Phthalocyanines bearing bulky cycloalkylmethyl substituents on non-peripheral sites

Article abstract of DOI:10.1016/j.tetlet.2009.07.016

Octasubstituted phthalocyanines bearing bulky (cyclopentyl)methyl- and (cyclohexyl)methyl-substituents in non-peripheral positions are prepared and characterised. The synthesis of the precursor phthalonitriles is achieved through nickel-catalysed cross-co

Full text of DOI:10.1016/j.tetlet.2009.07.016

Tetrahedron Letters 50 (2009) 5254–5256
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Tetrahedron Letters
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Phthalocyanines bearing bulky cycloalkylmethyl substituents
on non-peripheral sites
*
*
Andrew N. Cammidge , Chiung-Hui Tseng, Isabelle Chambrier, David L. Hughes, Michael J. Cook
School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Octasubstituted phthalocyanines bearing bulky (cyclopentyl)methyl- and (cyclohexyl)methyl-substitu-
ents in non-peripheral positions are prepared and characterised. The synthesis of the precursor phthalo-
nitriles is achieved through nickel-catalysed cross-coupling employing alkylzinc reagents. In the case of
the (cyclopentyl)methyl derivative the formal precursor is 5-hexenyl bromide which yields the cyclised
material exclusively on formation of the zinc reagent and subsequent cross-coupling.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 21 May 2009
Revised 23 June 2009
Accepted 3 July 2009
Available online 9 July 2009
Keywords:
Phthalocyanines
Cyclisation
Cross-coupling
Zinc reagents
Phthalocyanines are important molecular materials because of
the potential for such molecules to form the functional component
of optoelectronic devices.1,2 Their use in such applications typically
requires a combination of molecular (optical absorption/band gap,
redox, etc.) and bulk (solubility, processability, self-assembly,
mesophase formation, etc.) properties. For this reason, a large
number of phthalocyanine derivatives have been prepared. Such
modifications can focus on a combination of variation of the (or-
ganic) core structure (e.g. introduction of substituents to change
absorption and/or solubility properties) and the central metal ion
(more than 70 elements can be introduced) Figure 1.
One drawback to using phthalocyanines in cheap, mass produc-
tion devices is the difficulty in applying them through conventional
solution phase processes such as inkjet or screen printing. Simple
phthalocyanines have poor solubility and tend to be applied
through high-vacuum evaporation techniques. The solubility issue
has been overcome through preparation of substituted derivatives
and high solubilities can be achieved.3 We have paid particular
attention to phthalocyanines substituted in the so-called non-
peripheral positions4 and introduction of eight alkyl groups ren-
ders the phthalocyanines, and their metallated derivatives, freely
soluble in most organic solvents. However, at moderate-high con-
centrations the macrocycles self-assemble into higher aggregates.5
A potential strategy to overcome this (face-to-face) aggregation is
to increase the steric bulk of the substituent close to the phthalo-
cyanine core. Such perturbation also has the potential to distort the
phthalocyanine nucleus from planarity and induce useful spectral
changes.6 In this Letter we report two such derivatives where
(cycloalkyl)methyl substituents are introduced onto the non-
peripheral sites of the phthalocyanine core.
Our two target molecules are shown in Figure 2 and bear,
respectively, eight (cyclopentyl)methyl- and (cyclohexyl)methyl
substituents. As with most phthalocyanine syntheses the main
challenge rests with the preparation of appropriate phthalonitrile
precursors. 3,6-Dialkylphthalonitriles are prepared routinely in
our laboratories and a number of synthetic routes are available.7
Our preferred route (Scheme 1) employs Negishi coupling between
phthalonitrile ditriflate 3 and an alkylzinc halide, and we reasoned
that this procedure could be modified to achieve the synthesis of
(cyclohexyl)methyl-derivative 1.
(Cyclohexyl)methyl bromide is readily available but, in our
hands, its conversion into the corresponding alkylzinc reagent
(using activated zinc dust) proved inefficient and capricious. Con-
version into the corresponding iodide (Finkelstein reaction using
sodium iodide) avoided this problem and permitted smooth forma-
peripheral
sites
N
N
N
N
N
M
N
N
N
non-peripheral
sites
>70 elements
* Corresponding authors. Tel./fax: +44 (0)1603 592011.
E-mail address: a.cammidge@uea.ac.uk (A.N. Cammidge).
Figure 1. Phthalocyanine and simple sites for modification.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.016

A. N. Cammidge et al. / Tetrahedron Letters 50 (2009) 5254–5256
5255
ZnX
ZnX
X = Br
Zn*/THF, 0 ºC
X
71%
-
20%
N
N
N
N
N
N
N
N
X = I
HN
NH
Zn/DMF, 45 ºC
>80%
HN
NH
N
N
N
N
Scheme 3. Reaction of 5-hexenyl halides with zinc.
"
Br
"
ZnBr
2
1
Figure 2. Target phthalocyanines.
Ni(0)
40%
5
CH3
CH3
R
R
OTf
R
"
OTf
R
R
R
"
N
N
ZnBr
CN
CN
N
CN
CN
CN
CN
CN
CN
RZnX
Ni(0)
Li/C5H11OH
reflux
HN
NH
N
Ni(0)
45%
N
N
R
OTf
3
OTf
3
R
R
R
6
Scheme 1. Synthesis of non-peripherally substituted octaalkyl phthalocyanines.
Scheme 4. Synthesis of 3,6-bis[(cyclopentyl)methyl]phthalonitrile 6 from com-
mercial ‘5-hexenylzinc bromide’.
tion of (cyclohexyl)methylzinc iodide. The zinc reagent coupled
smoothly with ditriflate 3, despite its steric demand, to give the
dialkylphthalonitrile 48 (Scheme 2).
The phthalonitriles were cyclised to the corresponding phthalo-
cyanines using the standard conditions of lithium/refluxing penta-
nol (Scheme 5). Work-up with acetic acid afforded the metal-free
phthalocyanines which were purified by column chromatography.8
Isolated yields of pure material were consistently around 20%, and
typical for such phthalocyanine syntheses in our experience and
independent of scale, indicating that the steric demand had only
limited impact on the cyclisation reaction efficiency. UV–vis spec-
tra showed no evidence of broadening due to aggregation but were
Synthesis of (cyclopentyl)methyl derivative 6 by a similar route
was less straightforward because the corresponding iodide/bro-
mide was not readily available. However, a survey of the literature
revealed that formation of the zinc reagent from 5-hexenyl iodide/
bromide leads to ring closure to form varying proportions of the re-
quired (cyclopentyl)methylzinc halide. Reports are, however,
inconsistent. In the case of 5-hexenyl bromide (activated zinc,
THF) Rieke9 reports cyclisation of only ca. 20% and suggests that
the cyclisation occurs during formation of the zinc reagent. In con-
trast, Marek and Normant10 reported exclusive cyclisation when
the zinc reagent was prepared from 5-hexenyl iodide using zinc
in DMF at 45 °C (Scheme 3).
For our synthesis, where two couplings were required, exclusive
formation of (cyclopentyl)methylzinc halide was clearly required
to prevent formation of a complex mixture of products. A model
coupling reaction was therefore performed between 4-bromotolu-
ene and commercial11 5-hexenylzinc bromide under the conditions
employed in our typical phthalonitrile syntheses (Scheme 4).
Somewhat surprisingly, analysis of the crude product revealed that
the only cross-coupled product was the (cyclopentyl)methyl deriv-
ative 5 (it shows a distinctive doublet at d 2.60). Use of the same
commercial reagent led therefore to smooth formation of 3,6-
bis(cyclopentyl)methylphthalonitrile 68 without the need for fur-
ther refinement of reaction conditions or protocol.
N
N
N
N
CN
CN
Li/C5H11OH
HN
NH
reflux
then AcOH
N
N
20%
4
λmax 740 nm
1
Br
N
N
N
N
CN
CN
Li/C5H11OH
HN
NH
OTf
reflux
then AcOH
19%
N
N
CN
CN
CN
CN
NaI
I
6
ZnI
OTf
3
Zn*/BrCH2CH2Br
TMSCl/THF
Ni(0)
41%
4
λmax 735 nm
2
Scheme 2. Synthesis of 3,6-bis[(cyclohexyl)methyl]phthalonitrile 4.
Scheme 5. Synthesis of phthalocyanines 1 and 2.

5256
A. N. Cammidge et al. / Tetrahedron Letters 50 (2009) 5254–5256
References and notes
1. McKeown, N. B. Phthalocyanine Materials: Synthesis, Structure and Function;
CUP: Cambridge, 1998.
2. (a) de la Torre, G.; Claessens, C. G.; Torres, T. Chem. Commun. 2007, 2000–2015;
(b) Eichhorn, H. J. Porphyrins Phthalocyanines 2000, 4, 88–102.
3. (a) Pawlowski, G.; Hanack, M. Synthesis 1980, 287–289; (b) Duro, J. A.; Torres, T.
Chem. Ber. 1993, 126, 269–271; (c) Hanack, M.; Knecht, S.; Witke, E.; Haisch, P.
Synth. Metals 1993, 55, 873–878; (d) Cook, M. J. Mater. Sci. 1994, 5, 117–128; (e)
Chen, Y.; Hanack, M.; Blau, W.; Dini, D.; Liu, Y.; Lin, Y.; Bai, J. J. Mater. Sci 2006,
41, 2169–2185.
4. (a) Cook, M. J.; Daniel, M. F.; Harrison, K. J.; McKeown, N. B.; Thomson, A. J.
Chem. Commun. 1987, 1086–1088; (b) Cammidge, A. N.; Cook, M. J.; Harrison, K.
J.; McKeown, N. B. J. Chem. Soc., Perkin Trans. 1 1991, 3053–3058; (c) Burnham,
P.; Cook, M. J.; Gerrard, L. A.; Heeney, M. J.; Hughes, D. L. Chem. Commun. 2003,
2064–2065.
5. Snow, A. W. In: Porphyrin Handbook, Kadish, K. M.; Smith, K. M.; Guilard, R.,
Eds.; Academic Press: Elsevier Science USA, 2003; Vol. 17, pp. 129–176.
6. (a) Chambrier, I.; Cook, M. J.; Wood, P. T. Chem. Commun. 2000, 2133–2134; (b)
Kobayashi, N.; Fukuda, T.; Ueno, K.; Ogino, H. J. Am. Chem. Soc 2001, 123,
10740–10741; (c) Fukuda, T.; Homma, S.; Kobayashi, N. Chem. Eur. J. 2005, 11,
5205–5216.
7. (a) McKeown, N. B.; Chambrier, I.; Cook, M. J. J. Chem. Soc., Perkin Trans. 1 1990,
1169–1177; b Cook, M. J.; Henney, M. J. WO0142968 2002; Chem. Abstr. 135,
55020.; (c) Al-Raqa, S. J. Porphyrins Phthalocyanines 2006, 10, 55–62.
8. Synthesis of phthalonitrile 6. Bis(triphenylphosphine)nickel dichloride (0.154 g,
10 mol%) and triphenylphosphine (0.124 g, 20 mol%) were dissolved in dry THF
(10 ml) under argon. n-Butyllithium (0.2 ml, 20 mol%, 2.5 M in hexane) was
added to afford a blood-red solution. 3,6-Bis(trifluoromethanesulfonyloxy)-
phthalonitrile (1 g, 2.36 mmol) and lithium chloride (0.3 g, 7.1 mmol) were
added at once to the reaction mixture under a fast stream of argon. The resulting
brown solution was cooled to À78 °C. 5-Hexenylzinc bromide in THF
(7.58 mmol, 15.15 ml of a 0.5 M solution) was added dropwise over 15 min.
The solution was then left to warm to rt and stirring was continued overnight. A
5% aq solution of HCl (20 ml) was carefully added and the mixture was extracted
with ethyl acetate (2 Â 30 ml). The combined organic layers were successively
washed with a 5% aq solution of HCl (20 ml), a 5% aq solution of NaOH (20 ml) and
brine (20 ml), then dried (MgSO4), filtered and the solvents removed under
reduced pressure. The resulting brown oily residue was purified by column
chromatography on silica gel [eluent: petroleum ether (bp 40–60 °C)-
dichloromethane, 1:1] to give 6 (0.31 g, 45%). dH (400 MHz, acetone-d6) 7.74
(2H, s), 2.90 (4H, d, J 7.6), 2.26–2.11 (m, 2H), 1.73–1.64 (8H, m), 1.58–1.51 (4H,
m), 1.30–1.24 (m, 4H); dC (100 MHz, acetone-d6) 145.8, 134.5, 115.9, 115.7, 41.6,
39.8, 32.1, 24.6; mp 119–121 °C; Rf 0.5 [1:1 petroleum ether (bp 40–60 °C)/
dichloromethane]; HRMS (ES+) calcd 310.2278, obtained 310.2280 ([M+NH4]+,
100%); mmax (Nujol) 2221 (CN) cmÀ1. Phthalonitrile 4 was similarly prepared
(41%). dH (400 MHz, CDCl3) 7.41 (2H, s), 2.74 (4H, d, J 6.8), 1.73–1.61 (m, 12H),
1.23–1.15 (6H, m), 1.09–1.03 (4H, m); dC (100 MHz, CDCl3) 145.0, 134.1, 116.3,
115.7, 42.4, 39.7, 33.1, 26.4, 26.3; mp 125–126 °C; 0.41 [1:1 petroleum ether (bp
40–60 °C)/dichloromethane]; HRMS (ES+) calcd 338.2591, obtained 338.2592
Figure 3. X-ray crystal structure of 2.
red-shifted compared to straight-chain octaalkylphthalocyanines
(kmax 2 = 735 nm, 1 = 740 nm). Such spectral shifts are characteris-
tic of twisting in the phthalocyanine core.6 Crystals suitable for X-
ray structure determination were obtained for 2 (Fig. 3) and devi-
ation from planarity (a twist of ca. 12°) was clearly observed in the
solid state.12
In conclusion, we have reported the synthesis of non-periph-
erally substituted phthalocyanines bearing eight (cyclopentyl)-
methyl- and (cyclohexyl)methyl-substituents. The phthalonitrile
precursors were prepared from the corresponding zinc reagent
although, in the case of (cyclopentyl)methylzinc bromide, the
reagent was formally accessed from 5-cyclohexenyl bromide via
cyclisation. The phthalocyanines show red-shifted spectra indi-
cating that the steric demand of the substituents causes a twist
in the phthalocyanine core. The X-ray crystal structure of 2
clearly shows this twist in the solid state. UV–vis and 1H NMR
spectra show sharp peaks characteristic of non-aggregated
species.
([M+NH4]+, 100%);
m
max (Nujol) 2218 (CN) cmÀ1. Synthesis of phthalocyanine 2.
(100 mg, 0.342 mmol) was
3,6-Bis(cyclopentylmethyl)phthalonitrile
6
dissolved in hot pentan-1-ol (5 ml). Lithium metal (9.49 mg, 4 equiv) was
added in portions to the refluxing mixture. The solution was refluxed for 6 h. The
resulting green mixture was allowed to cool slightly and acetic acid (5 ml) was
added. This was stirred for 30 min until rt was achieved. Excess methanol (15 ml)
was added subsequently and the flask was placed in a fridge overnight. The
resulting green precipitate was filtered and washed with methanol. The solid
was purified by column chromatography over silica gel [eluent: petroleum ether
(bp 40–60 °C)]. The main green fraction afforded 2 which was recrystallised from
THF–methanol (19 mg, 19%). dH (400 MHz, C6D6) 7.79 (8H, s), 4.67 (16H, d, J 7.2),
2.86–2.65 (m, 8H), 1.90–1.30 (64H, m), À0.15 (2H, br s); mp > 300 °C; MALDI-MS
isotopic cluster at m/z 1171.8 [M+, 100%]; kmax (THF, log /MÀ1 cmÀ1) 735 (5.3),
e
706 (5.2), 360 nm; m
max (neat) 3301 (NH) cmÀ1. Phthalocyanine 1 was similarly
Acknowledgement
prepared (20% on reaction scales 100 mg and 370 mg). dH (400 MHz, C6D6) 7.82
(8H, s), 4.68 (16H, d, J 7.2), 2.32–2.15 (m, 8H), 2.10–1.09 (80H, m), À0.09 (2H, br
s); mp > 300 °C; MALDI-MS isotopic cluster at m/z 1283.9 [M+, 100%]; kmax
The authors are grateful for the support received from the
EPSRC Mass Spectrometry Service (Swansea).
(toluene, log
e
/MÀ1 cmÀ1) 740 (5.4), 709 (5.4), 363 nm; mmax (neat) 3297 (NH)
cmÀ1
.
9. Guijarro, A.; Rosenberg, D. A.; Rieke, R. D. J. Am. Chem. Soc. 1999, 121, 4155–4167.
10. Meyer, C.; Marek, I.; Courtenmanche, G.; Normant, J.-F. Synlett 1993, 266–268.
11. Sigma–Aldrich cat. # 498734.
Supplementary data
12. Crystallographic data have been deposited at the Cambridge Crystallographic
Data Centre, CCDC 723645 and can be obtained free of charge via http://
www.ccdc.cam.ac.uk/deposit.
Supplementary data (experimental and X-ray crystallography
details) associated with this article can be found, in the online ver-
sion, at doi:10.1016/j.tetlet.2009.07.016.