66
O. Ongayi et al. / Tetrahedron 66 (2010) 63–67
pressure affording an orange oil. The orange oil was diluted with
150 mL of DMSO and (750 mM, 2.85 g) of NaBH4 was slowly
added. The resulting solution was stirred under argon for 12 h
and then extracted into hexane and purified by silica gel chro-
matography using hexane for elution. The first band collected
was 4-bromophenylnonane (10.7 g, 76.3%). 1H NMR (CDCl3,),
not located. CCDC 745873, available from the Cambridge Crystal-
lographic Data Centre.
Biladienone 3a, C60H56N4O3$CH2Cl2, Mr¼966.01, triclinic, space
group P-1, a¼12.483(10), b¼13.993(12), c¼16.320(17) Å,
a
¼75.65(3),
b
¼75.83(3),
g
¼67.91(6)ꢀ, V¼2522(4) Å3, Z¼2, Mo-K
a
radiation (
l
¼0.71073 Å;
m
¼0.180 mmꢃ1), T¼110 K, 26 049 data by
d
(ppm), 7.42 (d, 2H, J¼8.4 Hz), 7.08 (d, 2H, J¼7.8 Hz), 2.60 (t, 2H,
Nonius Kappa CCD, R¼0.151 (F2>2
s) for 6470 unique data having
J¼7.6 Hz) 1.58–1.29 (m, 14H), 0.91 (t, 3H, J¼7.2 Hz). MS (FAB) m/z
282.16 (Mþ). 4-Bromophenylnonane (15 mM, 4.25 g) was dis-
solved in freshly distilled THF (50 mL) and the reaction mixture
cooled toꢃ78 ꢀC. n-BuLi (46 mM, 26.5 mL) was then added
dropwise and the mixture was stirred atꢃ78 ꢀC for 1 h. Dry DMF
(46 mM, 3.0 mL) was then added dropwise and the final mixture
stirred under argon for 1 h. The reaction mixture was allowed to
warm up to room temperature and then quenched with 100 mL
of 1 M HCl. The mixture was extracted into hexanes (3ꢂ100 mL),
washed with water (2ꢂ100 mL), dried over Na2SO4 and the sol-
vent removed under reduced pressure to give a yellow oil. 4-
Nonanylbenzaldehyde was purified by silica gel chromatography
using a 3:1 solution of hexane/ethyl acetate for elution to give an
qmax¼23.1ꢀ and 306 refined parameters. As a result of the small
number (1771) of unique intensities having I>2s(I), only O and
solvent Cl atoms were refined anisotropically. CCDC 745874, avail-
able from the Cambridge Crystallographic Data Centre.
4. Conclusions
It is shown that bilitrienones 2 are obtained from oxidation of
metal-free dodecasubstituted porphyrins 1 in the presence of
sodium nitrite, trifluoroacetic acid and air oxygen. Bilitrienone 2b is
obtained from the 5,10,15,20-tetra(p-nonanylphenyl)porphyrin 1b,
this being the first example of the unmodified metal-free open-
chain tetrapyrrole to be reported; the structure of 2b is character-
ized by X-ray crystallography. In the absence of the para-nonanyl
groups the initially-formed bilitrienone 2a undergoes a rapid and
spontaneous hydration reaction to give biladienone 3a as the major
isolated product. The molecular structure of 3a is also presented.
oil (2.3 g, 65% yield). 1H NMR (CDCl3,),
d (ppm), 10.0 (s, 1H), 7.82
(d, 2H, J¼8.4 Hz), 7.36 (d, 2H, J¼7.8 Hz), 2.74 (m, 2H) 1.69–1.29
(m, 14H), 0.93 (t, 3H, J¼7.2 Hz). MS (FAB) m/z 233.26 (Mþ).
3.1.2. Benzoylbiliverdins 2a and 3a. The compounds 2a and 3a were
prepared and characterized as we have previously described.24
Acknowledgements
3.1.3. Benzoylbiliverdins 2b and 3b. Porphyrin 1b (100 mg,
0.074 mmol) was dissolved in 2 mL of TFA and NaNO2 (30 mg,
0.45 mM) was added to the solution while stirring under air at room
temperature for 3 min. The reaction was quenched by pouring into
50 mL of water, followed by extraction with dichloromethane
(6ꢂ25 mL). The organic layers were washed with saturated aqueous
NaHCO3 (2ꢂ100 mL), then with water (100 mL), and dried over
anhydrous Na2SO4. The solvent was removed under vacuum and the
resulting residue was taken up in chloroform and purified by
alumina column chromatography using a gradient elution of chlo-
roform to 1% methanol in chloroform. The title biliverdin 2b was the
first green band eluted using pure chloroform (71 mg, 70%). The
benzoylbiliverdin 3b (violet color) was eluted next using 1% meth-
anol in chloroform solution (15 mg, 15%) yield. For the title biliver-
Support from the National Institutes of Health (CA 132861 to
K.M.S.) and the National Science Foundation (CHE 0911629 to
M.G.H.V.) is gratefully acknowledged.
References and notes
1. Ortiz de Montellano, P. R.; Auclair, K. In The Porphyrin Handbook; Kadish,
K. M., Smith, K. M., Guilard, R., Eds.; Academic: Boston, 2003; Vol. 12,
pp 183–210.
2. Kra¨utler, B. A. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R.,
Eds.; Academic: Boston, 2003; Vol. 13, pp 183–209.
3. (a) Frankenberg, N.; Lagarias, J. C. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: Boston, 2003; Vol. 13, pp 211–235; (b)
Gossauer, A. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R.,
Eds.; Academic: Boston, 2003; Vol. 13, pp 237–274.
4. Braslavsky, S. E.; Holzwarth, A. R.; Schaffner, K. Angew. Chem., Int. Ed. Engl. 1983,
22, 656–674.
5. Koerner, R.; Olmstead, M. M.; Ozarowski, A.; Balch, A. L. Inorg. Chem. 1999, 38,
3262–3263.
6. Stocker, R.; Yamamoto, Y.; McDonagh, A. F.; Glazer, A. N.; Ames, B. N. Science
1987, 235, 1043–1046.
7. Nakagami, T.; Taji, S.; Takahashi, M.; Yamanishi, K. Microbiol. Immunol. 1992, 36,
381–390.
8. Bennett, A.; Siegelman, H. W. In The Porphyrin; Dolphin, D., Ed.; Academic: New
York, NY, 1979; Vol. 6, pp 493–520.
9. Mori, H.; Otake, T.; Morimoto, M.; Ueba, N.; Kunita, N.; Nakagami, T.; Yamasaki,
N.; Taji, S. Jpn. J. Cancer Res. 1991, 82, 755–757.
10. Schmid, R.; McDonagh, A. F. Formation and metabolism of bile pigments in vivo
In. The Porphyrins; Dolphin, D., Ed.; Academic: New York, NY, 1979; Vol. 6, Part
A, pp 257–292.
11. Frydman, R. B.; Frydman, B. Acc. Chem. Res. 1987, 20, 250–256.
12. Smith, K. M.; Kishore, D. Tetrahedron 1983, 39, 1841–1847.
13. Cavaleiro, J. A. S.; Smith, K. M. J. Chem. Soc., Perkin Trans. 1 1973, 2149–2155.
14. (a) Boiadjiev, E. E.; Lightner, D. A. Tetrahedron: Asymmetry 2001, 12, 2551–2564;
(b) Kar, A. K.; Lightner, D. A. Tetrahedron 1998, 54, 12671–12690.
15. Smith, K. M. J. Chem. Soc., Perkin Trans. 1 1972, 1471–1475.
16. (a) Bonnett, R.; McDonagh, A. F. J. Chem. Soc., Chem. Commun. 1970, 237–238;
(b) Bonnett, R.; McDonagh, A. F. J. Chem. Soc., Perkin Trans. 1 1973, 881–888.
17. Crusats, J.; Suzuki, A.; Mizutani, T.; Ogoshi, H. J. Org. Chem. 1998, 63, 602–607.
18. (a) Evans, B.; Smith, K. M.; Cavaleiro, J. A. S. Tetrahedron Lett. 1976, 4863–4866;
(b) Evans, B.; Smith, K. M.; Cavaleiro, J. A. S. J. Chem. Soc., Perkin Trans. I 1978,
768–773.
din 2b: mp¼245–247 ꢀC. UV–vis (CH2Cl2) lmax 332 nm (
3 30,600),
447 (31,600), 683 (7800). MS (MALDI-TOF) m/z 1368.3 (Mþ).1H NMR
(CDCl3), d (ppm),12.80 (br s,1H),10.80 (br s,1H), 8.22–6.75 (m,16H),
2.76–1.33 (m, 96H), 0.94 (m, 12H): Anal. Calcd for C96H126N4O2: C,
80.05; H, 9.38; N 3.89. Found: C, 80.07; H, 9.07; N, 3.83. For biliverdin
3b: mp¼185–190 ꢀC; UV–vis (CH2Cl2) lmax 345 nm (
3 47 100),
576 nm (22 700). MS (MALDI-TOF) m/z 1386.4 (Mþ). 1H NMR
(CDCl3),
J¼8.0 Hz, 2H), 7.40 (d, J¼8.0 Hz, 2H), 7.3–7.1 (m, 12H), 6.10 (s, 1H),
2.7–1.24 (m, 96H), 0.94 (br s, 12H). 13C NMR (CDCl3),
(ppm), 172.2,
d (ppm), 11.52, 11.45 (2 br s, 2H), 8.86 (s, 1H), 7.56 (d,
d
163.5, 146.6, 145.3, 144.3, 143.5, 143.2, 139.6, 138.8, 137.7, 136.6,
135.6,135.1,134.2,133.5,131.1,129.8,128.9,128.5,128.3,127.2,125.3,
120.6,119.4, 74.1, 36.1, 35.8, 35.7, 32.1, 31.8, 31.6, 29.8, 29.7, 29.6, 29.5,
29.1, 24.9, 24.1, 23.4, 23.0, 22.9. Anal. Calcd for C96H128N4O3: C, 83.19;
H, 9.31; N, 4.04. Found: C, 82.98; H, 9.24; N, 4.12.
3.1.4. Crystal
molecular
structures. Bilatrienone
2b,
C96H126N4O2$H2O$MeOH, Mr¼1418.1, triclinic, space group P-1,
a¼14.222(5), b¼16.640(6), c¼19.510(10) Å,
a
¼92.097(14),
b¼103.467(15),
g
¼107.381(19)ꢀ, V¼4257(3) Å3, Z¼2, Mo-K
a radia-
tion (
l
¼0.71073 Å;
m
¼0.066 mmꢃ1), T¼110 K, 22 253 data by
19. Fuhrhop, J.-H.; Mauzerall, D. Photochem. Photobiol. 1971, 13, 453–458.
20. Wasser, P. K. W.; Fuhrhop, J.-H. Ann. N.Y. Acad. Sci. 1973, 206, 533–547.
21. Catalano, M. M.; Crossley, M. J.; Harding, M. M.; King, L. G. J. Chem. Soc., Chem.
Commun. 1984, 1535–1536.
22. Ongayi, O.; Fronczek, F.; Vicente, M. G. H. Chem. Commun. 2003, 2298–2299.
23. Bonnett, R.; Dimsdale, M. J. J. Chem. Soc., Perkin Trans. 1 1972, 2540–2548.
Nonius Kappa CCD, R¼0.122 (F2>2
s), for 11 688 unique data having
qmax¼23.0ꢀ and 906 refined parameters. Displacement parameters
are large for three of the nonanyl groups, and anisotropic
refinement of one of them was not possible. Solvent H atoms were