing amine - alkylamine - nucleophilic substitution

Publication History

Received: 13 January 2024

Accepted after revision: 19 March 2024

Accepted Manuscript online:
20 March 2024

Article published online:
02 April 2024

• References

• 1 Pattabiraman VR, Bode JW. Nature 2011; 480: 471
• 2a Bhutani P, Joshi G, Raja N, Bachhav N, Rajanna PK, Bhutani H, Paul AT, Kumar R. J. Med. Chem. 2021; 64: 2339
• 2b Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 2c McDonald S. J. Econ. Entomol. 1976; 69: 659
• 3 Sijbesma RP, Beijer FH, Brunsveld L, Folmer BJ. B, Hirschberg JH. K. K, Lange RF. M, Lowe JK. L, Meijer EW. Science 1997; 278: 1601
• 4a Ghosh AK, Brindisi M. J. Med. Chem. 2020; 63: 2751
• 4b Jagtap AD, Kondekar NB, Sadani AA, Chern JW. CurrMedChem 2017; 24: 622
• 5a Asahina Y, Araya I, Iwase K, Iinuma F, Hosaka M, Ishizaki T. J. Med. Chem. 2005; 48: 3443
• 5b Samadder P, Suchánková T, Hylse O, Khirsariya P, Nikulenkov F, Drápela S, Straková N, Vaňhara P, Vašíčková K, Kolářová H, Binó L, Bittová M, Ovesná P, Kollár P, Fedr R, Ešner M, Jaroš J, Hampl A, Krejčí L, Paruch K, Souček K. Mol. Cancer. Ther. 2017; 16: 1831
• 5c Scattolin T, Bortolamiol E, Visentin F, Palazzolo S, Caligiuri I, Perin T, Canzonieri V, Demitri N, Rizzolio F, Togni A. Chem. Eur. J. 2020; 26: 11868
• 6 Lei Z, Chang W, Guo H, Feng J, Zhang Z. Molecules 2023; 28: 3012
• 7 Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 8 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 9a Ojima I. J. Org. Chem. 2013; 78: 6358
• 9b Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315
• 9c Meanwell NA. J. Med. Chem. 2018; 61: 5822
• 10 Bouayad-Gervais S, Scattolin T, Schoenebeck F. Angew. Chem. Int. Ed. 2020; 59: 11908
• 11a Nielsen CD. T, Zivkovic FG, Schoenebeck F. J. Am. Chem. Soc. 2021; 143: 13029
• 11b Bouayad-Gervais S, Nielsen CD. T, Turksoy A, Sperger T, Deckers K, Schoenebeck F. J. Am. Chem. Soc. 2022; 144: 6100
• 12 Scattolin T, Bouayad-Gervais S, Schoenebeck F. Nature 2019; 573: 102
• 13 Zhang Z, He J, Zhu L, Xiao H, Fang Y, Li C. Chin. J. Chem. 2020; 38: 924
• 14 Liu J, Parker MF. L, Wang S, Flavell RR, Toste FD, Wilson DM. Chem 2021; 7: 2245
• 15 Tao M, Qian J, Chen Z, An L.-K, Wilson DM, Liu J. J. Org. Chem. 2023; 88: 15237
• 16 Bhutani P, Joshi G, Raja N, Bachhav N, Rajanna PK, Bhutani H, Paul AT, Kumar R. J. Med. Chem. 2021; 64: 2339
• 17 Kloeter G, Seppelt K. J. Am. Chem. Soc. 1979; 101: 347
• 18 Schindler CS, Forster PM, Carreira EM. Org. Lett. 2010; 12: 4102