Paper
3-Chloro-1-(4-methoxybenzyl)-4-phenyl-1H-pyrrol-2(5H)-one
RSC Advances
13C NMR (100 MHz, DMSO-d6): d 166.7, 160.3, 158.1, 150.7,
143.0, 133.5 (q, J ¼ 255.8 Hz, CF3), 129.6, 129.5, 129.3, 129.0,
125.5, 116.7, 104.4, 98.4, 55.4, 55.2, 54.1, 41.2; HRMS (ESI+)
calcd for (M + H)+ C20H18ClF3NO3: 412.0922, found: 412.0931.
3-Chloro-1-(2,4-dimethoxybenzyl)-4-(4-(triuoromethoxy)-
phenyl)-1H-pyrrol-2(5H)-one (9f). Flash chromatography (silica
gel, hexane–ethyl acetate ¼ 7 : 1) afforded 9f (343 mg, 40%) as a
viscous liquid. 1H NMR (400 MHz, DMSO-d6): d 7.84 (d, J ¼ 8.4
Hz, 2H), 7.48 (d, J ¼ 8.0 Hz, 2H), 7.08 (d, J ¼ 8.4 Hz, 1H), 6.49–
6.58 (m, 2H), 4.51 (s, 2H), 4.20 (s, 2H), 3.81 (s, 3H), 3.75 (s, 3H);
13C NMR (100 MHz, DMSO-d6): 166.8, 160.2, 158.0, 148.2, 141.8,
130.7, 130.6, 130.1, 129.2, 128.6 (q, J ¼ 255.8 Hz, CF3), 120.7,
119.4, 116.9, 114.1, 104.5, 98.4, 55.5, 55.3, 53.9, 40.1; HRMS
(ESI+) calcd for (M + H)+ C20H18ClF3NO4: 428.0871, found:
428.0874.
3-Chloro-4-(3-chlorophenyl)-1-(2,4-dimethoxybenzyl)-1H-pyr-
rol-2(5H)-one (9g). Flash chromatography (silica gel, hexane–
ethyl acetate ¼ 7 : 1) afforded 9g (326 mg, 43%) as a light yellow
oil. 1H NMR (400 MHz, DMSO-d6): d 7.75 (s, 1H), 7.68 (d, J ¼ 6.4
Hz, 1H), 7.51 (d, J ¼ 6.4 Hz, 2H), 7.10 (d, J ¼ 8.4 Hz, 1H), 6.59 (d,
J ¼ 2.0 Hz, 1H), 6.50 (d, J ¼ 8.4 Hz, 1H), 4.55 (s, 2H), 4.20 (s, 2H),
3.81 (s, 3H), 3.75 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 166.7,
160.3, 158.0, 142.3, 132.9, 131.4, 130.2, 129.0, 128.6, 128.1,
127.1, 116.7, 104.7, 98.4, 55.5, 55.2, 54.0, 40.3; HRMS (ESI+)
calcd for (M + H)+ C19H18Cl2NO3: 378.0658, found: 378.0662.
3-Chloro-1-(2,4-dimethoxybenzyl)-4-(3-(triuoromethyl)-
phenyl)-1H-pyrrol-2(5H)-one (9h). Flash chromatography (silica
gel, hexane–ethyl acetate ¼ 9 : 1) afforded 9h (371 mg, 45%) as a
light yellow oil. 1H NMR (400 MHz, DMSO-d6) d 8.05 (s, 1H), 8.01
(d, J ¼ 6.9 Hz, 1H), 7.80 (d, J ¼ 7.8 Hz, 1H), 7.73 (t, J ¼ 7.7 Hz,
1H), 7.11 (d, J ¼ 8.5 Hz, 1H), 6.59 (s, 1H), 6.49–6.59 (m, 1H), 4.52
(s, 2H), 4.23 (s, 2H), 3.82 (s, 3H), 3.75 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 167.8, 161.1, 158.7, 141.8, 132.2, 131.7,
130.6, 130.4, 129.3 (q, J ¼ 255.8 Hz, CF3), 128.8, 125.9, 125.8,
117.2, 104.6, 98.7, 55.6, 55.6, 54.5, 40.8; HRMS (ESI+) calcd for
(M + H)+ C20H18ClF3NO3: 412.0922, found: 412.0929.
(8). Flash chromatography (silica gel, hexane–ethyl acetate ¼
5 : 1) afforded 8 (471 mg, 50%) as a light yellow oil. 1H NMR (400
MHz, DMSO-d6): d 7.69–7.71 (m, 2H), 7.48–7.50 (m, 3H), 7.23 (d,
J ¼ 8.6 Hz, 2H), 6.92 (d, J ¼ 8.6 Hz, 2H), 4.58 (s, 2H), 4.16 (s, 2H),
3.73 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 167.1, 158.6,
141.0, 130.4, 130.1, 129.3, 129.2, 129.1, 129.0, 128.6, 128.5,
128.4, 128.3, 114.3, 96.5, 55.1, 53.4, 44.7; HRMS (ESI+) calcd for
(M + H)+ C18H17ClNO2: 314.0942, found: 314.0946.
3-Chloro-1-(2,4-dimethoxybenzyl)-4-phenyl-1H-pyrrol-2(5H)-
one (9a). Flash chromatography (silica gel, hexane–ethyl acetate
1
¼ 5 : 1) afforded 9a (468 mg, 68%) as a colourless oil. H NMR
(400 MHz, DMSO-d6) 7.68 (d, J ¼ 8.0 Hz, 2H), 7.39–7.52 (m, 3H),
7.09 (d, J ¼ 8.4 Hz, 1H), 6.59 (s, 1H), 6.50 (d, J ¼ 8.8 Hz, 1H), 4.50
(s, 2H), 4.18 (s, 2H), 3.81 (s, 3H), 3.75 (s, 3H); 13C NMR (100
MHz, DMSO-d6): d 167.1, 160.2, 158.0, 140.9, 130.5, 130.2, 129.7,
129.4, 128.7, 128.6, 128.5, 128.2, 116.9, 104.7, 98.4, 55.5, 55.2,
53.9, 40.2; HRMS (ESI+) calcd for (M + H)+ C19H19ClNO3:
344.1048, found: 344.1055.
3-Chloro-1-(2,4-dimethoxybenzyl)-4-(p-tolyl)-1H-pyrrol-2(5H)-
one (9b). Flash chromatography (silica gel, hexane–ethyl acetate
¼ 5 : 1) afforded 9b (394 mg, 55%) as a yellow solid; mp 107–109
ꢁC. 1H NMR (400 MHz, DMSO-d6): d 7.59–7.61 (m, 2H), 7.27 (d, J
¼ 8.0 Hz, 2H), 7.08 (d, J ¼ 8.4 Hz, 1H), 6.58 (d, J ¼ 2.4 Hz, 1H),
6.48–6.51 (m, 1H), 4.49 (s, 2H), 4.15 (s, 2H), 3.81 (s, 3H), 3.75 (s,
3H); 13C NMR (100 MHz, DMSO-d6): d 167.2, 160.2, 158.0, 149.1,
140.1, 139.5, 138.2, 130.2, 129.1, 128.9, 128.4, 126.5, 116.9,
104.7, 98.4, 55.5, 55.2, 53.8, 40.2; HRMS (ESI+) calcd for (M + H)+
C20H21ClNO3: 358.1204, found: 358.1212.
3-Chloro-4-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-1H-pyr-
rol-2(5H)-one (9c). Flash chromatography (silica gel, hexane–
ethyl acetate ¼ 7 : 1) afforded 9c (379 mg, 50%) as a colourless
oil. 1H NMR (400 MHz, DMSO-d6): d 7.74 (d, J ¼ 8.8 Hz, 2H), 7.55
(d, J ¼ 8.4 Hz, 2H), 7.09 (d, J ¼ 8.4 Hz, 1H), 6.59 (d, J ¼ 2.4 Hz,
1H), 6.50 (dd, J ¼ 8.4 and 6.4 Hz, 1H), 4.50 (s, 2H), 4.19 (s, 2H),
3.81 (s, 3H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3): d 167.0,
160.9, 158.6, 140.7, 134.7, 131.6, 130.2, 130.2, 130.1, 128.8,
128.5, 128.0, 117.2, 104.5, 98.7, 55.5, 55.4, 54.4, 40.7; HRMS
(ESI+) calcd for (M + H)+ C19H18Cl2NO3: 378.0658, found:
378.0662.
General procedure for the synthesis of 3-chloro-4-ayrl-1H-
pyrrol-2(5H)-one (10a, 10b, 14)
To a solution of 3-chloro-1-(2,4-dimethoxybenzyl)-4-aryl-1H-
pyrrol-2(5H)-one (1.5 mmol) in dichloroethane (10.0 mL) was
added TFA (4.5 mL) and the reaction mixture was stirred at 80
ꢁC for 2 h. Aer monitoring by TLC, the reaction mixture was
evaporated to dryness. It was then puried over silica gel
column chromatography using the solvent system hexane–ethyl
acetate to afford the corresponding pyrrol-2(5H)-one.
3-Chloro-1-(2,4-dimethoxybenzyl)-4-(4-methoxyphenyl)-1H-
pyrrol-2(5H)-one (9d). Flash chromatography (silica gel,
hexane–ethyl acetate ¼ 7 : 1) afforded 9d (389 mg, 52%) as a
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colourless oil. H NMR (400 MHz, DMSO-d6): d 7.81 (d, J ¼ 8.8
Hz, 2H), 6.86–7.09 (m, 3H), 6.58 (s, 1H), 6.49–6.51 (m, 1H), 4.49
(s, 2H), 4.14 (s, 2H), 3.81 (s, 6H), 3.75 (s, 3H); 13C NMR (100
MHz, DMSO-d6): d 167.3, 160.2, 159.4, 158.01, 147.7, 139.0,
130.0, 125.9, 121.7, 119.4, 116.9, 114.1, 113.6, 104.7, 98.4, 55.5,
55.1, 53.7, 40.1; HRMS (ESI+) calcd for (M + H)+ C20H21ClNO4:
374.1154, found: 374.1161.
3-Chloro-4-phenyl-1H-pyrrol-2(5H)-one (10a). Flash chroma-
tography (silica gel, hexane–ethyl acetate ¼ 3 : 1) afforded 10a
1
ꢁ
(198 mg, 68%) as a brown solid; mp 149–151 C. H NMR (400
MHz, DMSO-d6): d 8.63 (bs, 1H), 7.66 (d, J ¼ 7.2 Hz, 2H), 7.46 (t, J
3-Chloro-1-(2,4-dimethoxybenzyl)-4-(4-(triuoromethyl)phenyl)-
1H-pyrrol-2(5H)-one (9e). Flash chromatography (silica gel,
hexane–ethyl acetate ¼ 7 : 1) afforded 9e (330 mg, 40%) as a
¼ 8.0 and 6.8 Hz, 2H), 7.39 (d, J ¼ 7.2 Hz, 1H), 4.20 (s, 2H); 13
C
NMR (100 MHz, DMSO-d6): d 169.7, 142.8, 130.7, 129.4, 128.6,
128.5, 128.1 49.6; HRMS (ESI+) calcd for (M + H)+ C10H9ClNO:
194.0367, found: 194.0370.
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colourless oil. H NMR (400 MHz, DMSO-d6): d 7.94 (d, J ¼ 8.4
Hz, 2H), 7.68 (d, J ¼ 8.4 Hz, 2H), 7.25 (t, J ¼ 8.4 Hz, 1H), 6.45 (d, J
¼ 8.4 Hz, 2H), 4.64 (s, 2H), 4.05 (s, 2H), 3.85 (s, 3H), 3.80 (s, 3H);
3-Chloro-4-(p-tolyl)-1H-pyrrol-2(5H)-one (10b). Flash chro-
matography (silica gel, hexane–ethyl acetate ¼ 3 : 1) afforded
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