1,2,3 triazole benzyl methyl ketone

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. 

Methyl ketones lead to different triazoles, depending on the azide and ketone employed (Scheme 135).2 5 s Reaction of benzyl azide with acetone and acetophenone yields mostly one or both of the triazoles derived from 38 and 39 in Scheme 64. Methyl t-butyl ketone gives, in addition, a 4-triazenyl-... 

Preparation of Ketones. l-[(Trimethylsilyl)methyl]benzo-triazole reacts readily with acyl chlorides to provide the corresponding (benzotriazol-l-yl)methyl ketones in good yields. One example of such reactions is given in eq 1, and similar results are reported for reactions with benzoyl, acetyl, phenylacetyl, and other acyl chlorides. As shown by an example in eq 2, the benzo-triazolyl moiety in (benzotriazol-l-yl)methyl ketones is easily removed by reduction with zinc in acetic acid to provide the corresponding methyl ketones. To prepare higher ketones, lithi-ated l-[(trimethylsilyl)methyl]benzotriazole is alkylated first and then subjected to the regular reactions with acyl chlorides and zinc. Thus, in a reaction of l-[(trimethylsilyl)methyl]benzotriazole with -BuLi followed by benzyl bromide, l-[ l-(trimethylsilyl)-2-phenylethyljbenzotriazole is obtained in 81% yield. Subsequent treatment of this product with 4-methylbenzoyl chloride and then with zinc in acetic acid provides 4-methylphenyl 2-phenylethyl... 

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. 

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