DOI: 10.1039/C3OB42037J
Page 3 of 4
Organic & Biomolecular Chemistry
Interestingly, iodide could also realize the oxidative amidation
aldehydes or alcohols with ammonium. The straightforward
process described here is simple, highly effective, and makes use
of readily available starting materials, all of which should render
this method attractive for synthesizing primary amides.
of methyl ketones. For example, the oxidative amidation reaction
of acetophenone 4a with ammonium iodide provided primary
ketoamide 5a in 40% yield (Scheme 3). To the best of our
knowledge, the oxidative coupling reaction of methyl ketones
with ammonium salts/ammonia leading to -ketoamides has not
been reported.12
5
40 Acknowledgments
This work was supported financially by the National Program on
Key Basic Research Project of China (973 Program,
2013CB328900) and the National Science Foundation of China
(Grant No. 21202107); we also thank the Analytical & Testing
45 Center at Sichuan University for performing NMR analyses.
Notes and references
10 Scheme 3. Oxidative amidation of acetophenone
a
Key Laboratory of Green Chemistry & Technology, Ministry of
Education, College of Chemistry, Sichuan University, Chengdu 610064,
PR China.
50 Tel.: (86)-28-85415886; fax: (86)-28-85415886; E-mail:
To gain insight into the mechanism of the reaction, some
control experiments were set up. When benzonitrile was used
rather than aldehydes or alcohols, no obvious amide formation
15 was observed (Scheme 4, equation 1). Therefore, this
transformation does not proceed through a nitrile intermediate as
has been reported in the iodine or manganese oxide-promoted
systems.5, 7 When 20 mol % 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO, a radical scavenger) was added to the reaction mixture,
20 the amidation process was significantly inhibited (Scheme 4,
equation 2). In terms of these experimental results and the
previous reports,3, 13 a proposed mechanism is shown in scheme 5.
Alcohols are oxidized into aldehydes under the Et4NI/TBHP
system. Then, ammonia attacks aldehydes to generate
25 hemiaminal A, which can then be converted into amides via
dehydrogenation.
1
(a) M. J. Humphrey, R. A. Chamberlin, Chem. Rev. 1997, 97, 2243;
(b) T. Cupido, J.Tulla-Puche, J. Spengler, F. Albericio, Curr. Opin.
Drug Discovery Dev. 2007, 10, 768; (c) C. L. Allen, J. M. J.
Williams, Chem. Soc. Rev. 2011, 40, 3405; (d) V. R. Pattabiraman, J.
W. Bode, Nature 2012, 480, 471; (e) R. M. Wilson, J. L. Stock-dill,
X. Wu, X. Li,P. A. Vadola,P. K. Park, P. Wang, S. J. Danishef-sky,
Angew. Chem. 2012, 124, 2888; Angew. Chem. Int. Ed. 2012, 51,
2834.
55
60
2
3
(a) D. Dopp, H. Dopp, Eds. Methoden der Organischen Chemie
(Houben Weyl); Thieme: Stuttgart, 1985; Vol. E5 (2), 1024-1031; (b)
P. D. Bailey, T. J. Mills, R. Pettecrew, R. A. Price, Comprehensive
Organic Functional Group Transformations II, 2005, 5, 201-294; (c)
E. Valeur, M. Bradley, Chem. Soc. Rev., 2009, 38, 606.
(a) K. R. Reddy, C. U. Maheswari, M. Venkateshwar and M. L.
Kantam, Eur. J. Org. Chem. 2008, 21, 3619; (b) K. Ekoue-Kovi, C.
Wolf, Chem. Eur. J. 2008, 14, 6302; (c) A. J. A. Watson, J. M. J.
Williams, Science 2010, 329, 635; (d) C. Chen, S. H. Hong, Org.
Biomol. Chem. 2011, 9, 20; (e) J.-F. Soule, H. Miyamura, S.
Kobayashi, J. Am. Chem. Soc. 2011, 133, 18550.
65
70
4
5
(a) K. Nakagawa, H. Onoue, K. Minami, Chem. Commun. (London)
1966, 17-18; (b) C. Gunanathan, Y. Ben-David, D. Milstein, Science,
2007, 317, 790; (c) A. J. A. Watson, A. C. Maxwell, J. M. J.
Williams, Org. Lett. 2009, 11, 2667.
(a) K. Yamaguchi, H. Hobayashi, T. Oishi, N. Mizuno, Angew.
Chem. Int. Ed. 2012, 51, 544; (b) R. Nie,; J. Shi, S. Xia, L. Shen, P.
Chen, Z. Hou, F.-S. Xiao, J. Mater. Chem. 2012, 22, 18115.
S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. L. L.
Chai, A. Chen, J. Org. Chem. 2012, 77, 8007.
(a) J.-J. Shie, J.-M. Fang, J. Org. Chem. 2003, 68, 1158; (b) R.
Ohmura, M. Takahata, H. Togo, Tetrahedron Lett. 2010, 51, 4378.
For the recent reports on tetra-alkylammonium iodide catalytic
reactions, see: (a) M. Uyanik, H. Okamoto, T. Yasui, K. Ishihara,
Science 2010, 328, 1376; (b) M. Uyanik, D. Suzuki, T. Yasui, K.
Ishihara, Angew. Chem., Int. Ed. 2011, 50, 5331; (c) T. Froehr, C. P.
Sindlinger, U. Kloeckner, P. Finkbeiner, B. J. Nachtsheim, Org. Lett.
2011, 13, 3754; (d) M. Lamani, K. R. Prabhu, J. Org. Chem. 2011,
76, 9552; (e) L.-T. Li, J. Huang, H. -Y. Li, L.-J. Wen, P. Wang, B.
Wang, Chem. Commun. 2012, 48, 5187; (f) M. Uyanik, K. Ishihara,
ChemCatChem 2012, 4, 177; (j) J. A. Souto, D. Zian, K. Muñiz, J.
Am. Chem. Soc. 2012, 134, 7242; (h) E. Shi, Y. Shao, S. Chen, H. Y.
Hu, Z. J. Liu, J. Zhang, X. B. Wan, X. B. Org. Lett. 2012, 14, 2936.
(i) J. Xie, H. L. Jiang, Y. X. Cheng, C. J. Zhu, Chem. Commun.
2012, 48, 979; (j) Q. C. Xue, J. Xie, H. M. Li, Y. X. Cheng, C. J.
Zhu, Chem. Commun. 2013, 49, 3700.
75
Scheme 4. Control experiments
30
6
7
8
80
85
90
95
Scheme 5. A proposed mechanism
9
For the recent reports on iodide catalytic amidation, see: (a) Y.
Wang, D. Zhu, L. Tang, S. Wang, Z. Wang, Angew. Chem. Int. Ed.
2011, 50, 8917; (b) Z. J. Liu, J. Zhang, S. L. Chen, E. Shi, Y. Xu, X.
B. Wan, Angew. Chem. Int. Ed. 2012, 51, 3231; (c) J.-S. Tian, K.
Wai, J. Ng, J.-R. Wong, T.-P. Loh, Angew. Chem. Int. Ed. 2012, 51,
Conclusions
100
In summary, we have developed an efficient Et4NI-catalyzed
35 protocol for the formation of primary amides from benzylic