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Indion 190 Resin: A Green and Recyclable Catalyst for Facile and Efficient One-pot Synthesis of 3, 4-Dihydropyrimidin-2(1H)-one
Indion 190 Resin: A Green and Recyclable Catalyst for Facile and Efficient One-pot Synthesis of 3, 4-Dihydropyrimidin-2(1H)-one
Journal of the Korean Chemical Society. 2009. Apr, 53(2): 224-228
Copyright © 2009, The Korean Chemical Society
  • Received : August 08, 2008
  • Published : April 20, 2009
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About the Authors
Atul Chaskar
Farhat Jaffer
Bhushan Langi
Sampat Yewale
Akalpita Bodkhe

Abstract
Keywords
Recently Multi-component reactions (MCR’s) are governing importance due to its wide variety of applications in organic and medicinal chemistry. 1 MCR’s involves the reaction between three or more reactants in single reaction vessel to form new products, which essentially contain part of all starting materials. 1 MCR’s are diversity oriented efficient and speedy reactions, due to which they have received tremendous attention in the drug discovery process. 2 One of the MCR’s of current interest is the venerable Biginelli dihydropyrimidine synthesis. 3 Today 3,4-dihydropyrimidin-2(1 H )-ones (DHPM) and its derivatives have received considerable amount of attention due to its wide spectra of biological activities. Hence several attempts have been made to synthesize the DHPM ( 1 ).
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In the attempt to prepare DHPM different types of acidic catalyst such as H 2 SO 4 , 5 BF 3 ․EtOH/CuCl, 6 LaCl 3 ․7H 2 O with catalytic concentrated HCl, 7 CeCl 3 ․7H 2 O, 8 InCl 3 , 9 Heteropolyacids, 10 BiCl 3 , 11 Cu(OTf) 2 , 12 TMSCl, 13 LiClO 4 , 14 LiBr, 15 InBr 3 , 16 Phenyl Pyruvic acid, 17 FeCl 3 ․6H 2 O/HCl, 18 TMSI 19 and CdCl 2 20 have been used. Many of the above catalyst used are not ecofriendly and cause the problem during disposal. Further the methods used for synthesis of DHPM requires long reaction times, strong acidic condition, vigorous reaction conditions (high temperature) and they are difficult to handle on a large scale. The development of eco-friendly and recyclable catalytic system for Biginelli reaction is an active research area, in order to improve the reaction condition and yield. Hence we initiated the preparation of DHPM, by keeping in mind the development of green methodology and successfully attempted a single step efficient chemical method by using green catalyst, under mild condition.
Here in, we report a simple efficient and effective protocol for the synthesis of 3,4-dihydropyrimidin-2(1 H )-ones by one pot three component cyclocondensation reaction of 1,3 dicarbonyl compound (ethyl acetoacetate), aromatic aldehyde and urea using Indion 190 resin as a recyclable catalyst. An aldehydes, ethyl acetoacetate and urea in dichloromethane were stirred at reflux temperature in presence of Indion 190 resin. The reaction progress was monitored by TLC. After the completion of reaction, the reaction mixture and resin were separated by filtration. The solvent was removed under reduced pressure and the solid obtained was purified by recrystallisation from methanol. Isolated resin was washed with water, activated and reused for subsequent reaction. Physical and spectral data of known compounds are in agreement with those reported in the literature. 20
Indion 190 resin catalysed synthesis of Dihydropyrimidinones.
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Indion 190 resin catalysed synthesis of Dihydropyrimidinones.
A broad range of structurally diverse aromatic and heterocyclic aldehydes have been used in this condensation ( 1 ).α, β unsaturated aldehyde react selectively with aldehyde functional group whereas acid sensitive heterocyclic aldehydes exclusively gave dihydropyrimidones in high yield. We found that electron donating or withdrawing group on aromatic aldehydes gave almost good to excellent yield. Therefore the method can be use for wide range of reactants with different functional group. We have synthesized some novel compounds containing quinoline, pyrimidine, indole and coumarin units.
In conclusion, we have developed a simple, efficient and ecofriendly procedure for the synthesis of dihydropyrimidin-2(1 H )-ones by condensation of ethyl acetoacetate, aldehydes and urea in presence of inexpensive and recyclable catalyst Indion 190 resin at mild reaction conditions.
General Experimental Section
All commercial reagents are used as received without purification, and all solvents were reagent grade. The reaction mixture was stirred magnetically in a round bottom flask and was monitored by TLC using on 0.25 mm E-Merck silica gel 60 F 254 precoated glass plates, which were visualized with UV light, and then developed by using silica gel 60-120 mesh. Melting points were taken in open capillaries. The IR spectra were recorded on a Perkin-Elmer 257 spectrometer using KBr discs. 1 H NMR and 13 C NMR spectra in DMSO-d 6 were recorded on VXR-300 MHz using TMS as internal standard.
General Procedure
A mixture of an aldehyde (10 mmol), ethyl acetoacetate (10 mmol), urea or thiourea (15 mmol) and Indion 190 resin (2 gm) in dichloromethane (5 ml) was stirred at reflux temperature for the appropriate time (1.5-3.5 hr). After completion of the reaction, as indicated by TLC, the solvent was removed under reduced pressure. The residue was washed with water and recrystallised from methanol.
Analytical and Spectral data for selected compounds.
5-Ethoxycarbonyl-4-(3-1H-Indole)-6-methyl-3,4-dihydropyrimidin-2 (1H)–one (19)
IR (KBr): 3417, 3356, 3240, 2978, 1702, 1653, 1538, 1187, 1085, 870 cm -1
1H NMR DMSO-d6 (δ-ppm): 9.17 (s, 1H, NH), 7.04 (s, 1H, NH), 8.48 (s, 1H, NH), 7.76 (s, 1H), 7.18-7.34 (m, 4H), 5.23 (d, 1H, J = 3.7 Hz), 3.97 (q, 2H, J = 7.2 Hz), 2.24 (s, 3H), 1.15 (t, 3H, J = 7.2 Hz)
13C NMR DMSO-d6 (δ-ppm): 172.10, 155.25, 152.90, 136.90, 127.30, 123.20, 121.80, 119.10, 118.90, 111.15, 106.90, 104.35, 60.10, 34.15, 14.90, 13.90.
Elem. Anal. Calcd: C, 64.20 ; H, 5.72 ; N, 14.04 ; O, 16.04. Found : C, 63.89 ; H, 5.93 ; N, 14.37 ; O, 16.09.
5-Ethoxycarbonyl-4-(3-quinoline)-6-methyl-3,4-dihydropyrimidin-2 (1H)–one (20)
IR (KBr): 3408, 3365, 3280, 1698, 1640, 1513, 1227, 779 cm -1
1H NMR DMSO-d6 (δ-ppm): 9.25 (s, 1H, NH), 7.73 (s, 1H, NH), 8.32 (s, 1H), 7.63-7.79 (m, 4H), 7.80 (s, 1H), 5.12 (d, 1H, J = 2.8 Hz), 4.11 (q, 2H, J = 7.5 Hz), 2.28 (s, 3H), 1.09 (t, 3H, J = 7.5 Hz)
13C NMR DMSO-d6 (δ-ppm): 172.50, 155.25, 153.35, 148.10, 147.15, 135.05, 135.05, 129.10, 127.30, 126.45, 126.10, 104.50, 60.10, 53.00, 14.90, 13.90.
Elem. Anal. Calcd: C, 65.58 ; H, 5.50 ; N, 13.50 ; O, 15.42. Found : C, 65.63 ; H, 5.61 ; N, 13.42 ; O, 15.37.
5-Ethoxycarbonyl-4-(2-pyrimidine)-6-methyl-3,4-dihydropyrimidin-2(1H)–one (21)
IR (KBr): 3413, 3385, 3245, 2965, 1709, 1658, 1540, 1235, 1090, 780 cm -1
1H NMR DMSO-d6 (δ-ppm): 9.20 (s,1H, NH), 7.65 (s, 1H, NH), 8.42 (d, 2H, J = 7.5 Hz), 7.38(t, 1H, J = 7.5 Hz), 5.10(d, 1H, J = 3.5 Hz), 4.02 (q, 2H, J = 7.0 Hz), 2.23 (s, 3H), 1.11 (t, 3H, J = 7.0 Hz).
13C NMR DMSO-d6 (δ-ppm): 172.60, 168.70, 157.20, 155.85, 153.85, 119.90, 104.20, 60.10, 56.10, 15.15, 13.90
Elem. Anal. Calcd: C, 54.96 ; H, 5.38 ; N, 21.36 ; O, 18.30. Found : C, 54.84 ; H, 5.29 ; N, 22.04 ; O, 18.75.
5-Ethoxycarbonyl-4-(4-hydroxyl–2H(1)-benzopyran-2-one-3-yl)-6-methyl-3,4-dihydropyrimidin-2(1H)–one (24)
IR (KBr): 3389, 3240, 2943, 1721, 1705, 1619, 1562, 1235, 1123, 810 cm -1
1H NMR DMSO-d6 (δ-ppm): 11.85 (s, 1H, OH), 9.80 (s, 1H, NH), 7.69(s, 1H, NH), 7.30-7.80 (m, 4H), 4.85 (d, 1H, J = 3.5 Hz), 4.23 (q, 2H, J = 6.8 Hz), 2.35 (s, 3H), 1.21 (t, 3H, J = 6.8 Hz)
13C NMR DMSO-d6 (δ-ppm): 172.50, 171.20, 164.15, 155.10, 153.60, 152.20, 131.15, 129.80, 122.30, 121.10, 117.80, 116.25, 94.50, 60.20, 43.25, 15.15, 14.15
Elem. Anal. Calcd: C, 59.30 ; H, 4.68 ; N, 8.14 ; O, 27.88. Found : C, 59.24 ; H, 4.76 ; N, 8.07 ; O, 28.01.
Physical Properties of Indion 190 resin: macroporous resin, styrene DVB matrix, SO3- functional group, particle size range 0.42-1.2, Max. Operating temp. 150 ℃, total exchange capacity 4.7 meq/g. Some of these properties are similar to the properties of Amberlyst 15.
Acknowledgements
The authors are grateful to Ion Exchange (India) Ltd, Mumbai for providing gift samples of Indion 190 resin and University Grant Commission, New Delhi for financial support. The authors are thankful to Dr. S.T. Gadade, Principal, C. K. Thakur College for providing laboratory and other facilities.
References
Ugi I. , Domling A. , Horl W. 1994 Multicomponent Reactions in Organic Chemistry. Endeavour 18 115 -
Schreiber S. L. 2000 Science 287 1964 -    DOI : 10.1126/science.287.5460.1964
Biginelli P. 1893 Gazz. Chim. Ital. 23 360 -
Atwal K. S. , Swanson B. N. , Unger S. E. , Floyd D. M. , Moreland S. , Hedberg A. , O’Reilly B. C. 1991 J. Med. Chem. 34 806 -    DOI : 10.1021/jm00106a048
Folkers K. , Johnson T.B. 1933 J. Am. Chem. Soc. 55 2886 -    DOI : 10.1021/ja01334a043
Hu E.H. , Sidler D.R. , Dolling U.H. 1998 J. Org. Chem. 63 3454 -    DOI : 10.1021/jo970846u
Lu J. , Bai Y. , Wang Z. , Yang Ma, H. 2000 Tetrahedron Lett. 41 9075 -    DOI : 10.1016/S0040-4039(00)01645-2
Bose D. S. , Fatima L. , Mereyala H.B. 2003 J. Org. Chem. 68 587 -    DOI : 10.1021/jo0205199
Ranu B. C. , Hajara A. , Jana U. 2000 J. Org. Chem. 65 6270 -    DOI : 10.1021/jo000711f
Rafiee E. , Jafari H. 2006 Bioorg. Med. Chem. Lett. 16 2463 -    DOI : 10.1016/j.bmcl.2006.01.087
Ramalinga K. , Vijayalakshmi P. , Kaimala T. N. B. 2001 Synlett. 863 -    DOI : 10.1055/s-2001-14587
Paraskar A. S. , Dewkar G. K. , Sudalai A. 2003 Tetrahedron Lett. 44 3305 -    DOI : 10.1016/S0040-4039(03)00619-1
Zhu Y. L. , Huang S.L. , Pan Y.J. 2005 Eur. J. Org. Chem. 2354 -    DOI : 10.1002/ejoc.200400845
Yadav J.S. , Reddy B. V. S. , Srinivas R. , Venugopal C. , Ramalingam T. 2001 Synthesis 9 1341 -    DOI : 10.1055/s-2001-15229
Maiti G. , Kundua P. , Guin C. 2003 Tetrahedron Lett. 44 2757 -    DOI : 10.1016/S0040-4039(02)02859-9
Fu N. Y. , Yuan Y. F. , Cao Z. , Wang S.W. , Wang J.T. , Peppe C. 2002 Tetrahedron 58 4801 -    DOI : 10.1016/S0040-4020(02)00455-6
Abelman M.M. , Smith S. C. , James D. R. 2003 Tetrahedron Lett. 44 4559 -    DOI : 10.1016/S0040-4039(03)00985-7
Lu J. , Ma H. 2000 Synlett 63 -
Sabitha G. , Reddy G. S.K. , Reddy Ch. S. , Yadav J. S. 2003 Synlett 858 -    DOI : 10.1055/s-2003-38734
Narsaiah A. V. , Basak A. K. , Nagaiah K. 2004 Synthesis 1253 -