The project investigated the regioselectivity of 1,2,4-triazole with 1,1-diphenylepoxide. Typically N1 substitution was favoured over N4 substitution resulting in isomer ratios of 85-90/15-10. The kinetic factors affecting the regioselectivity were investigated and showed the importance of the 1,2,4-triazole anion. When 1,2,4-triazole reacted in the form of its ambident anion greater preference for the 1-isomer was observed. The use of low reactant concentrations and dipolar aprotic solvents were shown to increase the formation of the ambident anion. Under these favourable conditions the isomer ratio obtained was 95/5. Synthesis of new epoxides and subsequent reaction with 1,2,4-triazole had no effect on the regioselectivity. Thermodynamic control of the regioselectivity was then observed with the 1-alkyl-1,2,4-triazole being the thermally more stable isomer. The mechanism was shown to occur through the nucleophilic displacement of the triazole anion and formation of the epoxide. The 1-isomer was also seen to be the thermally more stable isomer regardless of the alkyl group and that it is formed in a ratio with the 4-isomer approaching the ratio found in the prototropic tautomer equilibrium of 1,2,4-triazole. Under thermodynamic control the equilibrium mixture was shown to be 99.3/0.7 by both experimental and theoretical (free energy diagrams) methods. From the literature other azoles are seen to exhibit thermodynamically controlled regioselectivity and are therefore also open to the predictive approach to their equilibrium isomer ratios from their respective prototropic tautomer equilibriums.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:639348 |
| Date | January 1991 |
| Creators | Wareman, P. J. |
| Publisher | Swansea University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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