Replacement of alcoholic OH by halogen

The /7-toluenesulfonate is used for replacement of alcoholic OH by iodine as for halogen exchange, usually with Nal in acetone, the reactivity of the toluenesulfonate corresponding approximately to that of the chloride.975 /7-Toluenesulfonates of primary alcohols usually react more readily than those of secondary alcohols. 

Halogen can be introduced into a molecule is several ways. An important method involves replacement of the OH unit of an alcohol with halogen. The hydrogen atom of an aUtyl fragment, particularly an allylic or benzylic fragment can be replaced with halogen by a free-radical mechanism. Both of these transformations will be examined in this section. 

As we saw in Sections 6.3A and 6.3D, haloalkanes can be prepared by the addition of HX and X2 to alkenes. They are also prepared by replacement of the —OH group of alcohols by halogen (Section 10.5). Many of the simpler low-molecular-weight haloalkanes are prepared by the halogenation of alkanes, illustrated here by treating 2-methylpropane with bromine at an elevated temperature. 

The second reaction proceeds much more energetically than the first, especially if preformed phosphorus halide is used. This is, however, not always necessary, at least not in the case of replacements by bromine and iodine in many cases the procedure is rather to produce the halide only during the reaction, either by dropping bromine from a separating funnel into a mixture of alcohol and red phosphorus or, as above, by adding finely powdered iodine. Like the former, this reaction can also be applied to polyhydric and to substituted alcohols indeed, it is possible to replace all the OH groups by halogens, and in particular also by chlorine. 

Direct substitution of F for OH by means of HF has no preparative importance. All the methods of preparing alkyl fluorides from alcohols proceed in principle by way of esters the alcohol is converted into the alkyl chloride, bromide, iodide, or / -toluenesulfonate, and then the halogen atom (see page 204) or the tosyloxy group (see page 229) is replaced by fluorine. 

It IS convenient m equations such as this to represent generic alcohols and alkyl halides as ROH and RX respectively where R stands for an alkyl group In addition to con venience this notation lets us focus more clearly on the functional group transformation that occurs the OH functional group of an alcohol is replaced as a substituent on car bon by a halogen usually chlorine (X = Cl) or bromine (X = Br)... 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Alcohols react with hydrogen halides by nucleophilic substitution. The OH group is replaced by a halogen water is the byproduct. In the reaction mechanism, the first step involves formation of an oxonium ion by the Lewis acid-base reaction of the hydrogen ion of the hydrogen halide and alcohol oxygen. The rest of the reaction occurs by one of the nucleophilic substitution mechanisms depending on structure of the alcohol. In the Sn2 reaction, the next step involves displacement of the water molecule by halide ion to form the final products. In the Sn1... 

If a hydrogen of an alkane is replaced by an OH, the compound becomes an alcohol if it is replaced by an NH2, the compound becomes an amine and if it is replaced by a halogen, the compound becomes an alkyl halide. 

Notice that the reagents that cause the OH group of a carboxylic acid to be replaced by a halogen are the same reagents that cause the OH group of an alcohol to be replaced by a halogen (Section 12.3). 

Careful hydrolysis of phosphonic amidochlorides with aqueous ammonia or dilute caustic soda replaces the halogen with OH and then forms the appropriate salt. A corresponding reaction with alcohols produces the phosphonamidate (phosphonamidic) ester (7.162), and in some cases reaction (7.163) can be carried out. Amido chlorides are converted into the corresponding fluorides by the action of alkali metal fluorides or alkali hydrogen fluorides. 

When substitution occurs at carbon, there are two possibilities. Either the carbon-oxygen bond is broken and the entire hydroxyl (-OH) group is replaced by the group being substituted for it (e.g., a halogen C-OH C-X [X=F, Cl, Br, I]) or substitution occurs elsewhere (as on the aromatic ring of a phenol or at a site distant from the hydroxyl [-OH] group of the alcohol). 

The three series we have looked at so far have contained just the two elements, carbon and hydrogen. However, it is easy to imagine a different series of molecules where one of the hydrogen atoms in the chain is replaced by, say, a halogen atom or a hydroxyl (-OH) group. This latter series of compounds is known as the alcohols. Table 10.4 gives some details of the early compounds of the alcohol homologous series. 

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