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Recent strategies in the synthesis of thiophene derivatives: highlights from the 2012–2020 literature

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Abstract

Thiophene-based analogs have been fascinated by a growing number of scientists as a potential class of biologically active compounds. Furthermore, they play a vital role for medicinal chemists to improve advanced compounds with a variety of biological effects. The current review envisioned to highlight some recent and particularly remarkable examples of the synthesis of thiophene derivatives by heterocyclization of various substrates from 2012 on.

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References

  1. Joule JA (2020) Five-membered ring systems: thiophenes and selenium/tellurium analogs and benzo analogs. In: Gribble GW, Joule JA (eds) Progress in heterocyclic chemistry. Elsevier, Amsterdam, pp 177–222

    Chapter  Google Scholar 

  2. Benabdellah M, Aouniti A, Dafali A et al (2006) Investigation of the inhibitive effect of triphenyltin 2-thiophene carboxylate on corrosion of steel in 2 M H 3 PO 4 solutions. Appl Surf Sci 252:8341–8347. https://doi.org/10.1016/j.apsusc.2005.11.037

    Article  CAS  Google Scholar 

  3. Larik FA, Faisal M, Saeed A et al (2018) Thiophene-based molecular and polymeric semiconductors for organic field effect transistors and organic thin film transistors. Springer, New York

    Book  Google Scholar 

  4. Anandan S, Manoharan S, Narendran NKS et al (2018) Donor-acceptor substituted thiophene dyes for enhanced nonlinear optical limiting. Opt Mater 85:18–25. https://doi.org/10.1016/j.optmat.2018.08.004

    Article  CAS  Google Scholar 

  5. Mishra R, Sharma PK (2015) A review on synthesis and medicinal importance of thiophene. Int J Eng Al Sci 1:46–59

    Google Scholar 

  6. Pillai AD, Rathod PD, Xavier FP et al (2005) Tetra substituted thiophenes as anti-inflammatory agents: exploitation of analogue-based drug design. Bioorg Med Chem 13:6685–6692. https://doi.org/10.1016/j.bmc.2005.07.044

    Article  CAS  PubMed  Google Scholar 

  7. Nasr T, Bondock S, Eid S (2014) Design, synthesis, antimicrobial evaluation, and molecular docking studies of some new thiophene, pyrazole, and pyridone derivatives bearing sulfisoxazole moiety. Eur J Med Chem 84:491–504. https://doi.org/10.1016/j.ejmech.2014.07.052

    Article  CAS  PubMed  Google Scholar 

  8. Jha K, Kumar S, Tomer I, Mishra R (2012) Thiophene: the molecule of diverse medicinal importance. J Pharm Res 5:560–566

    Google Scholar 

  9. Shah R, Verma PK (2018) Therapeutic importance of synthetic thiophene. Chem Cent J 12:137. https://doi.org/10.1186/s13065-018-0511-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Oertel R, Rahn R, Kirch W (1997) Clinical pharmacokinetics of articaine. Clin Pharmacokinet 33:417–425. https://doi.org/10.2165/00003088-199733060-00002

    Article  CAS  PubMed  Google Scholar 

  11. Gewald K, Schinke E, Böttcher H (1966) Heterocycles from CH-acidic nitriles, VIII. 2-Amino-thiophenes from methylene-active nitriles, carbonyl compounds, and sulfur. Chem Rep 99:94–100. https://doi.org/10.1002/cber.19660990116

    Article  CAS  Google Scholar 

  12. Li JJ (2009) Paal thiophene synthesis BT—name reactions: a collection of detailed mechanisms and synthetic applications. In: Li JJ (ed) Name reactions. Springer, Berlin, p 408. https://doi.org/10.1007/978-3-642-01053-8_187

    Chapter  Google Scholar 

  13. Li JJ, Corey EJ (2005) Name reactions in heterocyclic chemistry. Wiley, Hoboken

    Google Scholar 

  14. Wang Z (2010) Hinsberg thiophene synthesis. Comprehensive organic name reactions and reagents 1426–1429. https://doi.org/10.1002/9780470638859.conrr318

  15. He Y, Lou J, Wu K et al (2019) Copper-catalyzed radical C-C BOND CLEAVAGE and [4 + 1] annulation cascade of cycloketone oxime esters with enaminothiones. J Org Chem 84:2178–2190. https://doi.org/10.1021/acs.joc.8b03175

    Article  CAS  PubMed  Google Scholar 

  16. Chowdhury S, Chanda T, Koley S et al (2015) Organoindium mediated Csp 3 e S cross-coupling/migratory allenylation/thioannulation cascade: expedient synthesis of highly substituted thiophene frameworks. Tetrahedron 71:1844–1850. https://doi.org/10.1016/j.tet.2015.01.065

    Article  CAS  Google Scholar 

  17. Ge LS, Wang ZL, An XL et al (2014) Direct synthesis of polysubstituted 2-aminothiophenes by Cu(ii)-catalyzed addition/oxidative cyclization of alkynoates with thioamides. Org Biomol Chem 12:8473–8479. https://doi.org/10.1039/c4ob01534g

    Article  CAS  PubMed  Google Scholar 

  18. Wen M, Sun P, Luo X, Deng W (2018) Cu (II)-catalyzed one-pot synthesis of fully substituted dihydrothiophenes and thiophenes from thioamides and enynones. Tetrahedron 74:4168–4173. https://doi.org/10.1016/j.tet.2018.02.035

    Article  CAS  Google Scholar 

  19. Wu YN, Fu R, Wang NN et al (2016) Catalytic sulfur-enabled dehydrobicyclization of 1,6-enynes toward arylated indeno[1,2-c]thiophenes. J Org Chem 81:4762–4770. https://doi.org/10.1021/acs.joc.6b00692

    Article  CAS  PubMed  Google Scholar 

  20. Shukla G, Srivastava A, Yadav D, Singh MS (2018) Copper-catalyzed one-pot cross-dehydrogenative thienannulation: chemoselective access to naphtho[2,1-b]thiophene-4,5-diones and subsequent transformation to benzo[a]thieno[3,2-c]phenazines. J Org Chem 83:2173–2181. https://doi.org/10.1021/acs.joc.7b03092

    Article  CAS  PubMed  Google Scholar 

  21. Kurandina D, Gevorgyan V (2016) Rhodium thiavinyl carbenes from 1,2,3-thiadiazoles enable modular synthesis of multisubstituted thiophenes. Org Lett 18:1804–1807. https://doi.org/10.1021/acs.orglett.6b00541

    Article  CAS  PubMed  Google Scholar 

  22. Kim JE, Lee J, Yun H et al (2017) Rhodium-catalyzed intramolecular transannulation reaction of alkynyl thiadiazole enabled 5, n-fused thiophenes. J Org Chem 82:1437–1447. https://doi.org/10.1021/acs.joc.6b02614

    Article  CAS  PubMed  Google Scholar 

  23. Tan WW, Yoshikai N (2016) Copper-catalyzed coupling of 2-siloxy-1-alkenes and diazocarbonyl compounds: approach to multisubstituted furans, pyrroles, and thiophenes. J Org Chem 81:5566–5573. https://doi.org/10.1021/acs.joc.6b00904

    Article  CAS  PubMed  Google Scholar 

  24. Ishikawa S, Noda Y, Wada M, Nishikata T (2015) A copper-catalyzed formal [3 + 2]-cycloaddition for the synthesis of all different aryl-substituted furans and thiophenes. J Org Chem 80:7555–7563. https://doi.org/10.1021/acs.joc.5b01139

    Article  CAS  PubMed  Google Scholar 

  25. Acharya A, Vijay Kumar S, Saraiah B, Ila H (2015) One-pot synthesis of functionalized benzo[b]thiophenes and their hetero-fused analogues via intramolecular Cludeth C. Copper-catalyzed S-arylation of in situ generated enethiolates. J Org Chem 80:2884–2892. https://doi.org/10.1021/acs.joc.5b00032

    Article  CAS  PubMed  Google Scholar 

  26. Jiang H, Zeng W, Li Y et al (2012) Copper(I)-catalyzed synthesis of 2,5-disubstituted furans and thiophenes from haloalkynes or 1,3-diynes. J Org Chem 77:5179–5183. https://doi.org/10.1021/jo300692d

    Article  CAS  PubMed  Google Scholar 

  27. Shang R, Liu L (2011) Transition metal-catalyzed decarboxylative cross-coupling reactions. Sci China Chem 54:1670–1687. https://doi.org/10.1007/s11426-011-4381-0

    Article  CAS  Google Scholar 

  28. Irudayanathan FM, Edwin Raja GC, Lee S (2015) Copper-catalyzed direct synthesis of furans and thiophenes via decarboxylative coupling of alkynyl carboxylic acids with H2O or Na2S. Tetrahedron 71:4418–4425. https://doi.org/10.1016/j.tet.2015.05.017

    Article  CAS  Google Scholar 

  29. Franchetti P, Cappellacci L, Grifantini M et al (1995) Furanfurin and thiophenfurin: two novel tiazofurin analogues. synthesis, structure, antitumor activity, and interactions with inosine monophosphate dehydrogenase. J Med Chem 38:3829–3837. https://doi.org/10.1021/jm00019a013

    Article  CAS  PubMed  Google Scholar 

  30. Zhou X, Jia T, Luo Y et al (2020) Concise synthesis of thiophene C-nucleoside analogues bearing sugar residues and aromatic residues through dimerization and sulfur heterocyclization of sugar alkynes and substituted iodoethynylbenzene. Org Biomol Chem 18:1800–1805. https://doi.org/10.1039/c9ob02717c

    Article  CAS  PubMed  Google Scholar 

  31. Hamedani NF, Ghazvini M, Sheikholeslami-Farahani F, Bagherian-Jamnani MT (2019) ZnO nanorods as efficient catalyst for the green synthesis of thiophene derivatives: investigation of antioxidant and antimicrobial activity. J Heterocycl Chem. https://doi.org/10.1002/jhet.3884

    Article  Google Scholar 

  32. Aggarwal T, Kumar S, Verma AK (2016) Iodine-mediated synthesis of heterocycles: via electrophilic cyclization of alkynes. Org Biomol Chem 14:7639–7653. https://doi.org/10.1039/c6ob01054g

    Article  CAS  PubMed  Google Scholar 

  33. Santana AS, Carvalho DB, Cassemiro NS et al (2014) Synthesis of 3-iodothiophenes via iodocyclization of (Z) -thiobutenynes. Tetrahedron Lett 55:52–55. https://doi.org/10.1016/j.tetlet.2013.10.118

    Article  CAS  Google Scholar 

  34. Maity P, Ranu BC (2017) Iodine-catalyzed synthesis of chalcogenophenes by the reaction of 1,3-dienyl bromides and potassium selenocyanate/potassium sulfide (KSeCN/K2S). Adv Synth Catal 359:4369–4378. https://doi.org/10.1002/adsc.201701232

    Article  CAS  Google Scholar 

  35. Mancuso R, Pomelli CS, Chiappe C et al (2014) A recyclable and base-free method for the synthesis of 3-iodothiophenes by the iodoheterocyclisation of 1-mercapto-3-alkyne-2-ols in ionic liquids. Org Biomol Chem 12:651–659. https://doi.org/10.1039/c3ob41928b

    Article  CAS  PubMed  Google Scholar 

  36. Zali-boeini H (2015) Novel route to thiophene-2, 4-diamines. Synlett 26:1819–1822. https://doi.org/10.1055/s-0034-1378724

    Article  CAS  Google Scholar 

  37. Bilheri FN, Stein AL, Zeni G (2015) Synthesis of chalcogenophenes via cyclization of 1, 3-diynes promoted by iron (iii) chloride and dialkyl dichalcogenides. Adv Synth Catal. https://doi.org/10.1002/adsc.201401159

    Article  Google Scholar 

  38. Han T, Wang Y, Li H et al (2018) Synthesis of polysubstituted 3-aminothiophenes from thioamides and allenes via tandem thio-michael addition/oxidative annulation and 1,2-sulfur migration. J Org Chem 83:3–7. https://doi.org/10.1021/acs.joc.7b02616

    Article  CAS  Google Scholar 

  39. Zali-boeini H, Ghani M (2013) An aquatic pseudo-four-component reaction for the synthesis of highly substituted thiophenes. Synthesis. https://doi.org/10.1055/s-0032-1316866

    Article  Google Scholar 

  40. Han Y, Tang W, Yan C (2014) Gewald-type reaction of double activated 2, 3-diarylcyclopropanes with elemental sulfur for synthesis of polysubstituted. Tetrahedron Lett 55:1441–1443. https://doi.org/10.1016/j.tetlet.2014.01.043

    Article  CAS  Google Scholar 

  41. Su Z, Qian S, Xue S, Wang C (2017) DBU-mediated [4 + 1] annulations of donor-acceptor cyclopropanes with carbon disulfide or thiourea for synthesis of 2-aminothiophene-3-carboxylates. Org Biomol Chem 15:7878–7886. https://doi.org/10.1039/c7ob01886j

    Article  CAS  PubMed  Google Scholar 

  42. Reddy CR, Valleti RR, Reddy MD (2013) A thioannulation approach to substituted thiophenes from Morita-Baylis-hillman acetates of acetylenic aldehydes. J Org Chem 78:6495–6502. https://doi.org/10.1021/jo400567h

    Article  CAS  PubMed  Google Scholar 

  43. Novo D, Kao T, Peng B et al (2018) Temperature-controlled thiation of α-cyano-β-alkynyl carbonyl derivatives for de novo synthesis of 2-aminothiophenes and thieno [2, 3-c] isothiazoles. J Org Chem. https://doi.org/10.1021/acs.joc.8b01866

    Article  Google Scholar 

  44. Mcnabola N, Connor CJO, Roydhouse MD et al (2015) A one-pot synthesis of 3-nitrothiophene and 3-nitro-2-substituted thiophenes. Tetrahedron 71:4598–4603. https://doi.org/10.1016/j.tet.2015.05.032

    Article  CAS  Google Scholar 

  45. Shi W, Wan L, Hu Y et al (2015) Facile synthesis of 3-aldehyde-2-substituted thiophenes through with ynals. Tetrahedron Lett 56:2083–2085. https://doi.org/10.1016/j.tetlet.2015.03.023

    Article  CAS  Google Scholar 

  46. Bharathiraja G, Sathishkannan G, Punniyamurthy T (2016) Domino synthesis of tetrasubstituted thiophenes from 1,3-enynes with mercaptoacetaldehyde. J Org Chem 81:2670–2674. https://doi.org/10.1021/acs.joc.6b00231

    Article  CAS  PubMed  Google Scholar 

  47. Can E, Kılıç K, Sinem M et al (2015) Intermolecular heterocyclization of alkynones with 2-mercaptoacetaldehyde under metal-free conditions: synthesis of 2, 3-disubstituted thiophenes. Tetrahedron Lett 56:5386–5389. https://doi.org/10.1016/j.tetlet.2015.07.090

    Article  CAS  Google Scholar 

  48. Goswami L, Neog K, Sharma K, Gogoi P (2017) A metal-free cascade reaction of β-halo-α, β-unsaturated aldehydes and 1,4-dithiane-2,5-diols: synthesis of polycyclic 2-formylthiophenes. Org Biomol Chem 15:6470–6473. https://doi.org/10.1039/c7ob01641g

    Article  CAS  PubMed  Google Scholar 

  49. Kan X, Yang X, Hu F et al (2015) Et3N mediated synthesis of polysubstituted thiophenes from α-oxo ketene dithioacetals. Tetrahedron Lett 56:6198–6201. https://doi.org/10.1016/j.tetlet.2015.09.089

    Article  CAS  Google Scholar 

  50. Cheng B, Duan X, Li Y et al (2020) Development and application of pyridinium 1,4-zwitterionic thiolates: synthesis of polysubstituted thiophenes. Eur J Org Chem. https://doi.org/10.1002/ejoc.202000165

    Article  Google Scholar 

  51. Dagoneau D, Kolleth A, Lumbroso A et al (2019) Straightforward synthesis of 3-aminothiophenes using activated amides. Helv Chim Acta. https://doi.org/10.1002/hlca.201900031

    Article  Google Scholar 

  52. Hirotaki K, Hanamoto T (2013) Synthesis of 2-aryl-3-fluoro-5-silylthiophenes via a cascade reactive sequence. Org Lett 15:1226–1229. https://doi.org/10.1021/ol400141y

    Article  CAS  PubMed  Google Scholar 

  53. Li JJ (2014) Name reactions. Name reactions. https://doi.org/10.1007/978-3-319-03979-4

    Article  Google Scholar 

  54. Fricero P, Bialy L, Czechtizky W et al (2018) Synthesis of bifunctional thiophenes via fiesselmann condensation of ynone trifluoroborate salts. Org Lett 20:198–200. https://doi.org/10.1021/acs.orglett.7b03558

    Article  CAS  PubMed  Google Scholar 

  55. Irgashev RA, Steparuk AS, Rusinov GL (2018) A new convenient synthetic route towards 2-(hetero)aryl-substituted thieno[3,2-b]indoles using Fischer indolization. Org Biomol Chem 16:4821–4832. https://doi.org/10.1039/C8OB01110A

    Article  CAS  PubMed  Google Scholar 

  56. Zhang X, Wu M, Zhang J, Cao S (2017) Synthesis of N, N-disubstituted 2-aminothiophenes by the cyclization of gem-difluoroalkenes with β-keto thioamides. Org Biomol Chem 15:2436–2442. https://doi.org/10.1039/c7ob00368d

    Article  CAS  PubMed  Google Scholar 

  57. Xu HW, Ma GH, Jiang B, Tu SJ (2013) A new [2 + 2+1] heterocyclization for the synthesis of 2,3,5-trisubstituted thiophenes under microwave irradiation. Synthesis (Germany) 45:3392–3398. https://doi.org/10.1055/s-0033-1339917

    Article  CAS  Google Scholar 

  58. Wang Z, Qu Z, Xiao F et al (2018) One-pot synthesis of 2,3,5-trisubstituted thiophenes through three-component assembly of arylacetaldehydes, elemental sulfur, and 1,3-dicarbonyls. Adv Synth Catal 360:796–800. https://doi.org/10.1002/adsc.201701332

    Article  CAS  Google Scholar 

  59. Nguyen TTT, Le VA, Retailleau P, Nguyen TB (2020) Access to 2-amino-3-arylthiophenes by base-catalyzed redox condensation reaction between arylacetonitriles, chalcones, and elemental sulfur. Adv Synth Catal 362:160–165. https://doi.org/10.1002/adsc.201901235

    Article  CAS  Google Scholar 

  60. Agrawal AR, Kumar NR, Debnath S et al (2018) Radical-cascade avenue for 3,4-fused-ring-substituted thiophenes. Org Lett 20:4728–4731. https://doi.org/10.1021/acs.orglett.8b01577

    Article  CAS  PubMed  Google Scholar 

  61. Zhang G, Yi H, Chen H et al (2014) Trisulfur radical anion as the key intermediate for the synthesis of thiophene via the interaction between elemental sulfur and NaO t Bu. Org Lett 16:6156–6159. https://doi.org/10.1021/ol503015b

    Article  CAS  PubMed  Google Scholar 

  62. Liu W, Chen C, Liu H (2015) Synthesis of polysubstituted thiophenes via base-induced [2 + 2+1] cycloaddition reaction of alkynes and elemental sulfur. Adv Synth Catal 357:4050–4054. https://doi.org/10.1002/adsc.201500422

    Article  CAS  Google Scholar 

  63. Li JH, Huang Q, Rao W et al (2019) A trisulfur radical anion (S3-) involved sulfur insertion reaction of 1,3-enynes: sulfide sources control chemoselective synthesis of 2,3,5-trisubstituted thiophenes and 3-thienyl disulfides. Chem Commun 55:7808–7811. https://doi.org/10.1039/c9cc03604k

    Article  CAS  Google Scholar 

  64. Li JH, Huang Q, Wang SY, Ji SJ (2018) Trisulfur radical anion (S3•-) involved [1 + 2 + 2] and [1 + 3 + 1] cycloaddition with aromatic alkynes: synthesis of tetraphenylthiophene and 2-benzylidenetetrahydrothiophene derivatives. Org Lett 20:4704–4708. https://doi.org/10.1021/acs.orglett.8b02066

    Article  CAS  PubMed  Google Scholar 

  65. Chen L, Min H, Zeng W et al (2018) Transition-metal-free sulfuration/annulation of alkenes: economical access to thiophenes enabled by the cleavage of multiple C-H bonds. Org Lett 20:7392–7395. https://doi.org/10.1021/acs.orglett.8b03078

    Article  CAS  PubMed  Google Scholar 

  66. Wang T, An Z, Qi Z et al (2019) Ring-opening/annulation reaction of cyclopropyl ethanols: concise access to thiophene aldehydes: Via C-S bond formation. Org Chem Front 6:3705–3709. https://doi.org/10.1039/c9qo01014a

    Article  CAS  Google Scholar 

  67. Wang Z, Xue L, He Y et al (2014) Access to functionalized 3H-pyrrolo[2,3-c]quinolin-4(5H)-ones and thieno[2,3-c]quinolin-4(5H)-ones via domino reaction of 4-Alkynyl-3-bromoquinolin-2(1H)-ones. J Org Chem 79:9628–9638. https://doi.org/10.1021/jo501753p

    Article  CAS  PubMed  Google Scholar 

  68. Tang J, Ming L, Zhao X (2013) Sulfur heterocyclization and 1,3-migration of silicon in reaction of 1,3-diynes with sodium triisopropylsilanethiolate: one-pot synthesis of 2,5-disubstituted 3-(triisopropylsilyl)thiophenes. Synthesis (Germany) 45:1713–1718. https://doi.org/10.1055/s-0033-1338472

    Article  CAS  Google Scholar 

  69. Talbi I, Alayrac C, Lohier JF et al (2016) Application of ynamides in the synthesis of 2-(tosylamido)- and 2,5-bis(tosylamido)thiophenes. Org Lett 18:2656–2659. https://doi.org/10.1021/acs.orglett.6b01101

    Article  CAS  PubMed  Google Scholar 

  70. Pigulski B, Mȩcik P, Cichos J, Szafert S (2017) Use of Stable Amine-Capped Polyynes in the Regioselective Synthesis of Push-Pull Thiophenes. J Org Chem 82:1487–1498. https://doi.org/10.1021/acs.joc.6b02685

    Article  CAS  PubMed  Google Scholar 

  71. Ramulu BJ, Nagaraju AA, Chowdhury S et al (2015) Metal-free reagent dependent S-S and C-C homocoupling of a-enolic dithioesters at room temperature: direct access to fully substituted symmetrical thiophenes via chemoselective Paal–Knorr approach. Adv Synth Catal 357:530–538. https://doi.org/10.1002/adsc.201400828

    Article  CAS  Google Scholar 

  72. Ramulu BJ, Koley S, Singh MS (2016) Metal-free Brønsted acid mediated synthesis of fully substituted thiophenes via chemo- and regioselective intramolecular cyclization of α, α′-bis(β-oxodithioesters) at room temperature. Org Biomol Chem 14:434–439. https://doi.org/10.1039/c5ob02081f

    Article  CAS  PubMed  Google Scholar 

  73. Nandi GC, Singh MS (2016) P-TSA/base-promoted propargylation/cyclization of β-ketothioamides for the regioselective synthesis of highly substituted (hydro)thiophenes. J Org Chem 81:5824–5836. https://doi.org/10.1021/acs.joc.6b00342

    Article  CAS  PubMed  Google Scholar 

  74. Hulme C, Ayaz M, Martinez-Ariza G et al (2015) Recent advances in multicomponent reaction chemistry: applications in small molecule drug discovery. Small Mol Med Chem 21:145–187. https://doi.org/10.1002/9781118771723

    Article  Google Scholar 

  75. Moghaddam FM, Khodabakhshi MR, Latifkar A (2014) A one-pot multicomponent synthesis of polysubstituted thiophenes via the reactions of an isocyanide, a -haloketones, and b -ketodithioesters in water. Tetrahedron Lett 55:1251–1254. https://doi.org/10.1016/j.tetlet.2014.01.014

    Article  CAS  Google Scholar 

  76. Adib M, Rajai-daryasarei S, Pashazadeh R, Jahani M (2018) A consecutive four-component synthesis of polysubstituted thiophenes in aqueous medium. Eur J Org Chem. 2018:3001–3016. https://doi.org/10.1002/ejoc.201800361

    Article  CAS  Google Scholar 

  77. Rong L, Shen Y, Xiong G, Gong Y (2019) Synthesis of 2-nitrothiophenes via tandem henry reaction and nucleophilic substitution on sulfur from β-thiocyanatopropenals. J Heterocyclic Chem. https://doi.org/10.1002/jhet.3446

    Article  Google Scholar 

  78. Zubarev AA, Shestopalov AM, Larionova NA et al (2013) New regio-selective method of combinatorial synthesis of substituted thiophenes, thieno [3, 2- b] pyridines and other heterocycles via combination of ‘domino’ -type reactions. Tetrahedron 69:9648–9655. https://doi.org/10.1016/j.tet.2013.09.025

    Article  CAS  Google Scholar 

  79. Zubarev AA, Larionova NA, Rodinovskaya LA et al (2013) Synthesis of 2,5-asymmetrically substituted 3,4-diaminothieno[2,3- b]thiophenes by domino reaction. ACS Combin Sci 15:546–550. https://doi.org/10.1021/co400069v

    Article  CAS  Google Scholar 

  80. Lee S, Lee D, Song K et al (2014) Parallel synthesis of 2,4,5-trisubstituted thiophene-3-carbonitrile derivatives on traceless solid support. Tetrahedron 70:9183–9190. https://doi.org/10.1016/j.tet.2014.10.030

    Article  CAS  Google Scholar 

  81. Ransborg LK, Albrecht Ł, Weise CF et al (2012) Optically active thiophenes via an organocatalytic one-pot methodology. Org Lett 14:724–727. https://doi.org/10.1021/ol203237r

    Article  CAS  PubMed  Google Scholar 

  82. Thomas J, Jana S, Sonawane M et al (2017) A new four-component reaction involving the Michael addition and the Gewald reaction, leading to diverse biologically active 2-aminothiophenes. Org Biomol Chem 15:3892–3900. https://doi.org/10.1039/c7ob00707h

    Article  CAS  PubMed  Google Scholar 

  83. Luo X, Ge LS, An XL et al (2015) Regioselective metal-free one-pot synthesis of functionalized 2-aminothiophene derivatives. J Org Chem 80:4611–4617. https://doi.org/10.1021/acs.joc.5b00488

    Article  CAS  PubMed  Google Scholar 

  84. Mari G, Verboni M, De Crescentini L et al (2018) Assembly of fully substituted 2,5-dihydrothiophenes: via a novel sequential multicomponent reaction. Org Chem Front 5:2108–2114. https://doi.org/10.1039/c8qo00343b

    Article  CAS  Google Scholar 

  85. Mari G, De Crescentini L, Favi G et al (2018) 1,2-Diaza-1,3-diene-based multicomponent reactions in sequential protocols to synthesize arylamino-5-hydrazonothiophene-3-carboxylates. Eur J Org Chem 2018:6548–6556. https://doi.org/10.1002/ejoc.201801228

    Article  CAS  Google Scholar 

  86. Acharya A, Gautam V, Ila H (2017) Synthesis of thieno-fused five- and six-membered nitrogen and oxygen heterocycles via intramolecular heteroannulation of 4,5-substituted 3-amino or 3-hydroxy 2-functionalized thiophenes. J Org Chem 82:7920–7938. https://doi.org/10.1021/acs.joc.7b01153

    Article  CAS  PubMed  Google Scholar 

  87. Nedolya NA, Tarasova OA, Albanov AI, Trofimov BA (2017) A one-pot assembly of fully substituted alkyl 5-aminothiophene-2-carboxylates from allenes, isothiocyanates, and alkyl 2-bromoacetates. J Org Chem 82:7519–7528. https://doi.org/10.1021/acs.joc.7b01217

    Article  CAS  PubMed  Google Scholar 

  88. Nedolya NA, Tarasova OA, Albanov AI, Trofimov BA (2018) Expeditious scalable catalyst-free one-pot synthesis of 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles via sequential reactions of lithiated alkoxyallenes with isothiocyanates and 2-bromoacetonitrile. Synthesis (Germany) 50:1891–1900. https://doi.org/10.1055/s-0036-1591905

    Article  CAS  Google Scholar 

  89. Nedolya NA, Tarasova OA, Albanov AI, Trofimov BA (2018) A new facet of azatriene reactivity: a short cut to 5-amino-3-methyl-4-(1h-pyrrol-1-yl)thiophene-2-carboxylates and 5-Amino-3-methyl-4-(1H-pyrrol-1-yl)thiophene-2-carbonitriles. Eur J Org Chem 2018:1953–1963. https://doi.org/10.1002/ejoc.201800268

    Article  CAS  Google Scholar 

  90. Wen L, He T, Lan M et al (2013) Three-component cascade annulation of beta-ketothioamides promoted by CF3CH2OH: a regioselective synthesis of tetrasubstituted thiophenes three-component promoted by cascade annulation of β -ketothioamides synthesis of regioselective tetrasubstituted thi. J Org Chem 78:10617–10628. https://doi.org/10.1021/jo401397d

    Article  CAS  PubMed  Google Scholar 

  91. Yavari I, Malekafzali A (2013) Formation of highly functionalized thiophenes by reaction of tetramethylthiourea, acetylenic esters, and α -haloketones. J Heterocycl Chem 50:992–994. https://doi.org/10.1002/jhet

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, 14176, Iran

    Fahimeh Abedinifar, Elham Babazadeh Rezaei, Mahmood Biglar, Bagher Larijani & Mohammad Mahdavi

  2. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Halleh Hamedifar & Samira Ansari

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  1. Fahimeh Abedinifar
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  2. Elham Babazadeh Rezaei
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  3. Mahmood Biglar
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Abedinifar, F., Babazadeh Rezaei, E., Biglar, M. et al. Recent strategies in the synthesis of thiophene derivatives: highlights from the 2012–2020 literature. Mol Divers 25, 2571–2604 (2021). https://doi.org/10.1007/s11030-020-10128-9

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