γ-hydroxypropylation of 2,6-dialkyl(aryl)phenols with allyl alcohol and its derivatives

Article abstract of DOI:10.1134/S1070363210110101

The composition of the products of the reaction of 2,6-disubstituted phenols with allyl alcohol and its derivatives in an alkaline medium was investigated, the conditions for carrying out the reaction with the predominant formation of 4-(3-hydroxypropyl)-2,6-dialkyl(aryl)phenols were found, and its mechanism was suggested. The reaction was examined on an industrial scale. An important result is the practical demonstration of alkaline catalysis performed under homogeneous conditions with participation of phenols, when the used alkaline catalyst is recovered in the process without the formation of waste waters. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070363210110101

ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 11, pp. 2290–2297. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.P. Krysin, N.U. Khalikova, T.B. Khlebnikova, N.I. Nogina, V.I. Mamatyuk, 2010, published in Zhurnal Obshchei Khimii, 2010,
Vol. 80, No. 11, pp. 1826–1833.
γ-Hydroxypropylation of 2,6-Dialkyl(aryl)phenols
with Allyl Alcohol and Its Derivatives
A. P. Krysina, N. U. Khalikovaa, T. B. Khlebnikovab, N. I. Noginaa, and V. I. Mamatyuka
a Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Akad. Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: benzol@nioch.nsc.ru
b Boreskov Institute of Catalysis, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
e-mail: chleb@catalysis.nsk.ru
Received January 21, 2010
Abstract―The composition of the products of the reaction of 2,6-disubstituted phenols with allyl alcohol and
its derivatives in an alkaline medium was investigated, the conditions for carrying out the reaction with the
predominant formation of 4-(3-hydroxypropyl)-2,6-dialkyl(aryl)phenols were found, and its mechanism was
suggested. The reaction was examined on an industrial scale. An important result is the practical demonstration
of alkaline catalysis performed under homogeneous conditions with participation of phenols, when the used
alkaline catalyst is recovered in the process without the formation of waste waters.
DOI: 10.1134/S1070363210110101
The analysis of the literature data on alkylation of
phenols with olefins containing a double bond conjugated
with functional substituents COOAlk, CN [1], CONH2,
COAlk, CHO [2], ОН [3], reveals the stable interest to
this type of reactions. It can be seen, first of all, in the
research studies aiming at elaboration of selective
methods for the preparation of sterically hindered
phenols with a functional group in the aliphatic chain
of the para-substituent. Such phenols are used as
intermediates in the synthesis of nontoxic additives to
polymers produced on the industrial scale [4] as well
as for preparation of biologically active compounds
[5]. In connection with this, the reaction of 2,6-di-tert-
butylphenol (Iа) with allyl alcohol resulting in the
formation of 4-(3-hydroxypropyl)-2,6-di-tert-butylphenol
IIIа (or γ-propanol) [3] required detailed investigation
in order to reveal its synthetic potential for preparation
of phenols possessing a functional substituent in the γ-
position of the aliphatic chain of the para-substituent.
This investigation is the main goal of the present study.
The reaction of phenols with allyl alcohol is known
to proceed with the formation of ethers, which undergo
the Claisen rearrangement (thermally or catalytically)
into the о- or p-allylphenols [10]. This method was
used for preparation of 4-γ-hydroxypropylphenols in a
considerable amount as described in patent [11], where
it was declared that a new reaction of γ-hydroxyl-
propylation of phenols was discovered by the example
of the reaction of 2,6-di-tert-butylphenol with allyl
alcohol at 180–230°С in the presence of alkali leading
to compound IIIа in 60% yield. This Japanese invent-
tion was published 20 years later than our works had
been done and after we organized the production of
compound IIIа in Russia based on this reaction
[3, 12]. To improve the yield of γ-hydroxypropylphenols,
additional reagents were proposed in [13].
In the first experiments we have found that the
reaction of methyl ether of 2,6-di-tert-butylphenol with
allyl alcohol does not occur either in the absence or in
the presence of alkali. Neither in the alkaline medium
the reaction of 2,6-di-tert-butylphenol with methylallyl
ether nor with the allyl alcohol having two methyl
groups in the α-position takes place. The reaction of
2,6-di-tert-butylphenol with allyl alcohol was realized
when the temperature was raised to 140–170°С in the
4-γ-Hydroxypropylphenols are usually prepared by
reduction of the corresponding esters of 4-hydroxy-
phenylpropionic acids [6, 7] or by the reaction of
compound IIIа with 1,3-propanediol in alkaline
medium [8, 9].
2290

γ-HYDROXYPROPYLATION OF 2,6-DIALKYL(ARYL)PHENOLS
2291
presence of KOH, but the major products were
trisphenol II and bisphenols III, IV–IVа, the products
of condensation of 2,6-di-tert-butylphenol with com-
pounds formed in the process of oxidative trans-
formations of allyl alcohol. The structure of aliphatic
bridges in compounds II–IV is indicative of the nature
of their precursors, which can be acrolein, propionic
aldehyde, and formaldehyde, respectively.
OH
OH
OH
CH2=CHCH2OH
KOH
140−160oC
+
OH
HO
Iа
OH
IIIа
II
OH
R
R
+
HO
OH +
HO
OH
+
n
R1
R1
Alk
IV
Vа−VIIа
R = R1 = t-Bu; n = 1 (Vа), 0 (VIа), 3 (VIIа); Alk = CH3, C3H7.
Apart from phenols II, III, GC analysis of the
reaction mixture revealed the presence of 23% of
compound IIIа. Compound II is poorly soluble in
organic solvents and precipitated during the dissolution
of the reaction mixture. Its formation is favored when
carrying out the reaction in methanol.
The composition of side products also sharply
changed. However, the addition of water into the reac-
tion mass, or decrease of the amount of alkali again
result in the formation of bis- and trisphenols in the
CH2=CHCH2OH
Iа
IIIа + AlkOH
Na-IIIа
85−90%
3%
160−180oC
High exothermicity of this reaction inconspicuous
when performing on a laboratory scale or even in
reactors of up to 5 l capacity, is clearly exhibited under
the condition of industrial production, in reactors of
1 to 3 m3 capacity. In the heated to 160°С reaction
mass, first an inductive period is observed when no
visible changes occur (about 1 h), after which for 15 min
an exothermic process takes place with vigorous heat
evolution leading to the increase of pressure and
temperature in the reactor. This technologically
dangerous period of the reaction can be tracked in due
course and by emergency cooling of the reaction mass
to transfer the process to a smooth regime, without
increasing the pressure in the reactor above 3 at.
OH
OH
+ Vа−VIIа
+
+
O
O
3%
Alk
5−7%
The application of simplex method of mathematical
simulation of the experimental conditions with sub-
sequent realization in practice allowed to substantially
increase the content of γ-propanol IIIа in the reaction
mass, according to GC data, from 20 to 90% [12].
OH
VIII
3%
Alk = CH3, C2H5, n-C3H7.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 11 2010

2292
KRYSIN et al.
reaction. The introduction into the reaction mass of
anhydrous alcohols, methanol, ethanol or isopropanol,
which are the products of transformations of allyl
alcohol in the course of the reaction under
investigation, has no substantial effect on the composi-
tion of the products. This volatile fraction of alcohols
is distilled off from the reactor at atmospheric pressure
in ca. 3% yield. Ester VIII is accumulated in the still,
where its content reaches 30%. Apparently, the
presence of ester VIII known by its high antioxidant
activity [14, 15] is manifested in the properties of the
still bottoms, which, being added to polymers,
provides the required stabilization of the properties of
the polyolefin talc-filled compositions for cables [16].
phenol (Ib) with allyl alcohol in the presence of
sodium salt of 2-methyl-6-tert-butylphenol at 190–
200°С during 2 h. The formed reaction mass contained
72% of compound XI. According to patent [13], the
content of compound IIIb in the reaction mass can be
increased to 80% by addition into the original reaction
mixture of organomagnesium compounds, sodium
metal, and additives of tetraethoxytitanium.
In the reaction of 2,6-xylenol (Ic) with allyl alcohol
in an alkaline medium under the conditions of
synthesis of compound IIIa, along with product IIIc
diphenylmethane Vc is formed in comparable
amounts. The vacuum distillation does not allow the
isolation of compound IIIc from the reaction mixture.
When the temperature of the reaction was lowered to
130–140°С, the ratio IIIc:Vc became 4:1 permitting
the isolation of compound IIIc by simple distillation.
The reaction of 2,6-di-tert-butylphenol with large
excess of allyl alcohol in an alkaline medium proceeds
at the atmospheric pressure at reflux and leads to the
predominant formation of compound IIIa. However,
under industrial conditions this procedure has no te-
chnological advantages: the labor comsumption for the
recovery of highly toxic allyl alcohol increases and the
productivity of the reactor sharply decreases.
The reaction of 2,6-diphenylphenol (Id) with the
excess of allyl alcohol and alkali proceeds at 170°С
and requires a long time. The obtained reaction mass
contains 60% of compound IIId, which was earlier
obtained from 2,6-diphenylphenol in several steps
[18].
In the first stage of γ-oxypropylation of phenols, the
initiator of the reaction, sodium 2,6-di-tert-butyl-
phenolate, is prepared, in the presence of which the
reaction of 2,6-di-tert-butylphenol with allyl alcohol is
performed at 140–170°С. When the reaction is
completed the fraction of aliphatic alcohols containing
methanol, ethanol, propanol, and allyl alcohol in the
molar ratio of 1:1:0.3:3 is distilled off the reactor.
Then, in a vacuum the mixture of 2,6-di-tert-butyl-
phenol with 4-alkyl-2,6-di-tert-butylphenols (alkyl =
Me, Et, Pr) is distilled in 5–7% yield. Further
distillation gives γ-propanol IIIа of 95–97% purity.
Into the reactor containing the still bottoms, a new
portion of allyl alcohol and 2,6-di-tert-butylphenol is
charged and the process is repeated. As the catalyst at
this and subsequent stages acts the sodium salt of the
target product Na-IIIa. Up to 5–6 successive reaction
cycles can be performed without additional introduce-
tion of alkali into the reactor and without the formation
of waste waters. The yield of product IIIа is ca. 75%
[12].
As we see, there is no general protocol for one-step
preparation of 4-(γ-hydroxypropyl)-2,6-disubstituted
phenols. This is because of different acidity of the
starting phenols and their different propensity to
participate in radical redox processes. When the
process of alkylation of phenols is retarded, the side
reaction of transformation of alcohols into acids has a
negative effect on the composition of the products. We
have observed transformation of allyl alcohol into a
mixture of acids under the conditions of the studied
reaction. They react with alkali to give sodium salts
thus retarding the main process of alkylation of
phenols, and the formation of water during neutraliza-
tion may change the course of the reaction.
Based on this experience, we decided to examine
the possibility of multiple use of alkali by the example
of preparation of methylox XII by the reaction of 2,6-
di-tert-butylphenol with methyl acrylate in the pres-
ence of potassium salt of 2,6-di-tert-butylphenol [19].
However, we succeeded in realization of only one
additional operation of preparation of compound XII.
The reason lies in disappearance of alkalinity in the
reactor due to side reaction of alkaline hydrolysis of
the esters present in the reaction mass with the
formation of acids, which neutralize the alkaline
medium.
Compound IIIа purified by crystallization from
toluene forms transparent large cubic crystals with mp
72.0–72.5°С. In the literature for highly pure product
IIIа the mp 70–72°С was given [17].
3-(tert-Butyl-4-hydroxy-5-methylphenyl)propanol-1
(IIIb) we prepared by heating 2-methyl-6-tert-butyl-
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γ-HYDROXYPROPYLATION OF 2,6-DIALKYL(ARYL)PHENOLS
2293
The presence of substituents (CH3, Ph) in the 1 or 3
positions of allyl alcohol does not prevent its reaction
with 2,6-di-tert-butylphenol and leads to the formation
of the corresponding derivatives of compounds IIId–
IIIf. 1,1-Dimethylallyl alcohol does not enter the
reaction with 2,6-di-tert-butylphenol in alkaline medium.
OH
OH
R2
R1
R1
R2
R1
NaOH
CH2
+
+ CHR3=CHCHR4OH
HO
130−190oC
R3
R4
Iа−Id
R2
Vb, Vc
XVа−XVd
2
OH
IIIа−IIIg
Iа, R1 = R2 = t-Bu; Ib, R1 = t-Bu, R2 = CH3; Ic, R1 = R2 = CH3; Id, R1 = R2 = Ph; XVа, R3 = R4 = H; XVb, R3 = H, R4 =
CH3; XVc, R3 = CH3, R4 = H; XVd, R3 = Ph, R4 = H; IIIа, R1 = R2 = t-Bu, R3 = R4 = H; IIIb, R1 = t-Bu, R2 = CH3, R3 =
R4 = H; IIIc, R1 = R2 = CH3, R3 = R4 = H; IIId, R1 = R2 = Ph, R3 = R4 = H; IIIe, R1 = R2 = t-Bu, R3 = H, R4 = CH3; IIIf,
R1 = R2 = t-Bu, R3 = = CH3, R4 = H; IIIg, R1 = R2 = t-Bu, R3 = Ph, R4 = H; Vb, R1 = t-Bu, R2 = CH3; Vc, R1 = R2 = CH3.
In the reaction of 2,6-di-tert-butylphenol with cinnamic
alcohol XVd along with the major product IIIf from
the reaction mass benzyl alcohol XI, 4-benzyl-2,6-di-
tert-butylphenol (IX) and lactone X were isolated. The
formation of alcohol XI and compound IX is indicative
of the processes of splitting of the double bond of
cinnamic alcohol with generation of new agents alkylat-
ing compound Iа, whereas lactone X is formed, as we
have shown, in the parallel process when cinnamic
alcohol and alkali are heated under the reaction conditions.
OH
PhCH=CHCH2OH
O
CH2Ph
Iа
IIIе
+ PhCH2OH
+
+
NaOH
140−160oC
O
Ph
X
XI
IX
The obtained data are indicative of the fact that the
propensity of allyl alcohol XVa and its derivatives
XVb–Vd to enter the reaction with 2,6-di-tert-
butylphenol is connected with the presence in their
molecules of at least one hydrogen atom (α-H)
adjacent to the hydroxy group. Its oxidation with the
formation of carbonyl compounds is presumably the
key stage of γ-hydroxypropylation of phenols.
reaction of methyl acrylate with 2,6-di-tert-butyl-
phenol, this mechanism suggests the formation of 2,6-
di-tert-butylphenoxyl and the radical of the derivative
of allyl alcohol, whose recombination affords product
XII. The key role of the alkali metal and its unusual
location in the reaction complex are discussed in [20].
Similarly the reaction of 2,6-di-tert-butylphenol
with acrolein, which is the product of oxidation of allyl
alcohol can be represented. But at the stage of oxida-
tion of the allyl alcohol to acrolein the radical-con-
taining allyl alcohol is formed, which, according to
scheme, may be a species responsible for the reaction
of 2,6-di-tert-butylphenol with compounds having
double bond.
As to the mechanism of the reaction of 2,6-di-tert-
butylphenol with carbonyl compounds in alkaline
media, it was shown in [19] that the reaction of
phenols with carbonyl compounds proceeded with the
preliminary formation of two pecies: a phenoxyl
radical and the radical of alcohol. Being applied to the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 11 2010

2294
KRYSIN et al.
ONa
ArO
CH2CH=CHONa] + ArOH
[CH2=CHCH
CH2=CHCH2ONa
O
ONa
CH2=CHCH2OH; NaOH
IIIа
CH2CH=CHONa
+
−CH2=CHCHO
CH2CH2CHO
XIII VIII
It is known that aldehyde XIII can suffer trans-
formations in an alkaline medium to form ester VIII
[14], which was detected by us among the products of
the studied reaction. The main course of the reaction is
the reduction of aldehyde XIII into γ-propanol IIIа by
2,6-di-tert-butylphenol or alcohols present in the
reaction mass. We have examined the possibility of
such reduction and found that heating of ketone XIV
with allyl alcohol in the presence of alkali results in the
formation of phenol IIIe in 60% yield.
composition was calculated from spectra with resolu-
tion of 10000.
Preparation of bisphenols (IV, VIа, VIIа), tris-
phenol (II), and γ-propanol (IIIа). The mixture of
20.6 g (0.1 mol) of 2,6-di-tert-butylphenol, 12 g of
allyl alcohol, and 5.6 g of granulated KOH was heated
in a steel autoclave of 0.1 l capacity at 140°С with
stirring for 10 h. After neutralization, 21.3 g of oil was
obtained containing, from the GC data, 40% of the
starting 2,6-di-tert-butylphenol, 23% of γ-propanol
IIIа, 23% of 1,1-bis-(3.5-di-tert-butyl-4-hydroxyphenyl)-
propane (IV), and 13% of tris-1,1,3-(3,5-di-tert-butyl-
4-hydroxy-phenyl)propane (II). The oil was dissolved
in alcohol and the precipitate was filtered off to obtain
0.9 g of tris-1,1,3-(3,5-di-tert-butyl-4-hydroxyphenyl)-
OH
XVа
IIIe
NaOH
1
propane II as a white powder with mp 210–212°С. H
O
NMR spectrum (CCl4), δ, ppm: 1.41 s (t-Bu, 54 H),
2.14 q (2H, СН2), 2.39 t (2H, СН2), 3.62 t (1H, СН),
4.80 s (1H, ОН), 4.84 s (2H, ОН), 6.80 s (2H, Ar),
6.91 s (4H, Ar). HR–MS: m/z of MI 656.5123;
calculated for С45Н68О3, 656.5168.
CH3
XIV
In the present work we have found two different
conditions and two different in nature sets of products
of the reaction of 2,6-di-tert-butylphenol with allyl
alcohol. This may be indicative of the fact that the
reaction under consideration may follow different
mechanisms depending on the condition of performing
the process.
The filtrate was evaporated and placed into a
column with silica gel. Gradient elution with hexane–
ether gave 4.4 g (17%) of γ-propanol IIIа and 3.0 g
1
(6%) of bispropane IV with mp 154–156°С. H NMR
(CDCl3), δ, ppm: 0.87 t (3H, СН3), 1.42 s (36H, t-Bu),
1.66–2.12 m (2H, CH2), 3.57 t (1H, CH), 4.9 s (2H,
OH), 7.05 s (4H, Ar). HR–MS: m/z of MI 452.3654;
calculated for С31Н48О2, 452.3650.
EXPERIMENTAL
Melting points were determined on a Koeffler
1
Waste-free preparation of γ-propanol (IIIа). A
steel autoclave of 0.2 l capacity equipped with anchor
stirrer (v = 348 rpm) was charged with 2,6-di-tert-
butylphenol and NaOH and heated at 130°C for 2 h
with stirring and distillation of water in the stream of
nitrogen. Then the apparatus was charged with allyl
alcohol. The molar ratio Iа:NaOH:XVа was
1:0.29:1.38. The reaction mass was stirred keeping for
2.5 h at 160–180°C, then aliphatic alcohols were
heating block. Н NMR spectra were obtained on a
Bruker AV 300 spectrometer (300.13 MHz) from
solutions in ССl4, with TMS and СDCl3 as internal
standards. UV spectra were taken on a Specord UV–
VIS spectrometer from 1×10–4 molar solutions in
ethanol. IR spectra were registered on a Vektor-22
spectrophotometer (Bruker) in KBr or for 1% solutions
in CCl4. High resolution mass spectra were obtained
on a Finnigan MAT 8200 instrument, the elemental
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γ-HYDROXYPROPYLATION OF 2,6-DIALKYL(ARYL)PHENOLS
2295
distilled off, and the mixture of compound Ia with
methyl-, ethyl-, propyl-2,6-di-tert-butylphenols was
distilled in a vacuum of 3–5 mm Hg in the temperature
range 100–150°С. γ-Propanol (IIIа) is distilled at 170–
180°С (3–4 mm Hg). Then the reactor is charged with
the calculated amount of 2,6-di-tert-butylphenol and
allyl alcohol and the process is recycled as described
above.
2,6-di-tert-butylphenol, and 10% of high-boiling
derivatives of bis- and tris-phenols.
Preparation of 3-(3-tert-butyl-4-hydroxy-5-methyl-
phenyl)propanol-1 (IIIb). The autoclave of 100 ml
capacity equipped with stirrer was charged with 30.1 g
of 96% 2-methyl-6-tert-butylphenol (Ib) (0.176 mol)
and 3.6 g of 99% ground NaOH (0.088 mol), the
mixture was heated to 130°С, and water was distilled
off the reactor in a vacuum of 25 mm Hg with stirring
during 1 h. The reaction mass was cooled to 80°С and
17 ml of allyl alcohol (0.25 mol) was added. The
sealed autoclave was heated to 190°С (the temperature
was measured inside the reactor) and kept with stirring
for 2 h. Then the reactor was cooled to 80°С and the
content was neutralized with hydrochloric acid. The
cooled reaction mass was extracted with ether, the
extract was evaporated to obtain 30 g of viscous oil
containing 72% of compound IIIb and 14% of bis(3-
tert-butyl-4-hydroxy-5-methyl-phenyl)methane (Vb).
The vacuum distillation of the oil at 150–160°С (2–
3 mm Hg) gave 14.5 g (37.2%) of 3-(3-tert-butyl-4-
hydroxy-5-methylphenyl)propanol-1 IIIb with mp 61-
63°С (from hexane); mp 61–63°С [13]. UV spectrum
(ethanol): λmax 280 nm (log ε 3.32). 1H NMR (СCl4), δ,
ppm: 1.36 s (18H, t-Bu), 1.60–1.84 m (2H,
ArCH2CH2), 2.09 s (3H, ArCH3), 2.52 t (2H, ArCH2,
J 8 Hz), 3.40 t (2H, СН2ОН J 7 Hz), 6.66 d (1H, Ar,
J 1 Hz), 6.84 d (1H, Ar, J 1 Hz). The spectrum
coincides with that in [21]. HR–MS: m/z of MI
222.1618; calculated for С14Н22О2, 222.1620.
To stabilize the total amount of the reaction mass
from operation to operation (60–67 wt %) 15% of the
still bottoms was removed from the reactor.
After four successive operations, 199.46 g of 99%
2,6-di-tert-butylphenol, 77.8 g of allyl alcohol and
3.52 g of NaOH was used to afford 166.76 g of 99.6%
γ-propanol IIIа (yield 69%), 20.88 g of 2,6-di-tert-
butylphenol and 90.66 g of still bottoms, which after
removal of sodium salts and conversion of phenolates
into phenols contained 40% of compound IIIа, 30% of
ester VIII, 5% of the mixture of bis- and trisphenols.
The residue is oligomeric products of copolymerize-
tion of olefins with the products of the О- and С-
alkylation of 2,6-di-tert-butylphenol.
From 10 g of the neutralized still bottoms (рН = 6)
1.5 g of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl-
3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate VIII
was isolated by column chromatography on silica gel
with gradient elution with the mixture hexane–ether.
mp 102–105°С (mp 103–106°С, [14]). 1H NMR (СCl)4,
δ, ppm: 1.42 s (36Н, t-Bu), 1.80 m (2H, –СН2–), 2.51 t
(4H, ArCH2), 2.72 t (2H, СН2СОО), 4.10 t (2H,
ОСОСН2), 4.86 s (1H, ОН), 4.88 s (1H, ОН ), 6.87 s
(2H, Ar), 6.92 s (2H, Ar).
Preparation of 3-(3,5-dimethyl-4-hydroxy-phenyl)-
propanol-1 (IIIc). The reaction was performed in an
inert gas flow. A three-neck flask equipped with stirrer
and condenser was charged with 4 g (0.1 mol) of
NaOH and 14 ml of allyl alcohol. The mixture was
kept for 0.5 h at 90–100°С (bath temperature) until
complete dissolution of alkali. Then 6.1 g (0.05 mol)
of 2,6-dimethylphenol Ic was added, the temperature
of the bath was raised to 135°С, and the stirring was
kept for 18 h. After 7 h another portion of allyl alcohol
of 7 ml was added to the reactor. After the process the
reaction mixture was neutralized, extracted with ether,
the extract was washed with water and evaporated to
obtain 9.7 g of oil containing, according to GC, 40% of
3-(3,5-dimethyl-4-hydroxyphenyl)propanol-1 (IIIc),
13% of bis-(3,5-dimethyl-4-hydroxyphenyl)methane
(Vc) and 43% of 2,6-dimethylphenol (Ic). The oil was
distilled in a vacuum to give 2.7 g of the oil with bp
130–135°С (1 mm Hg), which crystallized upon
standing. mp of compound IIIc 65–68°С (from hexane
This procedure for preparation of γ-propanol IIIa
was successfully realized on a pilot plant on Altai-
khimprom (Yarovoe) with 13000 times scaling of the
charged quantities in a steel reactor of 3 m3 capacity
rated at reactions at the pressure up to 5 at. After three
successive stages of alkylation of 2,6-di-tert-butyl-
phenol with allyl alcohol 1.3 t of 97% γ-propanol IIIa
was obtained. By this and other characteristics the pro-
duct matches the acting standards.
Preparation of γ-propanol IIIа at atmospheric
pressure. A glass flask was charged with 5 g (0.024 mol)
of 2,6-di-tert-butylphenol, 6 g (0.15 mol) of NaOH,
and 14 g (0.24 mol) of allyl alcohol and heated for 6 h
at reflux (114°С). After neutralization of the reaction
mass the product was extracted with hexane and the
solvent removed to give 6 g of oil containing, from the
GC data, 87% of γ-propanol IIIа, 3% of the unreacted
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2296
KRYSIN et al.
with addition of alcohol) (68–69°С [23]). Found:
С11Н16О2, m/z 180.1150 (mass-spectrometrically). Cal-
culated: m/z 180.1150.
compound IIIe was obtained by column chromato-
graphy on silica gel (eluent hexane–ether).
Preparation of 3-phenyl-3-(3,5-di-tert-butyl-4-hyd-
roxyphenyl)propanol-1 (IIIg). A steel autoclave of
0.1 l capacity was charged with 20.6 g (0.1 mol) 2,6-
di-tert-butylphenol, 40.2 g (0.3 mol) of cinnamic
alcohol XVd, and 4.0 g (0.3 mol) of NaOH. The
reaction mass was stirred by rotating the autoclave for
5 h at 140°С, cooled, and treated as in method a. 50.5 g
of oil was obtained containing, from the GC data,
24.5% of compound IIIg, 3% of 4-benzyl-2,6-di-tert-
butylphenol IX, and 5% of compound XI. After
vacuum distillation, 6.2 g of oil was obtained with bp
60–75°С (1 mm Hg), which contained 60% of benzyl
alcohol XI (from GC analysis). This compound was
isolated by column chromatography on silica gel,
eluent hexane–ether 1:1 and identified by comparing
its spectral characteristics with those of the authentic
sample. 11.2 g of fraction (oil) with bp 140–170°С
(1 mm Hg) was placed in the column with silica gel
and eluted with the mixture hexane–ether 6:1 to obtain
4-benzyl-2,6-di-tert-butylphenol (IX), mp 58–59°С;
61°С [22]. UV spectrum (EtOH): λmax 265 nm (log ε
4-(3-Hydroxypropyl)-2,6-diphenylphenol (IIId).
A steel autoclave of 20 ml capacity was charged with
4.92 g (0.02 mol) of 2,6-diphenylphenol (Id), 6.8 ml
(0.1 mol) of allyl alcohol, and 0.8 g (0.02 mol) of
ground NaOH. The mixture was heated on a rocking
device at 170°С for 24 h. The cooled reaction mixture
was dissolved in ether, neutralized by hydrochloric
acid to рН 5, the organic layer was washed with water
and the solvent was removed to give 5.3 g of oil
containing, according to GC, 58% of compound IIId.
The product was purified by column chromatography
on silica gel, eluent benzene with ethyl acetate, to
afford 2.2 g of oil crystallized upon standing. The solid
mass was washed with hexane, mp 78–80°С (82°С
from benzene–hexane [18]). UV spectrum (ethanol), λ,
nm (log ε): 205 (4.31), 239 (3.70), 303 (3.65). IR
1
spectrum (ССl4), ν, cm–1: 3640, 3560 (ОН). Н NMR
(CCl4 + C6D6), δ, ppm: 1.7–1.9 m (2Н, СН2СН2СН2),
2.60 t (2H, ArCH2, J 7.5 Hz), 3.51 t (2H, J 6.0 Hz),
6.94 s (2Н, ArH), 7.1–7.5 m (10Н, С6Н5-Ar).
1
3.21), 271 nm (log ε 3.23), 278 nm (log ε 3.24). H
Preparation of 4-(3,5-di-tert-butyl-4-hydroxy-
phenyl)butanol-2 (IIIe). a. A steel autoclave of 50 ml
capacity was charged with 6.92 g (0.034 mol) of 2,6-
di-tert-butylphenol, 4.85 g (0.067 mol) of α-
methylallyl alcohol XVb and 1.36 g (0.034 mol) of
NaOH. The reaction mixture was stirred by rotating
the autoclave for 3.5 h at 140C°С, cooled, and treated
as in the previous experiment. 7 g of oil was obtained
containing, from the GC data, 45% of 2,6-di-tert-
butylphenol and 51% of compound IIId, which was
distilled in vacuum collecting 2.7 g of fraction with bp
152–155°С (1–2 mm Hg). After crystallization from
hexane, 2.09 g (22%) of compound (IIId) with mp 64–
65°С was obtained. UV spectrum (EtOH): λmax 276 nm
(log ε 3.22). 1H NMR (СCl4), δ, ppm: 1.16 d (3H, СН3,
J 6.5 Hz), 1.38 s (18H, t-Bu), 1.62–1.90 m (2H,
ArCH2CH2), 2.50 t (2H, ArCH2, J 8 Hz), 3.5-3.9 m
(1H, СНОН), 4.86 s (1H, ArОH), 6.85 s (2H, Ar).
HR–MS: m/z of MI 278.2250; calculated for С18Н30О2,
m/z 278.2250.
NMR (CCl4), δ, ppm: 1.38 s (18H, t-Bu), 3.85 s (2H,
СН2), 4.85 s (1H, ArОН), 6.87 s (2H, Ar), 6.97-7.30 m
(5H, Ph).
By further elution of the column with the mixture
hexane–ether 1:1 6.40 g (18%) of 3-phenyl-3-(3,5-di-
tert-butyl-4-hydroxyphenyl)propanol-1 (IIIg) was
isolated, mp 107–110°С (from hexane). UV spectrum
(EtOH): λmax 232 nm (log ε 3.85), 266 nm (log ε 3.19),
271 nm (log ε 3.19). 1H NMR (CCl4, δ): 1.36 s (18H, t-
Bu), 1.84–2.40 m (2H, СН2СН2ОН), 3.0 s (1H,
СН2ОН), 3.45 t (2H, ArCH2, J 7 Hz), 3.95 t (2H,
СН2ОН, J 8 Hz), 4.9 s (1H, ArОН), 6.9 s (2H, Ar),
6.95–7.30 m (5H, Ph). HR–MS: m/z of MI 340.2424;
calculated for С23Н32О2, m/z 340.2402.
Washing of the column with ether gave (4S,5R)-5-
benzyl-tetrahydro-4-phenylpyran-2-one (X) with mp
1
94.0–95.5°С (from ethanol). H NMR (CCl4 + C6D6),
δ, ppm: 2.26 m (1H, H-4), 2.2–2.4 m (1H, CHAPh),
2.49 m (1H, H-3ax), 2.65 m (1H, Н-3eq), 2.5–2.7 m
(1H, CHBPh), 2.77 m (1H, Н-5), 2.89 m (1H, Н-6аx),
4.16 m (1H, Н-6eq), 6.9–7.35 m (10H, Ar). HR–MS:
m/z of MI 266.1306; calculated for С18Н18О2, m/z
266.1306. The assignment of all signals was done with
use of europium shift reagent which was twice
introduced into the NMR tube with the solution of X
b. A steel autoclave of 50 ml capacity was charged
with 8.28 g (0.03 mol) 4-(3,5-di-tert-butyl-4-hydroxy-
phenyl)butanone-2 (XIV), 7.0 ml (0.1 mol) of allyl
alcohol and 1.2 g (0.03 mol) NaOH and heated at 140°С
for 3 h. After neutralization of the reaction mass 13.3 g
of oil was obtained, from which 5 g (0.18 mol, 60%) of
1
and the H NMR spectrum was taken. Then the
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γ-HYDROXYPROPYLATION OF 2,6-DIALKYL(ARYL)PHENOLS
2297
8. Furuya, A., Japan Patent no. 214238, 2008; C. A., 2008,
downfield shift of each proton in compound X was
plotted as a function of the added reagent and the H–H
coupling constants were calculated that allowed to
assign the compound the structure given in the scheme.
vol. 149, p. 378382.
9. Krysin, A.P., Pustovskikh, I.I., and Koptyug, V.A., Zh.
Obshch. Khim., 2010, vol. 80, no. 10, p. 1691.
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organicheskoi khimii (Nominal Reactions in Organic
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11. Inui, N. and Ishikawa, M., Japan Patent no. 64220,
2001; C. A., 2001, vol. 134, no. 14, p. 193209.
12. Krysin, A.P. and Khalikova, N.U., USSR Patent
Reaction of cinnamic alcohol with alkali. A steel
rotating autoclave of 50 ml capacity was charged with
10 g of cinnamic alcohol XVd and 1.0 g of NaOH and
kept rotating for 5 h at 140°С in the helium atmos-
phere. 7.85 g of the mixture containing, from the GC
analysis, 37% of benzyl alcohol XI, 23% of cinnamic
alcohol XVd and 23% of compound X was obtained.
no. 1814807, 1992; Byull. Izobret., 1995, no. 3, p. 231.
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