Newman–Kwart rearrangement explained

The Newman–Kwart rearrangement is a type of rearrangement reaction in which the aryl group of an O-aryl thiocarbamate, ArOC(=S)NMe₂, migrates from the oxygen atom to the sulfur atom, forming an S-aryl thiocarbamate, ArSC(=O)NMe₂.^{[1] [2] [3]} The reaction is named after its discoverers, Melvin Spencer Newman^[4] and Harold Kwart.^[5] The reaction is a manifestation of the double bond rule. The Newman–Kwart reaction represents a useful synthetic tool for the preparation of thiophenol derivatives.

Mechanism

The Newman–Kwart rearrangement is intramolecular. It is generally believed to be a concerted process, proceeding via a four-membered cyclic transition state (rather than a two-step process passing through a discrete reactive intermediate). The enthalpy of activation for this transition state is generally quite high for typical substrates (ΔH^‡ ~ 30 to 40 kcal/mol), necessitating high reaction temperatures (200 to 300 °C, Ph₂O as solvent or neat).^[6]

A Pd-catalyzed process and conditions under photoredox catalysis^[7] (both proceeding through complex multistep mechanisms) are known. These catalytic processes allow for much milder reaction conditions to be used (100 °C for Pd catalysis, ambient temperature for photoredox).

Use for preparation of thiophenols

The Newman–Kwart rearrangement is an important prelude to the synthesis of thiophenols. A phenol (1) is deprotonated with a base followed by treatment with a thiocarbamoyl chloride (2) to form an O-aryl thiocarbamate (3). Heating 3 to around 250 °C causes it undergo Newman–Kwart rearrangement to an S-aryl thiocarbamate (4). Alkaline hydrolysis or similar cleavage yields a thiophenol (5).^{[8] [9]}

See also

• Smiles rearrangement
• Chapman rearrangement

Notes and References

1. Book: Topics in Current Chemistry . Springer Berlin / Heidelberg . 0340-1022 . 275 . 2007 . Thione–Thiol Rearrangement: Miyazaki–Newman–Kwart Rearrangement and Others . 978-3-540-68099-4 . 131–161 . C. . Zonta . O. . De Lucchi . R. . Volpicelli . L. . Cotarca . 10.1007/128_065 . 23605512 .
2. The Newman–Kwart Rearrangement of O-Aryl Thiocarbamates: Substantial Reduction in Reaction Temperatures through Palladium Catalysis . J. N. . Harvey . J. . Jover . G. C. . Lloyd-Jones . J. D. . Moseley . P. M. . Murray . J. S. . Renny . . 2009 . 48 . 41 . 7612–7615 . 10.1002/anie.200903908 . 19746383.
3. Mechanism and Application of the Newman-Kwart O→S Rearrangement of O-Aryl Thiocarbamates . G. C. . Lloyd-Jones . J. D. . Moseley . J. S. . Renny . . 2008 . 2008 . 5 . 661–689 . 10.1055/s-2008-1032179 .
4. M. S. . Newman . H. A. . Karnes . The Conversion of Phenols to Thiophenols via Dialkylthiocarbamates . . 1966 . 31 . 12 . 3980–3984 . 10.1021/jo01350a023 .
5. H. . Kwart . E. R. . Evans . The Vapor Phase Rearrangement of Thioncarbonates and Thioncarbamates . . 1966 . 31 . 2 . 410–413 . 10.1021/jo01340a015.
6. Jacobsen . Heiko . Donahue . James P. . 2011-02-05 . Expanding the scope of the Newman–Kwart rearrangement — A computational assessment . Canadian Journal of Chemistry . en . 10.1139/v06-161.
7. Perkowski . Andrew J. . Cruz . Cole L. . Nicewicz . David A. . 2015-12-23 . Ambient-Temperature Newman–Kwart Rearrangement Mediated by Organic Photoredox Catalysis . Journal of the American Chemical Society . en . 137 . 50 . 15684–15687 . 10.1021/jacs.5b11800 . 0002-7863.
8. The Molecularity of the Newman−Kwart Rearrangement . Matthew . Burns . G. C. . Lloyd-Jones . J. D. . Moseley . J. S. . Renny . . 2010 . 75 . 19 . 6347–6353 . 10.1021/jo1014382 . 20812755 .
9. Thiophenols from Phenols: 2-Naphthalenethiol. Melvin S. Newman . Frederick W. Hetzel . Org. Synth.. 1971. 51. 139. 10.15227/orgsyn.051.0139.