Alkylation of pyrocatechol in tert-butyl alcohol-sulfuric acid-benzene

Article abstract of DOI:10.1134/S1070428011090089

Alkylation of pyrocatechol with tert-butyl alcohol in benzene in the presence of sulfuric acid gave 3,5-di-tert-butylbenzene-1,2-diol in a higher yield than in analogous reaction with tert-butyl alcohol. This result was rationalized by reduction of inhibitory effect of liberated water, formation of heterogeneous system, and occurrence of the alkylation process in nonpolar organic phase. Intermediate products were identified and found to undergo intra- and intermolecular tert-butyl group transfer with formation of more stable 3,5-di-tert-butylbenzene-1,2-diol. The formation of p-di-tert-butylbenzene indicated participation of benzene in crossalkylation processes. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011090089

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1310–1312. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.B. Vol’eva, T.I. Prokof’eva, I.S. Belostotskaya, N.L. Komissarova, D.B. Gorbunov, L.N. Kurkovskaya, 2011, published in Zhurnal
Organicheskoi Khimii, 2011, Vol. 47, No. 9, pp. 1293–1295.
Alkylation of Pyrocatechol in tert-Butyl Alcohol–
Sulfuric Acid–Benzene
V. B. Vol’eva, T. I. Prokof’eva, I. S. Belostotskaya, N. L. Komissarova,
D. B. Gorbunov, and L. N. Kurkovskaya
Emanuel’Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 119334 Russia
e-mail: komissarova@polymer.chph.ras.ru
Received February 4, 2011
Abstract—Alkylation of pyrocatechol with tert-butyl alcohol in benzene in the presence of sulfuric acid gave
3,5-di-tert-butylbenzene-1,2-diol in a higher yield than in analogous reaction with tert-butyl alcohol. This result
was rationalized by reduction of inhibitory effect of liberated water, formation of heterogeneous system, and
occurrence of the alkylation process in nonpolar organic phase. Intermediate products were identified and
found to undergo intra- and intermolecular tert-butyl group transfer with formation of more stable 3,5-di-tert-
butylbenzene-1,2-diol. The formation of p-di-tert-butylbenzene indicated participation of benzene in cross-
alkylation processes.
DOI: 10.1134/S1070428011090089
A procedure for the alkylation of pyrocatechols is
based on their reaction with tertiary alcohols in the
presence of protic acids. Most frequently, sulfuric and
phosphoric acids are used, as well as polymeric sul-
fonic acids. Alcohol acts as reagent and solvent. These
reactions are selective, and the only product is 3,5-di-
tert-alkylbenzene-1,2-diol; however, the yield does not
exceed 55–60% [1], presumably because of inhibitory
effect of water liberated during the process (Scheme 1).
phases (aqueous alcohol and benzene), and the equilib-
rium is displaced toward the products. Alkylation of
the substrate occurs at the phase boundary, and in-
hibitory effect of water is weakened.
Specific feature of the process in mixed medium is
generation in situ of a new acid catalyst, 4,6-di-tert-
butyl-2,3-dihydroxybenzenesulfonic acid (II), as well
as formation of a number of intermediate alkyl-substi-
tuted benzenediols III–VI and p-di-tert-butylbenzene
(Scheme 2) which are capable of undergoing intra- and
intermolecular alkyl group transfer. This was con-
firmed experimentally using 4-tert-butylbenzene-1,2-
diol (V) and 3,6-di-tert-butylbenzene-1,2-diol (IV) as
initial compounds. In both cases, the final product was
3,5-di-tert-butylbenzene-1,2-diol (I). Exchange of tert-
butyl groups between different tert-butyl-substituted
pyrocatechol derivatives was also revealed. For ex-
ample, compound I was formed in a solution of ben-
zenediols II and V in benzene in the absence of tert-
butyl alcohol. Benzene also participates in the cross-
alkylation process, as follows from the presence of
p-di-tert-butylbenzene in the reaction mixtures. The
ability of benzene to take up tert-butyl groups may be
utilized for mild dealkylation of tert-butyl-substituted
hydroxyaromatic compounds, which extends the po-
tential of positional tert-butyl protection. Compounds
I–VI underwent complete dealkylation by the action of
Scheme 1.
t-BuOH + H2SO4
t-BuOH2 HSO4
IP1
Me3C HSO4 + H2O
IP2
We examined the alkylation of pyrocatechol with
tert-butyl alcohol in the presence of sulfuric acid and
found that the yield of 3,5-di-tert-butylbenzene-1,2-
diol (I) can be considerably increased (up to 90%) by
carrying out the reaction in a mixture of tert-butyl
alcohol with benzene. Presumably, the presence of
benzene enhances hydrolytic stability of the alkylating
agent generated by reaction of t-BuOH with H2SO4.
Liberation of water in the binary system t-BuOH–
benzene affects the state of phase equilibrium, prod-
ucts of reversible reaction are distributed over different
1310

ALKYLATION OF PYROCATECHOL
1311
Scheme 2.
Bu-t
Bu-t
Bu-t
OH
OH
OH
OH
OH
OH
OH
H2SO4, PhH
+
t-BuOH
+
+
t-Bu
OH
t-Bu
SO3H
I
II
III
Bu-t
Bu-t
Bu-t
OH
OH
OH
OH
OBu-t
+
+
+
+
t-Bu
OH
Bu-t
IV
V
VI
H2SO4 in benzene with formation of an equivalent
amount of p-di-tert-butylbenzene (Scheme 3).
chols III and IV are formed via rearrangement of ether
VI with migration of tert-butyl group from the oxygen
atom to the nearest position in the benzene ring rather
than by direct alkylation.
Scheme 3.
Bu-t
Bu-t
Compounds III and IV were not detected in the
alkylation carried out in tert-butyl alcohol; their pos-
sible precursor, ether VI, was not detected as well. The
observed differences may be related to different struc-
tures of ion pairs formed by reaction of t-BuOH with
H2SO4 in t-BuOH (water-separated ion pair IP1) and
in benzene (dehydrated ion pair IP2; see Scheme 1).
Ion pair IP2 is a harder electrophile which is capable
of reacting at the oxygen atom of the hydroxy group as
a harder nucleophilic center of pyrocatechol.
OH
OH
OH
OH
H2SO4, PhH
+
Bu-t
Bu-t
In addition, intermediate isomerization and partial
dealkylation products, namely compounds I, III, and
V, are formed. The composition of the reaction mix-
ture and its variation during the process were moni-
tored by TLC using authentic samples. Compounds I–
VI are characterized by clearly different Rf values and
colors of spots developing on exposure of chromato-
grams to air [2]. It was especially interesting that we
succeeded in detecting in the reaction mixtures ortho-
substituted pyrocatechols III and IV; formation of the
latter in protic medium was not reported previously.
Compounds III and IV were synthesized by alkylation
of pyrocatechol with isobutylene catalyzed by titanium
bis-pyrocatechol complex [3]. Here, the selectivity of
ortho-alkylation is ensured by coordination of the sub-
strate and alkylating agent to the metal ion. The proc-
ess may be regarded as intracomplex transfer of the
substituting group.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
WH-250 spectrometer (250 MHz) from solutions in
CDCl3 using tetramethylsilane as internal reference.
Thin-layer chromatography was performed on Silufol
UV-254 plates using hexane–diethyl ether (15:1) as
eluent.
Pyrocatechol was purified by vacuum sublimation.
Commercially available benzenediols I and V and
p-di-tert-butylbenzene were used as reference com-
pounds. Pyrocatechols III and IV were synthesized by
alkylation of pyrocatechol with isobutylene catalyzed
by titanium bis-pyrocatechol complex according to the
procedure described in [2].
Selective ortho-substitution in the series of hy-
droxyaromatic compounds is also possible as a result
of intramolecular rearrangements of compounds sub-
stituted at the hydroxy group with migration of the
substituent into the ortho position of the ring (e.g.,
Fries and Claisen rearrangements). It is naturally to
presume that in our case ortho-substituted pyrocate-
Alkylation of pyrocatechol in the system
t-BuOH–H2SO4–benzene. Concentrated sulfuric acid,
10 ml, was added to a solution of 30 g (0.27 mol) of
pyrocatechol in a mixture of 80 ml of tert-butyl
alcohol and 100 ml of benzene, and the mixture was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

VOL’EVA et al.
1312
stirred for 3 h. Samples were withdrawn during the
process for TLC analysis. The reaction mixture initi-
ally contained compounds I (dark red), III (black), V
(light violet), and IV (green–brown), which were iden-
tified by Rf values and color of spots on the chromato-
grams. Pyrocatechol II was not reported previously,
and its isolation and identification are described below.
As the reaction progressed, p-di-tert-butylbenzene ap-
peared in the reaction mixture, while compounds III–
V disappeared. When the reaction was complete, the
mixture contained only p-di-tert-butylbenzene and
compounds I and II. A crystalline product separated
from the solution and was filtered off, washed with
water, and dried. The filtrate was extracted with diethyl
ether, the extract was dried over Na2SO4 and evaporat-
ed, and the residue was combined with the crystalline
product and dissolved in boiling hexane. By slow
cooling of the solution we succeeded in separating
compounds II [precipitated first, 4.5 g (5.6%)] and I
[57 g (92%)], mp 99–100°C [3].
hexane–benzene (5:1). Yield 2.9 g (96%), dark orange
crystals, mp 121°C. 1H NMR spectrum, δ, ppm: 1.26 s
(9H, t-Bu), 1.50 s (9H, t-Bu), 7.16 s (1H). Found, %:
C 55.81; H 6.54. C14H20O5S. Calculated, %: C 56.00;
H 6.67.
Alkylation of benzenediols IV and V in t-BuOH–
H2SO4–benzene was carried out in a similar way. The
results were identical to those obtained in the reaction
with unsubstituted pyrocatechol. Yield of I ~90%.
Dealkylation of compounds I and IV. Concen-
trated sulfuric acid, 1 ml, was added to a solution of
1.1 g (5 mmol) of compound I in 50 ml of benzene.
The mixture was stirred for 1 h, washed with water,
dried over Na2SO4, and evaporated, and the residue
was recrystallized from hexane to isolate 0.88 g (93%)
1
of p-di-tert-butylbenzene with mp 77–78°C. H NMR
spectrum, δ, ppm: 1.30 s (9H, t-Bu), 5.80 s (2H, Harom).
REFERENCES
4,6-Di-tert-butyl-2,3-dihydroxybenzenesulfonic
acid (II) was identified as 2,4-di-tert-butyl-5,6-dioxo-
cyclohexa-1,3-diene-1-sulfonic acid which was ob-
tained by oxidation of II with silver oxide in benzene.
Silver oxide, 7 g (30 mmol), was added to 3.02 g
(10 mmol) of compound II in 50 ml of benzene. The
mixture was stirred for 1 h and filtered, the filtrate was
evaporated, and the residue was recrystallized from
1. Schulze, H. and Flaig, W., Justus Liebigs Ann. Chem.,
1952, vol. 575, p. 231.
2. Belostotskaya, I.S., Komissarova, N.L., Dzhuaryan, E.V.,
and Ershov, V.V., Izv. Akad. Nauk SSSR, Ser. Khim., 1971,
p. 2816.
3. Belostotskaya, I.S., Komissarova, N.L., Dzhuaryan, E.V.,
and Ershov, V.V., Izv. Akad. Nauk SSSR, Ser. Khim., 1972,
p. 1594.
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