Synthesis of benzazetine derivatives by intramolecular iodoamination of o-(acylamino)styrene derivatives

Article abstract of DOI:10.1246/bcsj.78.886

The iodoamination of o-(acylamino)styrene derivatives using iodine and sodium hydrogencarbonate, producing 7-acyl-8-iodomethylbicyclo[4.2.0]-7-azaoct- 1,3,5-triene [1-acyl-2-(iodomethyl)benzazetine] derivatives, is described. Replacement of the iodo moiety by hydrogen or phenylthio group is also reported.

Full text of DOI:10.1246/bcsj.78.886

886 Bull. Chem. Soc. Jpn., 78, 886–889 (2005)
Ó 2005 The Chemical Society of Japan
Synthesis of Benzazetine Derivatives by Intramolecular Iodoamination
of o-(Acylamino)styrene Derivatives
ꢀ
Kazuhiro Kobayashi, Kazuna Miyamoto, Osamu Morikawa, and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552
Received October 22, 2004; E-mail: kkoba@chem.tottori-u.ac.jp
The iodoamination of o-(acylamino)styrene derivatives using iodine and sodium hydrogencarbonate, producing
7-acyl-8-iodomethylbicyclo[4.2.0]-7-azaoct-1,3,5-triene [1-acyl-2-(iodomethyl)benzazetine] derivatives, is described.
Replacement of the iodo moiety by hydrogen or phenylthio group is also reported.
The intramolecular haloamination reaction has been used
widely for the preparation of nitrogen heterocyclic com-
R1
R2
pounds.1 We investigated the potential of iodoamination in
the construction of benzazetine derivatives, and found that 1-
acyl-2-(iodomethyl)benzazetine derivatives could be synthe-
sized by treating o-(acylamino)styrene derivatives with I2/
NaHCO3.2,3 Benzazetine derivatives have received attention
as potential precursors for the generation of o-quinonemethide
monoimine intermediates.4 Although several reports on the
formation of benzazetine derivatives have appeared,5 few gen-
eral synthetic methods of this class of molecules have been de-
veloped.6 Herein, we wish to report on the results of our inves-
tigation, which offer simple access to the construction of
benzazetine derivatives.
NHCOR3
1
R1
R2
CH2I
NCOR3
I2, NaHCO3
MeCN, 0 °C
2a 88%; 2b 89%; 2c 96%
2d 78%; 2e 85%; 2f 93%
R1
R2
n-Bu3SnH
Me
NCOR3
benzene, rt
The intramolecular iodoamination of o-(acylamino)styrene
derivatives 1 could be easily achieved, as illustrated in
Scheme 1. Thus, the reaction of 1 with 3 equivalents eachꢁof
iodine and sodium hydrogencarbonate in acetonitrile at 0 C
proceeded smoothly to afford the 2-(iodomethyl)benzazetine
derivatives 2 in good yields. In order to confirm the (iodo-
methyl)benzazetine structure of 2, replacement of the iodine
of 2 by hydrogen was tried. The treatment of 2 with tributyltin
hydride at room temperature gave 2-methylbenzazetine deriv-
atives 3 in good yields. The possibility of the dihydroindole
structure of the products was excluded by these results. The
benzazetine structure was further confirmed by a FAB-mass
spectral analysis of 2a, excluding the possibility of the sym-
metrical dimer structure (see Experimental).
3a 85%; 3b 81%; 3c 95%
3d 88%; 3e 60%; 3f 94%
a R1 = Me, R2 = H, R3 = Me
b R1 = Me, R2 = H, R3 = CF3
c R1 = Me, R2 = H, R3 = Ph
d R1 = Ph, R2 = H, R3 = Me
e R1 = Ph, R2 = H, R3 = CF3
f R1 = Ph, R2 = Cl, R3 = Me
Scheme 1.
Me
PhSH, NaH
2a, c
CH2SPh
DMF, 0 °C
NCOR
The nucleophilic substitution of the iodine of 2 was per-
formed using sodium benzenethiolate, generated from ben-
zenethiol and sodium hydride, in DMF at 0 ꢁC to give 2-(phen-
ylthiomethyl)benzazetine derivatives 4 in satisfactory yields,
as shown in Scheme 2.
4a R = Me 55%
4c R = Ph 66%
Scheme 2.
In summary, we have shown that iodoamination of o-(acyl-
amino)styrene derivatives can offer a simple method for con-
structing benzazetine derivatives. The ready availability of
the starting materials and the ease of operation make the pres-
ent method attractive.
rected. The IR spectra were recorded on a Shimadzu FTIR-8300
spectrometer. The 1H NMR spectra were determined using SiMe4
as an internal reference in CDCl3 with a JEOL JNM-GX270 FT
NMR spectrometer operating at 270 MHz, or a JEOL ECP500
FT NMR spectrometer operating at 500 MHz. The 13C NMR spec-
trum was determined using SiMe4 as an internal reference with a
JEOL ECP500 FT NMR spectrometer operating at 125 MHz in
CDCl3. Low-resolution mass spectra (EI) were recorded on a
JEOL AUTOMASS 20 spectrometer (Center for Joint Research
Experimental
General. The melting points were determined on a Laboratory
Devices MEL-TEMP II melting-point apparatus and are uncor-
Published on the web May 6, 2005; DOI 10.1246/bcsj.78.886

K. Kobayashi et al.
Bull. Chem. Soc. Jpn., 78, No. 5 (2005)
887
and Development, this University). The FAB mass spectrum was
recorded using a xenone ionization technique with m-nitrobenzyl
alcohol as the matrix on a JEOL JMS-AX505 HA spectrometer
(Faculty of Agriculture, this University). Thin-layer chromatogra-
phy (TLC) was carried out on Merck Kieselgel 60 PF254. All of
the solvents used were dried over appropriate drying agents and
distilled under argon prior to use. All of the reactions were carried
out under argon.
anhydrous K2CO3. After evaporation of the solvent the residue
was purified by preparative TLC on SiO2 to give 2a (0.30 g,
82%); mp 70–72 ꢁC (hexane–Et2O); IR (KBr disk) 1645 and
1601 cmꢂ1 1H NMR (270 MHz, CDCl3) ꢀ 1.81 (3H, s), 2.17
;
(3H, s), 3.39 (1H, d, J ¼ 10:9 Hz), 3.58 (1H, d, J ¼ 10:9 Hz),
7.08 (1H, dd, J ¼ 7:6, 1.6 Hz), 7.1–7.25 (2H, m), and 7.29 (1H,
td, J ¼ 7:6, 1.6 Hz); 13C NMR (125 MHz) ꢀ 16.19, 21.80,
26.47, 77.28, 122.88, 124.57, 126.31, 126.50, 129.34, 138.16,
and 159.41; MS (EI) m=z (%) 301 (Mþ, 8.4) and 160 (100);
FAB-MS m=z 302.0 [ðM þ 1Þþ]. Found: C, 44.18; H, 4.16; N,
4.61%. Calcd for C11H12INO: C, 43.87; H, 4.02; N, 4.65%.
8-Iodomethyl-8-methyl-7-trifluoroacetylbicyclo[4.2.0]-7-aza-
oct-1,3,5-triene (2b): Rf 0.48 (1:4 AcOEt–hexane); IR (neat)
Starting Materials. N-[2-(1-Methylethenyl)phenyl]acetamide
(1a) and N-[2-(1-methylethenyl)phenyl]trifluoroacetamide (1b)
were prepared by the action of acetic anhydride and trifluoroacetic
anhydride, respectively, upon 2-(1-methylethenyl)aniline in pyri-
dine. 1a: 92%; mp 49–51 ꢁC (hexane–Et2O) (lit.7 52 ꢁC). 1b:
97%; mp 59–60 ꢁC (hexane); IR (KBr disk) 3266 and 1702
1668 and 1605 cmꢂ1 1H NMR (270 MHz, CDCl3) ꢀ 1.92 (3H,
;
1
cmꢂ1; H NMR (270 MHz, CDCl3) ꢀ 2.10 (3H, s), 5.06 (1H, s),
s), 3.53 (1H, d, J ¼ 11:2 Hz), 3.60 (1H, d, J ¼ 11:2 Hz), 7.12
(1H, dd, J ¼ 7:6, 1.6 Hz), and 7.25–7.45 (3H, m); MS (EI) m=z
(%) 355 (Mþ, 7.0) and 214 (100). Found: C, 36.87; H, 2.78; N,
3.54%. Calcd for C11H9F3INO: C, 37.21; H, 2.55; N, 3.94%.
7-Benzoyl-8-iodomethyl-8-methylbicyclo[4.2.0]-7-azaoct-1,3,
5-triene (2c): mp 98–101 ꢁC (hexane–Et2O); IR (KBr disk) 1624
and 1599 cmꢂ1; 1H NMR (500 MHz, CDCl3) ꢀ 1.94 (3H, s), 3.49
(1H, d, J ¼ 11:0 Hz), 3.67 (1H, d, J ¼ 11:0 Hz), 7.18 (1H, dd,
J ¼ 7:8, 0.9 Hz), 7.23 (1H, ddd, J ¼ 8:7, 7.8, 2.3 Hz), 7.33–
7.39 (2H, m), 7.45–7.49 (2H, m), 7.51 (1H, tt, J ¼ 7:3, 2.3 Hz),
and 8.25 (2H, dd, J ¼ 7:3, 2.3 Hz); MS (EI) m=z (%) 363 (Mþ,
14) and 222 (100). Found: C, 52.92; H, 3.84; N, 3.86%. Calcd
for C16H14INO: C, 52.91; H, 3.89; N, 3.86%.
7-Acetyl-8-iodomethyl-8-phenylbicyclo[4.2.0]-7-azaoct-1,3,
5-triene (2d): mp 132–134 ꢁC (hexane–CH2Cl2); IR (KBr disk)
1638 and 1595 cmꢂ1; 1H NMR (270 MHz, CDCl3) ꢀ 2.24 (3H, s),
3.90 (2H, s), 7.03 (1H, dd, J ¼ 7:6, 1.6 Hz), 7.20 (2H, t, J ¼ 7:6
Hz), and 7.3–7.4 (6H, m); MS (EI) m=z (%) 363 (Mþ, 7.7) and 222
(100). Found: C, 52.55; H, 4.03; N, 4.01%. Calcd for C16H14INO:
C, 52.91; H, 3.89; N, 3.86%.
5.48 (1H, s), 7.15–7.4 (3H, m), 8.27 (1H, d, J ¼ 8:2 Hz), and
8.48 (1H, br s). Found: C, 57.48; H, 4.41; N, 6.08%. Calcd for
C11H10F3NO: C, 57.64; H, 4.40; N, 6.11%. N-[2-(1-Methyleth-
enyl)phenyl]benzamide (1c) was prepared according to a reported
procedure.8 N-[2-(1-Phenylethenyl)phenyl]acetamide (1d) and N-
[2-(1-phenylethenyl)phenyl]trifluoroacetamide (1e) were prepared
by the action of acetic anhydride and trifluoroacetic anhydride,
respectively, upon 2-(1-phenylethenyl)aniline3g,9 in pyridine. 1d:
ꢁ
94%; mp 126–128 C (hexane–CH2Cl2) (lit.10 123–125 ꢁC). 1e:
95%; mp 56–59 ꢁC (hexane–Et2O); IR (KBr disk) 3386 and
1
1732 cmꢂ1; H NMR (270 MHz, CDCl3) ꢀ 5.40 (1H, d, J ¼ 1:0
Hz), 5.91 (1H, d, J ¼ 1:0 Hz), 7.25–7.4 (7H, m), 7.45 (1H, td,
J ¼ 7:3, 1.6 Hz), 7.81 (1H, br s), and 8.17 (1H, dd, J ¼ 8:2, 1.3
Hz). Found: C, 65.84; H, 4.21; N, 4.64%. Calcd for C16H12F3NO:
C, 65.98; H, 4.15; N, 4.81%. N-[4-Chloro-2-(1-phenylethenyl)-
phenyl]acetamide (1f) was prepared from 2-amino-5-chlorobenzo-
phenone as follows. The action of MeMgBr on 2-amino-5-chloro-
ꢁ
benzophenone in Et2O at 0 C gave 1-(2-amino-5-chlorophenyl)-
1-phenylethanol: 86%; mp 97–100 ꢁC (hexane–Et2O); IR (KBr
disk) 3455, 3359, and 1607 cmꢂ1
;
1H NMR (270 MHz, CDCl3)
8-Iodomethyl-8-phenyl-7-trifluoroacetylbicyclo[4.2.0]-7-aza-
ꢁ
ꢀ 1.86 (3H, s), 3.67 (3H, br), 6.55 (1H, d, J ¼ 8:6 Hz), 7.08
(1H, dd, J ¼ 8:6, 2.3 Hz), and 7.2–7.4 (6H, m). Found: C,
67.82; H, 5.90; N, 5.41%. Calcd for C14H14ClNO: C, 67.88; H,
5.70; N, 5.65%. This amino alcohol was heated at 250 ꢁC (no sol-
vent) according to the procedure developed by Smith and Living-
house11 to give 4-chloro-2-(phenylethenyl)aniline: 82%; Rf 0.68
oct-1,3,5-triene (2e): mp 109–111 C (hexane–Et2O); IR (KBr
1
disk) 1668 and 1602 cmꢂ1; H NMR (270 MHz, CDCl3) ꢀ 3.93
(1H, d, J ¼ 11:9 Hz), 4.02 (1H, d, J ¼ 11:9 Hz), 7.15 (1H, dd,
J ¼ 7:6, 1.6 Hz), and 7.3–7.5 (8H, m); MS (EI) m=z (%) 417
(Mþ, 24), 320 (39), and 193 (100). Found: C, 46.35; H, 2.95;
N, 3.33%. Calcd for C16H11F3INO: C, 46.07; H, 2.66; N, 3.36%.
7-Acetyl-3-chloro-8-iodomethyl-8-phenylbicyclo[4.2.0]-7-aza-
oct-1,3,5-triene (2f): mp 74–75 ꢁC (hexane–Et2O); IR (KBr
(1:2 EtOAc–hexane); IR (neat) 3471, 3383, and 1614 cmꢂ1
;
1H NMR (270 MHz, CDCl3) ꢀ 3.54 (2H, br), 5.35 (1H, d, J ¼
1:0 Hz), 5.80 (1H, d, J ¼ 1:0 Hz), 6.60 (1H, d, J ¼ 8:9 Hz),
7.10 (1H, dd, J ¼ 8:9, 2.3 Hz), and 7.25–7.4 (6H, m). Found:
C, 73.12; H, 5.38; N, 6.25%. Calcd for C14H12ClN: C, 73.20;
H, 5.27; N, 6.10%. This aminostyrene wasꢁacetylated with Ac2O
in pyridine to give 1f: 90%; mp 134–136 C (hexane–Et2O); IR
1
disk) 1643 and 1600 cmꢂ1; H NMR (500 MHz, CDCl3) ꢀ 2.24
(3H, s), 3.86 (1H, d, J ¼ 11:9 Hz), 3.88 (1H, d, J ¼ 11:9 Hz),
6.98 (1H, d, J ¼ 2:3 Hz), 7.13 (1H, d, J ¼ 8:2 Hz), 7.29 (1H,
dd, J ¼ 8:2, 2.3 Hz), and 7.34–7.41 (5H, m); MS (EI) m=z (%)
397 (Mþ, 5.6) and 256 (100). Found: C, 48.19; H, 3.31; N,
3.40%. Calcd for C16H13ClINO: C, 48.33; H, 3.30; N, 3.52%.
7-Acetyl-8,8-dimethylbicyclo[4.2.0]-7-azaoct-1,3,5-triene
(3a). A solution of 2a (0.16 g, 0.52 mmol) in benzene (3 mL)
containing n-Bu3SnH (0.29 g, 1.0 mmol) was stirred at room tem-
perature for 1 h. The solvent was evaporated to give a residue,
which was chromatographed on SiO2 (3:1 hexane–AcOEt) to give
3a (77 mg, 85%); Rf 0.39 (1:3 AcOEt–hexane); IR (neat) 1643
1
(KBr disk) 3219 and 1661 cmꢂ1; H NMR (500 MHz, CDCl3) ꢀ
1.79 (3H, s), 5.39 (1H, s), 5.89 (1H, s), 6.90 (1H, br s), 7.29–
7.38 (7H, m), and 8.14 (1H, d, J ¼ 8:7 Hz). Found: C, 70.91;
H, 5.29; N, 4.99%. Calcd for C16H14ClNO: C, 70.72; H, 5.19;
N, 5.15%.
7-Acetyl-8-iodomethyl-8-methylbicyclo[4.2.0]-7-azaoct-1,3,
5-triene (2a). Typical Procedure for the Iodoamination of 1:
To a stirred solution of 1a (0.21 g, 1.2 mmol) in MeCN (15 mL)
containing NaHCO3 (0.30 g, 3.6 mmol) at 0 ꢁC was added I2 (0.91
g, 3.6 mmol) portionwise. After stirring was continued for 1 h,
10% aqueous Na2S2O3 (15 mL) was added. Acetonitrile was
evaporated and the resulting mixture was extracted with Et2O
three times (10 mL each). The combined extracts were washed
with saturated aqueous NaHCO3 and then brine, and dried over
and 1603 cmꢂ1 1H NMR (270 MHz, CDCl3) ꢀ 1.61 (6H, s),
;
2.11 (3H, s), 7.07 (1H, dd, J ¼ 7:6, 1.3 Hz), 7.10 (1H, dd, J ¼
7:6, 1.3 Hz), 7.14 (1H, td, J ¼ 7:6, 1.3 Hz), and 7.24 (1H, td, J ¼
7:6, 1.3 Hz); MS (EI) m=z (%) 175 (Mþ, 38) and 160 (100).
Found: C, 75.28; H, 8.07; N, 7.80%. Calcd for C11H13NO: C,
75.40; H, 7.48; N, 7.99%.
8,8-Dimethyl-7-trifluoroacetylbicyclo[4.2.0]-7-azaoct-1,3,5-

888 Bull. Chem. Soc. Jpn., 78, No. 5 (2005)
Synthesis of Benzazetine Derivatives
triene (3b). A similar reaction of 2b with n-Bu3SnH at room
temperature for 6 h gave 3b: Rf 0.50 (1:4 AcOEt–hexane); IR
s), 3.38 (1H, d, J ¼ 13:7 Hz), 3.56 (1H, d, J ¼ 13:7 Hz), 7.08
(1H, tt, J ¼ 7:3, 2.3 Hz), 7.12–7.19 (4H, m), 7.24 (2H, dd,
J ¼ 7:8, 1.3 Hz), 7.30–7.32 (2H, m), 7.40 (2H, t, J ¼ 7:8 Hz),
7.47 (1H, tt, J ¼ 7:3, 2.3 Hz), and 8.09 (2H, dd, J ¼ 6:9, 1.8
Hz); MS (EI) m=z (%) 345 (Mþ, 5.1) and 222 (100). Found: C,
76.28; H, 5.55; N, 3.95; S 9.16%. Calcd for C22H19NOS: C,
76.49; H, 5.54; N, 4.05; S, 9.28%.
1
(neat) 1666 and 1607 cmꢂ1; H NMR (270 MHz, CDCl3) ꢀ 1.71
(6H, s), 7.1–7.15 (1H, m), and 7.25–7.35 (3H, m); MS (EI) m=z
(%) 229 (Mþ, 61) and 214 (100). Found: C, 57.58; H, 4.09; N,
5.99%. Calcd for C11H10F3NO: C, 57.64; H, 4.40; N, 6.11%.
7-Benzoyl-8,8-dimethylbicyclo[4.2.0]-7-azaoct-1,3,5-triene
(3c). A similar reaction of 2c with n-Bu3SnH at room tempera-
ture for 10 min gave 3c: Rf 0.71 (1:3 AcOEt–hexane); IR (neat)
We are indebted to Mrs. Miyuki Tanmatsu of this Depart-
ment for determining MS spectra and performing combustion
analyses. This work was partially supported by a Grant-in-Aid
for Scientific Research (C) 15550092 from Japan Society for
the Promotion of Science.
1622 and 1599 cmꢂ1 1H NMR (500 MHz, CDCl3) ꢀ 1.72 (6H,
;
s), 7.14–7.22 (2H, m), 7.28–7.33 (2H, m), 7.45 (2H, t, J ¼ 7:3
Hz), 7.49 (1H, tt, J ¼ 7:3, 1.3 Hz), and 8.15 (2H, dd, J ¼ 7:3,
1.3 Hz); MS (EI) m=z (%) 237 (Mþ, 34) and 222 (100). Found:
C, 80.95; H, 6.27; N, 5.75%. Calcd for C16H15NO: C, 80.98; H,
6.37; N, 5.90%.
References
7-Acetyl-8-methyl-8-phenylbicyclo[4.2.0]-7-azaoct-1,3,5-tri-
ene (3d). A similar reaction of 2d with n-Bu3SnH at room tem-
perature overnight gave 3d: mp 60–62 ꢁC (pentane); IR (KBr
1
For recent reports: K. T. Chang, K. C. Jang, H. Y. Park, Y.
K. Kim, K. H. Park, and W. S. Lee, Heterocycles, 55, 1173
(2001); A. D. Jones, D. W. Knight, and D. E. Hibbs, J. Chem.
Soc., Perkin Trans. 1, 2001, 1182; D. W. Knight, A. L. Redfern,
and J. Gilmore, J. Chem. Soc., Perkin Trans. 1, 2001, 2874; D.
W. Knight, A. L. Redfern, and J. Gilmore, J. Chem. Soc., Perkin
Trans. 1, 2002, 622; J. Barluenga, M. Trincado, E. Rubio, and
1
disk) 1643 and 1599 cmꢂ1; H NMR (270 MHz, CDCl3) ꢀ 1.98
(3H, s), 2.22 (3H, s), 7.03 (1H, dd, J ¼ 7:6, 1.3 Hz), 7.1–7.2
(2H, m), and 7.25–7.35 (6H, m); MS (EI) m=z (%) 237 (Mþ,
60), 222 (82), and 194 (100). Found: C, 80.64; H, 6.56; N,
5.83%. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90%.
8-Methyl-8-phenyl-7-trifluoroacetylbicyclo[4.2.0]-7-azaoct-
1,3,5-triene (3e). A similar reaction of 2e with n-Bu3SnH at
room temperature overnight gave 3e: mp 70–75 ꢁC (pentane);
IR (KBr disk) 1663 and 1604 cmꢂ1; 1H NMR (270 MHz, CDCl3)
ꢀ 2.08 (3H, s), 7.07 (1H, dd, J ¼ 7:3, 1.3 Hz), and 7.25–7.4 (8H,
m); MS (EI) m=z (%) 291 (Mþ, 100). Found: C, 66.11; H, 4.24; N,
4.65%. Calcd for C16H12F3NO: C, 65.98; H, 4.15; N, 4.81%.
7-Acetyl-3-chloro-8-methyl-8-phenylbicyclo[4.2.0]-7-azaoct-
1,3,5-triene (3f). A similar reaction of 2f with n-Bu3SnH at room
temperature overnight gave 3f: mp 158–161 ꢁC (hexane–Et2O);
IR (KBr disk) 1643 and 1599 cmꢂ1; 1H NMR (500 MHz, CDCl3)
ꢀ 1.96 (3H, s), 2.14 (3H, s), 6.99 (1H, d, J ¼ 2:3 Hz), 7.10 (1H, d,
J ¼ 8:7 Hz), 7.25 (1H, dd, J ¼ 8:7, 2.3 Hz), and 7.30–7.35 (5H,
m); MS (EI) m=z (%) 271 (Mþ, 32) and 228 (100). Found: C,
70.64; H, 5.09; N, 4.92%. Calcd for C16H14ClNO: C, 70.72; H,
5.19; N, 5.15%.
´
J. M. Gonzalez, Angew. Chem., Int. Ed., 42, 2406 (2003); S. H.
L. Verhelst, B. P. Martinez, M. S. M. Timmer, G. Lodder, G.
A. van der Marel, H. S. Overkleeft, and J. H. van Boom,
J. Org. Chem., 68, 9598 (2003); M. Amjad and D. W. Knight,
Tetrahedron Lett., 45, 539 (2004); S. G. Davies, R. L. Nicholson,
P. D. Price, P. M. Roberts, and A. D. Smith, Synlett, 2004, 901; A.
Lei, X. Lu, and G. Liu, Tetrahedron Lett., 45, 1785 (2004), and
references cited therein.
2
Nishida and his colleagues have reported that intramolecu-
lar haloamination of o-acetylamino-ꢁ-methylstyrenes gave 3-
halo-3-methyl-2,3-dihydro-1{H}-indoles: M. Arisawa, Y. Ando,
M. Yamanaka, M. Nakagawa, and A. Nishida, Synlett, 2002, 1514.
3
The utilities of o-aminostyrene derivatives for the prepara-
tion of benzo-analogues of nitrogen heterocycles are well known:
a) B. S. Lee, J. H. Lee, and D. Y. Chi, J. Org. Chem., 67, 7884
(2002). b) Y. Wada, T. Mori, and J. Ichikawa, Chem. Lett., 32,
1000 (2003). c) J. Ichikawa, Y. Wada, H. Miyazaki, T. Mori,
and H. Kuroki, Org. Lett., 5, 1455 (2003). d) C. M. Coleman
and D. F. O’Shea, J. Am. Chem. Soc., 125, 4054 (2003). e) B.
7-Acetyl-8-methyl-8-(phenylthiomethyl)bicyclo[4.2.0]-7-aza-
oct-1,3,5-triene (4a). To a stirred suspenꢁsion of NaH (60% in oil,
29 mg, 0.73 mmol) in DMF (2 mL) at 0 C was added PhSH (80
mg, 0.73 mmol) dropwise. After stirring for 1 h, a solution of 2a
(0.20 g, 0.66 mmol) in DMF (2 mL) was added dropwise. After
stirring for 5 h at the same temperature, the resulting mixture
was treated with saturated aqueous NH4Cl (15 mL) and organic
materials were extracted with Et2O three times (10 mL each).
The combined extracts were washed with water twice and then
brine once, and dried over anhydrous Na2SO4. Evaporation of
the solvent gave a residue, which was purified by preparative
TLC on SiO2 to afford 4a (0.10 g, 55%); Rf 0.24 (3:1 hexane–
C. G. Soderberg, J. A. Shriver, S. H. Cooper, T. L. Shrout, E. S.
¨
Helton, L. R. Austin, H. H. Odens, B. R. Hearn, P. C. Jones, T.
N. Kouadio, T. H. Ngi, R. Baswell, H. J. Caprara, M. D. Meritt,
and T. T. Mai, Tetrahedron, 59, 8775 (2003). f) C. Dong
and H. Alper, Tetrahedron: Asymmetry, 15, 35 (2004). g) K.
Kobayashi, K. Takagoshi, S. Kondo, O. Morikawa, and H.
Konishi, Bull. Chem. Soc. Jpn., 77, 553 (2004). h) Y. Takigawa,
H. Ito, K. Omodera, M. Ito, and T. Taguchi, Tetrahedron, 60,
1385 (2004). i) C. Theeraladanon, M. Arisawa, A. Nishida, and
M. Nakagawa, Tetrahedron, 60, 3017 (2004), and references cited
therein.
AcOEt); IR (neat) 1645 and 1602 cmꢂ1 1H NMR (500 MHz,
;
CDCl3) ꢀ 1.77 (3H, s), 1.88 (3H, s), 3.25 (1H, d, J ¼ 14:2 Hz),
3.44 (1H, d, J ¼ 14:2 Hz), 7.05 (1H, dd, J ¼ 8:7, 1.9 Hz),
7.10–7.18 (3H, m), 7.20–7.24 (3H, m), and 7.29 (2H, d, J ¼ 7:3
Hz); MS (EI) m=z (%) 283 (Mþ, 3.0) and 160 (100). Found: C,
71.99; H, 6.10; N, 5.01; S, 11.15%. Calcd for C17H17NOS: C,
72.05; H, 6.05; N, 4.94; S, 11.32%.
7-Benzoyl-8-methyl-8-(phenylthiomethyl)bicyclo[4.2.0]-7-aza-
oct-1,3,5-triene (4c). Prepared in a manner similar to that de-
scribed above for 4a; Rf 0.40 (5:1 hexane–AcOEt); IR (neat)
1626 and 1599 cmꢂ1 1H NMR (500 MHz, CDCl3) ꢀ 1.87 (3H,
;
4
E. M. Burgess and L. McCullagh, J. Am. Chem. Soc., 88,
1580 (1966); M. Fischer and F. Wagner, Chem. Ber., 102, 3486
(1969); M. Lancaster and D. J. H. Smith, J. Chem. Soc., Chem.
Commun., 1980, 471; W. Sander and J. Morawietz, Tetrahedron
Lett., 34, 1913 (1993); C. M. Geise and C. M. Hadad, J. Org.
Chem., 65, 8348 (2000); For a recent review: A. K. Sadana, R.
K. Saini, and W. E. Billups, Chem. Rev., 103, 1539 (2003).
5 M. Ikeda, S. Matsugashita, F. Tabusa, H. Ishibashi, and Y.
Tamura, J. Chem. Soc., Chem. Commun., 1975, 575; B. Jaques

K. Kobayashi et al.
Bull. Chem. Soc. Jpn., 78, No. 5 (2005)
889
´
P. Molina, M. Alajarın, and P. Sanchez-Andrada, Synthe-
´
and R. G. Wallace, Tetrahedron, 33, 581 (1977); P. Beak and G.
W. Selling, J. Org. Chem., 54, 5574 (1989).
8
sis, 1993, 225.
6
A general synthesis of 1,2-diarylbenzazetines via [2 + 2]
9
M. Harmata and M. Kahraman, Synthesis, 1995, 713.
cycloaddition reactions of benzyne with azomethines has recently
been reported: K. K. Singal and J. Kaur, Synth. Commun., 31,
2809 (2001).
10 T. Sato, S. Ishida, H. Ishibashi, and M. Ikeda, J. Chem.
Soc., Perkin Trans. 1, 1991, 353.
11 R. Smith and T. Livinghouse, Tetrahedron, 41, 3559
(1985).
7
D. Dopp and H. Weiler, Chem. Ber., 112, 3950 (1979).
¨