Halohydrin

General structure of a halohydrin, where X = I, Br, F, or Cl

Structure of the halohydrin 2-chloroethanol

In organic chemistry a halohydrin (also a haloalcohol or β-halo alcohol) is a functional group in which a halogen and a hydroxyl are bonded to adjacent carbon atoms, which otherwise bear only hydrogen or hydrocarbyl groups (e.g. 2-chloroethanol, 3-chloropropane-1,2-diol).^[1] The term only applies to saturated motifs, as such compounds like 2-chlorophenol would not normally be considered halohydrins.

Halohydrins may be categorized as chlorohydrins, bromohydrins, flurohydrins or iodohydrins depending on the halogen present.

Synthesis

Halohydrins are usually prepared by treatment of an alkene with a halogen (often bromine), in the presence of water.^[2] The reaction is a form of electrophilic addition, similar to the halogen addition reaction and proceeds with anti addition, leaving the newly added X and OH groups in a trans configuration. The basic chemical equation for this reaction is as follows:

C=C + X₂ + H₂O → X-C-C-OH (X represents a halogen, either Cl or Br).

When bromination is desired, N-bromosuccinimide (NBS) is preferable to bromine because fewer side-products are produced.

Halohydrins may also be prepared from the reaction of an epoxide with a hydrohalic acid, or a metal halide.^[3]

Reactions

In presence of a base, such as potassium hydroxide, a halohydrin may undergo internal S_N2 reaction to form an epoxide. This is the reverse of the formation reaction from an epoxide and can be considered a variant of the Williamson ether synthesis. Most of the world's supply of propylene oxide arises via this route.^[4]

Such reactions can form the basis of more complicated processes, for example epoxide formation is one of the key steps in the Darzens reaction.

Of halogenated halohydrins

2,2,2-trichloroethanol

Compounds such as 2,2,2-trichloroethanol, which contain several geminal halogens adjacent to a hydroxyl group may be considered halohydrins (although, strictly speaking, they fail the IUPAC definition) as they possess similar chemistry. In particular they also undergo intramolecular cyclisation to form dihaloepoxy groups. These species are both highly reactive and synthetically useful, forming the basis of the Jocic-Reeve, Bargellini and Corey–Link reactions.^[5]

Safety

As with any functional group, the hazards of halohydrins are difficult to generalize as they may form part of an almost limitless series of compounds, with each structure having different pharmacology. In general, simpler low molecular weight compounds are often toxic and carcinogenic (e.g. 2-chloroethanol, 3-MCPD) by virtue of being alkylating agents. This reactivity can be put to good use, for instance in the anti-cancer drug mitobronitol. A number of synthetic corticosteroids exist baring a fluorohydrin motif (Triamcinolone, Dexamethasone, Triamcinolone).

Misnomers

Despite their rather suggestive names epichlorohydrin and sulfuric chlorohydrin are not halohydrins.

See Also

• Cyanohydrin

References

1. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "halohydrins".
2. William Reusch. "Addition Reactions of Alkenes". Virtual Textbook of Organic Chemistry. External link in |work= (help)
3. Bonini, Carlo; Righi, Giuliana (1994). "Regio- and Chemoselective Synthesis of Halohydrins by Cleavage of Oxiranes with Metal Halides". Synthesis 1994 (03): 225–238. doi:10.1055/s-1994-25445.
4. Dietmar Kahlich, Uwe Wiechern, Jörg Lindner “Propylene Oxide” in Ullmann's Encyclopedia of Industrial Chemistry, 2002 by Wiley-VCH, Weinheim. doi:10.1002/14356007.a22_239 Article Online Posting Date: June 15, 2000
5. Snowden, T.S. (28 February 2012). "Recent applications of gem-dichloroepoxide intermediates in synthesis". Arkivoc 2012 (2): 24–40. doi:10.3998/ark.5550190.0013.204.