Simple porphyrin desymmetrization: 5,10,15,20-tetrakis(3-hydroxyphenyl) porphyrin (mTHPP) as a gateway molecule for peripheral functionalization

Article abstract of DOI:10.1002/ejoc.201402433

The rise in the demand of unsymmetrical porphyrin systems for applications such as photodynamic therapy and nonlinear optics mandates a concomitant development of simple and practical synthetic approaches. A new method for the rapid generation of unsymmetrical porphyrins from the same common and easily accessible symmetric porphyrin starting material is discussed herein. A library of unsymmetric mTHPP [5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin] derivatives were synthesized in good yields through simple nucleophilic substitution, esterification, and metal-catalyzed cross-coupling reactions. This method was optimized to generate a library of customized unsymmetrical porphyrins quickly for use in a variety of applications. A common meso-aryl-substituted porphyrin as the starting material was used to update the synthetic toolkit through a mixture of classical and modern chemistry. This approach was studied as an approach to the synthesis of picket fence porphyrin mimics and afforded such compounds in good yields with few synthetic steps. In addition, employing simple nucleophilic substitution chemistry was employed to access cofacial caged bis(porphyrin) systems in two synthetic steps. Copyright

Full text of DOI:10.1002/ejoc.201402433

FULL PAPER
DOI: 10.1002/ejoc.201402433
Simple Porphyrin Desymmetrization: 5,10,15,20-Tetrakis(3-hydroxyphenyl)-
porphyrin (mTHPP) as a Gateway Molecule for Peripheral Functionalization
Luke Rogers,[a] Emeralda Burke-Murphy,[a] and Mathias O. Senge*[a]
Keywords: Porphyrinoids / Nitrogen heterocycles / Macrocycles / Nucleophilic substitution / Cross-coupling
The rise in the demand of unsymmetrical porphyrin systems
for applications such as photodynamic therapy and nonlinear
optics mandates a concomitant development of simple and
practical synthetic approaches. A new method for the rapid
generation of unsymmetrical porphyrins from the same com-
mon and easily accessible symmetric porphyrin starting ma-
terial is discussed herein. A library of unsymmetric mTHPP
[5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin] derivatives
were synthesized in good yields through simple nucleophilic
substitution, esterification, and metal-catalyzed cross-cou-
pling reactions. This method was optimized to generate a li-
brary of customized unsymmetrical porphyrins quickly for
use in a variety of applications. A common meso-aryl-substi-
tuted porphyrin as the starting material was used to update
the synthetic toolkit through a mixture of classical and mod-
ern chemistry. This approach was studied as an approach to
the synthesis of picket fence porphyrin mimics and afforded
such compounds in good yields with few synthetic steps. In
addition, employing simple nucleophilic substitution chemis-
try was employed to access cofacial caged bis(porphyrin) sys-
tems in two synthetic steps.
tion approach that heavily relies on organometallic cou-
pling reactions and the preparation of the required coupling
partners are not trivial.[7,8]
Introduction
Since their discovery by Rothemund in 1935, symmetric
meso-aryl-substituted porphyrins have been the workhorses
of porphyrin chemistry, as they can be easily prepared in
high yielding one-pot reactions on a multigram scale.[1]
However, most applications such as photodynamic therapy
(PDT),[2] nonlinear optics (NLO),[3] solar energy conver-
sion,[4] and photosynthetic reaction center mimics[5] call for
unsymmetric porphyrin derivatives such as amphiphilic sys-
tems for PDT or push-pull systems for energy transfer and
optical studies. In the last decades, there have been vast im-
provements in the synthesis of unsymmetrical porphyrins
through either a total synthesis approach,[6] [2+2] or [3+1]
condensation reactions, or functionalization reactions. Es-
pecially the last two approaches, which were exemplified by
Lindsey’s large-scale syntheses[6b–6d] and our functionaliza-
tion approach for ABCD-type porphyrins[7] amongst
others, have found widespread use in the synthetic com-
munity. Drawbacks to these routes are the obvious plethora
of steps and synthetic manipulations that are needed to
yield the desired bilane as well as the ongoing problem of
the acid-catalyzed scrambling that is observed in the final
step of the total syntheses.[6e] Similarly, the functionaliza-
However, within reason, almost any desired meso-substi-
tuted porphyrin is now synthetically accessible through
these methods. Yet, in practical terms, the most widely used
approach is still a mixed pyrrole condensation. This syn-
thetic pathway has drawbacks that include tedious chroma-
tographic steps and low yields, and it cannot deliver the
plethora of unsymmetrical porphyrins that are necessary to-
day. Nowadays, the field of porphyrins is driven by applica-
[a] SFI Tetrapyrrole Laboratory, School of Chemistry, Trinity
Biomedical Sciences Institute,
152-160 Pearse Street, Trinity College Dublin, Dublin 2, Ireland
E-mail: sengem@tcd.ie
http://chemistry.tcd.ie/staff/people/mos/main%20index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402433.
Figure 1. Controlled functionalization of A4 porphyrins for the
synthesis of ABCD-type porphyrins.
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L. Rogers, E. Burke-Murphy, M. O. Senge
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tion-oriented research with significant contributions from
The starting point of the synthesis began with the re-
materials scientists and inorganic, physical, and medicinal quired alkyne source, which would be amenable to nucleo-
chemists who lack the synthetic capabilities that are neces- philic substitution reactions, and, thus, we chose propargyl
sary for the more involved syntheses. Thus, there is a press- bromide. The first difficulty that we encountered involved
ing need for simple and technically facile syntheses for un- the four equivalent phenol groups in mTHPP and the pos-
symmetrically substituted porphyrins. We herein report one sibility to maximize the yield of monosubstituted product
such approach, which relies on the monofunctionalization but limit the production of higher order reaction products.
of symmetric A4 porphyrins by using simple substitution By treating compound 2 with 5 equiv. of propargyl bromide
chemistry (see Figure 1).
for 5 h in the presence of K2CO3, we were successful in the
selective monofunctionalization of this porphyrin in 18%
yield (see Scheme 1). The alkynyl moiety of 4 then served
as a synthetic handle, upon which we could use a modified
Huisgen cycloaddition reaction[12a] between a bile acid
azide and, in this case, a terminal alkyne to give a 1,2,3-
triazole.[12b]
Results and Discussion
Synthetic Concept and Background
Our approach emerged from our interest in advancing
photodynamic cancer therapy (PDT) for esophageal cancer
through the synthesis of dual modality photosensitizers
(PS).[9] In this context, we wanted to conjugate a mono-
alkynyl-substituted porphyrin to a bile acid azide through
Optimization
Although a yield of 18% was sufficient to obtain enough
a click reaction to form a library of potential photosensitiz- material for the necessary click reaction, we next probed
ers. Instead of embarking on a long synthesis that employed the possibility of increasing the reaction yield through the
methods previously mentioned for the synthesis of a optimization of different reaction parameters. Keeping
monoalkynyl-porphyrin, we used a known porphyrin PS as DMF as the solvent, we first screened a series of weak
the core scaffold, upon which we could conjugate a number bases, and, as a result, K2CO3 gave the most satisfactory
of different biologically active bile acids.[10] The immediate yields. We then hoped that by using a stronger base, it
candidate of interest was 5,10,15,20-tetrakis(3-hydroxy- would be possible to reduce the amount of higher order
phenyl)chlorin (mTHPC, 1), an approved second generation substituted products in the crude reaction mixture and,
PS.[11] For synthetic ease, we first focused on the prep- therefore, drive the production of monofunctionalized ma-
aration of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin terial and ease the purification workload. Examples of this
(mTHPP, 2), the parent compound to mTHPC, which is a have been reported with regard to alkyl diol compounds,
highly soluble symmetric porphyrin and also a potent pho- which would normally give a statistical mixture of isomers
tosensitizer.[11c]
during attempts to obtain the monofunctionalized prod-
Interestingly, little research has been conducted into the uct.[13] The dianionic species that is formed when NaH is
controlled functionalization of tetrasubstituted hydroxypor- used as the base showed a statistical bias towards the func-
phyrins, which can be synthesized in multigram quantities. tionalization of only one hydroxy group in approximately
Our plan was to use 2 as a preformed porphyrin scaffold, 90%. A number of bases were screened, but K2CO3 and
through which we could selectively install a variety of func- NaH gave the best results for the reaction of 2 and prop-
tional groups by using inexpensive, simple, and reliable argyl bromide (see Table 1). Tests of different solvents indi-
chemistry. Once a library was generated, we then intended cate that DMF greatly outperformed other candidates, and
to synthesize a number of unsymmetrical porphyrins that although it can be difficult to remove in workup, its supe-
would be tailored for a variety of applications, in particular rior yields far outweighed this drawback. The final factors
PDT.
to be optimized were reaction time and temperature. The
Scheme 1. Monofunctionalization of mTHPC (1) and mTHPP (2, DMF = N,N-dimethylformamide).
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Simple Porphyrin Desymmetrization
studied reactions employed both optimized bases and prop- derivatives were observed by TLC and confirmed by
argyl bromide over a number of different time frames, and HRMS analysis, however, their syntheses and isolation have
a reaction time of 2 h was the best to monofunctionalize not been optimized within this current project. This demon-
mTHPP. TLC analysis proved extremely reliable as an ana- strates the potential for a pathway to obtain complicated
lytic tool, as each reaction consistently gave a predictable unsymmetrical porphyrin systems in high yields, on both
separation pattern.
small and large scales, with inexpensive and accessible start-
ing materials.
Table 1. Optimization of the monofunctionalization of 2 with pro-
pargyl bromide.
Entry
Base
Equiv. Solvent Time [h] Temp. Yield 3 [%]
Substrate Scope
1
2
3
4
5
6
7
8
K2CO3
K3PO4
TEA[a]
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaH
5
5
5
5
5
5
4
2
DMF
DMF
DMF
DCM[a]
dioxane
EtOAc
DMF
DMF
DMF
DMF
DMF
DMF
5
5
5
5
5
5
3
2
2
2
3
2
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50 °C
r.t.
18
14
15
–
–
2
35
48
15
45
23
15
To expand the scope of this synthetic methodology, a
library of reactants were selected that were amenable to nu-
cleophilic substitution chemistry but also contained a
chemically distinct functional group to use in a subsequent
functionalization reaction. A clear starting point to investi-
gate the robustness of this method involved the installation
of simple aryl or alkyl chains onto the parent mTHPP. Test
reactions were carried out using 1-iodopropane and benzyl
chloride (for conditions, see Table 1, Entry 10). These reac-
tions successfully afforded monofunctionalized porphyrin
products 6a and 7a, in 35 and 44% yield, respectively, and
again, by altering the reaction time and equivalents, higher
order substituted products could be obtained in good
yields. For example, the tetrasubstituted product could be
obtained in quantitative yields (see Table 2).
Next, we examined the reactivity of compounds with
other substituents present on the aryl ring, which, once in-
stalled onto mTHPP, could undergo subsequent metal-cata-
lyzed reactions. 4-Bromobenzyl bromide and 4-nitrobenzyl
bromide were chosen as suitable reagents to study the effect
that peripheral substituents had on the reaction rate and
yield. Monosubstituted derivatives 8a and 9a were isolated
in 43 and 35% yield, respectively, to indicate that there was
a high tolerance for different electronic substituents on the
aryl ring. Next, we examined the controlled esterification of
the peripheral OH groups. To investigate this, we used 2-
bromobenzoic acid and benzoic anhydride under various
reaction conditions. Most attempts failed, however, to pro-
duce significant amounts of the functionalized mTHPP.
Ultimately, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
(EDC) and 1-hydroxybenzotriazole (HOBt) were used to
produce 10a and 11a in yields of 40 and 37%, respectively.
Again, the tetrafunctionalized derivatives 10b and 11b
could be obtained in excellent yield. This creates the pos-
sibility to conjugate a myriad of biologically interesting
moieties such as sugars, bile acids, and beta-lactams, as the
carboxylic acid functional group is present in many bio-
logical molecules, to a symmetric porphyrin through a sim-
ple esterification reaction.
9
0.5
1
1
10
11
12
NaOH
r.t.
r.t.
superbase[b]
1
[a] TEA = triethylamine, DCM = dichloromethane. [b] Superbase:
2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane.
The optimized conditions for the monofunctionalization
of mTHPP with propargyl bromide included 1 equiv. of
NaH as the base with 2 equiv. of propargyl bromide in
DMF at room temperature for 2 h, which resulted in 45%
yield of the product and 30% of recovered starting material.
Although sodium hydride gave a slightly lower yield than
K2CO3, it was selected as the preferred option, as it pro-
duced minimal quantities of the higher substituted com-
pounds.
Higher substituted compounds were available by em-
ploying longer reaction times and increasing the equivalents
of K2CO3 and propargyl bromide. Tetrasubstituted product
5 was synthesized in near quantitative yield, with the di-
and trisubstituted species available in yields similar to that
of the monofunctionalized derivative. These yields, how-
ever, have not been optimized. The results indicate that one
can maximize the output of mono-, di-, tri-, and tetrasub-
stituted mTHPP by varying the reaction time, equivalents
of reagents, and employed base. The di- and trisubstituted
Next, we expanded this methodology to more modern
chemistry, such as metal-catalyzed cross coupling reactions.
Two of the more appealing approaches were the direct
metal-catalyzed coupling of the heteroatom to a substrate
or the transformation of an OH group into a functionality
that is susceptible to classic palladium-catalyzed reactions,
such as the Suzuki–Miyaura cross-coupling reaction.
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Table 2. Monofunctionalization of mTHPP (2) with a variety of different substrates.
Product
Reagent
Base
Equiv. Time [h] % Yield, mono (a)
Base
Equiv.
Time [h] % Yield tetra (b)
6
7
8
9
10
11
1-iodopropane
4-benzyl chloride
4-bromobenzyl bromide
4-nitrobenzyl bromide
2-bromobenzoic acid
benzoic anhydride
NaH
NaH
NaH
NaH
NaH
NaH
1
1
1
1
1
1
2
2.5
2
3
3
35
44
43
35
40
37
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
10
10
12
10
12
12
13
13
13
15
18
5
95
95
96
93
59
92
1
tionalized in a controlled manner in a similar fashion to the
nucleophilic substitution reactions.
Triflate and Tosylate Derivatives
Recent and classical publications have shown the capa-
However, reactions that used the optimized conditions
bility of triflate and tosylate groups to react in metal-cata- for the base K2CO3 produced very low yields of product
lyzed cross-coupling reactions under a variety of different by using both the triflate and tosylate reagents. Yet, upon
conditions and with a number of different catalysts.[14] The changing the base to pyridine, both trifluoromethanesul-
most widely known of these uses the triflate group in Su- fonyl chloride and 4-toluenesulfonyl chloride gave por-
zuki–Miyaura coupling reactions. To this end, we used pre- phyrins 12a and 13a in 37 and 35% yield, respectively.
viously optimized conditions to synthesize a range of “acti- Again, by increasing the equivalents of reagent and base,
vated” mTHPP derivatives, which could be selectively func- the tetrafunctionalized derivatives were obtained in excel-
Scheme 2. Controlled installation of tosyl and triflyl groups.
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Simple Porphyrin Desymmetrization
lent yields (for 12b, 92% yield and for 13b, 90% yield; see
Scheme 2).
First, zinc(II) porphyrin 14[12b,18] was treated with phen-
ylboronic acid in dioxane at room temperature. After stir-
ring for 18 h, TLC showed the formation of 15 as the major
product (39% yield) and two faint, closely running spots,
which turned out to be the two disubstituted species.[19] Af-
ter this first example of a Chan–Lam coupling being ap-
plied to a porphyrin system, (4-cyanophenyl)boronic acid
and (3-methoxyphenyl)boronic acid, as examples of systems
that are amenable to postfunctionalization reactions, were
tried as well. These reactions proceeded without any diffi-
culties, and monofunctionalized species 16 and 17 were syn-
thesized in 35 and 37% yield, respectively (see Table 3). All
three boronic acids produced satisfactory yields. As de-
scribed in the literature, this reaction seems to be tolerant
of a variety of substrates under mild reaction conditions.
This provides another synthetic pathway to unsymmetri-
cal porphyrins by using a basic, readily available symmetric
porphyrin. Boronic acids are easily installed into com-
pounds through standard synthetic methodology, and,
therefore, they present the potential for a wide variety of
molecules to be conjugated to these porphyrins. Although
the reactions above expand the synthetic toolkit for por-
phyrins, a demonstration of their practical utility in the syn-
thesis of unsymmetrical porphyrins or more complicated
systems might be warranted. Somewhat arbitrarily, we
chose picket fence porphyrins and cofacial bis(porphyrin)s
as case materials.
Chan–Lam Coupling
A number of reactions have been developed that involve
a hydroxy functional group undergoing a reaction with an-
other specific substrate in the presence of a metal. Examples
include the Buchwald–Hartwig reaction,[15] the Ullmann re-
action[16] and the Chan–Lam reaction.[17] After some initial
tests, the Chan–Lam reaction showed the most promising
results in terms of yield, reaction conditions, and purifica-
tion. The reaction involves the use of copper(II) acetate, a
boronic acid, and a hydroxy or amine functionality. It is a
versatile reaction, as it can proceed in a number of different
solvents, at room temperature, and in an open reaction ves-
sel. The reaction uses a stoichiometric amount of copper,
and, hence, metalloporphyrins were used to avoid copper
insertion. By using a metal-catalyzed reaction, we hoped
that we could achieve greater selectivity for the monosubsti-
tuted porphyrin with higher order substitution products as
only minor side products.
Table 3. Results of the Chan–Lam coupling reactions of 14 with
boronic acids (R1 = phenyl, 3-cyanophenyl, 3-methoxyphenyl).
Case Study 1 – Picket Fence Porphyrin
Picket fence porphyrins are a classic example of the im-
pact of biomimetic model compounds. They were in vogue
for many years ever since their synthesis by Collman et al.
in the 1970s,[20] as they provided researchers the first syn-
thetic model with which to investigate the binding of O2 in
heme proteins. Large libraries of these picket fence por-
phyrins were synthesized, but depending on the route se-
lected, their syntheses required a large number of steps,
challenging chromatographic purifications, and low yields.
We began with the synthesis of simple tetrasubstituted
porphyrins as examples of picket fence porphyrins. For ex-
ample, 2 was treated with 4-tert-butylbenzyl bromide or 1-
iodohexane under the optimized conditions to give por-
phyrins 18 and 19 (see Scheme 3). These reactions pro-
ceeded to give product in quantitative yield, however, sys-
tems such as these can also be easily prepared through con-
densation methods. For a more complicated example, we
targeted the related A3B-type porphyrins. By reducing the
equivalents and reaction times, we were able to synthesize
trisubstituted species from both 4-tert-butylbenzyl bromide
and 1-iodohexane in yields of 37 and 40%, respectively.
Once the trisubstituted species 20 was isolated from the
reaction mixture, the final free OH group was subjected to
a reaction with propargyl bromide. This reaction proceeded
in high yield and produced the stable picket fence porphyrin
mimic 22, that is, an A3B-type porphyrin with two different
“fence types”. Thus, by taking 2 as the starting material, a
Product Boronic acid
Equiv. Time [h] % Yield,
mono
15
16
17
phenylboronic acid
(3-cyanophenyl)boronic acid
(3-methoxyphenyl)boronic acid
1
1
2
13
18
13
39
35
37
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Scheme 3. Synthesis of picket fence porphyrins through new optimized procedure.
synthetically difficult class of porphyrin was produced in Case Study 2 – Cofacial Bis(porphyrin)s
two steps by using simple and cost-effective chemistry in far
greater yields than the alternative mixed condensation or
Other examples of porphyrin systems that are frequently
total synthesis route. By applying this approach to used in model studies are porphyrin arrays and, notably,
oTHPP,[21] the synthesized compounds could potentially cofacial bis(porphyrin)s. These serve as metalloenzyme[4a,22]
undergo a resolution of the atropisomers to afford the or special pair mimics in photosynthesis[23] and are suitable
α,α,α,α-derivative, that is, a true picket fence porphyrin.
models for multielectron redox reactions. Many of these re-
Scheme 4. Synthesis of the cofacial bis(porphyrin) cage 25.
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Simple Porphyrin Desymmetrization
General Procedure A. Microwave-Assisted Condensation of mTHPP
2:[18] Propionic acid (3.5 mL) and nitrobenzene (1.5 mL) were
added to a Pyrex Erlenmeyer flask (100 mL). Pyrrole (0.74 mL)
and 3-hydroxybenzaldehyde (1 mL) were added, and the reaction
vessel was sealed with hydrophilic cotton wool to prevent spillage
and, most importantly, avoid the buildup of pressure that is associ-
ated with the risk of a hazardous explosion. The yellowish reaction
mixture was placed at the center of the rotating plate in the micro-
wave oven and heated for 5 min (1 min periods intercalated by
3 min intervals with the power off to avoid overheating) at 640 W.
quire lengthy syntheses, can typically contain unstable
amide linker groups, and suffer from low yields. We wish to
extend the previously developed approach and apply it to
the synthesis of cofacial porphyrin cages.[24] By using alkyl
chains, we hoped that a degree of flexibility could be im-
parted into the cage system to enable the molecule to adopt
the optimum metal-metal distance that is needed for cata-
lytic activity or substrate binding. The synthesis proceeded
again with 2 as the starting material. Treating 2 with an
excess amount of 1,4-dibromobutane with K2CO3 as the The reaction was monitored over time by UV/Vis absorption spec-
troscopy. To the cooled crude reaction mixture was added MeOH,
and the resulting mixture was filtered. The filtrate was evaporated
under reduced pressure, and the resulting residue was dissolved in
ethyl acetate. Purification by flash chromatography on a silica gel
column (ethyl acetate/CH2Cl2, 1:1 v/v) gave a red fraction, which
was collected and recrystallized (ethyl acetate/n-hexane) to yield 2
(22% yield).
base afforded tetrasubstituted compound 24 in near quanti-
tative yield. The resultant primary alkyl bromide can again
undergo a simple nucleophilic substitution reaction with
1 equiv. of [5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin-
ato]cobalt(II) [CoIImTHPP, 24] to afford cofacial bis(por-
phyrin) 25 with a free base and cobalt(II) porphyrin unit in
a yield of 12% (see Scheme 4).[25]
General Procedure B. Monofunctionalization of mTHPP: mTHPP
(1 equiv.) was added to a round-bottomed flask (100 mL), and
DMF (10 mL) and NaH (1 equiv.) were added. The reaction was
stirred for 30 min under argon, and then the appropriate function-
alization reagent (2–3 equiv.) was added. The mixture was moni-
tored by TLC, and once full conversion was observed, the reaction
was terminated by the addition of CH2Cl2 (50 mL). The crude reac-
tion mixture was washed with distilled water (1ϫ 30 mL), saturated
aqueous NaHCO3 (1ϫ 30 mL), brine (1ϫ 30 mL), and distilled
water (2ϫ 30 mL). The organic phase was dried with anhydrous
The use of a cobalt porphyrin to synthesize the cage was
to exemplify the ease to make potential four-electron cata-
lysts. This simple synthesis can be modified to incorporate
linkers of different lengths and types along with the ability
to include different metal systems. With the wide range of
versatility from this method, other applications such as the
synthesis of artificial photosynthetic reaction centers are
possible.[5d,23a] The obvious strength of this synthetic path-
way is the choice of almost any metal center for the por-
phyrin core along with the option of having mixed metal sodium sulfate, filtered and then evaporated under reduced pres-
sure. The crude products were typically purified by chromatography
on silica gel column (CH2Cl2/n-hexane/MeOH, 3:1:0.2).
centers or even cofacial free base versus metal porphyrins
along with a variety of different linkers, all of which are
examples of reduced symmetry cage systems. These histori-
cally difficult compounds can now be made in two steps by
using simple, inexpensive, and reliable chemistry.
General Procedure C. Di-, Tri- and Tetrafunctionalization of
mTHPP: mTHPP (1 equiv.) was added to a round-bottomed flask
(100 mL), and DMF (10 mL) and K2CO3 (5–20 equiv.) were added.
The reaction was stirred for 30 min under argon, and then the ap-
propriate functionalization reagent (10–20 equiv.) was added. The
mixture was monitored by TLC, and once full conversion to the
desired degree of substitution was observed, the reaction was ter-
minated by the addition of CH2Cl2 (50 mL). The workup pro-
ceeded as described in general procedure B.
Conclusions
A library of monosubstituted mTHPP derivatives could
be successfully prepared through a number of simple reac-
tions pathways. By using historic phenolic chemistry, com-
pounds were synthesized through nucleophilic substitution,
esterification, and OH activation reactions. This chemistry
was updated for porphyrins by using the recently discovered
Chan–Lam copper-catalyzed coupling of a heteroatom with
a boronic acid. This allowed for the synthesis of some sim-
ple, unsymmetrical porphyrin systems and demonstrated
the ease with which one can quickly generate historically
cumbersome compounds such as picket fence and cofacial
porphyrins in few synthetic steps. Although this is certainly
not a “conditio sine qua non” for the optimum preparation
of unsymmetrical porphyrins, it presents a rapid, robust,
and cost-effective strategy for the synthesis of a variety of
soluble, unsymmetrical porphyrins that can be fine-tuned
for a plethora of applications by starting from one symmet-
ric parent porphyrin molecule.
General Procedure D. Chan–Lam Coupling of mTHPP: mTHPP
(1 equiv.) was added to a round-bottomed flask (100 mL), and di-
oxane (10 mL), CuII(OAc)2 (2 equiv.), boronic acid (2 equiv.), and
pyridine (0.2 mL) were added. The mixture was monitored by TLC,
and once full conversion to the desired degree of substitution
was observed, the reaction was terminated by the addition of
CH2Cl2 (50 mL). The workup proceeded as described in general
procedure B.
5,10,15,20-Tetrakis[3-(prop-2-yn-1-yloxy)phenyl]porphyrin (5): The
compound was synthesized by following general procedure C. A
50 mL round-bottomed flask that contained DMF (10 mL), 2
(400 mg, 0.59 mmol), K2CO3 (815 mg, 5.9 mmol), and propargyl
bromide (0.45 mL, 5.9 mmol) was stirred for 5 h to give 5 (392 mg,
0.472 mmol, 98% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.88
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz,
CDCl3, 25 °C): δ = –2.82 (br. s, 2 H, NH), 2.57 (s, 4 H, alkyne-H),
3
4.87 (s, 8 H, -CH2), 7.40 (d, JH,H = 7.81 Hz, 4 H, Ar-H), 7.65 (t,
Experimental Section
General Methods: The instrumentation and standard techniques
that were used are as reported.[26] Microwave reactions were carried
out with a Sharp El-254v microwave oven.
3JH,H = 7.81 Hz, 4 H, m-Ar-H), 7.85 (m, 8 H, Ar-H), 8.88 ppm (s,
8 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 56.1, 75.9,
78.6, 114.6, 119.6, 119.7, 121.4, 125.6, 127.6, 128.6, 133.8, 143.5,
143.51, 155.9, 157.2 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)]
Eur. J. Org. Chem. 2014, 4283–4294
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4289

L. Rogers, E. Burke-Murphy, M. O. Senge
FULL PAPER
= 419 [5.47], 512 [4.03], 546 [3.04], 590 [2.10], 646 [1.35] nm. HRMS
(MALDI): calcd. for C56H38N4O4 [M]+ 830.2893; found 830.2896.
[5.02], 515 [3.76], 547 [3.50], 590 [3.15], 647 [2.97] nm. HRMS
(MALDI): calcd. for C72H54N4O4 [M]+ 1038.4145; found
1038.4140.
5,10,15-Tris(3-hydroxyphenyl)-20-[(propoxy)phenyl]porphyrin (6a):
General procedure B was followed by using 2 (400 mg, 0.59 mmol),
NaH (14.2 mg, 0.59 mmol), and 1-iodopropane (0.12 mL,
1.2 mmol). The reaction was complete after 2 h to give 6a (149 mg,
0.32 mmol, 35% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.38
5-[3-(4-Bromobenzyloxy)phenyl]-10,15,20-tris(3-hydroxyphenyl)por-
phyrin (8a): General procedure B was followed by using 2 (400 mg,
0.59 mmol), NaH (14.2 mg, 0.59 mmol), and p-bromobenzyl brom-
ide (292 mg, 1.2 mmol). The reaction was complete after 2 h to give
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz, 8a (215 mg, 0.25 mmol, 43 % yield) as purple crystals; m.p.
CDCl3, 25 °C): δ = –2.88 (br. s, 2 H, NH), 0.87 (t, 3JH,H = 7.27 Hz, Ͼ300 °C. Rf = 0.2 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
3
3
3 H, -CH3), 1.87, (q, JH,H = 7.27 Hz, 2 H, -CH2), 4.08 (t, JH,H
=
NMR [400 MHz, (CD3)2SO, 25 °C]: δ = –2.98 (s, 2 H, -NH), 5.25
3
3
7.27 Hz, 2 H, OCH2), 7.17 (t, JH,H = 6.65 Hz, 3 H, Ar-H), 7.29
(s, 2 H, -CH2), 7.22 (d, 3JH,H = 7.73 Hz, 3 H, Ar-H), 7.42 (t, JH,H
(d, 3JH,H = 6.65 Hz, 1 H, Ar-H), 7.47 (t, 3JH,H = 6.65 Hz, 3 H, Ar-
= 7.73 Hz, 3 H, Ar-H), 7.57 (m, 12 H, Ar-H), 7.67 (t, JH,H
=
3
H), 7.61 (m, 7 H, Ar-H), 7.75 (m, 2 H, Ar-H), 8.79 (m, 2 H, Hβ), 7.73 Hz, 1 H, Ar-H), 7.76 (m, 1 H, Ar-H), 7.81 (m, 1 H, Ar-H),
8.85 (m, 6 H, Hβ) ppm. 13C NMR [100 MHz, (CD3)2SO2]: δ = 31.6,
36.6 69.7, 114.8, 119.7, 122.0, 127.1, 127.5, 126.2, 127.5, 154.6,
157.4, 162.7 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417
(5.02), 515 (3.76), 547 (3.50), 590 (3.13), 647 nm (2.95). HRMS
(MALDI): calcd. for C47H36N4O4 [M]+ 720.2737; found 720.2734.
8.77 (m, 2 H, Hβ), 8.88 (m, 6 H, Hβ), 9.87 (s, 3 H, -OH) ppm. 13C
NMR (150 MHz, CDCl3): δ = 69.1, 115.4, 115.5, 119.9, 120.3,
120.4, 121.4, 121.7, 122.3, 126.2, 128.1, 128.3, 128.4, 130.3, 131.9,
136.9, 142.8, 156.2, 156.9 ppm. UV/Vis (EtOAc): λmax [(log (ε/
m
–1 cm–1)] = 417 [5.40], 514 [4.07], 547 [3.67], 591 [3.58], 648
[3.47] nm. HRMS (MALDI): calcd. for C51H35BrN4O4 [M]+
846.1842; found 846.1861.
5,10,15,20-Tetra[(propoxy)phenyl]porphyrin (6b): General procedure
C was followed by using 2 (400 mg, 0.59 mmol), K2CO3 (815 mg,
5.9 mmol), and 1-iodopropane (0.6 mL, 5.9 mmol). The reaction
was complete after 13 h to give 6b (484 mg, 0.57 mmol, 95% yield)
as purple crystals; m.p. Ͼ300 °C. Rf = 0.95 (CH2Cl2/n-hexane/
5,10,15,20-Tetrakis[3-(4-bromobenzyloxy)phenyl]porphyrin (8b): Ge-
neral procedure C was followed by using 2 (400 mg, 0.59 mmol),
K2CO3 (815 mg, 5.9 mmol), and p-bromobenzyl bromide (1.75 g,
MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.1 mmol). The reaction was complete after 13 h to give 8b
3
–2.77 (s, 2 H, NH), 1.10 (t, JH,H = 7.4 Hz, 12 H, propyl), 1.91 (q,
(765 mg, 0.56 mmol, 96% yield) as purple crystals; m.p. Ͼ300 °C.
3JH,H = 7.4 Hz, 8 H, propyl), 4.13 (t, 3JH,H = 6.5 Hz, 8 H, OCH2), Rf = 0.91 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR
3
7.35 (m, 4 H, Ar-H), 7.64 (t, JH,H = 7.5 Hz, 4 H, m-Ar-H), 7.80 (400 MHz, CDCl3, 25 °C): δ = –2.91 (s, 2 H), 5.19 (s, 8 H, -OCH2),
(m, 8 H, Ar-H), 8.92 ppm (m, 8 H, Hβ) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 22.7, 29.7, 69.7, 114.2, 119.9, 121.0, 127.4,
127.5, 143.4, 157.5 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] =
418 [5.04], 515 [3.75], 547 [3.53], 590 [3.13], 647 [2.99] nm. HRMS
(MALDI): calcd. for C56H54N4O4 [M]+ 846.4145; found 846.4141.
7.32 (d, 3JH,H = 7.8 Hz, 4 H, Ar-H), 7.45 (d, 3JH,H = 8.64 Hz, 8 H,
o-C6H4Br), 7.65 (t, 3JH,H = 5.5 Hz, 4 H, m-Ar-H), 7.81 (s, 4 H, Ar-
3
3
H), 7.86 (d, JH,H = 6.2 Hz, 4 H, Ar-H), 8.04 (d, JH,H = 8.64 Hz,
8 H, Ar-H), 8.82 ppm (d, 3JH,H = 3.8 Hz, 8 H, Hβ) ppm. 13C NMR
(150 MHz, CDCl3): δ = 68.7, 114.5, 119.7, 121.5 123.5, 123.6,
123.9, 127.5, 127.9, 128.3, 128.5, 130.7, 143.4, 144.2, 147.4,
156.5 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.02],
515 [3.76], 547 [3.50], 592 [3.10], 647 [3.15] nm. HRMS (MALDI):
calcd. for C72H50Br4N4O4 [M]+ 1350.0566; found 1350.0520.
5-[(4-Benzyloxy)-10,15,20-tris(3-hydroxyphenyl)]porphyrin (7a): Ge-
neral procedure B was followed by using 2 (400 mg, 0.59 mmol),
NaH (14.2 mg, 0.59 mmol), and benzyl chloride (0.067 mL,
0.59 mmol). The reaction was complete after 2.5 h to give 7a
(199 mg, 0.23 mmol, 44% yield) as purple crystals; m.p. Ͼ300 °C. 5,10,15-Tris(3-hydroxyphenyl)-20-[3-(4-nitrobenzyloxy)phenyl]por-
Rf = 0.38 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR phyrin (9a): General procedure B was followed by using 2 (400 mg,
[400 MHz, (CD3)2SO, 25 °C]: δ = –2.99 (s, 2 H, NH), 5.29 (s, 2 H,
0.59 mmol), NaH (14.2 mg, 0.59 mmol), and p-nitrobenzyl bromide
(254 mg, 1.2 mmol). The reaction was complete after 3 h to give 9a
(187 mg, 0.23 mmol, 35% yield) as a purple powder; m.p. Ͼ300 °C.
Rf = 0.23 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v); 1H NMR
(400 MHz, CDCl3, 25 °C): δ = –2.99 (s, 2 H, NH), 5.44 (s, 2 H,
3
3
-CH2), 7.23 (d, JH,H = 7.41 Hz, 3 H, Ar-H), 7.33 (d, JH,H
=
3
7.41 Hz, 1 H, Ar-H), 7.39 (t, JH,H = 7.41 Hz, 3 H, Ar-H), 7.52 (d,
3JH,H = 7.41 Hz, 3 H, Ar-H), 7.59 (m, 9 H, Ar-H), 7.69 (m, 1 H,
Ar-H), 7.87 (s, 1 H, Ar-H), 8.82 (d, 3JH,H = 4.84 Hz, 2 H, Hβ), 8.82
3
3
(d, JH,H = 4.84 Hz, 6 H, Hβ), 9.88 (s, 3 H, -OH) ppm. 13C NMR
CH2), 7.20 (d, JH,H = 7.54 Hz, 4 H), 7.48 (m, 1 H, Ar-H), 7.59
3
3
(150 MHz, CDCl3): δ = 69.9, 115.5, 119.9, 120.4, 120.4, 122.3, (m, 12 H, Ar-H), 7.73 (t, JH,H = 6.43 Hz, 4 H), 8.21 (d, JH,H
=
122.4, 126.2, 128.3, 128.9, 130.9, 137.5, 142.8, 142.9, 156.2, 7.54 Hz, 3 H, Ar-H), 8.88 (m, 8 H, Hβ) ppm. 13C NMR (100 MHz,
157.3 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.41],
514 [4.08], 547 [3.69], 591 [3.59], 648 [3.48] nm. HRMS (MALDI):
calcd. for C51H36N4O4 [M]+ 768.2737; found 768.2740.
CDCl3): δ = 68.7, 115.5, 119.8, 120.4, 120.5, 121.6, 122.3, 124.8,
126.2, 128.3, 128.8, 133.8, 142.8, 146.0, 147.4, 147.5, 156.2 ppm.
UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.40], 514 [3.87],
547 [2.44], 591 [2.91], 647 [3.13] nm. HRMS (MALDI): calcd. for
C51H35N5O6 [M]+ 813.2587; found 813.2609.
5,10,15,20-Tetrakis[(3-benzyloxy)phenyl]porphyrin (7b): General
procedure C was followed by using 2 (400 mg, 0.59 mmol), K2CO3
(815 mg, 5.9 mmol), and 4-benzyl chloride (0.68 mL, 5.9 mmol).
The reaction was complete after 13 h to give 7b (582 mg,
0.56 mmol, 95% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.95
5,10,15,20-Tetrakis-[3-(4-nitrobenzyloxy)phenyl]porphyrin (9b): Ge-
neral procedure C was followed by using 2 (400 mg, 0.59 mmol),
K2CO3 (815 mg, 5.9 mmol), and 4-nitrobenzyl bromide (1.3 g,
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz, 5.9 mmol). The reaction was complete after 15 h to give 9b
CDCl3, 25 °C): δ = –2.60 (s, 2 H, NH), 5.32 (s, 8 H, -CH2), 7.41
(m, 4 H, Ar-H), 7.48 (t, JH,H = 7.07 Hz, 12 H, Ar-H), 7.59 (d,
(446 mg, 0.55 mmol, 93% yield) as a purple powder; m.p. Ͼ300 °C.
Rf = 0.9 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR
(400 MHz, CDCl3, 25 °C): δ = –2.92 (s, 2 H, NH), 5.19 (s, 8 H,
-OCH2), 7.32 (d, 3JH,H = 7.76 Hz, 4 H, Ar-H), 7.47 (m, 8 H, Ar-H),
7.65 (t, 3JH,H = 5.48 Hz, 4 H, m-Ar-H), 7.81 (d, 3JH,H = 5.48 Hz, 4
3
3JH,H = 7.57 Hz, 8 H, Ar-H), 7.74 (t, 3JH,H = 7.57 Hz, 4 H, Ar-H),
7.98 (d, 3JH,H = 7.57 Hz, 4 H, Ar-H), 8.03 (s, 4 H, Ar-H), 9.02 (m,
8 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 70.3,
114.6, 119.9, 121.6, 127.6, 127.7, 128.1, 128.6, 128.7, 128.8, 137.0,
143.5, 157.2 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417
3
H, Ar-H), 7.86 (d, JH,H = 6.24 Hz, 4 H, Ar-H), 8.04 (m, 8 H,
3
Ar-H), 8.82 ppm (d, JH,H = 3.84 Hz, 8 H, Hβ) ppm. 13C NMR
4290
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 4283–4294

Simple Porphyrin Desymmetrization
(150 MHz, CDCl3): δ = 68.7, 114.5, 119.7, 121.5 123.5, 123.6,
123.7, 123.9, 127.5, 127.9, 128.3, 128.5, 130.7, 143.4, 144.2, 147.4,
156.5 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.49],
514 [4.05], 547 [2.61], 591 [3.08], 647 [3.39] nm. HRMS (MALDI):
calcd. for C72H50N8O12 [M]+ 1218.3548; found 1218.3539.
v/v/v). 1H NMR (400 MHz, CDCl3, 25 °C): δ = –2.74 (s, 2 H), 7.54
3
3
(t, JH,H = 7.4 Hz, 8 H, m-Ar-H), 7.64 (t, JH,H = 7.1 Hz, 4 H, m-
Ar-H), 7.72 (d, 3JH,H = 7.8 Hz, 4 H, Ar-H), 7.86 (t, 3JH,H = 7.7 Hz,
4 H, Ar-H), 8.20 (m, 8 H, Ar-H), 8.34 (d, 3JH,H = 7.7 Hz, 8 H, Ar-
CH), 9.01 (s, 8 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3): δ =
119.1, 121.3, 127.8, 128.1, 128.6, 129.6, 130.3, 132.4, 133.7, 143.5,
149.6, 165.4 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417
[5.02], 515 [3.76], 547 [3.51], 590 [3.15], 646 [2.97] nm. HRMS
(MALDI): calcd. for C72H46N4O8 [M]+ 1094.3316; found
1094.3311.
5-[3-(2-Bromobenzoate)phenyl]-10,15,20-tris(3-hydroxyphenyl)por-
phyrin (10a): General procedure B was followed by using 2 (400 mg,
0.59 mmol), EDC (230 mg, 1.7 mmol), N-hydroxysuccinimide
(196 mg, 1.7 mmol), K2CO3 (235 mg, 1.7 mmol), and 2-bromo-
benzoic acid (338 mg, 1.7 mmol). The reaction was complete after
3 h to give 10a (206 mg, 0.24 mmol, 40% yield) as purple crystals;
m.p. Ͼ300 °C. Rf = 0.32 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v).
1H NMR (400 MHz, CDCl3, 25 °C): δ = –2.86 (br. s, 2 H, -NH),
5,10,15-Tris(3-hydroxyphenyl)-20-(3-trifluoromethylsulfonylphenyl)-
porphyrin (12a): General procedure B was followed by using 2
(400 mg, 0.59 mmol), pyridine (0.046 mL, 0.59 mmol), and the
triflate (0.12 mL, 1.2 mmol). The reaction was complete after 1 h
to give 12a (177 mg, 0.22 mmol, 37% yield) as purple crystals; m.p.
3
7.14 (s, 3 H, Ar-H), 7.39 (t, JH,H = 7.36 Hz, 2 H, Ar-H), 7.49 (m,
3
3
6 H, Ar-H), 7.70 (t, JH,H = 7.35 Hz, 6 H, Ar-H), 8.07 (d, JH,H
=
7.35 Hz, 2 H, Ar-H), 8.52 (s, 1 H, Ar-H), 8.80 (m, 4 H, Hβ), 8.89 Ͼ300 °C. Rf = 0.38 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
(m, 4 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3): δ = 114.8, 119.7,
121.0, 121.8, 123.9, 127.3, 127.7, 131.9, 134.6, 136.3, 143.6, 149.2,
149.3, 153.9 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417
[5.41], 514 [4.08], 547 [3.69], 591 [3.59], 648 [3.48] nm. HRMS
(MALDI): calcd. for C51H35BrN4O4 [M]+ 846.1842; found
846.1861.
NMR [400 MHz, (CD3)2SO, 25 °C]: δ = –2.99 (s, 2 H, NH), 7.22
(m, 4 H, o-Ar-H), 7.59 (m, 12 H, Ar-H), 8.86 (s, 8 H, Hβ), 9.87 (s,
3 H, OH) ppm. 19F NMR (400 MHz, CDCl3, 25 °C): δ = –39.42
(s) ppm. 13C NMR [100 MHz, (CD3)2SO, 25 °C]: δ = 115.5, 120.3,
122.3, 126.3, 128.3, 142.8, 156.2 ppm. UV/Vis (EtOAc): λmax
[(log(ε/m–1 cm–1)] = 417 [5.04], 513 [3.71], 547 [3.32], 591 [3.21], 647
[3.03] nm. HRMS (MALDI): calcd. for C45H29F3N4O6S [M]+
810.1760; found 810.1751.
5,10,15,20-Tetrakis[3-(2-bromobenzoyl)phenyl]porphyrin (10b): Ge-
neral procedure B was followed by using 2 (100 mg, 0.14 mmol),
EDC (228 mg, 1.4 mmol), N-hydroxysuccinimide (170 mg,
1.4 mmol), K2CO3 (203 mg, 1.4 mmol), and 2-bromobenzoic acid
(338 mg, 1.7 mmol). The reaction was complete after 6 h to give
10b (83 mg, 0.059 mmol, 59 % yield) as purple crystals; m.p.
Ͼ300 °C. Rf = 0.85 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
NMR [400 MHz, (CD3)2SO, 25 °C]: δ = –2.95 (2 H, NH), 7.51 (s,
5,10,15,20-Tetrakis[3-(trifluoromethylsulfonyl)phenyl]porphyrin
(12b): General procedure C was followed by using 2 (400 mg,
0.59 mmol), pyridine (0.46 mL, 5.9 mmol), and trifluoromethane-
sulfonyl chloride (0.63 mL, 5.9 mmol). The reaction was complete
after 8 h to give 12b (655 mg, 0.54 mmol, 92% yield) as purple
crystals; m.p. Ͼ300 °C. Rf = 0.95 (CH2Cl2/n-hexane/MeOH, 3:1:0.2
3
3
1
8 H, Ar-H), 7.78 (d, JH,H = 7.77 Hz, 8 H, Ar-H), 7.91 (t, JH,H
=
v/v/v). H NMR (400 MHz, CDCl3, 25 °C): δ = –2.79 (2 H, NH),
3
3
7.77 Hz, 5 H, Ar-H), 8.10 (m, 4 H, Ar-H), 8.20 (m, 7 H, Ar-H),
8.94 ppm (s, 8 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3): δ =
119.4, 121.3, 122.0, 128.1, 128.4, 128.7, 131.7, 132.1, 132.7, 134.3,
134.6, 142.9, 149.4, 164.9 ppm. UV/Vis (EtOAc): λmax [(log (ε/
7.79 (d, JH,H = 8 Hz, 4 H, Ar-H), 7.90 (t, JH,H = 7.65 Hz, 4 H,
Ar-H), 8.25 (s, 4 H, o-Ar-H), 8.31 (m, 4 H, Ar-H), 8.93 (s, 8 H,
Hβ) ppm. 13C NMR (150 MHz, CDCl3): δ = 114.18, 117.37,
118.19, 120.56, 121.12, 123.75, 127.23, 128.63, 134.42, 134.47,
m
–1 cm–1)] = 417 [5.40], 514 [4.08], 547 [3.68], 591 [3.59], 648 144.24, 148.35 ppm. 19F NMR (400 MHz, CDCl3, 25 °C): δ =
[3.49] nm. HRMS (MALDI): calcd. for C72H42Br4N4O8 [M]+
1405.9736; found 1405.9730.
–72.55 ppm (CF3) ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] =
415 [5.40], 512 [4.10], 545 [3.63], 589 [3.60], 645 [3.24] nm. HRMS
(MALDI): calcd. for C48H26F12N4O12S4 [M]+ 1206.0238; found
1206.0226.
20-(3-Benzoylphenyl)-5,10,15-tris(3-hydroxyphenyl)porphyrin (11a):
The compound was synthesized by following general procedure B.
A 50 mL round-bottomed flask that contained DMF (10 mL), 2
(400 mg, 0.59 mmol), NaH (14.2 mg, 0.59 mmol), and benzoic an-
5,10,15-Tris(3-hydroxyphenyl)-20-[3-(4-methylphenylsulfonyl)phen-
yl]porphyrin (13a): General procedure B was followed by using 2
hydride (133 mg, 0.59 mmol) was employed, and the reaction was (400 mg, 0.59 mmol), K2CO3 (244 mg, 1.8 mmol), and 4-tolu-
complete after 1 h to give 11a (170 mg, 0.21 mmol, 37% yield) as
purple crystals; m.p. Ͼ300 °C. Rf = 0.34 (CH2Cl2/n-hexane/MeOH,
3:1:0.2 v/v/v). 1H NMR [400 MHz, (CD3)2SO, 25 °C]: δ = –2.97 (s,
enesulfonyl chloride (448 mg, 2.3 mmol). The reaction was com-
plete after 2 h to give 13a (171 mg, 0.20 mmol, 35% yield) as purple
crystals; m.p. Ͼ300 °C. Rf = 0.29 (CH2Cl2/n-hexane/MeOH, 3:1:0.2
1
2 H, NH), 7.24 (m, 3 H, Ar-H), 7.59 (m, 11 H, Ar-H), 7.72 (t, v/v/v). H NMR (400 MHz, CDCl3, 25 °C): δ = –2.92 (2 H, NH),
3
3JH,H = 7.37 Hz, 1 H, Ar-H), 7.77 (d, JH,H = 7.67 Hz, 1 H, Ar-
H), 7.89 (t, 3JH,H = 8.11 Hz, 1 H, Ar-H), 8.21 (m, 4 H, Ar-H), 8.89
(m, 8 H, Hβ), 9.88 (br. s, 3 H, -OH) ppm. 13C NMR [100 MHz,
2.2 (s, 3 H, -CH3), 7.51 (m, 2 H, Ar-H), 7.59 (m, 4 H, Ar-H), 7.67
3
(m, 6 H, Ar-H), 7.76 (m, 4 H, Ar-H), 7.85 (d, JH,H = 8 Hz, 4 H,
3
3
Ar-H), 8.06 (d, JH,H = 4 Hz, 2 H, Hβ), 8.56 (m, JH,H = 4 Hz, 2
(CD3)2SO]: δ = 115.6, 118.9, 120.5, 120.6, 122.3, 125.7, 126.3, H, Hβ), 8.83 (d, 3JH,H = 4 Hz, 4 H, Hβ) ppm. 13C NMR (150 MHz,
128.3, 128.6, 129.3, 129.4, 130.3, 131.9, 132.1, 142.8, 149.7, 156.2,
CDCl3): δ = 21.5, 115.5, 119.1, 120.4, 120.5, 122.3, 124.3, 125.7,
165.3 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.02], 126.2, 128.2, 128.3, 128.4, 128.6, 129.3, 142.6, 142.8, 150.0, 150.4,
514 [3.76], 547 [3.50], 591 [3.13], 646 [2.96] nm. HRMS (MALDI):
154.7, 156.2 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417
[5.42], 514 [4.10], 547 [3.65], 591 [3.60], 649 [3.25] nm. HRMS
(MALDI): calcd. for C51H36N4O6S [M]+ 832.2356; found 832.2348.
calcd. for C51H34N4O5 [M]+ 782.2529; found 782.2531.
5,10,15,20-Tetrakis(3-benzoylphenyl)porphyrin (11b): The com-
pound was synthesized by following general procedure C. A 50 mL
round-bottomed flask that contained DMF (10 mL), 2 (100 mg,
5,10,15,20-Tetrakis[3-(4-methylphenylsulfonyl)phenyl]porphyrin
(13b): General procedure C was followed by using 2 (400 mg,
0.14 mmol), K2CO3 (204 mg, 1.4 mmol), and benzoic anhydride 0.59 mmol), pyridine (0.46 mL, 5.9 mmol), and 4-toluenesulfonyl
(400 mg, 1.77 mmol) was employed, and the reaction was complete
chloride (1.12 g, 5.9 mmol). The reaction was complete after 4 h to
after 7 h to give 11b (148 mg, 0.13 mmol, 92% yield) as purple
give 13b (687 mg, 0.53 mmol, 90% yield) as purple crystals; m.p.
crystals; m.p. Ͼ300 °C. Rf = 0.9 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 Ͼ300 °C. Rf = 0.91 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v); 1H
Eur. J. Org. Chem. 2014, 4283–4294
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4291

L. Rogers, E. Burke-Murphy, M. O. Senge
FULL PAPER
NMR (400 MHz, CDCl3, 25 °C): δ = –3.04 (s, 2 H, NH), 2.31 (s,
553 [5.40], 593 [4.78] nm. HRMS (MALDI): calcd. for
3
12 H, CH3), 7.32 (d, JH,H = 7.87 Hz, 8 H, Ar-H), 7.56 (m, 4 H, C51H36N4O5Zn [M]+ 846.1821; found 846.1819.
3
Ar-H), 7.72 (t, JH,H = 7.87 Hz, 5 H, Ar-H), 7.79 (m, 3 H, Ar-H),
5,10,15,20-Tetrakis[3-(4-tert-butylbenzyloxy)phenyl]porphyrin (18):
7.89 (d, 3JH,H = 7.87 Hz, 8 H, Ar-H), 8.06 (m, 4 H, Ar-H), 8.64 (s,
8 H, Hβ) ppm. 13C NMR (150 MHz, CDCl3): δ = 21.6, 118.5,
122.2, 127.9, 128.2, 128.6, 130.0, 132.4, 133.2, 143.4, 145.6,
148.2 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 416 [5.44],
513 [4.11], 546 [3.63], 590 [3.59], 646 [3.23] nm. HRMS (MALDI):
calcd. for C72H54N4O12S4 [M]+ 1294.2621; found 1294.2590.
General procedure C was followed by using 2 (400 mg, 0.59 mmol),
K2CO3 (815 mg, 6 mmol), and 4-tert-butylbenzyl bromide (1.4 mL,
12 mmol). The reaction was complete after 12 h to give 18 (707 mg,
0.56 mmol, 96% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.95
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz,
CDCl3, 25 °C): δ = –2.70 (s, 2 H, NH), 1.39 (s, 36 H, tBu-H), 5.28
3
(s, 8 H, -CH2), 7.49 (m, 20 H, tBu-Ar-H/Ar-H), 7.70 (t, JH,H
=
{5,10,15-Tris(3-hydroxyphenyl)-20-[3-(phenoxy)phenyl]-
porphyrinato}zinc(II) (15): General procedure D was followed by
using 14 (50 mg, 0.067 mmol), CuII(OAc)2 (19.98 mg, 0.11 mmol),
phenylboronic acid (26.99 mg, 0.22 mmol), and pyridine (0.2 mL)
in dioxane (10 mL). The reaction was complete after 12 h to give
15 (22 mg, 0.026 mmol, 39 % yield) as purple crystals; m.p.
Ͼ300 °C. Rf = 0.31 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
7.76 Hz, 4 H, m-Ar-H), 7.89 (d, 3JH,H = 7.24 Hz, 4 H, Ar-H), 7.95
(s, 4 H, Ar-H), 8.94 (s, 8 H, Hβ) ppm. 13C NMR (100 MHz,
CDCl3): δ = 27.0, 31.4, 70.2, 114.7, 119.9, 121.4, 125.6, 127.6,
127.7, 127.9, 133.9, 143.5, 151.1, 157.3 ppm. UV/Vis (EtOAc): λmax
[(log(ε/m–1 cm–1)] = 417 [5.02], 515 [3.76], 547 [3.50], 591 [3.16], 645
[2.98] nm. HRMS (MALDI): calcd. for C88H76N4O4 [M]+
1262.6649; found 1262.6635.
3
NMR [400 MHz, (CD3)2SO, 25 °C]: δ = 7.09 (t, JH,H = 7.46 Hz,
3
1 H, Ar-H), 7.15 (m, 3 H, Ar-H), 7.28 (d, JH,H = 7.90 Hz, 2 H,
5,10,15,20-Tetrakis[3-(hexyloxy)phenyl]porphyrin (19): General pro-
cedure C was followed by using 2 (400 mg, 0.59 mmol), K2CO3
(815 mg, 5.9 mmol), and 1-iodohexane (1.4 mL, 5.9 mmol). The re-
action was complete after 5 h to give 19 (569 mg, 0.56 mmol, 94%
yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.9 (CH2Cl2/n-hexane/
MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz, CDCl3, 25 °C): δ =
–2.81 (s, 2 H, NH), 0.88 (m, 28 H, alkyl-H), 1.55 (m, 6 H, alkyl-
3
Ar-H), 7.41 (t, JH,H = 7.46 Hz, 2 H, Ar-H), 7.45 (m, 1 H, Ar-H),
7.54 (m, 9 H, Ar-H), 7.69 (m, 1 H, Ar-H), 7.76 (t, 3JH,H = 7.76 Hz,
1 H, Ar-H), 7.91 (d, 3JH,H = 7.33 Hz, 1 H, Ar-H), 8.79 (d, 3JH,H
=
3
3.54 Hz, 6 H, Hβ), 8.80 (d, JH,H = 4.70 Hz, 6 H, Hβ), 9.75 (s, 3
H, -OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 114.3,
115.3, 117.9, 118.8, 120.7, 122.0, 123.2, 127.3, 127.4, 127.5, 127.7,
129.6, 129.7, 129.8, 131.5, 131.6, 131.7, 133.7, 136.6, 145.4 ppm.
UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 421 [6.83], 553 [5.40],
5.93 [4.78] nm. HRMS (MALDI): calcd. for C50H34N4O4Zn [M]+
816.1715; found 816.1710.
3
3
H), 1.87 (q, JH,H = 6.76 Hz, 8 H, -CH2), 4.14 (t, JH,H = 6.66 Hz,
8 H, -OCH2), 8.88 (d, JH,H = 4.64 Hz, 8 H, Hβ) ppm. 13C NMR
3
(100 MHz, CDCl3): δ = 22.6, 25.7, 29.4, 29.7, 31.6, 68.2, 114.2,
119.9, 121.0, 127.4, 127.5, 143.4, 157.5 ppm. UV/Vis (EtOAc): λmax
[(log(ε/m–1 cm–1)] = 417 [5.04], 515 [3.75], 547 [3.50], 589 [3.10], 648
[2.97] nm. HRMS (MALDI): calcd. for C68H78N4O4 [M]+
1014.6023; found 1014.602.
{5-[3-(3-Cyanophenoxy)phenyl]-10,15,20-tris(3-hydroxyphenyl)-
porphyrinato}zinc(II) (16): General procedure D was followed by
using 14 (50 mg, 0.067 mmol), CuII(OAc)2 (19.98 mg, 0.11 mmol),
(3-cyanophenyl)boronic acid (26.99 mg, 0.22 mmol), and pyridine
(0.2 mL) in dioxane (10 mL). The reaction was complete after 15 h
to give 16 (19.7 mg, 0.023 mmol, 35% yield) as purple crystals; m.p.
Ͼ300 °C. Rf = 0.31 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
NMR [400 MHz, (CD3)2SO, 25 °C]: δ = 7.17 (m, 3 H, Ar-H), 7.55
(m, 12 H, Ar-H), 7.64 (m, 2 H, Ar-H), 7.81 (m, 2 H, Ar-H), 8.01
(m, 1 H, Ar-H), 8.80 (s, 4 H, Hβ), 8.83 (s, 4 H, Hβ), 9.77 (s, 3 H,
-OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 112.8, 114.9,
118.9, 120.6, 120.62, 120.65, 120.7, 122.3, 126.2, 127.8, 131.7,
131.9, 144.4, 149.4, 149.5, 149.6, 149.9, 155.9 ppm. UV/Vis
(EtOAc): λmax [(log (ε/m–1 cm–1)] = 421 [6.81], 552 [4.92], 5.94
[4.39] nm. HRMS (MALDI): calcd. for C51H33N5O4Zn [M]+
841.1668; found 841.1665.
5-(3-Hydroxyphenyl)-10,15,20-tris[3-(4-tert-butylbenzyloxy)phenyl]-
porphyrin (20): General procedure C was followed by using 2
(400 mg, 0.59 mmol), K2CO3 (800 mg, 6 mmol), and 4-tert-but-
ylbenzyl bromide (1.4 mL, 6 mmol). The reaction was complete af-
ter 7 h to give 20 (382 mg, 0.34 mmol, 37% yield); m.p. Ͼ300 °C.
Rf = 0.82 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR
(400 MHz, CDCl3, 25 °C): δ = –2.68 (br. s, 2 H, NH), 1.40 (s, 27
H, tBu-H), 5.27 (s, 6 H, CH2), 7.48 (q, 3JH,H = 3.64 Hz, 18 H, tBu-
3
3
ArH, Ar-H), 7.69 (q, JH,H = 8.00 Hz, 3 H, Ar-H), 7.78 (d, JH,H
3
= 7.4 Hz, 1 H, Ar-H), 7.90 (t, JH,H = 7.12 Hz, 3 H, Ar-H), 7.97
(br. s, 3 H, Ar-H), 8.90 (d, JH,H = 4.64 Hz, 2 H, Hβ), 8.94 (d,
3
3JH,H = 8.36 Hz, 6 H, Hβ) ppm. 13C NMR (100 MHz, CDCl3): δ
= 31.4, 34.6, 70.2, 114.7, 114.8, 119.6, 119.9, 120.0, 121.5, 121.8,
125.6, 127.7, 133.9, 133.91, 143.4, 143.5, 143.6, 151.1, 153.8,
157.3 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.02],
515 [3.75], 548 [3.51], 590 [3.15], 647 [2.99] nm. HRMS (MALDI):
calcd. for C77H72N4O4 [M]+ 1116.5554; found 1116.5548.
{5,10,15-Tris(3-hydroxyphenyl)-20-[3-(3-methoxyphenyl)
phenyl]porphyrinato}zinc(II) (17): General procedure D was fol-
lowed by using 14 (70 mg, 0.095 mmol), CuII(OAc)2 (27.2 mg,
0.15 mmol), and (3-methoxyphenyl)boronic acid (44 mg,
0.29 mmol). The reaction was complete after 2 h to give 17 (30 mg,
0.035 mmol, 37% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.29
5,10,15-Tris[3-(hexyloxy)phenyl]-20-(3-hydroxyphenyl)porphyrin
(21): General procedure C was followed by using 2 (400 mg,
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR [400 MHz, 0.59 mmol), K2CO3 (815 mg, 5.9 mmol), and 1-iodohexane
3
(CD3)2SO, 25 °C]: δ = 3.76 (s, 3 H, -OCH3), 6.70 (d, JH,H
=
(1.4 mL, 5.9 mmol). The reaction was complete after 7 h to give 21
(313 mg, 0.33 mmol, 40% yield) as purple crystals; m.p. Ͼ300 °C.
3
8.01 Hz, 1 H, Ar-H), 6.87 (d, JH,H = 8.01 Hz, 2 H, Ar-H), 7.21
(d, 3JH,H = 8.01 Hz, 3 H, Ar-H), 7.34 (t, 3JH,H = 8.01 Hz, 1 H, Ar-
Rf = 0.96 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR
3
3
H), 7.50 (dd, JH,H = 8.01 Hz, 1 H, Ar-H), 7.58 (m, 9 H, Ar-H), (400 MHz, CDCl3, 25 °C): δ = –2.81 (s, 2 H, NH), 0.88 (t, JH,H
=
3
3
7.75 (s, 1 H, Ar-H), 7.80 (t, JH,H = 8.01 Hz, 1 H, Ar-H), 7.96 (d, 6 . 3 5 H z , 9 H , C H 3 ) , 1 . 1 6 ( t , J H , H = 7 . 3 2 H z , 1 4 H ,
3
3
3
3JH,H = 7.12 Hz, 1 H), 8.84 (d, JH,H = 4.32 Hz, 6 H, Hβ), 8.86 (d, -CH2), 2.81 (q, JH,H = 7.32 Hz, 10 H, -CH2), 4.14 (t, JH,H
=
3 JH , H = 4.71 Hz, 2 H, Hβ ), 9.80 (s, 3 H, -OH) ppm. 1 3 C
NMR(100 MHz, CDCl3, 25 °C): δ = 55.7, 105.4, 109.8, 111.3,
114.9, 119.4, 120.8, 120.9, 122.3, 126.2, 127.8, 131.0, 131.6, 131.9,
6.41 Hz, 6 H, OCH2), 7.31 (d, JH,H = 8.49 Hz, 3 H, Ar-H), 7.53
3
3
3
(t, JH,H = 7.91 Hz, 1 H, Ar-H), 7.61 (t, JH,H = 7.91 Hz, 3 H, Ar-
H), 7.70 (d, 3JH,H = 7.91 Hz, 1 H, Ar-H), 7.77 (t, JH,H = 8.49 Hz,
3
132.1, 144.3, 145.0, 149.4, 149.5, 149.6, 149.7, 155.3, 155.9, 6 H, Ar-H), 8.89 (m, JH,H = 3.91 Hz, 8 H, Hβ) ppm. 13C NMR
161.2 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] = 421 [6.85], (100 MHz, CDCl3, 25 °C): δ = 14.3, 22.4, 25.6, 29.1, 31.4, 68.1,
3
4292
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 4283–4294

Simple Porphyrin Desymmetrization
114.7, 115.5, 120.0, 120.1, 120.4, 120.41, 121.2, 122.3, 126.2, 127.5,
0.3 mmol) was placed in a round-bottomed flask that contained
DMF (40 mL). The flask was fitted with a dropping funnel that
128.3, 142.8, 142.9, 156.2, 157.5 ppm. UV/Vis (EtOAc): λmax
[(log(ε/m–1 cm–1)] = 417 [5.03], 515 [3.73], 546 [3.50], 591 [3.10], 647 contained a solution of Co(II)mTHPP (22.4 mg, 0.03 mmol) and
[2.98] nm. HRMS (MALDI): calcd. for C62H66N4O4 [M]+
930.5084; found 930.5080.
23 (40 mg, 0.03 mmol) in DMF (10 mL). This solution was added
dropwise over 24 h, and once the addition was complete, the reac-
tion mixture was stirred for an additional 12 h. The reaction mix-
ture was diluted with DCM, and the resulting solution was washed
multiple times with water, brine, and sodium hydrogen carbonate.
The solution was dried with Mg2SO4, and the solvent was removed
in vacuo. The resulting orange/purple solid was subjected to col-
umn chromatography, and the first orange band contained the de-
sired bis(porphyrin) 25 (6.3 mg, 0.0038 mmol, 12% yield) as red-
dish orange crystals; m.p. Ͼ300 °C. Rf = 0.85 (CH2Cl2/n-hexane/
MeOH, 3:1:0.2 v/v/v). 1H NMR (600 MHz, CDCl3, 25 °C): δ =
–2.77 (s, 2 H, NH), 2.06 (m, 8 H, -CH2), 2.16 (m, 10 H, -CH2),
5-[3-(Prop-2-yn-1-yloxyphenyl)]-10,15,20-tris[3-(4-tert-butylbenzyl-
oxy)phenyl]porphyrin (22): The compound was synthesized by fol-
lowing general procedure B. A 50 mL round-bottomed flask that
contained DMF (10 mL), 20 (100 mg, 0.15 mmol), NaH (3.5 mg,
0.15 mmol), and propargyl bromide (0.075 mL, 0.15 mmol) was
stirred for 2 h to give 22 (161 mg, 0.14 mmol, 95 % yield); m.p.
Ͼ300 °C. Rf = 0.93 (CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = –2.80 (s, 2 H, NH), 1.33 (s,
27 H, tBu-H), 2.6 (s, 1 H, alkynyl), 4.89 (s, 2 H, -CH2), 5.22 (s, 6
H, CH2), 7.44 (m, 16 H, Ar-H/tBu-Ar-H), 7.65 (t, 3JH,H = 8.36 Hz,
3
3.55 (m, 6 H, -CH2), 4.22 (t, 8 H, -CH2), 7.34 (d, JH,H = 7.62 Hz,
3
4 H, Ar-H), 7.81 (d, JH,H = 7.12 Hz, 3 H, Ar-H), 7.87 (s, 5 H,
8 H, Ar-H), 7.66 (t, 3JH,H = 7.62 Hz, 8 H, Ar-H), 7.79 (s, 8 H, Ar-
3
Ar-H), 8.86 ppm (d, JH,H = 9.68 Hz, 8 H, Hβ) ppm. 13C NMR
3
H), 7.84 (d, JH,H = 7.62 Hz, 8 H, Ar-H), 8.91 (m, 16 H, Hβ) ppm.
(100 MHz, CDCl3 25 °C): δ = 23.9, 31.4, 34.6, 56.1, 70.1, 75.8,
114.6, 114.7 119.9, 121.3, 125.6, 127.5, 127.6, 127.9, 133.8, 143.4,
143.5, 151.1, 156.0, 157.2 ppm. UV/Vis (EtOAc): λmax [(log (ε/
13C NMR (100 MHz, CDCl3, 25 °C): δ = 27.9, 29.4, 33.3, 66.9,
113.9, 119.7, 120.9, 127.3, 127.6, 143.3, 157.1 ppm. UV/Vis
(EtOAc): λmax [(log(ε/m–1 cm–1)] = 417 [5.04], 515 [3.75], 547 [3.50],
589 [3.09], 648 [2.96] nm. HRMS (MALDI): calcd. for
m
–1 cm–1)] = 417 [5.02], 515 [3.76], 547 [3.50], 590 [3.15], 647
[2.99] nm. HRMS (MALDI): calcd. for C80H74N4O4 [M]+
1154.5710; found 1154.5716.
C
104H84CoN8O8 [M]+ 1629.5588; found 1629.5509.
Supporting Information (see footnote on the first page of this arti-
5,10,15,20-Tetrakis[3-(4-bromobutoxy)phenyl]porphyrin (23): Gene-
ral Procedure C was followed by using 2 (400 mg, 0.59 mmol),
K2CO3 (815 mg, 6 mmol), and 1,4-dibromobutane (1.4 mL,
12 mmol). The reaction was complete after 5 h to give 23 (688 mg,
0.57 mmol, 96% yield) as purple crystals; m.p. Ͼ300 °C. Rf = 0.9
1
cle): H and 13C NMR spectra for all compounds.
Acknowledgments
(CH2Cl2/n-hexane/MeOH, 3:1:0.2 v/v/v). 1H NMR (400 MHz, This work was supported by a grant from the Science Foundation
CDCl3, 25 °C): δ = –2.67 (s, 2 H, NH), 2.03 (m, 8 H, -CH2), 2.14
Ireland (P.I. 09/IN.1/B2650).
(m, 8 H, -CH2), 3.52 (t, 3JH,H = 6.16 Hz, 8 H, -CH2), 4.19 (t, 3JH,H
3
= 5 Hz, 8 H, -CH2), 7.32 (d, JH,H = 8 Hz, 4 H, Ar-H), 7.67 (t,
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3JH,H = 5 Hz, 4 H, Ar-CH2), 7.86 (s, 4 H, o-Ar-H), 7.90 (d, 3JH,H
=
7.4 Hz, 4 H, Ar-CH2), 8.99 (s, 8 H, Hβ) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 28.0, 30.9, 32.5, 67.1, 114.1, 119.9, 121.2, 127.6,
127.8 143.5, 157.3 ppm. UV/Vis (EtOAc): λmax [(log(ε/m–1 cm–1)] =
417 [5.01], 515 [3.77], 547 [3.52], 590 [3.15], 647 [2.99] nm. HRMS
(MALDI): calcd. for C60H58Br4N4O4 [M]+ 1214.1192; found
1214.1183.
[5,10,15,20-Tetrakis(3-hydroxyphenyl)porphyrinato]cobalt(II) (24):
The preparation was carried out according to a reported pro-
cedure.[18] Compound 2 (100 mg) and cobalt(II) acetate (3 equiv.)
were added to a 100 mL Erlenmeyer flask that contained DMF
(10 mL). The flask was placed in the microwave, and the reaction
was run (3 ϫ 1 min intervals) at 300 W with the allocated time to
cool the reaction mixture for each interval. The reaction mixture
was dissolved in DCM, and the resulting solution was washed with
water (3ϫ 100 mL) to remove the residual DMF. The solvent was
removed in vacuo, and the product was purified by recrystallization
to yield 24 (106 mg 0.14 mmol, 98% yield) as an orange/purple
solid; m.p. Ͼ300 °C. Rf = 0.42 (CH2Cl2/n-hexane/MeOH, 3:1:0.2
1
3
v/v/v). H NMR [400 MHz, (CD3)2SO, 25 °C]: δ = 7.13 (d, JH,H
3
= 7.95 Hz, 4 H, Ar-H), 7.36 (s, 4 H, o-Ar-H), 7.40 (d, JH,H
=
3
7.32 Hz, 4 H, Ar-H), 7.49 (t, JH,H = 7.95 Hz, 4 H, m-Ar-H),
8.75 ppm (s, 8 H, Hβ), 9.81 (br. s, 4 H, -OH) ppm. 13C NMR
[100 MHz, (CD3)2SO, 25 °C]: δ = 115.5, 119.3, 121.3, 125.3, 128.5,
129.3, 130.6, 132.2, 132.8, 141.6, 142.3, 156.4 ppm. UV/Vis
(EtOAc): λmax [(log(ε/m–1 cm–1)] = 411 [6.24], 525 [5.09] nm. HRMS
(MALDI): calcd. for C44H28CoN4O4 [M]+ 735.1443; found
735.1435.
[6] a) J. S. Lindsey, in: The Porphyrin Handbook (Eds.: K. M. Kad-
ish, K. M. Smith, R. Guilard), Academic Press, San Diego,
2000, vol. 1, p. 45–118; b) P. D. Rao, S. Dhanalekshmi, B. J.
Littler, J. S. Lindsey, J. Org. Chem. 2000, 65, 7323–7344; c) J. S.
Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney, A. M.
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[5,10,15,20-Tetrakis(3-oxyphenyl)porphyrin]yltetrabutyl[5,10,15,20-
tetrakis(3-oxyphenyl)porphyrinato]cobalt(II) (25): K2CO3 (41 mg,
Eur. J. Org. Chem. 2014, 4283–4294
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4293

L. Rogers, E. Burke-Murphy, M. O. Senge
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Received: April 17, 2014
Published Online: May 27, 2014
4294
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 4283–4294