Aminering van hydroxyderivaten van halogeenazahetarenen

W.A. Roelfsema

Research output: Thesisinternal PhD, WU


In this thesis an introductory investigation is described on the reactivity of hydroxy derivatives of halogenopyridines and a bromohydroxyquinoline towards strong bases.

It is a sequel to earlier work on the effect of substituents present in the nucleus of halogenopyridines on the course of aminations of these substances (chapter 1).

Halogenohydroxy compounds were reacted with potassium amide or lithium piperidide, whereupon products were isolated, identified and determined quantitatively. Mechanisms were suggested interpreting the results obtained. Details about amination procedures and analyses of reaction mixtures are given in chapter 2.

When various halogenohydroxypyridines are reacted with potassium amide in liquid ammonia at -33°C, substitutions, cine-substitutions and ring contractions occur.

It was shown that part of the bromohydroxypyridines are aminated according to the elimination-addition (EA)mechanism via hydroxy-3,4-didehydropyridines as intermediates. The addition of ammonia to the triple bond in the intermediate is directed by the hydroxy group. Depending on this effect one or two aminohydroxy compounds are formed. Thus, cine-substitution takes place exclusively in the transformation of 3-bromo-5-hydroxypyridine via 5-hydroxy-3,4-didehydropyridine into 4-amino-5-hydroxypyridine. The amination of 4-bromo-2-hydroxypyridine follows a more complicated pattern, presumably involving two isomeric hydroxydidehydropyridines. It leads to the formation of a mixture of 3- and 4- amino-2-hydroxypyridine (chapter 3).

From both 2- and 3-bromo-4-hydroxypyridine, 2-amino-4-hydroxypyridine is formed. These reactions can be explained, assuming divergent AE-processes (chapter 4).

The amination of 2-bromo-6-hydroxypyridine takes place without rearrangement. Continued investigation is required to establish whether this process follows the AE pathway.

Remarkable results were met when studying the amination of 2-chloro-3-hydroxypyridine, 2-bromo-3-hydroxypyridine and three derivatives of the latter. These substances change into pyrrole derivatives. In contrast to the reaction of 3-amino-2-bromopyridine with potassium amide yielding 3-cyanopyrrole, the halogeno-hydroxypyridines are converted into pyrrole carbonamides, in which the substituent occupies the 2-position. A 3-substituted pyrrole derivative was obtained from our substrates however, when lithium piperidide was used as a reagent. Together with this product (i.e. pyrrole-3-carbopiperidide), 3-hydroxy-2-piperidinopyridine is obtained. The mechanism of the reactions of 2-halogeno-3- hydroxypyridines and those of the corresponding amino and methyl compounds are discussed (chapter 5).

Ring contraction takes place too in the amination with potassium amide, of 4-bromo-3-hydroxyquinoline i.e. a derivative of 4-bromo-3-hydroxypyridine from which no hydrogen bromide can be abstracted leading to the formation of a 4,5-didehydro compound. In this reaction oxindole is the product. Thus, along with the ring-fission a fragment of the chain is split off containing one carbon atom, yielding cyanide.

By the action of lithium piperidide or of piperidine at elevated temperature on 3-bromo-4-hydroxyquinoline the ring system remains unaltered. In the former case 3-hydroxy-4-piperidinoquinoline is formed as a substitution product, in the latter a cine-substitution results in the formation of 3-hydroxy-2-piperidinoquinoline.

Mechanisms were proposed for the reactions of 4-bromo-3-hydroxyquinoline; they were compared again with those, suggested for the aminations of the corresponding amino compound (chapter 6).

Original languageDutch
QualificationDoctor of Philosophy
Awarding Institution
  • den Hertog, H.J., Promotor, External person
Award date14 Mar 1972
Place of PublicationWageningen
Publication statusPublished - 1972


  • pyridines
  • piperidines
  • derivatives
  • quinolines
  • quinoline
  • indoles
  • chemical reactions
  • amines
  • pyrrole

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