Regiospecific β-functionalization of free-base porphyrins by pseudohalogens

Article abstract of DOI:10.1039/b718542a

Pseudohalogens based on iodine ('I-X') can be used to regiospecifically introduce chlorine atoms or acetoxy groups onto the β-positions of meso-tetraphenylporphyrins (TPPs). TPPs and a quinoxaline derivative were reacted with iodine monochloride to give mono- or di-chlorinated porphyrins, such that when two chlorine atoms were added they were placed antipodally on the porphyrin ring. Reaction of the porphyrins with a mixture of iodine and silver acetate gave the corresponding mono- and di-acetoxylated porphyrins. The acetoxylated porphyrins could be simply transformed to the corresponding hydroxyporphyrins with subsequent oxidation with the Dess-Martin periodinane, giving a simple new route to chlorin-α-diones and bacteriochlorin- tetraones. From the products of the reactions and a UV-visible spectroscopic study, it is proposed that the reactions proceed via a single electron transfer mechanism through a porphyrin cation radical intermediate. The Royal Society of Chemistry.

Full text of DOI:10.1039/b718542a

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www.rsc.org/obc
Volume 6 | Number 5 | 7 March 2008 | Pages 801–940
ISSN 1477-0520
ARTICLE
Paul L. Burn et al.
Regiospeciꢀc β-functionalization
of free-base porphyrins by
pseudohalogens
1477-0520(2008)6:5;1-C

PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Regiospecific b-functionalization of free-base porphyrins by pseudohalogens
Wei Zhang,a Matthew N. Wicksa and Paul L. Burn*b
Received 30th November 2007, Accepted 19th December 2007
First published as an Advance Article on the web 1st February 2008
DOI: 10.1039/b718542a
Pseudohalogens based on iodine (‘I–X’) can be used to regiospecifically introduce chlorine atoms or
acetoxy groups onto the b-positions of meso-tetraphenylporphyrins (TPPs). TPPs and a quinoxaline
derivative were reacted with iodine monochloride to give mono- or di-chlorinated porphyrins, such that
when two chlorine atoms were added they were placed antipodally on the porphyrin ring. Reaction of
the porphyrins with a mixture of iodine and silver acetate gave the corresponding mono- and
di-acetoxylated porphyrins. The acetoxylated porphyrins could be simply transformed to the
corresponding hydroxyporphyrins with subsequent oxidation with the Dess–Martin periodinane, giving
a simple new route to chlorin-a-diones and bacteriochlorin-tetraones. From the products of the
reactions and a UV–visible spectroscopic study, it is proposed that the reactions proceed via a single
electron transfer mechanism through a porphyrin cation radical intermediate.
b]porphyrin 1 as the substrate.1 1 was chosen as the substrate as the
3,5-di-t-butylphenyl groups provide good solubility and protect
the meso positions from reaction, and the quinoxalino group can
direct reaction at the 12- and/or 13-b-pyrrolic positions thus mak-
Introduction
The ability to functionalise the porphyrin outer periphery at
specific positions under mild conditions is a continuing challenge.
Porphyrins have been reported to undergo nucleophilic and
electrophilic substitution, as well as radical reactions.1–4 To get the
ing analysis of the products from the reaction simpler. When 1 was
reacted with 2.4 equivalents of iodine monochloride in chloroform
required control over the porphyrin reactivity it is often necessary
heated at reflux (Scheme 1) for four hours, 12-chloro-5,10,15,20-
to use a metal chelated porphyrin.1,4 The disadvantage of this is
that the final product may be required to have no metal or a
different metal chelated. The conditions required to remove the
chelated metal have to be compatible with the functionality on the
porphyrin outer periphery and this can limit the range of groups
that can be introduced. Therefore, methods that can be used to
attach functional groups onto the outer periphery of a free-base
porphyrin have an advantage as the required metal can be chelated
at a later stage of the synthesis. While many of the products isolated
from the reactions used to introduce functionality onto the por-
phyrin outer periphery fit the standard mechanistic rationale, there
are the occasional reports where an unusual substitution process
occurs. For example, treatment of a 5,15-diphenyl substituted free-
base porphyrin with N-iodosuccinimide leads to the ‘expected’
meso-iodinated product, arguably by electrophilic substitution,
but reaction with iodine monochloride leads to the meso-chloro
substituted product.5 This latter product clearly cannot occur via
a simple substitution reaction. We were therefore interested to
understand how this product was formed and to determine if the
reaction was specific for meso positions, and whether similar reac-
tions could be used for the introduction of other functional groups.
tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)quinoxalino[2,3-b]porphyrin 2 was
isolated in an excellent yield of 75%. These results show that when
the meso positions are blocked chlorination can take place on the
b-pyrrolic positions. To investigate the generality of the reaction we
treated 5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)porphyrin 4 with
five equivalents of iodine monochloride in chloroform heated at
reflux and this gave 2,12/13-dichloro-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-
t-butylphenyl)porphyrin 5 in 58% yield with 11% of the starting
material recovered. That is, the method can be used to introduce
more than one chlorine atom onto the porphyrin periphery. Impor-
tantly both chlorine atoms are attached to the b-pyrrolic positions
and the addition of the first chloro group directs the addition
of the second antipodally. To determine whether the reaction
was specific to the bulky meso-3,5-di-t-butylphenyl substituted
porphyrins we also carried out the dichlorination reaction with the
simple, less sterically hindered 5,10,15,20-tetraphenylporphyrin 6.
The reaction was carried out under similar conditions to those
used for the formation of 5 and the corresponding 2,12/13-
dichloro-5,10,15,20-tetraphenylporphyrin 7 was isolated in a 46%
yield with, in this case, a 23% yield of the starting porphyrin
recovered. Therefore this methodology can be used to simply
and mildly introduce chloro groups onto the periphery of meso-
tetraphenylporphyrins, opening the avenue for the introduction of
new functionalities by nucleophilic substitution reactions.1 While
the mechanism of the chlorination reaction will be discussed in
more detail later, it is important to note that chlorination of
relatively easily oxidised aromatics has been reported to occur
via a radical cation intermediate to which either a chloride anion
or iodine radical can add and it is likely a similar mechanism is at
play here.6,7 In these simple aromatic systems it has been shown
that solvent and steric hindrance can play important roles in the
product outcome of the reaction.6 In the work here, utilising the
Results and discussion
The first part of our investigation was to determine whether the
chlorination was specific for the meso positions and for this we
chose 5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)quinoxalino[2,3-
aDepartment of Chemistry, Chemistry Research Laboratory, University of
Oxford, Mansfield Road, Oxford, UK OX1 3TA
bCentre for Organic Photonics and Electronics, School of Molecular
and Microbial Sciences, University of Queensland, Chemistry Building,
Queensland, 4072, Australia
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Scheme 1 (i) ICl, CHCl3, reflux; (ii) I2, AgOAc, CHCl3; (iii) ICl, CHCl3–CH2Cl2, reflux.
relatively non-polar chloroform and having the meso substituents
that the iodine–silver nitrite mixture is known to give iodine
nitrite.13 It is therefore possible that the nitration using the
iodine–silver nitrite mixture also occurs via a similar mechanism
to the iodine monochloride reaction. That is, there is a single
electron transfer from the porphyrin to iodine nitrite to form
a charge transfer complex comprised of the porphyrin radical
cation, the iodine atom, and the nitrite ion followed by, under the
relatively non-polar solvent conditions, nucleophilic attack of the
nitrite ion.
(phenyl and 3,5-di-t-butylphenyl) ensures that the less sterically
demanding and more polar chloride anion adds preferentially
over the iodine atom. The fact that only the 12-chloro regioisomer
is isolated from the reaction of 1 is similar to that observed in
other electrophilic or radical reactions of chlorins. In the past
this has been simply attributed to the fact that the 18-p electron
aromatic pathway imparts alkenyl-like character to the double
bond antipodally to the chlorin moiety.1,8 However, this is not in
accord with molecular orbital calculations, which show that the
highest occupied molecular orbital density is not preferentially
located on the 12- and 13-positions.9,10 It may be that once the
porphyrin is oxidised, the stability of the radical cation is greatest
when the 18-p electron aromatic pathway is present, that is, the
reaction is under kinetic control. A similar argument could explain
the selectivity of the antipodal nature of the addition of the two
chloro groups on 4 and 6.
The in situ formation of a porphyrin radical cation intermediate
and subsequent nucleophilic attack is not dissimilar to early work
on porphyrin substitution reactions where a radical cation was
formed ex situ and then reacted with a range of nucleophiles.11
In these earlier studies a zinc chelated meso-tetraphenylporphyrin
was oxidised and then reacted with a range of anions including
nitrite, thiocyanate, pyridine and triphenylphosphine to form
the corresponding 2-substituted porphyrins. Interestingly the
reaction with the oxygen nucleophiles, methanol and water, caused
substitution on the meso position in spite of it being sterically
encumbered. In a similar vein it was later reported that a nitro
group could be introduced onto the b-pyrrolic position of a copper
chelated porphyrin by reaction with a mixture of iodine and silver
nitrite.12 Although the mechanism of this latter reaction was not
discussed in any detail it was assumed that the reaction occurred
via an in situ oxidation by iodine and subsequent ‘substitution
reaction’ with the nitrite anion. However, it is interesting to note
Given that iodine monochloride and iodine–silver nitrite are
effectively pseudohalogen ‘I–X’ reagents we were interested to see
whether the methodology could be used to introduce an acetoxy
group as the reaction of iodine with silver acetate gives iodine
acetate.14 Simple deprotection could give hydroxyporphyrins, with
subsequent oxidation leading to chlorin-a-diones that have been
used to build porphyrin arrays.15–18 We first reacted 1 (Scheme 1)
with a mixture of 2.5 equivalents of iodine and 3.8 equivalents of
silver acetate in chloroform at room temperature for 1.5 hours.
Acetoxylation occurred in the 12-position to give 3 in a 32%
yield with 44% of 1 being recovered. In addition, 5% of 12-
iodo-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)quinoxalino-[2,3-
b]porphyrin was also isolated. The fact that both the acetoxy and
iodo products were isolated lends strength to the argument that the
mechanism involving a porphyrin radical cation is at play. Unlike
the iodine monochloride reaction, in this case the acetoxy group
and iodine atom are both large and hence there is a reduction in the
steric discrimination, with some of the iodo product being formed.
We then extended the methodology to the reaction of the sim-
ple free-base porphyrin 5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)-
porphyrin 4 with the iodine–silver acetate (1.9 and 2.9 equiva-
lents respectively) mixture (Scheme 2). After 90 minutes at
room temperature 2-acetoxy-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butyl-
phenyl)porphyrin 8 was obtained in a yield of 37%. Again
the starting porphyrin 4 (36%) was recovered and there was
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Scheme 2 (i) I2, AgOAc, chloroform; (ii) a. K2CO3, CH2Cl2–MeOH; b. DMP, CH2Cl2; (iii) I2, AgOAc, CHCl3–CH3COOH.
a small amount (6%) of 2-iodo-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-
butylphenyl)porphyrin 9. In addition, 5% of 2,12/13-bisacetoxy-
5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)porphyrin 10 was also
formed. It is interesting to note that, unlike the case of the dichlo-
rination, the second acetoxy group is not exclusively attached
antipodally to the first. Nevertheless it was fairly straightforward
to separate 10 from 4, 8 and 9, as well as the other bis-acetoxylated
materials. In an effort to increase the yield of 8 we added a second
aliquot of the iodine–silver acetate mixture (to give a total of
4.2 and 6.4 equivalents of each reagent respectively) and this
improved the yield of 8 to 47%, with starting material 4 (17%),
iodo 9 (7%), and diacetoxy 10 (11%) also being isolated. We found
that adding a third aliquot of reagents did result in all the starting
material being consumed but this was at the cost of the reduction
in yield of the desired 8 to 14% without the concomitant increase
in the amount of 10, which was isolated in a 13% yield. It is
noteworthy that, while the acetoxylation occurs predominantly
on the b-pyrrolic positions, it is likely that the decomposition
pathway involves acetyloxylation of the meso carbons.11 As in the
case of the reaction with iodine monochloride, we were interested
to see whether the difference in steric bulk between the phenyl
and 3,5-di-t-butylphenyl meso substituents made a significant
difference to the product distribution. We reacted the simple meso-
tetraphenylporphyrin 6 with a similar ratio of iodine and silver
acetate (2.5 equivalents and 3.8 equivalents respectively), as in
the first reaction of 4, and the corresponding iodo 12, starting
material 6, and acetoxyporphyrin 11 were isolated in 5%, 43%,
and 32% respectively. This result again shows that the reaction is
more general for meso-phenyl substituted porphyrin derivatives.
With our interest of using porphyrin-a-diones as building blocks
for porphyrin arrays we investigated the conversion of the mono-
and di-acetates, 8 and 10 respectively to the chlorin-a-dione 13
and bacteriochlorin-tetraone 15. Porphyrin acetate 8 was depro-
tected with methanolic potassium carbonate to give 2-hydroxy-
5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-t-butylphenyl)porphyrin, which was
then oxidized to the chlorin-a-dione 13 (Scheme 2) using the Dess–
Martin periodinane (DMP),19 giving a 72% yield for the two steps.
Using the optimised conditions for the formation of 8 (a yield of
47%), this process gives an overall yield of the chlorin-a-dione 13
of 34% (41% conversion) in three simple steps from 4 rather than
the five or six step processes that are normally used. In a similar
process the diacetate 10 could be deprotected and oxidised with
DMP to give the bacteriochlorin-tetraone in 47% yield, giving an
overall three-step conversion of 4 to 15 of 6%. This again is a
much more straightforward process than has been reported in the
past for the synthesis of 15 and occurs with comparable yields.20,21
Interestingly the same overall yield of 15 from 4 can be achieved by
reacting chlorin-a-dione 13 with the iodine–silver acetate mixture
with subsequent deprotection and DMP oxidation. Chlorin-a-
dione 13 was converted to the corresponding acetoxychlorin-a-
dione 14 in 46% yield using acidified chloroform with the subse-
quent deprotection and oxidation to bacteriochlorin-tetraone 15
(Scheme 2) occurring in 41% yield. The bacteriochlorin-tetraone
15 was therefore synthesised in a 6% yield for the six steps from 4.
While the chlorination and acetoxylation reactions of the
porphyrin outer periphery seem to be reasonably general, it is
interesting to consider in more detail how the reactions proceed.
Electrophilic substitution can be discounted, as it would be the
iodine that would add in each case, as chlorine and oxygen are
more electronegative than iodine. Clearly it cannot be simple
nucleophilic substitution as there is there no leaving group on
the porphyrin ring and no activating chelating metal. As has
been stated earlier the chlorination, as opposed to iodination, of
relatively easily oxidised aromatic rings by iodine monochloride
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can occur via a single electron transfer pathway.6,7 That is, in the
first step the iodine monochloride forms a p- or encounter complex
with the aromatic ring, and then an electron is transferred from
the aromatic ring (oxidation) to the iodine monochloride to give
an intermediate charge transfer complex comprised of the radical
cation of the aromatic ring, the chloride anion, and the iodine
atom. This intermediate complex can then collapse by one of two
pathways. The first pathway involves the iodine atom adding to
the radical cation to form the iodo-substituted aromatic cation.
Subsequent loss of the proton forms the neutral iodo-substituted
aromatic ring with hydrogen chloride as the by-product. In the sec-
ond pathway the chloride anion adds giving the chloro-substituted
aromatic radical, which is oxidised by a second equivalent of iodine
monochloride to the corresponding cation. Loss of a proton leads
to the chloro-substituted ring and iodine and hydrogen chloride
are the initial by-products. We have illustrated the equivalent
pathway for a porphyrin substrate in Fig. 1 and, based on the
observed product outcomes, believe that this is the most likely
mechanism for the formation of the chlorinated porphyrins.
We therefore carried out the reaction of porphyrin 4 with iodine
monochloride in HFP. The absorption spectra at the different
stages are shown in Fig. 2. However, interpretation of the results
was not straightforward as the porphyrin and HFP have similar
pKas of around 9.3.23 This meant that when porphyrin 4 was
dissolved in HFP it was protonated and the solution turned green
[(i) in Fig. 2]. On addition of the iodine monochloride the colour
of the solution changed to red and two new peaks were observed
in the absorption spectrum at 549 nm and 715 nm [(ii) in Fig. 2].
The spectrum did not change appreciably over a period of a couple
of hours, but on heating the peak at 549 nm disappeared while the
longer wavelength peak remained [(iii) in Fig. 2] and the solution
turned green. The peak at 715 nm is close to that observed for por-
phyrin 4 dissolved in HFP and treated with hydrogen chloride (679
nm) and so is probably associated with a protonated product. TLC
analysis of the heated solution showed that a chlorinated product
was present. That is, the peak at 715 nm in (ii) of Fig. 2 may just
arise from product formation on the initial addition of the iodine
monochloride. The fact that the peak at 549 nm disappears during
product formation may imply that it is the signature of an inter-
mediate, which we propose could be the porphyrin radical cation.
Fig. 2 UV–visible spectra of 4: (i) in HFP, (ii) 2.5 h after addition of ICl,
and (iii) after heating. The spectra have been normalised for clarity.
If the chlorination and acetoxylation go via a similar mech-
anism then we might expect to see a similar absorption for the
intermediate in the latter reaction. We therefore carried out a
spectroscopic study of 4 with the iodine–silver acetate mixture,
and the absorption spectra for the sequence of steps is shown in
Fig. 3. This work was complicated by the fact that iodine is not
soluble in HFP. Indeed, addition of iodine to HFP caused no
change in the absorption spectrum of the protonated porphyrin
(not shown). However, on addition of silver acetate the spectrum of
the solution changed and there was a peak at 530 nm [(ii) in Fig. 3],
which is very close to the new peak observed during the iodination
reaction. In this case there was no absorption at longer wavelength
and even heating the reaction resulted in no acetoxylated product
being observed, even though a new absorption due to protonated
porphyrin 4 was seen [(iii) in Fig. 3]. The fact that no reaction
was observed is perhaps not surprising as it known that HFP
reduces the reactivity of nucleophiles (it is how the radical cation
is ‘stabilised’) and the acetate is a relatively poor nucleophile.
Therefore, since the reactions of 4 with iodine monochloride and
iodine and silver acetate lead to the chlorinated and acetoxylated
materials as the main products, and the intermediates that are
Fig. 1 Possible mechanism for the formation of the chlorinated product
from the reaction of the porphyrins with ICl.
In an effort to gather further evidence that this is the mechanistic
pathway, we first attempted to follow the chlorination of 4 spectro-
scopically with the reaction carried out in situ in chloroform under
the normal conditions, to see whether the absorption spectrum
of the radical cation could be observed. However, in common
with other reactive aromatic substrates, the reaction at room
temperature was too fast to allow observation of the absorption
spectrum of the intermediate radical cation and all that was seen
was the absorption spectrum of a protonated porphyrin. Analysis
of the solution by thin layer chromatography (TLC) showed that
a chlorinated product had formed. In one study on the reaction of
iodine monochloride with aromatic substrates it was reported that
1,1,1,3,3,3-hexafluoropropan-2-ol (HFP) could be used to stabilise
the radical intermediate in an iodine monochloride reaction.22
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12-Chloro-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)quinoxalino[2,3-b]porphyrin 2
A solution of iodine monochloride in chloroform (0.02 M, 2.5 cm3,
0.050 mmol) was added to a refluxing solution of 5,10,15,20-
tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)quinoxalino[2,3-b]porphyrin
1
(45 mg, 0.039 mmol) in chloroform (10 cm3). After 2 h a further
aliquot of iodine monochloride in chloroform (0.02 M, 2.5 cm3,
0.050 mmol) was added. The reaction mixture was heated at reflux
for a further 2 h and then allowed to cool to room temperature.
Saturated aqueous sodium thiosulfate solution (100 cm3) was
added and the organic layer was separated. The organic layer
was washed with saturated sodium thiosulfate solution (100 cm3),
dried over sodium sulfate, filtered and the solvent was removed.
The crude product was purified by column chromatography over
silica using a dichloromethane :light petroleum (1 : 8) mixture as
eluent to give 2 (35 mg, 75%) as a dark purple solid, mp >280 ◦C;
found: C, 82.1%; H, 8.0%; N, 6.9%; C82H95ClN6 requires C, 82.1%;
H, 8.0%; N, 7.0%; kmax (CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1))
299 (4.44), 337sh (4.54), 357 (4.61), 409sh (5.17), 435 (5.47), 530
(4.45), 568sh (3.75), 599 (4.16), 653 (3.00); 1H NMR (400.1 MHz;
CDCl3) d: −2.72 and −2.59 (2 × 1H, br s, NH), 1.480, 1.485, 1.51,
and 1.53 (72H, 4 × s, t-butyl H), 7.73–7.77 (2H, m, quinoxalino
Fig. 3 UV–visible spectra of 4: (i) in HFP, (ii) 1.5 h after addition of
I2–AgOAc, (iii) after heating, and (iv) 2.5 h after addition of ICl for
comparison. The spectra have been normalised for clarity.
formed on the addition of the reagents have absorptions in the UV–
visible spectra at similar wavelengths, this strongly suggests that
these reactions proceed via a single electron transfer mechanism
through a porphyrin radical cation intermediate.
H), 7.79 (1H, dd J2 ,4 = J6 ,4 = 2 Hz, C(4ꢀ)H), 7.80–7.84 (3H, m,
Experimental
ꢀ
ꢀ
ꢀ ꢀ
quinoxalino H and C(4ꢀ)H), 7.83 (1H, dd J2 ,4 = J6 ,4 = 2 Hz,
ꢀ
ꢀ
ꢀ ꢀ
1H NMR spectra of new compounds were recorded on Bru¨ker
DPX-400 (400 MHz), Bru¨ker DQX-400 (400 MHz), or Bru¨ker
AMX-500 (500 MHz) spectrometers. Chemical shifts (d) are
reported in parts per million (ppm) and are referenced to the
residual solvent peak. Multiplicities are reported as broad (br),
singlet (s), doublet (d), doublet of doublets (dd), or multiplet
(m) and coupling constants are reported to the nearest half
Hz. Infrared spectra were recorded using a KBr disc using a
Perkin-Elmer Paragon 1000 IR spectrometer or a Bru¨ker Tensor
27 FT-IR spectrometer. Values of the absorption maxima are
recorded in wavenumbers (cm−1). UV–vis spectra were measured in
spectrophotometric grade dichloromethane with a Perkin-Elmer
Lambda 14P UV–vis spectrometer. The absorption peaks are re-
ported with ‘sh’ indicating a shoulder. Mass spectra were recorded
on a Micromass Platform for ESI, or a Walters LCT Premier
ESI-ToF mass spectrometer. Accurate masses were measured on
a Bru¨ker MicroToF or a Micromass LCT spectrometer. Values
for m/z are quoted in Daltons. Melting points were measured
using a Gallenkamp melting point apparatus and are uncorrected.
Microanalyses were performed by Mr Stephen Boyer in SACS,
London Metropolitan University.
C(4ꢀ)H), 7.93 (2H, dd J2 ,4 = J6 ,4 = 1.5 Hz, C(4ꢀ)H), 7.95 (2H,
ꢀ
ꢀ
ꢀ ꢀ
d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H and C(6ꢀ)H), 7.96–7.97 (4H, m,
ꢀ
ꢀ
ꢀ ꢀ
ꢀ
C(2ꢀ)H and C(6ꢀ)H), 8.05 (2H, d, J4 ,2 = J4 ,6 = 1.5 Hz, C(2 )H and
ꢀ
ꢀ
ꢀ ꢀ
C(6ꢀ)H), 8.68 (1H, s, C(13)H), 8.91 (1H, dd, Jb,b = 5 Hz, JNH,b
=
1.5 Hz, b-pyrrolic H), 8.93 (1H, dd, Jb,b = 5 Hz, JNH,b = 1.5 Hz,
b-pyrrolic H), 9.03 (1H, dd, Jb,b = 5 Hz, JNH,b = 1.5 Hz, b-pyrrolic
H), 9.05 (1H, dd, Jb,b = 5 Hz, JNH,b = 1 Hz, b-pyrrolic H); m/z
(ESI-TOF) 1199.6 (MH+, 100%); C82H95ClN6H+ requires 1199.7
(MH+); Rf (light petroleum–dichloromethane; 5 : 1) = 0.30.
2,12/13-Dichloro-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)porphyrin 5
A solution of iodine monochloride in dichloromethane solution
(1 M, 0.72 cm3, 0.72 mmol) was added to a refluxing solution of
5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)porphyrin 4 (310 mg,
0.29 mmol) in chloroform (30 cm3). After 2 h a further aliquot
of iodine monochloride in dichloromethane (1 M, 0.72 cm3,
0.72 mmol) was added. The reaction mixture was heated at
reflux for a further 2 h and was then allowed to cool to room
temperature. Saturated aqueous sodium thiosulfate (100 cm3) was
added and the organic layer was separated. The organic layer
was washed with saturated aqueous sodium thiosulfate solution
(100 cm3), dried over anhydrous sodium sulfate, filtered, and
the solvent was removed. The residue was purified by column
chromatography over silica using a dichloromethane : light
petroleum mixture (1 : 6) as eluent to give ◦5 (190 mg, 58%) and
4 (35 mg, 11%). 5: purple solid, mp >280 C; found: C, 80.7%;
H, 8.25%; N, 4.9%; C76H92Cl2N4 requires C, 80.6%; H, 8.2%; N,
4.95%; kmax (CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 424 (5.56),
Petroleum spirit with a boiling point range of 40 to 60 ◦C
is referred to as light petroleum. Chloroform required for the
halogenation reactions was filtered through a short column of
neutral alumina (Brockmann activity 1; 150 mesh) purchased
from Aldrich. Chloroform required for the acetoxylation reac-
tions was filtered through a short column of acidic alumina
(Brockmann activity 1; 0.05–0.15 mm) purchased from Fluka.
All other reagents were purchased from commercial sources and
used without further purification. Where solvent mixtures are
used, the proportions are given in terms of volume. Thin layer
chromatography was performed with Merck aluminium plates
coated with silica gel F254. Column chromatography was performed
using the flash chromatography technique, with ACROS Organics
silica gel 0.035–0.07 mm.
1
490sh (3.60), 520 (4.00), 556 (3.72), 595 (3.71), 651 (3.79); H
NMR (400.1 MHz; CDCl3) d: −2.94 (2H, br s, NH), 1.49 (36H,
m, t-butyl H), 1.515 and 1.52 (36H, 2 × s, t-butyl H), 7.77 (2H, dd,
J2 ,4 = J6 ,4 = 2 Hz, C(4ꢀ)H), 7.80 (2H, dd, J2 ,4 = J6 ,4 = 1.5 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
C(4ꢀ)H), 7.91 (4H, m, C(2ꢀ)H and C(6ꢀ)H), 8.02 (4H, m, C(2ꢀ)H and
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 879–886 | 883
©

C(6ꢀ)H), 8.69 and 8.70 (2H, 2 × s, C(3)H and C(12)H/C(13)H),
8.84 and 8.91, and 8.87 (4H, comprised of 2 × br s {8.84 and 8.91}
and a tight ABq {8.87}, b-pyrrolic H); m/z (ESI-TOF) 1131.7
(98%), 1132.7 (81%), 1133.7 (100%), 1134.7 (55%), 1135.7 (27%),
1136.7 (11%), 1137.7 (4%); C76H92Cl2N4H+ (MH+) requires 1131.7
(100%), 1132.7 (85%), 1133.7 (99%), 1134.7 (64%), 1135.7 (35%),
1136.7 (15%), 1137.7 (5%); Rf (light petroleum–dichloromethane;
5 : 1) = 0.33. 4: a sample co-chromatographed with and had an
identical 1H NMR to an authentic sample.
C84H98N6O2H+ (MH+) requires 1223.7824 (100%), 1224.7856
(94%), 1225.7889 (44%), 1226.7921 (14%), 1227.7952 (3%); Rf
(light petroleum–dichloromethane; 2 : 1) = 0.24.
2-Acetoxy-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)porphyrin 8
To a solution of 5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)-
porphyrin 4 (6.70 g, 6.30 mmol) in chloroform (420 cm3) were
added silver acetate (3.00 g, 18.0 mmol) and iodine (3.00 g,
11.8 mmol). The reaction mixture was stirred at room temperature
in the dark under argon for 1.5 h and then filtered through
a short plug of silica gel using dichloromethane as the eluent.
The filtrate was collected and the solvent was removed, and the
residue was purified by column chromatography over silica using
a dichloromethane : light petroleum (gradient from 1 : 6 to 1 : 1) as
eluent to give 9 (0.48 g, 6%), 4 (2.38 g, 36%), 8 (2.62 g, 37%) and 10
(0.31 g, 5%). 9: red solid, mp >280 ◦C; found: C, 76.8%; H, 7.8%;
N, 4.6%; C76H93IN4 requires C, 76.7%; H, 7.9%; N, 4.7%; kmax
(CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 303 (4.19), 369sh (4.40),
424 (5.67), 489 (3.61), 520 (4.35), 556 (3.92), 595 (3.79), 651 (3.85);
1H NMR (400.1 MHz; CDCl3) d: −2.75 (2H, br s, NH), 1.52, 1.525,
12-Acetoxy-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)quinoxalino[2,3-b]porphyrin 3
To a solution of 5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)-
quinoxalino[2,3-b]porphyrin 1 (100 mg, 0.086 mmol) in chloro-
form (10 cm3) were added silver acetate (50 mg, 0.30 mmol) and
iodine (50 mg, 0.20 mmol). The reaction mixture was stirred at
room temperature in the dark under argon for 1.5 h and then
filtered through a short plug of silica using dichloromethane as the
eluent. The filtrate was collected, the solvent was removed and the
residue was purified by column chromatography over silica using
a dichloromethane : light petroleum mixture (gradient from 1 : 6
to 1 : 2) as eluent to give 12-iodo-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)quinoxalino[2,3-b]porphyrin (6.0 mg, 5%), 1 (44 mg,
44%) and 3 (34 mg, 32%). 12-Iodo-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-
tert-butylphenyl)quinoxalino[2,3-b]porphyrin: dark purple solid,
mp >280 ◦C; found: C, 76.2%; H, 7.4%; N, 6.4%; C82H95IN6
requires C, 76.3%; H, 7.4%; N, 6.5%); kmax (CH2Cl2)/nm
(log(e/dm−3 mol−1 cm−1)) 296 (4.28), 344sh (4.37), 364sh (4.42),
ꢀ
ꢀ
ꢀ ꢀ
1.53, and 1.54 (72H, 4 × s, t-butyl H), 7.80 (2H, dd, J2 ,4 = J6 ,4
=
2 Hz, C(4ꢀ)H), 7.82 (1H, dd, J2 ,4 = J6 ,4 = 2 Hz, C(4ꢀ)H), 7.83
ꢀ
ꢀ
ꢀ ꢀ
(1H, dd, J2 ,4 = J6 ,4 = 2 Hz, C(4ꢀ)H), 7.94 (2H, d, J4 ,2 = J4 ,6
=
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
2 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.06 (2H, d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H
and C(6ꢀ)H), 8.07–8.09 (4H, m, C(2ꢀ)H and C(6ꢀ)H), 8.82 and 8.84
(2H, ABq, JA,B = 4 Hz, b-pyrrolic H), 8.89–8.92 (3H, m, b-pyrrolic
H), 8.96 (1H, 1/2ABq, JA,B = 5 Hz, b-pyrrolic H), 9.21 (1H, s,
C(3)H); m/z (ESI) 1189.6 (100%); C76H93IN4H+ (MH+) requires
1189.6 (100%); Rf (light petroleum–dichloromethane; 5 : 1) = 0.26.
ꢀ
ꢀ
ꢀ ꢀ
1
413sh (5.03), 438 (5.31), 532 (4.32), 600 (4.01), 655 (2.98); H
NMR (400.1 MHz; CDCl3) d: −2.70 (1H, br s, NH), −2.54 (1H,
br s, NH), 1.48, 1.485, 1.53, and 1.54 (72H, 4 × s, t-butyl H), 7.73–
7.77 (2H, m, quinoxalino H), 7.81–7.84 (4H, m, quinoxalino H
1
4: a sample co-chromatographed with and had an identical H
◦
NMR to an authentic sample. 8: red solid, mp >280 C; found:
and C(4ꢀ)H), 7.92 (2H, dd, J2 ,4 = J6 ,4 = 2 Hz, C(4ꢀ)H), 7.95 (4H,
C, 83.6%; H, 8.7%; N, 4.9%; C78H96N4O2 requires C, 83.5%; H,
ꢀ
ꢀ
ꢀ ꢀ
m, C(2ꢀ)H and C(6ꢀ)H), 7.97 (2H, d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H
8.6%; N, 5.0%; mmax (KBr)/cm−1 1767 (C O); kmax (CH2Cl2)/nm
=
ꢀ
ꢀ
ꢀ ꢀ
and C(6ꢀ)H), 8.07 (2H, d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H and C(6ꢀ)H),
(log(e/dm−3 mol−1 cm−1)) 304 (3.86), 327sh (3.81), 371sh (4.05), 421
(5.34), 486 (3.26), 517 (3.95), 553 (3.61), 591 (3.42), 647 (3.38); 1H
NMR (400.1 MHz; CDCl3) d: −2.77 (2H, br s, NH), 1.53 (18H, s,
t-butyl H), 1.54 (18H, s, t-butyl H), 1.55 (36H, s, t-butyl H), 1.82
ꢀ
ꢀ
ꢀ ꢀ
8.93 (1H, dd, Jb,b = 5 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 8.95 (1H,
dd, Jb,b = 5 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 9.01 (1H, dd, Jb,b
=
5 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 9.05 (1H, dd, Jb,b = 5 Hz,
JNH,b = 1.5 Hz, b-pyrrolic H), 9.14 (1H, s, C(13)H); m/z (ESI-
TOF) 1291.5 (MH+, 100%); C82H95N6IH+ requires 1291.7 (MH+);
Rf (light petroleum–dichloromethane; 5 : 1) = 0.25. 1: a sample
(3H, s, CH3COO), 7.80 (4H, br m, C(4ꢀ)H), 8.00 (2H, d, J4 ,2
=
ꢀ
ꢀ
J4 ,6 = 1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.09 (2H, d, J4 ,2 = J4 ,6
=
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.10 (4H, d, J4 ,2 = J4 ,6 = 1.5 Hz,
ꢀ
ꢀ
ꢀ ꢀ
1
co-chromatographed with and had an identical H NMR to an
C(2ꢀ)H and C(6ꢀ)H), 8.61 (1H, s, C(3)H), 8.68 and 8.90 (2H, ABq,
authentic sample. 3: orange–brown solid, mp >280 ◦C; found: C,
JA,B = 5 Hz, b-pyrrolic H), 8.84 and 8.86 (2H, tight ABq, JA,B =
82.4%; H, 8.1%; N, 6.85%; C84H98N6O2 requires C, 82.45%; H,
5 Hz, b-pyrrolic H), 8.92 and 8.95 (2H, ABq, JA,B = 5 Hz, b-
pyrrolic H); m/z (ESI-TOF) 1121.7546 (100%), 1122.7572 (86%),
1123.7642 (32%), 1124.7635 (8%), 1125.7638 (2%); C78H96N4O2H+
(MH+) requires 1121.7606 (100%), 1122.7639 (87%), 1123.7672
(38%), 1124.7704 (11%), and 1125.7736 (2%); Rf (light petroleum–
dichloromethane; 2 : 1) = 0.27. 10: red solid, mp >280 ◦C; found:
C, 81.5%; H, 8.3%; N, 4.7%; C80H98N4O4 requires C, 81.45%; H,
8.1%; N, 6.9%; mmax (KBr)/cm−1 1766 (C O); kmax (CH2Cl2)/nm
=
(log(e/dm−3 mol−1 cm−1)) 294 (4.36), 339sh (4.40), 356 (4.45), 433
1
(5.35), 529 (4.28), 562 (3.74), 598 (4.00), 650 (2.97); H NMR
(400.1 MHz; CDCl3) d: −2.67 (1H, br s, NH), −2.61 (1H, br s,
NH), 1.48, 1.49, 1.52, and 1.54 (72H, 4 × s, t-butyl H), 1.79 (3H, s,
CH3COO), 7.72–7.76 (2H, m, quinoxalino H), 7.80–7.85 (4H, m,
C(4ꢀ)H and quinoxalino H), 7.92–7.94 (2H, m, C(4ꢀ)H), 7.96 (2H,
8.4%; N, 4.75%; mmax (KBr)/cm−1 1768 (C O); kmax (CH2Cl2)/nm
=
d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H and C(6ꢀ)H), 7.98 (2H, d, J4 ,2
=
(log(e/dm−3 mol−1 cm−1)) 307 (4.27), 379sh (4.44), 402sh (5.04), 421
(5.69), 489sh (3.67), 518 (4.38), 553 (3.96), 590 (3.87), 645 (3.77);
1H NMR (500.3 MHz; CD2Cl2) d: −2.93 (2H, br s, NH), 1.50,
1.51, 1.52 and 1.53 (72H, 4 × s, t-butyl H), 1.78 (6H, s, CH3COO),
7.77–7.78 (4H, m, C(4ꢀ)H), 7.95–7.97 (4H, m, C(2ꢀ)H and C(6ꢀ)H),
8.06–8.08 (4H, m, C(2ꢀ)H and C(6ꢀ)H), 8.53 and 8.55 (2H, 2 × s,
C(3)H and C(12)H or C(13)H), 8.63 (1H, br s, b-pyrrolic H), 8.67
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
J4 ,6 = 1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.00 (2H, d, J4 ,2 = J4 ,6
=
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
2 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.11 (2H, d, J4 ,2 = J4 ,6 = 2 Hz, C(2ꢀ)H
ꢀ
ꢀ
ꢀ ꢀ
and C(6ꢀ)H), 8.52 (1H, s, C(13)H), 8.72 and 9.01 (2H, ABq, JA,B
=
4.5 Hz, b-pyrrolic H), 8.95 and 9.06 (2H, ABq, JA,B = 4.5 Hz,
b-pyrrolic H); m/z (ESI-TOF) 1223.8216 (100%), 1224.8205
(93%), 1225.8266 (39%), 1226.8217 (11%), 1227.8259 (3%);
884 | Org. Biomol. Chem., 2008, 6, 879–886
This journal is
The Royal Society of Chemistry 2008
©

and 8.87 (2H, ABq, JA,B = 5 Hz, b-pyrrolic H), 8.92 (1H, br s,
b-pyrrolic H); m/z (ESI) 1179.6 (100%); C80H98N4O4H+ (MH+)
requires 1179.8 (100%); Rf (light petroleum–dichloromethane;
1 : 1) = 0.34.
5.0 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 8.77 (1H, dd, Jb,b = 5.0 Hz,
JNH,b = 1.5 Hz, b-pyrrolic H); m/z (ESI-TOF) 1151.8 (100%),
1152.8 (75%), 1153.8 (27%), 1154.8 (8%); C78H94N4O4H+ (MH+)
requires 1151.7 (100%), 1152.7 (90%), 1153.7 (41%), 1154.7 (12%);
Rf (light petroleum–dichloromethane; 2 : 1) = 0.13. 8: a sample
1
co-chromatographed with and had an identical H NMR to an
12,13-Dioxo-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-
butylphenyl)chlorin 13
authentic sample.
Potassium carbonate (100 mg, 0.72 mmol) was added to a solution
of 8 (95 mg, 0.088 mmol) in a dichloromethane : methanol
mixture (1 : 1) (18 cm3) under argon. The suspension was stirred
at room temperature in the dark for 6 h. Ether (20 cm3) and
water (10 cm3) were added to the reaction mixture. The organic
layer was separated, dried over anhydrous sodium sulfate, filtered,
and the solvent was removed. Dess–Martin periodinane (DMP)
(37 mg, 0.088 mmol) was added to a solution of the crude 2-
hydroxy-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)porphyrin in
dichloromethane (15 cm3). The reaction mixture was stirred at
room temperature in the dark under argon for 1 h before a second
aliquot of DMP (37 mg, 0.088 mmol) was added. The reaction
mixture was stirred for a further 0.5 h and then filtered through
a plug of silica gel using dichloromethane as the eluent. The
filtrate was collected and the solvent was removed. The residue
was purified by preparative thin layer chromatography using a
dichloromethane : light petroleum mixture (1 : 2) as eluent to give
13 (67 mg, 72%), a sample of which co-chromatographed with
[Rf (light petroleum–dichloromethane; 2 : 1) = 0.17] and had an
identical 1H NMR to an authentic sample.19
2,3,12,13-Tetraoxo-5,10,15,20-tetrakis(3,5-di-tert-
butylphenyl)bacteriochlorin 15
Method (i) via compound 10. Potassium carbonate (50 mg,
0.36 mmol) was added to a solution of 10 (50 mg, 0.042 mmol)
in a dichloromethane : methanol mixture (1 : 1) (14 cm3) under
argon. The suspension was stirred at room temperature in the
dark for 6 h. Ether (10 cm3) and water (10 cm3) were added to
the reaction mixture. The organic layer was separated, dried over
anhydrous sodium sulfate and filtered. The solvent was removed
and the crude 2,12/13-dihydroxy-5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-
tert-butylphenyl)porphyrin was dissolved in dichloromethane
(15 cm3). DMP (36 mg, 0.085 mmol) was added and the reaction
mixture was stirred at room temperature in the dark under argon
for 1 h. Another portion of DMP (36 mg, 0.085 mmol) was then
added and the reaction mixture was stirred for a further 0.5 h. The
reaction mixture was then filtered through a plug of silica using
dichloromethane as the eluent. The filtrate was collected and the
solvent was removed. The residue was purified by preparative thin
layer chromatography using a dichloromethane : light petroleum
mixture (1 : 2) as eluent to give 15 (22 mg, 47%), a sample of which
co-chromatographed with [Rf (light petroleum–dichloromethane;
2-Acetoxy-12,13-dioxo-5,10,15,20-tetrakis(3,5-di-tert-
butylphenyl)chlorin 14
1
1 : 1) = 0.42] and had an identical H NMR to the authentic
sample.20
To a solution of 13 (50 mg, 0.046 mmol) in a chloroform : acetic
acid mixture (1 : 1) (10 cm3) were added silver acetate (26 mg,
0.16 mmol) and iodine (26 mg, 0.10 mmol). The reaction mixture
was stirred at room temperature in the dark under argon for 4 h and
then poured into a saturated aqueous sodium bicarbonate solution
(30 cm3). Solid sodium bicarbonate was added until the pH =
8. The aqueous layer was extracted with dichloromethane (3 ×
5 cm3). The combined organic layers were dried over anhydrous
sodium sulfate, filtered, and then the solvent was removed. The
residue was purified by column chromatography over silica using
a dichloromethane : light petroleum mixture (gradient from 1 :
3 to 2 : 3) as eluent to give 14 (24 mg, 46%) and the starting
Method (ii) via compound 14. Potassium carbonate (25 mg,
0.18 mmol) was added to a solution of 14 (25 mg, 0.022 mmol) in
a dichloromethane : methanol mixture (1 : 1) (10 cm3) under argon.
The suspension was stirred at room temperature in the dark for 6 h.
Ether (10 cm3) and water (5 cm3) were added and the organic layer
was separated, dried over anhydrous sodium sulfate, and filtered.
The solvent was removed and the crude 2-hydroxy-12,13-dioxo-
5,10,15,20-tetrakis(3ꢀ,5ꢀ-di-tert-butylphenyl)chlorin was dissolved
in dichloromethane (2 cm3). DMP (9.0 mg, 0.022 mmol) was
added and the reaction mixture was stirred at room temperature
in the dark under argon for 0.5 h. Another portion of DMP
(9.0 mg, 0.022 mmol) was added and the reaction mixture was
stirred for a further 0.5 h. The mixture was filtered through a
plug of silica using dichloromethane as the eluent. The filtrate was
collected, the solvent was removed, and the residue was purified by
preparative thin layer chromatography using a dichloromethane :
light petroleum mixture (1 : 2) as eluent to give 15 (10 mg, 41%),
a sample of which co-chromatographed with and had an identical
1H NMR to an authentic sample.20
◦
material 8 (9 mg, 18%). 14: green solid, mp >280 C; found: C,
81.2%; H, 8.1%; N, 4.8%; C78H94N4O4 requires C, 81.35%; H,
8.2%; N, 4.9%; mmax (KBr)/cm−1 1767 (C O), 1728 (C O); kmax
(CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 389sh (5.06), 406 (5.32),
475 (4.35), 546sh (3.84), 613 (3.76), 673sh (3.70), 709sh (3.68),
=
=
1
781 (3.25); H NMR (400.1 MHz; CDCl3) d: −2.13 (1H, br s,
NH), −2.06 (1H, br s, NH), 1.48, 1.485, 1.50, and 1.52 (72H,
ꢀ
ꢀ
4 × s, t-butyl H), 1.76 (3H, s, CH3COO), 7.71 (2H, d, J4 ,2
=
=
J4 ,6 = 1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 7.72 (2H, d, J4 ,2 = J4 ,6
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
2,12/13-Dichloro-5,10,15,20-tetraphenylporphyrin 7
1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 7.74 (2H, dd, J2 ,4 = J6 ,4 = 1.5 Hz,
ꢀ
ꢀ
ꢀ ꢀ
C(4ꢀ)H), 7.75 (2H, dd, J2 ,4 = J6 ,4 = 1.5 Hz, C(4ꢀ)H), 7.90 (2H,
A solution of iodine monochloride in dichloromethane (1 M,
0.41 cm3, 0.41 mmol) was added to a solution of 5,10,15,20-
tetraphenylporphyrin 6 (100 mg, 0.16 mmol) in chloroform
(10 cm3) heated at reflux. After 2 h a further aliquot of iodine
monochloride in dichloromethane (1 M, 0.41 cm3, 0.41 mmol) was
ꢀ
ꢀ
ꢀ ꢀ
d, J4 ,2 = J4 ,6 = 1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.00 (2H, d, J4 ,2
=
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
J4 ,6 = 1.5 Hz, C(2ꢀ)H and C(6ꢀ)H), 8.37 (1H, s, C(3)H), 8.53 (1H,
ꢀ
ꢀ
dd, Jb,b = 5.0 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 8.56 (1H, dd,
Jb,b = 5 Hz, JNH,b = 1.5 Hz, b-pyrrolic H), 8.62 (1H, dd, Jb,b
=
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 879–886 | 885
©

added. The reaction mixture was heated at reflux for a further 2 h
and was then allowed to cool to room temperature. Saturated aque-
ous sodium thiosulfate (20 cm3) was added and the organic layer
was separated. The organic layer was washed with saturated aque-
ous sodium thiosulfate solution (20 cm3), dried over anhydrous
sodium sulfate, filtered, and the solvent was removed. The residue
was purified by column chromatography over silica using a chloro-
form : light petroleum mixture (from 1 : 3 to 1 : 2) as eluent to give
7 (51 mg, 46%) and 4 (23 mg, 23%). 7: purple solid, mp >300 ◦C;
found: C, 77.2%; H, 4.1%; N, 8.2%; C44H28Cl2N4 requires C, 77.3%;
H, 4.1%; N, 8.2%; kmax (CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 269
(4.10), 313 (4.11), 371sh (4.49), 421 (5.49), 488sh (3.48), 519 (4.29),
553 (3.61), 593 (3.71), 649 (3.72); 1H NMR (400.1 MHz; CDCl3) d:
−2.96 (2H, br s, NH), 7.71–7.82 (12H, m, meso-phenyl H), 8.08–
8.10 (4H, m, meso-phenyl H), 8.17–8.20 (4H, m, meso-phenyl H),
8.66 and 8.67 (2H, 2 × s, C(3)H and C(12)H/C(13)H), 8.78 and
8.91, and 8.82 and 8.85 (4H, comprised of 2 × br s {8.78 and 8.91}
and a tight ABq {8.82 and 8.85}, JA,B = 5 Hz, b-pyrrolic H); m/z
(ESI-TOF) 683.2 (100%); C44H28Cl2N4H+ (MH+) requires 683.7
(100%); Rf (light petroleum–dichloromethane; 2 : 1) = 0.21. 4: a
sample co-chromatographed with and had an identical 1H NMR
to an authentic sample.
b-pyrrolic H), 8.89 and 8.92 (2H, ABq, JA,B = 5 Hz, b-pyrrolic
H); m/z (ESI-TOF) 673.2 (100%); C46H32N4O2H+ (MH+) requires
673.8 (100%); Rf (light petroleum–dichloromethane; 2 : 3) = 0.16.
Conclusion
In conclusion we have shown that pseudohalogens can be used to
regiospecifically introduce functional groups onto the porphyrin b-
pyrrolic positions. The mechanism of addition most likely occurs
via a single electron transfer process and can be used to attach
chloro, nitro and acetoxy groups. The acetoxylation procedure
gives a new simple methodology for the preparation of chlorin-a-
diones and bacteriochlorin-tetraones in good yield.
Acknowledgements
We thank the Overseas Research Student Awards Scheme, EPSRC
and Merck Ltd for funding. Professor Paul Burn is the recipient
of an Australian Research Council Federation Fellowship (project
number FF0668728). We also thank B. Langley for the journal
cover design.
References
2-Acetoxy-5,10,15,20-tetraphenylporphyrin 11
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To a solution of 5,10,15,20-tetraphenylporphyrin 6 (100 mg,
0.16 mmol) in chloroform (10 cm3) were added silver acetate
(50 mg, 0.30 mmol) and iodine (50 mg, 0.20 mmol). The reaction
mixture was stirred at room temperature in the dark under argon
for 1.5 h and was then treated with a further aliquot of silver
acetate (50 mg, 0.30 mmol) and iodine (50 mg, 0.20 mmol). Half
an hour later, the mixture was filtered through a short plug of silica
gel using dichloromethane as the eluent. The filtrate was collected,
the solvent was removed, and the residue was purified by column
chromatography over silica using a chloroform : light petroleum
(gradient from 1 : 2 to 2 : 1) as eluent to give 12 (6 mg, 5%), 6
(43 mg, 43%) and 11 (35 mg, 32%). 12: purple solid, mp >300 ◦C;
found: C, 71.3%; H, 4.0%; N, 7.7%; C44H29IN4 requires C, 71.4%;
H, 4.0%; N, 7.6%; kmax (CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 250
(4.26), 273 (4.23), 308 (4.38), 403sh (5.06), 421 (5.66), 487 (3.58),
518 (4.38), 552 (3.79), 593 (3.80), 649 (3.74); 1H NMR (400.1 MHz;
CDCl3) d: −2.79 (2H, br s, NH), 7.75–7.85 (12H, m, meso-phenyl
H), 8.11–8.13 (2H, m, meso-phenyl H), 8.21–8.24 (6H, m, meso-
phenyl H), 8.77 and 8.79 (2H, tight ABq, JA,B = 5 Hz, b-pyrrolic
H), 8.84 and 8.86 (2H, tight ABq, JA,B = 5 Hz, b-pyrrolic H), 8.90
and 8.92 (2H, tight ABq, JA,B = 5 Hz, b-pyrrolic H), 9.16 (1H, s,
C(3)H); m/z (ESI-TOF) 741.1 (100%); C44H29IN4H+ (MH+)
requires 741.2 (100%); Rf (light petroleum–dichloromethane; 2 :
1) = 0.14. 6: a sample co-chromatographed with and had an
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1
identical H NMR to an authentic sample. 11: purple solid, mp
18 M. J. Crossley and J. A. McDonald, J. Chem. Soc., Perkin Trans. 1,
1999, 2429.
>300 ◦C; found: C, 82.0%; H, 4.7%; N, 8.2%; C46H32N4O2 requires
C, 82.1%; H, 4.8%; N, 8.3%; mmax (KBr)/cm−1 1755 (C O); kmax
19 P. L. Burn, R. Beavington and P. A. Rees, J. Chem. Soc., Perkin Trans.
=
1, 1998, 2847.
(CH2Cl2)/nm (log(e/dm−3 mol−1 cm−1)) 249 (4.17), 273 (4.15), 306
(4.15), 374sh (4.48), 417 (5.64), 484 (3.53), 514 (4.30), 549 (3.82),
589 (3.77), 644 (3.57); 1H NMR (400.1 MHz; CDCl3) d: −2.83 (2H,
br s, NH), 1.87 (3H, s, CH3COO), 7.75–7.79 (12H, m, meso-phenyl
H), 8.14–8.16 (2H, m, meso-phenyl H), 8.22–8.25 (6H, m, meso-
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phenyl H), 8.58 (1H, s, C(3)H), 8.71 and 8.87 (2H, ABq, JA,B
5 Hz, b-pyrrolic H), 8.81 and 8.82 (2H, tight ABq, JA,B = 5 Hz,
=
886 | Org. Biomol. Chem., 2008, 6, 879–886
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