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N-tert-Butylbenzenesulfinimidoyl chloride is a useful oxidant for organic synthesis reactions.^[1] It is a good electrophile, and the sulfimide S=N bond can be attacked by nucleophiles, such as alkoxides, enolates, and amide ions. The nitrogen atom in the resulting intermediate is basic, and can abstract an α-hydrogen to create a new double bond.

Preparation

This reagent can be synthesized quickly and in near-quantitative yield by reacting phenyl thioacetate with tert-butyldichloroamine in hot benzene. After the reaction is complete, the product can be isolated as a yellow, moisture-sensitive solid by vacuum distillation.^[2]

Mechanism

The first two steps in an oxidation reaction involving N-tert-butylbenzenesulfinimidoyl chloride are similar to a nucleophilic acyl substitution reaction. A nucleophile, such as an alkoxide (1), attacks the S=N bond in 2. The resulting intermediate (3) collapses and ejects chloride ion, which is a good leaving group. The resulting sulfimide has two resonance forms - 4a and 4b. Because of this, the nitrogen is basic, and via a five-membered ring transition state, it can abstract the hydrogen adjacent to the oxygen. This forms a new C=O bond and ejects a neutral sulfenamide (5), giving ketone 6 as the product. N-tert-Butylbenzenesulfinimidoyl chloride reacts with enolates, amides, and primary alkoxides by the same general mechanism.

The Swern oxidation, which converts primary and secondary alcohols to aldehydes and ketones, respectively, also uses a sulfur-containing compound (DMSO) as the oxidant and proceeds by a similar mechanism. In the Swern oxidation, elimination also occurs via a five-membered ring transition state, but the basic species is a sulfur ylide instead of a negatively charged nitrogen. Several other oxidation reactions also make use of DMSO as the oxidant and pass through a similar transition state (see #See also).

Reactions

Reacting an aldehyde with a Grignard reagent or organolithium and treating the resulting secondary alkoxide with N-tert-butylbenzenesulfinimidoyl chloride is a convenient one-pot reaction for converting aldehydes to ketones. While Grignards can be used for this reaction, organolithium compounds give higher yields, due to the higher reactivity of a lithium alkoxide compared to the corresponding magnesium salt. In some cases, an equivalent of DMPU, a Lewis base, will increase yields. For example, treating benzaldehyde with n-butyllithium and N-tert-butylbenzenesulfinimidoyl chloride in THF gives 1-phenyl-1-pentanone in good yield.^[3]

N-tert-Butylbenzenesulfinimidoyl chloride can also be used to synthesize imines from amines. Imines synthesized in this fashion have been shown to undergo a one-pot Mannich reaction with 1,3-dicarbonyl compounds, such as malonate esters and 1,3-diketones. In this example, Cbz-protected benzylamine is deprotonated using n-butyllithium, then treated with N-tert-butylbenzenesulfinimidoyl chloride to form the protected imine. Dimethyl malonate acts as the nucleophile and reacts with the imine to give the final product, a Mannich base.^[4]

References

^ ^a ^b ^c Matsuo, J.; Mukaiyama, T. (2001). "N-tert-Butylbenzenesulfinimidoyl Chloride". e-EROS Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X. hdl:10261/236866. ISBN 9780470842898. Retrieved 30 June 2012.
^ Barrett, A. G. M.; Gray, A. A.; Hill, M. S.; Hitchcock, P. B.; Procopiou, P. A.; White, A. J. P. (2006). "Imino Sulfinamidines: Synthesis and Coordination Chemistry of a Novel Class of Chiral Bidentate Ligands". Inorganic Chemistry. 45 (8): 3352–3358. doi:10.1021/ic052104m. PMID 16602794.
^ Crawford, J. J.; Henderson, K. W.; Kerr, W. J. (2006). "Direct and Efficient One-Pot Preparation of Ketones from Aldehydes Using N-tert-Butylphenylsulfinimidoyl Chloride". Organic Letters. 8 (22): 5073–5076. doi:10.1021/ol061903l. PMID 17048846.
^ Matsuo, J.; Tanaki, Y.; Ishibashi, H. (2006). "Oxidative Mannich Reaction of N-Carbobenzyloxy Amines with 1,3-Dicarbonyl Compounds". Organic Letters. 8 (19): 4371–4374. doi:10.1021/ol0618095. PMID 16956229.

External links

N-tert-butylbenzenesulfinimidoyl chloride on Organic Chemistry Portal

[eeros-1] Matsuo, J.; Mukaiyama, T. (2001). "N-tert-Butylbenzenesulfinimidoyl Chloride". e-EROS Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X. hdl:10261/236866. ISBN 9780470842898. Retrieved 30 June 2012.

[2] Barrett, A. G. M.; Gray, A. A.; Hill, M. S.; Hitchcock, P. B.; Procopiou, P. A.; White, A. J. P. (2006). "Imino Sulfinamidines: Synthesis and Coordination Chemistry of a Novel Class of Chiral Bidentate Ligands". Inorganic Chemistry. 45 (8): 3352–3358. doi:10.1021/ic052104m. PMID 16602794.

[3] Crawford, J. J.; Henderson, K. W.; Kerr, W. J. (2006). "Direct and Efficient One-Pot Preparation of Ketones from Aldehydes Using N-tert-Butylphenylsulfinimidoyl Chloride". Organic Letters. 8 (22): 5073–5076. doi:10.1021/ol061903l. PMID 17048846.

[4] Matsuo, J.; Tanaki, Y.; Ishibashi, H. (2006). "Oxidative Mannich Reaction of N-Carbobenzyloxy Amines with 1,3-Dicarbonyl Compounds". Organic Letters. 8 (19): 4371–4374. doi:10.1021/ol0618095. PMID 16956229.

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