Reactivity and selectivity of aryloxylium ions

Article abstract of DOI:10.1039/b009968f

The reactivity and selectivity of aryloxylium ions in acetonitrile-water mixtures are described. The 4-bromo-2,4,6-trialkylcyclohexa-2,5-dienones used as substrates were synthesised by electrophilic bromination in yields of 60% (3 R = Me) and 52% (7 R = B

Full text of DOI:10.1039/b009968f

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Reactivity and selectivity of aryloxylium ions
Anthony F. Hegarty* and Joseph P. Keogh
Department of Chemistry, University College Dublin, Dublin 4, Ireland
2
Received (in Cambridge, UK) 13th December 2000, Accepted 14th March 2001
First published as an Advance Article on the web 9th April 2001
The reactivity and selectivity of aryloxylium ions in acetonitrile–water mixtures are described. The 4-bromo-2,4,6-
trialkylcyclohexa-2,5-dienones used as substrates were synthesised by electrophilic bromination in yields of 60%
(3 R = Me) and 52% (7 R = But). Under solvolysis conditions 3 and 7 decompose cleanly via their respective
aryloxylium cations to the 4-hydroxy-2,4,6-trialkylcyclohexa-2,5-dienones 4 and 12. As the polarity of the solvent
increases, the observed rates of reaction increase by a factor of 36 (3) and 56 (7). A detailed study gave Grunwald–
Winstein ms values of 0.56 (3) and 0.63 (7). Addition of sodium bromide caused a common ion rate depression with
α = 22.1 (3) and α = 33.3 (7). Competitive azide trapping gave kaz : kMeOH = 3610 and kMeOH : kH O = 0.755, while the
2
lifetime of the cation 11 in water was estimated to be 0.55 µs. Sterically hindered alcohols (propan-2-ol, cyclohexanol)
do not trap the aryloxylium ions, instead products of reduction (the corresponding phenols) were formed in
quantitative yield. Following a careful search it was determined that these products did not arise from hydride
transfer from these alcohols.
trialkylcyclohexa-2,5-dienone. We now show that this generates
the corresponding oxocyclohexadienylium cation in solution
Introduction
Aryloxylium ions are six electron cationic species that are
(Scheme 1).
isoelectronic with carbenium and nitrenium ions. While the
reactivity and selectivity of arylnitrenium ions1 have been well
studied and in particular their carcinogenic activity,2 the chem-
istry of aryloxylium ions is less well understood. Aryloxylium
ions are intermediates in a number of reactions such as phen-
olic oxidations as shown by Pelter and co-workers3 and they
have also been implicated in biological processes such as iso-
flavone synthesis.4 The positive charge is not stable on the oxy-
gen and can be delocalised on to the ortho and para positions on
the ring5 (Scheme 1). Thus, nucleophiles generally react at the
Results and discussion
Products of reaction
The aryloxylium ion precursors, 4-bromo-2,4,6-trimethylcyclo-
hexa-2,5-dienone 3 (60%) and 4-bromo-2,4,6-tri-tert-butyl-
cyclohexa-2,5-dienone 7 (52%) were synthesised in good yield
via an electrophilic bromination of the starting phenols9
(Scheme 2).
Scheme 2
The bromide 3 was very unstable, decomposing to 3-bromo-
mesitol (3-bromo-2,4,6-trimethylphenol, 9) via the acid-
catalysed dienone–phenol rearrangement9 in non-aqueous
solution and to 4-bromomethyl-2,6-dimethylphenol (8) when
stored in the solid state.9 Therefore it was important to establish
initially the course of the reactions of 3 and 7 under good
ionizing conditions using acetonitrile–water mixtures. The
possible competing reactions of 3 in solution are shown in
Scheme 3.
A repetitive scan from 200 to 350 nm in 80 : 20 acetonitrile–
water indicates that the reaction of 3 proceeds cleanly through
a tight isosbestic point without a long-lived intermediate. A
large scale solvolysis reaction in aqueous acetonitrile indi-
cates the formation of only one solvent trapped product,
namely 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dienone 4.
There was no evidence of the ortho trapped product 6-hydroxy-
2,4,6-trimethylcyclohexa-2,4-dienone 10, but there was also
some decomposition of precursor 3 to phenol 8 (less than 10%).
The tert-butyl-substituted precursor 7 was a significantly
more stable precursor than 3, presumably as a result of the
Scheme 1
ring carbons in preference to the oxygen.3,5 Previous work on
these cations has focused on the distribution of products
between attack on the oxygen and attack on the ring carbons.6
Aryloxylium ions have also been generated by electro-
chemical7 and synthetic methods.5,8 The chemical methods
generally involved a leaving group on the oxygen. These leaving
groups have included tosylamines8 and pyridinium tetrafluoro-
borate5 in acidic conditions at high temperature. These pre-
cursors and conditions are not suitable to study the cations in
aqueous acetonitrile at 25 ЊC. Our method was to approach the
cation from a different route by synthesising the 4-bromo-2,4,6-
758
J. Chem. Soc., Perkin Trans. 2, 2001, 758–762
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b009968f

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Table 1 Observed rate constants for the reaction of 3 and 7 in
acetonitrile–water mixtures at 25 ЊC
3
7
% H2Oa
kobs/sϪ1
kobs/sϪ1
10
20
30
40
50
3.05 × 10Ϫ3
1.41 × 10Ϫ2
2.47 × 10Ϫ2
5.12 × 10Ϫ2
1.10 × 10Ϫ1
9.67 × 10Ϫ5
3.22 × 10Ϫ4
4.21 × 10Ϫ4
1.85 × 10Ϫ3
5.43 × 10Ϫ3
a % Water as volume.
Scheme 3
bulky tert-butyl groups blocking the reactive sites. However, in
this case we are concerned that in solution the cation 11 might
undergo a 1,2-methyl migration to form the more stable tertiary
cation (see Scheme 4).
Fig. 1 Grunwald–Winstein plot of log k vs. Y.11 3 (᭹) r = 0.996 and 7
(᭺) r = 0.993.
reactions yield only the cation trapped at the para position. The
products of the other possible reactions, if present, could have
1
been easily distinguished by H NMR analysis of the crude
reaction mixture and by the availability of their proton
chemical shifts.
Solvent and common ion effects
In order to identify both the reaction mechanism involved in
the conversion of 3 to 4 and 7 to 12 and the possible aryl-
oxylium ion intermediates, solvent and common ion effects
were examined. The observed pseudo-first-order rate constants
(Table 1) were measured at fixed wavelength against time scans
at 251 (3) and 255 nm (7). The observed rate constants
increased by a factor of 36 (3) and 56 (7) as the solvent polarity
was increased from 10 to 50% H2O. This increase was small
compared with previously observed values for reactions passing
through a compact cationic intermediate. A Grunwald–
Winstein plot10 (Fig. 1) measured the sensitivity of the reaction
to solvent polarity giving ms = 0.56 (3) and ms = 0.64 (7). These
values are significantly lower than those observed for simple
carbocation formation. For example, the tert-butyl cation has
an ms value of 1.0010 and reactions proceeding through tertiary
cationic intermediates usually have ms values of between 0.8
and 1.2.
The presence of an intermediate aryloxylium ion formed in
an SN1 reaction was unambiguously established however by the
observation of a common ion effect (Fig. 2). Addition of
sodium bromide resulted in a measurable rate depression in
80 : 20 acetonitrile–water at constant ionic strength (µ = 0.10
M). The slope of the lines in Fig. 2 (1/kobs vs. [NaBr]) gives the
mass law constants α = 22.1 (3) and α = 33.3 (7) respectively.
The rate constant for ionisation in the absence of added
bromide was calculated from the intercept of the plot as
kion = 1.19 × 10Ϫ2 sϪ1 for 3 and kion = 4.25 × 10Ϫ4 sϪ1 for 7 in 80%
acetonitrile–20% water. The mass law constants for 3 and 7
show that the selectivities of the cations 2 and 11 are similar.
The tert-butyl group does not increase the intrinsic stability and
therefore the selectivity of the cation 11 greatly, but it does slow
Scheme 4
A repetitive scan of the UV spectrum of 7 from 200 to
350 nm undergoing reaction in 80 : 20 acetonitrile–water
again indicates that the reaction proceeds cleanly, with a tight
isosbestic point, showing the absence of a long-lived inter-
mediate capable of shifting the isosbestic point. Large scale
solvolysis in aqueous acetonitrile yielded 4-hydroxy-2,4,6-tri-
tert-butylcyclohexa-2,5-dienone (12) as the sole product. Again
there was no solvent ortho trapped product and there was no
1,2-methyl migration to form 4-methylcyclohexa-2,5-dienone
14 under these conditions as shown by 1H NMR analysis. This
indicates that there is only one reactive site on the ring. These
J. Chem. Soc., Perkin Trans. 2, 2001, 758–762
759

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From the slope of the line in Fig. 3 the kaz : kMeOH ratio
was calculated to be 3610 MϪ1. Assuming that azide attack is
diffusion controlled (kaz = 5 × 109 sϪ1
M
Ϫ1) then the absolute
value of kMeOH = 1.4 × 106 sϪ1. From competition studies with
a solvent consisting of 80% acetonitrile, 10% MeOH and 10%
H2O, the ratio of kMeOH : kH O was calculated by determining
2
the ratio of integration of vinylic peaks at 6.59 ppm 12 and 6.54
ppm 17. The kMeOH : kH O ratio was calculated to be 0.755
2
[eqn. (3)].
kMeOH/kH O = ([17]/[12])([H2O]/[MeOH])
(3)
2
This is unexpected since MeOH is generally a superior nucleo-
phile for cations than is water. We attribute this inverse result to
the steric bulk of the tert-butyl groups, which preferentially
slows the methanol attack.
Fig. 2 Common ion effect 1/kobs vs. [NaBr] in 80% acetonitrile and
20% water for 1 (᭹) r = 0.964 and 7 (᭺) r = 0.977. 1/kobs for 7 divided by
50 for ease of presentation.
When the tert-butyl groups were replaced with methyl groups
the kMeOH : kH O ratio for the trapping of 2 was found to be
2
1.56. This shows the reduced steric hindrance of the methyl
group in this cation relative to the tert-butyl groups resulting in
the expected rates of methanol attack relative to water attack.
The kMeOH : kH O ratio is however low when compared with the
2
4-methylbenzyl cation that has a kMeOH : kH O ratio of 2.1.13
2
The selectivities of the cations 2 and 11 are low indicating
that the cations are unstable. The absolute value of kMeOH is
1.4 × 106 sϪ1 and this allows kH O to be calculated for 11 from
the ratio of kMeOH : kH O and k2H O was found to be 1.8 × 106
s
Ϫ1. This value allowed2us to calc2ulate the lifetime of cation 11
in water to be 0.55 µs. This oxocyclohexadienylium ion there-
fore has a similar lifetime to nitrenium ions14 in water such as
4-ethoxyphenylnitrenium ion which has a lifetime of 0.55 µs.
Reduction of dienones to phenols in propan-2-ol
The solvolysis of 7 in pure methanol gave the corresponding
4-methoxy derivative (17) as the sole product after 48 hours
(yield by H NMR analysis). The slow solvolysis of 3 and 7 in
Fig.
3
Azide trap (1/Faz vs. 1/[NaN3]) for 7. Solvent 50 : 50
acetonitrile–MeOH. Ionic strength was maintained at 0.015 M with
NaClO4 (r = 0.995). Product ratios were calculated from 1H proton
NMR analysis.
1
propan-2-ol did not yield the corresponding 4-isopropoxy
trapped product, instead mesitol (5) and 2,4,6-tri-tert-butyl-
phenol (6) were formed respectively. In the case of 7 the yield of
phenol was 13% with the remainder being unreacted starting
material after 48 hours. The rate of formation of phenol in this
solvent was sensitive to solvent polarity. In 50 : 50 acetonitrile–
propan-2-ol the yield of the reaction was 26% after 42 hours.
In 75 : 25 acetonitrile–propan-2-ol the yield was 49% after
42 hours, reflecting the increased yields as the ionizing power
of the medium was increased. The oxocyclohexadienylium
ion was not trapped by acetonitrile in a Ritter type reaction.15
The reduction was suppressed by the addition of competing
unhindered nucleophiles such as sodium azide and water, which
trapped the cation at the 4-position.
down the initial ionisation step, possibly due to the prevention
of solvent assistance by steric hindrance. These results parallel
those of Richard and co-workers who have shown that rates of
formation of α-substituted 4-methoxybenzyl cations vary con-
siderably but that the lifetime and trapping of the cations are
relatively unaffected by structure.12
Azide trap and lifetimes
The azide trap was used to calculate the ratio of azide attack to
solvolysis by methanol (Fig. 3) of 7 in 50 : 50 acetonitrile–
methanol mixtures (µ = 0.015 M). The product ratios were
determined by the ratio of integration for the vinylic hydrogens
at 6.59 (azide 16) and 6.54 ppm (methoxy 17). The fraction of
azide product was determined according to eqn. (1) and the
results were fitted to eqn. (2).
The mechanism of reduction could possibly involve a hydride
transfer from the propan-2-ol to the oxocyclohexadienylium
ion intermediate forming acetone, followed by aromatisation of
the dienone 15 to the phenol 6 (Scheme 5) or by direct hydride
transfer to the oxygen. An alternate mechanism involving
heterolysis of 3 and 7 to the anion and the bromonium ion is
also possible. However, careful 1H NMR experiments in
CD3CN in a sealed tube with benzene as a marker did not show
the presence of any acetone after the reaction had reached
completion. There was no formation of bromobenzene or
hypobromous products to support the bromonium ion mechan-
ism. In a separate experiment, the bromo compound 7 was also
stirred over seven days in 80 : 20 acetonitrile–cyclohexanol.
Cyclohexanol was used was used in place of propan-2-ol
because its high boiling point (158–162 ЊC) would prevent
the problem of evaporation of the possible ketone product as
the experiment proceeded. The reaction was complete with the
(1)
1/Faz = 1.00 + kMeOH[H2O]/kaz[NaN3]
(2)
Because the azide 16 and the hydroxy product 12 have similar
1H NMR spectra, the possibility of a product resulting from
water attack contributing to the product ratio was precluded by
careful IR and 13C NMR analysis. The characteristic hydroxy
peak at 3482 cmϪ1 in the infra-red spectra was absent in the
isolated crude mixture. Again from analysis of the H NMR
there was only attack at the para carbon with no evidence for
any attack at the ortho positions.
1
1
phenol 6 formed in quantitative yield (by H NMR analysis).
2,4-Dinitrophenylhydrazine was added to trap any cyclo-
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Experimental
General
Mesitol, 2,4,6-tri-tert-butylphenol, potassium bromide and
sodium bromide were commercially available and were used
without further purification. All solvents were HPLC grade
except diethyl ether. Solvents were dried by the standard liter-
ature procedures17 where indicated. The acetonitrile–water
mixtures were made from acetonitrile and doubly distilled
deionised water. The compositions in the text refer to a ratio of
volumes. Stock solutions of 3 and 7 were made up in dry
acetonitrile to 0.01 mol dmϪ3. Kinetics were monitored
spectrophotometrically using a Philips PU 8700 spectro-
photometer at 251 and 255 nm for compounds 3 and 7 respec-
tively. In all cases the rates were studied under pseudo-first-
order conditions by injecting 20 µl of stock solution into 2 cm3
acetonitrile–water mixtures for a final concentration of ca. 10Ϫ4
mol dmϪ3. Kinetic experiments were followed for seven half
lives and were repeated in triplicate. All rate constants agreed to
within 5%. In the common ion and azide trap experiments the
sodium salt was used in the amounts referred to in the text
(Figs. 2 and 3), and constant ionic strength was maintained
at 0.10 M and 0.015 M respectively with sodium perchlorate.
1H NMR spectra were recorded at 270 MHz on a JEOL
JMN-GX270 FT or a Varian Unity Inova 300 MHz spectro-
meter using CDCl3 as solvent and tetramethylsilane as a refer-
ence. Chemical shifts are quoted in ppm and coupling constants
in hertz. Infra-red spectra were run on a Galaxy Series FTIR
3000 and the samples were prepared using KBr discs.
Scheme 5
hexanone formed. On work-up, 1H NMR analysis showed that
there was no evidence for the formation of the correspond-
ing hydrazone of cyclohexanone. A control reaction of 2,4-
dinitrophenylhydrazine with cyclohexanone formed the desired
hydrazone as a yellow solid. The demonstration using 1H NMR
experiments and the attempted trapping with 2,4-dinitro-
phenylhydrazine indicate that there was no formation of the
corresponding ketones. The reduction of dienone 7 to phenol 6
proceeded in 50 : 50 acetonitrile–tert-butyl alcohol in a yield of
20% after 48 hours. The experimental evidence presented here
precludes a hydride transfer from the secondary alcohol to the
aryloxylium ion as the route to the reduction products, the
corresponding phenols.
In summary, the aryloxylium ions 2 and 11 were generated
in acetonitrile–water mixtures from precursors 3 and 7. The
aryloxylium ion is an unstable cation with the positive charge
effectively located on the para position with little delocalisation
of charge to other sites as judged by exclusive attack of
nucleophiles at the para position. This can be attributed to the
destabilising effect of the adjacent carbonyl when the positive
charge is located on the ortho position. The resonance contribu-
tor 2c is therefore more important than either 2b or 2d. This is
similar to biphenyl-4-ylnitrenium ions where semi-empirical
computer models indicate that attack at the ortho carbon is
thermodynamically favoured but that attack of water shows a
kinetic preference for attack at the para carbon.16 The aryl-
oxylium ion may be viewed as a carbonyl-destabilised cation.
The instability of the cation is reflected in the low sensitivity to
changes in solvent polarity and the small, but significant, com-
mon ion rate depression. The kMeOH : kH O ratio from competi-
tion studies, which was found to be 1.56 a2nd 0.755 for 3 and 7, is
smaller than that observed for other cations13 and is due to the
4-Bromo-2,4,6-trimethylcyclohexa-2,5-dienone (3)
Mesitol (1.36 g, 0.01 mol) was dissolved in diethyl ether
(20 cm3) and ten drops of pyridine in a 100 cm3 round-
bottom flask. Bromine (0.52 cm3, 1.2 mol) was dissolved in
water (20 cm3) containing potassium bromide (4.8 g) in a 50 cm3
flask. The reaction vessel was cooled to Ϫ20 ЊC on an ice–salt–
acetone bath. The bromine solution was slowly added to the
phenol solution with stirring over five to ten minutes. The reac-
tion mixture initially turned yellow, then orange, as the reaction
proceeded. After the addition was complete the reaction mix-
ture was allowed to stir for ten minutes. The reaction was
quenched in cold saturated sodium bicarbonate. The organic
layer was removed and dried over MgSO4. After filtration the
solvent was removed in vacuo at 0 ЊC to give 4-bromo-2,4,6-
trimethylcyclohexa-2,5-dienone (3) 9 as a yellow solid (1.296 g,
60%); δH (270 MHz) 1.91 (3H), 1.94 (6H), 6.87 (2H).
The dienone was made up to 0.01 mol dm3 in dry acetonitrile
and used in experiments within 4 h as it decomposes in solution
to 3-bromomesitol, mesitol and 4-bromomethyl-2,6-dimethyl-
phenol.
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7)
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) was pre-
pared in a similar manner with 2,4,6 tri-tert-butylphenol (2.62
g, 0.01 mol) as starting material. After removal of solvent at
0 ЊC in vacuo the solid was recrystallised with petroleum ether
(40–60 ЊC) to give 4-bromo-2,4,6-tri-tert-butylcyclohexa-2,5-
dienone (7) as yellow crystals (1.773 g, 52%); mp 80–81 ЊC
(lit.,18 80–81 ЊC); νmax/cmϪ1 1659 s (C᎐O), 1636 s (C᎐C); δ (270
unstable nature of the cation. The difference in kMeOH : kH O
between 3 and 7 indicates that trapping by solvent is sensitive to
2
᎐
᎐
H
MHz) 1.10 (9H), 1.25 (18H), 6.92 (2H).
the steric hindrance of the tert-butyl group. From the azide
trapping experiments kaz : kMeOH = 3610 MϪ1 and kMeOH : kH O
2
4-Hydroxy-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (12)
the lifetime of the cation 11 in water was found to be 0.55 µs.
With secondary alcohols, instead of trapping by the alcohol, a
slow reduction of 3 and 7 to the phenols 5 and 6 occurs via a
presumed radical mechanism. Future work will focus on the
mechanism of this reduction and on whether aryloxylium ions
are trapped by derivatives of guanine as is the case with the
arylnitrenium ions.3
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (10.0 g,
0.0293 mol) was dissolved in 60% acetonitrile and 40% water
and stirred overnight at 25 ЊC. The solvent was removed and the
white solid was recrystallised in petroleum ether (40–60 ЊC) to
give 4-hydroxy-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (12) as
white needles (7.26 g, 89%); mp 132–134 ЊC (lit.,18 132–134 ЊC);
J. Chem. Soc., Perkin Trans. 2, 2001, 758–762
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νmax/cmϪ1 3482 s (OH), 1659 s (C᎐O), 1625 s (C᎐C); δ (270
NMR Studies of propan-2-ol solvolysis
᎐
᎐
H
MHz) 0.98 (9H), 1.24 (18H), 6.59 (2H).
The reaction was followed in a sealed NMR tube. 4-Bromo-
2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.025 g, 0.0733
mmol) was dissolved in 1 cm3 d3-acetonitrile containing
propan-2-ol (0.021 cm3, 0.22 mmol) and benzene (0.013 cm3,
0.147 mmol). The reaction was followed over 24 hours by
analysing the 1H NMR as the reaction proceeded. A 300 MHz
1H NMR showed only one product after 24 hours, the phenol 6
(7.20 ppm). There was no evidence for acetone formation or the
products of a bromonium ion.
4-Methoxy-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (17)
This compound was prepared by the solvolysis of 7 (5.00 g,
0.0147 mol) in methanol at 25 ЊC overnight. The solvent was
removed to give 4-methoxy-2,4,6-tri-tert-butylcyclohexa-2,5-
dienone (13) as an orange solid. The product was recrystallised
in methanol to yield yellow needles (4.13 g, 94%); mp 58–59 ЊC
(lit.,20 58–59 ЊC); νmax/cmϪ1 2958 s (CH), 1658 s (C᎐O), 1645 s
᎐
(C᎐C); δ (270 MHz) 0.95 (9H), 1.20 (18H), 6.54 (2H).
᎐
H
Reduction of 7 in acetonitrile–cyclohexanol mixtures
4-Azido-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (16)21
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.129 g,
0.0381 mmol) was dissolved in 20 cm3 80 : 20 acetonitrile–
cyclohexanol. The reaction was stirred over seven days at 25 ЊC
in duplicate. The solvent was removed yielding a solid in the
first reaction. A 300 MHz 1H NMR showed the phenol 6 (7.20
ppm) as the sole product. 2,4-Dinitrophenylhydrazine (0.0755
g, 0.0381 mmol) was added to the second reaction mixture and
stirred at 25 ЊC overnight. The solvent was removed yielding a
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (1.35 g,
0.0039 mol) was dissolved in dry acetonitrile with excess
sodium azide (0.515 g, 0.0079 mol) and stirred overnight (0.843
g, 70%); mp 40–41 ЊC (lit.,21 40–40.5 ЊC); νmax/cmϪ1 2096 s (N3),
1675 s (C᎐O), 1645 s (C᎐C); δ (300 MHz) 0.90 (9H), 1.26
᎐
᎐
H
(18H), 6.59 (2H).
Competition reactions in water–methanol mixtures
1
red solid. A 300 MHz H NMR did not show any evidence of
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.020 g,
0.0587 mmol) was dissolved in 10 cm3 80% acetonitrile, 10%
water and 10% methanol. The reaction was stirred overnight at
25 ЊC. The solvent was removed, yielding a solid. A 300 MHz
1H NMR showed the presence of two products, the hydroxy 12
hydrazone formation. A sample of the hydrazone was pre-
pared (for comparison) as follows. 2,4-Dinitrophenylhydrazine
(0.0755 g, 0.0381 mmol) was dissolved in 20 cm3 80 : 20
acetonitrile–cyclohexanol. Cyclohexanone (0.040 cm3, 0.0381
mmol) was added to the reaction mixture and the reaction was
allowed to stir overnight at 25 ЊC. The solvent was removed
yielding the yellow hydrazone as the sole product. δH (300
MHz) 1.80 (6H, m), 2.45 (4H, m), 7.96 (1H, d, J = 9.37), 8.28
(1H, dd, J = 9.665, 2.636), 9.12 (1H, d, J = 2.343).
(6.59 ppm) and the methoxy 17 (6.54 ppm); kMeOH : kH O was
2
calculated using eqn. (3).
Solvolysis of 7 in propan-2-ol
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.100 g,
0.0587 mmol) was dissolved in 10 cm3 propan-2-ol. The reac-
tion was stirred for 48 hours at 25 ЊC. The solvent was removed
yielding a solid. A 300 MHz 1H NMR showed the presence of
two products, the bromo 7 (6.92 ppm) 87% and the phenol 6
(7.20 ppm) 13%. Yields were calculated by 1H NMR analysis.
Acknowledgements
We would like to thank Enterprise Ireland for a Basic Research
Scholarship and Dublin Corporation for their financial support
to JPK.
Reduction of 7 in acetonitrile–propan-2-ol mixture
References
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.100 g,
0.029 mmol) was dissolved in 20 cm3 50 : 50 (and in a separate
experiment 75 : 25) acetonitrile–propan-2-ol. The reaction was
stirred for 42 hours at 25 ЊC. The solvent was removed yielding
a solid. Both reactions yielded two products, the phenol 6 and
starting material 7. The yield of phenol 6 was 26% in the case of
the 50 : 50 mixture and 49% in the case of the 75 : 25 mixture.
1 J. C. Fishbein and R. A. McClelland, Can. J. Chem., 1996, 74, 1321.
2 (a) S. A. Kennedy, M. Novak and B. A. Kolb, J. Am. Chem.
Soc., 1995, 117, 574; (b) R. McClelland, A. Ahmad, A. P. Dicks and
V. E. Licence, J. Am. Chem. Soc., 1999, 121, 3303.
3 L. Kurti, P. Herczegh, J. Visy, M. Simonyi, S. Antus and A. Pelter,
J. Chem. Soc., Perkin Trans. 1, 1993, 1891.
4 A. Pelter, Tetrahedron Lett., 1968, 1, 897.
1
Yields were determined by H NMR analysis of peaks at 7.20
ppm for 6 and 6.92 ppm for 7.
5 R. A. Abramovitch, G. Alvernhe, R. Bartnik, N. L. Dassanayake,
M. N. Inbasekaran and S. Kato, J. Am. Chem. Soc., 1981, 103, 4558.
6 H. Iijima, Y. Endo, K. Shudo and T. Okamoto, Tetrahedron, 1984,
40, 4981.
Reduction of 7 in acetonitrile–tert-butyl alcohol mixture
7 A. Rieker, R. Beisswenger and K. Rieger, Tetrahedron, 1991, 47, 645.
8 W. R. Dolbier, L. Celewicz and K. Ohnishi, Tetrahedron Lett., 1989,
30, 4929.
9 A. Fischer and G. N. Henderson, Can. J. Chem, 1984, 61, 1045.
10 E. Grunwald and S. J. Winstein, J. Am. Chem. Soc., 1948, 70, 846.
11 T. W. Bentley, J. P. Dau-Schmidt, G. Llewellyn and H. Mayr, J. Org.
Chem., 1992, 57, 2387.
12 T. L. Amyes, I. W. Stevens and J. P. Richard, J. Org. Chem., 1993, 58,
6057.
13 A. Thibblin, J. Org. Chem., 1993, 58, 7427.
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.100 g,
0.029 mmol) was dissolved in 20 cm3 50 : 50 acetonitrile tert-
butyl alcohol. The reaction was stirred for 48 hours at 25 ЊC.
The solvent was removed yielding a solid. The reaction yielded
two products, the phenol 6 and starting material 7. The yield of
phenol 6 was 20% with the remainder being unreacted starting
material. Yields were determined by 1H NMR analysis of peaks
at 7.20 ppm for 6 and 6.92 ppm for 7.
14 M. Novak, M. J. Kahley, E. Eiger, J. S. Helick and H. E. Peters,
J. Am. Chem. Soc., 1993, 115, 9453.
Competition reactions in water–propan-2-ol mixture
15 A. B. Suttie, Tetrahedron Lett., 1969, 12, 953.
16 R. A. McClelland, D. Ren, D. Ghobrial and T. A. Gadosy, J. Chem.
Soc., Perkin Trans. 2, 1997, 451.
17 D. D. Perrin and W. L. F. Armarego, Purification of Laboratory
Chemicals, Pergamon Press, Oxford, 3rd edn., 1988.
18 P. Ronlon and V. D. Parker, J. Chem. Soc. C, 1971, 3214.
19 E. Mueller and K. Ley, Chem. Ber., 1955, 88, 601.
20 E. L. Dreher, H. Greisel, M. H. Khalifa and A. Rieker, Synthesis,
1978, 851.
4-Bromo-2,4,6-tri-tert-butylcyclohexa-2,5-dienone (7) (0.075 g,
0.22 mmol) was dissolved in 20 cm3 of 80 : 20 propan-2-ol–
water. The reaction was stirred overnight at 25 ЊC. The solvent
was removed yielding a solid. A 300 MHz 1H NMR showed the
presence of three products. The 80 : 20 solvent mixture gave a
product ratio of the phenol 6 (5%), starting material 7 (25%)
and 4-hydroxydienone 12 (70%). Yields were determined by 1H
NMR analysis of peaks at 7.20 ppm for 6, 6.92 ppm for 7 and
6.59 ppm for 12.
21 G. Fukata, N. Sakamoto and M. Tashiro, J. Chem. Soc., Perkin
Trans. 1, 1982, 2841.
762
J. Chem. Soc., Perkin Trans. 2, 2001, 758–762