Tricyclic Systems Derived from 2-Amino-1,8-Naphthyridines

Abstract

Methods available for the synthesis of 2-amino~1,8-
naphthyridines are described. A brief summary of their
physical properties is followed by a survey of the substitution:
reactions which these compounds undergo, and which can lead to
the formation of various tricyclic systems. The angular
systems formed are tetrazolo[1,5-a] [1,8] naphthyridines,
imidazo[1,2-a] [1,8] naphthyriaines, and pyrimido [1,2-a] [1,8]
naphthyridines; cyclisation in a linear fashion produces
anthyridines.

The antibacterial properties of some 1,8-naphthyridine
derivatives are discussed, in particular those of the
established antibacterial agent nalidixic acid (1-ethyl-7-methyl-
1,8-naphthyridin-4(1H)-one-3-carboxylic acid).

The practical work described in this thesis concerned the
preparation of some new 2-amino-1,8-naphthyridines from
2,6-diamino-4-ethoxypyridine, as well as known examples
prepared from 2,6-diaminopyridine.

The product of the reaction between 2,6-diaminopyridine
and benzoylacetone has been assigned the structure 7-amino-
4-methyl-2-phenyl-1,8-naphthyridine and not 7-amino-2-methyl-
4-phenyl-1,8-naphthyridine as given in the literature. This
assignment has been made on the results of spectroscopic studies.

Several new 2-vinylamino-1,8=-naphthyridines. were prepared
from the aminonaphthyridines; the three reagents employed
were diethyl ethoxymethylenenalonate, ethyl ethoxymethyleneacetoacetate
and ethyl ethoxymethylenecyanoacetate.

Several new examples of the pyrimido [1, 2-a] [1,8] naphthyridine
system have been prepared by the intramolecular electrophilic
cyclisation of 2-vinylamino-1,8=naphthyridines. Two new
anthyridines have been prepared; one of these was prepared
from a 2-vinylaminonaphthyridinone, and since all the
anthyridines in the literature which have been prepared have
been derived from 2-vinylaminonaphthyridinones, the significance
of this is discussed, and an explanation put forward regarding
the difficulties of preparing anthyridines from vinylamino~
naphthyridines bearing only alkyl or aryl substituents.

The other example of the anthyridine system formed,
3,7-dicarbethoxy-5~ethoxyanthyridin-4,6(1H,9H)-dione, was made
by a direct reaction with 2,6-diamino-4-ethoxypyridine, the
first recorded one-step synthesis of an anthyridine from a
pyridine.

Five new examples of the inidazo [1,2-a] [1,8] napnthyridine:
system have been prepared, by reaction of 2-amino-1,8-
naphthyridines with d-halocarbonyl compounds. Three of these
compounds contained one substituent in the imidazole ring,
and this substituent has been assigned to the position
furthest from the bridgehead nitrogen atom, on the basis of
n.m.r. studies on these and other imidazonaphthyridines.

Three new 2-acetamido-1,8-naphthyridine-3-carboxamides
have been prepared, and the cyclisation of these compounds:
has given three examples of a hitherto unreported heterocylcid
system, the pyrimido [4,5-b] [1,8] naphthyridines. N.m.r. and
mass spectroscopic data has been presented in support of the
structural assignments.

A selection of compounds prepared in the course of this
work has been submitted for inclusion in a screening programme
for new antimicrobial compounds. Three compounds were also
tested for anticonvulsant activity in rats. The results of
these tests are presented; these show that none of the
compounds submitted displayed any useful antimicrobial
or anticonvulsant properties.

Date of Award	1970
Original language	English