Nitropyridines—continued

The ion-pairs of nitropyridines continue to attract attention. Consistent with the substituent s being the primary residence for spin and charge in nitro anion-radicals, it was found that the counterion is associated with the oxygen atoms of the nitro group and lies on the C2 axis of the radical.80... 

Chloro-3-nitropyridine [5470-18-8] M 158.5, m 100-103°, 101-102°, 103-104° (sublimes), pK -2.6. Forms needles from H2O. Purified by continuous sublimation over a period of 2 weeks at 50-60°/0.1mm [Barlin J Chem Soc 2150 1964]. The N-oxide has m 99-100°(from CH2Cl2-Et20). [Taylor and Driscoll J Org Chem 25 1716 I960-, Ochiai and Kaneko Chem Pharm Bull Jpn 8 28 I960.]... 

Dimethyl-4-nitropyridine-N-oxide-dimethyl sulfate adduct (220 g, 0.75 mole) was dissolved in methanol (1.0 Itr) and the solution heated to reflux. A solution of ammonium persulfate (140 gm) in water (200 ml) was added dropwise over 4 hours after which reflux was continued for 4 hours. Methanol was distilled off under reduced pressure and the residue was basified to pH 10 by addition of caustic lye (105 ml). The mixture was extracted with dichloromethane (2 times 400 ml). The dichloromethane layer was dried over sodium sulfate and filtered. The product was used as its solution in dichloromethane for the next reaction. 

To the cooled dichloromethane solution of 3,5-dimethyl-2-hydroxymethyl-4-nitropyridine was added thionyl chloride (60 ml, 0.85 mole) dropwise over a period of 2 hours and stirring was continued for a further 2 hours. Methanol (10 ml) was added to destroy excess thionyl chloride and separated product was filtered under suction and washed with dichloromethane. The cake was dried in vacuum oven to yield 55 g of a cream colored product. Melting point was 124°-126°C. 

The synthesis of fluoroalkyl-substituted heterocycles is a subject of continuous interest this challenging issue has been presented in details in reviews [107,108]. It has been shown that trifluoromethyl carbanion, generated from (trifluoromethyl) trimethylsilane (the Ruppert reagent), adds easily to 2-chloro-3-nitropyridine. The produced o adducts can be oxidized with dimethyldioxirane (DMD) to form two isomeric 2-chloro-4-(and 6-)trifluoromethyl-3-hydroxypyridines (Scheme 30) [109]. 

To 35 0 mL of liquid ammonia, (2.0-2.3 mmol) 4-chloro-3-nitropyridine and double the amount (4-4.6 mmol) of potassium permanganate were added, and the mixture was stirred for 5 h. After evaporation of ammonia, 50 mL of water was added to the residue, and the mixture was continuously extracted with chloroform for 20 h. 

Catalytic reductions of substituted pyridinecarboxylic acids continue to play an important role in some syntheses of pyridoxol. Thus 4-carbethoxy-6-chloro-5-cyano-2-methyl-3-nitropyridine (X-132) is reduced over Raney Nickel in water to 3-amino-5-aminomethyl-4-carboxy-2-methylpyridine-4,5-lactam (X-133). - ... 

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