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Year: 2009

An efficient two-step synthesis of metal-free phthalocyaninesusing a Zn(II) template

Alzeer, J; Roth, P J C; Luedtke, N W

Alzeer, J; Roth, P J C; Luedtke, N W (2009). An efficient two-step synthesis of metal-free phthalocyanines using aZn(II) template. Chemical Communications, (15):1970-1971.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Chemical Communications 2009, (15):1970-1971.

Alzeer, J; Roth, P J C; Luedtke, N W (2009). An efficient two-step synthesis of metal-free phthalocyanines using aZn(II) template. Chemical Communications, (15):1970-1971.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Chemical Communications 2009, (15):1970-1971.

An efficient two-step synthesis of metal-free phthalocyaninesusing a Zn(II) template

Abstract

The templating effects of strongly coordinating ions like Co(II), Cu(II), and Zn(II) can dramaticallyimprove the yields of phthalocyanine synthesis. The main problem with this approach is the lack ofreported conditions for the subsequent removal of such ions to generate metal-free phthalocyanines.During our synthesis of guanidine-containing phthalocyanines we discovered a new demetallationreaction that, to the best of our knowledge, provides the first examples of Zn(II) removal withoutdestroying the phthalocyanine itself. This demetallation reaction appears to be general as it works forelectron rich, electron poor, and unsubstituted phthalocyanines. Zn(II)-templated cyclotetramerization,followed by Zn(II) removal provides a high-yielding route (80 - 90 %) to diverse, metal-freephthalocyanines. In contrast, the reported yields with existing methods are typically 10 - 60 %. Giventhe general importance of metal-free phthalocyanines in photovoltaic devices, chemical sensors, anddata storage devices, we are confident this new route to metal-free phthalocyanines will be of generalinterest.

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This journal is © The Royal Society of Chemistry [year] Journal Name, [year], [vol], 00–00 | 1

An efficient two-step synthesis of metal-free phthalocyanines using a Zn(II) template Jawad Alzeer,a Philippe J. C. Roth,a and Nathan W. Luedtke*a

Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X First published on the web Xth XXXXXXXXX 200X 5

DOI: 10.1039/b000000x

A new family of cationic phthalocyanines containing four guanidinium groups was synthesized in pyridine-HCl at 120 oC; under these conditions zinc was removed from both the starting materials and products to reveal a new synthetic route to metal-10

free phthalocyanines.

Initially observed as unexpected byproducts,1,2 an astonishing 5 x 1010 g of phthalocyanines and metallophthalocyanines (Pcs) are now synthesized per year.3 Their remarkable photophysical properties and extreme chemical, thermal, and 15

photostability makes Pcs ideal dyestuffs and useful components of synthetic catalysts, photovoltaic devices, chemical sensors and data storage devices.4-6 Pcs also have interesting in vivo applications as tattoo inks and sensitizers for photodynamic therapy.7 20

Phthalocyanines are prepared by high-temperature cyclo-tetramerization of phthalic acid or dicyano derivatives.4-12 Metal ion templates can dramatically enhance the yields of these reactions.4,6,8-10 To illustrate this effect, the cyclo-tetramerization of 4-nitrophthalic anhydride was conducted in 25

the presence or absence of Li(I), Mg(II), Cu(II), or Zn(II) using a modified Wyler procedure.9 Poor yields were obtained in the presence of LiCl, MgCl2, or in the absence of template, while near-quantitative yields were obtained in the presence of Cu(II) and Zn(II) (Scheme 1).† It is well known that 30

strongly coordinating ions like Mn(II) Fe(II), Co(II) Cu(II), Ni(II), Cu(II), and Zn(II) can dramatically improve the yields of such reactions, but their subsequent removal is thought to be difficult or even impossible without destruction of the Pc itself.8,10a Indeed, previous attempts to remove Zn(II) using 35

strong acids resulted in Pc decomposition, and no examples of Zn(II) demetallation are found in the literature.11 40

45

Scheme 1. Isolated yields for phthalocyanines formed in the presence or absence of LiCl, MgCl2, CuCl2, or ZnCl2. Yields are for the sum of all possible regioisomers. 50

Metal-free phthalocyanines are normally prepared by heating dicyano or diiminoisoindoline precursors in a high-boiling solvent and strong base. While these reactions can, in 55

some cases, furnish metal-free products in good to moderate yields,12 isolated yields ranging from 10 – 30% are also very common.13 Recently, inexpensive phthalic anhydride and phthalimide precursors have been utilized for metal-free Pc syntheses in yields ranging from 20 – 60% by heating a 60

mixture of hexamethyldisilazane, DMF, p-toluenesulfonic acid, and water at 150 oC.14 During our synthesis of guanidinium-containing phthalocyanines we discovered a new demetallation reaction that, together with the effective templating effects of Zn(II), provides a new high-yielding 65

route to metal-free phthalocyanines. 70

75

Scheme 2. Synthesis of guanidino phthalocyanines (GPcs). Counter ions for 2 – 4 are trifluoroacetate. 80

As part of our program aimed at developing new high-affinity G-quadruplex ligands, we became interested in the synthesis of cationic phthalocyanies containing guanidinium groups. This design was motivated by the impressive 85

translocation properties of oligo- and poly-guanidino peptides,15 and by the improved cellular uptake and enhanced RNA affinity of guanidinium-containing small molecules as compared to analogous ammonium-containing compounds.16 Guanidino phthalocyanines (GPcs) were synthesized by 90

reacting a known tetraamino-zinc-phthalocyanine (2)17 with various carbodiimides in a pyridine-HCl ionic liquid (4:1 molar ratio) at 120 oC (Scheme 2).† Under these relatively mild and neutral reaction conditions, Zn(II) was removed to furnish the metal-free GPcs 3 – 5 in isolated yields of 70 – 95

83%. The metal-free products 3 – 5 were characterized by UV-vis spectroscopy, RP HPLC, high resolution ESI MS, and 1H NMR. All analytical data were consistent with the complete removal of zinc during these reactions.† At first

Rpyridine-HCl 120 oC

N C N R

R = hydrogen (3), 70%R = isopropyl (4), 83%R = cyclohexyl (5), 74%

N

N

N

NN

NH N

HN

HNNH

HN NH

NH

NH

HN

HN

HN NH

NH

HNR

R

R

R

R

R

R

R

+

a)

b) H2O / TFAN

N

N

NN

NN

NZn

NH2

H2N NH2

H2N

+ +

+

tetraamino-zinc-phthalocyanine (2)

N

N

N

NN

NN

N

M, urea, nitrobenzeneO

O

OMo7(NH4)6O24 (0.1 mol %)O2N

M YieldH2 Li2 Mg Cu Zn

O2N

O2N

NO2

NO2

5% 5%10%93%98%

180 oC, 4 hr

<<

M

2 | Journal Name, [year], [vol], 00–00 This journal is © The Royal Society of Chemistry [year]

glance, we suspected that the combined electron-withdrawing effects of four guanidinium groups might facilitate Zn(II) removal, but under these conditions, demetallation was independent of the substitutents on the Pcs. To gauge the scope of this new demetallation reaction, a 5

variety of electron rich, electron poor, and unsubstituted phthalocyanines were heated in pyridine-HCl (4:1 molar ratio, lacking any carbodiimide) at 120 oC.‡ For all substrates tested, Zn(II) demetallation generated the metal-free phthalocyanines in high yield (Schemes 3 – 4). Other strongly coordinated 10

metal ions including Cu(II), Co(II), Ni(II), and Pd(II) were not removed under these conditions even when electron deficient GPcs were used (Scheme 3).18 The Zn(II) selectivity of these reactions might be explained by the formation of a ternary pyridine-Pc-Zn complex with square pyrimidal zinc 15

coordination and a non-planar, dome-shaped macrocycle prior to demetallation.19 20

25

Scheme 3. Demetallation of tetrasubstituted metallo phthalocyanines and isolated yields (“n.d.” = no product detected).18 30

35

Scheme 4. Demetallation of C4 symmetric zinc phthalocyanines and isolated yields. 40

It is well known that strongly chelating metal ion templates can dramatically improve the yields of cyclotetramerization under a wide variety of conditions using readily available starting materials (Scheme 1).4,6,8,10 The main problem with this approach has been the lack of reported conditions for the 45

subsequent removal of such ions to generate metal-free phthalocyanines.8,10a,11 During our synthesis of guanidinium-containing phthalocyanines we discovered a new demetallation reaction that, to the best of our knowledge, provided the first examples of Zn(II) removal without 50

destroying the phthalocyanine itself. This demetallation reaction appears to be general as it works for electron rich, electron poor, alkyl-, ether-, and even unsubstituted zinc phthalocyanines. Zn(II)-templated cyclotetramerization followed by Zn(II) removal, therefore provides a new high-55

yielding route to diverse, metal-free phthalocyanines. These products are, in turn, important starting materials for making Pcs and GPcs with variable metal centers. Given the industrial

and academic importance of these compounds, it is expected that this new demetallation reaction will find numerous 60

applications. This work was made possible by generous support from the Swiss National Science Foundation (grant #116868), the Herman Legerlotz Stiftung, and the University of Zürich.

Notes and references 65

a Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. Fax: +41 44 635 6891; Tel: +41 44 635 4244; E-mail: [email protected] † Electronic Supplementary Information (ESI) available: details regarding the synthesis and characterization of all new compounds are 70

available See DOI: 10.1039/b000000x/ ‡ Under these reaction conditions weakly bound metal ions like Sn(II) and Hg(II) were also removed from GPcs, and Zn(II) was quantitatively removed from porphyrins. 75

1. A. Braun, J. Tscherniac, Ber. Dtsch. Chem. Ges., 1907, 40, 2907. 2. H. de Diesbach, E.von der Weid, Helv. Chim. Acta., 1927, 10, 886. 3. P. Gregory, J. Porphyrins Phthalocyanines, 1999, 3, 468. 4. C. C. Leznoff, A. B. P. Lever, Phthalocyanines - Properties and

Applications, VCH, New York, vol. I – IV, 1989 – 1996. 80

5. H. Zollinger, Color Chemistry: Synthesis, Properties, and Applications of Organic Dyes and Pigments, Verlag Helvetica Chimica Acta & Wiley-VCH, Zürich, 3rd edn, 2003.

6. (a) A. L. Thomas, Phthalocyanine Research and Applications, CRC Press, Boca Raton, Ann Arbor, Boston, 1990; (b) F. H. Moser, A. L. 85

Thomas, The Phthalocyanines, CRC Press, Boca Raton, 1983, vol. 1. 7. (a) S. Ogura, K. Tabata, K. Fukushima, T. Kamachi, I. Okura, J

Porphyrins Phthalocyanines, 2006, 10, 1116; (b) E.A. Lukyanets, J. Porphyrins Phthalocyanines, 1999, 3, 424; (c) C. M. Allen, W. M. Sharman, J. E. Van Lier, J. Porphyrins Phthalocyanines, 2001, 5, 90

161; (d) J.-Y. Liu, X.-J. Jiang, W.-P. Fong, D. K. P. Ng, Org. Biomol. Chem., 2008, 6, 4560.

8. N. B. McKeown, Phthalocyanine Materials: Synthesis, Structure and Function, Cambridge University Press, Cambridge, 1998.

9. M. Wyler, 1940, US Pat. 2197458. 95

10. (a) J. W. Steed, D. R. Turner, K. J. Wallace, Core Concepts in Supramolecular Chemistry and Nanochemistry, John Wiley & Sons, 2007, p. 37; (b) D. K. MacFarland, C.M. Hardin, M.J. Lowe, J. Chem. Educ., 2000, 77, 1484; (c) H. Z. Gök, H. Kantekin, Y. Gök, G. Herman, Dyes Pigm., 2007, 75, 606; (d) M. N. Kopylovich, V. Y. 100

Kukushkin, M. Haukka, K. V. Luzyanin, A. J. L. Pombeiro, J. Am. Chem. Soc., 2004, 126, 15040.

11. W. J. Youngblood, J. Org. Chem., 2006, 71, 3345. 12. (a) H. Tomoda, S. Saito, S. Shiraishi, Chem. Lett., 1983, 3, 313; (b)

D. Wohrle, G. Schnurpfeil, G. Knothe, Dyes Pigm., 1992, 18, 91; (c) 105

C. H. Lee, D. K. P. Ng, Tetrahedron Lett., 2002, 43, 4211; (d) S. M. S. Chauhan, S. Agarwal, P. Kumari, Synth. Commun., 2007, 37, 2917; (e) W. Liu, C. H. Lee, H. W. Li, C. K. Lam, J. Z. Wang, T. C. W. Mak, D. K. P. Ng, Chem. Commun., 2002, 6, 628; (f) I. Özcesmeci, A. I. Okur, A. Gül, Dyes Pigm., 2007, 75, 761. 110

13. (a) Y. Z. Wu, H. Tian, K. C. Chen, Y. Q. Liu, D. B. Zhu, Dyes Pigm., 1998, 3, 317; (b) Y. Gök, H. Kantekin, A. Bilgin, D. Mendil, I. Degirmencioglu, Chem. Commun., 2001, 03, 285; (c) J. Rusanova, M. Pilkington, S. Decurtins, Chem. Commun., 2002, 19, 2236; (d) T.

N

N

N

NN

NN

NM

N

N

N

NN

HNN

NH

pyridine-HCl 120 oC, 17 h

R

RR

R

R R

R R

M R YieldZn(II)Zn(II) Zn(II) Zn(II) Zn(II) Pd(II) Co(II) Cu(II) Ni(II)

81%95%80%96%95% n.d. n.d. n.d. n.d.-

NO2 NH2

t-butyl amideguanidineguanidineguanidineguanidine

SO3

N

N

N

NN

NN

NZn

N

N

N

NN

HNN

NH

pyridine-HCl 120 oC, 17 h

R Yield91%

R

R

R

R

R

RR

R

R

R R

R

R

RR

R

H O(CH2)7CH3 85%

This journal is © The Royal Society of Chemistry [year] Journal Name, [year], [vol], 00–00 | 3

Muto, T. Temma, M. Kimura, K. Hanabusa, H. Shirai, Chem. Commun., 2000, 17, 1649.

14. H. Uchida, H. Yoshiyama, P. Y. Reddy, S. Nakamura, T. Toru, Synlett, 2003, 13, 2083.

15. P. A. Wender, W. C. Galliher, E. A. Goun, L. R. Jones, T. H. Pillow, 5

Adv. Drug Delivery Rev., 2008, 60, 452. 16 (a) N. W. Luedtke, T. J. Baker, M. Goodman, Y. Tor, J. Am. Chem.

Soc., 2000, 122, 12035; (b) N. W. Luedtke, P. Carmichael, Y. Tor, J. Am. Chem. Soc., 2003, 125, 12374.

17. (a) S.-H. Jung, J.-H. Choi, S.-M. Yang, W.-J. Cho, C.-S. Ha, Mater. 10

Sci. Eng., B, 2001, 85, 160; (b) F.-D. Cong, B. Ning, X.-G. Du, C.-Y. Ma, H.-F. Yu, B. Chen, Dyes Pigm., 2005, 66, 149.

18. Where "guanidine" = diisopropylguanidinium, and "amide" = NHC(O)CH2CH2CO2H.

19. (a) F. J. Yang, X. Fang, H. Y. Yu, J. D. Wang, Acta Crystallogr. Sect. 15

C: Cryst. Struct. Commun., 2008, 64, M375-M377. (b) J. W. Buchler, D. K. P. Ng, in The Porphyrin Handbook, eds. K. M. Kadish, K. M. Smith, R. Guilard, Academic Press, San Diego, CA, 2000, vol. 3.

20

Graphical Abstract: 25

A new family of cationic phthalocyanines containing four guanidinium groups was synthesized in pyridine-HCl at 120 oC; under these conditions zinc was removed from both the starting 30

materials and products to reveal a new synthetic route to metal-free phthalocyanines.

N

N

N

NN

NN

NO

O

OR

R

R

R

R

Znurea, ∆

N

N

N

NN

HNN

NH

R

R

R

R

∆pyridine-HClZnCl2

1

An efficient two-step synthesis of metal-free phthalocyanines using a

Zn(II) template

Jawad Alzeer, a Phillipe J. C. Roth,a and Nathan W. Luedtke*a

a Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057,

Zürich, Switzerland, [email protected]

~ Supporting Information ~

Materials and Methods

Pyridine, pyridine-HCl, ZnCl2, diisopropyl carbodiimide, and dicyclohexyl carbodiimide were

purchased from Fluka, 4-nitrophthalic anhydride from Aldrich, and cyanamide from Acros

Organics. All other reagents were obtained in the highest commercially available grades from

Sigma Aldrich. 1H-NMR spectra were measured on Bruker ARX-300 or AV-400 or AV-500 spectrometers

(Bruker, Karlsruhe, Germany). The chemical shift values are given in ppm relative to the residual

signal from d6-DMSO (δ = 2.50 ppm). The coupling constants J are given in Hz; resonance

multiplicity is described as s for singlet, d for doublet, dd for doublet of doublet, t for triplet, m

for multiplet; and br is used to indicate broad signals. All data processing was carried out with

Topspin and Xeasy (Bruker).

The mass spectra were measured by the Organic Chemistry Institute of the University of

Zürich. For the matrix-assisted laser desorption/ionization (MALDI) a Bruker Autoflex was used.

Low resolution electrospray ionization (ESI) mass spectra were measured using an Esquire LC

from Bruker. ESI high resolution mass spectra were measured on the MAT 900 from Finnigan.

Visible absorbance spectra were collected using a SpectraMax MP5 spectrophotometer in

Greiner Bio-one UV-Star 96-well plates (final volume = 200 µL). IR spectra were collected

using a JASCO FT/IR-4100 spectrometer equipped with an anvil sample compressor for matrix-

free data collection. The centrifugations were performed in an Eppendorf Centrifuge 5804 using

50 mL polypropylene tubes.

2

Elemental analysis was conducted by the Microanalysis Lab of the Institute of Organic

Chemistry at the University of Zürich. Indicated values are the average of two or more

independent measurements.

The purity of GPcs (compounds 3 – 5) was determined by RP HPLC using a dual pump

Varian (ProStar) system and a C18 Interchrom (250mm x 4.6mm; type D) reversed phase column.

Products were analyzed using a gradient of acetonitrile (HPLC grade, Fisher Scientific) in water,

each containing 0.1% trifluoroacetic acid (TFA).

Synthesis of Metal-Free Guanidino Phthalocyanines

While a large number of guanidinylation methods are known,1-3 common guanidinylation

reagents like N,N′-diBoc-N′′-(trifluoromethylsulfonyl)guanidine, and N,N′-diBoc-1H-pyrazole-1-

carboxamidine were not sufficiently reactive to modify the electron-poor amines of tetramino-

zinc-phthalocyanine (2). Carbodiimides were the very first reagents used for guanidinylation,4

and they proved highly effective for the perguanidinylation of tetramino-zinc-phthalocyanine (2).

The tetraguanidinium derivative 3 was synthesized by reacting 2 with 80 equivalents of

cyanamide in a pyridine-HCl ionic liquid (4:1 molar ratio) at 120 oC. Including one equivalent of

dimethylaminopyridine (DMAP) allowed the reaction to reach completion after 48 h. Compounds

4 and 5 did not require additional catalyst to reach completion after only 17 hours. These

reactions are to our knowledge, the first examples of using a pyridine-HCl ionic liquid as a

solvent and activator of guanidinylation. Evidence for complete demetallation of the GPc

products 3 – 5 was initially found using 1H NMR analysis. In d6-DMSO, these products have

broad, D2O-exchangeable resonances at approximately –0.2 ppm that integrate to two protons.

These signals are characteristic of N-H protons in the center of non-aggregated metal-free

phthalocyanines.5,6 Additional evidence for demetallation is found in the Q-band absorbance for

compounds 3 – 5, which is split into two major transitions (see Figure SI-1, page 10). The

purities of 3 – 5 were determined by RP HPLC to be > 95%. High resolution ESI MS is

consistent with the elemental composition of each product, and the isotope patterns observed by

low resolution ESI MS matches those simulated for the metal-free products (see Figure SI-2,

page 11).

3

Synthesis and Characterization

Tetranitro-metallophthalocyanines were prepared in the presence or absence of LiCl, MgCl2,

CuCl2, or ZnCl2 according to published procedures using nitrobenzene as a co-solvent.7 A

representative procedure, for zinc, is included below. Reactions using the other metals were

identical, except 2-fold more LiCl was used. All analytical data collected for the known

compounds 1, 2, 6, 7, and 9 were consistent with those already published.7,8,9

Tetranitro-zinc-phthalocyanine (1): Ammonium molybdate (13 mg, 0.01 mmol) was added to a

solution of 4-nitrophthalic anhydride (2.0 g, 10 mmol), urea (3.0 g, 50 mmol), and zinc chloride

(383 mg, 2.6 mmol) in nitrobenzene (15 mL). The mixture was stirred under N2 at 185oC. After 4

h, the reaction mixture was cooled and diluted with toluene (80 mL). The resulting precipitate

was collected by centrifugation. The solid was washed with toluene, water, MeOH/ether (1:9),

EtOAc/hexane (2:1), and dried to afford a dark green solid (2.0 g, 98%). IR (neat, cm-1): 1513,

1321, 1080, 754, 726; MALDI TOF MS (m/z): [M+H]+ calcd for C32H13N12O8Zn, 757.0; found

757.0.

Tetraamino-zinc-phthalocyanine (2): Tetraamino-zinc-phthalocyanine (2) was prepared

according to published procedures.7 Sodium sulfide nonahydrate (7.4 g, 30.9 mmol) was added to

a solution of tetranitro-zinc-phthalocyanine (1) (1.95 g, 2.5 mmol) in DMF (50 mL). The reaction

N

N

N

NN

NN

NZn

O2N

O2N

NO2

NO2

N

N

N

NN

NN

NZn

H2N

H2N

NH2

NH2

DMF, 65 oC, 4 hr

Na2S 9 H2O

tetranitro-zinc-phthalocyanine (1): tetramino-zinc-phthalocyanine (2):

N

N

N

NN

NN

NM

M, urea, nitrobenzeneO

O

OMo7(NH4)6O24 (0.1 mol %)O2N

O2N

O2N

NO2

NO2

180 oC, 4 hr

4

mixture was stirred under N2 and heated at 60oC. After 1.5 h, the mixture was cooled to room

temperature, diluted with ice water (150 mL) and the resulting precipitate collected by

centrifugation. The precipitate was repeatedly washed with MeOH/ether (1:9), EtOAc and dried

to afford a dark green solid (1.2 g, 75%). 1H-NMR (300 MHz, d6-DMSO) δ 8.93 (dd, J = 12, 9.0

Hz, 4H), 8.42 (d, J = 12.0 Hz, 4H), 7.38 (d, J = 9.0 Hz, 4H), 6.26 (br. s, 8(NH)); IR (neat, cm-1):

1603, 1490, 1344, 1092, 1044, 822, 743; MALDI TOF MS (m/z): [M+H]+ calcd for C32H21N12Zn,

637.1; found 637.1.

pyridine-HCl, DMAP120 oC, 48 hours

HN C NH

N

N

N

NN

NH N

HN

HNNH

NH

NH

NH2

NH2

NH2

H2N

NH2

H2N NH2

NH2+

a)

b) H2O / TFAN

N

N

NN

NN

NZn

NH2

H2N NH2

H2N

+ +


+

tetraguanidino-phthalocyanine TFA4 salt (3)

4OF3C

O-

Tetraguanidino-phthalocyanine · TFA4 salt (3): Tetramino-zinc-phthalocyanine (2) (35 mg,

0.055 mmoles), pyridine (2 mL), pyridine-HCl (1 g) and DMAP (8 mg, 0.06 mmol) were stirred

under N2 at 120 oC, and cyanamide (115 mg, 2.75 mmoles, 50 equiv) was added in three equal

portions over 48 hours. The reaction was removed from the heat, and 7 mL of acetic acid was

used to transfer the hot mixture into a polypropylene centrifuge tube. The resulting precipitate

was collected by centrifugation at 6’500 r.p.m. and washed repeatedly with acetic acid, EtOAc,

aq. NaHCO3, and water. The dark green solid was re-dissolved in TFA (2mL) and mixed with

water (5 mL). The resulting precipitate was collected by centrifugation, dissolved in a 1:3

mixture of acetonitrile and water containing 0.1% TFA (4 mL), and lyophilized to yield 46 mg

(70%) of a dark green solid. 1H-NMR (400 MHz, d6-DMSO) δ 10.68 (br. m, 4NH), 9.55 (br. m,

4H), 9.34 (br. s, 4H), 8.24 (br. m, 4H), 8.04 (br. s, 12NH), -0.25 (br. s, 2NH); MALDI TOF MS

(m/z): [M+H]+ calcd for C36H31N20, 743.3; found 743.3; HR-ESI MS (m/z): [M+1]+ calcd for

C36H31N20 743.3041; found 743.3037; UV-Vis (DMSO) λmax (nm) and ε (cm-1M-1): 342 (6.0 x

104), 677 (9.9 x 104), and 704 (1.0 x 105).

5

Tetrakis(diisopropylguanidino)-phthalocyanine · TFA4 salt (4): Tetramino-zinc-

phthalocyanine (2) (35 mg, 0.055 mmoles), pyridine (2 mL), pyridine-HCl (1 g), and

diisopropylcarbodiimide (400 µL, 2.6 mmoles, 47 equiv) were stirred under N2 at 120 oC for 17 h.

The reaction was removed from the heat, and 10 mL of H2O was used to transfer the hot mixture

into a polypropylene centrifuge tube. TFA (1.2 mL) was added, mixed, and the resulting

precipitate was collected by centrifugation at 6’500 r.p.m. The supernatant was removed and

mixed with TFA (1 mL), centrifuged, and the supernatant discarded. The combined precipitates

were sonicated with 0.1 N NaCl (7 mL) and then mixed with TFA (1.2 mL), centrifuged, and the

colorless supernatant was carefully removed. The resulting precipitate was sonicated in water (7

mL) and then mixed with TFA (1.2 mL), and the precipitate collected as before. The precipitate

was dissolved in TFA (2mL) and mixed with water (7 mL). The resulting precipitate was

collected by centrifugation, dissolved in a 1:3 mixture of acetonitrile and water containing 0.1%

TFA (4 mL), and lyophilized to yield 70 mg (83%) of a dark green solid. 1H-NMR (400 MHz, d6-

DMSO) δ 10.33 (s, 2NH), 10.29 (s, 2NH), 9.54 (d, J = 3 Hz, = 2H), 9.51 (d, J = 3 Hz = 2H),

9.28 (s, 2H), 9.15 (s, 2H), 8.35 (br. s, 8NH), 8.18 (m, 4H), 4.23 (m, 8H), 1.40 (m, 48H), -0.15 (br.

s, 2NH); MALDI TOF MS (m/z): [M+H]+ calcd for C60H79N20, 1079.7; found 1079.6; HR-ESI

MS (m/z): [M+H]+ calcd for C60H79N20, 1079.6797; found 1079.6798; UV-Vis (DMSO) λmax

(nm) and ε (cm-1M-1): 347 (5.4 x 104), 682 (8.49 x 104), and 710 (9.24 x 104).

pyridine-HCl120 oC, 17 hours

N C N

N

N

N

NN

NH N

HN

HNNH

NH

NH

NH

NH

NH

HN

NH

HN NH

HN+

a)

b) H2O / TFAN

N

N

NN

NN

NZn

NH2

H2N NH2

H2N

+ +


+

tetrakis(diisopropylguanidino)-phthalocyanine TFA4 salt (4)

4OF3C

O-

6

Tetrakis(dicyclohexylguanidino)-phthalocyanine · TFA4 salt (5): Tetramino-zinc-

phthalocyanine (2) (35 mg, 0.055 mmoles), pyridine (2 mL), pyridine-HCl (1 g), and

dicyclohexylcarbodiimide (227 mg, 1.1 mmoles, 20 equiv) were stirred under N2 at 120 oC for 17

h. The reaction was removed from the heat and 5 mL of H2O was used to transfer the hot mixture

into a polypropylene centrifuge tube, the resulting precipitate was collected by centrifugation at

6’500 r.p.m. and washed repeatedly with hot water (3 mL) and centrifuged. The dark green solid

was dissolved in acetonitrile (10 mL) and filtered. The filtrate was evaporated and passed over a

C18 reversed phase column (3:5, acetonitrile:water, containing 0.1% TFA). Evaporation of the

solvent yielded 75 mg (74%). 1H-NMR (400 MHz, d6-DMSO) δ 10.32 (br. s, 2NH), 10.30 (br. s,

2NH), 9.51 (t, J = 8.6 Hz, 2H), 9.40 (t, J = 8.0 Hz 2H), 9.30 (s, 2H), 9.15 (br. s, 2H), 8.35 (m,

8NH), 8.19 (br. s, 2H), 8.17 (br. s, 2H), 3.33 (m, 8H), 2.13 (m, 16H), 1.84 (m, 16H), 1.65 (m, 8H),

1.52 (m, 16H), 1.39 (m, 16H), 1.17 (m, 8H), -0.14 (br. s, 2NH); MALDI TOF MS (m/z): [M+H]+

calcd for C84H111N20, 1399.9; found 1399.8. HR-ESI (m/z): [M+1]+ calcd for C84H110N20,

1399.9301; found 1399.9303; UV-Vis (DMSO) λmax (nm) and ε (cm-1M-1): 347 (5.2 x 104), 682

(8.56 x 104), and 710 (9.69 x 104).


N C N

N

N

N

NN

NH N

HN

HNNH

NH

NH

NH

NH

NH

HN

NH

HN NH

HN+

a)

b) H2O / TFAN

N

N

NN

NN

NZn

NH2

H2N NH2

H2N

+ +


+

tetrakis(dicyclohexylguanidino)-phthalocyanine TFA4 salt (5)

4OF3C

O-

7

Tetranitro-phthalocyanine (6): Tetranitro-zinc-phthalocyanine (2) (35 mg, 0.046 mmoles),

pyridine (2 mL), and pyridine-HCl (1 g) were stirred under N2 at 110 oC for 17 h. The reaction

was removed from the heat, and 10 mL of H2O was used to transfer the hot mixture into a

polypropylene centrifuge tube. The resulting precipitate was collected by centrifugation at 6’500

r.p.m. The dark green precipitate was washed repeatedly with H2O, MeOH, and dried under high

vacuum to yield 26 mg (81%). IR (neat, cm-1): 3096, 1523, 1338, 1134, 1005, 841, 776, 734;

MALDI TOF MS (m/z): [M+H]+ calcd for C32H15N12O8, 695.1; found 695.2. Elemental analysis

C33H18N12O9 (·CH3OH) calc: C 54.55, H 2.50, N 23.13; found: C 54.84, H 2.48, N 23.4%.

Tetramino-phthalocyanine (7). Tetramino-zinc-phthalocyanine (2) (35 mg, 0.055 mmoles),

pyridine (2 mL), and pyridine-HCl (1 g) were stirred under N2 at 110 oC for 17 h. The reaction

was removed from the heat and 10 mL of H2O was used to transfer the hot mixture into a

polypropylene centrifuge tube. The resulting precipitate was collected by centrifugation at 6’500

r.p.m. The dark green precipitate was washed repeatedly with H2O, MeOH, EtOAc, and dried

under high vacuum to yield 30.2 mg (95%). 1H-NMR (400 MHz, d6-DMSO) δ 8.95 (m, 4H), 8.43

(br. s, 2H), 8.38 (d, J = 8 Hz, 2H), 7.45 (m, 4H), 6.5 (br. s, 8NH), 0.40 (br. m, 2NH); IR (neat,

cm-1): 3285, 3079, 1610, 1531, 1435, 1020, 815, 803, 704; MALDI TOF MS (m/z): [M]+ calcd

for C32H22N12, 574.2; found 574.2.

N

N

N

NN

NN

NZn

O2N

O2N

NO2

NO2

N

N

N

NN

HNN

NH

O2N

O2N

NO2

NO2

tetranitro-zinc-phthalocyanine (2) tetranitro-phthalocyanine (6)


N

N

N

NN

NN

NZn

H2N

H2N

NH2

NH2

N

N

N

NN

HNN

NH

H2N

H2N

NH2

NH2

tetraamino-zinc-phthalocyanine (2) tetraamino-phthalocyanine (7)


8

N

N

N

NN

NN

NZn

N

N

N

NN

HNN

NH

tetra-tert-butyl-zinc-phthalocyanine

tetra-tert-butyl-phthalocyanine (8)


Tetra-tert-butyl-phthalocyanine (8). Tetra-tert-butyl-zinc-phthalocyanine (94 mg, 0.11

mmoles), pyridine (5 mL), and pyridine-HCl (2.5 g) were stirred under N2 at 120 C for 17 h. The

reaction was removed from the heat, and water (10 mL) was added while the reaction was still

hot and the mixture allowed to cool. The resulting precipitate was collected by centrifugation at

6’500 r.p.m. The dark blue precipitate was washed repeatedly with H2O, MeOH, and dried under

high vacuum to yield 69 mg (80%). IR (neat, cm-1): 3291, 2954, 2365, 1616, 1482, 1392, 1258,

1090, 892, 826, 746: MALDI TOF MS (m/z): [M] calcd for C48H50N8, 738.4; found 738.3;

Elemental analysis C48H50N8 calcd: C 78.02, H 6.82, N 15.16; found: C 78.15, H 6.85, N 15.12%;

UV-Vis (CHCl3) λ max (nm) and ε (cm-1M-1): 340 (8.33 x 104), 665 (1.29 x 105), 700 (1.51 x

105).

Phthalocyanine (Pc) (9). Zinc-phthalocyanine (190 mg, 0.329 mmoles), pyridine (10 mL), and

pyridine-HCl (5 g) were stirred under N2 at 120 oC for 17 h. The reaction was removed from the

heat, and water (10 mL) was added while the reaction was still hot. The resulting precipitate was

collected by centrifugation at 6’500 r.p.m. The dark green-blue precipitate was washed with

water (20 mL), ethanol (20 mL), acetone (20 mL), and dried to yield 155 mg of product (91 %).

N

N

N

NN

NN

NZn

N

N

N

NN

HNN

NH

zinc-phthalocyanine (Zn-Pc) phthalocyanine (Pc) (9)


9

IR (neat, cm-1): 3272, 1500, 1436, 1333, 1321, 1117, 1093, 1001, 779, 750, 728, 718; MALDI

TOF MS (m/z): [M+H]+ calcd for C32H19N8, 515.2; found 515.2; Elemental analysis C32H18N8

calc: C 74.70, H 3.53, N 21.78; found: C 74.37, H 3.57, N 21.54%; Visible absorbance see

Figure SI-1 A).

N

N

N

NN

NN

NZn

N

N

N

NN

HNN

NH

octakis(octyloxy)-zinc-phthalocyanine octakis(octyloxy)-phthalocyanine (10)


O(CH2)7CH3

O(CH2)7CH3

O(CH2)7CH3

O(CH2)7CH3H3C(H2C)7O

H3C(H2C)7O

H3C(H2C)7O

H3C(H2C)7O O(CH2)7CH3

O(CH2)7CH3

O(CH2)7CH3

O(CH2)7CH3H3C(H2C)7O

H3C(H2C)7O

H3C(H2C)7O

H3C(H2C)7O

Octakis(octyloxy)-phthalocyanine (10). Octakis(octyloxy)-zinc-phthalocyanine (50 mg, 0.031

mmoles), pyridine (2 mL), and pyridine-HCl (1 g) were stirred under N2 at 120 C for 17 h. The

reaction was removed from the heat, and water (10 mL) was added while the reaction was still

hot and the mixture allowed to cool. The resulting precipitate was collected by centrifugation at

6’500 r.p.m. The dark green precipitate was washed repeatedly with H2O, MeOH, and dried

under high vacuum to yield 41 mg (85%). IR (neat, cm-1): 3287, 2981, 2850, 2361, 2336, 1611,

1449, 1381, 1272, 1199, 1099, 1019, 853, 744: MALDI TOF MS (m/z): [M] calcd for

C96H146N8O8, 1539.1; found 1539.0; Elemental analysis C96H146N8O8 calcd: C 74.86, H 9.55, N

7.28; found: C 74.68, H 9.44, N 7.28%; UV-Vis (CHCl3) λ max (nm) and ε (cm-1M-1): 344 (8.4 x

104), 665 (1.19 x 105), 704 (1.32 x 105)

10

A) B)

C) D)

Figure SI-1. Visible absorbance spectra of: A) 1.1 µM solutions of zinc phthalocyanine (Zn-Pc)

and the isolated metal-free phthalocyanine product (9) in 1-bromonaphthylene. These spectra

match reported standards.9 B) 2.1 µM solution of tetraguanidino-phthalocyanine · TFA4 salt (3)

in 0.1% TFA / DMSO; C) 1.4 µM solution of tetrakis(diisopropylguanidino)-phthalocyanine ·

TFA4 salt (4) in 0.1% TFA / DMSO; and D) 2.0 µM solution of tetrakis(dicyclohexylguanidino)-

phthalocyanine · TFA4 salt (5) in 0.1% TFA / DMSO. Under these conditions, all absorbance

spectra obey the Beer–Lambert law over a range of 0.3 – 10 µM.

500 600 700 800

0.0

0.1

0.2

0.3 Zn-PcPc (9)

Wavelength (nm)

AU

500 600 700 800

0.0

0.1

0.2

0.3tetrakis(diisopropylguanidino)phthalocyanine (4)

Wavelength (nm)

AU

500 600 700 800

0.0

0.1

0.2

0.3

0.4tetrakis(dicyclohexylguanidino)phthalocyanine (5)

Wavelength (nm)

AU

500 600 700 800

0.0

0.1

0.2

0.3

0.4tetraguanidinophthalocyanine (3)

Wavelength (nm)

AU

11

A) B)

C)

Figure SI-2. Isotope patterns according to low resolution ESI MS for A) tetraguanidino

phthalocyanine · TFA4 salt (3); B) tetrakis(diisopropylguanidino)-phthalocyanine · TFA4 salt (4);

and C) tetrakis(dicyclohexylguanidino)-phthalocyanine · TFA4 salt (5). High resolution ESI MS

gave results consistent with the expected molecular formulas of 3 – 5.

References

(1) Orner, B. P.; Hamilton, A. D. Journal of Inclusion Phenomena and Macrocyclic Chemistry 2001, 41, 141. (2) Suhs, T.; Konig, B. Mini-Reviews in Organic Chemistry 2006, 3, 315. (3) Zhou, S. W., Shaowu; Yang, Gaosheng; Li, Qinghai; Zhang, Lijun; Yao, Zijian; Zhou, Zhangkai; Song, Hai-bin Organometallics 2007, 26, 3755. (4) Weith, W. Chem Ber. 1873, 6, 1389. (5) Liu, W.; Lee, C. H.; Li, H. W.; Lam, C. K.; Wang, J. Z.; Mak, T. C. W.; Ng, D. K. P. Chemical Communications 2002, 628. (6) Terekhov, D. S.; Nolan, K. J. M.; McArthur, C. R.; Leznoff, C. C. Journal of Organic Chemistry 1996, 61, 3034. (7) Cong, F.-D. N., Bo; Du, Xi-Guang; Ma, Chun-Yu; Yu, Hai-Feng; Chen, Bin Dyes and Pigments 2005, 66, 149. (8) Todd, W. J.; Bailly, F.; Pavez, J.; Faguy, P. W.; Baldwin, R. P.; Buchanan, R. M. Journal of the American Chemical Society 1998, 120, 4887. (9) Whalley, M. Journal of the Chemical Society 1961, 866.

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