Alcohols to halides

Another general method for converting alcohols to halides involves reactions with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride, and phosphorus tribromide are the most common examples of this group of reagents. These reagents are suitable for alcohols that are neither acid sensitive nor prone to structural rearrangement. The reaction of alcohols with thionyl chloride initially results in the formation of a chlorosulfite ester. There are two mechanisms by which the chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as dioxane, solvent participation can lead to overall retention of configuration.7... 

Carboxylic acids can be converted to acyl chlorides and bromides by a combination of triphenylphosphine and a halogen source. Triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.100 Similarly, carboxylic acids react with the triphenyl phosphine-bromine adduct to give acyl bromides.101 Triphenviphosphine-iV-hromosuccinimide also generates acyl bromide in situ.102 All these reactions involve acyloxyphosphonium ions and are mechanistically analogous to the alcohol-to-halide conversions that are discussed in Section 3.1.2. 

There are a number of other useful methods for converting alcohols to halides. Avery mild method which is useful for compounds that are prone to allylic rearrangement involves prior conversion of the alcohol to the mesylate, followed by nucleophilic displacement with halide ion ... 

Scheme 3.1 gives some examples of the various alcohol-to-halide conversions that have been discussed. 

Haloalkyl pyrimidines can also be prepared from hydroxyalkyl derivatives by use of the standard reagents for the alcohol-to-halide conversion <1994HC(52)1, 1996CHEC-II(6)93>. 

SCHEME 6.16 Mechanism for phosphine mediated conversion of alcohols to halides. 

The transformation of an allylic alcohol to an allylic halide (equation 5) or the reverse reaction normally leads to a mixture of isomers of direct and allylic substitution products. Only when tertiary allylic alcohols are employed or a rearrangement leads to extended conjugation of double bonds does a transposition of functionality occur predominantly While a number of procedures have been developed for the conversion of allylic alcohols to halides without rearrangement, there seems to be only one reaction where a cleanly rearranged product is obtainable in a substitution of a primary or secondary allylic (and propargylic) hydroxy group to a chloride, that is by thionyl chloride in ether, probably by a cyclic SNi process. The regioselectivity is worse in other solvents and is lost in the presence of a base. In accordance with the mechanism it is a syn facial substitution, as has been demonstrated in cyclic cases (equa-... 

Incorporation of halogen into a molecule is important because halides are often precursors for substitution or elimination reactions. The ability to convert alcohols to halides is therefore an important functional group transformation. The transform is... 

Neopentyl alcohol is rather prone to rearrange during reactions designed to convert it to its halide, sihce it is seriously hindered toward direct displacement. Some results for conversion of neopentyl alcohol to halides are given below. The yields given are relative yields of the isomeric products ... 

Conversion of alcohols to halides can also be carried out by a two-step procedure involving isolation of sulfonate ester intermediates ... 

Conversion of alcohols to halides by the hydrogen halides can involve either Sn2 or SnI mechanisms. In primary substrates, in which ionization is difficult, halide ion displacement of water from the conjugate acid of the alcohol is presumably the dominant reaction ... 

Conversion of tertiary alcohols to halides by other reagents such as PBra or SOCI2 also proceeds through carbonium ion intermediates, so extensive racemization is normally observed. 

The pentachloride is most used. It will convert snlphonic acids to snlphonyl halides (12.276), alcohols to halides (12.277) and carboxylic acids to halides (12.278). Af-alkyl-substituted amides (12.279) and ketoximes (12.280) can be converted to nitriles and the Beckmann rearrangement promoted (12.281). 

Reactions involving these reagents are believed to proceed via various intermediates formed between than. The natnre of these intermediates depends upon the temperature, solvents, absence or presence of water, etc. Among the useful reactions are conversions of alcohols to halides (12.311) and epoxides to dichloroalkanes (12.312), and the formation of cyanides (12.313), isocyanides (12.314), carbodiimides (12.315) and isocyanates (12.316). 

In both SnI and Sn2 reactions, the leaving group is the halogen of an alkyl halide or the sulfonate group of a sulfonate ester. Both alkyl halides and sulfonate esters are prepared from alcohols. In Chapter 10, alcohols were prepared by the hydration reaction of alkenes, by oxymercuration-demercuration of alk-enes, or by hydroboration of alkenes. Other methods can be used to prepare alcohols, and they will be discussed at a later time. This section will describe several of the reactions used to convert alcohols to halides or sulfonate esters. 

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