Facile preparative redox chemistry of bis(4-dialkylaminophenyl)squaraine dyes

Article abstract of DOI:10.1016/S0040-4039(02)01857-9

Bis(4-dialkylaminophenyl)squaraine dyes are readily reduced in solution by borohydride to give alkali soluble leuco compounds, which exist in the 3-hydroxy-2,4-(4-dialkylaminophenyl)cyclobutenone tautomeric form. The leuco dyes can be oxidised rapidly back to the squaraine dye, thus providing a means of temporarily solubilising the squaraine dye in water. The leuco compounds undergo substitution reactions typical of vinylogous carboxylic acids.

Full text of DOI:10.1016/S0040-4039(02)01857-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7669–7671
Facile preparative redox chemistry of
bis(4-dialkylaminophenyl)squaraine dyes
John Griffiths* and Sooyoul Park
Department of Colour Chemistry, University of Leeds, Leeds LS2 9JT, UK
Received 8 August 2002; accepted 30 August 2002
Abstract—Bis(4-dialkylaminophenyl)squaraine dyes are readily reduced in solution by borohydride to give alkali soluble leuco
compounds, which exist in the 3-hydroxy-2,4-(4-dialkylaminophenyl)cyclobutenone tautomeric form. The leuco dyes can be
oxidised rapidly back to the squaraine dye, thus providing a means of temporarily solubilising the squaraine dye in water. The
leuco compounds undergo substitution reactions typical of vinylogous carboxylic acids. © 2002 Elsevier Science Ltd. All rights
reserved.
It is well known that certain classes of dye are reducible
to stable colourless leuco compounds, which can be
oxidised in air quantitatively back to the coloured
species. This reversible behaviour is made use of in
textile dyeing, photoimaging, redox indicators, and
enzyme assays.1 Carbonyl-based dye chromophores
that show such behaviour generally require at least two
mutually conjugated carbonyl groups, and the most
familiar of these are the quinone and indigoid dyes. It
is surprising that another important class of carbonyl
dye, namely the ubiquitous bis(4-dialkylaminophenyl)-
squaraine dyes, has not been investigated in this
respect. These dyes have many technical applications,
e.g. in xerography,2 solar cells,3 optical recording
media,4 and non-linear optics,5 but studies of their
redox properties have been confined to electrochemi-
cal,6 pulse-radiolytic and photochemical7 processes, and
in these studies, no attempts have been made to isolate
and characterise reduction products. We now report
that bis(4-dialkylaminophenyl)-squaraines 1 are readily
decolourised in solution by sodium borohydride to give
3-hydroxy-2,4-bis(4-dialkylaminophenyl)cyclobuten-one
leuco compounds 2,8 which can be air-oxidised back to
the squaraine dye in high yield. The leuco products are
easily isolated and undergo a range of reactions which
may be regarded as typical of vinylogous carboxylic
acids. The reduction—oxidation sequence is simple and
efficient, and extends synthetic possibilities in this class
of dye. Because the leuco compounds are soluble in
water at alkaline pH (in marked contrast to the parent
dye), this affords many new opportunities for extending
the chemistry and applications of squaraine dyes.
Examples would include their purification, morphologi-
cal modification, and incorporation into polymeric sub-
strates from an aqueous phase.
When an intense blue solution of 1a (3.7 mmol) in a
mixture of dichloromethane (30 cm3) and methanol (5
cm3) was treated with sodium borohydride (7.4 mmol),
complete decolourisation occurred after stirring for 30
minutes at room temperature. Neutralisation with ace-
tic acid followed by evaporation of the solvent gave a
colourless
solid,
which
was
extracted
into
dichloromethane and chromatographed rapidly over a
short column of silica gel in the same solvent. The
isolated colourless leuco compound 2a (45%) was char-
acterised by elemental analysis, mass spectrometry, and
NMR. It was converted in high yield (>98%) back to 1a
by air oxidation in solution. The sequence is sum-
marised in Scheme 1. The tautomeric structure 1a,
rather than the alternative 2,3-diaryl-1,3-cyclobutanone
structure, was assigned to the leuco dye on the basis of
its NMR spectrum9 and IR spectrum. Thus the two
1,4-disubstituted benzene rings were non-equivalent,
and the cyclobutenone H-4 was evident as a 1H singlet
at l 4.30.
The reduction–oxidation sequence observed for 1a
proved to be general for other dyes of this class, and
similar results were obtained for squaraines 1b–g. Their
leuco forms were isolated in yields of 45–80% after
purification. Typically 10−5 M solutions of these leuco
dyes in dichloromethane containing a little methanol
would take less than one hour to oxidise fully back to
the squaraine dye in air at room temperature, and
Keywords: squaraine dye; leuco-squaraine; redox reactions;
cyclobutenone.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01857-9

7670
J. Griffiths, S. Park / Tetrahedron Letters 43 (2002) 7669–7671
Scheme 1.
reaction efficiencies for the oxidative reversion were
higher than 80% in all cases, as determined spectropho-
tometrically. Oxidation could be effected more rapidly
with chloranil, ferric chloride, lead dioxide and iodine.
itation, derivatives of 1d with water solubilising groups
could be used more effectively.
The ease of air-oxidation of the leuco derivatives is in
part due to the acidic hydroxy group present in the
structure, and by analogy with leuco-quinones and
leuco-indigoids, O-alkylation or acylation should
increase the resistance of the system towards oxidation.
Treatment of 2a in dichloromethane with diazomethane
followed by column chromatography (silica gel 60/
CH2Cl2) afforded 3a as a colourless gum in 20% yield.
The NMR data11 were consistent with the enol ether
structure, and the MeO protons evident as a 3H singlet
at l 3.93, and the isolated cyclobutenone proton as a
1H singlet at l 4.70. As expected, 3a proved stable to
air oxidation in solution. Similar observations were
made for the O-methyl derivative 3c, which was
obtained in 44% yield from 2c.
Solutions of the leuco species in organic solvents or
water can be applied to polymeric substrates, e.g.
paper, and dried to give a colourless layer that develops
the colour of the squaraine dye on standing. The devel-
opment process is greatly accelerated by heating.
Another potential application of the leuco-squaraines is
as fluorogenic substrates for peroxidase enzyme assays.
For example, squaraine dye 1d is strongly red fluores-
cent in solution,10 and after reduction to the leuco
compound 2d this fluorescence naturally disappears. In
aqueous dilute hydrogen peroxide solution at ca. pH 9
containing horse-radish peroxidase, oxidation of 2d
back to 1d occurred much more rapidly than in the
absence of the enzyme, with the concomitant appear-
ance of the red emission from 1d. Although the useful-
ness of this reaction as an assay is restricted by the poor
solubility of 1d in water, resulting in its gradual precip-
Treatment of 2a with acetic anhydride gave the enol
acetate 4a, isolated in 45% yield after purification by
column chromatography. The NMR spectrum showed
the MeCO protons as a 3H singlet at l 2.10. The ester

J. Griffiths, S. Park / Tetrahedron Letters 43 (2002) 7669–7671
7671
was not as susceptible to air oxidation as 2a, but was
more reactive than 3a in this respect. This may be due
to the ease of hydrolysis of the enol acetate residue.
Nevertheless, acetylation provided a convenient means
of converting the leuco squaraines to derivatives that
were sufficiently stable for purification and storage, and
which, when required, could easily be converted back to
the squaraine dye by mild hydrolysis and air oxidation.
The leuco esters 4a–g were isolated in yields of 45–70%
after purification Interestingly, the derivative 4d proved
to be a fluorogenic substrate for horseradish peroxidase
in the same way that 2d did, but with the advantage that
competitive air oxidation was greatly reduced in this
case.
Oxidation of the leuco ester 4a, with lead dioxide gave
only the original squaraine dye 1a, whereas similar
oxidation of the methyl ether 3a and chloro derivative
5a gave new coloured products absorbing at longer
wavelengths than 1a, which were unstable under these
reaction conditions. These were presumably the
methoxy- and chloro-substituted cationic dyes, respec-
tively, analogous to 7, and these reactions are currently
under investigation, with a view to improving their
efficiency for preparative purposes.
Acknowledgements
Further substitution of the leuco squaraine system
proved possible by converting 2a to the vinylogous acid
chloride 5a. This was most conveniently achieved by
reaction of 2a with phosphorous oxychloride and a
catalytic amount of pyridine in dichloromethane at
room temperature for 4 h. The chloride was obtained as
a colourless oil in 48% yield after column chromatogra-
phy, and the structure was confirmed by mass spec-
trometry and NMR. The chlorine atom in 5a proved
labile, and for example could be replaced by amines.
We thank the EPSRC Mass Spectrometry Service at
Swansea for provision of services.
References
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Interestingly, each amino derivative 6 could be oxidised
in solution with chloranil or lead dioxide to give an
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3.93 (s, 3H), 3.35 (m, 8H), 1.15 (m, 12H).
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