Skip to content
2000
Volume 12, Issue 1
  • ISSN: 2213-3372
  • E-ISSN: 2213-3380

Abstract

Background

This study investigates the synthesis of dihydropyrimidinethiones using a multifunctional deep eutectic solvent (DES) composed of Choline chloride (ChCl) and ammonium thiocyanate. This DES serves as a catalyst, solvent, and reagent, providing a simple, high-yielding, and environmentally friendly method for dihydropyrimidinethione synthesis. The use of DES in this capacity offers several advantages, including reduced environmental impact, high efficiency, and ease of use, highlighting its potential as a sustainable alternative in organic synthesis.

Objective

The objective of this study is to investigate the application of a deep eutectic solvent (DES) composed of ChCl and ammonium thiocyanate as a catalytic solvent and reagent system for synthesizing dihydropyrimidinethiones. The aim is to simplify the reaction setup, improve yields, and enhance the green metrics of the process.

Methods

ChCl and ammonium thiocyanate were combined to form a DES catalyst-solvent system. Dihydropyrimidinethiones were synthesized in one-pot reactions at ambient temperature. Green metrics and DES recovery were evaluated. Comparative analysis with traditional methods was conducted.

Results

The DES efficiently catalyzed dihydropyrimidinethione synthesis with high yields. Simplified reaction setup, safe solvent properties, and favorable green metrics. DES was recoverable and reusable, outperforming traditional methods in efficiency and eco-friendliness.

Conclusion

The ChCl and ammonium thiocyanate DES demonstrated remarkable efficiency and eco-friendliness in dihydropyrimidinethione synthesis. The toxicity-free, multifunctional roles of the DES, serving as a catalyst, solvent, and reagent, highlight its novelty and potential as a sustainable alternative in organic chemistry. This study simplifies the synthesis process and improves yields and green metrics, showcasing the DES as a promising candidate for future research and industrial applications.

Loading

Article metrics loading...

/content/journals/cocat/10.2174/0122133372302803240415045313
2024-04-19
2025-04-06
Loading full text...

Full text loading...

References

  1. AndradeC.K.Z. AlvesL.M. Environmentally benign solvents in organic synthesis: Current topics.Curr. Org. Chem.20059219521810.2174/1385272053369178
    [Google Scholar]
  2. SahooT. PandaJ. SahuJ. SarangiD. SahooS.K. NandaB.B. SahuR. Green solvent: Green shadow on chemical synthesis.Curr. Org. Synth.202017642643910.2174/1570179417666200506102535 32370717
    [Google Scholar]
  3. SharmaA. WakodeS. SharmaS. FayazF. PottooF.H. Methods and strategies used in green chemistry: A review.Curr. Org. Chem.202024222555256510.2174/1385272824999200802025233
    [Google Scholar]
  4. AbbottA.P. BoothbyD. CapperG. DaviesD.L. RasheedR.K. Deep eutectic solvents formed between choline chloride and carboxylic acids: Versatile alternatives to ionic liquids.J. Am. Chem. Soc.2004126299142914710.1021/ja048266j 15264850
    [Google Scholar]
  5. SmithE.L. AbbottA.P. RyderK.S. Deep eutectic solvents (DESs) and their applications.Chem. Rev.201411421110601108210.1021/cr300162p 25300631
    [Google Scholar]
  6. PrabhuneA. DeyR. Green and sustainable solvents of the future: Deep eutectic solvents.J. Mol. Liq.202337912167610.1016/j.molliq.2023.121676
    [Google Scholar]
  7. FlorindoC. LimaF. RibeiroB.D. MarruchoI.M. Deep eutectic solvents: Overcoming 21st century challenges.Curr. Opin. Green Sustain. Chem.201918313610.1016/j.cogsc.2018.12.003
    [Google Scholar]
  8. PaivaA. MatiasA.A. DuarteA.R.C. How do we drive deep eutectic systems towards an industrial reality?Curr. Opin. Green Sustain. Chem.201811818510.1016/j.cogsc.2018.05.010
    [Google Scholar]
  9. AbbottA.P. CapperG. DaviesD.L. RasheedR.K. TambyrajahV. Novel solvent properties of choline chloride/urea mixturesElectronic supplementary information (ESI) available: spectroscopic data. See http://www.rsc.org/suppdata/cc/b2/b210714g/.Chem. Commun.200311707110.1039/b210714g 12610970
    [Google Scholar]
  10. FranciscoM. van den BruinhorstA. KroonM.C. Low-transition-temperature mixtures (LTTMs): A new generation of designer solvents.Angew. Chem. Int. Ed.201352113074308510.1002/anie.201207548 23401138
    [Google Scholar]
  11. ImperatoG. EiblerE. NiedermaierJ. KönigB. Low-melting sugar–urea–salt mixtures as solvents for Diels–Alder reactions.Chem. Commun.2005991170117210.1039/B414515A 15726181
    [Google Scholar]
  12. ImperatoG. HögerS. LenoirD. KönigB. Low melting sugar–urea–salt mixtures as solvents for organic reactions—estimation of polarity and use in catalysis.Green Chem.20068121051105510.1039/B603660K
    [Google Scholar]
  13. ImperatoG. VasoldR. KönigB. Stille reactions with tetraalkylstannanes and phenyltrialkylstannanes in low melting sugar‐urea‐salt mixtures.Adv. Synth. Catal.2006348152243224710.1002/adsc.200600248
    [Google Scholar]
  14. YuD. XueZ. MuT. Deep eutectic solvents as a green toolbox for synthesis.Cell Reports Phys. Sci.20223410080910083210.1016/j.xcrp.2022.100809
    [Google Scholar]
  15. ChenY. MuT. Application of deep eutectic solvents in biomass pretreatment and conversion.Green Energy Environ.2019429511510.1016/j.gee.2019.01.012
    [Google Scholar]
  16. RenH. ChenC. WangQ. ZhaoD. GuoS. The properties of choline chloride-based deep eutectic solvents and their performance in the dissolution of cellulose.BioResources20161125435545110.15376/biores.11.2.5435‑5451
    [Google Scholar]
  17. DengD. GaoB. ZhangC. DuanX. CuiY. NingJ. Investigation of protic NH4SCN-based deep eutectic solvents as highly efficient and reversible NH3 absorbents.Chem. Eng. J.201935893694310.1016/j.cej.2018.10.077
    [Google Scholar]
  18. WazeerI. HayyanM. Hadj-KaliM.K. Deep eutectic solvents: Designer fluids for chemical processes.J. Chem. Technol. Biotechnol.201893494595810.1002/jctb.5491
    [Google Scholar]
  19. ÜnlüA.E. ArıkayaA. TakaçS. Use of deep eutectic solvents as catalyst: A mini-review.Green Process. Synth.20198135537210.1515/gps‑2019‑0003
    [Google Scholar]
  20. de Oliveira VigierK. García-ÁlvarezJ. Deep Eutectic and Low‐melting Mixtures.Bio-Based Solvents. JeromeF. LuqueR. Hoboken, NJ, USAJohn Wiley & Sons20178311410.1002/9781119065357.ch4
    [Google Scholar]
  21. ZhangM. LiuY.H. ShangZ.R. HuH.C. ZhangZ.H. Supported molybdenum on graphene oxide/Fe3O4: An efficient, magnetically separable catalyst for one-pot construction of spiro-oxindole dihydropyridines in deep eutectic solvent under microwave irradiation.Catal. Commun.201788394410.1016/j.catcom.2016.09.028
    [Google Scholar]
  22. WangP. MaF.P. ZhangZ.H. l-(+)-Tartaric acid and choline chloride based deep eutectic solvent: An efficient and reusable medium for synthesis of N-substituted pyrroles via Clauson-Kaas reaction.J. Mol. Liq.201419825926210.1016/j.molliq.2014.07.015
    [Google Scholar]
  23. GaoG. WangP. LiuP. ZhangW. MoL. ZhangZ. Deep eutectic solvent catalyzed one-pot synthesis of 4,7-Dihydro-1 H -pyrazolo[3,4- b]pyridine-5-carbonitriles.Youji Huaxue201838484685810.6023/cjoc201711014
    [Google Scholar]
  24. JablonskýM. ŠkulcováA. ŠimaJ. Use of deep eutectic solvents in polymer chemistry–a review.Molecules201924213978401110.3390/molecules24213978 31684174
    [Google Scholar]
  25. ShanabK. NeudorferC. SchirmerE. SpreitzerH. Green solvents in organic synthesis: An overview.Curr. Org. Chem.201317111179118710.2174/1385272811317110005
    [Google Scholar]
  26. SreekumarK. TheresaL.V. MachingalS. Low melting mixtures: Neoteric solvents and/or catalysts for a green approach to organic reactions.Mini Rev. Org. Chem.202320321222610.2174/1570193X19666220314100418
    [Google Scholar]
  27. ThakurA. VermaM. BhartiR. SharmaR. Recent advances in utilization of deep eutectic solvents: An environmentally friendly pathway for multi-component synthesis.Curr. Org. Chem.202226329932310.2174/1385272826666220126165925
    [Google Scholar]
  28. LončarićM. SušjenkaM. MolnarM. An extensive study of coumarin synthesis via knoevenagel condensation in choline chloride based deep eutectic solvents.Curr. Org. Synth.20201729810810.2174/1570179417666200116155704 32418515
    [Google Scholar]
  29. RatnaniS. BargujarS. KhulbeM. KathuriaA. Applications of choline chloride-based deep eutectic solvents as sustainable media and catalyst in the synthesis of heterocyclic scaffolds.Curr. Org. Chem.202226874575510.2174/1385272826666220602105646
    [Google Scholar]
  30. Kumar TailorY. KhandelwalS. Kumar JainH. KumarM. Environmentally benign synthetic protocol for the synthesis of spiroquinazolinones using sustainable and recyclable choline chloride based deep eutectic mixture.Curr. Org. Synth.201512448449110.2174/157017941204150522190425
    [Google Scholar]
  31. BehaloM.S. AbdelmajeidA. AlyA.A. HebashK.A. MohamedE.A. Green and facile synthesis of pyrimidine derivatives using choline chloride-urea mixture as a deep eutectic solvent or cerium (IV) ammonium nitrate.Curr. Org. Chem.201923161771177710.2174/1385272823666190916144235
    [Google Scholar]
  32. AziziN. AlipourM. Eco-efficiency and scalable synthesis of bisamides in deep eutectic solvent.J. Mol. Liq.201520626827110.1016/j.molliq.2015.02.033
    [Google Scholar]
  33. GoreS. BaskaranS. KoenigB. Efficient synthesis of 3,4-dihydropyrimidin-2-ones in low melting tartaric acid–urea mixtures.Green Chem.2011134100910.1039/c1gc00009h
    [Google Scholar]
  34. GoreS. BaskaranS. KoenigB. Synthesis of pyrimidopyrimidinediones in a deep eutectic reaction mixture.Adv. Synth. Catal.2012354132368237210.1002/adsc.201200257
    [Google Scholar]
  35. DeviP. LambuM.R. BaskaranS. A novel one-pot method for the stereoselective synthesis of tetrahydropyrimidinones in a low melting mixture.Org. Biomol. Chem.202018224164416810.1039/D0OB00697A 32436516
    [Google Scholar]
  36. LiuP. HaoJ. ZhangZ. A general, effcient and green procedure for synthesis of dihydropyrimidine‐5‐carboxamides in low melting betaine hydrochloride/urea mixture.Chin. J. Chem.201634663764510.1002/cjoc.201500862
    [Google Scholar]
  37. GoreS. ChinthapallyK. BaskaranS. KönigB. Synthesis of substituted hydantoins in low melting mixtures.Chem. Commun. 201349445052505410.1039/c3cc41254g 23625044
    [Google Scholar]
  38. KothaS. GuptaN.K. AswarV.R. Multicomponent approach to hydantoins and thiohydantoins involving a deep eutectic solvent.Chem. Asian J.201914183188319710.1002/asia.201900744 31386259
    [Google Scholar]
  39. GoreS. BaskaranS. KönigB. Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures.Beilstein J. Org. Chem.202218133133610.3762/bjoc.18.37 35387381
    [Google Scholar]
  40. AliR. ChinnamA.K. AswarV.R. The double and triple role of L-(+)-tartaric acid and dimethyl urea: A prevailing green approach in organic synthesis.Curr. Org. Chem.202125555457910.2174/1385272825666210111111313
    [Google Scholar]
  41. KhatriC.K. PotadarS.M. ChaturbhujG.U. A reactant promoted solvent free synthesis of 3,4-dihydropyrimidin-2(1 H)-thione analogues using ammonium thiocyanate.Tetrahedron Lett.201758181778178010.1016/j.tetlet.2017.03.070
    [Google Scholar]
  42. KamalA. ChouhanG. A task-specific ionic liquid [bmim]SCN for the conversion of alkyl halides to alkyl thiocyanates at room temperature.Tetrahedron Lett.20054691489149110.1016/j.tetlet.2005.01.040
    [Google Scholar]
  43. AndreevI.A. RatmanovaN.K. AugustinA.U. IvanovaO.A. LevinaI.I. KhrustalevV.N. WerzD.B. TrushkovI.V. Protic ionic liquid as reagent, catalyst, and solvent: 1‐methylimidazolium thiocyanate.Angew. Chem. Int. Ed.202160147927793410.1002/anie.202016593 33433034
    [Google Scholar]
  44. LiuB. WeiF. ZhaoJ. WangY. Characterization of amide–thiocyanates eutectic ionic liquids and their application in SO2 absorption.RSC Advances2013372470247610.1039/c2ra22990k
    [Google Scholar]
  45. AbbottA.P. CapperG. DaviesD.L. RasheedR.K. TambyrajahV. Novel solvent properties of choline chloride/urea mixturesElectronic supplementary information (ESI) available: Apectroscopic data. See http://www.rsc.org/suppdata/cc/b2/b210714g/ Chem. Commun.2003391707110.1039/b210714g 12610970
    [Google Scholar]
  46. MorrisonH.G. SunC.C. NeervannanS. Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehicles.Int. J. Pharm.20093781-213613910.1016/j.ijpharm.2009.05.039 19477257
    [Google Scholar]
  47. DingJ.H. LiuY.F. TianZ.T. LinP.J. YangF. LiK. YangG.P. WeiY.G. Uranyl-silicotungstate-containing hybrid building units α-SiW 9 and γ-SiW 10 with excellent catalytic activities in the three-component synthesis of dihydropyrimidin-2(1 H)-ones.Inorg. Chem. Front.202310113195320110.1039/D2QI02653H
    [Google Scholar]
  48. NagarajaiahH. MukhopadhyayA. MoorthyJ.N. Biginelli reaction: An overview.Tetrahedron Lett.201657475135514910.1016/j.tetlet.2016.09.047
    [Google Scholar]
  49. RezayatiS. KalantariF. RamazaniA. SajjadifarS. AghahosseiniH. RezaeiA. Magnetic silica-coated picolylamine copper complex [Fe 3 O 4 @SiO 2 @GP/Picolylamine-Cu(II)]-catalyzed biginelli annulation reaction.Inorg. Chem.2022612992101010.1021/acs.inorgchem.1c03042 34962386
    [Google Scholar]
  50. ShaibunaM. KuniyilM.J.K. SreekumarK. Deep eutectic solvent assisted synthesis of dihydropyrimidinones/thiones via Biginelli reaction: Theoretical investigations on their electronic and global reactivity descriptors.New J. Chem.20214544207652077510.1039/D1NJ03879F
    [Google Scholar]
  51. AvudaiappanG. UnnikrishnanV. SreekumarK. Convenient synthesis of dihydropyridine and dihydropyrimidinethione derivatives using a porphyrin cored G1 PAMAM dendrimer as a homogeneous catalyst.ChemistrySelect20205250651410.1002/slct.201903597
    [Google Scholar]
  52. KumarG. BhargavaG. KumarR. Trio role of deep eutectic solvents in the green synthesis of 1,4-dihydropyridine synthesis via hantzsch reaction.Polycycl. Aromat. Compd.20234387238725110.1080/10406638.2022.2133905
    [Google Scholar]
  53. ClarkeC.J. TuW.C. LeversO. BröhlA. HallettJ.P. Green and sustainable solvents in chemical processes.Chem. Rev.2018118274780010.1021/acs.chemrev.7b00571 29300087
    [Google Scholar]
  54. NavarroC.A. SierraC.A. Ochoa-PuentesC. Evaluation of sodium acetate trihydrate–urea DES as a benign reaction media for the Biginelli reaction. Unexpected synthesis of methylenebis(3-hydroxy-5,5-dimethylcyclohex-2-enones), hexahydroxanthene-1,8-diones and hexahydroacridine-1,8-diones.RSC Advances2016670653556536510.1039/C6RA13848A
    [Google Scholar]
  55. Di GioiaM.L. CassanoR. CostanzoP. Herrera CanoN. MaiuoloL. NardiM. NicolettaF.P. OliverioM. ProcopioA. ProcopioA. Green synthesis of privileged benzimidazole scaffolds using active deep eutectic solvent.Molecules201924162885289910.3390/molecules24162885 31398916
    [Google Scholar]
  56. AlvimH.G.O. da Silva JúniorE.N. NetoB.A.D. What do we know about multicomponent reactions? Mechanisms and trends for the Biginelli, Hantzsch, Mannich, Passerini and Ugi MCRs.RSC Advances2014497542825429910.1039/C4RA10651B
    [Google Scholar]
  57. ClarkJ.H. MacquarrieD.J. SherwoodJ. The combined role of catalysis and solvent effects on the Biginelli reaction: Improving efficiency and sustainability.Chemistry201319165174518210.1002/chem.201204396 23436300
    [Google Scholar]
  58. TalrejaS.T. OzaP.M. RaoP.S. Radiation induced conversion of ammonium thiocyanate to thiourea.Bull. Chem. Soc. Jpn.196740102427242810.1246/bcsj.40.2427
    [Google Scholar]
  59. Ghorbani-ChoghamaraniA. TaghipourT. AzadiG. One‐pot, green and efficient synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones or thiones catalyzed by citric acid.J. Chin. Chem. Soc.201360101202120610.1002/jccs.201300118
    [Google Scholar]
  60. LiuQ. PanN. XuJ. ZhangW. KongF. Microwave-assisted and iodine-catalyzed synthesis of dihydropyrimidin-2-thiones via biginelli reaction under solvent-free conditions.Synth. Commun.201343113914610.1080/00397911.2011.593289
    [Google Scholar]
  61. ElmaghrabyA.M. MousaI.A. HarbA.A. MahgoubM.Y. Three component reaction: An efficient synthesis and reactions of 3,4-dihydropyrimidin-2(1 H)-ones and thiones using new natural catalyst.ISRN Org. Chem.20132013511310.1155/2013/706437 24052868
    [Google Scholar]
  62. HajjamiM. GhiasbeygiE. First catalyst- and solvent-free synthesis of 3,4-dihydropyrimidin-2(1H)-ones and -thiones.Russ. J. Org. Chem.201652342943210.1134/S1070428016030222
    [Google Scholar]
  63. AswinK. MansoorS.S. LogaiyaK. SudhanP.N. AhmedR.N. Facile synthesis of 3,4-dihydropyrimidin-2(1 H)-ones and -thiones and indeno[1,2- d]pyrimidines catalyzed by p -dodecylbenzenesulfonic acid.J. Taibah Univ. Sci.20148323624710.1016/j.jtusci.2014.03.005
    [Google Scholar]
  64. SelvakumarK. ShanmugaprabhaT. KumaresanM. SamiP. Heteropoly acid supported on activated natural clay-catalyzed synthesis of 3,4-dihydropyrimidinones/thiones through Biginelli reaction under solvent-free conditions.Synth. Commun.201848222323210.1080/00397911.2017.1396614
    [Google Scholar]
  65. MohammadiannejadK. Ranjbar-KarimiR. HaghighatF. Synthesis of new mixed-bistriarylmethanes and novel 3,4-dihydropyrimidin-2(1 H)one derivatives.New J. Chem.201943145543555010.1039/C8NJ05845H
    [Google Scholar]
  66. KhatriC.K. RekungeD.S. ChaturbhujG.U. Sulfated polyborate: A new and eco-friendly catalyst for one-pot multi-component synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones via Biginelli reaction.New J. Chem.20164012104121041710.1039/C6NJ03120J
    [Google Scholar]
  67. AzimiS. HaririM. Solvent-free and one-pot biginelli synthesis of 3, 4-Dihydropyrimidin-2 (1H)-Ones and 3, 4-Dihydropyrimidin-2 (1H)-Thiones using ionic liquid N, N-Diethyl-N-Sulfoethanammonium chloride {[Et3N–SO3H] Cl} as a green catalyst.Iran. Chem. Commun.2016411320
    [Google Scholar]
  68. MohammedS.M. MoustafaA.H. AhmedN. El-SayedH.A. MohamedA.S.A. Nano-K2CO3-catalyzed biginelli-type reaction: Regioselective synthesis, DFT study, and Antimicrobial activity of 4-Aryl-6-methyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thiones.Russ. J. Org. Chem.202258113614310.1134/S1070428022010195
    [Google Scholar]
  69. Madivalappa DavanagereP. MaitiB. 1,3-Bis(carboxymethyl)imidazolium chloride as a sustainable, recyclable, and metal-free ionic catalyst for the biginelli multicomponent reaction in neat condition.ACS Omega2021640260352604710.1021/acsomega.1c02976 34660965
    [Google Scholar]
  70. MalamiriF. BadriR. KhaksarS. SalahshourP. Choline chloride based eutectic solvent: A highly efficient reaction media for the synthesis of 3,4-dihydropyrimidin-2(1H)-thiones.J. Compos. Compd.202241215315710.52547/jcc.4.3.4
    [Google Scholar]
/content/journals/cocat/10.2174/0122133372302803240415045313
Loading
/content/journals/cocat/10.2174/0122133372302803240415045313
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test