1.7- Naphthyridin-8 -one, nitration

Several approaches to the synthesis of nitronaphthyridines and their derivatives are reported. Very common ones are those in which the construction of the nitronaphthyridine system was achieved by using nitro synthons (see Section II,A) or by nitration of the naphthyridine ring, although a successful nitration requires the presence of electron-donating substituents (see Section II,B). Furthermore, the oxidation of the amino group in aminonaphthyridines... 

Tlie presence of one or more electron-donating groups, such as the hydroxy substituent, is required to make easy nitration of the naphthyridines... 

Tlie 1,5-, 1,6-, 1,7-, and l,8-naphthyridin-4(lH)-ones (39a-39d) easily undergo nitration to afford the corresponding 3-nitro derivatives (40a-40d) in fair yields. 

Many reports deal with the preparation of numerous hydroxynitronaph-thyridones and nitronaphthyridinediones. By the nitration of 4-hydroxy-l,X-naphthyridin-2(lH)-ones (X = 5,6,7, and 8) (51a-51d) using nitric acid in acetic acid, the corresponding 3-nitro substituted compounds (52a-52d) were obtained in reasonable-to-good yield (75JMC726 77MI1 96MI1). 

Tlie products of nitration of 2-amino-5-phenyl-l,8-naphthyridin-7(8H)-one (63) vary depending on whether the reaction is carried out with nitric acid in sulfuric acid or in acetic anhydride (74GCI499). In sulfuric acid the phenyl ring was found to be nitrated more easily than the naphthyridine ring, yielding a mixture of 3- and 4-nitrophenyl derivatives (64) in acetic... 

Nitration of 2-amino-l,8-naphthyridin-5(8H)-one (67a) in acetic acid or in acetic anhydride does not occur in HNO3/H2SO4 the products obtained were difficult to separate (72GCI253). Hydrolysis of the amino group under nitration conditions has also been observed with 6- and 7-carboxy-2-aminonaphthyridin-5(8H)-ones (67b/67c), yielding the corresponding (68b/ 68c) (72GCI253). 

Nitration of naphthyridines occurs only when electron-donating groups are present in the 2- or (and) 4-position. Thus l,7-naphthyridine-4(l//)-one (40) can be mononitrated to give the 3-nitro compound (41) in 74% yield (60JCS1794) whilst the presence of two... 

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. 

Methyl-1,8-naphthyridin-4( 1 //)-one (37) on nitration gave 6-nitro-5-oxo-5,8-dihydro-l,8-naphthyridine-2-carboxylic acid (38) (HNO3, heat 55%).726... 

Unlike nitration, C-nitrosation cannot be forced at elevated temperatures because of the lability of nitrous acid. Thus nitrosation must be done at or below room temperature, and this requires the substrate to have a free unactivated position as well as at least two electron-releasing substituents. These criteria are met by 4-hydroxy-1-phenyl-l,8-naphthyridin-2( 1 //)-one (10, R = H), which does yield its 3-nitroso derivative (10, R = NO) (NaN02, AcOH, H20, 20°C 96%).892... 

Amino-l,8-naphthyridin-7(8H)-one (61a) and their 3-nitro and 6-nitro derivatives (61b) and (61c) respectively can be nitrated successfully. The nitro substituent enters preferentially at position 6, i.e., formation of 62a from 61a when position 6 is already occupied by a nitro group, the second nitro group is introduced at position 3, i.e., formation of 62b from 61c (69GCI823). It has been mentioned that diazotation of 61 (R=Ph) with sodium nitrite/sulfuric acid also gives the 3-nitro derivative [97JHC1501]. This reaction proceeds via nitrozation, in which the NO+ is the attacking electrophile. 

Several chelating or metal-complexing polymers were reported in Volume 1 of the series (p. 362). There is still considerable activity in this area and polystyrene remains one of the most widely-used supports. Selective chelate-forming ion-exchange resins were prepared from polystyrene by nitration followed by reduction, diazotization then coupling with aromatic amines and derivatives of phenol. Poly(styryl-l,8-naphthyridine) (7) also functions as a chelating agent with Cu ,... 

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