Studies in naphthyridine chemistry

Methyl naphthyridines and 5 out of the 6 possible parent naphthyridines were synthesized. A simple procedure for preparing 2, 7- and 4 -methyl-2,7-naphthyridine was developed. The nucleophilic substitution reactions of these naphthyridines with phenyllithium as the nucleophilic reagent were investigated. With 1, X-naphthyridines (X = 5,6,7,8) and phenyllithium, mono- and diphenyl derivatives were obtained. However, 2-phenyl-1,X-naphthyridine was the main product. With 2,7-naphthyridine, the product was the 1-phenyl derivative. Thus substitution occurred exclusively at the position α to the ring nitrogen. The reaction of 3-methyl-1, 8-naphthyridine with phenyllithium gave 3-methyl-2-phenyl-3-methyl-7-iphenyl-and2, 7-diphenyl-3-methyl-1, 8-naphthyridine. However, the predominant product was 3-methyl-2-phenyl-1, 8-naphthyridine. With 4-methyl-2, 7-naphthyridine, 4-methyl-1-phenyl- and 4-methyl-8 phenyl-2, 7-naphthyridine were obtained; the 1-phenylisomer was the main product. Thus the methyl substituent preferentially activated nucleophilic substitution in the ring to which it was attached. The above reactions were shown to go via an addition-elimination mechanism. The proof of this mechanism was the actual isolation and characterization of the σ-intermediates. A study of the mass spectral fragmentation pattern of phenylnaphthyridines showed that the characteristic fragments were the molecular ion (M[dot][superscript +]) , the M[dot][superscript +] -1 ion and the doubly charged molecular ion (M[superscript 2+]) . Unlike for the parent naphthyridines, the loss of HCN, C₂H₂ or C₆H₅CN in phenylnaphthyridines was not an important process. The doubly charged molecular ion was the most characteristic fragment