Next Article in Journal
Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives
Next Article in Special Issue
Green Chemistry Metrics with Special Reference to Green Analytical Chemistry
Previous Article in Journal
Lectins with Potential for Anti-Cancer Therapy
Previous Article in Special Issue
Selective C–C Coupling Reaction of Dimethylphenol to Tetramethyldiphenoquinone Using Molecular Oxygen Catalyzed by Cu Complexes Immobilized in Nanospaces of Structurally-Ordered Materials
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 20
Issue 3
10.3390/molecules20033811
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones Catalyzed by a Novel Brønsted Acidic Ionic Liquid under Solvent-Free Conditions

by
Yonghong Zhang
1,2,
Bin Wang
3,
Xiaomei Zhang
2,
Jianbin Huang
1 and
Chenjiang Liu
1,3,*
1
Key Laboratory of Petroleum and Gas Fine Chemicals of Ministry of Education, School of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, China
2
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
3
Physics and Chemistry Detecting Center, Xinjiang University, Urumqi 830046, China
*
Author to whom correspondence should be addressed.
Molecules 2015, 20(3), 3811-3820; https://doi.org/10.3390/molecules20033811
Submission received: 24 November 2014 / Revised: 15 February 2015 / Accepted: 17 February 2015 / Published: 26 February 2015
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Browse Figures
Versions Notes

Abstract

:
We report here an efficient and green method for Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea catalyzed by Brønsted acidic ionic liquid [Btto][p-TSA] under solvent-free conditions. Compared to the classical Biginelli reaction conditions, the present method has the advantages of giving good yields, short reaction times, near room temperature conditions and the avoidance of the use of organic solvents and metal catalyst.

Graphical Abstract

1. Introduction

Over the years, dihydropyrimidinones (DHPMs) and their derivatives have displayed a captivating assortment in natural, synthetic, pharmacological, therapeutic and bioorganic chemistry mainly due to their wide range of biological activities [1,2,3], and they are being studied because of their activities as calcium channel blockers, antihypertensive agents, alpha-la-antagonists and neuropeptide Y(NPY) antagonists [4,5]. Moreover, dihydropyrimidinethiones have been suggested to be useful building blocks for synthesis of natural products, such as the batzelladine family of polycyclic marine alkaloids [6,7], of which batzelladine alkaloids have been found to be potent HIV gp-120-CD4 inhibitors [8,9].
The most simple and straightforward procedure for the synthesis of DHPMs was first reported by the Italian chemist Pietro Biginelli in 1893, it involves a three-component one-pot condensation of benzaldehyde, ethyl acetoacetate and urea under strongly acidic conditions [10]. However, this reaction usually requires harsh conditions, long reaction times and affords low yields, particularly when substituted aromatic and aliphatic aldehydes are employed, which impede their applications. To overcome those disadvantages, several protocols for the synthesis of DHPMs have been developed to improve and modify this reaction by means of microwave irradiation [11,12], ultrasound irradiation [13], ionic liquids [14,15,16], and different types of acidic, base, metal oxide, nanoparticle, enzyme, phase transfer catalysts such as lanthanide triflate [17], H3BO3 [18], VCl3 [19], Sr(OTf)2 [20], PPh3 [21], Indium(III) halides [22], nanomagnetic-supported sulfonic acid [23], Iron(III) tosylate [24], Bis[(L)prolinato-N,O]Zn-water [25], 1-glycyl-3-methyl imidazolium chloride copper(II) Complex [26], KAl(SO4)2·12H2O supported on silica [27], FeCl3-supported nanopore silica [28], SiO2-CuCl2 [29], metal oxide-MWCNTs [30,31,32], Fe3O3 and boehmite nanoparticle [33,34], nanosilica-supported tin(II) chloride [35], graphite [36], trypsin [37], silica sulfuric acid [38], Mn(OAc)3·2H2O [39], Y(NO3)3·6H2O [40], In(OTf)3 [41], TaBr5 [42], Ce(NO3)3·6H2O [43], silica chloride [44], HCOOH [45], ytterbium chloride [46], TBAB [47] and so on. However, in spite of their potential utility, many of these reported one-pot protocols suffer from drawbacks such as the use of expensive reagents, volatile strong acidic conditions and long reaction times. Therefore, to avoid these limitations, the introduction of a milder and more efficient method accompanied with higher yields is needed.
Lately, Neto and coworker investigated and discussed the crucial role of catalyst and solvent effects for the Biginelli reaction [48]. Furthermore, in recent years, ionic liquids (ILs) are receiving a widespread attention as environmentally acceptable reaction medium or catalyst owing to their advantageous properties [49,50]. In particular, the synthesis of task-specific ILs with special functions according to the requirement of a specific reaction has become an attractive field [51,52]. In previous work, we reported Lewis acid catalyzed Biginelli reaction [53,54,55,56]. Aiming to developing green chemistry, in this work, we wish to report a simple, facile and efficient methodology for the synthesis of 3,4-dihydropyrimidin-2(1H)-(thio)ones via condensation of aldehyde, ethyl acetoacetate and urea or thiourea and employing the novel Brønsted acidic ionic liquid [Btto][p-TSA] (See Experimental Section) as catalyst for the first time (Scheme 1).
Molecules 20 03811 g001 550
Scheme 1. [Btto][p-TSA] catalyzed Biginelli reaction.
Scheme 1. [Btto][p-TSA] catalyzed Biginelli reaction.
Molecules 20 03811 g001

2. Results and Discussion

To evaluate the effect of the catalyst under different conditions systematically, we carried out the reaction of benzaldehyde, ethyl acetoacetate and urea as a model reaction and the results are presented in Table 1. Initially the effect of amount of [Btto][p-TSA] on the reaction was examined (entries 1–7) and 5 mol % of [Btto][p-TSA] afforded the best result (entry 5). Then, the influence of the reaction time on the yield was tested (entries 5, 8–10). It was found that higher yield was obtained when the reaction time was 30 min (Table 1, entry 10). The influence of the reaction temperature on the yield was investigated subsequently (entries 10, 11–12). It was found that 90 °C was still the best reaction temperature (Table 1, entry 10). For the sake of much milder condition to be developed, the reaction temperature at 30 °C was examined at last (Table 1, entries 13–15). The [Btto][p-TSA] was also successfully utilized in the Biginelli reaction under near room temperature condition. Although reaction time of 15 h (Table 1, entry 15) gave a little better yield than 10 h, we chose 10 h to save energy. Consequently, the best conditions at 30 °C were a 0.05:1:1:1.5 mole ratio of [Btto][p-TSA], benzaldehyde, ethyl acetoacetate and urea or thiourea for 10 h under solvent-free conditions.
Table
Table 1. Effect of catalyst [Btto][p-TSA] under different reaction conditions for condensation of benzaldehyde, ethyl acetoacetate and urea a.
Table 1. Effect of catalyst [Btto][p-TSA] under different reaction conditions for condensation of benzaldehyde, ethyl acetoacetate and urea a.
EntryCat. (mol %)Temp. (°C)TimeYield (%) b
119040 min69
229040 min82
339040 min86
449040 min80
559040 min94
669040 min81
7109040 min91
859010 min87
959020 min94
1059030 min96
1158030 min89
12510030 min95
135305 h63
1453010 h81
1553015 h82
a Reaction conditions: Benzaldehyde (3 mmoL), ethyl acetoacetate (3 mmoL), urea (4.5 mmoL) and catalyst under solvent-free conditions; b Isolated yield.
In order to study the scope of the procedure, a series of DHPMs were synthesized with the optimized conditions. The results are listed in Table 2. In all cases studied, the three-component reaction proceeded smoothly to give the corresponding DHPMs in excellent yields. Most importantly, aromatic aldehydes carrying either electron donating or electron withdrawing substituents reacted very well to give the corresponding DHPMs with high purity in good yields. Notably, this procedure is compatible with a wide range of functional groups such as methoxy, halides, nitro, hydroxy, etc. Beside those above, some sensitive groups also showed to be well tolerated by this method. For instance, furfural and cinnamaldehyde could afford the corresponding products in excellent yields as well. Thiourea has been used with similar success to provide corresponding S-dihydropyrimidinones analogues, which are also of interest due to their biological activities (entries 4q–s). The use of methyl acetoacetate as 1,3-dicarbonyl substrate in place of ethyl acetoacetate also gave good to excellent yields, as shown in Table 2 (entries 4t–u).
Table
Table 2. [Btto][p-TSA]-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones at 90 °C a.
Table 2. [Btto][p-TSA]-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones at 90 °C a.
EntryR1R2XYields b (%)Mp (°C) c
FoundFound
4aC6H5EtOO96202–204206 [26]
4b4-CH3O-C6H4EtOO97203–205205–207 [26]
4cC6H5-CH=CHEtOO98228–230230–232 [26]
4d4-F-C6H4EtOO92180–183182–184 [26]
4e3-Br-C6H4EtOO99183–185185–186 [41]
4f4-(CH3)2N-C6H4EtOO95250–253253–254 [19]
4g3-Cl-C6H4EtOO97194–196193–194 [12]
4h4-Cl-C6H4EtOO93207–210209–212 [26]
4i3-O2N-C6H4EtOO92225–227227–228 [27]
4j3-CH3O-4-HO-C6H3EtOO97232–233232–233 [38]
4k2- HO-C6H4EtOO88200–202199–201 [12]
4l3- HO-C6H4EtOO98165–167167–170 [26]
4m4-HO-C6H4EtOO98224–227227–228 [27]
4n3,4-(CH3O)2-C6H3EtOO96173–175174–176 [27]
4o2,4-(Cl)2-C6H3EtOO94250–252251–252 [12]
4p2-FurylEtOO79205–206202–204 [12]
4qC6H5EtOS98205–206207–208 [26]
4r4-HO-C6H4EtOS96200–202202–203 [26]
4s4- (CH3)2N-C6H4EtOS89207–209209–210 [26]
4tC6H5MeOO89211–213212–213 [26]
4u3-O2N-C6H4MeOO99272–275273–275 [26]
a Reaction conditions: Aldehyde (3 mmoL), β-ketoester (3 mmoL), urea or thiourea (4.5 mmoL), [Btto][p-TSA] (0.15 mmoL), with solvent-free conditions, stirred at 90 °C for 30 min; b Isolated yield; c Melting points are uncorrected.
At the same time, in order to further investigate this MCR at room temperature, a series of DHPMs were synthesized by using the new reaction set-up at room temperature. The results are summarized in Table 3. It can be observed that all the aldehydes have reacted with β-ketoester and urea at room temperature smoothly to afford the corresponding DHPMs in good to excellent yields. These much milder reaction conditions might make this useful method be promising in biorthogonal chemistry.
Table
Table 3. [Btto][p-TSA]-Catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones at room temperature a.
Table 3. [Btto][p-TSA]-Catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones at room temperature a.
EntryR1R2XYields b (%)Mp (°C) c
FoundReported (Lit.)
4aC6H5EtOO77202–205206 [26]
4b4-CH3O-C6H4EtOO89206–208205–207 [26]
4cC6H5-CH=CHEtOO88230–232230–232 [26]
4d4-F-C6H4EtOO90180–182182–184 [26]
4e3-Br-C6H4EtOO85182–185185–186 [41]
4g3-Cl-C6H4EtOO82190–192193–194 [12]
4h4-Cl-C6H4EtOO85210–212209–212 [26]
4i3-O2N-C6H4EtOO93225–226227–228 [27]
4j3-CH3O-4-HO-C6H3EtOO76230–233232–233 [38]
a Reaction conditions: Aldehyde (3 mmoL), β-ketoester (3 mmoL), urea or thiourea (4.5 mmoL), [Btto][p-TSA] (0.15 mmoL), with solvent-free condition, stirred at 30 °C for 10 h; b Isolated yield; c Melting points are uncorrected.

3. Experimental Section

All new compounds were characterized by 1H NMR, 13C NMR, MS spectra. The 1H NMR and 13C NMR spectra were obtained on a Varian Inova-400 spectrometer using CDCl3, D2O as solvent (shown in details in data part) and TMS as an internal standard. LC-MS analyses have been performed on a HP-1100 LC-MS. Melting points were determined using a Büchi B-540 instrument. All melting points are uncorrected.

3.1. General Procedure for the Synthesis of 3,4-Dihydropyrimidine-2(1H)-Ones and Thiones

To a mixture of aldehyde (3 mmoL), ethyl acetoacetate (3 mmoL), urea or thiourea (4.5 mmoL) and [Btto][p-TSA] (0.15 mmoL) was heated at 90 °C with no solvent for 30 min or at 30 °C under solvent-free condition for 10 h with magnetic stirring. The completion of the reaction was monitored by TLC. After cooling, the reaction mixture was poured onto crushed ice and stirred for 5 min. The separated solid was filtered under suction, washed with cold water thoroughly and then recrystallized from ethanol to afford the pure product. All products are known compounds, which were characterized by mp, IR and 1H-NMR spectra. The results are summarized in Table 2 and Table 3.

3.2. General Procedure for the Synthesis of [Btto][p-TSA]

1-Butyl-1,3-thiazolidine-2-thione (Btto): Under magnetic stirring, amounts of 1,3-thiazolidine-2-thione (50 mmoL) and tetrabutylammonium bromide (10 mmoL) were dissolved in 30% aqueous solution of sodium hydroxide (22.5 mL), 1-bromobutane (50 mmoL) was added. Then the mixture was heated at 90 °C for 12 h until two phases formed. The upper organic phase and lower water phase were separated with separating funnel. Later, the organic phase was washed with deionized water. Finally, the remaining deionized water was removed under vacuum at 100 °C for 3 h, giving Btto as red liquid.
1-Butyl-1,3-thiazolidine-2-thione paratoluenesulfate [Btto][p-TSA]: Under magnetic stirring, 1-Butyl-1,3-thiazolidine-2-thione (0.02 mol) and paratoluenesulfonic acid (0.02 mol) were mixed with dichloromethane (2 mL) and heated for 12 h at 90 °C. Then, a light yellow liquid zwitterion was formed and washed repeatedly with ether. After dried in vacuum (100 °C, 0.01 Torr), the IL [Btto][p-TSA] was obtained (Scheme 2).
Molecules 20 03811 g002 550
Scheme 2. Synthesis of [Btto][p-TSA].
Scheme 2. Synthesis of [Btto][p-TSA].
Molecules 20 03811 g002

3.3. Physical and Spectroscopic Data of Products

Compound [Btto][p-TSA]: Light yellow liquid. 1H NMR (400 MHz, CDCl3, TMS): δ: 0.90 (t, J = 7.2 Hz, 3H, CH3), 1.32–1.45 (m, 2H, CH2), 1.65–1.72 (m, 2H, CH2), 2.36 (s, 3H, CH3), 3.33 (t, J = 7.2 Hz, 2H, CH2), 3.73 (t, J = 8.8 Hz, 2H, CH2), 4.50 (t, J = 8.4 Hz, 2H, CH2), 7.18 (t, J = 8.0 Hz, 2H, ArH), 7.76 (t, J = 8.4 Hz, 2H, ArH), 7.98 (m, 1H); 13C NMR (100 MHz, CDCl3, TMS): δ: 13.45, 21.32, 21.45, 30.06, 33.05, 35.51, 55.19, 126.09, 128.88, 140.40, 140.91, 192.28; IR (KBr, ν/cm−1): 3441, 2960, 2932, 2872, 1741, 1648, 1205, 1183, 870, 687, 568; ESI-MS: m/z = 176 [M+], m/z = 171 [M−].

4. Conclusions

In conclusion, we have developed a novel Brønsted acidic ionic liquid [Btto][p-TSA] as an efficient catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones and thiones analogs by multicomponent Biginelli reaction for the first time. Our method offers several advantages such as mild reaction conditions, short reaction times, being environment-friendly and affording good yields.

Acknowledgments

We gratefully acknowledge support from the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China (2012211A015).

Author Contributions

Yonghong Zhang designed and performed research and analyzed the data, wrote the paper as well. Bin Wang performed NMR. Chenjiang Liu, Xiaomei Zhang and Jianbin Huang were the supervisor of the work. All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Kappe, C.O. Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog. Acc. Chem. Res. 2000, 33, 879–888. [Google Scholar]
  2. Kappe, C.O. Biologically active dihydropyrimidones of the Biginelli-type-a literature survey. Eur. J. Med. Chem. 2000, 35, 1043–1052. [Google Scholar] [CrossRef] [PubMed]
  3. Canto, R.F.S.; Bernardi, A.; Battastini, A.M.O.; Russowsky, D.; Eifler-Lim, V.L. Synthesis of Dihydropyrimidin-2-one/thione Library and Cytotoxic Activity against the Human U138-MG and Rat C6 Glioma Cell Lines. J. Braz. Chem. Soc. 2011, 22, 1379–1388. [Google Scholar] [CrossRef]
  4. Atwal, K.S.; Rovnyak, G.C.; Kimball, S.D.; Floyd, D.M.; Moreland, S.; Swanson, B.N.; Gougoutas, J.Z.; Schwartz, J.; Smillie, K.M.; Malley, M.F. Dihydropyrimidine calcium channel blockers. 2. 3-substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines. J. Med. Chem. 1990, 33, 2629–2635. [Google Scholar]
  5. Atwal, K.S.; Rovnyak, G.C.; O’Reilly, B.C.; Schwartz, J. Substituted 1,4-dihydropyrimidines. 3.1 synthesis of selectively functionalized 2-hetero-1,4-dihydropyrimidines. J. Org. Chem. 1989, 54, 5898–5907. [Google Scholar]
  6. Heys, L.; Moore, C.G.; Murphy, P.J. The guanidine metabolites of ptilocaulis spiculifer and related compounds; isolation and synthesis. Chem. Soc. Rev. 2000, 29, 57–67. [Google Scholar] [CrossRef]
  7. Berlinck, R.G.S.; Burtoloso, A.C.B.; Kossuga, M.H. The chemistry and biology of organic guanidine derivatives. Nat. Prod. Rep. 2008, 25, 919–954. [Google Scholar] [CrossRef] [PubMed]
  8. Patil, A.D.; Kumar, N.V.; Kokke, W.C.; Bean, M.F.; Freyer, A.J.; Brosse, C.D.; Mai, S.; Truneh, A.; Faulkner, D.J.; Carte, B.; et al. Novel alkaloids from the Sponge Batzella sp.: Inhibitors of HIV gp l20-human CD4 binding. J. Org. Chem. 1995, 60, 1182–1188. [Google Scholar]
  9. Snider, B.B.; Chen, J.; Patil, A.D.; Freyer, A.J. Synthesis of the tricyclic portions of batzelladines A, B and D. Revision of the stereoehemistry of batzelladines A and D. Tetrahedron Lett. 1996, 37, 6977–6980. [Google Scholar] [CrossRef]
  10. Biginelli, P. Aldureides of ethylic acetoacetate and ethylic oxaloacetate. Gazz. Chim. Ital. 1893, 23, 360–416. [Google Scholar]
  11. Banik, B.K.; Reddy, A.T.; Datta, A.; Mukhopadhyay, C. Microwave-induced bismuth nitrate-catalyzed synthesis of dihydropyrimidones via Biginelli condensation under solventless conditions. Tetrahedron Lett. 2007, 48, 7392–7394. [Google Scholar] [CrossRef]
  12. Safari, J.; Gandomi-Ravandi, S. Titanium dioxide supported on MWCNTs as an eco-friendly catalyst in the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones accelerated under microwave irradiation. New J. Chem. 2014, 38, 3514–3521. [Google Scholar] [CrossRef]
  13. Li, J.T.; Han, J.F.; Yang, J.H.; Li, T.S. An efficient synthesis of 3,4-dihydropyrimidin-2-ones catalyzed by NH2SO3H under ultrasound irradiation. Ultrason. Sonochem. 2003, 10, 119–122. [Google Scholar] [CrossRef] [PubMed]
  14. Peng, J.; Deng, Y. Ionic liquids catalyzed Biginelli reaction under solvent-free conditions. Tetrahedron Lett. 2001, 42, 5917–5919. [Google Scholar] [CrossRef]
  15. Zhu, A.; Li, Q.; Li, L.; Wang, J. One-pot synthesis of 3,4-dihydro-2(H)-pyrimidinones catalyzed by reusable acidic choline-based ionic liquids. Catal. Lett. 2013, 143, 463–468. [Google Scholar] [CrossRef]
  16. Rahman, M.; Sarkar, A.; Ghosh, M.; Majee, A.; Hajra, A. Catalytic application of task Specific ionic liquid on the synthesis of benzoquinazolinone derivatives by a multicomponent reaction. Tetrahedron Lett. 2014, 55, 235–239. [Google Scholar] [CrossRef]
  17. Ma, Y.; Qian, C.; Wang, L.; Yang, M. Lanthanide triflate catalyzed Biginelli reaction. One-pot synthesis of dihydropyrimidinones under solvent-free conditions. J. Org. Chem. 2000, 65, 3864–3868. [Google Scholar]
  18. Tu, S.; Fang, F.; Miao, C.; Jiang, H.; Feng, Y.; Shi, D.; Wang, X. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using boric acid as catalyst. Tetrahedron Lett. 2003, 44, 6153–6155. [Google Scholar] [CrossRef]
  19. Sabitha, G.; Reddy, G.S. K.K.; Reddy, K.B.; Yadav, J.S. Vanadium(III) chloride catalyzed Biginelli condensation: Solution phase library generation of dihydropyrimidin-(2H)-ones. Tetrahedron Lett. 2003, 44, 6497–6499. [Google Scholar] [CrossRef]
  20. Su, W.; Li, J.; Zheng, Z.; Shen, Y. One-pot synthesis of dihydropyrimidiones catalyzed by strontium(II) triflate under solvent-free conditions. Tetrahedron Lett. 2005, 46, 6037–6040. [Google Scholar] [CrossRef]
  21. Debache, A.; Amimour, M.; Belfaitah, A.; Rhouati, S.; Carboni, B. A one-pot Biginelli synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones catalyzed by triphenylphosphine as Lewis base. Tetrahedron Lett. 2008, 49, 6119–6121. [Google Scholar] [CrossRef]
  22. Fu, N.Y.; Yuan, Y.F.; Pang, M.L.; Wang, J.T.; Peppe, C. Indium(III) halides-catalyzed preparation of ferrocene-dihydropyrimidinones. J. Organomet. Chem. 2003, 672, 52–57. [Google Scholar] [CrossRef]
  23. Kolvari, E.; Koukabi, N.; Armandpour, O. A simple and efficient Synthesis of 3,4-dihydropyrimidin-2-(1H)-ones via Biginelli reaction catalyzed by nanomagnetic-supported sulfonic acid. Tetrahedron 2014, 70, 1383–1386. [Google Scholar] [CrossRef]
  24. Starcevich, J.T.; Laughlin, T.J.; Mohan, R.S. Iron(III) tosylate catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones via the Biginelli reaction. Tetrahedron Lett. 2013, 54, 983–985. [Google Scholar] [CrossRef]
  25. Siddiqui, Z.N. Bis[(L)prolinato-N,O] Zn-water: A green catalytic system for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones via the Biginelli reaction. Comptes Rendus Chimie 2013, 16, 183–188. [Google Scholar] [CrossRef]
  26. Karthikeyan, P.; Aswar, S.A.; Muskawar, P.N.; Bhagat, P.R.; Kumar, S.S. Development and efficient 1-Glycyl-3-methyl imidazolium chloride-copper(II) complex catalyzed highly enantioselective synthesis of 3, 4-dihydropyrimidin-2(1H)-ones. J. Organomet. Chem. 2013, 723, 154–162. [Google Scholar] [CrossRef]
  27. Azizian, J.; Mohammadi, A.A.; Karimi, A.R.; Mohammadizadeh, M.R. KAl(SO4)2·12H2O supported on silica gel as a novel heterogeneous system catalyzed Biginelli reaction one-pot synthesis of dihydropyrimidinones under solvent-free conditions. Appl. Catal. A Gen. 2006, 300, 85–88. [Google Scholar]
  28. Ahn, B.J.; Gang, M.S.; Chae, K.; Oh, Y.; Shin, J.; Chang, W. A Microwave-assisted synthesis of 3,4-dihydro-pyrimidin-2-(1H)-ones catalyzed by FeCl3-supported nanopore silica under solvent-free conditions. J. Ind. Eng. Chem. 2008, 14, 401–405. [Google Scholar] [CrossRef]
  29. Kour, G.; Gupta, M.; Rajnikant, S.P.; Gupta, V.K. SiO2-CuCl2: An efficient and recyclable heterogeneous catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. J. Mol. Catal. A Chem. 2014, 392, 260–269. [Google Scholar] [CrossRef]
  30. Safari, J.; Gandomi-Ravandi, S. MnO2-MWCNT nanocomposites as efficient catalyst in the synthesis of Biginelli-type compounds under microwave radiation. J. Mol. Catal. A Chem. 2013, 373, 72–77. [Google Scholar] [CrossRef]
  31. Safari, J.; Gandomi-Ravandi, S. A novel protocol for solvent-free synthesis of 4,6-Diaryl-3,4-Dihydropyrimidine-2(1H)-ones catalyzed by metal oxide—MWCNTs nanocomposites. J. Mol. Struct. 2014, 1074, 71–78. [Google Scholar] [CrossRef]
  32. Safari, J.; Gandomi-Ravandi, S. Biginelli reaction on Fe3O4-MWCNT nanocomposite: Excellent reactivity and facile recyclability of the catalyst combined with ultrasound irradiation. RSC Adv. 2013, 3, 17962–17967. [Google Scholar] [CrossRef]
  33. Zamani, F.; Izadi, E. Synthesis and characterization of sulfonated-phenylacetic acid coated Fe3O3 nanoparticles as a novel acid magnetic catalyst for Biginelli reaction. Catal. Commun. 2013, 42, 104–108. [Google Scholar] [CrossRef]
  34. Keivanloo, A.; Mirzaee, M.; Bakherad, M.; Soozani, A. Boehmite nanoparticle catalyst for the one-pot multicomponent synthesis of 3,4-dihydropyrimidin-2-(1H)-ones and thiones under solvent-free conditions. Chin. J. Catal. 2014, 35, 362–367. [Google Scholar] [CrossRef]
  35. Ghomi, J.S.; Teymuri, R.; Ziarati, A. A green synthesis of 3,4-dihydropyrimidine-2(1H)-one/thione derivatives using nanosilica-supported Tin(II) chloride as a heterogeneous nanocatalyst. Monatsh. Chem. 2013, 144, 1865–1870. [Google Scholar] [CrossRef]
  36. Dhumaskar, K.L.; Meena, S.N.; Ghadi, S.C.; Tilve, S.G. Graphite catalyzed solvent free synthesis of dihydropyrimidin-2(1H)-ones/thiones and their antidiabetic activity. Bioorg. Med. Chem. Lett. 2014, 24, 2897–2899. [Google Scholar] [CrossRef] [PubMed]
  37. Xie, Z.-B.; Wang, N.; Wu, W.-X.; Le, Z.-G.; Yu, X.-Q. Trypsin-catalyzed tandem reaction: One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones by in situ formed acetaldehyde. J. Biotechnol. 2014, 170, 1–5. [Google Scholar] [CrossRef] [PubMed]
  38. Salehi, P.; Dabiri, M.; Zolfigol, M.A.; Fard, M.A.B. Silica sulfuric acid: An efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett. 2003, 44, 2889–2891. [Google Scholar] [CrossRef]
  39. Kumar, K.A.; Kasthuraiah, M.; Reddy, C.S.; Reddy, C.D. Mn(OAc)3·2H2O-mediated three-component, one-pot, condensation reaction: An efficient synthesis of 4-aryl-substituted 3,4-dihydropyrimidin-2-ones. Tetrahedron Lett. 2001, 42, 7873–7875. [Google Scholar] [CrossRef]
  40. Nandurkar, N.S.; Bhanushali, M.J.; Bhor, M.D.; Bhanage, B.M. Y(NO3)3·6H2O: A novel and reusable catalyst for one pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions. J. Mol. Catal. A Chem. 2007, 271, 14–17. [Google Scholar] [CrossRef]
  41. Ghosh, R.; Maiti, S.; Chakraborty, A. In(OTf)3-catalysed one-pot synthesis of 3,4-dihydropyrimidin-2(lH)-ones. J. Mol. Catal. A Chem. 2004, 217, 47–50. [Google Scholar] [CrossRef]
  42. Ahmed, N.; van Lier, J.E. TaBr5-catalyzed Biginelli reaction: One-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under solvent-free conditions. Tetrahedron Lett. 2007, 48, 5407–5409. [Google Scholar] [CrossRef]
  43. Adib, M.; Ghanbary, K.; Mostofi, M.; Ganjali, M.R. Efficient Ce(NO3)3·6H2O-catalyzed solvent-free synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Molecules 2006, 11, 649–654. [Google Scholar] [CrossRef] [PubMed]
  44. Karade, H.N.; Sathe, M.; Kaushik, M.P. Synthesis of 4-aryl substituted 3,4-dihydropyrimidinones using silica-chloride under solvent free conditions. Molecules 2007, 12, 1341–1351. [Google Scholar] [CrossRef] [PubMed]
  45. Cheng, J.; Qi, D.Y. An efficient and solvent-free one-pot synthesis of dihydropyrimidinones under microwave irradiation. Chin. Chem. Lett. 2007, 18, 647–650. [Google Scholar] [CrossRef]
  46. Zhang, H.; Zhou, Z.; Yao, Z.; Xu, F.; Shen, Q. Efficient synthesis of pyrimidinone derivatives by ytterbium chloride catalyzed Biginelli-type reaction under solvent-free conditions. Tetrahedron Lett. 2009, 50, 1622–1624. [Google Scholar] [CrossRef]
  47. Ahmed, B.; Khan, R.A.; Habibullah; Keshari, M. An improved synthesis of Biginelli-type compounds via phase-transfer catalysis. Tetrahedron Lett. 2009, 50, 2889–2892. [Google Scholar] [CrossRef]
  48. Alvim, H.G.O.; Lima, T.B.; de Oliveira, A.L.; de Oliveira, H.C.B.; Silva, F.M.; Gozzo, F.C.; Souza, R.Y.; da Silva, W.A.; Neto, B.A.D. Facts, presumptions, and myths on the solvent-free and catalyst-free Biginelli reaction. What is catalysis for? J. Org. Chem. 2014, 79, 3383–3397. [Google Scholar]
  49. Welton, T. Room-temperature ionic liquids. Solvents for synthesis and catalysis. Chem. Rev. 1999, 99, 2071–2083. [Google Scholar]
  50. Pârvulescu, V.I.; Hardacre, C. Catalysis in ionic liquids. Chem. Rev. 2007, 107, 2615–2665. [Google Scholar] [CrossRef] [PubMed]
  51. Ranu, B.C.; Banerjee, S. Ionic liquid as catalyst and reaction medium. The dramatic influence of a task-specific ionic liquid, [bmIm]OH, in michael addition of active methylene compounds to conjugated ketones, carboxylic esters, and nitriles. Org. Lett. 2005, 7, 3049–3052. [Google Scholar]
  52. Qiao, K.; Hagiwara, H.; Yokoyama, C. Acidic ionic liquid modified silica gel as novel solid catalysts for esterification and nitration reactions. J. Mol. Catal. A Chem. 2006, 246, 65–69. [Google Scholar] [CrossRef]
  53. Liu, C.; Wang, J.; Li, Y. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-(thio)ones using strontium(II) nitrate as a catalyst. J. Mol. Catal. A Chem. 2006, 258, 367–370. [Google Scholar] [CrossRef]
  54. Zhang, X.; Li, Y.; Liu, C.; Wang, J. An efficient synthesis of 4-substituted pyrazolyl-3,4-dihydropyrimidin-2(1H)-(thio)ones catalyzed by Mg(ClO4)2 under ultrasound irradiation. J. Mol. Catal. A Chem. 2006, 253, 207–211. [Google Scholar] [CrossRef]
  55. Liu, C.J.; Wang, J.D. Copper(II) sulfamate: An efficient catalyst for the one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-ones and thiones. Molecules 2009, 14, 763–770. [Google Scholar] [CrossRef] [PubMed]
  56. Liu, C.J.; Wang, J.D. Ultrasound-assisted synthesis of novel 4-(2-phenyl-1,2,3-triazol-4-yl)-3,4-dihydropyrimidin-2(1H)-(Thio)ones catalyzed by Sm(ClO4)3. Molecules 2010, 15, 2087–2095. [Google Scholar] [CrossRef] [PubMed]
  • Sample Availability: All samples are available from the authors.

Share and Cite

MDPI and ACS Style

Zhang, Y.; Wang, B.; Zhang, X.; Huang, J.; Liu, C. An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones Catalyzed by a Novel Brønsted Acidic Ionic Liquid under Solvent-Free Conditions. Molecules 2015, 20, 3811-3820. https://doi.org/10.3390/molecules20033811

AMA Style

Zhang Y, Wang B, Zhang X, Huang J, Liu C. An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones Catalyzed by a Novel Brønsted Acidic Ionic Liquid under Solvent-Free Conditions. Molecules. 2015; 20(3):3811-3820. https://doi.org/10.3390/molecules20033811

Chicago/Turabian Style

Zhang, Yonghong, Bin Wang, Xiaomei Zhang, Jianbin Huang, and Chenjiang Liu. 2015. "An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones Catalyzed by a Novel Brønsted Acidic Ionic Liquid under Solvent-Free Conditions" Molecules 20, no. 3: 3811-3820. https://doi.org/10.3390/molecules20033811

Article Metrics

Back to TopTop