Ammoxidation of Methyl to Cyano Groups

This process was undoubtedly developed for the manufacture of pyrazinamide (Zinamide, etc.), a second-line drug for Mycobacterium tuberculosis infections, resistant to more effective and less toxic agents. Thus a mixture of 2-methyl-pyrazine (323), ammonia, oxygen, and steam is passed (at 400°C) over an alumina- or pumice-supported catalyst comprising one to three oxides of Ce, Cr, Mo, Mn, P, Sb, Ti, or (most importantly) V the main product (in up to 90% yield) is 

5-Dimethylpyrazine has been converted similarly into 2,5-pyrazinedicarboni-triiei263. 1299 3 rapid high-performance liquid chromatographic (HPLC) 

The addition of halogens or hydrogen halides to alkenyl- or alkynylpyrazines has been discussed in Section 3.2.4.3. However, such unsaturated substrates also 

3- Chloro-5-(hept-l-ynyl)-2,6-pyrazinediamine (330) gave 3-chloro-5-heptanoyl- 

6-pyrazinediamine (331) [Na2S, HC1, H20—MeOH, reflux, 30 min 89% perhaps via a dimercapto intermediate akin to (327)].817 

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