[21306-21-8]  · C6Cl6O  · 2,3,4,5,6,6-Hexachloro-2,4-cyclohexadien-1-one  · (MW 300.76)

(regioselective chlorination of ketones2 and phenols;3 a-chlorination of a,b-unsaturated ketones3)

Physical Data: mp 50-51 °C.

Solubility: sol dichloromethane, methanol, ethanol, DMF.

Form Supplied in: crystalline material; commercially available.

Preparative Method: chlorination of the sodium salt of pentachlorophenol at 0 °C (eq 1).2,4,5

Analysis of Reagent Purity: mp, 13C NMR.6

Handling, Storage, and Precautions: keep in a dark vessel, well protected from light to prevent isomerization (see below). The reagent should always be handled in a well-ventilated fume hood.

Regioselective ortho-Chlorination of Phenols and Naphthols.

The chlorination of phenol with 1 equiv of 2,3,4,5,6,6-hexachloro-2,4-cyclohexadien-1-one (1) in CCl4 under irradiation of a 100 W mercury lamp gave rise to 2-chlorophenol and 4-chlorophenol in a 92:8 ratio (eq 2).5 Similar selectivity was obtained for 4-methylphenol, which by direct chlorination with chlorine leads to mono-, di-, and trichloro derivatives, in addition to some oxidation products. Irradiation may not be necessary, as similar results are obtained on chlorination of phenols with this reagent in dichloromethane (sometimes in the presence of 25% DMF) at rt.3,7

The ability of this reagent to effect regioselective ortho-chlorination of phenols has been ascribed to charge transfer interactions and hydrogen bonding with the substrate (eq 3). The reagent can differentiate between phenols and phenolic ethers (eq 4).7 It should be stressed that the isomeric reagent 2,3,4,4,5,6-hexachlorocyclohexa-2,5-dien-1-one gives p-chlorination of phenols by similar complexation.3,7 Naphthols are chlorinated by 2,3,4,5,6,6-hexachloro-2,4-cyclohexadien-1-one to give o-chloronaphthols with even better selectivity than for phenols (eq 5).8 Regioselective ortho-chlorination of naphthols substituted with alkoxy groups is cleanly achieved (eqs 6 and 7).3,8 Again the isomeric 2,3,4,4,5,6-hexachloro derivative affords p-chlorinated naphthols preferentially.8

Selective a-Chlorination of Alkyl Aryl Ketones.

Enol derivatives of ketones can participate in donor-acceptor interactions with 2,3,4,5,6,6-hexachloro-2,4-cyclohexadien-1-one. The presence of an electron-rich aromatic ring is a necessary prerequisite for complex formation and the resulting a-chlorination. Aliphatic ketones do not form sufficiently stable complexes with the chlorinating reagent, and thus are not chlorinated.2 However, alkyl aryl ketones react smoothly with the reagent in ethanol at reflux to give high yields of 1-chloroalkyl aryl ketones (eqs 8-11).2,3 Chlorination of the aromatic nucleus is not observed in reactions of p-hydroxy aromatic ketones (eqs 9 and 10).

In DMF, however, selective chlorination of the aromatic system again takes precedence (eq 12).9

a,b-Unsaturated ketones are monochlorinated by this reagent at the a-position (eq 13).2,3


Care should be taken to avoid isomerization of 2,3,4,5,6,6-hexachloro-2,4-cyclohexadien-1-one to 2,3,4,4,5,6-hexachloro-2,5-cyclohexadien-1-one, because the regiochemical course of chlorinations with this reagent is different.3,5,7 The former reagent rearranges to the latter by treatment with acid or Aluminum Chloride, by heating, or upon irradiation.5

1. Lemaire, M.; Guy, A.; Hoa, H. A.; Guetté, J.-P. Janssen Chim. Acta 1987, 5, 3.
2. Guy, A.; Lemaire, M.; Guetté, J.-P. S 1982, 1018.
3. Lemaire, M.; Guy, A.; Guetté, J.-P. BSF 1985, 477.
4. Denivelle, L.; Fort, R. BSF 1956, 1834.
5. Guy, A.; Lemaire, M.; Guetté, J.-P. CC 1980, 8.
6. Hawkes, G. E.; Smith, R. A.; Roberts, J. D. JOC 1974, 39, 1276.
7. Guy, A.; Lemaire, M.; Guetté, J.-P. T 1982, 38, 2339.
8. Guy, A.; Lemaire, M.; Guetté, J.-P. T 1982, 38, 2347.
9. Lemaire, M.; Guy, A.; Guetté, J.-P. CR(2) 1984, 299, 693.

Norbert De Kimpe

University of Gent, Belgium

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.