Alkylation of p-cresol with camphene in the presence of aluminum-containing catalysts

Article abstract of DOI:10.1134/S106816201107003X

Alkylation of p-cresol with camphene was studied in the presence of aluminum-based catalysts (i-PrO)₃Al, AlH₃, AlCl ₃, (i-Bu)₂AlH, EtAlCl₂, and LiAlH₄. Aluminum isopropylate was a selective catalyst for the preparation of ortho-isobornylphenol, its activity being close to that of aluminum phenolate. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S106816201107003X

ISSN 1068ꢀ1620, Russian Journal of Bioorganic Chemistry, 2011, Vol. 37, No. 7, pp. 855–857. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.Yu. Chukicheva, I.V. Fedorova, O.A. Shumova, A.V. Kutchin, 2010, published in Khimija Rastitel’nogo Syr’ja, 2010, No. 4, pp. 63–66.
LOWꢀMOLECULARꢀWEIGHT
COMPOUNDS
Alkylation of pꢀCresol with Camphene in the Presence
of AluminumꢀContaining Catalysts
I. Yu. Chukicheva1, I. V. Fedorova, O. A. Shumova, and A. V. Kutchin
Institute of Chemistry, Komi Research Center, Ural Branch of Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar 167982, Russia
Received February 24, 2010
Abstract—Alkylation of
p
ꢀcresol with camphene was studied in the presence of aluminumꢀbased catalysts
ꢀBu)2AlH, EtAlCl2, and LiAlH4. Aluminum isopropylate was a selective catalyst
(
iꢀPrO)3Al, AlH3, AlCl3, (
i
for the preparation of orthoꢀisobornylphenol, its activity being close to that of aluminum phenolate.
Keywords: alkylation, camphene, cresol, terpenophenols
DOI: 10.1134/S106816201107003X
1
INTRODUCTION
occasionally, twoꢀdimensional NMR spectra (COSY
and HETCORR).
Certain aluminumꢀcontaining homogeneous cataꢀ
To purify the initial terpenophenols and analyze
volatile products, gas chromotography on a Shimadzu
GCꢀ2010AF chromatograph equipped with a flame
lysts, primarily aluminum phenolate, manifest high
selectivity in phenol orthoꢀalkylation reactions. The
use of aluminumꢀderived catalysts for phenol alkylaꢀ
tion has been described in many publications. The
most common are aluminum phenoxides [1, 2],
isobutelene fractions, 2ꢀsubstituted alkenes as olefins
[3–5]. The reaction is normally highly regioselective
and results in high product yields. As was reported,
aluminumꢀcontaining compounds interact smoothly
with phenols to give mixed aluminum phenoxides [6].
The use as alkylating reagents of terpeneꢀderived
compounds characterized by the tendency toward varꢀ
ious backbone rearrangements make these reactions
very peculiar and single terpenophenols out from the
entire class of alkylphenols.
ionization detector was performed using an SLBTM
ꢀ
5ms column (Supelco) (60 m
phase: poly{5% diphenyl/95% dimethylsiloxane};
temperature: 135–255 and 85–250 C; heating:
C/min) and helium as the carrier gas.
Thinꢀlayer chromatography was carried out on
× 0.25 mm, 0.5 μm;
°
6°
Sorbfil plates eluted with hexane, 5 : 1 hexane–ether,
and 3 : 1 hexane–ether. The products were separated
by column chromatography on silica gel (70/230
Alfa Aesar).
μm,
Alkylation of
cedure). Initial
at a 2 : 1 mol/mol ratio in all the experiments.
Calculated amounts of ꢀcresol , camphene 2,
p
ꢀcresol with camphene (general proꢀ
p
ꢀcresol and camphene were taken
1
2
Earlier we found that alkylation of pꢀcresol with
camphene in the presence of aluminum cresolate led
to orthoꢀisobornylphenols in high yields (84%) [7]. It
seemed important to compare the effect of various aluꢀ
minumꢀderived compounds for phenol alkylation. In
addition, we set a task of developing a convenient and
effective method to synthesize 2,6ꢀdiisobornylꢀ4ꢀ
methylphenol, which manifests a wide spectrum of
pharmacological activity [8, 9].
p
1
and the catalyst were heated at the given temperature
in a twoꢀhead flask with a thermometer and a reflux
condenser. The reaction was performed until a comꢀ
plete conversion of starting pꢀcresol 1 (GC and TLC
monitoring) was achieved. The reaction mixture was
cooled, dissolved in ether, and washed twice with HCl
solution in order to disintegrate the catalyst. The ether
extract was washed with 5% NaOH for removal of the
unreacted pꢀcresol and then with water to neutral pH.
EXPERIMENTAL
The organic extract was dried with anhydrous Na2SO4,
and the solvent was evaporated under reduced presꢀ
sure. The product mixture was separated by column
chromatography on silica gel (70/230 μm) eluted with
a petroleum ether–ether mixture by increasing the
portion of ether.
1H and 13C NMR spectra were recorded on Bruker
АМꢀ300 spectrometers (working frequencies 75 and
300 MHz, respectively) in CDCl3. As an internal stanꢀ
dard, chloroform resonances (for δH, 7.26 ppm, and
δC, 77.00 ppm) were used. Resonances were ascribed
using 13C NMR spectra in the JMOD mode and,
In the case of LiAlH4 as a catalyst, the reaction did
not proceed according to GC and TLC data.
1
Corresponding author: eꢀmail: chukichevaꢀiy@chemi.komisc.ru.
855

856
CHUKICHEVA et al.
Conditions and products of
pꢀcresol alkylation with camphene in the presence of aluminumꢀbased catalysts
Reaction prodicts, %
Reaction
Conversion
conditions
of
pꢀcresol, %
3(a)
3(b)
3(c)
4(a)
4(b)
4(c)
4(d)
5(a)
5(b)
5(c)
*
(iꢀPrO)3Al
26
180°C, 7 h
150°C, 15 h
140°C, 6 h
100°C, 12 h
99
99
–
–
–
–
–
3
–
–
–
3
12
4
–
4
–
–
–
–
52
29
5
10
26
–
7
18
–
–
–
–
–
AlCl3
11
AlH3
40
91
51
42
–
4
(iꢀBu)2AlH
100
3
44
2
–
–
–
(4ꢀMePhO)3Al + EtAlCl2
150°C, 3 h
(EtAlCl2⎯0.2%)
98
92
1
–
–
–
15
10
–
–
5
1
28
18
10
5
6
16
26
150°C, 3 h
25
–
24
3
–
(EtAlCl2⎯1%)
* Resinification products.
Ethyldichloroaluminum EtAlCl2 (А1, 1 and 0.2%)
was used as a cocatalyst for aluminum cresolate
(4ꢀCH3PhO)3Al).
Alkylation conditions and product yields are shown
in the table. Spectral characteristic of isolated terpeꢀ
RESULTS AND DISCUSSION
In this work, we reported studies of alkylation of
p
ꢀcresol with camphene in the presence of alumiꢀ
1
2
numꢀbased compounds at varied temperatures
nophenols (3–5) corresponded to published data [10]. (Scheme 1 and table).
R
OH
OH
OH
O
R
R
R
cat.
+ 2
+
+
1
2
3(a–c)
4(a–d)
5(a–c)
7
7
9
9
10
8
7
7
10
10
10
2
4
4
5
5
3
3
9
1
9
1
R = (a)
; (b)
; (c)
; (d)
2
2
6
6
1
1
2
H
H
6
4
6
4
5
3
5
3
H
H
8
8
8
The coupling of
p
ꢀcresol
1
and camphene
2
in the
Lewis acid AlCl3 and aluminum organic comꢀ
pounds are more active catalysts providing decreased
reaction temperatures. Although nearly complete
conversion was achieved, the selectivity in the case of
2,6ꢀdiisobornylꢀ4ꢀmethylphenol was rather low. Parꢀ
ticularly, in the presence of AlCl3 as a catalyst, a mixꢀ
presence of aluminum isopropylate performed at
180 C resulted in 69% of dialkylated products (table).
°
2,6ꢀDiisobornylꢀ4ꢀmethylphenol 5(a) was isolated as
a major product in a yield of 52%. The yield of
2ꢀisobornylꢀ4ꢀmethylphenol 4(a) was 26%.
ture of monoalkylꢀ
4
and dialkyl
5
products bearing
) subꢀ
When (
iꢀPrO)3Al was used, a mixed alkoxide of isoꢀ
isobornyl ( ), isocamphyl (
a
b), and isofenchyl (c
propylate and phenolate (
first formed, and then the latter was involved in the
alkylation reaction as a catalyst.
iꢀPrO)3 – nAl(PhO)n were
stituents was formed. Release of HCl also supported
the reduction in the reaction selectivity. The presence
of H+ resulted in intensification of side reactions.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 37
No. 7
2011

ALKYLATION OF
p
ꢀCRESOL WITH CAMPHENE
857
When pyridine or triethylamine were added to the
reaction mixture with the goal of restraining hydroꢀ
chloric acid, alkylation did not proceed. We can
assume that the nitrogen atom coordinated to the aluꢀ
minum atom and prevented phenol alkylation with
camphene within the organized coordination sphere
of aluminum [6].
ACKNOWLEDGMENTS
The authors are grateful to E.N. Zainullina, laboꢀ
ratory of physicochemical methods, Institute of
Chemistry, Komi Research Center, Ural Branch, Rusꢀ
1
sian Academy of Sciences, for recording of H and
13C NMR spectra. The work was supported by the
Federal Agency for Science and Innovations, contract
no. 02.740.11.0081.
In the presence of hydrides AlH3 and (
the initial phenol interacted with the hydrids to give a
mixed complex, for example, ( ꢀBu)2 – nAl(PhO)n,
iꢀBu)2AlH,
i
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perature to 100°C. The major products under these
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Alkylation of
in the presence of aluminumꢀbased catalysts
РrО)3Аl, АlН3, АlСl3, ( ꢀBu)2AlH, EtAlCl2, and
pꢀcresol with camphene was studied
(
iꢀ
i
LiAlH4. Aluminum phenolate was found to be the
most selective catalyst among the tested compounds.
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Khim. Rastit. Syr’ya, 2009, no. 3, pp. 63–68.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 37
No. 7
2011