Microwave-Enhanced Synthesis of Novel Pyridinone-Fused Porphyrins

Article abstract of DOI:10.1055/s-0028-1088205

Condensation adducts of the Ni(II) and Cu(II) complexes of P-amino-meio-tetraphencny BRAlporphcny BRArin with dimethcny BRAl acetcny BRAlenedicarboxcny BRAlate (DMAD) and diethcny BRAl ethoxcny BRAmethcny BRAlenemalonate were converted into the correspond

Full text of DOI:10.1055/s-0028-1088205

LETTER
1009
Microwave-Enhanced Synthesis of Novel Pyridinone-Fused Porphyrins
Synthesis of
N
ove
n
l
Pyridinone-
a
Fused PorphyrinsM. G. Silva,*a Baltazar Castro,a Maria Rangel,b Artur M. S. Silva,c Paula Brandão,d Vítor Felix,d
José A. S. Cavaleiro*c
a
REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal
Fax +351(22)0402659; E-mail: ana.silva@fc.up.pt
REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4099-003 Porto, Portugal
Department of Chemistry, QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
b
c
Fax +351(23)370084; E-mail: jcavaleiro@ua.pt
Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal
d
Received 1 December 2008
Dedicated to Professor Henk van der Plas on the occasion of his 80th birthday
CO2H
Abstract: Condensation adducts of the Ni(II) and Cu(II) complexes
Ph
Ph
M
HN
HN
of b-amino-meso-tetraphenylporphyrin with dimethyl acetylenedi-
carboxylate (DMAD) and diethyl ethoxymethylenemalonate were
converted into the corresponding esters of pyridinone-fused por-
phyrins by using three different cyclization protocols: conventional
heating, microwave irradiation, and Eaton’s reagent. High yields in
a short period of time were obtained by using the microwave-irradi-
ation protocol under closed-vessel conditions. The structure of the
copper(II) complex of pyridinone-fused porphyrin was confirmed
by X-ray crystallography.
CO2H
O
O
N
N
N
N
N
N
N
N
M
Ph
Ph
Ph
Ph
Ph
Ph
1a M = Ni
1b M = Cu
2a M = Ni
2b M = Cu
Key words: porphyrins, cyclizations, microwave irradiations
Figure 1 Structures of pyridinone-fused porphyrins 1 and 2
The development of new transformation methods of por-
phyrins, particularly those which provide the introduction
of an additional heterocyclic fused ring and/or a function-
alized group in a peripheral position of the macrocycle, is
of great interest in order to access new porphyrinic sys-
tems.1,2
dyes for solar cells and in medicine as photosensitizers for
cancer therapy (PDT).8a–8e
Nitrogen-containing heterocycles, particularly 4-quino-
lone derivatives, are present in a large number of biologi-
cally active compounds such as ciprofloxacin and
levofloxacin, which has been described to exhibit potent
antimicrobial activity.9 In order to improve the quinolone
pharmacological activity, the molecular structure of the
parent compound has been extensively modified. For in-
stance, the synthesis of dyad systems containing both qui-
nolone and other pharmacologically active molecule has
been described as a good strategy to discover new
drugs.2c,10 Considering the medicinal applications already
known for porphyrins and for quinolones, one might an-
ticipate that a porphyrin–pyridinone fused system could
bring significant improvements to such applications. Sev-
eral methodologies to prepare 4-quinolone derivatives
have been reported;11 however, the classical and most
popular method employs the well-known Gould–Jacobs
reaction.12 This reaction involves the condensation of
anilines with ethylenemalonate analogues followed by
thermal cyclization, at high temperatures, to give rise to
the desired quinolones. Owing to the increasing interest
on this family of compounds, important improvements to
promote the cyclization step have been reported. For in-
stance, the condensation adduct of 3-chloro-4-fluoro-
aniline with diethyl ethoxymethylenemalonate was
successfully cyclized using polyphosphoric acid or acidic
alumina, under microwave irradiation.13 Also, a mixture
b-Amino-substituted porphyrins have been widely used as
versatile starting materials for the synthesis of highly
functionalized porphyrins.3 Recent examples include the
three-component reaction of b-amino-meso-tetra-
phenylporphyrin, aromatic aldehydes and enol ethers,4
and the two-component reaction of b-amino-meso-tetra-
phenylporphyrin and enol ethers,5 both providing the syn-
thesis of pyrido[2,3-b]porphyrin derivatives. On the other
hand, the condensations of b-aminoporphyrin with a,b-
unsaturated carbonyl compounds6 and also with quino-
nes,7 afford a range of different p-extended heterocyclic
fused porphyrin derivatives.
Herein, we report the synthesis of two novel pyridinone-
fused porphyrins (1a and 2a; Figure 1) obtained from con-
densation of the nickel(II) complex of b-amino-meso-
tetraphenylporphyrin with dimethyl acetylenedicarboxy-
late (DMAD) and diethyl ethoxymethylenemalonate, fol-
lowed by cyclization and subsequent ester hydrolysis.
Such porphyrins and their free bases can have promising
applications in photoelectronics, namely for being used as
SYNLETT 2009, No. 6, pp 1009–1013
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088205; Art ID: D39808ST
© Georg Thieme Verlag Stuttgart · New York

1010
A. M. G. Silva et al.
LETTER
CO2Me
CO2Me
1
1'
2
2'
H
3'
CO2Me
CO2Me
Ph
Ph
Ni
HN
HN
Ph
NH2
3
4
21
19
20
22
CO2Me
18
17
16
4a
6
O
N
N
N
N
N
N
5
N
N
N
N
M
Ph
Ph
Ph
Ph
Ph
Ph
Ni
– MeOH
7
15
14
N
N
8
10
12
11
9
13
Ph
Ph
Ph
3
4a M = Ni
4c M = 2H
Scheme 1 Condensation–cyclization reaction of b-amino-meso-tetraphenylporphyrin with DMAD
of P2O5 and MeSO3H, known as Eaton’s reagent, allowed ments were performed in nitrobenzene since it is a good
the cyclization of a range of different anilines, producing microwave absorbing solvent (tan d = 0.589).20 Two micro-
4-quinolones in high yields and under mild conditions.14
wave apparatus were available: multimode and mono-
mode reactors. Using open vessel microwave irradiation
in a multimode reactor, the cyclization was complete after
40 minutes at 180 °C, leading to the expecting porphyrin
4a in an excellent yield of 93%.21a Switching the micro-
wave platform to a single-mode reactor using closed ves-
sel conditions and increasing reaction temperature to 220
°C, the complete cyclization took place in only 4 minutes
(88% yield of 4a).21b Comparing the results obtained in
the microwave-enhanced cyclizations using the multi-
mode and monomode reactors, it is remarkable the signif-
icant reduction of reaction times achieved when the
monomode reactor is used (entries 2 and 3, Table 1).
Based on such methodologies, three different protocols
were employed to access pyridinone-fused porphyrins 1a
and 2a: (a) cyclization under conventional heating (oil
bath), (b) cyclization under microwave irradiation, and (c)
acidic cyclization using Eaton’s reagent.
The initial condensation of the nickel(II) complex of b-
amino-meso-tetraphenylporphyrin with DMAD was per-
formed in toluene at 85 °C during 150 minutes, affording
the expected porphyrin
3 in good yield (78%,
Scheme 1).15,16 With porphyrin 3 in hand, the first attempt
to perform the cyclization was carried out by heating, in
an oil bath, a nitrobenzene solution of 3, at 200 °C. The
reaction progress was monitored by TLC and reached its
completion after 6 hours.17 The pyridinone-fused porphy-
rin 4a was then obtained in 74% of yield (entry 1,
Table 1).
When the reaction was performed with Eaton’s reagent
(P2O5 and MeSO3H) at moderate temperatures (50 °C, 2
h), instead of the expected porphyrin 4a, the reaction pro-
vides the metal-free cyclized porphyrin 4c, in 84% yield
(entry 4, Table 1).22,23 This is due to the strong acidic char-
acter of the Eaton’s reagent.
Table 1 Results Obtained in Cyclization of Porphyrin 3
The same experimental methodology using the three dif-
ferent protocols was applied to the synthesis of the pyri-
dinone-fused porphyrin 7a analogue (Scheme 2). The
starting porphyrin 5 was prepared in high yield (85%)
from the condensation of the nickel(II) complex of b-
amino-meso-tetraphenylporphyrin with diethyl ethoxy-
methylenemalonate, in refluxing toluene for 150 minutes.
Subsequent cyclization in nitrobenzene under classical
heating conditions (oil bath, 200 °C, 2 h), afforded the ex-
pected pyridinone-fused porphyrin 7a in 50% yield (entry
1, Table 2). Besides porphyrin 7a, a second product was
isolated and it was identified as porphyrin 8 (Figure 2);
this is presumably formed by hydrolysis and subsequent
decarboxylation of porphyrin 7a. We noticed that a longer
reaction time (6 h) leads to a dramatic decrease in the yield
of porphyrin 7a, promoting the formation of 8. In order to
avoid the hydrolysis and decarboxylation of 7a, the reac-
tion time was reduced to 1 hour; however, under these
conditions, the cyclization was not complete, and a 1:1
mixture of cyclized and uncyclized porphyrins 7a and 6 is
obtained.
Entry Method
Temp (°C) Time
Yield (%)
1
oil bath
200
180
220
50
6 h
74
93
88
84
2a
3b
4
MW open vessel
MW closed vessel
Eaton’s reagent
40 min
4 min
2 h
a Multimode reactor.
b Monomode reactor.
Although the 4-quinolones may exist in two tautomeric
forms (enol and keto forms),18 in the present case the
NMR analysis shows that porphyrin 4a exists exclusively
in the keto form.19 In fact, the 1H NMR spectrum showed
the presence of a broad singlet at d = 9.10 ppm corre-
sponding to the resonance of the NH proton which is in
agreement with the 13C NMR spectrum that showed a sig-
nal at d = 173.7 ppm corresponding to the resonance of the
ketone carbonyl group.
Aiming to improve the cyclization reaction outcome
(mainly by reducing the reaction time), we explored the
benefits of microwave irradiation. All microwave experi-
Surprisingly, when such a reaction was conducted under
open vessel microwave heating conditions in a multimode
reactor at 180 °C, the cyclization did not reach completion
Synlett 2009, No. 6, 1009–1013 © Thieme Stuttgart · New York

LETTER
Synthesis of Novel Pyridinone-Fused Porphyrins
1011
H
2'
H
H
2
1'
1
Ph
Ni
Ph
N
Ph
21
NH2
N
3
CO2Et
CO2Et
3'
19
H
OEt
20
22
4
CO2R
18
4a
O
N
N
N
N
N
N
N
N
N
5
17
16
EtO2C
CO2Et
6
M
Ph
Ph
Ph
Ph
Ph
Ni
Ph
– EtOH
7
15
14
N
N
N
8
10
12
11
9
13
Ph
Ph
Ph
5 R = Et
6 R = H
7a M = Ni
7c M = 2H
– EtOH
Scheme 2 Condensation–cyclization reactions of b-amino-meso-tetraphenylporphyrin with diethyl ethoxymethylenemalonate
free porphyrins 5 and 6 are the only isolated products; at
higher temperatures (80 °C, 2–5 hours) the metal-free por-
phyrin 8 is the isolated product.
Table 2 Results Obtained in Cyclization of Porphyrin 5
Entry Method
Temp (°C) Time
Yield (%)
1
oil bath
200
180
220
80
2 h
50
We were pleased to observe that such condensation–
cyclization reactions can be successfully extended to the
corresponding Cu(II) porphyrin complexes. The behavior
of these complexes is similar to that observed with the
Ni(II) ones.
2a
3b
4
MW open vessel
MW closed vessel
Eaton’s reagent
1 h
50
4 min
2–5 h
83
not obtained
The molecular structure of the Cu(II) complex of pyridi-
none-fused porphyrin 4c was determined by single-crystal
X-ray diffraction,24 and is presented in Figure 3; it con-
firms the presence of an a,b-unsaturated carbonyl group.
Indeed, the carbonyl and a-carbon atoms are connected by
a C–C single bond of 1.464(12) Å. The C=O and Ca=Cb
bonds have distances of 1.235(11) Å and 1.347(10) Å, re-
spectively, which are typical of double bonds. The Cu(II)
centre is bonded to four nitrogen donors of the porphyrin
macrocycle in a distorted square planar coordination envi-
ronment (see Figure 3, right) with Cu–N distances rang-
ing from 1.982(5) to 2.021(6) Å. The N4 coordination
plane displays a slight tetrahedral distortion of 0.056(3)
Å. These distances compare well with those found for oth-
er related Cu(II) porphyrin derivatives.25 Furthermore, the
pyrrole rings are tilted relatively to each other with dihe-
a Multimode reactor.
b Monomode reactor.
H
Ph
N
O
N
N
N
Ni
Ph
Ph
N
Ph
8
Figure 2 Structure of pyridinone-fused porphyrin 8
even after 1 hour of continuous irradiation. Also in this dral angles between consecutive rings varying between
case, a mixture of uncyclized and cyclized porphyrins 6 16.50(6) and 19.65(5)°. Comparable geometric arrange-
and 7a is obtained. However, when the cyclization is per- ments were found for other porphyrin metal complexes
formed at higher temperatures (220 °C) in a monomode containing fused groups such as in Ni(II) benzoporphyrin
reactor using closed-vessel conditions, the reaction is derivatives.26
complete in 4 minutes, providing the pyridinone-fused
Finally, the methyl and ethyl esters of the pyridinone-
porphyrin 7a in good yield (83%). Under these conditions,
fused porphyrins 4a and 7a were hydrolyzed with NaOH
the formation of the derivative 8 could be almost sup-
aqueous solutions to afford quantitatively the correspond-
ing carboxylic acid derivatives 1a and 2a (Figure 1).
pressed. We also observed that extending the reaction
time for more than 6 minutes an immediate decrease in the
yield of porphyrin 7a in benefit of 8 was observed. Thus,
In conclusion, we have established efficient synthetic
methodologies leading to novel porphyrin derivatives and
microwave cyclization under sealed-vessel conditions us-
further studies on their properties are currently under in-
ing a monomode reactor was found to be the method that
vestigation in our laboratories.
gives higher yields of porphyrin 7a (entries 2 and 3,
Table 2).
Acknowledgment
To our surprise all attempts using Eaton’s reagent as an al-
ternative method for cyclizing porphyrin 5 were unsuc-
cessful (entry 4, Table 2). In a series of experiments
Thanks are due to ‘Fundação para a Ciência e a Tecnologia–
FEDER’ for funding the Aveiro Research Unit – QOPNA and the
performed at 50 °C during 2–7 hours, a mixture of metal- project POCI/QUI/56214/2004. We also thank CEM for making
available to us a CEM Discover microwave reactor.
Synlett 2009, No. 6, 1009–1013 © Thieme Stuttgart · New York

1012
A. M. G. Silva et al.
LETTER
Figure 3 Molecular structure of Cu(II) complex of pyridinone-fused porphyrin 4c in two different views; top view showing the overall struc-
ture of the complex and a side view emphasizing the absence of planarity between the pyrrole rings. In this later view the phenyl rings have
been omitted for clarity.
(10) (a) Srivastava, B. K.; Solanki, M.; Mishra, B.; Soni, R.;
References and Notes
Jayadev, S.; Valani, D.; Jain, M.; Patel, P. R. Bioorg. Med.
Chem. Lett. 2007, 17, 1924. (b) Rivault, F.; Liébert, C.;
Burger, A.; Hoegy, F.; Abdallah, M. A.; Schalk, I. J.; Mislin,
G. L. A. Bioorg. Med. Chem. Lett. 2007, 17, 640. (c)Wang,
(1) For a review: Fox, S.; Boyle, R. W. Tetrahedron 2006, 62,
10039.
(2) For recent examples,see: (a) Lacerda, P. S. S.; Silva, A. M.
G.; Tomé, A. C.; Neves, M. G. P. M. S.; Silva, A. M. S.;
Cavaleiro, J. A. S.; Llamas-Saiz, A. L. Angew. Chem. Int.
Ed. 2006, 45, 5487. (b) Kadish, K. M.; Wenbo, E.; Sintic,
P. J.; Ou, Z.; Shao, J.; Ohkubo, K.; Fukuzumi, S.;
Govenlock, L. J.; McDonald, J. A.; Try, A. C.; Cai, Z.-L.;
Reimers, J. R.; Crossley, M. J. J. Phys. Chem. B 2007, 111,
8762. (c) Santos, F. C.; Cunha, A. C.; Souza, M. C. B. V.;
Tomé, A. C.; Neves, M. G. P. M. S.; Ferreira, V. F.;
Z.; Vince, R. Bioorg. Med. Chem. Lett. 2008, 18, 1293.
(11) For recent examples, see: (a) Jones, C. P.; Anderson, K. W.;
Buchwald, S. L. J. Org. Chem. 2007, 72, 7968. (b) Huang,
J.; Chen, Y.; King, A. O.; Dilmeghani, M.; Larsen, R. D.;
Faul, M. M. Org. Lett. 2008, 10, 2609; and references
therein.
(12) Gould, R. G.; Jacobs, W. A. J. Am. Chem. Soc. 1939, 61,
2890.
Cavaleiro, J. A. S. Tetrahedron Lett. 2008, 49, 7268.
(13) (a) Kidwai, M.; Misra, P.; Kumar, R.; Saxena, R. K.; Gupta,
(3) Jaquinod, L. In The Porphyrin Handbook, Vol. 1; Kadish, K.
R.; Bradoo, S. Monatsh. Chem. 1998, 129, 961. (b) Kidwai,
M.; Smith, K. M.; Guilard, R., Eds.; Academic Press: San
M.; Misra, P.; Dave, B.; Bhushan, K. R.; Saxena, R. K.;
Diego, 2000, Chap. 5, 212.
(4) Alonso, C. M. A.; Neves, M. G. P. M. S.; Tomé, A. C.; Silva,
A. M. S.; Cavaleiro, J. A. S. Tetrahedron Lett. 2001, 42,
8307.
(5) Alonso, C. M. A.; Serra, V. I. V.; Neves, M. G. P. M. S.;
Tomé, A. C.; Silva, A. M. S.; Paz, F. A. A.; Cavaleiro,
J. A. S. Org. Lett. 2007, 9, 2305.
(6) Alonso, C. M. A.; Neves, M. G. P. M. S.; Silva, A. M. S.;
Cavaleiro, J. A. S.; Hombrecher, H. K. Tetrahedron Lett.
1997, 38, 2757.
(7) Alonso, C. M. A.; Neves, M. G. P. M. S.; Tomé, A. C.; Silva,
Singh, M. Monatsh. Chem. 2000, 131, 1207.
(14) (a) Dorow, R. L.; Herrinton, P. M.; Hohler, R. A.; Maloney,
M. T.; Mauragis, M. A.; McGhee, W. E.; Moeslein, J. A.;
Strohbach, J. W.; Veley, M. F. Org. Process Res. Dev. 2006,
10, 493. (b) Zewge, D.; Chen, C. Y.; Deer, C.; Dormer, P.
G.; Hughes, D. L. J. Org. Chem. 2007, 72, 4276.
(15) Condensation Reaction
To a solution of (b-amino-meso-tetraphenylporphyrinato)-
nickel(II) (50 mg, 0.073 mmol) in toluene (5 mL), DMAD
(0.02 mL, 0.15 mmol) was added, and the resulting mixture
was heated at 85 °C under argon atmosphere for 150 min.
A. M. S.; Cavaleiro, J. A. S. Tetrahedron 2005, 61, 11866.
The reaction mixture was cooled to r.t. and purified by flash
(8) For recent examples. see: (a) Campbell, W. M.; Jolley,
chromatography using a 1:2 mixture of hexane–CH2Cl2 as
K. W.; Wagner, P.; Wagner, K.; Walsh, P. J.; Gordon,
eluent. The first fraction to be collected was a small amount
K. C.; Schmidt-Mende, L.; Nazeeruddin, M. K.; Wang, Q.;
Grätzel, M.; Officer, D. L. J. Phys. Chem. C 2007, 111,
11760. (b) Eu, S.; Hayashi, S.; Umeyama, T.; Matano, Y.;
Araki, Y.; Imahori, H. J. Phys. Chem. C 2008, 112, 4396.
(c) Park, J. K.; Lee, H. R.; Chen, J.; Shinokubo, H.; Osuka,
A.; Kim, D. J. Phys. Chem. C 2008, 112, 16691. (d) Mozer,
A. J.; Wagner, P.; Officer, D. L.; Wallace, G. G.; Campbell,
W. M.; Miyashita, M.; Sunahara, K.; Mori, S. Chem.
of starting porphyrin, followed by porphyrin 3, which was
collected and crystallized from CHCl3–MeOH to give 47 mg
(78% yield) of red crystals.
(16) Spectroscopic Data for [2-(2,3-Dimethoxycarbonyl-2-en-
1-yl)amino-5,10,15,20-tetraphenylporphyrinato]nickel
(II) (3)
1H NMR (500.13 MHz, CDCl3): d = 3.57 (s, 3 H, 2¢-OCH3),
3.66 (s, 3 H, 3¢-OCH3), 5.24 (s, 1 H, 3¢-H), 7.63–7.69 (m, 12
Commun. 2008, 4741. (e) Bonnett, R. Chemical Aspects of
Photodynamic Therapy; Gordon and Breach Science
Publishers: Amsterdam, 2000.
H, PhHmeta+para), 7.90–7.91 (m, 3 H, 3-H and PhHortho), 7.96–
8.00 (m, 6 H, PhHortho), 8.57 (d, J = 4.9 Hz, 1 H, b-H), 8.66
(d, J = 4.9 Hz, 1 H, b-H), 8.69–8.71 (m, 4 H, b-H), 9.01 (s,
1 H, 1¢-NH) ppm. 13C NMR (125.77 MHz, CDCl3): d = 51.1
(9) Mitscher, L. A. Chem. Rev. 2005, 105, 559.
Synlett 2009, No. 6, 1009–1013 © Thieme Stuttgart · New York

LETTER
(2¢-OCH3), 52.7 (3¢-OCH3), 94.1 (C-3¢), 117.3, 117.7, 118.8,
Synthesis of Novel Pyridinone-Fused Porphyrins
1013
was irradiated at 220 °C (1 min ramp to 220 °C and 3 min
hold at 220 °C, using 200 W maximum power). The reaction
mixture was then purified by flash chromatography using a
1:2 mixture of hexane–CH2Cl2 as eluent to give porphyrin 4a
(24 mg, 88% yield).
119.7, 120.5 (C-3), 126.81, 126.84, 126.90, 126.91, 127.5,
127.6, 127.66, 127.74, 127.8, 127.9, 128.12, 128.18, 131.71,
131.84, 132.04, 132.08, 132.13, 132.17, 132.6, 132.7, 133.0,
133.41, 133.45, 133.54, 133.6, 133.7, 139.1, 140.6, 140.7,
142.0, 142.28, 142.33, 142.6, 142.8, 143.4, 143.5, 146.9,
165.0 (2¢ -C=O), 168.4 (3¢ -C=O) ppm. UV/vis (CHCl3):
(22) Cyclization Reaction Using Eaton’s Reagent
A mixture of porphyrin 3 (50 mg, 0.060 mmol) and Eaton’s
reagent (0.4 mL) was heated at 50 °C for 150 min. The
reaction mixture was neutralized with an aq sat. soln of
Na2CO3. The aqueous layer was extracted three times with
CH2Cl2, and the organic layer was dried (anhyd Na2SO4) and
evaporated under vacuum to dryness. The resulting residue
was purified by flash chromatography using CHCl3 as eluent
and crystallized from CH2Cl2–n-hexane to give porphyrin 4c
(37 mg, 84% yield) as purple crystals.
(23) Spectroscopic Data for 2-Methoxycarbonyl-6,11,16,21-
tetraphenyl-1H-pyrido-4-one[2,3-b]porphyrin (4c)
1H NMR (300.13 MHz, CDCl3): d = –2.71 and –2.57 (2 s, 2
H, NH), 3.95 (s, 3 H, OCH3), 7.09 (d, J = 1.4 Hz, 1 H, 3-H),
7.74–7.79, 7.98–8.11, and 8.19–8.34 (3 m, 20 H, PhH),
8.69–8.74 (m, 3 H, b-H), 8.83, 8.87, and 9.01 (3 d, J = 5.0
Hz, 3 H, b-H), 9.24 (br s, 1 H, 1-NH) ppm. UV/vis (CHCl3):
l
max (log e) 422 (5.07), 537 (4.14), 567 (3.89) nm.
MS–FAB+: m/z = 828 [M + H], 827 [M]+. Anal. Calcd for
C50H35N5O4Ni: C, 72.48; H, 4.26; N, 8.45. Found: C, 72.66;
H, 4.06; N, 8.37.
(17) Cyclization Reaction Using an Oil Bath
A solution of porphyrin 3 (29 mg, 0.035 mmol) in
nitrobenzene (1.5 mL) was heated at 200 °C under argon
atmosphere for 6 h. The reaction mixture was then purified
by flash chromatography [CH2Cl2, then CH2Cl2–acetone
(95:5)] to remove the nitrobenzene and the product
pyridinone-fused porphyrin 4a. Porphyrin 4a was further
crystallized from CH2Cl2–MeOH to give the pure compound
(20 mg, 74% yield).
(18) The 4-quinolones could exist in two different forms: enol
and keto forms, however, usually these compounds exist
primarily in the keto form. For more information, see:
Mphahlele, M. J.; El-Hahas, A. M. J. Mol. Struct. 2004, 688,
129.
l
max (log e) = 425 (5.16), 523 (4.28), 556 (3.76), 596 (3.76),
651 (3.44) nm. MS–FAB+: m/z = 740 [M + H]+, 839 [M]+.
Anal. Calcd for C51H39N5O4·EtOH: C, 77.94; N, 8.91; H,
5.00. Found: C, 77.62; N, 8.70; H, 5.41.
(19) Spectroscopic Data for (2-Methoxycarbonyl-6,11,16,21-
tetraphenyl-1H-pyrido-4-one[2,3-b]porphyrinato)-
nickel (4a)
(24) X-ray Single-Crystal Determination
The X-ray data of porphyrin 4c–Cu(II) complex was
collected on a CCD Bruker APEX II using graphite
monochromatized Mo Ka radiation (l = 0.71073 Å) with the
crystal positioned at 35 mm from the CCD, and the spots
were measured using a counting time of 80 s. Data reduction
and empirical absorption were carried out using SAINT-NT
from Bruker aXS. The structure was solved by direct
methods and by subsequent difference Fourier syntheses and
refined by full matrix least squares on F2 using the SHELX-
97 system programs.27 The CH2Cl2 solvent molecule was
found disordered over three tetrahedral positions with
occupation factors of 0.333. In addition, the chlorine atoms
of one disorder component are also disordered occupying
two alternative positions with occupation factors of 0.166.
Anisotropic thermal parameters were used for all nonhy-
drogen atoms excluding the atoms of CH2Cl2, which were
refined with group isotropic temperature factors. The
hydrogen atoms of this molecule was not inserted in the
structure refinement while the hydrogen atoms of the copper
porphyrin derivative complex were included in refinement
in calculated positions with isotropic parameters equivalent
1.2 times those of the atom to which they are attached.
Crystal structure has been deposited with the Cambridge
Crystallographic Data Center and allocated with the deposit
number CCDC 710189.
1H NMR (300.13 MHz, CDCl3): d = 3.94 (s, 3 H, OCH3),
7.01 (d, J = 1.6 Hz, 1 H, 3-H), 7.63–7.71 and 7.88–8.08 (2
m, 20 H, PhH), 8.51 (d, J = 5.0 Hz, 1 H, b-H), 8.59–8.70 (m,
5 H, b-H), 9.10 (br s, 1 H, 1-NH) ppm. 13C NMR (75.47
MHz, CDCl3): d = 53.4 (OCH3), 114.9, 117.7 (C-3), 119.3,
120.1, 120.5, 126.6, 127.1, 127.5, 128.0, 128.3, 128.6,
129.3, 129.8, 131.2, 131.8, 132.3, 132.5, 132.7, 133.3,
133.65, 133.73, 133.83, 133.92, 137.9, 138.2, 140.04,
140.06, 142.29, 142.31, 142.49, 142.54, 142.7, 143.6, 146.1,
146.8, 162.8 (2 -C=O), 173.7 (4 -C=O) ppm. UV/vis
(CHCl3): lmax (log e) = 433 (5.25), 546 (4.17) nm.
MS–FAB+: m/z = 796 [M + H]+, 795 [M]+. HRMS–FAB:
m/z calcd for C49H31N5O3Ni [M + H]+: 796.1859; found:
796.1855. Anal. Calcd for C49H31N5O3Ni·3/2H2O: C, 71.46;
N, 8.50; H, 4.16. Found: C, 71.66; N, 8.40; H, 3.61.
(20) Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250.
(21) Cyclization Reaction
(a) Using a Multimode Reactor
A solution of porphyrin 3 (21 mg, 0.025 mmol) in
nitrobenzene (3.5 mL) under argon atmosphere was
irradiated at atmospheric pressure in a Milestone
MicroSynth microwave reactor (5 min ramp up to 180 °C
and 35 min hold at 180 °C, using 400 W maximum power).
The reaction mixture was then purified by flash
chromatography using a 1:2 mixture of hexane–CH2Cl2 as
eluent to give porphyrin 4a (19 mg, 93% yield).
(b) Using a Monomode Reactor
A solution of porphyrin 3 (28 mg, 0.034 mmol) in
nitrobenzene (1.5 mL) was placed in a 10 mL reaction vial,
which was then sealed under argon atmosphere and placed in
the cavity of a CEM microwave reactor. The reaction vial
(25) Allen, F. H. Acta Crystallogr., Sect. B: Struct. Sci. 2002, 58,
380.
(26) Silva, A. M. G.; Oliveira, K. T.; Faustino, M. A. F.; Neves,
M. G. P. M. S.; Tomé, A. C.; Silva, A. M. S.; Cavaleiro,
J. A. S.; Brandão, P.; Felix, V. Eur. J. Org. Chem. 2008, 704.
(27) Sheldrick, G. M. SHELX-97; University of Göttingen:
Germany, 1997.
Synlett 2009, No. 6, 1009–1013 © Thieme Stuttgart · New York