One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-lithiophenyl isothiocyanates with aldehydes or ketones

Article abstract of DOI:10.1016/j.tet.2010.10.010

An efficient one-pot method for the synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-dihydro-3,1-benzoxazine-2-thiones has been developed. Treatment of 2-bromophenyl isothiocyantes with butyllithium in THF at -78 °C generates 2-lithiophenyl isothi

Full text of DOI:10.1016/j.tet.2010.10.010

Tetrahedron 66 (2010) 9336e9339
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One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction
of 2-lithiophenyl isothiocyanates with aldehydes or ketones
*
Kazuhiro Kobayashi , Yuki Yokoi, Toshihide Komatsu, 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
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 August 2010
Received in revised form 4 October 2010
Accepted 4 October 2010
Available online 21 October 2010
An efficient one-pot method for the synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-dihydro-
3,1-benzoxazine-2-thiones has been developed. Treatment of 2-bromophenyl isothiocyantes with bu-
tyllithium in THF at ꢀ78 ꢁC generates 2-lithiophenyl isothiocyanates, which are allowed to react with
various carbonyl compounds, including aldehydes, ketones, and butanolide, to give the corresponding
desired products in moderate to good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
1,4-Dihydro-3,1-benzoxazine-2-thiones
2-Lithiophenyl isothiocyanates
Bromine-lithium exchange
Nucleophilic addition
Cyclization reaction
1. Introduction
R1
Br
R1
LI
°
C
-BuLi, THF, –78
Certain compounds having the 1,4-dihydro-3,1-benzoxazine-2-
thione skeleton have been reported to exhibit a broad spectrum of
biological activity.1 This class of heterocycles has been synthesized
by the treatment of the respective 1,4-dihydro-3,1-benzoxazin-2-
one derivatives with Lawesson’s reagent at rather high temper-
atures.1a,b,d To the best of our knowledge no one-pot syntheses
from readily available starting materials have been reported. In this
paper, we wish to report an efficient one-pot method for the
preparation of 1,4-dihydro-3,1-benzoxazine-2-thiones carrying one
or two substituents at the 4-position. We found that treatment
of 2-bromophenyl isothiocyanates with butyllithium generated
2-lithiophenyl isothiocyanates and that their reaction with various
aldehydes or ketones gave1,4-dihydro-3,1-benzoxazine-2-thiones.2
We report as well the synthesis of 1,4-dihydrospiro[3,1-benzox-
azine-4,20-tetrahydrofuran]-2-thiones utilizing butanolide in place
of aldehydes or ketones.
NCS
NCS
1a R1 = H
2
1b R1 = Cl
R2 R3
OLI
R1
2
3
°
R COR , –78 C
NCS
3
R2 R3
O
R2 R3
R1
R1
H3O+
O
N
H
S
N
S
2. Results and discussion
LI
4
5
The synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-
dihydro-3,1-benzoxazine-2-thiones 5 from 2-bromophenyl iso-
thiocyanates 1 via 2-lithiophenyl isothiocyanates 2 is illustrated
in Scheme 1. One of the starting materials, 2-bromophenyl
Scheme 1.
isothiocyanate 1a, was commercially available. The other starting
material, 2-bromo-4-chlorophenyl isothiocyanate 1b, was easily
prepared from commercially available 2-bromo-4-chlorobenzen-
amine. This aniline derivative was transformed into 2-bromo-4-
* Corresponding author. Tel./fax: þ81 857 31 5263; e-mail address: kkoba@
chem.tottori-u.ac.jp (K. Kobayashi).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.010

K. Kobayashi et al. / Tetrahedron 66 (2010) 9336e9339
9337
chlorophenyl isocyanide by the standard N-formylation with formic
acid3 followed by the dehydration of the resulting formamide with
phosphoryl chloride in the presence of triethylamine.4 This iso-
cyanide was then converted into the corresponding isothiocyanate
1b on treatment with sulfur in the presence of a catalytic amount of
selenium and excess triethylamine under conditions reported by
Fujiwara et al.5
considerably more complex mixtures of products. This is probably
due to less reactivity of this lactone toward the lithium intermediates
2 compared to butanolide.
In conclusion, we have developed a novel method for the
preparation of 1,4-dihydro-3,1-benzoxazine-2-thiones using the
reaction of 2-lithiophenyl isothiocyanates with aldehydes, ketones,
or a lactone. The present method may find some value in organic
synthesis, because: (1) this is the first generation of 2-lithiophenyl
isothiocyanates; (2) the starting materials are readily available; (3)
the operations are very simple.
The new 2-lithiophenyl isothiocyanates 2 were readily generated
by the treatment of 2-bromophenyl isothiocyanates 1 with an equi-
molar amount of butyllithium in THF at ꢀ78 ꢁC. These lithium
intermediates were immediately allowed to react with aldehydes or
ketones to form lithium 2-isocyanatobenzyloxide intermediates 3.
These intermediates quickly cyclized intramolecularly by the attack
of the alkoxide oxygen on the isothiocyanate carbon to give 1-lithio-
1,4-dihydro-3,1-benzoxazine-2-thione intermediates 4, which gave,
after the usual aqueous workup followed by purification by re-
crystallization, 4-monosubstituted or 4,4-disubstituted 1,4-dihydro-
3,1-benzoxazine-2-thiones 5 in satisfactory yields. The addition of
carbonyl compounds 5 min later on treatment of 1 with butyllithium
resulted in formation of complex mixtures of products containing
rather lower yields of the desired products. This implies that the
generation of the lithium intermediates was accomplished rapidly
and that they were unstable and decomposed even at ꢀ78 ꢁC. Both
aliphatic and aromatic carbonyl compounds proved suitable for the
present preparation. The isolated yields of the desired products range
from 50 to 79% as summarized in Table 1.
3. Experimental
3.1. General
All melting points were obtained on a Laboratory Device MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were
determined with a Shimadzu FTIR-8300 spectrophotometer as KBr
disks. 1H NMR spectra were determined 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. 13C NMR spectra were determined using TMS as an in-
ternal reference with a JEOL ECP500 FT NMR spectrometer oper-
ating at 125 MHz or a JEOL LA400 FT NMR spectrometer operating
at 100 MHz. Low-resolution MS spectra (CI) were measured with
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.
Table 1
Preparation of 1,4-Dihydro-3,1-benzoxazine-2-thiones 5
Entry
1
R2COR3
5 (Yield/%)a
3.2. Starting materials
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
EtCHO
PhCHO
5a (69)
5b (77)
5c (73)
5d (74)
5e (71)
5f (69)
5g (71)
5h (79)
5i (76)
5j (50)
5k (65)
5l (76)
5m (69)
5n (53)
All chemicals used in this study are commercially available.
3-ClC6H4CHO
3-MeOC6H4CHO
Naphthalene-1-carboxaldehyde
EtCOMe
Cyclohexanone
PhCOMe
1-(Thiophen-2-yl)ethanone
PhCOPh
EtCHO
3.2.1. N-(2-Bromo-4-chlorophenyl)formamide. This compound was
prepared in 87% yield by the standard N-formylation of 2-bromo-4-
chlorobenzeneamine with formic acid in toluene under azeotropic
conditions;3 a pale-yellow solid; mp 147 ꢁC (hexane/THF) (lit.,6
9
154 ꢁC); IR 3246, 1695, 1665 cmꢀ1 1H NMR (400 MHz, DMSO-d6)
;
10
11
12
13
14
d
7.45 (dd, J¼8.7, 2.0 Hz,1H), 7.79 (d, J¼2.0 Hz,1H), 8.03 (d, J¼8.7 Hz,
1H), 8.34 (s, 1H), 9.83 (s, 1H).
4-ClC6H4CHO
Cyclohexanone
PhCOMe
3.2.2. 1-Bromo-5-chloro-2-isocyanobenzene. This compound was
prepared in 75% yield by dehydration of the above formamide with
POCl3/Et3N in THF at 0 ꢁC;4 a pale-yellow solid; mp 38e40 ꢁC
a
Isolated yields.
(hexane/Et2O); IR (KBr) 2128 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
Subsequently, we foundthatwhen2-lithiophenylisothiocyanates
2 were treated with butanolide under the same conditions as de-
scribed above for the preparation of 5, a similar addition/cyclization
sequence occurred to afford the corresponding 1,4-dihydrospiro[3,1-
benzoxazine-4,20-tetrahydrofuran]-2-thiones 6 in moderate yields
as shown in Scheme 2. Unfortunately, however, several attempts to
prepare 1,4-dihydrospiro[3,1-benzoxazine-4,20-tetrahydropyran]-2-
thiones using pentanolide were unsuccessful; the reactions gave
d
7.34 (dd, J¼8.7, 2.0 Hz, 1H), 7.39 (d, J¼8.7 Hz,1H), 7.68 (d, J¼2.0 Hz,
1H). Anal. Calcd for C7H3BrClN: C, 38.84; H, 1.40; N, 6.47. Found: C,
38.82; H, 1.43; N, 6.33.
3.2.3. 1-Bromo-5-chloro-2-isothiocyanatobenzene (1b). This com-
pound was prepared in 86% yield by treating the above isocyanide
with sulfur in the presence of catalytic amount of selenium and
Et3N in THF at room temperature;5 a white solid; mp 21e23 ꢁC
(hexane); IR (KBr) 2068 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.19 (d,
J¼8.3 Hz, 1H), 7.27 (dd, J¼8.3, 2.5 Hz, 1H), 7.59 (d, J¼2.5 Hz, 1H).
Anal. Calcd for C7H3BrClNS: C, 33.83; H, 1.22; N, 5.63. Found: C,
33.78; H, 1.20; N, 5.53.
O
O
R1
°
–78 C
+
O
2
3.3. Typical procedure for the preparation of 1,4-dihydro-3,1-
benzoxazine-2-thiones 5 and 6
O
N
H
S
3.3.1. 4-Ethyl-1,4-dihydro-3,1-benzoxazine-2-thione (5a). To a stir-
red solution of 1a (0.21 g, 1.0 mmol) in THF (4 mL) at ꢀ78 ꢁC was
added n-BuLi (1.6 M solution in hexane; 1.0 mmol) dropwise. After
1 min propanal (58 mg, 1.0 mmol) was added and stirring was
6a R1 = H 50%
6b R1 = Cl 45%
Scheme 2.

9338
K. Kobayashi et al. / Tetrahedron 66 (2010) 9336e9339
continued for an additional 15 min. The mixture was diluted with
Et2O (10 mL) and saturated aqueous NH4Cl (10 mL) was added. The
layers were separated and aqueous layer was extracted with AcOEt
twice (10 mL each). The combined organic layers were washed with
brine, dried over anhydrous Na2SO4, and concentrated by evapo-
ration. The residue was triturated with Et2O/hexane (1:9, 10 mL),
and the precipitate was collected by filtration and recrystallized
from hexane/CHCl3 to give 5a (0.11 g, 59%); a pale-yellow solid; mp
208 ([Mþ1]þ, 100). Anal. Calcd for C11H13NOS: C, 63.74; H, 6.32; N,
6.76. Found: C, 63.81; H, 6.30; N, 6.51.
3.3.7. 10,40-Dihydrospiro[cyclohexane-1,40-[3,1]benzoxazine]-20-thi-
one (5g). A pale-yellow solid; mp 149e151 ꢁC (hexane/CHCl3); IR
(KBr) 3150, 1618, 1175 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 1.21e1.37
(m, 1H), 1.66e1.77 (m, 4H), 1.83e1.86 (m, 1H), 1.96e2.05 (m, 2H),
2.21e2.23 (m, 2H), 6.99 (dd, J¼7.8, 0.9 Hz, 1H), 7.13e7.17 (m, 2H),
7.23e7.29 (m, 1H), 10.59 (br s, 1H); 13C NMR (125 MHz, CDCl3)
90e92 ꢁC; IR (KBr) 3173, 1622, 1169 cmꢀ1
CDCl3)
;
1H NMR (500 MHz,
d
1.09 (t, J¼7.3 Hz, 3H), 1.99e2.11 (m, 2H), 5.40 (t, J¼6.0 Hz,
d 20.75, 24.87, 35.25, 85.60, 114.21, 123.02, 125.33, 126.97, 128.85,
1H), 6.89 (dd, J¼7.8, 0.9 Hz, 1H), 7.09 (d, J¼7.8 Hz, 1H), 7.16 (ddd,
J¼7.8, 7.3, 0.9 Hz, 1H), 7.30 (ddd, J¼7.8, 7.3, 0.9 Hz, 1H), 9.66 (br s,
131.72, 184.02; MS m/z 234 ([Mþ1]þ, 100). Anal. Calcd for
C13H15NOS: C, 66.92; H, 6.48; N, 6.00. Found: C, 66.89; H, 6.41;
N, 5.96.
1H); 13C NMR (125 Hz, CDCl3)
d 8.77, 27.97, 82.29, 114.02, 121.17,
124.43, 125.08, 129.24, 132.28, 184.81; MS m/z 194 ([Mþ1]þ, 100).
Anal. Calcd for C10H11NOS: C, 62.15; H, 5.74; N, 7.25. Found: C, 61.87;
H, 5.77; N, 7.13.
3.3.8. 4-Methyl-4-phenyl-1,4-dihydro-3,1-benzoxazine-2-thione
(5h). A pale-yellow solid; mp 194e196 ꢁC (hexane/CHCl3); IR (KBr)
3171,1620, 1178 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 2.09 (s, 3H), 6.97
3.3.2. 4-Phenyl-1,4-dihydro-3,1-benzoxazine-2-thione (5b). A pale-
yellow solid; mp 187e190 ꢁC (hexane/CHCl3); IR (KBr) 3175, 1618,
(d, J¼7.8 Hz, 1H), 7.22e7.37 (m, 8H), 10.21 (br s, 1H); 13C NMR
(125 MHz, CDCl3)
d 27.95, 87.14, 114.31, 125.07, 125.11, 125.43,
1163 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
6.40 (s, 1H), 6.88 (d,
125.49, 128.43, 128.45, 129.54, 132.26, 142.11, 184.45; MS m/z 256
([Mþ1]þ, 100). Anal. Calcd for C15H13NOS: C, 70.56; H, 5.13; N, 5.49.
Found: C, 70.28; H, 5.05; N, 5.45.
J¼7.3 Hz, 1H), 6.92 (d, J¼7.8 Hz, 1H), 7.12 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H),
7.32e7.37 (m, 3H), 7.40e7.42 (m, 3H), 9.48 (br s, 1H); 13C NMR
(125 MHz, CDCl3)
d 82.47, 113.77, 121.21, 125.13, 126.04, 128.00,
128.86, 129.48, 129.74, 132.80, 136.53, 184.68; MS m/z 242 ([Mþ1]þ,
100). Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80. Found: C,
69.43; H, 4.31; N, 6.01.
3.3.9. 4-Methyl-4-(thiophen-2-yl)-1,4-dihydro-3,1-benzoxazine-2-
thione (5i). A pale-yellow solid; mp 139e141 ꢁC (hexane/CHCl3); IR
(KBr) 3169, 1620, 1177 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 2.21 (s,
3H), 6.82 (d, J¼2.9 Hz, 1H), 6.89 (dd, J¼4.9, 3.9 Hz, 1H), 6.99 (d,
3.3.3. 4-(3-Chlorophenyl)-1,4-dihydro-3,1-benzoxazine-2-thione
J¼7.8 Hz, 1H), 7.19e7.32 (m, 3H), 7.36 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H),
(5c). A pale-yellow solid; mp 159e161 ꢁC (hexane/CHCl3); IR (KBr)
10.25 (br s, 1H); 13C NMR (125 MHz, CDCl3)
d 28.54, 84.46, 114.27,
124.58, 125.15, 125.30, 126.07, 126.56, 126.80, 129.90, 132.06, 146.10,
183.73; MS m/z 262 ([Mþ1]þ, 100). Anal. Calcd for C13H11NOS2: C,
59.74; H, 4.24; N, 5.36. Found: C, 59.53; H, 4.20; N, 5.28.
3173,1620,1159 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
6.36 (s,1H), 6.89
(d, J¼7.8 Hz, 1H), 6.95 (d, J¼7.8 Hz, 1H), 7.15 (dd, J¼7.8, 7.3 Hz, 1H),
7.28 (d, J¼7.3 Hz, 1H), 7.33e7.40 (m, 4H), 9.60 (br s, 1H); 13C NMR
(125 MHz, CDCl3)
d 81.49, 113.99, 120.50, 125.34, 125.89, 126.17,
128.05, 129.71, 130.04, 130.18, 132.72, 134.86, 138.47, 184.31; MS m/z
276 ([Mþ1]þ,100). Anal. Calcd for C14H10ClNOS: C, 60.98; H, 3.66; N,
5.08. Found: C, 60.86; H, 3.55; N, 5.06.
3.3.10. 4,4-Diphenyl-1,4-dihydro-3,1-benzoxazine-2-thione (5j)7. A
white solid; mp 226e228 ꢁC (hexane/CHCl3); IR (KBr) 3169, 1614,
1178 cmꢀ1
;
1H NMR (500 MHz, DMSO-d6)
d
6.68 (dd, J¼7.8, 1.4 Hz,
1H), 7.07e7.09 (m, 4H), 7.11 (d, J¼7.8 Hz, 1H), 7.15 (ddd, J¼7.8, 7.3,
3.3.4. 4-(3-Methoxyphenyl)-1,4-dihydro-3,1-benzoxazine-2-thione
1.4 Hz, 1H), 7.39e7.43 (m, 7H), 12.34 (br s, 1H).
(5d). A pale-yellow solid; mp 185e187 ꢁC (hexane/CHCl3); IR (KBr)
3181, 1618, 1153 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
3.80 (s, 3H),
6.34 (s, 1H), 6.91e6.94 (m, 5H), 7.12 (t, J¼7.3 Hz, 1H), 7.26e7.35 (m,
2H), 9.63 (br s, 1H); 13C NMR (125 MHz, CDCl3)
55.34, 82.29,
3.3.11. 6-Chloro-4-ethyl-1,4-dihydro-3,1-benzoxazine-2-thione
(5k). A white solid; mp 127e129 ꢁC (hexane/CHCl3); IR (KBr) 3165,
d
1618, 1159 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.10 (t, J¼7.3 Hz, 3H),
113.38, 113.72, 115.07, 120.20, 121.17, 125.14, 126.07, 129.75, 129.89,
132.76, 137.97, 159.91, 184.67; MS m/z 272 ([Mþ1]þ, 100). Anal.
Calcd for C15H13NO2S: C, 66.40; H, 4.83; N, 5.16. Found: C, 66.24; H,
4.65; N, 5.24.
2.04 (quint, J¼7.3 Hz, 2H), 5.37 (t, J¼7.3 Hz, 1H), 6.92 (d, J¼8.8 Hz,
1H), 7.09 (d, J¼2.4 Hz, 1H), 7.27 (dd, J¼8.8, 2.4 Hz, 1H), 10.37 (br s,
1H); 13C NMR (100 MHz, CDCl3)
d 8.74, 27.85, 81.74, 115.29, 122.84,
124.65, 129.33, 130.25, 130.90, 184.50; MS m/z 228 ([Mþ1]þ, 100).
Anal. Calcd for C10H10ClNOS: C, 52.75; H, 4.43; N, 6.15. Found: C,
52.72; H, 4.68; N, 6.19.
3.3.5. 4-(Naphthalen-1-yl)-1,4-dihydro-3,1-benzoxazine-2-thione
(5e). A pale-yellow solid; mp 175e178 ꢁC (hexane/CHCl3); IR (KBr)
3175, 1618, 1165 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
6.73 (d,
3.3.12. 6-Chloro-4-(4-chlorophenyl)-1,4-dihydro-3,1-benzoxazine-2-
J¼7.8 Hz, 1H), 6.99 (d, J¼8.2 Hz, 1H), 7.05 (dd, J¼7.8, 7.3 Hz, 1H),
7.06 (s, 1H), 7.33e7.36 (m, 2H), 7.45 (dd, J¼8.2, 7.3 Hz, 1H),
7.52e7.55 (m, 2H), 7.92e7.94 (m, 2H), 8.06e8.08 (m, 1H), 9.59 (br s,
thione (5l). A pale-yellow solid; mp 199e203 ꢁC (hexane/THF); IR
(KBr) 3163,1614,1155 cmꢀ1; 1H NMR (400 MHz, DMSO-d6)
d 6.68 (s,
1H), 7.10 (d, J¼8.8 Hz, 1H), 7.11 (d, J¼2.4 Hz, 1H), 7.35 (d, J¼8.8 Hz,
1H); 13C NMR (125 MHz, DMSO-d6)
d 78.76, 114.22, 121.03, 124.44,
2H), 7.45 (dd, J¼8.8, 2.4 Hz, 1H), 7.52 (d, J¼8.8 Hz, 2H), 12.45 (br s,
124.67, 125.22, 125.56, 126.15, 126.71, 127.07, 128.78, 129.58, 130.14,
130.67, 132.32, 133.52, 133.74, 183.46; MS m/z 292 ([Mþ1]þ, 100).
Anal. Calcd for C18H13NOS: C, 74.20; H, 4.50; N, 4.81. Found: C,
74.11; H, 4.21; N, 4.58.
1H); 13C NMR (100 MHz, DMSO-d6)
d 79.00, 116.17, 122.82, 125.47,
128.24, 129.04, 129.22, 129.64, 131.79, 133.96, 136.31, 182.84; MS m/
z 310 ([Mþ1]þ, 100). Anal. Calcd for C14H9Cl2NOS: C, 54.21; H, 2.92;
N, 4.52. Found: C, 53.92; H, 2.88; N, 4.49.
3.3.6. 4-Ethyl-4-methyl-1,4-dihydro-3,1-benzoxazine-2-thione
3.3.13. 60-Chloro-10,40-dihydrospiro[cyclohexane-1,40-[3,1]benzox-
(5f). A pale-yellow solid; mp 98e100 ꢁC (hexane/CHCl3); IR (KBr)
azine]-20-thione (5m). A pale-yellow solid; mp 203e206 ꢁC (hex-
3179,1620,1190 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
0.95 (t, J¼7.3 Hz,
ane/CHCl3); IR (KBr) 3156, 1616, 1178 cmꢀ1 1H NMR (400 MHz,
;
CDCl3) d 1.26e1.38 (m, 1H), 1.65e1.75 (m, 4H), 1.83e1.88 (m, 1H),
3H), 1.74 (s, 3H), 2.02e2.06 (m, 2H), 6.98 (d, J¼7.3 Hz, 1H), 7.08 (d,
J¼7.3 Hz, 1H), 7.15 (td, J¼7.3, 0.9 Hz, 1H), 7.28 (td, J¼7.3, 1.4 Hz, 1H),
1.92e2.05 (m, 2H), 2.19e2.23 (m, 2H), 6.89 (d, J¼8.3 Hz, 1H), 7.15 (d,
10.46 (br s, 1H); 13C NMR (125 MHz, CDCl3)
d 8.06, 26.31, 33.71,
J¼2.4 Hz, 1H), 7.24 (dd, J¼8.3, 2.4 Hz, 1H), 10.27 (br s, 1H); 13C NMR
88.06, 114.18, 123.87, 124.87, 125.22, 128.97, 131.66, 184.10; MS m/z
(100 MHz, DMSO-d6) d 20.66, 24.77, 35.13, 85.28, 115.38, 123.54,

K. Kobayashi et al. / Tetrahedron 66 (2010) 9336e9339
9339
128.63, 128.90, 130.34, 130.43, 183.76; MS m/z 268 ([Mþ1]þ, 100).
Anal. Calcd for C13H14ClNOS: C, 58.31; H, 5.27; N, 5.23. Found: C,
58.25; H, 5.25; N, 5.11.
256 ([Mþ1]þ, 100). Anal. Calcd for C11H10ClNO2S: C, 51.66; H, 3.94;
N, 5.48. Found: C, 51.73; H, 4.04; N, 5.54.
Acknowledgements
3.3.14. 6-Chloro-4-methyl-4-phenyl-1,4-dihydro-3,1-benzoxazine-2-
thione (5n). A white solid; mp 214e215 ꢁC (hexane/THF); IR (KBr)
This work was partially supported by a Grant-in-Aid for Scien-
tific Research (C) 22550035 from Japan Society for the Promotion of
Science. We thank Mrs. Miyuki Tanmatsu of Tottori University for
her assistance in determining mass spectra and performing com-
bustion analyses.
3158, 1616, 1176 cmꢀ1 1H NMR (400 MHz, DMSO-d6)
; d 2.02 (s,
3H), 7.04 (d, J¼8.3 Hz, 1H), 7.24 (d, J¼7.3 Hz, 2H), 7.31 (t, J¼7.3 Hz,
1H), 7.36 (t, J¼7.3 Hz, 2H), 7.47 (dd, J¼8.3, 2.0 Hz, 1H), 7.68 (d,
J¼2.0 Hz, 1H), 12.32 (br s, 1H); 13C NMR (100 MHz, DMSO-d6)
d
27.67, 85.50, 116.23, 125.05, 125.18, 127.23, 128.33, 128.526,
128.534, 129.55, 131.42, 142.17, 182.96; MS m/z 290 ([Mþ1]þ, 100).
Anal. Calcd for C15H12ClNOS: C, 62.17; H, 4.17; N, 4.83. Found: C,
62.14; H, 4.14; N, 4.60.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.10.010.
3.3.15. 1,4-Dihydrospiro[3,1-benzoxazine-4,20-tetrahydrofuran]-2-
thione (6a). A pale-yellow solid; mp 99e102 ꢁC (hexane/CHCl3); IR
References and notes
(KBr) 3169, 1620, 1167 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 2.18e2.25
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(m, 1H), 2.38e2.44 (m, 1H), 2.47e2.56 (m, 1H), 2.59e2.64 (m, 1H),
4.20e4.24 (m, 1H), 4.39e4.43 (m, 1H), 7.02 (d, J¼7.8 Hz, 1H), 7.19
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CHCl3); IR (KBr) 3153, 1618, 1165 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
d
2.17e2.26 (m, 1H), 2.32e2.39 (m, 1H), 2.46e2.57 (m, 1H),
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