Benzylic methylene compounds, potassium

In the presence of a very strong base, such as an alkyllithium, sodium or potassium hydride, sodium or potassium amide, or LDA, 1,3-dicarbonyl compounds can be converted to their dianions by two sequential deprotonations.79 For example, reaction of benzoylacetone with sodium amide leads first to the enolate generated by deprotonation at the more acidic methylene group between the two carbonyl groups. A second equivalent of base deprotonates the benzyl methylene group to give a dienediolate. 

Cottrell et al. at Merck Sharp and Dohme Research Laboratories reported a mild procedure that used potassium carbonate in dimethyl sulfoxide. These conditions were compatible with highly functionalized benzyl azides, and extended the substrate scope of active methylene compounds to acetoacetone and benzoylacetone. This extension provided access to acyl-1,2,3-triazoles 21 for the first time via the Dimroth triazole synthesis. 

Nonetheless, the usefulness of the method was somewhat limited due to the lability of triazole or active methylene compound under the vigorous reaction conditions employed. Thus, 1-substituted 5-amino-1//-1,2,3-triazoles are liable to undergo a Dimroth rearrangement to yield 4-substituted amino derivatives and also alkyl or benzyl azides with certain active methylene compounds give only moderate or poor yields of the desired products. Some success in improving the yields was achieved by the use of potassium t-butoxide as base at room temperature, which gave good yields of 5-amino-LW-l,2,3-triazoles 9 from benzyl and -hexyl azides with phenylacetonitrile 8 (Scheme 4.3) [5], but with methyl ketones, yields of the product were variable due to dimerization of the ketones and other side reactions. 

In 1991, Wright et al. reported a procedure for the preparation of substituted 1-benzyl-1//-1,2,3-triazoles 21 and 23 from benzyl azides 20 under very mild conditions (Scheme 4.7) [9]. Benzyl azides 20 reacted with active methylene compounds in DMSO induced by potassium carbonate at 35-40 C to give 1-benzyl-1//-1,2,3-triazoles 21 and 23 usually in good yield. Acetonitrile derivatives 10 gave 5-amino-l-benzyl-l//-l,2,3-triazoles 21, whereas diethyl malonate gave 5-hydroxy-l-benzyl-l//-l,2,3-triazoles. l//-l,2,3-Triazole-4-carboxylate esters and l//-l,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and P-diketones, respectively. Benzyl methyl ketone reacted to give a 5-methyl-4-phenyl-l//-l,2,3-triazole, but acetone and acetophenone failed to react. Other active methylene compounds that did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate, and ethyl nitroacetate. 

Markiewitz and Dawson separated oleflnic components of the poison ivy principle urushiol in active phenolic form by benzylation, chromatography, and debenzyla-tion with a dispersion of sodium-potassium alloy in ligroin. With this reagent debenzylation was effected without alteration in the position or geometrical configuration of mutliple olefinic bonds separated from one another by only one methylene group (sodium isomerizes such compounds to conjugated systems, which are then reduced by the metal). 

Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, ben larylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono- -methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate... 

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