1
3.52 min, 99.9%); mp 120–121 °C (lit.14a 112–113 °C); H
164.58, 147.88, 137.65, 135.57, 123.54, 36.89 (2C); MS (ES+)
227 (M + 1, 5%), 142 (60%), 101 (100%).
NMR (400 MHz, CDCl3) δ 8.12 (1H, d, J ) 8.4 Hz), 7.67
(1H, t, J ) 7.8 Hz), 7.41 (1H, t, J ) 7.8 Hz), 7.26 (1H, d, J )
8.0 Hz), 3.46 (3H, s), 3.41 (3H, s); 13C NMR (100.6 MHz,
CDCl3) δ 185.90, 147.21, 142.01, 134.42, 126.55, 126.49,
125.68, 43.50, 39.09; MS (ZQ) (ES+) 227 (M + 1, 100%).
Preparation of 4-Nitrophenyl-O-thiocarbamate (2b). O-Thio-
carbamate 2b was prepared on a 500 mmol scale according to
the method used for compound 2a, to yield the title compound
as a pale yellow solid (113 g, 99%). HPLC (tR 3.84 min,
3-Methyl-4-nitrophenyl-S-thiocarbamate (3c). A light buff
to mid brown solid. HPLC (tR 4.18 min); mp 74–75 °C; H
1
NMR (400 MHz, CDCl3) δ 7.97 (1H, d, J ) 8.5 Hz), 7.49
(1H, m), 7.46 (1H, dd, J ) 0.3, 1.8 Hz), 3.10 (3H, bs), 3.05
(3H, bs), 2.60 (3H, s); 13C NMR (100.6 MHz, CDCl3) δ 164.96,
149.03, 139.02, 135.30, 133.90, 133.31, 124.81, 36.97, 20.38;
MS (ZQ) (ES+) 241 (M + 1, 100%).
Representative Large-Scale Microwave Procedures. Prepa-
ration in Anton Paar Synthos 3000. Portions of O-thiocarbamate
2c (12.5 g each, 52.0 mmol) were charged to eight PTFE tubes
with DMA (50 mL each, 4 vol) with a magnetic stirring flea,
sealed in ceramic cases evenly distributed inside a 16-position
rotor, and placed in the cavity of an Anton Paar Synthos 3000
microwave reactor (total mass of 2c was 100 g, 416 mmol in
400 mL of DMA). One tube was fitted with a gas-bulb
thermometer; the temperature in the others was monitored by
IR-pyrometer. The reaction mixtures were heated with magnetic
stirring to 220 °C over 13 min with 1400 W available power,
held at 220 °C for 20 min, then cooled by fan air to 70–80 °C
over ∼40 min. The reaction mixtures were worked up in two
pairs of four combined tubes by adding water dropwise to each
(150 mL, 12 vol). Beige solids were precipitated in both cases,
which on cooling to room temperature were isolated by
filtration, each washed with further water (150 mL, 12 vol),
and dried in a vacuum oven at 50 °C to give S-thiocarbamate
3c as a light beige solid (46.6 and 46.2 g respectively; combined
yield 92.8 g, 93%). HPLC (tR 4.18 min, 100%); other data as
above.
Preparation in CEM MARS (example 1). O-Thiocarbamate
2b (75 g, 331 mmol) was dissolved in DMA (750 mL, 10 vol)
in a 3-L flask equipped with a fibre optic probe and placed in
the cavity of a CEM MARS microwave reactor fitted with a
water condenser externally. The reaction mixture was heated
with magnetic stirring to a vigorous reflux at 170 °C over 10
min with 1200 W available power, held at 170 °C for 2 h and
40 min, then cooled by fan air to 70–80 °C over 30 min. Water
(1500 mL, 20 vol) was added dropwise over 30 min, which
precipitated a beige solid that on cooling to room temperature
was isolated by filtration and washed with further water. The
product was dried in a vacuum oven at 50 °C to give
S-thiocarbamate 3b as a light beige solid (68.2 g, 91%). HPLC
(tR 3.38 min, 99.1%); other data as above.
1
99.6%); mp 140–142 °C (lit.14a 150–153 °C); H NMR (400
MHz, CDCl3) δ 8.27 (2H, d, J ) 8.8 Hz), 7.24 (2H, d, J ) 8.8
Hz), 3.47 (3H, s), 3.38 (3H, s); 13C NMR (100.6 MHz, CDCl3)
δ 186.21, 158.47, 145.38, 124.88, 123.86, 43.36, 38.96; MS
(ZQ) (ES+) 227 (M + 1, 100%).
Preparation of 3-Methyl-4-nitrophenyl-O-thiocarbamate (2c).
O-Thiocarbamate 2c was prepared on a 1.30 mol scale accord-
ing to the method used for compound 2a, to yield the title
compound as a buff coloured solid (307 g, 98%). HPLC (tR
1
4.52 min, 99.6%); mp 128–130 °C; H NMR (400 MHz,
CDCl3) δ 8.07 (1H, dd, J ) 7.7, 1.8 Hz), 7.07 (1H, d, J ) 1.8
Hz), 7.05 (1H, s), 3.46 (3H, s), 3.36 (3H, s), 2.63 (3H, s); 13
C
NMR (100.6 MHz, CDCl3) δ 186.33, 156.73, 146.30, 135.78,
126.83, 126.20, 121.51, 43.33, 38.91, 20.90; MS (ZQ) (ES+)
241 (M + 1, 100%).
Typical Small-Scale Microwave Procedures. Small-scale
microwave reactions were performed in thick-walled glass
sealed tubes in CEM Discover or Biotage Initiator focused 300
W microwave reactors with IR temperature monitoring and
noninvasive pressure transducer. In a typical procedure, 200
mg of O-thiocarbamate (2a-c) was dissolved in NMP (2.0 mL)
and heated to the required temperature with stirring for a fixed
time. The heating time to reach the set temperature was typically
45–90 s, depending on the scale, the maximum wattage supplied
(100–300 W) and the temperature required (140–250 °C). The
heating time is not included in the quoted hold time for any
given procedure; control studies show that the heating time has
a negligible effect on overall conversion during a 20 min
reaction time. The S-thiocarbamate products (3a-c) were
isolated either directly by aqueous drown-out from DMA or
NMP solutions or by extraction into MTBE followed by flash
silica gel chromatography and/or recrystallisation from methanol
if required.
Physical and Spectroscopic Data on Analytically Pure
S-Thiocarbamates (3a-c). 2-Nitrophenyl-S-thiocarbamate (3a).
A bright yellow oil or low melting solid. Rf 0.25 (2:1 isohexane/
ethyl acetate); HPLC (tR 2.67 min); mp 39–42 °C (lit.14a 30–32
°C); 1H NMR (400 MHz, CDCl3) δ 7.94 (1H, dd, J ) 7.6, 1.2
Hz), 7.70 (1H, d, J ) 7.6 Hz), 7.50–7.60 (2H, m), 3.19–2.95
(6H, bs); 13C NMR (100.6 MHz, CDCl3) δ 164.35, 152.34,
138.16, 132.18, 129.84, 124.76, 124.30, 37.09, 29.65; MS (ES+)
227 (M + 1, 100%).
Preparation in CEM MARS (example 2). O-Thiocarbamate
2c (85.2 g, 355 mmol) was dissolved in NMP (850 mL, 10
vol) in a 3-L flask equipped with a fibre optic probe and placed
in the cavity of a CEM MARS microwave reactor fitted with
a water condenser externally. The reaction mixture was heated
with magnetic stirring to 200 °C over 9 min with 1200 W
available power, held at 200 °C for 40 min, then cooled by fan
air to 70–80 °C over 30 min. Water (1700 mL, 20 vol) was
added and the reaction solution cooled to room temperature and
left to stand overnight. A black solid formed that was isolated
by filtration, displacement washed with water twice (250 mL
each), and dried in a vacuum oven at 50 °C to give S-
thiocarbamate 3c as a black solid (71.1 g, 83%). HPLC (tR 4.18
min, 99.8%); other data as above.
4-Nitrophenyl-S-thiocarbamate (3b). A pale yellow or buff
solid. Rf 0.33 (2:1 isohexane/ethyl acetate); HPLC (tR 3.38 min);
1
mp 118–120 °C (lit.14a 122–124 °C); H NMR (400 MHz,
CDCl3) δ 8.22 (2H, d, J ) 8.0 Hz), 7.68 (2H, d, J ) 8.0 Hz),
3.11 (3H, bs), 3.06 (3H, bs); 13C NMR (100.6 MHz, CDCl3) δ
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