LETTER
Synthesis of 3,1-Benzothiazines
2233
(11) Typical Experimental Procedure for the Preparation of
3. A solution of phenylacetylene (5.5 mL, 50 mmol) in Et3N
(50 mL) was added over 10 min to a stirred mixture of (4-
chloro-2-iodophenyl)formamide (14.1 g, 50 mmol),
Crystallographic Database (deposition number CCDC-
205334 and CCDC-205335 respectively). Copies of this
information can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK; fax:
+44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk.
(15) Dickstein, J. I.; Miller, S. I. In The Chemistry of the Carbon-
Carbon Triple Bond, Part 2; Patai, S., Ed.; Wiley: New
York, 1978, 813–955.
(16) (a) Kondo, Y.; Kojima, S.; Sakamoto, T. J. Org. Chem.
1997, 62, 6507. (b) Kondo, Y.; Kojima, S.; Sakamoto, T.
Heterocycles 1996, 43, 2741. (c) Sakamoto, T.; Kondo, Y.;
Iwashita, S.; Yamanaka, H. Chem. Pharm. Bull. 1987, 35,
1823. (d) Sakamoto, T.; Kondo, Y.; Yamanaka, H.
(Ph3P)2PdCl2 (702 mg, 1 mmol) and Cu2I2 (190 mg, 0.5
mmol) in Et3N (250 mL) under nitrogen and the resulting
mixture was stirred at ambient temperature for 4 h. Diethyl
ether (200 mL) was added, the resulting mixture was filtered
through a bed of Celite (5 × 0.5 cm), and the solid was
washed repeatedly with benzene (5 × 80 mL). Solvents and
Et3N were removed at reduced pressure from the filtrates.
The residual oil, which solidified rapidly, was dissolved in
benzene (200 mL) and chromatographed on silica (12 × 3.2
cm) with benzene for elution. The eluates (800 mL) were
concentrated to ca. 75 mL, hexane (200 mL) was added
gradually, and the resulting voluminous precipitate was
filtered off and washed with hexane to give the formamide
3b (12.5 g, 98% yield) as pale beige crystals, mp 117–118 °C
(cyclohexane–acetone). Also obtained: compound 3a, 96%
yield, mp 99–100 °C (benzene–hexane); compound 3c, 97%
yield, mp 98–100 °C(cyclohexane); compound 3d, 96%
yield, mp 180–182 °C (EtOH).
Heterocycles 1986, 24, 31. (e) Belley, M.; Scheigetz, J.;
Dubé, P.; Dolman, S. Synlett 2001, 222.
(17) Reaction of 3d with DBU. A solution of the amide 3d (580
mg, 2 mmol) and DBU (1.5 mL, 10 mmol) in THF (2 mL)
was kept at r.t. for 72 h. TLC then showed no starting
material to be present. The solution was taken up in benzene
(200 mL) and the resulting solution was washed with sat. aq
NaCl solution (100 mL) and dried. Chromatography of the
solid residue from the evaporated extracts on silica (10 × 2.0
cm) with benzene as eluent gave pale orange eluates.
Recrystallisation of the residue from the evaporated eluates
from benzene–acetone–hexane afforded 6d (314 mg, 57%)
as colourless needles, mp 139–140 °C (lit.20 mp 142 °C); 1H
NMR (400 MHz, DMSO-d6): d = 6.97 (d, 1 H, J3,NH = 2.1 Hz,
3-H), 7.25 (d, 1 H, J6,4 = 1.8 Hz, 6-H), 7.39 (tt, 1 H, 4¢-H),
7.49 (t, 2 H, 3¢- + 5¢-H), 7.58 (d, 1 H, J4,6 = 1.8 Hz, 4-H), 8.00
(dt, 2 H, 2¢- + 6¢-H), 11.00 (1 H, NH). 13C NMR (75 MHz,
DMSO-d6): d = 100.0 (C-3), 116.4 (C-5 or C-7), 118.2,
120.6, 123.9 (C-7 or C-5), 126.0 (C-3¢ + C-5¢), 128.2 (C-4¢),
128.7 (C-2¢ + C-6¢), 130.9, 131.0, 132.7, 141.0 (C-7a).
(18) NMR data for compounds 5a–d (CDCl3), 1H NMR at 400
MHz, 13C NMR at 75 MHz, and 19F NMR at 282.4 MHz
(CFCl3 as external 19F reference).
(12) Typical Experimental Procedure for the Preparation of
4: Celite (2 g) was added to a solution of the formamide 3b
(5.11 g, 20 mmol) in THF (50 mL) and the mixture was
stirred while P4S10 (6.67 g, 15 mmol) was added portionwise
over 1 min. The resulting mixture was boiled with stirring
for 20 min. Diethyl ether (100 mL) and then benzene (50
mL) were added and the solid was filtered off and washed
with diethyl ether (300 mL) and benzene (50 mL). The
combined filtrates were washed with sat. aq NaCl solution
(400 mL), dried, and the solvent was removed. The residue
was extracted with boiling benzene (200 mL) and the cooled
extract was chromatographed on silica (25 × 2.4 cm) with
benzene for elution. The residue from the evaporated eluates
(500 mL) was dissolved in acetone (40 mL) and cyclohexane
(120 mL). The solution was concentrated to ca. 40 mL,
cooled, and hexane (120 mL) was added, giving the
thioformamide 4b (2.94 g, 54%) as very pale yellow
crystals, mp 163–165 °C. Also obtained: compound 4a, 48%
yield, mp 102–103 °C (MeOH); compound 4c, 55% yield,
mp 102–105 °C (cyclohexane–hexane); compound 4d, 80%
yield, mp 156–159 °C(cyclohexane).
Compound 5a: 1H NMR: d = 6.98 (d, J2,a = 0.5 Hz, 1 H, a-
H), 7.26–7.40 (m, 8 H, Ph + 6-H + 7-H + 8-H), 7.58, (dt,
J
5,6 = 7.8 Hz, 1 H, 5-H), 8.19 (d, J2,a = 1.0 Hz, 1 H, 2-H).
13C NMR: d = 122.8 (C-4 or C-a), 123.8 (C-a or C-4), 124.1,
125.2, 127.5, 128.2 (C-3¢ + C-5¢ or C-2¢ +C-6¢), 128.9 (C-2¢
+ C-6¢ or C-3¢ + C-5¢), 129.1, 129.3, 129.8, 135.4 (C-4a or
C-8a), 141.3 (C-8a or C-4a), 149 (C-2).
(13) Typical Experimental for the Preparation of 5. DBU (4
mL, 27 mmol) was added to a solution of the thioformamide
4b (1.40 g, 5 mmol) in THF (5 mL) and the resulting solution
was kept at r.t. for 24 h, then dissolved in benzene (200 mL).
The solution was washed with sat. aq NaCl solution (200
mL) and the aqueous extract was extracted with more
benzene (100 mL). The benzene extracts were washed with
more sat. aq NaCl solution (200 mL × 2), dried, and solvent
was removed. The residual oil was extracted with boiling
benzene (40 mL) and the cooled extract was
chromatographed on silica (25 × 2.4 cm). Elution with
benzene gave (i)very pale yellow eluates (150 mL),(ii)
lemon-yellow eluates (300 mL) and left an intractable slow-
moving (Et2O–benzene) orange-red band on the column.
Fraction (i) yielded 5-chloro-2-phenylindole(6b) (52 mg,
5.7%), mp 185–190 °C (cyclohexane–hexane) (lit.19 mp 191
°C). Fraction(ii) gave (4Z)-4-benzylidene-6-chloro-4H-3,1-
benzothiazine(5b) (1.2 g, 75%) as yellow crystals, mp 82–84
°C (MeOH). Also obtained: compound 5a, 80% yield,
orange oil; compound 5c, 82% yield, mp 63–65 °C (MeOH);
compound 6c, 3.7% yield, mp 182–184 °C (cyclohexane);
compound 5d, 69% yield, mp 140–142 °C (cyclohexane).
(14) Detailed crystallographic data for 4d and 5d (excluding
structure factors) were deposited at the Cambridge
Compound 5b: 1H NMR: d = 6.97 (s, 1 H, a-H), 7.31–7.41
(m, 7 H, Ph + 7-H + 8-H), 7.57 (d, J5,7 = 1.84 Hz, 1 H, 5-H),
8.20 (s, 1 H, 2-H). 13C NMR: d = 122.6 (C-6 or C-4), 124.0
(C-a), 124.3 (C-4 or C-6), 126.3, 127.9, 128.4 (C-3¢ + C-5¢
or C-2¢ + C-6¢), 129.0 (C-2¢ + C-6¢ or C-3¢ + C-5¢), 129.7,
130.7, 134.4 (C-1¢ or C-4a), 135.1 (C-4a or C-1¢), 139.9 (C-
8a), 149.8 (C-2).
Compound 5c: 1H NMR d = 6.93 (s, 1 H, a-H), 7.05–7.10
(m, 1 H), 7.23–7.39 (m, 7 H), 8.13 (s, 1 H, 2-H). 13C NMR:
d = 110.4 (d, JF,C = 24.4 Hz, C-7 or C-5), 116.7 (d, JF,C = 22.5
Hz, C-5 or C-7), 123.1 (d, JF,C = 2.5 Hz, C-8a), 124.4 (d, JF,C
= 8.3 Hz, C-4a), 125.6 (C-a), 127.8 (C-4¢), 128.3 (C-3¢ + C-
5¢ or C-2¢ + C-6¢), 129.0 (C-2¢ + C-6¢ or C-3¢ + C-5¢), 131.4
(d, JF,C = 8.7 Hz, C-8), 135.1 (C-1¢), 137.7 (d, JF,C = 2.7 Hz,
C-4), 148.3 (d, JF,C = 2.2 Hz, C-2), 162.4 (d, JF,C-6 = 248.5
Hz, C-6). 19F NMR: d = –111.7.
Compound 5d: 1H NMR: d = 6.99 (s, 1 H, a-H), 7.30–7.45
(m, 5 H, Ph), 7.46 (d, 1 H, J5,7 = 2.3 Hz, 5- or 7-H), 7.51 (d,
J
7,5 = 2.3 Hz, 1 H, 7- or 5-H), 8.36 (d, J2,a = 1.1 Hz, 1 H, 2-
H). 13C NMR: d = 121.8, 123.2, 126.1, 128.3 (C-5 or C-7),
128.4 (C-3¢ + C-5¢), 128.6 (C-4¢), 129.2 (C-2¢ + C-6¢), 130.2
(C-7 or C-5), 134.1, 134.3, 134.7, 137.0, (C-8a), 151.8 (C-2).
(19) Brown, F.; Mann, F. G. J. Chem. Soc. 1948, 858.
(20) Carlin, R. R.; Fisher, E. E. J. Am. Chem. Soc. 1948, 70, 3421.
Synlett 2003, No. 14, 2231–2233 © Thieme Stuttgart · New York