The β-acyloxyalkyl radical rearrangement has been known since 1967 but its
mechanism is still not fully understood, despite considerable investigation. Since the
migration of a β-trifluoroacetoxy group generally proceeds more rapidly and with more varied regiochemistry than its less electronegative counterparts, this reaction was studied
in the hope of understanding more about the subtleties of the mechanism of the β- acyloxyalkyl radical rearrangement. The mechanism of the catalysed rearrangement of Nalkoxy-
2(1H)-pyridinethiones was also explored because preliminary studies indicated that the transition state (TS) for this process was isoelectronic with TSs postulated for the β-acyloxyalkyl radical and other novel rearrangements.
¶
A kinetic study of the rearrangement of the 2-methyl-2-trifluoroacetoxy-1-heptyl
radical in solvents of different polarity was undertaken using a radical clock method. Arrhenius equations for the rearrangement in each solvent were: hexane, log10[kr (s-1)] =
11.8±0.3 – (48.9±0.7)/ θ; benzene, log10[kr (s-1)] = 12.0±0.2 – (43.7±0.8)/ θ; and
propionitrile, log10[kr (s-1)] = 11.9±0.2 – (42.0±0.3)/ θ. Rate constants at 75˚C were:
hexane, kr = 2.9 × 104; benzene, kr = 2.8 × 105; and propionitrile, kr = 4.0 × 105 s-1.
The equilibrium constant for the reversible rearrangement at 80°C in benzene was 15.1 <K < 52.9.
¶
A regiochemical study with oxygen-labelled radicals revealed that trifluoroacetoxy
group migration occurs with 66-83% label transposition (3,2 shift). The proportion of
3,2 shift is decreased by polar solvent, high temperature and low concentration of the
reducing agent. Results of labelling experiments were consistent with cooperative 1,2
and 3,2 shifts, the former having Ea 9.5 kJmol-1 higher than the latter in benzene
solution.
¶
An esr study of nine β-oxygenated radicals revealed that the temperaturedependent
equilibrium conformation is controlled by a balance between steric and
stereoelectronic effects. The influence of the latter is increased by electron-attracting β-
substituents. Barriers to C α–C β rotation in β-oxyethyl radicals are approximately the same as for the propyl radical. Consequently, there is no significant through-space
interaction between the β-substituent and the unpaired electron.
¶
Experimental results were consistent with a mechanism involving a combination
of polarized 1,2 and 3,2 concerted shifts. The results may also be rationalised by the
intermediacy of a contact ion pair, as well as combinations of the three options.
¶
The rearrangement of N-alkoxy-2(1H)-pyridinethiones is catalysed by oxidants,
Lewis acids and protic acids. Pseudo first order kinetics are observed and there are
moderate solvent effects. The migration of a 1,1-dideuteroallyl group occurs almost
exclusively in a 1,4 sense. Migration of an enantiomerically enriched 1-phenylethyl
group proceeds with predominant retention of configuration in chloroform, but with
virtual racemisation in acetonitrile. Migrating groups do not become diffusively free
during the rearrangement. Substituents which stablise positive charge at C1 migrate more
rapidly. The bulk of evidence indicates that a catalyst activates the pyridinethione for
rearrangement by promoting aromatisation. Mass-spectrometric analysis of an isolated
intermediate and kinetic results are consistent with an intermolecular mechanism.
| Identifer | oai:union.ndltd.org:ADTP/216770 |
| Date | January 2003 |
| Creators | Harman, David Grant, harmandg@hotmail.com |
| Publisher | The Australian National University. Faculty of Science |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://www.anu.edu.au/legal/copyrit.html), Copyright David Grant Harman |
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