Facile Synthesis of 2-(2-Ethoxy-1,2-dioxoethyl)azoles

Oleksandr V. Geraschenko; Pavel V. Khodakovskiy; Oleg V. Shishkin; Pavel K. Mykhailiuk; Olga A. Zaporozhets; Andrey A. Tolmachev

doi:10.1055/s-0030-1260003

PAPER

Facile Synthesis of 2-(2-Ethoxy-1,2-dioxoethyl)azoles

Oleksandr V. Geraschenko^a,b, Pavel V. Khodakovskiy^a, Oleg V. Shishkin^c, Pavel K. Mykhailiuk*^a,b, Olga A. Zaporozhets^a, Andrey A. Tolmachev^a,b
^a Enamine Ltd., Oleksandra Matrosova Street 23, Kyiv 01103, Ukraine
^b Department of Chemistry, Kyiv National Taras Shevchenko University, Volodymyrska Street 64, Kyiv 01033, Ukraine
Fax: +380(44)2351273; e-Mail: Pavel.Mykhailiuk@gmail.com;
^c STC, ‘Institute for Single Crystals’, National Academy of Science of Ukraine, 60 Lenina Ave, Kharkiv 61001, Ukraine

Abstract

All articles of this category

Abstract

C-Acylation of N-substituted imidazoles with ethyl oxalyl chloride in the presence of N,N-diisopropylethylamine as a base afforded 2-(2-ethoxy-1,2-dioxoethyl)imidazoles in 83-95% yield. Application of this synthetic protocol to thiazoles and triazoles led to the corresponding 2-ethoxy-1,2-dioxoethyl derivatives in 40-51% yield.

Key words

azoles - acylations - glyoxylates - keto esters - heterocycles

Full Text

References

1a Waters KL. Chem. Rev. 1947, 41: 585

1b Cooper AJL. Ginos JZ. Meister A. Chem. Rev. 1983, 83: 321

1c Zamkova IA. Chekotylo OO. Geraschenko OV. Grygorenko OO. Mykhailiuk PK. Tolmachev AA. Synthesis 2010, 1692

2 Lavelle F. Expert Opin. Investig. Drugs 1999, 8: 903

3 Mitsunori O, Przewloka T, James D, Dinesh C, Rongzhen L, Masazumi N, Keizo K, and Lijun S. inventors; US 204090 (A1). ; Chem. Abstr. 2003, 139, 350631

4 Baxi S. Crandall DL. Meier TR. Wrobleski S. Hawley A. Farris D. Elokdah H. Sigler R. Schaub RG. Wakefield T. Myers D. Thromb. Haemost. 2008, 99: 739

5 Abraham E. Naum C. Bandi V. Gervich D. Lowry SF. Wunderink R. Schein RM. Macias W. Skerjanec S. Dmitrienko A. Farid N. Forgue ST. Jiang F. Crit. Care Med. 2003, 31: 718

6 Jacobsen JS. Comery TA. Martone RL. Elokdah H. Crandall DL. Oganesian A. Aschmies S. Kirksey Y. Gonzales C. Xu J. Zhou H. Atchison K. Wagner E. Zaleska MM. Das I. Arias RL. Bard J. Riddell D. Gardell SJ. Abou-Gharbia M. Robichaud A. Magolda R. Vlasuk GP. Bjornsson T. Reinhart PH. Pangalos MN. Proc. Natl. Acad. Sci. U.S.A. 2008, 105: 8754

7 At least 95 FDA-approved drugs contain the imidazole motif; see: Wishart DS. Knox C. Guo AC. Cheng D. Shrivastaya S. Tzur D. Gautam B. Hassanali M. Nucleic Acids Res. 2008, 36: Database issue D.901

8a Mueller B, Sauter H, Wingert H, Koenig H, Roehl F, Ammermann E, and Lorenz G. inventors; US5663185. ; Chem. Abstr. 1994, 120, 323576

8b Matthews DP, Mccarthy JR, Whitten JYP, and Broersma RJ. inventors; US 4810800. ; Chem. Abstr. 1989, 108, 167468

8c Nair MD. Sudarsanam V. Desai JA. Indian J. Chem. 1982, 21: 1027

8d Albrecht M. Kaim W. Z. Anorg. Allg. Chem. 2000, 626: 1341

8e Regel E. Buchel K. Liebigs Ann. Chem. 1977, 145

9 Shishkin OV. Konovalova IS. Gorb L. Leszczynski J. Struct. Chem. 2009, 20: 37