2- Nitro-l -naphthyridines

Tile same methodology as mentioned for the preparation of (9) was applied for the synthesis of 8-nitro-l,6-naphthyridines. Heating diethyl N- 3-nitropyridin-4-yl)aminomethylenemalonate (12) in diphenyl ether yields ethyl 8-nitro-l,6-naphthyridin-4(lH)-one 3-carboxylate (13) (63JCS4237, 30%) and acid treatment of 4-( y, y-diethoxypropylamino)-5-nitro-2-(/3,/3 -trifluoroethoxy)-pyridine (14) gives in a similar way 8-nitro-5-(/3, /3-triflu-oroethoxy)-l,2-dihydro-l,6-naphthyridine (15, 76%). Subsequent oxidation with chloranil, acid hydrolysis, and methylation with methyl iodide gives 8-nitro-6-methyl-l,6-naphthyridin-5(6H)-one (16,63%) (81JHC941). 

Analogously, 4-chloro-8-iiitro-l,6-iiaphthyridiiie (80, 68%) (63JCS4237), 8-chloro-5-iiitro-l,7-iiaphthyridiiie (97, 51%) (78JHC731), and 2-chloro-3,6-dinitro-l,8-naphthyridine (82, 66%) (85JHC761) were obtained from 8-nitro-l,6-naphthyridine-4(lH)-one, 5-nitro-l,7-naphthyridin-8(7H)-one, and 3,6-dinitro-l,8-naphthyridin-2(lH)-one, respeetively. 

Tlie pKa values of 3-iiitro-l,6-iiaphthyridiiie (pAT = 2.32) and 8-iiitro-l,6-iiaphthyridiiie (pAT = 2.59) were reported (63JCS4237). In contrast to 3-nitro-l,5-naphthyridine cation (166a), the cations of 3-nitro-l,6-naphthyri-dine and 8-nitro-l,6-naphthyridine form in aqueous solution covalent hydrates. Tire most likely structures for the hydrated cations are presented as 167A/167B and 168A/168B, respectively (63JCS4237). 

Proton magnetic resonance spectra (in CDCI3) of 3-nitro-l,5-naphthyri-dine (84a), 3-nitro-l,6-naphthyridine (84f), and 8-nitro-l,6-naphthyridine (81) have been measured and analyzed [66JCS(B)750]. 

The nitration of l,5-naphthyridin-2- and -4-one gave, in both cases, the 3-nitro derivative.64 The 2-oxo-3-nitro- and the 5-oxo-8-nitro-l,6-naphthyridines were obtained by Albert and Armarego58 from the corresponding parent oxo compounds under nitrating conditions. 

Nitro-1,6-naphthyridin-2( 1 //)-one gave 2-chloro-3-nitro-1,6-naphthyridine (10) (POCl3, reflux, 3 h 44%) 819 4-chloro-8-nitro-l,6-naphthyridine (75 min 68%)48 and 5-chloro-8-iodo-l,6-naphthyridine (likewise 64%)1042 were made similarly from the corresponding 1,6-naphthyridinones. 

By the same procedure 8-nitro-l,6-naphthyridine (81, 23%) was synthesized from 4-chloro-8-nitro-l,6-naphthyridine (80) (63JCS4237). 

Hydrolysis of 8-nitro-5-(/8,/3,/3-trifluoroethoxy)-l,6-naphthyridine (141) gave 8-nitro-l,6-naphthyridin-5(6H)-one, which was further methylated to 8-nitro-6-methyl-l,6-naphthyridin-5(6H)-one (16) (81JHC941). 

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