Improved syntheses of meso-tetraarylbenziporphyrins and observations of substituent effects on the diatropic characteristics of these formally nonaromatic carbaporphyrinoids

Article abstract of DOI:10.1016/j.tet.2009.09.060

Carbaporphyrinoid systems are widely investigated but improved routes to these systems are needed. A fairly direct route to tetraphenylbenziporphyrin has been reported previously starting from isophthalaldehyde and this approach has been adapted to make use of more easily accessible isophthalic acids. Isophthalic acid and 5-tert-butylisophthalic acid were converted into the related diacyl chlorides and reacted with excess benzene or chlorobenzene to give a series of diketones. These were reduced with sodium borohydride to give the corresponding dialcohols in virtually quantitative yields and this route allows the synthesis of >10 g quantities of these key intermediates. Reaction of these dicarbinols with pyrrole and benzaldehyde or 4-chlorobenzaldehyde in the presence of BF₃·Et₂O in dichloromethane, followed by oxidation with DDQ, gave a series of eight-different tetraarylbenziporphyrins in up to 32% yield. Although benziporphyrins are generally considered to be nonaromatic, they may exhibit trace amounts of global diatropic character and this appears to be enhanced by the presence of a tert-butyl group on the benzene moiety or the introduction of 4-chlorophenyl substituents. Addition of TFA to the NMR solutions generated dications that exhibit an unambiguous ring current effect where the internal CH proton NMR resonances appear upfield in the range of 5.05-5.65 ppm, while the external pyrrolic resonances show concomitant downfield shifts to give values between 7.08 and 7.86 ppm. A tert-butyl substituent again increased the diatropic character of the macrocycle, although replacement of meso-phenyl groups with more electron-withdrawing 4-chlorophenyl units had the opposite effect in this case. These results are consistent with the aromatic characteristics deriving from canonical forms that have [18]annulene substructures. Two examples of palladium(II) benziporphyrin complexes were prepared and these results demonstrate that the presence of 4-chlorophenyl or tert-butyl groupings do not have a negative impact on the formation of organometallic derivatives. The improved yields for the reported synthetic methodology and the new information that can be obtained by systematically altering the substitution patterns around the macrocyclic periphery will facilitate further development of the chemistry of benziporphyrins.

Full text of DOI:10.1016/j.tet.2009.09.060

Tetrahedron 65 (2009) 9527–9535
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journal homepage: www.elsevier.com/locate/tet
Improved syntheses of meso-tetraarylbenziporphyrins and observations
of substituent effects on the diatropic characteristics of these formally
nonaromatic carbaporphyrinoidsq
*
Timothy D. Lash , Valerie R. Yant
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Carbaporphyrinoid systems are widely investigated but improved routes to these systems are needed. A
fairly direct route to tetraphenylbenziporphyrin has been reported previously starting from iso-
phthalaldehyde and this approach has been adapted to make use of more easily accessible isophthalic
acids. Isophthalic acid and 5-tert-butylisophthalic acid were converted into the related diacyl chlorides
and reacted with excess benzene or chlorobenzene to give a series of diketones. These were reduced with
sodium borohydride to give the corresponding dialcohols in virtually quantitative yields and this route
allows the synthesis of >10 g quantities of these key intermediates. Reaction of these dicarbinols with
pyrrole and benzaldehyde or 4-chlorobenzaldehyde in the presence of BF3$Et2O in dichloromethane,
followed by oxidation with DDQ, gave a series of eight-different tetraarylbenziporphyrins in up to 32%
yield. Although benziporphyrins are generally considered to be nonaromatic, they may exhibit trace
amounts of global diatropic character and this appears to be enhanced by the presence of a tert-butyl
group on the benzene moiety or the introduction of 4-chlorophenyl substituents. Addition of TFA to the
NMR solutions generated dications that exhibit an unambiguous ring current effect where the internal
CH proton NMR resonances appear upfield in the range of 5.05–5.65 ppm, while the external pyrrolic
resonances show concomitant downfield shifts to give values between 7.08 and 7.86 ppm. A tert-butyl
substituent again increased the diatropic character of the macrocycle, although replacement of meso-
phenyl groups with more electron-withdrawing 4-chlorophenyl units had the opposite effect in this case.
These results are consistent with the aromatic characteristics deriving from canonical forms that have
[18]annulene substructures. Two examples of palladium(II) benziporphyrin complexes were prepared
and these results demonstrate that the presence of 4-chlorophenyl or tert-butyl groupings do not have
a negative impact on the formation of organometallic derivatives. The improved yields for the reported
synthetic methodology and the new information that can be obtained by systematically altering the
substitution patterns around the macrocyclic periphery will facilitate further development of the
chemistry of benziporphyrins.
Received 31 August 2009
Received in revised form 14 September
2009
Accepted 15 September 2009
Available online 18 September 2009
Keywords:
Benziporphyrins
Carbaporphyrins
Aromaticity
Organometallic complexes
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
In addition, these systems provide significant insights into the mac-
rocyclic aromatic properties of porphyrins and related conjugated
Carbaporphyrinoidsystems (e.g.,1), porphyrinanalogues with one
or more of the pyrrole subunits replaced by carbocyclic rings, have
been intensively investigated over the past 15 years.1–3 These
investigations, together with studies on the related N-confused
porphyrins 2,4–7 have led to the discovery of many unusual organo-
metallic derivatives aswellasrevealingintriguing chemicalreactivity.
macrocycles.1–3,8 Carbaporphyrins 19 and N-confused porphyrins 24–7
show highly diatropic characteristics, but other carbaporphyrinoid
structures exhibit a wide range of aromatic properties.1–3 Although
tropiporphyrins 310 and oxybenziporphyrins 4,11–14 like 1 and 2, give
proton NMR spectra where the internal CH resonance shows up near
ꢀ7 ppm, azuliporphyrins 5 show much reduced diatropicity with the
internal CH giving rise to a singlet near þ3 ppm,15–19 and benzipor-
phyrins 6a and 7a are generally considered to have no overall
macrocyclic aromaticity.11–13,20,21 Nevertheless, dimethoxybenzi-
porphyrins6band7bdoshowsomediatropiccharacter, thatisgreatly
enhanced upon protonation and even the dications derived from 6a
and 7a show a small but significant upfield shift to the internal CH
q
Part 51 in the series ‘Conjugated Macrocycles Related to the Porphyrins’. For
part 50, see Zhang, Z.; Ferrence, G. M.; Lash, T. D. Org. Lett. 2009, 11, 1249–1252.
* Corresponding author.
E-mail address: tdlash@ilstu.edu (T.D. Lash).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.060

9528
T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
(Scheme 3).22,23 Dibromodimethoxybenzenes 12 were metalated
with n-butyllithium and further treated with benzaldehyde to give
the dicarbinols 13.22,23 Further Lindsey-type condensation29 with
pyrrole and benzaldehydes gave good yields of the corresponding
tetraarylbenziporphyrins 9.22,23 The synthesis of dicarbinols 13
relies on the ability of the methoxy substituents to direct metal–
halogen exchange and other substituted benziporphyrins could not
be easily prepared by this approach. The related dialcohol 10a was
originally prepared in moderate yield by reacting a deficiency of
phenyllithium with isophthalaldehyde,21 although these yields can
be increased by using an excess of the organometallic reagent.23
However, dicarboxylic acids 14 are far more readily accessible than
the corresponding dialdehydes and are therefore more versatile
precursors to benziporphyrins. In addition, a series of dialcohols
10a–d (Scheme 4) can be synthesized without resorting to the use
of organolithium reagents.
NH
N
N
HN
N
HN
NH
Porphyrin
HN
1 (Benzocarbaporphyrin)
N
HN
N
NH
N
NH
3 (Tropiporphyrin)
2 (N-Confused Porphyrin)
Ph
O
CHO
N
HN
N
OHC
Ph
Ph
PhLi
N
HN
N
NH
HN
N
Ph
OH
Ph
5 (Azuliporphyrin)
4 (Oxybenziporphyrin)
8a
1. Pyrrole
Benzaldehyde
Ph
R
R
OH
10
Ar
BF3.Et2O CH2Cl2
2. DDQ
Me
R'
R'
Et
Et
R
R
Scheme 1.
N
N
Ar'
Ar
HN
N
HN
N
Ar
Me
1. ArCHO
Et
Et
Ar'
CHCl3
N
8 R = R' = H
BF3.Et2O
6 R = R' = H
7 R = OMe
Ar
Ar
9 R = OMe
2. DDQ
a. R' = H; b. R' = Me
HN
N
a. R' = H; b. R' = Me
NH
3
Benziporphyrins
Ar
11
resonance.13,22,23 Although the [18]annulene model for porphyrinoid
aromaticity1,24 can be considered to be na¨ıve,8,25 this interpretation
still provides the best explanations for the results obtained for these
macrocyclic structures.3 In this work, we examined the spectroscopic
properties of a series of meso-tetraaryl substituted benziporphyrins to
see whether substituent effects could reveal the presence of residual
macrocyclic diatropicity. In addition, an efficient and more versatile
route to tetraarylbenziporphyrins has been developed.26,27
Scheme 2.
OMe
Br
OMe
Ph
R
R
MeO
MeO
Ph
N
12
Br
Ar
1. 2 BuLi
2. PhCHO
HN
N
2. Results and discussion
The first syntheses of benziporphyrins11,12,20 were carried out
using the ‘3þ1’ variant on the MacDonald condensation28 where
isophthalaldehydes were condensed with tripyrranes in the pres-
ence of an acid catalyst, followed by oxidation. Although this ap-
proach gave good yields of meso-unsubstituted benziporphyrins 6
and 7, the methodology requires the use of tripyrranes that must be
prepared by multistep procedures. Stepien and Latos-Grazynski
Ar
R = H or Me
OMe
Ph
9
R
1. Pyrrole
Benzaldehyde
BF3.Et2O CHCl3
2. DDQ
OH
MeO
Ph
13
OH
Scheme 3.
subsequently reported
a more direct route to meso-tetraar-
ylbenziporphyrins 8 by reacting dicarbinol 10a with pyrrole and
benzaldehyde in the presence of BF3.Et2O in dichloromethane,
followed by oxidation with DDQ (Scheme 1).21 This route com-
plemented our investigations into the synthesis of meso-tetraar-
ylazuliporphyrins 11 from azulenes and aryl aldehydes, again using
one-pot Lindsey reaction conditions (Scheme 2).18,19 The same ap-
proach was also used to prepare dimethoxybenziporphyrins 9
Dicarboxylic acids 14a and 14b can easily be converted into the
corresponding diacyl chlorides 15 in quantitative yields by treat-
ment with thionyl chloride. In addition, phthaloyl chloride is
commercially available. These diacyl chlorides can be used to pre-
pare diketones under standard Friedel–Crafts acylation conditions
(Scheme 4).30 Reaction with excess benzene readily gave the
diphenyl diketones 16a and 16c, while good yields of the 1,3-bis(4-

T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
9529
R
below 12% in one case. Tetraphenylbenziporphyrin 8a has been
synthesized previously but the remaining macrocyclic products are
all new examples of this class of benziporphyrins. The reaction
conditions used in this work are based upon the methods developed
by Lindsey’s group for the synthesis of meso-tetraarylporphyrins.29
A total of six carbon–carbon bonds must be generated between the
original dialcohol 10, the three pyrrole units and the two aromatic
aldehydes. The initially generated reduced form of the macrocycle
(17; benziporphyrinogen) is then dehydrogenated to give the fully
conjugated system (Scheme 5). Clearly, many different products
could result in these reactions, including the formation of open-
chain structures such as 18, macrocyclic by-products such as meso-
tetraphenylporphyrin, and oligomeric or polymeric materials
(Scheme 5). The products are purified by column chromatography
on grade 3 basic alumina, but only a small amount of porphyrin is
observed as a by-product in these reactions. However, unidentified
dark materials possibly corresponding to oligomers or polymers are
retained by these columns. The isolated product fractions were then
recrystallized from chloroform–ligroin and the quoted yields cor-
respond to the samples obtained after recrystallization and drying in
vacuo. Useful trends could be seen in these studies. The presence of
tert-butyl substituents in 10c and 10d had no significanteffect on the
yields and this enabled the synthesis of four tert-butylbenzipor-
phyrins 8e–h. Chlorophenylcarbinols 10b and 10d gave inferior
yields of benziporphyrins 8 when reacted with pyrrole and benz-
aldehyde. However, phenylcarbinols 10a and 10c gave substantially
better yields of the isomeric benziporphyrins when reacted with
pyrrole and 4-chlorobenzaldehyde and again the chloroben-
zaldehyde gave better results than benzaldehyde in these reactions.
Although the chlorophenylcarbinols 10b and 10d gave the worst
results when reacted with benzaldehyde, they gave excellent yields
when reacted with pyrrole and 4-chlorobenzaldehyde. The latter
combination gave tetrakis(4-chlorophenyl)benziporphyrins 8d and
8h in 24% and 32% yields, respectively. Clearly, the judicious
R
CO2H
SOCl2
COCl
15
HO2C
14
ClOC
X
a. R = H; b. R = t-Bu
X
AlCl3
X = H or Cl
R
X
O
NaBH4
R
X
O
OH
16
For 10 and 16:
a. R = X = H
b. R = H, X = Cl
c. R = t-Bu, X = H
d. R = t-Bu, X = Cl
10
X
OH
1. Pyrrole
PhCHO or p-ClC6H4CHO
BF3.Et2O CH2Cl2
2. DDQ
Ar
R
N
Ar'
Ar
HN
N
8
Ar'
a. R = H, Ar = Ar' = Ph (13%)
b. R = H, Ar = Ph, Ar' = 4-ClC6H4 (22%)
c. R = H, Ar = 4-ClC6H4, Ar' = Ph (12%)
d. R = H, Ar = Ar' = 4-ClC6H4 (24%)
e. R = t-Bu, Ar = Ar' = Ph (12%)
f. R = t-Bu, Ar = Ph, Ar' = 4-ClC6H4 (19%)
g. R = t-Bu, Ar = 4-ClC6H4, Ar' = Ph (5.4%)
h. R = t-Bu, Ar = Ar' = 4-ClC6H4 (32%)
Ar
R
2 C4H5N
BF3.Et2O
Scheme 4.
10
HN
Ar
NH
chlorobenzoyl)benzenes 16b and 16d can be obtained using chlo-
robenzene.30 These diketones were then reduced with sodium
borohydride in ethanol to give the related dicarbinols 10 in ca. 95%
isolated yield. In this way, a series of dicarbinols is easily generated
and this allows the systematic introduction of varying combina-
tions of substituent groups.
Porphyrin
18
C4H5N
2 Ar'CHO
Ar
R
In earlier studies on the synthesis of tetraarylazuliporphyrins 11
and dimethoxybenziporphyrins 9,18,19,22,23 significantly improved
yields were obtained when 4-chlorobenzaldehyde was used as
a precursor to the porphyrinoid systems instead of benzaldehyde. In
the preparation of azuliporphyrins 11, 4-bromo- and 4-iodo-
benzaldehyde also gave superior results.19 In our studies on the
preparation of benziporphyrins 8a–h (Scheme 4), we sought to ad-
dress whether the presence of4-chlorogroupshada beneficialeffect
on the reactions of the carbinol precursor 10, as well as for the
benzaldehyde reactant. The four available dicarbinols 10 were in-
dividually reacted with pyrrole and benzaldehyde, or 4-chloro-
benzaldehyde, under the previously developed conditions.21,23
Although we have found chloroform to be a superior solvent for the
formation of tetraarylazuliporphyrins 11 or dimethoxybenzi-
porphyrins 9,18,19,22,23 this gave poor results for benziporphyrins 8a–
h. However, when the reactions are catalyzed with boron trifluoride
diethyl etherate in dichloromethane, followed by oxidation with
DDQ, moderate to good yields of the targeted benziporphyrins 8
could be obtained. There are eight combinations of the reactants and
the yields varied from 5–32%, although the isolated yield only drops
HN
HN
Oligomers and
Polymers
OH
Ar
Ar'
NH
Ar'
Ar
R
HN
[O]
Ar'
8
Ar
HN
NH
Ar'
Benziporphyrinogen
Scheme 5.
17

9530
T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
selection of reactants allows great improvements in the yields for
these important porphyrin analogues. However, a full assessment of
the origins of these differences in the yield of macrocycle is more
difficult to ascertain. There are a large number of intermediary steps
between the reactants and the final macrocyclic products and any
one of these steps would affect the outcome of these reactions
(Scheme 5). In addition, many of the condensation steps prior to
oxidation are reversible and the outcome will depend on the equi-
libria between the many open-chain (e.g., 18) and macrocyclic spe-
cies (e.g., 17) in the reaction solutions. However, the 4-chloro group
will increase the reactivity of the arylaldehyde and this is likely to be
responsible for the increased yields. On the other hand, the dicar-
binols would need to generate carbocation intermediates and the
chlorophenyl unit would not be effective in stabilizing this electro-
philic species. These factors rationalize the results for 8a–c and 8e–g,
but do not explain why a combination of chlorophenyl units in both
reactants gives the best yields of all. However, the chlorophenyl
groups would be expected to stabilize the benziporphyrinogen
structures 17 and may thereby decrease back reactions (acidolysis)
to open-chain species.
Ar
Ar
R
R
N
N
N
N
Ar'
Ar
Ar'
Ar
H
H
N
N
Ar'
Ar'
8'
8
TFA
Ar
Ar
R
R
N
N
N
N
H
H
H
H
Ar'
Ar
Ar'
Ar
H
H
N
N
Ar'
Ar'
2+
2+
8'H2
8H2
The availability of eight-different benziporphyrins allows us to
contrast the properties of these porphyrinoids and assess trends due
to substituent effects. The UV–vis spectra for 8a–h were all very
similar, showing a moderate Soret-like band between 413 and
420 nm and a broad peak in the far red region (Fig.1). The presence of
chlorophenyl units or a tert-butyl moiety gave rise to minor bath-
ochromic shifts. The Soret-like band of tetraphenylbenziporphyrin
8a in chloroform gave a lmax value of 413 nm, while the tert-butyl-
benziporphyrin 8e gave this band at 418 nm (Table 1). Comparisons
of 8b to 8f, 8c to 8g, and 8d to 8h, each of which differ by having an H
or a t-Bu group at position 3, showed a consistent 4–5 nm red shift
when the tert-butyl group was present. The chlorophenyl groups
exerted a smaller effect but nevertheless consistently gave higher
lmax values as the number of these units was increased. Addition of
TFA to solutions of benziporphyrins 8 produces the corresponding
dications 8H22þ (Scheme 6). These give stronger Soret-like bands in
the range of 459–469 nm and a broad absorption that extends be-
yond 900 nm (Fig.1). The dication also shows substituent effects that
lead to bathochromic shifts. The presence of a tert-butyl group leads
Scheme 6.
to a 2–3 nm red shift, while the presence of chlorophenyl units gave
up to a 7 nm shift to longer wavelength (Table 1). In this series, the
chlorophenyl units had a significantly larger effect at the 6,21-posi-
tions rather than the 11,16-positions (5–6 nm vs 2 nm).
Although benziporphyrins have generally been considered to be
nonaromatic porphyrinoids,12 diatropic properties can be ascribed to
the NMR data, particularly in the case of the diprotonated dications
8H22þ. The aromatic properties of porphyrins and related macrocycles
can be considered to be due to [18]annulene substructures.1 While
the precise nature of aromaticity in these systems is still being
assessed, the [18]annulene model has provided a self-consistent
framework that appears to explain the observed properties of these
systems. Benziporphyrins are cross-conjugated and would of ne-
cessity have to loose the 6p arene identity of their benzene rings to
become fully aromatic porphyrinoids. However, electron donating
effects can favor resonance contributors that can take on the re-
quired [18]annulene characteristics.1,13 In the case of free base ben-
ziporphyrins, canonical forms like 80 would fit the criteria, but this
type of structure would be expected to be a minor contributor due to
the formal loss of the benzene subunit and the requirement for
charge separation. Nevertheless, this may facilitate a small amount of
diatropic character that could be enhanced by the presence of suit-
able substitution patterns. Although strongly electron-donating
groups such as methoxy have been shown to greatly increase the
aromatic character of the benziporphyrin system,13,22,23 little is
known about the effects that would result from more subtle elec-
tronic interactions. The proton NMR data for benziporphyrins 8a–h
provide important information that gives insights into these issues.
If a porphyrinoid system has diatropic properties, the internal
protons (22-H and NH) should be shifted upfield while the external
protons will be shifted downfield. The three types of external
protons on the pyrrole units (positions 13,14 (2H, s), 9,18 (2H, d) and
8,19 (2H, d), respectively) provide the best data for comparison as
they are well removed from local inductive effects. The external
benzene protons at positions 2 and 4 can potentially give some
information but they are aligned above the adjacent phenyl sub-
stituents and this leads to a shielding factor that must also be taken
into account. Proton NMR spectra were run on benziporphyrins 8a–
h at approximately the same concentrations in CDCl3 on a Bruker
500 MHz instrument and the chemical shifts for selected reso-
nances are shown in Table 2. The three types of pyrrole protons
gave resonances near 6.5, 6.8, and 7.0 ppm, while the internal CH
appeared between 6.94 and 7.35 ppm and the NH was observed
Figure 1. UV–vis spectra of benziporphyrin 8h. Blue line: free base in chloroform. Red
line: dictation 8hH22þ in 1% TFA–chloroform.
Table 1
Wavelength values of the Soret-like bands for free base benziporphyrins 8a–h in
chloroform and dications 8H22þ in 1% TFA–chloroform
Benziporphyrin
lmax Free base
lmax Dictation 8H22þ
8a
8b
8c
8d
8e
8f
413 nm
415 nm
415 nm
416 nm
418 nm
419 nm
419 nm
420 nm
459 nm
461 nm
465 nm
466 nm
462 nm
464 nm
467 nm
469 nm
8g
8h

T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
9531
Table 3
Table 2
Selected proton NMR chemical shifts for benziporphyrins 8 in trace TFA–CDCl3 at
Selected proton NMR chemical shifts for benziporphyrins 8 in CDCl3 at 296 K
296 K
Ar
4
R
2
8
3
6
22-H
NHs
2,4-H
13,14-H
9,18-H
8,19-H
5
7
9
8aH22þ
8bH22þ
8cH22þ
8dH22þ
8eH22þ
8fH22þ
8gH22þ
8hH22þ
5.65
5.51
5.43
5.47
5.05
5.18
5.13
5.16
9.54, 10.75
9.05, 10.46
8.98, 10.39
9.11, 10.45
8.47, 10.14
8.95, 10.38
8.95, 10.36
9.09, 10.42
7.19
7.20
7.19
7.19
7.21
7.20
7.20
7.20
7.24
7.25
7.28
7.26
7.29
7.25
7.27
7.26
7.08
7.09
7.12
7.11
7.12
7.10
7.11
7.11
7.79
7.84
7.81
7.81
7.86
7.84
7.80
7.81
N
10
11
1
22 23
Ar
Ar'
21
20
24
N
25
N
H
12
13
19
17
15
16
Ar'
14
18
22-H
NH
2,4-H
13,14-H
9,18-H
8,19-H
8a
8b
8c
8d
8e
8f
7.35
7.30
7.29
7.24
7.05
7.00
6.98
6.94
10.30
10.25
10.26
10.21
10.14
10.10
10.12
10.07
7.01
7.00
6.99
6.99
7.04
7.03
7.03
7.03
6.76
6.74
6.77
6.75
6.78
6.77
6.79
6.77
6.54
6.52
6.56
6.54
6.56
6.54
6.57
6.56
7.21
7.23
7.17
7.19
7.24
7.26
7.19
7.22
chlorophenyl units would be expected to stabilize the increased
electron density on the macrocycle. Nevertheless, these shifts are
relatively small and show only a pale ghost of porphyrinoid aro-
maticity. This system is at the lower limit for where we can see
effects of this type, but they do mirror the shifts observed for more
aromatic porphyrinoids such as 9 and 11.18,19,23
8g
8h
Addition of TFA to these NMR solutions generates dicationic
species 8H22þ that show increased diatropic character (Table 3 and
Fig. 3). The internal CH gives rise to weakly coupled resonances be-
tween 5.05 and 5.65 ppm, an upfield shift of 1.7–2.0 ppm compared
to the corresponding free base benziporphyrins, and two types of NH
protons can now be seen at 8.47–9.54 ppm (1H) and 10.14–
10.75 ppm (2H). The dications show weak long range coupling
between the NHs and the external pyrrolic protons. The pyrrole
resonances are all shifted downfield by 0.48–0.64 ppm, while the
external benzene protons at positions 2 and 4 are deshielded by 0.17–
0.20 ppm. Although the downfield shifts can be partly attributed to
the 2þ charge on the system, these data are consistent with an in-
creased macrocyclic ring current for the dications 8a–h. Resonance
contributors with [18]annulene substructures (e.g., 80H22þ) nowaid in
charge delocalization and for this reason would be expected to be far
more favored for the dications than was the case for the free base
benziporphyrins. For these diprotonated benziporphyrins, the
presence of a tert-butyl moiety causes the 22-H to shift upfield by
0.31–0.60 ppm and upfield shifts can also be seen for the NH reso-
nances, particularly when the tetraphenylbenziporphyrins 8a and 8e
are compared. The presence of the 3-tert-butyl group is also asso-
ciated with a small downfield shift for the external proton
slightly downfield from 10 ppm (Fig. 2 and Table 2). Coupling could
also be seen between the external benzene protons (2,4-H) and the
internal 22-CH, and this is illustrated for the 500 MHz NMR spec-
trum of 8h, which shows a 4J coupled triplet and doublet at 6.94
and 7.03 ppm, respectively (Fig. 2). An analysis of the data for all
eight benziporphyrins shows that both the 22-H and NH reso-
nances are significantly shielded when a tert-butyl moiety is in-
troduced (upfield shifts of 0.14–0.31 ppm). Small upfield shifts for
these resonances can also be seen as the number of chlorophenyl
substituents is increased. However, the chemical shifts of the pyr-
rolic resonances are not significantly influenced by these structural
changes. The results appear to indicate that the free base porphy-
rins possess a very weak global ring current that is enhanced when
the tert-butyl or chlorophenyl units are present. These data are
consistent with our suggestion that the weak macrocyclic ring
current is due to dipolar resonance contributors like 80.23 The
contributor would be stabilized by the electron donating tert-butyl
group on the benzene ring, and the more electron-withdrawing
Ar
t-Bu
N
Ar
Ar
HN
N
Ar
Ar = p-ClC6H4
6.6 ppm
7.4 ppm
6.7
2,4-H 22-H
NH
5.16
ppm
6.95
ppm
10.2
7.03
ppm
ppm
7.8
7.7
7.6
7.5
7.4
7.3
7.2
ppm
7.4
7.3
7.2
7.1
7.0
6.9
6.8
6.7
ppm
Figure 3. Partial 500 MHz proton NMR spectrum of benziporphyrin dictation 8hH22þ in
Figure 2. Partial 500 MHz proton NMR spectrum of benziporphyrin 8h in CDCl3.
TFA–CDCl3 showing the internal CH as a long range coupled triplet at 5.16 ppm.

9532
T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
resonances. These results are consistent with the electron-donating
substituent stabilizing resonance contributors like 80H22þ. The in-
troduction of chlorophenyl groups has the opposite effect leading to
downfield shifts to the internal protons (22-H, NHs) and small up-
field shifts to the pyrrolic protons. This is the opposite trend to the
one observed for the free base benziporphyrins, but the increased
electron-withdrawing effects due to the chlorophenyl substituents
would destabilize the delocalized positive charges in 80H22þ whereas
they would exert a beneficial effect in canonical form 80. This
inverted trend was also seen for the more diatropic dimethoxy-
benziporphyrins 9.23 Interestingly, these effects appear to be much
larger for the 11,16-bis(4-chlorophenyl)benziporphyrins 8b and 8f
than for the 6,21-versions 8c and 8g, implying that the electron-
density at meso-positions 11 and 16 is lower than at positions 6 and
21. The benziporphyrins were also characterized by carbon-13 NMR
spectroscopy, mass spectrometry and combustion analysis. The
carbon-13 data for the dications 8H22þ in TFA–CDCl3 is worthy of
further note. In these spectra, the 22-CH was observed at the unusual
values of 93.6–94.5 ppm for 8a–d and the even lower value of 91.1–
92.3 ppm for the tert-butyl versions 8e–h (Fig. 4). This assignment
was confirmed by running HSQS spectra to show the 1H–13C corre-
lations, but the origin of this effect is not clear. The EIMS data showed
strong Mþ2H peaks, a feature of these compounds that had been
noted previously.12,20
Ar
R
N
N
Pd(OAc)2
Ar'
Ar
Pd
8
CH3CN-CHCl3
N
Ar'
19
a. R = t-Bu, Ar = Ar' = Ph
b. R = t-Bu, Ar = Ar' = p-ClC6H4
c. R = H, Ar = Ar' = Ph
Scheme 7.
Figure 5. UV–vis spectra of palladium(II) benziporphyrins in chloroform. Red line: Tet-
raphenylbenziporphyrin complex 19a. Blue line: Tetrakis(4-chlorophenyl)benziporphyrin
derivative 19b showing a split Soret-type absorption.
3. Conclusions
Efficient syntheses of tetraarylbenziporphyrins have been de-
veloped starting with isophthalic acids. This has allowed the
preparation of a series of benziporphyrins with varying number of
chlorophenyl substituents and with tert-butyl substituted benzene
subunits. These substituents exert subtle effects on the UV–vis and
NMR spectra for these porphyrinoids. The proton NMR data for the
free base porphyrins suggest that there is a trace of global aromatic
character in these formally nonaromatic macrocycles that is in-
creased by the presence of an electron-donating tert-butyl group
and the introduction of electron-withdrawing chlorophenyl sub-
stituents. Protonation gave dications, which exhibited increased
diatropic character that was again enhanced by the presence of
a tert-butyl moiety. However, chlorophenyl substituents slightly
decreased the diatropic character for these diprotonated species.
Two examples of palladium(II) complexes were prepared and these
results indicated that the presence of tert-butyl or chlorophenyl
substituents did not interfere with the formation of these stable
organometallic derivatives. The improved yields for this synthetic
approach, and the wealth of information that can be obtained by
systematically altering the substitution patterns around the mac-
rocyclic periphery, will allow further development of the chemistry
of these important porphyrin analogues.
Figure 4. Partial carbon-13 NMR spectrum of 8dH22þ in TFA–CDCl3 showing the ab-
normally upfield resonance for the 22-CH. A resonance at 116 ppm falls very close to
one of the lines for the CF3 quartet produced by the TFA.
Benziporphyrins can easily be converted into organometallic
derivatives31–36 and the palladium(II) derivatives of tert-butylben-
ziporphyrins 8e and 8h were also investigated. Reaction of 8e and
8h with palladium(II) acetate in refluxing chloroform–acetonitrile
gave good yields of the palladium derivatives 19a and 19b, re-
spectively (Scheme 7). The UV–vis spectrum 19a showed a Soret-
like band at 438 nm (Fig. 5), slightly red shifted compared to the
previously described palladium(II) complex 19c of tetraphe-
nylbenziporphyrin,21 and a series of broad absorptions between
500 and 900 nm. The tetrakis(4-chlorophenyl)benziporphyrin de-
rivative 19b gave a similar UV–Vis spectrum but in this case a split
Soret band was observed at 419 and 439 nm (Fig. 5). The pyrrole
protons in 19a and 19b showed up in the range of 7.00–7.21 ppm,
values that are slightly downfield compared to the data reported for
19c. The results are consistent with the palladium(II) derivatives
having slightly increased diatropic character compared to the free
base benziporphyrins and indicate that the tert-butyl group en-
hances this characteristic, as was the case for the free base and
dicationic forms of 8a–h, although the presence of chlorophenyl
substituents did not result in significant changes.
4. Experimental
4.1. General
Boron trifluoride etherate, aluminum chloride, 4-chloroben-
zaldehyde, phthaloyl chloride, 5-tert-butylphthalicacid, palladium(II)
acetate, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), thionyl
chloride and sodium borohydride were purchased from Aldrich or
Acros and were used without further purification. Commercially
available pyrrole and benzaldehyde were distilled prior to use.
Chromatography was performed using grade 3 basic alumina or
70–230 mesh silica gel. Melting points were determined in open

T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
9533
capillary tubes on a Mel-Temp apparatus and are uncorrected. Proton
and carbon-13 NMR data were obtained on a Varian Gemini 400 MHz
FT NMR spectrometer or a 500 MHz Bruker Avance III NMR spec-
trometer; funding for the latter instrument was provided by the
National Science Foundation under grant no. CHE-0722385. Mass
spectral determinations were conducted at the Mass Spectral Labo-
ratory, School of Chemical Sciences, University of Illinois at Urbana-
Champaign, and elementalanalyses were obtained from the School of
Chemical Sciences Microanalysis Laboratory at the University of
Illinois.
and gave the dicarbinol (5.88 g,14.2 mmol, 96%) as a white solid, mp
162–164 ꢁC. An analytical sample was obtained by recrystallization
from ethanol–water as fluffy white crystals, mp 163–165 ꢁC.1H NMR
(500 MHz, CDCl3):
doublets), 5.77 (2H, br d), 7.12–7.14 (1H, m), 7.28–7.31 (10H, m); 13C
NMR (CDCl3): 31.5, 35.1, 76.0,122.1,123.3 (2),128.1 (2),128.8,133.5,
d 1.27 (9H, s), 2.23–2.25 (2H, 2 overlapping
d
142.3, 143.7 (2), 152.4. Anal. calcd for C24H24Cl2O2: C, 69.40; H, 5.82.
Found: C, 69.23; H, 5.86.
4.2.5. 6,11,16,21-Tetraphenylbenziporphyrin (8a). Prepared in 13%
yield as reported previously.23 UV–vis (1% Et3N-CHCl3): lmax
(log10 3) 413 (4.82), 692 (sh, 3.99), 729 nm (4.00); UV–vis (1% TFA–
CHCl3): lmax (log10 3) 329 (4.46), 377 (4.39), 459 (5.04), 609 (3.67),
4.2. Synthetic procedures
4.2.1. 1,3-Dibenzoyl-5-tert-butylbenzene (16c). Several drops of
DMF were added to a stirred mixture of 5-tert-butylisophthalic acid
(10.01 g, 45.5 mmol) and thionyl chloride (50 mL) and the mixture
was refluxed for 1 h. The excess thionyl chloride was removed on
a rotary evaporator and the residual diacyl chloride was taken up in
benzene (400 mL) and cooled in an ice water bath. Anhydrous
aluminum chloride (15 g) was added, and the resulting mixture was
stirred at room temperature for 16 h and then at 60 ꢁC for 4 h. The
cooled reaction mixture was poured into a beaker of ice water
(300 g) and concentrated hydrochloric acid (45 mL). The pale yel-
low organic layer was separated and washed sequentially with
water, 5% aqueous sodium bicarbonate solution, and water. The
organic layer was dried over sodium sulfate and the solvent re-
moved under reduced pressure. Recrystallization from chloroform–
ligroin gave the diketone (10.52 g, 30.8 mmol, 68%) as off-white
crystals, mp 77.5–79 ꢁC (lit. mp30 80.5–82.5 ꢁC); 1H NMR (500 MHz,
665 (3.59), 900 nm (4.18); 1H NMR (500 MHz, CDCl3):
d 6.54 (2H, d,
J¼4.7 Hz), 6.76 (2H, s), 7.01 (2H, dd, J¼1.8, 7.8 Hz), 7.21 (2H, d,
J¼4.7 Hz), 7.32 (1H, t, J¼7.8 Hz), 7.35 (1H, br t, J¼1.6 Hz), 7.40–7.49
(20H, m), 10.30 (1H, br s); 1H NMR (500 MHz, TFA–CDCl3):
d 5.65
(1H, br t, J¼1.6 Hz), 7.08 (2H, d, J¼5.0 Hz), 7.19 (2H, dd, J¼1.7, 7.8 Hz),
7.24 (2H, br d, J¼1.0 Hz), 7.55–7.63 (14H, m), 7.69 (4H, t, J¼7.7 Hz),
7.74–7.80 (5H, m), 9.54 (1H, br s), 10.75 (2H, br s); 13C NMR (TFA–
CDCl3):
d 94.1, 116.7, 128.9, 129.1, 129.5, 130.5, 132.9, 133.6, 133.9,
135.4, 135.9, 136.4, 138.1, 138.3, 139.9, 144.3, 151.6, 152.3, 161.7.
4.2.6. 11,16-Bis(4-chlorophenyl)-6,21-diphenylbenziporphyrin
(8b). Nitrogen was bubbled through a solution of 1,3-bis(phenylhy-
droxymethyl)benzene23 (290 mg, 1.00 mmol) in dichloromethane
(900 mL) and the 1 L round bottom flask was covered with aluminum
foil to protect the solution from ambient light. Freshly distilled pyr-
role (208 mL, 3.00 mmol) was added to the stirred solution via a sy-
CDCl3):
d
1.39 (9H, s), 7.47–7.51 (4H, m), 7.60 (2H, tt, J¼1.3, 7.4 Hz),
ringe, followed by 4-chlorobenzaldehyde (281.2 mg, 2.00 mmol) and
2 mL of a 10% v/v solution of boron trifluoride etherate in dichloro-
methane. The mixture was stirred for 2 h and the initiallyclear yellow
solution turned orange and then red. DDQ (0.750 g) was added and
the resulting dark brown solutionwas stirred for 1 h. The solvent was
evaporated under reduced pressure and the residue was purified on
a grade 3 basic alumina column eluting with 50% dichloromethane–
hexanes. Trace amounts of 5,10,15,20-tetrakis(4-chlorophenyl)por-
phyrin and unidentified brown by-products eluted initially, followed
by an emerald green band that corresponded to the title benzipor-
phyrin. Recrystallization from chloroform–ligroin gave the macro-
cyclic product (155.6 mg, 0.224 mmol, 22%) as dark green crystals,
mp 295–297 ꢁC, dec; UV–vis (1% Et3N–CHCl3): lmax (log10 3) 415
(4.92), 692 (sh, 4.08), 729 nm (4.10); UV–vis (1% TFA–CHCl3): lmax
7.80–7.84 (2H, m), 7.93 (1H, t, J¼1.6 Hz), 8.08 (2H, d, J¼1.6 Hz); 13C
NMR (CDCl3):
137.7, 152.4, 196.5.
d 31.4, 35.3, 128.6, 129.1, 130.3, 130.8, 133.0, 137.4,
4.2.2. 1,3-Bis(phenylhydroxymethyl)-5-tert-butylbenzene (10c). 1,3-
Dibenzoyl-5-tert-butylbenzene (9.10 g, 26.6 mmol) was dissolved in
ethanol (100 mL) while gentle heating. The flask was cooled to room
temperature, sodium borohydride (1.12 g) was added, and the
mixture was stirred for a further 20 min. Water (100 mL) was added,
and the solution was heated on a boiling water bath for 20 min. The
solution was diluted with water (200 mL) and cooled in an ice bath.
The resulting precipitate was suction filtered and dried in vacuo
overnight to give the dialcohol (8.776 g, 25.4 mmol, 96%) as a white
solid, mp 109–112 ꢁC. An analytical sample was obtained by re-
crystallization from ethanol–water as small white needles, mp 109–
112 ꢁC. The proton NMR data for the dicarbinols 10 were consistent
with the presence of two diastereoisomers. 1H NMR (500 MHz,
(log10 3) 338 (4.54), 383 (4.48), 461 (5.15), 619 (3.72), 662 (3.72),
1
900 nm (4.30); H NMR (500 MHz, CDCl3):
d
6.52 (2H, d, J¼4.8 Hz),
6.74 (2H, s), 7.00 (2H, dd, J¼1.7, 7.8 Hz), 7.23 (2H, d, J¼4.8 Hz), 7.30
(1H, t, J¼1.6 Hz), 7.32 (1H, t, J¼7.8 Hz), 7.39–7.49 (18H, m), 10.25 (1H,
CDCl3):
5.85 (2H, br m), 7.22–7.25 (1H, m), 7.26–7.31 (3H, m), 7.33–7.40 (9H,
m); 13C NMR (CDCl3):
31.6, 35.0, 76.7 (2), 122.3, 123.1, 123.2, 126.7,
126.8, 127.7 (2), 128.7, 143.8, 143.9, 144.0 (2), 152.0. Anal. calcd for
C24H26O2: C, 83.20; H, 7.56. Found: C, 83.21; H, 7.79.
d
1.30 (9H, s), 2.23–2.26 (2H, 2 overlapping doublets), 5.82–
br s); 1H NMR (500 MHz, TFA–CDCl3):
d
5.51 (1H, t, J¼1.6 Hz), 7.09
(2H, dd, J¼1.5, 5.1 Hz), 7.20 (2H, dd, J¼1.6, 7.8 Hz), 7.25 (2H, d,
J¼1.4 Hz), 7.50 (4H, br d, J¼7.8 Hz), 7.55–7.60 (8H, m), 7.71 (4H, t,
J¼7.7 Hz), 7.77–7.83 (3H, m), 7.84 (2H, dd, J¼1.6, 5.1 Hz), 9.05 (1H, br
d
s), 10.46 (2H, br s); 13C NMR (TFA–CDCl3):
d 94.5, 115.5, 129.2, 129.6,
133.3, 133.6, 133.9, 134.6, 135.6, 136.5, 137.5, 138.3, 138.7, 139.5, 144.3,
151.8, 153.1, 161.3; HRMS (EI), m/z calcd for C46H29Cl2N3þ2H:
695.1895. Found: 695.1902. Anal. calcd for C46H29Cl2N3.1/10CHCl3: C,
78.36; H, 4.15; N, 5.95. Found: C, 78.73; H, 4.01; N, 5.94.
4.2.3. 1,3-Bis(4-chlorophenylhydroxymethyl)benzene (10b). Using
the foregoing procedure, diketone 16b30 (2.02 g, 5.69 mmol) gave
the dialcohol (1.945 g, 5.42 mmol, 95%) as a white solid, mp 124–
128 ꢁC. An analytical sample was obtained by recrystallization from
ethanol–water as a white powder, mp 125–127.5 ꢁC. 1H NMR
4.2.7. 6,21-Bis(4-chlorophenyl)-11,16-diphenylbenziporphyrin
(500 MHz, CDCl3):
d
2.31 (2H, br s), 5.82 (2H, br s), 7.22–7.25 (2H, m),
75.7,124.8,
(8c). Prepared by the foregoing procedure from dicarbinol 10b
7.26–7.32 (9H, m), 7.38–7.41 (1H, m); 13C NMR (CDCl3):
d
(359 mg, 1.00 mmol), benzaldehyde (205
mL, 2.00 mmol) and pyr-
126.2 (2),128.1 (2),128.9,129.2,133.6 (2),142.2,144.1 (2). Anal. calcd
for C20H16Cl2O2: C, 66.87; H, 4.49. Found: C, 66.76; H, 4.34.
role (208 L, 3.00 mmol). Recrystallization from chloroform–ligroin
m
gave the benziporphyrin (83.7 mg, 0.121 mmol, 12%) as dark green
crystals, mp >300 ꢁC; UV–vis (1% Et3N–CHCl3): lmax (log10 3) 415
(4.85), 693 (sh, 4.03), 738 nm (4.06); UV–vis (1% TFA–CHCl3): lmax
(log10 3) 333 (4.50), 381 (4.40), 465 (5.15), 620 (3.69), 674 (3.65),
4.2.4. 1,3-Bis(4-chlorophenylhydroxymethyl)-5-tert-butylbenzene
(10d). Diketone 16d30 (6.06 g, 14.7 mmol) was reduced with so-
dium borohydride (1.12 g) as described in the foregoing procedure
900 nm (4.17); 1H NMR (500 MHz, CDCl3):
d
6.56 (2H, d, J¼4.8 Hz),

9534
T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
6.77 (2H, s), 6.99 (2H, dd, J¼1.7, 7.7 Hz), 7.17 (2H, d, J¼4.8 Hz), 7.29
(1H, t, J¼1.6 Hz), 734–7.37 (5H, m), 7.40–7.48 (12H, m), 10.26 (1H, br
J¼1.6 Hz), 7.26 (2H, d, J¼4.8 Hz, partially obscured by solvent peak),
7.40–7.49 (18H, m), 10.10 (1H, br s); 1H NMR (500 MHz, TFA–CDCl3):
s); 1H NMR (500 MHz, TFA–CDCl3):
d
5.43 (1H, t, J¼1.6 Hz), 7.12 (2H,
d
1.09 (9H, s), 5.18 (1H, t, J¼1.6 Hz), 7.10 (2H, dd, J¼1.5, 5.0 Hz), 7.20
dd, J¼1.5, 5.0 Hz), 7.19 (2H, dd, J¼1.6, 7.8 Hz), 7.28 (2H, d, J¼1.4 Hz),
7.50 (4H, d, J¼8.5 Hz), 7.54 (4H, br s, J¼7.0 Hz), 7.58–7.66 (6H, m),
7.68 (4H, d, J¼8.5 Hz), 7.79–7.83 (3H, m), 8.98 (1H, br s), 10.39 (2H,
(2H, d, J¼1.5 Hz), 7.25 (2H, d, J¼1.4 Hz), 7.52 (4H, br d, J¼7.9 Hz), 7.56–
7.60 (8H, m), 7.72 (4H, t, J¼7.9 Hz), 7.80–7.83 (2H, m), 7.84 (2H, dd,
J¼1.5, 5.0 Hz), 8.95 (1H, br s), 10.38 (2H, br s); 13C NMR (TFA–CDCl3):
br s); 13C NMR (TFA–CDCl3):
d
93.6, 117.2, 129.2, 129.5, 129.9, 130.8,
d 30.6, 35.4, 92.3,115.1,128.89,128.94,129.4,133.1,133.3,133.5,134.7,
133.3, 133.6, 134.1, 135.9, 136.1, 136.3, 137.8, 137.95, 138.02, 140.4,
144.4, 150.0, 152.3, 161.8; HRMS (EI), m/z calcd for C46H29Cl2N3þ2H:
695.1895. Found: 695.1884. Anal. calcd for C46H29Cl2N3$1/10CHCl3:
C, 78.36; H, 4.15; N, 5.95. Found: C, 78.29; H, 4.06; N, 5.86.
135.0, 135.5, 137.0, 137.9, 138.1, 139.9, 144.2, 152.0, 152.8, 156.5, 161.0;
HRMS (EI), m/z calcd for C50H37Cl2N3þ2H: 751.2521. Found:
751.2524. Anal. calcd for C50H37Cl2N3: C, 79.99; H, 4.97; N, 5.60.
Found: C, 79.97; H, 4.80; N, 5.56.
4.2.8. 6,11,16,21-Tetrakis(chlorophenyl)benziporphyrin (8d). Prepared
by the foregoing procedure from dicarbinol 10b (359 mg,
1.00 mmol), 4-chlorobenzaldehyde (281.2 mg, 2.00 mmol) and
4.2.11. 3-tert-Butyl-6,21-bis(4-chlorophenyl)-11,16-diphenylbenzi-
porphyrin (8g). Prepared by the foregoing procedure from dicar-
binol 10d (415 mg, 1.00 mmol), benzaldehyde (205
mL, 2.00 mmol)
pyrrole (208
mL, 3.00 mmol). Recrystallization from chloroform–
and pyrrole (208 L, 3.00 mmol). Recrystallization from chloro-
m
ligroin gave the benziporphyrin (183.5 mg, 0.240 mmol, 24%) as
dark green crystals, mp >300 ꢁC; UV–vis (1% Et3N–CHCl3): lmax
(log10 3) 416 (4.92), 690 (sh, 4.12), 730 nm (4.14); UV–vis (1% TFA–
CHCl3): lmax (log10 3) 336 (4.57), 387 (4.45), 466 (5.14), 627 (3.75),
form–ligroin gave the benziporphyrin (40.9 mg, 0.054 mmol, 5.4%)
as dark green crystals, mp >300 ꢁC; UV–vis (1% Et3N–CHCl3): lmax
(log10 3) 419 (4.96), 698 (sh, 4.11), 746 nm (4.14); UV–vis (1% TFA–
CHCl3): lmax (log10 3) 329 (4.57), 385 (4.42), 467 (5.19), 629 (3.72),
670 (3.75), 900 nm (4.26); 1H NMR (500 MHz, CDCl3):
d
6.54 (2H, d,
672 (3.71), 900 nm (4.29); 1H NMR (500 MHz, CDCl3):
d 1.03 (9H, s),
J¼4.8 Hz), 6.75 (2H, s), 6.99 (2H, dd, J¼1.7, 7.8 Hz), 7.19 (2H, d,
6.57 (2H, d, J¼4.8 Hz), 6.79 (2H, s), 6.98 (1H, t, J¼1.6 Hz), 7.03 (2H, d,
J¼4.8 Hz), 7.24 (1H, br t, J¼1.6 Hz), 7.33–7.46 (16H, m), 10.21 (1H, br
J¼1.6 Hz), 7.19 (2H, d, J¼4.8 Hz), 7.37 (4H, d, J¼8.4 Hz), 7.41–7.49
s); 1H NMR (500 MHz, TFA–CDCl3):
d
5.47 (1H, t, J¼1.6 Hz), 7.11 (2H,
(14H, m), 10.12 (1H, br s); 1H NMR (500 MHz, TFA–CDCl3):
d 1.12
dd, J¼1.5, 5.0 Hz), 7.19 (2H, dd, J¼1.7, 7.8 Hz), 7.26 (2H, d, J¼1.5 Hz,
obscured by solvent peak), 7.47–7.50 (8H, m), 7.58–7.60 (4H, m),
7.68–7.71 (4H, m), 7.80–7.83 (3H, m), 9.11 (1H, br s), 10.45 (2H, br s);
(9H, s), 5.13 (1H, t, J¼1.5 Hz), 7.11 (2H, dd, J¼1.5, 5.0 Hz), 7.20 (2H, d,
J¼1.6 Hz), 7.27 (2H, d, J¼1.4 Hz), 7.51 (4H, d, J¼8.5 Hz), 7.56 (4H, br
d, J¼6.8 Hz), 7.58–7.65 (6H, m), 7.69 (4H, d, J¼8.5 Hz), 7.80 (2H, dd,
J¼1.5, 5.0 Hz), 8.95 (1H, br s),10.36 (2H, br s); 13C NMR (TFA–CDCl3):
13C NMR (TFA–CDCl3):
d 94.4, 115.8, 129.5, 129.60, 129.62, 133.4,
133.9, 134.5, 134.6, 136.2, 136.4, 137.5, 137.9, 138.00, 138.05, 140.7,
144.3, 150.7, 152.1, 161.5; HRMS (EI), m/z calcd for C46H27Cl4N3þ2H:
763.1115. Found: 763.1120. Anal. calcd for C46H27Cl4N3.1/6CHCl3: C,
70.78; H, 3.49; N, 5.36. Found: C, 70.80; H, 3.36; N, 5.41.
d 30.7, 35.5, 91.1, 116.9, 129.1, 129.3, 129.6, 130.5, 132.8, 133.7, 133.8,
136.3, 136.5, 137.2, 137.9, 138.2, 139.9, 144.3, 150.1, 152.3, 156.9,
161.5; HRMS (EI), m/z calcd for C50H37Cl2N3þ2H: 751.2521. Found:
751.2526. Anal. calcd for C50H37Cl2N3: C, 79.99; H, 4.97; N, 5.60.
Found: C, 80.03; H, 4.75; N, 5.57.
4.2.9. 3-tert-Butyl-6,11,16,21-tetraphenylbenziporphyrin (8e). Pre-
pared by the foregoing procedure from dicarbinol 10c (346 mg,
1.00 mmol), benzaldehyde (205 mL, 2.00 mmol) and pyrrole (208 mL,
3.00 mmol). Recrystallization from chloroform–ligroin gave the
benziporphyrin (82.8 mg, 0.121 mmol, 12%) as green crystals, mp
>300 ꢁC; UV–vis (1% Et3N–CHCl3): lmax (log10 3) 418 (4.83), 690 (sh,
3.96), 729 nm (3.96); UV–vis (1% TFA–CHCl3): lmax (log10 3) 329
(4.52), 380 (4.46), 462 (5.04), 610 (3.88), 668 (3.82), 900 nm (4.19); 1H
4.2.12. 3-tert-Butyl-6,11,16,21-tetrakis(4-chlorophenyl)benzipor-
phyrin (8h). Prepared by the foregoing procedure from dicarbinol
10d (415 mg, 1.00 mmol), 4-chlorobenzaldehyde (281.2 mg,
2.00 mmol) and pyrrole (208 mL, 3.00 mmol). Recrystallization from
chloroform–ligroin gave the benziporphyrin (261.2 mg, 0.318 mmol,
32%) as dark green crystals, mp >300 ꢁC; UV–vis (1% Et3N–CHCl3):
lmax (log10 3) 420 (4.98), 691 (sh, 4.11), 738 nm (4.14); UV–vis (1%
TFA–CHCl3): lmax (log10 3) 331 (4.59), 391 (4.46), 469 (5.19), 627
NMR (500 MHz, CDCl3):
d
0.99 (9H, s), 6.56 (2H, d, J¼4.8 Hz), 6.78 (2H,
s), 7.04 (2H, d, J¼1.5 Hz), 7.05 (1H, t, J¼1.5 Hz), 7.24 (2H, d, J¼4.8 Hz),
(3.80), 668 (3.81), 900 nm (4.31); 1H NMR (500 MHz, CDCl3):
d 1.03
7.39–7.50 (20H, m), 10.14 (1H, br s); 1H NMR (500 MHz, TFA–CDCl3):
(9H, s), 6.56 (2H, d, J¼4.8 Hz), 6.77 (2H, s), 6.94 (1H, t, J¼1.6 Hz), 7.03
d
1.09 (9H, s), 5.05 (1H, t, J¼1.6 Hz), 7.12 (2H, dd, J¼1.5, 5.0 Hz), 7.21
(2H, d, J¼1.6 Hz), 7.22 (2H, d, J¼4.8 Hz), 7.35–7.47 (16H, m),10.07 (1H,
(2H, d, J¼1.5 Hz), 7.29 (2H, d, J¼1.4 Hz), 7.55–7.65 (14H, m), 7.72 (4H, t,
J¼7.7 Hz), 7.82 (2H, tt, J¼1.1, 7.4 Hz), 7.86 (2H, dd, J¼1.6, 5.0 Hz), 8.47
br s); 1H NMR (500 MHz, TFA–CDCl3):
d 1.12 (9H, s), 5.16 (1H, t,
J¼1.6 Hz), 7.11 (2H, dd, J¼1.5, 5.0 Hz), 7.20 (2H, d, J¼1.5 Hz), 7.26 (2H,
d, J¼1.5 Hz, partially obscured by solvent peak), 7.50 (8H, d,
J¼8.5 Hz), 7.59 (4H, d, J¼8.6 Hz), 7.70 (4H, d, J¼8.5 Hz), 7.81 (2H, dd,
J¼1.5, 5.0 Hz), 9.09 (1H, br s), 10.42 (2H, br s); 13C NMR (TFA–CDCl3):
(1H, br s), 10.14 (2H, br s); 13C NMR (CDCl3):
d 31.0, 34.7, 107.4, 115.0,
127.2, 127.5, 128.1, 128.4, 130.0, 130.5, 131.4, 132.5, 133.4, 136.5, 137.8,
140.0, 143.2, 145.4, 147.8, 151.1, 156.6, 171.8; 13C NMR (TFA–CDCl3):
d
30.6, 35.4, 91.3, 116.6, 129.0, 129.1, 129.3, 130.5, 133.2, 133.4, 133.6,
d 30.6, 35.5, 91.8, 115.6, 129.3, 129.5, 133.2, 133.7, 134.7, 134.8, 136.4,
133.8, 135.6, 136.4, 138.0, 138.1, 139.8, 144.2, 151.8, 152.5, 156.8, 161.3;
HRMS (EI), m/z calcd for C50H39N3þ2H: 683.3300. Found: 683.3302.
Anal. calcd for C50H39N3$1/5CHCl3: C, 85.43; H, 5.60; N, 5.95. Found: C,
85.60; H, 5.67; N, 5.97.
137.3, 137.5, 137.9, 138.0, 140.4, 144.3, 151.0, 152.1, 157.1, 161.2; HRMS
(EI), m/z calcd for C50H35Cl4N3þ2H: 819.1741. Found: 819.1743. Anal.
calcd for C50H35Cl4N3: C, 73.27; H, 4.30; N, 5.13. Found: C, 73.48; H,
4.18; N, 5.16.
4.2.10. 3-tert-Butyl-11,16-bis(4-chlorophenyl)-6,21-diphenylbenzi-
porphyrin (8f). Prepared by the foregoing procedure from dicarbinol
10c (346 mg, 1.00 mmol), 4-chlorobenzaldehyde (281.2 mg,
4.2.13. [3-tert-Butyl-6,11,16,21-tetraphenylbenziporphyrinato]-
palladium(II) (19a). Palladium(II) acetate (8.0 mg) and acetonitrile
(10 mL) were added to a solution of benziporphyrin 8e (20.0 mg,
0.029 mmol) in chloroform (10 mL), and the mixture was stirred
under reflux for 2 h. The solutionwas cooled, washed with water and
evaporated under reduced pressure. The residue was chromato-
graphed on grade 3 basic alumina, eluting with 50% dichloro-
methane–hexanes, and recrystallized from chloroform–methanol to
give the palladium complex (14.7 mg, 0.019 mmol, 65%) as deep
purple crystals, mp >300 ꢁC; UV–vis (CHCl3): lmax (log10 3) 341
2.00 mmol) and pyrrole (208 mL, 3.00 mmol). Recrystallization from
chloroform–ligroin gave the benziporphyrin (142.7 mg, 0.190 mmol,
19%) as dark green crystals, mp >300 ꢁC; UV–vis (1% Et3N–CHCl3):
lmax (log10 3) 419 (4.97), 685 (4.11), 729 nm (4.12); UV–vis (1% TFA–
CHCl3): lmax (log10 3) 327 (4.55), 386 (4.49), 464 (5.17), 619 (3.75), 663
(3.75), 900 nm (4.31); 1H NMR (500 MHz, CDCl3):
d
0.99 (9H, s), 6.54
(2H, d, J¼4.8 Hz), 6.77 (2H, s), 7.00 (1H, t, J¼1.6 Hz), 7.03 (2H, d,

T.D. Lash, V.R. Yant / Tetrahedron 65 (2009) 9527–9535
9535
9. (a) Lash, T. D.; Hayes, M. J. Angew. Chem., Int. Ed.1997, 36, 840–842; (b) Lash, T. D.;
Hayes, M. J.; Spence, J. D.; Muckey, M. A.; Ferrence, G. M.; Szczepura, L. F. J. Org.
Chem. 2002, 67, 4860–4874; (c) Liu, D.; Lash, T. D. J. Org. Chem. 2003, 68,
1755–1761; (d) Lash, T. D.; Muckey, M. A.; Hayes, M. J.; Liu, D.; Spence, J. D.;
Ferrence, G. M. J. Org. Chem. 2003, 68, 8558–8570.
10. (a) Lash, T. D.; Chaney, S. T. Tetrahedron Lett. 1996, 37, 8825–8828; (b) Bergman,
K. M.; Ferrence, G. M.; Lash, T. D. J. Org. Chem. 2004, 69, 7888–7897.
11. Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533–2535.
(4.48), 415 (sh, 4.64), 438 (4.91), 545 (3.83), 573 (3.84), 721 (sh, 3.59),
791 (3.83), 872 nm (3.83); 1H NMR (500 MHz, CDCl3):
1.02 (9H, s),
7.01 (2H, d, J¼5.2 Hz), 7.14 (2H, d, J¼5.2 Hz), 7.21 (2H, s), 7.44–7.53
(12H, m), 7.58–7.63 (8H, m), 7.85 (2H, s); 13C NMR (CDCl3):
30.6,
34.1, 117.9, 126.4, 127.7, 127.8, 129.9, 132.7, 132.8, 133.7, 134.2, 135.5,
140.3, 140.9, 142.4, 142.5, 144.5, 145.6, 146.5, 152.5, 157.4; HRMS (EI),
m/z calcd for C50H37N3Pd: 785.2022. Found: 785.2023.
d
d
12. Lash, T. D.; Chaney, S. T.; Richter, D. T. J. Org. Chem. 1998, 63, 9076–9088.
13. Richter, D. T.; Lash, T. D. Tetrahedron 2001, 57, 3659–3673.
14. El-Beck, J. A.; Lash, T. D. Org. Lett. 2006, 8, 5263–5266.
4.2.14. [3-tert-Butyl-6,11,16,21-tetrakis(4-chlorophenyl)benzipor-
15. For an example of an azulisapphyrin, see: Lash, T. D.; Chaney, S. T. Angew. Chem., Int.
Ed. 1997, 36, 839–840; Richter, D. T.; Lash, T. D. J. Org. Chem. 2004, 69, 8842–8850.
16. (a) Lash, T. D.; Colby, D. A.; Graham, S. R.; Chaney, S. T. J. Org. Chem. 2004, 69,
8851–8864; (b) Lash, T. D.; El-Beck, J. A.; Ferrence, G. M. J. Org. Chem. 2007, 72,
8402–8415.
17. (a) Lash, T. D. Chem. Commun. 1998, 1683–1684; (b) Graham, S. R.; Colby, D. A.;
Lash, T. D. Angew. Chem., Int. Ed. 2002, 41, 1371–1374; (c) Colby, D. A.; Ferrence,
G. M.; Lash, T. D. Angew. Chem., Int. Ed. 2004, 43, 1346–1349.
phyrinato]palladium(II)
(19b). Benziporphyrin 8h (20.0 mg,
0.024 mmol) was reacted with palladium(II) acetate (6.8 mg) under
the foregoing conditions. The crude product was purified on a silica
column, eluting with dichloromethane, and recrystallized from
chloroform–methanol to give the palladium derivative (15.6 mg,
0.017 mmol, 70%) as dark maroon crystals, mp >300 ꢁC; UV–vis
(CHCl3): lmax (log10 3) 419 (4.81), 439 (4.91), 522 (sh, 3.77), 548
(3.86), 577 (3.88), 723 (sh, 3.57), 791 (3.82), 878 nm (3.84); 1H NMR
18. Colby, D. A.; Lash, T. D. Chem.dEur. J. 2002, 8, 5397–5402.
19. (a) Lash, T. D.; Colby, D. A.; Ferrence, G. M. Eur. J. Org. Chem. 2003, 4533–4548;
(b) El-Beck, J. A.; Lash, T. D. Eur. J. Org. Chem. 2007, 3981–3990.
20. Berlin, K.; Breitmaier, E. Angew. Chem., Int. Ed. Engl. 1994, 33, 1246–1247.
21. Stepien, M.; Latos-Grazynski, L. Chem.dEur. J. 2001, 7, 5113–5117.
22. Szymanski, J. T.; Lash, T. D. Tetrahedron Lett. 2003, 44, 8613–8616.
23. Lash, T. D.; Szymanski, J. T.; Ferrence, G. M. J. Org. Chem. 2007, 72, 6481–6492.
24. Vogel, E. J. Heterocycl. Chem. 1996, 33, 1461.
(500 MHz, CDCl3):
d
1.06 (9H, s), 7.00 (2H, d, J¼5.2 Hz), 7.12 (2H, d,
J¼5.2 Hz), 7.20 (2H, s), 7.46–7.54 (16H, m), 7.80 (2H, s); 13C NMR
(CDCl3):
d 30.7, 34.2, 116.8, 126.8, 128.1, 130.0, 133.8, 133.97, 133.99,
134.10, 134.12, 135.5, 138.5, 140.64, 140.67, 142.6, 143.4, 145.6, 147.0,
152.7, 157.4; HRMS (EI), m/z calcd for C50H33Cl4N3Pd: 921.0463.
Found: 921.0457.
25. Cyranski, M. K.; Krygowski, T. M.; Wisiorowski, M.; Hommes, N. J. R.; van, E.;
Schleyer, P.; von, R. Angew. Chem., Int. Ed. 1998, 37, 177.
26.
These results were presented, in part, at the following meeting: 233rd National
American Chemical Society Meeting, Chicago, Illinois, March 2007 (Yant, V.R.;
Lash, T.D. Book of Abstracts, CHED 585).
Acknowledgements
27. For syntheses of related porphyrin analogues, see: (a) Sim, E.-K.; Jeong, S.-D.;
Yoon, D.-W.; Hong, S.-J.; Kang, Y.; Lee, C.-H. Org. Lett. 2006, 8, 3355–3358;
(b) Lash, T. D.; Pokharel, K.; Serling, J. M.; Yant, Y. R.; Ferrence, G. M. Org. Lett.
2007, 9, 2863–2866; (c) Jeong, S.-D.; Hong, S.-J.; Park, K. J.; Ham, S.; Sessler, J. L.;
Lynch, V.; Lee, C.-H. J. Org. Chem. 2007, 72, 6232–6240.
This material is based upon work supported by the National
Science Foundation under Grant No. CHE-0616555 and the Petro-
leum Research Fund, administered by the American Chemical So-
ciety. VRY also acknowledges support from Abbott laboratories.
28. Lash, T. D. Chem.dEur. J. 1996, 2, 1197–1200.
29. (a) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.; Marguerettaz, A. M.
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1535–1547.
31. Stepien, M.; Latos-Grazynski, L.; Lash, T. D.; Szterenberg, L. Inorg. Chem. 2001,
40, 6892–6900.
32. Miyake, K.; Lash, T. D. Chem. Commun. 2004, 178–179.
Supplementary data
Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2009.09.060.
33. Stepien, M.; Latos-Grazynski, L.; Szterenberg, L.; Panek, J.; Latajka, Z. J. Am.
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References and notes
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