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

Abstract

A synthetically simple and convenient approach to tetrasubstituted thiophenes with rare combination of the alkoxy, amino, and cyano groups has been developed. The assembly of polyfunctionalized thiophene ring is implemented in one preparative step by sequential addition of isothiocyanate and 2-bromoacetonitrile to the lithiated (with n-BuLi) alkoxyallene. The reaction proceeds through in situ formation and intramolecular cyclization of cyanomethyl 2-alkoxy-N-buta-2,3-dienimidothioate (1-aza-1,3,4-triene).

Key words

alkoxyallenes - isothiocyanates - 2-bromoacetonitrile - 1-aza-1,3,4-trienes - 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles

• References

• 1a Campaigne E. In Comprehensive Heterocyclic Chemistry . Vol. 4. Katritzky AR. Rees CW. Elsevier; Oxford: 1984: 863
• 1b Nakayama J. In Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR. Rees CW. Scriven EF. V. Elsevier; Oxford: 1996: 607
• 1c Sato O. Nakayama J. In Comprehensive Heterocyclic Chemistry III . Vol. 3. Katritzky AR. Ramsden CA. Scriven EF. V. Taylor RJ. K. Elsevier; Amsterdam: 2008: 843
• 1d Lebedev MV. Nenajdenko VG. Balenkova ES. Synthesis 2001; 2124
• 1e Mancuso R. Gabriele B. Molecules 2014; 19: 15687
• 2a McKibben BP. Cartwright CH. Castelhano AL. Tetrahedron Lett. 1999; 40: 5471
• 2b Castanedo GM. Sutherlin DP. Tetrahedron Lett. 2001; 42: 7181
• 2c Thomae D. Perspicace E. Henryon D. Xu Z. Schneider S. Hesse S. Kirsch G. Seck P. Tetrahedron 2009; 65: 10453
• 2d Sathishkannan G. Srinivasan K. Chem. Commun. 2014; 50: 4062
• 2e Sahu SN. Gupta MK. Singh S. Yadav P. Panwar R. Kumar A. Ram VJ. Kumar B. Pratap R. RSC Adv. 2015; 5: 36979
• 2f Bharathiraja G. Sathishkannan G. Punniyamurthy T. J. Org. Chem. 2016; 81: 2670
• 3a Bohlmann F. Zdero C. Thiophene and its Derivatives, Part One . In Chemistry of Heterocyclic Compounds . Vol. 44. Gronowitz S. Wiley; New York: 1985: 261
• 3b Arnason JT. Philogène BJ. R. Morand P. Imrie K. Iyengar S. Duval F. Soucy-Breau C. Scaiano JC. Werstiuk ΝH. Hasspieler B. Downe ΑE. R. In Insecticides of Plant Origin, ACS Symposium Series #387. American Chemical Society; Washington DC: 1989. Chap. 12, 165
• 3c Ibrahim SR. M. Abdallah HM. El-Halawany AM. Mohamed GA. Phytochem. Rev. 2016; 15: 197
• 4a Russell RK. Press JB. In Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR. Rees CW. Scriven EF. V. Elsevier; Oxford: 1996: 679
• 4b Schatz J. Brendgen T. Schühle D. In Comprehensive Heterocyclic Chemistry III . Vol. 3. Katritzky AR. Ramsden CA. Scriven EF. V. Taylor RJ. K. Elsevier; Amsterdam: 2008: 931
• 4c Handbook of Thiophene-Based Materials: Applications in Organic Electronics and Photonics. Peperichka IF. Peperichka DF. Wiley; West Sussex: 2009
• 4d Roncali J. Chem. Rev. 1992; 92: 711
• 4e Rauchfuss TB. Prog. Inorg. Chem. 1991; 39: 259
• 4f Chan HS. O. Ng SC. Prog. Polym. Sci. 1998; 23: 1167
• 4g Barbarella G. Melucci M. Sotgiu G. Adv. Mater. 2005; 17: 1581
• 4h Ong BS. Wu Y. Li Y. Liu P. Pan H. Chem. Eur. J. 2008; 14: 4766
• 4i Roman G. Mini-Rev. Org. Chem. 2013; 10: 27
• 4j Abdou MM. Am. J. Chem. 2013; 3: 126
• 5a Sperry JB. Wright DL. Curr. Opin. Drug Discovery Dev. 2005; 8: 723
• 5b Molvi KI. Sudarsanam V. Patel MM. Haque N. J. Enzyme Inhibit. Med. Chem. 2008; 23: 819
• 5c Mishra R. Jha KK. Kumar S. Tomer I. Pharma Chem. 2011; 3: 38
• 5d Hwang K.-J. Kim H.-S. Han I.-C. Kim B.-T. Bull. Korean Chem. Soc. 2012; 33: 2585
• 5e Chaudhary A. Jha KK. Kumar S. J. Adv. Sci. Res. 2012; 3: 03
• 5f Ruppel JV. Snyder NL. Thompson AD. Farnsworth TW. In Heterocyclic Chemistry in Drug Discovery . Li JJ. Wiley; New York: 2013: 119
• 5g Gramec D. Peterlin ML. Sollner DM. Chem. Res. Toxicol. 2014; 27: 1344
• 5h Vinh NB. Devine SM. Munoz L. Ryan RM. Wang BH. Krum H. Chalmers DK. Simpson JS. Scammells PJ. Chem. Open 2015; 4: 56
• 6a Kilbourn MR. Nucl. Med. Biol. 1989; 16: 681
• 6b Uckun FM. Pendergrass S. Maher D. Zhu D. Tuel-Ahlgren L. Mao C. Venkatachalam TK. Bioorg. Med. Chem. Lett. 1999; 9: 3411
• 6c Corral C. Lissavetzky J. Manzanares I. Darias V. Expόsito-Orta MA. Conde JA. M. Sánchez-Mateo CC. Bioorg. Med. Chem. 1999; 7: 1349
• 6d Zhang A. Zhou G. Rong S.-B. Johnson KM. Zang M. Kozikowski AP. Bioorg. Med. Chem. Lett. 2002; 12: 993
• 6e King LA. Drug Test. Anal. 2014; 6: 808
• 7a Mishra A. Ma C.-Q. Bäuerle P. Chem. Rev. 2009; 109: 1141
• 7b Ie Y. Yoshimura A. Takeuchi D. Osakada K. Aso Y. Chem. Lett. 2011; 40: 1039
• 7c Livi F. Carlé JE. Bundgaard E. Top. Heterocycl. Chem. 2015; 39: 203
• 8a Zotti G. Gallazzi MC. Zerbi G. Meille SV. Synth. Met. 1995; 73: 217
• 8b Borghese A. Geldhof G. Antoine L. Tetrahedron Lett. 2006; 47: 9249
• 8c Matharu A. Huddleston P. Jeeva S. Wood M. Chambers-Asman D. Dyes Pigm. 2008; 78: 89
• 8d Hergué N. Frère P. Roncali J. Org. Biomol. Chem. 2011; 9: 588
• 8e Savitha G. Hergué N. Guilmet E. Allain M. Frère P. Tetrahedron Lett. 2011; 52: 1288
• 8f Tietz JI. Seed AJ. Sampson P. Org. Lett. 2012; 14: 5058
• 9a Puterova Z. Krutosikova A. Heterocycl. Compd. 2010; 1
• 9b Hartmann H. Gerstner P. Rohde D. Org. Lett. 2001; 3: 1673
• 9c Su YZ. Lin JT. Tao Y.-T. Ko C.-W. Lin S.-C. Sun S.-S. Chem. Mater. 2002; 14: 1884
• 9d Barnes DM. Haight AR. Hameury T. McLaughlin MA. Mei J. Tedrow S. Toma JD. R. Tetrahedron 2006; 62: 11311
• 9e Vasileiadis M. Kazantsev AV. Karamertzanis PG. Adjiman CS. Pantelides CC. Acta Crystallogr., Ser. B 2012; 68: 677
• 9f Kaki VR. Akkinepalli RR. Deb PK. Pichika MR. Synth. Commun. 2015; 45: 119
• 10a Dohi T. Ito M. Yamaoka N. Morimoto K. Fujioka H. Kita Y. Tetrahedron 2009; 65: 10797
• 10b Yu L. Acc. Chem. Res. 2010; 43: 1257
• 10c Prakasam A. Rajeswari G. Anbarasan PM. Elixir Int. J. 2015; 33298
• 10d Harty EL. Ha AR. Warren MR. Thompson AL. Allan DR. Goodwin AL. Funnell NP. Chem. Commun. 2015; 51: 10608
• 11a Afifi TH. Adv. Colour Sci. Technol. 2003; 6: 63
• 11b Abd-El-Aziz AS. Afifi TH. Dyes Pigm. 2005; 70: 8
• 11c Al-Mousawi SM. El-Apasery MA. Mahmoud HM. Molecules 2013; 18: 7081
• 11d Sabnis RW. Color. Technol. 2016; 132: 49
• 12 Hoischen D. Schallner O. Elbe H.-L. Gayer H. Kunisch F. Wachendorff-Neumann U. Kuck K.-H. Drewes MW. Liping Y. Min W. Qing Z. PCT Int. Appl. WO 2004067527 A1 20040812, 2004
• 13 Gaber HM. Bagley MC. Eur. J. Chem. 2011; 2: 214
• 14 Molvi KI. Vasu KK. Yerande SG. Sudarsanam V. Haque N. Eur. J. Med. Chem. 2007; 42: 1049
• 15 Kunda PK. Rao JV. Mukkanti K. Induri M. Reddy GD. Trop. J. Pharm. Res. 2013; 12: 566
• 16 Srivastava S. Das B. Prasad YR. Pharm. Lett. 2012; 4: 1214
• 17 Fogue PS. Lunga PK. Fondjo ES. De Dieu Tamokou J. Thaddee B. Tsemeugne J. Tchapi AT. Kuiate J.-R. Mycoses 2012; 55: 310
• 18 Molvi KI. Mansuri M. Sudarsanam V. Patel MM. Andrabi SM. Haque N. J. Enzyme Inhib. Med. Chem. 2008; 23: 829
• 19a Valant C. Aurelio L. Devine SM. Ashton TD. White JM. Sexton PM. Christopoulos A. Scammells PJ. J. Med. Chem. 2012; 55: 2367
• 19b Pandya DH. Sharma JA. Jalani HB. Pandya AN. Sudarsanam V. Kachler S. Klotz KN. Vasu KK. Bioorg. Med. Chem. Lett. 2015; 25: 1306
• 20a Vardanyan R. Hruby V. Synthesis of Best-Seller Drugs . Academic Press; London: 2016: 94
• 20b Li JJ. Johnson DS. Sliskovic DR. Roth BD. Contemporary Drug Synthesis . Wiley; New York: 2004: 96
• 21 Jagiello M. Kanska U. Nevozhay D. Boratynski J. Acta Biochim. Pol. 2010; 57: 83
• 22a Puterová Z. Andicsová A. Végh D. Tetrahedron 2008; 64: 11262
• 22b Puterová Z. Krutošíková A. Végh D. ARKIVOC 2010; (i): 209
• 22c Bolduc A. Mallet C. Skene WG. Sci. China Chem. 2013; 56: 3
• 23a Sherif SM. Hussein AM. Monatsh. Chem. 1997; 128: 687
• 23b Su W. Guo S. Hong Z. Chen R. Tetrahedron Lett. 2010; 51: 5718
• 23c Hergué N. Mallet C. Savitha G. Allain M. Frère P. Roncali J. Org. Lett. 2011; 13: 1762
• 24a Bera MK. Hommes P. Reissig H.-U. Chem. Eur. J. 2011; 17: 11838
• 24b Yu S. Xiong M. Xie X. Liu Y. Angew. Chem. Int. Ed. 2014; 53: 11596
• 24c Mohan DC. Ravi C. Rao SN. Adimurthy S. Org. Biomol. Chem. 2015; 13: 3556
• 24d Shao Z. Fu S. Wei M. Zhou S. Liu Q. Angew. Chem. Int. Ed. 2016; 55: 14653
• 25a Racane L. Tralic-Kulenovic V. Fiser-Jakic L. Boykin DW. Karminski-Zamola G. Heterocycles 2001; 55: 2085
• 25b Meijer L. Vierfond J.-M. Mettey Y. Eur. Patent Appl. EP 1388541 A1 20040211, 2004
• 25c Bamborough P. Christopher JA. Cutler GJ. Dickson MC. Mellor GW. Morey JV. Patel CB. Shewchuk LM. Bioorg. Med. Chem. Lett. 2006; 16: 6236
• 25d Yerra R. Naresh K. Jayaveera KN. Int. J. Pharm. Tech. Res. 2012; 4: 648
• 25e Tsantrizos YS. Poirier J. Sebag M. Berghuis A. Park J. Wim de Schutter J. PCT Int. Appl. WO 2014078957 A1 20140530, 2014
• 26a Yen MS. Wang IJ. Dyes Pigm. 2004; 61: 243
• 26b Wu Y. Wigglesworth AJ. Liu P. US Patent Appl. Publ. US 20130140494 A1 20130606, 2013
• 26c Qi A. Wang Z. Guo H. Li X. Zhongnan Daxue Xuebao (Ziran Kexue Ban) 2015; 46: 1999
• 26d Zheng L. Ho LY. Khan SA. Soft Matter 2016; 12: 8654
• 26e Shaik B. Han J.-H. Song DJ. Kang H.-M. Lee S.-G. Can. J. Chem. 2016; 94: 553
• 26f Li S. Yan J. Li C.-Z. Liu F. Shi M. Chen H. Russell TP. J. Mater. Chem. A 2016; 4: 3777
• 27a Brandsma L. Tarasova OA. Vvedensky VYu. de Yong RL. P. Verkruijsse HD. Klyba LV. Nedolya NA. Trofimov BA. Russ. J. Org. Chem. 1999; 35: 1228
• 27b Pinto IL. Jarvest RL. Serafinowska HT. Tetrahedron Lett. 2000; 41: 1597
• 27c Katritzky AR. Wang X. Denisenko A. J. Org. Chem. 2001; 66: 2850
• 28a Tarasova OA. Nedolya NA. Vvedensky VYu. Brandsma L. Trofimov BA. Tetrahedron Lett. 1997; 38: 7241
• 28b Sridhar M. Rao RM. Baba NH. K. Kumbhare RM. Tetrahedron Lett. 2007; 48: 3171
• 28c Wang K. Kim D. Domling A. J. Comb. Chem. 2010; 12: 111
• 28d Jalani HB. Pandya AN. Pandya DH. Sharma JA. Sudarsanam V. Vasu KK. Tetrahedron Lett. 2012; 53: 6927
• 28e Bourgeaux M. Vomscheid S. Skene WG. Synth. Commun. 2007; 37: 3551
• 29a Aurelio L. Flynn BL. Scammells PJ. Aust. J. Chem. 2009; 62: 402
• 29b Lee S. Lee D. Song K.-S. Liu K.-H. Gong Y.-D. Lee T. Tetrahedron 2014; 70: 9183
• 29c Das VK. Harsh SN. Karak N. Tetrahedron Lett. 2016; 57: 549
• 29d Moussallem C. Olivier S. Grolleau J. Allain M. Mallet C. Savitha G. Gohier F. Frère P. Chem. Eur. J. 2016; 22: 6510
• 29e Savitha G. Moussallem C. Allain M. Gohier F. Frère P. Chem. Asian J. 2017; 12: 1935
• 29f Tremblay MH. Skalski T. Gautier Y. Pianezzola G. Skene WG. J. Phys. Chem. C 2016; 120: 9081
• 30 Venkata Rao K. Balakumar C. Lakshmi Narayana B. Pran Kishore D. Rajwinder K. Raghuram Rao A. Tetrahedron Lett. 2013; 54: 1274
• 31 Nedolya NA. Brandsma L. Tarasova OA. Albanov AI. Trofimov BA. Russ. J. Org. Chem. 2011; 47: 659
• 32 Brandsma L. Nedolya NA. Tarasova OA. Klyba LV. Sinegovskaya LM. Trofimov BA. Russ. J. Org. Chem. 1999; 35: 928
• 33 Nedolya NA. Tarasova OA. Albanov AI. Trofimov BA. J. Org. Chem. 2017; 82: 7519
• 34a Brandsma L. Eur. J. Org. Chem. 2001; 4569
• 34b Brandsma L. Nedolya NA. Synthesis 2004; 735
• 35 Brandsma L. Vvedensky VYu. Nedolya NA. Tarasova OA. Trofimov BA. Tetrahedron Lett. 1998; 39: 2433
• 36a Hoff S. Brandsma L. Arens JF. Recl. Trav. Chim. Pays-Bas 1968; 87: 916
• 36b Tarasova OA. Tatarinova IV. Vakul’skaya TI. Khutsishvili SS. Prozorova GF. Mikhaleva AI. Trofimov BA. J. Organomet. Chem. 2013; 745–746: 1
• 37 Trofimov BA. Nedolya NA. Gerasimova VV. Voronkov MG. Sulfur Lett. 1988; 8: 73