Methods based upon alkyl halides

The disconnection strategies summarised on p. 586 reveal that the nucleophilic organometallic reagents derived from alkyl halides (e.g. R MgX, RLi) require 

The Grignard reaction has been improved by the use of phenyl diethyl orthoformate, which may be prepared by an ester exchange reaction between equimolar amounts of triethyl orthoformate and phenol.113 

One of the most important reagent equivalents of the donor formyl synthon is 1,3-dithiane (see Chapter 1, p. 21). However the use of this reagent equivalent is not widely found for the synthesis of simple aldehydes since other methods may be economically more appropriate. An example of specific formylation by the use of 1,3-dithiane is illustrated in Expt 6.66. Disodium tetracarbonylferrate(n) 

THE HYDROLYSIS AND DECARBOXYLATION OF a./( EP0XY ESTERS (GLYCIDIC ESTERS 

Glycidic esters are prepared by the reaction of an aldehyde or ketone with an a-haloester in the presence of base (sodium ethoxide, sodamide, finely divided sodium or potassium t-butoxide) (the Darzens glycidic ester condensation). 

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Methods based upon alkyl halides (Expt 5.82). 

A variation of the use of thiourea for converting alkyl halides into thiols uses N-acetylthiourea although reaction with an alkyl halide in refluxing EtOH is slow, a separate hydrolysis step is not required and the method may prove useful for the synthesis of water- or alkali-sensitive thiols. Other methods based upon thiocarbonyl derivatives are exemplified by the addition of allylic Grignard reagents to thioketones, giving 7-unsaturated... 

Although several methods have been reported, the synthesis of iV-monoalkylhydroxylamines from alkyl halides or sulfonates has remained difficult. Relating to this a new preparation of A -alkylhydroxyl-amines is based upon N-alkylation of isoxazole derivative (52). Besides 2-propyl iodide several primary alkyl halides have been described as the alkyladon agent in this procedure (equation 23). ... 

The Wurtz reaction as a method of alkylating germanium tetrachloride has never achieved the popularity of the Grignard reaction, chiefly because the difficulty of control makes it reasonably successful only as a means of preparing the fully substituted tetraalkyls or tetraaryls. The partially substituted germanium halides appear only in low yields since the reaction as usually conducted goes to complete substitution. One explanation is based upon the heterogeneity of the system. The sodium is unavoidably... 

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