· t-Butyl Hypochlorite
· (MW 108.57)
(reagent for ionic2 or radical3 chlorination of hydrocarbons; N-chlorination;4 oxidation of alcohols,5 sulfides,6 and selenides7)
Physical Data: bp 79.6 °C/750 mmHg; d 0.9583 g cm-3.
Solubility: sparingly sol H2O; sol alcohol, CCl4, and CHCl3.
Form Supplied in: commercially available as neat liquid.
Preparative Method: usually prepared by the method of Mintz and Walling.8
Purification: distillation is possible but can be hazardous, and is reported not to improve purity.
Handling, Storage, and Precautions: avoid exposure of the reagent to light; store protected from light in a refrigerator or freezer.
Under typical radical conditions, t-BuOCl can effect chlorination of a range of substrates, including alkanes, alkenes, ethers, epoxides, and aldehydes.3 Reaction occurs by hydrogen abstraction from the substrate by the t-BuO&bdot; radical, this process showing the expected selectivity pattern of primary < secondary < tertiary (eq 1).3a,c The reaction can be initiated by irradiation or by the use of chemical initiators such as Azobisisobutyronitrile3a or trialkylboranes.3c Reaction with alkenes results in allylic chlorination,3d,e whereas ethers3b and epoxides3f give products arising from attack at the position a to oxygen (eqs 2 and 3) and aldehydes give the corresponding acid
chlorides (eq 4).3b
Ionic Reactions with Alkenes and Arenes.
Allylic chlorination with double bond rearrangement can also be effected by t-BuOCl under nonradical conditions in nonprotic solvents.2 This process appears facile with particularly electron-rich alkenes, or if a catalyst such as Boron Trifluoride Etherate is employed (eq 5). If an alcohol is used as the solvent then b-chloro ethers are obtained via electrophilic addition (eq 6).9
Chlorination of aromatics can also be effected by use of the t-BuOCl-BF3.OEt2 reagent combination,9 or by the use of t-BuOCl in the presence of silica10 or certain zeolites (eq 7).11 Activated aromatics react with t-BuOCl alone, whereas deactivated systems do not react, even in the presence of catalysts under forcing conditions. The modified o/p selectivity in the presence of zeolite is notable. Chlorination of other types of systems, such as aminoquinones12 and indoles,13 has also been reported (eqs 8 and 9).
Chlorination at Nitrogen.
Chlorination of a wide range of nitrogen-containing systems to give chloroamines and related compounds, or products derived thereof, is an important use for t-BuOCl.4 Examples include the hydroxylation of penicillins (eq 10)4a-c and a method for the asymmetric synthesis of amines via amino ester intermediates (eq 11).4d Both methods involve N-chlorination followed by dehydrochlorination and nucleophilic addition by the solvent.
The oxidation of secondary alcohols, using t-BuOCl in the presence of Pyridine, gives high yields of the corresponding ketones (eq 12),5 whereas in the absence of pyridine both the ketone and a-chloro ketone are usually formed (eq 13),3b the latter products probably arising from the initially formed ketones via chlorination by chlorine generated in situ.
The oxidation of sulfoxides using t-BuOCl is very well established and can be used to prepare either cis- or trans-substituted thiane oxide products (eqs 14 and 15). Oxidation of selenides and tellurides is also possible in an analogous fashion, to give selenoxides and telluroxides (or their hydrates), respectively.7
Other types of reaction involving t-BuOCl which have been reported include cyclization of unsaturated peroxides to give chloroalkyl 1,2-dioxolanes (eq 16),14 a ring expansion reaction of isopropenylcycloalkenols (eq 17),15 and a dehydrogenation protocol for the synthesis of tetraethynylethylenes (eq 18).16
- 1. (a) Anbar, M.; Ginsburg, D. CRV 1954, 54, 925. (b) Hausweiler, A. MOC 1963, 6/2, 487.
- 2. (a) Meijer, E. W.; Kellogg, R. M.; Wynberg, H. JOC 1982, 47, 2005. (b) Ravindranath, B.; Srinivas, P. IJC(B) 1985, 24, 163.
- 3. (a) Walling, C.; Jacknow, B. B. JACS 1960, 82, 6108. (b) Walling, C.; Mintz, M. J. JACS 1967, 89, 1515. (c) Hoshi, M.; Masuda, Y.; Arase, A. CL 1984, 195. (d) Walling, C.; Thaler, W. JACS 1961, 83, 3877. (e) Beckwith, A. L. J.; Westwood, S. W. AJC 1983, 36, 2123. (f) Walling, C.; Fredericks, P. S. JACS 1962, 84, 3326.
- 4. (a) Firestone, R. A.; Christensen, B. G. JOC 1973, 38, 1436. (b) Baldwin, J. E.; Urban, F. J.; Cooper, R. D. G.; Jose, F. L. JACS 1973, 95, 2401. (c) Koppel, G. A.; Koehler, R. E. JACS 1973, 95, 2403. (d) Yamada, S.; Ikota, N.; Achiwa, K. TL 1976, 1001. (e) Awad, R.; Hussain, A.; Crooks, P. A. JCS(P2) 1990, 1233. (f) Zey, R. L. JHC 1988, 25, 847.
- 5. Milovanovic, J. N.; Vasojevic, M.; Gojkovic, S. JCS(P2) 1988, 533.
- 6. (a) Jalsovszky, I.; Ruff, F.; Kajtar-Peredy, M.; Kucsman, A. S 1990, 1037. (b) Johnson, C. R.; McCants Jr., D. JACS 1965, 87, 1109. (c) Rigau, J. J.; Bacon, C. C.; Johnson, C. R.; JOC 1970, 35, 3655.
- 7. (a) Kobayashi, M.; Ohkubo, H.; Shimizu, T. BCJ 1986, 59, 503. (b) Detty, M. R. JOC 1980, 45, 274.
- 8. Mintz, M. J.; Walling, C. OSC 1973, 5, 183.
- 9. Walling, C.; Clark, R. T. JOC 1974, 39, 1962.
- 10. Smith, K.; Butters, M.; Paget, W. E.; Nay, B. S 1985, 1155.
- 11. Smith, K.; Butters, M.; Nay, B. S 1985, 1157.
- 12. Moore, H. W.; Cajipe, G. S 1973, 49.
- 13. Büchi, G.; Manning, R. E. JACS 1966, 88, 2532.
- 14. Bloodworth, A. J.; Tallant, N. A. TL 1990, 31, 7077.
- 15. Johnson, C. R.; Herr, R. W. JOC 1973, 38, 3153.
- 16. Hauptmann, H. AG(E) 1975, 14, 498.
Nigel S. Simpkins
University of Nottingham, UK
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