Halohydrin

In organic chemistry ahalohydrin(also ahaloalcoholorβ-halo alcohol) is afunctional groupin which ahalogenand ahydroxylare bonded to adjacentcarbonatoms, which otherwise bear only hydrogen orhydrocarbylgroups (e.g.2-chloroethanol,3-chloropropane-1,2-diol).The term only applies to saturated motifs, as such compounds like2-chlorophenolwould not normally be considered halohydrins. Megatons of some chlorohydrins, e.g.propylene chlorohydrin,are produced annually as precursors to polymers.

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

Structure of the halohydrin2-chloroethanol

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

Synthesis

From alkenes

Halohydrins are usually prepared by treatment of analkenewith a halogen, in the presence of water. The reaction is a form ofelectrophilic addition,with the halogen acting as electrophile.In that regard, it resembles thehalogen addition reactionand proceeds withanti addition,leaving the newly added X and OH groups in atrans configuration.The chemical equation for the conversion of ethylene to ethylene chlorohydrin is:

H₂C=CH₂+ Cl₂+ H₂O → H₂(OH)C-CH₂Cl + HCl

When bromination is desired,N-bromosuccinimide(NBS) can be preferable tobrominebecause fewer side-products are produced.

Bromohydrin formation

From epoxides

Halohydrins may also be prepared from the reaction of anepoxidewith ahydrohalic acid,or a metal halide.

This reaction is produced on an industrial scale for the production of chlorohydrin precursors to two important epoxides,epichlorohydrinandpropylene oxide.At one time,2-chloroethanolwas produced on a large scale as a precursor toethylene oxide,but the latter is now prepared by the direct oxidation of ethylene.

From 2-chloro acids

2-Chlorocarboxylic acids can be reduced withlithium aluminium hydrideto the 2-chloroalcohols. The required 2-chlorocarboxylic acids are obtained in a variety of ways, including theHell–Volhard–Zelinsky halogenation.2-Chloropropionic acidis produced by chlorination ofpropionyl chloridefollowed by hydrolysis of the 2-chloropropionyl chloride.Enantiomericallypure (S)-2-chloropropionic acid and several related compounds can be prepared from amino acids viadiazotization.

Reactions

In presence of a base halohydrins undergo internalS_N2 reactionto formepoxides.Industrially, the base iscalcium hydroxide,whereas in the laboratory, potassium hydroxide is often used.

This reaction is the reverse of the formation reaction from anepoxideand can be considered a variant of theWilliamson ether synthesis.Most of the world's supply ofpropylene oxidearises via this route.

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

Halogenated halohydrin

2,2,2-trichloroethanol

Compounds such as2,2,2-trichloroethanol,which contain multiplegeminalhalogens adjacent to a hydroxyl group may be considered halohydrins (although, strictly speaking, they fail theIUPACdefinition) 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 theJocic–Reeve reaction,Bargellini reactionandCorey–Link reaction.

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 beingalkylating agents.This reactivity can be put to good use, for instance in the anti-cancer drugmitobronitol.A number of syntheticcorticosteroidsexist bearing a fluorohydrin motif (triamcinolone,dexamethasone).

Misnomers

Despite their rather suggestive namesepichlorohydrinandsulfuric chlorohydrinare not halohydrins, although the former is most commonly produced using a chlorohydrin intermediate.

See also

• Cyanohydrin