Reactions of Tetramethylbenzenedicarbonitriles and Tetramethylbenzonitriles with Fuming Nitric Acid. A New Route to Some Substituted Phthalides and 1,3-Dihydroisobenzofuran-1-imines

The reaction of tetramethylbenzenedicarbonitriles and tetramethylbenzonitriles with fuming nitric acid (d=1.5) has been investigated at room temperature in the dark. 2,4,5,6-Tetramethylbenzene-1,3-dicarbonitrile and 2,3,5,6-tetramethylbenzene-1,4-dicarbonitrile gave, after aqueous work-up, 4-cyano-5,6,7-trimethyl- and 5-cyano-4,6,7-trimethylphthalides, respectively, in high yields, while 3,4,5,6-tetramethylbenzene-1,2-dicarbo-nitrile produced appreciable amounts of two cyanonitro-3-cyclohexen-1-ones in addition to 7-cyano-4,5,6-trimethylphthalide. Similarly, 2,3,4,6- and 2,3,5,6-tetramethylbenzonitriles afforded 4-nitro-5,6,7-trimethyl- and 5-nitro-4,6,7-trimethylphthalides, respectively, along with the expected nitro compounds. In contrast, 2,3,4,5-tetramethylbenzonitrile underwent normal nitration, giving 6-nitro derivative as the sole product. The phthalide formation was found to proceed through 1,3-dihydroisobenzofuran-1-imines presumably derived from the initially formed o-cyanobenzyl nitrates. The reaction appears to provide potential utility in the synthesis of some substituted phthalides and 1,3-dihydroisobenzofuran-1-imines.