The Chichibabin amination of diazines geometrical isomerism in anions of aromatic amines

J. Breuker

Research output: Thesisinternal PhD, WU


The first part of this thesis describes investigations into the mechanistic aspects of the Chichibabin amination of some diazines in liquid ammonia containing potassium amide.<p/>The nucleophilic attack of the amide ion on 4-phenylpyrimidine readily takes place at C-2, due to its low electron density, and at C-6 because of the thermodynamic stability of the resulting σ-adduct. The former kinetically determined C-2 adduct isomerizes into the latter as shown by NMR spectros copy. Both adducts, but no analogous isomerization are observed in 4- <em>t</em> -butyl-pyrimidine. In 5-phenylpyrimidine an adduct on C-2 is not formed.<p/>Phenylpyrazine initially undergoes nucleophilic addition in KNH <sub><font size="-1">2</font></sub> /NH <sub><font size="-1">3</font></sub> at all three unsubstituted pyrazine carbon atoms. The C-5 adduct is thermodynamically. the most stable one.<p/>Amination of 4-phenylpyrimidine in <sup><font size="-1">15</font></SUP>N-labeled KNH <sub><font size="-1">2</font></sub> /NH <sub><font size="-1">3</font></sub> clearly shows that a ring opening-ring closure sequence (the S <sub><font size="-1">N</font></sub> (ANRORC) mechanism) must be in volved in the formation of the main product 2-amino-4- phenylpyrimidine. Quenching of the reaction with ammonium salt is an essential requirement for this mechanism. The conclusion is that the intermediate 6-amino-1,6-dihydro-4-phenylpyrimidine undergoes the ring opening. In the amination of 5-phenylpyrimidine the product 2-amino-5-phenylpyrimidine is also formed via an acyclic intermediate. In contrast, 4- <em>t</em> -butylpyrimidine, pyrazine and phenyl-pyrazine do not follow this S <sub><font size="-1">N</font></sub> (ANRORC) mechanism.<p/>The second part of this thesis deals with the occurrence of geometrical isomerism in the anions of aromatic amino compounds. NMR spectroscopy reveals the presence of two isomers of azaaromatic amines in liquid ammonia containing potassium amide, and even of anilines, in which the rotational barrier is lower. Coalescence is observed on increasing the temperature.<p/>The <sup><font size="-1">1</font></SUP>H and <sup><font size="-1">13</font></SUP>C NMR spectra are assigned to the <em>syn</em> - and <em>anti</em> -isomers. In all anions the <em>ortho</em> -hydrogen atom in the <em>syn</em> position relative to the lone pair of the exocyclic nitrogen atom resonates at lower field than in the <em>anti</em> position.<p/>In contrast, the <em>ortho</em><sup><font size="-1">13</font></SUP>C atoms do not show such a straightforward rela tionship in the anions of amino- as well as (methylamino)pyridines. In the former ions the signal of the <em>ortho</em> -carbon in the syn position relative to the nitrogen lone pair is found at <em>higher</em> field than in the <em>anti</em> position, whereas in the (methylamino)pyridine anions this signal is observed at <em>lower</em> field.<p/>With these data it is shown that the presence of a methyl substituent <em>ortho</em> to the amino group in aminopyridine anions causes a preference for the iso mer in which the amino hydrogen and the methyl group are directed towards each other. The conclusion is that the effective size of the lone pair is larger than that of an amino hydrogen, probably due to solvation. Stabilization of the preferred isomer by other effects, however, cannot be excluded.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • van der Plas, H.C., Promotor
Award date28 Apr 1982
Place of PublicationWageningen
Publication statusPublished - 1982


  • azines
  • pyridazines
  • pyrimidines
  • purines
  • chemical reactions
  • amines
  • reaction mechanism


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