Synthesis and characterization of monoisomeric 1,8,15,22-substituted (A3B and A2B2) phthalocyanines and phthalocyanine-fullerene dyads

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Synthesis and Characterization of Monoisomeric 1,8,15,22-Substituted

(A₃B and A₂B₂) Phthalocyanines and Phthalocyanine-Fullerene Dyads

Jenni Ranta,* Tatu Kumpulainen, Helge Lemmetyinen, and Alexander Efimov*

Department of Chemistry and Bioengineering, Tampere University of Technology, P.O.Box 541,

FIN-33101 Tampere, Finland

jenni.ranta@tut.fi; alexandre.efimov@tut.fi

Received May 12, 2010

Synthesis and characterization of three phthalocyanine-fullerene (Pc-C₆₀) dyads, corresponding

monoisomeric phthalocyanines (Pc), and building blocks, phthalonitriles, are described. Six novel

bisaryl phthalonitriles were prepared by the Suzuki-Miyaura coupling reaction from trifluoro-

methanesulfonic acid 2,3-dicyanophenyl ester and various oxaborolanes. Two phthalonitriles were

selected for the synthesis of A₃B- and A₂B₂-type phthalocyanines. Phthalonitrile 4 has a bulky 3,5-di-

tert-butylphenyl substituent at the R-phthalo position, which forces only one regioisomer to form and

greatly increases the solubility of phthalocyanine. Phthalonitrile 8 has a 3-phenylpropanol side chain

at the R-position making further modifications of the side group possible. Synthesized monoisomeric

A₃B- and A₂B₂-type phthalocyanines are modified by attachment of malonic residues. Finally,

fullerene is covalently linked to phthalocyanine with one or two malonic bridges to produce Pc-C₆₀

dyads. Due to the monoisomeric structure and increased solubility of phthalocyanines, the quality of

NMR spectra of the compounds is enhanced significantly, making detailed NMR analysis of the

structures possible. The synthesized dyads have different orientations of phthalocyanine and full-

erene, which strongly influence the electron transfer (ET) from phthalocyanine to fullerene moiety.

Fluorescence quenchings of the dyads were measured in both polar and nonpolar solvents, and in all

cases, the quenching was more efficient in the polar environment. As expected, most efficient

fluorescence quenching was observed for dyad 20b, with two linkers and phthalocyanine and

fullerene in face-to-face orientation.

Introduction

as electron acceptor have been synthesized and studied by

many research groups.^1-15

Phthalocyanines (Pc’s), structural analogues of porphy-

rins, are planar 18 π-electron aromatic macrocycles perfectly

suited for their integration in light energy conversion sys-

tems. Compared to porphyrins, phthalocyanines have an

advantage of a higher absorption around 700 nm where the

maximum of the solar photon flux occurs. During the past

decade several systems bearing Pc as electron donor and C₆₀

The structural characterization and photochemical studies

of phthalocyanines have always been a challenge for re-

searchers due to the poor solubility and the number of

ꢀ

(1) Sastre, A.; Gouloumis, A.; Vazquez, P.; Torres, T.; Doan, V.;

Schwartz, B. J.; Wudl, F.; Echegoyen, L.; Rivera, J. Org. Lett. 1999, 1 (11),

1807–1810.

5178 J. Org. Chem. 2010, 75, 5178–5194

Published on Web 07/02/2010

DOI: 10.1021/jo100766h

r

2010 American Chemical Society

Ranta et al.

JOCArticle

regioisomers formed during the reaction. Cyclotetrameriza-

tion of monosubstituted phthalonitriles usually results in the

formation of four regioisomers. These four isomers possess

C_4h, C_s, C_2v, and D_2hmolecular symmetry and, assuming a

statistical distribution, are prepared in a relative yield of

1:4:2:1, respectively.¹⁶In some cases these isomers can be

separated from each other by HPLC methods.^17,18The

presence of isomers has few important consequences. Apart

from differences in absorption spectra¹⁸and redox poten-

tials, different isomers offer different positions for further

substitution. The latter means that covalent bonding of

phthalocyanine with another chromophore (e.g., fullerene)

produces a mixture of regioisomerical dyads, which differ

not only by phthalocyanine substituents positions, but as

well by location of interchromophore bridges. To overcome

this problem, few approaches are usually employed. One is to

use a chelated atom in the phthalocyanine’s central cavity as

a binding site for the second component of the dyad.¹⁹

Another option is to link the dyad components only by one

bridge at the R- or β-phthalo position of Pc. Finally, two

bridges can be located at the same phthalo ring, which makes

the geometry of the dyad more predictable.²⁰Complemen-

tary to such arrangements of functional bridge, the use of R,R

or β,β bis-substituted phthalonitriles in phthalocyanine

synthesis allows the isomer formation to be completely

avoided. However, these methods are not suitable for the

synthesis of 1,8,15,22-substituted phthalocyanines with two

linkers or functional substituents.

The need for selective synthetic approaches in Pc synthesis

was discussed long ago.²¹While so-called A₃B-type phtha-

locyanines are relatively easy to prepare by expanding sub-

phthalocyanines, and the adjacently substituted AABB

macrocycles by the templated approach, the oppositely sub-

stituted ABAB structures can be synthesized chiefly by

statistical condensation. This means that the yield of ABAB

Pc will not exceed 12.5%, which could be acceptable if the

whole product would be a single regioisomer. Indeed, from

the viewpoint of analysis and characterization the isomer

with C_4hsymmetry is preferred. Numerous attempts to pre-

pare such molecules demonstrated that the C_4hisomer for-

mation is favored by low reaction temperature (usually

80 °C), use of specific alkoxide (mostly lithium octoxide),

and bulky substituents at position 3 of phthalonitriles.

Impressive results in the synthesis of monoisomeric R-sub-

stituted phthalocyanines were achived,^16,22-25but to our

knowledge these phthalocyanines were not used as compo-

nents in dyads.

Here we propose the approach to functionalized mono-

isomeric phthalocyanines using sterically restricting substi-

tuents in R-phthalo positions of the macrocycle. As we have

found, the proper substituent at the 3-position of phthaloni-

trile plays the major role in controlling the isomers formation

regardless the reaction temperature and alkoxide employed.

We have designed and synthesized 3-(di(tert-butyl)phenyl)-

phthalonitrile, which produced corresponding C_4hphthalo-

cyanine with high yield and selectivity. The structure of the

1

product was evident from H NMR and was additionally

supported by COSY and gHSQC measurements. We have

found that combining 3-(di(tert-butyl)phenyl)phthalonitrile

with other 3-arylphthalonitriles in mixed synthesis yielded

the same “cartwheel” isomers of A₃B, AABB, and ABAB

phthalocyanines.

Following this approach, we have synthesized a set of Pc-

C₆₀dyads, where fullerene is covalently linked to monoiso-

meric phthalocyanine. Phthalocyanines and the dyads are

well soluble in variety of solvents, which improves the quality

of the NMR analysis and simplifies further photochemical

studies and applications.

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The mutual orientation and distance between donor and

acceptor have been recognized as important factors in dyad

design.^14,26-29We have designed our dyads so that the bridge

between fullerene and phthalocyanine is similar in length to

that of previously synthesized porphyrin-fullerene dyads.²⁸

We prepared a set of molecules in which dyad 20a has

one linker whereas dyads 20b and 20c have two linkers in

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A. J.; Carbonell, E.; de Miguel, G.; Guldi, D. M.; Echegoyen, L.; Torres, T.

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J. Org. Chem. Vol. 75, No. 15, 2010 5179

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1,15- and 1,8-positions, respectively. In the case of dyad 20b

the phthalocyanine and fullerene moieties are oriented

face-to-face while in dyad 20c they are oriented face-to-edge.

As expected, in dyad 20b with face-to-face orientation the

electron transfer from phthalocyanine to fullerene is the

most efficient, as evidenced by steady-state fluorescence

measurements.

to prepare bulky phthalonitrile 4, as well as hydroxyl-func-

tionalized phthalonitriles 8 (Scheme 1) and 12-14 (Scheme 2),

by Suzuki-Miyaura coupling using trifluoromethanesulfonic

acid 2,3-dicyanophenyl ester 3 as the key intermediate³¹bear-

ing the phthalonitrile fragment, and the corresponding oxa-

borolanes 1, 7, 9-11 as arylboronic components.

Synthesis of Trifluoromethanesulfonic Acid 2,3-Dicyano-

phenyl Ester 3. 3-Hydroxyphthalonitrile 2 was prepared

according to literature procedure.³⁰The product 2 was

treated with trifluoromethanesulfonyl chloride and triethy-

lamine in dichloromethane at 0 °C followed by warming to

ambient temperature. The reaction mixture was then stirred

overnight to give trifluoromethanesulfonic acid 2,3-dicya-

nophenyl ester 3 in 89% yield.

Results and Discussion

The design of phthalocyanines is with no doubt a question

of phthalonitrile chemistry. Unlike benzaldehydes in por-

phyrin synthesis, the choice of commercially available phtha-

lonitriles is rather limited both in number and variety of the

substituents. This especially concerns 3-substituted phthalo-

nitriles, from which no compounds with bulky groups are

commercially available. Our previous efforts in making

3-substituted phthalonitriles¹⁴and their corresponding phtha-

locyanines and dyads have demonstrated that 3-aryloxyphtha-

lonitriles are not sterically restricting enough to produce a

“cartwheel” C_4hisomer with good selectivity. Even at lower

temperatures (<90 °C) the yield of this isomer did not exceed

50%, and the separation of monoisomeric product was not

possible. Neither did the choice of alkoxide help in solving the

problem; albeit the “cartwheel” formation was evidently more

efficient when the Pc synthesis was done with litium octoxide,

but further purification of the reaction products from octanol

solution was always problematic, if possible at all. A possible

explanation is that the aryloxy (or alkoxy) group does not

protrude in plane with the Pc macrocycle due to sp³-hybridiza-

tion of the oxygen atom, which allows the substituents to lift

off the plane and form a “card pile” thus not restricting the

formation of 4,5-substituted phthalocyanines. Compared to

aryloxy group, the aryl group at the R-phthalo position is more

“straight” and rigid, and therefore is suitable for direct syn-

thesis of 1,8,15,22-substituted Pcs.^31,32It should be noted that

octakis[R-aryl]phthalocyanines are also known,^33,34but the

presence of the aryl group at position 3 of the phthalonitrile

does not guarantee the C_4hisomer formation. On the other

hand, octaarylphthalocyanines are sufficiently nonplanar

macrocycles, which are prepared at high temperatures with

moderate yields, thus the sterical hindrance of the R-aryl sub-

stituent should be combined with mild conditions of macro-

cyclization if a “cartwheel” phthalocyanine needs to be synthe-

sized.

Borylation Reaction. The synthesis of the dioxaborolane

1a was optimized by using 1-bromo-3,5-di-tert-butylbenzene

as starting material. Different borylation reagents (4,4,5,5-

tetramethyl-1,3,2-dioxaborolane and bis(pinacolato)dibo-

ron), bases (KOAc and Et₃N), solvents (THF, DMSO, and

dioxane), and catatalysts (PdCl₂(dppf) CH₂Cl₂, Pd(OAc)₂,

3

and Pd(PPh₃)₄) were used to maximize the yield. Reaction

time was varied from 12 h to 4 days, and temperatures were

varied from room temperature to 100 °C. When 4,4,5,5-

tetramethyl-1,3,2-dioxaborolane was used as borylation

reagent and Et₃N as base with different catalysts, no product

formation was observed. Bis(pinacolato)diboron as borylation

reagent, KOAc as base, PdCl₂(dppf ) CH₂Cl₂as catalyst, and

3

DMSO or dioxane as solvent gave better results. When the

reaction mixture was stirred at 80 °C for 4 days in DMSO,

the dimer 1b was formed. We suggested that by reducing the

reaction time or temperature it should be possible to suppress

the formation of compound 1b and increase the yield of target

product 1a. In further experiments at the room temperature,

even after 3 days of stirring neither the product 1a nor the

dimer 1b was observed. However, when the temperature was

set to 80 °C and reaction time to 12-24 h the target product 1a

was formed in 75-94% yields. The best yield (94%) was

obtained with bis(pinacolato)diboron as borylation agent,

KOAc as base, DMSO as solvent, and PdCl₂(dppf) CH₂Cl₂

3

as catalyst when the reaction mixture was heated at 80 °C for

24 h. Optimization conditions are shown in Table 1.

Synthesis of the dioxaborolane 7a was more complex. At

first, 3-(3-bromophenyl)propionic acid was reduced to 3-(3-

bromophenyl)propan-1-ol 5 with BH₃THF. The hydroxy

3

group was then protected to give acetic acid 3-(3-bromo-

phenyl)propyl ester 6, which was necessary for further

Suzuki coupling, since the unprotected hydroxyl derivative

did not produce the target phthalonitrile at all. Borylation of

compound 6 was optimized by using KOAc/DMSO/PdCl₂-

We have designed the phthalonitriles so that one phtha-

lonitrile has solubility-improving substituents and another

one bears a functional substituent. As a solubility-improving

and sterically restricting group we decided to use the di(tert-

butyl)phenyl fragment. Similar phthalonitrile was prepared

with low yield by Brewis et al.¹⁶by reaction of 3-nitrophtha-

lonitrile with the corresponding phenol. Synthesis of 3-aryl-

phthalonitriles with functional groups (hydroxy, carboxy,

amino) by Suzuki coupling is not yet described. We decided

(dppf ) CH₂Cl₂as base/solvent/catalyst combination. The

3

reaction time was varied from 6 to 21 h, while the tempera-

ture was set to 80 °C. Yields of 85% and 51% were obtained

for the product 7a in 6 and 21 h, respectively, and the dimer

7b was isolated in trace amounts. The optimization condi-

tions are shown in Table 2.

Synthesis of Phthalonitriles by the Suzuki-Miyaura Coup-

ling Reaction. The phthalonitriles 4 and 8a were synthesized

from trifluoromethanesulfonic acid 2,3-dicyanophenyl ester

3 and the corresponding dioxaborolane 1a or 7a by the

Suzuki-Miyaura coupling reaction. The reaction conditions

for synthesis of di(tert-butyl)phenylphthalonitrile 4 were

optimized by using different bases (KOAc and K₃PO₄)

(30) Leznoff, C. C.; Drew, D. M. Can. J. Chem. 1996, 74, 307–318.

(31) Sugimori, T.; Okamoto, S.; Kotoh, N.; Handa, M.; Kasuga, K.

Chem. Lett. 2000, 10, 1200–1201.

(32) Mikhalenko, S. A.; Gladyr, S. A.; Luk’yanets, E. A. Zh. Org. Khim.

1972, 8 (2), 341–343.

(33) Kobayashi, N.; Fukuda, T.; Ueno, K.; Ogino, H. J. Am. Chem. Soc.

2001, 123, 10740–10741.

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(18), 5205–5216.

5180 J. Org. Chem. Vol. 75, No. 15, 2010

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SCHEME 1. Synthesis of Phthalonitriles 4 and 8

and solvents (dioxane, DMSO, and toluene/water 1:1).

PdCl₂(dppf ) CH₂Cl₂was used as catalyst in all experi-

of dioxaborolanes, which required repetitive and time-

consuming chromatographic purification. It is interest-

ing to note that deprotection of acetoxy groups during

Suzuki coupling occurred to a much higher degree for

hydroxyethoxyphthalonitriles 13 and 14, while deprotected

phthalonitriles 8b and 12b were isolated only in minor

amounts.

Synthesis of A₄-Type Phthalocyanines 15-17. The syn-

thesis of phthalocyanines 15-17 is presented in Scheme 3.

The aim was to find phthalonitriles, which produce phtha-

locyanines with a reduced number of regioisomers, and to

determine the yields of A₄-type Pc’s. The product 15 with

tert-butyl groups was evidently a good candidate, but the

main challenge was to select the hydroxyl-containing phtha-

lonitrile for further reactions, as it was not evident which of

the phthalonitriles 8, 12-14 was the best suitable for efficient

phthalocyanine synthesis and further Pc-fullerene dyad pre-

paration.

3

ments, the reaction time was set to 22-24 h, and the

temperature was varied from 80 to 90 °C. When KOAc

was used as base, no product formation was observed.

However, the combination of K₃PO₄as base and toluene/

water 1:1 mixture as solvent gave the yield of target

compound 4 as high as 86% in 24 h at 90 °C. Reaction

conditions are shown in Table 3.

The synthesis of phthalonitrile 8a was carried out in the

presence of K₃PO₄and PdCl₂(dppf) CH₂Cl₂with toluene/

3

water 1:1 mixture as solvent at 90 °C. Yields of 50% and 68%

were obtained in 5 and 20 h, respectively. In addition to the

protected product 8a, also a small amount of the deprotected

compound 8b was observed (Table 4).

We have also prepared a few other dioxaborolanes

9a-11a and phthalonitriles 12a-14a (Scheme 2). Com-

pounds 12-14 differ by the position and length of the hydro-

xyl-terminated bridge, which can be used for further func-

tionalization. However, the yields of dioxaborolanes 10a

and 11a were lower and the purification procedure was

difficult due to a significant amount of dimer formed in

the reaction. The mobility of the dimers was very close to that

Phthalocyanine 15 with di-tert-butylphenyl substituents

was synthesized first to ensure that only one regioisomer

forms in the reaction. The syntheses were carried out in two

different solvents (butanol, pentanol), and with different

lithium alkoxide concentrations. Reaction time was varied

J. Org. Chem. Vol. 75, No. 15, 2010 5181

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SCHEME 2. Synthesis of Compounds 9-14a,b^a

^aReaction conditions: (I) NaBH₄, EtOH, 0 °C, 1 h; (II) acetic anhydride, DMAP, pyridine, rt, 3 d; (III) bis(pinacolato)diboron, KOAc, PdCl₂(dppf)

3

CH₂Cl₂, 80 °C, 4 h, DMSO; (IV) 2-chloroethanol, K₂CO₃, acetone, 60 °C, 7 d; (V) acetic anhydride, DMAP, pyridine, 58 °C, 16 h;

(VI) bis(pinacolato)diboron, KOAc, PdCl₂(dppf) CH₂Cl₂, 80 °C, 22 h, DMSO; (VII) 2-chloroethanol, K₂CO₃, acetone, 54 °C, 4d; (VIII) acetic

3

anhydride, DMAP, pyridine, rt, 17 h; (IX) bis(pinacolato)diboron, KOAc, PdCl₂(dppf) CH₂Cl₂, 80 °C, 17.5 h, DMSO.

3

TABLE 1. Optimization Conditions of the Synthesis of Compound 1a

borylation agent

base

catalyst

solvent

temp/°C

time/h

product (yield/%)

4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Et₃N

KOAc

PdCl₂(dppf) CH₂Cl₂

3

THF

DMSO

dioxane

DMSO

80

100

80

rt

80

48

24

48

24

72

96

72

12

24

Pd(OAc)₂

Pd(PPh₃)₄

PdCl₂(dppf) CH₂Cl₂

3

PdCl₂(dppf) CH₂Cl₂

3

bis(pinacolato) diboron

1b

3

PdCl₂(dppf) CH₂Cl₂

3

1a (83)

1a (75)

1a (94)

3

PdCl₂(dppf) CH₂Cl₂

3

TABLE 2. Optimization Conditions of the Synthesis of Compound 7a

borylation agent

base

catalyst

solvent

temp/°C

time/h

yield/%

bis(pinacolato)diboron

KOAc

PdCl₂(dppf) CH₂Cl₂

3

DMSO

80

21

6

51

85

PdCl₂(dppf) CH₂Cl₂

3

from 5 to 22 h. The best yield was achieved when compound 4

was refluxed in lithium pentoxide/pentanol for 5 h (Table 5).

After purification the monoisomeric phthalocyanine 15 was

obtained in 23% yield, which is much higher than the results

published¹⁶for similar tetrakis[3,5-di(tert-butyl)-4-hydroxy-

phenyl]phthalocyanine. The NMR data and isomer ana-

lysis will be discussed in the next section, but it should be

noticed that only the C_4hisomer formed efficiently at high

5182 J. Org. Chem. Vol. 75, No. 15, 2010

Ranta et al.

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TABLE 3. Optimization Conditions of the Synthesis of Compound 4

TABLE 5. Optimization Conditions of Phthalocyanine 15

compd 4 (mg)

solvent (mL)

lithium/mg

time/h

yield/%

base

catalyst

solvent

temp/°C time/h yield/%

100

50

pentanol (5)

butanol (5)

pentanol (5)

4.4

2.2

5.0

21.2

22

5

7.5

1.2

11

KOAc PdCl₂(dppf) CH₂Cl₂dioxane

KOAc PdCl₂(dppf) CH₂Cl₂DMSO

K₃PO₄PdCl₂(dppf) CH₂Cl₂toluene/water 1:1

80

90

22

24

3

86

5

23

by column chromatography on silica eluting with CHCl₃/

EtOH 10:1.

TABLE 4. Optimization Conditions of the Synthesis of Compound 8a

base catalyst solvent

temp/°C time/h yield/%

Phthalocyanine 17 was also synthesized, but the yield was

low, and the purification was difficult due to poor solubility

of the compound. In addition, three different regioisomers

were formed in the reaction, and the ¹H NMR spectrum was

complex due to aggregation of phthalocyanines.

K₃PO₄PdCl₂(dppf) CH₂Cl₂toluene/water 1:1

3

90

5

20

50

68

K₃PO₄PdCl₂(dppf) CH₂Cl₂toluene/water 1:1

3

SCHEME 3. Synthesis of Phthalocyanines 15-17

Phthalonitriles 13-14 were not suitable for efficient phth-

alocyanine synthesis. Few attempts to prepare correspond-

ing phthalocyanines in lithium pentoxide/pentanol at the

boiling point and in lithium octoxide/octanol at 95 °C were

done, but in all cases the hydroxyethoxy side chains ex-

changed partly to alkoxide groups from solvent, thus form-

ing a complex mixture of products with low yield of the target

Pc. Taking into account the troublesome preparation of

phthalonitriles 13-14, we decided to choose phthalonitriles

4 and 8a, which produced one and two Pc regioisomers,

respectively, for further reactions. We expected that two or

three di-tert-butylphenyl substituents in the phthalocyanine

core are enough to ensure the formation of monoisomeric

phthalocyanines 18a-c.

Synthesis of Phthalocyanines 18-19a-c and Dyads 20a-c.

The syntheses of phthalocyanines 18-19a-c and the dyads

20a-c are presented in Scheme 4. Phthalocyanines 18a-c

were prepared by heating the mixture of phthalonitriles 4 and

8a (molar ratio 7:5) in lithium pentoxide/pentanol at 85 °C

for 23 h. During the reaction, the protective acetyl groups

were cleaved by lithium pentoxide. Altogether seven different

phthalocyanines formed in the reaction from which phthalo-

cyanines 18a-c were separated and purified for further reac-

tions.

In the next reaction, tert-butyl esters of malonic acid were

attached to the hydroxyl groups of phthalocyanines 18a-c

to yield phthalocyanines 19a-c. Synthesis was done in

dichloromethane with a 2-fold excess of tert-butylmalonate

and 2-chloro-1-methylpyridium iodide, and a 4-fold excess of

triethylamine per hydroxy group. Reaction mixtures were stirred

overnight at room temperature, and the yields of the products

19a-c after purification were 86%, 56%, and 76%, respectively.

In the synthesis of the dyads 20a-c, C₆₀-fullerene (1.1 equiv/

malonate group) was dissolved in toluene, iodine (1 equiv/

malonate group) and phthalocyanine 19a-c were then added,

and the reaction mixture was stirred for 15 min under argon

atmosphere. A 3-fold excess of DBU per malonate group was

added and the reaction mixture was stirred 2 h at room tem-

perature under argon atmosphere. The first purification of the

dyads was done by column chromatography immediately after

the completion of the reaction to avoid decomposition of the

target compound by residual iodine. Further purification of

the dyads 20b,c was carried out on HPTLC glass plates (Silica

gel 60 F₂₅₄, Merck).

temperature in pentanol, which greatly simplified further

purification of the product.

Phthalocyanine 16 was synthesized from phthalonitrile 8a

in lithium octoxide/octanol solution. The reaction mixture

was stirred under argon atmosphere at 60 °C for 3 days. The

protective acetyl groups cleaved during the reaction, and

tetrahydroxyphthalocyanine was precipitated out by hexane

addition. After purification, C_4hphthalocyanine 16 was

obtained as the main product in 43% yield. Another regio-

isomer formed in the reaction as the minor product (13%).

Separation of the two regioisomers was achieved easily

NMR Analysis. The structural characterization of phtha-

locyanines has always been difficult since Pc’s usually have

poor solubility and form a number of regioisomers. We

designed phthalocyanines to have only one regioisomer

J. Org. Chem. Vol. 75, No. 15, 2010 5183

Ranta et al.

JOCArticle

SCHEME 4. Synthesis of Phthalocyanines 18a-c and 19a-c and Dyads 20a-c^a

^aReagents and conditions: (i) tert-butyl malonate, 2-chloro-1-methylpyridinium iodide, triethylamine, DCM, 1day, rt; (ii) I₂, DBU, C₆₀, 2 h, rt.

and good solubility in different solvents. These factors

improve the quality and applicability of the NMR analysis

significantly.

In the ¹H NMR spectrum of phthalocyanine 15 (Figure 1),

the peaks are well resolved and sharp. Similar to the data

reported by Bian²³and Gorlach, the signal of R-phthalo

18

€

5184 J. Org. Chem. Vol. 75, No. 15, 2010

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FIGURE 1. The structure and ¹H NMR spectrum of compound 15

in CDCl₃.

FIGURE 2. The structure and ¹H NMR spectrum of compound 16

in CDCl₃/MeOD.

protons (A) is well distinguishable and can be found as a

doublet of doublets at 8.4 ppm. The protons of the di(tert-

butyl)phenyl ring give rise to two singnals: a triplet of one

proton (E) at 7.95 ppm, and a doublet of two protons (D and F)

at 7.87 ppm. Two other phthalo-protons (B and C) produce a

multiplet consisting of overlapping doublet and doublet of

doublets between 7.98 and 8.02 ppm. Signals for tert-butyl

protons (b) are observed at 1.5 ppm as a singlet and NH-

protons (a) are found at -0.3 ppm as a sharp singlet. The H,

H-COSY spectrum (see the Supporting Information) shows

clearly the coupling between signals at 8.4 and 8.02-7.98

ppm, and at 7.95 and 7.87 ppm, thus demonstrating the con-

jugation within separated aromatic rings. The C,H-gHSQC

(see the Supporting Information) spectrum shows each pro-

ton signal correlating to only one respective carbon, namely

8.4-123, 8.02-132, 7.98-129, 7.95-122, and 7.87-124 ppm.

The only explanation for such a clear spectrum is that only one

highly symmetrical regioisomer is present in the sample, other-

wise the signals (especially those of phthalo-protons) would

have much higher multiplicity, and many C,H-correlations

would be observed in gHSQC. Indeed, this highly symmetrical

compound could be either C_4hor D₂type, but from the sterical

point of view the C_4hPc is much more favorable. Considering

the facts mentioned above and previous literature exam-

ples,^18,23we assign the structure of compound 15 as 1,8,15,22-

tetrakis[(3,5-di-tert-butyl)phenyl]phthalocyanine.

previous experience,¹⁴the signals of side substituents split into

a few multiplets if more than one isomer is present in the

sample, the same way as R-phthalo protons do. For compound

16, however, the simplicity of NMR signals is evidence for a

highly symmetrical monoisomeric structure, which is 1,8,15,

22-tetrakis[3-(3-hydroxypropyl)phenyl]phthalocyanine.

1

The H NMR spectra of the monofunctionalized com-

pounds 18-20a in CDCl₃are presented in Figure 3. Signal

assignments are based on COSY and gHSQC data (see the

Supporting Information). In the aromatic region of the

spectrum of 18a signals of the R-phthalo protons G and A

are found at 8.70-8.64 and 8.45-8.38 ppm, respectively.

The signal of proton G is a doublet of doublets, which

indicates that only one isomer is present in the sample. Three

protons A are nonequivalent and produce a narrow multiplet

around 8 ppm, which correspond well to the spectrum of 15.

As revealed by H,H-COSY, a doublet around 8.12 ppm with

additional fine structure originates from the proton at posi-

tion M. The doublet is coupled with the signals of protons at

positions L and K, which in turn appear as a triplet at 7.79

ppm and as a doublet at 7.70 ppm, respectively. The multi-

plet at 8.09-8.06 ppm is due to the protons at positions H

and J. Overlapped signals of protons at positions B and C

appear as a multiplet at 8.06-7.98 ppm. The proton at posi-

tion E gives a singlet at 7.96 ppm, which is overlapped with

the multiplet of the proton at position I. The multiplet at

7.91-7.87 ppm corresponds to the six protons at positions D

and F. In the aliphatic region of the spectrum of compound

18a three signals for -CH₂- protons are visible: a quartet at

3.77 ppm, a triplet at 3.04 ppm, and a multiplet at 2.16-2.05

ppm corresponding to the protons at positions e, c, and d,

respectively. Signals for tert-butyl protons (b) are observed

at 1.51 ppm and -NH protons (a) are found at -0.29 ppm as

a singlet.

In the ¹H NMR spectrum of the main isomer of phthalo-

cyanine 16 (Figure 2) the peaks are well distinguishable as

well, though broadened due to aggregation of the macro-

cycles. In fact, whereas compound 15 was well soluble in neat

CDCl₃, the product 16, which had four hydroxyl groups, was

soluble only upon addition of MeOD, which affected the

chemical shifts. Thus, R-phthalo protons (G) show a doublet

with no fine structure at 8.4 ppm. Another doublet at 8.04

ppm originates from the proton M of the 3-(3-hydroxy-

propyl)phenyl group. Two other phthalo-protons (H and I)

and proton of the aryl ring (J) form a multiplet at 8.00-7.88

ppm, and the rest of the aryl protons (K and L) produce a

multiplet at 7.7.3-7.60 ppm. The signals of the alkyl chain

protons appear as a sharp triplet, triplet, and quintet at 3.71 (e),

2.93 (c), and 2.05 ppm (d), respectively. According to our

The aromatic region of the spectrum of 19a is almost

identical with that of 18a. The signal of the proton at position

M is shifted to higher frequency (8.14 ppm), and the signal

of the proton at position K is shifted to lower frequency (7.68

ppm). In the aliphatic region of the spectrum of 19a four

signals for methylene groups are observed instead of three: a

quartet at 4.27 ppm, a singlet at 3.27 ppm, a triplet at 3.04

J. Org. Chem. Vol. 75, No. 15, 2010 5185

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FIGURE 3. Structures of compounds 18-20a (above) and ¹H

NMR spectra of compounds 18-20a (below) in CDCl₃.

FIGURE 4. Structures of compounds 18-20b (above) and ¹H NMR

spectra of compounds 18-20b (below) in CDCl₃.

ppm, and a multiplet at 2.26-2.12 ppm corresponding to the

protons at positions e, f, c, and d, respectively. The signals for

protons at positions e and d are shifted to higher frequency,

and one additional singlet appears at 3.27 ppm correspond-

ing to the -CH₂- protons of the malonic linker. Signals for

tert-butyl protons at position b (1.51 ppm) and -NH pro-

tons at position a (-0.29 ppm) are identical with those of 18a.

tert-Butyl ester protons of the malonic linker group (g) are

observed at 1.39 ppm.

¹H NMR spectra of ABAB-type compounds 18-20b are

presented in Figure 4. Two doublets of doublets are visible at

8.7 and 8.4 ppm, corresponding to two pairs of R-phthalo

protons (G and A) of symmetrical isomer. Unlike in A₃B Pc’s

18a-19a, the protons D-E of two di(tert-butyl)phenyl

groups of 18b-19b are magnetically equivalent and produce

a sharp triplet and doublet at 7.95 and 7.88 ppm.

In the spectrum of dyad 20b R-phthalo protons at posi-

tions G and A are observed as a doublet of doublets at 8.54

and 8.22 ppm, respectively. The signals from other aromatic

protons appear as a set of multiplets in the region 8.12-7.72

ppm, which can be explained by the close proximity of the

fullerene sphere. In the aliphatic region, the signals for -CH₂-

protons are visible as multiplets at 4.79-4.52, 3.22-2.93, and

2.43-2.25 ppm. The signal of the dyad oxymethylene protons e

around 4.6 ppm is split into two due to asymmetry introduced

by fullerene addition. Eighteen tert-butyl protons at position g

are observed as a singlet at 1.51 ppm and the 36 tert-butyl

protons at position b are found as a singlet at 1.44 ppm. NH

protons (a) of the dyad are visible as a singlet at -0.47 ppm.

Mass Spectrometry. The identification of the chromato-

graphically pure compounds was proved by mass spectro-

metry. A high-resolution ESI-TOF instrument was used in

measurements. To obtain an accurate mass value, the solu-

tion of reference compound (leucine enkephaline) was in-

fused simultaneously with analyte, and the experimental

spectra were processed according to the routine of accurate

mass measurements (peak centering and lock-mass TOF

correction).

The spectrum of the dyad 20a differs significantly from the

spectra of 18a and 19a. In the aromatic region of the spec-

trum, the signal of the R-phthalo proton at position G is

shifted to lower frequency (8.56 - 8.52 ppm) and the signal of

the R-phthalo protons at position A is split into two: a

doublet of doublets at 8.43 ppm corresponding to one proton

and a multiplet at 8.36-8.30 ppm corresponding to two

protons. The difference can be explained by the shielding

effect of fullerene, which apparently forms a stable confor-

mer with phthalocyanine, even though the two chromo-

phores are linked by one flexible bridge only. The signals

of protons at positions H-J, M, B-C, and E appear as two

multiplets at 8.07-7.99 and 7.99-7.91 ppm. In the dyad, the

six protons at positions D and F give three doublets at 7.89,

7.85, and 7.82 ppm. The doublets are partly overlapped with

the triplet at 7.81 ppm, which is the signal of the proton at

position L. A doublet is observed at 7.71 ppm, which

corresponds to the proton at position K. In the aliphatic

region the signals of -CH₂- protons at positions e, c, and d

appear as a triplet at 4.54 ppm, another triplet at 3.06 ppm,

and a multiplet at 2.37-2.25 ppm, respectively. The singlet

that is visible at 3.27 ppm in the spectrum of compound 19a

disappears due to the attachment of fullerene. tert-Butyl

ester protons of the malonic linker (g) appear as a singlet

at 1.55 ppm and the tert-butyl protons of phthalocyanine

(b) are observed as a singlet at 1.54 ppm and as two over-

lapping singlets at 1.48 ppm. NH protons (a) are visible as a

singlet at -0.36 ppm.

The mass spectra of compounds 19-20a are shown in

Figure 5. In the spectrum of phthalocyanine 19a, the [M]^þ

peak was observed at m/z 1354.7708. For the “single handed”

dyad 20a the [M]^þpeak was found at m/z 2072.7576.

The mass spectra of compounds 19-20b are shown in

Figure 6. For phthalocyanine 19b the [M þ Na]^þpeak was

observed at m/z 1465.7451. Molecular ion peak [M þ H]^þ

appeared at m/z 2159.7175 for the dyad 20b.

5186 J. Org. Chem. Vol. 75, No. 15, 2010

Ranta et al.

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FIGURE 7. Mass spectra of compounds 19-20c. 19c: [M]^þ(left);

and 20c: [M - H]^-(right).

FIGURE 5. Mass spectra of compounds 19-20a. 19a: [M]^þ(left);

and 20a: [M]^þ(right).

FIGURE 8. Absorption spectra of 19a and 20a in toluene.

indicating interaction between the chromophores in the

dyads.¹⁴

Steady-State Fluorescence. Steady-state emissions were

measured in polar (benzonitrile) and nonpolar (toluene)

solvents. Emission spectra of the dyad 20a and the corres-

ponding reference 19a in benzonitrile are given in Figure 11.

The spectrum of the dyad (red line) has been multiplied by 18

(dotted line) for comparison. Similarly, the emissions of the

dyads 20b and 20c in benzonitrile are 395 and 194 times

weaker, respectively, compared to those of 19b and 19c

(Figures 12 and 13), indicating that electron transfer (ET)

from phthalocyanine to fullerene may be the cause of the

quenching.¹⁴In addition, the emission spectra of the dyads

20b and 20c are red-shifted by 9 and 5 nm, respectively,

compared to the spectra of compounds 19b and 19c.

In toluene, the emissions of compounds 20a-c are

quenched 13.5, 12.9, and 6.3 times, respectively. The emis-

sion spectrum of compound 20b is red-shifted by 10 nm

compared to compound 19b, and the spectrum of compound

20c is red-shifted by 6 nm compared to compound 19c.

Results from the steady-state fluorescence measurements

are collected to Table 6.

FIGURE 6. Mass spectra of compounds 19-20b. 19b: [M þ Na]^þ

(left); and 20b: [M þ H]^þ(right).

The mass spectra of compounds 19-20c are shown in

Figure 7. For phthalocyanine 19c, the [M]^þpeak appeared at

m/z 1442.7501. In the spectrum of the dyad 20c the [M - H]^-

peak was found at m/z 2157.7124.

Steady-State Absorption. Steady-state absorption spectra

were measured in toluene. Figures 8-10 show the absorption

spectra of compounds 19-20a-c. For the reference com-

pounds 19a-c the Q bands around 700 nm were split into

two having absorption maxima at 675 and 709 nm. The Q

bands of the dyads 20a-c were similar in shape, but red-

shifted by 2 nm for the dyad 20a and by 6 nm for the dyads

20b and 20c compared to the spectra of the reference com-

pounds. In addition, the spectra of the dyads were broadened

J. Org. Chem. Vol. 75, No. 15, 2010 5187

Ranta et al.

JOCArticle

FIGURE 9. Absorption spectra of 19b and 20b in toluene.

FIGURE 12. Fluorescence spectra of 19b and 20b in benzonitrile

excited at 606 nm. The spectrum of dyad 20b has been multiplied by

395 for comparison as indicated in the figure.

FIGURE 10. Absorption spectra of 19c and 20c in toluene.

FIGURE 13. Fluorescence spectra of 19c and 20c in benzonitrile

excited at 601 nm. The spectrum of dyad 20c has been multiplied by

194 for comparison as indicated in the figure.

Conclusions

We have designed and prepared six novel bisaryl phtha-

lonitriles by Suzuki-Miyaura coupling from trifluoro-

methanesulfonic acid 2,3-dicyanophenyl ester and a set of

oxaborolanes. Phthalonitriles 4 and 8 (with two tert-butyl or

one hydroxypropyl substituents, correspondingly) produced

phthalocyanines with C_4hsymmetry with high selectivity and

good yields. A₃B- and A₂B₂-type phthalocyanines substi-

tuted at 1,8,15,22-positions were synthesized by mixed

phthalonitrile condensation and were successfully isolated.

Phthalocyanines were further modified by a covalent full-

erene moiety attachment to yield a set of Pc-C₆₀dyads. Dyad

20a has one linker whereas dyads 20b and 20c have two

linkers. In dyad 20b, phthalocyanine and fullerene are in

a face-to-face orientation, but in dyad 20c they are in a face-

to-edge orientation. The orientation affects strongly the

electron transfer from phthalocyanine to fullerene moiety.³⁵

Fluorescence quenchings of all the dyads were measured in

toluene and benzonitrile. In all cases, fluorescence quenching

was strongest in benzonitrile, and, as expected, for dyad 20b,

with the face-to-face orientation.

FIGURE 11. Fluorescence spectra of 19a and 20a in benzonitrile

excited at 606 nm. The spectrum of dyad 20a has been multiplied by

18 for comparison as indicated in the figure.

Porphyrin-fullerene dyads show distinct exciplex emis-

sion in the region 700-950 nm, but for Pc-C₆₀dyads the

emission of exciplex is not so clearly visible.¹⁴The dyads 20b

and 20c (Figures 12 and 13) show stronger emission around

775-825 nm compared to the reference compounds 19b and

19c. That feature will be studied more carefully by time-

resolved spectroscopy methods in our research.³⁵

1

The products were characterized by H NMR and mass

spectrometry. The analysis of NMR spectra clearly indicates

that synthesized phthalocyanines possess a 1,8,15,22-sub-

stitution pattern. Thus, we propose a way to selectively

prepare monoisomeric phthalocyanines with high yields.

(35) Lemmetyinen, H.; Kumpulainen, T.; Niemi, M.; Efimov, A.; Ranta,

J.; Stranius, K.; Tkachenko N. V., Photochem. Photobiol. Sci. Submitted for

publication.

5188 J. Org. Chem. Vol. 75, No. 15, 2010

Ranta et al.

JOCArticle

TABLE 6. Quenching of Compounds 20a-c in Benzonitrile and

Toluene at Different Excitation Wavelengths

the solvent was evaporated under reduced pressure. The product

was purified by column chromatography on silica 100 eluting

with acetone. Recrystallization from glacial acetic acid gave the

product 2 (702 mg, 65%) as a yellow solid. ¹H NMR (300 MHz,

DMSO) δ 12.04 (s, 1H, arom OH), 7.69 (t, J = 8.03 Hz, 1H,

arom H), 7.52 (dd, J₁= 7.7 Hz, J₂= 0.9 Hz, 1H, arom H), 7.36

(dd, J₁= 8.6 Hz, J₂= 0.9 Hz, 1H, arom H); ¹³C NMR (75 MHz,

DMSO) δ 161.3, 135.4, 124.7,121.7,116.1, 114.9, 114.2, 100.8;

MS (ESI-TOF, negative mode, acetonitrile) m/z 143.0256 [M -

H]^-(calcd 143.0245 [C₈H₄N₂O - H]^-).

λ_exc

(nm)

λ_max.

(nm)

quenching quenching

(%)

compd

solvent

(times)

20a

benzonitrile

606

618

645

599

619

656

606

624

642

651

667

598

619

635

652

661

601

626

636

657

662

602

611

640

663

719

713

714

727

729

726

725

726

725

726

725

720

18.1

17.4

17.2

13.5

13.3

13.4

395

326

409

337

419

12.4

10.3

12.9

11.6

14.1

194

177

193

183

192

6.3

94.5

94.2

92.6

92.5

99.8

99.7

99.8

99.7

99.8

92.0

90.3

92.3

91.4

92.9

99.5

99.4

99.5

84.2

82.5

83.9

85.7

toluene

20b

benzonitrile

Synthesis of Trifluoromethanesulfonic Acid 2,3-Dicyanophenyl

Ester (3). 3-Hydroxyphthalonitrile 2 (50 mg, 0.35 mmol) was

dissolved in DCM (5 mL). Et₃N (50 μL, 0.35 mmol) was added

and the reaction mixture was stirred at room temperature for

30 min under argon atmosphere. The reaction mixture was

cooled to 0 °C on an ice bath and trifluoromethanesulfonyl

chloride (40 μL, 0.35 mmol) was slowly added. The resulting

mixture was stirred at 0 °C for 30 min, followed by stirring for

16 h at room temperature. Diethyl ether (10 mL) was added and

the mixture was filtered, washed with brine (10 mL), dried over

MgSO₄, and evaporated. The triflate 3 was purified by column

chromatography on silica 100 eluting with CHCl₃. The product

toluene

20c

benzonitrile

toluene

1

3 (86 mg, 89%) was obtained as a pale yellow solid. H NMR

(300 MHz, CDCl₃) δ 7.90 (m, 2H, arom H), 7.77 (dd, J₁= 6.8

Hz, J₂= 2.8 Hz 1H, arom H); ¹³C NMR (75 MHz, CDCl₃) δ

150.5, 135.4, 133.1, 127.2, 120.9, 118.6, 116.6, 114.1, 110.6; ¹⁹F

NMR (282 MHz, CDCl₃) -72.58; MS (ESI-TOF, negative

mode, acetone) m/z 274.9731 [M - H]^-(calcd 274.9738 [C₉H₃-

F₃N₂O₃S - H]^-).

5.7

6.2

7.0

The structures we have discovered have enhanced symmetry

and bear functional groups, and can be used to construct

high-ordered supramolecular assemblies.

Synthesis of 3⁰,5⁰-Di-tert-butylbiphenyl-2,3-dicarbonitrile (4).

2-(3,5-Di-tert-butylphenyl)-4,4,5,5-tetramethyl[1,3,2]dioxaboro-

lane 1 (300 mg, 0.95 mmol), trifluoromethanesulfonic acid 2,3-

dicyanophenyl ester 3 (262 mg, 0.95 mmol), K₃PO₄(604.9 mg,

Experimental Section

2.85 mmol), and PdCl₂(dppf) CH₂Cl₂(38.8 mg, 0.048 mmol)

3

were stirred in a mixture of toluene (10 mL) and water (10 mL) at

90 °C for 24 h. The reaction mixture was cooled to room

temperature and diluted with water and toluene. The organic

layer was separated, washed with water (2 ꢀ 30 mL), dried over

MgSO₄, and filtered. The solvent was evaporated under reduced

pressure. The crude product was purified by column chromato-

graphy on silica 60 eluting with CHCl₃. The product 4 (257 mg,

85%) was obtained as a light brown solid. ¹H NMR (300 MHz,

CDCl₃) δ 7.83-7.74 (m, 3H, arom H), 7.56 (t, J = 1.8 Hz, 1H,

arom H), 7.38 (d, J = 1.8 Hz, 2H, arom H), 1.38 (s, 18H, tert-

butyl H); ¹³C NMR (75 MHz, CDCl₃) δ 151.8, 148.7, 135.8,

134.4, 132.9, 131.9, 123.8, 123.3, 117.5, 116.0, 115.7, 114.7, 35.3,

31.5; MS (ESI-TOF, positive mode, CHCl₃/EtOH) m/z 317.2018

[M þ H]^þ(calcd 317.2020 [C₂₂H₂₄N₂þ H]^þ).

Synthesis of 2-(3,5-Di-tert-butylphenyl)-4,4,5,5-tetramethyl-

[1,3,2]dioxaborolane (1a). 1-Bromo-3,5-di-tert-butylbenzene

(600 mg, 2.2 mmol), bis(pinacolato)diboron (622 mg, 2.45 mmol),

potassium acetate (657 mg, 6.7 mmol), and PdCl₂(dppf) CH₂Cl₂

3

(90 mg, 0.11 mmol) were loaded into a 40 mL vial. The vial was

flushed with argon for 5 min. Dry DMSO (20 mL) was added and

the reaction mixture was stirred at 80 °C for 20 h, and then cooled

to room temperature. The dark brown solution was diluted with

toluene, then the organic layer was washed with water (3ꢀ50 mL),

dried over MgSO₄, and filtered. The solvent was evaporated under

reduced pressure. The crude product was purified by column

chromatography on silica 100 eluting with hexane/ethyl acetate

15:1. The product 1a (663 mg, 94%) was obtained as a white solid.

1a: ¹H NMR (300 MHz, CDCl₃) δ 7.66 (d, J = 2.0 Hz, 2H, arom

H), 7.54 (t, J = 2.0 Hz, 1H, arom H), 1.34 (s, 18 H, tert-butyl H),

1.34 (s, 12 H, methyl H); ¹³C NMR (75 MHz, CDCl₃) δ 180.1,

150.1, 129.0, 125.8, 83.8, 35.0, 31.7, 25.1; MS (ESI-TOF, positive

mode, acetone/acetonitrile) m/z 317.1258 [M þ H]^þ(calcd

317.2656 [C₂₀H₃₃BO₂þ H]^þ). The dimer 1b was not observed

in this reaction, but it was formed when the reaction mixture was

stirred at 80 °C for 4 days. 1b: ¹H NMR (300 MHz, CDCl₃) δ 7.43

(t, J = 1.87 Hz, 2H, arom H), 7.37 (d, J = 1.87 Hz, 4H, arom H),

1.38 (s, 36H, tert-butyl H); ¹³C NMR (75 MHz, CDCl₃) δ 151.1,

142.5, 122.4, 121.2, 35.2, 31.8.

Synthesis of 3-(3-Bromophenyl)propan-1-ol (5). 3-(3-Bromo-

phenyl)propionic acid (1.008 g, 4.36 mmol) was dissolved in

THF (20 mL), then the mixture was cooled on an ice bath under

argon atmosphere for 40 min. BH₃THF (7 mL, 7 mmol) was

3

added dropwise to the solution. The reaction mixture was stirred

on an ice bath for 1 h, and then refluxed under argon atmosphere

for 1 h. The reaction was quenched with water (4 mL). The

solvents were evaporated, and the residue was extracted with

CHCl₃(40 mL). The organic layer was washed with H₂O/

NaHCO₃(2 ꢀ 80 mL), and then with water (80 mL). The solvent

was evaporated under reduced pressure. The product 5 (900 mg,

96%) was obtained as a colorless oil. ¹H NMR (300 MHz,

CDCl₃) δ 7.28-7.25 (m, 1H, arom H), 7.25-7.20 (m, 1H, arom

H), 7.08-6.99 (m, 2H, arom H), 3.55 (t, J = 6.3 Hz, 2H,

-CH₂-), 2.58 (t, J = 7.5 Hz, 2H, -CH₂-), 2.01 (s, 1H, -OH),

1.82 (m, 2H, -CH₂-); ¹³C NMR (75 MHz, CDCl₃) δ 144.5,

131.8, 130.2, 129.5, 127.5, 122.7, 62.2, 34.1, 32.0.

Synthesis of 3-Hydroxyphthalonitrile (2)³⁰. 3-Nitrophthaloni-

trile (2.0 g, 11.6 mmol) was dissolved in DMSO (30 mL) and

K₂CO₃(1.8 g, 12.7 mmol) and NaNO₂(0.8 g, 11.6 mmol) were

added. The reaction mixture was refluxed for 30 min under

argon atmosphere and then cooled to room temperature. The

reaction mixture was diluted with water (45 mL) and the mixture

was acidified to pH 3 with 2 M HCl and centrifuged. The pellets

were collected, resuspended in water, and centrifuged again. The

supernatant liquid was discarded and the residue was washed

with methanol. The crude product was dissolved in acetone and

Synthesis of Acetic Acid 3-(3-Bromophenyl)propyl Ester (6).

3-(3-Bromophenyl)propan-1-ol 5 (900 mg, 4.1 mmol) was dis-

solved in pyridine (30 mL). Acetic anhydride (0.765 mL,

J. Org. Chem. Vol. 75, No. 15, 2010 5189

Ranta et al.

JOCArticle

8 mmol) and DMAP (36 mg, 0.3 mmol) were added. The

reaction mixture was stirred at room temperature overnight.

The solvent was evaporated under reduced pressure. The oily

residue was dissolved in CHCl₃(40 mL) and washed first with

diluted HCl (pH 3, 80 mL) and then with water (3 ꢀ 80 mL). The

solvent was evaporated under reduced pressure to yield the

product 6 (950 mg, 93%) as a colorless oil. ¹H NMR (300

MHz, CDCl₃) δ 7.27-7.21 (m, 2H, arom H), 7.10-6.98 (m, 2H,

arom H), 3.98 (t, J = 6.5 Hz, 2H, -CH₂-), 2.57 (t, J = 7.5 Hz,

2H, -CH₂-), 1.96 (s, 3H, -CH₃), 1.91-1.78 (m, 2H, -CH₂-);

¹³C NMR (75 MHz, CDCl₃) δ 171.4, 143.8, 131.7, 130.3, 129.5,

127.4, 122.8, 63.9, 32.1, 30.2, 21.3.

7.49-7.32 (m, 4H, arom H), 3.69 (t, J = 6.45 Hz, 2H, -CH₂-),

2.82 (t, J = 7.78 Hz, 2H, -CH₂-), 2.00-1.89 (m, 2H, -CH₂-),

1.42 (s, br, 1H, -OH).

Synthesis of Acetic Acid 3-(4,4,5,5-Tetramethyl[1,3,2]dioxa-

borolan-2-yl)benzyl Ester (9a). (3-Bromophenyl)methanol: NaBH₄

(228 mg, 6 mmol) was added to a mixture of ethanol (4.4 mL) and

m-bromobezaldehyde (1.28 mL, 11 mmol) on an ice bath. The

reaction mixture was stirred on an ice bath for 1 h. The solvent was

evaporated under reduced pressure. The white solid was dissolved

in water. The water layer was washed with ether (3 ꢀ 30 mL). The

organic layers were combined, dried with MgSO₄, and filtered.

The solvent was evaporated under reduced pressure. The product

1

Synthesis of Acetic Acid 3-[3-(4,4,5,5-Tetramethyl[1,3,2]-

dioxaborolan-2-yl)phenyl]propyl Ester (7a). Acetic acid 3-(3-bro-

mophenyl)propyl ester 6 (272.7 mg, 1.06 mmol), bis(pinaco-

lato)diboron (334.4 mg, 1.32 mmol), potassium acetate (323.9

(1.95 g, 95%) was obtained as a colorless liquid. H NMR (300

MHz, CDCl₃) δ 7.53 (s, br, 1H, arom H), 7.44-7.39 (m, 1H, arom

H), 7.31-7.26 (m, 1H, arom H), 7.24 (t, J = 7.5 Hz, 1H, arom H),

4.67 (d, J = 5.6 Hz, 2H, -CH₂-), 1.78 (br, 1H, -OH). Acetic acid

3-bromobenzyl ester: (3-Bromophenyl)methanol (880.4 mg, 4.71

mmol) was dissolved in pyridine (20 mL), then DMAP (57.5 mg,

0.47 mmol) and acetic anhydride (0.89 mL, 9.4 mmol) were added,

and the reaction mixture was stirred over the weekend at room

temperature. The solvent was evaporated under reduced pressure.

The reaction mixture was diluted with CHCl₃and washed with

water (3 ꢀ 20 mL). The solvent was evaporated under reduced

pressure. The crude product was purified on silica 100 eluting with

CHCl₃. The product (1.06 g, 98%) was obtained from the first

fraction as a colorless oil. ¹H NMR (300 MHz, CDCl₃) δ 7.51 (m,

1H, arom H), 7.47-7.42 (m, 1H, arom H), 7.30-7.25 (m, 1H,

arom H), 7.22 (t, J = 7.5 Hz, 1H, arom H), 5.06 (s, 2H, -CH₂-),

2.11 (s, 3H, -CH₃). Acetic acid 3-(4,4,5,5-tetramethyl[1,3,2]dioxa-

borolan-2-yl)benzyl ester (9a): Acetic acid 3-bromobenzyl ester

mg, 3.3 mmol), and PdCl₂(dppf) CH₂Cl₂(44.9 mg, 0.055

3

mmol) were suspended in DMSO (10 mL). The vial was flushed

with argon for 10 min and sealed. The reaction mixture was

stirred at 80 °C for 6 h and then cooled to room temperature.

The dark brown solution was diluted with toluene and the

organic layer was washed with water (3 ꢀ 50 mL). The solvent

was evaporated under reduced pressure. The crude product

was purified on Combiflash Companion, using hexane/ethyl

acetate gradient (flow rate: 30 mL/min, hexane 100% (2 min),

hexane 100% to hexane/ethyl acetate 70:30 (8 min), hexane/

ethyl acetate 70:30 (5 min), hexane 100% (1 min)). The product

7a (275 mg, 85%) was obtained as a colorless oil from the

second fraction (t_R= 6 min). 7a: ¹H NMR (300 MHz, CDCl₃)

δ 7.67-7.61 (m, 2H, arom H), 7.31-7.27 (m, 2H, arom H), 4.08

(t, J = 6.6 Hz, 2H, -CH₂-), 2.69 (t, J = 7.6 Hz, 2H, -CH₂-),

2.06 (s, 3H, -CH₃), 2.02-1.90 (m, 2H, -CH₂-), 1.35 (s, 12H,

methyl H); ¹³C NMR (75 MHz, CDCl₃) δ 171.4, 140.7, 135.0,

132.8, 131.8, 128.3, 84.0, 83.7, 64.2, 32.4, 30.5, 25.2, 25.0, 21.5;

MS (ESI-TOF, positive mode, CHCl₃/MeOH) m/z 327.1707

[M þ Na]^þ(calcd 327.1747 [C₁₇H₂₅BO₄þ Na]^þ). The dimer 7b

(180.8 mg, 0.8 mmol) CH₂Cl₂, bis(pinacolato)diboron (220.5

3

mg, 0.87 mmol), potassium acetate (232.6 mg, 2.37 mmol), and

PdCl₂(dppf) CH₂Cl₂(32.3 mg, 0.04 mmol) were loaded into a 40

3

mL vial. The vial was flushed with argon for 5 min. Dry DMSO

(10 mL) was added and the reaction mixture was stirred at 80 °C

for 4 h, and then cooled to room temperature. The dark brown

solution was diluted with toluene, then the organic layer was

washed with water (3 ꢀ 50 mL), dried over MgSO₄, and filtered.

The solvent was evaporated under reduced pressure. The crude

product was purified by Combiflash chromatography eluting with

hexane/ethyl acetate gradient (flow rate: 30 mL/min, hexane/ethyl

acetate 9:1 (1 min), hexane/ethyl acetate 9:1 to hexane/ethyl acetate

1:1 in 5 min, hexane/ethyl acetate 1:1 (4 min), hexane/ethyl acetate

3:7 (2 min)). The product 9a (145.3 mg, 67%) was obtained as

a colorless oil from the second fraction (t_R= 2 min). The dimer 9b

(10.9 mg, 5%) was obtained from the third fraction as side product

(t_R=3 min). 9a: ¹H NMR (300 MHz, CDCl₃) δ 7.81-7.74 (m, 2H,

arom H), 7.48-7.42 (m, 1H, arom H), 7.41-7.32 (m, 1H, arom H),

5.10 (s, 2H, -CH₂-), 2.09 (s, 3H, -CH₃), 1.34 (s, 12H, -CH₃);

¹³C NMR (75 MHz, CDCl₃) δ 171.1, 135.3, 134.84, 134.79, 131.4,

128.3, 84.1, 66.6, 25.0, 21.3; MS (ESI-TOF, positive mode, CHCl₃/

MeOH) m/z 299.1421 [M þ Na]^þ(calcd 299.1433 [C₁₅H₂₁B₂O₄þ

Na]^þ). 9b: ¹H NMR (300 MHz, CDCl₃) δ7.58-7.52 (m, 4H, arom

H), 7.44 (t, J= 7.47 Hz, 2H, arom H), 7.38-7.32 (m, 2H, arom H),

5.17 (s, 4H, -CH₂-), 2.12 (s, 6H, -CH₃); MS (ESI-TOF, positive

mode, CHCl₃/MeOH) m/z 299.1314 [M þ H]^þ(calcd 299.1283

[C₁₈H₁₈O₄þ H]^þ).

was observed only in trace amount in the third fraction (t_R

=

8 min). 7b: ¹H NMR (300 MHz, CDCl₃) δ 7.44-7.32 (m, 6H,

arom H), 7.19-7.15 (m, 2H, arom H), 4.12 (t, J = 6.64 Hz, 4H,

-CH₂-), 2.76 (t, J = 7.55 Hz, 4H, -CH₂-), 2.06 (s, 6H,

-CH₃), 2.02-1.93 (m, 4H, -CH₂-).

Synthesis of Acetic Acid 3-(2⁰,3⁰-Dicyanobiphenyl-3-yl)propyl

Ester (8a). Acetic acid 3-[3-(4,4,5,5-tetramethyl[1,3,2]dioxabo-

rolan-2-yl)phenyl]propyl ester 7 (200 mg, 0.66 mmol), trifluor-

omethanesulfonic acid 2,3-dicyanophenyl ester 3 (181.6 mg,

0.66 mmol), K₃PO₄(420.2 mg, 1.98 mmol), and PdCl₂(dppf)

3

CH₂Cl₂(27 mg, 0.033 mmol) were stirred in a mixture of toluene

(5 mL) and water (5 mL) at 90 °C for 20 h. The reaction mixture

was cooled to room temperature and diluted with toluene and

water. The organic layer was washed with water (3 ꢀ 30 mL),

dried over MgSO₄, and filtered. The solvent was evaporated

under reduced pressure. The crude product was purified by

Combiflash chromatography eluting with hexane/ethyl acetate

gradient (flow rate: 30 mL/min, hexane/ethyl acetate 9:1 (1 min),

hexane/ethyl acetate 9:1 to hexane/ethyl acetate 1:3 (8 min),

hexane/ethyl acetate 1:3 (3 min), hexane 100% (1 min)). The

product 8a (130 mg, 65%) was obtained as a greenish oil from

the second fraction (t_R= 6 min). 8a: ¹H NMR (300 MHz,

CDCl₃) δ 7.82-7.75 (m, 3H, arom H), 7.49-7.42 (m, 1H, arom

H), 7.40-7.31 (m, 3H, arom H), 4.12 (t, J = 6.5 Hz, 2H,

-CH₂-), 2.79 (t, J = 7.5 Hz, 2H, -CH₂-), 2.06 (s, 3H, -CH₃),

2.05-1.96 (m, 2H, -CH₂-); ¹³C NMR (75 MHz, CDCl₃) δ

171.4, 147.6, 142.4, 136.7, 134.4, 133.1, 132.2, 129.9, 129.4,

128.9, 126.6, 117.6, 115.9, 115.5, 114.6, 63.7, 32.3, 30.2, 21.1;

MS (ESI-TOF, positive mode, CHCl₃/MeOH) m/z 305.1313 [M

þ H]^þ(calcd 305.1290 [C₁₉H₁₆N₂O₂þ H]^þ). Side product 8b

was obtained from the third fraction (t_R= 10 min). 8b: ¹H

NMR (300 MHz, CDCl₃) δ 7.83-7.74 (m, 3H, arom H),

Synthesis of Acetic Acid 2-[3-(4,4,5,5-Tetramethyl[1,3,2]dioxa-

borolan-2-yl)phenoxy]ethyl Ester (10a). 2-(3-Bromophenoxy)-

ethanol: 3-Bromophenol (0.5 g, 2.89 mmol), acetone (20 mL),

and K₂CO₃(3.2 g. 23.1 mmol) were mixed in a 40 mL vial.

2-Chloroethanol (0.39 mL, 5.78 mmol) was added and the solu-

tion was stirred at 60 °C for 7 days. The reaction mixture was

cooled and filtered. The filtration residue was washed with acetone

(60 mL). Organic solutions were combined and water (3 mL) was

added. The solvents were distilled off at atmospheric pressure.

The oily residue was dissolved in CHCl₃then washed with water

(4 ꢀ 100 mL), and the solvent was evaporated under reduced

5190 J. Org. Chem. Vol. 75, No. 15, 2010

Ranta et al.

JOCArticle

pressure. The oily residue of 2-(3-bromophenoxy)ethanol was

used in the next step without further purification. Acetic acid

2-(3-bromophenoxy)ethyl ester: 2-(3-Bromophenoxy)ethanol

(627 mg, 2.89 mmol) was dissolved in pyridine (15 mL). Acetic

anhydride (0.57 mL, 5.78 mmol) and DMAP (36 mg, 0.29 mmol)

were added and the reaction mixture was stirred at 58 °C

overnight. The yellow solution was evaporated. The oily residue

was dissolved in CHCl₃(30 mL) and washed with water (5 ꢀ 100

mL), and then the solvent was evaporated under reduced

-CH₂-), 4.17 (t, J = 4.74 Hz, 2H, -CH₂-), 2.07 (s, 3H,

-CH₃), 1.34 (s, 12H, -CH₃); MS (ESI-TOF, positive mode,

MeOH) m/z 260.9965 [M þ H]^þ(calcd 260.9950 [C₁₀H₁₁BrO₃þ

H]^þ). Acetic acid 2-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-

phenoxy]ethyl Ester 11a: Acetic acid 2-(2-bromophenoxy)ethyl ester

(300 mg, 1.16 mmol), bis(pinacolato)diboron (326 mg, 1.28 mmol),

potassium acetate (343 mg, 3.5 mmol), and PdCl₂(dppf) CH₂Cl₂

3

(47 mg, 0.058 mmol) were loaded into a 40 mL vial. The vial was

flushed with argon for 5 min. Dry DMSO (10 mL) was added and

the reaction mixture was stirred at 80 °C for 17.5 h, and then cooled

to room temperature. The dark brown solution was diluted with

toluene, then the organic layer was washed with water (3 ꢀ 50 mL),

dried over MgSO₄, and filtered. The solvent was evaporated under

reduced pressure. The crude product was purified by Combiflash

chromatography eluting with hexane/ethyl acetate gradient (flow

rate: 30 mL/min, hexane 100% (2 min), hexane 100% to hexane/

ethyl acetate 7:3 in 7 min, hexane/ethyl acetate 7:3 (5 min), hexane

100% (1 min)). The product 11a (143 mg, 60%) was obtained as a

colorless oil from the second fraction (t_R= 7 min). The dimer 11b

was obtained from the third fraction as side product (t_R= 10 min).

11a: ¹H NMR (300 MHz, CDCl₃) δ 7.63 (dd, J₁= 7.23 Hz, J₂=

1.85 Hz, 1H, arom H), 7.42-7.32 (m, 1H, arom H), 6.97 (t, J=7.40

Hz, 1H, arom H), 6.84 (d, J = 8.41 Hz, 1H, arom H), 4.43 (t, J =

5.21 Hz, 2H, -CH₂-), 4.17 (t, J = 5.04 Hz, 2H, -CH₂-), 2.07 (s,

3H, -CH₃), 1.34 (s, 12 H, -CH₃); ¹³C NMR (75 MHz, CDCl₃) δ

171.1, 163.4, 136.4, 132.5, 121.2, 112.7, 83.7, 67.0, 63.3, 25.0, 21.1;

MS (ESI-TOF, positive mode, CHCl₃/MeOH) m/z 307.1731 [M þ

H]^þ(calcd 307.1720 [C₁₆H₂₃BO₅þ H]^þ). 11b: MS (ESI-TOF,

positive mode, CHCl₃/MeOH) m/z 381.1352 [M þ Na]^þ(calcd

381.1314 [C₂₀H₂₂O₆þ Na]^þ).

1

pressure. H NMR (300 MHz, CDCl₃) δ 7.20-7.05 (m, 3H,

arom H), 6.89-6.81 (m, 1H, arom H), 4.41 (t, J = 4.99, 2H,

-CH₂-), 4.14 (t, J = 5.22, 2H, -CH₂-), 2.10 (s, 3H, -CH₃);

MS (ESI-TOF, positive mode, methanol) m/z 260.9955 [M þ H]^þ

(calcd 260.9950 [C₁₀H₁₁BrO₃þ H]^þ). Acetic acid 2-[3-(4,4,5,5-

tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxy]ethyl ester 10a: Acetic

acid 2-(3-bromophenoxy)ethyl ester (284.2 mg, 1.1 mmol), bis-

(pinacolato)diboron (334.4 mg, 1.32 mmol), potassium acetate

(323.9 mg, 3.3 mmol), and PdCl₂(dppf) CH₂Cl₂(44.9 mg, 0.055

3

mmol) were loaded into a 40 mL vial. The vial was flushed with

argon for 5 min. Dry DMSO (10 mL) was added and the reaction

mixture was stirred at 80 °C for 22 h, and then cooled to room

temperature. The dark brown solution was diluted with toluene,

then the organic layer was washed with water (3 ꢀ 50 mL), dried

over MgSO₄, and filtered. The solvent was evaporated under

reduced pressure. The crude product was purified by Combiflash

chromatography eluting with hexane/ethyl acetate gradient (flow

rate: 30 mL/min, hexane 100% (1 min), hexane 100% to hexane/

ethyl acetate 7:3 in 8 min, hexane/ethyl acetate 7:3 (5 min), hexane

100% (1 min)). The product 10a (100 mg, 30%) was obtained as a

colorless oil from the third fraction (t_R= 6 min). Side product 10b

was not collected. 10a: ¹H NMR (300 MHz, CDCl₃) δ 7.45-7.40

(d, J = 6.94 Hz, 1H, arom H), 7.36-7.27 (m, 3H, arom H), 4.42 (t,

J = 4.96 Hz, 2H, -CH₂-), 4.21 (t, J = 4.96 Hz, 2H, -CH₂-),

2.10 (s, 3H, -CH₃), 1.34 (s, 12H, -CH₃); ¹³C NMR (75 MHz,

CDCl₃) δ 171.2, 158.1, 129.2, 127.8, 119.6, 118.7, 84.0, 66.0, 63.1,

25.0, 21.0; MS (ESI-TOF, positive mode, methanol) m/z 329.1549

[M þ Na]^þ(calcd 329.1539 [C₁₆H₂₃BO₅þ Na]^þ).

Synthesis of Acetic Acid 2⁰,3⁰-Dicyanobiphenyl-3-ylmethyl

Ester (12a). Acetic acid 3-(4,4,5,5-tetramethyl-[1,3,2]dioxabo-

rolan-2-yl)benzyl ester 9a (100 mg, 0.36 mmol), trifluorometha-

nesulfonic acid 2,3-dicyanophenyl ester 3 (100 mg, 0.36 mmol),

K₃PO₄(229.2 mg, 1.08 mmol), and PdCl₂(dppf) CH₂Cl₂(14.7

3

mg, 0.018 mmol) were stirred in a mixture of toluene (5 mL) and

water (5 mL) at 90 °C for 24 h. The reaction mixture was cooled

to room temperature, then diluted with water and toluene. The

organic layer was separated, washed with water (2 ꢀ 30 mL), dried

over MgSO₄, and filtered. The solvent was evaporated under

reduced pressure. The crude product was purified by column

chromatography on silica 100 eluting with CHCl₃/EtOH 18:1.

The protected product 12a (61.2 mg, 62%) was obtained from the

second fraction (t_R=6 min) as a light brown solid. The depro-

tected compound 12b (19.2 mg, 7%) was obtained from the third

fraction as side product (t_R= 10 min). 12a: ¹H NMR (300 MHz,

CDCl₃) δ 7.84-7.76 (m, 3H, arom H), 7.56-7.50 (m, 4H, arom

H), 5.19 (s, 2H, -CH₂-), 2.13 (s, 3H, -CH₃); ¹³C NMR (75

MHz, CDCl₃) δ 171.1, 147.2, 137.4, 137.0, 134.4, 133.3, 132.4,

129.6, 129.5, 128.7, 128.6, 117.6, 115.8, 115.3, 114.8, 65.8, 21.1;

MS(ESI-TOF, positivemode, CHCl₃/MeOH) m/z299.0782 [M þ

Na]^þ(calcd. 299.0797 [C₁₇H₁₂N₂O₂þ Na]^þ). 12b: ¹H NMR (300

MHz, DMSO-d₆) δ 8.15 (dd, J₁= 6.48 Hz, J₂= 2.50 Hz, 1H,

arom H), 7.96 (d, J = 4.42 Hz, 1H, arom H), 7.95 (s, 1H, arom H),

7.54 (m, 4H, arom H), 5.32 (t, J = 5.74 Hz, 1H, -OH), 4.58 (d,

J = 5.74 Hz, 2H, -CH₂-); ¹³C NMR (75 MHz, DMSO-d₆) δ

146.3, 143.5, 136.3, 134.7, 134.1, 132.9, 128.7, 127.5, 127.2, 126.7,

116.3, 116.0, 115.8, 113.3, 62.5; MS (ESI-TOF, positive mode,

MeOH) m/z 257.0686 [M þ Na]^þ(calcd 257.0691 [C₁₅H₁₀N₂O þ

Na]^þ).

Synthesis of Acetic Acid 2-[2-(4,4,5,5-Tetramethyl[1,3,2]dioxa-

borolan-2-yl)phenoxy]ethyl Ester (11a). 2-(2-Bromophenoxy)-

ethanol: 2-Bromophenol (0.5 g, 2.89 mmol), acetone (15 mL),

and K₂CO₃(3.2 g, 23.1 mmol) were mixed in a 40 mL vial.

2-Chloroethanol (0.39 mL, 5.78 mmol) was added and the solu-

tion was stirred at 54 °C for 4 days. The reaction mixture

was cooled and filtered. The filtration residue was washed with

acetone (60 mL). Organic solutions were combined and water

(3 mL) was added. The solvents were distilled off at atmospheric

pressure. The oily residue was dissolved in CHCl₃then washed

with water (3 ꢀ 100 mL), and the solvent was evaporated under

reduced pressure. The oily residue of 2-(2-bromophenoxy)-

ethanol was used in the next step without further purification.

MS (ESI-TOF, positive mode, MeOH) m/z 238.9685 [M þ Na]^þ

(calc. 238.9684 [C₈H₉BrO₂þ Na]^þ). Acetic acid 2-(2-bromophe-

noxy)ethyl ester: 2-(2-Bromophenoxy)ethanol (1.07 g, 4.9 mmol)

was dissolved in pyridine (20 mL). Acetic anhydride (0.94 mL, 9.8

mmol) and DMAP (60 mg, 0.49 mmol) were added and the

reaction mixture was stirred at room temperature overnight.

The solvent was evaporated, and the oily residue was dissolved

in CHCl₃(30 mL) and washed with water (5 ꢀ 100 mL). The

solvent was evaporated under reduced pressure. The residual

yellow oil was dissolved in CHCl₃(20 mL). The organic layer

was washed with HCl (pH 3, 80 mL) and then with water (4 ꢀ

80 mL). The solvent was evaporated under reduced pressure.

The crude product was purified by Combiflash chromatography

eluting with CHCl₃(flow rate: 30 mL/min). The product (1.15 g,

91%) was obtained from the first fraction. ¹H NMR (300 MHz,

CDCl₃) δ 7.63 (dd, J₁= 7.52 Hz, J₂= 1.96 Hz, 1H, arom H),

7.42-7.33 (m, 1H, arom H), 6.97 (t, J = 7.20 Hz, 1H, arom H),

6.84 (d, J = 8.34 Hz, 1H, arom H), 4.43 (t, J = 5.23 Hz, 2H,

Synthesis of Acetic Acid 2-(2⁰,3⁰-Dicyanobiphenyl-3-yloxy)-

ethyl Ester (13a). Acetic acid 2-[3-(4,4,5,5-tetramethyl[1,3,2]-

dioxaborolan-2-yl)phenoxy]ethyl ester 10a (50 mg, 0.16 mmol),

trifluoromethanesulfonic acid 2,3-dicyanophenyl ester 3 (44.2

mg, 0.16 mmol), K₃PO₄(104 mg, 0.49 mmol), and PdCl₂(dppf)

3

CH₂Cl₂(6.5 mg, 0.008 mmol) were stirred in a mixture of

toluene (3 mL) and water (3 mL) at 90 °C for 24 h. The reaction

mixture was cooled to room temperature, then diluted with

J. Org. Chem. Vol. 75, No. 15, 2010 5191

Ranta et al.

JOCArticle

water and toluene. The organic layer was separated, washed

with water (2 ꢀ 30 mL), dried over MgSO₄, and filtered. The

solvent was evaporated under reduced pressure. The crude

product was purified by Combiflash chromatography eluting

with hexane/ethyl acetate gradient (flow rate: 30 mL/min,

hexane/ethyl acetate 9:1 (1 min), hexane/ethyl acetate 9:1 to

hexane/ethyl acetate 1:1 in 7 min, hexane/ethyl acetate 1:1 (7 min)).

The protected product 13a (28.1 mg, 57%) was obtained as a white

solid from the second fraction (t_R= 6.5 min). The deprotected

compound 13b (7.3 mg, 17%) was obtained from the third fraction

(t_R= 12 min) as side product. 13a: ¹H NMR (300 MHz, CDCl₃) δ

7.86-7.74 (m, 3H, arom H), 7.44 (t, J = 8.06 Hz, 1H, arom H),

7.14 (d, J = 7.54, 1H, arom H), 7.10-7.02 (m, 2H, arom H), 4.45

(t, J = 5.28 Hz, 2H, -CH₂-), 4.24 (t, J = 4.53 Hz, 2H, -CH₂-),

2.11 (s, 3H, -CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 171.3. 158.9,

147.2, 138.0, 134.3, 133.1, 132.4, 130.6, 121.7, 117.5, 116.1, 115.8,

115.3, 115.2, 114.7, 66.4, 62.8, 21.2; MS (ESI-TOF, positive mode,

MeOH) m/z 329.0916 [M þ Na]^þ(calcd. 329.0902 [C₁₈H₁₄N₂O₃þ

temperature and diluted with CHCl₃, then the organic layer was

washedwithwater(3ꢀ 50 mL). The solvent was evaporated under

reduced pressure. The crude product was purified by column

chromatography on silica 100 eluting with CHCl₃. The product 15

(11.6 mg, 23%) was obtained from the first fraction as a dark

greensolid. ¹H NMR (300 MHz, CDCl₃) δ 8.40 (dd, J₁= 7.32 Hz,

J₂= 1.27 Hz, 4H, arom H), 8.02 (dd, J₁= 7.46 Hz, J₂= 1.41 Hz,

4H, arom H), 8.00-7.94 (m, 8H, arom H), 7.87 (d, J = 1.74 Hz,

8H, arom H), 1.50 (s, 72 H, -CH₃), -0.32 (s, br, 2H, -NH); ¹³

C

NMR (75 MHz, CDCl₃) δ 150.8, 141.4, 140.3, 132.1, 129.1, 124.4,

122.9, 122.1, 35.5, 32.1, 29.9; MS (ESI-TOF, negative mode,

CHCl₃/EtOH) m/z 1266.7869 [M - H]^-(calcd 1266.7853

[C₈₈H₉₈N₈- H]^-).

Synthesis of 3,3⁰,3⁰⁰,3⁰⁰⁰-(29H,31H-Phthalocyanine-1,8,15,22-

tetrayltetra-3,1-phenylene)tetrapropan-1-ol (16). Lithium shots

(400 mg, 57.6 mmol) and octanol (40 mL) were refluxed under

argon atmosphere for 1 h. Acetic acid 3-(2⁰,3⁰-dicyanobiphenyl-

3-yl)propyl ester 8a (20 mg, 0.066 mmol) was added to warm

lithium octoxide solution (5 mL) under argon atmosphere. The

reaction mixture was stirred at 60 °C over the weekend. The dark

green solution was cooled to room temperature, and diluted

with H₂O/MeOH 1:1 solution. The organic layer was washed

with water (2 ꢀ 30 mL), then water and methanol were evapo-

rated under reduced pressure. Hexane (60 mL) was added to the

residual octanol/phthalocyanine mixture, which was then left to

crystallize overnight. The precipitate was filtered, washed with

hexane and ether, and then dissolved in CHCl₃/EtOH mixture.

The solvents were evaporated under reduced pressure. The

crude product was purified by column chromatography on silica

100 eluting with CHCl₃/EtOH 10:1. Two fractions were ob-

served. The product 16 (7.4 mg, 43%) was obtained from the

second fraction as a blue solid. Another regioisomer (2.2 mg,

1

Na]^þ). 13b: H NMR (300 MHz, CDCl₃) δ 7.84-7.74 (m, 3H,

arom H), 7.45 (t, J = 7.92 Hz, 1H, arom H), 7.16-7.04 (m, 3H,

arom H), 4.16 (t, J = 4.19 Hz, 2H, -CH₂-), 4.04 - 3.96 (br, 2H,

-CH₂-), 1.25 (s, 1H, -OH); ¹³C NMR (75 MHz, DMSO) δ

158.8, 146.0, 137.8, 134.8, 134.0, 132.9, 130.1, 121.0, 116.3, 116.0,

115.86, 115.83, 114.8, 113.5, 69.8, 59.6; MS (ESI-TOF, positive

mode, MeOH/DMSO) m/z 387.0789 [M þ Na]^þ(calcd 287.0797

[C₁₆H₁₂N₂O₂þ Na]^þ).

Synthesis of Acetic Acid 2-(2⁰,3⁰-Dicyanobiphenyl-2-yloxy)-

ethyl Ester (14a). Acetic acid 2-[2-(4,4,5,5-tetramethyl[1,3,2]-

dioxaborolan-2-yl)phenoxy]ethyl ester 11a (96 mg, 0.31 mmol),

trifluoromethanesulfonic acid 2,3-dicyanophenyl ester 3 (85 mg,

0.31 mmol), K₃PO₄(197 mg, 0.93 mmol), and PdCl₂(dppf)

3

CH₂Cl₂(12.7 mg, 0.0155 mmol) were stirred in a mixture of

toluene (4 mL) and water (4 mL) at 110 °C for 14 h. The reaction

mixture was cooled to room temperature and diluted with water

and toluene. The organic layer was separated, washed with

water (4 ꢀ 100 mL), dried over MgSO₄, and filtered. The solvent

was evaporated under reduced pressure. The crude product was

purified by Combiflash chromatography eluting with hexane/

ethyl acetate gradient (flow rate: 30 mL/min, hexane/ethyl

acetate 9:1 (1 min), hexane/ethyl acetate 9:1 to hexane/ethyl

acetate 1:1 in 4 min, hexane/ethyl acetate 1:1 (9 min), hexane

100% (1 min)). The protected product 14a (34 mg, 39%) was

obtained from the second fraction (t_R= 6 min). The depro-

tected compound 14b (21 mg, 28%) was obtained from the third

fraction as side product (t_R= 12 min). 14a: ¹H NMR (300 MHz,

CDCl₃) δ 7.82-7.66 (m, 3H, arom H), 7.45 (t, J = 7.98 Hz, 1H,

arom H), 7.25 (dd, J₁= 6.81 Hz, J₂= 1.74 Hz, 1H, arom H),

7.10 (t, J = 7.39 Hz, 1H, arom H), 7.02 (d, J = 8.25 Hz, 1H,

arom H), 4.37-4.28 (m, 2H, -CH₂-), 4.27-4.19 (m, 2H,

-CH₂-), 2.09 (s, 3H, -CH₃); ¹³C NMR (75 MHz, CDCl₃) δ

171.3, 155.4, 144.5, 135.2, 132.8, 132.0, 131.6, 131.0, 126.1,

121.8, 117.1, 116.6, 116.1, 115.5, 112.3, 66.5, 62.4, 21.2; MS

(ESI-TOF, positive mode, CHCl₃/MeOH) m/z 329.0902 [M þ

Na]^þ(calcd 329.0902 [C₁₈H₁₄N₂O₃þ Na]^þ). 14b: ¹H NMR (300

MHz, CDCl₃) δ 7.82-7.67 (m, 3H, arom H), 7.46 (t, J = 7.95

Hz, 1H, arom H), 7.25 (dd, J₁=7.65 Hz, J₂= 1.84 Hz, 1H, arom

H), 7.14-7.02 (m, 2H, arom H), 4.19 (t, J = 4.90 Hz, 2H,

-CH₂-), 3.91 (q, br, 2H, -CH₂-), 2.00 (t, br, J = 6.27 Hz,

1H, -OH); ¹³C NMR (75 MHz, CDCl₃) δ 155.5, 144.8, 135.6,

133.1, 132.2, 131.8, 131.3, 125.9, 121.7, 116.8, 116.6, 116.0, 112.7,

105.0, 70.0, 61.5; MS (ESI-TOF, positive mode, CHCl₃/MeOH)

m/z 287.0807 [M þ Na]^þ(calcd 287.0797 [C₁₆H₁₂N₂O₂þ Na]^þ).

Synthesis of 1,8,15,22-Tetrakis[(3,5-di-tert-butyl)phenyl]phtha-

locyanine (15). Lithium shots (21.2 mg, 3.05 mmol) were dissolved

in pentanol (5 mL) at heating under argon atmosphere. 3⁰,5⁰-Di-

tert-butylbiphenyl-2,3-dicarbonitrile 4 (50 mg, 0.16 mmol) was

added, and the reaction mixture was flushed with argon and

refluxed for 5 h. The dark green solution was cooled to room

1

13%) was obtained from the first fraction. 16: H NMR (300

MHz, CDCl₃þ MeOD) δ 8.40 (d, J = 6.92 Hz, 4H, arom H),

8.04 (d, J = 7.16 Hz, 4H, arom H), 8.01-7.88 (m, 8H, arom H),

7.75-7.62 (m, 12 H, arom H), 3.71 (t, J = 6.45 Hz, 8H,

-CH₂-), 2.93 (t, J = 8.12 Hz, 8H, -CH₂-), 2.11-1.98 (m,

8H, -CH₂-); MS (ESI-TOF, negative mode, MeOH) m/z

1049.4500 [M - H]^-(calcd 1049.4503 [C₆₈H₅₈N₈O₄- H]^-);

¹³C NMR (75 MHz, DMSO-d₆) δ 142.1, 139.83, 139.82, 131.0,

129.4, 128.3, 128.0, 61.0, 35.0, 32.6.

Synthesis of 1,8,15,22-Tetrakis[3-(hydroxymethyl)phenyl]phtha-

locyanine (17). Lithium shots (3.5 mg, 0.51 mmol) were dissolved

in pentanol (5 mL) at heating under argon atmosphere. Acetic

acid 3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzyl ester

9a (70 mg, 0.25 mmol) was added, and the reaction mixture was

flushed with argon and refluxed for 5 h. The dark green solution

was cooled to room temperature and diluted with CHCl₃, then the

organic layer was washed with water (3 ꢀ 40 mL). The solvent was

evaporated under reduced pressure. In TLC three different green

fractions were visible. The crude product was purified by column

chromatography on silica 100 eluting with CHCl₃/EtOH 10:1.

Purification of the products is very difficult due to insolubility of

phthalocyanines. ¹H NMR spectra of the fractions were complex

due to aggregation of phthalocyanines. MS (ESI-TOF, positive

mode, CHCl₃/MeOH) m/z 939.3442 [M þ H]^þ(calcd 939.3407

[C₆₀H₄₂N₈O₄þ H]^þ).

Synthesis of Phthalocyanines (18a-c): 3-{3-[8,15,22-Tris(3,5-

di-tert-butylphenyl)-29H,31H-phthalocyanin-1-yl]phenyl}propan-

1-ol (18a), 3,3⁰-{[8,22-Bis(3,5-di-tert-butylphenyl)-29H,31H-phth-

alocyanine-1,15-diyl]di-3,1-phenylene}dipropan-1-ol (18b), 3,3⁰-

{[8,15-Bis(3,5-di-tert-butylphenyl)-29H,31H-phthalocyanine-1,22-

diyl]di-3,1-phenylene}dipropan-1-ol (18c).Lithium shots (100 mg, 14.4

mmol) were dissolved in pentanol (10 mL) at heating under argon

atmosphere. 3⁰,5⁰-Di-tert-butylbiphenyl-2,3-dicarbonitrile 4 (70 mg,

0.22 mmol) and acetic acid 3-(2⁰,3⁰-dicyanobiphenyl-3-yl)propyl ester

8a (50 mg, 0.16 mmol) were added. The reaction mixture was flushed

with argon and stirred at 80 °C for 23 h. The dark green solution was

5192 J. Org. Chem. Vol. 75, No. 15, 2010

Ranta et al.

JOCArticle

cooled to room temperature and diluted with CHCl₃. The organic

layer was washed with water (3 ꢀ 30 mL) and the solvents were

evaporated under reduced pressure. Altogether seven different phtha-

locyanines were formed in the reaction from which phthalocyanines

18a-c were separated and purified for further reactions. The reaction

products 18a-c were separated by column chromatography on silica

60 eluting at first with CHCl₃and then with CHCl₃/ethanol 10:1.

Compound 18a was obtained from the second green fraction, and 18b

and 18c were obtained from the third and fourth fractions, respec-

tively. Compound 18a was further purified by column chromatogra-

phy on silica 60 eluting with CHCl₃. The product 18a (8.8 mg, 18%)

8.44-8.37 (m, 3H, arom H), 8.14 (d, J = 7.46 Hz, 1H, arom H),

8.10-7.94 (m, 12H, arom H), 7.79 (t, J = 7.46 Hz, 1H, arom H),

7.68 (d, J = 7.64 Hz, 1H, arom H), 4.27 (t, J = 6.55 Hz, 2H,

-CH₂-), 3.27 (s, 2H, -CO-CH₂-CO-), 3.04 (t, J = 7.82 Hz,

2H, -CH₂-), 2.25-2.14 (m, 2H, -CH₂-), 1.51 (d, J = 1.68 Hz,

54H, tert-butyl H), 1.39 (s, 9H, tert-butyl H), -0.29 (s, 2H,

-NH); ¹³C NMR (75 MHz, CDCl₃) δ 167.2, 165.9, 150.69,

105.68, 150.66, 141.6, 141.4, 140.9, 140.6, 140.21, 140.20, 140.19,

140.0, 132.4, 132.23, 132.17, 130.9, 129.4, 129.2, 129.1, 128.7,

128.3, 128.1, 124.3, 123.2, 123.0, 122.3, 122.11, 122.10, 122.07,

82.1, 77.4, 64.9, 43.1, 35.4, 32.5, 32.0, 30.4, 28.0; UV/vis

(toluene) λ_max, nm (ε, M^-1cm^-1) 340 (43728), 612 (17900),

645 (25504), 674 (84039), 708 (98490); MS (ESI-TOF, positive

mode, CHCl₃/MeOH) m/z 1354.7711 [M]^þ(calcd 1354.7708

[C₉₀H₉₈N₈O₄]^þ).

1

was obtained as a green solid. H NMR (300 MHz, CDCl₃) δ

8.70-8.64 (m, 1H, arom H), 8.43-8.38 (m, 3H, arom H), 8.14-8.10

(m, 1H, arom H), 8.09 (d, J = 1.80 Hz, 1H, arom H), 8.08-8.05 (m,

3H, arom H), 8.05-8.00 (m, 4H, arom H), 7.99 (s, 1H, arom H),

7.98-7.95 (m, 3H, arom H), 7.91-7.87 (m, 6H, arom H), 7.79 (t, J=

7.56 Hz, 1H, arom H), 7.70 (d, J = 7.92 Hz, 1H, arom H), 3.77 (t,

J = 6.44 Hz, 2H, -CH₂-), 3.05 (t, J=7.93 Hz, 2H, -CH₂-),

2.16-2.05 (m, 2H, -CH₂-),1.51(d,J= 0.75 Hz, 36H, tert-butyl H),

1.50 (s, 18H, methyl H), -0.29 (s, 2H, -NH); ¹³C NMR (75 MHz,

CDCl₃) δ 150.69, 150.68, 150.66, 141.62, 141.57, 141.4, 140.6, 140.21,

140.19, 140.1, 132.4, 132.24, 132.17, 131.0, 129.4, 129.17, 129.12,

128.4, 128.3, 128.2, 124.3, 123.2, 123.0, 122.3, 122.12, 122.07, 62.6,

35.4, 34.5, 32.5, 32.0; MS (ESI-TOF, negative mode, CHCl₃/MeOH)

m/z 1211.7081 [M - H]^-(calcd 1211.7003 [C₈₃H₈₈N₈O - H]^-).

Phthalocyanines 18b and 18c were separated by column chromato-

graphy on silica 60 eluting with CHCl₃. 18b was purified by column

chromatography on silica 60 eluting with CHCl₃/ethanol 10:1. The

product 18b (13.1 mg, 28%) was obtained as a green solid. ¹H NMR

(300 MHz, CDCl₃) δ 8.70 (m, 2H, arom H), 8.39 (dd, J₁= 7.20 Hz,

J₂= 1.50 Hz, 2H, arom H), 7.86-8.04 (m, 8H, arom H), 8.01 (m,

3H, arom H), 7.98-7.94 (m, 3H, arom H), 7.88 (d, J = 1.90 Hz, 4H,

arom H), 7.79 (t, J = 7.50 Hz, 2H, arom H), 7.70 (d, J = 7.70 Hz,

2H, arom H), 3.76 (t, J = 6.30 Hz, 4H, -CH₂-), 3.04 (t, J = 7.90

Hz, 4H, -CH₂-), 2.15-2.04 (m, 4H, -CH₂-), 1.50 (s, 36H, tert-

butyl H), -0.28 (s, 2H, -NH); ¹³C NMR (75 MHz, CDCl₃) δ150.7,

141.65, 141.57, 140.5, 140.2, 140.1, 132.4, 132.2, 131.0, 129.4, 129.2,

128.4, 128.3, 128.2, 124.2, 123.2, 122.4, 122.1, 62.6, 35.4, 34.5, 32.5,

32.0, 31.7; MS (ESI-TOF, positive mode, CHCl₃/MeOH) m/z

1159.6279 [M]^þ(calcd 1159.6261 [C₇₈H₇₈N₈O₂]^þ). 18c was purified

by column chromatography on silica 60 eluting with CHCl₃/ethanol

10:1. The product 18c (13.8 mg, 29%) was obtained as a green solid.

¹H NMR (300 MHz, CDCl₃) δ 8.69-8.61 (m, 2H, arom H), 8.40

(dd, J₁= 7.15 Hz, J₂= 1.40 Hz, 2H, arom H), 8.14-7.94 (m, 14H,

arom H), 7.88 (dd, J₁= 4.36 Hz, J₂= 1.92 Hz, 4H, arom H), 7.79 (t,

J = 7.41 Hz, 2H, arom H), 7.69 (d, J = 7.61 Hz, 2H, arom H), 3.77

(m, 4H, -CH₂-), 3.04(t, J=7.40Hz, 4H, -CH₂-), 2.16-2.04 (m,

4H, -CH₂-), 1.50(d, J= 2.32 Hz, 36H, tert-butyl H), -0.30 (s, 2H,

-NH); ¹³C NMR (75 MHz, CDCl₃) δ 168.5, 161.1, 152.0, 150.48,

150.47, 141.42, 141.41, 141.40, 141.3, 140.5, 140.33, 140.29, 140.1,

140.0, 139.94, 139.92, 137.8, 135.8, 135.2, 132.7, 132.1, 130.7, 128.9,

128.1, 125.2, 124.05, 124.03, 122.85, 122.76, 122.2, 76.5, 62.32,

62.30, 53.4, 35.2, 35.1, 34.3, 31.7, 31.4, 21.4; MS (ESI-TOF, negative

mode, CHCl₃/MeOH/acetonitrile) m/z 1157.6212 [M-H]^-(calcd

1157.6169 [C₇₈H₇₈N₈O₂- H]^-).

Synthesis of 2,2⁰-[[8,22-Bis(3,5-di-tert-butylphenyl)-29H,31H-

phthalocyanine-1,15-diyl]bis(3,1-phenylenepropane-3,1-diyl)] 3,3⁰-

Di-tert-butyl Dimalonate (19b). 3,3⁰-{[8,22-Bis(3,5-di-tert-butyl-

phenyl)-29H,31H-phthalocyanine-1,15-diyl]di-3,1-phenylene}

dipropan-1-ol 18b (6.3 mg, 5 μmol), tert-butyl malonate (3.2 mg,

20 μmol), 2-chloro-1-methylpyridinium iodide (5.1 mg, 20 μmol)

and Et₃N (5.6 μL, 40 μmol) were stirred in DCM (5 mL) at room

temperature for 1 day. The reaction mixture was diluted with

CHCl₃and the organic layer was washed with water (3 ꢀ 30 mL).

The solvent was evaporated under reduced pressure. The crude

product was purified by column chromatography on silica 60

eluting with CHCl₃. The product 19b (7.2 mg, 53%) was obtained

as a green solid. ¹H NMR (300 MHz, CDCl₃) δ 8.70-8.62 (m, 2H,

arom H), 8.39 (dd, J₁= 6.95 Hz, J₂= 1.59 Hz, 2H, arom H), 8.14

(d, J = 7.80 Hz, 2H, arom H), 8.09 (d, J = 2.81 Hz, 2H, arom H),

8.07 (s, 2H, arom H), 8.05-7.99 (m, 5H, arom H), 7.98-7.95 (m,

3H, arom H), 7.88 (d, J = 1.83 Hz, 4H, arom H), 7.79 (t, J = 7.56

Hz, 2H, arom H), 7.68 (d, J = 7.68 Hz, 2H, arom H), 4.26 (t, J =

6.46 Hz, 4H, -CH₂-), 3.26 (s, 4H, -CO-CH₂-CO-), 3.03 (t,

J = 8.17 Hz, 4H, -CH₂-), 2.25-2.12 (m, 4H, -CH₂-), 1.50 (s,

36H, tert-butyl H), 1.38 (s, 18H, tert-butyl H), -0.29 (s, 2H,

-NH); ¹³C NMR (75 MHz, CDCl₃) δ 167.2, 166.3, 165.9, 150.7,

141.7, 140.9, 140.6, 140.2, 140.0, 132.5, 130.9, 129.5, 129.5, 129.3,

128.7, 128.36, 128.34, 128.2, 124.2, 123.2, 122.3, 122.1, 82.1, 81.8,

64.9, 44.5, 43.1, 35.4, 32.5, 32.0, 30.4, 28.1, 28.0; UV/vis (toluene)

λ

_max, nm (ε, M^-1cm^-1) 341 (38519), 612 (12725), 645 (18171), 675

(61809), 709 (71615); MS (ESI-TOF, positive mode, CHCl₃/

MeOH 1:1) m/z 1466.7505 [M þ Na]^þ(calcd 1466.7438 [C₉₂-

H₉₈N₈O₈þ Na]^þ).

Synthesis of 2,2⁰-[[8,15-Bis(3,5-di-tert-butylphenyl)-29H,31H-

phthalocyanine-1,22-diyl]bis(3,1-phenylenepropane-3,1-diyl)] 3,3⁰-

Di-tert-butyl Dimalonate (19c). 3,3⁰-{[8,15-Bis(3,5-di-tert-butyl-

phenyl)-29H,31H-phthalocyanine-1,22-diyl]di-3,1-phenylene}

dipropan-1-ol 18c (5.0 mg, 4 μmol), tert-butyl malonate (2.6 mg,

16 μmol), 2-chloro-1-methylpyridinium iodide (4.1 mg, 16 μmol),

and Et₃N (4.5 μL, 32 μmol) were stirred in DCM (5 mL) at room

temperature for 1 day. The reaction mixture was diluted with

CHCl₃and the organic layer was washed with water (3 ꢀ 30 mL).

The solvent was evaporated under reduced pressure. The crude

product was purified by column chromatography on silica 60

eluting with CHCl₃. The product 19c (5.8 mg, 73%) was obtained

asa greensolid. ¹HNMR (300MHz, CDCl₃) δ8.68-8.61 (m, 2H,

arom H), 8.40 (d, J = 7.02 Hz, 2H, arom H), 8.13(d, J = 7.39 Hz,

2H, arom H), 8.09-8.04 (m, 4H, arom H), 8.04-7.99 (m, 5H,

arom H),7.99-7.93 (m, 3H, arom H), 7.87 (dd, J₁= 4.60 Hz,

J₂= 1.84 Hz, 4H, arom H), 7.79 (t, J = 7.70 Hz, 2H, arom H),

7.71-7.65 (m, 2H, arom H), 4.26 (m, 4H, -CH₂-), 3.26 (d, J =

2.43 Hz, 4H, -CO-CH₂-CO-), 3.03 (t, J = 7.56 Hz, 4H,

-CH₂-), 2.25-2.12 (m, 4H, -CH₂-), 1.50 (d, J =2.50 Hz, 36H,

tert-butyl H), 1.39 (d, J = 1.97 Hz, 18H, tert-butyl H), -0.29 (s,

2H, -NH);UV/vis(toluene) λ_max, nm (ε, M^-1cm^-1) 341 (51583),

612 (19697), 645 (28047), 675 (92713), 709 (107582); ¹³C NMR

(75 MHz, CDCl₃) δ 167.21, 167.20, 165.9, 150.70, 150.69, 141.7,

Synthesis of tert-Butyl 3-{3-[8,15,22-Tris(3,5-di-tert-butyl-

phenyl)-29H,31H-phthalocyanin-1-yl]phenyl}propyl Malonate (19a).

3-{3-[8,15,22-Tris(3,5-di-tert-butylphenyl)-29H,31H-phthalo-

cyanin-1-yl]phenyl}propan-1-ol 18a (12 mg, 0.01 mmol), tert-

butyl malonate (3.2 mg, 0.02 mmol), 2-chloro-1-methylpyridi-

nium iodide (5.1 mg, 0.02 mmol), and Et₃N (5.6 μL, 0.04 mmol)

were stirred in DCM (5 mL) at room temperature for 1 day. The

reaction mixture was diluted with CHCl₃and the organic layer

was washed with water (3 ꢀ 30 mL). The solvent was evaporated

under reduced pressure. The crude product was purified by

column chromatography on silica 60 eluting with CHCl₃. The

product 19a (13.6 mg, 86%) was obtained as a green solid.

¹H NMR (300 MHz, CDCl₃) δ 8.69-8.63 (m, 1H, arom H),

J. Org. Chem. Vol. 75, No. 15, 2010 5193

Ranta et al.

JOCArticle

141.5, 140.94, 140.91, 140.6, 140.23, 140.17, 140.15, 140.0, 132.5,

132.4, 132.3, 132.2, 130.8, 129.54, 129.49, 129.24, 129.18, 128.7,

128.4, 128.3, 128.2, 128.1, 124.16, 124.24, 123.2, 123.0, 122.5,

122.3, 122.13, 122.12, 122.09, 82.1, 65.0, 64.9, 43.1, 35.4, 32.50,

32.47, 32.0, 30.43, 30.41, 28.02, 28.01; MS (ESI-TOF, positive

mode, CHCl₃/MeOH) m/z 1442.7507 [M]^þ(calcd 1422.7501

[C₉₂H₉₈N₈O₈]^þ).

chromatography on silica 60 eluting with CHCl₃and then on

HPTLC glass plates (Silica gel 60 F₂₅₄, Merck) eluting with

toluene. The product 20b (2.7 mg, 22%) was obtained as a green

solid. ¹H NMR (300 MHz, CDCl₃) δ 8.53 (dd, J₁= 7.1 Hz, J₂=

1.4 Hz, 2H, arom H), 8.22 (dd, J₁= 7.4 Hz, J₂= 1.0 Hz, 2H,

arom H), 8.12-8.02 (m, 4H, arom H), 8.00-7.94 (m, 3H, arom

H), 7.94-7.85 (m, 9H, aromH), 7.81-7.72 (m, 6H, arom H),

4.79-4.51 (m, 4H, -CH₂-), 3.21-2.86 (m, 4H, -CH₂-),

2.41-2.20 (m, 4H, -CH₂-), 1.51 (s, 18H, tert-butyl H), 1.44 (s,

Synthesis of Dyad 20a. C₆₀(9.4 mg, 13.1 μmol) was dissolved

in toluene (100 mL) on ultrasonic bath for 15 min. I₂(3.0 mg,

11.9 μmol) and tert-butyl 3-{3-[8,15,22-tris(3,5-di-tert-butyl-

phenyl)-29H,31H-phthalocyanin-1-yl]phenyl}propyl malonate

19a (16.1 mg, 11.9 μmol) were added and the reaction flask

was flushed with argon for 15 min. DBU (5.3 μL, 35.7 μmol) was

added and the reaction mixture was stirred at room temperature

for 2 h under argon atmosphere. Water (1 mL) was added and

the solvents were evaporated under reduced pressure. The crude

product was purified by column chromatography on silica 60

eluting with CHCl₃. The product 20a (15.0 mg, 61%) was

36H, tert-butyl H), -0.47 (s, 2H, -NH); UV/vis (toluene) λ_max

,

nm (ε, M^-1cm^-1) 325 (43140), 621 (8762), 682 (30087), 715

(36320); MS (ESI-TOF, positive mode, CHCl₃/EtOH) m/z

2160.7285 [M þ H]^þ(calcd 2160.7305 [C₁₅₂H₉₄N₈O₈þ H]^þ).

Synthesis of Dyad 20c. C₆₀(10.8 mg, 15.0 μmol) was dissolved

in toluene (80 mL) on ultrasonic bath for 15 min. I₂(6.9 mg, 27.2

μmol) and 2,2⁰-[[8,15-bis(3,5-di-tert-butylphenyl)-29H,31H-

phthalocyanine-1,22-diyl]bis(3,1-phenylenepropane-3,1-diyl)]

3,3⁰-di-tert-butyl dimalonate 19c (19.6 mg, 13.6 μmol) were added

and the reaction mixture was flushed with argon for 15 min. DBU

(12.2 μL, 81 μmol) was added and the reaction mixture was stirred

at room temperature for 2 h under argon atmosphere. Water

(1 mL) was added and the solvents were evaporated under

reduced pressure. The crude product was purified by column

chromatography on silica 60 eluting with CHCl₃and then on

HPTLC glass plates (Silica gel 60 F₂₅₄, Merck) eluting with

toluene. The product 20c (10.1 mg, 34%) was obtained as a green

solid. ¹H NMR(300 MHz, CDCl₃) δ 8.47-8.20 (m, 4H, arom H),

8.15-7.59 (m, 22H, arom H), 4.86 (m, 4H, -CH₂-), 3.33-2.63

(m, 4H, -CH₂-), 2.47-1.97 (m, 4H, -CH₂-), 1.61-1.44 (m,

54H, tert-butyl H), -0.46 to -0.71 (m, 2H, -NH); UV/vis

(toluene) λ_max, nm (ε, M^-1cm^-1) 324 (88204), 619 (27832), 681

(100044), 715 (117381); MS (ESI-TOF, negative mode, CHCl₃/

MeOH) m/z 2158.7148 [M - H]^-(calcd 2158.7139 [C₁₅₂H₉₄N₈O₈

- H]^-).

1

obtained as a green solid. H NMR (300 MHz, CDCl₃) δ 8.54

(dd, J₁= 5.9 Hz, J₂= 2.9, 1H, arom H), 8.43 (dd, J₁= 7.0 Hz,

J₂= 1.7 Hz, 1H, arom H), 8.36-8.30 (m, 2H, arom H), 8.06 -

8.00 (m, 5H, arom H), 8.00-7.91 (m, 8H, arom H), 7.89 (d, J =

1.8 Hz, 2H, arom H), 7.85 (d, J = 1.8 Hz, 2H, arom H), 7.82 (d,

J = 1.8 Hz, 2H, arom H), 7.81 (t, J = 7.6 Hz, 1H, arom H), 7.71

(d, J = 7.6 Hz, 1H, arom H), 4.54 (t, J = 5.6 Hz, 2H, -CH₂-),

3.06 (t, J = 7.5 Hz, 2H, -CH₂-), 2.16 - 2.25 (m, 2H, -CH₂-),

1.55 (s, 9H, tert-butyl H), 1.54 (s, 18H, tert-butyl H), 1.48 (d, J =

1.29 Hz, 36H, tert-butyl H), -0.36 (s, 2H, -NH); UV/vis

(toluene) λ_max(ε, M^-1cm^-1) 333 (63056), 616 (10625), 651

(15595), 677 (41516), 710 (47868) nm; MS (ESI-TOF, positive,

CHCl₃/MeOH) m/z 2073.7573 [M]^þ(calcd 2073.7588 [C₁₅₀

-

H₉₆N₈O₄]^þ).

Synthesis of Dyad 20b. C₆₀(4.5 mg, 6.3 μmol) was dissolved in

toluene (80 mL) on ultrasonic bath for 15 min. I₂(2.9 mg, 11.4

μmol) and 2,2⁰-[[8,22-bis(3,5-di-tert-butylphenyl)-29H,31H-

phthalocyanine-1,15-diyl]bis(3,1-phenylenepropane-3,1-diyl)]

3,3⁰-di-tert-butyl dimalonate 19b (8.2 mg, 5.7 μmol) were added

and the reaction mixture was flushed with argon for 15 min. DBU

(5.1 μL, 34.2 μmol) was added and the reaction mixture was

stirred at room temperature for 2 h under argon atmosphere.

Water (1 mL) was added and the solvents were evaporated under

reduced pressure. The crude product was purified by column

Acknowledgment. Financial support from the Academy

of Finland and TEKES is greatly acknowledged.

Supporting Information Available: ¹Hand¹³CNMRspectra

of selected compounds. This material is available free of charge via

the Internet at http://pubs.acs.org.

5194 J. Org. Chem. Vol. 75, No. 15, 2010

Article Doi

Synthesis and characterization of monoisomeric 1,8,15,22-substituted (A3B and A2B2) phthalocyanines and phthalocyanine-fullerene dyads

DOI: 10.1021/jo100766h

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Article abstract of DOI:10.1021/jo100766h

Full text of DOI:10.1021/jo100766h

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