NIR chromophores from small acetylenic building blocks: A Diels-Alder approach to octaalkynylphthalocyanines

Article abstract of DOI:10.1039/b006114j

Two new routes to cross-conjugated 3,4-dimethylenehexa-1,5-diynes, both starting from dialkynyl 1,2-diones, have been devised. Whereas triisopropylsilyl-protected diketones could be diolefinated in a bis-Wittig reaction with methylenetriphenylphosphorane, their aryl-terminated congeners had to be subjected to the conditions of the Peterson olefination (trimethylsilylmethylmagnesium chloride and subsequent dehydration of the resulting diol with thionyl chloride). The reactivity of the diethynylbutadienes towards standard dienophiles was found to be low and alternative thermal reactions compete with [4 + 2] cycloadditions. However, dicyanoacetylene was shown to be an effective cycloaddition partner leading, after aromatisation, to the corresponding dicyanodiethyriylbenzenes. These were cyclotetramerised with magnesium butanolate in butanol to furnish octaalkynylphthalocyanines, thereby completing a concise, three-step synthesis of these NIR chromophores of relevance to photodynamic forms of therapy. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b006114j

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NIR chromophores from small acetylenic building blocks:
a Diels–Alder approach to octaalkynylphthalocyanines
Rüdiger Faust* and Frieder Mitzel
1
University College London, Department of Chemistry, 20 Gordon Street, London,
UK WC1H 0AJ. E-mail: r.faust@ucl.ac.uk
Received (in Cambridge, UK) 28th July 2000, Accepted 7th September 2000
First published as an Advance Article on the web 27th October 2000
Two new routes to cross-conjugated 3,4-dimethylenehexa-1,5-diynes, both starting from dialkynyl 1,2-diones,
have been devised. Whereas triisopropylsilyl-protected diketones could be diolefinated in a bis-Wittig reaction
with methylenetriphenylphosphorane, their aryl-terminated congeners had to be subjected to the conditions of the
Peterson olefination (trimethylsilylmethylmagnesium chloride and subsequent dehydration of the resulting diol with
thionyl chloride). The reactivity of the diethynylbutadienes towards standard dienophiles was found to be low and
alternative thermal reactions compete with [4 ϩ 2] cycloadditions. However, dicyanoacetylene was shown to be an
effective cycloaddition partner leading, after aromatisation, to the corresponding dicyanodiethynylbenzenes. These
were cyclotetramerised with magnesium butanolate in butanol to furnish octaalkynylphthalocyanines, thereby
completing a concise, three-step synthesis of these NIR chromophores of relevance to photodynamic forms of
therapy.
Introduction
Organic chromophores with sizable absorptions and/or emis-
sions at the far red end of the visible spectrum or beyond con-
tinue to play important roles as functional components in areas
as diverse as laser printing, optical displays and a range of
medicinal applications.1,2 An intriguing example of the poten-
tial of near infrared (NIR) chromophores is the utilisation of
selected members of this class of compounds as photosensitiser
in the photodynamic treatment of various forms of cancers
(photodynamic tumour therapy, PDT).3–7 Some of the key
requirements for efficient PDT agents are their accessibility
by external light when embedded in organic tissue and their
solubility in cellular fluids. In general, appropriately substi-
tuted nitrogen-containing macrocycles based on porphyrin8 or
phthalocyanine9 backbones are invoked to address these points.
We are currently developing synthetic strategies for the rapid
assembly of NIR chromophores from small acetylenic building
blocks. In addition to the advantageous brevity and flexibility
of such a modular approach, the resulting chromophores will
benefit from peripheral acetylene substitution in their optical
properties (bathochromically and hyperchromically shifted
absorptions relative to non-acetylenic analogues) as well as in
terms of their solubility, which is governed by functionalities at
the acetylene termini. Acetylenic NIR chromophores should
therefore be interesting candidates to be explored for their
suitability as PDT agents.
We have previously devised two complementary routes to two
such acetylenic building blocks, namely to the hexa-1,5-diyne-
3,4-diones 110,11 and to the corresponding dimiines 212 and have
3
13 and the latter into the highly absorbent nickel(0) dialkynyl-
diazabutadiene complex 4.14 In an effort to further extend this
concept, we have now targeted the hydrocarbon π-system 3,4-
dimethylenehexa-1,5-diyne 515 as a third acetylenic building
block in this series. The buta-1,3-diene substructure of 5 can be
envisioned to participate in [4 ϩ 2] cycloaddition reactions and
can therefore aid in the construction of macrocyclic (NIR)
chromophores with peripheral acetylene substitution. For
example, the Diels–Alder reaction of 5 with dicyanoacetylene
will furnish, after aromatization, the corresponding dicyano-
benzenes, from which phthalocyanine derivatives like 6 are
readily available. We disclose herein two new syntheses for
demonstrated the feasibility of our modular approach to NIR
chromophores by converting the former building block into
phthalocyanine-related octaalkynyltetrapyrazinoporphyrazines
3746
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b006114j

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previously inaccessible derivatives of 5 and their transform-
ation to octaalkynylphthalocyanines 6 by a novel Diels–Alder
strategy with dicyanoacetylene.
other hand, did react at Ϫ78 ЊC in THF with the phosphorus
ylide to give the desired product 5a, but the yield of only 19%
after chromatographic purification is in the same disappoint-
ingly low region as that reported for the analogous conversion
of benzil (Scheme 1).
Scheme 1
While the successful preparation of 5a is encouraging and
gives access to a previously inaccessible derivative of this class
of compounds, the bis-Wittig methodology is clearly not suit-
able for the synthesis of aryl-terminated dimethylenehexa-
diynes. We have therefore explored the Peterson olefination
reaction18 as an alternative route. Thus, treating the acetylenic
diones 1a–c with two equivalents of trimethylsilylmethyl-
magnesium chloride in refluxing Et2O furnished the bis-ethynyl
diols 6a–c in 53–81% yield (Scheme 2). Surprisingly, all
Results and discussion
The first members of the family of 3,4-dimethylenehexa-1,5-
diynes 5 have previously been prepared by Hopf et al.15 After
some ill-fated attempts, it was found that a nickel-mediated
coupling of selected magnesium acetylides to 2,3-dichlorobuta-
1,3-diene furnished the desired target molecules. However, the
procedure was found to be suitable only for the preparation of
derivatives of 5 bearing simple alkyl or trimethylsilyl substi-
tuents at the acetylene termini. These substituents leave the
reactive cross-conjugated π-system of 5 relatively unprotected,
rendering the compounds vulnerable to polymerisation at room
temperature. The authors specifically point out that more
versatile aryl or more protective triisopropylsilyl substituents
could not be incorporated into the backbone of 5 along this
route, which instead leads to the corresponding butadiynes
via oxidative acetylene coupling.15 Since aryl substituents are
particularly well-suited to modify the solubility of acetylenic
chromophores we set out to explore synthetic alternatives to
substituted dimethylenehexadiynes.
A conceptually different strategy to obtain the 3,4-dimethyl-
enehexa-1,5-diynes could conveniently start from the acetylenic
1,2-diones 1 which we have recently made available in a single
step by the copper-mediated alkynylation of oxalyl chloride11
and which, in principle, should be amenable to diolefination.
However, from the outset a transformation of this kind was
deemed to be difficult in the light of the problems encountered
in attempts to diolefinate simple aliphatic or aromatic
diketones.16,17 Benzil, for example, a non-acetylenic relative of
1b and 1c, could only be converted to 2,3-diphenylbuta-1,3-
diene in 15% yield by the reaction with methylenetriphenyl-
phosphorane.16 It is therefore not surprising that our attempts
to obtain hydrocarbons 5 from acetylenic diones using a stan-
dard bis-Wittig protocol were blessed with mixed success.
The aryl-terminated alkynyl diketones 1b and 1c, for example,
decomposed upon treatment with methylenetriphenylphos-
phorane in THF, and although all the starting material was
consumed, no product could be isolated. The more robust
triisopropylsilyl-protected acetylenic 1,2-diketone 1a, on the
Scheme 2
attempts to generate the CC double bonds by the formal two-
fold elimination of hydroxymethylsilanes from the isolated diols
6a–c using potassium hydride,18 sulfuric acid,18 or butyllithium
followed by methylsulfonyl chloride19 failed. However, and
most gratifyingly, the CC double bonds of 5 could be estab-
lished in a one-pot procedure by treating the alkoxide inter-
mediates formed in the preparation of the diols 6a–c with thio-
nyl chloride.18 The desired aryl dimethylenehexadiynes 5b and
5c, were isolated in 20% yield. The mesylate-assisted elimin-
ation to form 5a, on the other hand, was sluggish leaving a pale
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751
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yellow oil after column chromatography that, in addition to 5a,
contained significant amounts of unidentified by-products. It
therefore appears that the two methods presented here for the
preparation of dimethylenehexadiynes are complementary to
one another, with the Wittig reaction suitable for the triiso-
propylsilyl-protected derivative, and the Peterson olefination
for aryl-terminated representatives.
Compounds 5 were obtained either as colourless solids (5a,
5c) or as a pale yellow oil (5b). All the derivatives rapidly turn
yellow upon exposure to air, with 5a being the most stable and
5b being the most sensitive compound. The modest yields in the
above transformations, while not at all unexpected in the light
of previous work and the marked sensitivity of the material, are
perhaps partially compensated by the short overall synthetic
sequence and the ready availability of the starting materials.
Numerous efforts to further improve the outcome of the diole-
fination of the acetylenic 1,2-diones 1 failed. In addition to
broad variations of the reaction parameters for the above pro-
cedures, none of the titanium-based olefination protocols using
either the Petasis reagent Cp Ti᎐CH (prepared in situ from
᎐
2
2
Cp2TiMe2 in PhMe at 60 ЊC)20 or a heterogeneous mixture of
21,22
Scheme 3
TiCl4–Zn–CH2Br2 at room temperature in CH2Cl2
proved
to be successful.
converted into octaalkynylphthalocyanines, although with dif-
ferent peripheral substituents.27,28 The cyclotetramerisation of
9a and 9b to the corresponding phthalocyanine derivatives 10a
and 10b proceeded smoothly by refluxing the former with mag-
nesium butanolate in butanol and furnished the macrocycles as
dark green solids in yields of 38 and 17%, respectively (Scheme
4). Noteworthy is the ease with which the two phthalocyanines
With the new 3,4-dimethylenehexa-1,5-diynes in hand, we
explored their behaviour in [4 ϩ 2] cycloaddition reactions.
Much to our surprise and apparently unlike the aliphatic
analogues previously prepared by Hopf et al.,15 compounds
5a–c turned out to be rather unreactive diene components in
Diels–Alder reactions. Unfortunately, the reluctance of these
compounds to take part in cycloadditions is accompanied by
a marked thermal instability and by the formation of dimeric
cyclooctadiene side products via radical routes15 so that the use
of more forcing reaction conditions is not a viable option. For
example, 5c did not react with three equivalents of dimethyl
maleate in CDCl3 at room temperature for 18 hours. When the
mixture was heated to 60 ЊC 5c decomposed within 3 hours and
1
no cycloaddition product was detectable by H NMR spec-
troscopy. Likewise, no cyclisation was observed with 5a in the
presence of either five equivalents of dimethyl acetylenedicarb-
oxylate (toluene, reflux) or 15 equivalents of dimethyl maleate
(toluene, 90 ЊC, 8 h). This behaviour is in marked contrast to the
reported reactivity of trimethylsilyl-protected 3,4-dimethylene-
hexa-1,5-diene15 in which case the reaction with identical dieno-
philes furnished the corresponding cyclohexene adducts in
yields exceeding 40%. We suspect that the more bulky substitu-
ents at the termini of the acetylenes in 5a–c render the adoption
of a planar s-cis conformation in these compounds more
difficult, thereby favouring alternative thermal pathways and
polymerisation. However, by exposing 5a in refluxing THF for
8 h or 5b in THF for 62 h at room temperature to excess
dicyanoacetylene 7,23,24 touted as one of the most reactive acet-
ylenic dienophiles, we were able to isolate the corresponding
cycloaddition products (Scheme 3). Again, dimerisation and
polymerisation were clearly observed in both cases, despite the
addition of traces of hydroquinone. The yields of isolated
products are only moderate, but an increase of reaction tem-
perature or time, or the use of Lewis acids (e.g. BCl3), or
conducting the reaction in 5 M ethereal lithium perchlorate
solution25 had no beneficial influence on the outcome of the
experiments. Although the isolation of the 1,2-dicyano-4,5-
diethynylcyclohexadienes 8 is possible, they show a pronounced
tendency to aromatise in the presence of air and were best
directly converted to dicyanobenzenes 9a,b by treatment of the
crude product of the cycloaddition reaction with DDQ in
toluene.
Scheme 4
The successful cycloaddition of dimethylenehexadiynes and
dicyanoacetylene has opened up a new route to substituted
dicyanobenzenes which are well established precursors for
various metallated and metal-free phthalocyanine derivatives.26
Indeed, 1,2-dicyano-4,5-diethynylbenzenes have previously been
can be purified and handled. Owing to the bulkiness of the
substituted aryl and the triisopropylsilyl substituents, the
compounds show little tendency to aggregate and are quite
3748
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751

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ppm) as reference. Infrared spectra were recorded on Perkin
Elmer 1600 FT-IR and Shimadzu 8700 FT-IR spectrometers.
Mass spectra were obtained on a VG ZAB-SE (EI, FAB),
a Micromass Quattro-LC (APCI) or a Fisons VG TOF
Spectrometer (MALDI-TOF) using trans-indole-3-acrylic acid
as matrix. UV–Vis–NIR spectra were recorded on a Perkin-
Elmer Lambda 40. Melting points were determined on a
Reichert hotstage or with the help of an electrothermal melt-
ing point apparatus (open capillaries) and are uncorrected.
Elemental analyses were obtained on a Perkin-Elmer 2400
CHN analyser. Flash column chromatography was carried
out under positive pressure from a compressed air line using
Merck Kieselgel (230–400 mesh) unless otherwise indicated.
Analytical thin layer chromatography was performed using
precoated aluminium-backed plates (Merck Kieselgel 60
F254) and visualised by UV light, basic potassium per-
manganate solution or 50% sulfuric acid. Gel permeation
chromatography (GPC) was performed on a polystyrene
resin crosslinked with 1% divinylbenzene (Bio-beads 1-SX,
Bio-Rad), pre-swollen in THF. Reactions were carried out
under argon in oven-dried glassware. Solvents were purified
according to standard procedures29 and were freshly distilled
prior to use. The synthetic procedure for 1a has been previously
described,11 and those for the new derivatives 1b and 1c are
given below. 4-tert-Butylphenylacetylene30 has been obtained
from 4-tert-butylstyrene31 and 3,5-di-tert-butylphenylacetyl-
ene was prepared according to ref. 32. All other reagents
are available from commercial suppliers and were used as
received.
Fig. 1 UV–Vis–NIR spectrum of (a) 10a and (b) 10b in THF at room
temperature.
soluble in common nonpolar organic solvents, properties which
facilitate their purification by column and gel permeation
chromatography.
The most remarkable feature in the electronic absorption
spectra of the octaalkynylphthalocyanines (Fig. 1) is their high
intensity, long wavelength absorption at 713 (10a) and 723 nm
(10b), respectively. The slightly bathochromically shifted
absorptions of the latter indicate that fine-tuning of the spectral
properties of the octaalkynylphthalocyanines by peripheral
substituents is a valid possibility. Shape and intensity (ε =
372600 for 10a and ε = 421400 dm3 molϪ1 cmϪ1 for 10b) of
these so-called Q-bands are characteristic for non-aggregated
phthalocyanines. The bands are hyper- and bathochromically
shifted compared to those of the corresponding octaalkynyl-
tetrapyrazinoporphyrazines (e.g. λmax = 674 nm, ε = 314600 MϪ1
1,6-Bis(3,5-di-tert-butylphenyl)hexa-1,5-diyne-3,4-dione 1b
Compound 1b was prepared as for 1c (see below). The crude
product was filtered through a pad of silica (CH2Cl2) and
recrystallised from EtOAc yielding 1b (1.77g, 49%) as yellow
needles: mp 182 ЊC (from EtOAc, decomp.) (Found: C, 84.5; H,
8.9. C34H42O2 requires C, 84.6; H, 8.8%); λmax(CH2Cl2)/nm 253
l
Ϫ1 for the octaazaanalogue of 10a).13 Since penetration of light
through organic tissue increases with increasing wavelength,3
the bathochromically shifted absorptions of acetylenic
phthalocyanines renders them promising candidates for
PDT applications and work is currently in progress to identify
suitable prototypes.
(ε/dm3 molϪ1 cmϪ1 24600) and 344 (23900); νmax(CHCl3/cmϪ1
)
3012, 2971, 2187, 1663, 1226 and 1046; δH (400 MHz; CDCl3)
1.3 (36H, s, C(CH3)3), 7.5 (4H, d, J 1.8, aromatic CH), 7.6 (2H,
t, J 1.8, aromatic CH); δC (100.5 MHz; CDCl3) 31.2, 34.9, 85.4,
102.0, 118.2, 126.6, 128.2, 151.5, 173.0; m/z (EI, 70 eV) 482
(Mϩ, 2.5%), 241 (Mϩ/2, 100).
Conclusion
1,6-Bis(4-tert-butylphenyl)hexa-1,5-diyne-3,4-dione 1c
In this work we have provided a new route to octaalkynyl-
phthalocyanines, a class of compounds of significant interest
inter alia in the field of photodynamic cancer therapy. The
cornerstones of our approach are two new ways of preparing
previously inaccessible 3,4-dimethylenehexa-1,5-diynes from
dialkynyl 1,2-diones. The transformation of these buta-1,3-
dienes into octaalkynylphthalocyanines was effected by a
Diels–Alder [4 ϩ 2] cycloaddition of the former with dicyano-
acetylene, followed by aromatisation and cyclotetramerisation
of the resulting dicyanobenzenes. While the sensitivity and the
reactivity of the acetylenic dienes necessitate a compromise on
yields, the overall synthetic sequence to the target chromo-
phores is with three steps remarkably concise and does not
suffer from problems arising from the presence of regioisomeric
mixtures.
To a cooled (0 ЊC) solution of 4-tert-butylphenylacetylene (2.63
g, 16.6 mmol) in THF (20 ml) was added BuLi (10.4 ml of a 1.6
M solution in hexane, 16.6 mmol). The solution was stirred for
10 min and then transferred via cannula into a cooled (0 ЊC)
solution of CuBr (2.39 g, 16.6 mmol) and LiBr (2.89 g, 33.3
mmol) in THF (100 ml). The resulting yellow suspension was
stirred for 15 min at that temperature before a precooled (0 ЊC)
solution of oxalyl chloride (0.96 g, 7.6 mmol) in THF (20 ml)
was added dropwise. Stirring was continued for an additional
10 min and the reaction was hydrolysed by the addition of
saturated aqueous ammonium chloride (80 ml) and 1 M HCl
(20 ml). The layers were separated and the aqueous layer was
extracted with Et2O (100 ml). The combined organic layers were
dried over MgSO4 and the solvents were evaporated to leave
a brown oil. This was filtered through a pad of silica (Et2O)
furnishing the crude product as a brown solid. Recrystallisation
from EtOH yielded 1c (1.56g, 56%) as yellow needles: mp 142–
143 ЊC (from EtOH) (Found: C, 84.6; H, 7.0. C26H26O2 requires
C, 84.3; H, 7.0%); λmax(CH2Cl2)/nm 255 (ε/dm3 molϪ1 cmϪ1
20200) and 338 (19400); νmax(CHCl3/cmϪ1) 3031, 2972, 2190,
1664 and 1210; δH (400 MHz; CDCl3) 1.3 (18H, s, C(CH3)3),
7.5 (4H, d, J 8.5, aromatic CH), 7.6 (4H, d, J 8.5, aromatic CH);
δC (100.5 MHz; CDCl3) 31.0, 35.2, 86.2, 100.8, 116.1, 125.9,
133.8, 155.8, 172.7; m/z (EI, 70 eV) 370 (Mϩ, 0.4%), 185 (Mϩ/2,
100).
Experimental
1H NMR spectra were recorded in CDCl3 or THF–CDCl3 on
Bruker AMX400 and Bruker DRX500 spectrometers and are
reported as follows: chemical shift, δ (ppm) [number of protons,
multiplicity, coupling constant
J (Hz) and assignment].
Residual protic solvent CHCl3 (δH = 7.24 ppm) was used as the
internal reference. 13C NMR spectra were recorded on the same
spectrometers operating at frequencies of 100.5 MHz and 126
MHz, respectively, using the central signal of CDCl3 (δC = 77.0
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751
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1,6-Bis(triisopropylsilyl)-3,4-bis(trimethylsilylmethyl)hexa-1,5-
diyne-3,4-diol 6a
material had been consumed. The reaction was quenched by the
addition of saturated aqueous ammonium chloride solution (50
ml) and extracted with hexanes (50 ml). The layers were separ-
ated, the organic layer was dried (MgSO4) and the solvents were
evaporated in vacuo leaving a dark brown oil which was sub-
jected to flash chromatography (hexanes) yielding 5a (110 mg,
19%) as a white solid. The compound turns yellow upon
exposure to air: mp 50–52 ЊC (from hexanes) (Found: C, 74.8;
H, 11.2. C26H46Si2 requires C, 75.3; H, 11.2%); λmax(CH2Cl2)/nm
To a refluxing solution of diketone 1a11 (500 mg, 1.2 mmol) in
Et2O (10 ml) was added dropwise over 5 min Me3SiCH2MgCl
(2.6 ml of a 1.0 M solution in Et2O, 2.6 mmol). Heating under
reflux was continued for 1 h. The mixture was cooled to room
temperature and quenched by the addition of saturated aque-
ous ammonium chloride solution (25 ml). The layers were sep-
arated and the aqueous layer was extracted with Et2O (2 × 25
ml). The combined organic layers were dried (MgSO4) and the
solvent evaporated in vacuo to leave a pale yellow oil, which was
purified by flash chromatography (5% EtOAc in hexanes), yield-
ing diol 6a as a mixture of diastereomers. Diastereomer A:
(282 mg, 39%) pale yellow oil, diastereomer B (301 mg, 42%)
229 (ε/dm3 molϪ1 cmϪ1 15700) and 247 (19800); νmax(KBr/cmϪ1
)
2943, 2864, 2156, 1462, 1167, 993, 950, 907, 881 and 664;
δH (400 MHz; CDCl3) 1.1 (42H, s, Si(CH(CH3)2)3), 5.7 (2H, s,
CHaHb), 6.1 (2H, s, CHaHb); δC (100.5 MHz; CDCl3) 11.2, 18.6,
94.2, 103.2, 125.1, 129.0; m/z (EI, 70 eV) 414 (Mϩ, 13.4%), 371
(Mϩ Ϫ C3H7, 86.1), 329 (Mϩ Ϫ C6H13, 100).
white solid: mp 92–93 mp ЊC (from pentane); νmax(CHCl3/cmϪ1
)
3439, 2943, 2166, 1464, 1246, 997 and 847; δH (400 MHz;
CDCl3) diastereomer A: 0.1 (18H, s, Si(CH3)3), 1.1 (42H, s,
Si(CH(CH3)2)3), 1.1–1.3 (4H, br m, CH2), 2.5 (2H, s, OH); dia-
stereomer B: 0.1 (18H, s, Si(CH3)3), 1.1 (42H, s, Si(CH(CH3)2)3),
1.2 (2H, d, J 14.5, CHaHb), 1.4 (2H, d, J 14.5, CHaHb), 2.5 (2H,
s, OH); δC (100.5 MHz; CDCl3) diastereomer A: 0.2, 11.2,
18.7, 77.6, 87.0, 110.1 (the CH2 carbon was not observed);
diastereomer B: 0.2, 11.2, 18.6, 26.1 (br), 78.5, 87.1, 108.7; m/z
(FAB) 617.4018 (C32H66O2Si4Na requires 617.4038; m/z
(APCIϩ) 617.5 ([M ϩ Na]ϩ, 100%).
1,6-Bis(3,5-di-tert-butylphenyl)-3,4-dimethylenehexa-1,5-diyne
5b
To a refluxing solution of diketone 1b (800 mg, 1.66 mmol) in
Et2O (20 ml) was added dropwise over 5 min Me3SiCH2MgCl
(3.32 ml of a 1.0 M solution in Et2O, 3.32 mmol). Heating was
continued for 1 h. The reaction mixture was cooled to 0 ЊC and
thionyl chloride (0.24 ml, 3.32 mmol) was added via syringe.
After stirring at this temperature for 1 h the reaction was
quenched by the addition of saturated aqueous ammonium
chloride solution (40 ml) and extracted with Et2O (40 ml). The
organic extract was washed with water (40 ml) and brine (40
ml), dried (MgSO4) and the solvent was evaporated in vacuo to
leave a brown oil. This was subjected to flash chromatography
(10% CH2Cl2 in hexane) yielding compound 5b (300 mg, 38%)
as a yellowish oil which was prone to polymerisation upon
exposure to air and upon heating: λmax(CH2Cl2)/nm 260 (ε/dm3
molϪ1 cmϪ1 21600), 273 (22100), 288 (20200) and 332sh (7200);
νmax(CHCl3/cmϪ1) 3007, 2904, 2870, 2208, 1589, 1477, 1367,
1250, 1142, 907 and 877; δH (400 MHz; CDCl3) 1.3 (36H, s,
C(CH3)3), 5.9 (2H, s, CHaHb), 6.2 (2H, s, CHaHb), 7.37 (4H, d,
J 1.9, aromatic CH), 7.43 (2H, t, J 1.8, aromatic CH); δC (100.5
MHz; CDCl3) 31.3, 34.8, 84.7, 93.6, 121.8, 123.0, 124.3, 125.8,
129.0, 150.9; m/z (FAB) 479.3660 (MHϩ), C36H47 requires
479.3678; m/z (EI, 70 eV) 478 (Mϩ, 51.20%), 219 (100), 147
(100).
1,6-Bis(3,5-di-tert-butylphenyl)-3,4-bis(trimethylsilylmethyl)-
hexa-1,5-diyne-3,4-diol 6b
Diol 6b was prepared starting from 1b using the procedure
described for 6a. The crude brown oil obtained was purified by
flash chromatography (CH2Cl2–hexanes 1:1) yielding 6b (288
mg, 53%) as a white solid (only one diastereoisomer observed):
mp 138–141 ЊC (from hexanes) (Found: C, 76.5; H, 10.3.
C42H66O2Si2 requires C, 76.5; H, 10.1%); νmax(KBr/cmϪ1) 3523,
2964, 2193, 1591, 1246, 1032, 876 and 704; δH (400 MHz;
CDCl3) 0.2 (18H, s, Si(CH3)3), 1.3 (36H, s, C(CH3)3), 1.4 (2H, d,
J 14.5, CHaHb), 1.5 (2H, d, J 14.5, CHaHb), 2.7 (2H, s, OH), 7.3
(4H, d, J 1.8, aromatic CH), 7.4 (2H, t, J 1.8, aromatic CH);
δC (100.5 MHz; CDCl3) 0.2, 25.5 (br), 31.3, 34.7, 78.5, 87.2,
89.3, 121.6, 122.9, 125.8, 150.8; m/z (EI, 70 eV) 658 (Mϩ, 2.5%),
329 (Mϩ/2, 14.7), 239 (Mϩ/2 Ϫ Si(CH3)3OH, 100).
1,6-Bis(4-tert-butylphenyl)-3,4-dimethylenehexa-1,5-diyne 5c
3,4-Bis(trimethylsilylmethyl)-1,6-bis(4-tert-butylphenyl)hexa-
1,5-diyne-3,4-diol 6c
Diene 5c was prepared starting from 1c using the procedure
described for 5b. Removal of the solvents left a brown oil which
was filtered through a pad of silica (washed with 150 ml of
hexanes) to furnish a yellow solid. This was washed with a small
amount of hexanes to give pure 5c (113 mg, 19%) as a white
solid. The compound turns yellow upon exposure to air and
polymerizes upon heating above 130 ЊC. λmax(CH2Cl2)/nm 261
(ε/dm3 molϪ1 cmϪ1 66600), 276 (72300), 291 (62100) and 336
(3000); νmax(CHCl3/cmϪ1) 3011, 2965, 2210, 1504, 1364, 1268,
1104, 906 and 837; δH (400 MHz; CDCl3) 1.3 (18H, s,
C(CH3)3), 5.8 (2H, s, CHaHb), 6.2 (2H, s, CHaHb), 7.3 (4H, d,
J 8.4, aromatic CH), 7.4 (4H, d, J 8.4, aromatic CH); δC
(100.5 MHz; CDCl3) 31.1, 34.8, 85.2, 92.6, 119.8, 124.1,
125.4, 128.9, 131.3, 151.8; m/z (FAB) 367.2417 (MHϩ), C28H31
requires 367.2426; m/z (EI, 70 eV) 366 (Mϩ, 84.2%), 351
(Mϩ Ϫ CH3, 100).
Diol 6c was prepared starting from 1c using the procedure
described for 6a. The crude brown solid obtained was purified
by flash chromatography (15% EtOAc in hexanes) yielding 6c
(255 mg, 56%) as a white solid (only one diastereomer
observed): mp 172–175 ЊC (from Et2O–hexanes) (Found: C,
74.65; H, 9.2. C34H50O2Si2 requires C, 74.7; H, 9.2%); νmax
-
(CHCl3/cmϪ1) 3553, 3017, 2968, 2222, 1505, 1365, 1249, 1018
and 838; δH (400 MHz; CDCl3) 0.2 (18H, s, Si(CH3)3), 1.3 (18H,
s, C(CH3)3), 1.3 (2H, d, J 14.6, CHaHb), 1.4 (2H, d, J 14.4,
CHaHb), 2.6 (2H, s, OH), 7.3 (8H, m, aromatic CH); δC (100.5
MHz; CDCl3) 0.2, 25.3 (br), 31.1, 34.8, 78.3, 86.2, 89.9, 119.6,
125.3, 131.3, 151.7; m/z (EI, 70 eV) 546 (Mϩ, 6.7%), 273 (Mϩ/2,
35.9), 183 (Mϩ/2 Ϫ Si(CH3)3OH, 100).
1,6-Bis(triisopropylsilyl)-3,4-dimethylenehexa-1,5-diyne 5a
Dicyanoacetylene 723,24
To a cooled (0 ЊC) suspension of methyltriphenylphosphonium
bromide (1.03 g, 2.87 mmol) in THF (40 ml) was added BuLi
(1.79 ml of a 1.6 M solution in hexanes, 2.87 mmol). The reac-
tion was stirred for 45 min at room temperature. The resulting
orange solution was cooled to Ϫ78 ЊC and a solution of dike-
tone 1a (600 mg, 1.4 mmol) in THF (6 ml) was added dropwise.
The mixture was stirred for an additional 30 min at this tem-
perature until the TLC control indicated that all the starting
A three-neck flask, fitted with a mechanical stirrer and a
glass tube leading to a cold trap (Ϫ78 ЊC) was charged with
tetrahydrothiophene 1,1-dioxide (70 ml, previously dried by
distillation from phosphorus pentaoxide) and phosphorus
pentaoxide (17 g, 0.06 mol). The apparatus was thoroughly
flushed with argon before a homogeneous suspension of
acetylenedicarboxamide (5 g, 0.045 mol) in tetrahydrothiophene
1,1-dioxide (25 ml) was added dropwise under vigorous stirring
3750
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751

View Article Online
over 30 min at 110 ЊC and a pressure of ca. 12 Torr. After the
addition was complete, the temperature was raised to 120 ЊC
and the mixture stirred for another 15 min. During this period,
7 condensed in the cold trap as colourless needles (ca. 2.0 g).
The material turns black within a few minutes upon exposure to
air but was stable for weeks when stored in an atmosphere of
argon at Ϫ20 ЊC. δC (100.5 MHz; CDCl3) 55.1, 103.1.
[2,3,9,10,16,17,23,24-Octakis(3,5-di-tert-butylphenylethynyl)-
phthalocyaninato]magnesium(II) 10b
Phthalocyanine 10b was prepared starting from phthalonitrile
9b as described for 10a. The crude product was purified by flash
chromatography (eluting first with CH2Cl2, then with 10% Et2O
in CH2Cl2), followed by GPC (THF), yielding 10b (4.0 mg,
17%) as dark green solid. λmax(THF)/nm 255 (ε/dm3 molϪ1 cmϪ1
65900), 278 (87700), 307 (89700), 391 (177100), 649 (60600),
689 (48300), 723 (421400). δH (400 MHz; THF–CDCl3) 1.3
(144H, s, C(CH3)3), 7.5 (8H, s, aromatic CH), 7.6 (16H, s, aro-
matic CH), 9.6 (8H, s, aromatic CH); δC (100.5 MHz; THF–
CDCl3) 29.9, 33.5, 86.9, 95.3, 121.6, 121.9, 124.9, 125.4, 125.6,
136.8, 149.7, 152.6; m/z (MALDI-TOF) 2254 ([M ϩ Na]ϩ
requires 2256.4, 100%).
4,5-Bis(triisopropylsilylethynyl)phthalonitrile 9a
A solution of diene 5a (260 mg, 0.628 mmol), dicyanoacetylene
723,24 (190 mg, 2.50 mmol) and hydroquinone (15 mg) in THF
(5 ml) was heated under reflux. After 5 h another two equiva-
lents of dicyanoacetylene (95 mg, 1.26 mmol) were added. After
8 h, TLC control indicated that all the starting material had
been consumed. The solvent was evaporated in vacuo and the
dark brown residue taken up in toluene (5 ml). DDQ (712 mg
3.14 mmol) was added and the solution was heated under reflux
for 24 h. The solvent was evaporated and the residue subjected
to flash chromatography (CH2Cl2–hexanes 1:1) yielding 9a
(105 mg, 34%) as a white solid: mp 117–118 ЊC (from pentane)
(Found: C, 73.6; H, 9.25; N, 5.8. C30H44N2Si2 requires C, 73.7;
H, 9.1; N, 5.7%); λmax(CH2Cl2)/nm 230sh (ε/dm3 molϪ1 cmϪ1
15700), 254sh (32800), 268 (52600), 311 (20300) and 339sh
(5500); νmax(CHCl3/cmϪ1) 2949, 2864, 2235, 1581, 1464, 1254,
1069, 997, 883 and 833; δH (400 MHz; CDCl3) 1.1 (42H, s,
Si(CH(CH3)2)3), 7.8 (2H, s, aromatic CH); δC (126 MHz;
CDCl3) 11.2, 18.6, 102.0, 104.5, 114.0, 114.5, 130.4, 138.0;
m/z (EI, 70 eV) 488 (Mϩ, 4.0%), 445 (Mϩ Ϫ C3H7, 80.6), 403
(Mϩ Ϫ C6H13, 100).
Acknowledgements
We wish to acknowledge the support of University College
London for start-up funds and the provision of a Provost
Studentship to F. M.
References
1 J. Fabian, H. Nakazumi and M. Matsuoka, Chem. Rev., 1992, 92,
1197.
2 Infrared Absorbing Dyes, ed. M. Matsuoka, Plenum Press,
New York, 1990.
3 R. Bonnett, Chem. Soc. Rev., 1995, 19.
4 L. Milgrom and S. MacRobert, Chem. Br., March 1998, 45.
5 M. Ochsner, Photochem. Photobiol., 1997, 39, 1.
6 M. Ochsner, Arzneim. Forsch., 1997, 47(II), 1185.
7 R. Bonnett, Rev. Contemp. Pharmacother., 1999, 10, 1.
8 B. Franck and A. Nonn, Angew. Chem., 1995, 107, 1941.
9 I. Rosenthal, in Phthalocyanines—Properties and Applications,
ed. C. C. Leznoff and A. B. P. Lever, VCH, Weinheim, 1996, vol. 4,
pp. 481–514.
10 R. Faust and C. Weber, Liebigs Ann. Chem., 1996, 1235.
11 R. Faust, C. Weber, V. Fiandanese, G. Marchese and A. Punzi,
Tetrahedron, 1997, 53, 14655.
12 R. Faust, B. Göbelt, C. Weber, C. Krieger, M. Gross, J.-P.
Gisselbrecht and C. Boudon, Eur. J. Org. Chem., 1999, 205.
13 R. Faust and C. Weber, J. Org. Chem., 1999, 64, 2571.
14 R. Faust, B. Göbelt and C. Weber, J. Organomet. Chem., 1999, 578,
193.
4,5-Bis(3,5-di-tert-butylphenylethynyl)phthalonitrile 9b
Phthalonitrile 9b was prepared starting from 5b using a pro-
cedure analogous to that described for 9a. The reaction time
in THF was 62 h at room temperature. The dark brown oil
obtained was subjected to flash chromatography (CH2Cl2–
hexanes 1:1) yielding 9b (30 mg, 10%) as a white solid: mp 248–
251 ЊC (from hexane, decomp.) (Found: C, 86.7; H, 7.95; N, 4.8.
C40H44N2 requires C, 86.9; H, 8.0; N, 5.1%); λmax(CH2Cl2)/nm
240 (ε/dm3 molϪ1 cmϪ1 32400), 281 (56200), 315 (35700) and 357
(27700); νmax(CHCl3/cmϪ1) 3007, 2964, 2240, 2210, 1591, 1469,
1248, 1063 and 907; δH (400 MHz; CDCl3) 1.3 (36H, s,
C(CH3)3), 7.36 (4H, d, J 1.8, aromatic CH), 7.44 (2H, t, J 1.8,
aromatic CH), 7.9 (2H, s, aromatic CH); δC (100.5 MHz;
CDCl3) 31.2, 34.8, 84.4, 101.9, 113.8, 114.8, 120.5, 124.5, 126.1,
131.2, 136.3, 151.2; m/z (EI, 70 eV) 552 (Mϩ, 90.2%), 57
([C(CH3)3]ϩ, 100).
15 H. Hopf, M. Theurig, P. G. Jones and P. Bubenitschek, Liebigs Ann.
Chem., 1996, 1301.
16 A. de Groot, B. Evenhuis and H. Wynberg, J. Org. Chem., 1968, 33,
2214.
17 T. Niemi, P. L. Coe and S. J. Till, J. Chem. Soc., Perkin Trans. 1,
2000, 1519.
18 D. J. Ager, Synthesis, 1984, 384.
19 F. A. Carey and J. R. Toler, J. Org. Chem., 1976, 41, 1966.
20 N. A. Petasis and E. I. Bzoweij, J. Am. Chem. Soc., 1990, 112, 6392.
21 L. Lombardo, Tetrahedron Lett., 1982, 23, 4293.
22 K. Takai, Y. Hotta, K. Oshima and H. Nozaki, Bull. Chem. Soc.
Jpn., 1980, 53, 1698.
[2,3,9,10,16,17,23,24-Octakis(triisopropylsilylethynyl)-
phthalocyaninato]magnesium(II) 10a
23 H. Hopf and B. Witulski, in Modern Acetylene Chemistry, ed. P. J.
Stang and F. Diederich, Wiley-VCH, Weinheim, 1995, pp. 33–66.
24 V. Jäger, in Methoden der Organischen Chemie (Houben-Weyl),
ed. E. Müller, Thieme, Stuttgart, 1977, vol. V/2a, 677.
25 P. A. Grieco, J. J. Nunes and M. D. Gaul, J. Am. Chem. Soc., 1990,
112, 4595.
26 C. C. Leznoff, in Phthalocyanines—Properties and Applications,
ed. C. C. Leznoff and A. B. P. Lever, VCH Publishers, Weinheim,
1989, vol. 1, pp. 1–54.
27 D. S. Terekhov, K. J. M. Nolan, C. R. McArthur and C. C. Leznoff,
J. Org. Chem., 1996, 61, 3034.
28 C. C. Leznoff, Z. Li, H. Isago, A. M. D’Ascanio and D. S. Terekhov,
J. Porphyrins Phthalocyanines, 1999, 3, 406.
29 D. D. Perrin and W. L. F. Armarego, Purification of Laboratory
Chemicals, Pergamon Press, Oxford, 1988.
30 R. W. Bott, C. Eaborn and D. R. A. Wilson, J. Chem. Soc., 1965, 384.
31 Organization, ed. H. J. O. Beezer, 19th edn., Johann Ambrosius
Barth, Heidelberg, pp. 269, 249.
32 D. Philp, V. Gramlich, P. Seiler and F. Diederich, J. Chem. Soc.,
Perkin Trans. 2, 1995, 875.
A mixture of phthalonitrile 9a (20.0 mg, 41 µmol) and a solu-
tion of Mg(OBu)2 in BuOH (0.5 ml of a 1.0 M solution previ-
ously prepared by heating a suspension of Mg turnings (97.5
mg, 4.0 mmol) and a crystal of iodine in BuOH (4.0 ml) under
reflux for 4 h) was heated under reflux for 2 h. The solvent
was evaporated in a Kugelrohr apparatus leaving a dark green
solid, which was purified first by flash chromatography (10%
EtOAc→20% EtOAc in hexanes), then by GPC with THF as
eluent yielding 10a (7.7 mg, 38%) as a dark green solid (Found:
C, 71.2; H, 9.15; N, 5.2. C120H176N8Si8Mgؒ2H2O requires C,
71.5; H, 9.0; N, 5.55%); λmax(THF)/nm 261 (ε/dm3 molϪ1 cmϪ1
61200), 279 (41200), 311 (47300), 382 (138900), 641 (49500),
680 (39100), 713 (372600); δH (400 MHz; THF–CDCl3) 1.3
(168H, s, Si(CH(CH3)2)3), 9.5 (8H, s, aromatic CH); δC (100.5
MHz; THF–CDCl3) 11.1, 18.1, 96.0, 106.2, 125.4, 127.6, 137.4,
152.8; m/z (MALDI-TOF) 2001 ([M ϩ Na]ϩ requires 2000.2,
100%).
J. Chem. Soc., Perkin Trans. 1, 2000, 3746–3751
3751