Alkylation of phenol by nerol in the presence of organoaluminum compounds

Article abstract of DOI:10.1007/s10600-012-0303-4

Alkylation of aluminum phenolate by nerol and of phenol by nerol in the presence of the organoaluminum compounds aluminum phenolate and aluminum isopropylate was studied. The reaction products were isolated and characterized. Several features of the proce

Full text of DOI:10.1007/s10600-012-0303-4

Chemistry of Natural Compounds, Vol. 48, No. 4, September, 2012 [Russian original No. 4, July–August, 2012]
ALKYLATION OF PHENOL BY NEROL IN THE
PRESENCE OF ORGANOALUMINUM COMPOUNDS
*
I. Yu. Chukicheva, I. V. Fedorova,
A. A. Koroleva, and A. V. Kuchin
UDC 547.562.1+547.599.2
+547.562.1ꢀ162+547.263ꢀ162
Alkylation of aluminum phenolate by nerol and of phenol by nerol in the presence of the organoaluminum
compounds aluminum phenolate and aluminum isopropylate was studied. The reaction products were isolated
and characterized. Several features of the process were determined. It was found that ortho-substitution of
the aromatic ring occurred primarily. In several instances nerol was cyclized. The fraction of allyl
rearrangement was insignificant.
Keywords: phenol, nerol, aluminum phenolate, aluminum isopropylate, alkylation.
Prenylphenols and their oxidized forms, prenylquinones, are classified as biosynthetic natural compounds. Geranyl
derivatives of phenols exhibit a high level of biological activity [1, 2]. One method for preparing analogs of such natural
compounds is alkylation. Under the conditions of this reaction, the effects of temperature and catalysts can modify the terpene
substituent (closure into heterocyclic and carbocyclic structures). This is responsible for a variety of resulting products and
can produce compounds with novel structures and possibly with specific biological activity. Therefore, great significance is
placed on elucidation of the features of the alkylation reaction, owing to which the preparation of certain products can be
targeted. In this respect, the effects of the catalyst, reaction temperature regime, and structure of the alkylating agent on the
composition of the alkylation products must be studied.
Previously reported studies [3–5] provided a basis for proposing that alkylation in the presence of organoaluminum
catalysts occurred in the Al coordination sphere, the result of which was the formation primarily of ortho-alkylated phenols, in
particular, in yields reaching 73% via the reaction of phenol with geraniol [(PhO) Al catalyst] [6, 7].
3
Herein results from the alkylation of aluminum phenolate (PhO) Al by nerol (2) (cis-isomer of geraniol) and of
3
phenol (1) by nerol (2) using catalytic amounts of Al-containing compounds [(PhO) Al and (i-PrO) Al] are reported. The
3
3
product composition was studied as a function of reaction temperature and amount and type of Al-containing catalyst
(Scheme 1, Table 1).
Alkylation of (PhO) Al by nerol (2) and of phenol (1) by nerol (2) in the presence of equimolar amounts of
3
(i-PrO) Al occurred with 93–98% conversion.
3
Monoterpenes 3 and 4 were obtained in overall yield 47% upon refluxing the reagents in benzene using (PhO) Al.
3
Furthermore, products of C-alkylation, the principal one of which was ortho-alkylated phenol 9 (26%), were isolated in yields
up to 35%. Polymerization products represented 4% of the mix. Increasing the reaction temperature to 120°C without using
a solvent formed ethers 5 and 14 in yields of 14 and 10%, respectively. The overall amount of 3 and 4 in this instance
decreased to 5% whereas the yield of polymerization products increased to 32%. Alkylation of (PhO) Al by 2 at 140°C gave
3
primarily chromane-type ethers 6, 7, 15, and 16 in overall yield 74%. Compounds 15 and 16 contained two aromatic rings.
Furthermore, bisphenol 17 was formed in 3% yield. A side product of ortho-alkylated phenol 18 was isolated pure and
characterized structurally.
Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, 167982, Syktyvkar,
Ul. Pervomaiskaya, 48, Russian Federation, fax: (8212) 21 84 77, e-mail: chukicheva-iy@chemi.komisc.ru. Translated from
Khimiya Prirodnykh Soedinenii, No. 4, July–August, 2012, pp. 485–489. Original article submitted January 13, 2012.
©
0009-3130/12/4804-0535 2012 Springer Science+Business Media, Inc.
535

OH
+
OH
1
2
(PhO) Al or ( i-PrO) Al
3
3
8
7
10
10
10
10
9
3
1
5
8
11
12
8
7
9
7
3
5
3
9
O1
11
O
5
8
1
9
12
1
9
6
O
2
1
O
7
7
8
8
4
6
8
3
5
7
10
10
9
10
1
8
10
8
OH
OH
1
3
12
5
3
HO
11
1
9
HO
11
9
14
1
7
8
9
9
12
10
11
8
10
8
10
9
5
1
3
7
8
1
9
9
3
12
O
11'
6
1'
1
8
OH
12'
O
OH
13
14
15
OH 8
11
12
10
OH
12
9
9
9
7
3
5
11
1
7
O
11'
11'
14'
14'
5
1
HO
HO
10
16
17
18
Scheme 1
Alkylation of 1 by 2 using equimolar amounts of (i-PrO) Al at 120 and 140°C formed a complicated C-alkylation
3
product mixture (37–40%). Apparently the reaction occurred with isomerization of the terpene substituent and addition of it
to both the ortho- and para-positions of the phenol aromatic ring. The fraction of chromanes among the identified products
obtained under these reaction conditions was 44% (120°C) and 32% (140°C). Their structures corresponded to 7, 8, 15, and
16. Chromane 8, which was obtained in the reactions using (i-PrO) Al, was not formed in the presence of (PhO) Al. The
3
3
yield of polymerized compounds reached 15–17%. Compound 1 was not alkylated by 2 upon refluxing in benzene for 4 h.
The reaction of 1 and 2 in the presence of catalytic amounts of (PhO) Al and (i-PrO) Al occurred at temperatures
3
3
above 160°C and formed a mixture of O- and C-alkylation products. The reaction at 160°C occurred with 40–60% conversion;
at 180°C, 90% (Table 1), regardless of the catalyst used. However, the nature of the organoaluminum compound affected the
composition of the alkylation products. Primarily ortho-nerylphenol 9 (35 and 44%) was formed by using (PhO) Al at 160
3
and 180°C, respectively; phenylneryl ether 5 (50%, 160°C), by using (i-PrO) Al.
3
A study of the alkylation of phenol by nerol in the presence of organoaluminum compounds showed that primarily
ortho-substitution of the aromatic ring occurred. In certain instances, nerol underwent cyclization. The fraction of allyl
rearrangement was negligible. The yield of alkylation products as a function of reaction temperature and ratio of reagents and
catalyst was followed when (PhO) Al was used. A stoichiometric ratio of catalyst and reagents provided practically complete
3
conversion of the starting compounds. However, a detailed study of the reaction products showed that the fraction of side
products was large in the range 80–120°C. These were hydrocarbons at 80°C (47%) and polymerization products of them at
120°C. Primarily tetrahydro-2,6-methanobenzo[b]oxacines (41%) and diarylalkanoids (36%) were formed at 140°C. This
could be used for practical purposes considering the activity of natural diarylalkanoids [8]. Catalytic alkylation involving
(PhO) Al occurred with high conversion of the starting reagents at 180°C. Highly selective formation (44%) of ortho-nerylphenol
3
9 was observed. However, polymerization products and resins (19%) were formed in significant quantities under these conditions.
536

TABLE 1. Conditions and Products of Phenol Alkylation by Nerol
Ratio of reaction products, %
(PhO)3Al = 10%
of starting phenol,
PhOH–nerol 1:1
( -PrO) Al = 10%
of starting phenol,
PhOH–nerol 1:1
i
3
( -PrO) Al–PhOH–nerol
i
3
(PhO)3Al–nerol 1:1
1:1:1
Product
Reaction conditions
80 Ñ, 4 h,
C6H6
120 C,
4 h
140 Ñ,
1 h
160 Ñ,
1 h
180 Ñ,
6 h
120 C,
4 h
140 Ñ,
4 h
160 Ñ,
1 h
180 Ñ,
1 h
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
Conversion,%
93
47
14
–
–
–
26
–
–
6
3
–
–
–
–
–
4
–
95
5
14
–
–
–
29
–
–
6
4
10
–
–
–
–
32
–
97
–
–
18
23
–
–
–
–
40
–
18
–
–
–
35
6
–
18
3
14
–
90
5
5
–
–
–
44
–
–
16
2
9
–
–
–
–
19
–
95
2
–
98
3
–
60
–
50
–
–
–
25
–
–
12
8
–
–
–
–
–
5
–
90
13
–
6
–
–
23
–
–
25
–
8
–
–
–
–
25
–
3, 4
5
–
1
6
18
12
–
–
1
–
–
–
10
4
–
–
17
36
17
11
–
–
10
–
–
–
–
3
–
–
15
40
7
8
9
10
11
12
13
13
14
–
24
9
3
1
15
–
–
–
6
16
17
18
*
**
9
–
______
*Polymerization products; **complicated mixture of C-alkylation products.
The reaction occurred with high conversion to form up to 36–40% of a difficultly separated mixture of C-alkylation
products at 120–140°C in the presence of a stoichiometric amount of (i-PrO) Al. Furthermore, 15–17% of the products were
3
polymerized compounds. Catalytic alkylation in the presence of (i-PrO) Al at 160°C occurred with 60% conversion of the
3
starting reagents and gave good yields of nerylphenyl ether (50%) and ortho-nerylphenol 9 (25%). The analogous reaction at
180°C was complicated by polymerization (25%) although it occurred with high conversion (90%). The ratio of ortho- and
para-nerylphenol was 23 and 25%, respectively.
The structures of the products were confirmed by NMR spectral methods. Thus, the PMR spectrum of 8 exhibited
three singlets characteristic of protons for three methyls at 1.40 ppm, 1.65, and 1.73. A multiplet corresponding to H-3 on the
double bond appeared in the range 5.16–5.18 ppm. The resonance of quaternary C-6 bonded to oxygen was found at
13
74.63 ppm in the C NMR spectrum of 8. Resonances of C atoms of the double bond (C-2 and C-3) were observed at 130.59
and 124.29 ppm, respectively. Elemental analyses and the ratio of integrated intensities of resonances for the aromatic and
terpene substituent protons confirmed that 15–17 each contained two aromatic rings. Chromanes 15 and 16 had resonances in
13
the C NMR spectrum for quaternary C atom C-5 bonded to an O atom at 76.48 and 76.34 ppm, respectively. Resonances for
protons of para-substituted aromatic ring (AB system) were observed in PMR spectra of phenols 16 and 17.
EXPERIMENTAL
13
PMR and C NMR spectra were recorded in CDCl at room temperature on a Bruker Avance II 300 spectrometer
3
(300 and 75 MHz, respectively). The internal standards were CD(H)Cl resonances (ꢁ 7.25 ppm, ꢁ 76.90 ppm). Resonances
3
H
C
13
were assigned using C NMR spectra recorded in JMOD mode and two-dimensional NMR spectroscopy (HSQC, COSY,
NOESY). IR spectra were recorded as thin layers on a Shimadzu IR Prestige 21 IR-Fourier spectrometer. Elemental analyses
were performed on a Vario Microcube Elementar CHNS analyzer. The course of reactions was monitored using TLC
TM
on Sobrfil plates and GC on a Shimadzu GC-2010AF chromatograph using an SLB -5ms capillary column (Supelco,
60 m ꢂ 0.25 mm, 0.5 ꢃm, 70–230°C temperature regime, 6°C/min heating rate, flame-ionization detector, He carrier gas).
Column chromatography used Alfa Aesar 70/230 ꢃm silica gel. Compounds 3–18 were detected by spraying plates with an
537

alcohol solution of vanillin with subsequent heating to 100–150°C and by using KMnO solution. Phenol (chemically
4
pure) and nerol (Alfa Aesar) were used in the reactions. The catalysts were (i-PrO) Al (Alfa Aesar) and (PhO) Al
3
3
(synthesized in situ).
Alkylation of (PhO) Al by Nerol. A 100-mL two-necked flask equipped with a thermometer and reflux condenser
3
was charged with phenol (1, 1.8 g, 19.5 mmol), heated to 160°C, treated in portions with Al turnings (0.17 g, 6.5 mmol), held
at this temperature until the Al dissolved completely, cooled to room temperature, and treated with nerol (2, 1.0 g, 6.5 mmol).
The reaction was carried out at 80°C (in benzene) and 120 and 140°C (without solvent). The course of the reaction was
followed using TLC (hexane:Et O, 3:1, detector alcohol solution of vanillin:H SO ). When the reaction was finished, the
2
2
4
mixture was cooled, diluted with Et O, treated with HCl solution (10%) to decompose the catalyst, and washed with NaOH
2
solution (5%) and H O until neutral. The organic layer was dried over anhydrous Na SO . The solvent was removed. The
2
2
4
products were separated by column chromatography over SiO (petroleum ether:Et O with increasing fraction of Et O). The
2
2
2
reagents were added simultaneously if (i-PrO) Al was used. The work up of the reaction mixture and the separation of
3
reaction products were carried out by the method described above.
Alkylation of Phenol by Nerol in the Presence of (PhO) Al and (i-PrO) Al. A 100-mL two-necked flask equipped
3
3
with a thermometer and reflux condenser was charged with phenol (0.62 g, 6.5 mmol), heated to 160°C, and treated in small
portions with Al turnings (0.0054 g, 0.2 mmol). After the Al was completely dissolved, the solution was cooled to 40°C and
treated with nerol (2, 1 g, 6.5 mmol). For (i-PrO) Al (10% of starting phenol), the reagents were added simultaneously. The
3
reaction was carried out at 160°C until nerol was completely converted (GC and TLC monitoring). The work up of the
reaction mixture and separation of reaction products were carried out by the method described above.
(Z)-3,7-Dimethylocta-1,3,6-triene (3), light-yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.70 (3H, s, CH -8), 1.77 (3H, s, CH -9), 1.81 (3H, s, CH -10), 2.76–
3
3
3
3
2.78 (2H, m, H-5), 4.98–5.02 (2H, m, H-1), 5.17–5.20 (1H, m, H-2), 5.55–5.58 (1H, m, H-4), 6.75–6.88 (1H, m, H-6).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.84 (C-8), 20.50 (C-10), 23.70 (C-9), 28.00 (C-5), 108.40 (C-1),
3
120.80 (C-6), 131.84 (C-4), 132.10 (C-7), 133.10 (C-3), 134.91 (C-2).
1-Methyl-4-(1-methylethenyl)cyclohexene (4), light-yellow oil. The spectral data agreed with those in the literature [9].
–1
(E)-(3,7-Dimethylocta-2,6-dienyloxy)benzene (5), light-yellow oil. IR spectrum (KBr, ꢅ, cm ): 1604, 1592 and
1500 (ꢅ C=C of aromatic ring), 756 (ꢁ CH, out-of-plane vibrations of mono-substituted aromatic ring), 1242 (ꢅ =C–O), 1460
and 1380 [=C(CH ) ], 1676 (ꢅ C=C of nerol), 835 (ꢁ CH of nerol).
3 2
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.67 (3H, s, CH -9), 1.75 (3H, s, CH -8), 1.86 (3H, s, CH -10),
3
3
3
3
2.19–2.20 (4H, m, 2H-4, 2H-5), 4.55–4.57 (2H, m, H-1), 5.18–5.21 (1H, m, H-6), 5.58 (1H, t, J = 6.0, H-2), 6.96–6.99 (3H, m,
1H-12, 1H-14, 1H-16), 7.33 (2H, t, J = 8.4, 1H-13, 1H-15).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.70 (C-10), 22.32 (C-8), 24.28 (C-9), 26.64 (C-5), 32.46 (C-4),
3
64.40 (C-1), 114.68 (C-12, C-16), 120.50 (C-14), 120.58 (C-2), 123.74 (C-6), 129.42 (C-13, C-15), 132.19 (C-7), 141.55
(C-3), 158.89 (C-11).
3,8
1-Isopropyl-10-methyl-2-oxatricyclo[7.3.1.0. ]trideca-3(8),4,6-triene (6), light-yellow oil. The spectral data agreed
with those in the literature [10, 11].
3,8
10-Isopropyl-1-methyl-2-oxatricyclo[7.3.1.0. ]trideca-3(8),4,6-triene (7), light-yellow oil. The spectral data agreed
with those in the literature [10, 11].
2-Methyl-2-(4-methylpent-3-enyl)chromane (8), yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.40 (3H, s, CH -7), 1.65 (3H, s, CH -8), 1.73 (3H, s, CH -1), 1.82–1.91
3
3
3
3
(6H, m, 2H-9, 2H-4, 2H-5), 2.14–2.17 (2H, m, H-10), 5.16–5.18 (1H, m, H-3), 6.76–6.88 (1H, m, H-13), 6.91–7.03 (2H, m,
1H-15, 1H-14), 7.09 (1H, m, H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 19.94 (C-4), 20.05 (C-8), 22.32 (C-7), 22.16 (C-10), 24.29 (C-1),
3
30.72 (C-9), 38.42 (C-5), 74.63 (C-6), 117.32 (C-13), 119.54 (C-15), 121.32 (C-11), 124.29 (C-3), 127.85 (C-16), 129.40
(C-14), 130.59 (C-2), 153.02 (C-12).
–1
2-(3,7-Dimethylocta-2,6-dienyl)phenol (9), yellow oil. IR spectrum (KBr, ꢅ, cm ): 3472 (ꢅ OH), 1260 (ArOH),
3040 (ꢅ Car H), 1612 and 1594 (ꢅ C=C aromatic ring), 754 and 884 (ꢁ CH ortho-substituted aromatic ring), 1334 and 1492
as
(ꢁ CH , CH , CH), 1380 (ꢁ CH ), 1676 and 835 (ꢅ C=C, ꢁ CH of nerol).
3
2
s
3
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.66 (3H, s, CH -8), 1.68 (3H, s, CH -9), 1.83 (3H, s, CH -10),
3
3
3
3
2.16–2.27 (4H, m, 2H-4, 2H-5), 3.41–3.44 (2H, m, H-1), 5.18–5.19 (1H, m, H-6), 5.20 (1H, s, OH), 5.39 (1H, t, J = 7.05,
H-2), 6.81–6.94 (2H, m, 1H-13, 1H-15), 7.14–7.18 (2H, m, 1H-14, 1H-16).
538

13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.69 (C-9), 23.45 (C-10), 25.73 (C-8), 26.41 (C-5), 29.47 (C-1),
3
32.05 (C-4), 115.69 (C-13), 120.74 (C-15), 122.50 (C-2), 123.87 (C-6), 126.96 (C-11), 127.52 (C-14), 129.95 (C-16), 132.24
(C-7), 138.48 (C-3), 154.37 (C-12).
2-(3,7-Dimethylocta-1,6-dien-3-yl)phenol (10), yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.64 (3H, s, CH -10), 1.72 (6H, s, CH -9, CH -8), 2.02–2.26 (4H, m,
3
3
3
3
2H-5, 2H-4), 5.11–5.13 (1H, m, H-6), 5.30–5.38 (2H, m, H-1), 5.91–5.93 (1H, m, H-2), 5.20 (1H, s, OH), 6.83 (1H, m, H-13),
7.14–7.16 (3H, m, 1H-14, 1H-15, 1H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.72 (C-9), 25.05 (C-10), 25.64 (C-8), 25.76 (C-5), 32.02 (C-4),
3
40.62 (C-3), 113.51 (C-1), 120.65 (C-13), 122.27 (C-15), 122.57 (C-6), 127.44 (C-16), 128.67 (C-14), 132.95 (C-7), 133.98
(C-11), 142.48 (C-2), 149.37 (C-12).
2-(6-Isopropyl-3-methylcyclohex-2-enyl)phenol (11), light-yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.05 (6H, s, CH -8, CH -9), 1.23–1.32 (1H, m, H-4), 1.66 (3H, s,
3
3
3
CH -10), 1.59–1.96 (5H, m, 2H-3, 2H-6, 1H-7), 2.76–2.79 (1H, m, H-5), 5.17–5.18 (1H, m, H-2), 5.30 (1H, s, OH), 6.77–6.85
3
(1H, m, H-13), 6.91–6.97 (1H, m, H-15), 7.02–7.15 (2H, m, 1H-14, 1H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.14 (C-9), 17.77 (C-8), 23.62 (C-10), 26.95 (C-3), 34.78 (C-7),
3
34.89 (C-4), 37.41 (C-5), 38.74 (C-6), 115.08 (C-13), 117.99 (C-2), 118.79 (C-15), 127.28 (C-14), 127.99 (C-16), 134.11
(C-1), 153.83 (C-12).
–1
4-(3,7-Dimethylocta-2,6-dienyl)phenol (12), yellow oil. IR spectrum (KBr, ꢅ, cm ): 3380 (ꢅ OH), 2972 and 2864
(ꢅ ꢅ CH , CH ), 1672 (ꢅ C=C of nerol), 1454 and 1380 [ꢅ =C(CH ) ], 3040 (ꢅ C–H aromatic ring), 1618, 1604, and 1516
as
s
3
2
s
3 2
(ꢅ C=C of aromatic ring), 828 (ꢁ C–H para-substituted aromatic ring).
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.66 (3H, s, CH -8), 1.76 (3H, s, CH -9), 1.83 (3H, s, CH -10),
3
3
3
3
2.16–2.27 (4H, m, 2H-4, 2H-5), 3.33–3.35 (2H, m, H-1), 5.19–5.20 (1H, m, H-6), 5.22 (1H, s, OH), 5.39 (1H, t, J = 7.06,
H-2), 6.83–6.94 (2H, m, 1H-13, 1H-15), 7.14–7.18 (2H, m, 1H-14, 1H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.69 (C-9), 23.45 (C-10), 25.73 (C-8), 26.41 (C-5), 29.47 (C-4),
3
32.05 (C-1), 115.69 (C-13, C-15), 120.74 (C-15), 122.50 (C-2), 123.87 (C-6), 130.00 (C-12, C-16), 132.24 (C-7), 133.87
(C-11), 138.48 (C-3), 154.31 (C-14).
4-(5,7-Dimethylocta-1,6-dien-4-yl)phenol (13), yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.34 (3H, s, CH -10), 1.65 (3H, s, CH -9), 1.66 (3H, s, CH -8),
3
3
3
3
2.16–2.17 (4H, m, 2H-4, 2H-5), 5.10–5.19 (1H, m, H-6), 5.24–5.34 (2H, m, 2H-1), 5.46 (1H, s, OH), 5.92–6.01 (1H, m, H-2),
6.78 (2H, d, J = 8.4, 1H-13, 1H-15), 7.07 (2H, d, J = 8.4, 1H-12, 1H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.67 (C-9), 23.42 (C-10), 25.71 (C-8), 23.42 (C-5), 39.73 (C-3),
3
42.03 (C-4), 111.86 (C-1), 115.22 (C-13, C-15), 123.47 (C-6), 129.37 (C-12, C-16), 132.87 (C-7), 133.85 (C-11), 144.87
(C-2), 153.76 (C-14).
–1
Bis-(3,7-dimethyl-2,6-octadienyl)ether (14), light-yellow oil. IR spectrum (KBr, ꢅ, cm ): 1676 (ꢅ C=C of nerol),
1456 and 1380 [ꢅ =C(CH ) ], 1108 and 1088 (ꢅ C–O–C).
s
3 2
s
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.65 (6H, s, CH -9, CH -9ꢀ), 1.72 (6H, s, CH -8, CH -8ꢀ), 1.80
3
3
3
3
3
(6H, s, CH -10, CH -10ꢀ), 2.12–2.20 (8H, m, 2H-4, 2H-4ꢀ, 2H-5, 2H-5ꢀ), 3.97–3.99 (4H, m, 2H-1, 2H-1ꢀ), 5.14–5.17 (2H, m,
3
3
1H-6, 1H-6ꢀ), 5.41 (2H, t, J = 6.6, 1H-2, 1H-2ꢀ).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 17.64 (C-9, C-9ꢀ), 23.59 (C-10, C-10ꢀ), 25.69 (C-8, C-8ꢀ), 26.43
3
(C-5, C-5ꢀ), 32.30 (C-4, C-4ꢀ), 66.27 (C-1, C-1ꢀ), 122.13 (C-2, C-2ꢀ), 123.97 (C-6, C-6ꢀ), 131.86 (C-7, C-7ꢀ), 140.14 (C-3,
C-3ꢀ).
–1
2-[1,1-Dimethyl-4-(2-methylchroman-2-yl)butyl]phenol (15), yellow oil. IR spectrum (KBr, ꢆꢅ, cm ): 3531
(ꢅ OH), 2953 and 2866 (ꢅ ꢅ CH , CH ), 1581 and 1604 (ꢅ C=C aromatic ring), 1446 and 1380 [ꢅ =C(CH ) ], 1242
as
s
3
2
s
3 2
(ꢅ =C–O), 752 (ꢁ C–H ortho-substituted aromatic ring).
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.26 (3H, s, CH -6), 1.45 (6H, s, CH -7, CH -8), 1.60–1.63 (2H, m,
3
3
3
3
H-4), 1.74–1.81 (4H, m, 2H-2, 2H-3), 1.91–1.94 (2H, m, 2H-9), 2.72–2.77 (2H, m, 2H-10), 4.92 (1H, s, OH), 6.66–6.69 (1H,
m, H-13ꢀ), 6.83–6.96 (3H, m, 1H-14ꢀ, 1H-13, H-15), 7.08–7.16 (3H, m, H-15ꢀ, H-16ꢀ, H-14), 7.25–7.26 (1H, m, H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢆꢁ, ppm): 19.31 (C-3), 22.15 (C-10), 24.29 (C-6), 28.24 (C-7, C-8), 30.81
3
(C-9), 38.03 (C-1), 40.38 (C-4), 41.35 (C-2), 76.48 (C-5), 116.44 (C-13ꢀ), 117.31 (C-13), 119.57 (C-15), 120.55 (C-15ꢀ),
121.34 (C-11), 127.05 (C-16), 127.24 (C-14), 128.20 (C-14ꢀ), 129.45 (C-16ꢀ), 134.56 (C-11ꢀ), 153.99 (C-12), 154.18 (C-12ꢀ).
C H O .
22 28
2
539

4-[1,1-Dimethyl-4-(2-methylchroman-2-yl)butyl]phenol (16), light-yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm, J/Hz): 1.26 (3H, s, CH -6), 1.32 (6H, s, CH -7, CH -8), 1.41–1.43 (2H, m,
3
3
3
3
2H-4), 1.55–1.65 (4H, m, 2H-2, 2H-3), 1.73–1.81 (2H, m, 2H-9), 2.71–2.78 (2H, m, 2H-10), 5.05 (1H, s, OH), 6.81 (2H, d,
J = 8.6, 1H-13ꢀ, 1H-15ꢀ), 6.84–6.89 (2H, m, 1H-13, H-15), 7.08–7.13 (2H, m, 1H-16, 1H-14), 7.23 (2H, d, J = 8.6, H-12ꢀ,
H-16ꢀ).
13
C NMR spectrum (100 MHz, CDCl , ꢁ, ppm): 18.85 (C-3), 22.12 (C-10), 24.24 (C-6), 28.27 (C-7, C-8), 30.83
3
(C-9), 37.20 (C-1), 40.36 (C-4), 45.06 (C-2), 76.34 (C-5), 114.85 (C-13ꢀ, C-15ꢀ), 117.31 (C-13), 119.60 (C-15), 121.27 (C-11),
126.84 (C-12ꢀ, C-16ꢀ), 127.27 (C-16), 129.45 (C-14), 141.85 (C-11ꢀ), 153.12 (C-12), 153.92 (C-14ꢀ). C H O .
22 28
–1
2
4-(1,1,5-Trimethyl-7-o-phenylheptan-1-yl)phenol (17), yellow oil. IR spectrum (KBr, ꢅ, cm ): 3525.88 and 3410
(ꢅ OH), 1244 (ArOH), 1606 and 1583 (ꢅ C=C aromatic ring), 754 (ꢁ C–H, ortho-substituted aromatic ring), 1446 (ꢁ CH ,
3
CH , CH), 1367 (ꢁ CH methyl), 830 (ꢁ C–H para-substituted aromatic ring).
2
s
3
PMR spectrum (300 MHz, CDCl , ꢆꢁ, ppm): 1.28 (6H, s, CH -8, CH -9), 1.37–1.42 (2H, m, 2H-5), 1.72 (3H, s,
3
3
3
CH -10), 1.83–1.85 (2H, m, 2H-6), 2.15–2.35 (2H, m, 2H-4), 3.54–3.55 (2H, m, 2H-1), 5.15 (2H, s, OH), 5.29–5.33 (1H, m,
3
H-2), 6.65–6.67 (1H, m, H-13), 6.79–6.83 (2H, m, 1H-13ꢀ, 1H-15ꢀ), 6.86–6.89 (1H, m, H-15), 7.08–7.13 (2H, m, 1H-12ꢀ,
1H-16ꢀ), 7.18–7.21 (2H, m, H-14, H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 20.90 (C-10), 23.50 (C-5), 24.24 (C-9), 24.40 (C-8), 30.83 (C-1),
3
37.10 (C-7), 40.36 (C-4), 45.06 (C-6), 114.85 (C-13ꢀ, C-15ꢀ), 116.60 (C-13), 120.40 (C-15), 121.27 (C-2), 121.24 (C-11),
127.27(C-12ꢀ, C-16ꢀ), 127.95 (C-14), 129.41 (C-16), 135.85 (C-3), 141.72 (C-11ꢀ), 153.22 (C-14ꢀ), 154.41 (C-12). C H O .
22 28
2
2-[1-Methyl-1-(4-methylcyclohex-3-en-1-yl)ethyl]phenol (18), light-yellow oil.
PMR spectrum (300 MHz, CDCl , ꢁ, ppm): 1.34 (3H, s, CH -9), 1.41 (3H, s, CH -8), 1.65 (3H, s, CH -10), 1.85–
3
3
3
3
2.31 (6H, m, 2H-3, 2H-5, 2H-6), 2.49–2.51 (1H, m, H-4), 4.92 (1H, s, OH), 5.33–5.35 (1H, m, H-2), 6.60–6.66 (1H, m, H-13),
6.72–6.75 (1H, m, H-15), 7.09–7.11 (1H, m, H-14), 7.23–7.25 (1H, m, H-16).
13
C NMR spectrum (75 MHz, CDCl , ꢁ, ppm): 23.40 (C-10), 23.70 (C-8), 24.40 (C-9), 24.70 (C-5), 27.50 (C-6),
3
31.70 (C-3), 39.6 (C-4), 40.30 (C-7), 116.69 (C-13), 120.34 (C-2), 121.50 (C-15), 128.30 (C-16), 129.90 (C-14), 133.92
(C-1), 135.55 (C-11), 154.37 (C-12).
ACKNOWLEDGMENT
The work was supported by the Russian Academy of Sciences Research under the auspices of the RAS Otd. Khim.
Nauk Mater. (OKhNM) Program “Medicinal and Biomolecular Chemistry (Project No. 09-T-3-1023).
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