Synthesis and basic properties of 5-aza-2,3,7,8,12,13,17,18- octamethylporphyrin

Article abstract of DOI:10.1134/S1070363208100265

5-Aza-2,3,7,8,12,13,17,18-octamethylporphyrin was synthesized and its basic properties were studied by means of spectrophotometric titration. Protonation of nitrogen atoms in the tetrapyrrolic macrocycle with the ethanolic sulfuric acid is found to be a two-step process. Corresponding ionization constants and the concentration ranges of existence of mono-and dicationic forms of the azaporphyrin under investigation are evaluated.

Full text of DOI:10.1134/S1070363208100265

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 10, pp. 1972–1976. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © Yu.B. Ivanova, Yu.I. Chyrakhin, A.S. Semeikin, R.S. Kumeev, N.Zh. Mamardashvili, 2008, published in Zhurnal Obshchei Khimii,
2008, Vol. 78, No. 10, pp. 1736–1740.
Synthesis and Basic Properties
of 5-Aza-2,3,7,8,12,13,17,18-octamethylporphyrin
Yu. B. Ivanovaa, Yu. I. Chyrakhina, A. S. Semeikinb,
R. S. Kumeeva, and N. Zh. Mamardashvilia
a Institute of Solution Chemistry, Russian Academy of Sciences,
ul. Akademicheskaya 1, Ivanovo, 153045 Russia
e-mail: ybi@isc-ras.ru
b Ivanovo State University of Chemistry and Technology, Ivanovo, Russia
Received May 15, 2008
Abstract—5-Aza-2,3,7,8,12,13,17,18-octamethylporphyrin was synthesized and its basic properties were
studied by means of spectrophotometric titration. Protonation of nitrogen atoms in the tetrapyrrolic macrocycle
with the ethanolic sulfuric acid is found to be a two-step process. Corresponding ionization constants and the
concentration ranges of existence of mono- and dicationic forms of the azaporphyrin under investigation are
evaluated.
DOI: 10.1134/S1070363208100265
Recognition and selective binding of anions in
solutions is an important problem of modern chemistry
and the material sciences. Analysis of the reported data
[1–5] shows that with the purpose of creation of
molecular devices for detecting anions the polypyrrole
macrorings are widely investigated. In such system the
anion is bound due to formation of several H-bonds
with the proton-donating NH-groups of the pyrrole
rings. A characteristic example is evaluation of the
anion concentrations in solutions using such
fluorescent dye as 3,12,13,22-tetraethyl-8,17-bis-[di-
(hydroxyethyl)aminocarbonylethyl]-2,7,18,23-tetrame-
thylsapphyrin. The faults of this method are the
relatively low sensitivity and the narrow range of the
substrate concentrations (10–3–10–1 M) that can be
evaluated.
tor of the halide ions [7]. The method developed
permits to detect the halide ions in the substrate
concentration range 10–6–10–1 M that exceeds signif-
icantly the level of the above-mentioned analog on the
basis of neutral sapphyrin derivative [1].
In the presented work with the purpose of
enhancing sensitivity and extending the range of the
evaluated concentrations of halide ions in solutions we
synthesized 5-aza-2,3,7,8,13,17,18-octamethylporphy-
rin and studied its basic properties in the solutions of
sulfuric acid in ethanol. The process of protonation of
nitrogen atoms of the tetrapyrrole macroring is shown
to proceed in two steps at the intracyclic nitrogen
atoms [Eqs. (1), (2)].
kb1
H2P + H+
H3P+,
(1)
We have offered prevoiusly [6] to use the
protonated forms of porphyrins as the receptors for the
halide ions (Hal–). In part, it was shown by means of
the direct titration of 3,7,13,17-tetramethyl-2,8,12,18-
tetrabutylporphyrines mono (H3P+) and dications
(H4P2+)with the solutions of halide salts that therewith
stable H4P2+·Hal– and H4P2+·2Hal– complexes are
formed in acetonitrile. On the basis of analysis of the
dependences of the fluorescence intensity and lifetime
on the concentration of iodide ions in solution was
offered to use H4P2+ as a molecular fluorescent recep-
kb2
H3P+ + H+
H4P2+.
(2)
Here H2P, H3P+, and H4P2+ are the molecular, mono-,
and diprotonated forms of corresponding porphyrin.
The concentration range of existence of mono- and
dicationic forms of target porphyrin and corresponding
ionization constants were evaluated.
5-Aza-2,3,7,8,12,13,17,18-octamethylporphyn was
prepared in 69% yield by the reaction of 1,19-
1972

SYNTHESIS AND BASIC PROPERTIES
1973
dibromo-2,3,7,8,12,13,17,18-octamethylbiladiene a,c-
dihydrobromide with sodium azide in DMF. The key
1,19-dibromo-2,3,7,8,12,13,17,18-octamethylbiladiene
a,c-dihydrobromide was synthesized by condensation
of 5,5'-dicarboxy-3,3',4,4'-tetramethyldipyrrolylmethane
with two equivalents of 2-bromo-3,4-dimethyl-5-
formylpyrrole under the action of hydrobromic acid in
methanol.
Me
CO2H
Me
Me
Me
Me
Me
Me
NH
NH
(1) PhCOCl, DMF
(2) Br2, AcOH
+
Br
CHO
N
H
N
H
CO2H
Me
III
I
II
HBr, MeOH
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
+
NH HN
NH
N
NaN3, DMF
2Br−
Br
N
+
HN
NH
HN
N
Me
Me
Me
Me
Me
IV
V
protonated form of the substance V and may be
described by the Eq. (1). Further increase in the acid
concentration leads to appearance of new set of
To the acid–base interactions of azaporphyrins with
acids the intracyclic (pyrrolenine) as well as the
extracyclic (meso) nitrogen atoms can be involved.
Therefore it is principally important to establish the
number and the location of electron-donating reaction
centers in the macroring. Ionization studies of the
compound V in the ethanol–sulfuric acid mixtures by
means of the spectrophotometric titration showed that
protonation of tetrapyrrole macroring is accompanied
by the consequent (depending on the acid concentra-
tion) formation of two sets of spectral curves. Each set
has its own assembly of the isobestic points (Fig. 1).
A
2.0
1.0
0.0
The study of ionization of compound V in the
1×10–5–3×10–4 M concentration range of sulfuric acid
(related to the first set of spectral curves) showed the
existence of one step on the corresponding titration
curve. It is a strait line with the slope angle tangent
close to unity (Fig. 2). That means that the acid-base
interaction in the system of compounds V–C2H5OH–
H+ in the above-mentioned range of the sulfuric acid
concentrations leads to formation of the mono-
550
600
λ, nm
Fig. 1. Alterations in the electron absorption spectra of the
V–C2H5OH–H2SO4 system [Cporph 1.81×10–5 M, C(H2SO4)
1×10–5–6×10–4 M].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008

1974
A
IVANOVA et al.
(b)
(a)
(b)
(a)
A
A
A
1.4
1.2
2.10
2.05
2.00
1.95
1.90
1.85
1.80
1.75
2
1.0
0.8
0.6
1.0
0.0
35 40 45 50
8
16 24
C×105, M
C×105, M
1
0
500
600
λ, nm
600
λ, nm
Fig. 2. (a) The curve of spectrophotometric titration of the
product V (1.81×10–5 M) with sulfuric acid (1×10–5–
3×10–4 M) at the wavelength λ 598 nm (298 K). (b) Altera-
tions in the electron absorption spectra of the V–
C2H5OH–H2SO4 system [Cporph 1.81×10–5 M, C(H2SO4)
1×10–5–3×10–4 M].
Fig. 3. (a) The curve of spectrophotometric titration of the
product V (1.81×10–5 M) with sulfuric acid (3.21×10–4–
6×10–4 M) in ethanol at the wavelength λ = 598 nm (298 K).
(b) Alterations in the electron absorption spectrum in the
V–C2H5OH–H2SO4 system [Cporph 1.81×10–5 M, C(H2SO4)
3.21×10–4–6×10–4 M].
spectral curves forming another assembly with its own
set of isobestic points (Fig. 3).
Porphyrin
Kb1
VI1
63
V
353
398
The presence of one step only on the corresponding
titration curve of azaporphyrin in the acid
concentration range 3.21×10–4–6×10–4 M (correspond-
ing to the second set of spectral curves) permits to
describe the protonation of monoprotonated form of
the macroring by the Eq. (2).
Kb2
65
The values of ionization constants of the
compounds V and VI and the concentration ranges of
existence of their mono- and dicationic forms show
that in the solution of sulfuric acid in ethanol the basic
properties of the porphyrins V and VI are comparable.
At the same time formation of the cations V is
accompanied by the clear and easily identified
responce in the visible range of the absorption
spectrum (Fig. 4) that creates the conditions for more
effective control of physicochemical processes taking
place with the participation of tetrapyrrole chromo-
phore as compared to the compound VI.
The transformation of the two-band electron ab-
sorption spectrum of moderate intensity [λmax 535 nm
(log ε 3.74), λmax 612 nm (log ε 3.8)] to the one-band
[λmax 590 nm (log ε 4.07)] electron absorption
spectrum of high intensity (Fig. 1) observed in the
course of the macrocycle protonation according to the
published data [11] and the results obtained by us [10]
confirms that just the intracyclic nitrogen atoms are
protonated. Hence, nitrogen atoms in the meso-posi-
tions of the macrocycle V do not take part in the acid-
base interactions. The spectral changes established
permit to calculate the corresponding stepwise
ionization constants by means of the standard proce-
dure [6, 10]. The constants of formation of the
protonated forms H3P+ and H4P2+ in the H2P–C2H5OH–
H2SO4 system [Cporph ~ 1.5×10–5–1.8×10–5 M, C(H2SO4)
2×10–6–6×10–4 M] are the following:
Thus, in the presented work mesomonoazapor-
phyrin V was synthesized and its basic properties were
studied by means of spectrophotometric titration.
Protonation of the intracyclic nitrogen atoms of the
tetrapyrrole chromophore synthesized in the solution
of sulfuric acid in ethanol is found proceeding in two
1
VI is 3,7,13,17-tetramethyl-2,8,12,18-tetrabutylporphyrin [6].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008

SYNTHESIS AND BASIC PROPERTIES
1975
steps. The corresponding ionization constants and the
A
concentration ranges of existence of tetrapyrrolic
mono- and dications are evaluated. The data obtained
show that application of the synthesized azaporphyrin
as a key substance for creation of pH-switching molec-
ular optical devices with the purpose of detecting and
selective binding of anions in solutions is promising.
0.5
2
1
EXPERIMENTAL
1H NMR spectra were taken on a Bruker VC-200
(200 MHz) spectrometer in CDCl3 against internal
TMS. Electron impact mass spectra were obtained on a
MX-1310 spectrometric complex, the ionizing electron
energy 70 eV, the ionization chamber temperature
150–200°C. Spectrophotometric titration of azapor-
phyrin with sulfuric acid in ethanol was carried out on
a Varian Cary 100 spectrophotometer. Experimental
procedure and treating of the data obtained are
described in [6, 10]. The protonation constants were
calculated according to the Eqs. (3) and (4).
500
600
700
λ, nm
Fig. 4. The electron absorption spectrum of the compounds
(1) V and (2) VI in the H4P2–C2H5OH–H2SO4 system
[Cporph ~1.5×10–5–1.8×10–5 M, C(H2SO4) 1×10–4–6×10–4 M]
at 298 K.
of water. The mixture obtained was filtered, the filtrate
was acidified with the diluted hydrochloric acid, and
the precipitate formed was filtered off, washed with
water and dried on air at 30°C. Yield 3.3 g (98%).
рkb1 = Н0 + log [C(H3Р+)/C(H2Р)],
рkb2 = Н0 + log [C(H4Р2+)/C(H3Р+)].
(3)
(4)
1,19-Dibromo-2,3,7,8,12,13,17,18-octamethyl b i l -
adien-a,c dihydrobromide (IV). Pyrrole II, 0.7 g, and
0.5 g of dipyrrolylmethane III were dissolved in 20 ml
of boiling methanol. A solution obtained was treated
with 5 ml of concentrated hydrobromic acid, cooled,
and kept for 12 h at 5°C. The precipitate formed was
filtered off, washed consequently with cooled
methanol and ether, and dried in air at room
temperature. Yield 0.9 g (71%). Electron absorption
spectrum, λmax, nm (log ε): 459 (4.83), 536 (5.06)
(methylene chloride). The product was used without
further purification.
The error of evaluation of the corresponding
constants was 3–5%.
2-Formyl-5-bromo-3,4-dimethylpyrrole (II). To a
solution of 6.8 g of 3,4-dimethylpyrrole I [8] in 40 ml
of benzene and 20 ml of DMF 9 ml of benzoyl
chloride was added with stirring and cooling. The
mixture obtained was stirred for 1 h, the precipitate
formed was filtered off, washed with benzene, dried
and dissolved in 35 ml of acetic acid. The solution
obtained was treated with 3.5 ml of bromine. The
reaction mixture was stirred for 15 min, and then
treated with a solution of 12 g of sodium acetate
trihydrate in 100 ml of water and heated on a water
bath for 0.5 h. The precipitate formed was filtered off,
dried in air at room temperature and crystallized from
5-Aza-2,3,7,7,12,13,17,18-octamethylporphyn (V).
A mixture of 0.5 g of biladiene-a,c IV, 0.3 g of sodium
azide, and 50 ml of DMF was boiled for 0.5 h. Then
the reaction mixture was poured to 200 ml of water,
the precipitate formed was filtered off, washed with
water, and dried in air at 70°C. The product obtained
was dissolved in a mixture of 1 ml of trifluoroacetic
acid and 50 ml of chloroform, the solution obtained
was filtered and treated with 2 ml of diethylamine. The
precipitate formed was filtered off, washed with
chloroform, and dried in air at 70°C. Yield 0.2 g
(69%). The electron absorption spectrum, λmax, nm
(log ε): 612 (4.18), 561 (3.80), 538 (4.20), 503 (3.81),
376 (4.95) (tetrachloroethane). Mass spectrum, m/z
(Irel, %): 424.55(77), [M + 1].
1
methanol. Yield 9.9 g (68%). H NMR spectrum
(CDCl3, HMDS), δ, ppm: 9.23 (1H, CHO); 2.17 s (3H,
3-CH3), 1.83 s (3H, 4-CH3).
5,5'-Dicarboxy-3,3',4,4'-tetramethyldipyrrolyl-
methane (III). A solution of 4.0 g of 5,5'-bis(ethoxy-
carbonyl)-3,3',4,4'-tetramethyldipyrrolylmethane [9] in
100 ml of ethanol was heated to boil and treated with a
solution of 3.0 g of potassium hydroxide in 20 ml of
water. The reaction mixture was refluxed for 4 h,
ethanol was distilled off in a vacuum at room
temperature, and the residue was diluted with 100 ml
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008

1976
IVANOVA et al.
Korean Chem. Soc., 2003, vol. 24, p. 661.
ACKNOWLEDGMENTS
5. Gale, P.A., Sessler, J.L., and Kral, V., Chem Commun.,
1998, p. 1.
This work was financially supported by Russian
Fundation for Basic Research (grant no. 08-03-00009,
08-03-90000-Bel) and the Program no. 7 of the
Department of Chemistry and the Mateial Sciences of
Russian Academy of Sciences “Chemistry and Physico-
chemistry of Supramolecular Systems and Clusters.”
6. Ivanova, Yu.B., Sheinin, V.B., and Mamardashvili, N.Zh.,
Zh. Obshch. Khim., 2007, vol. 77, no. 8, p. 1380.
7. Kruk, N.N., Starukhin, A.S., Mamardashvili, N.Zh.,
Sheinin, V.B., and Ivanova, Yu.B., Zh. Prikl. Spektr.,
2007, vol. 74, no. 6, p. 750.
8. Ichimura, K., Ichikava, S., and Imamura, K., Bull.
Chem. Soc. Japan., 1976, vol. 49, no. 4, p. 1157.
9. Berezin, M.B., Semeikin, A.S., and V’yugin, A.I., Zh.
Fiz. Khim., 1996, vol. 70, no. 8, p. 1364.
REFERENCES
1. Sessler, J.L., Davis, J.M., Kral, V., Kimbrough, T., and
Lynch, V., Org. Biol. Chem., 2003, vol. 1, p. 4113.
2. Gale, P.A., Sessler, J.L., Allen, W.E., Tvermoes, N.A.,
and Lynch, V., Chem. Commun., 1997, p. 665.
3. Sessler, J.L., Anzenbacher, P., Miyaji, H., Jursikova, K.,
Bleasdale, E.R., and Gale, P.A., Ind. Eng. Chem., Res.,
2000, vol. 39, p. 3471.
10. Ivanova, Yu.B., Churakhina, Yu.I., and Mamardashvi-
li, N.Zh., Abstract of Papers, VII School Conf. of Young
Scientists of the SNG States on the Chemistry of
Porphyrins and Related Compounds, 2007, Odessa, p. 86.
11. Dzilin’ski, K., Vrublevskii, A.I., Sinyakov, G.N., and
Gurinovich, G.R., Rus. J. Appl. Spectr., 1980, vol. 33,
no. 1, p. 114.
4. Hong, S.L., Ka, J.W., Won, D.H., and Lee, C.H., Bull.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008