1,8-Naphthyridine Reissert reactions

The Reissert reaction with 1,6-naphthyridine-1-oxide (124), as well as with HCN in methanol, forms 2-cyano-1,6-naphthyridine (125). 

The 1,6-naphthyridine-6-oxide (126) and 1,6-naphthyridine-1,6-dioxide (127) form the 5-cyano (128) and 2,5-dicyano (130) compounds, respectively, when subjected to Reissert reaction conditions.52 The 5-oxo isomer (129) is a by-product in the 6-oxide reaction. Cyano-l,6-naphthyridines are obtained when the 1,6-di-JV-oxide (127) is treated with potassium cyanide in the presence of potassium ferricyanide.76-77 Methanolic potassium cyanide yields the 5-cyano-, 5-carboxamido-, and 2-methoxy-l,6-naphthyridines (128, 131, and 132, respectively) when reacted with 1,6-naphthyridine 1,6-dioxide (127).78... 

Naphthyridine underwent a Reissert reaction with indole and benzoyl chloride to give l-benzoyl-2-(indol-3-yl)-1,2-dihydro-1,5-naphthyridine (25) (reactants, PhMe, reflux, 4 h 68%) some 2,6-bisheteroarylation occurred when Me2NCHO was used as solvent.791... 

Note These esters have been made by primary synthesis (see Chapter 1), by the Reissert reaction (see Section 2.1.3), by esterification of 1,5-naphthyridine-carboxylic acids (see Section 7.1), and by various passenger introductions (see several chapters). Other possible routes have not been used. 

Note Although simple C-alkylation of 1,6-naphthyridine is rare, concomitant C-alkylation and A-acylations are well represented (see Reissert reactions below). 

Proton and 13C-NMR spectroscopy has been used to detect the cr-adducts formed between the reaction of naphthyridines and the amide ion <83AHC(33)95>. Proton, 13C, and 3,P NMR spectroscopy has been used to elucidate the nature of the product formed between 1,8-naphthyridine (4), trimethyl-phosphite and an appropriate acid chloride in a Reissert reaction. 1,2-Addition is determined to... 

Many of the papers dealing with the synthesis and reactions of Reissert compounds routinely include spectral data. These data are consistent with the structures assigned and with previously reported spectral data for Reissert compounds. It should be noted that comparisons of data of this type was used to assign the structures 4 and 5, which were assigned to the Reissert compounds from 1,7- ° and 1,6-naphthyridine. A detailed spectral study of Reissert salts led to the assignment of structure 19. 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

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