Synthesis and thermal transformations of allyl aryl ethers of adamantane series

Article abstract of DOI:10.1134/S1070363214040057

Allyl aryl ethers of adamantane series were obtained by reacting (E)-1-(adamant-1-yl)-3-bromoprop-1-ene with phenol or ethyl salicylate. The features of thermal transformations of allyl aryl ethers containing bulky adamantane scaffold were investigated. It has been found that the composition of the reaction products is largely dependent on temperature, time and nature of the solvent. When a nucleophilic solvent was used, the reaction proceeded via formal substitution of phenoxy fragment with nucleophilic species prevailing in the reaction medium.

Full text of DOI:10.1134/S1070363214040057

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 4, pp. 632–636. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © M.R. Baimuratov, M.V. Leonova, Yu.N. Klimochkin, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 4, pp. 552–
556.
Synthesis and Thermal Transformations of Allyl Aryl Ethers
of Adamantane Series
M. R. Baimuratov, M. V. Leonova, and Yu. N. Klimochkin
Samara State Technical University, ul. Molodogvardeiskaya 244, Samara, 443100 Russia
e-mail: baymuratovmr@yandex.ru
Received July 1, 2013
Abstract―Allyl aryl ethers of adamantane series were obtained by reacting (E)-1-(adamant-1-yl)-3-
bromoprop-1-ene with phenol or ethyl salicylate. The features of thermal transformations of allyl aryl ethers
containing bulky adamantane scaffold were investigated. It has been found that the composition of the reaction
products is largely dependent on temperature, time and nature of the solvent. When a nucleophilic solvent was
used, the reaction proceeded via formal substitution of phenoxy fragment with nucleophilic species prevailing
in the reaction medium.
DOI: 10.1134/S1070363214040057
Search for new synthesic approaches to functional
derivatives based on transformations of unsaturated
substrates of framework structure remains an important
area of research in the chemistry of adamantane.
Thermal rearrangement of allyl aryl ethers are well
known and often used in organic synthesis [1–6]. The
presence of bulky framework fragment in the γ-
position of the allyl unit opens new possibilities of
using thermal transformations in the synthesis of
compounds of the adamantane series virtually
unavailable by other methods. The investigation of
thermal transformation features of allyl aryl ethers
containing bulky adamantane scaffold will expand the
knowledge on the possible routes of these reactions.
The main method of synthesis of allyl aryl ethers is
the alkylation of phenolates with allyl halides. The
reaction of (E)-1-(adamant-1-yl)-3-bromoprop-1-ene I
with phenol IIa or ethyl salicylate IIb in the presence
of potassium carbonate in boiling acetone gave the
corresponding allyl ethers IIIa or IIIb (Scheme 1).
Bromide I reacted with phenol in the presence of
sodium hydride in toluene under reflux for 2 h to
afford a 1 : 1 mixture of two products (by GC-MS):
ether IIIa and ortho-substituted phenol IVa as a C-
allylated product. The resulting mixture was separated
by column chromatography on silica gel.
Scheme 1.
R
a
IIа, IIb
O
+
Br
IIIа, IIIb
I
OH
+IIа
b
O
+
IIIа
IVа
a, K2СО3, acetone, 3 h (IIIa), 5 h (IIIb), Δ; b, NaH, toluene, 2 h, heating. R = H (а), COOC2H5 (b).
632

SYNTHESIS AND THERMAL TRANSFORMATIONS OF ALLYL ARYL ETHERS
633
Scheme 2.
OH
NaH, Δ
+
IIа + IIIа + IVа +
Br IIа
Ad
Ad
toluene
I
V
Ad = adamant-1-yl.
Scheme 3.
OH
O
O
а
IIIа, IIIb
IIа, IIb
OH +
O
O
+
VIb
VIа
OH
b (IIIа)
VIа, VIb
+
+
OH
IVа
IVb
а, diethylene glycol, heating, 0.5 h; b, diethylene glycol, heating, 10 h.
2,6-Di-[(E)-3-(adamant-1-yl)prop-2-en-1-yl]phenol
V was obtained along with compounds IIIa and IVa
when the reaction time was 15 h.
due to the presence of bulky substituent in the γ-
position of the allyl moiety. Some examples of Claisen
rearrangement leading to the formation of products
with the retention of the structure of the allyl unit have
been known [7, 10–12].
In this case, phenol IIa was also detected among
the reaction products. It is presumable that in the
initially formed allyl ether IIIa a splitting of the C–O
bond occurred followed by the allylation of phenol IIa
or ortho-substituted phenol IVa to give the product V
(Scheme 2).
Heating of ethers IIIa and IIIb in diethylene glycol
for 0.5 h resulted in the reallylation products, isomeric
alcohols VIa and VIb in a ratio of 9 : 1 (by GC-MS).
Synthesis of long-chain adamantyloxyalkanols
similar to VIa is of interest for their use as lipophilic
modifiers when creating antiviral drugs [13, 14]. Thus,
the data [14, 15] show a considerable influence of the
aliphatic chain length and the presence of hinge
oxygen atoms on the biological activity of nucleoside
phosphonates (Scheme 3).
The formation of 2,6-disubstituted phenols along
with the major products of thermal rearrangement has
been known [7]. A possibility of ether IIIa disproportiona-
tion into product V and phenol IIa is not excluded.
Reaction of bromide I with ethyl salicylate under
these conditions yields ether IIIb as a single product.
This is due to deactivating effect of ethoxycarbonyl
group on the aromatic ring.
Heating of ether IIIa in diethylene glycol for 10 h
gave rise to ortho- and para-substituted phenols IVa
and IVb (2.5 : 1) as a result of thermal rearrangement,
along with compounds VIa and VIb.
We failed to carry out the thermal Claisen
rearrangement of allyl ethers IIIa and IIIb. The
rearrangement products with retention of the structure
of the allyl unit were detected, whereas the Claisen
rearrangement is a concerted pericyclic process
involving [3.3]-sigmatropic shift and should lead to the
products with inverted allyl unit [8, 9]. The absence of
the intramolecular rearrangement products is probably
Thermal rearrangement of allyl ether IIIb in ethyl
salicylate resulted in the products of ortho- and para-
substitution VIIa and VIIb in a ratio of 1 : 1.2
1
(according to H NMR spectra). The resulting mixture
of isomers was separated by column chromatography
on silica gel eluting with petroleum ether (Scheme 4).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

634
BAIMURATOV et al.
Scheme 4.
COOC2H5
COOC2H5
OH
IIb, Δ
O
VIIa, VIIb
IIIb
Study of thermal transformations of allyl aryl ethers
of adamantane series showed that the composition of
the reaction products is significantly dependent on
temperature, time, and nature of the solvent used.
When a nucleophilic solvent was used, the reaction
proceeded via formal substitution of phenoxy fragment
with nucleophilic species prevailing in the reaction
medium. The formation of ortho- and para-substituted
phenols with retention of the allyl unit indicates the
intermolecular reaction pathway.
(12). Found, %: С 85.2; H 8.94. C19H24О. Calculated,
%: С 85.03; H 9.01.
Ethyl 2-[(E)-3-(adamant-1-yl)prop-2-en-1-yloxy]-
benzoate (IIIb) was prepared similarly. Yield 85%,
colorless oil. IR spectrum, ν, cm–1: 3024, 2977 (СНAr),
2900, 2846 (СНAd), 1731(C=O), 1600 (С=C), 1450
(СН2), 1303, 1249 (C–Ost), 1080 (С–О–С), 968
1
(СН=СН, trans). H NMR spectrum, δ, ppm (J, Hz):
1.34 t (3Н, СН3, J 7.3), 1.56–1.70 m (12H, СН2Ad),
4.32 q (2H, СН2-СН3, J 7.3), 4.52 d (2H, =СНСН2, J
5.5), 5.51 d.t (1H, =СНСН2, J1 16.0, J2 5.5), 5.68 d
(1Н, =СН, J 16.0), 6.89–6.93 m (2H, СНAr), 7.33–7.38
m (1H, СНAr), 7.73–7.75 m (1H, СНAr). 13C NMR
spectrum, δС, ppm: 14.45, 28.45, 34.91, 36.89, 42.05,
60.78, 70.31, 114.02, 119.68, 120.24, 121.18, 131.56,
133.12, 145.84, 158.34, 166.56. Mass spectrum, m/z
(Irel, %): 340 (5) [M]+, 296 (7), 205 (5), 175 (100), 147
(12), 135 (40), 119 (22), 93 (48), 91 (40), 79(37), 55
(16). Found, %: С 77.39; H 8.17. C22H28О3.
Calculated, %: С 77.61; H 8.29.
EXPERIMENTAL
1H and 13C NMR spectra in CDCl3 were recorded
on a JEOL JNM ECX-400 instrument operating at
400 MHz. IR spectra (KBr) were registered on a
Shimadzu IRAffinity-1 spectrometer. Mass spectra
were obtained on
a
gas chromatograph-mass
spectrometer Thermo Finnigan DSQ (capillary column
BPX-5, 30 × 0.32, 70 eV). Elemental analysis was
performed on an EuroVector EA-3000 EA elemental
analyzer using L-cystine as a reference.
(E)-3-(Adamant-1-yl)-1-phenoxyprop-2-ene (IIIa).
A mixture of 2.2 g (0.023 mol) of phenol, 5.6 g
(0.022 mol) of bromide I, 3.2 g (0.023 mol) of
potassium carbonate in 20 mL of acetone was refluxed
for 3 h. The mixture was poured into water and
extracted with toluene. The extract was washed with
water and dried over sodium sulfate. Toluene was
evaporated in a vacuum. Yield 4.95 g (85%), pale
yellow oil. IR spectrum, ν, cm–1: 3058, 3031 (CHAr),
2904, 2846 (СНAd), 1666 (С=С), 1450 (СН2), 1380,
1299, 1238, 1218 (С–О–С), 1172, 1029, 968 (СН=СН,
trans), 752 (CHAr). 1H NMR spectrum, δ, ppm (J, Hz):
1.59–1.91 m (12H, СН2Ad), 2.02–2.12 m (3Н, СНAd),
4.55 d (2H, ОСН2, J 7.5), 5.62 d.t (1Н, =СНСН2, J1
16.5, J2 7.5), 5.75 d (1Н, =СН, J 16.5), 6.94–7.06 m
(3Н, СНAr), 7.29–7.40 m (2Н, СНAr). 13C NMR
spectrum, δС, ppm: 28.59, 34.88, 36.88, 42.02, 69.28,
114.81, 119.97, 120.60, 129.35, 146.12, 158.87. Mass
spectrum, m/z (Irel, %): 268 (6) [M]+, 176 (14), 175
(100), 147 (5), 135 (17), 105 (16), 93 (27), 79 (23), 55
Reaction of (E)-1-(adamant-1-yl)-3-bromoprop-
1-ene with sodium phenolate. To a mixture of 1.9 g
(0.02 mol) of phenol and 0.8 g (0.033 mol) of sodium
hydride in 30 mL of toluene was added 5 g (0.02 mol)
of bromide I in 10 mL of toluene and the reaction
mixture was refluxed for 2 h. Then the reaction
mixture was poured into water, the organic layer was
separated, and the aqueous layer was extracted with
toluene. The extracts were combined, washed with
water, and dried over sodium sulfate. The solvent was
evaporated, and the resulting mixture of IIIa and IVa
was separated by column chromatography on silica gel
eluting with petroleum ether. 2-[(E)-3-(Adamant-1-yl)-
prop-2-en-1-yl]phenol (IVa). Yield 36%, white
crystals, mp 54–56°C. IR spectrum, ν, cm–1: 3282
(ОН), 3035 (CHAr), 2896 (СНAd), 2846 (СНAd), 1593
(С=С), 1454 (СН2), 1388, 1342, 1230 (С–О), 1176
(С–ОН), 1095, 1041, 972 (СН=СН, trans), 748, 736
1
(CHAr). H NMR spectrum, δ, ppm (J, Hz): 1.53–1.86
m (12H, СН2Ad), 1.92–2.11 m (3Н, СНAd), 3.37 d (2H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

SYNTHESIS AND THERMAL TRANSFORMATIONS OF ALLYL ARYL ETHERS
635
=СНСН2, J 8), 5.29 s (1Н, ОН), 5.48 d.t (1Н,
=СНСН2, J1 16.0, J2 8), 5.60 d (1Н, =СН, J 16.0),
6.80–6.96 m (2Н, СНAr), 7.06–7.22 m (2Н, СНAr). 13C
NMR spectrum, δС, ppm: 28.51, 35.02, 35.10, 36.91,
42.35, 116.12, 120.79, 122.71, 125.88, 127.94, 130.26,
144.99, 154.91. Mass spectrum, m/z (Irel, %): 268 (19)
[M]+, 135 (100), 107 (70), 93 (41), 91 (45), 79 (72), 77
(49), 53 (17). Found, %: С 85.2; H 8.94. C19H24О.
Calculated, %: С 85.03; H 9.01.
Thermolysis of ethyl 2-[(E)-3-(adamant-1-yl)-
prop-2-en-1-yloxy]benzoate (IIIb). A mixture of 2 g
(0.007 mol) of IIIb and 8 g (0.048 mol) of IIb was
heated at 200°C for 2 h. Ethyl salicylate was distilled
off in a vacuum at 110°C (10 mm Hg). A mixture of o-
and p-isomers VIIa and VIIb was separated by
column chromatography on silica gel eluting with
petroleum ether. Ethyl 3-[(E)-3-(adamant-1-yl)prop-
2-en-1-yl]-2-hydroxybenzoate (VIIa). Yield 30%,
colorless oil. IR spectrum, ν, cm–1: 3210 (OH), 3097,
2981 (СНAr), 2904, 2846 (СНAd), 1670 (C=O), 1612
(С=C), 1450 (СН2), 1296, 1246 (C–Ost), 1087 (С–О–С),
2,6-Di[(E)-3-(adamant-1-yl)prop-2-en-1-yl]phenol
(V) was prepared similarly under reflux for 15 h. The
products mixture was separated by column chroma-
tography eluting with petroleum ether. Yield 23%,
white crystals, mp 106–108°C. IR spectrum, ν, cm–1:
3471 (ОН), 3031 (CHAr), 2900 (СНAd), 2846 (СНAd),
1658, 1589 (С=С), 1458 (СН2), 1338, 1265, 1207 (С–
О), 1103, 1041, 987, 972 (СН=СН, trans), 763, 744
1
972 (СН=СН, trans), 756. H NMR spectrum, δ, ppm
(J, Hz): 1.44 t (3Н, СН3, J 7.1), 1.61–1.79 m (12Н,
СН2Ad), 1.98–2.06 m (3Н, СНAd), 3.42 d (2Н,
=СНСН2, J 5.3), 4.42 q (2Н, СН2СН3, J 7.1), 5.45–
5.55 m (2Н, СН=СН), 6.84 t (1Н, СНAr, J 7.6), 7.35
d.d (1Н, СНAr, J1 7.6, J2 1.5), 7.76 d.d (1Н, СНAr, J1
7.6, J2 1.5), 11.21 s (1Н, ОН). 13C NMR spectrum, δС,
ppm: 14.35, 28.73, 32.66, 34.92, 37.12, 42.61, 61.40,
112.05, 118.61, 122.29, 127.70, 129.95, 135.38,
143.91, 159.85, 170.77. Mass spectrum, m/z (Irel, %):
340 [M]+ (4), 295 (1), 165 (1), 135 (100), 107 (5), 93
(7), 79 (5). Found, %: С 77.39; H 8.17. C22H28О3.
Calculated, %: С 77.61; H 8.29.
1
(CHAr). H NMR spectrum, δ, ppm (J, Hz): 1.53–1.76
m (24Н, СН2Ad), 1.93–2.03 m (6Н, СНAd), 3.40 d (4Н,
СН2СН=, J 5.5), 5.40 br. s (1Н, ОН), 5.44 d.t (2Н,
СН2-СН=, J1 16.0, J2 5.5), 5.51 d (2Н, СН=, J 16.0),
6.80 t (1Н, СНAr, J 7.3), 6.98 d (2Н, СНAr, J 7.3). 13C
NMR spectrum, δС, ppm: 28.56, 34.60, 34.96, 36.97,
42.42, 120.31, 122.83, 126.78, 128.28, 144.34, 153.20.
Mass spectrum, m/z (Irel, %): 442 (5) [M]+, 307 (5), 145
(2), 136 (10), 135 (100), 107 (9), 93 (13), 79 (11), 67
(4). Found, %: С 86.73; H 9.44. C32H42О. Calculated,
%: С 86.82; H 9.56.
Ethyl 5-[(E)-3-(adamant-1-yl)prop-2-en-1-yl]-2-
hydroxybenzoate (VIIb). Yield 36%, colorless oil. IR
spectrum, ν, cm–1: 3197 (OH), 3024 (СНAr), 2904,
2850 (СНAd), 1681 (C=O), 1612 (С=C), 1450 (СН2),
1292, 1253 (C–Ost), 1087 (С–О–С), 972 (СН=СН,
2-{2-[(E)-3-(Adamant-1-yl)prop-2-en-1-yloxy]-
ethoxy}ethanol (VIa). A mixture of 0.007 mol of
ether IIIa or IIIb and 20 mL of diethylene glycol was
heated for 0.5 h, then poured into water and extracted
with diethyl ether. The extract was washed with 40%
aqueous sodium hydroxide solution, with water, and
dried over sodium sulfate. The solvent was evaporated,
and the product was purified by column chromato-
graphy on silica gel eluting with cyclohexane. Yield
57%, pale yellow oil. IR spectrum, ν, cm–1: 3440 (ОН),
2904 (СНAd), 2846 (СНAd), 1454 (СН2Ad), 1346, 1118
(С–О), 1073, 972 (СН=СН, trans). 1H NMR spectrum,
δ, ppm (J, Hz): 1.55–1.71 m (12H, СН2Ad), 1.95–2.05
m (3Н, СНAd), 2.72 br. s (1Н, ОН), 3.55–3.76 m (8Н,
СН2О), 3.97 d (2Н, =СНСН2, J 6.4), 5.38 d.t (1Н,
=СНСН2, J1 15.6, J2 6.4), 5.54 d (1Н, =СН, J 15.6).
13C NMR spectrum, δС, ppm: 28.45, 34.86, 36.90,
42.13, 61.85, 69.08, 70.50, 72.61, 72.64, 120.76,
146.29. Mass spectrum, m/z (Irel, %): 280 [М]+ (1), 237
(2), 191 (5), 175 (11), 145 (3), 135 (100), 117 (9), 93
(15), 79 (14), 67 (7), 45 (34). Found, %: С 72.67; H
9.94. C17H28О3. Calculated, %: С 72.82; H 10.06.
1
trans), 794, 717. H NMR spectrum, δ, ppm (J, Hz):
1.41 t (3Н, СН3, J 7.1), 1.56–1.75 m (12Н, СН2Ad),
1.94–2.03 m (3Н, СНAd), 3.24 d (2Н, =СНСН2, J 5.3),
4.39 q (2Н, СН2СН3, J 7.1), 5.32–5.43 m (2Н,
СН=СН), 6.90 d (1Н, СНAr, J 8.5), 7.26 d.d (1Н,
СНAr, J1 8.5, J2 2.3), 7.63 d (1Н, СНAr, J 2.3), 10.68 s
(1Н, ОН). 13C NMR spectrum, δС, ppm: 14.28, 28.60,
34.86, 37.00, 38.12, 42.53, 61.39, 112.24, 117.50,
123.41, 129.27, 131.92, 136.07, 143.95, 160.02, 170.33.
Mass spectrum, m/z (Irel, %): 340 [M]+ (25), 295 (7),
204 (7), 192 (15), 179 (10), 161 (25), 147 (6), 135
(100), 105 (10), 93 (10), 79 (13). Found, %: С 77.68;
H 8.36. C22H28О3. Calculated, %: С 77.61; H 8.29.
ACKNOWLEDGMENTS
This work was financially supported by the Ministry
of Education and Science (contract 14.B37.21.1917,
16.552.11.7076 GC). Scientific research was
performed using the equipment of the Research Centre
for joint use “Study of physicochemical properties of
substances and materials.”
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BAIMURATOV et al.
9. Woodward, R.B. and Hoffmann, R.J., Am. Chem. Soc.,
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