1,8-Naphthyridine tautomerism

Tautomerism in 4,8-dioxygenated 1,5-naphthyridines 163 has been studied by UV speetroseopy in aqueous solution. Under these eonditions, the eompounds exist predominantly as the bis-pyridone tautomers 163a (78JOC1331). 

The keto-enol tautomerism in 4-hydroxy- 1,5-naphthyridine (14) has been studied spectroscopically in solution and in the solid state.32 The keto form (15) is said to predominate in polar solvents and the enol form (14) in nonpolar solvents. 

The infrared absorption bands of the carbonyl and the N-H stretching regions have been reported for several other hydroxy-naphthyridines, although no conclusion was offered as to the position of a possible keto-enol tautomerism.38,84... 

We have used 2,7-disubstituted naphthyridines with hydroxy and amido groups to achieve a variety of molecular structures including M and P helices. A combination of X-ray crystallography and theoretical calculations on model compounds (B3LYP/6-31+G ) was used to discuss the tautomerism and the hydrogen bonds of compounds 106-111 [114], Compound 111 was used in the calculations instead of 108. 

The conversion of a tautomeric 1,5-naphthyridinone into the corresponding chloro- or bromo-l,5-naphthyridine is usually done by heating for several hours with neat phosphoryl chloride or phosphoryl bromide, respectively. A mixture of phosphoryl chloride and phosphorus pentachloride has been used for a few difficult cases. In addition, exceptional reactions have been reported in which a nontautomeric /V-alkyl-1,5-naphthyridinone or a hydroxymethyl-1,5-naphthyridine was used successfully as substrate. The following examples illustrate the foregoing possibilities. 

The term oxy-1,5-naphthyridine includes the tautomeric and nontautomeric 1,5-naphthyridinones, extranuclear hydroxy-l,5-naphthyridines, alkoxy-and aryloxy-... 

This chapter summarizes the sparse data on 1,5-naphthyridines with substituents that are joined directly or indirectly to the nucleus through a sulfur atom. Included are any tautomeric or nontautomeric 1,5-naphthyridinethiones, extranuclear mercapto-1, 5-naphthyridines, alkylthio-1,5-naphthyridines, bis(l,5-naphthyridinyl) sulfides or disulfides, 1,5-naphthyridine sulfoxides or sulfones, and 1,5-naphthyridinesulfonic acids or their derivatives. However, several categories have no known representatives. 

TAUTOMERIC/NONTAUTOMERIC 1,6-NAPHTHYRIDINONES AND EXTRANUCLEAR HYDROXY-1,6-NAPHTHYRIDINES... 

Many tautomeric and nontautomeric naphthyridinones have been made by primary synthesis (see Chapter 8) and a few by ozonolysis of alkylidene-l,6-naphthyridines (see Section 9.2.2) or by hydrolysis of halogeno-l,6-naphthyridines (see Section 10.4.2). Other preparative routes are illustrated by the following examples. 

Chloro- (33, R = C1) gave 2-azido-7-ethoxy-5-phenyl-l, 8-naphthyridine (33, R = N3), formulated as the tautomeric tetrazolo[l,5-a][l,8]naphthyridine (33a) (NaN3, Me2NCHO, reflux -80%).718... 

Because of a perceived importance of amino substituents for biological activities in 1,8-naphthyridines, e.g.,359 422 478 526 1395,1410 sucjj derivatives have been widely investigated, for example, with respect to their ionization,1043 NMR spectra,174 mass spectra, fluorescence properties, tautomerism, and conversion into cyanine-type dyes.768... 

Naphthyridin-2(1 //)-ones 66 were prepared from pyrano[4,3-/ ]pyridine-2,7-diones 67 by successive treatment with NH3, HBr and Zn in acetic acid (1993H1). It was believed that the attack of the ammonia molecule on the C(5) atom led to pyran ring opening. Subsequent decarboxylation afforded a tautomeric mixture of substituted tetrahydropyridines 68a,b. Dinitrile 69 generated by elimination of ammonia underwent cyclization under the action of HBr to form 1,6-naphthyridine derivative 70. Dehydrobromination with Zn in acetic acid gave the final products 66. 

All bands in the IR spectra of several substituted 1,5-naphthyridines have been assigned the spectrum of 1,5-naphthyridine 1 was compared with the spectrum of 5-substituted quinoline (1963MI1). IR spectroscopy was used to study the keto-enol tautomerism of 4-hydroxy-1,5-naphthyridine in solution and in the solid state it was found that the keto form predominates in polar solvent and the enol form in nonpolar solvent (1967MI2). 

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