Synthesis and functionalization of β-alkyl-meso-triarylcorroles

Article abstract of DOI:10.1142/S1088424615500613

After the definition of efficient synthetic routes for the preparation of triarylcorroles, the functionalization of these macrocycles is becoming a necessary and challenging field of research. One important synthetic step is the introduction of substituents able to influence the electronic distribution in the macrocyclic ring. A valuable target would be a corrole macrocycle with some β-pyrrole positions occupied by methyl groups, while exploiting other positions to introduce electron-withdrawing substituents. To explore the scope of this approach, we investigated the bromination and the nitration of the corrole ring and the desired products have been obtained in moderate to good yield. The successful preparation of selectively halogenated corroles is particularly interesting since they are suitable substrates for the preparation of more complex partially alkylated structures using modern cross coupling methodologies.

Full text of DOI:10.1142/S1088424615500613

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2015; 19: 865–873
DOI: 10.1142/S1088424615500613
Published at http://www.worldscinet.com/jpp/
Synthesis and functionalization of b-alkyl-meso-
triarylcorroles
Giuseppe Pomaricoa, Manuela Stefanellia, Sara Nardisa, Sara Lentinia,
Daniel O. Ciceroa, Gregory T. McCandlessb,c, Kevin M. Smith*b◊
and Roberto Paolesse*a◊
a Department of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Roma, Italy
b Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
c Department of Chemistry, The University of Texas at Dallas, Richardson, TX 75080, USA
Received 20 February 2015
Accepted 1 April 2015
ABSTRACT: After the definition of efficient synthetic routes for the preparation of triarylcorroles,
the functionalization of these macrocycles is becoming a necessary and challenging field of research.
One important synthetic step is the introduction of substituents able to influence the electronic
distribution in the macrocyclic ring. A valuable target would be a corrole macrocycle with some
b-pyrrole positions occupied by methyl groups, while exploiting other positions to introduce electron-
withdrawing substituents. To explore the scope of this approach, we investigated the bromination and
the nitration of the corrole ring and the desired products have been obtained in moderate to good yield.
The successful preparation of selectively halogenated corroles is particularly interesting since they are
suitable substrates for the preparation of more complex partially alkylated structures using modern cross
coupling methodologies.
KEYWORDS: corrole, bromination, nitration.
on carbons 2, 3, 17 or 18 occurs much more readily than
INTRODUCTION
on positions 7, 8, 12 and 13.
The accomplishment of synthetic procedures for
Taking in account the potential application of
the preparation of 5,10,15-triarylcorroles starting from
corroles in different fields, such as for example optical
commercially available precursors [1, 2] has permitted
and photovoltaic devices, we have been interested in
widespread investigation of the functionalization of
exploiting regioselectivity of electrophilic aromatic
the macrocycle [3]. Whereas the developed synthetic
substitution found in corrole chemistry.
chemistry of porphyrins offers a wide choice of
To fulfil this synthetic target, an interesting target could
methodology, in the case of corrole this chemistry is more
challenging, since the reduced symmetry for corrole can
afford a complex mixture of regioisomers [4]. However,
be a b-alkyl-meso-aryl corrole, i.e. a macrocycle having
some b-pyrrolic positions functionalized with alkyl
groups. Since in the corrole ring the A and D pyrroles are
unexpected regioselectivity has been often observed,
the most reactive for functionalization reactions, we have
which simplifies corrole functionalization: since the
focused on the preparation of a corrole (Fig. 1), which,
pyrroles directly linked, designated A and D, are usually
to the best of our knowledge, has not been previously
more reactive than those next to the 10 meso-position
(called B and C), the introduction of functional groups
reported.
Once the target macrocycle has been synthesized, a
second step in our work would be investigation of the
functionalizationreactionsofsuchanelectronicallylopsided
species. Among the different substitutions of corroles,
◊ SPP full member in good standing
those convenient for our goal are the bromination and the
nitration reactions. Both these modification of tetrapyrrole
*Correspondence to: Kevin M. Smith, email: kmsmith@lsu.
edu; Roberto Paolesse, email: roberto.paolesse@uniroma2.it
Copyright © 2015 World Scientific Publishing Company

866
G. POMARICO ET AL.
CH2Cl2 on a Cary 50 spectrophotometer. 1H NMR
spectra were recorded at 300 K either using a Bruker
AV300 spectrometer operating at 300 MHz or with a
Bruker Avance 600 spectrometer operating at 600 MHz
with a 5 mm inverse broad-band equipped with z-axis
gradients. Chemical shifts are given in ppm relative to
residual CHCl3 (7.26 ppm for 1H and 77.16 ppm MHz for
13C). All data were processed with TopSpin. Mass spectra
(FAB mode) were recorded on a VGQuattro spectrometer
in the positive-ion mode using m-nitrobenzyl alcohol
(Aldrich) as matrix.
7
5
3
6
8
4
B
2
A
9
N
NH
22
1
10
21
19
24
23
11
12
NH
HN
18
D
C
16
14
17
15
13
Synthesis
2-Benzoyl-3,4-dimethyl-pyrrole(3). 2-Carboxyethyl-
3,4-dimethyl-5-benzoylpyrrole (2) (800 mg, 2.95 mmol)
and NaOH (1.41 g, 35.4 mmol) were dissolved in
ethylene glycol (30 mL), and the mixture was stirred at
reflux under nitrogen for 90 min. After this period, the
mixture was cooled down, diluted with water (100 mL)
and extracted with CHCl3. The organic phase was dried
over anhydrous Na2SO4 and the solvent was removed
under reduced pressure. The residue oil was directly used
Fig. 1. Molecular structure of the target corrole 1
peripheral positions strongly influence the electronic
structure of the macrocycle [5, 6] and allow the preparation
of substrates to be exploited in the formation of more
complex architectures by a bottom-up approach: in the case
of brominated compounds, these are common substrates for
the palladium catalyzed cross-coupling reactions [7], such
as those developed by Heck [8], Stille [9], Suzuki [10] and
Sonogashira [11]. The nitration is the first step to prepare
new substrates useful for so-called “click chemistry” [12,
13]. For this last reaction, different conditions have been
mainly optimized [14, 15] for the preparation of the 3-NO2,
and 3,17-(NO2)2 derivatives, either using the free base or Cu
complexes, even though a wide range of differently mono
or polynitrated products have been obtained by changing
the reaction conditions [16, 17].
The regioselective bromination of corrole is more
difficult and the complete substitution of the ring is
usually observed, thus avoiding the separation of complex
regioisomers [5]. However some examples of synthetic
routes for the preparation of selectively brominated
corroles have been recently reported [18].
In this work we present the synthesis of the target
7,8,12,13-tetramethyl-5,10,15-triphenylcorrole 1, together
with some related bromo- and nitro-derivatives.
1
for the following step. H NMR (300 MHz, CDCl3): d,
ppm 8.90 (br s, 1 H, NH pyrrole), 7.66 (d, 2 H, J = 6.72
Hz, o-H benzoyl), 7.49–7.44 (m, 3 H, m, p-H benzoyl),
6.84 (s, 1 H, a-H pyrrole), 2.10 (s, 3 H, b-methyl), 1.89
(s, 3 H, b-methyl). Anal. calcd. for C13H13NO: C, 78.36;
H, 6.58; N, 7.03%. Found C, 78.42; H, 6.64; N, 7.00%.
Yield 85% (496 mg).
1,9-Dibenzoyl-2,3,7,8-tetramethyl-5-phenyldi-
pyrromethane (4). Pyrrole 3 (800 mg, 4.04 mmol)
was dissolved in ethanol (10 mL) and stirred to reflux;
a solution of benzaldehyde (205 mL, 2.02 mmol) in
ethanol (2 mL) was added dropwise, and then few drops
of concentrated HCl were added and the solution color
turned from orange to purple. The solvent was removed
under reduced pressure and the residue was purified by
chromatography using a short silica gel column eluted
with CHCl3; the eluted product was examinated by
exposure of the TLC plate to bromine vapor, whereupon
the dipyrromethane appeared as a red-pink spot, while
the tripyrrane is violet. The final product was obtained
1
as a brown oil. H NMR (300 MHz, CDCl3): d, ppm
8.57 (s, 2 H, NH pyrrole), 7.59 (d, 4 H, J = 6.81 Hz,
o-H benzoyl), 7.51–7.35 (m, 9 H, m, p-H benzoyl + m,
p-H meso phenyl), 7.17 (d, 2 H, J = 6.84 Hz o-H meso
phenyl), 5.60 (s, 1 H, meso H), 1.92 (s, 6 H, b-methyl),
1.84 (s, 6 H, b-methyl). Anal. calcd. for C33H30N2O2: C,
81.45; H, 6.21; N, 5.76%. Found C, 81.51; H, 6.26; N,
5.72%. Yield 70% (687 mg).
EXPERIMENTAL
General
1,9-Bis(benzoylcarbinol)-2,3,7,8-tetramethyl-5-
phenyldipyrromethane (5). Dipyrromethane 4 (600 mg,
1.23 mmol) was dissolved in THF/methanol (50 + 17 mL)
and NaBH4 (50 equiv, 2.32 g) was added in small portions
during 30 min under vigorous stirring at room temperature.
The mixture was stirred for a further 90 min and then water
Silica gel 60 (70-230 mesh, Sigma Aldrich) or basic
alumina oxide (Type T, Merck) were used for column
chromatography. Reagents and solvents (Aldrich) were
of the highest grade available and were used without
further purification. UV-vis spectra were recorded in
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 866–873

SYNTHESIS AND FUNCTIONALIZATION OF b-ALKYL-MESO-TRIARYLCORROLES
867
was added. The solvent was reduced to a small volume and
mixture (10 mL of TFA + 40 mL of CH2Cl2) were added
and the mixture was stirred under nitrogen for a further
30 min. The mixture was diluted with CH2Cl2 (10 mL)
and after 10 min chloranil (167 mg) was added. The
mixture was stirred for 20 min before the addition of
a satured solution of Cu(OAc)2 in methanol. The final
solution was stirred at reflux for 20 min. The solvent
was removed and the residue was purified as above.
extracted with CHCl3. The organic phase was dried over
anhydrous Na2SO4 and immediately used for the corrole
synthesis. Yield 90% (542 mg).
7,8,12,13-Tetramethyl-5,10,15-triphenylcorrole
(1). Compound 5 (281 mg, 0.65 mmol) was dissolved in
50 equiv. (2.26 mL) of pyrrole and 130 mL of a solution
of TFA in CH3CN (10 mL in 1 mL) was added and the
resulting solution was stirred at room temperature for
10 min. The solution was transferred to a larger flask
containing 260 mL of CH2Cl2, and after 10 min a solution
of DDQ (442 mg) in THF (2 mL) was added under
vigorous stirring. After 1 h the solvent was removed
under vacuum and the residue was purified by passage
through a silica gel plug eluted with chloroform; the
fractions containing the porphyrinoid derivatives were
collected and purified again by column chromatography
(basic Al2O3 grade T) eluted with CH2Cl2. The first
green band was collected and crystallized from CH2Cl2/
CH3OH, yielding 15 mg (4%) of the titled corrole. mp
>ꢀ300°C. UV-vis (CH2Cl2): lmax, nm (log e) 429 (4.31),
Yield 12% (50 mg), mp >300°C. UV-vis (CH2Cl2): lmax
,
1
nm (log e) 410 (4.50), 560 (3.46), 623 (3.22). H NMR
(300 MHz, CDCl3): d, ppm 7.76 (d, 2 H, J = 4.33 Hz,
b-pyrrole), 7.69 (d, 4 H, J = 7.22 Hz, phenyl), 7.62 (d, 2 H,
J = 4.33 Hz, b-pyrrole), 7.58–7.53 (m, 5 H, phenyl),
7.51–7.42 (m, 6 H, phenyl), 1.61 (s, 6 H, b-methyl),
1.34 (s, 6 H, b-methyl). MS (FAB): m/z (%) 642 [M]+
(100). Anal. calcd. for C41H31CuN4: C, 76.55; H, 4.86; N,
8.71%. Found C, 76.60; H, 4.92 N, 8.64.
2,3,7,8,12,13-Hexamethyl-5,10,15,20-tetraphenyl-
porphyrin (7). mp >ꢀ300°C. UV-vis (CH2Cl2): lmax, nm
(log e) 439 (5.37), 537 (4.13), 586 (3.91), 612 (3.74) 669
1
(3.49). H NMR (300 MHz, CDCl3): d, ppm 8.34 (br s,
1
575 (3.56), 658 (3.53). H NMR (300 MHz, CDCl3): d,
2 H, b-pyrrole), 8.30–8.27 (m, 4 H, phenyl), 8.23–8.20
(m, 4 H, phenyl), 7.78–7.75 (m, 12 H, phenyl), 2.13 (s,
6 H, b-methyl), 2.03 (s, 6 H, b-methyl), 1.85 (s, 6 H,
b-methyl), -2.37 (br s, 2 H, inner NH). Anal. calcd. for
C50H42N4: C, 85.93; H, 6.06; N, 8.02%. Found C, 85.88;
H, 6.01; N, 8.07.
ppm 8.88 (d, 2 H, J = 3.96 Hz, b-pyrrole), 8.45 (d, 2 H,
J = 3.45 Hz, b-pyrrole), 8.20 (d, 4 H, J = 7.15 Hz, phenyl),
8.14–8.09 (m, 2 H, phenyl), 7.77–7.69 (m, 9 H, phenyl),
2.40 (s, 6 H, b-methyl), 2.10 (s, 6 H, b-methyl). Anal.
calcd. for C41H34N4: C, 84.51; H, 5.88; N, 9.61%. Found
C, 84.58; H, 5.83; N, 9.55%.
[2,3,7,8,12,13-Hexamethyl-5,10,15,20-tetraphenyl-
[7,8,12,13-Tetramethyl-5,10,15-triphenylcorrolato]
Cu (6). Method A. This corrole was prepared similarly
as described for 1, but a saturated solution of Cu(AcO)2
in methanol was added 30 min after the oxidant addition;
the mixture was then stirred at reflux for 20 min. The
solvent was removed under vacuum and the residue was
purified by passage through a silica gel plug eluted with
CHCl3; the fraction containing the corrole contaminated
with the Cu complex of porphyrin 7 (5:1 ratio) was
collected, the solvent reduced to a small volume and
purified again by a silica gel TLC with CH2Cl2/hexane
(2:3) as eluting system. The brown fraction containing
the corrole was collected and crystallized from CH2Cl2/
CH3OH.Yield 5% (21 mg). Method B. Dipyrromethane 5
(281 mg, 0.65 mmol) and 50 equiv. of pyrrole (2.26 mL)
were dissolved in CH3OH (70 mL), then 0.25 M HCl
(70 mL) was added and the mixture was stirred for 2 h.
After this period the suspension was extracted with
CHCl3, the organic phase was washed with water, dried
over anhydrous Na2SO4, diluted up to 120 mL with
CHCl3 and 630 mg of chloranil (630 mg) was added.
The mixture was stirred for 30 min, and then a satured
solution of Cu(OAc)2 in methanol was added and the
resulting mixture was stirred at reflux for a further
20 min. The solvent was removed and the residue
was purified as above. Yield 4% (17 mg). Method C.
Dipyrromethane 5 (281 mg, 0.65 mmol) was dissolved in
50 equiv. (2.26 mL) of pyrrole and stirred under nitrogen
flux for 10 min; then 8 mL of a solution of CH2Cl2/TFA
porphyrinato]Zn. mp >ꢀ300°C. UV-vis (CH2Cl2): lmax,
1
nm (log e) 444 (5.37), 581 (4.39). H NMR (300 MHz,
CDCl3): d, ppm 8.34 (br s, 2 H, b-pyrrole), 8.29–8-27
(m, 4 H, phenyl), 8.22–8.21 (m, 4 H, phenyl), 7.77–7.52
(m, 12 H, phenyl), 2.13 (s, 6 H, b-methyl), 2.03 (s, 6 H,
b-methyl), 1.85 (s, 6 H, b-methyl). Anal. calcd. for
C50H40N4Zn: C, 78.78; H, 5.29; N, 7.35%. Found C,
78.87; H, 5.36; N, 7.30.
Nitration of [7,8,12,13-tetramethyl-5,10,15-
triphenylcorrolato]Cu. Copper corrole 6 (34 mg,
0.053 mmol) was dissolved in DMF (8 mL) and the
mixture was heated to reflux. AgNO2 (8 mg, 0.053 mmol,
1 equiv) and NaNO2 (33 mg, 0.477 mmol, 9 equiv) were
added and the reaction progress was monitored by UV-vis
spectrometry and TLC analysis (silica gel/CH2Cl2). After
8 min brine was added to quench the reaction and the
precipitate filtered off on paper. The residue was dissolved
in CHCl3, dried over anhydrous Na2SO4, and purified using
a silica gel column eluted with CH2Cl2. A first olive green
fraction was the mononitroderivative 8 and the following
bright green fraction was the dinitroderivative 9.
[3-NO2-7,8,12,13-tetramethyl-5,10,15-triphenyl-
corrolato]Cu (8). Crystallized from CH2Cl2/CH3OH.
Yield 34% (12 mg), mp >300°C. UV-vis (CH2Cl2):
l
max, nm (log e) 381 (sh), 420 (4.64), 591 (3.95), 671
1
(3.80). H NMR (600 MHz, CDCl3): d, ppm 8.14 (s,
1 H, b-pyrrole H-2), 7.76 (d, 1 H, J = 4.32 Hz, b-pyrrole
H-18), 7.69 (d, 1 H, J = 4.32 Hz, b-pyrrole H-17),
7.65 (d, 4 H, J = 8.55 Hz, 5,15-o-phenyl), 7.62–7.58
Copyright © 2015 World Scientific Publishing Company
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868
G. POMARICO ET AL.
(m, 3 H, 5,10,15-p-phenyl), 7.55 (d, 2 H, J = 6.85 Hz,
10-o-phenyl), 7.51 (t, 2 H, J = 8.22 Hz, 15-m-phenyl),
7.47 (t, 2 H, J = 7.92 Hz, 10-m-phenyl), 7.42 (t, 2 H, J =
8.86 Hz, 5-m-phenyl), 1.62 (s, 3 H, b-methyl C-13), 1.46
(s, 3 H, b-methyl C-7), 1.41 (s, 3 H, b-methyl C-8), 1.30
(s, 3 H, b-methyl C-12). 13C NMR (600 MHz, CDCl3):
d, ppm 158.89 (a-pyrrole C-9), 157.13 (a-pyrrole C-6),
156.35 (a-pyrrole C-14), 153.03 (a-pyrrole C-11),
150.40 (a-pyrrole C-16), 144.43 (a-pyrrole C-19),
143.47 (b-pyrrole C-7 or C-8), 143.26 (b-pyrrole C-12
or C-13), 142.66 (10-phenyl C-ipso), 142.78 (b-pyrrole
C-7 or C-8), 141.70 (a-pyrrole C-1 or C-4), 141.69
(5-phenyl C-ipso), 140.73 (a-pyrrole C-1 or C-4),
140.54 (b-pyrrole C-12 or C-13), 140.51 (b-pyrrole C-3),
139.72 (15-phenyl C-ipso), 131.35 (meso C-5 or C-15),
129.52 (5 or 15-phenyl C-orto), 129.01 (5,10,15-phenyl
C-para), 128.94 (10-phenyl C-orto), 128.69 (5-phenyl
C-meta), 128.60 (10-phenyl C-meta), 128.44 (15-phenyl
C-meta), 128.33 (b-pyrrole C-17), 127.59 (5 or 15-phenyl
C-orto), 124.51 (meso C-10), 123.73 (meso C-5 or C-15),
121.07 (b-pyrrole C-18) 114.32 (b-pyrrole C-2), 13.56
(b-Methyl C-7), 13.30 (b-Methyl C-12), 12.79 (b-Methyl
C-13), 12.61 (b-Methyl C-8). MS (FAB): m/z (%) 690
[M + H]+ (100). Anal. calcd. for C41H30CuN5O2: C, 71.55;
H, 4.39; N, 10.18%. Found C, 71.51; H, 4.33 N, 10.22%.
[3,17-(NO2)2-7,8,12,13-tetramethyl-5,10,15-tri-
phenylcorrolato]Cu (9). Crystallized from CH2Cl2/
CH3OH. Yield 23% (9 mg), mp >ꢀ300°C. UV-vis
(CH2Cl2): lmax, nm (log e) 430 (4.72), 605 (4.02), 685
(3.86). 1H NMR (300 MHz, CDCl3): d, ppm 8.04 (s, 2 H,
b-pyrrole H-2, 18), 7.66–7.58 (m, 8 H, phenyl), 7.51–7.44
(m, 7 H, phenyl), 1.52 (s, 6 H, b-methyl), 1.38 (s, 6 H,
b-methyl). MS (FAB): m/z (%) 734 [M]+. Anal. calcd. for
C41H29CuN6O4: C, 67.16; H, 3.99; N, 11.46%. Found C,
67.02; H, 4.04 N, 11.52%.
Bromination of [7,8,12,13-tetramethyl-5,10,15-
triphenylcorrolato]Cu. Copper corrole 6 (60 mg, 0.093
mmol) was dissolved in spectroscopic grade CHCl3
(ethanol free) (20 mL) and a solution of Br2 in CHCl3
(70 mL/4 mL) was added dropwise, monitoring the
course of the reaction by UV-vis spectrometry and TLC
analysis (silica gel/CH2Cl2). After 5 min the reaction was
quenched with a few drops of pyridine, then washed with
an aqueous solution of Na2S2O5 (20% w/v), dried over
anhydrous Na2SO4, solvent reduced to a small volume
and residue purified using a silica gel column eluted with
CH2Cl2. The first olive green fraction was collected and
identified as the tetrabrominated copper derivative 10,
while the second fraction, bright green in color, as the
corresponding free base 11.
C41H27Br4CuN4: C, 51.36; H, 2.84; N, 5.84%. Found C,
51.31; H, 2.76 N, 5.90%.
2,3,17,18-Br4-7,8,12,13-tetramethyl-5,10,15-tri-
phenylcorrole (11). Crystallized from CH2Cl2/CH3OH.
Yield 18% (5 mg), mp >ꢀ300°C. UV-vis (CH2Cl2):
l
max, nm (log e) 425 (4.76), 450 (4.68), 589 (4.03), 670
1
(4.28). H NMR (300 MHz, CDCl3): d, ppm 8.02–7.97
(m, 6 H, phenyl), 7.76–7.68 (m, 9 H, phenyl), 2.10 (s,
6 H, b-methyl), 1.91 (s, 6 H, b-methyl). MS (FAB): m/z
(%) 897 [M]+ (100). Anal. calcd. for C41H27Br4CuN4: C,
54.82; H, 3.37; N, 6.24%. Found C, 54.90; H, 3.43 N,
6.18%.
RESULTS AND DISCUSSION
The first step of our work was the preparation of the
target corrole; we choose to modify the corrole framework
by introducing methyl groups at b-positions of pyrroles B
and C, with the aim to obtain the 7,8,12,13-tetramethyl-
5,10,15-triphenylcorrole 1 (Fig. 1), which keeps the more
reactive pyrrole positions (2, 3, 17 and 18) still available
for the introduction of other substituents. The synthetic
pathway for the preparation of the target molecule is
shown in Scheme 1.
Since the desired corrole cannot be obtained by a
statistical approach (one pot condensation of pyrrole,
dialkylpyrrole and arylaldehyde), due to the different
reactivity of unsubstituted and 3,4-disubstituted pyrrole,
a rational approach was applied. The procedure for the
formation of 1 can be divided in two main steps, where
the first is the preparation of a suitable dipyrromethane-
biscarbinol (5) followed by the cyclization of this
intermediate with an excess of pyrrole. This synthetic
pathway resembles the procedure reported for the
preparation of arylcorroles or arylporphyrins bearing
different meso-substituents by a dipyrromethane-diketone
precursor [19–21].
The multistep procedure leading to 1 starts with
the preparation of 2 [22], which then underwent
decarboxylation under alkaline conditions. The
a-free pyrrole 3 thereby obtained was reacted with
a stoichiometric amount of benzaldehyde in acidic
ethanol, and following purification yielded the desired
dipyrromethane 4. The two benzoyl groups were reduced
to the more reactive carbinol moieties by reaction with
NaBH4 [23], giving the dipyrromethane 5.
We initially adopted the same reaction conditions
reported for the preparation of corrole bearing three
different aryl groups [20]. Biscarbinol (5) wasdissolved in
50 equivalents of pyrrole and a solution of TFA in CH3CN
was added; after 10 min the mixture was diluted with
CH2Cl2, stirred for a further 10 min, and then a solution
of DDQ in THF was added to induce the oxidation of
bilane to corrole 1. The UV-vis spectrum of the reaction
mixture did not provide evidence of the corrole formation
because of the presence of many by-products, mainly
[2,3,17,18-Br4-7,8,12,13-tetramethyl-5,10,15-tri-
phenylcorrolato]Cu (10). Crystallized from CH2Cl2/
CH3OH. Yield 21% (16 mg), mp >ꢀ300°C. UV-vis
(CH2Cl2): lmax, nm (log e) 414 (4.81), 570 (4.06), 646
1
(3.77). H NMR (300 MHz, CDCl3): d, ppm 7.62–7.38
(m, 15 H, phenyl), 1.53–1.41 (m, 12 H, b-methyl).
MS (FAB): m/z (%) 959 [M]+ (100). Anal. calcd. for
Copyright © 2015 World Scientific Publishing Company
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SYNTHESIS AND FUNCTIONALIZATION OF b-ALKYL-MESO-TRIARYLCORROLES
869
i
ii
PhOC
CO2Et
PhOC
N
H
N
H
NH HN
COPh
PhOC
2
3
4
iii
HN
N
NH
HN
iv
CH(OH)Ph
Ph(HO)HC
NH HN
5
1
Scheme 1. Synthetic pathway for the preparation of corrole 1. Reaction conditions: (i) NaOH, ethylene glycol, reflux, 90 min;
(ii) benzaldehyde, ethanol, reflux, HCl; (iii) NaBH4, THF/CH3OH, r.t., 90 min; (iv) pyrrole, catalyst, solvent, oxidant, r.t.
open chain derivatives; a first chromatographic separation
was done using a silica gel plug eluted with CHCl3. The
fractions collected were subject to a second purification
on basic alumina, which yielded a small amount of a
green compound characterized by a large Soret band and
two Q-bands at 429, 575 and 658 nm, respectively. The
of the desired product. A subsequent chromatographic
separation afforded the product 6, contaminated with a
small amount of another compound having a very similar
Rf as revealed by TLC analysis (silica gel, CH2Cl2/
hexanes 2:3).
The identification of the reaction by-product was done
by separation of it on preparative TLC. The first red band
fraction was characterized as a Cu-porphyrin (Rf = 0.67),
due to its Soret band at 428 nm and only one Q-band at
561 nm, which closely resembles the UV-vis spectrum
of a Cu-tetraphenylporphyrin. The second brown band
corresponded to the desired Cu-corrole 6 (Rf = 0.64), as
confirmed by the UV-vis (Fig. 2) and 1H NMR spectra
(see Supporting information). The formation of 6 was
also confirmed by X-ray analysis, although only a low
resolution structure was obtained due to incomplete
data acquistion due to instrument failure during data
collection. Although the structure is not of adequate
quality for publication, it was good enough to clearly
indicate the formation of 6 (Fig. 3), and to demonstrate
that the corrole framework has a “saddled” conformation
similar to previously published structures [27, 29]. During
the attempt to prepare the corrole free base, no porphyrin-
like product was collected. A plausible explanation for
the different results obtained is possibly due to the larger
basicity reported for the highly substituted porphyrins
[30, 31], which are easily protonated even in the mild
acid conditions. The mixture leading to corrole and
porphyrin was initially purified on silica gel (an acid
support) possibly forming a dicationic species not eluted
during the chromatographic step. The formation of this
1
pattern of the H NMR signals was in agreement with
the corrole formation: namely, two doublets (2 protons
each) at 8.45 and 8.88 ppm, with J values consistent with
those of b-pyrrolic protons of arylcorrole, and two sharp
singlets (6 protons each) at 2.40 and 2.10 ppm for the
methyl substituents.
Attempts to grow single crystals for a definitive
characterization of 1 failed. After a few days the color
of the corrole solution turned from green to pink, and
the UV-vis spectrum revealed the decomposition of
the product. This result showed that 1 was sensitive
to ambient light and to the presence of air that trigger
the decomposition process, forming a biliverdine-
like product [24]. Corroles are generally sensitive to
oxidation and/or photodecomposition, and in the case of
1 this feature was even increased by the presence of the
alkyl groups. To circumvent this drawback the reaction
was repeated introducing a simple variation that was
successful in the preparation of triaryl-tetrabenzocorrole
or the 5,10,15-triferrocenylcorrole [25, 26]: instead of
isolating the free base, the corresponding Cu complex
was prepared by addition of a methanolic solution
of Cu(OAc)2 just after the oxidation of the bilane to
corrole. The coordination of the copper cation increases
the stability of the macrocycle, allowing the isolation
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870
G. POMARICO ET AL.
NH
N
N
HN
7
Fig. 4. Structure of the hexamethyl-tetraphenylporphyrin 7
three broad singlets at 1.85, 2.03 and 2.13 ppm (6H each)
suggested the presence of three pyrrole rings bearing
the methyl groups and only one b-unsubstituted pyrrole,
while the typical broad signal centerd at -2.37 ppm
for the inner NH confirms the free base nature of the
macrocycle. In the aromatic region, three not well-
resolved signals, integrating 2, 4 and 4 H, respectively,
were assigned to the b-pyrrole and some phenyl ring
protons. The low resolution is due either to steric
hindrance between alkyl and aryl substituents, or by
some conformational equilibrium of the macrocycle [34].
The coordination of Zn gave a better-resolved spectrum,
showing a singlet (2H) at 8.34 ppm that can be attributed
Fig. 2. UV-vis spectra in CH2Cl2 of 1 (full line) and 6 (dashed
line)
N
N
Cu
N
N
1
to the unsubstituted b-pyrrole; the H NMR spectrum
obtained for this compound is very similar to that reported
in the literature for the hexaethyl-tetraphenylporphyrin
[35]. The regioselective formation of this porphyrin is
quite surprising, since its formation could be reasonably
attributed to the ring-scrambling that occurred under the
reaction conditions. Nevertheless, the formation could
be of synthetic interest since the multi-step methodology
reported in the literature is quite complicated, but the
overall yields are quite comparable.
Once the corrole formation had been confirmed, we
tried alternative synthetic routes for the preparation of
this macrocycle, with the aim to improve the yields of
the reaction. Two different procedures were investigated;
in both cases the Cu-complex was prepared to take
advantage of the higher stability of the metal-derivative
compared with the corresponding free base. The second
method tested was one reported by Gryko [36] for the
preparation of triarylcorrole in a methanol–water solvent
mixture; the procedure was adapted to our starting
material. Dipyrromethane 5 and a 50-fold excess of
pyrrole were dissolved in the solvent mixture and HCl
was added. The solution became purple and after a
few minutes, the formation of a white suspension was
observed. Work up of the reaction, followed by the
oxidation of the bilane to corrole and by Cu insertion,
afforded corrole 6 in comparable yield to that reported
for the previously described method.
Fig. 3. Molecular and X-ray structure of 6
porphyrin-like product is due to the reaction between
dipyrromethane-biscarbinol and pyrrole under reversible
conditions [32].
The paramagnetic nature of the Cu-porphyrin ruled
out its H NMR characterization; to confirm the nature
1
of the macrocycles, the mixture containing the porphyrin
and the corrole was subject to Cu demetalation by the
procedure reported for accomplishing this with corrole
complexes [33], and also works for Cu-porphyrins.
The purification carried out by a basic alumina column
eluted with CH2Cl2 afforded two fractions: the first
(green) fraction was characterized as 1 by comparison
1
of UV-vis and H NMR spectra with those previously
obtained. The second fraction, red in color, was identified
as the porphyrin derivative 7 (Fig. 4); the red-shift for
the Soret band (17 nm with respect to b-unsubstituted
tetraphenylporphyrin) suggests a certain degree of
distortion of the macrocycle due to the crowding of
1
the peripheral positions. The H NMR spectrum of this
compound did not unequivocally clarify its structure:
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SYNTHESIS AND FUNCTIONALIZATION OF b-ALKYL-MESO-TRIARYLCORROLES
871
Finally we tested the effectiveness of the procedure
ROESY spectrum a dipolar interaction between the
singlet belonging to the H close the –NO2 group and a
doublet of one of the hydrogens on the unsubstituted
pyrrole was observed (see Supporting information).
Since this interaction can occur only between atoms
spatially close to each other (H2–H18), we can deduce
that the functionalization occurred on position 3, leading
to the formation of corrole 8. Furthermore, the interaction
between the H17 and the ortho protons of the adjacent
phenyl ring, furnished further proof of the site of nitration.
A second emerald green fraction was also isolated (Rf:
0.81) from the reaction. The higher polarity of this product
with respect to 8 suggested the formation of a polynitrated
product, as corroborated by the mass spectrum, where a
peak at m/z 734 was present. In this case it is expected
that substitution likely occurs at position 3 and 17. The
singlet (2 H) at 8.04 ppm confirmed the formation of the
symmetrical disubstituted nitro derivative 9. It should
be noted that the product yields were lower than those
obtained for the analogous triarylcorrole complex [15]
and that the mono- and bis-substituted product ratio was
also different, with an increase of the bis-nitro corrole
product. Both results could be attributed to the presence
of the peripheral methyl groups, making 6 more liable to
the oxidation, which is the initial step for the reaction.
Finally the bromination reaction of 6 was initially
investigated using a mild reagent such as NBS (Fig. 5).
A small excess of NBS (with respect the four positions
to be functionalized) was reacted with the Cu-corrole in
refluxing CHCl3. After a few minutes a severe broadening
of the Soret band and the complete disappearance
of the Q-bands was observed. TLC analysis showed
the presence of only base-line material; these results
suggested the complete decomposition of the Cu-corrole.
Similar results were obtained when the reaction was
repeated at room temperature. We can again attribute this
result to the sensitivity of 6 to the oxidative conditions of
the reaction.
previously reported for the preparation of triarylcorrole
[37]; even if this method is based on the reaction of a
10 fold excess of pyrrole vs. aldehyde, for sake of
consistency with the other investigations, a 50 fold
excess of pyrrole (vs. dipyrromethane-biscarbinol) was
employed. The target corrole was also obtained using this
procedure, and it gave the best results in terms of yield
(12%). Although not exciting, it is noteworthy that the
yield calculated with respect to 5 is not unusual in the
case of corrole and comparable with those reported for
some triarylcorroles obtained by a one-step condensation
of arylaldehyde and pyrrole [5, 37].
Two different functionalization reactions were
successfully carried out on corrole 6: the nitration and the
bromination reactions (Fig. 5). The nitration reaction was
performed following the method recently reported [15],
which drives the reaction toward the formation of the
mononitro derivative as the main product, together with a
small amount of dinitro substituted corrole. Compound 6
was reacted with 1 equivalent ofAgNO2 and 9 equivalents
of NaNO2 in refluxing DMF. The silver nitrite acts as
oxidant, promoting the formation of a p radical cation
species that undergoes nucleophilic attack by the nitrite
anion from the NaNO2. The UV-vis spectrum and TLC
analysis after a few minutes showed almost complete
disappearance of the starting material. Purification of
the reaction mixture afforded a first, major band (silica
gel, CH2Cl2: Rf 0.86), olive green in color, which was
collected and characterized by UV-vis (Fig. 6), 1H NMR,
1
and mass spectrometry. The H NMR analysis showed
one singlet and two doublets (1H each) in the region of
the b-pyrrole protons, which suggested the formation
of a mono-nitroderivative; this was confirmed by the
mass analysis where a peak at m/z+ = 689 was observed.
Although we did not obtain a suitable crystal to confirm
on which carbon the substitution had taken place, it can
be presumed that the nitration occurred on C-3 because
of the higher reactivity observed for this position in
previous cases of the nitration reaction. To confirm this
hypothesis, a 2D NMR analysis was performed. In the
A different approach was then carried out using
elemental bromine. The procedure for the complete
bromination of Cu-corrole [5, 38] was slightly modified
Br
Br
Br
Br
O2N
O2N
Br
Br
Br
Br
N
N
N
N
N
N
N
N
N
N
N
N
N
NH
NH
Cu
Cu
Cu
HN
O2N
8
9
10
11
Fig. 5. Products of the nitration (8, 9) and bromination (10, 11) of 6
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872
G. POMARICO ET AL.
Fig. 6. UV-vis spectra in CH2Cl2 of 8 (full line) and 9 (dashed
Fig. 7. UV-vis spectra in CH2Cl2 of 10 (full line) and 11 (dashed
line)
line)
by decreasing the equivalents of Br2, since the positions
available for the bromination were four instead of eight;
for this reason we used half of the equivalent compared
with those reported in the original paper. Br2 was added
dropwise and after 5 min no more starting material
was detected by TLC. The reaction was immediately
quenched by addition of pyridine; chromatographic
purification (silica gel, CH2Cl2) afforded two products.
The first band, olive green in color was identified as the
desired tetrabrominated derivative 10, characterized by a
low solubility that negatively affected the characterization
methanol solution. The product obtained has the same
spectroscopical pattern of 10, confirming that 11 is
derived from the demetallation of 10 in the reaction
conditions. The reaction yields were however lower
than those of the corresponding triarylcorroles, and this
result could be reasonably attributed to the sensitivity of
6 to oxidative decomposition and to its low solubility as
previously described.
CONCLUSION
1
of the product. The H NMR spectrum was quite broad,
A synthetic route for the preparation of b-alkyl-
meso-arylcorroles has been investigated, and the first
example of such a corrole has been synthesized. The
route involves the preparation of a methyl-substituted
dibenzoyl dipyrromethane, which was reduced and then
the corresponding biscarbinol was reacted with pyrrole
to obtain the bilane precursor of the target corrole.
The addition of copper ion after the oxidation step
resulted in a significant increase of the reaction yields,
due to protection of the corrole ring from oxidative
decomposition. Nitration and bromination reactions were
performed on the copper corrole complex, giving the
corresponding functionalized corroles in moderate yields.
The developed synthetic routes open the way for the
preparation of novel corrole derivatives that could be of
interest for opto-electronic applications and these studies
are ongoing in our laboratories.
but is was however possible to determine the complete
bromination of the b-pyrrolic positions, since only the
multiplets for the phenyl rings were observed around
7.50 ppm; a complex pattern of singlets for the methyl
groups were present at 1.53–1.41 ppm. The second
fraction showed a split Soret band and two Q-bands in the
UV-vis spectrum (Fig. 7). Also in this case the 1H NMR
analysis confirmed that bromination had taken place on
all four b-pyrrole positions available, while the FAB mass
spectrum showed a molecular peak corresponding the
free base 11, suggesting an unexpected demetalation of
10 in the bromination reaction conditions. It is important
to note that the low solubility of 10 requires particular
care in the reaction work-up. At the end of the reaction
the solvent should be reduced to a small volume to carry
out the chromatographic separation; if the reaction
mixture is led to dryness, it is difficult to redissolve 10 in
CH2Cl2 and most of the corrole derivative is irreversibly
adsorbed on the top of the column. In this case the
chromatographic purification afforded only 11, strongly
reducing the reaction yields. We would like to thank a
referee that helped us to clarify this point.
Supporting information
1H and 13C NMR, FAB mass spectra of compounds and
low resolution crystal data of 6 (Table S1, Figs S1–S16)
are given in the supplementary material. This material is
available free of charge via the Internet at http://www.
worldscinet.com/jpp/jpp.shtml.
To confirm the nature of both the substances, free base
11 was reacted with Cu(OAc)2 in refluxing chloroform/
Copyright © 2015 World Scientific Publishing Company
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SYNTHESIS AND FUNCTIONALIZATION OF b-ALKYL-MESO-TRIARYLCORROLES
873
19. Rao DP, Dhanalekshmi S, Littler BJ and Lindsey
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