Preparation of Alkyl and Aryl Halides

Reaction with alcohols and phenols. Horner and co-workers introduced use of the reagents for the preparation of alkyl and aryl halides from alcohols or phenols, and Wiley and co-workers established that the reagents have considerable advantage over phosphorus pentahalides in the C—OH—C—X conversion and discussed the mechanism. For the preparation of n-butyl bromide the Wiley group added bromine under nitrogen to a solution of n-butanol and triphenylphosphine in dimethyl-formamide until 2 drops persisted in giving the solution an orange tint. Volatile... 

Next to the formation of Grignard reagents, the most important application of this reaction is the conversion of alkyl and aryl halides to organolithium compounds, but it has also been carried out with many other metals, (e.g., Na, Be, Zn, Hg, As, Sb, and Sn). With sodium, the Wurtz reaction (10-93) is an important side reaction. In some cases, where the reaction between a halide and a metal is too slow, an alloy of the metal with potassium or sodium can be used instead. The most important example is the preparation of tetraethyl lead from ethyl bromide and a Pb—Na alloy. 

The addition of Grignard reagents to isocyanates gives, after hydrolysis, N-substituted amides. This is a very good reaction and can be used to prepare derivatives of alkyl and aryl halides. The reaction has also been performed with... 

The process is usually called the Wurtz reaction if alkyl halides are employed, the Fittig reaction if aryl halides are used, or the Wurtz-Fittig reaction if it is carried out with a mixture of alkyl and aryl halides. Although all the reactions lead to more than one product when a mixture of two different halides is employed, the Wurtz-Fittig reaction shows a remarkable tendency bo unite two dissimilar fragments, w-Butyl-benzene, for example, can be prepared from bromobenzene and n-butyl bromide in yields of 65 to 70 per cent.6... 

It is extremely widely applicable, for Grignard reagents can be prepared from almost every type of alkyl and aryl halide except the fluorides. 

The range of applicability of the Wittig reaction has in recent years become extremely extensive and there have been reports of its use for the preparation of alkyl- and aryl-substituted alkenes, unsaturated aldehydes, ketones, and carboxylic acid derivatives, vinyl halides, and vinyl ethers. In the preparation of these compounds there is often the possibility of cis-trans isomerism Bestmann and Kratzer1003 state that the trans-olefin is always obtained when an alkylidenetricyclohexylphosphorane is used, and Schlosser and Christ-... 

Mitsunobu and Wada first reported the use of the Mitsunobu reaction in the preparation of ethers in 1972. Since then, the Mitsunobu reaction has become a useful alternative to the reaction of phenols with alkyl halides. Other sufficiently acidic alcohols with a p a of less than 13 may also react under the Mitsunobu reaction conditions. Interestingly, unactivated, less acidic alcohols will form ethers when reacting in an intramolecular manner. The figures below show a number of applications of the Mitsunobu reaction in the preparation of alkyl and aryl ethers. 

An improved method for the preparation of nitriles and thiocyanates from halides with benzyltrimethylammonium salts and a convenient preparation of both aliphatic and aromatic nitriles from aldehydes through N,N,N-trimethylhydrazonium salts have been reported. Nitriles can be easily converted into amidines with ammonium halides . Acylisocyanates can be conveniently prepared from amides with oxalyl chloride . A simple preparation of alkyl and aryl carbamates with N-carbonylsulfamic acid... 

Cadmium alkyl and aryl halides, RCdX, as weU as cadmium allyls have been prepared by Grignard reactions but, as yet, have not realized any commercially important uses despite reactivity toward a number of organic and inorganic materials. 

As in the case with the other members of group IVA, the mixed alkyl and aryl halides of lead are also known, and their reactions with water, alcohols, amines, and other organic compounds can be used to prepare a large number of other derivatives. 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

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