Polysubstituted phthalocyanines by nucleophilic substitution reactions on hexadecafluorophthalocyanines

Article abstract of DOI:10.1039/b313253f

Nucleophilic substitution reactions on hexadecafluorophthalocyaninato zinc(II) with a variety of O, N, C, and S nucleophiles led to narrowly defined mixtures of polysubstituted phthalocyanines, some of which are completely inaccessible by classical phthalonitrile condensation reactions.

Full text of DOI:10.1039/b313253f

Polysubstituted phthalocyanines by nucleophilic substitution reactions on
hexadecafluorophthalocyanines
Clifford C. Leznoff* and José L. Sosa-Sanchez†
Department of Chemistry, York University, Toronto, Ontario, Canada M3J 1P3. E-mail: leznoff@yorku.ca;
Fax: (416) 736 5936; Tel: (416) 736 2100 ext 33838
Received (in Cambridge, UK) 21st October 2003, Accepted 28th November 2003
First published as an Advance Article on the web 13th January 2004
Nucleophilic substitution reactions on hexadecafluorophthalo-
cyaninato zinc(II) with a variety of O, N, C, and S nucleophiles
led to narrowly defined mixtures of polysubstituted phthalocya-
nines, some of which are completely inaccessible by classical
phthalonitrile condensation reactions.
a hexacyanobenzene derivative has never been accomplished.
Reactions of 1a–e with 2 gave phthalocyanines 3a–e in which, on
average, 12, 8, 12, 14, and 16 fluoro groups had been replaced,
respectively.
For all the examples above, the benefit of using a relatively
soluble starting Pc material (2) became apparent. Relatively low
temperatures between 65–120 °C could be used depending on the
degree of substitution expected and on the nature of the solvent.
Former investigations using a pre-formed Pc precursor had a more
limited scope due to the extremely low solubility of the starting
material (MPc or Cl16MPc). In addition, it has been established that
fluoroaryl compounds undergo nucleophilic substitution with
different nucleophiles at an increased rate in the order of 102 to 103
times faster than other halogen analogs.8 Therefore the use of
hexadecafluorophthalocyanines as starting materials seemed a
good choice for the substitution reaction using different nucleo-
philes. In this respect, the fact that a broad range of nucleophilic
reagents with O, N, C and S atoms could be used was, by itself an
attractive feature to follow this new approach. Many Pc compounds
that cannot be prepared from a phthalonitrile or other known
precursors could be obtained.4 Moreover, for one nucleophile that
works well with this new method a series of compounds with
The use of the phthalocyanine (Pc) moiety in materials having
technological applications has been demonstrated over the years.1
Most of the current research in phthalocyanine chemistry empha-
sizes the usefulness of Pc materials that stems from their
characteristic properties.2 Nevertheless in the most recently
discovered applications of economic relevance1,2 good solubility of
the Pc material is a necessary requirement.
So far, two main strategies have been followed to obtain novel
mononuclear Pc compounds with increased solublity. In the first,
condensation of a substituted phthalonitrile precursor leads to a Pc
product functionalized on the peripheral and/or non-peripheral
positions around the macrocycle. Another strategy is the possibility
of starting with a pre-formed easily prepared substituted Pc and
functionalizing the substituents afterwards.
For metallophthalocyanines (MPcs) with central elements with
valence states higher than two, axial substitution with bulky ligands
has been used as well, as a method to obtain a more soluble
product.3 From our experience, starting from a preformed Pc
precursor would be more advantageous since suitable phthalonitrile
precursors are not always readily available and in other instances do
not always yield Pc compounds.4
Only two previous examples of solubilizing Pcs by substitution
of the benzo sites have been found in the patent literature. In one
report a rather unreactive starting material was used and therefore
quite stringent reaction conditions were used.5 In the second report,
hexadecasubstituted Pcs6 were prepared by nucleophilic substitu-
tion of hexadecachlorophthalocyanines.7 Here the complete lack of
solubility of the Pc precursor makes nucleophilic substitution
reactions unreliable. Since hexadecafluorophthalocyanines are
readily made and even commercially available we conceived of a
more direct way to obtain new soluble Pcs by nucleophilic
substitution reactions as described in Scheme 1.
In a general synthesis twenty equivalents per fluoro group of the
nucleophile precursors 1a–e reacted with an equimolar amount of
n-butyllithium under an argon atmosphere in diglyme at a suitable
temperature. Then one equiv. of hexadecafluorophthalocyaninato
zinc (2) is added and the reaction mixture is heated to around 100
°C for 8 h. In an alternative method, when the nucleophile by itself
is reactive enough, the activation step using n-butyllithium can be
eliminated and the Pc starting material can react with a solution of
this nucleophile (1b) alone, either neat or in an appropriate solvent.
In another synthesis, when KCN (1d) is used as the nucleophile, a
cyclic polyether, e.g. 18-crown-6, can be used to activate the
nucleophilic species as a naked ion. This reaction allowed us to
obtain a mixture of tetradeca- and hexadecacyano phthalocyanines
as identified by MALDI-TOF analysis. Although the yield of this
particular reaction was low, the alternative approach starting from
† On sabbatical leave from Centro de Investigación en Dispositivos
Semiconductores, Instituto de Ciencias de la Benemérita Universidad
Autónoma de Puebla, Blvd. 14 Sur y Av. San Claudio, Ciudad Uni-
versitaria, Puebla Pue., CP 72570 México.
Scheme 1
338
C h e m . C o m m u n . , 2 0 0 4 , 3 3 8 – 3 3 9
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

similar structure can be prepared for correlation studies such as the
application of ligand electrochemical parameters9 to the design of
new MPcs for a particular technological use. An apparent drawback
of this new methodology that is anticipated is that, since there is a
possibility of substitution on sixteen different sites on the Pc
macrocycle, there is a possibility of obtaining mixtures of products.
For nucleophiles having medium steric effects, as many as 12
substituents (3a,c), other than fluoro, can be found in the product,
but for highly hindered nucleophiles (3b) between 8–10 morpho-
lino groups can be identified in the final products. The similarity of
physical properties of the products obtained in these mixtures does
not allow, at present, for isolation of a single pure compound.
There is some spectroscopic evidence of what seems to be a
different pattern of sequential substitution of the Pc precursor
compared to that of a phthalonitrile. When tetrafluorophthalonitrile
is subjected to a nucleophilic substitution under basic conditions,
positions 4 and 5 (that correspond to the peripheral sites on the Pc
after condensation) are substituted first.4 In the case of the
hexadecafluorophthalocyanines, the non-peripheral positions ap-
pear to be substituted first. This fact was inferred from the
1
observation of the H NMR and UV-Vis spectra of 3c in which
twelve fluorine atoms have been substituted by neopentoxy groups.
The NMR spectrum shows the singlets expected for the alkoxy
–OCH2 protons at 4.85 ppm for the non-peripheral and at 4.30 ppm
for the peripheral neopentoxy groups. These assignments are made
based on some previous NMR studies of hexadeca- and octaneo-
pentoxy phthalocyanines.10 The integral ratio of 2 : 1 for non-
peripheral versus peripheral protons supports the idea of having two
substituents on the non-peripheral positions and only one sub-
stituent on a peripheral site of each benzo ring of the Pc product. A
comparison of the Q-band absorptions in the UV-Vis spectra of
different polyneopentoxyphthalocyanine derivatives and that of the
tetrafluorododecaneopentoxyphthalocyanine (3c) reported here
seems to support the idea of the non-peripheral substitution
occurring first. The lmax for the latter lies at around 750–752 nm
just between the corresponding maxima for a peripheral octaneo-
pentoxyphthalocyanine (lmax = 672 nm) or a non-peripheral
octaneopentoxy phthalocyanine (lmax = 748 nm) and that of a
hexadecaneopentoxy derivative (lmax = 758 nm).10
Fig. 1 MALDI of 3b, having 7–10 morpholino groups.
Notes and references
‡ Synthesis of tetrafluorododecaneopentoxyphthalocyanine zinc is de-
scribed below. In a 100 mL Schlenk type flask fitted with a condenser, 40
mL of diglyme were placed under an argon atmosphere. Then 811 mg (9.2
mmol) of neopentyl alcohol were introduced. When all alcohol had
dissolved, 4.3 mL of 1.6 M n-BuLi in hexane were added. To this 20 mg
(0.023 mmol) of F16ZnPc were added and heated to 110–130 °C. After 8 h
the crude product was isolated by precipitation into water and subsequent
neutralization of the aqueous suspension. The final product was obtained
after chromatographic purification using flash silica-gel and a mixture of
toluene–ethyl acetate 20 : 1 as eluent to give 3c in 53% yield based on a
dodecasubstituted product; MALDI-MS for C92H132F4N8O12Zn (m/z
intensity, %) (M+ 1682.0, 100); for C87H121F5N8O11Zn (M+ 1614.9, 37).
Fortunately, the distribution of polysubstituted compounds
obtained after completion of the reaction is narrow‡. It is important
to mention here that for certain technological applications where
the solubility is important, the latter fact is beneficial. It is well
known that a mixture of different Pc compounds of similar structure
is more soluble than a pure Pc material, due to disruption of
aggregation phenomena.
MALDI analysis of all the products obtained shows that a
mixture of at least three polysubstituted products is obtained after
the reaction is completed (Fig. 1, for MALDI of 3b). Most
importantly, MALDI-TOF analysis has proven to be indispensable
in following the extent of the substitution reactions. The degree of
substitution depends markedly on the steric effect of the nucleo-
phile as well as on the nucleophilicity, the temperature and the time
required to complete the reaction. For nucleophiles with a low steric
effect or high nucleophilic capabilities, the maximum degree of
substitution is 16 (2CN and 2S(CH2)7CH3) in 6% and 41% yields
respectively.
1 (a) C. C. Leznoff and A. B. P. Lever (Eds), Phthalocyanines: Properties
and Applications, VCH, New York, Vol. 1–4; 1989–1996; (b) N. B.
McKeown, Phthalocyanine Materials: Synthesis, Structure and Func-
tion, Cambridge University Press, Cambridge, 1998.
2 (a) A. B. P. Lever, Adv. Inorg. Chem. Radiochem., 1965, 7, 27; (b) F. M.
Moser and A. L. Thomas, The Phthalocyanines, Vols. 1 & 2, CRC
Press, Boca Raton, FL, 1983.
3 J. L. Sosa-Sanchez, A. Galindo, D. Gnecco, S. Bernès, G. R. Fern, J.
Silver, A. Sosa-Sanchez and R. G. Enriquez, J. Porphyrins Phthalocya-
nines, 2002, 6, 198.
4 (a) N. Bhardwaj, PhD Thesis, York University, Toronto, Canada, 2001;
(b) J. M. Birchall, R. N. Haszeldine and J. O. Morley, J. Chem. Soc. (C),
1970, 456.
5 J. W. Rathke, M. J. Chen and C. M. Fendrick, US Patent No. 4,001,695
B2, Nov. 4, 1997.
6 (a) W. Eberhardt and M. Hanack, Synthesis, 1997, 95; (b) M. J. Cook,
A. J. Dunn, S. D. Howe, A. J. Thomson and K. J. Harrison, J. Chem.
Soc., Perkin Trans. 1, 1988, 2453.
7 (a) P. J. Duggan and P. F. Gordon, Eur. Pat. Appl., EP 155780, 1985; (b)
S. J. Reynolds and P. Gregory, Eur. Pat. Appl., EP 787732, 1997.
8 H. Bader, A. Hansen and F. J. McCarty, J. Org. Chem., 1966, 31,
2310.
9 A. B. P. Lever, Inorg. Chem., 1990, 29, 1271.
10 N. Bhardwaj, J. Andraos and C. C. Leznoff, Can. J. Chem., 2002, 80,
141.
In summary, we have developed a more direct synthetic route to
polysubstituted Pc materials of enhanced solubility using as starting
material a commercially available pre-formed Pc precursor.
Multisubstituted phthalocyanines can be tailor-made, having the
appropriate solubility, electrochemical, photochemical and medical
parameters necessary for a wide variety of applications.
C h e m . C o m m u n . , 2 0 0 4 , 3 3 8 – 3 3 9
339