One-pot synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones from 2-(2-Isocyanophenyl)ethanols via the corresponding isothiocyanates

Article abstract of DOI:10.3987/COM-11-12142

An efficient method for the preparation of 4,5-dihydro-3,1- benzoxazepine-2(1H)-thiones under mild conditions has been developed. 2-(2-Isocyanophenyl)ethanols, easily accessible by treating 1-isocyano-2- (lithiomethyl)benzenes with aldehydes or ketones, w

Full text of DOI:10.3987/COM-11-12142

HETEROCYCLES, Vol. 83, No. 4, 2011
883
HETEROCYCLES, Vol. 83, No. 4, 2011, pp. 883 - 889. © The Japan Institute of Heterocyclic Chemistry
Received, 19th January, 2011, Accepted, 21st February, 2011, Published online, 2nd March, 2011
DOI: 10.3987/COM-11-12142
ONE-POT SYNTHESIS OF 4,5-DIHYDRO-3,1-BENZOXAZEPINE-2(1H)-
THIONES FROM 2-(2-ISOCYANOPHENYL)ETHANOLS VIA THE
CORRESPONDING ISOTHIOCYANATES
Shuhei Fukamachi, Hisatoshi Konishi, and Kazuhiro Kobayashi*
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 – An efficient method for the preparation of 4,5-dihydro-3,1-
benzoxazepine-2(1H)-thiones under mild conditions has been developed.
2-(2-Isocyanophenyl)ethanols, easily accessible by treating 1-isocyano-2-
(lithiomethyl)benzenes with aldehydes or ketones, were converted into the
corresponding isothiocyanates on treatment with sulfur in the presence of a
catalytic amount of selenium and excess triethylamine. These isothiocyanato
alcohols were then treated with sodium hydride to give 4,5-dihydro-3,1-
benzoxazepine-2(1H)-thione derivatives in one pot.
Compounds having the 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione structure are an important class of
molecules, because this structure is found in some biologically active compounds.1 However, very few
practical methods for the preparation of the 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives have
been reported. Suda et al. have reported on the conversion of 4,5-dihydro-3,1-benzoxazepin-2(1H)-one
derivatives into the corresponding thione derivatives by the treatment with Lawesson’s reagent.1c In this
paper, we describe a facile synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones from
1-isocyano-2-methylbenzenes via a three-step procedure.
The synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives (4) from 1-isocyano-2-
methylbenzenes (1), via 2-(2-isocyanophenyl)ethanols (2), is illustrated in Scheme 1. The requisite
isocyano alcohols (2) were prepared by the lithiation of 1 with LDA followed by the reaction with
aldehydes or ketones according to the procedure reported by Ito et al.2,3 The yields of 2 are generally good
(Table 1). The reaction could be applicable to aldehydes and ketones carrying !-hydrogens, such as
propanal, acetone, cyclohexanone, and acetophenone (Entries 1 and 4–6). However, as can be seen from
Entries 8 and 9, the yields of the products (2j) and (2k) from 1-isocyano-2,4-dimethylbenzene are
somewhat lower than those of the others. This may be ascribed to simultaneous slight lithiation of

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HETEROCYCLES, Vol. 83, No. 4, 2011
4-methyl group.
R2
R2
R1
R1
Me
NC
R1
R3
R3
1. 2LDA, diglyme, -78 °C
2. R2COR3, -78 °C
S, cat.Se
OH
NC
Et3N, THF, reflux
OH
NCS
1
2
3
R2
R1
R3
NaH, 0 °C
O
N
S
H
4
Scheme 1
Table 1. Preparations of 4,5-Dihydro-3,1-benzoxazepine-2(1H)-thione Derivatives (4) via 2-(2-
Isocyanophenyl)ethanols (2)
Entry
1
R1
H
H
H
H
H
H
H
Me
Me
Cl
Cl
OMe
OMe
R2
H
H
H
Me
R3
Et
Ph
2 (Yield/%)a
2a (86)b
2b (97)b
2c (93)
2d (88)b
2e (94)
2f (84)
4 (Yield/%)a
4a (78)
4b (85)
4c (0)
4d (66)
4e (87)
4f (61)
4g (0)
4h (80)
4i (89)
4j (62)
4k (61)
4l (86)
2
3
4
5
6
7
8
9
10
11
12
13
thiophen-2-yl
Me
-(CH2)5-
Me
Ph
H
H
H
H
H
H
Ph
Ph
Ph
4-MeC6H4
2g (88)
2h (67)
2i (64)
naphthalen-2-yl
4-ClC6H4
Ph
2j (74)
2k (70)
2l (81)
2m (97)
3-MeOC6H4
4m (85)
a Isolated yields. b The synthesis of these compounds has been reported by Ito et al.2,3
Compounds (2) thus obtained were converted into the corresponding isothiocyanates (3) on treatment
with sulfur in the presence of a catalytic amount of selenium and excess Et3N in THF at reflux
temperature under the same conditions as reported by Fujiwara et al.4 These isothiocyanates were then,
without isolation, treated with an equimolar amount of sodium hydride at 0 ˚C to generate the
corresponding sodium alkoxide intermediates, which cyclized by the attack of the alkoxide oxygen on the
isothiocyanate carbon. The cyclization proceeded immediately and cleanly. The completion of each step
of the sequence was monitored by TLC (silica gel) analyses. The usual aqueous workup and subsequent
purification by recrystallization of the crude products afforded the desired products (4) in one pot from 2.
The results are summarized in Table 1. The yields are fair to good as a whole. The 4,4-disubsutituted

HETEROCYCLES, Vol. 83, No. 4, 2011
885
derivatives (4d-f) could also be obtained in generally good yields (Entries 4-6). However, in the reaction
of 1-(2-isocyanophenyl)-2,2-diphenylethan-2-ol (2g) (Entry 7), its clean conversion into the
corresponding isothiocyanates (3g) could be confirmed by TLC analysis, but treatment of this
isothiocyanate with sodium hydride resulted in the formation of a complex mixture of products, in which
only trace of the desired product (4g) was detected as a mixture with structurally undefined products by
1H NMR. This result may be ascribed to the crowdedness at the 4-position of the product due to two
phenyl groups. The reaction of 2-(2-isocyanophenyl)-1-(thiophen-2-yl)ethanol (2c) was also gave a
similar result (Entry 3), though the reaction for this is unclear.
In conclusion, we have demonstrated that 2-(2-isocyanophenyl)ethanols can been utilized for the one-pot
synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones. Since the method employs readily available
starting materials and is experimentally simple, it may be of value in organic synthesis.
EXPERIMENTAL
The melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are
1
uncorrected. IR spectra were determined with a Shimadzu FTIR-8300 spectrophotometer. The H NMR
spectra were determined using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer
operating at 500 MHz. The 13C NMR spectra were determined using TMS as an internal reference with a
JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low- and high-resolution MS spectra (EI,
70 eV) were measured by a JEOL JMS AX505 HA spectrometer. TLC was carried out on a Merck
Kieselgel 60 PF254. Column chromatography was performed using WAKO GEL C-200E. All of the
organic solvents used in this study were dried over appropriate drying agents and distilled prior to use.
Starting Materials. 1-Isocyano-2-methylbenzenes (1) were prepared according to the procedure reported
previously by Ito et al.5 All other chemicals used in this study were commercially available.
2-(2-Isocyanophenyl)ethanols (2). These compounds were prepared by treating the respective
1-isocyano-2-lithiomethybenzenes, generated from 1-isocyano-2-methylbenzenes (1) and LDA, with
aldehydes or ketones according to the procedure reported by Ito et al.2 Physical, spectral, and analytical
data for new compounds follow.
2-(2-Isocyanophenyl)-1-(thiophen-2-yl)ethanol (2c): a yellow oil; Rf 0.35 (1:4 EtOAc–hexane); IR
(neat) 3412, 2120 cm-1; 1H NMR (CDCl3) " 2.20 (d, J = 3.9 Hz, 1H), 3.12 (dd, J = 13.7, 8.3 Hz, 1H), 3.20
(dd, J = 13.7, 5.3 Hz, 1H), 5.26–5.30 (m, 1H), 6.95–6.98 (m, 2H), 7.26–7.35 (m, 4H), 7.38 (d, J = 7.8 Hz,
1H). HR-MS. Calcd for C13H11NOS: M, 229.0561. Found: m/z 229.0533.
1-[(2-Isocyanophenyl)methyl]cyclohexanol (2e): a pale-yellow oil; Rf 0.36 (1:4 THF–hexane); IR (neat)
3466, 2120 cm-1; 1H NMR (CDCl3) " 1.27 (s, 1H), 1.53–1.63 (m, 10H), 2.93 (s, 2H), 7.26 (td, J = 7.8, 1.8
Hz, 1H), 7.34 (td, J = 7.8, 1.4 Hz, 1H), 7.38 (dd, J = 7.8, 1.8 Hz, 1H), 7.39 (dd, J = 7.8, 1.4 Hz, 1H).
HR-MS. Calcd for C14H17NO: M, 215.1310. Found: m/z 215.1316.

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1-(2-Isocyanophenyl)-2-phenylpropan-2-ol (2f): a pale-yellow oil; Rf 0.32 (1:5 THF–hexane); IR (neat)
1
3445, 2122 cm-1; H NMR (CDCl3) " 1.63 (s, 3H), 1.79 (s, 1H), 3.16 (d, J = 13.7 Hz, 1H), 3.30 (d, J =
13.7 Hz, 1H), 7.14–7.16 (m, 1H), 7.24–7.36 (m, 7H), 7.44 (dd, J = 7.3, 1.4 Hz, 1H). HR-MS. Calcd for
C16H15NO: M, 237.1154. Found: m/z 237.1170.
1-(2-Isocyanophenyl)-2,2-diphenylethan-2-ol (2g): a pale-yellow oil; Rf 0.33 (1:6 THF–hexane); IR
(neat) 3412, 2122 cm-1; 1H NMR (CDCl3) " 2.28 (s, 1H), 3.78 (s, 2H), 6.76 (d, J = 7.8 Hz, 1H), 7.08 (td, J
= 7.8, 0.9 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.24–7.39 (m, 11H). HR-MS. Calcd for C21H17NO: M,
299.1310. Found: m/z 299.1308.
2-(2-Isocyano-5-methylphenyl)-1-phenylethanol (2h): a yellow oil; Rf 0.33 (1:5 THF–hexane); IR
(neat) 3418, 2118 cm-1; 1H NMR (CDCl3) " 1.95 (d, J = 3.2 Hz, 1H), 2.34 (s, 3H), 3.04 (dd, J = 13.7, 9.1
Hz, 1H), 3.17 (dd, J = 13.7, 4.1 Hz, 1H), 5.00–5.03 (m, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.09 (s, 1H), 7.26
(d, J = 7.8 Hz, 1H), 7.30 (tt, J = 7.3, 1.8 Hz, 1H), 7.36 (td, J = 7.3, 1.8 Hz, 2H), 7.41 (dd, J = 7.3, 1.8 Hz,
2H). HR-MS. Calcd for C16H15NO: M, 237.1154. Found: m/z 237.1129.
2-(2-Isocyano-5-methylphenyl)-1-(4-methylphenyl)ethanol (2i): colorless crystals; mp 100–102 ˚C
1
(hexane–Et2O); IR (KBr) 3350, 2118 cm-1 ; H NMR (CDCl3) " 1.87 (d, J = 3.2 Hz, 1H), 2.34 (s, 3H),
2.36 (s, 3H), 3.03 (dd, J = 13.7, 9.1 Hz, 1H), 3.15 (dd, J = 13.7, 4.1 Hz, 1H), 4.97–5.00 (m, 1H), 7.06 (d,
J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 2H).
Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 81.11; H, 6.77; N, 5.53.
2-(5-Chloro-2-isocyanophenyl)-1-(naphthalen-2-yl)ethanol (2j): a pale-yellow solid; mp 106–108 ˚C
(hexane–CH2Cl2); IR (KBr) 3412, 2141 cm-1 ; 1H NMR (CDCl3) " 2.06 (d, J = 3.4 Hz, 1H), 3.14 (dd, J =
13.7, 8.6 Hz, 1H), 3.25 (dd, J = 13.7, 4.0 Hz, 1H), 5.16–5.20 (m, 1H), 7.26 (dd, J = 8.6, 2.3 Hz, 1H), 7.31
(d, J = 8.6 Hz, 1H), 7.38 (d, J = 2.3 Hz, 1H), 7.47–7.52 (m, 2H), 7.54 (dd, J = 7.8, 1.8 Hz, 1H), 7.83–7.88
(m, 4H). Anal. Calcd for C19H14ClNO: C, 74.15; H, 4.58; N, 4.55. Found: C, 74.16; H, 4.62; N, 4.40.
2-(5-Chloro-2-isocyanophenyl)-1-(4-chlorophenyl)ethanol (2k): a yellow solid; mp 79–81 ˚C
1
(hexane–Et2O); IR (KBr) 3354, 2124 cm-1 ; H NMR (CDCl3) " 2.01 (d, J = 2.9 Hz, 1H), 3.03 (dd, J =
14.3, 9.2 Hz, 1H), 3.13 (dd, J = 14.3, 4.0 Hz, 1H), 4.97–5.00 (m, 1H), 7.26 (dd, J = 8.6, 2.3 Hz, 1H),
7.30–7.35 (m, 6H). Anal. Calcd for C15H11Cl2NO: C, 61.67; H, 3.79; N, 4.79. Found: C, 61.44; H, 3.93; N,
4.50.
2-(2-Isocyano-5-methoxyphenyl)-1-phenylethanol (2l):
a
pale-yellow solid; mp 62–63 ˚C
1
(hexane–Et2O); IR (KBr) 3420, 2118 cm-1 ; H NMR (CDCl3) " 2.00 (d, J = 2.9 Hz, 1H), 3.06 (dd, J =
13.7, 9.1 Hz, 1H), 3.17 (dd, J = 13.7, 4.4 Hz, 1H), 3.77 (s, 3H), 5.00–5.04 (m, 1H), 6.75 (s, 1H), 6.77 (d,
J = 7.8 Hz, 1H), 7.30–7.42 (m, 6H). Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C,
75.80; H, 6.06; N, 5.67.
2-(2-Isocyano-5-methoxyphenyl)-1-(3-methoxyphenyl)ethanol (2m): a yellow oil; Rf 0.26 (1:3
1
EtOAc–hexane); IR (neat) 3418, 2118 cm-1; H NMR (CDCl3) " 1.97 (d, J = 3.4 Hz, 1H), 3.05 (dd, J =

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13.7, 8.6 Hz, 1H), 3.17 (dd, J = 13.7, 4.0 Hz, 1H), 3.78 (s, 3H), 3.81 (s, 3H), 4.98–5.01 (m, 1H),
6.75–6.85 (m, 3H), 6.97 (s, 1H), 6.98 (d, J = 7.8 Hz, 1H), 7.26–7.32 (m, 2H). HR-MS. Calcd for
C17H17NO3: M, 283.1208. Found: m/z 283.1183.
Typical Procedure for the Preparation of 4,5-Dihyro-3,1-benzoxazepine-2(1H)-thiones (4).
4-Ethyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4a). A mixture of 2a (0.27 g, 1.5 mmol), Et3N
(0.38 g, 3.8 mmol), sulfur (58 mg, 1.8 mmol), and selenium (3.6 mg, 45 µmol) in THF (5 mL) was stirred
at reflux temperature for 1 h. After cooling to 0 ˚C, NaH (60% in oil; 72 mg, 1.8 mmol) was added, and
stirring was continued for an additional 30 min at the same temperature. Saturated aqueous NH4Cl (10
mL) was added and organic materials were extracted with AcOEt three times (10 mL each), and the
combined extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated by
evaporation. The residual solid was recrystallized from hexane-CH2Cl2 to give 4a (0.24 g, 78 %); a beige
solid; mp 88–90 ˚C (hexane–CH2Cl2); IR (KBr) 3181, 1153 cm-1; 1H NMR (CDCl3) " 1.09 (t, J = 7.3 Hz,
3H), 1.72–1.80 (m, 1H), 1.89–1.97 (m, 1H), 3.10 (dd, J = 16.4, 1.4 Hz, 1H), 3.21 (dd, J = 16.4, 8.2 Hz,
1H), 4.60–4.64 (m, 1H), 6.99 (dd, J = 7.8, 0.9 Hz, 1H), 7.08 (td, J = 7.8, 0.9 Hz, 1H), 7.12 (dd, J = 7.8,
1.4 Hz, 1H), 7.21 (td, J = 7.8, 1.4 Hz, 1H), 9.53 (br s, 1H); 13C NMR (CDCl3) " 9.83, 28.19, 39.05, 86.82,
119.79, 124.93, 127.38, 127.86, 130.48, 136.44, 188.90; MS m/z 207 (M+, 17), 177 (30), 162 (100). Anal.
Calcd for C11H13NOS: C, 63.74; H, 6.32; N, 6.76. Found: C, 63.70; H, 6.42; N, 6.70.
4-Phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4b): a pale-yellow solid; mp 147–149 ˚C
(hexane–EtOAc); IR (KBr) 3160, 1148 cm-1; 1H NMR (DMSO-d6) " 3.31 (dd, J = 16.9, 2.3 Hz, 1H), 3.54
(dd, J = 16.9, 7.8 Hz, 1H), 5.80 (dd, J = 7.8, 2.3 Hz, 1H), 7.07 (td, J = 7.3, 0.9 Hz, 1H), 7.20 (d, J = 7.3,
1.4 Hz, 1H), 7.23 (td, J = 7.3, 1.4 Hz, 1H), 7.30 (dd, J = 7.3, 0.9 Hz, 1H), 7.36 (t, J = 7.3 Hz, 1H), 7.40 (t,
13
J = 7.3 Hz, 2H), 7.47 (d, J = 7.3 Hz, 2H), 11.64 (s, 1H); C NMR (DMSO-d6) " 40.47, 85.89, 120.43,
124.52, 126.37, 127.50, 128.07, 128.39, 128.45, 130.62, 137.03, 139.48, 187.83; MS m/z 255 (M+, 7.0),
225 (45), 210 (100). Anal. Calcd for C15H13NOS: C, 70.56; H, 5.13; N, 5.49. Found: C, 70.68; H, 5.17; N,
5.37.
4,4-Dimethyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4d): beige crystals; mp 144–146 ˚C
1
(hexane–CH2Cl2); IR (KBr) 3175, 1153 cm-1; H NMR (CDCl3) " 1.52 (s, 6H), 3.06 (s, 2H), 7.02 (d, J =
13
7.8 Hz, 1H), 7.14–7.18 (m, 2H), 7.25–7.29 (m, 1H), 9.85 (br s, 1H); C NMR (CDCl3) " 27.74, 44.68,
92.70, 119.99, 125.75, 128.09, 128.93, 130.49, 136.66, 188.37; MS m/z 207 (M+, 48), 132 (100). Anal.
Calcd for C11H13NOS: C, 63.74; H, 6.32; N, 6.76. Found: C, 63.69; H, 6.25; N, 6.76.
Spiro[cyclohexane-1,4’-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione] (4e): yellow crystals; mp
153–155 ˚C (hexane–CH2Cl2); IR (KBr) 3160, 1167 cm-1; 1H NMR (CDCl3) " 1.31–2.04 (m, 10H), 3.04 (s,
13
2H), 7.02 (d, J = 7.8 Hz, 1H), 7.13–7.15 (m, 2H), 7.23–7.26 (m, 1H), 9.99 (s, 1H); C NMR (CDCl3)
" 22.02, 25.19, 36.04, 43.47, 93.95, 119.88, 125.58, 127.93, 128.26, 130.61, 136.66, 188.37; MS m/z 247
(M+, 20), 172 (100). Anal. Calcd for C14H17NOS: C, 67.98; H, 6.93; N, 5.66. Found: C, 67.83; H, 6.62; N,

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5.49.
4-Methyl-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4f): a beige solid; mp 111–113 ˚C
(hexane–CH2Cl2); IR (KBr) 3165, 1144 cm-1; 1H NMR (CDCl3) " 1.84 (s, 3H), 3.48 (d, J = 16.0 Hz, 1H),
3.52 (d, J = 16.0 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 7.05–7.06 (m, 2H), 7.14–7.22 (m, 2H), 7.266 (dd, J =
13
7.8, 1.8 Hz, 1H), 7.273 (t, J = 7.8 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 9.67 (br s, 1H); C NMR (CDCl3)
" 30.60, 45.05, 94.31, 119.67, 124.74, 125.45, 127.58, 127.95, 128.00, 128.33, 130.74, 136.40, 142.64,
187.80; MS m/z 269 (M+, 8.5), 209 (62), 194 (100). Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61; N,
5.20. Found: C, 71.25; H, 5.61; N, 5.13.
7-Methyl-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4h): a white solid; mp 126–128 ˚C
(hexane–CH2Cl2); IR (KBr) 3185, 1161 cm-1; 1H NMR (CDCl3) " 2.29 (s, 3H), 3.26 (dd, J = 16.8, 1.8 Hz,
1H), 3.59 (dd, J = 16.8, 8.7 Hz, 1H), 5.67 (dd, J = 8.7, 1.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.92 (d, J =
1.4 Hz, 1H), 7.04 (dd, J = 8.4, 1.4 Hz, 1H), 7.35–7.43 (m, 5H), 9.14 (s, 1H); 13C NMR (CDCl3) " 20.57,
41.87, 86.48, 119.94, 126.04, 127.16, 128.66 (two overlapped C’s), 128.70, 131.01, 134.02, 134.96,
138.65, 188.31; MS m/z 269 (M+, 6.1), 209 (100). Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61; N, 5.20.
Found: C, 71.14; H, 5.50; N, 5.04.
7-Methyl-4-(4-methylphenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4i): colorless crystals; mp
158–160 ˚C (hexane–CH2Cl2); IR (KBr) 3175, 1161 cm-1; 1H NMR (CDCl3) " 2.28 (s, 3H), 2.36 (s, 3H),
3.24 (dd, J = 16.0, 1.8 Hz, 1H), 3.59 (dd, J = 16.0, 9.2 Hz, 1H), 5.64 (dd, J = 9.2, 1.8 Hz, 1H), 6.87 (d, J
= 8.2 Hz, 1H), 6.91 (d, J = 1.8 Hz, 1H), 7.02 (dd, J = 8.2, 1.8 Hz, 1H), 7.19 (d, J = 8.2 Hz, 2H), 7.30 (d, J
13
= 8.2 Hz, 2H), 9.41 (s, 1H); C NMR (CDCl3) " 20.58, 21.15, 41.81, 86.42, 119.83, 126.05, 127.16,
128.61, 129.35, 131.08, 134.02, 134.89, 135.70, 138.56, 188.48; MS m/z 283 (M+, 5.0), 223 (100). Anal.
Calcd for C17H17NOS: C, 72.05; H, 6.05; N, 5.66. Found: C, 72.06; H, 6.13; N, 5.63.
7-Chloro-4-(naphthalen-2-yl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4j): a pale-yellow solid;
1
mp 171–173 ˚C (EtOAc); IR (KBr) 3219, 1165 cm-1; H NMR (DMSO-d6) " 3.43 (dd, J = 16.7, 1.7 Hz,
1H), 3.66 (dd, J = 16.7, 9.2 Hz, 1H), 5.99 (dd, J = 9.2, 1.7 Hz, 1H), 7.31–7.36 (m, 3H), 7.53–7.56 (m,
13
2H), 7.61 (dd, J = 8.6, 1.8 Hz, 1H), 7.91–8.00 (m, 4H), 11.77 (s, 1H); C NMR (DMSO-d6) " 40.49,
85.43, 122.10, 124.27, 125.27, 126.51, 126.53, 127.39, 127.61, 128.01, 128.23, 128.25, 130.06, 130.28,
132.51, 132.73, 136.05, 136.65, 187.68; MS m/z 339 (M+, 5.0), 273 (100). Anal. Calcd for C19H14ClNOS:
C, 67.15; H, 4.15; N, 4.12. Found: C, 66.87; H, 4.27; N, 3.84.
7-Chloro-4-(4-chlorophenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4k): a yellow solid; mp
120–122 ˚C (hexane–EtOAc); IR (KBr) 3183, 1153 cm-1; 1H NMR (CDCl3) " 3.28 (dd, J = 16.7, 2.3 Hz,
1H), 3.53 (dd, J = 16.7, 8.6 Hz, 1H), 5.69 (dd, J = 8.6, 2.3 Hz, 1H), 6.91 (d, J = 8.6 Hz, 1H), 7.11 (d, J =
2.3 Hz, 1H), 7.22 (dd, J = 8.6, 2.3 Hz, 1H), 7.34 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 9.12–9.37
13
(br, 1H); C NMR (CDCl3) " 41.43, 85.71, 121.50, 127.52, 128.42, 128.81, 129.15, 130.47, 130.68,
134.95, 135.02, 136.70, 188.50; MS m/z 322 (M+, 8.6), 262 (100). Anal. Calcd for C15H11Cl2NOS: C,

HETEROCYCLES, Vol. 83, No. 4, 2011
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55.57; H, 3.42; N, 4.32. Found: C, 55.66; H, 3.40; N, 4.21.
7-Methoxy-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4l): colorless needles; mp 177–178
˚C (EtOAc); IR (KBr) 3183, 1153 cm-1; 1H NMR (CDCl3) " 3.28 (dd, J = 16.7, 2.3 Hz, 1H), 3.56 (dd, J =
16.7, 8.6 Hz, 1H), 3.73 (s, 3H), 5.69 (dd, J = 8.6, 2.3 Hz, 1H), 6.61 (d, J = 2.7 Hz, 1H), 6.77 (dd, J = 8.6,
2.7 Hz, 1H), 6.96 (d, J = 8.6 Hz, 1H), 7.32–7.41 (m, 5H), 9.52 (s, 1H); 13C NMR (CDCl3) " 41.97, 55.65,
86.76, 113.46, 115.58, 121.46, 126.17, 128.83 (two overlapped C’s), 129.12, 130.10, 138.75, 156.94,
188.14; MS m/z 285 (M+, 25), 225 (100). Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found:
C, 67.29; H, 5.30; N, 4.95.
7-Methoxy-4-(3-methoxyphenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4m): a pale-yellow
solid; mp 149–150 ˚C (hexane–EtOAc); IR (KBr) 3160, 1148 cm-1; 1H NMR (DMSO-d6) " 3.27 (dd, J =
16.7, 2.3 Hz, 1H), 3.47 (dd, J = 16.7, 8.6 Hz, 1H), 3.70 (s, 3H), 3.75 (s, 3H), 5.71 (dd, J = 8.6, 2.3 Hz,
1H), 6.82–6.84 (m, 2H), 6.92 (dd, J = 8.6, 2.3 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 2.3 Hz, 1H),
13
7.20 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 11.56 (s, 1H); C NMR (DMSO-d6) " 40.34, 55.12,
55.31, 85.91, 112.05, 113.10, 113.76, 115.13, 118.42, 121.81, 129.54, 129.76, 130.53, 141.15, 156.02,
159.23, 186.95; MS m/z 315 (M+, 8.7), 255 (100). Anal. Calcd for C17H17NO3S: C, 64.74; H, 5.43; N, 4.44.
Found: C, 64.52; H, 5.42; N, 4.33.
ACKNOWLEDGEMENT
This work was partially financial supported by a Grand-in-Aid for Scientific Research (C) 22550035 from
Japan Society for the Promotion of Science. We thank Mrs. Miyuki Tanmatsu of this university for
recording mass spectra and performing combustion analyses.
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