Selective monomethylation

Selective monomethylation reactions of methylene-active compounds with dimethylcarbonate. An example of clean synthesis... 

Selective monomethylation of dicarboxylic acids has been reported using A/ /wi a as an additive (eq 9) " It is thought that one of the two carboxylic acid groups is bound to the surface of the alumina and is therefore not available for reaction. Carboxylic acids that are engaged as lactols will also undergo methylation with diazomethane to provide the methyl ester and aldehyde (eq 10). ... 

Alkylation of Phenylacetonitrile. Phenylacetonitrile is very selectively monomethylated with DMC into 2-phenylpropionitrile over alkali ion-exchanged zeolites, as mentioned before, [reaction (13)] (58). Phenylacetonitrile is also methylated with methanol over alkali ion-exchanged zeolites (58). 

Direct PT-catalyzed methylation of 2-nitroanilines gives selectively N-monomethylated products. Methylation of 2,4-dinitroanilines and 4-nitroanilines does not proceed under these conditions as selective monomethylation (eq. 30). 

Under conditions of kinetic control (excess of 2-methoxypropene - catalytic p-toluenesulphonic acid) the four diacetonides (2)-(5) were formed from ribitol in 36, 3,12, and 5% yield, respectively, the last two being new compounds. Similarly, erythritol gave 50% and 18%, respectively of the known diacetals (6) and (7) and, in addition, the new 1,3 2,4-derivative (8) as a minor product. With the same reagent, 4,l, 6 -trichloro-4,l, 6 -trideoxy-gfl/acto-sucrose reacted to give the 2, 3 -monoacetonide (9) and traces of the 6-0-(2-methoxy-prop-2-yl) derivative (10). The partial acetylation of these compounds and their conversion to selectively monomethylated products is covered in Chapter 5, and improved procedures for the preparation of di- and tri-O-isopropylidene derivatives of myoinositol in Chapter 18. 

The monomethylation of carbanions derived from 1,3-cyclohexanedione and acetylacetone has been described (eqs 1 and 2) Selective monomethylation of (3-diketones is dependent upon the base employed variable amounts of O-methylation, dimethylation, and carbon-carbon bond cleavage may occur. The tetraethylammonium enolate of p-diketones reportedly provides higher yields of C-methylation without competing side reactions (eq 3). Dimethylation is sometimes a desired reaction pathway. In this case, a large excess of both methyl iodide and base favors the dimethylated product (eq 4). Recently, the combination of a potassium base and a catalytic amount of 18-Crown-6 (eq 5) has been described to provide a higher yield of dimethylation, ... 

---