Amination of meso-bromophenyl(polyalkyl)porphyrins: Synthesis of porphyrins containing a hydroxypiperidine fragment

Article abstract of DOI:10.1134/s1070428008030184

5,15-Bis(4-bromophenyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin and 5-(4-bromophenyl)-13,17-dibutyl-2,3,7,8,12,18-hexamethylporphyrin were synthesized, and their palladium-catalyzed amination with a number of cyclic secondary amines, including hydroxypiperidines, was studied [Pd(OAc) ₂, ligand, THF or dioxane, t-BuONa, 80-100°C]. The reactions of the meso-bromophenylporphyrins with piperidine and morpholine gave the corresponding amination products in quantitative yield. The amination with hydroxypiperidines required excess amine (3 equiv per bromine atom) and excess base (6-8 equiv) and was accompanied by formation of hydrodebromination products; in the reactions with the bis(bromophenyl)derivative, mixed products resulting from amination at one phenyl group and reductive debromination at the other were also formed. The yields of the amination products varied from good {75-50percent in the reactions with 4-hydroxypiperidine and trans-3-hydroxy-4-[4-(2- fluorophenyl)piperazin-1-yl]piperidine} to moderate (20-50percent, 3-hydroxypiperidine) and poor [11-25percent, trans-3,4-dihydroxypiperidine and trans-3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine].

Full text of DOI:10.1134/s1070428008030184

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 3, pp. 421–431. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © G.A. Artamkina, P.K. Sazonov, M.M. Shtern, G.V. Grishina, I.S. Veselov, A.S. Semeikin, S.A. Syrbu, O.I. Koifman, I.P. Beletskaya,
2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 3, pp. 423–433.
Amination of meso-Bromophenyl(polyalkyl)porphyrins:
Synthesis of Porphyrins Containing a Hydroxypiperidine
Fragment
G. A. Artamkinaa, P. K. Sazonova, M. M. Shterna, G. V. Grishinaa, I. S. Veselova,
A. S. Semeikinb, S. A. Syrbub, O. I. Koifmanb, and I. P. Beletskayaa
a Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: galina@elorg.chem.msu.ru
b Ivanovo State University of Chemical Technology, Ivanovo, Russia
Received July 24, 2007
Abstract—5,15-Bis(4-bromophenyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin and 5-(4-bromo-
phenyl)-13,17-dibutyl-2,3,7,8,12,18-hexamethylporphyrin were synthesized, and their palladium-catalyzed
amination with a number of cyclic secondary amines, including hydroxypiperidines, was studied [Pd(OAc)2,
ligand, THF or dioxane, t-BuONa, 80–100°C]. The reactions of the meso-bromophenylporphyrins with
piperidine and morpholine gave the corresponding amination products in quantitative yield. The amination with
hydroxypiperidines required excess amine (3 equiv per bromine atom) and excess base (6–8 equiv) and was
accompanied by formation of hydrodebromination products; in the reactions with the bis(bromophenyl)
derivative, mixed products resulting from amination at one phenyl group and reductive debromination at the
other were also formed. The yields of the amination products varied from good {75–50% in the reactions with
4-hydroxypiperidine and trans-3-hydroxy-4-[4-(2-fluorophenyl)piperazin-1-yl]piperidine} to moderate (20–
50%, 3-hydroxypiperidine) and poor [11–25%, trans-3,4-dihydroxypiperidine and trans-3-hydroxy-4-(4-hy-
droxypiperidin-1-yl)piperidine].
DOI: 10.1134/S1070428008030184
It is known that porphyrins possess versatile and
sometimes unique properties which underlie their
diverse applications, in particular as agents for therapy
and diagnostics [1–3]. The goal of the present work
was to create new pharmacological models, i.e., com-
pounds whose molecules contain two pharmacophoric
fragments (porphyrin macroring and piperidine ring)
and their functionalized derivatives. Development of
studies in the field of synthesis of such compounds has
been stimulated by our recent data on the anti-HIV ac-
tivity of trans-3,4-dihydroxypiperidines [4].
of two pharmacophoric fragments in a single molecule
may be useful from the viewpoint of medical applica-
tions, e.g., for photodynamic therapy of cancer, fluo-
rescent diagnostics, and design of new antiviral agents.
OH
OH
HO
OH
H
HO
OH
OH
OH
N
N
R
R = H, Me.
OH
For this purpose, we synthesized previously un-
known bis(bromophenyl)- and mono(bromophenyl)-
porphyrins I and II. Compound I was obtained ac-
cording to the procedure described in [6] by condensa-
tion of bis(4-ethyl-3-methyl-1H-pyrrol-2-yl)methane
[7] with p-bromobenzaldehyde in methylene chloride
in the presence of chloroacetic acid, followed by
oxidation of intermediate porphyrinogen with tetra-
chloro-1,4-benzoquinone (Scheme 1).
N
R
OH
R'
These piperidine derivatives are structurally and
stereochemically simpler analogs of a new class of in-
hibitors of replication of HIV and other viruses, poly-
hydroxypiperidine alkaloids [4, 5]. Taking the above
stated into account, we anticipated that a combination
421

ARTAMKINA et al.
422
Scheme 1.
Cl
Cl
Et
Et
(1) H+; (2)
O
O
Me
Me
Me
Me
Me
Me
Et Et
NH
N
N
CHO
Cl
Cl
Br
Br
+
HN
Br
N
N
H
H
Et
Et
I
Scheme 2.
Me
Me
Me
Bu
Me
Me
+
Bu Bu
Me
Me
NH
HN
HBr, MeOH
CHO
HN
NH
N
N
H
N
H
H
Me
Bu
Me
Me
Me
Me
Me
Bu
Bu
NH
N
N
4-BrC6H4CHO, BuOH, HBr
Br
HN
Me
Me
Me
II
e.g., [9–12] and references therein). Only in the recent
years, some publications on the amination and amida-
tion of meso-bromoporphyrins and (bromophenyl)por-
phyirins have appeared [13–16]. The amination reac-
tion is fairly complex even with simple aryl halides,
and its success depends on the number of factors,
including the nature of amine and ligand in the palla-
dium complex used as catalyst. Palladium-catalyzed
amination of hydroxypiperidines was not studied
previously. However, this problem seems to be fairly
complex, taking into account that hydroxypiperidines
having a secondary hydroxy group can act as strong
reducing agents. Therefore, it was reasonable to begin
study on the amination of bromophenylporphyrins I
and II with simpler amines, such as piperidine and
morpholine or even aniline. Gao et al. [15] reported on
the amination of bis(bromophenyl)- and tetrakis-
(bromophenyl)porphyrins, but no data on reactions
with cyclic secondary amines were given. As noted in
[13], attempts to effect amination of meso-bromopor-
The reaction of bis(3-butyl-4-methyl-1H-pyrrol-2-
yl)methane dihydrobromide with 3,4-dimethyl-1H-pyr-
role-2-carbaldehyde according to the procedure re-
ported in [8] gave biladiene-ac dihydrobromide having
no substituents in the α- and α′-positions, and its subse-
quent condensation with p-bromobenzaldehyde led to
the formation of meso-(4-bromophenyl)porphyrin II
(Scheme 2). Polyalkyl-substituted porphyrins, such as
I and II, attract interest as closest analogs of natural
porphyrins. As far as we know, their amination was
not reported.
Physical, chemical, and biological properties of
porphyrins are known to strongly depend on the nature
of peripheral substituents [1]. Therefore, much atten-
tion is given to the development of methods for intro-
duction of various groups into the porphyrin macro-
ring. Modern approaches to modification of porphyrins
utilize catalytic reactions (such as Sonoganashira,
Suzuki, and Stille) to build up new C–C bonds (see,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

AMINATION OF meso-BROMOPHENYL(POLYALKYL)PORPHYRINS:
423
Scheme 3.
Et
Et
Et
Et
Me
Me
Me
Me
Me
Me
Me
NH
N
NH
N
N
N
RR'NH
Br
NRR'
Br
RR'N
HN
HN
Me
Et
Et
Et
Et
Et
I
IIIa–IIIe
Et
Et
Et
Me
Me
Me
Me
Me
Me
NH
NH
N
N
+
RR'N
+
HN
HN
N
N
Me
Me
Me
Me
Et
Et
Et
Et
IVa–IVg
V
Me
Me
Bu
Bu
Bu
Me
Me
Me
NH
NH
N
N
N
RR'NH
Br
RR'N
HN
HN
N
Bu
Me
Me
Me
Me
Me
VIb, VId, VIe, VIg, VIh
II
Me
Me
Bu
Me
NH
N
+
HN
N
Bu
Me
Me
Me
VII
NH2
HO
HO
NH
NH
NH
NH
NH
RR′NH =
(a),
(b),
(c),
(d),
(e),
(f),
O
HO
HO
HO
F
HO
(g),
(h).
HO
N
NH
N
N
NH
phyrins with piperidine and morpholine were unsuc-
cessful. Takahami et al. [14] succeeded in aminating
the nickel complex of meso-bromoporphyrin with pi-
peridine, but in this case additional problems related to
the synthesis of porphyrin complexes and subsequent
demetalation of the amination products are involved.
Aniline successfully reacted with both meso-bromo-
porphyrin [13] and poly(bromophenyl)porphyrins [15].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

ARTAMKINA et al.
424
Table 1. Amination of 5,15-bis(4-bromophenyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin (I)
Yield, %
Run
no.
Tempera-
ture, °C
Amine
Ligand
BINAP
Solvent
THF
Base
IIIa–IIIf IVa–IVf
V
01 Aniline, 4 equiv
100
100
100
100
100
Cs2CO3,
4 equiv
80.0
02 Piperidine, 20 equiv
L1
L2
L4
L4
THF
t-BuONa,
4 equiv
10.5
b81.5b
82.0
63.5
–
08
–
03 Piperidine, 20 equiv
THF
Cs2CO3,
4 equiv
04 Piperidine, 20 equiv
Dioxane t-BuONa,
4.5 equiv
05 Piperidine, 20 equiv
Dioxane t-BuONa,
76.5
4 equiv
06 Morpholine, 5 equiv
t-BuONa,
Dioxane
100
100
L2
L3
82.5
44.0
4 equiv.
07 4-Hydroxypiperidine, 6 equiv
08 4-Hydroxypiperidine, 6 equiv
09 4-Hydroxypiperidine, 6 equiv
10 4-Hydroxypiperidine, 6 equiv
11 4-Hydroxypiperidine, 20 equiv
12 3-Hydroxypiperidine, 6 equiv
13 3-Hydroxypiperidine, 6 equiv
14 3-Hydroxypiperidine, 6 equiv
15 3-Hydroxypiperidine, 6 equiv
16 3-Hydroxypiperidine, 6 equiv
Dioxane t-BuONa,
30
21
25
27
16 equiv
080
100
100
(t-Bu)3P·HBF4 Dioxane t-BuONa,
07.0
08.0
43.0
26
43
05
14 equiv
(t-Bu)3P·HBF4 THF
t-BuONa,
16 equiv
L3
THF
t-BuONa,
16 equiv
t-BuONa,
8 equiv
100
100
L3
L3
Dioxane
45.0
19.0
27
23
Traces
0.19.5
Dioxane t-BuONa,
20 equiv
080
080
080
080
L3
L6
L5
Dioxane t-BuONa,
20.0
33
9
18
0.13.5
19
20 equiv
Dioxane t-BuONa, Traces
20 equiv
Dioxane t-BuONa, Traces
9
20 equiv
(t-Bu)3P·HBF4 Dioxane t-BuONa,
11.0
28
28
16 equiv
17 trans-3,4-Dihydroxypiperidine,
t-BuONa,
18 equiv
c
c
080
L3
Dioxane
35
6 equiv
18 trans-3,4-Dihydroxypiperidine,
t-BuONa,
18 equiv
080
080
(t-Bu)3P·HBF4 Dioxane
Traces
–
11
25
47
34
6 equiv
19 trans-3-Hydroxy-4-(4-hydroxypiperi-
(t-Bu)3P·HBF4 Dioxane t-BuONa,
din-1-yl)piperidine·2HCl, 3 equiv
28 equiv
a
b
c
Reaction time 24 h.
Reaction time 72 h.
An inseparable mixture of unidentified products was obtained.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

AMINATION OF meso-BROMOPHENYL(POLYALKYL)PORPHYRINS:
425
Table 2. Amination of 5-(4-bromophenyl)-13,17-dibutyl-2,3,7,8,12,18-hexamethylporphyrin (II)a
Yield, %
VIb, VId–VIf VII
Run
no.
Amine
Ligand
Solvent
THF
Base
01 Piperidine, 20 equiv
L4
L4
L3
L3
L3
L4
L3
L3
L4
t-BuONa, 4 equiv
77.5
83.5
53.0
70.0
44.0
–
–
02 Piperidine, 20 equiv
Dioxane t-BuONa, 4 equiv
Dioxane t-BuONa, 4.5 equiv
Dioxane t-BuONa, 8 equiv
Dioxane t-BuONa, 4 equiv
Dioxane t-BuONa, 24 equiv
Dioxane t-BuONa, 7 equiv
Dioxane t-BuONa, 8 equiv
Dioxane t-BuONa, 8 equiv
–
03 4-Hydroxypiperidine, 3 equiv
04 4-Hydroxypiperidine, 3 equiv
05 4-Hydroxypiperidine, 20 equiv
06 4-Hydroxypiperidine, 20 equiv
07 3-Hydroxypiperidine, 20 equiv
b08b 3-Hydroxypiperidine, 20 equiv
b09b 3-Hydroxypiperidine, 20 equiv
45
17
45
90
48
45
41
41.0
50.0
12.5
trans-3-Hydroxy-4-(4-hydroxypiperidin-
1-yl)piperidine·2HCl, 3 equiv
b10b
t-Bu3P·HBF4 Dioxane t-BuONa, 16 equiv
L3 Dioxane t-BuONa, 16 equiv
18.0
56.0
48
34
1-(2-Fluorophenyl)-4-(trans-3-hydroxypi-
peridine-4-yl)piperazine·3HCl, 3 equiv
11
a
At 100°C, reaction time 24 h.
At 80°C.
b
In our experiments, the amination of bis(bromo-
Except for ligand L1 which ensured a very poor
yield of the target product (IIIb; Table 1, run. no. 2),
all other ligands (L2–L4) were approximately equally
effective: the yields of IIIb ranged from 76.5 to 82%
(Table 1, run nos. 3–5). Both THF and dioxane are
appropriate solvents (Table 1, run nos. 3, 5). As shown
in [13, 14], dioxane, as well as toluene, was ineffective
in the amination of meso-bromoporphyrins, and the
best results were obtained using THF as solvent. Tetra-
hydrofuran was also used as solvent in the amination
of poly(bromophenyl)porphyrins [15]. We selected di-
oxane for the sake of convenience. Replacement of
dioxane by THF did not affect the results of the reac-
tion of 4-hydroxypiperidine with bis(bromophenyl)-
phenyl)porphyrin I with aniline in tetrahydrofuran
using BINAP as ligand and Cs2CO3 as base (Table 1,
run no. 1) gave the corresponding anilino-substituted
derivative in high yield. In the general case, the amina-
tion of bromophenylporphyrins I and II is illustrated
by Scheme 3. Using the reaction of porphyrin I with
piperidine as an example, we examined the effects of
solvent (THF, dioxane), base (t-BuONa, Cs2CO3), and
ligand {2-(dicyclohexylphosphino)biphenyl (L1),
2-(di-tret-butylphosphino)biphenyl (L2), 2-(dicyclo-
hexylphosphino)-2′-(dimethylamino)biphenyl (L3), and
rac-1-[2-(diphenylphosphino)ferrocenyl]ethyl methyl
ether (L4)} on the product yield.
PPh2
PPh2
PCy2
P(Bu-t)2
PCy2
NMe2
BINAP
L1
L2
L3
Me
OMe
PPh2
P(Bu-t)2
PR2
PR2
Fe
Fe
NMe2
R = 2-(i-Pr)C6H4
L4
L5
L6
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ARTAMKINA et al.
426
[17]). An additional evidence in favor of regioselective
reaction at the nitrogen atom was obtained from the
1H NMR spectrum of VId. The signal prom protons
in the α-position with respect to the nitrogen atom is
located in a weaker field (δ 3.66 ppm against 3.1 ppm
in the spectrum of initial 4-hydroxypiperidine), where-
as the position of the CHOH signal changes insignif-
icantly (δ 3.77 and 3.65 ppm for compound VId and
4-hydroxypiperidine, respectively).
porphyrine I (Table 1, run nos. 7, 10). The reaction
in the presence of sodium tert-butoxide occurred at
a much higher rate (reaction time ~20 h) than in the
presence of cesium carbonate (~72 h; Table 1, cf. run
nos. 3 and 4, 5). The amination of bromophenylpor-
phyrin II with piperidine afforded compound VIb in
high yield, 77.5% in THF and 83.5% in dioxane (L4;
Table 2, run nos. 1, 2). Likewise, the reaction of bis-
(bromophenyl)porphyrin I with morpholine in the
presence of ligand L2 involved no difficulties, and
amination product IIIc was formed in 82.5% yield
(Table 1, run no. 6). Thus the amination of porphyrins
I and II with piperidine and morpholine in the system
dioxane–Pd(OAc)2 (2–3 mol %) using ligands L2–L4
(3–4.5 mol %) and t-BuONa (4 equiv per bromine
atom) at 100°C fairly smoothly produces the target
products in high yields (77–82%).
As is typical of catalytic amination of polyhalo-
arenes, in the reactions of hydroxypiperidines with
bis(bromophenyl)porphyrin I the contribution of side
reduction processes increases (Scheme 3; Table 1, run
nos. 7–16). 4-Hydroxypiperidine reacted with com-
pound I to give amination product IIId still in a fairly
good yield (44–45%), the yield of partially reduced
product IVd was 27–30%, while only traces of the
complete reduction product (compound V) were de-
tected (Table 1, run nos. 7, 10, 11). The use of a large
excess of the amine, as in the reaction with mono-
bromo derivative II, had no appreciable effect on the
product yield (Table 1, run nos. 7, 10, 11). In the reac-
tion of bis(bromophenyl)porphyrin I with 3-hydroxy-
piperidine, all possible products (IIIe, IVe, and V)
were formed (Table 1, run nos. 12–16). As with 4-hy-
droxypiperidine, the most effective ligand was L3, but
even in this case the yield of amination product IIIe
did not exceed 19–20% (Table 1, run nos. 12, 13). On
the other hand, monoamination product IVe was
formed in a considerably larger yield (33%), so that
the overall yield of amination products (53%) becomes
even greater than in the reaction of 3-hydroxypiperi-
dine with bromophenylporphyrin II.
The reactions of bromophenylporphyrins with hy-
droxypiperidines were not so smooth and were accom-
panied by formation of considerable amounts of the
reduction products (Scheme 3). Nevertheless, using
ligand L3 in the reaction of porphyrin II with 4-hy-
droxypiperidine we succeeded in obtaining compound
VId in a fairly high yield (~70%), while the yield of
reduction product VII was 17% (Table 2, run no. 4).
The amount of base in reactions with hydroxypiperi-
dines should be increased in accordance with the
hydroxypiperidine concentration. Reduction of the
amount of base from 8 to 4–4.5 equiv (Table 2, run
nos. 3–5) resulted in lower yield of the amination prod-
uct (VId, 44–53%), and the yield of hydrodebromina-
tion product VII increased to 45%. Ligand L4 turned
out to be ineffective in this reaction (Table 2, run
no. 6). Under analogous conditions, the reaction of
porphyrin II with 3-hydroxypiperidine gave 41–50%
of amination product VIe, and the yield of reduction
product VII simultaneously increased (Table 2, run
nos. 7, 8). Here, ligand L4 was also weakly effective
(Table 2, run no. 9).
Taking into account the above difficulties, we tried
to use in the reaction under study some other ligands,
1,1-bis[(2-isopropylphenyl)phosphino]ferrocene (L5),
2-dimethylamino-2′-[di(tert-butyl)phosphino]biphenyl
(L6), and (t-Bu)3P·HBF4. Ligands L5 and L6 turned out
to be ineffective: compound IIIe was formed only in
trace amount, while the yield of IVe was as poor as
9%, and the reaction was accompanied by tarring
(Table 1, run nos. 14, 15). In the presence of (t-Bu)3P·
HBF4 the yield of bis-amination product IIIe was
lower than in the presence of L3, though the yield of
monoamino derivative IVe changed insignificantly
(Table 1, cf. run nos. 12, 13 and 16). The difference in
the effects of (t-Bu)3P·HBF4 and L3 was much stronger
in the reaction with 4-hydroxypiperidine: the yield of
IIId decreased from 44–45 to 7–8% (Table 1, cf. run
nos 7, 10, 11 and 8, 9). Lowering the temperature to
Hydroxypiperidines are difunctional nucleophiles,
and their arylation may involve both nitrogen and
13
oxygen atoms. However, comparison of the C NMR
spectra of amination product VId and 4-hydroxypiperi-
dine [17] showed that the reaction occurred only at
the nitrogen atom. The position of the CHOH signal
(δC 67.65 ppm) in the spectrum of VId was almost
the same as in the spectrum of 4-hydroxypiperidine
(δC 67.8 ppm), whereas the signal from the carbon
atoms linked to nitrogen (δC 47.28 ppm) was displaced
by almost 3 ppm (δC 44.4 ppm for 4-hydroxypiperidine
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AMINATION OF meso-BROMOPHENYL(POLYALKYL)PORPHYRINS:
427
80°C almost did not affect the reaction course with
porphyrins I and II (Table 1, run nos. 13–16; Table 2,
run nos. 7, 8).
phino]biphenyl (Stream), (t-Bu)3P·HBF4 (Dal’khim
Ltd.), and 3-hydroxy- and 4-hydroxypiperidines (Ferak
Berlin) were used without additional purification.
rac-1-[2-(Diphenylphosphino)ferrocenyl]ethyl methyl
ether [18], dichloro{1,1-bis[(2-isopropylphenyl)phos-
phino]ferrocene}palladium(II) [19], bis(4-ethyl-3-
methyl-1H-pyrrol-2-yl)methane, bis(3-butyl-4-methyl-
1H-pyrrol-2-yl)methane [7], trans-3′,4-dihydroxy-1,4′-
bipiperidine dihydrochloride [20], and trans-1-(3-hy-
droxypiperidin-4-yl)-4-(2-fluorophenyl)piperazine
trihydrochloride [20] were synthesized by known
methods.
It was reasonable to presume that reactions of
bromophenylporphyrins with dihydroxypiperidines
should involve even more difficulties. In fact, bis-
(bromophenyl)porphyrin I reacted with trans-3,4-dihy-
droxypiperidine and trans-3-hydroxy-4-(4-hydroxy-
piperidin-1-yl)piperidine to give mainly hydrode-
bromination product V (Table 1, run nos. 17–19).
Monoamination product IVf derived from trans-3,4-
dihydroxypiperidine was isolated in 11% yield only in
the presence of (t-Bu)3P·HBF4 as ligand (Table 1, run
no. 18). Ligand L3 gave rise to an inseparable mixture
of products containing almost no compound IVf.
Somewhat larger yield of monoamination product IVg
(25%) was obtained in the reaction of trans-3-hy-
droxy-4-(4-hydroxypiperidin-1-yl)piperidine with bis-
(bromophenyl)porphyrin I (Table 1, run no. 19). Like-
wise, the reaction of the same amine with bromo-
phenylporphyrin II gave 18% of VIg and 48% of
reduction product VII (Table 2, run no. 10). On the
other hand, porphyrin II reacted with trans-1-(3-hy-
droxypiperidin-4-yl)-4-(2-fluorophenyl)piperazine
containing only one hydroxy group (Table 2, run
no. 11) to produce amination product VIh in a fairly
good yield (56%).
trans-Piperidine-3,4-diol. A solution of 0.4 g
(1.93 mmol) of trans-1-benzylpiperidine-3,4-diol in
15 ml of ethanol was hydrogenated over 0.1 g of
10% Pd/C at room temperature over a period of three
days. The catalyst was filtered off, and the solvent and
liberated toluene were removed under reduced pres-
sure. Yield 0.2 g (90%), colorless crystalline substance,
Rf 0.3 (Alufol, CH2Cl2–EtOH, 1 :2), mp 99–100°C
(from EtOH–Et2O). Found: [M]+ 117. C5H11NO2. Cal-
culated: M 117.4.
5,15-Bis(4-bromophenyl)-2,8,12,18-tetraethyl-
3,7,13,17-tetramethylporphyrin (I). A solution of
1.0 g (~10 mmol) of chloroacetic acid in 20 ml of
methylene chloride was added to a solution of 1.2 g
(5.2 mmol) of bis(4-ethyl-3-methyl-1H-pyrrol-2-yl)-
methane and 0.96 g (5.2 mmol) of 4-bromobenzal-
dehyde in 400 ml of methylene chloride under stirring
at 20°C in a carbon dioxide atmosphere. The mixture
was stirred for 4 h, a solution of 1.9 g (7.8 mmol) of
tetrachloro-1,4-benzoquinone in 50 ml of THF was
added, and the mixture was stirred for 16 h at 20°C
and evaporated to dryness under reduced pressure. The
residue was treated with a 5% solution of sodium hy-
droxide, and the precipitate was filtered off, washed
with water, and dried at 75°C. Yield 2.1 g. The crude
product was dissolved in 150 ml of methylene chloride
containing 2 ml of trifluoroacetic acid, the solution
was filtered, and the filtrate was neutralized with 5 ml
of diethylamine. After 2 h, the precipitate was filtered
off, washed with methylene chloride, and dried at
Thus palladium-catalyzed amination of meso-
(bromophenyl)- and meso-bis(bromophenyl)porphyrins
with secondary cyclic amines leads to the correspond-
ing amino derivatives in high (piperidine, morpholine)
or moderate yields (hydroxypiperidines).
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker Avance 400 spectrometer at 400 MHz for
13
1H and 100.57 MHz for C using tetramethylsilane as
internal reference. The mass spectra (MALDI) were
obtained on a Bruker Daltonics Autoflex II instrument
(N2 laser, λ = 337 nm; accelerating voltage 19 kV,
positive ion detection).
1
75°C. Yield 1.5 g (73%). H NMR spectrum (CDCl3–
Dioxane and tetrahydrofuran were purified and
dehydrated by standard methods and were stored over
potassium diphenylketyl. Cesium carbonate was dried
at 200°C under reduced pressure. Sodium tert-butoxide
(Lancaster), palladium(II) acetate, 2-(di-tert-butyl-
phosphino)biphenyl, 2-(dicyclohexylphosphino)bi-
phenyl, 2-(dicyclohexylphosphino)-2′-(dimethylamino)-
biphenyl, 2-dimethylamino-2′-[di(tert-butyl)phos-
CF3COOH, 99:1), δ, ppm: 10.20 s (2H, 10-H, 20-H),
8.17 d (4H), 8.08 d (4H), 3.73 q (8H, CH2), 2.27 s
(12H), 1.36 t (12H, CH3), –1.94 s (4H, NH). Found:
m/z 788.87 [M + H]+. C44H44Br2N4. Calculated:
[M + H] 789.19.
8,12-Dibutyl-2,3,7,13,17,18-hexamethylbiladi-
ene-ac dihydrobromide. Concentrated hydrobromic
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ARTAMKINA et al.
428
acid, 2 ml, was added to a solution of 0.65 g
(2.27 mmol) of bis(3-butyl-4-methyl-1H-pyrrol-2-yl)-
methane and 0.6 g (4.54 mmol) of 3,4-dimethyl-1H-
pyrrole-2-carbaldehyde in 30 ml of methanol, and the
mixture was stirred for 2 h at 20°C. The precipitate
was filtered off, washed with methanol and diethyl
ether, and dried. Yield 1.4 g (93%). Electronic absorp-
tion spectrum (chloroform), λmax, nm (ε×10–3): 523
(113.8), 457 (25.5).
washings were combined and filtered or subjected to
centrifugation. We thus isolated almost pure com-
pounds IIIa–IIIc and VIb. If necessary, the products
were purified by column chromatography on alumi-
num oxide (VIb, IIIa) or silica gel (IIIb, IIIc).
a. Isolation and purification of amination products
VId–VIf and IVf. The residue obtained after centrif-
ugation was dissolved in chloroform, neutral alumi-
num oxide (5–40 μm) was added, the solution was
evaporated, and the residue was applied to a column
charged with aluminum oxide. Compounds VId and
VIe were isolated using chloroform–petroleum ether
(40:60); reduction product VII was eluted first, and
then compound VId or VIe left the column. Com-
pounds IVf and VIf were isolated by elution with
chloroform–methanol (95:5) after isolation of reduc-
tion product V or VII.
5-(4-Bromophenyl)-13,17-dibutyl-2,3,7,8,12,18-
hexamethylporphyrin (II). A solution of 1.4 g
(2.12 mmol) of 8,12-dibutyl-2,3,7,13,17,18-hexameth-
ylbiladiene-ac dihydrobromide, 0.8 g (4.32 mmol) of
4-bromobenzaldehyde, and 0.5 ml of concentrated
hydrobromic acid in 50 ml of butanol was heated to
the boiling point and maintained boiling for 4 h, 0.3 g
(1.2 mmol) of iodine was added, and the mixture was
heated for 15 min under reflux. The solvent was
removed by steam distillation, the precipitate was
filtered off, washed with water, dried at 70°C, and
dissolved in chloroform, and the solution was applied
to a column charged with aluminum oxide. The first
colored fraction was collected and evaporated to
a minimal volume. The product was precipitated with
methanol, filtered off, washed with methanol, and
b. Isolation of amination products IIId, IIIe, IVd,
and IVe. The residue obtained after centrifugation was
dissolved in chloroform containing 1–2% of methanol
and 0.1% of trifluoroacetic acid, and the solution was
subjected to chromatography on silica gel (Merck, 40–
60 μm). After elution of compound V, the concentra-
tion of methanol in the eluent was gradually raised to
4–6% (IVd, IVe) or 10–15% (IIId, IIIe). The eluate
was evaporated to a volume of 1–2 ml, triethylamine
was added to the residue until the color changed from
black–green to bright red, the mixture was diluted with
methanol to a volume of 5–8 ml, and the precipitate
was separated by centrifugation, washed with metha-
nol, subjected to centrifugation again, and dried under
reduced pressure. Alternatively, porphyrin bases were
isolated by filtration of acidic fractions obtained after
chromatography through a layer of neutral aluminum
oxide (5–40 μm) and subsequent evaporation.
1
dried at 70°C. Yield 0.52 g (37%). H NMR spectrum
(CDCl3), δ, ppm: 10.15 s (2H, 10-H, 20-H), 9.94 s
(1H, 15-H), 7.86 q (4H, AB system), 4.02 t (4H, CH2),
3.62 s (6H, CH3), 3.53 s (6H, CH3), 2.46 s (6H, CH3),
2.30 m (4H, CH2), 1.82 m (4H, CH2), 1.14 t (6H, CH3),
–3.3 br.s (2H, NH). Found: m/z 660.95 [M + H]+.
C40H45BrN4. Calculated: [M + H] 661.28.
General procedure for the amination of porphy-
rins I and II. A reactor was filled with argon and
charged with 0.025–0.06 mmol of bromophenylpor-
phyrin I or II, 0.15–1 mmol of the corresponding
amine, 0.3–0.8 mmol of base, 1–2 mol % of Pd(OAc)2,
1.5–4 mol % of ligand, and 5 ml of THF or dioxane.
The mixture was degassed, the reactor was filled with
argon, and the mixture was stirred at 80–100°C until
the initial porphyrin disappeared (according to the
TLC data or MALDI spectra). When the reaction was
performed in the presence of t-BuONa, the mixture
was evaporated under reduced pressure, 3–5 ml of
methanol was added, the precipitate was separated by
centrifugation, washed with methanol or acetone, sub-
jected again to centrifugation, and dried under reduced
pressure. When the reaction was performed using
Cs2CO3 as base, the solution was separated from the
solid residue by decanting, and the residue was washed
with the corresponding solvent. The solution and the
2,8,12,18-Tetraethyl-3,7,13,17-tetramethyl-5,15-
bis[4-(phenylamino)phenyl]porphyrin (IIIa)
(Table 1, run no. 1) was obtained from 39 mg
(0.05 mmol) of compound I and 42 mg (0.45 mmol) of
aniline using 130 mg (0.4 mmol) of Cs2CO3, 1.12 mg
(0.005 mmol) of Pd(OAc)2, and 6.2 mg (0.01 mmol) of
BINAP in 5 ml of THF. Yield 33.7 mg (80%). 1H NMR
spectrum (CDCl3–CF3COOH, 99:1), δ, ppm: 10.10 s
(2H, 10-H, 20-H), 8.08 d (4H), 7.54 d (4H), 7.50–
7.41 m (10H), 7.16 t (2H), 3.70 q (8H, CH2), 2.33 s
(12H, CH3), 1.36 t (12H, CH3), –1.86 s (4H, NH).
Found: m/z 813.1 [M + H]+. C56H56N6. Calculated:
[M + H] 813.5.
13,17-Dibutyl-2,3,7,8,12,18-hexamethyl-5-(4-pi-
peridinophenyl)porphyrin (VIb) (Table 2, run no. 2)
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AMINATION OF meso-BROMOPHENYL(POLYALKYL)PORPHYRINS:
429
was obtained from 33 mg (0.05 mmol) of porphyrin II
and 0.1 ml (1 mmol) of piperidine using 19 mg
(0.02 mmol) of t-BuONa, 1.14 mg (0.0053 mmol) of
Pd(OAc)2, and 4.3 mg (0.01 mmol) of ligand L4 in
5 ml of dioxane. Yield 27.5 mg (82%). 1H NMR spec-
trum (CDCl3), δ, ppm: 10.13 s (2H, 10-H, 20-H),
9.92 s (1H, 15-H), 7.81 d (2H), 7.26 d (2H), 4.03 t
(4H, CH2), 3.62 s (6H, CH3), 3.52 s (6H, CH3), 3.45 m
(4H, CH2), 2.52 s (6H, CH3), 2.27 m (4H, CH2),
1.91 m (4H, CH2), 1.75 m (6H, CH2), 1.12 t (6H, CH3),
–3.19 s (1H, NH), –3.31 s (1H, NH). Found: m/z 666.34
[M + H]+. C45H55N5. Calculated: [M + H] 666.45.
13,17-Dibutyl-2,3,7,8,12,18-hexamethyl-5-
phenylporphyrin (VII). H NMR spectrum (CDCl3),
1
δ, ppm: 10.16 s (2H, 10-H, 20-H), 9.95 s (1H, 15-H),
8.04 d (2H), 7.81 t (1H), 7.73 t (2H), 4.04 t (4H, CH2),
3.63 s (6H, CH3), 3.54 s (6H, CH3), 2.45 s (6H, CH3),
2.31 m (4H, CH2), 1.80 m (4H, CH2), 1.17 t (6H, CH3),
–3.2 br.s (2H, NH). 13C NMR spectrum (CDCl3), δC,
ppm: 145.66, 144.13, 143.68, 142.73, 140.14, 137.76,
136.74, 135.95 (pyrrole); 132.99, 128.12, 127.44
(Carom); 118.72 (C5); 96.47 (C10, C20); 95.63 (C15);
35.18, 26.11, 23.00 (CH2); 14.75, 14.14, 12.06, 11.66
(CH3). Found: m/z 583.44 [M + H]+. C40H46N4. Calcu-
lated: [M + H] 583.38.
2,8,12,18-Tetraethyl-3,7,13,17-tetramethyl-5,15-
bis(4-piperidinophenyl)porphyrin (IIIb) (Table 1,
run no. 4) was obtained from 39.4 mg (0.05 mmol) of
porphyrin I and 0.1 ml (1 mmol) of piperidine using
38 mg (0.4 mmol) of t-BuONa, 2.2 mg (0.01 mmol) of
Pd(OAc)2, and 5.5 mg (0.0185 mmol) of ligand L2 in
5 ml of THF. Yield 32.5 mg (82%). 1H NMR spectrum
(CDCl3–CF3COOH, 99:1), δ, ppm: 10.23 s (2H, 10-H,
20-H), 8.51 d (4H), 8.14 d (4H), 3.92 m (8H, CH2),
3.72 q (8H, CH2), 2.30 m (8H, CH2), 2.17 s (12H,
CH3), 1.93 m (4H, CH2), 1.35 t (12H, CH3), –1.91 s
(4H, NH). Found: m/z 797.5 [M + H]+. C54H64N6. Cal-
culated: [M + H] 797.2.
13,17-Dibutyl-5-[4-(4-hydroxypiperidin-1-yl)-
phenyl]-2,3,7,8,12,18-hexamethylporphyrin (VId).
1H NMR spectrum (CDCl3), δ, ppm: 10.13 s (2H,
10-H, 20-H), 9.92 s (1H, 15-H), 7.60 d (2H), 7.01 d
(2H), 4.02 t (4H, CH2), 3.77 m (1H), 3.66 m (2H),
3.61 s (6H, CH3), 3.52 s (6H, CH3), 2.99 m (2H),
2.41 s (6H, CH3), 2.31 m (4H, CH2), 1.99 m (2H),
1.70–1.84 m (6H), 1.17 t (6H, CH3), –3.2 br.s (2H,
NH). 13C NMR spectrum (CDCl3), δC, ppm: 145.54,
144.73, 143.55, 142.72, 139.99, 137.40, 137.00, 135.82
(pyrrole); 151.03, 133.41, 133.26, 115.03 (Carom);
118.87 (C5); 96.34 (C10, C20); 95.41 (C15); 67.65
(CHOH); 47.22 (CH2N); 35.16, 33.84, 26.08, 23.00
(CH2); 14.85, 14.12, 11.99, 11.58 (CH3). Found:
m/z 682.51 [M + H]+. C45H55N5O. Calculated:
[M + H] 682.44.
2,8,12,18-Tetraethyl-3,7,13,17-tetramethyl-5,15-
bis(4-morpholinophenyl)porphyrin (IIIc) (Table 1,
run no. 6) was obtained from 47 mg (0.060 mmol) of
porphyrin I and 0.08 ml (1 mmol) of morpholine using
50 mg (0.52 mmol) of t-BuONa, 2.24 mg (0.01 mmol)
of Pd(OAc)2, and 6 mg (0.02 mmol) of ligand L2 in
5 ml of dioxane. After centrifugation, the precipitate
was dissolved in chloroform containing 2% of metha-
nol and 0.1% of trifluoroacetic acid, and the product
was precipitated with triethylamine, washed with
Reaction of porphyrin II with 3-hydroxypiperi-
dine (Table 2, run no. 8). The reaction was performed
using 34.7 mg (0.0523 mmol) of porphyrin I, 15 mg
(0.15 mmol) of 3-hydroxypiperidine, 38 mg (0.4 mmol)
of t-BuONa, 1.1 mg (0.005 mmol) of Pd(OAc)2, and
4.0 mg (0.01 mmol) of ligand L3 in 5 ml of dioxane.
Following method a, we isolated 12 mg (41%) of com-
pound VII and 17 mg (50%) of porphyrin VIe.
1
methanol, and dried. Yield 40 mg (82%). H NMR
spectrum (CDCl3–CF3COOH, 99:1), δ, ppm: 10.06 s
(2H, 10-H, 20-H), 8.12 d (4H), 7.39 d (4H), 4.06 m
(8H, CH2), 3.67 q (8H, CH2), 3.56 m (8H, CH2), 2.24 s
(12H), 1.36 t (12H, CH3), –1.48 s (4H, NH). Found:
m/z 801.3 [M + H]+. C52H60N6O2. Calculated: [M + H]
801.5.
13,17-Dibutyl-5-[4-(3-hydroxypiperidin-1-yl)-
phenyl]-2,3,7,8,12,18-hexamethylporphyrin (VIe).
1H NMR spectrum (CDCl3), δ, ppm: 10.13 s (2H,
10-H, 20-H), 9.93 s (1H, 15-H), 7.75 d (2H), 7.17 d
(2H), 4.08 m (1H), 4.03 t (4H, CH2), 3.62 s (6H, CH3),
3.48–3.59 m (2H), 3.52 s (6H, CH3), 3.23–3.39 m
(3H), 2.47 s (6H, CH3), 2.29 m (4H, CH2), 1.95 m
(1H), 1.72–1.99 m (2H), 1.79 m (4H, CH2), 1.15 t (6H,
CH3), –3.2 br.s (2H, NH). Found: m/z 682.40 [M + H]+.
C45H55N5O. Calculated: [M + H] 682.44.
Reaction of porphyrin II with 4-hydroxypiper-
idine (Table 2, run no. 4). The reaction was performed
using 33 mg (0.05 mmol) of porphyrin II, 15 mg
(0.15 mmol) of 4-hydroxypiperidine, 40 mg
(0.42 mmol) of t-BuONa, 1.35 mg (0.006 mmol) of
Pd(OAc)2, and 4.8 mg (0.0122 mmol) ligand L3 in
5 ml of dioxane. According to method a we isolated
5 mg (17%) of VII and 24 mg (70%) of VId.
Reaction of porphyrin II with trans-3-hydroxy-
4-(4-hydroxypiperidin-1-yl)piperidine (Table 2, run
no. 10). The reaction was performed using 33 mg
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

ARTAMKINA et al.
430
of dioxane. Following method b, we isolated 13 mg
(30%) of compound IVd and 22 mg (44%) of IIId.
(0.05 mmol) of compound II, 40 mg (0.15 mmol) of
3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine dihy-
drochloride, 77 mg (0.8 mmol) of t-BuONa, 2.24 mg
(0.01 mmol) of Pd(OAc)2, and 4.35 mg (0.015 mmol)
of (t-Bu)3P·HBF4 in 5 ml of dioxane. Following meth-
od a, we isolated 14 mg (48%) of compound VII and
7 mg (18%) of porphyrin VIg.
2,8,12,18-Tetraethyl-5,15-bis[4-(4-hydroxypiper-
idin-1-yl)phenyl]-3,7,13,17-tetramethylporphyrin
1
(IIId). H NMR spectrum (CDCl3–CF3COOH–
CD3OD, 94:1:5), δ, ppm: 10.09 s (2H, 10-H, 20-H),
8.28 d (4H), 7.84 d (4H), 4.15–4.02 m (6H), 3.55–
3.68 m (12H), 2.38 m (4H), 2.16 s (12H), 2.08–2.00 m
(4H), 1.33 t (12H, CH3). Found: m/z 829.56 [M + H]+.
C54H64N6O2. Calculated: [M + H] 829.51.
13,17-Dibutyl-5-{4-[trans-3-hydroxy-4-(4-hy-
droxypiperidin-1-yl)piperidin-1-yl]phenyl}-2,3,7,8,-
1
12,18-hexamethylporphyrin (VIg). H NMR spec-
trum (CDCl3), δ, ppm: 10.13 s (2H, 10-H, 20-H),
9.93 s (1H, 15-H), 7.84 d (2H), 7.26 d (2H), 4.34 m
(1H), 4.04 t (4H, CH2), 3.90 m (1H), 3.76 m (1H),
3.62 s (6H, CH3), 3.52 s (6H, CH3), 3.05–2.7 m
(4H), 2.51 s (6H, CH3), 2.55–2.4 m (2H), 2.28 m
(4H, CH2), 2.1–1.46 m (8H), 1.77 m (4H, CH2), 1.13 t
(6H, CH3), –3.2 br.s (1H, NH), –3.3 br.s (1H, NH).
Found: m/z 781.61 [M + H]+. C50H64N6O2. Calculated:
[M + H] 781.51.
2,8,12,18-Tetraethyl-5-[4-(4-hydroxypiperidin-1-
yl)phenyl]-3,7,13,17-tetramethyl-15-phenylporphy-
rin (IVd). H NMR spectrum (CDCl3–CF3COOH,
99:1), δ, ppm: 10.22 s (2H, 10-H, 20-H), 8.53 d (2H),
8.26 m (2H), 8.14 d (2H), 7.93 m (3H), 4.42 m (1H),
4.18 t (2H), 3.95 m (2H), 3.73 q (8H, CH2), 2.60 m
(2H), 2.3–2.2 m (2H), 2.22 s (6H), 2.18 s (6H), 1.35 t
(12H, CH3), –1.97 br.s (4H, NH). Found: m/z 730.49
[M + H]+. C49H55N5O. Calculated: [M + H] 730.44.
1
Reaction of porphyrin II with trans-4-(2-fluoro-
phenyl)-1-(3-hydroxypiperidin-4-yl)piperazine
(Table 2, run no. 11). The reaction was performed
using 33 mg (0.05 mmol) of porphyrin II, 58.7 mg
(0.15 mmol) of trans-4-(2-fluorophenyl)-1-(3-hy-
droxypiperidin-4-yl)piperazine trihydrochloride, 80 mg
(0.83 mmol) of t-BuONa, 2.8 mg (0.0125 mmol) of
Pd(OAc)2, and 6.7 mg (0.015 mmol) of ligand L3 in
5 ml of dioxane. Following method a, we isolated
10 mg (34%) of compound VII and 24 mg (56%) of
porphyrin VIh.
Reaction of porphyrin I with 3-hydroxypiperi-
dine (Table 1, run no. 13). The reaction was performed
using 39 mg (0.05 mmol) of porphyrin I, 32 mg
(0.32 mmol) of 3-hydroxypiperidine, 77 mg (0.8 mmol)
of t-BuONa, 2.2 mg (0.01 mmol) of Pd(OAc)2, and
7.9 mg (0.02 mmol) of ligand L3 in 5 ml of dioxane.
Following method b, we isolated 5.7 mg (18%) of com-
pound V, 12 mg (33%) of IVe, and 9 mg (20%) of
porphyrin IIIe.
2,8,12,18-Tetraethyl-5,15-bis[4-(3-hydroxypiper-
idin-1-yl)phenyl]-3,7,13,17-tetramethylporphyrin
1
(IIIe). H NMR spectrum (CDCl3–CF3COOH–
13,17-Dibutyl-5-(4-{trans-4-[4-(2-fluorophenyl)-
CD3OD, 97:1:2), δ, ppm: 10.02 s (2H, 10-H, 20-H),
8.09 d (4H), 7.48 d (4H), 4.11 m (2H), 3.86 m (2H),
3.7–3.6 m (12H), 3.28–3.41 m (4H), 2.20 s (12H),
2.10 m (2H), 1.91 m (2H), 1.73 m (2H), 1.34 t (12H,
CH3). Found: m/z 829.45 [M + H]+. C54H64N6O2. Cal-
culated: [M + H] 829.51.
piperazin-1-yl]-3-hydroxypiperidin-1-yl}phenyl)-
2,3,7,8,12,18-hexamethylporphyrin (VIh). H NMR
1
spectrum (CDCl3), δ, ppm: 10.14 s (2H, 10-H, 20-H),
9.93 s (1H, 15-H), 7.87 d (2H), 7.29 d (2H), 7.14–
6.97 m (4H), 4.34 m (1H), 4.04 t (4H, CH2), 4.12–
3.96 m (2H), 3.63 s (6H, CH3), 3.53 s (6H, CH3), 3.35–
3.2 m (4H), 3.08 m (2H), 2.98 m (1H), 2.81 m (2H),
2.52 s (6H, CH3), 2.35–2.23 m (1H), 2.28 m (4H,
CH2), 2.05 m (1H), 1.95–1.85 m (2H), 1.77 m (4H,
CH2), 1.13 t (6H, CH3), –3.3 br.s (2H, NH). Found:
m/z 860.43 [M + H]+. C55H66FN7O. Calculated:
[M + H] 860.53.
2,8,12,18-Tetraethyl-15-[4-(3-hydroxypiperidin-
1-yl)phenyl]-3,7,13,17-tetramethyl-5-phenylporphy-
1
rin (IVe). H NMR spectrum (CDCl3–CF3COOH,
99:1), δ, ppm: 10.21 s (2H, 10-H, 20-H), 8.53 d (2H),
8.26 m (2H), 8.14 d (2H), 7.93 m (3H), 4.60 m (1H),
3.97 m (1H), 3.87 m (3H), 3.73 q (8H, CH2), 2.58 m
(1H), 2.22 s (6H), 2.18 s (6H), 2.0–2.3 m (3H), 1.38 t,
1.36 t (12H, CH3), –1.93 s, –1.95 s (4H, NH). Found:
m/z 730.34 [M + H]+. C49H55N5O. Calculated; [M + H]
730.44.
Reaction of porphyrin I with 4-hydroxypiperi-
dine (Table 1, run no. 7). The reaction was carried out
using 48 mg (0.06 mmol) of porphyrin I, 36 mg
(0.36 mmol) of 4-hydroxypiperidine, 92 mg
(0.95 mmol) of t-BuONa, 2.24 mg (0.01 mmol) of
Pd(OAc)2, and 8 mg (0.02 mmol) of ligand L3 in 5 ml
2,8,12,18-Tetraethyl-3,7,13,17-tetramethyl-5,15-
1
diphenylporphyrin (V). H NMR spectrum (CDCl3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

AMINATION OF meso-BROMOPHENYL(POLYALKYL)PORPHYRINS:
δ, ppm: 10.24 s (2H, 10-H, 20-H), 8.08 d (4H), 7.83–
REFERENCES
431
7.72 m (6H), 4.03 q (8H, CH2), 2.50 s (12H, CH3),
1.78 t (12H, CH3), –2.40 br.s (2H, NH). Found:
m/z 631.25 [M + H]+. C44H46N4. Calculated: [M + H]
631.38.
1. Porfiriny: spektroskopiya, elektrokhimiya, primenenie
(Porphyrins: Spectroscopy, Electrochemistry, and Ap-
plications), Enikolopyan, N.S., Ed., Moscow: Nauka,
1987.
Reaction of porphyrin I with trans-3,4-dihy-
droxypiperidine (Table 1, run no. 18). The reaction
was performed using 39.6 mg (0.050 mmol) of porphy-
rin I, 35 mg (0.3 mmol) of trans-3,4-dihydroxypi-
peridine, 86 mg (0.9 mmol) of t-BuONa, 2.2 mg
(0.010 mmol) of Pd(OAc)2, and 5.1 mg (0.018 mmol)
of (t-Bu)3P · HBF4 in 5 ml of dioxane. Following
method a, we isolated 15 mg (47%) of compound V
and 4.0 mg (11%) of IVf.
2. Boyle, R.W. and Dolphin, D., Photochem. Photobiol.,
1996, vol. 64, p. 469.
3. Ali, H. and van Lier, J.F., Chem. Rev., 1999, vol. 99,
p. 2379.
4. Grishina, G.V., Borisenko, A.A., Nosan’, Z.G., Ashke-
nadze, L.D., Veselov, I.S., Zefirov, N.S., Karamov, E.V.,
and Kornilaeva, G.V., Dokl. Ross. Akad. Nauk, 2003,
vol. 391, p. 487.
5. Huryn, S.K. and Okabe, M., Chem. Rev., 1992, vol. 92,
p. 1745.
15-[4-(trans-3,4-Dihydroxypiperidin-1-yl)-
6. Semeikin, A.S., Lyubimova, T.V., and Golubchi-
phenyl]-2,8,12,18-tetraethyl-3,7,13,17-tetramethyl-
kov, O.A., Zh. Prikl. Khim., 1993, vol. 66, p. 710.
1
5-phenylporphyrin (IVe). H NMR spectrum
7. Kuvshinova, E.M., Pukhovskaya, S.P., Semeikin, A.S.,
and Golubchikov, O.A., Russ. J. Gen. Chem., 2004,
vol. 74, p. 1610.
(CDCl3–CF3COOH–CD3OD, 97:1:2), δ, ppm: 10.08 s
(2H, 10-H, 20-H), 8.23 m (2H), 8.11 d (2H), 7.87 m
(3H), 7.43 d (2H), 4.19 m (1H), 4.06 m (1H), 3.80 m
(1H), 3.66 m (9H), 3.18 t (1H), 3.01 t (1H), 2.22 s
(6H), 2.17 s (6H), 1.8–2.25 m (2H), 1.36 t (12H, CH3).
Found: m/z 746.33 [M + H]+. C49H55N5O2. Calculated:
[M + H] 746.44.
8. Dolphin, D., Johnson, A.W., Zeng, J., and van Der
Brock, P., J. Chem. Soc. C, 1966, p. 880.
9. Sharman, W.M. and van Lier, J.F., J. Porphyrins
Phthalocyanines, 2000, vol. 4, p. 441.
10. Shanmugathasan, S., Jonson, J.F., Edwards, C.,
Matthews, E.R., Dolphin, D., and Royle, R.W.,
J. Porphyrins Phthalocyanines, 2000, vol. 4, p. 228.
Reaction of porphyrin I with trans-3-hydroxy-4-
(4-hydroxypiperidin-1-yl)piperidine (Table 1, run
no. 19). The reaction was carried out using 39.6 mg
(0.050 mmol) of porphyrin I, 82 mg (0.3 mmol) of
3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine dihy-
drochloride, 154 mg (1.6 mmol) of t-BuONa, 2.24 mg
(0.010 mmol) of Pd(OAc)2, and 4.4 mg (0.015 mmol)
of (t-Bu)3P·HBF4 in 5 ml of dioxane. Following meth-
od a, we isolated 10.3 mg (34%) of compound V and
10.5 mg (25%) of IVg.
11. Shi, B. and Royle, R.W., J. Chem. Soc., Perkin Trans. 1,
2002, p. 1347.
12. Shi, D.F. and Wheelhouse, R.T., Tetrahedron Lett.,
2002, vol. 43, p. 9341.
13. Chen, Y. and Zhang, X.P., J. Org. Chem., 2003, vol. 68,
p. 4432.
14. Takahami, T., Hayashi, M., Hino, F., and Suda, K.,
Tetrahedron Lett., 2003, vol. 44, p. 7353.
15. Gao, G.-Y., Chen, Y., and Zhang, X.P., J. Org. Chem.,
2,8,12,18-Tetraethyl-15-{4-[trans-3-hydroxy-4-
(4-hydroxypiperidin-1-yl)piperidin-1-yl]phenyl}-
3,7,13,17-tetramethyl-5-phenylporphyrin (IVg).
1H NMR spectrum (CDCl3), δ, ppm: 10.22 s (2H, 10-H,
20-H), 8.06 d (2H), 7.86 m (2H), 7.70–7.80 m (3H),
7.25 d (2H), 4.32 m (1H), 4.02 q (8H, CH2), 3.87 m
(1H), 3.69 m (1H), 3.09 m (1H), 2.6–3.0 m (5H), 2.54 s
(6H), 2.48 s (6H), 2.26 m (1H), 1.5–2.0 m (7H), 1.77 t
(12H, CH3), –2.44 s (2H, NH). Found: m/z 829.63
[M + H]+. C54H64N6O2. Calculated: [M + H] 829.51.
2003, vol. 68, p. 6215.
16. Gao, G.-Y., Chen, Y., and Zhang, X.P., Org. Lett., 2004,
vol. 6, p. 1837.
17. ACD Library of FT NMR Spectra. Ver. 1.11, Aldrich,
1999.
18. Hayashi, T., Mise, T., Fukashima, M., Kagotani, M.,
Nagashima, N., Hamada, Y., Matsumoto, A., Kawaka-
mi, S., and Kumada, M., Bull. Chem. Soc. Jpn., 1980,
vol. 53, p. 1138.
19. Gusev, O.V., Peganova, T.Y.A., Kalsin, A.M., Volog-
din, N.V., Petrovskii, P.V., Lyssenko, K.A., Tsvet-
kov, A.V., and Beletskaya, I.P., Organometallics, 2006,
vol. 25, p. 2750.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 05-03-32658) and by the President of the Russian
Federation (program for support of leading scientific
schools, project no. HI-6059.2006.3).
20. Ganina, O.G., Veselov, I.S., Grishina, G.V., Fedo-
rov, A.Yu., and Beletskaya, I.P., Izv. Ross. Akad. Nauk,
Ser. Khim., 2006, p. 1583.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008