An alternative approach to amino porphyrins

Article abstract of DOI:10.1002/jhet.410

(Chemical Equation Presented) Modified nitration of tetraphenylporphyrin at para of phenyl with HNO₃/Cl₃CCOOH and one-pot nitration of free tetraarylporphyrins to metalized 2-nitroporphyrin in high yield are described. A novel reduce

Full text of DOI:10.1002/jhet.410

September 2010
An Alternative Approach to Amino Porphyrins
1221
a,b
Shi Weimin, Shen Qi, Wang Yucheng, Lan Lihong,
a,b
a,b
a,b
a,b
and Tao Jingchao *
a
Department of Chemistry, Zhengzhou University, Zhengzhou 450052, People’s Republic of China
b
New Drug Research and Development Center, Zhengzhou University, Zhengzhou 450052,
People’s Republic of China
*E-mail: jctao@zzu.edu.cn
Received October 13, 2009
DOI 10.1002/jhet.410
Published online 11 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
Modified nitration of tetraphenylporphyrin at para of phenyl with HNO /Cl CCOOH and one-pot
3
3
nitration of free tetraarylporphyrins to metalized 2-nitroporphyrin in high yield are described. A novel
reducer of Zn/HCOONH has been developed for above nitro of porphyrin into amino effectively.
4
J. Heterocyclic Chem., 47, 1221 (2010).
INTRODUCTION
phyrin [3], so modifying its porphyrin macrocycle or
aryl around was an available way to get various novel
porphyrins [4]. The nitration modification has been
investigated in detail by many reagents [5]. The sort of
porphyrin containing amino function has wide use in the
architecture of porphyrins with extended p-system,
chlorines, porphyrin assembly, supermolecule propertie
[6].
Over the last three decades, functionalization of por-
phyrins has received considerable attention for introduc-
ing functions into porphyrins could varied the properties
of porphyrins and afford availability of diverse porphy-
rin architecture by arising a energetic bond for further
functionalization [1]. Therefore, fairish efforts were
underway in various laboratories to explore novel and
available approach to modify porphyrins [2]. meso-Tet-
raarylporphyrin (TAP) including tetraphenylporphyrin
We have afforded access to nitro TPP by nitration of
para of phenyl, which was transformed into widely use-
ful amino function for subsequent modification [7].
(
TPP) is one of the most readily available synthetic por-
V
C
2010 HeteroCorporation

1
222
S. Weimin, S. Qi, W. Yucheng, L. Lihong, and T. Jingchao
Vol 47
Scheme 1. Synthesis of amino porphyrin via nitration and reduction.
Herein, we report the synthesis of TAP by modified
Alder–Longo method condensing pyrrole with acid sen-
sitive 3,4-methylenndioxyphenylaldehyde, sequent modi-
fied nitration of phenyl, as well as one-pot nitration of
porphyrin periphery. A rapid and efficient process for
reduction of nitro group at phenyl or b of porphyrin into
amino has been developed.
tion. In chloroform, TPP was translated into porphyrins
4b and 5b at room temperature under air condition with
total yield 81%.
In the molecule of TAP, b-site of pyrrolic is another
active site as well as para-site of phenyl, and nitration at
this site with various reagents and the further reduction
had been investigated in detail by many researchers [8].
The earlier works showed that there were two steps,
including metallization of free porphyrins with chloride
or acetate and nitration using nitrate salt. Cuprous ion
was found to readily insert into core of free porphyrins
during treatment with cuprous ion, implying that metal-
lization and nitration both could be likely conducted by
sole cuprous nitrate. The previous nitration through two
steps may be pieced together. The attempt to ‘‘one-pot’’
nitration with acetic anhydride and cuprous nitrate was
successful in excellent yield. Nitration of free base por-
RESULTS AND DISCUSSION
On account of the fact that meso-TPP 1b was particu-
larly readily prepared, it should be a handy way to
achieve a variety of substituted porphyrins by introduc-
ing suitable group to TPP, especially at the phenyl rings.
A few workers reported phenyl para nitration of TPP
with fuming nitric acid, or NaNO /TFA (trifluoroacetic
2
acid). As shown in Scheme 1, condensation of pyrrole
with aromatic aldehyde in refluxing xylene under meta-
nitrobenzoic acid provided porphyrin 1a and 1b in mod-
erate yield of somewhat 50%. The starting porphyrin
TPP was subjected to nitration to afford porphyrin con-
taining mono and bis-nitro phenyl. Instead of TFA/
phyrins 1a and 1b by Cu(NO3)2 and Ac O for 2 h
resulted in 2a and 2b with nitro group at b-site.
Nitrobenzenes were successfully converted into corre-
2
sponding azoaryl by Zn/HCOONH [9], similarly, we
4
would prepare azoaryl porphyrin [10] from nitro com-
pound. As shown in Scheme 1, an unpredicted amino
porphyrin was achieved starting with 4b under similar
conditions. No azoaryl products came into being no mat-
ter how we regulated the reaction conditions, such as
NaNO , which was used in the Smith’s method, the
2
solid trichloroacetic acid and concentrated nitric acid
was found to be effect, preferable control for this reac-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
An Alternative Approach to Amino Porphyrins
1223
temperature, stoichiometry of reagent, solvent, and reac-
tion times. Treatment of nitro porphyrins 4b and 5b at
room temperature in CHCl3 with large excess Zn/
was washed with water (4 ꢁ 150 mL), and dried over magne-
sium sulfate. Solvent was removed with evaporation under
reduced pressure. The crude product was purified by column
chromatography to provide 4b (370 mg, 36%) and 5b (506
mg, 45%).
HCOONH gave rapidly corresponding amino porphyr-
4
ins over a few minutes in yield up to 90%. As alike as
4
General procedure for nitration of b at porphyrin. To a
solution of porphyrins in Ac O and chloroform, Cu(NO ) was
2 3 2
b and 5b with para-nitrophenyl porphyrin, easy reduc-
tion of 2a and 2b with nitro at b-site produced 3a and
added. The mixture was heated to reflux, kept for 2 h. Solvent
was evaporated in a vacuum. Purification on silica gel gave
nitro porphyrins in yields of about 90%.
3
b in high yield.
Most reductions of nitro were actualized by SnCl2/
(
2-nitro-5,10,15,20- tetra (3,4-methylendioxy)phenylpor-
HCl or hydrogenation with Pd/C. However, many func-
tions were sensitive to strong acid, as well as the hard-
ness of separating inorganic objects was trying.
Although Pd/C is high efficient, it is somewhat incon-
stant. An attempt of reduction was unsuccessful, the
great mass of material spared when crude nitration prod-
uct from TPP was performed with Pd/C. The value of
here process is nevertheless very obvious: milder condi-
tions, simpler experimental procedure.
phyrinato)copper-II (2a). Porphyrin 1a (500 mg, 0.8 mmol) in
Ac O (20 mL, 0.2 mol) by Cu(NO ) ꢂ3H O (800 mg, 3.3
2
3 2
2
mmol) gave porphyrin 2a in yield 86%. IR: NO 1508, 1345
2
ꢀ
1
cm . UV: kmax 432, 552.5, 595.5 nm. Anal. Calcd. for
C H CuN O : C, 64.25; H, 3.03; N, 7.80. Found: C, 64.33;
27
48
5 10
H, 3.09; N, 7.65.
General procedure for reduction of nitro function to
amino function. To a solution of nitro porphyrins in CHCl3,
4
Zn powder, and HCOONH was added with fierce stirring.
The mixture was kept at room temperature for a little of 5
min. The solid inorganic was removed by filtration. Solution
of porphyrin was washed by water, followed by drying with
magnesium sulfate. Solvent was evaporated in a vacuum. The
crude product was purified on a silica gel column, providing
amino porphyrins in yield of 82–90%.
(2-Amino-5,10,15,20-tetra (3,4-methylendioxy)phenylpor-
phyrinato)copper-II (3a). Porphyrin 2a (200 mg, 0.8 mmol) in
CHCl3 (50 mL) with Zn powder (5.0 g, 0.1 mol) and
In summary, we have shown an effective nitration at
para of phenyl of tetraphenylporphyirn with HNO3/
Cl CCOOH, and ‘‘one-pot’’ nitration of free TAPs by
3
Cu(NO ) /(CH CO) O excellently. The process for
3
2
3
2
reduction of nitro at above porphyrins into amino using
Zn/HCOONH4 was rapid, convenient, and excellent.
Further transformation for application of amino porpyr-
ins is underway.
HCOONH
IR: NH , 3475, 1483, 1247, 1036 cm . UV: kmax 419, 547,
96nm. Anal. Calcd. for C48 29CuN : C, 66.47; H, 3.37; N,
.07. Found: C, 66.32; H, 3.43; N, 8.16.
4
(8.0 g, 0.1 mol) gave porphyrin 3a in yield 86%.
ꢀ
1
2
5
8
H
5 8
O
EXPERIMENTAL
General. Pyrrole was purchased from Aldrich and distilled
under reduced pressure immediately before use. All other
reagents and solvents were used as received from Aldrich. Sol-
vents were reagent grade unless otherwise specified and were
dried and distilled by standard method. The UV-visible spectra
Acknowledgments. This project was supported by National Nat-
ural Science Foundation of China (20772113, 20505015) and
Natural Science Foundation Henan Education Department
(
2006150026).
1
were obtained on a Perkin-Elmer LS-5B spectrofluroimeter. H
NMR spectra were recorded on BRUKER AVANCE DMX
RERENCES AND NOTES
[1] Kadish, K. M.; Smith, K. M.; Guilard R. The porphyrin
500 spectrometer. Elementary analyses were obtained on a
Carlo Erba 1106 Elemental Analyzer.
Porphyrins 1b, 1a were synthesized by literature methods
Handbook; Academic Press: San Diego, 2000–2003; Vol. 1–20.
[2] (a) Arnold, D. P.; Johnson, A. W.; Mahendram, M. J Chem
Soc Perkin Trans 1978, 1, 366; (b) Jiang, X.; Nurco, D. J.; Smith, K.
M. J Chem Soc Chem Commun 1996, 1759; (c) Yeung, M.; Ng, A. C.
H.; Drew, M. G. B.; Vorpagel, E.; Breitung, E. M.; McMahon, R. J.;
Ng, D. K. P. J Org Chem 1998, 63, 7143.
[
7]. Spectra of porphyrins 1b–7b were agreement with
literature.
,10,15,20-Tetra
5
(3,4-methylendioxy)phenylporphyrin
1
(
(
7
1a). Porphyrin 1a was synthesized in yield 48%. H NMR
deuterichloroform): d 8.92–8.80 (8H, m, b -pyrrole), 7.70–
[
3] (a) Adler, A. D.; Longo, F. R.; Finarelli, J. D. J Org Chem
.63 (m, 8H), 7.24–7.17 (m, 8H), 6.25 (s, 4H), ꢀ2.73 (s, 2H).
1
5
967, 39, 476; (b) Lindsey, J. S.; Wagner, R. W. J Org Chem 1989,
4, 828.
UV k : 419.0, 516.0, 554.0, 597.0, 648.0 nm. Anal. Calcd.
max
H N O : C, 72.90; H, 3.82; N, 7.09. Found: C, 72.73;
30 4 8
for C48
H, 3.91; N, 7.17.
-(4-Nitrophenyl)-10,15,20-triphenyl-porphyrin (4b) and
,10-di(4-nitrophenyl)-15,20-diphenyl-porphyrin (5b). To
solution of porphyrin 1b (1 g, 1.6 mmol) and trichloroacetic
acid (30 g) in chloroform (100 mL) was slowly added HNO
6.0 mL, 75%, 15.5 mmol) over 2 min with fierce stir at room
[
4] (a) Tabushi, I.; Kugimiya, S. J Am Chem Soc 1986, 108,
6926; (b) Tommaso, A. V.; Timothy, K. Inorg Chem 1999, 38, 2246;
5
(
c) Burrell, A. K.; Campbell, W. M.; Officer, D. L.; Gordon, K. C.;
McDonald, M. R. J Chem Soc Dalton Trans 1999, 19, 3349.
5] (a) Anura, W; Lanurent, J; Daniel, J. N.; Smith, K. M. Tet-
5
a
[
3
rahedron 2001, 57, 4261; (b) Guangzhen, G. M.; James, B. R.; Skov,
K. A. Can J Chem 1994, 72, 1894.
(
temperature under atmosphere. The mixture was stirred for 5
min. Reaction was quenched with water, and the mixture was
neutralized with ammonium hydroxide aqueous solution to pH
[
6] (a) Crossly, N. J.; Burn, P. L.; Langford, S. J.; Pyke, S. M.;
Stark, A. G. J Chem Soc Chem Commun 1991, 1567; (b) Seaaler, J.
L.; Brown, C. T.; O’Connor, D.; Springs, S. L.; Wang, R.; Sathiosat-
ham, M.; Hirose, T. J Org Chem 1998, 63, 7370; (c) Promarak, V.;
¼
7. Chloroform (100 mL) was added, and the organic layer
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1
224
S. Weimin, S. Qi, W. Yucheng, L. Lihong, and T. Jingchao
Vol 47
Burn, P. L. J Chem Soc Perkin Trans 2001, 1, 14; (d) Starnes, S. D.;
Arundundram, S.; Saunders, C. H. Tetrahedron Lett 2002, 43, 7785.
B.; Smith, K. M.; Cavaleiro, J. A. S. J Chem Soc Perkin Trans 1978,
1, 768.
[
7] (a) Wu, J.; Shi, W. M.; Wu, D. Chem Lett 2004, 33, 460;
b) Wu, J.; b. Shi, W. M.; Zhang, G.; Dai, G. F.; Zhang, Y. X.; Zhao,
J.; Tao, J. C. Bioorg Med Chem 2008, 16, 5665.
8] (a) Baldwin, J. E.; Crossley, M. J.; Bernardis, J. Tetrahe-
[9] (a) Gowda, S.; Gowda, D. C. Synthesis 2002, 4, 460; (b)
Srinivasa, G. R.; Abiraj, K.; Gowda, D. C. Syn Commu 2003, 33,
4221.
(
[
[10] (a) Hombrecher, H. K.; L u¨ dtke, K. Tetrahedron 1993, 49,
9489; (b) Autret, M.; Plouzennec, M. Le; Moinet, C.; Simonneaux, G.
J Chem Soc Chem Commun 1994, 1169.
dron 1982, 38, 685; (b) Catalano, M. M.; Crossley, M. J.; Harding, M.
M.; King, L. G. J Chem Soc Chem Commun 1984, 1535; (c) Evans,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet