Palladium-catalysed amination of bromofluorans and an investigation of their thermochromic behaviour

Article abstract of DOI:10.1016/j.dyepig.2011.06.018

The palladium-catalysed amination of readily accessible bromofluorans and bromobenzo[a]fluorans has been accomplished with a series of anilines and morpholine. The resulting aminofluorans generated intense black shades upon formulation in methyl stearate containing bisphenol A. The route provides an alternative approach to various amino substituted fluorans without the need of a series of individual diphenylamine intermediates.

Full text of DOI:10.1016/j.dyepig.2011.06.018

Dyes and Pigments 92 (2011) 524e530
Contents lists available at ScienceDirect
Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
Palladium-catalysed amination of bromofluorans and an investigation
of their thermochromic behaviour
,
Farid Azizian a, Amanda J. Field b, John Griffiths b, B. Mark Heron b
*
a St Mary Cray Research, Sun Chemical Ltd, St Mary Cray, Orpington, Kent BR5 3PP, UK
b Department of Colour Science, School of Chemistry, University of Leeds, Leeds LS2 9JT, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The palladium-catalysed amination of readily accessible bromofluorans and bromobenzo[a]fluorans has
been accomplished with a series of anilines and morpholine. The resulting aminofluorans generated
intense black shades upon formulation in methyl stearate containing bisphenol A. The route provides an
alternative approach to various amino substituted fluorans without the need of a series of individual
diphenylamine intermediates.
Received 24 May 2011
Received in revised form
10 June 2011
Accepted 13 June 2011
Available online 21 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Thermochromism
Fluoran
Benzofluoran
Colour former
Pd-catalysed amination
Functional dye
1. Introduction
the Pd-catalysed amination reaction for the direct amination of
bromo-substituted fluorans and benzo[a]fluorans.
Interest in functional dye systems continues at a pace as
a consequence of technological developments and more wide-
spread applications [1e3] particularly in the areas of sensors and
probes for a variety of organic and inorganic analytes [4] and dyes
for solar cell applications [5]. The (thio)xanthene unit [6] forms the
core of many functional dyes including rhodamines [7], rosamines
[8], thiofluoresceins [9] and fluorans [10].
Transition metal-catalysed arylation [11] and amination reac-
tions [12] have been widely employed in organic syntheses to
facilitate efficient transformations that would otherwise necessi-
tate many sequential steps. However, such transition metal-
catalysed techniques have only very recently been applied to the
preparation of functional dye systems such as rhodols and ros-
amines. In the former, a methoxymethyl (MOM) protected fluo-
rescein monotriflate was successfully aminated at the 30-position
with a variety of amines under Pd(OAc)2eBINAP catalysis (Scheme
1) [13] and in the latter an aryl moiety was introduced into the 9-
2. Experimental
2.1. Equipment
Unless otherwise stated, reagents were used as supplied. 20-
Bromo-60-di(n-butylamino)-30-methylfluoran (Vermillion DCF)
was obtained from Sun Chemical (France) Ltd. NMR spectra were
recorded on a Bruker Avance 400 MHz instrument (1H NMR
400 MHz, 13C NMR 100 MHz) for sample solutions in CDCl3 with
tetramethylsilane as an internal reference unless indicated other-
wise. All compounds were homogeneous by TLC, Merck TLC
aluminium sheets either silica gel 60 F254 (cat. No 105554) or
neutral aluminium oxide 60 F254 (cat. No 105550), using a range of
eluent systems of differing polarity. Flash column chromatography
was performed on chromatography silica gel (Fluorochem,
35e70
mm particle size distribution). All percentage yields are
position of
a xanthene unit through PdCl2(PPh3)2-mediated
unoptimised. Reflectance spectra of the new thermochromic
compounds in methyl stearate containing bisphenol A [ratio of
fluoran:bisphenol A:methyl stearate ¼ 5:1:15] as a thin film
sandwiched between two glass microscope slides were recorded
using a Datacolor Spectraflash 500 (Xe flash simulating natural
daylight, diffuse illumination, collected at 8ꢀ to normal), with
coupling of a triarylboroxin to a 9-trifloxyxanthene (Scheme 2)
[14]. We now describe our preliminary results on the application of
* Corresponding author. Tel.: þ44 0 1133432925; fax: þ44 0 1133432947.
E-mail address: b.m.heron@leeds.ac.uk (B.M. Heron).
0143-7208/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.dyepig.2011.06.018

F. Azizian et al. / Dyes and Pigments 92 (2011) 524e530
525
O
O
to afford the title compound as pale pink crystals in 70% yield, m.p.
173e175 ꢀC, nmax (cmꢂ1) 1749.4, 1348.9, 1194.5, 664.8, dH 1.17 (6H, t,
J ¼ 7.2, (CH3CH2)2N), 3.36 (4H, q, J ¼ 7.2, (CH3CH2)2N), 6.36 (1H, dd,
J ¼ 8.8 and 2.5, 70-H), 6.44 (1H, d, J ¼ 2.5, 50-H), 6.55 (1H, d, J ¼ 8.8,
80-H), 6.86 (1H, d, J ¼ 2.4, 10-H), 7.27 (2H, m, 40-H and 7-H), 7.45 (1H,
dd, J ¼ 8.8 and 2.4, 30-H), 7.66 (2H, m, 5-H and 6-H), 8.04 (1H, d,
J ¼ 7.2, 4-H), found [M þ H]þ ¼ 450.0701 C24H20BrNO3 requires
[M þ H]þ ¼ 450.0705.
Pd(OAc)2, BINAP,
Cs2CO3, R1R2NH
O
O
dioxane 100 o
C
MOMO
O
OTf
MOMO
O
NR1R2
Scheme 1. Pd-Catalysed amination of a protected fluorescein.
specular excluded, UV 100%, small aperture setting, four flashes and
a single measurement. FTIR spectra were recorded using a Perkin
Elmer Spectrum One spectrophotometer equipped with a diamond
probe ATR attachment (neat sample). Mass spectra were recorded
at the National EPSRC Mass Spectrometry Service Centre, Swansea.
2.4. 90-Diethylaminobenzo[a]fluoran 3
20-[(4-Diethylamino)-2-hydroxybenzoyl]benzoic acid 1 (1 g;
3.2 mmol) and 2-naphthol (0.42 g; 2.9 mmol) were added por-
tionwise to methanesulfonic acid (98%, 6 mL), ensuring the
temperature did not exceed 25 ꢀC. The reaction mixture was then
stirred at 20e25 ꢀC for 24 h, with monitoring by TLC (silica/70%
ethyl acetate in hexane). The reaction mixture was poured into ice
water (20 mL) and neutralised. The precipitate was collected by
vacuum filtration and washed with water (3 ꢁ 25 mL). The solid
intermediate was then added to sodium hydroxide (1%, aq, 5 mL)
and heated to 75e80 ꢀC for 4 h. Vacuum filtration of the solution
afforded pink crystals, which were washed with hexane containing
a little diethyl ether to afford the title compound as off-white
microcrystals in 67% yield, m.p. 218e220 ꢀC (Lit. m.p. 215e217 ꢀC
[15]), nmax (cmꢂ1) 1754.3, 1352.8, 1197.1, dH 1.16 (6H, t, J ¼ 7.2,
(CH3CH2)2N), 3.34 (4H, q, J ¼ 7.2, (CH3CH2)2N), 6.49 (1H, dd, J ¼ 8.8
and 2.4, 100-H), 6.59 (2H, m, 80-H and 110-H), 7.00 (1H, d, J ¼ 8.8, 10-
H), 7.21 (2H, dd, J ¼ 8.8 and 2.4, 20-H and 30-H), 7.43 (1H, d, J ¼ 7.6,
60-H), 7.61 (2H, d, J ¼ 7.6, 50-H and 7-H), 7.78 (2H, m, 5-H and 6-H),
8.04 (1H, dd, J ¼ 8.8 and 2.4, 40-H), 8.22 (1H, d, J ¼ 7.6, 4-H).
2.2. Synthesis of 90-diethylamino-30-bromobenzo[a]fluoran 2
20-[4-(Diethylamino)-2-hydroxybenzoyl]benzoic acid 1 (5 g;
16 mmol)and6-bromo-2-naphthol (3.57 g;16 mmol)wereheated at
120e125 ꢀC in sulphuric acid (85%, 25 g) for 4 h. The reaction mixture
was poured into ice water (75 mL) and a green/purple solid was
precipitated by adding NaOH (2 M, aq, w15 mL). The precipitate was
collected by vacuum filtration and washed with water (3 ꢁ 50 mL).
The precipitatewas suspended in a mixture of water (25mL), sodium
hydroxide (1.25 g; 52 mmol) and toluene (75 mL) and heated under
reflux for 0.5 h. The toluene layer was separated, washed with
sodium hydroxide solution (3.5%, aq, 2 ꢁ 25 mL) and water
(2 ꢁ 25 mL), and reduced in volume to w25 mL. The precipitate
formed on cooling was collected by vacuum filtration and washed
with a small amount of cold toluene (10 mL) to afford the product as
pale pink microcrystals in 27% yield, m.p. 227e230 ꢀC, nmax (cmꢂ1
)
1754.7, 1351.7, 1198.2, 665.3, dH 1.05 (6H, t, J ¼ 7.2, (CH3CH2)2N), 3.33
(4H, q, J ¼ 7.2, (CH3CH2)2N), 6.36 (1H, dd, J ¼ 8.8 and 2.4, 100-H), 6.43
(1H, d, J ¼ 2.7, 80-H), 6.50 (1H, d, J ¼ 8.8, 110-H), 6.92 (1H, dd, J ¼ 8.8
and 2.4, 60-H), 7.09 (1H, d, J ¼ 7.2, 7-H), 7.21 (1H, dd, J ¼ 8.8 and 2.4, 20-
H), 7.45 (1H, d, J ¼ 8.8, 10-H), 7.58 (2H, m, 5-H and 6-H), 7.79 (1H, d,
J ¼ 8.8, 50-H), 7.92 (1H, d, J ¼ 2.4, 40-H), 8.12 (1H, d, J ¼ 7.2, 4-H), dC
12.50, 44.46, 84.22, 96.90, 105.86, 109.00, 109.05, 117.95, 119.64,
123.50, 125.25, 125.46, 136.90, 128.21, 129.45, 130.13, 130.31, 131.03,
131.48, 132.47, 135.27, 149.11, 150.65, 151.35, 155.27, 170.01, found
[M þ H]þ ¼ 500.0850 C28H22BrNO3 requires [M þ H]þ ¼ 500.0856.
2.5. 30-Diethylaminofluoran 5
20-[4-(Diethylamino)-2-hydroxybenzoyl]benzoic acid 1 (5 g;
16 mmol) was added to sulphuric acid (98%, 40 g) at room
temperature and dissolved. Phenol (1.49 g; 16 mmol) was then
added to the foregoing cooled solution and the mixture was stirred
at 10e20 ꢀC for 5 h. The reaction mixture was then poured into ice
water (150 mL) and a purple solid was precipitated by adding NaOH
(10%, aq). This was collected by vacuum filtration and washed with
water. The precipitate was then suspended in sodium hydroxide
(10%, aq, 30 mL) and toluene (60 mL), and was heated by reflux for
2 h. The cold toluene layer was then separated, washed with
sodium hydroxide (3.5%, aq, 2 ꢁ 15 mL) and water (2 ꢁ 15 mL), and
evaporated to w25 mL. The precipitate formed on cooling was then
collected by vacuum filtration and washed with a small amount of
cold toluene (10 mL) to afford the title compound as pale pink
crystals in 62% yield, m.p. 128e130 ꢀC, nmax (cmꢂ1) 1748.0, 1351.2,
1196.5, dH 1.16 (6H, t, J ¼ 7.2, (CH3CH2)2N), 3.38 (4H, q, J ¼ 7.2,
(CH3CH2)2N), 6.37 (1H, dd, J ¼ 9.0 and 2.8, 70-H), 6.41 (1H, d, J ¼ 2.8,
50-H), 6.75 (1H, d, J ¼ 8.8, 80-H), 6.96 (1H, d, J ¼ 2.4, 10-H), 7.20 (2H,
m, 40-H and 7-H), 7.51 (2H, dd, J ¼ 9 and 2.4, 20-H and 30-H), 7.66
2.3. Synthesis of 20-bromo-60-diethylaminofluoran 4
4-Bromoanisole (2.99 g; 16 mmol) was added to a solution of 20-
[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid 1 (5 g; 16 mmol)
in sulphuric acid (98%, 40 g) and the mixture was stirred at
10e20 ꢀC for 5 h. The reaction mixture was then poured into ice
water (150 mL) and a purple solid was precipitated by adding NaOH
(10%, aq, 20 mL). The precipitate was collected by vacuum filtration
and washed with water (3 ꢁ 25 mL). The solid was suspended in
sodium hydroxide (10%, aq, 30 mL) and toluene (60 mL), and heated
under reflux for 2 h, and then allowed to cool. The toluene layer was
then separated, washed with sodium hydroxide (3.5%, aq,
2 ꢁ 25 mL) and water (2 ꢁ 25 mL), and evaporated to w25 mL. The
precipitate formed on cooling was then collected by vacuum
filtration and washed with a small amount of cold toluene (10 mL)
(2H, m, 5-H and 6-H), 8.04 (1H, d,
J
¼
7.2, 4-H), found
[M þ H]þ ¼ 372.1590 C24H21NO3 requires [M þ H]þ ¼ 372.1594.
2.6. General method for the Pd-catalysed amination of
bromofluorans
Ar
B
Sodium t-butoxide (6 mmol), the bromofluoran (2 mmol), the
appropriate amine (3 mmol), tri-(t-butyl)phosphonium tetra-
fluoroborate (4 mol%) and Pd2(dba)3 (5 mol%) were placed in
a 100 mL round bottomed flask under N2. Anhydrous toluene
(25 mL), previously bubbled N2 for 15 min, was added via a transfer
needle and the mixture was heated to 70 ꢀC until TLC examination
revealed that no further reaction had occurred. The reaction
O
B
O
B
OTf
Ar
Y
Ar
O
Ar
TfO
X
PdCl2(PPh3)2 (10 mol%)
Me2N
Y
NMe2
Na2CO3, then aq. HX
Me2N
NMe2
Y = O, S, Se, Te
Scheme 2. Pd-Catalysed arylation of 9-trifloxyxanthenes.

526
F. Azizian et al. / Dyes and Pigments 92 (2011) 524e530
mixture was poured into cold, dilute HCl (0.01 M, aq, 200 mL) and
extracted with CH2Cl2 (2 ꢁ 100 mL). The combined organic extracts
were washed with dilute NaOH (0.1 M, aq, 50 mL) and water
(2 ꢁ 50 mL), dried over sodium sulphate and evaporated to afford
the crude product which was purified by column chromatography
(30% ethyl acetate in toluene) and recrystallisation (ethyl acetate in
hexane). The following compounds were obtained by this protocol:
d, J ¼ 2.3, 40-H), 7.58 (2H, m, 5-H and 6-H), 7.69 (1H, d, J ¼ 8.9, 60-H),
7.85 (2H, m, Ar-H), 8.12 (1H, m, 4-H), dC 11.49, 13.40, 20.04, 27.93,
37.79, 43.28, 43.41, 59.24, 59.36, 83.27, 83.75, 95.88, 104.93, 107.88,
112.74, 113.74, 117.35, 117.86, 120.56, 122.76, 123.04, 123.80, 126.17,
127.21, 128.33, 130.46, 131.51, 134.22, 146.59, 148.02, 149.81, 154.51,
165.71, 169.29, 170.17, found [M þ H]þ ¼ 585.2384 C37H32N2O5
requires [M þ H]þ ¼ 585.2389.
2.6.1. 30-Anilino-90-diethylaminobenzo[a]fluoran
2.6.5. 90-Diethylamino-30-morpholinobenzo[a]fluoran
7a from 2 and aniline after column chromatography and
recrystallisation as pink microcrystals in 19% yield, m.p.
200e204 ꢀC [16], nmax (cmꢂ1) 3378.4, 1740.3, 1236.1, dH 1.15 (6H, t,
J ¼ 7.2, (CH3CH2)2N), 3.33 (4H, q, J ¼ 7.2, (CH3CH2)2N), 5.90 (1H, s,
NH), 6.35 (1H, dd, J ¼ 8.8 and 2.4, 100-H), 6.43 (1H, d, J ¼ 2.8, 80-H),
6.51 (1H, d, J ¼ 8.8, 110-H), 6.85 (1H, dd, J ¼ 8.8 and 2.4, 20-H), 6.92
(3H, m, Ar-H,10-H), 7.06 (4H, m, Ar-H, 7-H), 7.13 (1H, d, J ¼ 2.4, 40-H),
7.28 (1H, d, J ¼ 9.0, 60-H), 7.55 (2H, m, 5-H and 6-H), 7.65 (1H, d,
J ¼ 9.0, 50-H), 8.11 (1H, m, 4-H), dC 12.52, 44.42, 84.82, 96.90, 106.05,
108.71, 108.75, 113.20, 118.11, 118.76, 120.34, 121.21, 123.56, 124.90,
125.13, 126.15, 126.95, 128.26, 129.29, 131.21, 132.51, 135.14, 138.11,
139.39, 142.58, 149.02, 149.60, 150.85, 155.65, 170.38, found
[M þ H]þ ¼ 513.2169 C34H28N2O3 requires [M þ H]þ ¼ 513.2178.
7e from 2 and morpholine after column chromatography as pale
beige microcrystals in 57% yield, m.p. 140e144 ꢀC, nmax (cmꢂ1
)
1750.0, 1306.9, 1227.0, dH (DMSO-d6) 1.16 (6H, t,
J
¼
7.2,
(CH3CH2)2N), 3.14 (4H, m, eCH2NCH2e), 3.34 (4H, q, J ¼ 7.2,
(CH3CH2)2N), 3.83 (4H, m, eCH2OCH2e), 6.36 (1H, dd, J ¼ 8.8 and
2.4, 100-H), 6.44 (1H, d, J ¼ 2.4, 80-H), 6.54 (1H, d, J ¼ 8.8, 110-H), 6.90
(1H, dd, J ¼ 8.8 and 2.4, 20-H), 6.99 (1H, d, J ¼ 8.8, 10-H), 7.06 (1H, d,
J ¼ 2.4, 40-H), 7.10 (1H, m, 7-H), 7.36 (1H, d, J ¼ 9.0, 60-H), 7.57 (2H,
m, 5-H and 6-H), 7.78 (1H, d, J ¼ 9.0, 50-H), 8.12 (1H, m, 4-H), dC
(DMSO-d6) 12.94, 21.88, 29.45, 44.85, 49.65, 67.23, 85.17, 94.13,
97.33, 106.49, 109.15, 112.04, 119.58, 124.01, 125.14, 125.70, 126.14,
127.47, 128.66, 129.61, 131.85, 132.85, 135.51, 138.29, 147.72, 149.42,
150.05, 151.35, 156.05, 170.72, found [M þ H]þ ¼ 507.2265
C
32H30N2O4 requires [M þ H]þ ¼ 507.2278.
2.6.2. 90-Diethylamino-30-(4-methoxyanilino)benzo[a]fluoran
7b from 2 and p-anisidine after column chromatography as pale
2.6.6. 60-Di-n-butylamino-20-(4-methoxyanilino)-30-methylfluoran
7g from 6 and p-anisidine after column chromatography as very
pale redepurple microcrystals in 68% yield, m.p. 142e145 ꢀC, nmax
(cmꢂ1) 3394.1, 1746.8, 1240.4, dH 0.95 (6H, t, J ¼ 7.2, (CH3CH2
CH2CH2)2N), 1.33 (4H, sextet, J ¼ 7.2, (CH3CH2CH2CH2)2N), 1.56 (4H,
quintet, J ¼ 7.2, (CH3CH2CH2CH2)2N), 2.40 (3H, s, CH3), 3.26 (4H, t,
J ¼ 7.6, (CH3CH2CH2CH2)2N), 3.42 (1H, bs, NH), 3.74 (3H, s, OCH3),
6.32 (1H, dd, J ¼ 8.8 and 2.4, 70-H), 6.38 (1H, d, J ¼ 2.4, 50-H), 6.52
(1H, d, J ¼ 8.8, 80-H), 6.65 (2H, m, Ar-H), 6.74 (2H, m, Ar-H), 6.88 (1H,
s, 10-H), 7.16 (1H, s, 40-H), 7.18 (1H, dd, J ¼ 7.2 and 1.2, 7-H), 7.65 (2H,
m, 5-H and 6-H), 8.02 (1H, dd, J ¼ 7.2 and 1.2, 4-H), dC 13.98, 20.28,
23.00, 29.26, 50.79, 55.72, 83.39, 97.51, 104.46, 108.57, 114.78,
116.42, 118.09, 118.86, 118.90, 124.00, 125.04, 126.99, 128.74, 129.72,
131.12, 134.98, 139.90, 140.47, 150.81, 152.57, 152.71, 152.78, 157.96,
pink microcrystals in 58% yield, m.p. 150e154 ꢀC, nmax (cmꢂ1
)
3374.7, 1736.9, 1237.0, dH 1.15 (6H, t, J ¼ 7.2, (CH3CH2)2N), 3.33 (4H,
q, J ¼ 7.2, (CH3CH2)2N), 3.84 (3H, s, OCH3), 5.51 (1H, s, NH), 6.35 (1H,
dd, J ¼ 8.8 and 2.4, 100-H), 6.43 (1H, d, J ¼ 2.8, 80-H), 6.51 (1H, d,
J ¼ 8.8,110-H), 6.75 (1H, dd, J ¼ 9.2 and 2.4, 20-H), 6.85 (2H, m, Ar-H),
6.92 (1H, d, J ¼ 9.2, 10-H), 7.05 (2H, m, Ar-H), 7.13 (1H, m, 7-H), 7.16
(1H, d, J ¼ 2.4, 40-H), 7.32 (1H, d, J ¼ 9.2, 60-H), 7.55 (2H, m, 5-H and
6-H), 7.65 (1H, d, J ¼ 9.2, 50-H), 8.11 (1H, m, 4-H), dC 12.52, 21.07,
44.42, 60.42, 84.82, 96.90, 106.06, 108.74, 113.22, 118.09, 118.72,
120.37, 121.24, 123.58, 124.87, 125.09, 126.18, 126.99, 128.23, 129.31,
131.19, 132.52, 135.16, 138.08, 139.41, 142.60, 148.99, 149.59, 150.90,
155.60, 170.35, found [M þ H]þ ¼ 543.2274 C35H30N2O4 requires
[M þ H]þ ¼ 543.2278.
169.44 found [M
þ
H]þ
¼
563.2906 C36H38N2O4 requires
2.6.3. 90-Diethylamino-30-(4-trifluoromethylanilino)benzo[a]
fluoran
[M þ H]þ ¼ 563.2910.
7c from 2 and 4-trifluoromethylaniline after column chroma-
tography as pale yellow microcrystals in 86% yield, m.p.137e140 ꢀC,
nmax (cmꢂ1) 3368.2, 1740.0, 1235.3, 1096.8, dH 1.16 (6H, t, J ¼ 7.2,
(CH3CH2)2N), 3.35 (4H, q, J ¼ 7.2, (CH3CH2)2N), 5.95 (1H, s, NH), 6.38
(1H, dd, J ¼ 8.8 and 2.4, 100-H), 6.43 (1H, d, J ¼ 2.8, 80-H), 6.51 (1H, d,
J ¼ 8.8, 110-H), 6.92 (1H, dd, J ¼ 8.8 and 2.4, 20-H), 7.02 (3H, m, Ar-H,
10-H), 7.13 (1H, m, 7-H), 7.41 (1H, d, J ¼ 9.0, 60-H), 7.47 (3H, m, Ar-H,
40-H), 7.58 (2H, m, 5-H and 6-H), 7.75 (1H, d, J ¼ 9.0, 50-H), 8.10 (1H,
d, J ¼ 7.2, 4-H), dC 12.51, 78.12, 44.44, 84.78, 96.90, 105.93, 108.86,
114.22, 115.55, 116.25, 119.00, 121.44, 121.80, 123.58, 124.99, 125.30,
125.92,126.56,126.93,127.23,128.23,129.04,129.36,131.38,132.25,
135.24, 137.41, 146.33, 149.08, 150.83, 155.51, 170.33, found
[M þ H]þ ¼ 581.2030 C35H27N2O3F3 requires [M þ H]þ ¼ 581.2047.
3. Discussion
In order to assess the versatility of the palladium-catalysed
coupling reaction three bromo-substituted fluorans were examined
as substrates, 30-bromo-90-diethylaminobenzo[a]fluoran 2, 20-
bromo-60-diethylaminofluoran 4 and a commercial sample of 20-
bromo-60-di(n-butylamino)-30-methylfluoran
6 [17]. Fluorans 2
and 4 were derived from the common ketoacid 1 which was
readily available from the FriedeleCrafts reaction between 3-
diethylaminophenol and phthalic anhydride in toluene [18]. Heat-
ing 1 with either 6-bromo-2-naphthol or 4-bromoanisole in 85%
sulphuric acid gave, after basification and purification, the requisite
bromofluorans 2 and 4 in moderate yield (Scheme 3). As a conse-
quence of reported instances where debromination had occurred
during the attempted preparation of bromofluorans via this general
method [19] careful structural characterisation of 2 and 4 was
undertaken.
2.6.4. 90-Diethylamino-30-(4-ethoxycarbonylanilino)benzo[a]
fluoran
7d from 2 and ethyl 4-aminobenzoate after column chroma-
tography and recrystallisation as fawn microcrystals in 53% yield,
m.p. 99e102 ꢀC, nmax (cmꢂ1) 3349.7, 1737.6, 1686.0, 1595.2, 1280.3,
1172.8, dH 1.15 (6H, t, J ¼ 7.2, (CH3CH2)2N), 1.36 (3H, t, J ¼ 7.2,
OCH2CH3), 3.34 (4H, q, J ¼ 7.2, (CH3CH2)2N), 4.32 (2H, q, J ¼ 7.2,
OCH2CH3), 6.37 (1H, dd, J ¼ 8.8 and 2.4, 100-H), 6.41 (1H, d, J ¼ 2.4,
80-H), 6.45 (1H, bs, NH), 6.52 (1H, d, J ¼ 8.8, 110-H), 6.95 (4H, m, Ar-
H, 10-H, 20-H), 7.10 (1H, m, 7-H), 7.36 (1H, d, J ¼ 8.9, 60-H), 7.45 (1H,
The key 1H NMR signals employed for the characterisation of 2
were the ortho-coupled doublet at
d
7.45 (J ¼ 9.2 Hz, 10-H), a double
doublet at
doublet at
d
7.21 (J ¼ 9.2 and 2.4 Hz, 20-H) and the meta-coupled
d
7.92 (J ¼ 2.4 Hz, 40-H) which confirmed the position of
the bromine atom. A group of mutually coupled signals resonating
upfield of these signals assigned tothe bromonaphthalene unit were
assigned to 110-H (
d
6.50, d, J ¼ 8.8 Hz), 100-H (
6.37, dd, J ¼ 8.8 and
d

F. Azizian et al. / Dyes and Pigments 92 (2011) 524e530
527
O
O
CO2H
PhMe
reflux
+
O
Et2
N
OH
Et2N
OH
1
O
6-bromo-2-naphthol
or 2-naphthol
4-bromoanisole
or phenol
H2SO4
H2SO4
4
4
O
O
O
3
3
2'
X
6
O
O
O
1'
4'
Br
Me
X
4'
7'
n-Bu2N
10'
N
O
Et2
O
Et2
N
O
8'
5'
6'
6
2
4
, X = Br
, X = Br
3, X = H
5, X = H
Scheme 3. Preparation of fluorans and bromofluorans.
2.6 Hz) and80-H(
d
6.43, d, J ¼ 2.6Hz) whichconfirmedthelocationof
the diethylamino group on the xanthene core (Fig. 1). The presence
1
Fig. 1. H NMR spectrum of 90-diethylamino-30-bromobenzo[a]fluoran 2.
of the lactone carbonyl was confirmed by 13C NMR spectroscopy
with a signalat d
170.0 [20] and also bya C]O stretch at 1754 cmꢂ1 in
the infrared spectrum. Mass spectrometry gave the expected
molecular ions M þ Hþ ¼ 500.2 and 502.2 in a ca. 1:1 ratio (Br79 and
Br81) which confirmed the incorporation of the bromine atom.
The 1H NMR spectrum of 4 displayed a similar grouping of
aminations have been widely investigated and have featured in
reviews which highlight the apparenteasewithwhich this amination
occurs [12]. From the considerable body of work undertaken in this
area it is apparent that an exceptionally wide range of aryl halides and
amines can be coupled together and that an extensive range of cata-
lysts, ligands and solvents have been employed.
The Pd source employed throughout this study was Pd2(dba)3
since this has been widely employed in Pd-catalysed aminations
[22]. The ligand employed was tris(t-butyl)phosphine, used as the
more convenient tris(t-butyl)phosphonium fluoroborate salt with
the free phosphine liberated in situ using an additional equivalent
of sodium tert-butoxide. Thus heating a solution of 2 in anhydrous
toluene (previously bubbled with nitrogen for 15 min) containing 1
eq. of the aniline, 2 eq. of t-BuONa, t-Bu3P$HBF4 (4 mol%) and
Pd2(dba)3 (5 mol%) gave, after 24 h at 70 ꢀC, a reaction mixture
signals at ca.
and the protons of the furanone moiety were assigned to signals at
7.27 (multiplet including 40-H),
7.66 (m) and
d 6.4 assigned to the Et2N substituted xanthene unit
d
d
d
8.04 (d, J ¼ 7.2 Hz)
for 7-H, 5-H and 6-H, and 4-H respectively. The incorporation of the
bromine atom was confirmed by mass spectrometry with
M þ Hþ ¼ 450.2 and 452.2 and the lactone carbonyl stretching band
appeared at 1749 cmꢂ1 in the infrared spectrum.
Withthe requiredbromofluorans tohand examinationof theirPd-
catalysed amination reaction was next explored (Scheme 2). In 1994
Buchwald et al. and Hartwig et al. independently published work on
the coupling of aryl halides with amines using palladium catalysis in
the presence of a base [21]. Since then, palladium-catalysed
O
O
Pd2(dba)3 (5 mol%),
Br
X
t-Bu3P.HBF4 (4 mol%),
O
O
NaOt-Bu, PhMe
amine,
N2, 70 oC
Et2N
O
2
Et2N
7a
O
X = Ph(H)N
7b X = 4-MeOC6H4(H)N
7c
X = 4-F3CC6H4(H)N
7d X = 4-EtO2CC6H4(H)N
7e X = morpholinyl
O
O
O
O
O
H
N
OMe
N
n-Bu2N
O
Me
Et2N
O
7g
7f
O
O
H
H
N
N
O
O
Et2N
O
O
NEt2
7h
Scheme 4. Pd-catalysed amination reactions of bromofluorans.

528
F. Azizian et al. / Dyes and Pigments 92 (2011) 524e530
80.00
containing none of the original bromofluoran 2 and two new
components which, although poorly resolved on TLC, were sepa-
rated by column chromatography. The faster running red colouring
component was identified as the benzo[a]fluoran 3 (10%) by
comparison of physical and spectroscopic data with an indepen-
dently synthesised sample. The debromination of aromatic
bromides in Pd-catalysed reactions is a frequently encountered
problem [23].
The more polar purpleeblack colouring compound was char-
acterised as the target 30-anilinofluoran 7a albeit in a disappoint-
ingly low isolated yield of 19% (Scheme 4), in spite of the relatively
high conversion indicated by TLC analysis of the reaction mixture. It
is likely that the low isolated yield of pure 7a is in part attributed to
a combination of the poor resolution between the two products and
the chromatographic purification process which results in some
ring-opening of the fluorans on the chromatography silica. The 1H
70.00
60.00
50.00
40.00
30.00
20.00
10.00
0.00
400
450
500
550
600
650
wavelength (nm)
Fig. 2. Reflectance spectra of 7b in methyl stearate containing bisphenol A at rt (lower
NMR spectrum for 7a displayed a singlet for the NH group at d 5.90
line) and at ca. 50 ꢀC (upper line).
confirming the success of the coupling process. The naphthalene
ring protons in close proximity to the 30-aniline group gave rise to
signals at
d
6.85 (dd, J ¼ 8.8 and 2.4 Hz, 20-H),
d
6.92 (m, 10-H) and
Amination of bromofluoran 4 with morpholine resulted in
a complex reaction product from which unrecovered 4 (17%) and
debrominated fluoran 5 (35%) could be isolated but the known red-
developing (TLC) diaminofluoran 7f [25] remained impure.
However, treatment of 6 with p-anisidine proceeded smoothly
under identical conditions to afford 7g in 68% yield in spite of the
sterically important proximal methyl group. Attempts to accom-
plish a double amination with 1,4-diaminobenzene, thereby linking
two molecules of 2 together, to afford 7h gave a complex reaction
product by TLC which indicated a new purpleeblack colouring
species had formed but which could not be resolved by chroma-
tography. Further investigations of Pd-catalysed aminations with
other secondary amines and diamines are in hand.
The colour forming properties of the new fluorans in methyl
stearate containing bisphenol A as the acidic developer were next
examined. At room temperature each of the new aminofluoran
formulations appeared intensely coloured with 7b appearing
blueeblack, 7cee purpleeblack and 7g a greeneblack in agreement
with established colourestructure trends [19]. Upon warming to ca.
50 ꢀC each of the foregoing formulations faded to near colourless
with 7b and 7c displaying very weak residual pale yellow and pale
pink shades, respectively. Selected reflectance spectra recorded at
room temperature (rt) and at ca. 50 ꢀC are presented in Figs. 2e4
and illustrate the significant contrast between the ring-opened
coloured and ring-closed colourless forms and the broad absorp-
tion over the full range of the visible spectrum confirming the near
d
7.13 (d,
J
¼
2.4 Hz, 40-H). The expected signals for the
diethylamino-substituted xanthene unit appeared at
6.35 (100-H) and 6.51 (110-H). The robustness of the lactone ring
towards the amination conditions was confirmed by the presence
of a low field multiplet at 8.11 assigned to 4-H, a low field signal at
170.4 in the 13C NMR spectrum for the C]O group and
d
6.43 (80-H),
d
d
d
d
a stretching bond at 1740 cmꢂ1 (C]O) in the infrared spectrum.
Additional confirmation of the amination of 2 came from the
infrared stretching band for the NH group, which appeared in the
expected region at 3378 cmꢂ1. There are only a very limited number
of examples of 30-anilino substituted benzo[a]fluorans described in
the patent literature and these have been obtained by a more
traditional and lengthy strategy involving the preparation of 6-
anilino-2-methoxynaphthalene by an Ullmann reaction [24] and
its subsequent reaction with a ketoacid [16].
Repeating the amination of 2 with a series of electron rich and
electron deficient anilines gave the 30-anilinobenzo[a]fluorans
7bed in 53e86% yield and amination of 2 with morpholine gave
a respectable yield of 7e (57%). The structure of each of the new
amino substituted benzo[a]fluorans 7be7e was confirmed by NMR
spectroscopy which indicated an upfield shift of the naphthalene
ring protons adjacent to the new amine function and the aniline NH
(7bed) appeared as a slightly broadened signal between
6.5. In the 13C NMR spectrum the lactone C]O group resonated at
ca. 170, typical for the fluoran unit [20].
d 5.5 and
d
d
80.00
80.00
70.00
60.00
50.00
40.00
30.00
20.00
10.00
0.00
70.00
60.00
50.00
40.00
30.00
20.00
10.00
0.00
400
450
500
550
600
650
400
450
500
550
600
650
wavelength (nm)
wavelength (nm)
Fig. 3. Reflectance spectra of 7c in methyl stearate containing bisphenol A at rt (lower
Fig. 4. Reflectance spectra of 7e in methyl stearate containing bisphenol A at rt (lower
line) and at ca. 50 ꢀC (upper line).
line) and at ca. 50 ꢀC (upper line).

F. Azizian et al. / Dyes and Pigments 92 (2011) 524e530
529
O
methyl stearate,
NHAr
bisphenol A,
cool
NHAr
HO2C
O
methyl stearate,
bisphenol A,
warm
Et2N
O
Et2N
O
7
colourless (very weak association between
bisphenol A and fluoran at ca. 50 oC)
coloured (strong association between
bisphenol A and fluoran at rt)
Scheme 5. Reversible colour forming process of benzo[a]fluorans 7 in methyl stearate containing bisphenol A.
[8] Wu L, Burgess K. Synthesis and spectroscopic properties of rosamines with
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development between colour forming fluorans and acidic devel-
opers such as bisphenol A are well established [26].
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The amination of bromo-fluorans and benzo[a]fluorans was
accomplished employing Pd2(dba)3 and tris(t-Bu)3P as the cata-
lysteligand combination. Electronically rich and electronically
deficient anilines coupled in moderate to good yield to 30-bromo-90-
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black shades on formulation with bisphenol A in methyl stearate.
Using an identical method amination of 20-bromo-60-di(n-butyla-
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withmorpholinegave contrastingresults withthe former proceeding
efficiently and the latter suffering from extensive debromination of
the substrate.
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This preliminary study has illustrated that a series of desirable
black colouring fluorans can be readily obtained by a simple ami-
nation protocol applied to common, readily available bromo-
substituted precursors thus obviating the need to access a wide
variety of diarylamine intermediates which require delicate
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CityofLondonare thankedfora millenniumgrantforthepurchaseof
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