Jul-Aug 2003
A Novel Diacetylenic Bilirubin
711
1450, 1385, 1163, 1084, 801, 561 cm-1; 1H-nmr (dimethylsulfox-
ide-d6): d 0.99 (3H, t, J = 7.2 Hz), 1.02-1.09 (6H, m), 1.76 (3H,
s), 2.02 (6H, s), 2.54-2.64 (4H, m), 2.67 (2H, q, J = 7.2 Hz), 5.88
(1H, s), 9.57 (1H, s), 9.88 (1H, br.s), 11.17 (1H, br.s), 12.2 (1H,
br.s) ppm; 13C-nmr (dimethylsulfoxide-d6): d 8.5, 9.5, 10.0, 15.0,
16.1, 16.3, 17.1, 17.4, 17.5, 73.0, 77.0, 78.3, 79.2, 95.7, 112.3,
117.0, 125.5, 127.0, 127.5, 128.4, 128.9, 130.0, 132.4, 135.3,
147.8, 172.5, 178.7 ppm.
washed with cold ethyl acetate to afford a 60% yield of the final
acetylenic dipyrrole dialdehyde (3b) as a yellow powder.
Compound 3b has been reported previously [20] but without full
experimental and spectral details. It had mp 305-308 °C; uv-visible
spectral data in Table 1; ir (KBr): 3436, 3230, 2837, 1626, 1446,
1390, 1263, 1094, 894, 767 cm-1; 1H-nmr (dimethylsulfoxide-d6): d
1.07 (6H, t, J = 7.5 Hz), 2.03 (6H, s), 2.67 (4H, q, J = 7.5 Hz), 9.56
(2H, s), 12.1 (2H, br.s) ppm; 13C-nmr (dimethylsulfoxide-d6): d
9.45, 6.3, 17.2, 86.9, 118.4, 125.4, 129.7, 135.4, 178.4 ppm.
Anal. Calcd for C27H29N3O2 (427.5): C, 75.85; H, 6.84; N,
9.83. Calcd for C27H29N3O2•1/4H2O (432.0): C, 75.06; H, 6.88;
N, 9.72. Found: C, 75.02; H, 6.52; N, 9.90.
1,4-Bis(5-formyl-4-ethyl-3-methyl-2-pyrrolyl)-butadiyne (3a).
To a solution of tetrakis(triphenyphosphine)palladium(0) (18
mg, 0.016 mmole), copper(I) iodide (10.7 mg, 0.059 mmole) and
dry triethylamine (0.2 ml) in dry benzene (10 ml), was added a
mixture of pyrrole 4 (124 mg, 0.77 mmole) and chloroacetone
(0.06 ml, 0.078 mmol) in dry benzene (5 ml) in one portion. The
black mixture was stirred at room temperature for 20 hours, after
which the solvent was evaporated. The residue was passed
through a column of silica gel using chloroform as eluent, and the
product was further purified by radial chromatography followed
by recrystallization from ethyl acetate to give yellow crystals
(113 mg, 92%) of 3a. They had mp 222-225 °C; uv-visible spec-
tral data in Table 1; ir (solid film): 3955, 2987, 2305, 1599, 1422,
1265, 1154, 896, 740, 705 cm-1; 1H-nmr: d 1.21 (6H, t), 2.14 (6H,
s, J = 7.6 Hz), 2.73 (4H, q, J = 7.6 Hz), 8.98 (2H, br.s), 9.26 (2H,
(3,7-Diethyl-2,8-dimethyldipyrrin-1(10H)-one-9-yl)-(4-ethyl-5-
formyl-3-methyl-1H-pyrrol-2-yl)acetylene (2b).
Using the procedure above for 1a and 2a, tripyrrole 2b was
produced in 30% yield. This compound has mp > 250 °C (dec);
uv-visible spectral data in Table 1; ir (KBr): 3329, 2965, 2181,
1
1661, 1630, 1446, 1383, 1241, 1093, 801, 668 cm-1; H-nmr
(dimethylsulfoxide-d6): d 1.00 (3H, t, J = 7.5 Hz), 1.08 (6H, m, J
= 7.2 Hz), 1.76 (3H, s), 2.04 (3H, s), 2.06 (3H, s), 2.46 (2H, q, 7.5
Hz), 2.68 (4H, q, 7.2 Hz), 5.89 (1H, s), 9.53 (1H, s), 9.99 (1H,
1
br.s), 10.9 (1H, br.s), 12.1 (1H, br.s) ppm; H-nmr: d 1.13-1.15
(6H, t, J = 7.2 Hz), 1.34 (2H, t, J = 7.6 Hz), 1.88 (3H, s), 2.13
(3H, s), 2.16 (3H, s), 2.54 (4H, m, J = 7.2 Hz), 2.74 (2H, q, J =
7.6 Hz), 6.07 (1H, s), 8.96 (1H, br.s), 9.59 (1H, s), 10.42 (1H,
br.s), 10.98 (1H, br.s) ppm; 13C-nmr (dimethylsulfoxide-d6): d
8.53, 9.58, 9.97, 15.1, 16.2, 16.4, 17.2, 17.5, 18.0, 86.4, 88.3,
96.2, 113.7, 119.1, 124.4, 124.9, 125.62, 125.65, 129.2, 129.4,
131.2, 131.3, 147.7, 172.5, 178.0 ppm.
1
s) ppm; H-nmr (dimethylsulfoxide-d6): d 1.06 (6H, t, J = 7.5
Hz), 2.02 (6H, s) 2.66 (4H, q, J = 7.5 Hz), 9.57 (2H, s), 12.31
(2H, br.s) ppm; 13C-nmr: d 9.45, 16.2, 17.1, 74.9, 80.4, 117.2,
128.8, 129.4, 136.3, 177.2 ppm.
Anal. Calcd. for C20H20N2O2 (320.4): C, 74.98; H, 6.29; N,
8.74. Calcd. for C20H20N2O2•1/4H2O (324.9): C, 73.93; H, 6.36;
N, 8.62. Found: C, 74.02; H, 6.47; N, 8.67.
Anal. Calcd C25H29N3O2 (403.5): C, 74.41; H, 7.24; N, 10.41.
Found: C, 74.03; H, 7.33; N, 10.15.
Acknowledgments.
10,10a,10b,10c-Tetradehydro-10a,10b,10c-trishomo-etiobilirubin-
IIb (1a) and (3,7-Diethyl-2,8-dimethyldipyrrin-1(10H)-one-9-yl)-
(4-ethyl-5-formyl-3-methyl-1H-pyrrol-2-yl)diacetylene (2a).
We thank the U.S. National Institutes of Health (HD 17779)
for generous support of this work.
To the solution of 4-ethyl-3-methyl-5- p-toluene-sul-
fonylpyrrolin-2-one (10) (1.5 mmoles), dipyrrole dialdehyde (3a)
(0.5 mmole), tri-n-butylphosphine (0.75 mmole) in anhydrous
tetrahydrofuran (15 ml) was added a solution of 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU) (0.21 ml) in anhydrous tetrahydro-
furan (2.5 ml) in one portion under N2. The mixture was stirred at
room temperature for 24 hours, after which the solvents were
removed under vacuum. The residue was chromatographed on a
short column of silica gel, eluting first with hexane and then with
ethyl acetate-dichloromethane (gradually from 1:3 to 1:1, by vol-
ume). Two principle products (1a and 2a) were separated, and
after the evaporation of solvents, the products were recrystallized
from hot ethyl acetate.
REFERENCES AND NOTES
[1] H. Falk, The Chemistry of Linear Oligopyrroles and Bile
Pigments. Springer Verlag: New York, Vienna, 1989.
[2] R. V. Person, B. R. Peterson and D. A. Lightner, J. Am. Chem.
Soc., 116, 42 (1994).
[3] Q. Chen, M. T. Huggins, D. A. Lightner, W. Norona and A. F.
McDonagh, J. Am. Chem. Soc., 121, 9253 (1999).
[4] D. P. Shrout and D. A. LightnerSynthesis, 1062(1990).
[5] The syntheses of 3a and b follow the outline described in the
preparation of the permethyl analogs: D. H. Cho, J. H. Lee and B. H.
Kim, J. Org. Chem., 64, 8048 (1999).
[6] L. J. Cheng and J. S. Ma Synth. Commun., 24, 2771 (1994).
[7] R. Grigg, A. W. Johnson and G. Shelton, Liebigs Ann. Chem.,
746, 32 (1971).
1a: Yield 40%. This compound has mp > 400 °C; uv-visible
spectral data in Table 1; ir (KBr): 3323, 2965, 2123, 1657, 1558,
1
1474, 1382, 1266, 1107, 668 cm-1; H-nmr (dimethylsulfoxide-
[8a] T. Thyrann and D. A. Lightner, Tetrahedron Lett., 36, 4345
(1995); [b] P. Bobál, and D. A. Lightner, J. Heterocyclic Chem., 1219
(2001).
d6): d 0.97-1.08 (12H, m), 1.76 (6H, s), 2.02 (6H, s), 2.50-2.56
(8H, m), 5.88 (2H, s), 9.89 (2H, br.s), 11.12 (2H, br.s) ppm; the
13C-nmr could not be obtained on a 500 MHz nmr instrument
even, in dimethylsulfoxide-d6 solvent due to the extreme insolu-
bility of the pigment.
Anal. by HRMS (FAB, 3-NBA): Calcd for C34H38N4O2
(534.2995); Found 534.2976, D= 1.9 mDa, error 3.5 ppm.
2a: Yield 15%. This compound has mp > 310 °C; uv-visible
spectral data in Table 1; ir (KBr): 3429, 2964, 2186, 1667, 1631,
[9] K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett.,
4467 (1975). For reasons not entirely clear, diacetylenic dipyrrole dialde-
hyde (3b) was obtained in this step in yields ranging from 10-60%.
Oxygen in the air has a marked influence on this reaction.
[10a] N. Jux, P. Koch, H. Schmickler and J. Lex, Angew. Chem. Int.
Ed. Engl., 29, 1385 (1990); [b] D. O. Martire, N. Jux, P. F. Aramendia, R.
M. Negri, J. Lex, S. E. Braslavsky, K. Schaffner and E. Vogel, J. Am.
Chem. Soc., 114, 9969 (1992).