2633
R. Jangir et al.
Paper
Synthesis
In summary, starting from inexpensive and readily
available starting materials we have demonstrated a new
efficient synthesis of trichochrome skeletons. The sulfuryl
chloride mediated stereoselective halogenation of benzo-
thiazinylacetates is noteworthy from the point of view of
basic chemistry. The present approach to trichochrome is
general in nature and it will be useful in the design of sever-
al symmetrical/unsymmetrical natural/unnatural conge-
ners of bibenzothiazinylidenediones.
MS (ESI): m/z (%) = 260 (100) [M + Na]+.
Ethyl 2-(3-Oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl)acetate (7b)
Following the typical procedure for 7a using acid 5 and EtOH gave a
crystalline solid; yield: 1.15 g (92%); mp 122–123 °C.
IR (CHCl3): 3206, 1739, 1670 cm–1
.
1H NMR (200 MHz, CDCl3): δ = 1.29 (t, J = 8 Hz, 3 H), 2.61 (dd, J = 18, 8
Hz, 1 H), 3.07 (dd, J = 16, 6 Hz, 1 H), 4.03 (dd, J = 16, 6 Hz, 1 H), 4.21 (q,
J = 8 Hz, 2 H), 6.91 (d, J = 8 Hz, 1 H), 7.03 (t, J = 8 Hz, 1 H), 7.20 (t, J = 8
Hz, 1 H), 7.32 (d, J = 8 Hz, 1 H), 9.12 (br s, 1 H).
13C NMR (50 MHz, CDCl3): δ = 14.1, 34.2, 38.0, 61.2, 117.2, 119.1,
124.2, 127.4, 128.1, 135.9, 167.2, 170.1.
MS (ESI): m/z (%) = 274 (100) [M + Na]+.
Melting points are uncorrected. 1H NMR spectra were recorded on
200 MHz, 400 MHz, and 700 MHz NMR spectrometers using TMS as
an internal standard. 13C NMR spectra were recorded on 200 (50
MHz), 400 (100 MHz), 500 (125 MHz), and 700 NMR spectrometers
(175 MHz). Mass spectra were recorded on a MS-TOF mass spectrom-
eter. HRMS (ESI) were recorded using a Orbitrap (quadrupole plus ion
trap) and TOF mass analyzer. IR spectra were recorded on an FT-IR
spectrophotometer. Column chromatographic separations were car-
ried out on silica gel (60–120 mesh). Commercially available o-ami-
nothiophenol, maleic anhydride, SO2Cl2, and n-decyl bromide were
used.
Methyl (E/Z)-2-Chloro-2-(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-
2-ylidene)acetate (9a); Typical Procedure
To a stirred slurry of methyl ester 7a (118 mg, 0.50 mmol) in n-hex-
ane (10 mL) was added SO2Cl2 (0.25 mL, 2.50 mmol) in dropwise fash-
ion at 25 °C. The mixture was refluxed for 1 h and then allowed to
cool to r.t. The mixture was slowly quenched with solid NaHCO3 (250
mg) and it was further stirred for 1 h. The mixture was concentrated
in vacuo and the obtained residue was dissolved in EtOAc (25 mL).
The organic layer was washed with water (25 mL) and brine (25 mL),
and dried (Na2SO4). The organic layer was concentrated in vacuo and
the residue was purified by column chromatography (silica gel,
EtOAc–petroleum ether, 2:8) to give a yellow crystalline solid; yield:
95 mg (71%); ratio E/Z 1:19; mp 196–198 °C.
2-(3-Oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl)acetic Acid (5)
To a stirred solution of maleic anhydride (4, 2.45 g, 25 mmol) in Et2O
(40 mL) was added o-aminothiophenol (2, 3.13 g, 25 mmol) in a drop-
wise fashion at 25 °C under argon; the mixture was stirred for 1 h.
The separated precipitate was filtered on a Buchner funnel and
washed with Et2O (25 mL). The obtained product was dried under
vacuum to give pure acid 5; yield: 5.50 g (98%); mp 181–182 °C
(MeOH).
IR (CHCl3): 3315, 1727, 1665 cm–1
.
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 3.91 (s, 3 H), 6.93 (d, J = 8
Hz, 1 H), 7.08 (t, J = 8 Hz, 1 H), 7.20 (t, J = 8 Hz, 1 H), 7.25 (d, J = 8 Hz, 1
H), 9.98 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 53.4, 115.8, 117.3, 124.3,
124.4, 124.7, 125.4, 127.2, 132.6, 156.9, 164.4.
MS (ESI): m/z (%) = 292/294 (9/5) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C11H8O3NClNaS: 291.9806; found:
IR (CHCl3): 3204, 1699, 1662 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.43 (dd, J = 16, 8 Hz, 1 H), 2.85 (dd,
J = 16, 8 Hz, 1 H), 3.79 (dd, J = 8, 8 Hz, 1 H), 6.99 (d, J = 8 Hz, 1 H), 6.70
(t, J = 8 Hz, 1 H), 7.21 (t, J = 8 Hz, 1 H), 7.33 (d, J = 8 Hz, 1 H), 10.67 (s, 1
H), 12.54 (br s, 1 H).
291.9800.
13C NMR (50 MHz, DMSO-d6): δ = 33.7, 37.5, 117.1, 118.2, 123.1,
127.3, 127.6, 136.9, 165.7, 171.1.
MS (ESI): m/z (%) = 246 (100) [M + Na]+.
Ethyl (E/Z)-2-Chloro-2-(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-
ylidene)acetate (9b)
Following the typical procedure for 9a using ethyl ester 7b gave a yel-
low crystalline solid; yield: 105 mg (75%); ratio E/Z 1:19; mp 151–
153 °C.
Methyl 2-(3-Oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl)acetate
(7a); Typical Procedure
To a stirred solution of acid 5 (1.12 g, 5.00 mmol) in MeOH (25 mL)
was added catalytic amount of concd H2SO4 at 25 °C. The mixture was
stirred for 12 h and concentrated in vacuo. The obtained residue was
dissolved in EtOAc (50 mL) and the organic layer was washed with
water (25 mL) and brine (25 mL), and dried (Na2SO4). The organic lay-
er was concentrated in vacuo and the residue was purified by column
chromatography (silica gel, EtOAc–petroleum ether, 3:7) to give the
methyl ester 7a as a crystalline solid; yield: 1.10 g (93%); mp 142–
143 °C.
IR (CHCl3): 3191, 1734, 1669 cm–1
.
1H NMR (200 MHz, CDCl3): δ (Z-isomer) = 1.37 (t, J = 8 Hz, 3 H), 4.38
(q, J = 8 Hz, 2 H), 6.95 (dd, J = 8, 2 Hz, 1 H), 7.07 (dt, J = 8, 2 Hz, 1 H),
7.20 (dt, J = 8, 2 Hz, 1 H), 7.25 (dd, J = 8, 2 Hz, 1 H), 10.27 (br s, 1 H).
13C NMR (50 MHz, CDCl3,): δ (Z-isomer) = 13.8, 62.7, 115.8, 117.3,
123.9, 124.3, 125.1, 125.3, 127.1, 132.7, 157.1, 163.9.
MS (ESI): m/z (%) = 306/308 (52/18) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C12H10O3NClNaS: 305.9962;
IR (CHCl3): 3200, 1745, 1668 cm–1
.
found: 305.9964.
1H NMR (200 MHz, CDCl3): δ = 2.62 (dd, J = 16, 8 Hz, 1 H), 3.08 (dd, J =
16, 8 Hz, 1 H), 3.74 (s, 3 H), 4.02 (dd, J = 8, 6 Hz, 1 H), 6.92 (dd, J = 8, 2
Hz, 1 H), 7.03 (dt, J = 8, 2 Hz, 1 H), 7.21 (dt, J = 8, 2 Hz, 1 H), 7.32 (dd,
J = 8, 2 Hz, 1 H), 9.16 (br s, 1 H).
13C NMR (50 MHz, CDCl3): δ = 34.0, 38.0, 52.2, 117.3, 119.0, 124.0,
127.4, 128.1, 135.9, 167.2, 170.5.
Methyl (E/Z)-2-(7-Bromo-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-
2-ylidene)-2-chloroacetate (9c)
To a stirred solution of methyl ester 9a (50 mg, 0.185 mmol) in glacial
AcOH (5 mL) was added Br2 (148 mg, 0.92 mmol) at 25 °C and the
mixture was stirred for 5 h. The mixture was concentrated in vacuo
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2631–2634