Sulfinamide

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General structure of sulfinamides, showing both correct zwitterionic and "expanded octet" simplified convention Sulfinamide structure.png
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).

Contents

Structure

Structure of Davis' sulfinamide (p-tolylsulfinamide), highlighting the pyramidal nature of the S center ZIJGUW.png
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 and more broadly as 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. [4] [5] [6]

Sulfinamides arise in nature by the addition of nitroxyl (HNO) to thiols: [7]

RSH + HNO → RS(O)NH2

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<span class="mw-page-title-main">Imine</span> Organic compound or functional group containing a C=N bond

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<span class="mw-page-title-main">Sulfonium</span> Cation of the form [SR3]+

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<span class="mw-page-title-main">Sulfenic acid</span> Organosulfur compound of the form R–SOH

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<span class="mw-page-title-main">Sulfenyl chloride</span> Chemical group (R–S–Cl)

In organosulfur chemistry, a sulfenyl chloride is a functional group with the connectivity R−S−Cl, where R is alkyl or aryl. Sulfenyl chlorides are reactive compounds that behave as sources of RS+. They are used in the formation of RS−N and RS−O bonds. According to IUPAC nomenclature they are named as alkyl thiohypochlorites, i.e. esters of thiohypochlorous acid.

<span class="mw-page-title-main">Thiosulfinate</span> Functional group

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<span class="mw-page-title-main">Sulfenamide</span> Molecules of the form >N–S–

In organosulfur chemistry, sulfenamides are a class of organosulfur compounds characterized by the general formula R−S−N(−R)2, where the R groups are hydrogen, alkyl, or aryl. Sulfenamides have been used extensively in the vulcanization of rubber using sulfur. They are related to the oxidized compounds known as sulfinamides and sulfonamides.

<span class="mw-page-title-main">Sulfinyl halide</span> Class of chemical compounds

Sulfinyl halide have the general formula R−S(O)−X, where X is a halogen. They are intermediate in oxidation level between sulfenyl halides, R−S−X, and sulfonyl halides, R−SO2−X. The best known examples are sulfinyl chlorides, thermolabile, moisture-sensitive compounds, which are useful intermediates for preparation of other sufinyl derivatives such as sulfinamides, sulfinates, sulfoxides, and thiosulfinates. Unlike the sulfur atom in sulfonyl halides and sulfenyl halides, the sulfur atom in sulfinyl halides is chiral, as shown for methanesulfinyl chloride.

<i>N</i>-Sulfinyl imine

N-Sulfinyl imines are a class of imines bearing a sulfinyl group attached to nitrogen. These imines display useful stereoselectivity reactivity and due to the presence of the chiral electron withdrawing N-sulfinyl group. They allow 1,2-addition of organometallic reagents to imines. The N-sulfinyl group exerts powerful and predictable stereodirecting effects resulting in high levels of asymmetric induction. Racemization of the newly created carbon-nitrogen stereo center is prevented because anions are stabilized at nitrogen. The sulfinyl chiral auxiliary is readily removed by simple acid hydrolysis. The addition of organometallic reagents to N-sulfinyl imines is the most reliable and versatile method for the asymmetric synthesis of amine derivatives. These building blocks have been employed in the asymmetric synthesis of numerous biologically active compounds.

<span class="mw-page-title-main">Sulfonamide</span> Organosulfur compounds containing –S(=O)2–N< functional group

In organic chemistry, the sulfonamide functional group is an organosulfur group with the structure R−S(=O)2−NR2. It consists of a sulfonyl group connected to an amine group. Relatively speaking this group is unreactive. Because of the rigidity of the functional group, sulfonamides are typically crystalline; for this reason, the formation of a sulfonamide is a classic method to convert an amine into a crystalline derivative which can be identified by its melting point. Many important drugs contain the sulfonamide group.

References

  1. 1 2 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. 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{{cite journal}}: CS1 maint: multiple names: authors list (link); Collected Volumes, vol. 10, p. 47.
  5. Ruano, J. L.; Alemán, J.; Parra, A.; Cid, M. B. (2007). "PREPARATION OF N-p-TOLYLSULFONYL-(E)-1-PHENYLETHYLIDENEIMINE". Organic Syntheses . 84: 129{{cite journal}}: CS1 maint: multiple names: authors list (link).
  6. Ramachandar, T.; Wu, Y.; Zhang, J.; Franklin A. Davis (2006). "(S)-(+)-2,4,6-TRIMETHYLBENZENESULFINAMIDE". Organic Syntheses . 83: 131{{cite journal}}: CS1 maint: multiple names: authors list (link).
  7. 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.