The efficient synthesis of substituted 2-methylbenzofurans

Article abstract of DOI:10.1007/s10593-019-02443-3

[Figure not available: see fulltext.] The efficient synthesis of substituted 2-methylbenzofurans by aromatization of accessible allyl-substituted cyclohex-2-enones in the presence of iodine followed by dehydroiodination of the 2-iodomethyl-2,3-dihydrobenz

Full text of DOI:10.1007/s10593-019-02443-3

DOI 10.1007/s10593-019-02443-3
Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
The efficient synthesis of substituted 2-methylbenzofurans
Sergei G. Mikhalyonok1, Aliaxandr S. Arol1, Dmitri A. Litvinau1,
Nina M. Kuz'menok1, Vladimir S. Bezborodov1*
1 Organic Chemistry Department, Belarusian State Technological University,
13a Sverdlova St., Minsk 220006, Republic of Belarus;
e-mail: v_bezborodov@yahoo.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(3), 205–211
Submitted November 14, 2018
Accepted after revision February 18, 2019
O
CH2I
O
Me
O
CH2
I2
KOH
R1
R1
R1
i-PrOH
, 1 h
88–95%
i-PrOH
, 1–1.5 h
83–91%
CH2I
O
Me
CH2
O
O
I2
KOH
R1
R2
R1
R1
R2
R2
i-PrOH
, 1–1.5 h
61–74%
i-PrOH
, 1 h
61–88%
R1 = Me, Br, Ph, 4-MeC6H4, 4-MeOC6H4, 6-MeO-naphthalen-2-yl,
4-(trans-4-ethylcyclohexyl)phenyl; R2 = H, Et
The efficient synthesis of substituted 2-methylbenzofurans by aromatization of accessible allyl-substituted cyclohex-2-enones in the
presence of iodine followed by dehydroiodination of the 2-iodomethyl-2,3-dihydrobenzofuran intermediate is described.
Keywords: aryl vinyl ketones, benzofurans, cyclohexenones, aromatization, iodocyclization.
Benzofuran is a fundamental structural unit in a variety
of biologically active natural products as well as synthetic
materials. Benzofuran derivatives, including substituted
2,3-dihydrobenzofurans and methylbenzofurans are of
great interest because of their application in pharmacology
and wide distribution in nature.1–6 Substituted dihydro-
benzofurans and methylbenzofurans have been used in the
pharmaceutical industry for the preparation of drugs with
antimicrobial, antiviral, antioxidative, antifungal, anti-
neoplastic, and other properties.7,8 The unique structural
features of benzofuran and wide array of its biological
activity made it privileged structure in drug discovery.
Due to the great biological importance of this scaffold,
investigation of various synthesis methods and structural
modifications of benzofuran derivatives have now become
an important goal for several research groups. As a result,
various methods for the synthesis of substituted
2,3-dihydrobenzofurans and methylbenzofurans have been
described.1–6,9–11 Typically, the routes leading to these com-
pounds include cyclization of substituted o-allylphenols,
using various catalysts or solid-phase synthesis,12 or dehydro-
halogenation of substituted 2-iodomethyl-2,3-dihydro-
benzofurans, formed by the treatment of substituted
o-allylphenols with I2,13 or iodo- and bromoenolcyclization
of 2-(2-propenyl)cyclohexanediones and 2-(2-propenyl)-
cyclohexenone derivatives using I2 in MeOH.14 Unfortu-
nately, the utilization of expensive catalysts, sophisticated
reagents, long reaction times, and low yields of the desired
products limit the application of these methods for the
preparation of substituted dihydrobenzofurans and methyl-
benzofurans.
It is known that o-alkylphenols can be synthesized by
aromatization of the corresponding 6-substituted cyclohex-
2-enones with high yields.15,16 3,6-Disubstituted cyclohex-
2-enones can be easily prepared by condensation of the
corresponding Mannich salt with the 2-substituted aceto-
acetic ester (or substituted methyl benzyl ketones) and are
accessible intermediates for further chemical trans-
formations into various substituted benzenes and biphenyls
as earlier reported by us.17–19 In continuation of these investi-
gations and our quest to develop an effective route for the
preparation of substituted 2-methylbenzofurans we were
interested in the synthesis of allyl-substituted cyclohex-
2-enones and their aromatization in the presence of I2.
0009-3122/19/55(3)-0205©2019 Springer Science+Business Media, LLC
205

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
Scheme 1
Starting 6-allyl-3-arylcyclohex-2-enones 1a–e were
2,2-bisallylindan-1-one 13 is formed, and similar investi-
gations reported earlier22,23 the interaction of 3,6-disubsti-
tuted cyclohex-2-enones 6, 7, 8a,b with allyl bromide in
these conditions didn't lead to the formation of bis-allylated
byproducts 10a–d (Scheme 2). 2-Allyl-3,6-disubstituted
cyclohex-2-enones 9a–d were prepared in 50–57% yield.
We continued with the transformation of 2-allyl-substi-
tuted cyclohex-2-enones 1a–e and 9a–d to the cor-
responding benzofurans through the stage of aromatization
of cyclohexenone fragment and investigation of the
possibility to use saturated cyclic allyl ketones for the
preparation analogous furan derivatives. The aromatization
of 6-allyl-3-arylcyclohex-2-enones 1a–e, 2-allyl-substituted
cyclohex-2-enones 9a–d was carried out under previously
reported conditions.14,15,17 The conversion of 6-allyl-3-aryl-
cyclohex-2-enones 1a–e and 2-allyl-substituted cyclohex-
2-enones 9a–d in the presence of I2 proceeded smoothly
through the formation of the possible intermediate o-allyl-
phenol, which in situ in reaction with of I2 gave the
required products – substituted 2-iodomethyl-2,3-dihydro-
benzofurans 14a–e, 16a–d in up to 91% yield (Scheme 3).
Further investigations have shown that 2-iodomethyl-
synthesized by Michael addition of aryl vinyl ketones 3a–e,
generated in situ from the corresponding Mannich salts 2a–e,
to 2-allylacetoacetic ester 4 in boiling dioxane in the
presence of a base (Scheme 1).17–19 Intermediate 1,5-diketones
5a–e undergo intramolecular aldol condensation to cyclic
compounds 5'a–e, leading to the corresponding substituted
cyclohex-2-enones 1a–e. The similar transformations were
also used for the preparation of 6-ethyl-3-(4-methoxy-
phenyl)cyclohex-2-enone 6 and 6-ethyl-3-(6-methoxy-
2-naphthyl)cyclohex-2-enone 7. The realization of this
process in the presence of KOH in dioxane allowed us to
prepare the desired products 1a–e, 6, 7 in 66–80% yield
without isolation of intermediates or use of any auxiliary
agents or phase-transfer catalysts.
The alkylation of substituted cyclohex-2-enones 6, 7,
8a,b and indan-1-one (11) by allyl bromide at room
temperature in the presence of t-BuOK20 or NaH21 was
used for regioselective preparation of 2-allyl-substituted
cyclohex-2-enones 9a–d and 2-allylindan-1-one 12
(Scheme 2). It should be noted that in contrast to the
alkylation of indan-1-one (11), when bisallylation product
Scheme 2
Scheme 3
1
O
O
1
2
CH2I
2
7
CH2
I2
6
3
6
R
3
R
i-PrOH
, 1–1.5 h
83–91%
4
5
5
4
1a–e
14a–e
Me
O
KOH
a R = Ph, b R = 4-MeC6H4
c R = 4-MeOC6H4
d R = 4-(trans-4-ethylcyclohexyl)phenyl
e R = 6-MeO-naphthalen-2-yl
i-PrOH
, 1h
88–95%
R
15a–e
CH2I
O
Me
CH2
O
O
KOH
I2
R1
R2
R1
R2
R1
R2
i-PrOH
, 1 h
61–88%
i-PrOH
, 1–1.5 h
61–74%
17a–d
9a–d
16a–d
9, 16, 17 a R1 = Me, b R1 = Br, c R1 = 4-MeOC6H4,
d R1 = 6-MeO-naphthalen-2-yl, a,b R2 = H, c,d R2 = Et
206

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
Table 1. Important correlations in 1H–13C HSQC
In summary, an efficient and effective method for the
preparation of substituted 2,3-dihydrobenzofurans and
2-methylbenzofurans using aromatization of accessible
allyl-substuted cyclohex-2-enones in the presence of
iodine, followed by dehydroiodination of the intermediate
2-iodomethyl-2,3-dihydrobenzofurans has been developed.
The method is simple and economical, has several
advantages over the other routes and can be used for the
preparation of diverse substituted 2,3-dihydrobenzofurans
and benzofurans possessing biological or pharmacological
activity.
and 1H–13C HMBC spectra of compound 15b
Correlation with H atoms Correlations with H atoms
in 1H–13С HSQC spectrum in 1H–13С HMBC spectrum
Atom δС, ppm
Experimental
C-1
C-2
C-3
C-4
C-5
C-6
14.2
Н-1
–
Н-3
–
Н-5
Н-6
–
–
1H and 13C NMR spectra were recorded on Bruker
Avance 400 (400 and 100 MHz, respectively) and Bruker
Avance 500 (500 and 126 MHz, respectively) spectrometers
in CDCl3, residual solvent peaks were used as internal
standards (7.26 ppm for 1H nuclei, 77.2 ppm for 13C nuclei).
Elemental analysis was performed on a PerkinElmer 2400
Series II CHNS/O analyzer, halogens were determined by
published methods.24 Melting points were determined on a
BÜCHI B-540 digital melting point apparatus.
155.9
102.4
128.2
120.0
121.8
1-СH3
1-СH3, Н-5
H-3, Н-6, Н-8
–
Н-8
–
Н-6
C-7 136.7 (2C)
C-8
C-9
C-10
C-11
C-12
109.0
155.4
138.7
127.1
129.5
Н-8
–
–
Н-11
Н-12
–
H-3, Н-5, Н-8
Н-6, Н-8, Н-12
Н-12
Н-11, 14-СH3
–
Synthesis of 6-allylcyclohex-2-enones 1a–e and
6-ethylcyclohex-2-enones 6, 7 (General method). A mixture
of 1-aryl-3-(N,N-dimethylamino)propan-1-one hydro-
chloride 2a–e (0.1 mol), ethyl 2-acetylpent-4-enoate (4)
(0.11 mol) and KOH (0.35 mol) was stirred in dioxane
(100 ml) at reflux for 3.5–4 h. The reaction mixture was
cooled, acidified with 5% aqueous H2SO4 to pH 5–6. The
precipitate was filtered off, washed with H2O, and
crystallized from i-PrOH.
C-13 136.7 (2C)
C-14 21.1
Н-14
Н-12
2,3-dihydrobenzofurans 14a–e, 16a–d can be easily converted
to the corresponding substituted 2-methylbenzofurans 15a–e,
17a–d in the presence of KOH in boiling i-PrOH in 61–
95% yield (Scheme 3). The transformations of compounds
1a–e, 9a–d can be interpreted as the domino process, which
includes: (a) formation of the furan ring, (b) dehydroiodination
of 2-iodomethyl-2,3-dihydrobenzofurans 14a–e, 16a–d,
(c) 1,3-sigmatropic shift in the allylic system.
6-Allyl-3-phenylcyclohex-2-en-1-one (1a). Yield 15.4 g
(73%), white solid, mp 66.3–67.9°C (mp 49°C25). 1H NMR
spectrum (400 МHz), δ, ppm: 7.53 (2H, d, J = 7.9, Н Ph);
7.44–7.33 (3H, m, Н Ph); 6.42 (1H, s, 2-CН); 5.85–5.79
(1Н, m, СН=СН2); 5.13–5.05 (2Н, m, СН=СН2); 2.90–
2.68 (2Н, m, 4-CН2); 2.44–2.35 (1Н, m, 6-CН); 2.28–2.12
(2Н, m, СН2СН=СН2); 1.94–1.82 (2H, m, 5-CН2).
13C NMR spectrum (100 MHz), δ, ppm: 200.7; 158.8;
138.6; 136.2; 129.7; 129.0; 126.7; 125.1; 116.7; 45.6; 33.7;
27.5; 27.4. Found, %: C 84.80; H 7.52. C15H16O.
Calculated, %: C 84.87; H 7.60.
The structures of all synthesized compounds were
1
confirmed by H and 13C spectral data. Although some of
the compounds were reported earlier, analytical data were
in good correlation with the literature reported. The structure of
compound 15b was also confirmed by two-dimensional
1H–13С HMBC and 1H–13С HSQC experiments. (Table 1).
Unfortunately, treatment of 2-allylindan-1-one 12 with
1 equiv of I2 in boiling i-PrOH does not give furan derivative
18 and interaction with 2 equiv of N-iodosuccinimide in
CH2Cl2 at room temperature leads to unsaturated byproducts,
possibly through the formation of unstable bisiodo inter-
mediate 19 and its further dehydroiodination (Scheme 4).
6-Allyl-3-(4-methyphenyl)cyclohex-2-en-1-one (1b).
1
Yield 15.82 g (70%), white solid, mp 47.0–51.6°С. H NMR
spectrum (500 МHz), δ, ppm (J, Hz): 7.44 (2H, d, J = 8.2,
H Ar); 7.21 (2H, d, J = 8.2, H Ar); 6.41 (1H, s, 2-CН); 5.86–
5.79 (1Н, m, СН=СН2); 5.15–5.02 (2H, m, СН=СН2); 2.89–
2.63 (3Н, m, 4-CH2); 2.45–2.38 (1Н, m, 6-CH); 2.38 (3Н,
s, СН3); 2.29–2.12 (2Н, m, СН2СН=СН2); 1.91–1.76 (1H,
m, 5-CH2). 13C NMR spectrum (126 MHz), δ, ppm: 201.0;
158.6; 140.3; 136.2; 135.5; 129.4; 125.9; 124.2; 116.7;
45.2; 33.8; 27.4; 27.2; 21.3. Found, %: C 84.85; H 7.99.
C16H18O. Calculated, %: C 84.91; H 8.02.
Scheme 4
6-Allyl-3-(4-methoxyphenyl)cyclohex-2-en-1-one (1c).26
Yield 17.18 g (71%), white solid, mp 72.5–73.7°C.
1H NMR spectrum (400 МHz), δ, ppm (J, Hz): 7.43 (2H, d,
J = 7.9, Н Ar); 6.93 (2H, d, J = 7.9, Н Ar); 6.42 (1H, s,
2-CН); 5.86–5.78 (1Н, m, СН=СН2); 5.13–5.05 (2Н, m,
СН=СН2); 3.84 (3Н, s, ОСН3); 2.90–2.68 (2Н, m, 4-CН2);
207

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
2.40 (1Н, m, 6-CН); 2.28–2.12 (2Н, m, СН2СH=CH2);
201.9; 158.6; 158.0; 135.3; 133.3; 130.2; 128.4; 127.1;
125.8; 124.4; 123.7; 119.4; 105.6; 55.3; 47.0; 27.2; 26.9;
22.2; 11.4. Found, %: C 81.35; H 7.08. C19H20O2. Calcu-
lated, %: C 81.40; H 7.19.
1.94–1.82 (2H, m, 5-CН2). 13C NMR spectrum (100 MHz),
δ, ppm: 200.8; 161.1; 158.0; 136.2; 130.5; 127.5; 123.2; 116.6;
114.0; 55.3; 45.1; 33.8; 27.3; 27.0. Found, %: C 79.23; H 7.32.
C16H18O2. Calculated, %: C 79.31; H 7.49.
3-Bromocyclohex-2-en-1-one (8b) was prepared according
to the literature procedure.27 Yield 5.6 g (86%), yellow oil,
6-Allyl-3-[4-(trans-4-ethylcyclohexyl)phenyl]cyclohex-
2-en-1-one (1d). Yield 25.76 g (80%), white solid, mp 76.4–
1
bp 65–66°C (2.0 mm). H NMR spectrum (500 МHz),
1
77.9°C. H NMR spectrum (400 МHz), δ, ppm (J, Hz):
δ, ppm (J, Hz): 6.47 (1Н, t, J = 1.1, 2-CН); 2.83 (2Н, dt,
J = 6.1, J = 1.6, CH2); 2.42 (2H, t, J = 6.1, CH2); 2.15–2.05
(2Н, m, CH2). Found, %: C 41.06; H 3.90; Br 45.44.
C6H7BrO. Calculated, %: C 41.17; H 4.03; Br 45.65.
7.47 (2H, d, J = 7.9, Н Ar); 7.25 (2H, d, J = 7.9, Н Ar);
6.42 (1H, s, 2-CН); 5.84–5.79 (1Н, m, СН=СН2); 5.13–
5.05 (2Н, m, СН=СН2); 2.90–2.68 (2Н, m, 4-CН2); 2.50
(1H, t, J = 12.3, 1-CН Cy); 2.40–2.37 (1Н, m, 6-CН); 2.28
–2.12 (2Н, m, СН2СH=CH2); 1.94–1.82 (6H, m, 5-CН2,
2,6-CH2 Cy); 1.52–1.06 (7H, m, CH2CН3, 3,5-CH2 Cy,
4-CH Cy); 0.91 (3H, t, J = 7.2, CH2CН3). 13C NMR spectrum
(100 MHz), δ, ppm: 200.9; 158.6; 147.7; 136.2; 135.6;
128.9; 126.0; 124.2; 116.7; 45.2; 43.7; 33.8; 31.2; 29.9;
29.0; 27.4; 27.2; 24.9; 11.5. Found, %: C 85.57; H 9.29.
C23H30O. Calculated, %: C 85.66; H 9.38.
Synthesis of 2-allylcyclohex-2-enones 9a–d (General
method). A solution of t-BuOK (536 mg, 4.78 mmol,
1.1 equiv) in t-BuOH (10 ml) was stirred under N2 for a
few minutes, then a solution of the respective cyclohex-
2-enone 6, 7, 8a,b (4.34 mmol) in t-BuOH was added, and
stirring at room temperature was continued for 1 h. Then
allyl bromide (0.41 ml, 4.78 mmol, 1.1 equiv) was added,
and the formation of 2-allyl-substituted cyclohex-2-en-
1-one was controlled by TLC, eluent petroleum ether –
EtOAc. 1% HCl (50 ml) was added after 24–30 h to the
resultant reaction mixture and the solution was extracted
with CH2Cl2 (3×25 ml). The organic extracts were
combined, dried over MgSO4, and concentrated under
reduced pressure. The resultant crude was purified by
column chromatography, eluent petroleum ether – EtOAc.
2-Allyl-3-methylcyclohex-2-en-1-one (9a).28 Yield 0.33 g
(50%), colorless oil. 1H NMR spectrum (500 МHz), δ, ppm
(J, Hz): 5.80–5.71 (1Н, m, СН=СН2); 4.94 (1Н, d,
J = 16.0, CH=СH2); 4.93 (1Н, d, J = 10.0, CH=СН2); 3.07
(2Н, d, J = 6.1, СН2CH=CH2); 2.38 (2Н, t, J = 6.8,
4(6)-CН2 enone); 2.35 (2Н, t, J = 6.8, 6(4)-CН2 enone);
1.95 (2Н, quint, J = 6.8, 5-CН2 enone); 1.94 (3Н, s, СН3).
13C NMR spectrum (126 MHz), δ, ppm: 198.1; 156.8;
135.7; 133.0; 114.2; 37.6; 32.8; 29.1; 22.2; 21.1. Found, %:
C 79.85; H 9.33. C10H14O. Calculated, %: C 79.96; H 9.39.
2-Allyl-3-bromocyclohex-2-en-1-one (9b).29 Yield 0.47 g
(50%), colorless oil. 1H NMR spectrum (500 МHz), δ, ppm
(J, Hz): 5.81–5.72 (1Н, m, СН=СН2); 5.08 (1Н, dd,
J = 16.7, J = 1.3, CH=СН2); 5.01 (1Н, dd, J = 10.3, J = 1.3,
CH=СН2); 3.22 (2Н, d, J = 6.4, СН2CH=CH2); 2.93 (2Н, t,
J = 6.7, CH2); 2.47 (2Н, t, J = 6.7, CH2 enone); 2.04 (2Н,
quin, J = 6.7, 5-CH2 enone). 13C NMR spectrum (126 MHz),
δ, ppm: 194.6; 147.9; 138.1; 133.5; 115.9; 37.8; 37.4; 33.7;
22.8. Found, %: C 50.15; H 5.09; Br 36.99. C9H11BrO.
Calculated, %: C 50.26; H 5.16; Br 37.15.
6-Allyl-3-(6-methoxynaphthalen-2-yl)cyclohex-2-en-
1-one (1e). Yield 19.27 g (66%), white solid, mp 111.3–
1
114.0°С. H NMR spectrum (500 МHz), δ, ppm (J, Hz):
7.93 (1Н, d, J = 1.6, Н-1); 7.75 (1Н, d, J = 9.0, H Ar); 7.71
(1Н, d, J = 8.7, H Ar); 7.62 (1Н, dd, J = 8.7, J = 1.6, Н-3);
7.17 (1Н, dd, J = 9.0, J = 2.2, Н-7); 7.11 (1Н, d, J = 2.2,
Н-5); 6.54 (1Н, d, J = 1.6, 2-CH); 5.90–5.80 (1Н, m,
CH2СН=СН2); 5.11 (1Н, d, J = 17.9, CH2СН=СН2); 5.08
(1Н, d, J = 10.9, CH2СН=СН2); 3.93 (3Н, s, OСН3); 2.96
(1Н, dt, J = 18.0, J = 4.8, CH2 enone); 2.88–2.80 (1Н, m,
CH2 enone); 2.75–2.67 (1Н, m, CH2 enone); 2.47–2.39
(1Н, m, 6-CH); 2.31–2.16 (2Н, m, CH2СН=СН2); 1.93–
1.84 (1Н, m, CH2 enone). 13C NMR spectrum (126 MHz),
δ, ppm: 200.9; 158.7; 158.4; 136.2; 135.3; 133.3; 130.2;
128.4; 127.2; 125.9; 124.4; 123.8; 119.5; 116.8; 105.6;
55.3; 45.3; 33.8; 27.4; 27.1. Found, %: C 82.11; H 6.95.
C20H20O. Calculated, %: C 82.16; H 6.90.
6-Ethyl-3-(4-methoxyphenyl)cyclohex-2-en-1-one (6).
Yield 16.33 g (71%), white solid, mp 72.5–73.7°C.
1H NMR spectrum (500 МHz), δ, ppm (J, Hz): 7.52 (2H, d,
J = 8.6, Н Ar); 6.92 (2H, d, J = 8.6, Н Ar); 6.37 (1H, s,
2-CН); 3.84 (3Н, s, ОСН3); 2.82 (1Н, dt, J = 18.2, J = 5.1,
4-CН2); 2.71 (1Н, dddd, J = 18.2, J = 9.1, J = 4.5, J = 1.5,
4-CН2); 2.27–2.18 (2Н, m, 5-CH2); 1.98–1.80 (2Н, m,
CH2CH3); 1.55–1.43 (1Н, m, 6-CH); 0.98 (3H, t, J = 7.2,
CH2CН3). 13C NMR spectrum (126 MHz), δ, ppm: 202.0;
161.1; 157.8; 130.6; 127.5; 123.2; 114.0; 55.3; 46.9; 27.1;
26.8; 22.2; 11.4. Found, %: C 78.15; H 7.74. C15H18O2.
Calculated, %: C 78.23; H 7.88.
2-Allyl-6-ethyl-3-(4-methoxyphenyl)cyclohex-2-en-1-one
1
(9c). Yield 0.63 g (54%), colorless oil. H NMR spectrum
(500 МHz), δ, ppm (J, Hz): 7,18 (2Н, d, J = 8.7, H Ar);
6,90 (2Н, d, J = 8.7, H Ar); 5.87–5.77 (1Н, m, СН=СН2);
4.91 (1Н, d, J = 10.3, CH=СН2); 4.85 (1Н, dd, J = 17.3,
J = 1.9, CH=СН2); 3.82 (3Н, s, ОСН3); 2.94 (2Н, s, CH2);
2.65 (2Н, t, J = 6.0, CH2); 2.30–2.22 (1Н, m, CH2 enone);
2.20–2.13 (1Н, m, CH2 enone); 1.96–1.79 (2Н, m, CH2
enone); 1.53–1.43 (1Н, m, CH2 enone); 0.97 (3Н, t, J = 7.4,
CH2СН3). 13C NMR spectrum (126 MHz), δ, ppm: 201.1;
159.3; 156.3; 137.3; 133.4; 133.2; 128.3; 114.5; 113.6;
55.2; 47.4; 32.1; 31.3; 27.0; 22.5; 11.4. Found, %: C 79.86;
H 8.07. C18H22O2. Calculated, %: C 79.96; H 8.20.
6-Ethyl-3-(6-methoxynaphthalen-2-yl)cyclohex-2-en-
1-one (7). Yield 21.28 g (76%), white solid, mp 108.9–
1
109.9°С. H NMR spectrum (500 МHz), δ, ppm (J, Hz):
7.93 (1H, s, Н-1); 7.75 (1H, d, J = 8.9, H Ar); 7.72 (1H, d,
J = 8.9, H Ar); 7.62 (1H, dd, J = 8.5, J = 1.8, Н-3); 7.17
(1H, dd, J = 8.9, J = 2.5, Н-7); 7.12 (1H, d, J = 2.5, Н-5);
6.52 (1H, d, J = 1.0, 2-CН enone); 3.92 (3Н, s, ОСН3);
2.95 (1Н, dt, J = 18.0, J = 4.4, CН2 enone); 2.87–2.78 (1Н,
m, CН2 enone); 2.32–2.22 (2Н, m, CH2 enone); 1.90–1.85
(2Н, m, CH2CH3); 1.57–1.46 (1Н, m, 6-CH); 1.00 (3H, t,
J = 7.5, CH2CН3). 13C NMR spectrum (126 MHz), δ, ppm:
208

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
2-Allyl-6-ethyl-3-(6-methoxynaphthalen-2-yl)cyclohex-
2-(Iodomethyl)-6-phenyl-2,3-dihydro-1-benzofuran (14a).
1
2-en-1-one (9d). Yield 0.79 g (57%), colorless oil. H NMR
Yield 2.0 g (85%), white solid, decomposes upon heating.
1H NMR spectrum (400 МHz), δ, ppm (J, Hz): 7.53 (2H, d,
J = 7.7, Н Ph); 7.41–7.35 (3H, m, Н Ph); 7.18 (1H, d,
J = 7.4, Н-5 dihydrobenzofuran); 7.09 (1H, d, J = 7.4, Н-4
dihydrobenzofuran); 7.00 (1H, s, Н-7 dihydrobenzofuran);
4.92 (1H, quin, J = 5.1, 2-CН dihydrobenzofuran); 3.50–
3.30 (3H, m, 3-CН2 dihydrobenzofuran, CH2I); 3.06 (1Н,
dd, J = 9.7, J = 6.1, 3-CН2 dihydrobenzofuran). 13C NMR
spectrum (100 MHz), δ, ppm: 159.8; 143.4; 142.1; 129.4;
129.2; 128.1; 127.6; 124.5; 119.7; 108.1; 82.0; 35.8; 8.9.
Found, %: C 53.46; H 3.81; I 37.52. C15H13IO. Calculated, %:
C 53.59; H 3.90; I 37.75.
spectrum (500 МHz), δ, ppm (J, Hz): 7.74 (1Н, d, J = 8.4,
H Ar); 7.72 (1Н, d, J = 8.4, H Ar); 7.65 (1Н, s, Н-1); 7.31
(1Н, dd, J = 8.4, J = 1.6, Н-3); 7.17 (1Н, dd, J = 8.8,
J = 2.5, Н-7); 7.15 (1Н, dd, J = 2.5, Н-5); 5.90–5.81 (1H,
m, СН=СН2); 4.95 (1Н, dd, J = 10.1, J = 1.7, CH=СH2);
4.95 (1Н, dd, J = 17.0, J = 1.7, CH=СН2); 3.93 (3Н, s,
ОСН3); 3.03–2.92 (2H, m, CH2); 2.77–2.72 (2H, m, CH2);
2.36–2.28 (1H, m, CH2 enone); 2.26–2.18 (1H, m, CH2
enone); 2.01–1.86 (2H, m, CH2 enone); 1.58–1.48 (1H, m,
CH2 enone); 1.00 (3H, t, J = 7.5, CH2СН3). 13C NMR
spectrum (126 MHz), δ, ppm: 201.1; 158.1; 156.7; 137.2;
136.2; 134.0; 133.6; 129.6; 128.3; 126.7; 125.7; 125.5;
119.3; 114.6; 105.6; 55.3; 47.5; 32.1; 31.4; 27.2; 22.5;
11.5. Found, %: C 82.29; H 7.44. C22H24O2. Calculated, %:
C 82.46; H 7.55.
2-(Iodomethyl)-6-(p-tolyl)-2,3-dihydro-1-benzofuran
(14b). Yield 2.21 g (90%), white solid, decomposes upon
1
heating. H NMR spectrum (500 МHz), δ, ppm (J, Hz):
7.44 (2H, d, J = 7.6, Н Ar); 7.26–7.17 (3H, m, H Ar); 7.09
(1H, d, J = 8.0, H Ar); 7.00 (1H, s, H Ar); 4.97–4.89 (1Н,
m, 2-CН dihydrobenzofuran); 3.49–3.32 (3H, m, 3-CН2
dihydrobenzofuran, CH2I); 3.07 (1Н, dd, J = 16.0, J = 6.4,
3-CН2 dihydrobenzofuran); 2.38 (3H, s, CH3). 13C NMR
spectrum (126 MHz), δ, ppm: 159.7; 141.9; 138.2; 137.1;
129.4; 126.9; 125.0; 124.5; 119.8; 108.1; 82.0; 35.8; 21.1;
8.9. Found, %: C 54.80; H 4.30; I 36.30. C16H15IO.
Calculated, %: C 54.88; H 4.32; I 36.24.
Compounds 12 and 13 were prepared according to the
literature procedure.21a
2-Allyl-2,3-dihydro-1H-inden-1-one (12).21b Purified
by column chromatography, eluent petroleum ether – EtOAc,
1
17:1. Yield 0.73 g (28%), colorless oil. H NMR spectrum
(500 МHz), δ, ppm (J, Hz): 7.75 (1H, d, J = 7.4, H-7); 7.58
(1H, dt, J = 7.4, J = 1.1, H-6); 7.45 (1H, d, J = 7.4, H-4);
7.36 (1H, t, J = 7.4, H-5); 5.85–5.75 (1H, m, CH=CH2);
5.14–5.09 (1H, m, CH=CH2); 5.06–5.03 (1H, m,
CH=CH2); 3.28 (1H, dd, J = 17.4, J = 7.8, CH2); 2.86 (1H,
dd, J = 17.4, J = 3.9, CH2); 2.80–2.67 (2H, m, CH2); 2.30–
2.21 (1H, m, CH2). 13C NMR spectrum (126 MHz), δ, ppm:
208.1; 153.8; 136.7; 135.5; 134.8; 127.3; 126.6; 123.9;
116.9; 46.5; 35.5; 32.0. Found, %: C 83.66; H 6.97.
C12H12O. Calculated, %: C 83.69; H 7.02.
2-Iodomethyl-6-(4-methoxyphenyl)-2,3-dihydro-1-benzo-
furan (14c). Yield 2.13 g (83%), white solid, decomposes
1
upon heating. H NMR spectrum (400 МHz), δ, ppm
(J, Hz): 7.43 (2H, d J = 7.7, Н Ar); 6.93 (2H, d, J = 7.9, Н Ar);
7.18 (1H, d, J = 7.4, Н-5 dihydrobenzofuran); 7.09 (1H, d,
J = 7.4, Н-4 dihydrobenzofuran); 7.00 (1H, s, Н-7 dihydro-
benzofuran); 4.92 (1H, quin, J = 5.1, 2-CН dihydrobenzo-
furan); 3.84 (3Н, s, ОСН3); 3.50–3.30 (3H, m, 3-CН2
dihydrobenzofuran, CH2I); 3.06 (1Н, dd, J = 9.7, J = 6.1,
3-CН2 dihydrobenzofuran). 13C NMR spectrum (100 MHz),
δ, ppm: 159.8; 159.2; 141.5; 133.6; 128.0; 125.0; 124.2;
119.6; 114.1; 107.9; 82.0; 55.3; 35.8; 8.9. Found, %:
C 52.35; H 4.04; I 34.48. C16H15IO2. Calculated, %:
C 52.48; H 4.13; I 34.65.
2,2-Diallyl-2,3-dihydro-1H-inden-1-one (13).30 Purified
by column chromatography, eluent petroleum ether – EtOAc,
1
17:1. Yield 1.06 g (33%), colorless oil. H NMR spectrum
(500 МHz), δ, ppm (J, Hz): 7.72 (1H, d, J = 7.7, H-7); 7.57
(1H, dt, J = 7.7, J = 1.1, H-6); 7.41 (1H, d, J = 7.7, H-4);
7.34 (1H, t, J = 7.7, H-5); 5.63–5.54 (1H, m, CH=CH2);
5.06 (2H, dd, J = 17.1, J = 1.7, CH=CH2); 4.97 (2H, d,
J = 10.6, CH=CH2); 3.02 (2H, s, CH2); 2.44 (2H, dd, ,
J = 13.7, J = 6.9, CH2CH=CH2); 2.31 (2H, dd, J = 13.7,
J = 8.0, CH2CH=CH2). 13C NMR spectrum (126 MHz),
δ, ppm: 210.0; 153.0; 136.7; 134.9; 133.3; 127.3; 126.4;
123.8; 118.5; 52.2; 41.7; 36.0. Found, %: C 84.80; H 7.57.
C15H16O. Calculated, %: C 84.87; H 7.60.
6-[4-(trans-4-Ethylcyclohexyl)phenyl]-2-iodomethyl-
2,3-dihydro-1-benzofuran (14d). Yield 2.81 g (90%),
1
white solid, decomposes upon heating. H NMR spectrum
(400 МHz), δ, ppm (J, Hz): 7.47 (2H, d, J = 7.9, Н Ar);
7.25 (2H, d, J = 7.9, Н Ar); 7.18 (1H, d, J = 7.4, Н-5
dihydrobenzofuran); 7.09 (1H, d, J = 7.4, Н-4 dihydro-
benzofuran); 7.00 (1H, s, Н-7 dihydrobenzofuran); 4.92
(1H, quin, J = 5.1, 2-CН dihydrobenzofuran); 3.50–3.30
(3H, m, 3-CН2 dihydrobenzofuran, CH2I); 3.06 (1Н, dd,
J = 9.7, J = 6.1, 3-CН2 dihydrobenzofuran); 2.50 (1H, t,
J = 12.3, 1-CН Cy); 1.94–1.82 (4H, m, 2,6-CH2 Cy); 1.52–
1.06 (7H, m, CH2CН3, 3,5-CH2 Cy, 4-CH Cy); 0.91 (3H, t,
J = 7.2, CH2CН3). 13C NMR spectrum (100 MHz), δ, ppm:
159.8; 146.1; 143.8; 138.8; 129.4; 128.5; 127.9; 124.7;
119.8; 108.8; 82.1; 44.4; 39.0; 35.9; 34.2; 33.4; 30.2; 11.6;
9.0. Found, %: C 61.74; H 6.02; I 28.30. C23H27IO.
Calculated, %: C 61.89; H 6.10; I 28.43.
Synthesis of 6-aryl-2-iodomethyl-2,3-dihydro-1-benzo-
furans 14a–e and 2-iodomethyl-2,3-dihydro-1-benzo-
furans 16a,c (General method). A mixture of allyl-
substituted cyclohex-2-enones 1a–e, 9a–d (7 mmol), I2
(2.2 g, mmol, 1.2 equiv) was stirred in i-PrOH (10 ml)
under reflux for 1–1.5 h, cooled, diluted with H2O
(100 ml). If solid products were crystallized in the reaction
mixture they were filtered off, washed with cold H2O, and
recrystallized from i-PrOH. In case of liquid products,
reaction mixture was extracted with CH2Cl2 (3×15 ml).
The organic extracts were combined, dried over MgSO4,
and concentrated. The resulting crude was purified
by column chromatography, eluent petroleum ether –
EtOAc, 20:1.
2-(Iodomethyl)-6-(6-methoxynaphthalen-2-yl)-2,3-di-
hydro-1-benzofuran (14e). Yield 2.65 g (91%), white
solid, decomposes upon heating. 1Н NMR spectrum
209

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
(500 МHz), δ, ppm (J, Hz): 7.92 (1Н, s, Н-1 naphthalene);
hexenones 9b,d in one-pot manner without isolation of the
intermediate 2-iodomethyl derivatives 16b,d.
7.77 (1Н, d, J = 9.0, Н-8 naphthalene); 7.75 (1Н, d, J = 8.7,
Н-4 naphthalene); 7.65 (1Н, dd, J = 8.7, J = 1.9, Н-3
naphthalene); 7.23 (1Н, s, Н-7(4) dihydrobenzofuran); 7.21
(1Н, dd, J = 7.7, J = 1.3, Н-5 dihydrobenzofuran); 7.16
(1Н, dd, J = 9.0, J = 2.6, Н-7 naphthalene); 7.14 (1Н, d,
J = 2.6, Н-5 naphthalene); 7.12 (1Н, s, Н-4(7) dihydro-
benzofuran); 4.97–4.93 (1Н, m, 2-CН dihydrobenzofuran);
3.93 (3Н, s, OСН3); 3.48 (1Н, dd, J = 10.3, J = 4.8, CH2I);
3.44 (1Н, dd, J = 16.0, J = 9.0, 3-CН2 dihydrobenzofuran);
3.38 (1Н, dd, J = 10.3, J = 7.7, CH2I); 3.09 (1Н, dd,
J = 16.0, J = 6.4, 3-CН2 dihydrobenzofuran). 13C NMR
spectrum (126 MHz), δ, ppm: 159.8; 155.7; 144.0; 134.4;
131.0; 130.7; 130.1; 129.2; 128.5; 128.0; 126.6; 124.6;
119.9; 119.6; 110.9; 106.9; 82.0; 55.5; 35.8; 8.9. Found, %:
C 57.61; H 4.03; I 30.37. C20H17IO2. Calculated, %:
C 57.71; H 4.12; I 30.49.
2-Methyl-6-phenyl-1-benzofuran (15a).31 Yield 0.93 g
1
(89%), white solid, mp 52.1–54.1°C. Н NMR spectrum
(400 МHz), δ, ppm (J, Hz): 7.61 (1H, s, Н-7 benzofuran);
7.57 (2H, d, J = 7.9, Н Ph); 7.47 (1H, d, J = 7.9, Н-4
benzofuran); 7.41 (1H, d, J = 7.9, Н-5 benzofuran); 7.46–
7.38 (3H, m, Н Ph); 6.38 (1H, s, H-3 benzofuran); 2.46
(3H, s, CН3). 13C NMR spectrum (100 MHz), δ, ppm:
156.1; 155.4; 141.6; 136.8; 128.8; 128.4; 127.9; 127.0;
122.0; 120.1; 109.2; 102.5; 14.2. Found, %: C 86.43;
H 5.72. C15H12O. Calculated, %: C 86.51; H 5.81.
2-Methyl-6-(p-tolyl)-1-benzofuran (15b). Yield 0.98 g
1
(88%), white solid, mp 49.4–50.9°C. H NMR spectrum
(500 МH), δ, ppm (J, Hz): 7.60 (1H, s, Н-7 benzofuran);
7.52 (2Н, d, J = 8.1, Н Ar); 7.49 (1Н, d, J = 8.0, H Ar);
7.42 (1Н, dd, J = 8.0, J = 1.5, Н-5 benzofuran); 7.26 (2Н,
d, J = 8.1, Н Ar); 6.37 (1H, s H-3 benzofuran); 2.47 (3H, d,
J = 1.0, CН3 benzofuran); 2.40 (1H, s, CН3C6H4). 13C NMR
spectrum (126 МHz), δ, ppm: 155.9 (C-2); 155.4 (C-9);
138.7 (C-10); 136.7 (C-7,13); 129.5 (C-12); 128.2 (C-4);
127.1 (C-11); 121.8 (C-6); 120.0 (C-5); 109.0 (C-8); 102.4
(C-3); 21.1 (C-14); 14.2 (C-1). Found, %: C 86.37; H 6.21.
C16H14O. Calculated, %: C 86.45; H 6.35.
2-(Iodomethyl)-4-methyl-2,3-dihydro-1-benzofuran (16a).
Yield 1.17 g (61%), yellow oil. 1H NMR spectrum (500 МHz),
δ, ppm (J, Hz): 7.03 (1Н, t, J = 7.7, Н-6 dihydrobenzo-
furan); 6.68 (1Н, d, J = 7.7, Н-5 dihydrobenzofuran); 6.61
(1Н, d, J = 7.7, Н-7 dihydrobenzofuran); 4.95–4.85 (1Н, m,
2-CН dihydrobenzofuran); 3.44 (1Н, dd, J = 10.0, J = 4.8,
CH2I); 3.32 (1Н, dd, J = 10.0, J = 8.0, CH2I); 3.30 (1Н, dd,
J = 16.0, J = 9.0, 3-CН2 dihydrobenzofuran); 2.93 (1Н, dd,
J = 16.0, J = 6.4, 3-CН2 dihydrobenzofuran); 2.24 (3Н, s,
CH3). 13C NMR spectrum (126 MHz), δ, ppm: 159.8;
136.9; 129.6; 128.8; 122.1; 109.9; 82.0; 35.8; 19.3; 9.0.
Found, %: C 43.70; H 3.98; I 46.17. C10H11IO. Calculated,
%: C 43.82; H 4.05; I 46.30.
7-Ethyl-2-(iodomethyl)-4-(4-methoxyphenyl)-2,3-dihydro-
1-benzofuran (16c). Yield 2.04 g (74%), colorless oil.
1H NMR spectrum (500 МHz), δ, ppm (J, Hz): 7.39 (2Н, d,
J = 8.7, Н Ar); 7.06 (1Н, d, J = 7.7, Н-6 dihydrobenzo-
furan); 6.97 (2Н, d, J = 8.7, Н Ar); 6.88 (1Н, d, J = 7.7,
Н-5 dihydrobenzofuran); 4.96–4.85 (1Н, m, 2-CН dihydro-
benzofuran); 3.82 (3Н, s, ОСН3); 3.47 (1Н, dd, J = 16.0,
J = 9.0, 3-CН2 dihydrobenzofuran); 3.44 (1Н, dd, J = 4.5,
J = 9.9, CH2I); 3.33 (1Н, dd, J = 9.9, J = 7.7, CH2I); 3.10
(1Н, dd, J = 16.0, J = 6.4, 3-CН2 dihydrobenzofuran); 2.62
(2Н, q, J = 7.4, СН2СН3); 1.24 (3Н, t, J = 7.4, СН2СН3).
13C NMR spectrum (126 MHz), δ, ppm: 159.4; 159.0;
135.8; 131.4; 130.6; 128.9; 126.1; 125.5; 123.9; 114.7;
82.5; 55.8; 36.3; 22.8; 14.9; 9.0. Found, %: C 54.73;
H 4.80; I 32.04. C18H19IO2. Calculated, %: C 54.84;
H 4.86; I 32.19.
Synthesis of 6-aryl-2-methyl-1-benzofurans 15a–e
and 2-methyl-1-benzofurans 17a–d (General method).
A mixture of 2-iodomethyl-2,3-dihydro-1-benzofurans 14a–e
or 16a,c (5 mmol), KOH (1 g, 17.5 mmol, 3.5 equiv) in
i-PrOH (10 ml) was refluxed for 1 h, cooled, diluted with
H2O (50 ml). If solid products were crystallized in the
reaction mixture they were filtered off, washed with cold
H2O, and recrystallized from i-PrOH. In case of liquid
products, reaction mixture was extracted with CH2Cl2
(3×15 ml). The organic extracts were combined, dried over
MgSO4, and concentrated. The resulting crude was purified
by column chromatography, eluent petroleum ether –
EtOAc 20:1. Benzofurans 17b,d were prepared from cyclo-
6-(4-Methoxyphenyl)-2-methyl-1-benzofuran (15c).
Yield 1.05 g (88%), white solid, mp 63.2–65.2°C. 1H NMR
spectrum (400 МHz), δ, ppm (J, Hz): 7.61 (1H, s, Н-7
benzofuran); 7.43 (2H, d, J = 7.9, Н Ar); 7.47 (1H, d, J = 7.9,
Н-4 benzofuran); 7.39 (1H, d, J = 7.9, Н-5 benzofuran);
6.98 (2H, d, J = 7.9, Н Ar); 6.38 (1H, s, H-3 benzofuran);
3.84 (3Н, s, ОСН3); 2.46 (3H, с, CН3). 13C NMR spectrum
(100 MHz), δ, ppm (J, Hz): 160.0; 156.0; 155.5; 138.1;
133.3; 130.1; 128.6; 127.5; 126.9; 119.6; 114.2; 108.9;
55.4; 14.3. Found, %: C 80.51; H 5.85. C16H14O2.
Calculated, %: C 80.65; H 5.92.
6-[4-(trans-4-Ethylcyclohexyl)phenyl]-2-methyl-1-benzo-
furan (15d). Yield 1.51 g (95%), white solid, mp 113.8–
1
115.8°C. H NMR spectrum (400 МHz), δ, ppm (J, Hz):
7.61 (1H, s, Н-7 benzofuran); 7.54 (2H, d, J = 7.9, Н Ar);
7.47 (1H, d, J = 7.9, Н-4 benzofuran); 7.41 (1H, d, J = 7.9,
Н-5 benzofuran); 7.28 (2H, d, J = 7.9, Н Ar); 6.38 (1H, s,
H-3 benzofuran); 2.51 (1H, t, J = 12.3, 1-CН Cy); 2.46
(3H, s, CН3 benzofuran); 1.94–1.82 (4H, m, 2,6-CH2 Cy);
1.52–1.06 (7H, m, CH2CН3, 3,5-CH2 Cy, 4-CH Cy); 0.91
(3H, t, J = 7.2, CH2CН3). 13C NMR spectrum (100 MHz),
δ, ppm (J, Hz): 155.9; 155.4; 146.7; 139.1; 136.8; 128.2;
127.2; 127.1; 121.9; 120.0; 109.0; 102.5; 44.3; 39.1; 34.3;
33.2; 30.0; 14.1; 11.5. Found, %: C 86.59; H 8.11.
C23H26O. Calculated, %: C 86.75; H 8.23.
6-(6-Methoxynaphthalen-2-yl)-2-methyl-1-benzofuran
1
(15e). Yield 1.27 g (88%), white solid. H NMR spectrum
(500 МHz), δ, ppm (J, Hz): 7.99 (1Н, d, J = 1.3, Н-1
naphthalene); 7.79 (2Н, d, J = 8.5, Н-4,8 naphthalene);
7.74 (1Н, dd, J = 8.5, J = 1.9, Н-3 naphthalene); 7.72 (1Н,
s, Н-7 benzofuran); 7.54 (1Н, dd, J = 8.0, J = 1.2, Н-5
benzofuran); 7.53 (1Н, d, J = 8.0, Н-4 benzofuran); 7.17
(1Н, dd, J = 8.5, J = 2.6, Н-7 naphthalene); 7.15 (1Н, d,
J = 2.6, Н-5 naphthalene); 6.40 (1Н, s, H-3 benzofuran);
3.93 (3Н, s, OСН3); 2.49 (3Н, d, J = 1.0, CН3). 13C NMR
210

Chemistry of Heterocyclic Compounds 2019, 55(3), 205–211
spectrum (126 MHz), δ, ppm: 155.9; 155.6; 155.4; 144.8;
References
133.8; 131.0; 130.2; 130.0; 129.6; 128.7; 128.1; 127.6;
126.5; 125.9; 119.7; 118.9; 106.8; 102.5; 55.5; 14.2.
Found, %: C 83.32; H 5.55. C20H16O2. Calculated, %:
C 83.31; H 5.59.
1. Heravi, M. M.; Zadsirjan, V.; Hamidi, H.; Hajiabbas, P.;
Amiri, T. RSC Adv. 2017, 7, 24470.
2. Malik, S.; Nadir, U. K.; Pandey, P. S. Tetrahedron 2009, 65, 3918.
3. Kokubo, K.; Harada, K.; Mochizuki, E.; Oshima, T.
Tetrahedron Lett. 2010, 51, 955.
2,4-Dimethyl-1-benzofuran (17a). Yield 0.45 g (61%),
1
4. Kadieva, M. G.; Oganesyan, E. T. Chem. Heterocycl. Compd.
1997, 33, 1245. [Khim. Geterotsikl. Soedin. 1997, 1443.]
5. Ukhin, L. Yu.; Belousova, L. V.; Orlova, Zh. I.; Korobov, M. S.;
Borodkin, G. S. Chem. Heterocycl. Compd. 2002, 38, 1174.
[Khim. Geterotsikl. Soedin. 2002, 1339.]
colorless oil. H NMR spectrum (500 МHz), δ, ppm (J, Hz):
7.23 (1Н, d, J = 8.0, Н-7 benzofuran); 7.09 (1Н, t, J = 8.0,
Н-6 benzofuran); 6.96 (1Н, d, J = 8.0, Н-5 benzofuran);
6.38 (1Н, s, H- benzofuran); 2.46 (3Н, s, СН3); 2.45 (3Н, s,
СН3). 13C NMR spectrum (126 MHz), δ, ppm: 156.0;
155.4; 130.7; 130.5; 123.8; 123.5; 108.5; 102.7; 19.5; 14.2.
Found, %: C 82.07; H 6.81. C10H10O. Calculated, %:
C 82.16; H 6.90.
6. Naik, R.; Harmalkar, D. S.; Xu, X.; Jang, K.; Lee, K. Eur. J.
Med. Chem. 2015, 90, 379.
7. Teo, C. C.; Kon, O. L.; Sim, K. Y.; Ng, S. C. J. Med. Chem.
1992, 35, 1330.
8. Gfesser, G. A.; Faghih, R.; Bennani, Y. L.; Curtis, M. P.;
Esbenshade, T. A.; Hancock, A. A.; Cowart, M. D. Bioorg.
Med. Chem. Lett. 2005, 15, 2559.
4-Bromo-2-methyl-1-benzofuran (17b). Yield 0.73 g
1
(69%), yellow oil. H NMR spectrum (500 МHz), δ, ppm
(J, Hz): 7.23 (1Н, d, J = 8.0, Н-7 benzofuran); 7.09 (1Н, t,
J = 8.0, Н-6 benzofuran); 6.96 (1Н, d, J = 8.0, Н-5
benzofuran); 6.38 (1Н, s, H-3 benzofuran); 2.47 (3Н, s,
СН3). 13C NMR spectrum (126 MHz), δ, ppm: 156.2;
154.4; 130.6; 125.4; 124.0; 112.9; 109.7; 102.8; 14.2.
Found, %: C 51.30; H 3.30; Br 37.88. C9H7BrO.
Calculated, %: C 51.22; H 3.34; Br 37.86.
9. Szlosek-Pinaud, M.; Diaz, P.; Martinez, J.; Lamaty, F.
Tetrahedron 2007, 63, 3340.
10. Hocke, C.; Prante, O.; Lober, S.; Hubener, H.; Gmeiner, P.;
Kuwert, T. Bioorg. Med. Chem. Lett. 2004, 14, 3963.
11. Enders, D.; Niemeier, O.; Straver, L. Synlett 2006, 3399.
12. Zhang, Y. J.; Wang, Y. G. Appl. Organomet. Chem. 2012, 26, 212.
13. Yadav, A. K.; Singh, B. K.; Singh, N.; Tripathi, R. P.
Tetrahedron Lett. 2007, 48, 6628.
7-Ethyl-4-(4-methoxyphenyl)-2-methyl-1-benzofuran
1
14. Mphahlele, M. J.; Moekwa, T. B. Org. Biol. Chem. 2005, 3, 2469.
15. Mphahlele, M. J. Molecules 2009, 14, 5308.
(17c). Yield 1.17 g (88%), white solid. H NMR spectrum
(500 МHz), δ, ppm (J, Hz): 7.53 (2H, d, J = 8.8, Н Ar);
7.16 (1H, d, J = 7.7, Н-5 benzofuran); 7.08 (1H, d, J = 7.7,
Н-6 benzofuran); 7.00 (2H, d, J = 8.8, Н Ar); 6.54 (1H, s,
H-3 benzofuran); 3.86 (3Н, s, СН3О); 2.94 (2Н, q, J = 7.7,
СН2CH3); 2.50 (3Н, s, СН3); 1.37 (3Н, t, J = 7.7, CH2СН3).
13C NMR spectrum (126 MHz), δ, ppm: 159.7; 155.0;
152.9; 133.1; 129.3; 127.4; 127.3; 124.8; 122.9; 122.0; 114.6;
101.9; 55.8; 22.4; 14.9; 14.2. Found, %: C 81.03; H 6.74.
C18H18O2. Calculated, %: C 81.17; H 6.81.
16. Downes, A. M.; Gill, N. S.; Lions, F. J. Am. Chem. Soc. 1950,
72, 3464.
17. Bezborodov, V. S.; Dabrowski, R. Mol. Cryst. Liq. Cryst. Sci.
Technol., Sect. A 1997, 299, 1.
18. Dabrowski, R.; Bezborodov, V. Liq. Cryst. 2006, 33, 1487.
19. Bezborodov, V. S.; Lapanik, V. I.; Sasnouski, G. M.; Haase, W.
Liq. Cryst. 2013, 40, 1383.
20. Vekariya, R. H.; Liu, R.; Aubé, J. Org. Lett. 2014, 16, 1844.
21. (a) Kotha, S; Ali, R; Tiwari, A. Synthesis 2014, 2471. (b) Vig, O. P.;
Gandhi, R. P.; Gulati, R. K. J. Ind. Chem. Soc. 1957, 34, 281.
22. (a) Atwater, N. W. J. Am. Chem. Soc. 1960, 82, 2847.
(b) Chandrasekhar, S.; Reddy, Ch. R. Tetrahedron:
Asymmetry 2002, 13, 261.
7-Ethyl-4-(6-methoxynaphthalen-2-yl)-2-methyl-1-benzo-
furan (17d). Yield 1.14 g (72%), white solid, mp 102.2–
1
103.5°C. H NMR spectrum (500 МHz), δ, ppm (J, Hz):
7.98 (1Н, s, Н-1 naphthalene); 7.83 (1H, d, J = 8.5, H Ar);
7.80 (1H, d, J = 9.5, H Ar); 7.73 (1H, dd, J = 8.5, J = 1.7,
H Ar); 7.31 (1H, d, J = 7.5, Н-5(6) benzofuran); 7.21–7.17
(2H, m, H Ar); 7.15 (1H, d, J = 7.5, Н-6(5) benzofuran);
6.63 (1H, d, J = 1.0, H-3 benzofuran); 3.86 (3Н, s, СН3О);
2.98 (2Н, q, J = 7.5, СН2CH3); 2.50 (3Н, s, СН3); 1.40 (3Н,
t, J = 7.5, CH2СН3). 13C NMR spectrum (126 MHz),
δ, ppm: 157.7; 155.4; 153.5; 135.9; 133.5; 131.8; 129.6;
129.1; 127.4; 127.1; 126.9; 126.7; 126.1; 122.7; 122.3;
119.0; 105.6; 102.4; 55.3; 22.8; 14.3; 14.2. Found %:
C 83.61; H 6.37. C22H20O2. Calculated, %: C 83.52;
H 6.37.
23. Brocksom, T. J.; Brocksom, U.; Frederico, D. Tetrahedron
Lett. 2004, 45, 9289.
24. (a) Newman, D. G.; Tomlinson, C. Microchim. Acta 1961, 49,
73. (b) Schöniger, W. Microchim. Acta 1956, 44, 869.
25. Bradley, S. A.; Bresnan, B. J.; Draper, S. M.; Gerathy, N. W. A.;
Jaffares, M.; McCabe, T.; McMurry, T. B. H.; O'Brien, J. E.
Org. Biomol. Chem. 2011, 9, 2959
26. Yamamoto, E.; Gokuden, D.; Nagai, A.; Kamachi, T.;
Yoshizawa, K.; Hamasaki, A.; Ishida, T.; Tokunaga, M. Org.
Lett. 2012, 14, 6178.
27. Shih, C.; Swenton, J. S. J. Org. Chem. 1982, 47, 2825.
28. Prakash, C.; Mohanakrishnan, A. K. Eur. J. Org. Chem. 2008,
9, 1535.
29. Masters, K.-S.; Flynn, B. L. Adv. Synth. Catal. 2009, 351, 530.
30. Grenning, A. J.; Tunge, J. A. J. Am. Chem. Soc. 2011, 133, 14785.
31. Hashmi, A. S. K.; Wölfle, M. Tetrahedron 2009, 65, 9021.
This study was supported by the Belarusian State
Technological University.
211