Synthesis of meso-substituted ABCD-type porphyrins by functionalization reactions

FULL PAPER

DOI: 10.1002/ejoc.200901113

Synthesis of meso-Substituted ABCD-Type Porphyrins by Functionalization

Reactions

Mathias O. Senge,*^[a,b]Yasser M. Shaker,^[a]Monica Pintea,^[a]Claudia Ryppa,^[c]

Sabine S. Hatscher,^[c]Aoife Ryan,^[a]and Yulia Sergeeva^[a]

Keywords: Porphyrinoids / Tetrapyrroles / C–C coupling / Conformation analysis

Considerable progress has been made in recent years in the

search for synthetic methods leading to functionalized por-

phyrins, especially for modification of either the β- or meso

positions. For the latter, total synthesis based on condensa-

tion methods or partial synthesis through functionalization of

preformed porphyrin have emerged as possible methods.

The increasing number of possible technical and medicinal

applications for unsymmetrically meso-substituted porphyr-

ins requires straightforward methods for the preparation of

the so-called ABCD-porphyrins, i.e., porphyrins with up to

four different meso substituents. Here, we describe new stra-

tegies for the synthesis of ABCD-type porphyrins based on

porphyrin reactions with organolithium reagents and the use

of Pd-catalyzed coupling reactions. With the whole repertoire

of contemporary functionalization methods, a comprehensive

analysis and comparison of the various strategies for A-, AB-,

A₂B-, ABC-, A₂BC- and ABCD-type porphyrins is given. In

addition, we report on the synthesis of new functionalized

derivatives for some of these porphyrin classes. In practical

terms and taking an applied-science-oriented approach, the

synthesis of unsymmetrically meso-substituted porphyrins is

best accomplished by a combination of well-developed con-

densation methods with subsequent functionalization by

organolithium compounds or transition-metal-catalyzed cou-

pling protocols. The methods described are suitable for the

preparation of porphyrins for many divergent applications

ranging over amphiphilic porphyrins for photodynamic ther-

apy, push-pull systems for optical applications and chiral sys-

tems useful in catalysis to donor–acceptor systems suitable

for electron-transfer studies.

Overall, porphyrins are probably the most widely studied

class of natural products whose studies have impacted al-

Introduction

Porphyrins are a unique class of compounds that are most any modern scientific field.^[1]From a chemical view-

ubiquitous in nature and function in a wide variety of roles point, their importance is related to their chemical proper-

ranging from oxygen transport, electron transfer and oxi- ties, i.e., their photochemical (energy and exciton transfer),

dation catalysts to photosynthesis. Thus, these widely dis- redox (electron transfer, catalysis), and coordination prop-

tributed and important tetrapyrrolic cofactors play crucial erties (metal and axial ligand binding), and their conforma-

roles in many biochemical and technical processes. These tional flexibility (functional control).^[2]

range from impaired biosynthesis (porphyrias), photodyn-

amic cancer therapy (PDT), malaria, neuropsychiatric dis-

orders to industrial applications as sensors, optical materi-

als, oxidation catalysis and in supramolecular chemistry.

The various applications and their biochemical relevance

are related by a common denominator in the underlying

chemistry of these compounds. Current applications require

the synthesis of unsymmetrically substituted porphyrins, i.e.

systems with different substituents in a regiochemically de-

fined manner. Next to the naturally occurring β-substituted

porphyrins (e.g., the chlorophylls and hemes) typical exam-

ples are the so-called ABCD-porphyrins (1), where four dif-

ferent meso substituents are present (2).^[3]The type and ar-

rangement of these substituents then defines different appli-

cations. To name a few, residues with functional groups

suitable for small molecule binding may be used for cataly-

sis, a mixture of polar and nonpolar residues yields amphi-

philic porphyrins suitable for photodynamic therapy and a

mix of electron donating and withdrawing groups will give

push-pull porphyrins for applications in nonlinear optics.^[4]

[a] School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity

College Dublin,

Dublin 2, Ireland

Fax: +999-353-1-896-8536

E-mail: sengem@tcd.ie

[b] Medicinal Chemistry, Institute of Molecular Medicine, Trinity

Centre for Health Sciences, Trinity College Dublin, St James’s

Hospital,

Dublin 8, Ireland

[c] Institut für Chemie, Universität Potsdam,

Karl-Liebknecht-Str. 24-25, 14476 Golm, Germany

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.200901113.

Eur. J. Org. Chem. 2010, 237–258

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Future progress in this area obviously depends on the

synthetic accessibility of porphyrins. While – theoretically –

almost any desired β-substituted porphyrin can be prepared

based on historical contributions from eminent chemists

such as Willstätter, Fischer, Woodward, Eschenmoser and

Smith^[5a]there were still limitations in the preparation of

meso-substituted porphyrins. Due to their symmetry and

simple preparation most of the applications currently under

study use 5,10,15,20-tetrasubstituted porphyrins (3) and a

significant body of methods has been developed for the

modification of the β-positions in such systems.^[5b]

In principle, there are three ways to access the more

interesting

unsymmetrical ABCD-type

compounds

(Scheme 1). These are the disconnection into a bilane 5 or

any combination of pyrrole building blocks 6 that can be

used in [2+2] or [3+1] condensation reactions.^[6]Theoretic-

ally possible is also a mixed condensation using pyrrole 4

and various aldehydes which is still used by many research-

ers for systems with lower symmetry. Here, the number of

regioisomers formed is too large and the necessary purifica-

tion and separation workup is too cumbersome if possible

at all. Note, that most of these reactions involve acid-cata-

lyzed condensation reactions, often resulting in significant

scrambling of the pyrrole units thus limiting the type of

substituents that can be used.

The most significant contributions in this area of ABCD-

porphyrin “total synthesis” were made by the group of

Lindsey.^[6b]Examples for new developments are the synthe-

sis of 1-bromo-19-acylbilanes by acid-catalyzed condensa-

tion of 1-acyldipyrromethanes and 9-bromodipyrrometh-

ane-1-carbinols followed by intramolecular cyclization of

the 1-bromo-19-acylbilanes in the presence of a metal salt

in a noncoordinating solvent and the synthesis of 1-pro-

tected 19-acylbilanes by acid-catalyzed condensation 1-acyl-

dipyrromethanes and 9-protected dipyrromethane-1-carb-

inols with subsequent transformation of the 1-protected 19-

acylbilane under basic, metal-templating conditions to give

the corresponding metalloporphyrins.^[7]

Scheme 1. Retrosynthetic analysis of ABCD-type porphyrins.

lithium reagents for the synthesis of various tetrapyrrole

classes.^[13–16]

In a strategic sense the preparation of ABCD-type por-

phyrins by functionalization requires the use of the less-

substituted precursors, e.g. 7, and ultimately use of unsub-

stituted porphyrin 8. The latter then allows for preparation

of a mono-substituted A-type porphyrin (7, R²= R³= H)

followed by subsequent regiochemical introductions of the

B-, C- and D-type residues. With recent advances in the

synthesis of 8^[17]and the preparation of A-type porphyrins

through condensation and functionalization reactions^[18]all

necessary parts for partial synthesis of ABCD-porphyrins

are now in hand. Based on our current interest in the appli-

cation of porphyrins for photodynamic cancer therapy

(PDT) and optical applications^[19]we here present a com-

prehensive analysis of the application of the currently avail-

able synthetic strategies for the meso functionalization of

porphyrins. This study aims to evaluate the applicability

and limitations of these methods for the preparation of

ABCD-type porphyrins in general. We also report on the

synthesis of new functionalized derivatives for some of the

different ABCD-porphyrin classes.

We have taken an alternative approach focusing on par-

tial synthesis starting with preformed porphyrins, i.e. en-

visioning a step-wise introduction of the four meso substitu-

ents in 2. The last decades have seen a surge in novel func-

tionalization reactions of porphyrins, many based on C–

C coupling reactions which has put this approach within

Results and Discussion

A preparation of ABCD-type porphyrins through func-

possibility.^[8]By now many A₂BC- and A₃B-type por- tionalization requires a step-wise approach, i.e., starting

phyrins have been prepared starting with the easily access- from A-porphyrins and through sequential introduction of

ible 5,15-disubstituted porphyrins^[3,9–12]and from bromi- more residues going to the ABCD-type systems. Thus, for

nated precursor compounds often based on Heck-type reac- practical purposes, we start in our discussion with the least

tions. In this context we have developed the use of organo- substituted systems.

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

Synthesis of A-Type Porphyrins

12 and the respective aldehyde carrying the meso substitu-

ent.^{[3,9–11,20]}An example for the synthesis of a 5,15-disubsti-

tuted porphyrin with new functional groups is the synthesis

of the bisdioxaborolan porphyrin 14 from dipyrromethane

and the respective aldehyde in 58% yield. Metallation with

nickel acetylacetonate gave the respective metal complex 15.

The related 5,10-disubstituted derivatives are accessible via

similar methods but typically give much lower yields.^[21]

Here compound 16 could be prepared in very low yield

(0.4%). Total syntheses have been reported for example

5,10-diphenylporphyrin.^[22]5,15-Disubstituted porphyrins

are also often derived from mixed condensation such as

AB-type porphyrin syntheses (vide infra).

These porphyrins are accessible either by substitution of

porphyrin (“porphine”) with RLi or by mixed condensa-

tion.^[18]One example for the latter is the mixed condensa-

tion of dipyrromethane, 2-hydromethylpyrrole and methyl

4-formylbenzoate to give 9 in 8% yield. Another example

is the preparation of compound 13 by condensation of the

5-substituted dipyrromethane 11 (derived from the aldehyde

10) with dipyrromethane 12 and trimethyl orthoformiate in

4% yield. Typically such condensations give 2–12% yield

and the formation of the A-type porphyrin is accompanied

by the respective 5,15-A₂-type system, which can be easily

removed by chromatography.^[18]Preparation from in situ

generated porphyrin and reaction with RLi is attractive but

works well best for reactions involving ca. 100 mg of start-

ing material. Large scale syntheses are still best performed

via mixed condensations.

Synthesis of AB-Type Porphyrins

Two possibilities exist for the preparation of 5,15-AB

porphyrins. One involves classic mixed condensation reac-

tions. In practical terms this is still a facile reaction and

for certain residues allows quick generation of the desired

compounds and can even be controlled to give only the tar-

get compound as the main product.^[11,23]In simple ap-

proaches, often product mixtures are encountered. Never-

theless, the different polarities mostly allow for a quick

chromatographic separation of the compounds. For exam-

ple, the preparation of 17 from dipyrromethane and alde-

hyde gives a yield of 23% but is accompanied by formation

of 18 (14%) and 19 (14%). In a similar manner use 2-meth-

oxybenzaldehyde and tolylaldehyde gave 20 in 22% yield

while tolylaldehyde and 2,4,6-trimethoxybenzaldehyde gave

the 5,15-AB porphyrin 21 in 15% yield. Further examples

are illustrated in Scheme 2.

More elegant might be a synthesis using C–C coupling

reactions. The use of Heck-type coupling reactions is still

problematic due to limited access to the necessary monob-

romo derivatives.^[24]An alternative might be the use of reac-

tions with LiR. However, initially we were not too con-

vinced, as studies with 2,3,7,8,12,13,17,18-octaethylporphy-

rin and other systems had shown a preference for formation

of the 5,10-AB derivatives over the 5,15-AB regioiso-

mers.^[13–16]Nevertheless, we attempted some reactions of 5-

substituted aryl and alkylporphyrins with LiR reagents un-

der our standard conditions (Scheme 3).

Synthesis of A₂-Type Porphyrins

The synthesis of 5,15-disubstituted A₂-type porphyrins is

well established by now. Their preparation is easily ac-

complished by a [2+2] condensation using dipyrromethane

Reaction of the sterically hindered tert-butylporphyrin 32

with nBuLi gave a mixture of the two possible regioisomers

38 and 39 accompanied by higher alkylated products. Varia-

tions of the reaction conditions did not change this situa-

tion. With hexyllithium the 5,15-regioisomer 40 was iso-

lated as the main product in low yield. Using dimethylami-

nophenyllithium again the 5,15-regioisomer 41 was isolated

in better yield but was accompanied by small amounts of

the respective butyl derivative 38.

The ethylpropyl porphyrin 33 gave quite satisfactory

yields with hexyl (59%) and phenyllithium (69%) but

showed a clear preference for the formation of the 5,10-

regioisomer (42 and 43, respectively). We tried to optimize

the synthesis of 42 by variation of the number of equiva-

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Scheme 2. Synthesis of AB-porphyrins via condensation reagents.

lents of hexyllithium. Depending on the number of equiva- materials for the investigation of reactions at the meso posi-

lents used (1.5, 2.5, 3.5, 4.5, 5.5) the yields varied over a tion.^[9]Using S_NAr reactions they can easily be converted

broad range (42, 52, 59, 29, 44%, respectively) with into the respective A₂B-porphyrins without any regiochem-

3.5 equiv. being the optimum which makes sense as 2 equiv. ical problems.^[13b,15]For example, using 58^[11]as starting

will be required to neutralize the N-H. Use of the aryl- material the two porphyrins 59 and 60 could be prepared

lithium reagent 4-(dimethylamino)phenyllithium gave a easily in 71 and 77% yield, respectively (Scheme 4).

mixture of the two regioisomers 44 and 45 accompanied by

the higher substituted porphyrins 46 and 47. Similarly, in

the case of the 5-arylporphyrins 34 and 35 the formation of

both regioisomers was observed with a clear preference for

the 5,10 isomer.

Synthesis of ABC-Type Porphyrins

First we investigated the reaction of 5,15-AB-type por-

phyrins with RLi reagents to yield ABC-porphyrins

(Scheme 5). Similar to the situation for A₂B-porphyrins

only one product can be formed and the reactions typically

proceeded in very good yields. Using various alkyl and aryl-

lithium reagents the ABC-porphyrins 61–64 and 67–71 were

obtained in yields ranging from 47 to 90%. Some of these

free bases were converted into the respective manganese(III)

complexes for later oxidation catalyst studies.^[25]As one ex-

ample for possible applications we prepared the 5,10-meso-

meso-strapped porphyrin derivative 72 in good yields

through reaction of 20 with 2-methoxyphenyllithium, de-

protection of the methyl ether with BBr₃followed by reac-

tion with 1,12-dibromododecane.

Obviously, 5,10-type AB-porphyrins can be used for the

preparation of ABC-porphyrins as well. A comparison of

the reactivity of 44 and 45 shows that the 5,10-AB por-

phyrins do react but give lower yields in line with the sta-

bility of the intermediate anion.^[16]Note, that such por-

phyrins could also be derived from the attempted syntheses

Clearly, the reaction of porphyrins with RLi for the prep-

aration of AB-type porphyrins is difficult to control and

offers advantages only for very specific cases. Note, that for

the reaction of 5-alkylporphyrins with RLi the yields are

comparable to those obtained from mixed condensations.

Here, the latter offer the advantage of larger scale and easier

chromatographic separation. The main benefit of the pres-

ent method lies in an easier access to the otherwise inaccess-

ible 5,10-regioisomer. Alternatively, use of an excess of alk-

yllithium reagent offers an entry into A₂B-porphyrins from

the monosubstituted precursors. E.g., reaction of 36 with

hexyllithium gave the trisubstituted porphyrin 55 in 54%

yield. A similar reactivity was observed for 37, although in

this case only the 5,15-A₂B porphyrin 57 could be isolated

from the product mixture.

Synthesis of A₂B-Type Porphyrins

5,15-A₂-type porphyrins are conveniently prepared from of ABCD-type porphyrins through reaction of AB-por-

aldehydes and dipyrromethanes and present useful starting phyrins with R¹Li/R²I (vide infra).

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

nation reactions have been applied to the meso position of

porphyrins.^[26]In order to access the monobromo deriva-

tives of the AB-type porphyrins we used 1.1 equiv. of NBS

for the bromination. Nevertheless, as shown in Scheme 6

the reaction is difficult to control and both the mono- and

dibrominated derivatives were formed roughly in a 1:1 ratio

with overall yields of 80–90%. However, their polarities are

quite different and they are easily separated by column

chromatography.

Pd-catalyzed reactions have found widespread use in por-

phyrin chemistry. These coupling reaction offers several ad-

vantages: availability of the reagents, mild reaction condi-

tions, tolerance for a broad range of functional groups,

small amount of catalysts and application in one pot syn-

thesis and appropriate conditions have been developed for

porphyrins.^[27]

[4-(Carboxymethyl)phenyl]boronic acid was treated with

porphyrins 22 and 31 and afforded the desired products 82

and 86 in 87% and 89% yield, respectively. Likewise, the

styrene-type derivative 84 was prepared in 46% yield. Reac-

tion of 31 with 3-nitrophenylboronic acid gave 85 in 82%

yield. Reaction of the same boronic acid with porphyrin 27

yielded product 83 in 46% yield. Note, that 3-nitrophenyl

residues in AB-diarylporphyrins have recently been iden-

tified by Banfi et al. as having potential for PDT and thus

appropriate systems were ABCD-type targets for us.^[28]

Note, that the 5,15-dibromo derivatives 77, 79, and 81 offer

an additional entry into 5,15-A₂BC compounds, which

show promise as push-pull systems for optical applica-

tions.^[19b]

Scheme 3. Synthesis of AB-porphyrins by reaction with LiR rea-

gents.

Synthesis of A₂BC-Type Porphyrins

Use of A₂B-porphyrins as starting materials offers again

two possibilities: Pd-type couplings of the bromo deriva-

tives and direct substitution with LiR reagents. The latter

strategy has been employed quite successfully before.^[11,12,14]

Reaction of A₂B-Porphyrins with RLi

In extension of our earlier studies we investigated some

additional reagents and A₂B-type porphyrins (Scheme 7).

While porphyrin 90 reacted in good to excellent yields with

various alkyl- and aryllithium reagents attempts to use RLi

with electron-withdrawing groups such as p-nitro- and p-

bromophenyllithium only recovered starting material. Like-

wise, p-methoxyaryllithium or use of the in situ prepared

lithiated ester of ethyl 4-bromobutyrate gave no reaction.

Similar results were found for porphyrin 89 and addition-

ally, we could show that reaction with 4-ethynylphenyllith-

ium gave the porphyrin 91 in low yield.

Porphyrins such as 89 bearing a p-ethynyl group have

potential uses in superstructured materials, porphyrin ar-

rays, light-harvesting systems and porphyrin-based materi-

als such as push-pull porphyrins via Glaser or Heck cou-

Scheme 4. Synthesis of A₂B-porphyrins via S_NAr.

An alternative approach to ABC-porphyrins is the use of pling.^[29,30]For example, reaction of 94 under Glaser condi-

AB-type systems, attempt a selective monobromination of tions gave the bisporphyrins 95 in excellent yield

one meso position and then use Pd-catalyzed reactions for (Scheme 8). Couplings of compounds such as 94 and trans-

introduction of the C-residue. Both iodination and bromi- diiodides could give new unsymmetrical, linear trisubsti-

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Scheme 5. Synthesis of ABC-porphyrins via S_NAr.

tuted porphyrins which may be used as model compounds gave the phlorin 98 in 28%. These results are in line with

for investigations of larger array systems.

results described by Krattinger and Callot.^[32]The phlorins

The studies shown in Scheme 7 were then extended to are stable against oxidants and this reaction opened a route

the utilization of meso-trisubstituted porphyrin 88 to carry for the conversion of free base porphyrins to phlorins with

different alkyl residues in the “C” position using butyllith- a variety of different meso substituents.^[33]

ium reagents with an increasing degree in steric demand.

Next we investigated the reactivity of A₂B-porphyrins

Reactions of n-, sec-, and tert-butyllithium reagents with 88 with aryl groups in the B position. Typically, attacking a

were utilized to study the scope of their reactivity towards meso position opposite to one carrying an aryl group is dif-

the meso position under the same reaction conditions. n- ficult due to steric hindrance of the mesomeric benzylic

and sec-butyllithium reacted in a similar manner to form anion stabilization.^[16]While the synthesis of some A₂BC-

the unsymmetrical porphyrins 90^[11]and 91 in yields of 31 type porphyrins by this method was successful the yields

and 25%, respectively. Reaction with the more hindered obtained of these A₂BC-porphyrins were lower than those

tert-butyllithium proceeded in a different manner although of A₂BC-porphyrins formed when B was an alkyl group.

the attack was still directed to the more reactive meso posi- For example, porphyrin 60 did not react with p-ethynyl-

tion. Here, phlorin 96 was formed in 20% yield instead of phenyllithium or n-butyllithium. Likewise, the use of elec-

porphyrin 92. The NMR spectroscopic data are typical for tron-rich porphyrins gave mixed results. For example, 5-(4-

a nonaromatic conjugated system with pyrrolic signals in aminophenyl)-10,20-diphenylporphyrin reacted readily with

the δ = 6–7 ppm range. The formation of phlorin 96 indi- 4-(dimethylamino)phenyl or butyllithium^[11]while 5-(4-

cates that the free meso position in 88 is more reactive aminophenyl)-10,20-bis(3-methoxyphenyl)porphyrin

re-

towards tBuLi than β-positions as no chlorin was separated acted only with butyllithium^[11]but not with p-hydroxy-

in this case. A similar behaviour was found for 59 which phenyllithium or 2-methoxyphenyllithium.

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

Scheme 8. Glaser coupling of 94 to 95.

Reaction of A₂-Porphyrins with R¹Li/R²I

Earlier we had shown that the nickel(II) complexes of

A2-porphyrins can be accomplished through the addition

of electrophilic reagents such as alkyl iodide “after the hy-

drolysis step” of the RLi reaction followed by oxidation

with atmospheric oxygen permits the preparation of func-

tionalized unsymmetric tetrasubstituted porphyrins.^[14]This

method was then extended to the respective free base por-

phyrins.^[12]While the yields were low to moderate in the

range of 20–45%, the method is still advantageous when

compared to related mixed condensations or multi-step syn-

theses. Attempts to extend the reaction to 5,15-dialkylpor-

phyrins confirmed these limitations (Scheme 9).

Scheme 6. Synthesis of ABC-porphyrins via Suzuki reactions.

Porphyrin 98 was formed in only 8% yield, while 99 and

100 were obtained in 18 and 21%, respectively. In all three

cases the target compounds were formed as the minor prod-

uct. The main products (24–28%) were the respective tri-

substituted A₂B-porphyrins formed by substitution with

only R²from the organolithium reagent. A similar reaction

was observed for reaction of 18 with 4-aminophenyllithium

and propyl iodide. Here the A₂BC-porphyrin 101 was

formed in 20% yield accompanied by porphyrin 102 in 16%

yield. Clearly, this reaction is only useful in certain cases.

Use of a 5,15-AB-type porphyrin also allowed the forma-

tion of a 5,10-A₂BC-type porphyrin porphyrin in low yield.

Scheme 7. Synthesis of A₂BC-porphyrins via S_NAr.

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tively (Scheme 11). In a similar manner, reaction of 51 with

n-butyllithium/n-propyl iodide gave porphyrin 108 and re-

action with n-butyllithium/n-pentyl iodide gave compound

107 in 13 and 18% yield, respectively (Scheme 11).

Scheme 9. Synthesis of A₂BC-porphyrins via anion trapping.

Here, reaction of hexyllithium at the meso position and the

carbonyl position of 17 followed by reaction with propyl

iodide gave the porphyrin 103 (18%) accompanied by 104

(14%) (Scheme 10).

Scheme 11. Reactions of 51 with R¹Li/R²I combinations.

Typically, three to five equivalents of the organolithium

reagents were used and more than ten equivalents of alkyl

iodides. Complete trapping of the anionic complex formed

with electrophiles required long reaction times under heat-

ing (12–24 h at 70 °C) after addition of RI. Nevertheless,

the reaction appears difficult to control. Reaction of 51

with sec-butyllithium/n-propyl iodide or with sec-butyllith-

ium/n-pentyl iodide in dry THF and subsequently hydroly-

sis with water and oxidation with DDQ yielded the new free

base ABC-porphyrin 111 in 14% yield without formation

of the meso-tetrasubstituted porphyrin. Similarly, 51 re-

acted with phenyllithium in dry THF followed by addition

of 3-iodopropionic acid or with phenyllithium followed by

addition of 3-(iodomethyl)pyridine hydrogen iodide under

the same conditions to the ABC-porphyrin 110 in 45%

yield, again without any formation of ABCD-porphyrins.

Mechanistically the formation of the ABC-porphyrins can

be explained by a shift in the equilibrium from the carban-

ionic intermediate to a phlorin-type intermediate. This is

more easily hydrolyzed and oxidized to the ABC-porphyrin

than undergoing an electrophilic attack.

Scheme 10. Synthesis of an 5,10-A₂BC-porphyrin via anion trap-

ping.

Synthesis of ABCD-Type Porphyrins

On the basis of the outline given above three approaches

were investigated. These include one-pot anion trapping re-

actions, sequential RLi reactions and Pd-catalyzed reac-

tions of bromoporphyrins.

One-Pot Reactions

Treatment of 51 with p-hydroxyphenyllithium/n-pentyl

First we investigated the synthesis of ABCD-type por- iodide or with p-hydroxyphenyllithium/n-propyl gave no re-

phyrins through a one pot reaction. As described, this was action. In contrast reaction with phenyllithium/5-iodouracil

based on the reaction of porphyrins with RLi with forma- (dissolved in 2 mL DMF) or with p-hydroxyphenyllithium/

tion of an anionic intermediate^[16]that can be trapped with 3-(iodomethyl)pyridine hydrogen iodide in dry THF and

electrophiles followed by oxidation.^[12,14]For example, the boiling the reaction mixture resulted in the formation of

5,15-disubstituted AB-type porphyrin [5-hexyl-15-(4-meth- polar blue and black materials, indicating ring-opening re-

oxyphenyl)porphyrin] (51) was treated with phenyllithium actions.

in dry THF with formation of an anion that could be

Similar observations were made with porphyrin 112. For

trapped with alkyl iodides (n-propyl iodide or n-pentyl io- example, reaction with n-butyllithium/n-propyl iodide or

dide) to yield the tetra-meso-substituted free base ABCD- with n-butyllithium/n-pentyl iodide gave only the ABC-por-

porphyrins 105 and 106 in yields of 25 and 14%, respec- phyrin 113 in 15% yield. Various other combinations of

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

organolithium reagents and alkyl, aryl or heterocyclic pounds were biologically relevant ABCD-porphyrins carry-

iodides together with a wide varity of AB-porphyrins with ing both precursors for p-hydroxyphenyl groups and vari-

different functional groups were tested for the synthesis of ous alkyl chains.

ABCD-porphyrins but failed to do so. In some cases this is

Here, porphyrin 51 was reacted to the ABC-porphyrin

probably due to the inability of the in situ formed ABC- 114 by the addition of n-butyllithium. The compound was

porphyrin intermediate to react with the electrophilic iodide not characterized but added directly to a solution of p-hy-

reagents.

droxyphenyllithium followed by addition of water and

DDQ to form the ABCD-porphyrin 5-butyl-10-hexyl-15-p-

hydroxyphenyl-20-(4-methoxyphenyl)porphyrin (115) in

60% yield (Scheme 12). Using a similar sequence with por-

phyrin 112, PhLi and 4-hydroxyphenyllithium, porphyrin

117 was obtained in 37% yield. Similar results were ob-

tained when using ABC-type porphyrins for conversion to

the respective ABCD-type systems (see below). The results

indicate that the two-step synthesis might be the method of

choice for the preparation of functionalized ABCD-por-

phyrin in acceptable yields as the complete synthetic path-

way gave higher overall yields compared to the one-pot pro-

cedure.

Reaction of ABC-Porphyrins with RLi

Obviously another possibility is the use of ABC-type

porphyrins for reactions with RLi, formally as the last step

in a sequence of four reactions starting with porphyrin to

yield ABCD-porphyrins. Scheme 13 outlines some of the re-

sults. For example, preparation of the ABCD-type por-

phyrin 118 was possible through reaction of 62 with 4-

methoxyphenyllithium in 40% yield. In a similar manner

the porphyrins 119 to 122 were accessible in varying yields.

In order to prevent β-addition reactions the number of RLi

equivalents has to be kept at a minimum for the conversion

ABC Ǟ ABCD. To some extent, this accounts for the rela-

tively low yields encountered in these reactions.

Sequential Reactions with RLi

Next, we attempted the preparation of ABCD-type por-

phyrins by a two-step synthesis through functionalization

of the respective AB-porphyrins by two S_NAr reactions with

organolithium reagents, first to the ABC-porphyrins (see

above) and then to ABCD-type porphyrins. Target com-

Scheme 13. Transformation of ABC-porphyrins to ABCD-por-

phyrins via S_NAr.

Nevertheless, these reactions show that, in principle, it

is possible to sequentially substitute porphyrin with four

different residues using RLi reagents. Admittedly, this

method works much better, i.e. with higher yields, for the

more soluble octaethylporphyrins where introduction of the

Scheme 12. Transformation of AB-porphyrins to ABCD-por-

phyrins.

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245

M. O. Senge et al.

FULL PAPER

first three meso residues can be accomplished in quantita- porphyrin and boron coupling partner used. In some cases

tive yield and only introduction of the D residue gives lower (e.g. 127) debromination of the starting material (to 85) was

yields.^[34]

observed. The dibromo derivative 125 was also subjected to

the coupling conditions to investigate the reactivity of the

two different bromo residues. Reaction with 3-nitrophen-

ylboronic acid gave a mixture of the doubly substituted

Synthesis of ABCD-Porphyrins Through Pd-Catalyzed

Reactions

Having the ABC-type porphyrins in hand, another pos- product 134 and compound 133 where only the porphyrin

sibility for the construction of ABCD-type porphyrins was meso bromo residue had reacted.

obvious. This involved bromination of the ABC-porphyrins,

followed by Pd-catalyzed C–C couplings. The bromination

Structural Studies

of ABC-porphyrins was achieved easily in good yields. For

example, compounds 123 and 124 were obtained in 71 and

77% yield, respectively (Scheme 14). Upon reaction of 82

with NBS a new reaction was observed. The product 125

showed that both meso bromination and bromination of the

2,4,6-trimethoxyphenyl residue had occurred in 54% yield.

Similar reactions have been observed in the literature for

other systems.^[35]

Despite many attempts only two crystals of sufficient

quality for single-crystal X-ray determination could only be

grown for two compounds. These were the closely related

5,15-dibromo compounds 79 (Figure 1) and 81 (Figure 2)

which differ only in the steric demand of one meso aryl

residue (2,4,6-trimethoxyphenyl in 79 vs. 3,4,5-trimethoxy-

phenyl in 81). As expected for an unsymmetrical com-

pound^[36]79 forms weakly π-stacked dimers in the crystal

with a hexyl chain on the same face as a neighbouring aryl

group, i.e. antiparallel layers. In compound 81 the inter-

molecular separation is much larger and parallel layers are

formed. The closest contact observed is a Br–CH₂interac-

tion (Br2···H10G, 2.883 Å). As shown in Table 1 both struc-

tures exhibit only very minor deviations from planarity. The

largest deviations are observed for the b-positions (0.03–

Figure 1. View of the molecular structure of 79 in the crystal.

Hydrogen atoms have been omitted for clarity; thermal ellipsoids

are for 50% occupancy.

Scheme 14. Transformation of ABC-porphyrins to ABCD-por-

phyrins via Suzuki reactions.

The bromo-ABC-porphyrins were then subjected to Su-

zuki coupling conditions similar to those used for the prep-

aration of ABC-porphyrins from AB-type systems (see

above). As shown in Scheme 14 the reactions works well,

Figure 2. View of the molecular structure of 81 in the crystal.

Hydrogen atoms have been omitted for clarity; thermal ellipsoids

although the yields vary significantly and depend on the are for 50% occupancy.

246

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

0.27 Å in 77 and 0.15–0.32 Å in 81). These deviations are in the sequence AǞABǞABCǞABCD porphyrins can

in line with crystal packing and minor steric effects to be give almost any desired ABCD-porphyrins.

expected for this class of compounds.^[38]

Table 1. Selected structural and conformation parameters [Å] for

79 and 81.

Experimental Section

General Methods: All chemicals used were of analytical grade and

Compound

79

81

purified before use. Dichloromethane was dried with phosphorus

pentoxide followed by distillation; THF was dried with sodium fol-

lowed by distillation. Silica gel 60 (Merck) was used for column

chromatography unless otherwise noted. Analytical thin-layer

chromatography (TLC) was carried out using silica gel 60 plates

(fluorescence indicator F₂₅₄; Merck). Melting points are uncor-

rected and were measured with a Reichert Thermovar instrument.

NMR spectra were recorded using a Bruker AM 270 instrument

(270 MHz), a Bruker DPX 400 (400.13 MHz for ¹H NMR and

100.61 MHz for ¹³C NMR) or a Bruker AV 600 (600.13 MHz for

¹H NMR and 150.90 MHz for ¹³C NMR) instrument. Chemical

shifts are given in ppm and referenced to the TMS signal as internal

standard. The assignment of the signals was confirmed by 2D spec-

tra (COSY, HMBC, HMQC) except for those porphyrins with low

solubility. Electronic absorption spectra were recorded with a Spe-

cord S10 instrument (Zeiss) using CH₂Cl₂as solvent. Mass spectra

were recorded using a Varian MAT711 or MAT112S mass spec-

trometer using the EI technique with a direct insertion probe and

an excitation energy of 80 eV. FAB spectra were recorded with CH-

5 DF instrument from Varian. HRMS data were determined using

a Micromass TOF instrument fitted with an EI probe. Elemental

analyses were performed with a Perkin–Elmer 240 analyzer. Data

for single-crystal X-ray determinations were collected using Rigaku

Saturn-724 system complete with CCD detector utilizing Mo-K_α

radiation.

[times ]^[a]

2.064

0.013

0.06

0.04

0.11

0.07

0.02

2.056

0.039

0.15

0.09

0.11

0.08

0.09

0.07

Ξ^[b]

∆24^[c][37]

[d]

∆C_m

δC-5^[e]

δC-10^[e]

δC-15^[e]

δC-20^[e]

[a] Core size, average vector length from the geometric centre of

the four nitrogen atoms to the nitrogen atoms. [b] Core elongation

parameter defined as the difference between the vector lengths

(|N21–N22| + |N23–N24|)/2 – (|N22–N23| + |N21–N24|)/2. [c]

Average deviation of the 24 macrocycle atoms from their least-

squares plane. [d] Average deviation of the C_mcarbon atoms from

the 4N-plane. [e] Average deviation of the C_mcarbon atom from

the 4N-plane.

In conformational terms the main difference between

both compounds is the tilt angle between the trimethoxy-

phenyl residue and the least-squares-plane of the macro-

cycle. In compound 81 the tilt angle is 94.4°, i.e. the residue

is orthogonal to the molecular plane. In the compound 79

the tilt angle is 70.6° which is more in line with those of

other meso arylporphyrins.^[36a]

Starting Materials: 5-(tert-Butyl)porphyrin (32), 33, 34, 39,^[18]5,15-

bis(3-methoxyphenyl)porphyrin (58),^[11]48,^[11]87,^[11]88,^[11]5-(4-

ethynylphenyl)-10,20-diphenylporphyrin (96),^[15]5,15-dihexylpor-

phyrin (18),^[11]5-hexyl-15-(4-methoxyphenyl)porphyrin (51),^[11]and

Conclusions

A full analysis of the synthesis of all members of the

ABCD-type porphyrin series by using porphyrin reactions 5-hexyl-15-(3,5-dimethoxyphenyl)porphyrin (112),^[11]were pre-

pared following published procedures.

with organolithium reagents and Pd-catalyzed coupling re-

actions has been given. As shown, the synthesis of the 5,15-

A₂starting materials is still best accomplished by condensa-

5-(4-Methoxycarbonylphenyl)porphyrin (9): Dry dichloromethane

(2 L) was placed in a three-necked-flask equipped with magnetic

tion methods. Reaction of A-porphyrins with RLi works stirrer, gas inlet (argon) and a reflux condenser. Dipyrromethane

(600 mg, 4 mmol), 2-(hydroxymethyl)pyrrole (680 µL, 7.8 mmol),

and methyl 4-formylbenzoate (630 mg, 3.8 mmol) were added. The

flask was shielded from ambient light and then 1.40 mL (1.8 mmol)

of trifluoroacetic acid were added and the reaction mixture was

stirred for 18 h at 20 °C. After this time, 2.72 g (12 mmol) of DDQ

suspended in 100 mL of dry dichloromethane were added and the

mixture was stirred for 1 h. Next, 3 mL of triethylamine were added

and the reaction mixture was stirred for 15 min. The reaction mix-

ture was filtered through followed by chromatography on silica

using dichloromethane as eluent. The first fraction was porphyrin

but is somewhat problematic due to the formation of re-

gioisomers and multiple alkylation products. Here ad-

ditional synthetic developments are required.^[24]Neverthe-

less, the AB-porphyrins are suitable starting materials for

ABC-type systems through nucleophilic substitution, and

the reactions give good yield. Additionally, Pd-catalyzed re-

actions of appropriately brominated systems can be used,

but they require the separation of the mono- and dibromo

starting materials. The ABC-porphyrins can be transformed

with RLi reagents to the respective ABCD-type systems, (≈ 10 mg), followed by the title compound and traces of 5,15-bis-

[4-(methoxycarbonyl)phenyl]porphyrin. Recrystallization from

CH₂Cl₂/MeOH gave 128 mg of red crystals (0.29 mmol; 8%); m.p.

Ͼ300 °C. R_f= 0.77 (CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃, TMS):

δ = –3.60 (br. s, 2 H, NH), 4.15 (s, 3 H, COOCH₃), 8.33 (m, 2 H,

phenyl-H), 8.46 (m, 2 H, phenyl-H), 9.06 (d, J = 4 Hz, 2 H, β-

pyrrole-H), 9.41 (d, J = 4 Hz, 2 H, β-pyrrole-H), 9.50 (m, 4 H, β-

pyrrole-H), 10.25 (s, 1 H, C15-H), 10.33 (s, 2 H, C10-H and C20-

H) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 400 (4.85), 422 (3.77),

586 (3.54). MS (EI, 80 eV, 140 °C): m/z (%) = 444 (100) [M⁺], 429

(1) [M⁺– CH₃], 413 (1) [M⁺– CH₃O], 385 (9) [M⁺– C₂H₃O₂],

but the yields are somewhat unsatisfactory and for sterically

hindered systems side reactions may be observed. Similarly,

AB-systems can be converted via RLi/RI to ABCD-por-

phyrins, again with low yields. Here, use of Pd-catalyzed

reactions is preferred although the RLi method gives easier

access to alkyl-substituted systems. Monobromination of

ABC-porphyrins proceeds well, and the subsequent cou-

pling reactions give acceptable yields. In order to optimize

the overall yields, a combination of both methods is neces-

sary. Overall, a use of either method for the individual steps 222 (1) [M²⁺]. HRMS: calcd. for C₂₈H₂₀N₄O₂444.15863; found

Eur. J. Org. Chem. 2010, 237–258

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247

M. O. Senge et al.

FULL PAPER

444.15649. C₂₈H₂₀N₄O₂(444.49): calcd. C 75.66, H 4.54, N 12.60;

found C 75.98, H 4.76, N 12.23.

dissolved in toluene (200 mL) and stirred for 4 d at 110 °C. The

crude reaction mixture was passed through a filter containing silica

gel, using CH₂Cl₂as eluent. The solvent was evaporated and the

resulting residue was recrystallized from dichloromethane/meth-

3,5-Bis(tert-butyl)benzaldehyde (10): Prepared in 58% yield follow-

ing the procedure given by Newman and Lee;^[39]m.p. 84 °C; lit.

84–85 °C. ¹H NMR (250 MHz, CDCl₃, TMS): δ = 9.99 (s, 1 H,

CHO), 7.71 (m, 3 H, Ar-H_o, Ar-H_p), 1.35 [s, 18 H, C(CH₃)₃] ppm.

¹³C NMR (63 MHz, CDCl₃): δ = 193.16, 151.87, 136.24, 128.87,

124.13, 34.97, 31.31 ppm. MS (40 °C, 80 eV): m/z = 219 (3) [M +

1]^·+, 218 (16) [M]^·+, 203 (100) [M – CH₃]^·+, 175 (3) [M – C₃H₇]^·+),

57 (3) [M – C₁₁H₁₃O]^·+).

1

anol to yield purple crystals (0.75 mmol, 86%); m.p. Ͼ300 °C. H

NMR (400 MHz, CDCl₃, TMS): δ = 9.97 (s, 2 H, meso-H), 9.21

(m, 2 H, β-pyrrole-H), 8.95 (m, 2 H, β-pyrrole-H), 8.2 (d, J = 7 Hz,

2 H, β-pyrrole-H), 8.11 (d, J = 7 Hz, 2 H, β-pyrrole-H), 7.97 (d, J

= 7.6 Hz, 2 H, Ph-H), 7.89 (d, J = 7.6 Hz, 2 H, Ph-H), 1.53 (s, 24

H, CH₃) ppm. UV/Vis(THF): λ_max.(logε) = 400 (5.2), 515 (4.17),

546 nm (3.94). HRMS: calcd. for C₄₄H₄₂B₂N₄O₄Ni 770.2746;

found 770.2750.

5-[3,5-Bis(tert-butyl)]dipyrromethane (12): Prepared in 48% yield

following the procedure given by Beavington and Burn.^{[40] 13}C

NMR (63 MHz, CDCl₃): δ = 150.80, 140.84, 132.94, 122.67,

120.81, 116.96, 108.25, 107.10, 44.45, 34.79, 31.44 ppm.

5,10-Bis[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]por-

phyrin (16): Tripyrrane (2 g, 8.8 mmol), pyrrole (0.6 g, 8.88 mmol)

and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde

(4.22 g, 18.2 mmol) were added under Ar at room temperature to

a 2 L three-necked flask containing 1 L of dichloromethane. After

30 min, TFA (0.127 g, 0.888 mmol) was added, and mixture was

stirred for 12 h. Then four equiv. of DDQ (8 g, 35.2 mmol) were

added and stirring was continued for 60 min at room temp. fol-

lowed by addition of 1 mL NEt₃. The crude reaction mixture was

passed through a filter containing silica gel, eluting with CH₂Cl₂.

The solvent was evaporated to near dryness and then absorbed

onto 5 g of silica gel. The absorbed sample was added to the top

of the column containing silica gel and with n-hexane/acetone (1:1,

v/v). The product was isolated as purple crystals in 0.4% yield

(27 mg); m.p. Ͼ300 °C. ¹H NMR (400 MHz, CDCl₃, TMS): δ =

10.27 (s, 2 H, meso-H), 9.49 (s, 2 H, β-pyrrole-H), 9.37 (d, J =

4.08 Hz, 2 H, β-pyrrole-H), 9.04 (d, J = 4.68 Hz, 2 H, β-pyrrole-

H), 8.93 (s, 2 H, β-pyrrole-H), 8.26 (dd, J = 7.6 Hz, 8 H, Ph-H),

1.58 (s, 24 H, CH₃), –3.34 (br. s, 2 H, NH) ppm. ¹³C NMR

(400 MHz, CDCl₃): δ = 24.61, 29.27, 83.7, 119.5, 103.84, 132.57,

133.73, 144.58 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 407 (4.55),

503 (3.28), 576 (2.79), 630 nm (2.30). HRMS: calcd. for

C₄₄H₄₄B₂N₄O₄714.4666; found 715.3685.

5-[3,5-Bis(tert-butyl)]porphyrin (13): Dipyrromethane (0.34 g,

2.3 mmol) and the 5-substituted dipyrromethane 12 (2.3 mmol)

were dissolved in 1.2 L dichloromethane and degassed under Ar

for 10 min. Next, trimethyl formiate (38 mL, 0.35 mmol) was added

and the solution treated dropwise with a solution of trichloroacetic

acid (17.65 g, 108 mmol) in 460 mL dichloromethane. The mixture

was stirred for 4 h at room temp. and then mixed with pyridine

(31.2 mL, 0.39 mol) and stirring was continued for another 17 h.

The solution was purged with oxygen for 10 min for oxidation and

filtered through silica gel. After removal of the solvent in vacuo

column chromatography (n-hexane/ethyl acetate; 5:1, v/v) gave a

purple solid as the main fraction after removal of the solvent

(23 mg, 0.05 mmol, 4%); m.p. 273 °C. ¹H NMR (400 MHz, CDCl₃,

TMS): δ = 10.32 (s, 2 H, meso-H^10,20), 10.24 (s, 1 H, meso-H¹⁵),

9.49 (AB, ³J_12,13= 4.6, ³J_17,18= 4.6 Hz, 2 H, β-pyrrole-H^12,18), 9.46

(AB, ³J_12,13= 4.6, ³J_17,18= 4.6 Hz, 2 H, β-pyrrole-H^13,17), 9.41 (AB,

3

³J_2,3= 4.6, J_7,8= 4.6 Hz, 2 H, β-pyrrole-H^2,8), 9.14 (AB, J_2,3

=

4.6, ³J_7,8= 4.6 Hz, 2 H, β-pyrrole-H^3,7), 8.12 (m, 2 H, Ar-H_o), 7.83

(m, 1 H, Ar-H_p), 1.55 [s, 18 H, C(CH₃)₃], –3.58 (bs, 2 H, NH) ppm.

¹³C NMR (126 MHz, CDCl₃): δ = 149.00, 140.70, 131.71, 131.17,

130.99, 130.10, 121.15, 104.56 (C10, C20), 103.30 (C15), 35.08

(C31, C35), 31.76 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 401 (5.33),

497 (4.19), 528 (3.44), 569 (3.70), 623 (2.78). MS (160–170 °C,

80 eV): m/z = 499 (36) [M + 1]^·+, 498 (100) [M]^·+. HRMS: calcd.

for C₃₄H₃₄N₄498.27835; found 498.27444.

General Procedure for the Synthesis of AB-Type Porphyrins (Mixed

Condensation): A three-necked flask equipped with magnetic stirrer,

gas inlet (argon) and a reflux condenser was charged with 2 L

dichloromethane. Dipyrromethane (1200 mg, 8.2 mmol), the ap-

propriate aldehyde (4.14 mmol), and the other appropriate alde-

hyde (4.15 mmol) were added. Then 140 µL (1.8 mmol) TFA were

added and the reaction mixture was stirred for 16 h at 20 °C. Next

DDQ (2.77 g, 12.2 mmol) in 100 mL of dry dichloromethane was

added and the mixture was stirred for 1 h. Subsequently, 6 mL of

NEt₃were added and the reaction mixture was filtered through

600 mL of silica, eluting with dichloromethane. Column

chromatography eluting with dichloromethane gave the fractions

which were recrystallized from CH₂Cl₂/MeOH to yield purple crys-

tals.

5,15-Bis[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]por-

phyrin (14): Dipyrromethane (1.38 g, 9.25 mmol) and 4-(4,4,5,5-tet-

ramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (2.25 g, 9.71 mmol)

were added to a 2 L three-necked flask containing dichloromethane

(1 L) under Ar. After 30 min TFA (0.1 g, 0.925 mmol) was added

and the mixture was stirred for 12 h. Next two equiv. DDQ (4.2 g,

18.5 mmol) were added and stirring was continued for 60 min at

room temp. followed by addition of 1 mL triethylamine. Without

evaporation of solvent, the crude reaction mixture was passed

through a filter containing silica gel, using dichloromethane as elu-

ent. The solvent was evaporated and the resulting residue was

recrystallized from dichloromethane/methanol to give purple crys-

5-Hexyl-15-(4-methoxycarbonylphenyl)porphyrin (17): The pro-

cedure followed that given above using dipyrromethane (1200 mg,

8.2 mmol), methyl 4-formylbenzoate (680 mg, 4.14 mmol), and

heptanal (0.580 mL, 4.15 mmol). Column chromatography eluting

with dichloromethane gave three fractions which were recrystallized

from CH₂Cl₂/MeOH to yield purple crystals. The first fraction was

5,15-dihexylporphyrin (18), 181 mg, 0.378 mmol, 18%), the second

fraction 5-hexyl-15-(4-methoxycarbonylphenyl)porphyrin (17,

525 mg, 0.99 mmol; 23%), and the third fraction 5,15-bis(4-meth-

oxycarbonylphenyl)porphyrin (19, 168 mg, 0.29 mmol, 14%). 17:

M.p. 256 °C. R_f= 0.37 (CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃,

TMS): δ = –3.05, –3.04 (each s, 1 H, NH), 0.92 (t, J = 7 Hz, 3 H,

CH₂CH₃), 1.41 (m, 2 H, CH₂CH₃), 1.53 (m, 2 H, CH₂CH₂CH₃),

1

tals (1.92 g, 58.2%); m.p. Ͼ 300 °C. H NMR (400 MHz, CDCl₃,

TMS): δ = 10.35 (s, 2 H, meso-H), 9.42 (d, J = 4.64 Hz, 4 H, β-

pyrrole-H), 9.1 (d, J = 4.64 Hz, 4 H, β-pyrrole-H), 8.3 (dd, J =

9.065 Hz, 8 H, Ph-H), 1.55 (s, 24 H, CH₃), –3.1 (br. s, 2 H, NH)

ppm. ¹³C NMR (400 MHz, CDCl₃): δ = 133.97, 132.86, 131.24,

130.57, 104.90, 83.70, 28.91, 24.62, 24.42 ppm. UV/Vis (THF):

λ_max.(logε) = 406 (4.42), 502 (4.21), 535 (3.95), 576 (3.84), 631 nm

(364). HRMS: calcd. for C₄₄H₄₄B₂N₄O₄714.4666; found 715.3600.

{5,15-Bis[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phen-

yl]porphyrinato}nickel(II) (15): Free base porphyrin 14 (626.5 mg,

0.877 mmol) and nickel acetylacetonate (900 mg, 3.51 mmol) were

248

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meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

1.80 (m, 2 H, CH₂CH₂CH₂CH₃), 2.59 (m, 2 H, CH₂CH₂CH₂- H), 9.69 (d, J = 5.26 Hz, 1 H, β-pyrrole-H), 9.79 (m, J = 4.68 Hz,

CH₂CH₃), 4.11 (s, 3 H, COOCH₃), 5.01 (t, J = 8 Hz, 2 H, 2 H, β-pyrrole-H, meso-H), 10.06 (s, 1 H, meso-H) ppm. ¹³C NMR

CH₂CH₂CH₂CH₂CH₂CH₃), 8.33 (m, 2 H, Ph-H), 8.43 (m, 2 H, (100 MHz, CDCl₃, TMS): δ = 13.6, 13.7, 19.2, 22.2, 22.5, 23.2,

Ph-H), 8.93 (d, J = 5 Hz, 2 H, β-pyrrole-H), 9.36 (d, J = 5 Hz, 2 26.6, 28.9, 29.2, 29.7, 30.5, 31.4, 32.3, 35.0, 36.6, 36.9, 40.2, 102.0,

H, β-pyrrole-H), 9.43 (d, J = 5 Hz, 2 H, β-pyrrole-H), 9.61 (d, J =

5 Hz, 2 H, β-pyrrole-H), 10.22 (s, 2 H, meso-H) ppm. UV/Vis

(CH₂Cl₂): λ_max.(logε) = 407 (5.18), 503 (4.07), 536 (3.63), 576,

640 nm (3.55). HRMS: calcd. for C₃₄H₃₂N₄O₂528.2525; found

528.2749. C₃₄H₃₂N₄O₂(528.65): calcd. C 77.25, H 6.10, N 10.60;

found C 77.21, H 6.49, N 10.99.

103.3, 120.2, 125.5, 127.4, 128.3, 129.1, 129.2, 130.0, 130.4, 130.7,

131.0, 167.2 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 412 (4.81), 513

(3.80), 551 (3.32), 591 (3.47), 645 nm (3.10). HRMS: calcd. for

C₂₈H₃₁N₄423.2549; found 423.2553.

5-tert-Butyl-15-[4-(dimethylamino)phenyl]porphyrin (41): A 250-mL

Schlenk flask was charged with 4-bromo-N,N-dimethylaniline

(11 equiv.) dissolved in 20 mL diethyl ether. A 2.5  solution of

nBuLi in hexane (1 equiv.) was added dropwise over 45 min under

Ar at –78 °C. The cold bath was removed and the solution stirred

for 2 h at room temp. A 100-mL Schlenk flask was charged with a

solution of the porphyrin 32 (53 mg, 0.14 mmol, 1 equiv.) in 50 mL

THF and cooled to –70 °C. This solution was then added to the

solution of the in situ generated LiR reagent (cooled to –40 to

–70 °C, 11 equiv.). The colour changed from red to green-brown.

The cold bath was removed and the solution stirred for 2 h at room

temp. Next 5 mL water in 5 mL THF was added and this was ac-

companied by a colour change to green. The solution was stirred

for 30 min followed by addition of 10 equiv. DDQ which resulted

in a colour change to red. The mixture was filtered through silica

gel and then neutral alumina eluting with dichloromethane fol-

lowed by removal of the solvent in vacuo. Column chromatography

on silica gel (CH₂Cl₂/n-hexane = 1:3, v/v and CH₂Cl₂/n-hexane =

5,15-Bis(4-methoxycarbonylphenyl)porphyrin (19): Obtained from

1

the synthesis of 17; m.p. Ͼ300 °C. R_f= 0.11 (CH₂Cl₂). H NMR

(400 MHz, CDCl₃, TMS): δ = –3.13 (s, 2 H, NH), 4.12 (s, 6 H,

COOCH₃), 8.37 (m, 4 H, Ph-H), 8.45 (m, 4 H, Ph-H), 9.13 (d, J =

5 Hz, 4 H, β-pyrrole-H), 9.38 (d, J = 5 Hz, 4 H, β-pyrrole-H), 10.18

(s, 2 H, meso-H) ppm. UV/Vis (CH₂Cl₂): λ_max.= 405, 506, 534, 574,

639 nm. HRMS: calcd. for C₃₆H₂₆N₄O₄578.1954; found 578.2314.

C₃₆H₂₆N₄O₄(578.63): calcd. C 74.73, H 4.53, N 9.68; found C

74.51, H 4.78, N 9.57.

General Procedure for the Synthesis of 5,15-AB-Type Porphyrins

(Organolithium Reaction): For example, 5-(tert-butyl)porphyrin

(32, 100 mg, 0.272 mmol) was dissolved in 80 mL dry THF under

argon and the reaction mixture was cooled to –78 °C. nBuLi

(0.435 mL, 1.088 mmol) was added dropwise over 15 min via sy-

ringe. The cold bath was removed and stirring continued 1.5 h at

room temperature. 0.5 mL H₂O was added and stirring continued

15 min. Then DDQ (243.3 mg, 1.088 mmol) was added in 10 mL

THF and the reaction mixture was stirred for an additional hour.

The reaction mixture was filtered through silica gel, followed by

evaporation of the solvent.

1:7, v/v) gave 5-n-butyl-15-tert-butylporphyrin (38) (2 mg,

Ͻ

0.01 mmol, 5%) as the first fraction. The title compound 41 fol-

lowed as the second fraction to yield purple crystals after

recrystallization from CH₂Cl₂/MeOH (19 mg, 0.04 mmol, 36%);

m.p. 270 °C (decomp.). R_f= 0.4 (CH₂Cl₂/n-hexane, 9:1, v/v). ¹H

NMR (300 MHz, CDCl₃, TMS): δ = 10.07 (s, 2 H, meso-H), 9.85

5-(n-Butyl)-15-(tert-butyl)porphyrin (38): Prepared according to the

general procedure using 5-(tert-Butyl)porphyrin (32, 100 mg,

0.272 mmol), nBuLi (0.435 mL, 1.088 mmol) and DDQ (243.3 mg,

1.088 mmol). The crude reaction mixture was purified by column

chromatography eluting with n-hexane/CH₂Cl₂(2:1, v/v). The first

fraction was 5-(n-butyl)-15-(tert-butyl)porphyrin (38, 20 mg,

0.047 mmol, 17%) as purple crystals, the second fraction 5-(n-

butyl)-10-(tert-butyl)porphyrin (39, 8 mg, 0.018 mmol, 7%) as pur-

ple crystals, followed by starting material (10 mg, 0.027 mmol,

10%). Compound 38: M.p. Ͼ 300 °C. R_f= 0.6 (n-hexane/CH₂Cl₂,

1:1, v/v). ¹H NMR (400 MHz, CDCl₃, TMS): δ = –1.97 (s, 2 H,

NH), 1.15 (t, J = 7.0 Hz, 3 H, CH₂CH₂CH₂CH₃), 1.81 (m, 2 H,

CH₂CH₂CH₂CH₃) 2.50 (m, 2 H, CH₂CH₂CH₂CH₃), 2.61 [s, 9 H,

C(CH₃)₃], 4.94 (t, J = 7.6 Hz, 2 H, CH₂CH₂CH₂CH₃), 9.24 (d, J

= 4.68 Hz, 2 H, β-pyrrole-H), 9.34 (d, J = 4.1 Hz, 2 H, β-pyrrole-

H), 9.50 (d, J = 4.68 Hz, 2 H, β-pyrrole-H), 9.86 (d, J = 4.68 Hz, 2

H, β-pyrrole-H), 10.06 (s, 2 H, meso-H) ppm. ¹³C NMR (100 MHz,

CDCl₃, TMS): δ = 13.7, 23.1, 29.2, 33.4, 39.8, 40.0, 40.3, 103.9,

119.1, 127.1, 129.7, 130.7, 131.0, 141.4, 143.0, 146.6, 147.7 ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 405 (4.68), 509 (3.62), 542 (3.52),

542 (3.52), 636 nm (3.22). MS (EI, 250 °C, 80 eV): m/z = 450 (100)

[M]^·+, 435 (72) [M – CH₃]⁺, 394 (10) [M – C₄H₉+ H]^·+, 379 (7)

3

(AB, J = ³J = 4.8 Hz, 2 H, β-pyrrole-H^3,7), 9.26 (AB, J = J =

4.7 Hz, 2 H, β-pyrrole-H^12,18), 9.23 (AB, J = J = 4.8 Hz, 2 H, β-

pyrrole-H^2,8), 9.10 (AB, ³J = ³J = 4.7 Hz, 2 H, β-pyrrole-H^13,17),

8.12 (AB, ³J = ³J = 8.2 Hz, 2 H, Ar-H_o), 7.15 (AB, ³J = ³J =

8.2 Hz, 2 H, Ar-H_m), 3.23 [s, 6 H, N(CH₃)₂], 2.60 [s, 9 H,

C(CH₃)₃], –1.93 (br. s, 2 H, NH) ppm. ¹³C NMR (75 MHz,

CDCl₃): δ = 150.04, 148.10, 147.61, 143.90, 142.10, 135.96, 131.09,

131.06, 130.62, 130.13, 128.78, 126.66, 120.14, 111.38, 104.69,

40.90, 40.73, 40.41 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 413

(4.78), 513 (4.07), 554 (4.07), 581 (3.89), 641 nm (3.70). MS

(250 °C, 80 eV): m/z = 485 (92) [M]^·+, 470 (100) [M – CH₃]⁺, 429

3

(25) [M – CH₃– C₂H₃N]⁺, 243 (23) [M]²⁺, 295 (30) [M – CH₃]²⁺

.

HRMS: calcd. for C₃₂H₃₁N₅485.2579; found 485.2562.

General Procedure for the Synthesis of 5,10-AB-Type Porphyrins: A

250-mL Schlenk flask was charged with the porphyrin (1 equiv.)

in 50 mL THF under Ar and cooled to –70 °C. The LiR reagent

(hexylllithium, 3.5 equiv. of a 2.5  solution in hexane) was added

dropwise over 15 min and the colour changed from red to green-

brown. The cold bath was removed and the solution stirred for

30 min at room temp. Next water (1 mL in 5 mL THF) was added

and the colour changed to green. The solution was stirred for

15 min and then oxidized with DDQ followed by stirring for a fur-

ther 30 min accompanied by a colour change to red. The mixture

was fitered through silica gel eluting with dichloromethane and the

solvents removed in vacuo.

[M – C₅H₁₁]⁺, 323 (17) [M – C₄H₉+ H – C₅H₁₁]⁺, 225 (3) [M]²⁺

.

HRMS: calcd. for C₂₈H₃₁N₄423.2549; found 423.2551.

5-(n-Butyl)-10-(tert-butyl)porphyrin (39): Derived from the synthe-

1

sis of 38; m.p. Ͼ 300 °C. R_f= 0.4 (n-hexane/CH₂Cl₂, 1:1, v/v). H

NMR (400 MHz, CDCl₃, TMS): δ = –2.41 (s, 2 H, NH), 1.15 (t, J

=

7.01, Hz,

3

H, CH₂CH₂CH₂CH₃), 1.81 (m,

2

H,

5-(1-Ethylpropyl)-10-hexylporphyrin (42): Prepared using the gene-

CH₂CH₂CH₂CH₃), 2.52 (m, 2 H, CH₂CH₂CH₂CH₃), 2.46 [s, 9 H, ral procedure given above using porphyrin 33 (1 equiv.) and hexyl-

C(CH₃)₃], 4.93 (t, J = 7.6 Hz, 2 H, CH₂CH₂CH₂CH₃), 9.11 (d, J llithium (3.5 equiv. of a 2.5  solution in hexane). Column

= 4.67 Hz, 1 H, β-pyrrole-H), 9.2 (d, J = 4.67 Hz, 1 H, β-pyrrole-

chromatography on silica gel eluting with CH₂Cl₂/n-hexane (1:1,

H), 9.25 (m, 3 H, β-pyrrole-H), 9.5 (d, J = 4.68 Hz, 1 H, β-pyrrole- v/v) gave a first fraction containing a mixture of di- and higher

Eur. J. Org. Chem. 2010, 237–258

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249

M. O. Senge et al.

FULL PAPER

alkylated species followed by the title compound as purple crystals

after recrystallization from CH₂Cl₂/MeOH/H₂O (37.1 mg,

0.38 mmol) in 40 mL of dry THF at –80 °C. The reaction mixture

was stirred for 5 h (TLC control). Subsequently, a mixture of 2 mL

0.08 mmol, 59%); m.p. 135 °C. R_f= 0.46 (n-hexane/CH₂Cl₂, 1:1, of water in 3 mL of THF was added for hydrolysis. After stirring

1

v/v). H NMR (500 MHz, CDCl₃, TMS): δ = 10.06 (s, 1 H, meso-

H¹⁵), 10.01 (s, 1 H, meso-H²⁰), 9.79 (m, 1 H, β-pyrrole-H⁷), 9.73

(m, 1 H, β-pyrrole-H³), 9.65 (m, 1 H, β-pyrrole-H⁸), 9.62 (AB,

³J_H12,H13= 4.7 Hz, 1 H, β-pyrrole-H¹²), 9.33 (m, 4 H, β-pyrrole-

of the mixture for 20 min, a solution of 10 equiv. of DDQ in THF

(0.03 ) was added and the reaction mixture was stirred for another

60 min at room temperature. Subsequently, the mixture was filtered

through silica gel and the organic solvent was removed under vac-

uum. Final purification was achieved by column chromatography

H^2,13,17,18), 5.14 [m, 1 H, m, CH(CH₂)₂], 5.09 (t, J = 8.2 Hz, 2 H,

3

CH₂C₅H₁₁), 3.00, 2.84 [m, 4 H, CH(CH₂)₂], 2.60 (m, 2 H, and elution with ethyl acetate/n-hexane (1:4, v/v) yielding the title

CH₂CH₂C₄H₉), 1.87 (m, 2 H, C₂H₄CH₂C₃H₇), 1.55 (m, 2 H,

compound (163 mg, 0.27 mmol, 71%) as purple crystals; m.p.

C₃H₆CH₂C₂H₅), 1.43 (m, 2 H, C₄H₈CH₂CH₃), 0.97 (t, ³J = 7.4 Hz, Ͼ300 °C. R_f= 0.52 (ethyl acetate/n-hexane, 1:4, v/v). ¹H NMR

3

3 H, C₅H₁₀CH₃), 0.96 (t, J = 7.3 Hz, 6 H, CH₂CH₃), –3.22 (br. s, (300 MHz, CDCl₃, TMS): δ = –2.91 (s, 2 H, NH), 4.02 (s, 6 H,

2 H, NH) ppm. ¹³C NMR (126 MHz, CDCl₃): δ ≈ 130 (C2, C3, OCH₃), 7.41 (m, 2 H, Ph-H), 7.71–7.92 (m, 9 H, Ph-H), 8.29 (m,

C7, C8, C12, C13, C17, C18), 123.21 (C5), 120.14 (C10), 103.11

(C15), 102.84 (C20), 50.53, 39.06, 36.10, 34.83, 31.94, 30.40, 22.78,

14.13 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 406 (5.58), 504 (4.14),

534 (3.37), 579 (3.60), 634 nm (3.08). MS (EI, 80 eV): m/z = 464

(100) [M]^·+, 435 (93) [M – C₂H₅]⁺, 393 (20) [M – C₅H₁₁]⁺, 364 (11)

2 H, Ph-H), 8.96 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 9.02 (d, J =

5.0 Hz, 2 H, β-pyrrole-H), 9.12 (d, J = 5.0 Hz, 2 H, β-pyrrole-H),

9.33 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 10.19 (s, 1 H, meso-H) ppm.

¹³C NMR (300 MHz, CDCl₃): δ = 55.06, 104.34, 113.09, 118.94,

120.21, 126.12, 127.19, 130.96, 134.05, 142.11, 142.64, 157.66 ppm.

[M – C₅H₁₁– C₂H₅]^·+, 335 (10) [M – C₅H₁₁– 2C₂H₅]⁺, 232 (11) UV/Vis (CH₂Cl₂): λ_max.(logε) = 413 nm (5.17), 441 (3.94), 508

[M]²⁺. HRMS: calcd. for C₃₁H₃₇N₄465.3018; found 465.3035.

(4.23), 541 (3.73), 582 (3.77), 637 nm (3.52). MS (EI, 80 eV): m/z

(%): 598 (100) [M⁺], 567 (10) [M⁺– 2CH₃– H], 522 (8) [M⁺

–

General Procedure for the Synthesis of 5,15-AB₂/A₂-Type Por-

phyrins: A 25-mL Schlenk flask was charged with dried porphyrin

(0.05 mmol) dissolved in 10 mL THF. The solution was cooled to

–80 °C and treated with 0.2 mmol of a 2.5  solution of hexyllith-

ium (80 µL). The colour changed from red to green-brown and

after 10 min changed to purple. The cold bath was removed and

the solution stirred for 15 min at room temp. Next water (1 mL)

was added and stirring was continued for 15 min. This was ac-

companied by a colour change to yellow-brown. Then DDQ

(0.1 mmol, 23 mg) in 0.4 mL THF was added and the mixture

stirred for 15 min until the colour had changed to dark red. The

mixture was filtered through silica gel and the solvent removed in

vacuo.

C₆H₄], 491 (8) [M⁺– 2CH₃– C₆H₅], 299 (86) [M⁺⁺]. HRMS: calcd.

for C₄₀H₃₀N₄O₂598.2368; found 598.2356.

5-(4-Hydroxyphenyl)-10,20-bis(3-methoxyphenyl)porphyrin (60): n-

Butyllithium (4 mL of a 2.5  solution in hexane, 10 mmol) was

added under argon to a 100-mL Schlenk flask charged with a solu-

tion of p-bromophenol (0.87 g, 5 mmol) in 10 mL of dry diethyl

ether at 0 °C. After addition of n-butyllithium the cold bath was

removed and stirring was continued for 18 h at room temperature.

To the vigorously stirred mixture was added rapidly a solution of

5,15-bis(3-methoxyphenyl)porphyrin (58, 200 mg, 0.38 mmol) in

40 mL of dry THF under argon. Further workup followed the pro-

cedure for 59. Final purification by column chromatography on

silica gel and elution with ethyl acetate/n-hexane (1:1, v/v) gave the

title compound (182 mg, 0.29 mmol, 77%) as purple crystals; m.p.

Ͼ300 °C. R_f= 0.54 (ethyl acetate/n-hexane, 2:1, v/v). ¹H NMR

(300 MHz, CDCl₃, TMS): δ = 4.01 (s, 6 H, OCH₃), 6.89 (d, J =

7.5 Hz, 2 H, Ph-H), 7.37 (d, J = 7.5 Hz, 2 H, Ph-H), 7.66 (t, 2 H,

Ph-H), 7.88 (m, 4 H, Ph-H), 7.90 (s, 1 H, OH), 7.97 (d, J = 7.5 Hz,

2 H, Ph-H), 8.91 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 9.00 (d, J =

5.0 Hz, 2 H, β-pyrrole-H), 9.12 (d, J = 5.0 Hz, 2 H, β-pyrrole-H),

9.32 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 10.17 (s, 1 H, meso-H) ppm.

¹³C NMR (300 MHz, CDCl₃): δ = 55.06, 104.22, 112.95, 118.91,

120.25, 127.38, 131.01, 134.33, 135.06, 142.67, 154.87, 157.62 ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 414 (5.17), 445 (4.06), 508 (4.17),

542 (3.61), 582 (3.64), 655 nm (3.39). MS (EI, 80 eV): m/z (%): 614

(38) [M⁺], 307 (40) [M⁺⁺]. HRMS: calcd. for C₄₀H₃₀N₄O₃

614.2317; found 614.2288.

5-(3,5-Di-tert-butylphenyl)-10,15-dihexylporphyrin (56): Prepared

following the above general procedure using porphyrin 13 (23 mg,

0.05 mmol) and a 2.5  solution of hexyllithium(80 µL, 0.2 mmol).

Column chromatography eluting with n-hexane/CH₂Cl₂(1:1, v/v)

gave a purple solid (6 mg, 0.01 mmol, 18%); m.p. 192 °C. ¹H NMR

(500 MHz, CDCl₃, TMS): δ = 10.00 (s, 1 H, meso-H²⁰), 9.61, 9.57

3

(AB, J = 4.8 Hz, 2 H, β-pyrrole-H^12,13), 9.54 (AB, J = 4.6 Hz, 1

H, β-pyrrole-H¹⁷), 9.50 (AB, J = 4.6 Hz, 1 H, β-pyrrole-H⁸), 9.31

3

(AB, J = 4.6 Hz, 1 H, β-pyrrole-H¹⁸), 9.21 (AB, J = 4.7 Hz, 1 H,

β-pyrrole-H²), 8.95 (AB, J = 4.7 Hz, 2 H, β-pyrrole-H^3,7), 8.05 (d,

3

J = 1.9 Hz, 2 H, Ar-H_o), 7.79 (t, J = 1.9 Hz, 1 H, Ar-H_p), 5.05,

5.00 (t, J = 8.1 Hz, 4 H, -CH₂CH₂CH₂CH₂CH₂CH₃), 2.57 (m, 4

H, -CH₂CH₂CH₂CH₂CH₂CH₃), 1.84 (m, 4 H, -CH₂CH₂CH₂CH₂-

CH₂CH₃), 1.55 (m, 4 H, -CH₂CH₂CH₂CH₂CH₂CH₃), 1.53 [s, 9 H,

C(CH₃)₃], 1.41 (m, 4 H, -CH₂CH₂CH₂CH₂CH₂CH₃), 0.94 (t, J =

7.3 Hz, 6 H, -CH₂CH₂CH₂CH₂CH₂CH₃), –2.91 (s, 2 H, NH) ppm. General Procedure for the Synthesis of ABC-Type Porphyrins: Por-

¹³C NMR (63 MHz, CDCl₃, TMS): δ = 148.85, 140.93, 132.52,

phyrin (0.1 mmol) was dissolved in THF and cooled to –78 °C.

131.27, 130.80, 129.85, 128.47, 127.91, 127.91, 128.24, 120.96,

Hexyllithium was added dropwise over the course of 15 min. The

120.42, 119.29, 103.38, 39.06, 38.80, 36.17, 35.33, 35.06, 31.76, cold bath was removed and stirring was continued for another

30.34, 22.77, 14.14 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 413

(5.50), 511 (4.19), 545 (3.78), 588 (3.65), 644 nm (3.54). MS (EI,

80 eV): m/z = 668 (46) [M + 1]^·+, 667 (100) [M]^·+, 610 (9) [M –

C₄H₉]^·+, 596 (14) [M – C₅H₁₁]^·+, 539 (12) [M – C₉H₂₀]^·+, 525 (30)

[M – C₁₀H₂₂]^·+. HRMS: calcd. for C₄₁H₄₈N₄596.38790; found

596.38421.

15 min. This was followed by addition of 0.5 mL water in 5 mL

THF, stirring for 15 min and addition of 6 mL of a solution of

DDQ in THF. The mixture was stirred for 20 min and then filtered

through neutral alumina washing with dichloromethane.

5-Hexyl-10-(4-methylphenyl)-20-(2,4,6-trimethoxyphenyl)porphyrin

(61): Prepared following the above standard procedure using por-

phyrin 21 (55 mg, 0.1 mmol). Column chromatography eluting with

neat dichloromethane gave the title compound as the single product

as a purple solid (59 mg, 0.09 mmol, 90 %); m.p. Ͼ300 °C. ¹H

NMR (500 MHz, CDCl₃, TMS): δ = 10.09 (s, 1 H, meso-H), 9.60

5,15-Bis(3-methoxyphenyl)-10-phenylporphyrin (59): Phenyllithium

(2 mL of a 1.8  solution in hexane, 0.06 mmol) was slowly added

(ca. 1 h) under argon to a 100-mL Schlenk flask charged with a

solution of 5,15-bis(m-methoxyphenyl)porphyrin (58, 200 mg,

250

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Eur. J. Org. Chem. 2010, 237–258

meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

(m, 2 H, β-pyrrole-H), 9.30 (m, 2 H, β-pyrrole-H), 8.90 (m, 4 H,

(3.55). MS (FAB⁺, 3 kV) = : m/z = calcd. for C₄₂H₄₀ClMnN₄O₃

3

β-pyrrole-H), 8.21 (d, J = 7.35 Hz, 2 H, tolyl-H_m), 7.56 (d, J =

738.21694; found 738.0 (9.0) [M]^·+, 703.0 (100.0) [M – Cl]⁺.

3

7.35 Hz, 2 H, tolyl-H_o), 6.68 (s, 2 H, Ar-H_o), 5.04 (t, J = 8.09 Hz,

5,10-Bis(2-hydroxyphenyl)-15-(4-methylphenyl)porphyrin (71): A

solution of 70 (200 mg of the atropisomeric mixture, 0.33 mmol) in

500 mL dichloromethane was treated dropwise with 1.3 mL BBr₃

solution (13 mmol) over the course of 1 h. The mixture was stirred

for 16 h at room temp. and then poured onto ice and treated with

NaHCO₃until neutral. The solution was diluted with dichloro-

methane and the organic phase extracted three times with water.

After drying of Na₂SO₄the solvent was removed in vacuo. Column

chromatography on silica gel eluting with neat dichloromethane

gave one product fraction which yielded a red-brown solid (120 mg,

0.21 mmol, 62 %); m.p. Ͼ 300 °C. ¹H NMR (500 MHz, CDCl₃,

TMS): δ = 10.14 (s, 1 H, meso-H), 9.29 (m, 2 H, β-pyrrole-H^2,18),

8.99 (m, 1 H, β-pyrrole-H¹⁷), 8.90 (m, 5 H, β-pyrrole-H^3,7,8,12,13),

8.27 (m, 2 H, tolyl-H_o), 8.10 (m, 2 H, Ar-H_o), 7.90 (m, 2 H, Ar-

H_p), 7. 06 (m, 2 H, tolyl-H_m), 7.21 (m, 4 H, Ar-H_m), –2.70 (bs, 2

H, NH) ppm. UV/Vis (CH₂Cl₂): λ_max.(log ε) = 413 (5.21), 509

(3.81), 544 (3.12), 584 (3.05), 639 nm (2.42). MS (290 °C, 80 eV):

m/z = 584.0 (100.00) [M]^·+). HRMS: calcd. for C₃₉H₂₈N₄O₂

584.22123; found 584.22125.

2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 4.11 (s, 3 H, p-OCH₃), 3.50 (s, 6

H, m-OCH₃), 2. 70 (s, 3 H, C₆H₄-CH₃), 2. 56 (m, 2 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 1.83 (m, 2 H, CH₂CH₂CH₂CH₂-

CH₂CH₃), 1.54 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.43 (m, 2 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 1.00 (t, ³J = 7.30 Hz, 3 H,

CH₂CH₂CH₂CH₂CH₂CH₃), –3.05 (bs, 2 H, NH) ppm. ¹³C NMR

(126 MHz, CDCl₃): δ = 161.99, 161.12, 148.41–145.14, 142.371,

139.80, 137.14, 134.50, 131.02–130.50, 127.25, 119.12–118.56,

104.00, 102.87, 91.00, 56.06, 55.64, 38.81, 35.51, 31.93, 30.34,

22.75, 21.51, 14.14 ppm. UV/Vis (CH₂Cl₂): λ_max.(log ε) = 413

(5.45), 511 (4.53), 543 (4.09), 585 (4.03), 641 nm (3.81). MS

(270 °C, 8 kV): m/z = 650.0 (100.00) [M]^·+, 579.0 (71.47) [M –

C₅H₁₁]⁺, 325.0 (10.91) [M]²⁺. HRMS: calcd. for C₄₂H₄₂N₄O₃

650.32569; found 650.32575.

5-(2-Methoxyphenyl)-10-(4-methylphenyl)-20-(2,4,6-trimethoxyphen-

yl)porphyrin (63): The free base porphyrin 21 (113 mg, 0.2 mmol)

was dissolved in 40 mL abs. THF and cooled to –40 °C. The LiR

reagent was added under vigorous stirring, the cold bath removed

and the mixture stirred for 1 h. The LiR reagent was prepared by

dissolving 1 g bromoanisol (5.4 mmol) in 15 mL abs. ethyl ether in

a Schlenk tube. Next 2.2 mL BuLi (2.5  in n-hexane, 5.5 mmol)

were added dropwise over 30 min at –78 °C. The cold bath was

removed and the mixture stirred for 1 h at room temp. After mixing

the two components the red mixture slowly turned brown. Next,

5 mL water in 5 mL THF were added and stirring continued for

30 min. Oxidation was achieved by stirring under air for 16 h. The

mixture was filtered through neutral alumina and washed with

dichloromethane. Column chromatography eluting with CH₂Cl₂/n-

hexane (1:2, v/v) yielded the target compound as purple crystals

after recrystallization from CH₂Cl₂/MeOH (90 mg, 0.13 mmol,

67%); m.p. Ͼ 320 °C. ¹H NMR (500 MHz, CDCl₃, TMS): δ =

5,10-[2,2Ј(-Dodecamethyleneoxy)diphenyl]-15-(4-methylphenyl)por-

phyrin (72): A solution of 100 mg of the dihydroxyporphyrin 71

(0.2 mmol) and 400 mg K₂CO₃in 25 mL DMF was heated to

100 °C. Over the course of 4 h 81.5 mg 1,12-dibromodecane

(0.25 mmol dissolved in 10 mL DMF) were added dropwise and

heating continued for another 3 h. The solution was cooled and

treated with saturated aq. ammonium chloride. After addition of

50 mL dichloromethane the organic phase was washed three times

with water and dried with Na₂SO₄. The solvent was removed in

high vacuum and column chromatography with CH₂Cl₂/n-hexane

(1:2, v/v) gave the title compound as a purple solid (90 mg,

0.12 mmol, 60 %); m.p. 300 °C. ¹H NMR (500 MHz, CDCl₃,

TMS): δ = 10.14 (s, 1 H, meso-H), 9.26 (m, 2 H, β-pyrrole-H^2,18),

8.97 (AB, ³J = 4.41 Hz, 1 H, β-pyrrole-H¹⁷), 8.89 (AB, ³J =

3

10.23 (s, 1 H, meso-H), 9.33 (m, 4 H, β-pyrrole-H), 9.08 (d, J =

3

4.54 Hz, 2 H, β-pyrrole-H), 9.02 (d, J = 4.54 Hz, 2 H, β-pyrrole-

3

5.50 Hz, 1 H, β-pyrrole-H¹³), 8.83 (AB, J = 4.41 Hz, 2 H, β-pyr-

3

H), 8.16 (d, J = 7.81 Hz, 2 H, tolyl-H_o), 7.61 (d, J = 7.45 Hz, 2

H, tolyl-H_m), 6.63 (s, 2 H, OMe-Ar-H_m), 4.12 (s, 3 H, p-OH₃), 3.53

(s, 6 H, o-OH₃), 2.71 (s, 3 H, C₆H₄-CH₃), –3.05 (bs, 2 H, NH) ppm.

¹³C NMR (126 MHz, CDCl₃): δ = 162.03, 161.21, 159.29, 148.84–

146.42, 139.13, 137.20, 135.42, 134.60, 131.56–130.08, 127.46,

119.62, 111.95, 104.02, 91.09, 56.00, 55.59, 55.47, 21.47 ppm. UV/

Vis (CH₂Cl₂): λ_max.(logε) = 407 (5.23), 504 (4.03), 539 (3.60), 575

(3.55), 630 nm (3.01). MS (FAB⁺, 3 eV): m/z. = calcd. for

C₄₃H₃₆N₄O₄672.27366; found 673.0 (100.00) [M + H]⁺.

C₄₃H₃₆N₄O₄(672.78): calcd. C 76.77, H 5.39, N 8.33; found C

76.55, H 5.70, N 8.57.

3

role-H^3,12), 8.75 (AB, J = 4.41 Hz, 2 H, β-pyrrole-H^7,8), 8.09 (m,

4 H, Ar-H_o), 7.76 (m, 2 H, Ar-H_p), 7.56, (d, ³J = 8.09 Hz, 2 H,

tolyl-H_m), 7.34 (m, 4 H, Ar-H_m), 3.86 (m, 4 H, alkyl chain), 0.86

(m, 6 H, alkyl chain), –0.81 (m, 8 H, alkyl chain), –1.11 (m, 6 H,

alyl chain), –2.92 (bs, 2 H, NH) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε)

= 415 (5.39), 511 (4.22), 545 (3.82), 582 (3.71), 635 nm (3.36). MS

(300 °C, 80 eV): m/z = 750.0 (100.00) [M]⁺, 375.0 (9.62) [M]²⁺

.

HRMS: calcd. for C₅₁H₅₀N₄O₂750.39338; found 750.39341.

C₅₁H₅₀N₄O₂(750.98): calcd. C 81.57, H 6.71, N 7.46; found C

81.23, H 6.80, N 7.59.

Chloro{5,10-[2,2Ј-(dodecamethyleneoxy)diphenyl]-15-(4-methylphen-

yl)porphyrinato}manganese(III) (73): The free base porphyrin 72

(100 mg, 0.13 mmol) was dissolved in 50 mL DMF and heated with

60 mg MnCl₂·4H₂O to reflux. After coolinig to room temp. the

mixture was filtered through neutral alumina (Brockman grade

III). Column chromatography eluting with dichloromethane gave

several minor fractions and the metal complex as the main fraction.

Evaporation of the solvent followed by column chromatography

eluting with neat dichloromethane gave the title compound (60 mg,

0.07 mmol, 55%); m.p. Ͼ300 °C. UV/Vis (CH₂Cl₂): λ_max.(logε) =

380 (4.40), 405 (3.77), 487 (4.90), 597 (3.95), 629 nm (2.91). MS

(FAB⁺, 3 kV): m/z = calcd. for C₅₁H₄₈ClMnN₄O₂838.28463; found

838.0 (7.0) [M]^·+, 803.0 (100.0), [M – Cl]⁺.

General Procedure for the Metallation with Manganese Chloride:

Free base porphyrin (100 mg, 0.14 mmol) was dissolved together

with 150 mg MnCl₂·4H₂O in 25 mL acetic acid (96%) and 7 mL

acetic anhydride. The solution was heated for 4 h at 110 °C. After

cooling to room temp. dichloromethane was added and the organic

phase washed several times with water. The organic solvent was

evaporated and the residue dried under high vacuum.

Chloro[5-hexyl-10-(4-methylphenyl)-20-(2,4,6-trimethoxyphenyl)por-

phyrinato]manganese(III) (65): Prepared following the above gene-

ral procedure using porphyrin 61 (100 mg, 0.14 mmol) and

MnCl₂·4H₂O (150 mg). Column chromatography eluting with

dichloromethane gave a minor compound followed by the metal

complex. Evaporation of the solvent gave a gree-red residue (99 mg,

0.12 mmol, 88%); m.p. Ͼ300 °C. UV/Vis (CH₂Cl₂): λ_max.(logε) =

370 (4.38), 405 (4.40), 479 (4.60), 581 (3.71), 614 (3.66), 643 nm

General Procedure for Bromination of 5,15-AB-Type Porphyrins:

The porphyrin (1 equiv.) was dissolved in 100 mL of chloroform

and cooled to 0 °C. Pyridine (1.0 mL) was added to act as an acid

Eur. J. Org. Chem. 2010, 237–258

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251

M. O. Senge et al.

FULL PAPER

scavenger. NBS (1.1 equiv.) was added directly to the flask, and the

reaction was followed by TLC. When the reaction reached comple-

tion it was quenched with 10 mL of acetone. The solvents were

evaporated under reduced pressure, and the product was dissolved

in CH₂Cl₂followed by filtration through silica gel.

(CH₂Cl₂): λ_max.(logε) = 414 (5.00), 510 (4.00), 544 (3.52), 584

(3.60), 640 nm (3.42). HRMS (ES⁺): calcd. for C₄₁H₃₉N₄O₅[M +

H]⁺667.2920; found 667.2938.

5-(4-Ethynylphenyl)-15-hexyl-10,20-bis(3-methoxyphenyl)porphyrin

(89): n-Butyllithium (2 mL of a 2.5  solution in n-hexane,

2.5 mmol) was added under argon to a 50-mL Schlenk flask

charged with a solution of p-bromophenylethyne (0.45 g, 2.5 mmol)

in 10 mL of dry diethyl ether at –70 °C. The reaction mixture was

then warmed to –40 °C and THF was added dropwise until the

aryllithium was formed as a white-bright pink suspension. To this

vigorously stirred mixture was added rapidly a solution of 5-hexyl-

10,20-bis(3-methoxyphenyl)porphyrin (87, 50 mg, 0.082 mmol) in

30 mL of dry THF under argon. The mixture changed from deep

purple to brown within 30 min. The reaction mixture was stirred

for 2 h (TLC control). Subsequently, a mixture of 2 mL of water in

3 mL of THF was added for hydrolysis. After stirring of the mix-

ture for 20 min, a solution of 10 equiv. of DDQ in THF (0.03 )

was added and the reaction mixture was stirred for another 60 min

at room temperature. Subsequently, the mixture was filtered

through silica gel and the organic solvent was removed under vac-

uum or washed with enough n-hexane. Final purification was

achieved by column chromatography and elution with ethyl acetate/

n-hexane (1:10, v/v) and yielded the title compound (7 mg,

0.1 mmol, 12%) as purple crystals; m.p. Ͼ300 °C. R_f= 0.49 (ethyl

5,15-Dibromo-10-(n-butyl)-20-(2,4,6-trimethoxyphenyl)porphyrin

(77): Prepared following the general bromination procedure given

above using 5-butyl-15-(2,4,6-trimethoxyphenyl)porphyrin (22,

160 mg, 0.3 mmol), NBS (58.51 mg, 0.33 mmol) and acetone

(10 mL). The products were separated using column chromatog-

raphy (n-hexane/CH₂Cl₂, 2:1, v/v). The first fraction was 5,15-di-

bromo-10-butyl-20-(2,4,6-trimethoxyphenyl)porphyrin (77, 90 mg,

0.13 mmol, 43%) as purple crystals, the second fraction gave 5-

bromo-10-butyl-20-(2,4,6-trimethoxyphenyl)porphyrin (76, 60 mg,

0.098 mmol, 33%) as purple crystals. Data for 77: M.p. Ͼ 300 °C.

1

R_f= 0.5 (n-hexane/CH₂Cl₂, 1:1, v/v). H NMR (600 MHz, CDCl₃,

TMS): δ = –2.75 (s, 2 H, NH), 1.13 (t, J = 7.53 Hz, 3 H,

CH₂CH₂CH₂CH₃), 1.77 (m, 2 H, CH₂CH₂CH₂CH₃), 2.41 (m, 2 H,

CH₂CH₂CH₂CH₃), 3.57 (s, 6 H, OCH₃), 4.15 (s, 3 H, p-OCH₃),

4.72 (t, J = 8.28, Hz, 2 H, CH₂CH₂CH₂CH₃), 6.62 (s, 2 H, Ar-H),

8.82 (s, 2 H, β-pyrrole-H), 9.31 (s, 2 H, β-pyrrole-H), 9.56 (d, J =

4.52 Hz, 2 H, β-pyrrole-H), 9.59 (d, J = 4.15 Hz, 2 H, β-pyrrole-

H) ppm. ¹³C NMR (150 MHz, CDCl₃): δ = 14.0, 23.4, 29.5, 34.9,

40.7, 55.4, 55.8, 56.2, 90.6, 91.4, 91.8, 102.5, 111.4, 112.6, 121.7,

157.3, 160.3, 160.8, 162.0 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) =

422 (4.95), 522 (4.14), 556 (4.01), 603 (3.53), 661 nm (3.74). HRMS

(ES⁺): calcd. for C₃₃H₃₁N₄O₃Br₂[M + H]⁺691.0740; found

691.0742.

1

acetate/n-hexane, 1:5, v/v). H NMR (400 MHz, CDCl₃, TMS): δ

= –2.72 (s, 2 H, NH), 0.94 (t, J = 7.2 Hz, 3 H, CH₂CH₂CH₂-

CH₂CH₂CH₃), 1.28 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.56 (m,

2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.84 (m, 2 H, CH₂CH₂CH₂-

CH₂CH₂CH₃), 2.61 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 3.34 (s,

1 H, HCϵC), 4.02 (s, 6 H, OCH₃), 5.05 (t, J = 8.1 Hz, 2 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 7.38 (m, 2 H, Ph-H), 7.69 (m, 2 H,

Ph-H), 7.82 (m, 4 H, Ph-H), 7.89 (d, J = 7.6 Hz, 2 H, Ph-H), 8.19

(d, J = 7.6 Hz, 2 H, Ph-H), 8.78 (d, J = 5.0 Hz, 2 H, β-pyrrole-

H^2,8), 8.88 (d, J = 5.0 Hz, 2 H, β-pyrrole-H^12,18), 8.98 (d, J =

5.0 Hz, 2 H, β-pyrrole-H^3,7), 9.51 (d, J = 5.0 Hz, 2 H, β-pyrrole-

H^13,17) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 449 (5.10), 440 (3.97),

486 (3.32), 560 (2.15), 581 (3.05), 656 nm (4.29). HRMS: calcd.

for C₄₈H₄₂N₄O₂706.3308; found [M + 1] 707.3365. C₄₈H₄₂N₄O₂

(706.89): calcd. C 81.56, H 5.99, N 7.93; found C 81.41, H 6.35, N

8.17.

General Procedure for Suzuki Coupling: A Schlenk flask was

charged with K₃PO₄(20 equiv.) and anhydrous THF (60 mL) un-

der argon. Then the porphyrin (1 equiv.), arylboronic acid or aryl-

boronic ester (10 equiv.) and Pd(PPh₃)₄(0.1 equiv.) were added.

The reaction was heated at reflux temperature for 12–24 h (TLC

control) and protected from light. After completion, the solvent

was removed under reduced pressure and the residue was dissolved

in CH₂Cl₂. The mixture was washed with saturated NaHCO₃, H₂O,

and brine and then dried with Na₂SO₄. The organic solvent was

evaporated and the crude product was purified by flash chromatog-

raphy.

5-(n-Butyl)-10-(4-methoxycarbonylphenyl)-15-(2,4,6-trimethoxy-

phenyl)porphyrin (82): Using the above general Suzuki coupling

procedure 5-bromo-10-(n-butyl)-20-(2,4,6-trimethoxyphenyl)por-

phyrin 76 (150 mg, 0.245 mmol), 4-methoxycarbonylphenyl bo-

ronic acid (440.9 mg, 2.45 mmol), Pd(PPh₃)₄(28.31 mg,

0.0245 mmol) and K₃PO₄(1041 mg, 4.9 mmol) in THF (50 mL)

were used. Silica gel column chromatography (n-hexane/CH₂Cl₂,

1:1, v/v) afforded the product as purple crystals (145 mg,

0.217 mmol, 89%); m.p. Ͼ 300 °C. R_f= 0.42 (n-hexane/ethyl ace-

tate, 10:1, v/v). ¹H NMR (400 MHz, CDCl₃, TMS): δ = –2.83 (s, 2

H, NH), 1.15 (t, J = 7.02 Hz, 3 H, CH₂CH₂CH₂CH₃), 1.85 (m, 2

5-(sec-Butyl)-15-hexyl-10,20-diphenylporphyrin (91): sec-Butyllith-

ium (1 mL of a 2.5  solution in hexane, 2.5 mmol) was added

under argon to a 50-mL Schlenk flask charged with a solution of

5-hexyl-10,20-diphenylporphyrin (88, 50 mg, 0.09 mmol) in 30 mL

of dry THF at –80 °C. The mixture changed from deep purple to

brown within 30 min. The reaction mixture was stirred for 3 h

(TLC control). Further workup followed the procedure for 89 and

column chromatography and elution with ethyl acetate/n-hexane

(1:8, v/v) yielded the title compound (13 mg, 0.02 mmol, 25%) as

purple crystals; m.p. Ͼ300 °C. R_f= 0.75 (ethyl acetate/n-hexane,

1:5, v/v). ¹H NMR (400 MHz, CDCl₃, TMS): δ = –2.56 (s, 2 H,

H, CH₂CH₂CH₂CH₃), 2.56 (m, 2 H, CH₂CH₂CH₂CH₃), 3.54 (s, 6 NH), 0.91 (t, J = 7.6 Hz, 3 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.10–

H, OCH₃), 4.13 (s, 3 H, p-OCH₃), 4.14 (s, 3 H, OCH₃), 5.06 (t, J 1.31 [m, 5 H, CH(CH₃)(CH₂CH₃), CH₂CH₂CH₂CH₂CH₂CH₃],

= 8.18 Hz, 2 H, CH₂CH₂CH₂CH₃), 6.62 (s, 2 H, Ar-H), 8.31 (d, J 1.44 (m,

2

H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.88 (m,

2

H,

= 8.18 Hz, 2 H, Ar-H), 8.45 (d, J = 8.19 Hz, 2 H, Ar-H), 8.73 (d,

J = 5.26 Hz, 1 H, β-pyrrole-H), 8.86 (d, J = 4.68 Hz, 2 H, β-pyr-

role-H), 8.96 (d, J = 4.1 Hz, 1 H, β-pyrrole-H), 9.11 (m, 2 H, Ar-

H), 9.27 (d, J = 4.1 Hz, 1 H, β-pyrrole-H), 9.38 (d, J = 4.67 Hz, 1

H, β-pyrrole-H), 9.51 (d, J = 4.68 Hz, 1 H, β-pyrrole-H), 9.61 (d,

J = 4.68 Hz, 1 H, β-pyrrole-H), 10.10 (s, 1 H, meso-H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 13.7, 23.2, 29.2, 34.5, 40.4, 51.9,

55.2, 90.4, 103.7, 110.6, 111.4, 117.2, 119.8, 126.8, 127.1, 127.7,

128.8, 129.7, 133.9, 147.5, 160.6, 161.5, 167.0 ppm. UV/Vis

CH₂CH₂CH₂CH₂CH₂CH₃), 2.42 [d, 7.4 Hz, 3

J

=

CH(CH₃)(CH₂CH₃)], 2.52 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃),

3.75 [m, 2 H, CH(CH₃)(CH₂CH₃)], 4.98 (t, J = 7.6 Hz, 2 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 5.32 [m, 1 H, CH(CH₃)(CH₂CH₃)],

7.77 (m, 6 H, Ph-H), 8.22 (m, 4 H, Ph-H), 8.86 (d, J = 5.0 Hz, 4

H, β-pyrrole-H^2,8,12,18), 9.43 (d, J = 5.0 Hz, 2 H, β-pyrrole-H^13,17),

9.57 (d, J = 5.0 Hz, 2 H, β-pyrrole-H^3,7) ppm. UV/Vis (CH₂Cl₂):

λ_max.(logε) = 441 (5.08), 486 (3.38), 514 (3.15), 581 (3.42), 656 nm

(4.17). HRMS: calcd. for C₄₂H₄₂N₄602.3409; found [M + 1]

252

www.eurjoc.org

Eur. J. Org. Chem. 2010, 237–258

meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

603.3487. C₄₂H₄₂N₄(602.82): calcd. C 83.68, H 7.02, N 9.29; found

C 83.17, H 7.20, N 9.50.

3 H, NH) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 376 (5.03), 435

(4.82), 578 (4.84), 656 (4.17) nm.^[31]

[5-(4-Ethynylphenyl)-10,20-diphenylporphyrinato]zinc(II) (94): The

free base porphyrin 5-(4-ethynylphenyl)-10,20-diphenylporphyrin

(93, 100 mg, 0.18 mmol) was dissolved in 100 mL dichloromethane.

At room temperature 5 mL MeOH (dry) and 0.6 g of zinc(II) ace-

tate were added and the mixture stirred for 30 min. After washing

three times with water the organic phase was dried with Na₂SO₄,

concentrated in vacuo and chromatography on alumina (dichloro-

methane/n-hexane, 1:5, v/v) to give 98 mg of 94 (1.5 mmol, 82%)

5-(tert-Butyl)-5,24-dihydro-10,20-bis(3-methoxyphenyl)-15-phenyl-

porphyrin (97): tert-Butyllithium (2 mL of a 1.8  solution in hex-

ane, 0.06 mmol) was slowly added (ca. 1 h) under argon to a 50-

mL Schlenk flask charged with a solution of 5-phenyl-10,20-bis(3-

methoxyphenyl)porphyrin (59, 35 mg, 0.06 mmol) in 30 mL of dry

THF. The mixture was heated to 50 °C and stirred for 30 min. Sub-

sequently, a mixture of 2 mL of water in 3 mL of THF was added

for hydrolysis. After stirring of the mixture for 20 min, a solution

after recrystallization from CH₂Cl₂/MeOH; m.p. Ͼ 300 °C. R_f= of 10 equiv. of DDQ in THF (0.02 ) was added and the reaction

0.43 (dichloromethane/n-hexane, 1:5, v/v, alumina). ¹H NMR

mixture was stirred for another 60 min at room temperature. Sub-

(250 MHz, CDCl₃, TMS): δ = 3.30 (s, 1 H, HCϵC), 7.65–7.75 (m, sequently, the mixture was filtered through silica gel and the or-

3

6 H, Ph-H), 7.85 (d, J = 7.4 Hz, 2 H, Ph-H), 8.20–8.30 (m, 6 H,

Ph-H), 8.80–9.0 (each d, ³J = 5.0 Hz, 4 H, β-pyrrole-H), 9.20 (d, Final purification was achieved by column chromatography and

³J = 5.0 Hz, 2 H, β-pyrrole-H), 9.40 (d, ³J = 5.0 Hz, 2 H, β-pyrrole-

elution with ethyl acetate/n-hexane (1:8, v/v) and gave the title com-

H), 10.20 (s, 1 H, meso-H) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = pound (11 mg, 0.016 mmol, 28%) as purple crystals; m.p. 226 °C.

ganic solvent was removed under vacuum or washed with n-hexane.

413 (5.31), 539 (3.93), 562 nm (4.10). MS (EI, 80 eV, 170 °C), m/z

(%): 626 (100) [M⁺], 313 (7) [M²⁺]. HRMS: calcd. for C₄₀H₂₄N₄Zn

626.1449; found 626.1452.

R_f= 0.47 (ethyl acetate/n-hexane, 1:1, v/v). ¹H NMR (400 MHz,

CDCl₃, TMS): δ = 1.28 [s, 9 H, C(CH₃)₃], 3.91 (s, 6 H, OCH₃),

5.33 (s, 1 H, H⁵), 6.01–6.43 (m, 4 H, β-pyrrole-H), 6.53–6.66 (m, 4

H, β-pyrrole-H), 6.87 (m, 2 H, Ar-H), 7.06–7.15 (m, 4 H, Ar-H),

7.37 (m, 3 H, Ar-H), 7.51 (m, 4 H, Ar-H), 9.88, 10.02 and 10.65

(each s, 3 H, NH) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 350 (4.85),

453 (4.69), 577 (5.11), 656 (4.15) nm.^[31].

1,4-Bis[(4-phenyl-10,20-diphenylporphyrinato-5-yl)zinc(II)]butane-

1,3-diyne (95): Porphyrin 94 (50 mg, 0.08 mmol) was dissolved in

30 mL dichloromethane and CuCl (457 mg, 44.57 mmol) and

0.6 mL TMEDA were added slowly. The reaction mixture was

stirred for 3 h at room temperature and washed 5 times with water

(100 mL each). The organic phase was dried with Na₂SO₄and the

solvent removed in vacuo. Chromatographic work-up on alumina

eluting with dichloromethane gave the dimer (41 mg pink crystals,

0.033 mmol, 82% after recrystallization from CH₂Cl₂/MeOH); m.p.

Ͼ 300 °C. R_f= 0.76 (dichloromethane/THF: 10:1, v/v, silica gel).

¹H NMR (250 MHz, CDCl₃, TMS): δ = 7.60–7.65 (d, J = 7.6 Hz,

5-Hexyl-10,20-bis(3-methoxyphenyl)-15-[(3-pyridyl)methyl]porphyr-

in (98): n-Hexyllithium (1 mL of a 2.5  solution in hexane) was

slowly added under argon to a 100-mL Schlenk flask charged with

a solution of 5,15-bis(3-methoxyphenyl)porphyrin (58, 100 mg,

0.19 mmol) in 40 mL of dry THF at –80 °C under argon. After

15 min the solution was treated with a solution of 300 mg

(0.86 mmol) 3-(iodomethyl)pyridine hydrogen iodide dissolved in

4 H, Ph-H), 7.70–7.80 (m, 12 H, Ph-H), 7.90–7.95 (d, J = 7.6 Hz, 4 mL DMF and stirred for 24 h and heated to 75 °C (TLC control).

4 H, Ph-H), 8.20–8.25 (d, J = 7.4 Hz, 8 H, Ph-H), 8.80 (m, 8 H, Subsequently, a mixture of 2 mL of water in 3 mL of THF was

β-pyrrole-H), 9.05 (d, β-pyrrole-H, ³J = 5.0 Hz, 4 H), 9.40 (d, β- added for hydrolysis. After stirring of the mixture for 20 min, a

3

pyrrole-H, J = 5.0 Hz, 4 H), 10.25 (s, 2 H, meso-H) ppm. UV/Vis

(CH₂Cl₂): λ_max.(logε) = 416 (5.23), 460 (3.89), 544 nm (4.00). MS

(EI, 80 eV, 170 °C), m/z (%): 1250 (43) [M⁺], 600 (52) [M²⁺– C₂H₂],

524 (64) [M²⁺– C₈H₆]. FAB(+) calcd. for C₈₀H₄₇N₈Zn₂1251.57;

found 1251.

solution of 10 equiv. of DDQ in THF (0.04 ) was added and the

reaction mixture was stirred for another 60 min at room tempera-

ture. Subsequently, the mixture was filtered through silica gel and

the organic solvent was removed under vacuum. Final purification

was achieved by column chromatography on silica gel and elution

with ethyl acetate/n-hexane (1:8, v/v) and yielded the title com-

pound (8 mg, 0.01 mmol, 6%) as purple crystals and the trisubsti-

tuted porphyrin (28%). Data for 98: M.p. Ͼ300 °C. R_f= 0.35 (ethyl

5-(tert-Butyl)-15-hexyl-5,24-dihydro-10,20-diphenylporphyrin (96):

tert-Butyllithium (1 mL of a 2.5  solution in hexane, 2.5 mmol)

was added under argon to a 50-mL Schlenk flask charged with a

solution of 5-hexyl-10,20-diphenylporphyrin (88, 50 mg,

0.09 mmol) in 30 mL of dry THF at –80 °C. The reaction mixture

was stirred for 5 h (TLC control). Subsequently, a mixture of 2 mL

of water in 3 mL of THF was added for hydrolysis. After stirring

of the mixture for 20 min, a solution of 10 equivalents of DDQ in

THF (0.03 ) was added and the reaction mixture was stirred for

another 60 min at room temperature. Subsequently, the mixture

was filtered through silica gel and the organic solvent was removed

under vacuum. Final purification was achieved by column

chromatography and elution with ethyl acetate/n-hexane (1:6, v/v)

yielding the title compound (11 mg, 0.02 mmol, 20%) as purple

crystals; m.p. 227 °C. R_f= 0.43 (ethyl acetate/n-hexane, 1:1, v/v).

¹H NMR (400 MHz, CDCl₃, TMS): δ = 0.91 (t, J = 6 Hz, 3 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 1.09 (m, 2 H, CH₂CH₂CH₂CH₂-

CH₂CH₃), 1.28 [s, 9 H, C(CH₃)₃] 1.44 (m, 2 H, CH₂CH₂CH₂CH₂-

1

acetate/n-hexane, 1:1, v/v). H NMR (400 MHz, CDCl₃, TMS): δ

= –2.62 (s, 2 H, NH), 0.91 (t, J = 7.2 Hz, 3 H, CH₂CH₂CH₂-

CH₂CH₂CH₃), 1.23 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.54 (m,

2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.83 (m, 2 H, CH₂CH₂CH₂-

CH₂CH₂CH₃), 2.55 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 4.03 (s,

6 H, OCH₃), 4.99 (t, J = 8.1 Hz, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃),

6.38 (s, 2 H, pyridyl-CH₂), 7.01 (m, 2 H, pyridyl-H), 7.35 (m, 3 H,

2 Ar-H, 1 pyridyl-H), 7.66 (m, 2 H, Ar-H), 7.79 (m, 4 H, Ar-H),

8.38 (s, 1 H, pyridyl-H), 8.95 (m, 4 H, β-pyrrole-H^2,8,12,18), 9.33 (d,

J = 5.0 Hz, 2 H, β-pyrrole-H^13,17), 9.48 (d, J = 5.0 Hz, 2 H, β-

pyrrole-H^3,7) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 420 (5.07), 485

(3.74), 516 (3.62), 551 (2.92), 593 (3.04), 655 nm (4.00). HRMS:

calcd. for C₄₆H₄₃N₅O₂697.3416; found [M

+ 1] 698.3516.

C₄₆H₄₃N₅O₂(697.88): calcd. C 79.17, H 6.21, N 10.04; found C

79.44, H 6.51, N 9.92.

CH₂CH₃), 1.88 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 2.47 (m, 2 H, 3-(5,15-Dihexyl-10-phenylporphyrin-20-yl)propionic

CH₂CH₂CH₂CH₂CH₂CH₃), 4.13 (t, 6 Hz, H, Phenyllithium (0.6 mL of a 1.8  solution in hexane, 0.018 mmol)

CH₂CH₂CH₂CH₂CH₂CH₃), 5.32 (s, 1 H, 5-H), 6.04–6.47 (m, 4 H, was slowly added under argon to a 50-mL Schlenk flask charged

Acid

(99):

J

=

2

β-pyrrole-H), 6.51–6.85 (m, 4 H, β-pyrrole-H), 7.14–7.59 (m, 6 H,

Ph-H), 7.87–7.96 (m, 4 H, Ph-H), 10.39, 10.57 and 10.94 (s each,

with a solution of 5,15-dihexylporphyrin (18, 80 mg, 0.167 mmol)

in 30 mL of dry THF at r.t. under argon. After 15 min the solution

Eur. J. Org. Chem. 2010, 237–258

www.eurjoc.org

253

M. O. Senge et al.

FULL PAPER

was treated with a solution of 200 mg (1 mmol) 3-iodopropionic

acid dissolved in 5 mL THF and stirring for 24 h (TLC control).

Subsequently, a mixture of 2 mL of water in 3 mL of THF was

added for hydrolysis. After stirring of the mixture for 20 min, a

solution of 10 equiv. of DDQ in THF (0.03 ) was added and the

reaction mixture was stirred for another 60 min at room tempera-

ture. Subsequently, the mixture was filtered through silica gel and

the organic solvent was removed under vacuum. Final purification

was achieved by column chromatography on silica gel and elution

with ethyl acetate/n-hexane (1:10, v/v) yielded the title compound

(19 mg, 0.03 mmol, 18%) as purple crystals and the respective tri-

substituted porphyrin (27%). Data for 99: M.p. Ͼ300 °C. R_f= 0.47

(ethyl acetate/n-hexane, 1:7, v/v). ¹H NMR (400 MHz, CDCl₃,

(3.64), 656 nm (4.28). HRMS: calcd. for C₄₇H₆₁N₅695.4926; found

[M + 1] 696.5008. C₄₇H₆₁N₅(696.03): calcd. C 81.09, H 8.84, N

10.07; found C 81.29, H 8.59, N 9.98. Data for 102: purple crystals;

m.p. Ͼ300 °C. R_f= 0.55 (ethyl acetate/n-hexane, 1:6, v/v). ¹H NMR

(400 MHz, CDCl₃, TMS): δ = –2.75 (s, 2 H, NH), 0.92 (t, J =

7.2 Hz,

6

H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.14 [m,

6

H,

N(CH₂CH₂CH₃)₂], 1.28 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃),

1.37–1.51 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.85–1.94 [m, 8 H,

CH₂CH₂CH₂CH₂CH₂CH₃, N(CH₂CH₂CH₃)₂], 2.58 (m,

4 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 3.56 [m, 4 H, N(CH₂CH₂CH₃)₂], 5.02

(m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 7.04 (d, J = 7.5 Hz, 2 H, Ar-

H), 8.04 (d, J = 7.5 Hz, 2 H, Ar-H), 8.99 (d, J = 5.0 Hz, 2 H, β-

pyrrole-H), 9.34 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 8.44 (d, J =

TMS): δ = –2.65 (s, 2 H, NH), 0.91 (t, J = 7.2 Hz, 6 H, 5.0 Hz, 2 H, β-pyrrole-H), 9.56 (d, J = 5.0 Hz, 2 H, β-pyrrole-H),

CH₂CH₂CH₂CH₂CH₂CH₃), 1.20 (m, 4 H, CH₂CH₂CH₂CH₂- 10.03 (s, 1 H, meso-H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

CH₂CH₃), 1.55 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.86 (m, 4 H, 11.22, 13.74, 20.23, 22.31, 29.29, 29.82, 31.51, 34.55, 38.15, 52.75,

CH₂CH₂CH₂CH₂CH₂CH₃), 2.57 (m, 6 H, CH₂CH₂CH₂CH₂- 102.72, 109.26, 118.57, 120.45, 126.46, 127.58, 129.33, 130.91,

CH₂CH₃, CH₂CH₂COOH), 3.72 (t,

J

=

6.4 Hz,

2

H,

131.91, 135.36, 144.73, 147.23 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε)

CH₂CH₂COOH), 4.98 (t, J = 8.1 Hz, 4 H, CH₂CH₂CH₂CH₂- = 434 (5.11), 585 (3.78), 656 nm (4.11). HRMS: calcd. for

CH₂CH₃), 7.77 (m, 3 H, Ph-H), 8.21 (m, 2 H, Ph-H), 8.88 (m, 4

H, β-pyrrole-H^3,7,13,17), 9.44 (m, 4 H, β-pyrrole-H^2,8,12,18), 10.56 (s,

1 H, COOH) ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 418 (5.08), 440

(3.94), 517 (3.79), 552 (3.91), 593 (3.88), 655 nm (4.09). HRMS:

calcd. for C₄₁H₄₆N₄O₂626.3621; found 626.4512. C₄₁H₄₆N₄O₂

(626.84): calcd. C 78.56, H 7.40, N 8.94; found C 78.76, H 7.80, N

9.21.

C₄₄H₅₅N₅653.4457; found [M + 1] 653.4491. C₄₄H₅₅N₅(653.95):

calcd. C 80.81, H 8.48, N 10.71; found C 81.09, H 8.71, N 10.43.

5,10-Dihexyl-15-[4-(dihexyl-hydroxymethyl)phenyl]-20-propylpor-

phyrin (103) and 5,10-Dihexyl-15-[4-(dihexyl-hydroxymethyl)phenyl]-

porphyrin (104): n-Hexyllithium (2 mL of a 2.5  solution in hex-

ane, 5 mmol) was added under argon to a 100-mL Schlenk flask

charged with a solution of 5-hexyl-15-(4-methylcarboxyphenyl)por-

phyrin (17, 40 mg, 0.07 mmol) in 40 mL of dry THF under argon.

5,15-Dihexyl-10-[4-(dipropylamino)phenyl]-20-propylporphyrin (101)

and 5,15-Dihexyl-10-[4-(dipropylamino)phenyl]porphyrin (102): n- The mixture changed from deep purple to brown within 30 min.

Butyllithium (4 mL of a 2.5  solution in hexane, 10 mmol) was

added under argon to a 100-mL Schlenk flask charged with a solu-

tion of p-bromoaniline (1 g, 5 mmol) in 10 mL of dry diethyl ether

at 0 °C. After addition of n-BuLi the cold bath was removed and

stirring was continued for another 2 h at room temperature. To the

vigorously stirred mixture was added rapidly a solution of 5,15-

dihexylporphyrin (18, 150 mg, 0.313 mmol) in 40 mL of dry THF.

The mixture changed from deep purple to brown within 30 min.

After 1 h the solution was treated with 1 mL propyl iodide

(10 mmol) and stirred for 12 h and heated to 70 °C (TLC control).

Subsequently, a mixture of 2 mL of water in 3 mL of THF was

added for hydrolysis. After stirring of the mixture for 20 min, a

solution of 10 equiv. of DDQ in THF (0.03 ) was added and the

reaction mixture was stirred for another 60 min at room tempera-

ture. Subsequently, the mixture was filtered through silica gel and

the organic solvent was removed under vacuum. Final purification

was achieved by column chromatography on silica gel and elution

with ethyl acetate/n-hexane (1:10, v/v). The first fraction consisted

of 101 (43 mg, 0.06 mmol, 20%) and the second fraction of 102

(34 mg, 0.05 mmol, 16%). Data for 101: purple crystals; m.p.

Ͼ300 °C. R_f= 0.63 (ethyl acetate/n-hexane, 1:6, v/v). ¹H NMR

(400 MHz, CDCl₃, TMS): δ = –2.57 (s, 2 H, NH), 0.92 (t, J =

After 1 h the solution was treated with 0.5 mL propyl iodide

(0.52 mmol) and stirring for 12 h and heating to 70 °C (TLC con-

trol). Subsequently, a mixture of 2 mL of water in 3 mL of THF

was added for hydrolysis. After stirring of the mixture for 20 min,

a solution of 10 equiv. of DDQ in THF (0.02 ) was added and

the reaction mixture was stirred for another 60 min at room tem-

perature. The mixture was filtered through silica gel and the organic

solvent was removed under vacuum. Final purification was

achieved by column chromatography and elution with acetone/n-

hexane (1:5, v/v). The first fraction consisted of 103 (11 mg,

0.013 mmol, 18%) and the second fraction of 104 (8 mg,

0.01 mmol, 14%). Data for 103: Purple crystals; m.p. Ͼ300 °C. R_f

= 0.31 (acetone/n-hexane, 1:5, v/v). ¹H NMR (400 MHz, CDCl₃,

TMS): δ = –2.60 (s, 2 H, NH), 0.96–1.15 [t, J = 7.2 Hz, 12 H,

CH₂CH₂CH₂CH₂CH₂CH₃,

C(OH)CH₂CH₂CH₂CH₂CH₂CH₃],

1.23 [m, H, CH₂CH₂CH₂CH₂CH₂CH₃, C(OH)CH₂CH₂-

8

CH₂CH₂CH₂CH₃], 1.41–1.65 [m, 16 H, CH₂CH₂CH₂CH₂-

CH₂CH₃, C(OH)CH₂CH₂CH₂CH₂CH₂CH₃, C(OH)CH₂CH₂CH₂-

CH₂CH₂CH₃, C(OH)CH₂CH₂CH₂CH₂-CH₂CH₃], 1.81–1.91 (m, 7

H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₃), 2.12 [m,

4 H,

C(OH)CH₂CH₂CH₂CH₂CH₂CH₃], 2.55 (m, 6 H, CH₂CH₂CH₂-

CH₂CH₂CH₃, CH₂CH₂CH₃), 4.98 (m, 6 H, CH₂CH₂CH₂CH₂-

H, CH₂CH₃, CH₂CH₂CH₃), 7.78 (d, J = 7.5 Hz, 2 H, Ar-H), 8.17 (m,

7.2 Hz,

6 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.11 [m, 6

N(CH₂CH₂CH₃)₂], 1.25 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 6 H, Ar-H), 8.87 (d, J = 5.0 Hz, 2 H, β-pyrrole-H^13,17), 9.43 (m, 2

1.37–1.51 (m, 7 H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₃), H, β-pyrrole-H^2,18), 9.54 (m, 4 H, β-pyrrole-H^3,7,8,12) ppm. ¹³C

1.84–1.93 [m, 8 H, CH₂CH₂CH₂CH₂CH₂CH₃, N(CH₂CH₂CH₃)₂], NMR (100 MHz, CDCl₃): δ = 13.67, 22.20, 22.38, 23.29, 28.99,

2.56 (m, 6 H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₃), 3.55 [m, 29.31, 31.52, 35.01, 35.38, 36.84, 38.28, 38.47, 42.82, 117.61,

4 H, N(CH₂CH₂CH₃)₂], 4.99 (m, 6 H, CH₂CH₂CH₂CH₂CH₂CH₃, 118.28, 118.68, 118.90, 123.10, 126.83, 127.35, 127.88, 133.74,

CH₂CH₂CH₃), 7.04 (d, J = 7.5 Hz, 2 H, Ar-H), 8.05 (d, J = 7.5 Hz, 140.02, 145.33 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 418 (5.18),

2 H, Ar-H), 9.02–9.11 (m, 4 H, β-pyrrole-H), 9.45 (m, 4 H, β- 519 (3.50), 553 (3.78), 601 (3.88), 655 nm (3.75). HRMS: calcd. for

pyrrole-H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 11.22, 13.76,

14.59, 20.13, 20.24, 22.34, 29.22, 29.85, 31.27, 31.52, 32.63, 34.56,

35.03, 37.15, 38.16, 38.21, 50.71, 52.74, 109.24, 109.44, 117.84,

118.35, 118.57, 126.48, 127.55, 128.86, 146.52 ppm. UV/Vis

C₅₄H₇₄N₄O 794.5862; found 794.5725. Data for 104: Purple crys-

tals; m.p. Ͼ300 °C. R_f= 0.31 (acetone/n-hexane, 1:5, v/v). ¹H NMR

(400 MHz, CDCl₃, TMS): δ = –2.88 (s, 2 H, NH), 0.93–1.15 [t, J

= 7.2 Hz, 12 H, CH₂CH₂CH₂CH₂CH₂CH₃, C(OH)CH₂CH₂CH₂-

(CH₂Cl₂): λ_max.(logε) = 436 (5.10), 486 (4.32), 511 (4.29), 581 CH₂CH₂CH₃], 1.23 [m, 8 H, CH₂CH₂CH₂CH₂CH₂CH₃, C(OH)-

254

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Eur. J. Org. Chem. 2010, 237–258

meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

CH₂CH₂CH₂CH₂CH₂CH₃], 1.41–1.73 [m, 16 H, CH₂CH₂CH₂- chromatography and elution with ethyl acetate/n-hexane (1:15, v/v)

CH₂CH₂CH₃, C(OH)CH₂CH₂CH₂CH₂CH₂CH₃, C(OH)CH₂CH₂- yielded the title compound (15 mg, 0.023 mmol, 13%) as purple

CH₂CH₂CH₂CH₃, C(OH)CH₂CH₂CH₂CH₂C-H₂CH₃], 1.82–1.90 crystals, trisubstituted porphyrin (9%) and starting material (7%);

(m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 2.09 [m, 4 H, C(OH)- m.p. Ͼ300 °C. R_f= 0.57 (ethyl acetate/n-hexane, 1:5, v/v). ¹H NMR

CH₂CH₂CH₂CH₂CH₂CH₃], 2.57 (m,

4

H, CH₂CH₂CH₂-

(400 MHz, CDCl₃, TMS): δ = –2.63 (s, 2 H, NH), 0.87 (m, 6 H,

CH₂CH₂CH₃), 5.06 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 7.79 (d, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₃), 1.37 (m, 5 H,

J = 7.5 Hz, 2 H, Ar-H), 8.21 (d, J = 7.5 Hz, 2 H, Ar-H), 8.87 (d,

J = 5.0 Hz, 2 H, β-pyrrole-H^13,17), 9.34 (d, 2 H, β-pyrrole-H^2,18),

CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₃), 1.56 (m,

4 H,

CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₃), 1.86 (m, 6 H,

9.54 (m, 4 H, β-pyrrole-H^3,7,8,12), 10.03 (s, 1 H, meso-H) ppm. ¹³C CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂-

NMR (100 MHz, CDCl₃): δ = 13.66, 22.18, 29.29, 29.88, 29.90,

31.31, 34.87, 35.66, 38.37, 38.64, 42.80, 103.03, 117.77, 119.06,

120.08, 123.29, 127.81, 130.38, 133.91, 138.72, 139.38, 145.41 ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 435 (5.10), 486 (3.11), 514 (2.57),

581 (3.42), 656 nm (3.72). HRMS: calcd. for C₅₁H₆₈N₄O 752.5393;

found 752.4981.

CH₃), 2.56 (m, 6 H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂-

CH₂CH₃, CH₂CH₂CH₂CH₃), 4.13 (s, 3 H, OCH₃), 5.02 (m, 6 H,

CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₂-

CH₃), 7.33 (d, J = 8 Hz, 2 H, Ar-H), 8.11 (d, J = 8 Hz, 2 H, Ar-

H), 8.85 (d, J = 5 Hz, 2 H, β-pyrrole-H), 9.40 (d, J = 5 Hz, 2 H,

β-pyrrole-H), 9.52 (d, J = 5 Hz, 2 H, β-pyrrole-H), 9.55 (d, J =

5 Hz, 2 H, β-pyrrole-H) ppm. UV/Vis (CH₂Cl₂): λ_max.(lgε) = 442

(5.09), 486 (3.51), 548 (3.27), 581 (3.51), 656 nm (4.27). HRMS:

5-Hexyl-10-phenyl-15-(4-methoxyphenyl)-20-propylporphyrin (105):

PhLi (0.8 mL of a 1.8  solution in hexane, 0.02 mmol) was slowly

added (ca. 1 h) under argon to a 100-mL Schlenk flask charged

with a solution of 5-hexyl-15-(4-methoxyphenyl)porphyrin (105,

100 mg, 0.19 mmol) in 40 mL of dry THF. The mixture was heated

to 50 °C and stirred for 30 min. After 1 h the solution was treated

with 0.7 propyl iodide (7.1 mmol) and stirring for 20 h and heating

to 70 °C (TLC control). Subsequently, a mixture of 2 mL of water

in 3 mL of THF was added for hydrolysis. After stirring of the

mixture for 20 min, a solution of 10 equiv. of DDQ in THF

(0.06 ) was added and the reaction mixture was stirred for another

60 min at room temperature. Subsequently, the mixture was filtered

through silica geland the organic solvent was removed under vac-

uum. Final purification was achieved by column chromatography

(ethyl acetate/n-hexane = 1:10, v/v) yielded the title compound

(31 mg, 0.05 mmol, 25%) as purple crystals, besides the respective

trisubstituted porphyrin (14%) and starting material (8%); m.p.

Ͼ300 °C. R_f= 0.76 (ethyl acetate/n-hexane, 1:5, v/v). ¹H NMR

(400 MHz, CDCl₃, TMS): δ = –2.61 (s, 2 H, NH), 0.99 (t, J =

calcd. for C₄₂H₅₀N₄O 626.3984; found [M

+ 1] 627.4061.

C₄₂H₅₀N₄O (626.89): calcd. C 80.47, H 8.04, N 8.94; found C

80.67, H 6.95, N 8.63.

5-[4-(Dipropylamino)phenyl]-10-hexyl-20-(4-methoxyphenyl)porphyr-

in (109): n-Butyllithium (2 mL of a 2.5  solution in hexane,

5 mmol) was added under argon to a 100-mL Schlenk flask charged

with a solution of p-bromoaniline (0.5 g, 2.5 mmol) in 10 mL of

dry diethyl ether at 0 °C. After addition of nBuLi the cold bath

was removed and stirring was continued for another 2 h at room

temperature. To the vigorously stirred mixture was added rapidly

a solution of 5-hexyl-15-(4-methoxyphenyl)porphyrin (51, 100 mg,

0.19 mmol) in 40 mL of dry THF under argon at –80 °C. The mix-

ture changed from deep purple to brown within 30 min. After 1 h

the solution was treated with 1 mL propyl iodide (10 mmol) and

stirring for 12 h and heating to 70 °C (TLC control). Subsequently,

a mixture of 2 mL of water in 3 mL of THF was added for hydroly-

sis. After stirring of the mixture for 20 min, a solution of 10 equiv.

8.1 Hz, 6 H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₃), 1.34 (m, 2 of DDQ in THF (0.03 ) was added and the reaction mixture was

H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.41 (m, 2 H, CH₂CH₂CH₂- stirred for another 60 min at room temperature. The mixture was

CH₂CH₂CH₃), 1.86 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 2.57 (m, filtered through silica gel and the organic solvent was removed un-

4 H, CH₂CH₂CH₂CH₂CH₂CH₃, CH₂CH₂CH₃), 4.09 (s, 3 H, der vacuum. Final purification was achieved by column chromatog-

OCH₃), 5.02 (t, J = 8.1 Hz, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃, raphy and elution with ethyl acetate/n-hexane (1:10, v/v) yielding

CH₂CH₂CH₃), 7.25 (d, J = 8 Hz, 2 H, Ph-H), 7.79 (m, 3 H, Ph-

the title compound (41 mg, 0.06 mmol, 31%) as purple crystals;

H), 8.15 (d, J = 8 Hz, 2 H, Ph-H), 8.27 (m, 2 H, Ph-H), 8.81 (m, some starting material (13%) was recovered, too; m.p. Ͼ300 °C. R_f

2 H, β-pyrrole-H^13,17), 8.98 (m, 2 H, β-pyrrole-H^2,18), 9.43 (m, 2

= 0.54 (ethyl acetate/n-hexane, 1:8, v/v). ¹H NMR (400 MHz,

H, β-pyrrole-H^3,12), 9.56 (m, 2 H, β-pyrrole-H^7,8) ppm. ¹³C NMR CDCl₃, TMS): δ = –2.81 (s, 2 H, NH), 0.92 (t, J = 7.2 Hz, 3 H,

(100 MHz, CDCl₃): δ = 13.79, 14.58, 22.36, 29.33, 29.88, 31.33, CH₂CH₂CH₂CH₂CH₂CH₃), 1.13 [m, 6 H, N(CH₂CH₂CH₃)₂],

31.53, 35.25, 37.10, 38.45, 55.12, 111.71, 118.16, 119.24, 119.49, 1.27 (m,

126.22, 126.75, 127.13, 128.35, 134.07, 135.14, 141.99, 158.86 ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 444 (4.97), 487 (4.30), 601 (4.03),

2

H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.57 (m,

CH₂CH₂CH₂CH₂CH₂CH₃), 1.83–1.94 [m,

CH₂CH₂CH₂CH₂CH₂CH₃, N(CH₂CH₂CH₃)₂], 2.61 (m,

2

H,

6

2

657 nm (4.28). HRMS: calcd. for C₄₂H₄₂N₄O 618.3358; found [M CH₂CH₂CH₂CH₂CH₂CH₃), 3.54 [m, 4 H, N(CH₂CH₂CH₃)₂], 4.12

+ 1] 619.3425. C₄₂H₄₂N₄O (618.82): calcd. C 81.52, H 6.84, N 9.05;

found C 81.63, H 7.05, N 8.97.

(s, 3 H, OCH₃), 5.04 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 7.05 (d,

J = 7.5 Hz, 2 H, Ar-H), 7.34 (d, J = 7.5 Hz, 2 H, Ar-H), 8.05 (d,

J = 7.5 Hz, 2 H, Ar-H), 8.15 (d, J = 7.5 Hz, 2 H, Ar-H), 8.88–9.01

(d, J = 5.0 Hz, 2 H, β-pyrrole-H), 9.02–9.13 (d, J = 5.0 Hz, 2 H,

β-pyrrole-H), 9.28–9.37 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 9.51–

9.61 (d, J = 5.0 Hz, 2 H, β-pyrrole-H), 10.09 (s, 1 H, meso-H) ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 443 (5.09), 486 (3.81), 585 (3.67),

656 nm (4.22). HRMS: calcd. for C₄₅H₄₉N₅O 675.3937; found [M

+ 1] 676.4039. C₄₅H₄₉N₅O (675.92): calcd. C 79.96, H 7.31, N

10.36; found C 79.65, H 7.05, N 10.01.

5-Butyl-10-hexyl-20-(4-methoxyphenyl)-15-pentylporphyrin (107):

nBuLi (0.4 mL of 2.5  solution in hexane, 1 mmol) was slowly

added under argon to a 100-mL Schlenk flask charged with a solu-

tion of 5-hexyl-15-(4-methoxyphenyl)porphyrin (51, 100 mg,

0.19 mmol) in 40 mL of dry THF at –80 °C under argon. After

15 min the solution was treated with 0.8 mL n-pentyl iodide

(6.1 mmol) and stirred for 12 h (TLC control). Subsequently, a mix-

ture of 2 mL of water in 3 mL of THF was added for hydrolysis.

After stirring of the mixture for 20 min, a solution of 10 equiv. of

DDQ in THF (0.03 ) was added and the reaction mixture was

stirred for another 60 min at room temperature. Subsequently, the

mixture was filtered through silica gel and the organic solvent was

removed under vacuum. Final purification was achieved by column

5-Hexyl-15-(4-methoxyphenyl)-10-phenylporphyrin (110): Phen-

yllithium (0.8 mL of a 1.8  solution in hexane, 0.02 mmol) was

slowly added (ca. 1 h) under argon to a 100-mL Schlenk flask

charged with a solution of 5-hexyl-15-(4-methoxyphenyl)porphyrin

(51, 100 mg, 0.19 mmol) in 40 mL of dry THF. The mixture was

Eur. J. Org. Chem. 2010, 237–258

www.eurjoc.org

255

M. O. Senge et al.

FULL PAPER

heated to 50 °C and stirred for 30 min. Subsequently, a mixture of

2 mL of water in 3 mL of THF was added for hydrolysis. After

stirring of the mixture for 20 min, a solution of 10 equiv. of DDQ

in THF (0.06 ) was added and the reaction mixture was stirred

for another 60 min at room temperature. The mixture was filtered

through silica gel and the organic solvent was removed under vac-

uum. Column chromatography (ethyl acetate/n-hexane, 1:10, v/v)

gave the title compound (51 mg, 0.088 mmol, 45%) as purple crys-

tals besides starting material (8%); m.p. Ͼ300 °C. R_f= 0.69

(ethyl acetate/n-hexane, 1:5, v/v). ¹H NMR (400 MHz, CDCl₃,

5-(n-Butyl)-15-[4-(dimethylamino)phenyl]-10-(1-ethylpropyl)-20-hex-

ylporphyrin (121): The synthesis followed the standard procedures

using nBuLi (0.03 mL, 0.09 mmol of a 2.5  solution in n-hexane),

5-[4-(dimethylamino)phenyl]-10-(1-ethylpropyl)-20-hexylporphyrin

(67, 42 mg, 0.07 mmol) and oxidation with air overnight. Column

chromatography on silica gel (CH₂Cl₂with 1% NEt₃) gave only

the product after recrystallization from CH₂Cl₂/MeOH as purple

crystals (8.3 mg, 0.01 mmol, 18%); m.p. 212 °C. R_f= 0.40 (CH₂Cl₂/

n-hexane, 2:1, v/v). ¹H NMR (500 MHz, CDCl₃, TMS): δ = 9.67

(m, 1 H, β-pyrrole-H⁸), 9.57 (AB, ³J = ³J = 4.8 Hz, 2 H, β-pyrrole-

3

TMS): δ = –2.87 (s, 2 H, NH), 0.95 (t, J = 8.1 Hz, 3 H, H^3,7), 9.53 (AB, J = J = 4.8 Hz, 4 H, β-pyrrole-H^2,12), 9.40 (AB,

CH₂CH₂CH₂CH₂CH₂CH₃), 1.32 (m, 2 H, CH₂CH₂CH₂CH₂- ³J = 4.7 Hz, 1 H, β-pyrrole-H¹⁸), 8.89 (m, 2 H, β-pyrrole-H^13,17),

CH₂CH₃), 1.53 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.85 (m, 2 H, 8.01 (AB, ³J = ³J = 8.6 Hz, 2 H, Ar-H_o), 7.11 (AB, ³J = ³J =

CH₂CH₂CH₂CH₂CH₂CH₃), 2.56 (m,

CH₂CH₂CH₃), 4.11 (s, 3 H, OCH₃), 5.05 (t, J = 8.1 Hz, 2 H,

CH₂CH₂CH₂CH₂CH₂CH₃), 7.31 (d, J = 8 Hz, 2 H, Ph-H), 7.82

2

H, CH₂CH₂CH₂-

8.6 Hz, 2 H, Ar-H_m), 5.02 [m, 3 H, CH(CH₂)₂, CH₂C₃H₇], 4.93 (t,

³J = 8.0 Hz, 2 H, CH₂C₅H₁₁), 3.23 [s, 6 H, N(CH₃)₂], 2.86 [m, 4

H, CH(CH₂)₂], 2.58 (m, 2 H, CH₂CH₂C₂H₅), 2.52 (m, 2 H,

(m, 3 H, Ph-H), 8.16 (d, J = 8 Hz, 2 H, Ph-H), 8.25 (m, 2 H, Ph- CH₂CH₂C₄H₉), 1.90 (m, 2 H, C₂H₄CH₂CH₃), 1.82 (m, 2 H,

H), 8.85–8.91 (d, J = 5 Hz, 2 H, β-pyrrole-H^13,17), 8.96–9.03 (d, J

= 5 Hz, 2 H, β-pyrrole-H^8,12), 9.31–9.39 (d, J = 5 Hz, 2 H, β-pyr-

role-H^2,18), 9.51–9.61 (d, J = 5 Hz, 2 H, β-pyrrole-H^3,7), 10.14 (s,

C₂H₄CH₂C₃H₇), 1.52 (m, 2 H, C₃H₆CH₂C₂H₅), 1.41 (m, 2 H,

3

C₄H₈CH₂CH₃), 1.19 (t, J = 7.4 Hz, 3 H, C₃H₆CH₃), 0.95 (t, J =

3

³J = 7.4 Hz, 6 H, CH₂CH₃), 0.94 (t, J = 7.2 Hz, 3 H, C₅H₁₀CH₃),

1 H, meso-H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.74), –2.64 (br. s, 2 H, NH) ppm. ¹³C NMR (126 MHz, CDCl₃): δ =

22.31, 29.85, 31.50, 34.73, 38.37, 55.13 (C_OCH3), 103.82, 111.93,

118.26, 119.45, 119.61, 126.04, 127.03, 127.20, 127.93, 130.61,

130.75, 131.09, 131.37, 133.63, 134.01, 135.23, 142.43, 142.64,

158.93 ppm. UV/Vis (CH₂Cl₂): λ_max.(logε) = 441 (4.97), 548 (2.76),

596 (3.34), 644 nm (3.95). HRMS: calcd. for C₃₉H₃₆N₄O 576.2889;

found [M + 1] 577.2946. C₃₉H₃₆N₄O (576.74): calcd. C 81.22, H

6.29, N 9.71; found C 81.47, H 6.32, N 9.58.

150.22, ≈ 145, 135.39, ≈ 131.9, 130.66, ≈ 129.1, ≈ 128.8, ≈ 128.4,

≈ 127.8, 122.10, 119.08, 110.62, 50.26, 41.20, 40.63, 38.77, 35.80,

34.54, 32.02, 30.31, 23.83, 22.83, 13.96 ppm. UV/Vis (CH₂Cl₂):

λ_max.(logε) = 420 (4.81), 522 (3.98), 559 (3.88), 600 (3.60), 658 nm

(3.72). MS TOF, MS, (ES⁺, 70 eV): m/z = 640 (10) [M]^·+, 320 (100)

[M]²⁺. HRMS: calcd. for C₄₃H₅₄N₅640.7379; found 640.4355.

5-Butyl-10-hexyl-20-(4-ethynylphenyl)-15-(3-methoxyphenyl)por-

phyrin (122): The synthesis followed the standard procedures using

5-Butyl-10-hexyl-15-(4-hydroxyphenyl)-20-(4-methoxyphenyl)por-

phyrin (115): n-Butyllithium (2 mL of a 2.5  solution in hexane,

10 mmol) was added under argon to a 50-mL Schlenk flask charged

with a solution of p-bromophenol (0.43 g, 2.5 mmol) in 10 mL of

dry diethyl ether at 0 °C. After addition of nBuLi the cold bath

was removed and stirring was continued for 18 h at room tempera-

ture. To the vigorously stirred mixture was added rapidly a solution

of 5-butyl-10-hexyl-20-(4-methoxyphenyl)porphyrin (114, 40 mg,

0.07 mmol) in 30 mL of dry THF under argon. Subsequently, a

mixture of 2 mL of water in 3 mL of THF was added for hydrolysis.

After stirring of the mixture for 20 min, a solution of 10 equiv. of

DDQ in THF (0.03 ) was added and the reaction mixture was

stirred for another 60 min at room temperature. Subsequently, the

mixture was filtered through silica gel and the organic solvent was

removed under vacuum. Final purification was achieved by column

chromatography and elution with ethyl acetate/n-hexane (1:8, v/v)

yielded the title compound (28 mg, 0.04 mmol, 60%) as purple

crystals; 8% starting material were recovered; m.p. Ͼ300 °C. R_f=

0.52 (ethyl acetate/n-hexane, 1:2, v/v). ¹H NMR (400 MHz, CDCl₃,

TMS): δ = –2.66 (s, 2 H, NH), 0.95 (t, J = 7.5 Hz, 3 H,

5-butyl-10-hexyl-15-(3-methoxyphenyl)porphyrin

(68,

60 mg,

0.107 mmol), 4-bromoethynylphenyl (292.47 mg, 1.615 mmol),

nBuLi (1.3 mL, 3.231 mmol), H₂O (0.5 mL) and DDQ (288.2 mg,

1.26 mmol). Column chromatography on silica gel (n-hexane/

CH₂Cl₂= 4:1, v/v) followed by a second column using n-hexane/

CH₂Cl₂(1:1) gave the title compound as purple crystals (7 mg

0.01 mmol, 10%); m.p. Ͼ300 °C. R_f= 0.66 (CH₂Cl₂/n-hexane, 1:1,

1

v/v). H NMR (400 MHz, CDCl₃, TMS): δ = –2.69 (s, 2 H, NH),

0.96 (t, J = 7.01 Hz, 3 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.17 (t, J =

7.01 Hz, 3 H, CH₂CH₂CH₂CH₃), 1.43 (m, 2 H, CH₂CH₂CH₂-

CH₂CH₂CH₃), 1.53 (m, 4 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.86 (m,

4 H, CH₂), 2.57 (m, 4 H, CH₂), 3.34 (s, 1 H, CH), 4.00 (s, 3 H,

OCH₃), 5.02 (m, 4 H, CH₂), 7.35 (m, 1 H, Ar-H), 7.65 (t, J =

7.6 Hz, 1 H, Ar-H), 7.78 (m, 2 H, Ar-H), 7.90 (d, J = 8.18 Hz, 2

H, Ar-H), 8.17 (d, J = 8.18 Hz, 2 H, Ar-H), 8.73 (d, J = 4.68 Hz,

1 H, β-pyrrole-H), 8.81 (d, J = 4.67 Hz, 1 H, β-pyrrole-H), 8.85 (d,

J = 4.67 Hz, 1 H, β-pyrrole-H), 8.93 (d, J = 4.68 Hz, 1 H, β-pyr-

role-H), 9.48 (m, 2 H, β-pyrrole-H), 9.61 (s, 2 H, β-pyrrole-H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 13.7, 22.6, 23.2, 28.9, 30.5, 31.4,

34.9, 35.2, 38.4, 40.5, 52.9, 55.0, 67.5, 83.3, 112.9, 117.0, 118.0,

119.8, 119.9, 120.9, 127.0, 130.0, 133.9, 142.6, 143.1, 157.4 ppm.

UV/Vis (CH₂Cl₂): λ_max.(logε) = 418 (5.03), 518 (3.57), 553 (3.29),

592 (3.01), 644 nm (3.04). HRMS (ES⁺): calcd. for C₄₅H₄₅N₄O [M

+ H]⁺657.3593; found 657.357.

CH₂CH₂CH₂CH₂CH₂CH₃), 1.15 (t,

J

=

7.5 Hz,

3

H,

CH₂CH₂CH₂CH₃), 1.29 (m, 2 H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.53

(m,

2

H, CH₂CH₂CH₂CH₂CH₂CH₃), 1.89 (m,

4

3

H,

CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₂CH₃), 2.57 (m,

CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₂CH₃), 4.11 (s,

OCH₃), 5.01 (t,

J

=

7.8 Hz,

4

H, CH₂CH₂CH₂CH₃, Crystal Structure Determinations: Growth and handling of crystals

CH₂CH₂CH₂CH₂CH₂CH₃), 7.15 (d, J = 7.5 Hz, 2 H, Ar-H), 7.30 followed the concept developed by Hope.^[41]Intensity data were

(d, J = 7.5 Hz, 2 H, Ar-H), 8.04 (d, J = 7.5 Hz, 2 H, Ar-H), 8.11

(d, J = 7.5 Hz, 2 H, Ar-H), 8.78 (s, 2 H, β-pyrrole-H^17,18), 8.97 (d,

J = 5 Hz, 2 H, β-pyrrole-H^2,13), 9.45 (d, J = 5 Hz, 2 H, β-pyrrole-

collected at 108 K with a Rigaku Saturn-724 system complete with

CCD detector utilizing Mo-K_αradiation (λ = 0.71073 Å). The in-

tensities were corrected for Lorentz, polarization and extinction ef-

H^3,12), 9.59 (s, 2 H, β-pyrrole-H^7,8) ppm. UV/Vis (CH₂Cl₂): λ_max.fects. The structures were solved with Direct Methods using the

(logε) = 446 (5.08), 486 (3.36), 581 (3.15), 615 (3.39), 656 nm (4.24). SHELXTL PLUS program system^[42a]and refined against |F²| with

HRMS: calcd. for C₄₃H₄₄N₄O₂648.3464; found 648.2985.

C₄₃H₄₄N₄O₂(648.85): calcd. C 79.60, H 6.84, N 8.63; found C

79.99, H 7.05, N 8.58.

the program XL from SHELX-97 using all data.^[42b]Non-hydrogen

atoms were refined with anisotropic thermal parameters. Hydrogen

atoms were generally placed into geometrically calculated positions

256

www.eurjoc.org

Eur. J. Org. Chem. 2010, 237–258

meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

[8] M. G. H. Vicente, in: The Porphyrin Handbook (Eds.: K. M.

and refined using a ridging model. The N-H hydrogen atoms were

located in difference maps and refined using the standard riding

model. Crystal data for 77: C₃₅H₃₄N₄O₃Br₂, M = 718.46, triclinic,

Kadish, K. M. Smith, R. Guilard), Academic Press, San Diego,

2000, vol. 1, p. 149–199; S. Shanmugathasan, C. Edwards,

R. W. Boyle, Tetrahedron 2000, 56, 1025–1046; A. K. Burrell,

D. L. Officer, P. G. Plieger, D. C. W. Reid, Chem. Rev. 2001,

101, 2751–2796; M. O. Senge, J. Richter, J. Porphyrins Phthalo-

cyanines 2004, 8, 934–953; S. Horn, K. Dahms, M. O. Senge,

J. Porphyrins Phthalocyanines 2008, 12, 1053–1077; H. Shino-

kubo, A. Osuka, Chem. Commun. 2009, 1011–1021.

¯

space group P1, a = 8.0071(14), b = 11.7648(18), c = 17.446(3) Å,

α = 98.114(11), β = 99.002(9), γ = 104.531(10)°, V = 1543.1(5) Å³,

Z = 2, T = 108 K, µ (Mo-K_α) = 2.670 cm^–1, 11705 reflections

measured, 5398 unique reflections measured (R_int= 0.0722), 401

parameters, 4486 reflections with IϾ2.0σ(I), refinement against

|F²|, R1[IϾ2.0σ(I)] = 0.0339, wR2 (all data) = 0.0859, S = 0.957,

ρ_max.= 0.514. Crystal data for 81: C₃₅H₃₄N₄O₃Br₂, M = 718.46,

[9] a) J. S. Lindsey, H. C. Hsu, I. C. Schreiman, Tetrahedron Lett.

1986, 27, 4969–4970; b) J. S. Manka, D. S. Lawence, Tetrahe-

dron Lett. 1989, 30, 6989–6992.

¯

triclinic, space group P1, a = 7.9861(11), b = 11.6530(15), c =

[10] a) M. Taniguchi, M. N. Kim, D. Ra, J. S. Lindsey, J. Org.

Chem. 2005, 70, 275–285; b) O. B. Locos, D. P. Arnold, Org.

Biomol. Chem. 2006, 4, 1–10; c) D. M. Shen, C. Liu, Q. Y.

Chen, Synlett 2007, 3068–3072; d) T. Takanami, M. Yotsukura,

W. Inoue, F. Hino, K. Suda, Heterocycles 2008, 76, 439–453,

and references cited therein.

[11] A. Wiehe, Y. M. Shaker, J. C. Brandt, S. Mebs, M. O. Senge,

Tetrahedron 2005, 61, 5535–5564.

[12] Y. M. Shaker, M. O. Senge, Heterocycles 2005, 65, 2441–2450.

17.173(2) Å, α = 90.5430(10), β = 98.012(2), γ = 107.818(2)°, V =

1504.3(3) Å³, Z = 2, T = 108 K, µ (Mo-K_α) = 2.739 cm^–1, 32735

reflections measured, 8937 unique reflections measured (R_int

=

0.0217), 401 parameters, 8070 reflections with IϾ2.0σ(I), refine-

ment against |F²|, R1[IϾ2.0σ(I)] = 0.0338, wR2 (all data) = 0.0823,

S = 01.046, ρ_max.= 0.612.

CCDC-749453 (for 77) and -749454 (for 81) contain the supple-

mentary crystallographic data for this paper. These data can be

obtained free of charge from The Cambridge Crystallographic

Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

[13]

a) W. W. Kalisch, M. O. Senge, Angew. Chem. Int. Ed. 1998,

37, 1107–1109; b) M. O. Senge, X. Feng, J. Chem. Soc. Perkin

Trans. 1 2000, 3615–3621; c) M. O. Senge, W. W. Kalisch, I.

Bischoff, Chem. Eur. J. 2000, 6, 2721–2738; d) M. O. Senge,

Acc. Chem. Res. 2005, 38, 733–743.

Supporting Information (see also the footnote on the first page of

this article): Synthetic procedures and analytical data for com-

pounds 20–22, 25–28, 30, 31, 40, 43–50, 52–55, 57, 62, 64, 66–70,

74–81, 83–86, 100, 106, 108, 111, 113, 117–119, and 123–135.

[14]

[15]

X. Feng, M. O. Senge, Tetrahedron 2000, 56, 587–590.

X. Feng, M. O. Senge, J. Chem. Soc. Perkin Trans. 1 2001,

1030–1038.

[16]

X. Feng, I. Bischoff, M. O. Senge, J. Org. Chem. 2001, 66,

8693–8700.

Acknowledgments

[17]

[18]

S. Neya, N. Funasaki, Tetrahedron Lett. 2002, 43, 1057–1058.

a) A. Wiehe, C. Ryppa, M. O. Senge, Org. Lett. 2002, 4, 3807–

3809; b) C. Ryppa, M. O. Senge, S. S. Hatscher, E. Kleinpeter,

P. Wacker, U. Schilde, A. Wiehe, Chem. Eur. J. 2005, 11, 3427–

3442.

a) M. B. Bakar, M. Oelgemöller, M. O. Senge, Tetrahedron

2009, 65, 7064–7078; b) M. Zawadzka, J. Wang, W. J. Blau,

M. O. Senge, Chem. Phys. Lett. 2009, 477, 330–335.

M. J. Gunter, L. N. Mander, J. Org. Chem. 1981, 46, 4791–

4795.

This work was supported by grants from Science Foundation Ire-

land (SFI Research Professorship 04/RP1/B482) and the Health

Research Board (HRB Translational Research Award 2007 TRA/

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Received: September 30, 2009

Published Online: December 1, 2009

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Article Doi

Synthesis of meso-substituted ABCD-type porphyrins by functionalization reactions

DOI: 10.1002/ejoc.200901113

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