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3699
6 (90% yield) as a white solid. ESI-mass: m/z 277.052 [M+Na]+, mp,
and 1H NMR spectrum were consistent with those reported in
literature.16,23
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-
3-carboxaldehyde (1d). Off-white needles (>95%yield), mp 160 °C.
FT-IR (neat, cmÀ1) v: 2782 (w), 1679 (s), 1588 (s), 1503 (s), 1298
(s), 1106 (s); 1H NMR (CDCl3 400 MHz) ppm: 10.00 (s, 1H), 7.73
(d, 2H, J = 8.6 Hz), 7.46 (m, 3H), 7.22 (d, 2H, J = 8.6 Hz), 7.16 (m,
2H), 6.95 (s, 1H), 3.02 (s, 3H), 2.40 (s, 3H). 13C NMR (CDCl3
100 MHz) ppm: 186.69, 161.30, 140.30, 139.33, 138.04, 135.89,
133.70, 129.04, 128.55, 128.44, 125.40, 111.10, 109.57, 44.20,
11.44. ESI-mass: m/z 362.083 [M+Na]+; Elem. Anal. for C19H17NO3S
calcd C, 67.25; H, 5.05; N, 4.13. Found C, 67.33; H, 5.00; N, 4.18.
General procedure for the synthesis of pyrrole-3-carboximes
(2a–d). To a solution of aldehyde 1 (1 mmol) in ethanol (5 mL),
hydroxylamine chloride water solution (1 mmol in 4 mL of water)
and sodium acetate (1 mmol) were added. The reaction was re-
fluxed for 1 h and a half. At the end the precipitated formed was
filtered and collected to give the oxime 2 as white powder.
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[4-fluoro-phenyl]-
1H-pyrrole-3-carboxime (2a). White powder (>95%yield). FT-IR
(neat, cmÀ1) v: 3285 (w), 1596 (s), 1518 (s), 1307 (s), 1149 (s),
956 (s), 774 (s); 1H NMR (400 MHz, DMSO-d6): (ppm) 10.94 (s,
1H), 10.61 (s, 1H), 8.11 (s, 1H), 7.70 (d, 4H, J = 40 8.4 Hz), 7.42–
7.31 (m, 9H), 7.21 (d, 4H, J = 8.4 Hz), 6.74 (s, 2H), 3.15 (s, 6H),
2.13 (s, 6H); 13C NMR (CDCl3 100 MHz) ppm: 159.66, 148.20,
138.92, 138.11, 136.73, 135.19, 133.30, 128.81,128.50, 123.22,
117.13, 116.10, 106.98, 47.88, 10.96; ESI-mass: m/z 395.084
[M+Na]+; Elem. Anal. for C19H17FN2O3S calcd C, 61.29; H, 4.60; N,
7.52. Found C, 61.25; H, 4.64; N, 7.58.
General procedure for the synthesis of diarylpyrroles (7a–d).
Following the procedure for the Paal–Knorr reaction, a solution
of 6 (0.58 g, 2.28 mmol), the opportune aniline (2.28 mmol) and
p-toluenesulfonic acid (30 mg, 0.17 mmol) in ethanol (2 mL) was
microwave irradiated using a CEM apparatus for 45 min at 160 °C
(150 W, internal pressure of 150 psi). The reaction mixture was
cooled and concentrated. The crude material was purified by chro-
matography on aluminum oxide with a 3:1 cyclohexane/ethyl ace-
tate mixture, as the eluant, to give the expected 1,5-diarylpyrrole 7
as white needles in satisfactory yield.
1-(4-Fluorophenyl)-2-methyl-5-(4-(methylsulfonyl)phenyl)-
1H-pyrrole (7a). ESI-mass: m/z 352.083 [M+Na]+, mp, and 1H NMR
spectrum were consistent with those reported in literature.16,23
1-(3-Fluorophenyl)-2-methyl-5-(4-(methylsulfonyl)phenyl)-
1H-pyrrole (7b). ESI-mass: m/z 352.091 [M+Na]+, mp, and 1H NMR
spectrum were consistent with those reported in literature.16,23
1-(3,4-Difluorophenyl)-2-methyl-5-(4-methylsulfonyl)phenyl)-
1H-pyrrole (7c). ESI-mass: m/z 370.075 [M+Na]+, mp, and 1H NMR
spectrum were consistent with those reported in literature.16,23
2-Methyl-5-(4-(methylsulfonyl)phenyl)-1-phenyl-1H-pyrrole
(7d). ESI-mass: m/z 334.092 [M+Na]+, mp, and 1H NMR spectrum
were consistent with those reported in literature.16,23
General procedure for the synthesis of pyrrole-3-carbaldehy-
des (1a–d). To a solution of dimethylformamide (8.3 mmol) in
dichloromethane (10 mL) at 0 °C, in
a
round-bottomed flask
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluoro-phenyl]-
1H-pyrrole-3-carboxime (2b). White powder (>95%yield). FT-IR
(neat, cmÀ1) v: 3292 (w), 1590 (s), 1510 (s), 1297 (s), 50 1140
(s), 950 (s), 766 (s); 1H NMR (400 MHz, DMSO-d6) ppm: 10.98 (s,
1H), 10.65 (s, 1H), 8.14 (s, 1H), 7.78 (d, 4H, J = 8.6 Hz), 7.53–7.43
(m, 2H), 7.36–7.33 (m, 6H), 7.18 (d, 4H, J = 8.4 Hz), 6.77 (s, 2H),
3.19 (s, 6H), 2.19 (s, 6H). 13C NMR (CDCl3 100 MHz) ppm: 163.55,
149.00, 143.00, 138.88, 138.21, 55 135.20, 133.10, 131.00,
128.77, 128.43, 117.21, 117.10, 112.28, 107.28, 106.90, 47.99,
11.06. ESI-mass: m/z 395.084 [M+Na]+; Elem. Anal. for
equipped with a stirring bar, phosphoryl chloride (8.4 mmol)
was added dropwise. After 30 min a solution of 7 (3.2 mmol in
10 mL of 100 dichloromethane) was added over 3 min and then
refluxed for 1 h. The reaction mixture was cooled down to rt, di-
luted with saturated carbonate solution (50 mL) and extracted
with dichloromethane. The organic layer was washed with brine
(200 mL) and water (200 mL) and dried over sodium sulfate.
After filtration and concentration, the crude material was crystal-
lized using ethyl acetate to give the aldehyde as an off-white
solid.
C19H17FN2O3S calcd C, 61.29; H, 4.60; N, 7.52. Found C, 61.27; H,
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[4-fluoro-phenyl]-
1H-pyrrole-3-carboxaldehyde (1a). White needles (>95% yield).
ESI-mass: m/z 357,082 [M+Na]+; Elem. Anal. for C19H16FNO3S calcd
C, 63.85; H, 4.51; N, 3.92. Found C, 63.82; H, 4.55; N, 3.98; data, mp,
1H and 13C NMR spectra were consistent with those reported in the
literature.23
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluoro-phenyl]-
1H-pyrrole-3-carboxaldehyde (1b). Off-white needles (>95% yield),
mp 170 °C. FT-IR (neat, cmÀ1) v: 2770 (w), 1673 (s), 1590 (s), 1506
(s), 1300 (s), 1140 (s); 1H NMR (DMSO-d6 400 MHz) ppm: 9.93 (s,
1H), 7.85 (m, 1H), 7.52 (m, 1H), 7.40 (m, 2H), 7.31 (m, 1H,
J = 8.6 Hz), 7.08 (d, 2H, J = 8.6 Hz), 6.94 (s, 1H), 3.17 (s, 3H), 2.37
(s, 3H). 13C NMR (CDCl3 100 MHz) ppm: 187.09, 163.43, 142.70,
138.91, 138.11, 137.00, 131.54, 128.84, 128.55, 117.40, 117.02,
116.03, 112.03, 107.02, 106.82, 44.33, 10.89; ESI-mass: m/z
380.073 [M+Na]+; Elem. Anal. for C19H16FNO3S calcd C, 63.85; H,
4.51; N, 3.92. Found C, 63.80; H, 4.57; N, 3.95.
4.63; N, 7.50.
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[3,4-ifluorophe-
nyl]-1H-pyrrole-3-carboxime (2c). White powder (>95%yield). FT-
IR (neat, cmÀ1) v: 3280 (w), 1582 (s), 1522 (s), 1300 (s), 1117(s),
943 (s), 760 (s); 1H NMR (400 MHz, DMSO-d6): (ppm) 10.98 (s,
1H), 10.66 (s, 1H), 8.14 (s, 1H), 7.79 (d, 4H, J = 8.5 Hz), 7.64–7.69
(m, 2H), 7.66 (m, 2H), 7.43–7.23 (m, 5H), 7.15 (m, 2H), 6.77 (s,
2H), 3.19 (s, 6H), 2.19 (s, 6H). 13C NMR (CDCl3 100 MHz) ppm:
153.35, 148.33, 146.30, 138.98, 138.56, 138.31, 135.10, 133.13,
128.87, 128.53, 118.61, 117.70, 117.44, 108.88, 106.89, 48.01,
11.12. ESI-mass: m/z 413.075 [M+Na]+; Elem. Anal. for
C19H16F2N2O3S calcd C, 58.45; H, 4.13; N, 7.18. Found C, 58.50; H,
4.10; N, 7.20.
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-
3-carboxime (2d). White powder (>95%yield). FT-IR (neat, cmÀ1) v:
3280 (w), 1599 (s), 1520 (s), 1289 (s), 1167 (s), 75 955 (s), 770 (s);
1H NMR 400 MHz, DMSO-d6): (ppm) 10.92 (s, 1H), 10.59 (s, 1H),
8.10 (s, 1H), 7.68 (d, 4H, J = 8.6 Hz), 7.45–7.32 (m, 11H), 7.23 (d,
4H, J = 8.6 Hz), 6.76 (s, 2H), 3.10 (s, 6H), 2.15 (s, 6H). 13C NMR
(CDCl3 100 MHz) ppm: 148.23, 141.22, 138.98, 138.16, 135.11,
133.17, 129.43, 128.89, 128.63, 80 125.66, 121.65, 106.91,
117.24, 47.66, 11.02. ESI-mass: m/z 377.094 [M+Na]+; Elem. Anal.
for C19H18N2O3S calcd C, 64.39; H, 5.12; N, 7.90. Found C, 64.42;
H, 5.15; N, 7.88.
2-Methyl-5-[4-(methylsulfonyl)phenyl]-1-[3,4-difluoro-phe-
nyl]-1H-pyrrole-3-carboxaldehyde
(1c).
Off-white
needles
(>95%yield), mp 178 °C. FT-IR (neat, cmÀ1) v: 2785 (w), 1671 (s),
1592 (s), 10 1500 (s), 1304 (s), 1133(s); 1H NMR (CDCl3
400 MHz) ppm: 9.97 (s, 1H), 7.77 (m, 3H), 7.55 (m, 1H), 7.36 (d,
2H, J = 8.7 Hz), 7.22 (m, 1H), 6.98 (s, 1H), 3.20 (s, 3H), 2.39 (s,
3H). 13C NMR (CDCl3 100 MHz) ppm: 187.09, 163.03, 150.31,
140.70, 138.90, 138.10, 137.09, 131.50, 128.93, 128.59, 118.03,
117.33, 15 109.22, 108.8, 107.02, 44.39, 10.99; ESI-mass: m/z
398.064 [M+Na]+; Elem. Anal. for C19H15F2NO3S calcd C, 60.79; H,
4.03; N, 3.73. Found C, 61.00; H, 3.99; N, 3.78.
General procedure for the synthesis of pyrrole-3-carbonitriles
(3a–d). A solution of 2,4,6-trichloro[1,3,5]triazine (1 mmol) in
0.2 mL of dimethylformamide was stirred for 30 min at room
temperature. Carboxime
2 (1 mmol), dissolved in 1.5 mL of