Four-Atom-Linked Capped Porphyrins
J . Org. Chem., Vol. 61, No. 10, 1996 3301
Ta ble 2. CO Bin d in g to Hem oglobin a n d Ca p p ed
(56), 165 (100), 149 (54), 121 (36), 91 (80); HRMS calcd for
C18H20O6S m/ e 364.0981, found 364.0965.
P or p h yr in s (25 °C)
1,2,4,5-Tet r a k is(2′-(o-(1′′,3′′-d ioxola n -2′′-yl)p h en oxy)-
eth oxy)ben zen e (5). A 250-mL three-necked round-bottom
flask was equipped with an N2 inlet, a dropping funnel, a
powder addition funnel, and a magnetic stir bar. Degassed
DMSO (150 mL) was added to the flask, and the flask was
purged with N2 for 15 min. 1,2,4,5-Tetrahydroxybenzene (4)
(0.5 g, 3.5 mmol)29 was then dissolved with stirring, followed
by finely powdered KOH (3.15 g, 56.3 mmol). After the
solution was stirred for 1 min powdered acetal 3 (10 g, 27.4
mmol) was added all at once and the resultant mixture was
stirred at room temperature for 1 h. Then the contents of the
flask were poured into 500 mL of stirred saturated brine. The
semisolid agglomerate that resulted was allowed to float to
the top of the brine. Filtration through a large Bu¨chner funnel
afforded the crude product as a semisolid glass. This was
purified by chromatography through a 4 × 30 cm column of
silica (2% MeOH/CHCl3 eluent) followed by recrystallization
from CHCl3/hexane to give the pure product 5 (1.88 g, 2.1
mmol, 59%) as a white microcrystalline powder: mp 123-125
°C; 1H NMR (CDCl3) δ 3.96 (m, 8H), 4.10 (m, 8H), 4.26 (m,
8H), 4.29 (m, 8H), 6.13 (s, 4H), 6.74 (s,2H), 6.88 (d, 4H), 6.98
(t, 4H), 7.27 (dt, 4H), 7.51 (dd, 4H); 13C NMR (CDCl3) δ 65.15,
67.25, 69.01, 98.99, 107.45, 112.15, 120.82, 126.24, 127.02,
130.22, 143.76, 156.79; FAB MS (3-nitrobenzyl alcohol) m/ e
933 (26, Na adduct), 910 (100), 866 (7), 718 (5.2), 307 (16); FAB
HRMS calcd for C50H54O16 m/ e 910.3412, found 910.3409.
compd
hemoglobin
P1/2(CO) (Torr)
ref
∼1 × 10-3
5.4 × 10-3
2.6 × 10-4
100
38, 39
16
36
13
13
Fe(C2-Cap)(1-MeIm)
Fe(OC3OPor)(1-MeIm)
Fe(OC2OPor)(1-MeIm)
Fe(OC(CO)NPor)(1-MeIm)
>7.7 × 104
104 Torr (100 atm).13 Because H2(OC2NPor) is sensitive
to light and air, no attempts have been made to metalate
it and study CO and O2 binding. But from the structure
of H2(OC2NPor) (Table 1) we expect its Fe derivatives will
also have very large P1/2
(CO)
values.
Exp er im en ta l Section
Gen er a l P r oced u r es. With the following exceptions all
solvents and reagents were used as purchased. DMSO was
deoxygenated with the freeze-pump-thaw technique just
prior to use. Propionic acid was refluxed over K2Cr2O7,
followed by two fractional distillations. Pyrrole was distilled
just prior to use. Pyridine was dried over 4 Å molecular sieves.
Methylene chloride (in the synthesis of 13 only) was distilled
from K2CO3. Literature procedures were followed in the
preparation of meso-R,R,R,R-tetra(o-aminophenyl)porphyrin
(TAPP) (12),21,28 2-(2′-hydroxyethoxy)benzaldehyde (1),6 and
1,2,4,5-tetrahydroxybenzene (4).29
1,2,4,5-T e t r a k is (2′-(o-fo r m y lp h e n o x y )e t h o x y )b e n -
zen e (6). The tetraacetal 5 (720 mg, 0.79 mmol) was dissolved
in refluxing acetone (50 mL). To the refluxing solution was
added 1 drop of sulfuric acid. After about 2 min a precipitate
formed. The suspension was refluxed for an additional 10 min.
The contents of the flask were cooled to 15 °C, filtered, washed
with 5% Et3N/acetone, acetone, and ether, and then dried to
give the tetraaldehyde 6 (460 mg, 0.63 mmol, 79%) as a white
fluffy powder, mp 168-169 °C. Recrystallization from CHCl3
increased the melting point to 173.5 °C: 1H NMR (DMSO-d6)
δ 4.33 (t, 8H), 4.37 (t, 8H), 6.89 (s, 2H), 7.04 (t, 4H), 7.21 (d,
4H), 7.61 (m, 8H), 10.27 (s, 4H); 13C NMR (DMSO-d6, 70 °C) δ
67.75, 68.48, 106.90, 113.80, 120.59, 124.60, 127.11, 135.63,
143.16, 160.48, 188.71; FAB MS (3-nitrobenzyl alcohol) m/ e
757 (65, Na adduct), 735 (100), 613 (30); EI MS (3-nitrobenzyl
alcohol) m/ e 734 (28), 434 (26), 368 (100); FAB HRMS calcd
for C42H38O12 m/ e 734.2363, found 734.2365.
2-(2′-(Tosyloxy)eth oxy)ben za ld eh yd e (2). A 1-L three-
necked round-bottom flask was equipped with a thermometer,
nitrogen inlet, and dropping funnel and was charged with CH2-
Cl2 (500 mL), hydroxy aldehyde 1 (109 g, 0.66 mol),6 and
p-toluenesulfonyl chloride (207.6 g, 1.0 mol). The flask was
cooled to 5 °C and purged for 10 min. Triethylamine (110.2
g, 1.1 mol) was then dropped in over 20 min; the temperature
of the flask was maintained at 10-15 °C with the use of an
ice bath. The contents were stirred for 12 h with gradual
warming to room temperature. The contents were transferred
to a 2-L separatory funnel and washed with 500 mL each of
water, 5% HCl, and water. The organic layer was then dried
with MgSO4 and concentrated on a rotary evaporator (45 °C
bath). The crude product was recrystallized once from CH3-
OH and once from 80%HOAc/20%H2O to give the aldehyde 2
(110 g, 0.34 mol, 52%) as colorless prisms or flakes: mp 108-
110 °C; 1H NMR (CDCl3) δ 2.45 (s, 3H), 4.29 (m, 2H), 4.43 (m,
2H), 6.88 (d, 1H), 7.04 (t, 1H), 7.33 (d, 2H), 7.51 (m, 1H), 7.79
(d, 3H), 10.17 (s, 1H); 13C NMR (CDCl3) δ 21.71, 65.84, 67.89,
112.33, 121.47, 124.90, 127.90, 128.32, 130.06, 132.51, 135.97,
145.44, 160.22, 189.40; MS (CHCl3) m/ e 320 (30), 213 (9), 199
(27), 165 (12), 155 (17), 148 (68); HRMS calcd for C16H16O5S
m/ e 320.0718, found 320.0708.
2-(2′-(Tosyloxy)eth oxy)ben za ld eh yd e Eth ylen e Aceta l
(3). 2-(2′-(Tosyloxy)ethoxy)benzaldehyde (2) (20 g, 62 mmol),
ethylene glycol (6.1 g, 102 mmol), p-toluenesulfonic acid (100
mg), and benzene (125 mL) were placed in a 500 mL round-
bottom flask equipped with a magnetic stir bar, a Dean-Stark
trap, and a condenser. The mixture was stirred and held at
reflux for 12 h and then cooled. An additional 125 mL of
benzene was added, followed by triethylamine (5 mL). The
benzene solution was then transferred to a separatory funnel,
washed with water (2 × 100 mL), and filtered through a Na2-
SO4 cone into a tared 500 mL round-bottom flask. The
benzene was removed on a rotary evaporator, and traces of
benzene were removed under high vacuum. The solid 3 so
obtained (20 g, 55 mmol, 89%), mp 75-78 °C, was of sufficient
purity for use in the next step: 1H NMR δ 3.43 (s, 3H), 4.00
(m, 2H), 4.12 (m, 2H), 4.21 (m, 2H), 4.38 (m, 2H), 6.03 (s, 1H),
6.78 (d, 1H), 7.00 (t, 1H), 7.25 (t, 1H), 7.31 (d, 2H), 7.50 (dd,
1H), 7.80 (d, 2H); 13C NMR (CDCl3) δ 21.56, 65.09, 65.92, 67.89,
98.93, 112.09, 121.23, 126.44, 127.06, 127.74, 128.17, 129.74,
130.11, 132.66, 144.79, 156.06; MS (CHCl3) m/ e 364 (47), 199
H2(OC2OP or ) (7). A 1-L two-necked round-bottom flask
equipped with a condenser, magnetic stir bar, and an air
injection inlet was charged with 600 mL of doubly distilled
propionic acid. The acid was brought to near reflux, where-
upon the tetraaldehyde 6 (1.0 g, 1.74 mmol) was added. The
mixture was heated at reflux while being stirred. When the
aldehyde had all dissolved, freshly distilled pyrrole (730 mg,
10.9 mmol) was added and a trickle of air (120 mL/min) was
blown through the refluxing solution. After 1.25 h the
propionic acid was completely removed by distillation under
reduced pressure. The dry, purple-black residue that re-
mained was dissolved with 200 mL of hot CHCl3, filtered
through Celite, and loaded onto a 5 × 30 cm silica gel column.
Flash chromatography (neat CHCl3, increasing to 5% MeOH/
CHCl3) gave a fast-running fraction that was collected and
reeluted through silica (2 columns: 1% MeOH/CHCl3 followed
by 1% acetone/CH2Cl2). The dark red band so obtained was
collected, concentrated to dryness on a rotary evaporator, and
recrystallized from CH2Cl2/hexane to give the product (99 mg,
0.15 mmol, 10.7%) as a lustrous purple powder: UV-vis
(CHCl3) λmax (log ꢀ) 402 (sh, 4.92), 421 (5.56), 484 (sh, 3.48),
518 (4.24), 551 (3.68), 591 (3.75), 647 (3.37); 1H NMR (CDCl3)
δ -3.16 (s, 2H), 2.41 (m, 4H), 2.55 (m, 4H), 3.63 (s, 2H), 3.69
(m, 4H), 3.85 (m, 4H), 7.35 (d, 4H), 7.50 (t, 4H), 7.76 (t, 4H),
8.28 (d, 4H), 8.71 (s, 8H); 13C NMR (DMSO-d6, 70 °C) δ 67.76,
71.37, 106.90, 121.43, 129.05 (broad), 129.91, 131.62 (broad),
134.37, 134.52, 139.88, 160.28; FAB MS (3-nitrobenzyl alcohol)
m/ e 925 (100); FAB HRMS calcd for C58H44O8N4‚H+ m/ e
925.3237, found 925.3260. Anal. Calcd for C58H44N4O8: C,
75.31; H, 4.79; N, 6.06. Found: C, 75.03; H, 5.01; N, 5.90.
(28) Collman, J . P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.; Lang,
G.; Robinson, W. T. J . Am. Chem. Soc. 1975, 97, 1427-1439.
(29) Anslow, W. K.; Raistrick, H. J . Chem. Soc. 1939, 1446-1457.