8630
S. Neya et al. / Tetrahedron Letters 45(2004) 8629–8630
hydroxide and water. The chloroform layer containing
crude 1 was evaporated to dryness. The residue, washed
on a centrifuge with small portions of methanol until
colorless, was purified by silica-gel column chromatog-
raphy with chloroform. The fast-moving red band was
collected and evaporated to dryness. Recrystallization
from chloroform/methanol afforded 74mg of 1 (64%
yield). The visible absorption spectrum in dichlorometh-
ane was identical with that reported in the literature.11
Anal. Calcd for C20H14N4: C, 77.40; H, 4.55; N, 18.05.
Found: C, 77.69; H, 4.61; N, 17.70. MS: m/z 310
(M+). 1H NMR (400MHz, CDCl3, d): 10.37 (s, 4H,
meso-H), 9.53 (s, 8H, pyrrole-H), À3.96 (br s, 2H, NH).
NH
N
N
N
HN
N
H
4
2
NH
N
NH
N
N
N
HN
HN
1
3
References and notes
Scheme 1. Synthesis of 1 from pyrrole 4. Conversion of 2 to 1 has been
already reported.11
1. (a) Kim, J. B.; Adler, A. D.; Longo, F. R. In The
Porphyrins; Dolphin, Ed.; Academic Press: New York,
1978; Vol. 1, pp 85–100; (b) Frank, B.; Nonn, A. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1795–1811.
2. According to the Sigma catalogue in 2004, the price for
5mg of porphine (product code, P7259) is 477 US dollars.
3. (a) Eisner, U.; Linstead, R. P. J. Chem. Soc. 1955, 3742–
3749; (b) Krol, S. J. Org. Chem. 1959, 24, 2065–2067; (c)
Longo, F. R.; Throne, E. J.; Adler, A. D.; Dym, S. J.
Heterocycl. Chem. 1975, 12, 1305–1309.
4. Rothemund, P. J. Am. Chem. Soc. 1936, 58, 625–628.
5. Fischer, H.; Gleim, W. Liebigs Ann. Chem. 1936, 521, 157–
160.
6. Neya, S.; Yodo, H.; Funasaki, N. J. Heterocycl. Chem.
1993, 30, 549–550.
The reaction temperature is much higher than 90°C
applied for the de-tert-butylation of 2.11 The higher
temperature may arise from the flat macrocycle of 3 with
the tert-butyl groups on the less crowded b-pyrrole car-
bons. It is notable that the carbon atom bearing tert-bu-
tyl group is constrained into an sp3-carbon like
conformation upon proton attachment.15 In porphyrin
2, the meso-carbons are inherently constrained16 due
to the tert-butyl substituents on the crowded meso-
bridges. Thus, the de-tert-butylation for non-planar 2
is feasible at lower temperature.
7. Taniguchi, S.; Hasegawa, H.; Nishimura, M.; Takahashi,
M. Synlett 1999, 73–74.
The above method has several advantages. Pyrrole 4 is
easily derived from pyrrole.12,17 Porphyrin 3 is available
from pyrrole 4 in multi-gram quantities with 20–29%
yield after brief reflux in a small volume of acetic acid.12
Deaeration and dehydration are unnecessary for the
acetic acid whereas a large amount of oxygen-free and
dry dichloromethane is required to prepare 2.16 In addi-
tion, the expensive oxidizing agent 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone, necessary for 2,16 is not
used. The 64% yield of 1 from 3 is satisfactory and com-
parable with 74% reported for analogous reaction for
2.11 Easy de-tert-butylation of 3 makes this porphyrin
a superior precursor for 1. In conclusion, we developed
a new route to 1. The route as well as our previous meth-
odology11 facilitates the access to porphine.
8. (a) Schlo¨zer, R.; Fuhrhop, J.-H. Angew. Chem., Int. Ed.
Engl. 1975, 14, 363; (b) Nudy, L. R.; Schieber, C.; Longo,
F. R.; Agarwala, V. S. Heterocycles 1987, 26, 1797–1803;
(c) Shi, D.-F.; Wheelhouse, R. T. Tetrahedron Lett. 2002,
43, 9341–9342; (d) Hatcher, S.; Senge, M. O. Tetrahedron
Lett. 2003, 44, 157–160.
9. Sato, T.; Tanaka, N.; Neya, S.; Funasaki, N.; Iizuka, T.;
Shiro, Y. Biochim. Biophys. Acta 1992, 1121, 1–7.
10. Neya, S.; Funasaki, N.; Sato, T.; Igarashi, N.; Tanaka, N.
J. Biol. Chem. 1993, 268, 8935–8942.
11. Neya, S.; Funasaki, N. Tetrahedron Lett. 2002, 43, 1057–
1058.
12. Whitlock, B. J.; Whitlock, H. W.; Alles, H. J. Am. Chem.
Soc. 1974, 96, 3959–3965.
13. Saleh, S. A.; Tashtoush, H. I. Tetrahedron 1998, 54,
14157–14177.
14. Cerfontain, H.; Arends, J. M. Recl. Trav. Chim. Pays-Bas
1966, 85, 358–366.
15. Hendrickson, J. B.; Cram, D. J.; Hammond, G. S. Organic
Chemistry, 3rd ed.; McGraw-Hill: New York, 1970; pp
668–670.
16. Senge, M. O.; Bischoff, I.; Nelson, N. Y.; Smith, K. M. J.
Porphyrins Phthalocyanines 1999, 3, 99–116.
2. Experimental
b-Tetra(tert-butyl)porphyrin12 3 (200mg) was dissolved
in sulfuric acid (14mL), and water (6mL) was added
dropwise. Nitrogen was bubbled over 10min through
the solution for deaeration. The mixture was subse-
quently heated at 190–200°C under nitrogen atmos-
phere for 15min. 1-Butanol (40mL) and chloroform
(200mL) were added to the cooled solution before being
washed until neutrality with dilute aqueous sodium
´
17. (a) Anderson, H. J.; Loader, C. E.; Xu, R. X.; Le, N.;
Gogan, N. L.; McDonald, R.; Edwards, L. G. Can. J.
Chem. 1985, 63, 896–902; (b) Muller-Westerhoff, U. T.;
¨
Swiegers, G. F. Synth. Commun. 1994, 24, 1389–1393; (c)
Zelikin, A.; Shastri, V.; Langer, R. J. Org. Chem. 1999, 64,
3379–3380.