Conjugated Macrocycles Related to the Porphyrins
J . Org. Chem., Vol. 64, No. 21, 1999 7981
(5 mL), and exhaustively extracted with ether and ethyl
acetate. The combined organic solutions were dried over
sodium sulfate and evaporated, and the residue was recrystal-
lized from ethanol to give the diformylpyrrole (1.59 g; 47%) as
buff-colored crystals, mp 178-178.5 °C. Further recrystalli-
zation from ethanol gave an analytical sample as fluffy white
microneedles: mp 178.5-179 °C; IR (Nujol mull): ν 3156 (NH
str), 1661, 1639 (CdO str) cm-1; 1H NMR (CDCl3): δ 2.66 (3H,
s), 7.33 (1H, d, J ) 2.4 Hz), 9.51 (1H, s), 9.93 (1H, s), 10.10
(1H, br s); 13C NMR (CDCl3): δ 12.73, 122.70, 124.38, 132.04,
143.82, 179.82, 185.93; 13C NMR (DMSO-d6): δ 11.7, 121.3,
123.1, 131.9, 143.8, 179.7, 185.7. Anal. Calcd for C7H7NO2: C,
61.31; H, 5.14; N, 10.21. Found: C, 61.17; H, 5.17; N, 10.15.
5-Eth ylp yr r ole-2,4-d ica r boxa ld eh yd e (13c). Prepared
from 2-ethylpyrrole (1.00 g) by the foregoing procedure.
Recrystallization from carbon tetrachloride gave the dialde-
hyde (0.95 g; 60%) as off-white crystals: mp 132 °C, with
softening at 112 °C; IR (Nujol mull): ν 3242 (NH str), 1666,
1633 (CdO str) cm-1; 1H NMR (CDCl3): δ 1.36 (3H, t, J ) 7.6
Hz), 3.09 (2H, q, J ) 7.6 Hz), 7.37 (1H, d, J ) 2.3 Hz), 9.52
(1H, s), 9.95 (1H, s), 10.43 (1H, br s); 13C NMR (CDCl3): δ
13.8, 20.5, 123.3, 123.4, 131.8, 150.1, 179.8, 185.7. Anal. Calcd
for C8H9NO2‚1/10H2O: C, 62.82; H, 6.06; N, 9.15. Found: C,
62.86; H, 5.95; N, 9.11.
8,12,13,17-Tetr a eth yl-3,7,18-tr im eth yl-2-a za -21-ca r ba -
p or p h yr in (14b ). Tripyrranedicarboxylic acid 12 (100 mg)
was stirred with TFA (1 mL) under nitrogen at room temper-
ature for 2 min. The mixture was diluted with dichloromethane
(99 mL) and 5-methylpyrrole-2,4-dicarboxaldehyde (13b; 30
mg) immediately added in a single portion. The resulting
solution was stirred overnight under nitrogen and then washed
with water, 0.1% ferric chloride solution, water, and saturated
sodium bicarbonate (the aqueous solutions were back-extracted
with chloroform at each stage in the extractions). The solvent
was removed under reduced pressure and the residue chro-
matographed first on Grade II neutral alumina, eluting with
chloroform, and then on silica gel eluting with 5% methanol-
chloroform. Column fractions were assessed by TLC and UV-
vis spectroscopy. The green product fractions were washed
with 10% aqueous hydrochloric acid, evaporated, and recrys-
tallized from chloroform-petroleum ether (60-90°) to give the
hydrochloride salt (62-72 mg; 53-61%) as dark blue crystals,
mp > 300 °C. Alternatively, the free base could be recrystal-
lized from chloroform-methanol as a dull purple powder: mp
> 300 °C; UV-vis (1% Et3N-CHCl3): λmax (log ꢀ) 353 (4.44),
422 (4.905), 516 (4.03), 554 (3.88), 614 (3.54), 678 (3.49); UV-
vis (1 equiv of TFA-CHCl3; monocation): λmax (log ꢀ) 338 (4.50),
421 (4.88), 442 (4.68), 529 (3.94), 571 (4.11), 637 (3.72), 697
(3.96); UV-vis (1% TFA-CHCl3; dication): λmax (log ꢀ) 337
(4.48), 425 (4.88), 456 (3.94), 578 (3.87), 620 (3.87), 706 (3.97);
1H NMR (CDCl3; 20 °C): δ -6.30 (1H, s), -3.84 (1H, br s),
-3.72 (1H, br s), 1.78-1.85 (12H, m), 3.51 (3H, s), 3.55 (3H,
s), 3.60 (3H, s), 3.84-4.02 (8H, m), 9.54 (1H, s), 9.64 (1H, s),
9.70 (1H, s), 10.01 (1H, s); 1H NMR (4 drops TFA-CDCl3;
dication): δ -4.04 (1H, s), -1.7 (1H, br s), -1.04 (1H, s), -0.94
(1H, s), 1.65 (3H, t), 1.68 (3H, t), 1.75 (6H, two overlapping
triplets), 3.34 (3H, s), 3.42 (3H, s), 3.64 (3H, s), 3.8-3.91 (8H,
m), 9.49 (1H, s), 9.54 (1H, s), 9.90 (1H, s), 10.00 (1H, s), 12.79
(1H, br s); 1H NMR (CDCl3 + 1 drop concentrated HCl): δ
-4.43 (1H, s), 0.78 (1H, s), 0.86 (1H, s), 1.25 (1H, s), 1.67-
1.79 (12H, m), 3.38 (3H, s), 3.40 (3H, s), 3.84 (3H, s), 3.81-
3.87 (8H, m), 9.49 (1H, s), 9.57 (1H, s), 9.87 (1H, s), 10.47 (1H,
s), 16.72 (1H, br s); 1H NMR (CDCl3 + 1 drop concentrated
HBr): δ -4.39 (1H, s), 0.46 (1H, s), 0.53 (1H, s), 1.17 (1H, s),
1.63-1.78 (12H, m), 3.38 (6H, s), 3.84 (3H, s), 3.8-3.9 (8H,
m), 9.49 (1H, s), 9.58 (1H, s), 9.88 (1H, s), 10.58 (1H, s), 16.55
(1H, br s); 1H NMR (CDCl3 + 1 drop concentrated HI): δ -3.93
(1H, s), 0.03 (1H, s), 0.10 (1H, s), 0.15 (1H, s), 1.65-1.80 (12H,
m), 3.34 (3H, s), 3.37 (3H, s), 3.67 (3H, s), 3.77-3.86 (8H, m),
9.45 (1H, s), 9.52 (1H, s), 9.88 (1H, s), 10.37 (1H, s), 14.79 (1H,
br s); 13C NMR (CDCl3): δ 11.4, 11.5, 17.4, 17.5, 17.6, 18.5,
18.6, 19.6, 19.7, 20.1, 94.3, 95.9, 101.6, 102.9, 106.6, 132.9,
134.1, 134.2, 134.9, 135.7, 136.8, 137.7, 137.9, 138.1, 144.7,
145.3, 154.0, 155.1, 165.9; 13C NMR (TFA-CDCl3): δ 11.2,
11.6, 14.7, 16.2, 16.3, 17.0, 17.1, 19.6 (2), 19.7, 19.8, 94.7, 96.3,
Con clu sion s
The “3 + 1” methodology provides an excellent high-
yielding route to heptaalkyl-substituted N-confused por-
phyrins, although it was necessary to develop suitable
reaction conditions to facilitate this chemistry. In par-
ticular, brief treatment with ferric chloride provided a
superior method for dehydrogenating the dihydro inter-
mediate to the aromatic porphyrinoid. NH exhange in
the macrocyclic cavity for these N-confused porphyrins
is slow on the NMR time scale even at room temperature,
and the data implies that there is a strong preference
for a single tautomeric species. Addition of acid results
in the formation of mono- and diprotonated structures
that retain aromatic character, but the dications of these
“etio” N-confused porphyrins show indications of strong
anion pairing in solution. The nickel(II) organometallic
complex of trimethyl N-confused porphyrin 14b was
generated and this rather unstable species was shown
to have lost most of its aromatic character. However,
addition of acid resulted in C-protonation to generate a
new aromatic cation that slowly demetalated over the
period of several hours. Clearly, the “etio” series of
N-confused porphyrins have somewhat different spectro-
scopic and chemical properties than their better known
meso-tetraaryl cousins and the improved synthetic pro-
cedures to these porphyrinoids will allow their chemistry
to be fully explored.
Exp er im en ta l Section
2-Ethylpyrrole, oxalyl chloride, DMF, nitromethane, dichlo-
romethyl methyl ether, and TFA were purchased from Aldrich
Chemical Co. and used without further purification. Chroma-
tography was performed using Grade 3 neutral alumina or 70-
230 mesh silica gel. EI and FAB mass spectral determinations
were made at the Mass Spectral Laboratory, School of Chemi-
cal Sciences, University of Illinois at Urbana-Champaign,
supported in part by a grant from the National Institute of
General Medical Sciences (GM 27029). Elemental analyses
were obtained from the School of Chemical Sciences Mi-
croanalysis Laboratory at the University of Illinois.
2-Meth ylp yr r ole (15). Ethyl 5-methylpyrrole-2-carboxylate
(16; 12.50 g),40 sodium hydroxide (10.0 g), and ethylene glycol
(100 mL) were stirred in a 250 mL round-bottomed flask under
an atmosphere of nitrogen and heated on an oil bath at 180-
185 °C for 6 h. The mixture was cooled, diluted with water,
and extracted with dichloromethane. The organic extracts were
dried over sodium sulfate, the solvent was removed on a rotary
evaporator, and the residue was distilled to give the title
pyrrole (5.35 g; 81%) as a colorless oil: bp 154 °C; IR (neat):
1
ν 3381 cm-1 (NH str); H NMR (CDCl3): δ 2.35 (3H, s), 5.98
(1H, br m), 6.19-6.22 (1H, m), 6.70-6.72 (1H, m), 7.90 (1H,
br s); 13C NMR (CDCl3): δ 13.2, 106.1, 108.7, 116.5, 127.8.
5-Meth ylp yr r ole-2,4-d ica r boxa ld eh yd e (13b). A solution
of oxalyl chloride in 1,2-dichloroethane (4 mL) was added
dropwise over a period of 20 min to a mixture of DMF (2.00 g)
and 1,2-dichloroethane (6 mL) while maintaining the temper-
ature of the reaction mixture at 0 °C with the aid of an ice-
salt bath. The resulting white precipitate was stirred at room
temperature for 15 min. The mixture was then cooled with an
ice bath and a solution of 2-methylpyrrole (15; 2.00 g) in 1,2-
dichloroethane added dropwise over 20 min. The resulting
solution was stirred at room temperature for a further 15 min,
nitromethane (3.60 g) was added, and the mixture was cooled
to 0 °C. Aluminum chloride (7.30 g) was cautiously added,
followed by the rapid addition of dichloromethyl methyl ether
(3.4 mL). After the highly exothermic reaction had subsided,
the ice bath was removed and the mixture stirred at room
temperature for 30 min. The mixture was poured into ice-
water, further acidified with concentrated hydrochloric acid