A convenient hydrogenation method for the synthesis of metallo- mesoporphyrin IX dimethyl esters via self-catalyzed CoCl2-NaBh 4 reagent system

Article abstract of DOI:10.1002/cjoc.201200581

A convenient protocol has been developed for the hydrogenation of metallo-protoporphyrin IX dimethyl esters (MPPDMEs) to their mesoporphyrin analogues using CoCl₂-NaBH₄ reagent system. Metallo-porphyrin complexes were found to perform as self-catalysts in this procedure. This method provides several advantages such as safe and simple procedure, short reaction time, high yields and low cost. Copyright

Full text of DOI:10.1002/cjoc.201200581

FULL PAPER
DOI: 10.1002/cjoc. 201200581
A Convenient Hydrogenation Method for the Synthesis of
Metallo-mesoporphyrin IX Dimethyl Esters via
Self-catalyzed CoCl2-NaBH4 Reagent System
Xu, Shichao(徐士超)
Wang, Huan(王欢)
Hu, Bingcheng*(胡炳成)
Huang, Xiuyou(黄修有)
Liu, Zuliang(刘祖亮)
Hu, Tianjing(胡田菁)
Lou, Xingkun(娄兴焜)
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
A convenient protocol has been developed for the hydrogenation of metallo-protoporphyrin IX dimethyl esters
(MPPDMEs) to their mesoporphyrin analogues using CoCl2-NaBH4 reagent system. Metallo-porphyrin complexes
were found to perform as self-catalysts in this procedure. This method provides several advantages such as safe and
simple procedure, short reaction time, high yields and low cost.
Keywords protoporphyrin, catalytic hydrogenation, mesoporphyrin, cobalt chloride, sodium borohydride
alcoholic medium at room temperature.[14-17] It is prom-
ising to explore a much safer and efficient method to
prepare MPDs or MMPDs using sodium borohydride
hydrogenation system. We report in this paper a self-
catalyzed CoCl2-NaBH4 reagent system for the hydro-
genation of protoporphyrin IX dimethyl ester (PPDME)
and its metal complexes (MPPDME, Scheme 1). Met-
allo-porphyrins were found to act as self-catalysts in this
protocol and greatly accelerated the hydrogenating
process. This simple and efficient method may open up
the possibility of a more convenient and economical
process for the synthesis of MPDs.
Introduction
Metallo-porphyrin complexes are important 18π-
conjugated organic molecules and have been exten-
sively used in a variety of chemical, biological, and
clinical studies to mimic the active sites of enzymes.[1-4]
Metallo-mesoporphyrin IX complexes (MMPCs) have
often been the preferred choice because of their greater
stability than semi-synthetic metallo-protoporphyrin IX
complexes (MPPCs) or metallo-hematoporphyrin IX
complexes (MHPCs) and their closer relation to the
naturally occurred porphyrins than the metal complexes
of totally synthetic tetraphenylporphyrins (TPPs).[5-10]
MMPCs have been prepared by the hydrogenation of
MPPCs or the metallation of the hydrogenation products
of protoporphyrin IX derivatives (PPDs). The hydro-
genation of MPPCs and PPDs is traditionally performed
under the catalysis of noble metal compounds using H2
as hydrogen donor.[5,6,11-13] Besides high-cost issues as-
sociated with the noble metal catalysts, the major draw-
backs of these systems are complicated approaches and
time-consuming procedures because of the requirement
of a heterogeneous H2-hydrogenation system. Further-
more, hydrogen is easily ignited and presents consider-
able hazards at high temperature, particularly on the
large scale. Finding inexpensive, simple and secure hy-
drogenation system for the preparation of MMPCs still
remains a challenge.
Experimental
Chemicals and reagents
Organic solvents were dried before use. Other
chemicals were of analytical grade obtained from com-
mercial sources and used without further purification.
PPDME was synthesized and purified from hemin 1
according to reported procedure.[18] MPPDME 2b—2f
were synthesized according to the typical metal inser-
tion method as described in literature.[19]
Equipments and apparatus
Melting points were determined on a Kofler hot-
1
stagemicroscope and are uncorrected. H NMR spectra
Sodium borohydride in the presence of transition
metal halides, behaves as a homogeneous hydrogenating
agent when the reaction is carried out in THF, DMF or
were obtained on a Bruker Avance III 500 MHz spec-
trometer, with tetramethylsilane (TMS) and CDCl3 as
the internal standard and stated solvent. For FTIR spec-
*
E-mail: hubingcheng@yahoo.com; Tel.: 0086-25-8431-5030; 0086-25-8431-5030
Received June 14, 2012; accepted July 16, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200581 or from the author.
Chin. J. Chem. 2012, 30, 2461—2465
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2461

Xu et al.
FULL PAPER
Scheme 1 Hydrogenation of NPPDME
N
N
Cl N
Fe
N
N
N
N
N
N
N
N
d
a, b, c
X
X
N
CO2H
CO2CH3
CO2CH3
CO2H
CO2CH3
CO2CH3
1
2
3
X = 2H (2a, 3a), FeCl (2b, 3b), Co (2c, 3c), MnCl (2d, 3d), Ni (2e, 3e), Cu (2f, 3f), Zn (2g, 3g), Sn (2h, 3h)
(a) HCOOH, Fe, reflux, 0.5 h; (b) CH3OH, H2SO4, reflux, 0.5 h (The product is 2a); (c) DMF, MClx•nH2O (from 2a, M＝Fe, Co, Mn, Ni, Cu, Zn and Sn),
reflux; (d) DMF, CoCl2•6H2O, NaBH4, r.t.
tra, a Thermo Nicolte IS10 IR instrument was applied.
ESI-MS results were recorded on a Finnigan TSQ
Quantum Mass Spectrometer (using electrospray ioniza-
tion source). Elemental analysis was completed on a
Perkin-Elmer PE-2400 elemental analyzer.
found C 72.44, H 7.03, N 9.57.
FeClMPDME (3b)
Obtained as black solid
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
ether＝1∶1∶5, m.p.＞300 ℃); H NMR (500 MHz,
CDCl3): paramagnetic; IR (KBr): 2925 (m, νCH), 2863
1
(w, νCH), 1709 (s, νC O), 1439 (w, δ
), 1382 (m, δ CH ),
＝
CH2
3
Self-catalyzed hydrogenation of MPPDME by CoCl2-
NaBH4 reagent system
1201 (m, νC O), 1147 (w), 1041 (w), 939 (w), 842 (w),
—
－
＋
＋
1
705 (m) cm ; ESI -MS (35 eV) m/z: 648 [M－Cl] ,
575 [M－CH2COOCH3－Cl]＋, 560 [M－CH2CH2C-
OOCH3－Cl]＋, 502 [M－2CH2COOCH3－Cl]＋. Anal.
calcd for FeClC36H40N4O4: C 63.21, H 5.89, N 8.19;
found C 63.46, H 6.01, N 8.34.
A solution of 2 (1.53 mmol) in the mixture of
CH2Cl2 and DMF (30 mL, volume ratio 1∶1) was
treated successively with CoCl2•6H2O (0.76 mmol) and
NaBH4 (15.85 mmol, dissolved in 15 mL DMF; added
for three times in less than 10 min) under N2 atmosphere
and then stirred at 25 ℃ (total reaction time was listed
in Table 3). After hydrogenation, the result mixture was
transformed into 200 mL water and extracted with 300
mL CH2Cl2. The organic phase was collected and
washed for three times with water to remove DMF. The
crude product was purified by column chromatography
(300—400 mesh silica gel). The filtrate was collected
and evaporated to dryness to afford MMPDME as
brownish, red or black solids. All synthesized com-
CoMPDME (3c) Obtained as brownish solid
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
ether)＝1∶1∶5, m.p.＞300 ℃]; H NMR (500 MHz,
1
CDCl3): paramagnetic; IR (KBr): 2947 (m, νCH), 2864
(w, νCH), 1727 (s, νC O), 1439 (m, δ
), 1386 (m,
＝
CH2
δ CH ), 1240 (m, νC O), 1165 (w), 1054 (w), 962 (w),
—
3
－
＋
1
833 (w), 705 (m) cm ; ESI -MS (35 eV) m/z: 651
[M]＋, 578 [M－CH2COOCH3]＋, 563 [M－CH2CH2-
COOCH3]＋, 505 [M－2CH2COOCH3]＋. Anal. calcd for
CoC36H40N4O4: C 66.35, H 6.19, N 8.60; found C 66.11,
H 6.31, N 8.74.
1
pounds were structurally characterized by H NMR,
FTIR, ESI-MS and elemental analysis.
MnClMPDME (3d)
Obtained as black solid
MPDME (3a) Obtained as brownish solid [V(ethyl
acetate)∶ V(dichloromethane)∶ V(petroleum ether)＝
1∶6∶14, m.p.: 215—217 ℃]; H NMR (500 MHz,
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
ether)＝1∶1∶5, m.p.＞300 ℃]; H NMR (500 MHz,
CDCl3) δ: paramagnetic; IR (KBr): 2947 (m, νCH), 2863
1
1
CDCl3) δ: 10.11 (s, 1H, 20-H), 10.10 (s, 2H, 5-, 15-H),
10.09 (s, 1H, 10-H), 4.41 (t, JHH＝7.5 Hz, 4H, 13-,
17-β-CH2, α to carbonyl), 4.09 (q, JHH＝7.5 Hz, 4H, 3-,
8-CH2CH3), 3.67, 3.66, 3.65, 3.64 (4s, 18H, 2-, 7-, 12-,
18-CH3 and 13-, 17-OCH3), 3.29 (t, JHH＝7.5 Hz, 4H,
13-, 17-α-CH2, α to carbonyl), 1.84 (t, JHH＝7.5 Hz, 6H,
3-, 8-CH2CH3), －3.76 (s, 2H, NH); IR (KBr): 3345 (m,
(w, νCH), 1731 (s, νC O), 1435 (m, δ
), 1355 (m,
＝
CH2
δ CH ), 1200 (m, νC O), 1165 (w), 1055 (w), 957 (w),
—
－
3
＋
1
833 (m), 718 (m) cm ; ESI -MS (45 eV) m/z: 647 [M－
Cl]＋, 574 [M－CH2COOCH3－Cl]＋, 559 [M－CH3－
CH2COOCH3－Cl]＋, 501 [M－2CH2COOCH3－Cl]＋.
Anal. calcd for MnClC36H40N4O4: C 63.30, H 5.90, N
8.20; found C 63.53, H 5.79, N 8.37.
νNH), 2960 (m, νCH), 2874 (w, νCH), 1733 (s, νC O), 1459
—
NiMPDME (3e) Obtained as light brownish solid
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
ether)＝3∶5∶25, m.p.＞300 ℃]; 1H NMR (500 MHz,
CDCl3) δ: 9.76 (s, 2H, 20, 5-H), 9.75 (s, 2H, 10, 15-H),
4.25 (t, JHH＝7.0 Hz, 4H, 13-, 17-β-CH2, α to carbonyl),
3.92, 3.91 (2q, JHH＝7.5 Hz, 4H, 3-, 8-CH2CH3), 3.70,
3.69, 3.50, 3.49, 3.47, 3.46 (6s, 18H, 2-, 7-, 12-, 18-CH3
(m, δCH ), 1373 (m, δCH ), 1238 (m, νC O), 1153 (w),
—
2
3
1099 (w), 1045 (m), 940 (w), 832 (w), 737 (m), 681 (m)
－
1
＋
＋
cm ; ESI -MS (50 eV) m/z: 595 [M＋H] , 580 [M－
CH3＋H]＋, 565 [M－2CH3＋H]＋, 551 [M－CH2CH3－
CH3＋H]＋, 507 [M－CH2CH2COOCH3－CH3＋H]＋.
Anal. calcd for C36H42N4O4: C 72.70; H 7.12; N 9.42;
2462
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2461—2465

Convenient Hydrogenation Method for the Synthesis of Metallo-mesoporphyrin IX Dimethyl Esters
and 13-, 17-OCH3), 3.18, 3.17 (2t, JHH＝7.5 Hz, 4H, 13-,
17-α-CH2, α to carbonyl), 1.77, 1.76 (2t, JHH＝7.5 Hz,
6H, 3-, 8-CH2CH3); IR (KBr): 2921 (m, νCH), 2855 (w,
IX dimethyl ester (PPDME) or its metal complexes
(MPPDME) were reduced in this procedure to provide
corresponding vinyl saturated products. To optimize the
experimental conditions for the hydrogenation of MPP-
DME in this system, CoPPDME was selected as the
model using different solvents at room temperature.
Several organic solvents, such as CH2Cl2, CH3CN,
DMF, ethanol, methanol, n-hexane and THF were ap-
plied in this procedure to further explore the solvent
effects on the reaction (Table 1, Entries 1—7). The re-
sults indicated that the use of polar aprotic solvents such
as CH3CN, DMF or THF generated higher yields of the
desired products than protic solvents or non-polar sol-
vents. It has reported that in CoCl2-NaBH4 hydrogena-
tion system, the formation of “CoH2” is the key step (Eq.
1).[20] In polar solvents, CoH2 seemed to be stabilized by
extensive solvation, which promoted the hydrogenation
of vinyl groups. However, protic solvents such as
methanol and ethanol might react with CoH2, leading to
the fast decomposition of CoH2 and the quenching of
this procedure. More interestingly, the introducing of
CH2Cl2 in DMF was found to be a more efficient sol-
vent in our process because of the high solubility of
MPPDME in CH2Cl2. Thus, the catalyzed hydrogena-
tion reaction was carried out in the mixture of CH2Cl2
and DMF to improve the unsatisfactory results (Table 1,
Entries 8—12), and the mixture at the volume ratio of
1∶2 gave the better yield (87%).
νCH), 1731 (s, νC O), 1435 (w, δ
), 1377 (m, δ CH ),
＝
CH2
3
1220 (m, νC O), 1156 (m), 931 (w), 833 (w), 714 (m)
—
－
＋
＋
1
cm ; ESI -MS (35 eV) m/z: 651 [M＋H] , 578 [M－
CH2COOCH3＋H]＋, 505 [M－2CH2COOCH3＋H]＋.
Anal. calcd for NiC36H40N4O4: C 66.38, H 6.19, N 8.60;
found C 66.65, H 6.05, N 8.44.
CuMPDME (3f) Obtained as black solid [V(ethyl
acetate)∶ V(dichloromethane)∶ V(petroleum ether)＝
1
1∶1∶5, m.p.＞300 ℃]; H NMR (500 MHz, CDCl3)
δ: paramagnetic; IR (KBr): 2916 (m, νCH), 2859 (w, νCH),
1736 (s, νC O), 1435 (m, δ
), 1382 (m, δCH3), 1196 (w,
＝
CH2
νC O), 1161 (m), 1054 (w), 940 (w), 833 (w), 709 (m)
—
－
＋
＋
1
cm ; ESI -MS (42 eV) m/z: 656 [M＋H] , 583 [M－
CH2COOCH3＋H]＋, 569 [M－CH2CH2COOCH3＋H]＋,
510 [M － 2CH2COOCH3 ＋ H] ＋ . Anal. calcd for
CuC36H40N4O4: C 65.89, H 6.14, N 8.54; found C 65.61,
H 6.23, N 8.71.
ZnMPDME (3g) Obtained as bright red solid
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
1
ether)＝1∶1∶5, m.p.＞300 ℃]; H NMR (500 MHz,
CDCl3) δ: 9.61 (s, 1H, 20-H), 9.51 (s, 1H, 5-H), 9.47 (s,
1H, 15-H), 9.45 (s, 1H, 10-H), 4.24, 4.18 (2t, JHH＝7.5
Hz, 4H, 13-, 17-β-CH2, α to carbonyl), 3.93, 3.84 (2q,
J
HH＝7.5 Hz, 4H, 3-, 8-CH2CH3), 3.68, 3.66, 3.51, 3.45,
3.43, 3.39 (6s, 18H, 2-, 7-, 12-, 18-CH3 and 13-, 17-
OCH3), 3.15, 3.12 (2t, JHH＝7.5 Hz, 4H, 13-, 17-α-CH2,
α to carbonyl), 1.78, 1.73 (2t, JHH＝7.5 Hz, 6H, 3-, 8-
CH2CH3); IR (KBr): 2916 (m, νCH), 2856 (w, νCH), 1731
Table 1 Solvent effects on the reaction
Entry Reaction medium Volume ratio Time/min Yield/%
(s, νC O), 1434 (m, δ
), 1374 (m, δ CH ), 1179 (m),
＝
CH2
3
－
1
1
2
CH2Cl2
—
—
50
40
20
30
30
70
20
20
20
20
20
20
32
54
75
16
8
1144 (m), 1053 (m), 964 (w), 831 (m), 751 (w) cm ;
ESI＋ -MS (42 eV) m/z: 657 [M＋H]＋ , 628 [M－
CH2CH3＋H]＋, 583 [M－CH2COOCH3]＋, 570 [M－
CH2CH2COOCH3＋H]＋. Anal. calcd for ZnC36H40N4O4:
C 65.70, H 6.13, N 8.51; found C 65.86, H 6.01, N 8.66.
SnMPDME (3h) Obtained as bright red solid
[V(ethyl acetate) ∶ V(dichloromethane)∶ V(petroleum
ether)＝6∶50∶1, m.p.＞300 ℃]; 1H NMR (500 MHz,
CDCl3) δ: 10.72 (s, 1H, 20-H), 10.66 (s, 1H, 5-H), 10.61
CH3CN
3
DMF
—
4
Ethanol
—
5
Methanol
n-Hexane
THF
—
6
—
0
7
—
51
48
60
71
87
77
8
CH2Cl2/DMF
CH2Cl2/DMF
CH2Cl2/DMF
CH2Cl2/DMF
CH2Cl2/DMF
4∶1
2∶1
1∶1
1∶2
1∶4
(s, 1H, 15-H), 10.57 (s, 1H, 10-H), 4.58, 4.57 (2t, JHH
＝
9
7.5 Hz, 4H, 13-, 17-β-CH2, α to carbonyl), 4.24, 4.23
(2q, JHH＝7.5 Hz, 4H, 3-, 8-CH2CH3), 3.83, 3.82, 3.80,
3.66, 3.60 (5s, 18H, 2-, 7-, 12-, 18-CH3 and 13-, 17-
OCH3), 3.43, 3.42 (2t, JHH＝7.5 Hz, 4H, 13-, 17-α-CH2,
α to carbonyl), 2.00, 1.99 (2t, 6H, JHH＝7.5 Hz, 3-, 8-
CH2CH3); IR (KBr): 2922 (m, νCH), 2868 (w, νCH), 1730
10
11
12
CoCl NaBH →CoH 2BH 2NaCl
(1)
＋
＋
＋
2
4
2
3
(s, νC O), 1434 (m, δ
), 1352 (m, δ CH ), 1197 (w,
＝
CH2
3
In order to investigate the roles of different con-
stituents, such as CoCl2 and NaBH4 each played in this
reaction, the influence of CoCl2 and NaBH4 on this re-
action was studied. It was observed from Figure 1 that
excess amount of NaBH4 was necessary for this hydro-
genation procedure. The yields of CoPPDME increased
with the increasing amount of NaBH4 and reached a
plateau at the mole ratio of NaBH4 to vinyl 5.18. The
variation in the amount of CoCl2 also had effective in-
νC O), 1163 (s), 1059 (m), 971 (m), 835 (m), 709 (m)
—
－
＋
＋
1
cm ; ESI -MS (42 eV) m/z: 711 [M] , 637 [M－
CH2COOCH3]＋ , 565 [M－2CH2C OOCH3]＋ . Anal.
calcd for SnC36H40N4O4: C 60.78, H 5.67, N 7.88; found
C 60.95, H 5.52, N 7.73.
Results and Discussion
The carbon-carbon double bonds of protoporphyrin
Chin. J. Chem. 2012, 30, 2461—2465
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2463

Xu et al.
FULL PAPER
fluences on this reaction. The yield of the CoMPDME
got the best result at the mole ratio of vinyl groups to
CoCl2 4.03.
Table 2 Catalytic hydrogenation of MPPDME in NaBH4-
CoCl2 system
Entry
Product
t/min
Yield/%
2
1
2
3
4
5
6
7
8
9
PPDME
PPDME
2a MPDMEa 3a 60
2a MPDMEb 3a 30
42
73
88
87
85
79
62
83
76
FePPDME 2b FeMPDME 3b 20
CoPPDME 2c CoMPDME 3c 20
MnPPDME 2d MnMPDME 3d 20
NiPPDME 2e NiMPDME 3e 25
CuPPDME 2f CuMPDME 3f
35
ZnPPDME 2g ZnMPDME 3g 20
SnPPDME 2h SnMPDME 3h 35
a
In the absence of cobalt tetraphenylporphyrin (CoTPP). b In the
presence of similar mole amount of CoTPP.
reagent systems for the hydrogenation of MPPCs or
PPDs has been well summarized by James and cowork-
ers.[6] Comparing with previous methods,[6] the hydro-
genation procedure explored in our letter has several
advantages: (1) CoCl2 is used to substitute costly noble
metal compounds and the organic solvents such as
CH2Cl2 and DMF are used as received. Thus, the ex-
perimental procedure proposed in our letter is more
economical; (2) the hydrogenation of CoPPDME in
CoCl2-NaBH4 hydrogenation system could be com-
pleted in less than 20 min with higher yields, much
more efficient than reported procedures; (3) without the
requirement of a hydrogen atmosphere, the work-up
system is more simple; (4) the impurities such as CoCl2,
by-products and excessive amount of MPPDME or
NaBH4 can be easily removed by extraction or filtration
through a SiO2 plug using CH2Cl2 (containing ethyl
acetate, petroleum ether or methanol) as eluent.
Although the transformation of metallo-porphyrins
in this reaction is not completely understood, the
mechanism of iron porphyrin catalyzed hydrogenation
of alkenes and alkynes using NaBH4 as hydrogen donor
has been well established by Kano and co-workers.[21]
In metallo-porphyrin catalyzed CoCl2-NaBH4 hydro-
genation system, “CoH2” (Eq. 1) is more active than
NaBH4. Thus, the transformation of metallo-porphyrins
in this protocol can be explained as illustrated in
Scheme 2. σ-Alkylmetal complex 4, which was thought
to be the key intermediate in this reaction, was formed
Figure 1 Effect of NaBH4 on the reaction.
With the optimized conditions in hand, various PPDs
were applied to show the generality and scope of the
new protocol (Table 2, Entries 1—6). As it could be
seen from Table 2, all the listed porphyrins can react
efficiently with NaBH4 to give the desired products.
More significantly, the hydrogenation of PPDME cata-
lyzed by CoTPP (Table 2, Entry 2) or MPPDME (Table
2, Entry 3—9) was faster with higher yields than that
without metal atoms in the porphyrin center in absence
of CoTPP (PPDME, Table 2, Entry 1). The causation of
the complicated diversification could be explained with
the reasons as follows: (1) The catalytic activity of
CoCl2 was obviously limited by the coordination interaction
between cobalt and excess amount of PPDME since the
complex of cobalt PPDME could be easily formed in
organic solvents such as DMF and THF. (2) Alkenes and
alkynes could be reduced by NaBH4 to their corre-
sponding saturated organic compounds under the ca-
talysis of metallo-porphyrins in anaerobic organic sol-
vents.[21] Thus, we proposed here the metal atom in
mesoporphyrin complexes played similar roles as assis-
tant-catalysts, which accelerated the hydrogenation of
vinyl groups and forestalled the hydroboration of vinyl
with CoCl2-NaBH4 generated BH3 to form RCH2-
CH2OH.[22]
The comparison of the results obtained from various
Scheme 2 Mechanism of metallo-porphyrins self-catalyzed hydrogenation in CoCl2-NaBH4 system
M
M
CoH2
M
M
M
M
M
+
2
4
5
3
M
represents metallo-porphyrins appearing in this protocol in this scheme
represents MPPDME in this scheme
M
2464
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2461—2465

Convenient Hydrogenation Method for the Synthesis of Metallo-mesoporphyrin IX Dimethyl Esters
[3] Heinecke, J.; Ford, P. C. Coord. Chem. Rev. 2010, 254, 235.
[4] Xu, S.; Liu, W.; Hu, B.; Cao, W.; Liu, Z. J. Photochem. Photobiol.,
A 2012, 227, 32.
by the ligation of vinyl groups to the metal atoms in
porphyrin center in the first step. In polar solvents, 4
was easily transformed to 5 because of the stabilizing of
5 by the extensive solvation. When 5 was surrounded by
polar solvent molecules with CoH2, the proton easily
transferred from CoH2 to 5 to afford 3.
[5] Baker, E. W.; Ruccia, M.; Corwin, A. H. Anal. Biochem. 1964, 8,
512.
[6] Rebouças, S. J.; James, B. R. Tetrahedron Lett. 2006, 47, 5119.
[7] Lara, F. A.; Lins, U.; Bechara, G. H.; Oliveira, P. L. J. Exp. Biol.
2005, 208, 3093.
[8] Rubaltelli, F. F. Drugs 1998, 56, 23.
Conclusions
[9] Kappas, A.; Drummond, G. S.; Munson, D. P.; Marshall, J. R. Pedi-
atrics 2001, 108, 1374.
In summary, a convenient and efficient protocol was
developed for the preparation of a variety of metallo-
mesoporphyrin IX dimethyl esters. The advantages of
this method such as ready availability of starting mate-
rials, simplicity of experimental procedures, safety of
reaction conditions and satisfactory yields make the de-
veloped method an attractive and useful method for the
synthesis of mesoporphyrin IX derivatives.
[10] Cui, Q.-L.; Xu, S.-C.; Sun, C.-G.; Hu, B.-C. Chem. J. Chinese U.
2010, 32, 2311.
[11] Caughey, W. S.; Alben, J. O.; Fujimoto, W. Y.; York, J. L. J. Org.
Chem. 1966, 31, 2631.
[12] Muir, H. M.; Neuberger, A. Biochem. J. 1949, 45, 163.
[13] Fuhrhop, J.-H.; Smith, K. M. In Porphyrins and Metalloporphyrins,
Ed.: Smith, K. M., Elsevier, Amsterdam, 1975, Chapter 19, p. 773.
[14] Leutenegger, U.; Madin, A.; Pfaltz, A. Angew. Chem., Int. Ed. Engl.
1989, 28, 60.
Acknowledgement
[15] Dhawan, D.; Grover, S. K. Synth. Commun. 1992, 22, 2405.
[16] Ranu, B. C.; Samanta, S. Tetrahedron 2003, 59, 7901.
[17] Sharma, P. K.; Kumar, S.; Kumar, P.; Nielsen, P. Tetrahedron Lett.
2007, 48, 8704.
This project is financially supported by Jiangsu
Natural Science Foundation (No. BK2009386), NUST
research founding (No. 2010GJPY043) and Program
Granted for Scientific Innovation Research of College
Graduate in Jiangsu Province (No. 20CXLX11_0268).
[18] Liang, Y. MSc Dissertation, Anhui University of Science and Tech-
nology, Huainan, 2006 (in Chinese).
[19] Guo, H. Y. MSc Dissertation, Jilin University, Changchun, 2005 (in
Chinese).
[20] Periasamy, M.; Thirumalaikumar, M. J. Organomet. Chem. 2000,
609, 137.
References
[21] Kano, K.; Takeuchi, M.; Hashimoto, S.; Yoshida, Z. J. Chem. Soc.,
Chem. Commun. 1991, 1728.
[1] Collman, J. P.; Boulatov, R.; Sunderland, C. J.; Fu, L. Chem. Rev.
2004, 104, 561.
[22] Slama, J. T.; Smith, H. W.; Willson, C. G.; Rapoport, H. J. Am. Chem.
Soc. 1975, 97, 6556.
[2] Wu, L.; Lei, J.; Zhang, X.; Ju, H. Biosens. Bioelectron. 2008, 24,
644.
(Pan, B.; Qin, X.)
Chin. J. Chem. 2012, 30, 2461—2465
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2465