Uncatalyzed Condensation Reactions between Aromatic Aldehydes and Thiobarbituric Acid in Water

Chinese Chemical Letters Vol. 14, No. 12, pp 1239- 1241, 20031239http://www. imm.ac .cn/journalccl.htmlUncatalyzed Condensation Reactions between Aromatic Aldehydesand Thiobarbituric Acid in WaterBing Qin YANG* , Jun LU, Min TIANDepartment of Chemistry, Northwest University, Xi an 710069Abstract: A series of 5- arylidenethiobarbituric acids were prepared from aromatic aldehydes andthiobarbituric acid in water without catalyst conditions in good yields. The structures werecharacterized by elemental analysis, IR and 'H NMR spectra.Keywords: 5- Arylidene thiobarbituric acid, uncataly zed reaction, environmentally benignsynthesis.Eco-benign version of organic reactions is potential candidates for the synthesis ofbiologically active compounds'. Recently, microwave assisted synthesis, sonication, .solid-phase methods and other environmentally friendly reaction in organic synthesishave been paid considerable attention and are becoming an increasingly populartechnology2. The use of water as solvent in organic chemistry under uncataly zedconditions was particularly eco- friendly because of cheap, uninflammable and not toxic.This technique was discovered by Breslows in the 1980s. 5-Arylidene thiobarbituricacids are widely used as precursors for the synthesis of bioactive derivatives+ and itsderivatives are also very important intermediates in organic reactions'.Cross aldol-typecondensation of thiobarbituric acid with aromatic aldehydes using acetic acid as acatalyst is available for the preparation'.In this paper, we describe a rapid andconvenient method for the synthesis of 5-arylidene thiobarbituric acids underuncataly zed conditions using water as the solvent (Scheme 1). All the reactions werecarried out at 95-100 C for 45 min in water and the results were summarized in TableScheme 1Q20ArCHO +-NH95-100°C ArCH=o"E-mail: chemdir@ nwu.edu.cn中国煤化工MHCNMH G.1240Bing Qin YANG et al.Table 1 Synthesis of 5-arylidenethiobarbituric acidsEntryArYields" (%)_4(CH)NCH487.33t66.83c82.434HOCH488.63e3,4-(CH2O)CH361.63f4-CH,OCH95.43g2,4-CLCH383.03H2-HOCH450.4( nr-CH)Fe( n-CH)_85.4* * isolated yields.It is interesting that the reaction easily occurs in water although the mechanisminvolves a net dehydration to the alcoholic intermediate obtained by nucleophilic attackof the active methylene neighbouring to the carbonyl groups. We propose that waterhelps the thiobarbituric acid dissociation, due to its high a value, that generates thenucleophilic species able to attack the carbonium of the aldehyde. It also makes theproduct easily to be isolated and this method can be employed in many kinds of aromaticaldehydes in liquid or solid forms.ExperimentalThiobarbituric acid was prepared according to the literture .Synthesis of 5-arylidene thiobarbituric acidsA mixture of 4-dimethylaminobenzaldehyde (10 mmol) and thiobarbituric acid (10 mmol)in water (40 mL) was stirred at 95-100C for 45 min. Then the solid was filtered andwashed subsequently with boiling water, ethebenzylidene thiobarbituric acid 3a was obtained in 87.3% yield, mp> 250C; 'H NMR(DMSO-d, 400 MHz，δppm:) 3.16 (s, 6H), 6.83 (d, 2H,J =9.2 H2), 8.16 (s, 1H),8.47 (d, 2H,J= 9.2 Hz,), 12.03 (s, 1H), 12.13 (s, 1H); IR (KBr) D: 3455, 3114, 1646,1493, 1233 cmi'. Anal. Calcd. for G;HjN,O2S: C 56.73, H 4.73, N 15.27; found C56.96, H 4.46, N 15.20.All products 3a-i were characterized by IR, H NMR andelemental analysis.In conclusion, a simple synthetic route for 5-arylidene thiobarbituric acids by thecondensation reaction of aromatic aldehydes with thiobarbituric acid in water withoutcatalyst is described. This new method is a simple, good-yielding and environmentallyfriendly process.AcknowledgmentsWe gratefully acknowledge the Natual Science Foundation of Shaan' xi Province (No. 2000H03)for support of this work.中国煤化工MHCNMH G.Uncatalyzed Condensation Reactions between Aromatic1241.Aldehydes and Thiobarbituric Acid in WaterReferences1. J. S. Wilkes, Green Chem, 2002,4, 73.2. A. Loupy, A. Petit, J. Hamelin, F. Texier- Boullet, P. Jacquault, D. Mathe, Synthesis, 1998,1213.R. Breslow, D. C. Rideout,J. Am. Chem. Soc., 1980, 102, 7816.B .Reijo, H. Ekki, wo 9117151, 1991 (CA.. 1992, 116, 59398c )H. Ikeda, Y. Kawabe, T. Sakai, K. Kawasaki, Chem. Lett. 1989, 1803.A. I. D' yachkov, B. A. Ivin, N. A. Smorygo, E. G. Sochilin, Zh. Org. Khim., 1976, 12, 1115.7. N. T. Fan, Examples of OrgSynthesis, Beijing University of Science and TechnologyganPress, Bejing, 1995, p.Received November 27, 2002中国煤化工MHCNMH G.