A microwave-assisted synthesis of triphenodioxazines [TPDOs]

Article abstract of DOI:10.1016/j.tet.2010.06.085

A convenient and efficient method for the synthesis of triphenodioxazines [TPDOs] 1 by oxidative cyclisation of 2,5-bis-(arylamino)-3,6-dichlorocyclohexa- 2,5-diene-1,4-diones 6 using potassium persulfate as the oxidising agent in 9597% sulfuric acid trig

Full text of DOI:10.1016/j.tet.2010.06.085

Tetrahedron 66 (2010) 6761e6764
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A microwave-assisted synthesis of triphenodioxazines [TPDOs]
,
b
,
,
c
Muhammad NajeebUllah a c, David W. Knight a , Munawar Ali Munawar ,
*
Muhamad Yaseenx c, Fusillo Vincenzo a
a School of Chemistry, Cardiff University, Main College, Park Place, Cardiff CF10 3AT, UK
b Pakistan Council of Scientific and Industrial Research Laboratories, Lahore, Pakistan
c Institute of Chemistry, University of the Punjab, Lahore, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient and efficient method for the synthesis of triphenodioxazines [TPDOs] 1 by oxidative cyc-
lisation of 2,5-bis-(arylamino)-3,6-dichlorocyclohexa-2,5-diene-1,4-diones 6 using potassium persulfate
as the oxidising agent in 95‑97% sulfuric acid triggered by microwave irradiation is described.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 23 April 2010
Received in revised form 9 June 2010
Accepted 24 June 2010
Available online 3 July 2010
Keywords:
Triphenodioxazines
TPDO
Dyes
Oxidative cyclisation
Microwave
Cl
1. Introduction
R1
R1
NH2
O
Cl HO
H2N
Triphenodioxazines [TPDOs] 1 are well known compounds,
which have many applications in different fields of life, notably in
the dyeing of a diversity of materials1 including widespread use in
a variety of fibres such as textiles,2 leathers and papers.3 They are
also used in printing and as polymer dyes,4 as laser5 and fluorescent
dyes6 and as polymer photo-stabilizers.7 Such compounds also find
applications in the field of inks, especially in their use as compo-
nents of printing inks, electrophotographic toners and developers,
powder coating materials and cosmetics.8 There are also examples
of applications in optical recording systems and in optoelectronic
devices, such as optical computing, sensor protection and dynamic
holography.9
The basic chemistry of their preparation involves either
a condensation cyclisation, which may proceed directly or in-
directly, or an oxidative cyclisation (Scheme 1). In the direct
condensation/cyclisation method, 2 equiv of an o-aminophenol
3 is condensed with 1 equiv of p-chloranil 2 in the presence of
a base to remove the hydrogen chloride produced. Such re-
actions usually work well in alcoholic or water/alcohol mixtures
or simply in aqueous medium. In the indirect method, 1 equiv of
OH Cl
O
1 equiv. 3
Cl
2
3
3
Cl
R1
Δ, base
N
O
Cl
O
H2O, (ROH)
1 = R2
R
Cl
4
Cl
R2
HO
R1
R2
N
O
N
H2N
O
5
Cl
1
[O]
Cl
H
N
R1
R2
O
O
N
H
Cl
6
Scheme 1.
* Corresponding author. E-mail address: knightdw@cardiff.ac.uk (D.W. Knight).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.085

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M. NajeebUllah et al. / Tetrahedron 66 (2010) 6761e6764
an o-aminophenol 3 is condensed with p-chloranil 2 to produce
a l,2,4-trichloro-3H-aryloxazin-3-one intermediate 4, which on
further condensation with another equivalent of an o-amino-
phenol 5 gives unsymmetrical TPDO compounds [1; R1sR2].10
However, in these methods, both the amino and hydroxyl
groups of an aminophenol are reactive towards nucleophilic
displacement of the chlorine atoms in chloranil, creating a pos-
sibility of anilide formation as side reactions. Furthermore, the
method is limited to easily condensable aminophenols on both
sides.
equivalent of a dianilide intermediate 6) in 95‑97% concentrated
sulfuric acid from ambient temperature to 75 ꢀC during around
15 min. The results are presented in Table 1.
Table 1
The oxidative cyclisation of dianilides 6 into symmetrical TPDOs 1 using concd
H2SO4/persulfate under microwave conditions [50 W]
Cl
H
N
O
R
On the other hand, oxidative cyclisations feature the ring
closure of 2,5-bis-(arylamino)-3,6-dichlorocyclohexa-2,5-diene-
1,4-dione intermediates 6 to form triphenodioxazines 1. The
advantage of this approach is mainly associated with the fact that
the simpler substituted anilines required to form the initial
symmetrical or unsymmetrical benzoquinones 6 are much more
readily available than the corresponding o-aminophenols 3 and 5
required in the condensation cyclisations. Such ring closures of
the intermediate p-benzoquinones 6 normally require the use of
very high boiling solvents, such as nitrobenzene, chloronaph-
thalens or o-dichlorobenzene under reflux and using benzoyl
chloride or p-toluenesulfonyl chloride as oxidising agents; typical
reaction times are 3‑9 h.11 These very high temperatures required
by these methods unsurprisingly induce the formation of con-
siderable amounts of side products.
Alternative protocols were therefore developed in which the
intermediates 6 were cyclised in oleum using the sulfur trioxide
present as the oxidising agent. However, in this method the re-
actants and/or products can be prone to sulfonation at their various
activated positions. In order to tackle this problem, persulfates or
other compatible oxidants are used along with oleum, thereby
suppressing any sulfonation side reactions.12
In the patent literature, examples of alternative oxidants include
halogens, peroxides, iodine or benzoquinones in combination with
sulfuric acid under reflux.4,13 The reaction times are also relatively
lengthy, ranging from 4 to 12 h, giving plenty of opportunity for
product decomposition. The overall yields obtained from many of
these reactions are therefore often quite low and the desired
product(s) are formed along with a number of side products. Some
improved and more modern methods include the use of hyper-
valent iodine reagents as oxidising agents.14 Although the reported
yields are good, the method requires the use of expensive and
potentially dangerous reagents.
In view of these limitations and difficulties, we reasoned that, as
all of the oxidative cyclisation conditions required heating, such
syntheses could possibly be much improved by the application of
microwaves, as is the case in so many other synthetic trans-
formations. Examples of the application of microwave irradiation to
the improvement of a vast range of synthetic transformation are
now legion, and, in general, offer the combined advantages of
higher yields achieved in much shorter reaction times.15 Herein, we
report that this indeed seems to be the case in examples of TPDO
synthesis.
Cl
R
O
N
H
N
O
O
N
R
Cl
[O]
6
R
Cl
1
Entry
R
Reaction time
Temperature
% Yield
1
2
3
4
a¼p-NH2
b¼p-OMe
c¼p-Me
15 min
15 min
20 min
40 min
25e75 ꢀ
C
62
73
71
0
25e60 ꢀC
25e75 ꢀC
d¼p-O2N
25e95 ꢀ
C
This novel method has thus reduced the preparation time of
such triphenodioxazines 1aec from many hours to just 15 min
using this reagent combination. The method has also reduced the
temperature required to drive the reactions to completion. By using
microwave irradiation, the reaction can be carried out from 25 to
75 ꢀC. Higher temperatures can also be used but this tends to result
in extensive decomposition of the potassium persulfate. Of course,
as the temperature is increased, potassium persulfate starts to
decompose more quickly. Hence, we preferred the compromise of
a moderate temperature and use of 2.2e2.5 mol equiv of potassium
persulfate in order to compensate for some decomposition of this
oxidant. Two mole equivalents of this oxidant are required for
cyclising 1 mol equiv of intermediate 6 as there are two reactive
sites in the molecule, and 0.2e0.5 mol equiv to compensate the
decomposition in the presence of concd H2SO4. In addition, the
shorter reaction times also compensated for the gradual de-
composition of the potassium persulfate. The best temperature
range was found to be 70‑75 ꢀC at which the reactions were com-
pleted within 15 min. At lower temperatures, when persulfate de-
composition is less, the reaction times required for completion
were longer and hence 15 min at 75 ꢀC was an optimum
compromise.
We also studied the electronic effects of substituents and found
that these had a great influence on the cyclisation process. In
examples of electron donating groups, the cyclisations all worked
well under the foregoing conditions while no cyclisation was
observed when the powerful electron-withdrawing para-nitro
substituent was present, even under prolonged irradiation for
35‑40 min. This effect has been reported previously.14 By contrast,
in an example having a powerful electron donating group, such as
methoxy (entry 2), the reaction proved somewhat faster and was
completed within 15 min but at slightly lower temperatures of
between 25‑60 ꢀC.
2. Results
For this study, we chose to examine a combination of potas-
sium persulfate and concentrated sulfuric acid for the synthesis
of symmetrical TPDOs 1 from the corresponding bis-(arylamino)
derivatives 6.4,13 The present microwave method is certainly
convenient and economical and routinely delivers 70‑75% yields
of the desired products 1. After a number of trials, we settled on
the following procedure, which in detail involves heating
0.30‑0.32 mmol of an intermediate 2,5-bis-(arylamino)-3,6-
dichlorocyclohexa-2,5-diene-1,4-dione 6 with 0.80 mmol of po-
tassium persulfate (2.2‑2.5 equiv of potassium persulfate for each
The present microwave-assisted method for the preparation
of triphenodioxazines 1 is carried out at a maximum tempera-
ture of 75 ꢀC and is complete within 15e20 min using very
cheap potassium persulfate as oxidising agent in 95‑97% H2SO4
and certainly has the potential for large scale applications,
particularly in a microwave flow system,16 although, as in the
related methods, it too is limited to examples wherein the aryl
groups are electron-rich: the p-nitro derivative failed to
cyclised.

M. NajeebUllah et al. / Tetrahedron 66 (2010) 6761e6764
6763
3. Experimental
(17), 158 (19), 127 (78), 106 (23), 84 (53); calcd for C20H16Cl2N2O2: C,
62.03; H, 4.16; N, 7.23. Found: C, 61.90; H, 4.15; N, 7.21.
3.1. General information
3.3. General procedure for the preparation of
triphenodioxazines [TPDOs] 1
All reagents were purchased from Aldrich and were used as
received. The microwave instrument used was a CEM DISCOVERY.
1H NMR spectra were recorded using a Bruker DPX spectrometer
operating at 400 MHz. All NMR measurements were carried out at
30 ꢀC and chemical shifts are reported as ppm on the delta scale
A p-benzoquinone intermediate 6 (0.32 mmol) was mixed and
finely ground with potassium persulfate (0.80 mmol) and the
resulting powder transferred to a microwave tube to which 95‑97%
concentrated sulfuric acid (2.5 mL) was then added. The tube was
then capped and subjected to microwave irradiation at 25‑75 ꢀC
and 50 W power for a period of 15 min with stirring. After the re-
action was completed, the tube was cooled and its contents poured
into 10 g of crushed ice. The resulting precipitate was removed by
suction filtration and washed with water until the filtrate showed
no acidity. Analytical samples could be secured by dissolving
a small quantity of a crude product in DMF and applying the
resulting solution to a silica gel column and eluting with 1:1 EtOAc/
petroleum ether. The bulk triphenodioxazines 1 obtained in the
present study were recrystallized from DMF. The percentage yield
of the isolated and purified triphenodioxazine compounds are
given in Table 1.
downfield from tetramethylsilane (TMS:
d
¼0.00). Coupling con-
stants (J) are reported in hertz. UVevis spectra were measured
using a JASCO-v-570 spectrophotometer. Infrared spectra were
recorded from KBr discs using a Nicolet Impact-410 FTIR spectro-
photometer. Low resolution mass spectra were obtained using a VG
Platform II Quadrupole spectrometer operating in the electron
impact (EI, 70 eV) or atmospheric pressure chemical ionization
(ApcI) modes, as stated. High resolution mass spectrometric data
were obtained using the ionization modes specified. Melting points
were determined using a Kofler hot stage apparatus and are un-
corrected. Elemental analyses were obtained using a PerkineElmer
2400 Elemental Microanalyser.
3.2. Preparation of benzoquinone intermediates 617
3.3.1. 2,9-Diamino-6,13-dichlorotriphenodioxazine 1a. By the gen-
eral procedure, oxidative cyclisation of the benzoquinone 6a gave
the TPDO 1a as a purple powder, mp >300 ꢀC; lmax (DMF)/nm 560;
nmax (KBr)/cmꢁ1 3345, 3219, 2364, 2342, 1529, 1445, 1318, 1271,
1242, 1208, 1130, 1024, 898, 873; dH (DMSO-d6) 6.02 (4H, br s,
2ꢂNH2), 6.62 (2H, d, J 2.3 Hz, 1- and 8-H), 6.68 (2H, dd, J 8.6, 2.3 Hz,
3- and 10-H), 7.41 (2H, d, J 8.6 Hz, 4- and 11-H); calcd for
C20H10Cl2N4O2: C, 56.12; H, 2.62; N, 14.54. Found: C, 55.93; H, 2.61;
N, 14.19.
3.2.1. 2,5-Bis-(4-aminophenylamino)-3,6-dichlorocyclohexa-2,5-di-
ene-1,4-dione 6a. To a stirred solution of p-phenylenediamine
(4.00 g, 37.0 mmol) in water (10 mL) maintained between 40‑45 ꢀC
was added an intimate mixture of sodium bicarbonate (3.20 g,
38.1 mmol) and p-chloranil (4.55 g, 18.5 mmol) in small portions.
Stirring was continued for 1 h and then the temperature of the re-
action mixture was increased to 60 ꢀC and maintained at this value
for a further 2 h. The course of the reaction was monitored by silica
gel TLC [EtOAc/hexanes (30:70)þ2% MeOH]. The reaction mixture
was then cooled and the resulting precipitate isolated by suction
filtration. The solid was washed extensively with cold and hot water
and then finally with ethanol and dried under vacuum. The product
6a was obtained as a brown solid (6.56 g, 77%). An analytical sample
was secured by dissolving a little of the product in DMF/acetone
followed by separation using silica gel column chromatography (2:3
EtOAc/hexanes). The pure product 6a showed mp >300 ꢀC; nmax
(KBr)/cmꢁ13380, 3252,1651,1575,1514,1490,1434,1329,1291,1256,
1197,1170,1084,1016, 890, 757; dH (DMSO-d6) 5.98(4H, br s, 2ꢂNH2),
6.71 (4H, d, J 8.5 Hz, 4ꢂAreH), 6.95 (4H, d, J 8.5 Hz, 4ꢂAreH), 9.57
(2H, s, 2ꢂNH); calcd for C18H14Cl2N4O2: C, 55.54; H, 3.63; N, 14.39.
Found: C, 55.54; H, 3.61; N, 14.32.
3.3.2. 6,13-Dichloro-2,9-dimethoxytriphenodioxazine 1b. By the gen-
eral procedure, oxidative cyclisation of the benzoquinone 6b gave
the TPDO 1b as a purple solid, mp >300 ꢀC [lit.17 mp >360 ꢀC]; lmax
(DMF)/nm 540.5; nmax (KBr)/cmꢁ1 3040, 2980, 2936, 1630, 1609,
1600, 1560, 1548, 1480, 1440, 1250, 1220, 1150, 1115, 1100, 1049,
1020, 850; dH (DMSO-d6) 3.83 (6H, s, 2ꢂOMe), 7.10 (2H, d, J 2.4 Hz,
1- and 8-H), 7.20 (2H, dd, J 8.7, 2.4 Hz, 3- and 10-H), 7.58 (2H, d, J
8.7 Hz, 4- and 11-H); calcd for C20H12Cl2N2O4: C, 57.85; H, 2.91; N,
6.75. Found: C, 57.67; H, 2.90; N, 6.73.
3.3.3. 6,13-Dichloro-2,9-dimethyltriphenodioxazine 1c. By the gen-
eral procedure, oxidative cyclisation of the benzoquinone 6c gave
the TPDO 1c as a red solid, mp >300 ꢀC [lit.17 mp >360 ꢀC]; lmax
(DMF)/nm 532; nmax (KBr)/cmꢁ1 3030, 2980, 1625, 1570, 1550, 1480,
1440, 1409, 1290, 1245, 1150, 1120, 1110, 1085, 1070, 1020, 850, 830,
792, 730, 700; dH (DMSO-d6) 2.40 (6H, s, 2ꢂMe), 6.99 (2H, d,
J¼2.2 Hz, 1- and 8-H), 7.08 (2H, dd, J¼8.4, 2.2 Hz, 3- ad 10H), 7.46
(2H, d, J¼8.4 Hz, 4- and 11-H); calcd for C20H12Cl2N2O2: C, 62.68; H,
3.16; N, 7.31. Found: C, 62.50; H, 3.15; N, 7.29.
3.2.2. 2,5-Bis-(4-methoxyphenylamino)-3,6-dichlorocyclohexa-2,5-
diene-1,4-dione 6b. Benzoquinone 6b was prepared according to
the foregoing procedure17 on
a similar scale staring with
p-methoxyaniline and was isolated in similar yield as a brown solid,
mp 282 ꢀC (decomp.), [lit.17 mp 298 ꢀC]; nmax (KBr)/cmꢁ1 3221,
3013, 1651, 1609, 1568, 1510, 1486, 1417, 1322, 1306, 1244, 1195, 1171,
1112, 1032, 1012, 948, 894, 800; dH (DMSO-d6) 3.76 (6H, s, 2ꢂOMe),
6.90 (4H, d, J 8.3 Hz, 4ꢂAreH), 7.11 (4H, d, J 8.3 Hz, 4ꢂAreH), 9.62
(2H, s, 2ꢂNH); m/z (EI) 418 (Mþ, (35Cl); 64%), 386 (57), 350 (41), 250
(7), 174 (22), 146 (8), 108 (45), 84 (15); calcd for C20H16Cl2N2O4: C,
57.30; H, 3.85; N, 6.68. Found: C, 57.21; H, 3.84; N, 6.66.
4. Conclusion
We report herein a new microwave method for the preparation
of triphenodioxazines [TPDOs] 1. This new method has reduced the
time of reaction from a number of hours to just 15 min and de-
creased the temperature from 150‑200 ꢀC to 25‑75 ꢀC.
3.2.3. 2,5-Bis (p-tolylamino)-3,6-dichlorocyclohexa-2,5-diene-1,4-di-
one 6c. Benzoquinone 6c was prepared in similar yield by the fore-
going procedure17 from 4-methylaniline and showed mp >300 ꢀC
[lit.17 mp >310 ꢀC (decomp.)]; nmax (KBr)/cmꢁ1 3232,1648,1610,1561,
1510, 1475, 1404, 1322, 1307, 1248, 1198, 1172, 1109, 1034, 1020, 944,
890, 800; dH (DMSO-d6) 3.34 (6H, s, 2ꢂMe), 7.05 (4H, d, J 8.2 Hz,
4ꢂAreH), 7.15 (4H, d, J 8.2 Hz, 4ꢂAreH), 9.63 (2H, s, 2ꢂNH); m/z 388
(Mþ, (35Cl); 100%), 371 (17), 355 (51), 336 (9), 315 (38), 267 (32), 192
Acknowledgements
We gratefully acknowledge a grant given from the Higher Ed-
ucation Commission of Pakistan under the IRSIP programme to
support PhD students (to MN).

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