10.1002/ejoc.202100363
European Journal of Organic Chemistry
COMMUNICATION
[2]
[3]
a) P. Wang, T. Cai, N. Taniguchi, Nitric Oxide Donors: For
Pharmaceutical and Biological Applications, 2005, 1-390; b) P. G. Wang,
M. Xian, X. Tang, X. Wu, Z. Wen, T. Cai, A. J. Janczuk, Chem. Rev.,
2002, 102, 1091-1134.
NO2 radical, which undergoes rapid dimerization to generate N2O4.
A NO+ cation is then generated through equilibrium. Finally, a
nucleophilic attack of the amine on NO+ generates the desired
product. At the same time, protons are reduced at the cathode
with the formation of H2.
a) C. L. Bumgardner, K. S. McCallum, J. P. Freeman, J. Am. Chem. Soc.,
1961, 83, 4417-4419; b) D. Seebach, D. Enders, Angew. Chem. Int. Ed.,
1975, 14, 15-32; c) T. Olszewska, M. J. Milewska, M. Gdaniec, H.
Małuszyńska, T. Połoński, J. Org. Chem., 2001, 66, 501-506.
R. López-Rodríguez, J. A. McManus, N. S. Murphy, M. A. Ott, M. J. Burns,
Org. Process Res. Dev., 2020, 24, 1558-1585.
[4]
[5]
a) G. Neurath and M. Dünger, Chem. Ber., 1964, 97, 2713-2714; b) M.
A. Zolfigol, A. Bamoniri, Synlett, 2002, 2002, 1621-1624; c) B. Célariès,
C. Párkányi, Synthesis, 2006, 2006, 2371-2375; d) S. P. Borikar, V. Paul,
Synth. Commun., 2010, 40, 654-660.
[6]
[7]
M. A. Zolfigol, Synth. Commun., 1999, 29, 905-910.
A. C. Chaskar, B. P. Langi, A. Deorukhkar, H. Deokar, Synth. Commun.,
2009, 39, 604-612.
[8]
[9]
J.-Y. Hou, Y.-L. Wang, J.-Y. Wang, J. Chem. Res., 2003, 2003, 626-627.
P. Gaur and S. Banerjee, Synth. Commun., 2019, 49, 2270-2279.
[10] a) G. Verardo, A. G. Giumanini, P. Strazzolini, Tetrahedron, 1990, 46,
4303-4332; b) D. Roche, C. Lardy, L. Tournier, M. Prunier, E. Valeur,
Tetrahedron Lett., 2010, 51, 2277-2280; c) P. Chaudhary, S. Gupta, N.
Muniyappan, S. Sabiah, J. Kandasamy, Green Chem., 2016, 18, 2323-
2330; d) X. Guo, C. Lv, Q. Mahmood, L. Zhou, G. Xu, Q. Wang, Org.
Chem. Front., 2019, 6, 3401-3407; e) X. Jia, P. Li, Y. Shao, Y. Yuan, H.
Ji, W. Hou, X. Liu, X. Zhang, Green Chem., 2017, 19, 5568-5574; f) S. L.
Yedage, B. M. Bhanage, J. Org. Chem., 2017, 82, 5769-5781; g) Y. He,
Z. Zheng, Y. Liu, J. Qiao, X. Zhang, X. Fan, Org. Lett., 2019, 21, 1676-
1680.
Scheme 6. Plausible mechanism.
In summary, we report on the development of a straight-
forward, acid free and convenient route to activate the widely
commercially available potassium nitrite for use in N-nitrosation
reactions. The reaction proceeds under exogenous-oxidant-free
and acid-free electrochemical oxidation conditions, and a diverse
collection of valuable N-nitrosation products were obtained in
moderate to high yields. Notably, this electrochemical approach
maintains excellent functional group tolerance and can be
extended as a strategy for use in pharmaceutical research.
Further detailed mechanistic studies regarding this transformation
are currently under way in our laboratory.
[11] a) E. H. White, J. Am. Chem. Soc., 1955, 77, 6008-6010; b) S. Goldstein,
G. Czapski, J. Am. Chem. Soc., 1996, 118, 3419-3425; c) N. S.
Nudelman, A. E. Bonatti, Synlett, 2000, 2000, 1825-1827; d) N. Iranpoor,
H. Firouzabadi, A. R. Pourali, Synth. Commun., 2005, 35, 1517-1526; e)
E. H. White, W. R. Feldman, J. Am. Chem. Soc., 1957, 79, 5832-5833.
[12] L. Castedo, R. Riguera, M. P. Vázquez, J. Chem. Soc., Chem. Commun.,
1983, 301-302.
[13] M. A. Zolfigol, M. H. Zebarjadian, G. Chehardoli, H. Keypour, S.
Salehzadeh, M. Shamsipur, J. Org. Chem., 2001, 66, 3619-3620.
[14] a) A. S. Demir, A. S. Mahasneh, H. Aksoy, Z. Gercek, Synth. Commun.,
1992, 22, 2607-2611; b) J. Zhang, J. Jiang, Y. Li and X. Wan, J. Org.
Chem., 2013, 78, 11366-11372; c) N. Sakai, M. Sasaki, Y. Ogiwara,
Chem. Commun., 2015, 51, 11638-11641; d) S. Azeez, P. Chaudhary,
P. Sureshbabu, S. Sabiah, J. Kandasamy, Asian J. Org. Chem., 2018, 7,
2113-2119.
Experimental Section
General procedure for electrochemical N-nitrosation of
secondary amines: In an oven-dried undivided three-necked
flask (25 mL) equipped with a stir bar, secondary amines 1 (0.50
n
mmol), KNO2 2 (2.5 mmol), CH2Cl2 (7 mL) with Bu4NBF4 (0.30
[15] For selected reviews, see: a) Y. Jiang, K. Xu, C. Zeng, Chem. Rev., 2018,
118, 4485-4540; b) M. Yan, Y. Kawamata and P. S. Baran, Chem. Rev.,
2017, 117, 13230-13319; c) S. Möhle, M. Zirbes, E. Rodrigo, T. Gieshoff,
A. Wiebe, S. R. Waldvogel, Angew. Chem. Int. Ed., 2018, 57, 6018-6041;
d) P. Gandeepan, L. H. Finger, T. H. Meyer, L. Ackermann, Chem. Soc.
Rev., 2020, 49, 4254-4272; e) M. D. Kärkäs, Chem. Soc. Rev., 2018, 47,
5786-5865; f) S. Tang, Y. Liu, A. Lei, Chem, 2018, 4, 27-45; g) C. Ma, P.
Fang, T.-S. Mei, ACS Catal., 2018, 8, 7179-7189; h) J. C. Siu, N. Fu, S.
Lin, Acc. Chem. Res., 2020, 53, 547-560; i) P. Xiong, H.-C. Xu, Acc.
Chem. Res., 2019, 52, 3339-3350.
mmol) as an electrolyte were combined and added. The flask was
equipped with platinum electrodes (1.5 cm×1.5 cm×0.3 mm) as
cathode, carbon rod (Φ 6 mm, about 10 mm immersion depth in
solution) as the anode. The reaction mixture was stirred and
electrolyzed at a constant current of 5 mA under room
temperature for 4 h. After completion of the reaction, as indicated
by TLC and GC-MS, the pure product was obtained by flash
column chromatography on silica gel (petroleum ether : ethyl
acetate = 50 : 1).
[16] J.-P. Zhao, L.-j. Ding, P.-C. Wang, Y. Liu, M.-J. Huang, X.-L. Zhou, M.
Lu, Adv. Synth. Catal., 2020, 362, 5036-5043.
[17] a) B. Su, L. Li, Y. Hu, Y. Liu, Q. Wang, Adv. Synth. Catal., 2012, 354,
383-387; b) G. V. Zyryanov, D. M. Rudkevich, Org. Lett., 2003, 5, 1253-
1256; c) E. Bosch, J. K. Kochi, J. Org. Chem., 1994, 59, 3314-3325; d)
M. A. Zolfigol, M. H. Zebarjadian, I. Mohammadpoor-Baltork, M.
Shamsipur, Synth. Commun., 2002, 32, 2803-2808.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (No. 21702081).
[18] a) T. Broder, D. Silvester, L. Aldous, C. Hardacre, R. Compton, J. Phys.
Chem. B, 2007, 111, 7778-7785; b) V. Bryantsev, J. Uddin, V. Giordani,
W. Walker, G. Chase, D. Addison, J. Am. Chem. Soc., 2014, 136, 3087-
3096.
Keywords: Electrochemical synthesis • N-nitrosation • Acid free
• Potassium Nitrite
[1]
D. L. H. Williams, Nitrosation Reactions and the Chemistry of Nitric Oxide,
Elsevier, Amsterdam, 2004.
4
This article is protected by copyright. All rights reserved.