Synthesis of porphyrinylamide and observation of N-methylation-induced trans-cis amide conformational alteration

Article abstract of DOI:10.1016/j.tet.2013.10.069

We synthesized porphyrinylamide 4b and its N-methylated derivative 5b. Direct N-methylation of porphyrinylamides 4 proved unsuccessful, so 5b was obtained via N-methylation of 5-aminoporphyrin 10 with potassium hexamethyldisilazide. The secondary amide 4b

Full text of DOI:10.1016/j.tet.2013.10.069

Tetrahedron 69 (2013) 10927e10932
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Synthesis of porphyrinylamide and observation of N-methylation-
induced transecis amide conformational alteration
,
a
b
c
Mio Matsumura a, Aya Tanatani a , Tomoyo Kaneko , Isao Azumaya , Hyuma Masu ,
*
Daisuke Hashizume d, Hiroyuki Kagechika e, Atsuya Muranaka f
,
,
*
,g,
*
Masanobu Uchiyama f
a Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
b Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
c Chemical Analysis Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
d Materials Characterization Support Unit, RIKEN Center for Emergent Matter Science (CEMS), Wako-shi, Saitama 351-0198, Japan
e Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
f Advanced Elements Chemistry Research Team and Elements Chemistry Laboratory, RIKEN, Wako-shi, Saitama 351-0198, Japan
g Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 May 2013
Received in revised form 21 October 2013
Accepted 23 October 2013
Available online 29 October 2013
We synthesized porphyrinylamide 4b and its N-methylated derivative 5b. Direct N-methylation of por-
phyrinylamides 4 proved unsuccessful, so 5b was obtained via N-methylation of 5-aminoporphyrin 10
with potassium hexamethyldisilazide. The secondary amide 4b exists in trans-amide form, while N-
methylated amide 5b exists in the cis-amide form, both in solution and in the crystal. Thus, N-methyl-
ation of the amide bond of 4b resulted in trans to cis conformational alteration.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Porphyrinylamide
Conformation
Crystal structure
1. Introduction
Porphyrin and related chromophores are functional macro-
molecules that play important roles in many biological processes,
including photosynthetic reaction.1 In order to develop artificial
functional molecules, various porphyrin-related models have been
synthesized, including porphyrins covalently linked with porphy-
rin2 (i.e., porphyrin dimers) or other functional aromatic mole-
cules.3 The three-dimensional structures of such molecules have
a significant influence on functionality. Therefore, in the synthesis
of such supramolecular structures, it is important to control the
conformations of the molecular components.
We have reported that amide bonds of aromatic secondary
amides show strong conformational preference; for example,
benzanilide (1) takes the trans-amide form, while N-methyl-
benzanilide (2) exists as the cis-amide form in the crystal,4 and
predominantly as the cis-amide form in solution5 (Fig. 1). The cis
Fig. 1. Conformational alteration of benzamide upon N-methylation.
conformational preference is also observed with related functional
groups (amidine, urea,4,6 guanidine7). We considered that this
conformational property could be utilized to construct interesting
three-dimensional aromatic structures, including helical poly-
amides,8 and aromatic multi-layers.9 Furthermore, some aromatic
amide bonds alter their conformations in response to external
stimuli,10 and this phenomenon could be applicable to develop
molecular switches or sensors. Here we focused on utilizing the
strong conformational preference of amide bonds to construct
porphyrin derivatives with unique three-dimensional architecture.
Several porphyrin derivatives in which the amide bond is attached
directly to the porphyrin ring have been synthesized.11 However, to
* Corresponding authors. Tel./fax: þ81 3 5978 2716 (A.T.); fax: þ81 48 467 2869
(A.M.); fax: þ81 3 5841 0732 (M.U.); e-mail addresses: tanatani.aya@ocha.ac.jp
(A. Tanatani), atsuya-muranaka@riken.jp (A. Muranaka), uchiyama@mol.f.u-tokyo.
ac.jp (M. Uchiyama).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.10.069

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M. Matsumura et al. / Tetrahedron 69 (2013) 10927e10932
our knowledge, there are no reports about their amide conforma-
tional studies. Aida and co-workers reported interesting phenom-
ena that flipping of the meso-amido group of chiral porphyrins
occurred upon heating or irradiation with visible light.12 We believe
that an in-depth understanding of three-dimensional structure of
these meso-amido porphyrins is of great importance in connection
with rational design of functional molecules.
Taking into account synthetic convenience and physicochemical
properties, such as solubility, we selected 2,3,7,8,12,13,17,18-
octaethylporphyrin (3, OEP) as the starting porphyrin molecule
and synthesized N-porphyrinylbenzamide 4 and its N-methylated
derivative 5 (Fig. 2). Here, we report the synthesis of 4 and 5, and
we describe the N-methylation-induced conformational alteration
of porphyrinylamides.
nickel-coordinated porphyrin 10 did not occur, the nickel-
coordinated porphyrinylamide 4b was prepared from 4a by re-
action with Ni(acac)2 in 55% yield.
Amide N-methylation of compound 4a using methyl iodide and
sodium hydride afforded a complex mixture with the N-methyl-
amide 5a (6%). The reaction of 9 with formic acid and acetic anhy-
dride afforded the formamide derivative (47% yield with 41%
recovery of 9), but it could not be reduced to a methylamino group by
borane-dimethylsulfide complex. The nickel-coordinated compound
10 also exhibited lower reactivity toward methylation using sodium
hydride as a base (Table 1, entry 1). Therefore, we examined in detail
the reaction conditions for N-methylation of compound 10. While
the reaction using tert-butyl lithium as a base did not proceed (entry
2), the reaction using excess amounts of potassium hydride and
methyl iodide afforded only the N,N-dimethylated product (entry 3).
Then, we focused on the utility of potassium salt as a base; the re-
action using potassium tert-butoxide (entry 4) or potassium hex-
amethyldisilazide (KHMDS, entry 5) resulted in moderate conversion
of 10 to N-methylamine 11, together with the N,N0-dimethylated by-
product. Finally, the reaction (entry 7) using KHMDS (1.5 equiv) and
methyl iodide (1.1 equiv) afforded N-methylamine 11 in 29% yield
with 67% recovery of 10. KHMDS was also an effective base in the
benzoylation of 11, and compound 5b was obtained in 34% yield. The
optimized conditions for N-methylation and benzoylation of Ni
porphyrinylamine will be applied to synthesis of other porphyr-
inylamides, including 4b from 10, or porphyrinyl diamides, whose
synthetic methods and properties will be published elsewhere.
Fig. 2. Structures of N-porphyrinylbenzamides.
2. Results and discussion
Table 1
Introduction of a nitro group at the meso position of OEP (3) was
performed according to the reported procedure (Scheme 1).13 Thus,
after zinc coordination of OEP (3), compound 6 was nitrated with
silver nitrite,14 followed by demetalation to afford 8 in 81% yield (3
steps). Reduction of 8 with tin chloride in concentrated hydro-
chloric acid gave aminoporphyrin 9 in 97% yield. Amide bond for-
mation of 9 with benzoyl chloride in the presence of pyridine or
triethylamine as a base did not proceed, and the reactivity of the
amino group of 9 seemed to be low. However, treatment of 9 with
n-butyl lithium, followed by addition of benzoyl chloride, afforded
the secondary amide 4a in 59% yield. Since amide formation of the
N-Methylation of compound 10 in THF
Entry
Base, equiv
CH3I, equiv
Reaction
time (h)
Yield of
11 (%)
Recovery
of 10 (%)
1
2
3
4
5
6
7
NaH
tert-BuLi
KH
tert-BuOK
KHMDS
KHMDS
KHMDS
1.3
2.0
7.1
1.1
2.5
1.5
1.5
1.1
1.7
2.0
1.7
1.5
3.7
1.1
21
2
4
4
3
7
0
74
93
da
40
45
35
67
da
18
21
21
29
1
3
a
Only the N,N-dimethylated compound was formed, as determined by 1H NMR.
Scheme 1. (a) (AcO)2Zn, CH2Cl2, MeOH, rt; (b) AgNO2, CH2Cl2, CH3CN, rt; (c) concd HCl, AcOH, rt; (d) SnCl2, concd HCl, rt; (e) n-BuLi, PhCOCl, ꢀ78 ꢁC to rt; (f) Ni(acac)2, CH3Cl, MeOH,
reflux; (g) CH3I, base, THF, ꢀ78 ꢁC to rt (see Table 1); (h) KHMDS, PhCOCl, THF, ꢀ78 ꢁC to rt.

M. Matsumura et al. / Tetrahedron 69 (2013) 10927e10932
10929
Table 3
The conformations of the porphyrinylamides in solution were
examined by 1H NMR spectroscopy (Fig. 3). The signals of phenyl
protons were observed at 7.6e8.2 ppm for the secondary amide 4b,
while those of the tertiary amide 5b were shifted to higher field by
1.0e1.4 ppm. The upfield shift was larger than that observed in N-
methylbenzanilide (0.04e0.60 ppm),5 because of the strong ring
current effect of the porphyrin. The chemical shift difference of the
protons in porphyrin ring between 4b (9.52 and 9.53 ppm) and 5b
(9.53 and 9.51 ppm) was little, since the ring current effect of
phenyl group is less than that of porphyrin ring. These results in-
dicate that compound 5b exists in cis-amide form, with the phenyl
group located over the porphyrin ring, while the secondary amide
4b exists in trans-amide form. The 1H NMR spectra of the por-
phyrinylamides 4b and 5b in CD2Cl2 did not indicate the occurrence
of an equilibrium between trans and cis conformers, even at lower
temperature (193 K) (data not shown).
Selected torsion and dihedral angles of porphyrinylamides
4b
5ba
Torsion angle
PheCO (ꢁ)
3.30
179.06
81.44
22.79, 38.56
ꢀ1.29, ꢀ4.03
85.63, 89.62
COeNR (ꢁ)
RNeporb (ꢁ)
Dihedral angle
Ph vs porb (ꢁ)
Ph vs amide (ꢁ)
Amide vs porb (ꢁ)
84.67
3.73
81.50
89.16, 76.34
22.92, 40.39
87.06, 88.97
a
Two independent molecules exist in the unit cell.
Porphyrin (Por) planes were determined based on the four nitrogen atoms of the
b
porphyrin rings.
the secondary amide and N-methylated amide have the porphyrin
and the phenyl rings in a perpendicular relationship, but with
different orientations to each other (Fig. 4).
Both types of porphyrinylamides showed unique crystal packing
structures. The secondary amide 4b has a hydrogen bond network
between the intermolecular amide bonds, and the NH$OC distance
ꢀ
is 2.01 A. The phenyl ring is located between two porphyrin rings.
The dihedral angle between the phenyl ring and the nearest por-
phyrin ring is 66.5ꢁ. The distance between the porphyrin ring and
ꢀ
the nearest hydrogen atom on the phenyl ring is 2.25 A. Thus, in-
termolecular distorted T-shaped interaction between the porphyrin
ring and the phenyl ring appears to exist in the crystal of 4b. On the
other hand, intermolecular offset parallel structures of porphyrin
rings were observed in the crystal of 5b. The distances between
ꢀ
ꢀ
adjacent porphyrins are 3.39 A and 3.33 A (Fig. 5).
3. Conclusion
Porphyrin derivatives with a secondary or tertiary amide bond
at the meso position were synthesized, and their crystal and solu-
tion conformations were evaluated. Introduction of an N-methyl
group caused conformational alteration of the trans-form of sec-
ondary N-porphyrinylbenzamide to the cis-form, both in the crystal
and in solution. These conformational properties of porphyr-
inylamides may be useful to develop functional porphyrins with
unique three-dimensional structures and dynamic behaviors, such
as environmental responsiveness.
Fig. 3. 1H NMR spectra (aromatic region) of porphyrinylamides (a) 4b and (b) 5b in
CDCl3. The phenyl protons ortho, meta, and para to the amide bond are shown as o, m,
and p, respectively.
Next, X-ray crystallographic analyses of 4b and 5b were per-
formed to determine the conformations of the porphyrinylamides
in the crystal (Table 2). As expected from the 1H NMR study, the
secondary amide 4b had trans-amide structure in the crystal, while
the N-methylated amide 5b existed in cis-amide form. The por-
phyrin ring of 5b is nearly planar. In the crystal structure of 4b, on
the other hand, the porphyrin ring is distorted due to coordination
of a THF molecule to the Ni atom. The amide bond in each crystal
structure is planar with a dihedral angle of less than 5ꢁ, and the
amide plane is nearly perpendicular to the porphyrin ring (81.50ꢁ
for 4b, and 87.06ꢁ or 88.97ꢁ for 5b), presumably due to steric effects
of the 3,7-substituents of the porphyrin ring (Table 3). Thus, both
4. Experimental
4.1. Synthesis
4.1.1. Synthesis of zinc (II) 2,3,7,8,12,13,17,18-octaethylporphyrin
(6). A solution of zinc (II) acetate (366 mg, 2.65 mmol) in metha-
nol (10 ml) was added to
a solution of 2,3,7,8,12,13,17,18-
octaethylporphyrin13 (3, 403 mg, 0.753 mmol) in dichloro-
methane (400 ml), and the mixture was stirred at room tempera-
ture for 1 h. After concentration, the residue was used for the next
reaction without further purification. 1H NMR (400 MHz, CDCl3)
Table 2
Crystallographical data of porphyrinylamides 4b and 5b
Crystal
4b
5b
Recrn solvent
Formula
THF/n-hexane
AcOEt/MeOH
C44H51N5NiO
Triclinic
P-1
11.9778(9)
13.5511(14)
24.579(3)
89.445(5)
76.558(4)
67.871(4)
3580.9(6)
4
d
10.16 (s, 4H), 4.13 (q, 16H, J¼7.8 Hz), 1.94 (t, 24H, J¼7.8 Hz).
C43H49N5NiO$THF
Crystal system
Space group
Orthorhombic
Pbca
9.9475(15)
24.103(4)
33.359(6)
d
4.1.2. Synthesis of zinc (II) 2,3,7,8,12,13,17,18-octaethyl-5-
nitroporphyrin (7).14
solution of silver nitrite (146 mg,
A
ꢀ
a (A)
ꢀ
b (A)
0.956 mmol) in acetonitrile (45 ml) was added slowly to a suspen-
sion of zinc (II) 2,3,7,8,12,13,17,18-octaethylporphyrin (6, 636 mg)
and iodine (136 mg) in dichloromethane (620 ml) and acetonitrile
(280 ml) under an Ar atmosphere. The mixture was stirred for 5 h,
then filtered over Celite, and the filtrate was concentrated. The
residue was purified by silica gel column chromatography
(chloroformen-hexane 1:1) to give zinc (II) 2,3,7,8,12,13,17,18-
octaethyl-5-nitroporphyrin (7, 393 mg, 81%) as a red purple solid.
ꢀ
c (A)
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
d
d
3
ꢀ
V (A )
Z
7998(2)
8
R1
wR2
0.0598
0.1604
0.0629
0.1427

10930
M. Matsumura et al. / Tetrahedron 69 (2013) 10927e10932
Fig. 4. Crystal structures of (a) 4b and (b) 5b (5b has two independent molecules in the unit cell). There is disorder in the region of the C16eC20 carbons, including two ethyl
groups, in 4b.
Fig. 5. Crystal packing structures of (a) 4b and (b) 5b (top: side view, bottom: top views).
1H NMR (400 MHz, CDCl3)
d
9.79 (s, 2H), 9.40 (s, 1H), 4.01 (q, 4H,
HRMS (ESIþ) calcd for C36H43N5O2 [MþH]þ: 580.3646, found:
J¼7.8 Hz), 3.96 (m, 8H), 3.78 (q, 4H, J¼7.3 Hz), 1.93 (t, 6H, J¼7.8 Hz),
580.3631; IR (KBr) 3450, 3268, 2966, 2929, 2871, 1524 cmꢀ1
.
1.85 (m, 12H), 1.73 (t, 6H, J¼7.3 Hz); 13C NMR (150 MHz, CDCl3)
d
147.03,146.86,145.81,145.59,142.11,141.84,139.41,138.03,128.82,
4.1.4. Synthesis of 5-amino-2,3,7,8,12,13,17,18-octaethylporphyrin
(9). Tin chloride (679 mg, 3.58 mmol) was added to a solution of
2,3,7,8,12,13,17,18-octaethyl-5-nitroporphyrin (8, 358 mg) in con-
centrated hydrochloric acid (220 ml). The mixture was stirred for
16 h, then poured into water, and extracted with chloroform.
The organic layer was washed with brine, dried over sodium
sulfate, and concentrated. The residue was purified by silica
gel column chromatography (chloroformen-hexane 7:3, then
methanolechloroform 1:19) to give 5-amino-2,3,7,8,12,13,17,18-
octaethylporphyrin (9, 316 mg, 91%) as a purple solid. 1H NMR
97.82, 97.07, 20.55, 19.68, 19.08, 18.58, 18.42, 18.35, 18.22; HRMS
(ESIþ) calcd for C36H43N5O2Zn [MþH]þ: 642.2781, found: 642.2773;
IR (KBr) 3438, 2963, 2930, 2870, 1529 cmꢀ1
.
4.1.3. Synthesis of 2,3,7,8,12,13,17,18-octaethyl-5-nitroporphyrin
(8). Concentrated hydrochloric acid (110 ml) was added to a solu-
tion of zinc (II) 2,3,7,8,12,13,17,18-octaethyl-5-nitroporphyrin (7,
393 mg, 0.611 mmol) in acetic acid (200 ml) at room temperature.
After 3 h, water was added, and the whole was extracted with
chloroform. The organic layer was washed successively with water,
saturated sodium bicarbonate, and water. The organic layer was
dried over sodium sulfate, and concentrated. The residue was used
for the next reaction without further purification. 1H NMR
(400 MHz, CDCl3) d 9.53 (s, 2H), 9.17 (s, 1H), 6.53 (s, 2H), 3.75e3.94
(m, 16H), 1.73e1.85 (m, 24H), ꢀ1.15 (br s, 2H); 13C NMR (150 MHz,
CDCl3)
d 148.59, 142.52, 142.23, 140.46, 139.76, 139.17, 136.41,
134.24, 132.50, 96.88, 90.94, 22.07, 19.53, 19.44, 19.43, 18.51, 18.17,
(400 MHz, CDCl3)
d
10.23 (s, 2H), 10.06 (s, 1H), 4.04e4.13 (m, 12H),
17.90, 15.82; HRMS (ESIþ) calcd for C36H43N5O2 [MþH]þ: 550.3904,
3.73 (q, 4H, J¼7.3 Hz), 1.90e1.95 (m, 18H), 1.70 (t, 6H, J¼7.3 Hz),
found: 550.3893; IR (KBr) 3403, 2963, 2929, 2869, 1619 cmꢀ1
.
ꢀ3.59 (br s, 1H), ꢀ3.81 (br s, 1 H); 13C NMR (150 MHz, CDCl3)
d
143.32, 142.80, 141.68, 141.50, 139.60, 138.46, 136.36, 130.12,
4.1.5. Synthesis of N-(2,3,7,8,12,13,17,18-octaethylporphyrin-5-yl)
127.56, 96.86, 92.20, 22.01, 19.37, 19.23, 18.25, 17.97, 17.72, 16.36;
benzamide (4a). A solution of 2.6 M n-butyl lithium in n-hexane

M. Matsumura et al. / Tetrahedron 69 (2013) 10927e10932
10931
(150
m
L, 0.390 mmol) was added to a solution of 5-amino-
0.029 mmol) was added at room temperature. The mixture was
stirred for 3 h, then evaporated, and the residue was dissolved in
chloroform. This solution was washed with water and brine, dried
over sodium sulfate, and concentrated. The residue was purified by
silica gel column chromatography (CHCl3en-hexane 1:4) to give
nickel(II) 5-N-methylamino-2,3,7,8,12,13,17,18-octaethylporphyrin
2,3,7,8,12,13,17,18-octaethylporphyrin (9, 67 mg, 0.122 mmol) in dry
THF (10 mL) under an Ar atmosphere at ꢀ78 ꢁC. Then, a solution of
benzoyl chloride (17.5 mg, 0.125 mmol) in dry THF (5 mL) was
added. After 100 min, the mixture was poured into water, and
extracted with chloroform. The organic layer was washed with
brine, dried over sodium sulfate, and concentrated. The residue was
purified by silica gel column chromatography (methanolechloro-
form 1:19) to give N-(2,3,7,8,12,13,17,18-octaethylporphyrin-5-yl)
benzamide (4a) (47.0 mg, 59%). Red needles (THFen-hexane); mp
(11, 5 mg, 29%) as a purple solid. 1H NMR (400 MHz, CDCl3)
d 9.17
(s, 2H), 9.07 (s, 1H), 4.98 (q, 1H, J¼5.7 Hz), 3.85 (q, 4H, J¼5.7 Hz),
3.68e3.76 (m, 12H), 2.90 (d, 3H, J¼5.7 Hz), 1.62e1.75 (m, 24 H); 13
C
NMR (150 MHz, CDCl3)
d 143.02, 142.71, 141.96, 141.81, 140.70,
290 ꢁC (dec); 1H NMR (400 MHz CDCl3)
d
10.13 (2H, s), 9.98 (s, 1H),
138.64, 136.85, 133.74, 130.12, 96.75, 93.35, 41.74, 30.29, 29.70,
8.44 (d, 2H, J¼6.8 Hz), 7.75e7.80 (m, 3H), 4.06 (q, 12H, J¼7.8 Hz),
3.82e3.93 (m, 4H), 1.91 (t, 12H, J¼7.8 Hz), 1.84 (t, 6H, J¼7.8 Hz), 1.67
(t, 6H, J¼7.8 Hz), ꢀ3.32 (br s, 2 H); 13C NMR (150 MHz, CDCl3)
21.82, 19.42, 19.40, 18.15, 18.03, 17.80, 16.96; HRMS (ESIþ) calcd for
C
36H43N5O2 [MþH]þ: 620.3258, found: 620.3251; IR (KBr) 3436,
2961, 2927, 2866, 1508 cmꢀ1
.
d
145.36, 144.25, 143.32, 142.16, 141.33, 139.96, 134.64, 132.46,
129.23, 127.35, 110.57, 97.09, 96.41, 67.96, 25.60, 21.99, 19.78, 19.70,
18.49, 18.47, 17.68; HRMS (ESIþ) calcd for C43H52N5O [MþH]þ:
654.4166, found: 654.4171; IR (KBr) 3307, 3283, 2963, 2930, 2836,
4.1.9. Synthesis of nickel(II) N-methyl-N-(2,3,7,8,12,13,17,18-
octaethylporphyrin-5-yl)benzamide (5b). A solution of 0.5
KHMDS in toluene (0.135 mL, 0.067 mmol) was added to a sol-
ution of nickel(II) 5-N-methylamino-2,3,7,8,12,13,17,18-
M
1644 cmꢀ1
.
octaethylporphyrin (11, 28 mg, 0.045 mmol) in dry THF (8 ml)
under an Ar atmosphere at ꢀ78 ꢁC. After 1 h, a solution of 0.0453 M
benzoyl chloride in THF (0.1 ml, 0.045 mmol) was added at room
temperature. The mixture was stirred for 30 min, then evaporated
to afford a residue, which was dissolved in chloroform. This solu-
tion was washed with water and brine, dried over sodium sulfate,
and concentrated. The residue was purified by silica gel column
chromatography (CHCl3en-hexane 7:13) to give nickel(II) N-
methyl-N-(2,3,7,8,12,13,17,18-octeathylporphyrin-5-yl)benzamide
(5b, 11 mg, 34%). Red plates (AcOEt/MeOH); mp 290 ꢁC (dec); 1H
4 .1. 6 . S y n t h e s i s o f n i c k e l ( I I ) N - ( 2 , 3 , 7 , 8 ,12 ,13 ,17 ,18 -
octaethylporphyrin-5-yl)benzamide (4b). A solution of nickel(II)
acetylacetonate (71.9 mg, 0.280 mmol) in methanol (5 ml)
was added slowly to
a
solution of N-(2,3,7,8,12,13,17,18-
octaethylporphyrin-5-yl)benzamide (4a, 55 mg, 0.084 mmol) in
chloroform (100 ml). The mixture was refluxed for 1 d, then
evaporated to afford a residue, which was dissolved in chloroform.
This solution was washed with water and brine, dried over sodium
sulfate, and concentrated. The residue was purified by silica gel
column chromatography (chloroform) to give nickel(II)
NMR (400 MHz, CDCl3)
d 9.53 (s, 1H), 9.51 (s, 2H), 6.83 (dd, 1H,
N-(2,3,7,8,12,13,17,18-octaethylporphyrin-5-yl)benzamide
32.8 mg, 55%). Red plates (THFen-hexane); mp 290 ꢁC (dec); 1H
NMR (400 MHz, CDCl3) 9.80 (s, 1H), 9.53 (s, 2H), 8.22 (d, 2H,
J¼7.3 Hz), 7.64e7.71 (m, 3H), 3.68e3.90 (m, 16H), 1.67e1.79 (m,
24 H); 13C NMR (150 MHz, CDCl3)
145.27, 143.22, 143.08, 142.15,
140.62, 140.08, 139.00, 138.28, 134.45, 132.25, 129.11, 127.10, 109.08,
96.88, 96.39, 29.7, 22.35, 19.62, 19.56, 19.46, 18.22, 18.20, 17.58;
HRMS (ESIþ) calcd for C43H49N5NiO [M] þ: 709.3285, found:
709.3281; IR (KBr); 3430, 2963, 2929, 2869, 1647 cmꢀ1; UVevis
(CHCl3): lmax (nm) (log ε) 404 (5.02), 526 (3.81), 562 (4.08).
(4b,
J¼7 Hz, 2 Hz), 6.70 (tt, 1H, J¼7 Hz), 6.45 (t, 1H, J¼7 Hz), 4.23 (s, 3H),
3.75e3.89 (m,16H),1.74e1.79 (m,12H),1.67 (t, 6H, J¼7.3 Hz),1.26 (t,
d
6H, J¼7.3 Hz); 13C NMR (150 MHz, CDCl3)
d 171.50, 145.51, 143.35,
143.28, 142.51, 141.61, 140.55, 140.24, 139.40, 135.19, 129.13, 128.76,
126.90, 119.96, 96.95, 96.37, 45.01, 21.01, 19.55, 19.52, 19.38, 18.06,
18.05, 17.98, 17.53; HRMS (ESIþ) calcd for C44H52N5NiO [MþH]þ:
724.3519, found: 724.3510; IR (KBr) 3427, 2963, 2930, 2869,
1634 cmꢀ1; UVevis (CHCl3): lmax (nm) (log ε) 405 (4.23), 527 (3.01),
565 (3.30).
d
4.2. X-ray crystallography
4.1.7. Synthesis of nickel(II) 5-amino-2,3,7,8,12,13,17,18-
octaethylporphyrin (10). A solution of nickel(II) acetylacetonate
(536 mg, 2.09 mmol) in methanol (50 ml) was added to a solution
of 5-amino-2,3,7,8,12,13,17,18-octaethylporphyrin (9, 316 mg,
0.575 mmol) in chloroform (600 ml). The mixture was refluxed for
100 min, then evaporated to afford a residue, which was dissolved
in chloroform. This solution was washed with water and brine,
dried over sodium sulfate, and concentrated. The residue was pu-
rified by silica gel column chromatography (chloroformen-hexane
1:1, then chloroform) to give nickel(II) 5-amino-2,3,7,8,12,13,17,18-
octaethylporphyrin (10, 320 mg, 91%) as a purple solid. 1H NMR
Diffraction data were collected on a Rigaku AFC-8 diffractometer
equipped with a Saturn70 CCD detector, using monochromated Mo
ꢀ
Ka
radiation (
l
¼0.71073 A) for 5b or synchrotron radiation for 4b.
The crystal structures were solved by the direct method with
SHELXS-9715 and SIR200416 software for 4b and 5b, respectively,
and refined using full-matrix least-squares SHELXL-97. All non-
hydrogen atoms were refined anisotropically. All hydrogen atoms
were calculated geometrically for 4b and located on the difference
Fourier maps for 5b, and refined as riding models. The crystallo-
graphic data are given in Table 2 and supplementary CIF files, and
have been deposited with the Cambridge Crystallographic Data
Centre (CCDC908654 for 4b, and CCDC914053 for 5b).
(400 MHz, CDCl3)
d 9.08 (s, 2H), 8.94 (s, 1H), 5.43 (br, 2H), 3.80 (q,
4H, J¼7.3 Hz), 3.65e3.74 (m, 12H), 1.66e1.72 (m, 24H); 13C NMR
(150 MHz, CDCl3)
d 143.32, 142.82, 141.69, 141.51, 139.61, 138.49,
136.39, 130.16, 127.57, 96.87, 92.22, 29.70, 22.02, 19.37, 19.23, 18.24,
17.96, 17.71, 16.36; HRMS (ESIþ) calcd for C36H43N5O2 [MþH]þ:
606.3101, found: 606.3103; IR (KBr) 3493, 3392, 2959, 2928, 2867,
1617 cm-1.
Acknowledgement
The synchrotron radiation experiment was performed at the
BL38B1 of SPring-8 with the approval of the Japan Synchrotron
Radiation Research Institute (JASRI) (Proposal No. 2008B1981).
4.1.8. Synthesis of nickel(II) 5-(methylamino)-2,3,7,8,12,13,17,18-
octaethylporphyrin (11). A solution of 0.5 M KHMDS in toluene
(0.082 mL, 0.041 mmol) was added to a solution of nickel(II)
References and notes
5-amino-2,3,7,8,12,13,17,18-octaethylporphyrin
(10,
17
mg,
0.028 mmol) in dry THF (10 ml) under an Ar atmosphere at ꢀ78 ꢁC.
1. Deisenhofer, J.; Epp, O.; Miki, K.; Huber, R.; Michel, H. Nature 1985, 318,
618e624.
After 1 h, a solution of 0.293 M benzoyl chloride in dry THF (0.1 ml,

10932
M. Matsumura et al. / Tetrahedron 69 (2013) 10927e10932
2. (a) Maes, W.; Dehaen, W. Eur. J. Org. Chem. 2009, 4719e4752; (b) Chachisvilis,
M.; Chirvony, V. S.; Shulga, A. M.; Ka1llebring, B.; Larsson, S.; Sundstrom, V. J.
9. Tanatani, A.; Kagechika, H.; Azumaya, I.; Fukutomi, R.; Ito, Y.; Yamaguchi, K.;
Shudo, K. Tetrahedron Lett. 1997, 38, 4425e4428.
€
Phys. Chem. 1996, 100, 13857e13866; (c) Senge, M. O.; Gerzevske, K. R.; Vicente,
G. H.; Forsyth, T. P.; Smith, K. M. Angew. Chem., Int. Ed. Engl. 1993, 32, 750e753;
(d) Osuka, A.; Nakajima, S.; Nagata, T.; Maruyama, K.; Toriumi, K. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 582e584; (e) Fillers, J. P.; Ravichandran, K. G.; Abdal-
muhdi, I.; Tulinsky, A.; Chang, C. K. J. Am. Chem. Soc. 1986, 108, 417e424.
3. Satake, A.; Kobuke, Y. Tetrahedron 2005, 61, 13e41.
4. Yamaguchi, K.; Shudo, K. J. Agric. Food Chem. 1991, 39, 793e796.
5. Itai, A.; Toriumi, Y.; Tomioka, N.; Kagechika, H.; Azumaya, I. Tetrahedron Lett.
1989, 30, 6177e6180.
6. (a) Ganis, P.; Avitabile, G.; Benedetti, E.; Pedone, C.; Goodman, M. Proc. Natl.
Acad. Sci. U.S.A. 1970, 67, 426e433; (b) Lepore, G.; Migdal, S.; Blagdon, D. E.;
Goodman, M. J. Org. Chem. 1973, 38, 2590e2594; (c) Lepore, U.; Lepore, G. C.;
Ganis, P.; Germain, G.; Goodman, M. J. Org. Chem. 1976, 41, 2134e2137.
7. Tanatani, A.; Yamaguchi, K.; Azumaya, I.; Fukutomi, R.; Shudo, K.; Kagechika, H.
J. Am. Chem. Soc. 1998, 120, 6433e6442.
10. Okamoto, I.; Takahashi, Y.; Sawamura, M.; Matsumura, M.; Masu, H.; Katagiri,
K.; Azumaya, I.; Nishino, M.; Kohama, Y.; Morita, N.; Tamura, O.; Kagechika, H.;
Tanatani, A. Tetrahedron 2012, 68, 5346e5355.
11. (a) Ichimura, K. Bull. Chem. Soc. Jpn. 1978, 51, 1444e1449; (b) Gao, G.-Y.; Chen, Y.;
Zhang, X. P. Org. Lett. 2004, 6, 1837e1840; (c) Feng, D.-J.; Wang, G.-T.; Wu, J.;
Wang, R.-X.; Li, Z.-T. Tetrahedron Lett. 2007, 48, 6181e6185; (d) Takanami, T.;
Wakita, A.; matsumoto, J.; Sekine, S.; Suda, K. Chem. Commun. 2009, 101e103.
12. (a) Konishi, K.; Miyazaki, K.; Aida, T.; Inoue, S. J. Am. Chem. Soc. 1990, 112,
5639e5640; (b) Konishi, K.; Mori, Y.; Aida, T.; Inoue, S. Inorg. Chem. 1995, 34,
1292e1294; (c) Matsumura, M.; Tanatani, A.; Azumaya, I.; Masu, H.; Hashizume,
D.; Kagechika, H.; Muranaka, A.; Uchiyama, M. Chem. Commun. 2013, 2290e2292.
13. Sessler, J. L.; Mozaffari, A.; Johnso, M. R. Organic Syntheses Collect. Vol. 9, 1998,
p 242.
14. Crossley, M. J.; King, L. G.; Pyke, S. M.; Tansey, C. W. J. Porphyrins Phthalocyanines
2002, 6, 685e694.
8. Tanatani, A.; Yokoyama, A.; Azumaya, I.; Takakura, Y.; Mitsui, C.; Shiro, M.;
Uchiyama, M.; Muranaka, A.; Kobayashi, N.; Yokozawa, T. J. Am. Chem. Soc. 2005,
127, 8553e8561.
15. A short history of SHELX: Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112e122.
16. Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.; Cascarano, G. L.; De Caro,
L.; Giacovazzo, C.; Polidori, G.; Spagn, R. J. Appl. Crystallogr. 2005, 38, 381e388.