´
T. Zielinski, J. Jurczak / Tetrahedron 61 (2005) 4081–4089
4088
If not stated otherwise, all reagents were obtained from
commercial sources and used as received. The column
chromatography was carried out using Merck Kieselgel 60
(230–400 mesh), the thin-layer chromatography was carried
out using Merck Kieselgel F254 plates.
C18H15N3O2Na [MCNa]C: 328.1056 found: 328.1074;
Anal. calcd for C18H15N3O2: C 70.81, H 4.95, N 13.76,
found: C 70.74, H 4.99, N 13.65.
4.1.4. 1H-Pyrrole-2,5-dicarbothioic acid bis-butylamide
(3a). The 1H-pyrrole-2,5-dicarboxylic acid butylamide 2a
(265 mg, 1 mmol) and the Lawesson’s reagent (0.8 g,
2 mmol) were suspended in dry THF (20 ml), and the
mixture was refluxed for one day under argon. The solvent
was evaporated in vacuo and the reaction product was
purified by column chromatography on silica gel (CH2Cl2).
The resulting crude product was recrystallised from
C2H4Cl2/pentane. Yield 90%.
4.1.1. 1H-Pyrrole-2,5-dicarboxylic acid (8). The acid 8
was prepared by hydrolysis of the 1H-pyrrole-2,5-dicar-
boxylic acid monomethyl ester 7.21 The ester (2.8 g) was
stirred with a solution of NaOH (12 g) in water (100 ml) at
60 8C for 3 h, and the reaction mixture was acidified with
concentrated HCl. The precipitated crystals were filtered off
and washed with 2 M HCl to give pyrrole-2,5-dicarboxylic
acid in 90%.
Yellow crystals, mp 114–115 8C; 1H NMR (200 MHz
DMSO) dZ10.86 (s, 1H, NH-pyrrole), 10.07 (t, 2H, J1Z
5.6 Hz, CSNH), 6.96 (d, 2H, J1Z2.4 Hz, H-pyrrole), 3.68
(dt, 4H, J1Z7.0 Hz, J2Z5.6 Hz, CH2NH), 1.64 (m, 4H,
Colourless crystals, mp decomposition at 250 8C (lit. dc. at
250 8C);25 1H NMR (200 MHz DMSO) dZ12.75 (bs, 2H,
COOH), 12.20 (s, 1H, NH-pyrrole), 6.74 (d, 2H, J1Z
2.4 Hz, H-pyrrole).
CH2), 1.34 (m, 4H, CH2), 0.91 (t, 6H, J1Z7.2 Hz, CH3); 13
C
NMR (50 MHz CDCl3) dZ184.9, 134.6, 106.0, 45.5, 30.4,
20.2, 13.7; HR EI calcd for C14H23N3S2 MC: 297.1333
found: 297.1332; Anal. calcd for C14H23N3S2: C 56.53, H
7.79, N 14.12, S 21.56, found: C 56.74, H 7.75, N 14.15, S
21.51.
4.1.2. 1H-Pyrrole-2,5-dicarboxylic acid bis-butylamide
(2a). To the suspension of pyrrole-2,5-dicarboxylic acid 8
(1 g, 6.5 mmol) in dry CH2Cl2 (25 ml) thionyl chloride
(4.7 ml, 64 mmol) was added, followed by two drops of
DMF. The mixture was refluxed overnight to become a
clear, yellow solution. The solvent and the excess of thionyl
chloride were removed in vacuo. After dissolving the
resulting acid chloride 9 in dichloromethane (15 ml) and
cooling to 0 8C, a solution of butylamine (3.2 ml, 33 mmol)
in 2 ml CH2Cl2 was added with intensive stirring. The
reaction was stirred overnight, and then the solvent was
removed in vacuo. The solid was washed with 2 M HCl,
water and ether. The resulting crude product was
recrystallised from ethyl acetate. Yield 72%.
4.1.5. 1H-Pyrrole-2,5-dicarbothioic acid bis-phenyl-
amide (3b). The 1H-pyrrole-2,5-dicarboxylic acid bis-
phenylamide 2b (305 mg, 1 mmol) and Lawesson’s reagent
(0.8 g, 2 mmol) were suspended in dry THF (50 ml), and the
mixture was refluxed over night under argon. The solvent
was evaporated in vacuo. The residue was washed with
CH2Cl2 and filtered off. The solid was purified by flash
chromatography on silica gel using the following eluents:
hexane/CH2Cl2 1:1 (150 ml), CH2Cl2 (150 ml), CH2Cl2/
THF 1:1 (100 ml). The CH2Cl2/THF fraction gave crude
thioamide 3b which was recrystallised from THF/hexane.
Yield 80%.
1
Colourless crystals, mp 195–197 8C; H NMR (200 MHz
DMSO) dZ11.66 (s, 1H, NH-pyrrole), 8,22 (t, 2H, J1Z
5.4 Hz, CONH), 6.72 (d, 2H, J1Z2.2 Hz, H-pyrrole), 3.22
(dt, 4H, J1Z5.8 Hz, J2Z6.8 Hz, CH2NH), 1.46 (m, 4H,
Yellow crystals, mp 242–244 8C; 1H NMR (200 MHz
DMSO) dZ11.52 (s, 2H, CSNH), 11.13 (s, 1H, NH-
pyrrole), 7.71 (d, 4H, J1Z7.6 Hz, o-Ph), 7.46 (dd, 4H, J1Z
7.9 Hz, J2Z7.9 Hz, m-Ph), 7.33–7.25 (m, 4H, p-PhCH-
pyrrole); 13C NMR (50 MHz CDCl3) dZ183.8, 139.6,
135.8, 129.0, 126.9, 125.5, 112.0; HR EI calcd for
C18H15N3S2 MC: 337.0707 found: 337.0702; Anal. calcd
for C18H15N3S2: C 64.07, H 4.48, N 12.45, S 19.00, found:
C 63.88, H 4.45, N 12.39, S 18.41.
CH2), 1.32 (m, 4H, CH2), 0.90 (t, 6H, J1Z7.2 Hz, CH3); 13
C
NMR (50 MHz DMSO) dZ160.2, 129.3, 111.8, 38.7, 31.7,
20.1, 14.2; HR ESI calcd for C14H23N3O2Na [MCNa]C:
288.1682 found: 288.1698; Anal. calcd for C14H23N3O2: C
63.37, H 8.74, N 15.84, found: C 63.55, H 8.40, N 15.81.
4.1.3. 1H-Pyrrole-2,5-dicarboxylic acid bis-phenylamide
(2b). Acid chloride 9 was prepared as described for diamide
2a, starting from 0.5 g (3.2 mmol) of acid 8. After
dissolving the acid chloride in dry dichloromethane
(15 ml) and cooling it to 0 8C, the solution of aniline
(1.4 ml, 16 mmol) in 2 ml CH2Cl2 was added with intensive
stirring, and a precipitate appeared. The reaction was stirred
overnight, and then the precipitate was filtered off and
thoroughly washed with ether, 2 M HCl and water. The
resulting amide 2b was recrystallised from methanol/
dichloromethane mixture. Yield 92%.
Acknowledgements
Financial support from the State Committee for Scientific
Research (Project # T09A 087 21) is gratefully
acknowledged.
1
Colourless crystals, mp 248–286 8C; H NMR (200 MHz
DMSO) dZ12.26 (s, 1H, NH-pyrrole), 10,12 (s, 2H,
CONH), 7.75 (d, 4H, J1Z7.6 Hz, o-Ph), 7.37 (dd, 4H,
J1Z7.8 Hz, J2Z7.8 Hz, m-Ph), 7.13–7.07 (m, 4H, p-PhC
H-pyrrole); 13C NMR (50 MHz DMSO) dZ158.6, 139.4,
129.8, 129.2, 124.0, 120.5, 133.6; HR ESI calcd for
Supplementary data
Supplementary data associated with this article can be