Peracid oxidations, isoquinoline

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

The oxidation of isoquinoline has also been examined using mthenium tetroxide. In this instance, the surprising observation that phthaUc acid is the only significant product (58%) was made this fact is both important and difficult to explain (145). Isoquinoline is also oxidized to its N-oxide by peracids. Isoquinoline N-oxide [1532-72-5] has also been obtained from 2-(2,4-dinitrophenyl)isoquinolinium chloride [33107-14-1] by refluxing with hydroxjiamine hydrochloride in concentrated hydrochloric acid (146). 

Reaction of peracids with quinolines and isoquinolines affords the corresponding A-oxides. Typical conditions are treatment of heterocycles with RCO2H in the presence of H2O2 at -100 C or /w-CPBA at 0 C. The quinoline/isoquinoline nitrogen atom reacts less readily with peracids than the tertiary amines. Large substituents and electron-withdrawing groups slow the reaction. 

Quinoline and isoquinoline A-oxides, formed by the action of peracids in quinoline and isoquinoline core, are useful synthetic precursors as they possess both electrophilic and nucleophilic character. The positive charge on nitrogen or the negative charge on oxygen atom can be delocalized to the a-or y-positions, depending on demand fi-om the reagent used. 

Reactions with Oxidizing Agents. Isoquinoline readily forms the IV-oxide when treated with peracids. Treatment of isoquinoUne with alkaline KMn04, ozone, or fuming nitric acid will form a mixture of pyridine-3,4-dicarboxylic acid and phthalic acid. ... 

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