Halide Alkyl, homologation

This homologation of an oxime ether may have wider application for coupling of alkyl halides to other substrates such as acrylic esters (equation II). 

Radical homologation. This tin pinacolate is known to generate trimethyltin radicals at 60° and appears to be superior to tributyltin hydride as a source of stannyl radicals for addition of alkyl halides to O-benzylformaldoxime (equation I).1 Iodides, bromides, and selenides can be used as radical precursors. The same... 

Since alkyl phenyl teUurides are easily prepared from alkyl hahdes and phenyltel-luromethyllithium, procedure C constitutes a homologation of alkyl halides. 

In 1990, Hahn and Tompkins reported an interesting multi-carbon homologation of alkyl halides by the reaction of magnesium carbenoid with a Grignard reagent (Scheme 2) . 

Nitro compounds. Aliphatic nitro compounds are acidic. They are freed from alcohols or alkyl halides by standing for a day with concentrated sulphuric acid, then washed with water, dried with magnesium sulphate followed by calcium sulphate and distilled. The principal impurities are isomeric or homologous nitro compounds. In cases where the nitro compound was originally prepared by vapour phase nitration of the aliphatic hydrocarbon, fractional distillation should separate the nitro compound from the corresponding hydrocarbon. Fractional crystallisation is more effective than fractional distillation if the melting point of the compound is not too low. 

The 2-substituted thiothiazolines have also been shown to be convenient reagents for effecting the iodomethylation and iodopropenylation of alkyl halides (72TL2743). After alkylation of the anion of 2-methylthiothiazoline or 2-allylthiothiazoline, the product is simply stirred with methyl iodide in DMF to furnish the homologated iodide (607 Scheme 134). 

The two schemes showing homologation of halides through alkylation of phenylthiomethyllithium as the key step for carbon-carbon bond formation illustrate the potential of this reagent [303],... 

Alkoxy or 2,2-dialkoxy nitriles.10 Ketals or orthoesters are converted into 2-alkoxy or 2,2-dialkoxy nitriles, respectively, by reaction with cyanotrimethylsilane in the presence of SnCl2 or BF3-0(C2H5)2 as catalyst. A typical reaction is the preparation of dimethoxyacetonitrile (1), which is a useful reagent for conversion of alkyl halides to the homologous methyl carboxylate (equation I). 

Several authors have demonstrated the feasibility of the alkylation of a MSMA substrate to obtain the homologous RSMA via reaction of the corresponding a-silylcarbanion with an alkyl halide. Treatment with LDA of (allyl)(pyrrazolylmethyl) silane gives a carbanion that on trapping with methyl iodide, leads to the unique formation of the corresponding RSMA derivative without traces of compounds that could have resulted from the allylic system. However, when. v-butyllithium is used instead of LDA, partial methylation of this system also occurs.66... 

One-carbon homologation. The products 3) obtained by reaction of 2 with alkyl halides can be converted under mild conditions lo one-carbon homologated aldehydes, carboxylic acids, or enol methyl ethers. 

Alkynes. Primary alkyl halides react with dichloromethyllithium in the presence of HMPT (1 equiv.) to form homologated 1,1-dichloroalkanes in 60-90% yield. Several methods have been used for dehydrochlorination of the products. A new method is the reaction with 3 equiv. of n-butyllithium to form a lithium... 

Aldehydes. The reagent can serve as a formyl anion equivalent, which is unmasked by thermolysis. An example of the use of 1 for conversion of an alkyl halide into the corresponding homologous aldehyde is shown in equation (1). 

Synthesis of aldehydes and ketones. This substance can function as a protected cyanohydrin of formaldehyde in an extension of Stork and Maldonado s synthesis of ketones from aldehydes, RCHO —> RCOR, by way of cyanohydrins (4, 300-301). Thus the anion of 1, generated with LDA, does not undergo self-condensation, but can be alkylated the product on hydrolysis gives the homologous aldehyde of the alkyl halide. Thus the reagent serves as the latent anion of formaldehyde, HC=0. An example is shown in equation (I). 

In a new variation for the two-carbon homologation of alkyl halides to give aldehydes, 2,4,4,6-letraniethyl-5,6-dihydro-l,3-(4H)-oxazine is first converted into the stable, crystalline methiodide salt (S) by treatment with 4.0 eq. of methyl iodide in the dark for 20 hr. The salt (5) is treated with sodium hydride in dry DMF at room temperature. The alkyl halide is then added and the reaction mixture is stirred at SO-5S° until... 

Basic Character.—The alkyl amines then are analogous to alkyl halides, and we find a corresponding homologous series, e.g.j methyl amine, ethyl amine, propyl amine, etc. They are strongly basic compounds, in fact, they are of especial interest because they are more strongly basic than the ammonia from which they are derived. 

Homologous Series of Alcohols.—As, hydroxyl substitution products of the hydrocarbons the alcohols form an homologous series analogous to that of the alkyl halides or halogen substitution products. Methyl and ethyl alcohol are thus the first two members of such a series derived from the methane or paraffin hydrocarbons. 

General Properties.—From Tables IX and X the homologous nature of the series of alcohols can readily be seen to be of exactly the same character as in the case of the hydrocarbons and alkyl halides. The rising of the boiling point in the normal series and the falling in each... 

---