Methyl sulfate, reaction with alkoxides

The reaction of alkyl sulfates with alkoxide ions is quite similar to 10-12 in mechanism and scope. Other inorganic esters can also be used. One of the most common usages of the reaction is the formation of methyl ethers of alcohols and phenols by treatment of alkoxides or aroxides with methyl sulfate. The alcohol or phenol can be methylated directly, by treatment with dimethyl sulfate and alumina in cyclohexane. Carboxylic esters sometimes give ethers when treated with alkoxides (Bal2 mechanism, p. 473) in a very similar process (see also 10-24). 

Sulfonates react with a variety of nucleophiles. Synthesis of M A -bis(trifluoro-methyl)aminotnfluoromethanesulfonate and its reactions with nucleophiles were investigated [33] (equation 31) (Table 13). Nucleophilic attack occurs at either nitrogen or sulfur amines give complex mixtures [33]. Polyfluoroalkyl fluorosul-fates react with amines, alcohols, or alkoxides to yield polyfluoroalkyl sulfamates and dialkyl sulfates, respectively [34] (equation 32) (Table 13). In these reactions. 

An accelerated diastereoselective variant of the amide acetal Claisen rearrangement is the reaction between the lithium alkoxide of ( )- or (Z)-2-butenol with salts derived from alkylation of propanamides or fluoroacetamides with methyl triflate or dimethyl sulfate. This reaction yields directly the [3,3] sigmatropic rearrangement products of the corresponding N.O-ketene acetals at room temperature, e.g., formation of 7/8 and 12/13 (Table 8)4fiI-462. 

PROBLEM 7.13 Treatment of an alkoxide with dimethyl sulfate leads to methyl ethers. Write a mechanism for this reaction. 

Other methylation procedures of value in the pol3rsaccharide field have been advocated. Methylation of a solution of the polysaccharide in tetra-hydrofuran with solid sodium hydroxide and dimethyl sulfate can be used to totally methylate an already partially methylated polysaccharide. Etherification takes place readily the solvent appears to stabilize the alkoxide intermediate in the reaction long enough to facilitate ether formation at the expense of competing side reactions. Another useful methylation procedure involves treatment of the polysaccharide with methyl iodide and thallous hydroxide. 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

In fact, the reaction of alkoxides with alkyl halides or alkyl sulfates is an important general method for the preparation of ethers, and is known as the Williamson synthesis. Complications can occur because the increase of nucleo-philicity associated with the conversion of an alcohol to an alkoxide ion always is accompanied by an even greater increase in eliminating power by the E2 mechanism. The reaction of an alkyl halide with alkoxide then may be one of elimination rather than substitution, depending on the temperature, the structure of the halide, and the alkoxide (Section 8-8). For example, if we wish to prepare isopropyl methyl ether, better yields would be obtained if we were to... 

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