Bicyclic Heterocyclic Systems Derived from 1, 3, 4-Trisubstituted Pyridines

  • Arthur Bradley

Student thesis: Doctoral ThesisDoctor of Philosophy


The preparation of |,3,4-trisubstituted pyridines and their conversion
into bicyclic systems are reviewed.

The work described in this thesis concerns the preparation of 1,3,4-
trisubstituted pyridines, by both existing and novel routes, and the
conversion of these precursors into bicyclic systems.

Nucleophilic displacement of the nitro group in 4-nitronicotinic acid
l-oxide by amines and alcohols gives a series of 3,4-disubstituted pyridine
l-oxides; with methyl hydrazine as the nucleophile, ring closure occurs
to give 3-hydroxy-2-methyIpyrazolo[4, 3-c] pyridine 5-oxide.

Several new 1,3,4-trisubstituted-1,2,5,6-tetrahydropyridines are
prepared by reduction of the appropriate pyridinium iodides with sodium
borohydride. The reduction of 3,4-dimethoxycarbonyl-I-methyl pyridinium
iodide by sodium borohydride gives the expected tetrahydro derivative and
3,4-dimethoxycarbony!-I-methylpyrid-6-one; the pyridone was also prepared
by oxidation of the quaternary salt using potassium ferricyanide. The
reaction of 3,4-diethoxycarbonyl-I-methyl pyridinium iodide and l-ethyl-3,4-
dimethoxycarbony! pyridinium iodide with sodium borohydride gave the
corresponding pyrid-6-ones. An investigation into the unexpected course
of this reaction is described, and a possible mechanism is proposed.

Two main routes are employed for the synthesis of pyrido[4, 3-d]
pyrimidine 6-oxides. Condensation of 4-aminonicotinic acid l-oxide with
formamide and urea gives the corresponding pyridopyrimidinones. Treatment
of 4-aminonicotinic acid l-oxide with aroy! halides gives the appropriate
-2-ary|pyrido[4, 3-4] [I, 3]oxazin-4-one 6-oxides; the reaction of the pyridooxazine 6-oxides with ammonia generally gives the diamtdes, whereas reaction with hydrazine under similar conditions gives the 3-aminopyrido [4, 3-d] pyrimidin-4(3H)-one 6-oxides. The mechanisms of these reactions are

The reaction of substituted pyridine o-diesters with hydrazine gives
the corresponding pyrido[3,4-d] pyridazinones, and the ring closure of
4-N-(3-toly1) aminonicotinic acid l-oxide and 4-N-(3-methoxypheny!)nicotinic
acid l-oxide using sulphuric acid gives the appropriate benzonaphthyridtnes.

The infrared spectra of the substituted pyridines and of the bicyclic
systems, and some of the n.m.r. spectra, are recorded.

The mass spectra of the substituted pyridines and of the bicyclic
Systems are recorded, and possible fragmentation pathways for several of
these compounds are suggested.
Date of Award1973
Original languageEnglish


  • Bicyclic heterocyclic systems
  • 1
  • 3
  • 4-trisubstituted pyridines

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