Efficient Synthesis of (Z)-4-((Substituted phenylamino)methyl­idene)isoquinoline-1,3(2H,4H)-diones Using the Eschenmoser Coupling Reaction

Abstract

A novel synthetic strategy involving the Eschenmoser coupling reaction of 4-bromoisoquinoline-1,3(2H,4H)-diones with substituted thioformanilides, thioacetanilides, and thiobenzanilides gave 18 (Z)-4-((substituted phenylamino)methylidene)isoquinoline-1,3(2H,4H)-diones. The reaction occurs under mild conditions (DMF or MeCN, 25–60 °C) without any base or thiophile and in good yields (43–95%). Furthermore, for the synthesis of starting thioformanilides carrying basic substituents, a new thioacylation protocol was developed that involves a thioacylating agent formed from carbon disulfide and lithium triethylborohydride.

Key words

Eschenmoser coupling reaction - 4-bromoisoquinoline-1,3(2H,4H)-diones - thioamides - thioacylation - bromination

Publication History

Received: 21 September 2023

Accepted after revision: 25 October 2023

Accepted Manuscript online:
25 October 2023

Article published online:
29 November 2023

• References

• 1 Mayer SC, Banker AL, Boschelli F, Di L, Johnson M, Hess Kenny C, Krishnamurthy G, Kutterer K, Moy F, Petusky S, Ravi M, Tkach D, Tsou H.-R, Xu W. Bioorg. Med. Chem. Lett. 2008; 18: 3641
• 2a Tsou H.-R, Otteng M, Tran T, Floyd MB. Jr, Reich M, Birnberg G, Kutterer K, Ayral-Kaloustian S, Ravi M, Nilakantan R, Grillo M, McGinnis JP, Rabindran SK. J. Med. Chem. 2008; 51: 3507
• 2b Tsou H.-R, Liu X, Birnberg G, Kaplan J, Otteng M, Tran T, Kutterer K, Tang Z, Suayan R, Zask A, Ravi M, Bretz A, Grillo M, McGinnis JP, Rabindran SK, Ayral-Kaloustian S, Mansour TS. J. Med. Chem. 2009; 52: 2289
• 2c Tsou H.-R, Ayral-Kaloustian S, Birnberg GH, Floyd MB, Kaplan J, Kutterer KM. K, Liu X, Nilakantan R, Otteng MA, Tang Z, Zask A, Reich M, Tran T. WO Patent 2007075783A3, 2007
• 3 Wolfbeis OS, Trummer I, Knierzinger A. Liebigs Ann. Chem. 1981; 811
• 4 Higashiyama K, Toyama M, Otomasu H. Chem. Pharm. Bull. 1986; 34: 3015
• 5 Marek L, Váňa J, Svoboda J, Hanusek J. J. Org. Chem. 2021; 86: 10621
• 6a Senaweera S, He T, Cui H, Aihara H, Wang Z. Med. Chem. Res. 2021; 30: 371
• 6b Quiclet-Sire B, Zard SZ. Chem. Commun. 2002; 2306
• 7a Sanchez S, Bateson JH, O’Hanlon PJ, Gallagher T. Org. Lett. 2004; 6: 2781
• 7b Stowell JC, Ham BM, Esslinger MA, Duplantier AJ. J. Org. Chem. 1989; 54: 1212
• 7c Borths CJ, Chan J, Burke BJ, Larsen RD. Synlett 2009; 3139
• 7d Todd AR, Bergel F, Karimullah, Keller R. J. Chem. Soc. 1937; 361
• 8 Bergman J, Pettersson B, Hasimbegovic V, Svensson PH. J. Org. Chem. 2011; 76: 1546
• 9 Marek L, Kolman L, Váňa J, Svoboda J, Hanusek J. Beilstein J. Org. Chem. 2021; 17: 527
• 10 Marek L, Váňa J, Svoboda J, Hanusek J. Beilstein J. Org. Chem. 2023; 19: 808
• 11 Corsaro A, Perrini G, Testa MG, Chiacchio U. Phosphorus, Sulfur Silicon Relat. Elem. 1992; 71: 197
• 12a Pal A, Koduri ND, Wang Z, Lopez Quiroz E, Chong A, Vuong M, Rajagopal N, Nguyen M, Roberts KP, Hussaini SR. Tetrahedron Lett. 2017; 58: 586
• 12b Pal A, Hussaini SR. ACS Omega 2019; 4: 269
• 12c Secka J, Pal A, Acquah FA, Mooers BH. M, Karki AB, Mahjoub D, Fakhr MK, Wallace DR, Okada T, Toyooka N, Kuta A, Koduri N, Herndon D, Roberts KP, Wang Z, Hileman B, Rajagopal N, Hussaini SR. RSC Adv. 2022; 12: 19431
• 13a Sarges R, Howard HR, Koe BK, Weissman A. J. Med. Chem. 1989; 32: 437
• 13b Bouchikhi F, Rossignol E, Sancelme M, Aboab B, Anizon F, Fabbro D, Prudhomme M, Moreau P. Eur. J. Med. Chem. 2008; 43: 2316
• 13c Roth GJ, Heckel A, Colbatzky F, Handschuh S, Kley J, Lehmann-Lintz T, Lotz R, Tontsch-Grunt U, Walter R, Hilberg F. J. Med. Chem. 2009; 52: 4466
• 14 Cantagrel G, de Carné-Carnavalet B, Meyer C, Cossy J. Org. Lett. 2009; 11: 4262