Synthesis and spectral properties of [3-(heptyloxy)phenoxy]acetic acid and its derived meso-sibstituted tetrabenzoporphyrins

Article abstract of DOI:10.1134/S1070363208090259

3-Heptyloxyphenol was obtained by reaction of resorcinol with 1-bromoheptane. Further alkylation with monochloroacetc acid resulted in the synthesis of [3-(heptyloxy)phenoxy]acetic acid. Heating of the latter with phthalimide in the presence of zinc aceta

Full text of DOI:10.1134/S1070363208090259

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 9, pp. 1802–1807. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.E. Galanin, L.A. Yakubov, G.P. Shaposhnikov, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 9, pp. 1572–
1577.
Synthesis and Spectral Properties
of [3-(Heptyloxy)phenoxy]acetic Acid
and Its Derived meso-Sibstituted Tetrabenzoporphyrins
N. E. Galanin, L. A. Yakubov, and G. P. Shaposhnikov
Ivanovo State Chemical Technological University
pr. F. Engel’sa 7, Ivanovo, 153000 Russia
e-mail: ttoc@isuct.ru
Received April 4, 2008
Abstract―3-Heptyloxyphenol was obtained by reaction of resorcinol with 1-bromoheptane. Further alkylation
with monochloroacetc acid resulted in the synthesis of [3-(heptyloxy)phenoxy]acetic acid. Heating of the latter
with phthalimide in the presence of zinc acetate afforded zinc complexes of meso-[(3-heptyloxy)phenoxy]
tetrabenzoporphyrins whose demetalization gave free porphyrin bases. Spectral properties of the synthesized
compounds were studied.
DOI: 10.1134/S1070363208090259
meso-Substituted tetrabenzoporphyrins are now
intensively studied. The interest in them is defined by
the fact that these compounds possess quite valuable
physicochemical and spectral properties for application
as materials for photodynamic cancer therapy [1–4]
and nonlinear optics [5, 6]. Such properties of meso-
substituted tetrabenzoporphyrins makes urgent
synthesis of new compounds of this group for their
further studies in various aspects.
excess of resorcinol (II) in the presence of K2CO3 in
DMF under reflux for 7 h to obtain 3-(heptyloxy)
phenol (III). Using a large excess of resorcinol (II)
allowed us to avoid dialkylation forming 1,3-bis-
(heptyloxy)benzene. Thus, compound III is formed by
Scheme 1.
Scheme 1.
OC7H15
OH
K2CO3
In the recent time new methods of synthesis of a
significant number of meso-arylsubstituted tetrabenzo-
porphyrins have been developed. However, the
information concerning meso-aryloxy-substituted tetra-
benzoporphyrins is scarce [7], even though such
compounds can be fairly interesting for practical
purposes. We failed to find in the literature any
information on the synthesis and properties of meso-
phenoxy-substituted tetrabenzoporphyrins containing
bulky substituents in the phenoxy group, which is
connected, in our opinion, with the absence of methods
for preparation of substituted phenoxyacetic acids.
Therefore, in the present work we set ourselves the
task to develop a method for synthesis of [3-
(heptyloxy)phenoxy]acetic acid (I) and its derived
meso-substituted tetrabenzoporphyrins.
+ BrC7H15
OH
OH
III
II
Compound III is a viscous light yellow liquid
readily soluble in most organic solvents. Its
composition and structure were confirmed by
elemental analysis and vibrational and 1Н NMR
spectroscopy.
The IR spectrum of phenol III shows a broad band
in the region of 3580 cm–1 due to hydroxyl О–Н
vibrations, a strong band in the region of 2987 cm–1
due to stretching vibrations of alkyl С–Н bonds, and
bands at 1221 and 1188 cm–1, which correspond to С–
О vibrations and thus confirm presence of an ether
group.
Acid I was obtained by a two-step procedure. In the
first step, we reacted 1-bromoheptane with a fivefold
1802

SYNTHESIS AND SPECTRAL PROPERTIES
1803
The 1Н NMR spectrum of compound III contains a
multiplet in the region of 6.98–6.71 ppm, cor-
responding to the resonance of four protons of the
benzene ring. The singlet at 4.84 ppm belongs to the
hydroxyl proton, the triplet in the region of 3.82–
3.76 ppm, to two α-СН2 protons, the multiplet in the
region of 1.44–1.28 ppm, to 10 protons of the remain-
OC7H15
ing five methylene groups, and the triplet at 0.89 ppm,
to three protons of the terminal methyl group.
In the second step, by the alkylation of phenol III
with monochloroacetic acid in the presence of K2CO3
in DMF we obtained acid I (Scheme 2).
OC7H15
K2CO3
+ ClCH2CO2H
OCH2CO2H
OH
III
I
Compound I is a wax-like yellow substance readily
soluble in chloroform, benzene, and acetone, soluble in
aqueous alkali, and practically insoluble in water. Its
composition and structure were also confirmed by
elemental analysis and vibrational and 1Н NMR
spectroscopy.
porphyrin compounds, both readily soluble in organic
solvents. These compounds were identified as zinc
meso-mono[(3-heptyloxy)phenoxy]tetrabenzoporphiri-
nate (V) and meso-trans-bis[(3-heptyloxy)phenoxy]
tetrabenzoporphirinate (VI). The synthesis of metal
complexes V and VI can be representhed by the above
Scheme 2.
The IR spectrum of acid I is similar to that of
phenol III, except that the former spectrum contains a
band at 1722 cm–1, which attests presence of a carboxy
group.
We suggest that in this case, due to weaker steric
hindrances, specifically a trans-substituted tetrabenzo-
porphyrin VI is formed. Quantum-chemical calcula-
tions of compound VI and zinc meso-cis-bis[(3-
heptyloxy)phenoxy]tetrabenzoporphirinate by the
semiempirical АМ1 method showed that the energy
gain from the formation of compound VI as compared
with the cis isomer is 28.88 kJ mol–1. This is caused, as
follows from the calculations, by a stronger planarity
and, hence, aromaticity of the porphyrin V molecule.
1
In the Н NMR spectrum of compound I, in the
weakest field region (7.17–7.06 ppm) we observe a
multiplet from the 5-H proton of the benzene ring and
a multiplet in the region of 6.57–6.46 ppm from the 2-,
4-, and 6-H protons. In a stronger field region, there
are a triplet at 3.94–3.88 ppm from two protons of the
methylene group neighboring to carboxyl, a multiplet
at 1.76–1.73 ppm from two protons of the alkoxyl α-
methylene group, a multiplet at 1.43–1.28 ppm from
10 protons of the remaining five methylene groups,
and, finally, a triplet at 0.89 ppm from three protons of
the terminal methyl group.
By treatment of solutions of compounds V and VI
in chloroform with concentrated hydrochloric acid we
synthesized meso-mono[(3-heptyloxy)phenoxy]tetra-
benzoporphyrin
(VII)
and
meso-trans-bis[(3-
heptyloxy)phenoxy]tetrabenzoporphyrin (VIII), res-
pectively. They were also purified by column
chromatography.
We attempted to synthesize zinc meso-tetra[(3-
heptyloxy)phenoxy]tetrabenzoporphyrinate by reaction
of phthalimide VI with acid I in the presence of zinc
oxide. However, upon heating of the reagents at 340°С
for 2 h, a brown melt formed that did not contain even
traces of the target compound. When zinc oxide was
replaced by zinc acetate, the reaction mixture became
green, which gave evidence for the formation of
tetrabenzoporphyrin. In this case, the reaction
proceeded at 320°С and was complete in 30–40 min.
Chromatographic separation of the reaction mixture
showed that, along with unsubstituted zinc
tetrabenzoporphirinate, it contained only two
Porphyrins V–VIII are dark red crystalline
substances readily soluble in a wide series of organic
solvents. Their compositions and structures were
1
confirmed by elemental analysis and vibrational, Н
NMR, and electronic spectroscopy.
The IR spectra of porphyrins V–VIII contain a
series of similar absorption bands formed by vibrations
of alkyl С–Н bonds (2990–2973 cm–1), С–О bonds
(1228, 1186 cm–1), and C–C and C–N bonds (1494 and
1
1464 cm–1). The Н NMR spectrum of complex VI
contains in a weak-field region a multiplet at 8.33–
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 9 2008

1804
GALANIN et al.
Scheme 2.
O
N
N
N
N
OC7H15
Zn(OAc)2
+
Zn
NH
O
O
OC7H15
OCH2CO2H
I
IV
V
H15C7O
N
N
N
N
Zn
+
O
O
OC7H15
VI
8.14 ppm form three meso-protons of the macrocycle,
a multiplet at 7.98–7.65 ppm from 16 protons of the
benzene rings in the isoindole fragments, a multiplet at
6.62–6.32 ppm from four protons of the benzene ring
of the meso-substituent. In a stronger field, a multiplet
at 1.78–1.76 ppm from two alkoxyl α-methylene
protons, a multiplet at 1.41–1.25 ppm from 10 protons
of the remaining five methylene groups, and, finally, a
triplet at 0.88 ppm from three protons of the terminal
we observe, in the Soret region, a weak diffuse band
(446 nm) that is absent from the spectrum of zinc
tetrabenzoporphirinate. This band is assignable to
charge transfer from the electron-donor substituent
onto the macrocycle. In the spectrum of metal-free
prophyrin VII (Fig. 1, spectrum 2), the respective band
at 443 nm is much stronger, and an additional band at
677 nm appears, which, too, is assignable to charge
transfer. The presence in the electronic absorp-
tion spectra of charge transfer bands is also
characteristic of other unsymmetrical tetrabenzo-
porphyrins [9].
1
methyl group. The Н NMR spectrum of complex VI
is similar to that of compound V, but the signals of
protons of the meso-substituent are enhanced, while
those of meso-protons are weaker. In the strongest
In the case of meso-disubstituted porphyrins VI and
VIII (Fig. 2), again, there are two charge-transfer
bands in the Soret region. However, while in the
spectrum of zinc complex VI (Fig. 2, spectrum 1)
these bands have maxima at 441 and 460 nm, in the
spectrum of metal-free compound VIII (Fig. 2, 2)
these bands are slightly stronger, and their maxima are
shifted red by 6 and 9 nm, respectively. The long-wave
charge-transfer band has a maximum at 709 nm, that
is, red shifted from that of meso-mono-substituted
tetrabenzoporphyrin VI by 32 nm.
1
field region of the Н NMR spectra of metal-free
porphyrins VII and VIII we observe signals of
endocyclic imino groups (–2.22 and –2.15 ppm,
respectively).
The electronic absorption spectra of porphyrins V–
VIII (Figs. 1 and 2) are quite similar to the spectra of
unsubstituted tetrabenzoporphyrin and its zinc
complex in terms of the positions of band maxima [8].
This fact suggests that the alkoxy-substituted phenoxy
groups in the meso positions of porphyrins V–VIII
only slightly affect the molecular geometry. However,
in the spectrum of compound V (Fig. 1, spectrum 1),
To confirm the above assumption that meso-
substitution only slightly affects the geometry of
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SYNTHESIS AND SPECTRAL PROPERTIES
1805
D
D
1.5
1.0
0.5
0.0
1.0
0.5
1
2
1
2
0.0
400
500
600
700 λ, nm
400
500
600
700 λ, nm
Fig. 1. Electronic absorption spectra of benzene solutions
of (1) V and (2) VII.
Fig. 2. Electronic absorption spectra of benzene solutions
of (1) VI and (2) VIII.
compounds VII and VIII, we carried out quantum-
chemical calculations of the respective molecules by
the АМ1 method. The calculation results are depicted
in Fig. 3. As seen, molecule VII (Fig. 3a) is planar,
while molecule VIII (Fig. 3b) is slightly saddle-
distorted, but the isoindole fragments deviates from the
conventional plane defined by nitrogen atoms by no
more than 8°.
in films on TlI glass. Elemental analysis was carried
out on a FlashEA 1112 CHNS–O Analyzer.
3-(Heptyloxy)phenol (III). A mixture of 11.0 g of
resorcinol (II), 3.5 g of 1-bromoheptane, 5.5 g of
K2CO3 and 30 ml of DMF was stirred under reflux for
6 h, cooled, diluted with 50 ml of water, acidified with
HCl to рН 2, and extracted with two 30-ml portion of
CCl4. The combined extracts were washed con-
secutively with 10% NaOH, water, 10% HCl, and
water, and the organic solvent was then distilled off.
Yield 3.2 g (78%), viscous light yellow liquid, readily
soluble in benzene, acetone, chloroform, CCl4. IR
Thus, the electronic optical properties of
tetrabenzoporphyrins
with
alkoxy-substituted
phenoxyacetic acid residues in the meso positions are
defined by electronic effects of the substituents only,
unlike meso-phenyltetrabenzoporphyrins [10–12]
whose spectral properties mostly controlled by the
degree of planarity distortion of the macrocycle.
1
spectrum , ν, cm–1: 3580, 2987, 1221, 1188. Н NMR
spectrum, δ, ppm: 6.98–6.71 m (4Н), 4.84 s (1Н),
3.82–3.76 t (2Н), 1.44–1.28 m (10Н), 0.89 t (3Н).
Found, %: С 75.01; Н 10.12. С13Н20О2. Calculated, %:
С 74.96; Н 9.68.
EXPERIMENTAL
[3-(Heptyloxy)phenoxy]acetic acid (I). A mixture
of 3.0 g of phenol III, 2.0 g of monochloroacetic acid,
4.5 g of K2CO3, and 20 ml of DMF was stirred under
reflux for 6 h, cooled, diluted with 30 ml of water, and
acidified with HCl to рН 2. The precipitate dropped
was filtered off, washed with water, and dried. Yield
The electronic absorption spectra were registered
on a Hitachi UV-2001 spectrophotometer. The Н
NMR spectra were taken on a Bruker WM-250
instrument (250 MHz) in CDCl3, internal reference
TMS. The IR spectra were recorded on an Avatar 360
FT-IR spectrophotometer in the region 400–4000 cm–1
1
(а)
(b)
Fig. 3. Geometry of compounds (a) VII and (b) VIII, as given by AM1 calculations.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 9 2008

1806
GALANIN et al.
3.2 g (83%), wax-like yellow substance readily soluble
in chloroform, benzene, acetone, soluble in aqeous
alkali, and insoluble in water. IR spectrum , ν, cm–1:
was removed, and the residue was dissolved in
chloroform and passed through a column of activity
grade II alumina (eluent chloroform ), collecting the
main green zone.
1
3582, 2983, 1722, 1220, 1181. Н NMR spectrum, δ,
ppm: 7.17–7.06 m (1Н), 6.57–6.46 m (3Н), 3.94–3.88
t (2Н), 1.76–1.73 m (2Н), 1.43–1.28 m (10Н), 0.89 t
(3Н). Found, %: С 67.89; Н 8.63. С15Н22О4.
Calculated, %: С 67.65; Н 8.33.
meso-Mono[(3-heptyloxy)phenoxy]tetrabenzopor-
phyrin (VII), yield 0.07 g (76%), dark green powder,
mp 167°С, readily soluble in benzene, chloroform,
acetone, and DMF. Electronic absorption spectrum
(benzene), λmax, nm (log ε): 677 (3.97), 663 (4.16), 614
(4.37), 603 (4.42), 567 (3.98), 443 (4.96), 430 (5.13),
417 (4.93), 389 (4.35). IR spectrum , ν, cm–1: 3232,
Condensation of acid I с phthalimide in the
presence of zinc acetate. A mixture of 2.0 g of acid I,
1.1 g of phthalimide IV and 2.0 g of zinc acetate
dihydrate was heated for 40 min at 320°С, cooled,
dissolved in chloroform, and passed through a column
of activity grade II alumina (eluent chloroform–
acetone, 5:1 w/w), and a green zone was collected. The
solvent was removed, and the residue was dissolved in
benzene and passed again through an alumina column
(eluent benzene). The mixture separated into two green
zones containing, respectively, compounds VI and V.
1
2991, 1492, 1477, 1233, 1180. Н NMR spectrum, δ,
ppm: 8.31–8.19 m (3Н), 7.88–7.62 m (16Н), 6.61–6.38
m (4Н), 1.78–1.77 m (2Н), 1.42–1.28 m (10Н), 0.89 t
(3Н), –2.22 s (2Н). Found, %: С 83.13; Н 5.88; N
6.94. C49H40N4О2. Calculated, %: С 82.10; Н 5.62; N
7.82.
meso-trans-Bis[(3-heptyloxy)phenoxy]tetrabenzo-
porphyrin (VIII), yield 0.06 g (65%), dark green
powder, mp 153°С, readily soluble in benzene, chloro-
form, acetone, and DMF. Electronic absorption spec-
trum (benzene), λmax, nm (log ε): 709 (3.74), 662
(4.30), 605 (4.41), 598 (4.41), 565 (4.00), 469 (4.33),
447 (4.46), 428 (4.96), 414 (4.92), 386 (4.44). IR
spectrum , ν, cm–1: 3239, 2999, 1487, 1455, 1275,
Zinc
meso-mono[(3-heptyloxy)phenoxy]tetra-
benzoporphyrinate (V), yield 0.14 g (10%), dark
green powder readily soluble in benzene, chloroform,
acetone, and DMF. Electronic absorption spectrum
(benzene), λmax, nm (log ε): 626 (4.66), 579 (4.05), 446
(4.34), 427 (5.18), 403 (4.49). IR spectrum , ν, cm–1:
1
1
2990, 1494, 1464, 1228, 1186. Н NMR spectrum, δ,
1177. Н NMR spectrum, δ, ppm: 8.35–8.28 m (2Н),
ppm: 8.33–8.14 m (3Н), 7.98–7.65 m (16Н), 6.62–6.32
m (4Н), 1.78–1.76 m (2Н), 1.41–1.25 m (10Н), 0.88 t
(3Н). Found, %: С 75.88; Н 5.02; N 6.88.
C49H38N4О2Zn. Calculated, %: С 75.43; Н 4.91; N
7.18.
7.90–7.71 m (16Н), 6.68–6.25 m (8Н), 1.73–1.71 m
(4Н), 1.45–1.28 m (20Н), 0.89 t (6Н), –2.15 s (2Н).
Found, %: С 80.91; Н 6.48; N 5.89. C62H58N4О4.
Calculated, %: С 80.67; Н 6.33; N 6.07.
ACKNOWLEDGMENTS
Zinc meso-trans-bis[(3-heptyloxy)phenoxy]tetra-
benzoporphirinate (VI), yield 0.11 g (6%), dark
green powder, readily soluble in benzene, chloroform,
acetone, and DMF. Electronic absorption spectrum
(benzene), λmax, nm (log ε): 627 (4.76), 580 (4.13), 460
(4.22), 441 (4.72), 427 (5.22), 403 (4.51). IR
This work was financially supported by the Russian
Foundation for Basic Research (project no. 07-03-
00427).
REFERENCES
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spectrum , ν, cm–1: 2993, 1499, 1460, 1225, 1181. Н
NMR spectrum, δ, ppm: 8.34–8.20 m (2Н), 7.94–7.68
m (16Н), 6.63–6.30 m (8Н), 1.79–1.76 m (4Н), 1.43–
1.28 m (20Н), 0.89 t (6Н). Found, %: С 75.99; Н 5.96;
N 5.01. C62H56N4О4Zn. Calculated, %: С 75.48; Н
5.72; N 5.68.
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