Synthesis of 1,2-dihydro-3-benzoxepins by the reaction of 2-lithio-β-methoxystyrenes with epoxides followed by hydriodic acid catalyzed cyclization

Article abstract of DOI:10.3987/COM-09-11869

5-Substituted 1,2-dihydro-3-benzoxepins can be prepared in reasonable overall yields from α-substituted 2-bromo-β-methoxystyrenes. Thus, the reaction of α-substituted 2-lithio-β-mefhoxystyrenes, generated by the bromine-lithium exchange between α-substituted 2-bromo-β-methoxystyrenes and butyllithium, with epoxides gives the corresponding 2-(methoxyvinyl)phenethyl alcohols. These undergo cyclization with a loss of methanol on treatment with a catalytic amount of hydriodic acid to give the desired products.

Full text of DOI:10.3987/COM-09-11869

HETEROCYCLES, Vol. 81, No. 3, 2010
699
HETEROCYCLES, Vol. 81, No. 3, 2010, pp. 699 - 705. © The Japan Institute of Heterocyclic Chemistry
Received, 4th November, 2009, Accepted, 24th December, 2009, Published online, 28th December, 2009
DOI: 10.3987/COM-09-11869
SYNTHESIS OF 1,2-DIHYDRO-3-BENZOXEPINS BY THE REACTION
OF 2-LITHIO-ꢀ-METHOXYSTYRENES WITH EPOXIDES FOLLOWED
BY HYDRIODIC ACID CATALYZED CYCLIZATION
Kazuhiro Kobayashi,* Hiroo Hashimoto, Toshiyuki Nagaoka, Yuu Shirai,
and Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology,
Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan; E-mail: kkoba@chem.tottori-u.ac.jp
Abstract – 5-Substituted 1,2-dihydro-3-benzoxepins can be prepared in
reasonable overall yields from ꢁ-substituted 2-bromo-ꢀ-methoxystyrenes. Thus,
the reaction of ꢁ-substituted 2-lithio-ꢀ-methoxystyrenes, generated by the
bromine-lithium exchange between ꢁ-substituted 2-bromo-ꢀ-methoxystyrenes
and
butyllithium,
with
epoxides
gives
the
corresponding
2-
(methoxyvinyl)phenethyl alcohols. These undergo cyclization with a loss of
methanol on treatment with a catalytic amount of hydriodic acid to give the
desired products.
In previous papers, we reported that 2-lithio-ꢀ-methoxystyrene derivatives were versatile intermediates
for the preparation of mainly heterocyclic compounds.1 We first demonstrated that the reaction of these
lithium compounds with various nitriles gives directly isoquinoline derivatives through a successive
addition-substitution sequence.1a Subsequently, we found that isochromene,1b 2-methoxyindene,1c
isoquinolin-1(2H)-one,1d and isothiochroman derivatives1e could be obtained by the reactions with other
electrophiles, such as carbonyl compounds,1b,c isocyanates,1d and isothiocyanates,1e followed by
hydriodic acid-catalyzed or -mediated cyclization of the resultant corresponding adducts, respectively.
As a continuation of these studies, we envisaged that the reaction of 2-lithio-ꢀ-methoxystyrene
derivatives with epoxides, followed by a similar cyclization with hydriodic acid should give
1,2-dihydro-3-benzoxepin derivatives. We wish to report here that the reaction of ꢁ-substituted
2-lithio-ꢀ-methoxystyrene derivatives with epoxides, such as isobutene oxide and propylene oxide, gave
1-[2-(2-methoxyvinyl)phenyl]propan-2-ol derivatives (2), which on treatment with a catalytic amount of

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hydriodic acid to give 5-substituted 1,2-dihydro-3-benzoxepins (5) in reasonable yields. The previously
synthesized compounds having this skeleton are ethyl 2-(7,8-dimethoxy-1,2-dihydro-3-
benzoxepin-5-yl)acetate2 and 6,9-diiodo-1,2-dihydro-3-benzoxepin.3
Our two-step synthesis of 1,2-dihydro-3-benzoxepin derivatives (5) from 2-bromo-ꢀ-methoxystyrene
derivatives (1) was conducted as illustrated in Scheme 1. Thus, treatment of 1 with butyllithium in
diethyl ether at 0 ˚C generated 2-lithio-ꢀ-methoxystyrene derivatives, which were then treated with
epoxides, such as isobutene oxide and propylene oxide. The attack of these lithium compounds on these
epoxides proceeded relative slowly (about 1 h) to produce the 1-[2-(2-methoxyvinyl)phenyl]propan-2-ol
derivatives (2) after aqueous workup. Unfortunately, the reaction of 2-lithio-(ꢀ-methoxy-ꢁ-
phenyl)styrene, derived from 1a, with styrene oxide gave an intractable mixtures of products, though the
reason for this is not clear yet.
R2
R2
R2
Br
R1
OMe
R1
R1
OMe
OMe
conc. HI (cat.)
1. n-BuLi, Et2O, 0 ˚C
OH
R3
OH
R3
MeCN, 0 ˚C
O
2.
, 0 ˚C
Me
R3
Me
Me
2
1a R1 = H, R2 = Ph
3
1b R1 = H, R2 = m-Tol
1c R1 = H, R2 = p-Tol
1d R1 = H, R2 = 4-FC6H4
1e R1 = H, R2 = 4-ClC6H4
1f R1 = H, R2 = Me
1g R1 = OMe, R2 = Ph
R2
R2
OMe
R1
R1
– MeOH, – H+
O
OH
R3
R3
Me
Me
5
4
Scheme 1
Table 1. Preparation of 1,2-Dihydro-3-benzoxepin Derivatives (5)
Entry
1
R3 in epoxide
2 (Yield/%;a E:Zb)
2a (65; 5:5)
2b (55; 3:7)
2c (57; 5:5)
2d (58; 4:6)
2e (57; 5:5)
2f (63; 4:6)
2g (58; 4:6)
2h (58; 5:5)
2i (59; 6:4)
2j (65; 4:6)
5 (Yield/%)a
5a (60)
5b (42)
5c (57)
5d (45)
5e (54)
5f (54)
1
2
3
4
5
6
7
8
9
10
1a
1a
1b
1b
1c
1d
1e
1f
Me
H
Me
H
Me
Me
Me
Me
H
5g (60)
5h (52)
5i (46)
1f
1g
Me
5j (61)
aYields of isolated, purified products. bApproximate values.

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701
These methoxyvinyl alcohols (2) thus obtained were treated with a catalytic amount of hydriodic acid in
acetonitrile at 0 ˚C. The starting materials were consumed immediately as expected, and the desired
products (5) were obtained, via intermediates (3) and (4), after the usual workup and subsequent
purification by preparative TLC on silica gel. The results of the preparation of 5 from 1, via 2, are
summarized in Table 1, which indicates that the yields of the both products (2) and (5) are generally
moderate to fair. The cyclization products from the respective adducts of 1 with propylene oxide (5b, 5d,
and 5h) were obtained in somewhat lower yields than those from 1 with isobutene oxide, though the
reason for this is difficult to explain at the present time. The attempted cyclization of the adduct of 1a
with 1,2-epoxy-3-methoxypropane gave a poor result. When the adduct was subjected to similar
cyclization conditions, a complex mixture of products was obtained. Not so high yields in the
cyclization step forming 5 may be attributable to the liability of the methoxyvinyl moiety toward
oligomerization under such acidic conditions. A similar explanation has been given previously in the
preparation of 4-substituted isochromenes.1b
In conclusion, we have demonstrated the first general construction of 1,2-dihydro-3-benzoxepin
derivatives. The present method may find some value in synthesis; the ready availability of the starting
materials and simplicity of operations combine to make the present method useful. Further studies to
utilize 2-lithio-ꢀ-methoxystyrene intermediates for the construction of rare or useful heterocyclic
systems are in progress.
EXPERIMENTAL
All melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are
uncorrected. IR spectra were determined with a Shimadzu FTIR-8300 spectrophotometer. The 1H NMR
spectra were determined in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR
spectrometer operating at 500 MHz or a JEOL LA400 FT NMR spectrometer operating at 400 MHz.
13
The C NMR spectra were determined in CDCl3 using TMS as an internal reference with a JEOL
ECP500 FT NMR spectrometer operating at 125 MHz. Low-resolution MS spectra were measured by a
JEOL JMS AX505 HA spectrometer. TLC was carried out on a Merck Kieselgel 60 PF254. Column
chromatography was performed using Merck Kieselgel 60 (0.063–0.200 mm). All of the organic
solvents used in this study were dried over appropriate drying agents and distilled prior to use.
Starting Materials. 2-Bromo-ꢀ-methoxystyrenes (1) were prepared by a previously reported our
procedure.1 All other chemicals used in this study were commercially available.
Typical Procedure for the Preparation of 1-[2-(2-Methoxyvinyl)phenyl]propan-2-ol Derivatives (2).
1-[2-(2-Methoxy-1-phenylethenyl)phenyl]-2-methylpropan-2-ol (2a). To a stirred solution of 1a (0.27
g, 0.92 mmol) in Et2O (6 mL) at 0 ˚C was added dropwise n-BuLi (1.6M in hexane; 0.92 mmol). After 1
h, 2,2-dimethyloxiran (66 mg, 0.92 mmol) was added and stirring was continued for an additional 1 h.

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The mixture was quenched with saturated aqueous NH4Cl (15 mL) and extracted with Et2O three times
(10 mL each). The combined extracts were dried over anhydrous Na2SO4 and evaporated. The residue
was purified by preparative TLC on silica gel to afford 2a (0.16 g, 65%): a pale-yellow oil; a mixture of
1
stereoisomers (E:Z = ca. 5:5); Rf 0.13 (1:5 AcOEt–hexane); IR (neat) 3427, 1633 cm–1; H NMR (500
MHz) ꢀ 1.10 (3H, s), 1.15 (3H, s), 1.48 (0.5H, s), 1.83 (0.5H, s), 2.56 (1H, s), 2.57 (1H, s), 3.70 (1.5H,
s), 3.77 (1.5H, s), 6.25 (0.5H, s), 6.67 (0.5H, s), 7.09–7.37 (9H, m). Anal. Calcd for C19H22O2: C, 80.82;
H, 7.85. Found: C, 80.73; H, 8.01.
1-[2-(2-Methoxy-1-phenylethenyl)phenyl]propan-2-ol (2b): a pale-yellow oil; a mixture of
1
stereoisomers (E:Z = ca. 3:7); Rf 0.21 (1:4 AcOEt–hexane); IR (meat) 3404, 1636 cm–1; H NMR (500
MHz) ꢀ 1.06 (0.9H, d, J = 6.0 Hz), 1.15 (2.1H, d, J = 6.0 Hz), 1.30 (0.3H, d, J = 4.1 Hz), 1.78 (0.7H, br
s), 2.48 (0.3H, dd, J = 13.7, 8.2 Hz), 2.51 (0.7H, dd, J = 13.7, 8.9 Hz), 2.57 (0.3H, dd, J = 13.7, 4.6 Hz),
2.62 (0.7H, dd, J = 13.7, 3.7 Hz), 3.71 (2.1H, s), 3.78 (0.9H, s), 3.78–3.85 (0.3H, m), 3.91–3.96 (0.7H,
m), 6.22 (0.3H, s), 6.70 (0.7H, s), 7.10–7.36 (9H, m). Anal. Calcd for C18H20O2: C, 80.56; H, 7.51.
Found: C, 80.49; H, 7.81.
2-Methyl-1-{2-[1-(3-Methylphenyl)-2-methoxyethenyl]phenyl}propan-2-ol (2c): a pale-yellow oil; a
1
mixture of stereoisomers (E:Z = ca. 5:5); Rf 0.21 (1:7 AcOEt–hexane); IR (neat) 3418, 1634 cm–1; H
NMR (500 MHz) ꢀ 1.11 (3H, s), 1.16 (3H, s), 1.51 (0.5H, s), 1.87 (0.5H, s), 2.28 (3H, s), 2.57 (2H, s),
3.70 (1.5H, s), 3.77 (1.5H, s), 6.22 (0.5H, s), 6.66 (0.5H, s), 6.87 (1H, d, J = 7.8 Hz), 6.93–6.99 (1.5H,
m), 7.10–7.17 (2H, m), 7.24–7.34 (3.5H, m). Anal. Calcd for C20H24O2: C, 81.04; H, 8.16. Found: C,
81.87; H, 7.38.
1-{2-[1-(3-Methylphenyl)-2-methoxyethenyl]phenyl}propan-2-ol (2d): a pale-yellow oil; a mixture of
1
stereoisomers (E:Z = ca. 4:6); Rf 0.21 (1:7 AcOEt–hexane); IR (neat) 3403, 1634 cm–1; H NMR (500
MHz) ꢀ 1.07 (1.2H, d, J = 7.3 Hz), 1.15 (1.8H, d, J = 7.3 Hz), 1.30 (0.4H, br s), 1.78 (0.6H, br s), 2.28
(3H, s), 2.44–2.65 (2H, m), 3.69 (1.8H, s), 3.77 (1.2H, s), 3.82–3.88 (0.4H, m), 3.91–3.97 (0.6H, m),
6.19 (0.4H, s), 6.68 (0.6H, s), 6.88 (1.2H, d, J = 7.8 Hz), 6.93–6.99 (1.6H, m), 7.10–7.31 (5.2H, m).
Anal. Calcd for C19H22O2: C, 80.82; H, 7.85. Found: C, 80.61; H, 7.74.
2-Methyl-1-{2-[1-(4-Methylphenyl)-2-methoxyethenyl]phenyl}propan-2-ol (2e): a pale-yellow oil; a
1
mixture of stereoisomers (E:Z = ca. 5:5); Rf 0.29 (1:5 THF–hexane); IR (neat) 3441, 1634 cm–1; H
NMR (500 MHz) ꢀ 1.11 (3H, s), 1.15 (3H, s), 1.51 (0.5H, s), 1.87 (0.5H, s), 2.298 and 2.303 (combined
3H, 2s), 2.57 (2H, s), 3.69 (1.5H, s), 3.76 (1.5H, s), 6.21 (0.5H, s), 6.64 (0.5H, s), 6.98 (1H, d, J = 8.2
Hz), 7.04 (1H, d, J = 8.2 Hz), 7.06 (1H, d, J = 8.2 Hz), 7.23 (1H, d, J = 8.2 Hz), 7.25–7.33 (4H, m). Anal.
Calcd for C20H24O2: C, 81.04; H, 8.16. Found: C, 81.00; H, 8.29.
1-{2-[1-(4-Fluorophenyl)-2-methoxyethenyl]phenyl}-2-methylpropan-2-ol (2f): a pale-yellow oil; a
1
mixture of stereoisomers (E:Z = ca. 4:6); Rf 0.24 (1:6 AcOEt–hexane); IR (neat) 3389, 1637 cm–1; H
NMR (500 MHz) ꢀ 1.11 (2.4H, s), 1.16 (3.6H, s), 1.56 (0.4H, br s), 1.85 (0.6H, br s), 2.535 (1.2H, s),

HETEROCYCLES, Vol. 81, No. 3, 2010
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2.542 (0.8H, s), 3.70 (1.8H, s), 3.78 (1.2H, s), 6.23 (0.4H, s), 6.61 (0.6H, s), 6.90–6.97 (2.8H, m), 7.05
(1.2H, dd, J = 8.7, 5.5 Hz), 7.20–7.37 (4H, m). Anal. Calcd for C19H21FO2: C, 75.97; H, 7.05. Found: C,
75.75; H, 7.34.
1-{2-[1-(4-Chlorophenyl)-2-methoxyethenyl]phenyl}-2-methylpropan-2-ol (2g): a pale-yellow oil; a
1
mixture of stereoisomers (E:Z = ca. 4:6); Rf 0.24 (1:5 AcOEt–hexane); IR (neat) 3410, 1635 cm–1; H
NMR (500 MHz) ꢀ 1.11 (2.4H, s), 1.15 (3.6H, s), 1.59 (0.4H, br s), 1.81 (0.6H, br s), 2.53 (2H, s), 3.71
(1.8H, s), 3.79 (1.2H, s), 6.25 (0.4H, s), 6.67 (0.6H, s), 7.02 (1.2H, d, J = 8.7 Hz), 7.18–7.35 (6.8H, m).
Anal. Calcd for C19H21ClO2: C, 72.03; H, 6.68. Found: C, 71.12; H, 6.63.
2-Methyl-1-[2-(2-methoxy-1-methylethenyl)phenyl]propan-2-ol (2h): a pale-yellow oil; a mixture of
1
stereoisomers (E:Z = ca. 5:5); Rf 0.29 (1:5 THF–hexane); IR (neat) 3441, 1668 cm–1; H NMR (500
MHz) ꢀ 1.19 (3H, s), 1.23 (3H, s), 1.54 (0.5H, s), 1.85 (1.5H, d, J = 1.4 Hz), 1.91 (1.5H, d, J = 1.4 Hz),
2.00 (0.5H, s), 2.80 (1H, s), 2.88 (1H, s), 3.53 (1.5H, s), 3.66 (1.5H, s), 5.94 (0.5H, q, J = 1.4 Hz), 5.99
(0.5H, q, J = 1.4 Hz), 7.11–7.32 (4H, m). Anal. Calcd for C14H20O2: C, 76.33; H, 9.15. Found: C, 76.28;
H, 9.09.
1-[2-(2-Methoxy-1-methylethenyl)phenyl]propan-2-ol (2i): a colorless oil; a mixture of stereoisomers
1
(E:Z = ca. 6:4); Rf 0.25 (1:5 AcOEt–hexane); IR (neat) 3418, 1668 cm–1; H NMR (400 MHz) ꢀ 1.23
(1.2H, d, J = 7.3 Hz), 1.25 (1.8H, d, J = 7.3 Hz), 1.48 (0.6H, br s), 1.84 (1.2H, d, J = 1.5 Hz), 1.90 (1.8H,
d, J = 1.5 Hz), 1.99 (0.4H, br s), 2.63–2.86 (2H, m), 3.52 (1.2H, s), 3.66 (1.8H, s), 4.00–4.07 (1H, m),
5.91 (0.6H, q, J = 1.5 Hz), 6.00 (0.4H, q, J = 1.5 Hz), 7.08–7.27 (4H, m). Anal. Calcd for C13H18O2: C,
75.69; H, 8.80. Found: C, 75.71; H, 8.72.
1-[4-Methoxy-2-(2-methoxy-1-phenylethenyl)phenyl]-2-methylpropan-2-ol (2j): a pale-yellow oil; a
1
mixture of stereoisomers (E:Z = ca. 4:6); Rf 0.20 (1:5 AcOEt–hexane); IR (neat) 3453, 1634 cm–1; H
NMR (500 MHz) ꢀ 1.09 (3.6H, s), 1.14 (2.4H, s), 1.45 (0.4H, s), 1.84 (0.6H, s), 2.48 (1.2H, s), 2.49
(0.8H, s), 3.71 (1.8H, s), 3.78 (1.2H, s), 3.82 (1.8H, s), 3.83 (1.2H, s), 6.27 (0.4H, s), 6.67 (0.6H, s), 6.81
(0.4H, d, J = 2.7 Hz), 6.85–6.88 (1.6H, m), 7.11 (1H, d, J = 7.8 Hz), 7.15–7.17 (1H, m), 7.22–7.27 (3.2H,
m), 7.36 (0.8H, d, J = 7.3 Hz). Anal. Calcd for C20H24O3: C, 76.89; H, 7.74. Found: C, 77.02; H, 7.72.
Typical Procedure for the Preparation of Dihydrobenzoxepine Derivatives (5). 2,2-Dimethyl-5-
phenyl-1,2-dihydro-3-benzoxepin (5a). To a stirred solution of 2a (0.16 g, 0.60 mmol) in MeCN (6
mL) at 0 ˚ C was added a drop of concentrated hydriodic acid. After 5 min, saturated aqueous NaHCO3
(10 mL) was added, and MeCN was evaporated. The organic materials were extracted with Et2O twice
(15 mL each). The combined extracts were washed with brine, dried over anhydrous Na2SO4, and
evaporated. The residue was purified by preparative TLC on silica gel to afford 5a (89 mg, 60%): a
pale-yellow oil; Rf 0.34 (1:30 AcOEt–hexane); IR (neat) 1607 cm–1; 1H NMR (500 MHz, CDCl3) ꢀ 1.31
(6H, s), 2.92 (2H, s), 6.72 (1H, s), 6.94 (1H, dd, J = 8.7, 1.8 Hz), 7.12–7.18 (3H, m), 7.27–7.34 (5H, m);
13C NMR ꢀ 27.83, 46.85, 87.51, 124.38, 126.10, 126.17, 126.77, 128.26, 128.91, 129.42, 129.55, 137.86,

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HETEROCYCLES, Vol. 81, No. 3, 2010
137.99, 140.77, 142.94; MS (EI) m/z 250 (M+, 59), 207 (71), 192 (100). Anal. Calcd for C18H18O: C,
86.36; H, 7.25. Found: C, 86.19; H, 7.21.
2-Methyl-5-phenyl-1,2-dihydro-3-benzoxepin (5b): a pale-yellow oil; Rf 0.47 (1:29 AcOEt–hexane);
IR (neat) 1607 cm–1; 1H NMR (500 MHz) ꢀ 1.36 (3H, d, J = 6.4 Hz), 3.01–3.08 (2H, m), 4.46–4.49 (1H.
13
m), 6.62 (1H, s), 6.88 (1H, d, J = 7.3 Hz), 7.05–7.11 (3H, m), 7.26–7.34 (5H, m); C NMR ꢀ 21.80,
43.79, 79.73, 119.83, 125.83, 126.02, 126.58, 128.23, 128.64, 129.51, 130.17, 137.35, 138.93, 141.92,
143.96; MS (EI) m/z 236 (M+, 92), 207 (100). Anal. Calcd for C17H16O: C, 86.40; H, 6.82. Found: C,
86.32; H, 7.05.
2,2-Dimethyl-5-(3-methylphenyl)-1,2-dihydro-3-benzoxepin (5c): a pale-yellow oil; Rf 0.41 (hexane);
1
IR (neat) 1606 cm–1; H NMR (400 MHz) ꢀ 1.30 (6H, s), 2.33 (3H, s), 2.91 (2H, s), 6.71 (1H, s), 6.95
13
(1H, dd, J = 6.4, 2.3 Hz), 7.07–7.11 (3H, m), 7.12–7.18 (3H, m), 7.22 (1H, dd, J = 8.2, 7.3 Hz); C
NMR ꢀ 21.39, 27.79, 46.83, 87.61, 124.67, 126.05, 126.15, 126.63, 127.55, 128.15, 128.96, 129.38,
130.24, 137.83, 137.95, 137.98, 140.61, 142.73; MS (EI) m/z 264 (M+, 100). Anal. Calcd for C19H20O2:
C, 86.32; H, 7.63. Found: C, 86.09; H, 7.85.
2-Methyl-5-(3-methylphenyl)-1,2-dihydro-3-benzoxepin (5d): a pale-yellow oil; Rf 0.48 (1:19
1
AcOEt–hexane); IR (neat) 1606 cm–1; H NMR (400 MHz) ꢀ 1.35 (3H, d, J = 6.6 Hz), 2.34 (3H, s),
3.02–3.06 (2H, m), 4.44–4.51 (1H, s), 6.61 (1H, m), 6.89 (1H, d, J = 6.9 Hz), 7.05–7.12 (6H, m), 7.22
(1H, dd, J = 7.7, 6.9 Hz); 13C NMR ꢀ 21.39, 21.78, 43.75, 79.73, 119.92, 125.78, 126.00, 127.25, 127.34,
128.10, 128.61, 129.56, 130.90, 137.41, 137.79, 138.89, 141.78, 143.79; MS (EI) m/z 250 (M+, 100).
Anal. Calcd for C18H18O: C, 86.36; H, 7.25. Found: C, 86.26; H, 7.09.
2,2-Dimethyl-5-(4-methylphenyl)-1,2-dihydro-3-benzoxepin (5e): a white solid; mp 79–80 ˚C
(hexane–THF); IR (KBr) 1607 cm–1; 1H NMR (400 MHz) ꢀ 1.30 (6H, s), 2.37 (3H, s), 2.90 (2H, s), 6.71
13
(1H, s), 6.95 (1H, dd, J = 6.9, 2.2 Hz), 7.12–7.18 (7H, m); C NMR ꢀ 21.10, 27.77, 46.82, 87.77,
124.70, 126.05, 126.15 (two overlapped C’s), 128.92, 128.98, 129.39, 136.49, 137.71 (two overlapped
C’s), 138.02, 142.47; MS (EI) m/z 264 (M+, 100). Anal. Calcd for C19H20O: C, 86.32; H, 7.63. Found: C,
86.03; H, 7.54.
5-(4-Fluorophenyl)-2,2-dimethyl-1,2-dihydro-3-benzoxepin (5f): a pale-yellow oil; Rf 0.24 (hexane);
IR (neat) 1606 cm–1; 1H NMR (500 MHz) ꢀ 1.30 (6H, s), 2.92 (2H, s), 6.67 (1H, s), 6.89 (1H, dd, J = 8.2,
2.3 Hz), 7.02 (2H, t, J = 8.7 Hz), 7.13–7.18 (3H, m), 7.23 (2H, dd, J = 8.7, 5.5 Hz); MS (EI) m/z 268
(M+, 100). Anal. Calcd for C18H17FO: C, 80.57; H, 6.39. Found: C, 80.48; H, 6.42.
5-(4-Chlorophenyl)-2,2-dimethyl-1,2-dihydro-3-benzoxepin (5g): a pale-yellow solid; mp 56–58 ˚C
(hexane–Et2O); IR (KBr) 1607 cm–1; 1H NMR (500 MHz) ꢀ 1.29 (6H, s), 2.92 (2H, s), 6.68 (1H, s), 6.89
(1H, d, J = 8.2 Hz), 7.12–7.17 (3H, m), 7.20 (2H, d, J = 8.2 Hz), 7.29 (2H, d, J = 8.2 Hz); MS (EI) m/z
284 (M+, 69), 241 (87), 226 (100). Anal. Calcd for C18H17ClO: C, 75.92; H, 6.02. Found: C, 75.63; H,
6.14.

HETEROCYCLES, Vol. 81, No. 3, 2010
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2,2,5-Trimethyl-1,2-dihydro-3-benzoxepin (5h): a pale-yellow oil; Rf 0.49 (hexane); IR (neat) 1620
cm–1; 1H NMR (500 MHz) ꢀ 1.23 (6H, s), 2.02 (2H, d, J = 1.4 Hz), 2.81 (3H, s), 6.47 (1H, s), 7.09 (1H,
d, J = 7.3 Hz), 7.13 (1H, td, J = 7.3, 1.4 Hz), 7.26 (1H, ddd, J = 7.8, 7.3, 1.4 Hz), 7.30 (1H, dd, J = 7.8,
1.4 Hz);13C NMR ꢀ 19.27, 27.71, 47.21, 84.40, 113.33, 125.57, 125.63, 126.33, 129.52, 137.16, 138.47,
140.52; MS (CI) m/z 189 [(M+1)+, 100]. Anal. Calcd for C13H16O: C, 82.94; H, 8.57. Found: C, 83.04; H,
8.72.
2,5-Dimethyl-1,2-dihydro-3-benzoxepin (5i): a colorless oil; Rf 0.43 (hexane);IR (neat) 1622 cm–1; 1H
NMR (500 MHz) ꢀ 1.31 (3H, d, J = 6.4 Hz), 2.02 (3H, s), 2.92 (1H, dd, J = 15.1, 6.4 Hz), 2.96 (1H, d, J
= 14.7 Hz), 4.31 (1H, quint, J = 6.4 Hz), 6.49 (1H, s), 7.05 (1H, d, J = 7.3 Hz), 7.10 (1H, t, J = 7.3 Hz),
7.23 (1H, dd, J = 7.8, 7.3 Hz), 7.31 (1H, d, J = 7.8 Hz) );13C NMR ꢀ 20.43, 21.67, 44.20, 77.81, 109.12,
125.37, 126.22, 126.28, 128.68, 137.58, 138.43, 141.48; MS (CI) m/z 175 [(M+1)+, 100]. Anal. Calcd
for C12H14O: C, 82.72; H, 8.10. Found: C, 82.93; H, 8.11.
7-Methoxy-2,2-dimethyl-5-phenyl-1,2-dihydro-3-benzoxepin (5j): a pale-yellow oil; Rf 0.68 (1:5
1
AcOEt–hexane); IR (neat) 1607 cm–1; H NMR (500 MHz) ꢀ 1.29 (6H, s), 2.86 (2H, s), 3.65 (3H, s),
6.49 (1H, d, J = 2.7 Hz), 6.71 (1H, s), 6.72 (1H, dd, J = 8.2, 2.7 Hz), 7.08 (1H, d, J = 8.2 Hz), 7.27–7.34
(5H, m); 13C NMR ꢀ 27.70, 46.01, 55.18, 87.53, 111.79, 114.33, 124.41, 126.81, 128.27, 129.54, 130.30,
130.57, 138.96, 140.53, 143.20, 158.00; MS (EI) m/z 280 (M+, 100). Anal. Calcd for C19H20O2: C, 81.40;
H, 7.19. Found: C, 81.18; H, 7.29.
ACKNOWLEDGEMENTS
We are grateful to Mrs. Miyuki Tanmatsu of this university for determining mass spectra and performing
combustion analyses.
REFERENCES
1. (a) K. Kobayashi, K. Hayashi, K. Miyamoto, O. Morikawa, and H. Konishi, Synthesis, 2006, 2934;
(b) K. Kobayashi, T. Nagaoka, S. Fukamachi, Y. Shirai, O. Morikawa, and H. Konishi, Synthesis,
2007, 3032; (c) K. Kobayashi, Y. Shirai, T. Nagaoka, and H. Konishi, Synth. Commun., 2009, 39,
2866; (d) K. Kobayashi, K. Hayashi, C. Num, S. Fukamachi, and H. Konishi, Heterocycles, 2008,
75, 1225; (e) K. Kobayashi, D. Nakai, and H. Konishi, Heterocycles, 2008, 75, 3025.
2. S.-Y. Chou and C.-H. Chen, Tetrahedron Lett., 2006, 47, 6045.
3. S. Das and A. Basak, Synlett, 2008, 501.
4. F. T. F. Narsais, P. Breant, and G. Queguiner, J. Heterocycl. Chem., 1988, 25, 81.