Side-Chain Fragmentation of Arylalkanol Radical Cations
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5959
on the â carbon.17 We have no explanation for this discrepancy
apart from the fact that in the above systems most of the charge
should reside on the nitrogen atom, whereas in the radical cations
of 5-7, the charge is predominantly located on the aromatic
ring. Differences in charge distribution in the radical cations
may result in the different structural response of the C-H Vs
C-C bond cleavage competition in the two systems. It may
also be relevant that the reactions of the amino alcohols were
carried out in a non-aqueous solvent.
role of the side-chain OH groups in assisting the cleavage of
the CR-Câ bond. The path leading to the cleavage of the C-C
bond is strongly disfavored when a 4-methoxy group is present
in the ring, probably because it opposes the accumulation of
positive charge on the scissile C-C bond in the transition state
leading to the cleavage. The presence of an OH group on CR
or Câ enhances the rate of C-C bond cleavage, the effect being
much larger than that of the OCH3 group, and the efficiency of
such assistance is almost the same for R- and â-OH groups, in
spite of the fact that the C-C bond breaking is homolytic in
the former case and heterolytic in the latter. On the basis of
the kinetic solvent isotope effect values, k(H2O)/k(D2O), for the
fragmentation reactions of 5•+ and 6•+, obtained by pulse
radiolysis experiments, hydrogen bonding or specific solvation
in conjunction with carbonyl group formation appear to be the
key factors determining the enhancing effect of the R- and â-OH
groups on the rate of C-C bond cleavage.
Finally, information has been obtained on how substituents
on the scissile C-C bond influence the relative importance of
the electron transfer and fragmentation steps with respect to
the rate of the oxidation induced by Co(III)W. When only one
group (OH or OCH3) is present in the side chain (either on CR
or Câ) the fragmentation step or both the electron transfer and
fragmentation steps contribute to the overall oxidation rate.
However, with an OH group on both carbons of the scissile
bond, the rate of C-C bond cleavage becomes so fast that the
electron transfer step is rate determining.
We now discuss the results of the reaction of threo-1-(4-
methoxyphenyl)-1,2-propanediol (threo-9) with Co(III)W. The
radical cation undergoes exclusive C-C bond cleavage with
formation of 4-methoxybenzaldehyde. Kinetically, the oxidation
of threo-9 displays clean second-order kinetics (Table 4),
different from the substrates discussed above. Clearly, the
cleavage of the C-C bond in the radical cation is sufficiently
fast as to make the electron transfer rate determining. As a
result, no effect of AcOK on the reaction rate is observed. We
also found that the reactivity of threo-9 is identical to that of a
mixture of threo- and erythro-9, which indicates identical
reactivity for the two diastereomers, in perfect line with a rate
determining electron transfer step (the two diastereoisomers
should have the same oxidation potential). It is rewarding to
note that the directly determined rate constant for the oxidation
of threo-9 (1.2 × 10-2 M-1 s-1), which refers to the electron
transfer step (k1), is very similar to that calculated by eq 2 for
the electron transfer step in the oxidation of 7, as expected.
For the dimethyl ether of 9, the study was hampered by the
conversion of the R-OCH3 group into an OH group, which
occurs with a rate at least comparable with that of the oxidation
process. Thus, it can only be estimated that the oxidation of
10 (an erythro-threo mixture) with Co(III)W is at least 20 times
slower than that of 9. This strong decrease in reactivity is in
line with the role of the OH group (R or â) in assisting the
cleavage of the C-C bond, as already discussed (see eqs 9 and
10).
Finally, it is noted that with metal-induced oxidative frag-
mentations of alcohols, the observation that the alcohol (or the
diol) is more reactive than the corresponding ether is often taken
as evidence for complexation of the substrate with the oxidant
involving the OH group.43 On this basis, a radical cation
mechanism is generally discarded. However, this conclusion
is probably not justified since the results presented here clearly
show that C-C bond cleavage in R- and (or) â-OH substituted
alkylaromatic radical cations is much faster than in the corre-
sponding OCH3 substituted species, due to the possibility for
O-H deprotonation and, more importantly, formation of car-
bonyl products.
Experimental Section
Potassium 12-tungstocobaltate(III) was prepared as described
previously.19 1-(4-Methoxyphenyl)-2-propanol (2) was prepared by
reaction of 4-methoxyphenylacetone with NaBH4 in 2-propanol: bp
98-99 °C (0.26 mbar) (lit.44 bp 119 °C (4 mmHg)).
1-(4-Methoxyphenyl)-1,2-propanediol (9). The threo isomer was
prepared by reaction of trans-anethole with potassium permanganate
in CH2Cl2 in the presence of benzyltriethylammonium chloride45 and
identified by 1H-NMR46 and GC-MS; mp 61.5-62.5 °C (lit.46 mp 63-
64 °C). The erythro-threo mixed diols were prepared as described
previously.47
1-(4-Methoxyphenyl)-2-methoxy-1-propanol (erythro-threo mix-
ture) was prepared by a three-step synthesis. 2-Methoxypropionitrile
was prepared by reaction of trimethylsilyl cyanide with acetaldehyde
dimethylacetal in the presence of boron trifluoride-etherate:48 bp 110-
115 °C (lit.49 110-113 °C). 2-Methoxypropionitrile was reacted with
4-methoxyphenyl magnesium bromide in anhydrous tetrahydrofuran
to yield 4-methoxyphenyl 1-methoxyethyl ketone. The ketone was
reduced with NaBH4 in 2-propanol to yield 1-(4-methoxyphenyl)-2-
methoxy-1-propanol (erythro-threo mixture). For 1H-NMR,50 13C-
NMR, EIMS, and elemental analysis data see the supporting informa-
tion.
1-(4-Methoxyphenyl)-2-methoxy-1-propanol acetate (erythro-
threo mixture) was prepared by reaction of the corresponding alcohol
Summary and Conclusions
1
with acetic anhydride in pyridine. For H-NMR,50 13C-NMR, EIMS,
The results reported in this paper provide insight into the
effects of structure upon the competition between CR-H and
CR-Câ bond cleavage in arylalkanol radical cations and on the
and elemental analysis data see the supporting information.
1-Phenyl-2-(4-methoxyphenyl)ethanol (5), 1-(4-methoxyphenyl)-
2-phenylethanol (6), and 1-(4-methoxyphenyl)-2,2-dimethyl-1-pro-
(39) Another possibility might be that the R-hydroxy-substituted radical
cation is first deprotonated to form a benzyloxy radical, which then
undergoes a fast â-fragmentation reaction, as also proposed by Albini40
and Kochi41 to rationalize the C-C bond cleavage in photogenerated pinacol
radical cations. However, there is clear evidence that benzyl alcohol radical
cations undergo CR-H and not O-H deprotonation,42 and moreover we
cannot envisage any mechanism by which the charge can be transferred
from the aromatic ring to the oxygen atom since there is no direct interaction
between the π system and the O-H bond.
(44) Winstein, S. J. Am. Chem. Soc. 1952, 74, 1140-1147.
(45) Ogino, T.; Mochizuki, K. Chem. Lett. 1979, 443.
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Org. Chem. 1962, 27, 4461-4465.
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(50) The assignment of the erythro and threo forms for 1-(4-methox-
yphenyl)-2-methoxy-1-propanol and its acetate was done by comparison
of their NMR data with those of erythro and threo forms of 1,2-disubstituted
1-arylpropanes. Barba, I.; Chinchilla, R.; Gomez, C. J. Org. Chem. 1990,
55, 3270-3272.
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