Steric and electronic effects of substituents on the yield of 5,15-substituted octaalkylporphines

Article abstract of DOI:10.1023/A:1013936027631

The electronic and steric effects of peripheral substituents on the yield of 5,15-diphenyloctaalkyl-porphines were studied. It was found that the electronic nature of substituents in the starting benzaldehydes exerts almost no yield effect. At the same time, there is some optimal size of substituents, which provides the highest possible yield of porphyrins.

Full text of DOI:10.1023/A:1013936027631

Russian Journal of General Chemistry, Vol. 71, No. 10, 2001, pp. 1656 1659. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 10, 2001,
pp. 1747 1750.
Original Russian Text Copyright
2001 by Syrbu, Lyubimova, Semeikin.
Steric and Electronic Effects of Substituents on the Yield
of 5,15-Substituted Octaalkylporphines
S. A. Syrbu, T. V. Lyubimova, and A. S. Semeikin
Ivanovo State University of Chemical Engineering, Ivanovo, Russia
Received April 19, 2000
Abstract The electronic and steric effects of peripheral substituents on the yield of 5,15-diphenyloctaalkyl-
porphines were studied. It was found that the electronic nature of substituents in the starting benzaldehydes
exerts almost no yield effect. At the same time, there is some optimal size of substituents, which provides the
highest possible yield of porphyrins.
In connection with investigations into the role of
porphyrins in biological systems, of great interest are
5,15-dipenyl-substituted octaalkylporphines I. These
compounds combine merits of two the most well-
understood classes of synthetic porphyrins: meso-
tetraphenylporphyrins II and -oktaalkylporphines
III, since they are more close to natural compounds
than porphyrins II and, in addition, may have groups
amenable to modification.
The aim of the present work was to study the elec-
tronic and steric effects of substituents in the posi-
tion of the starting dipyrrolylmethanes IV (R1 and R2)
and aldehydes (R3) on the yield of porphyrins I.
R1
R2
NH
+ R3CHO
R2
R2
Ph
NH
R2
R2
R2
R3
R1
N
NH
N
N
NH
R3
R1
IV
Ph
Ph
R2
R2
HN
HN
N
R1
R2
R1
R3
R1
R1
R3
HN
HN
NH
R2
R2
Ph
II
H+
[O]
I
I
R2
NH
R2
R1
R1
R1
N
NH
R2
V
HN
N
R1
R1
By the procedure described in [1] we prepared a
series of porphyrins I having various - and meso-
substituents (Table 1). The starting dipyrrolylme-
thanes IV were synthesized from substituted 5-ethoxy-
carbonyl-2-methylpyrroles as described in [2].
R2
R2
III
Earlier we developed a facile synthesis of por-
phyrins I by the condensation of tetraalkyldipyrrolyl-
methanes IV with aldehydes in chloroform in the
presence of a strong organic acid to porphyrinogens
V, followed by in situ oxidation of the latter with
benzoquinone derivatives [1].
By studying the steric effects of substituents in
dipyrrolylmethanes (R2) on the yield of porphyrins I
(Table 1) we found that increase in the length of 3-
and 3 -alkyl substituents in dipyrrolylmethanes IV has
an only slight yield effect, whereas introduction of the
1070-3632/01/7110-1656$25.00 2001 MAIK Nauka/Interperiodica

STERIC AND ELECTRONIC EFFECTS OF SUBSTITUENTS
Table 1. Yield and properties of 5,15-disubstituted octaalkylporphines I
Electronic absorption spectrum,
1657
Porphyrin
Found, %
Calculated, %
Yield,
%
max, nm (log )
Rf
Formula
R1
R2
R3
Ph
I
II III IV Soret
C
H
N
C
H
N
H
Me
61 0.23 621 571 533 502 405 84.0 5.6 10.4 C36H30N4
(3.09) (3.70) (3.53) (4.11) (5.31)
83.4 5.8 10.8
83.4 5.8 10.8
83.4 5.8 10.8
Me
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
66 0.36 626 576 534 506 410 83.8 5.5 10.3 C36H30N4
(3.39) (3.73) (357) (4.14) (5.27)
Me Me
Me Et
Me Pr
Me Bu
Me Pent
Me Hex
68
619 575 542 508 409 84.0 5.4 10.6 C40H38N4
(3.03) (3.82) (3.70) (4.19) (5.29)
64 0.40 625 574 540 508 410 83.1 6.3 10.6 C44H46N4
(3.46) (3.92) (3.82) (4.28) (5.40)
83.6 6.7
83.9 7.9
84.0 8.4
84.1 8.8
84.3 9.2
87.4 6.1
83.7 7.4
83.9 7.9
84.1 8.4
9.8
8.2
7.6
7.1
6.5
6.4
8.9
8.2
7.5
47 0.45 625 574 540 508 409 83.2 8.3 8.5 C48H54N4
(3.45) (3.86) (3.78) (4.22) (5.31)
54 0.50 622 575 541 508 410 83.4 8.8 6.8 C52H62N4
(3.42) (3.90) (3.73) (4.27) (5.38)
41 0.55 625 575 541 509 410 83.8 9.0 7.2 C56H70N4
(3.37) (3.89) (3.77) (4.25) (5.34)
41 0.23 625 574 542 509 410 83.9 9.5 6.6 C60H78N4
(3.19) (3.68) (3.56) (4.04) (4.97)
Me Ph
CH2
23 0.36 627 577 543 510 414 87.9 5.8 6.3 C64H54N4
(3.42) (3.93) (3.80) (4.32) (5.39)
Et Me
43 0.66 629 580 546 514 412 84.2 7.3 8.5 C44H46N4
(3.67) (3.87) (3.70) (4.17) (5.20)
Et Et
46 0.40 627 575 542 508 410 83.4 8.2 8.4 C48H54N4
(3.30) (3.87) (3.76) (4.25) (5.35)
Bu Me
Me Et
Me Bu
Me Bu
Et Et
16 0.45 630 582 547 517 413 84.7 8.1 7.2 C52H62N4
(3.69) (3.89) (3.72) (4.13) (5.21)
29 0.50 620 566 532 499 398 80.8 7.7 11.5 C32H38N4
(3.83) (3.91) (4.06) (4.18) (5.21)
80.3 8.0 11.7
H
26 0.55 620 567 534 498 400 81.9 8.9 9.2 C40H54N4
(3.62) (3.72) (3.90) (4.00) (5.08)
81.3 9.2
81.5 9.4
81.3 9.2
82.3 10.4
9.5
9.1
9.5
7.4
Me
Et
45 0.41 623 583 551 514 413 81.9 9.3 8.8 C42H58N4
(2.80) (3.81) (3.64) (4.22) (5.32)
37 0.36 647 579 543 sh 512 412 81.8 9.1 9.3 C40H54N4
(3.20) (3.79) (3.58) (4.20) (5.34)
Me Bu
Me Bu
Me Bu
Me Bu
Hex
21 0.66 623 581 547 513 413 82.9 10.2 6.9 C52H78N4
(2.82) (3.82) (3.60) (4.22) (5.36)
4-NO2
C6H4
52 0.27 627 577 544 510 410 75.7 7.0 9.7 C36H30N6O4 75.0 7.3 10.1
(3.52) (3.93) (3.88) (4.28) (5.29)
3-NO2
C6H4
60 0.36 629 577 544 510 411 75.5 7.1 9.7 C36H30N6O4 75.0 7.3 10.1
(3.48) (3.92) (3.88) (4.26) (5.25)
2-NO2
C6H4
45 0.29; 632 579 546 512 411 75.5 7.5 9.9 C36H30N6O4 75.0 7.3 10.1
0.22 (3.62) (3.91) (3.90) (4.23) (5.24)
Me Bu
4-OMe
C6H4
56 0.30 624 575 543 510 412 80.0 8.5 7.3 C54H66N4O2 80.8 8.3
(3.60) (3.89) (3.75) (4.26) (5.39)
7.0
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 10 2001

1658
SYRBU et al.
Table 2. 1H NMR spectra of 5,15-disubstituted octaalkylporphines I, , ppm
Porphyrin
R2
NH
meso-H
R1
R2
R3
R1
R3
Me
Me
Me
Me
Et
Pr
Ph
Ph
Ph
2.76 sa
2.21 s
2.29 s
10.20 s
10.23 s
10.17 s
2.16 s
2.38 s
2.17 s
3.14 s
8.17 m, 7.87 m
8.11 m, 7.78 m
8.14 m, 7.90 m
2.75 q, 1.08 t
3.59 t, 1.75 m,
0.98 t
Me
Me
Bu
Ph
Ph
2.42 s
2.37 s
10.17 s
10.24 s
2.41 s
2.46 s
3.91 t, 2.07 m,
1.63 m, 1.03 t
3.98 t, 2.20 m,
1.72 m, 1.53 m,
0.96 m
7.98 m, 7.68 m
8.08 m, 7.72 m
Pent
Me
Hex
Ph
2.37 s
10.17 s
2.40 s
3.82 t, 2.19 m,
1.55 m, 1.46 m,
0.86 t
8.13 m, 7.77 m
Et
Et
Bu
Me
Et
Me
Ph
Ph
Ph
2.31 s
2.37 s
2.32 s
10.06 s
10.33 s
10.12 s
2.79 q, 1.08 t 3.44 s
2.77 q, 1.08 t 2.84 q, 1.08 t
2.81 t, 1.4 m, 3.45 s
1.01 t
7.94 m, 7.70 m
8.06 m, 7.83 m
7.99 m, 7.72 m
Me
Me
Et
Bu
H
H
4.06 s
3.82 s
10.01 s
9.91 s
3.47 s
3.47 s
2.83 q, 1.08 t
3.92 t, 2.19 m,
1.64 m, 1.11 t
3.91 t, 2.20 m,
1.65 m, 1.06 t
3.91 t, 2.09 m,
1.63 m, 1.10 t
3.87 t, 2.03 m
1.66 m, 1.02 t
3.91 t, 2.00 m,
1.65 m, 1.06 t
3.85 t, 2.10 m,
1.67 m, 1.03 t
3.93 t, 2.14 m;
1.67 m; 1.03 t
3.99 t, 2.18 m,
1.67 m, 1.09 t
Me
Me
Me
Me
Me
Me
Me
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Hex
2.44 s
2.49 s
2.47 s
2.41 s
2.49 s
2.48 s
2.45 s
10.17 s
10.20 s
10.17 s
10.17 s
10.12 s
10.18 s
10.19 s
2.37 s
2.27 s
2.33 s
2.41 s
2.42 s
2.50 s
2.53 s
2.69 t, 1.65 m,
1.42 m, 0.84 t
8.39 d, 7.96 d
4-NO2C6H4
3-NO2C6H4
2-NO2C6H4
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
8.92 m, 7.77 m
8.52 m, 8.08 m,
7.77 m
7.82 d, 7.14 d,
4.00 s
7.61 m, 7.55 m,
3.88 s
7.78 m, 7.65 m,
3.66 s
a
With addition of trifluoroacetic acid.
bulky benzyl residue reduces the yield considerably.
This result implies that bulky substituents in the 3
and 3 positions of dipyrrolylmethanes prevent forma-
The yield of porphyrins I also decreases with in-
creasing size of 4- and 4 -substituents in dipyrrolyl-
methanes (R1), which is probably associated with
tion of conformation IVA, which is required for con- steric hindrance to condensation.
densation, and dipyrrolylmethanes are present pri-
marily in the energetically more favorable transoid
The steric effects of substituents in aldehydes on
conformation IVB.
the yield of porphyrins I is a more complicated case
R1 R2 (Table 1). In going from formaldehyde to acetic al-
dehyde the yield of porphyrins I strongly increases.
Further increase in the alkyl chain length (R3 = Et)
NH
NH
HN
R1
R1
R1
NH
and a change to benzaldehyde only slightly affect the
yield of porphyrin I. However, at R3 = Hex the yield
is slightly decreased, while with aldehydes with a
R2
R2
A
R2
B
IV
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 10 2001

STERIC AND ELECTRONIC EFFECTS OF SUBSTITUENTS
1659
branched alkyl chain (R3 = i-Pr, s-hexyl) no por-
phyrins are formed at all, probably, by steric reasons,
too.
BS-497 spectrometer at 100 MHz (internal reference
HMDS) (Table 2). The purity of the products was
confirmed by elemental analysis and TLC on Silufol
plates (eluent benzene heptane, 1:1). Samples for
elemental analysis were dried in a vacuum for 4 h at
the boiling point of toluene.
The experimental evidence (Table 1) shows that
the electronic nature of substituents and their position
in the starting benzaldehydes have almost no effect
of the yield of of porphyrins I, and only with 2,6-di-
5,15-Disubstituted octaalkylporphines I. To a
substituted benzaldehydes the yield is strongly re- solution of dipyrrolylmethane IV {prepared from
duced, or, in certain cases (R3 = 2,6-Cl2C6H3, 2,6-
Me2C6H3), porphyrins I are not formed at all.
2.3 mmol of corresponding 5,5 -bis(ethoxycarbonyl)-
pyrrolylmethane by the procedure described in [1]}
and 2.3 mmol of corresponding aldehyde in 200 ml of
chloroform we added with stirring under CO2 a solu-
tion of 3 mmol of chloroacetic acid in 30 ml of chloro-
form. The mixture was stirred in the dark for 4 h,
treated with 3.5 mmol of o-chloranil, and heated
under reflux for 1 h or left to stand for 12 h at room
temperature. The solvent was removed, the residue
was washed with 5% aqueous sodium hydroxide and
water, and dried at room temperature until constant
weight. For purification the porphyrin was dissolved
in 50 ml of chloroform and subjected to chromato-
graphy first on alumina (activity grade II) and then on
Silica gel L 100/250, eluent chloroform. The solvent
was evaporated to 5 ml, and the porphyrin was pre-
cipitated with 30 ml of methanol, filtered off, and
dried at room temperature until constant weight. The
yields and properties of the resulting porphyrins are
listed in Table 1.
It should be noted that condensations of dipyrro-
lylmethanes IV with aldehydes under the action of
acids may involve, depending on conditions, rearran-
gement both of the starting dipyrrolylmethanes and of
porphyrinogens V [3]. As a result, the reaction mix-
tures contain admixtures (1 3%) of meso-mono-
substituted or meso-unsubstituted porphyrins. The
yield of these by-products becomes comparable with
the yield of the major product, and under certain
conditions they may turn to be the only porphyrins
resulting from the synthesis. However, owing to the
lower polarity, the by-products are readily separable
from the major products and can be identified by the
hypsochromic shift of bands (by 5 10 nm) in the elec-
tronic absorption spectra.
Thus, as follows from the resulting data, the yield
of porphyrins I is mostly affected by steric effects of
substituents in the starting dipyrrolylmethanes IV and
aldehydes; therewith, there is some optimal size of
substituents, which provides the highest possible yield
of porphyrins I.
REFERENCES
1. Semeikin, A.S., Lyubimova, T.V., and Golubchi-
kov, O.A., Zh. Prikl. Khim., 1993, vol. 66, no. 3,
pp. 710 712.
EXPERIMENTAL
2. Berezin, M.B., Semeikin, A.S., and V’yugin, A.I., Zh.
Fiz. Khim., 1996, vol. 70, no. 8, pp. 1364 1367.
The electronic absorption spectra were measured
on a Specord M-400 instrument in chloroform. The
1H NMR spectra in CDCl3 were measured on a Tesla
3. Gunter, M.J. and Mander, L.N., J. Org. Chem., 1981,
vol. 46, no. 23, pp. 4792 4795.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 10 2001