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Review
. 2021 Oct 1;11(51):32394-32407.
doi: 10.1039/d1ra04368d. eCollection 2021 Sep 27.

Direct synthesis of sulfenamides, sulfinamides, and sulfonamides from thiols and amines

Yan Cao  1 , Shahrzad Abdolmohammadi  2 , Roya Ahmadi  3 , Alibek Issakhov  4   5 , Abdol Ghaffar Ebadi  6 , Esmail Vessally  7
Affiliations
Review

Direct synthesis of sulfenamides, sulfinamides, and sulfonamides from thiols and amines

Yan Cao et al. RSC Adv. .

Abstract

Needless to say that organosulfur compounds with sulfur-nitrogen bonds have found various applications in diverse fields such as pharmaceuticals, agrochemicals, polymers, and so forth. Three major groups of such compounds are sulfenamides, sulfinamides, and sulfonamides which have been widely applied as building blocks in medical chemistry. Owing to their significant role in drug design and discovery programs, the search for and development of efficient, environmentally friendly, and economic processes for the preparation of the title compounds is of great importance in the pharmaceutical industry. Recently, oxidative coupling of thiols and amines, two readily available low-cost commodity chemicals, has emerged as a highly useful method for synthesizing structurally diverse sulfenamides, sulfinamides, and sulfonamides in a single step. Since this strategy does not require additional pre-functionalization and de-functionalization steps, it considerably streamlines synthetic routes and substantially reduces waste generation. This review will focus on recent advances and achievements in this attractive research arena.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. General structure of sulfenamides (I), sulfinamides (II), sulfonamides (III), and some related compounds.
Fig. 2
Fig. 2. Direct synthesis of sulfenamides, sulfinamides, and sulfonamides from thiols and amines.
Scheme 1
Scheme 1. Taniguchi's synthesis of sulfenamides 3.
Scheme 2
Scheme 2. Plausible mechanism of Cu-catalyzed cross-coupling of thiols 1 and amines 2.
Scheme 3
Scheme 3. DIB-promoted S–N coupling of N-heterocyclic thiols 4 with amines 5.
Scheme 4
Scheme 4. Proposed reaction mechanism for the formation of S-heteroaryl sulfenamides 6.
Scheme 5
Scheme 5. (a) TEMPO-catalyzed oxidative coupling of 2-mercaptobenzothiazole 7 with alkylamines 8; (b) synthesis of 2-benzothiazolesulfenamide derivatives 11via co-catalyzed reaction of 2-mercaptobenzothiazole 7 with amines 10.
Scheme 6
Scheme 6. (a) I2-catalyzed cross-dehydrogenative coupling of thiophenol 12 with anilines 13; (b) putative mechanism for the formation of N,S-diaryl sulfenamides 14.
Scheme 7
Scheme 7. Zhang–Qian's synthesis of sulfenamides 17.
Scheme 8
Scheme 8. Electrochemical oxidant- and catalyst-free synthesis of S-heteroaryl sulfenamides 20 through dehydrogenative S–H/N–H coupling of heteroaryl thiols 18 with alkyl amines 19.
Scheme 9
Scheme 9. A plausible mechanism for the reaction in Scheme 8.
Scheme 10
Scheme 10. Synthesis of sulfinamides 23 from aryl thiols 21 and tert-butylamine 22 catalyzed by PdCl2–CuI binary catalyst.
Scheme 11
Scheme 11. Cu-catalyzed synthesis of aryl sulfinamides 26 from aryl thiols 24 and amines 25 in the presence of air.
Scheme 12
Scheme 12. Morandi's synthesis of unprotected sulfinamides 28.
Scheme 13
Scheme 13. Proposed mechanism for Fe-catalyzed amino-oxidation of thiols 27.
Scheme 14
Scheme 14. I2-mediated synthesis of N-unsubstituted sulfonamides 30 from thiols 29 and ammonia.
Scheme 15
Scheme 15. Mechanism of reaction between thiols 29 and ammonia in the presence of I2 and tBuOOH.
Scheme 16
Scheme 16. Direct synthesis of sulfonamides 33 from thiols 31 and amines 32 through the action of I2O5.
Scheme 17
Scheme 17. Proposed mechanism of I2O5-mediated sulfonylation of amines 32 with arylthiols 31.
Scheme 18
Scheme 18. Luisi–Bull's synthesis of primary sulfonamides 35.
Scheme 19
Scheme 19. Electrochemical oxidative coupling of thiols 36 and amines 37 in flow cells.
Scheme 20
Scheme 20. Proposed mechanism for the electrosynthesis of sulfonamides 38.
Scheme 21
Scheme 21. β-MnO2-catalyzed oxidative sulfonamidation of (hetero)aromatic thiols 39 with ammonia.
Scheme 22
Scheme 22. Plausible mechanistic pathway for the reaction in Scheme 21.
None
Shahrzad Abdolmohammadi
None
Roya Ahmadi
None
Abdolghaffar Ebadi
None
Esmail Vessally
See this image and copyright information in PMC

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