Methylation Purdie method

For the methylation of the free hydroxyl groups of a partially esterified carbohydrate, e.g., of a partially acetylated compound, only the Purdie method is available. Although liquid ammonia does not react with esters at — 70°C., there is a danger of saponification if the temperature of the reaction mixture is allowed to rise before all the ammonia has been removed. The aqueous alkali employed in the methods of Haworth or Menzies will, of course, remove ester groups by hydrolysis. 

For maximum efficiency, methylation should be a single-phase reaction and so those methods employing aqueous alkali are most suitable for water-soluble compounds and the Purdie method for non-polar compounds. A carbohydrate which is initially soluble in water e.g., starch, dextran) may be less soluble when partially methylated and for this reason an inert solvent e.g., acetone, dioxane, carbon tetrachloride) is often introduced during the later stages of a methylation with dimethyl sulfate. It is interesting to note that methyl a-D-glucopyranoside forms a trithallium derivative which is insoluble in water and consequently the introduction of more than three methoxyl groups by the Menzies method... 

As far as concerns the ease of isolation of the methylated product, the Purdie method possesses advantages, because the excess silver oxide and the silver iodide produced are easily removed by filtration and the excess methyl iodide by distillation. It is sometimes necessary to use a long purification procedure in order to free a methylated product obtained by one of the other methods from all traces of inorganic impurities (e.g., sodium sulfate, sodium methyl sulfate, thallous sulfate or sodium iodide). 

The relative costs of the various methods of methylation are not important in small-scale work, but must be taken into consideration when large quantities of reagents are employed. On this account the Purdie method has serious limitations, for neither methyl iodide nor silver oxide is a cheap commodity and, furthermore, six or more treatments may be necessary, each requiring a four-fold excess of silver oxide and a six-fold excess of methyl iodide. 

Methylation of a carbohydrate is most practically achieved by using the Hakomori procedure,9 which has largely replaced the Purdie, Haworth, and Kuhn methylation methods. 

In Purdie and Irvine s method778 hydroxy compounds are alkylated by alkyl iodides in the presence of silver oxide. This method is of particular significance for methylation of carbohydrates, where, to avoid its oxidation, the reducing group is protected by glycosidation. 

Haworth originally devised the procedure of methylation in aqueous solution with dimethyl sulfate and sodium hydroxide [I] similarly, the method of benzylation [2] with benzyl chloride and powdered alkali hydroxide (with or without an additional solvent) and the old methylation procedure of Purdie and Irvine [3] are slow... 

Purdie and Irvine used methyl iodide in presence of silver oxide in methylating sugars. W. C. Denham and H. Woodhouse used dimethyl sulphate and alkali in methylating cellulose, and the obvious step of using this method in methylating sugars and polysaccharides was taken by Haworth. ... 

American Viscose was the dominant rayon company at the time and well-puriBed dissolving grade wood cellulose was constantly improved thanks to fundamental research on methods of carbohydrate analysis. Purves had originally studied at St. Andrews University where Haworth, Hirst, Purdy and Irvine pioneered the methylation techniques which were essential for chemical structure determination. 

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