Sulfinamide

Not to be confused with sulfonamide, sulfamide, or sulfinylamine.

General structure of sulfinamides, showing both correct zwitterionic and "expanded octet" simplified convention

In organosulfur chemistry, sulfinamide is a functional group with the structure R−S(O)−NR₂ (where R = alkyl or aryl). ^[1] This functionality is composed of a sulfur-carbon (S−C) single bond, a sulfur-nitrogen (S−N) single bond, and a sulfur-oxygen (S-O) bond (see Sulfoxide for the nature of this bond). ^[2] As a non-bonding electron pair is present on the sulfur, the sulfur atom is a stable stereogenic centre, and so these compounds are chiral. They are sometimes referred to as S-chiral sulfinamides. Sulfinamides are amides of sulfinic acid (R−S(O)OH).

Structure

Structure of Davis' sulfinamide (p-tolylsulfinamide), highlighting the pyramidal nature of the S center

Sulfinamides do not undergo inversion. They can therefore be synthesised and/or isolated in enantiopure forms. This has led to their use as chiral ammonia equivalents. Chiral sulfinamides such as tert-butanesulfinamide, p-toluenesulfinamide ^{[4] [5]} and 2,4,6-trimethylbenzenesulfinamide ^[6] are all chiral auxiliaries.

Synthesis

Sulfinamides are traditionally produced by the reaction of sulfinyl chlorides with primary or secondary amines. ^[1] They also arise by the addition of Grignard reagents to sulfinylamines, followed by protonation:

RMgX + R'N=S=O → RS(O)(NR'MgX)

RS(O)(NR'MgX) + H₂O → RS(O)(NR'H) + "MgX(OH)"

Yet another route entails peracid-oxidation of sulfenylphthalimides, which gives sulfinylphthalimides.

Examples

A common sulfinamide is tert-butanesulfinamide (Ellman's sulfinamide), p-toluenesulfinamide (Davis' sulfinamide), and mesityl sulfinamide. ^{[7] [8] [9]}

Sulfinamides arise in nature by the addition of nitroxyl (HNO) to thiols: ^[10]

RSH + HNO → RS(O)NH₂

References

1. J. G. Tillett (1981). "Sulphinamides". In Saul Patai (ed.). Sulphinic Acids, Esters and Derivatives. PATAI'S Chemistry of Functional Groups. John Wiley & Sons. pp. 185–215. doi:10.1002/9780470772270.ch7. ISBN   978-0-471-91918-6.
2. Brecher, Jonathan (2008-01-01). "Graphical representation standards for chemical structure diagrams (IUPAC Recommendations 2008)". Pure and Applied Chemistry. 80 (2): 277–410. doi:10.1351/pac200880020277. ISSN   1365-3075.
3. Eccles, K. S.; Morrison, R. E.; Daly, C. A.; O'Mahony, G. E.; Maguire, A. R.; Lawrence, S. E. (2013). "Co-crystallisation Through Halogen Bonding with Racemic or Enantiopure Sulfinamides". CrystEngComm. 15 (37): 7571–7575. doi:10.1039/C3CE40932E.
4. Dean L. Fanelli, Joanna M. Szewczyk, Yulian Zhang, G. Venkat Reddy, David M. Burns, Franklin A. Davis (2000). "Sulfimines (Thiooximine S-Oxides): Asymmetric Synthesis of Methyl (R)-(+)-β-Phenylalanate from (S)-(+)-N-(Benzylidine)-p-Toluenesulfimade". Organic Syntheses. 77: 50. doi:10.15227/orgsyn.077.0050.
5. José Luis García Ruano, José Alemán, Alejandro Parra, M. Belén Cid (2007). "Preparation of N-p-Tolylsulfonyl-(E)-1-Phenylethyleideneimine". Organic Syntheses. 84: 129. doi:10.15227/orgsyn.084.0129.
6. "(S)-(+)-2,4,6-Trimethylbenzenesulfinamide". Organic Syntheses. 83: 131. 2006. doi:10.15227/orgsyn.083.0131.
7. Fanelli, D. L.; Szewczyk, J. M.; Zhang, Y.; Reddy, G. V.; Burns, D. M.; Davis, F. A. (2000). "SULFINIMINES (THIOOXIMINE S-OXIDES): ASYMMETRIC SYNTHESIS OF METHYL (R)-(+)-β-PHENYLALANATE FROM (S)-(+)-N-(BENZYLIDENE)-p-TOLUENESULFINAMIDE". Organic Syntheses . 77: 50; Collected Volumes, vol. 10, p. 47.
8. Ruano, J. L.; Alemán, J.; Parra, A.; Cid, M. B. (2007). "PREPARATION OF N-p-TOLYLSULFONYL-(E)-1-PHENYLETHYLIDENEIMINE". Organic Syntheses . 84: 129.
9. Ramachandar, T.; Wu, Y.; Zhang, J.; Franklin A. Davis (2006). "(S)-(+)-2,4,6-TRIMETHYLBENZENESULFINAMIDE". Organic Syntheses . 83: 131.
10. Keceli, Gizem; Toscano, John P. (2014-06-10). "Reactivity of C-Terminal Cysteines with HNO" . Biochemistry. 53 (22): 3689–3698. doi:10.1021/bi500360x. ISSN   0006-2960. PMID   24869490.