Hydrolysis of alkyl halides

Hydrolysis of alkyl halides (Section 8.1) A reaction useful only with substrates that do not undergo E2 elimination readily. It is rarely used for the synthesis of alcohols, since alkyl halides are normally prepared from alcohols. 

Halide ions can be formed by hydrolysis of alkyl halides, as shown for AgCl precipitation [28] ... 

Hydrolysis of alkyl halides 0-4 Hydrolysis of inorganic esters 0-6 Hydrolysis of enol ethers, acetals, or ortho esters... 

Biological Hydrolysis of Alkyl Halides with Glutathione. One widespread hydrolysis approach used by organisms involves the use of the tripeptide, glutathione (GSH) ... 

Many of the common laboratory methods for the preparation of alcohols have been discussed in previous chapters or will be considered later thus to avoid undue repetition we shall not consider them in detail at this time. Included among these methods are hydration (Section 10-3E) and hydroboration (Section 11-6D), addition of hypohalous acids to alkenes (Section 10-4B), SN1 and Sn2 hydrolysis of alkyl halides (Sections 8-4 to 8-7) and of allylic and benzylic halides (Sections 14-3B and 14-3C), addition of Grignard reagents to carbonyl compounds (Section 14-12), and the reduction of carbonyl compounds (Sections 16-4E and 16-5). These methods are summarized in Table 15-2. 

Some indication of the importance of the solvent interactions is afforded by the observation that of the thousands of reactions which have been studied in solution, less than 20 have been capable of comparative study in the gas phase. The study of ionic reactions has been almost completely restricted to solutions for reasons which are quite understandable ionic processes are virtually nil in the gas phase at temperatures below 1000 K. However, this accounts for most of the solution reactions studied, since, as we shall see, most reactions between polar molecules involve ionic species as intermediates. Thus such common reactions as the hydrolysis of alkyl halides or of esters do not proceed at measurable rates in the gas phase (at least not at temperatures at which other, competing reactions are not dominant). The only large class of reactions which proceed conveniently in both gas and liquid states is the free radical class, and undoubtedly as... 

Hydrolysis of alkyl halides can be dramatically facilitated by the presence of a nitrogen or sulfur attached to the carbon alpha to the halide (neighboring group participation) effect (e.g., melphalan hydrolysis) [20]. 

Alcohols may be prepared by the hydrolysis of alkyl halides and esters, the reduction of carbonyl compounds, the addition of carbanions to carbonyl groups and the hydration of alkenes. Although these reactions are discussed in detail in the separate sections concerning these functional groups, they are brought together here to show the inter-relationship of these functional groups with alcohols. 

A. Attack by OH at an Alkyl Carbon 10-1 Hydrolysis of Alkyl Halides Hydroxy-de-halogenation... 

Hydrolysis of alkyl halides is severely limited as a method of synthesizing alcohols, since alcohols are usually more available than the corresponding halides indeed, the best general preparation of halides is from alcohols. The synthesis of benzyl alcohol from toluene, however, is an example of a useful application of this method. 

Although the hydrolysis of alkyl halides to alcohols has been extensively investigated, an alternative two-step sequence involving substitution with carboxylate ion is more practical for the preparation of alcohols. Activation of the carboxylate anion prepared by the reaction of the acid with a base can be achieved (i) by use of a polar aprotic solvent and (ii) by use of aprotic apolar solvents under phase transfer catalysis, polymer conditions, or with crown ethers. 

We will now examine how the enthalpy and entropy effects can interact in a simple reaction, before we examine each in a little more detail. Write down a general chemical equation for the hydrolysis of alkyl halides. We will look at the entropy effects first, because these are often simpler. 

Lightstone, F.C., et al. (1997). Non-cnzymatic and enzymatic hydrolysis of alkyl halides a haloalkane dehalogenation enzyme evolved to stabilize the gas-phase transition state of an SN2 displacement reaction. Proc. Natl. Acad. Sci. USA 94, 8417-8420... 

Acyclic hydroxy compounds by hydrolysis of alkyl halides... 

Hence the larger the n value, the stronger the nucleophile, and the smaller the [nucl]50o/o. As already pointed out earlier, the [nucl]50o/o values given in Table 2 show that in uncontaminated freshwaters, hydrolysis is by far the most important nucleophilic substitution reaction. Furthermore, since the hydrolysis of a carbon-halogen bond is generally not catalyzed by acids, one can assume that the hydrolysis rate of aliphatic halides will be independent of pH at typical ambient conditions (i.e., pH < 10). In this context it is also important to note that no catalysis of the hydrolysis of alkyl halides by solid surfaces has been observed (El-Amamy and Mill, 1984 Haag and Mill, 1988). In salty or contaminated waters, reactions of organic chemicals with nucleophiles other than water or j hydroxide ion may be important. Zafiriou (1975), for example, has demonstrated j that in seawater ([Cl ] 0.5 M), a major sink for naturally produced methyl j iodide is transformation to methyl chloride j... 

Hydrolysis of alkyl halides is carried out in practice by boiling them with aqueous alkali, with a suspension of alkaline-earth carbonates, or with a suspension of lead(n) oxide. A two-stage process is often used, in which the halide is converted by treatment with an alkali acetate into the ester which is then hydrolysed. This route is particularly useful for synthesis of 1,2-diols because hydrolysis of 1,2-dihalides usually gives poor yields owing to formation of by-products. 

Corrosion of Apparatus. Corrosion may be caused by the catalyst used in the alkylation or by the hydrogen halides formed by hydrolysis of alkyl halides. In the preparation of the N-alkyl compounds, the original amines or the alkylamines formed have an inhibiting action against corrosion. However, there are many cases in which the agents used in alkylation are corrosive. In the alkylation of aniline to diethylaniline by heating aniline and ethyl alcohol, sulfuric acid cannot be used, because it will form ether consequently, hydrochloric acid is employed, but these conditions are so corrosive that the steel autoclaves used to resist the pressure must be fitted with replaceable enameled liners. 

---