2-Chloro-3,5-dinitro-l,8-naphthyridine

Attempts to obtain 5-nitro-l,7-naphthyridine and 3,6-dinitro-l,8-naph-thyridine (83) from the corresponding 8-chloro-5-nitro-l,7-naphthyridine and 2-chloro-3,6-dinitro-l,8-naphthyridine using the similar reaction failed (85JHC761 98MI2). However, 3,6-dinitro-l,8-naphthyridine (83) could be prepared in 21% yield by hydrazino-dechlorination of 2-chloro-3,6-dinitro-1,8-naphthyridine (82) and subsequent cupric sulfate oxidation of the intermediate 2-hydrazino-3,6-dinitro-l,8-naphthyridine (93LA471). 

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. 

Taking into account the high reactivity of the chloro atoms in 2-chloro-3-nitro- (99a, 99d, and 99f), 7-chloro-3-nitro- (99e and 99g), 2,7-dichloro-3-nitro- (99c), and 2-chloro-3,6-dinitro-l,8-naphthyridines (99b), a great variety of 2- (or 7-) substituted amino products [99, = NHCH3, N(CH3)Ph,... 

Dinitro-1,8-naphthyridin-2(l//)-one gave 2-chloro-3,6-dinitro-l,8-naphthyr-idine (8) (POCl3, reflux, 8 h 60%).1128... 

Using the same methodology, a number of 3,6-dinitro-l,8-naphthyridines (87a-87g) were converted with the LMA/PP system into the methylamino products (94). Tire methylamino group usually enters at position 4, but in cases where a chloro or methoxy substituent is present at C-2, 2,4-bis(methylamino) derivatives were isolated (97MI3). 

Deuterio-3-iiitro-l,6-iiaphthyridiiie (168) was prepared from 4-chloro-3-iiitro-l,6-iiaphthyridiiie (166) by a reaction with tosyl hydrazide and subsequent hydrolysis of the 4-tosylhydrazino derivative (167) with Na2C03/ D2O solution (83RTC359). 7-Deuterio-l,8-naphthyridin-2(lH)-one was prepared by heating l,8-naphthyridin-2(lH)-one with deuterium oxide at 230°C for 35 h (85JHC761). Tliis deuterio compound could be converted into 2-chloro-(or 2-ethoxy-) 7-deuterio-3,6-dinitro-l,8-naphthyridine. 

The compounds 87a and 87b are aminated at position 4, yielding the 4-amino compound (88a, 40%) and the 2,4-diamino compound (88b, 11%) respectively the 2-ethoxy compound (87c), however, undergoes amination at position 4 as well at position 5, giving a mixture of the 4-amino compound (88c, 20%) and the 5-amino compound (89a, 14%).Tlie 2-chloro compound (87d) yields a highly complex reaction mixture from which the 5-amino compound (89b), the 2,4-diamino derivative (88b), and 2,5-diamino-l,8-naphthyridine (89c) could be isolated. l-Ethyl-3-nitro-l,8-naphthyridin-2(lH)-one (90a) and 3,6-dinitro-l-ethyl-l,8-naphthyridin-2(lH)-one (90b) were aminated exclusively in the 4-position to give compounds 91a (62%) and 91b (45%), respectively (93LA471). 

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