A quantitative one-pot synthesis method for industrial azo pigments with recyclable wastewater

Article abstract of DOI:10.1039/c8gc03982h

Most industrial azo pigments are synthesized by diazotization in one pot and then coupling in another. This two-pot process has been transformed into a one-pot method by adding granular PTFE (polytetrafluoroethylene) to a mechanically agitated aqueous mixture of NaNO₂, HCl, a diazo component and a coupling component. This method avoids the step of using a base or a surfactant to dissolve the coupling component. The reactions were fast and quantitative. The granular PTFE, wastewater and excess HCl were then reused 11 times without deteriorating the reaction rate and product purity. Altogether, 22 industrial pigments and 3 azo compounds were synthesized and the reaction can produce up to 22.7 g of product in the laboratory. Some reactions require less than 2 equiv. of HCl and a mechanism explaining this is proposed. In addition, an o-nitro group effect is advanced to explain the differences in coupling reaction rates for o-, m- and p-nitroaniline.

Full text of DOI:10.1039/c8gc03982h

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: G. Feng, M. Zhu,
L. Liu and C. Li, Green Chem., 2019, DOI: 10.1039/C8GC03982H.
This is an Accepted Manuscript, which has been through the
Volume 18 Number
7 7 April 2016 Pages 1821–2242
Royal Society of Chemistry peer review process and has been
accepted for publication.
Green
Chemistry
Accepted Manuscripts are published online shortly after
Cutting-edge research for a greener sustainable future
www.rsc.org/greenchem
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1463-9262
CRITICAL REVIEW
G. Chatel et al.
Heterogeneous catalytic oxidation for lignin valorization into valuable
chemicals: what results? What limitations? What trends?
rsc.li/green-chem

Please do not adjust margins
Page 1 of 8
Green Chemistry
View Article Online
DOI: 10.1039/C8GC03982H
Journal Name
ARTICLE
Quantitative one-pot synthesis method for industrial azo
pigments with recyclable wastewater
Guangyuan Feng,a Meiling Zhu,a Lei Liub and Chunbao Li*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Most industrial azo pigments are synthesized by diazotization in one pot and then coupling in another. This two-pot
process has been transformed into a one-pot method by adding granular PTFE (polytetrafluoroethylene) to a mechanically
agitated aqueous mixture of NaNO2, HCl, a diazo component and a coupling component. This method avoids the step of
using a base or surfactant to dissolve the coupling component. The reactions were fast and quantitative. The granular
PTFE, wastewater and excess HCl were then reused 11 times without deteriorating the reaction rate and product purity.
Altogether, 22 industrial pigments and 3 azo compounds were synthesized and the reaction can produce up to 22.7 g of
product in the laboratory. Some reactions require less than 2 equiv of HCl and a mechanism explaining this is proposed. In
addition, an o-nitro group effect is advanced to explain the differences in coupling reaction rates for o-, m- and p-
nitroaniline.
www.rsc.org/
of the coupling component. It is estimated that the production of
Introduction
one ton of pigments uses 120-380 tons of water and in 2010, in just
China alone, this resulted in 2.69-8.51×107 tons of wastewater.2,8,11
Azo compounds are used in many fields such as printing,1 paints,1
color photography,2 textile,3 chemical research,4 materials,5
biopharmaceutical research,6 and metallochromic indicators.7 In
2010, ca 560,000 tons of industrial organic pigments were produced
worldwide and 59% of that was azo pigments, valued at more than
7 billion dollars.2,8 Several types of reactions are used to synthesis
azo compounds including azo coupling reaction, the Mills reaction,
the Wallach reaction, the reduction of azoxybenzenes, the
oxidation of anilines, the dehydrogenation of arylhydrazines, and
the dimerization reaction of diazonium salts.9
Azo coupling reactions are widely used for the preparation of azo
pigments on an industrial scale. There are three types of coupling
methods: direct coupling, indirect coupling, and the “Pendulum”
technique.10 In the direct coupling method, the coupling
component is first dissolved in an alkaline solution. The solution is
filtered and then acid is added to form a suspension, to which the
diazonium compound is added. In the indirect method, a clarified
Further few of the reactions are quantitative and the waste brine
from these reactions are environmentally hazardous and toxic to
aquatic life as well as being aesthetically unacceptable.12,13 The
treatment of these wastewaters is very costly.
Therefore many efforts have been made to make these reactions
green. These have included using solid acids to replace HCl,14 using
HNO3(ac)/HCl(g) to replace NaNO2,15 using a CO2/H2O system to
synthesize the diazonium salts,16 using clay catalysts like bentonite,
kaolin or K10 for the diazotization reactions,17 and solventless
syntheses.18 However, the yields for these methods are not
quantitative and in some cases the products had to be purified by
chromatography. In another report, a suspension of the coupling
compound was achieved by simply heating the coupling compound
in water but this took a long time and required two vessels,
although it was claimed to be a one-pot reaction.19
In previous work, our research group has used granular PTFE to
make organic solvent-mediated reactions green.20,21,22 Herein, we
report the application of this approach to the synthesis of azo
compounds. Granular PTFE was added to a mechanically agitated
aqueous mixture of a diazo component, a coupling component, HCl
and NaNO2 to produce a variety of azo compounds. The mother
liquid was then reused in another cycle after adding 1.0 equiv of
fresh HCl. The wastewater, granular PTFE and excess HCl could be
recycled 11 times.
acidic diazonium salt solution is introduced into
a solution
containing the alkaline coupling compound. In the “Pendulum”
technique, a constant pH is maintained by adding a dilute NaOH
solution to the coupling reaction.
All these methods require more than 1.0 equiv of base to
transform the coupling components into their salts, and this base
then has to be neutralized. This results in large amounts of waste
brine. In some cases, surfactants are used to enhance the solubility
a. Department of Chemistry, School of Science, Tianjin University, 135 Yaguan Road,
Jinnan District, Tianjin 300354, P. R. China. E-mail: lichunbao@tju.edu.cn.
b. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute
of Pharmaceutical Research, Tianjin 300193, P. R. China.
Electronic Supplementary Information (ESI) available. See
DOI: 10.1039/x0xx00000x
Results and discussion
Initially the synthesis of Pigment Red 1 (Table 1, 1) was investigated
by mechanically stirring a mixture of 2-naphthol (1 g), p-nitroaniline
(1.05 equiv), HCl (1.25 equiv), H2O (3 mL), a solution of NaNO2 (1.10
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 2 of 8
ARTICLE
Journal Name
equiv, in 2 mL of H2O) and granular PTFE (2.5 g) at 40 °C for 2 h large energy-savings. Traditionally azo couplings are a three-step
View Article Online
DOI: 10.1039/C8GC03982H
(Table 1, entry 1). After filtration and drying the product, a two-pot reaction but this synthesis is one-step and one-pot and
quantitative yield of 1 was obtained. Increasing the amount of HCl therefore represents a great improvement in pot efficiency.
to 2 equiv and lowering the reaction temperature to rt shortened Table 1 Optimization of the synthesis of Pigment Red 1 (1)a
the reaction time from 2 h to 5 min and still resulted in a
quantitative yield (Table 1, entry 2). Further increasing the amount
NH2
OH
of HCl to 3.5 equiv did not change the performance of the reaction
(Table 1, entry 3). The same was true when the amount of H2O was
increased to 8 mL (Table 1, entry 4). However, when the amount of
H2O was reduced to 0 mL, the reaction was incomplete (81% in 120
min) (Table 1, entry 5). Quantitative yields were also obtained in 5
min when the 2 equiv of HCl was replaced with 2 equiv of H2SO4,
H3PO4 or HBF4 (Table 1, entries 6-8). Traditionally HCl has been used
in the synthesis of azo pigment, so it was chosen. Based on these
results the optimal amounts of water and HCl for this reaction are 3
mL and 2 equiv respectively and the optimal temperature is rt.
Six azo products were then prepared using this one-pot
procedure (Table 2, 1-6). The products were collected by simple
filtration, washed with water and then dried. All the reactions were
quantitative and fast (5-90 min). Some of the reaction times could
be shortened by adjusting the amount of acid. For example, using
2.35 equiv of HCl to prepare 4 and 5 shortened the reaction time
(Table 2, entries 8 and 10). The amount of HCl was reduced to less
than 2 equiv by conducting the reactions at rt (Table 2, entries 6
and 11) or 40 °C (Table 2, entries 2 and 4). The reaction rate
differences for entries 7 and 9 can be attributed to the different
solubilities of acetoacetanilide (32290 mg/L) and 2’,4’-
dimethylacetoacetanilide (3327.9 mg/L).23 Since the former is more
soluble, it reacts faster.
N
HCl, NaNO2
N
+
H2O, granular PTFE
OH
NO2
1, Pigment Red 1
NO2
Acid
H2O
T
t
Conversionb Isolated
Entry Acid
(equiv) (mL) (°C) (min) (%)
yield (%)
1
2
3
4
5
6
7
8
HCl
HCl
HCl
HCl
HCl
1.25
2
3
3
3
8
0
3
3
3
40
rt
rt
rt
rt
rt
rt
rt
120
5
100
100
100
100
81
>99
>99
>99
>99
-
3.5
2
5
5
2
120
5
H2SO4
H3PO4
HBF4
2
100
100
100
>99
>99
>99
2
5
2
5
aReaction conditions: 2-naphthol (1 g), p-nitroaniline (1.05 equiv), NaNO2
(1.10 equiv, in 2 mL of H2O), acid, H2O, granular PTFE (2.5 g), mechanical
stirring (400 rpm). bDetermined by 1H NMR.
In the classical synthesis of azo pigments, the diazotization and
azo coupling reactions need two pots. The diazotization is often
carried out at 0 °C and here this was done at rt, so this represents a
Table 2 One-pot synthesis of azo compounds in the presence of granular PTFEa
HCl, NaNO2
H2O, granular PTFE
Azo compound
Coupling component + Ar-NH2
Coupling component = 2-naphthol, acetoacetanilides, 4-tert-butylphenol
HCl
(equiv)
t
Isolated
yield (%)
Entry
1
Product
T (oC)
rt
(min)
2
5
>99
>99
OH
N
N
2
1.25
40
90
NO2
, Pigment Red 1
1
O
O
N
N
3
4
2
rt
90
45
>99
>99
H
N
1.25
40
NO2
, Pigment Yellow 4
2
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 3 of 8
Green Chemistry
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C8GC03982H
>99
O
O
5
6
7
2
rt
rt
rt
40
45
30
N
H
N
N
NO2
1.5
>99
>99
3
, Pigment Yellow 1
2
NH
HN
O
O
O
O
N
N
N
N
Cl
Cl
8
9
2.35
2
rt
rt
20
45
>99
>99
4
, Pigment Yellow 12
HN
NH
O
O
O
O
N
N
N
N
10
11
2.35
1.25
rt
rt
20
60
>99
>99
Cl
Cl
5
, Pigment Yellow 13
N
N
OH
NO2
6
aReaction conditions: coupling component (1 g), aromatic primary amine (1.05 equiv), HCl, H2O (3 mL), NaNO2 (1.10 equiv, in 2 mL of H2O), granular PTFE (2.5
g), mechanical stirring (400 rpm).
In order to save water and avoid using excess HCl, the reaction whereas in the classical procedure this proton is not
recyclability of the reaction media in the synthesis of 3 was tested. reused and has to be neutralized by 1 equiv of base.
The mother liquid, PTFE and washing water from the filtration were
used in a second cycle. In addition to the reaction reagents
H2ONO
OH
N
N
H2N
(acetoacetanilide, 4-methyl-2-nitroaniline and NaNO2), 1.1 equiv of
HCl was added to acidify NaNO2 in the next cycle. The first cycle was
complete in 45 min and the second cycle only needed 30 min. This
procedure was repeated 11 times and quantitative yields were
obtained in all cases. The reaction time was 30 min for all the cycles
after the first one which is because the HCl accumulated with
subsequent cycles. At the end of 11th cycle, the volume of the
mother liquid and washing water was 15.5 mL.
Ar
NaNO2
HNO2
H
+
H
Ar
-H
H2O
+H
H
N
H
O
N
Ar
I
Ar
N
Ar
H
Ar
N
OH
N
O
OH
H
N
H
N
H
N
OH
OH
OH
-H2O
Theoretically, more than 2 equiv of HCl are required to carry out
the diazotization and coupling reactions. However, less than 2 equiv
of HCl were needed for the syntheses of 1, 2, 3 and 6 (Table 2). A
proposed mechanism for this reaction is shown in Scheme 1. First
NaNO2 is converted into HNO2 using 1 equiv of HCl. The protonated
nitrous acid then nitrosates aniline to form I, and I couples with 2-
naphthol to form II. The deprotonation of II produces III and then a
H2O molecule is eliminated to yield the final product. The proton
liberated in the conversion of II to III is then used to protonate
nitrous acid. As seen from the mechanism, the 1 equiv of H+
liberated after the coupling reaction is reused to continue the
III
II
Scheme 1 Proposed mechanism for the synthesis of azo pigments
using less than 2 equiv of HCl.
When this one-step, one-pot procedure was applied to other
pigments, the reaction mixture agglomerated around the granular
PTFE and the reaction was incomplete. This problem was solved by
performing the one-pot reaction in two steps. First a mixture of 2-
chloro-4-nitroaniline (1.05 equiv), HCl (3 equiv), H2O (3 mL), NaNO2
(1.10 equiv, in 2 mL of H2O) and granular PTFE (2.5 g) was stirred for
20 min and then 2-naphthol (1 g) was added to the reaction mixture
(Table 3, entry 1). The product was collected by simple filtration,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 4 of 8
ARTICLE
Journal Name
washed with water and then dried. The reaction was quantitative.
When the amount of H2O was increased from 3 to 8 mL, the
View Article Online
DOI: 10.1039/C8GC03982H
One major difference between our synthesis and the classical
reaction results were the same (Table 3, entry 2). However, when 0 method is the use of granular PTFE in the agitated the reaction.
mL of H2O was used (Table 3, entry 3), the reaction was incomplete Therefore, the effect of the ratio of substrate to granular PTFE was
(conversion 75%, 120 min). Lowering the amount of HCl from 3 investigated using the synthesis of Pigment Red 4 (Table 4, 7). First
equiv to 2 or 1.25 equiv also led to incomplete reactions (Table 3, a mixture of 2-chloro-4-nitroaniline (1.05 equiv), HCl (3 equiv) in
entries 4 and 5).
H2O (3 mL), NaNO2 (1.10 equiv, in 2 mL of H2O) and granular PTFE
was stirred at rt for 20 min and then 2-naphthol (1 g) was added. To
1 g of 2-naphthol were added 0.5 g, 1.5 g, 2.5 g, 5 g, and 10 g of
granular PTFE respectively (Table 4, entries 1-5). With 0.5 g granular
PTFE (Table 4, entry 1), a yield of only 79% was achieved at 60 min.
With 1.5 g granular PTFE, the reaction was over in 60 min (Table 4,
entry 2) and for 2.5 g, 40 min was required (Table 4, entry 3). When
5 or 10 g granular PTFE (Table 4, entries 4-5) was used, the
reactions were complete in 10 min. The reaction rate with 1.5 g
granular PTFE is acceptable (2-naphthol:granular PTFE = 1:1.5).
When the amount of 2-naphthol was increased to 5 g and the
granular PTFE to 7.5 g, the reaction took 60 min (Table 4, entry 6, 2-
naphthol:granular PTFE = 1:1.5). When the scale of the reaction was
further increased (Table 4, entry 7, 10 g of 2-naphthol, 12 g of
granular PTFE; 2-naphthol:granular PTFE = 1:1.2), the reaction was
complete in 20 min. If the amount of granular PTFE was reduced to
10 g, then the reaction took 60 min (Table 4, entry 8, 2-
naphthol:granular PTFE = 1:1). These results show that when the
reaction scale is increased from 1 to 10 g, the ratio of 2-naphthol to
granular PTFE is increased from 1:1.5 to 1:1.
Table 3 Optimization of the synthesis of Pigment Red 4 (7)a
OH
NH2
NO2
(1) HCl, NaNO2, H2O,
granular PTFE, rt, 20 min
N
Cl
N
Cl
(2) 2-naphthol
NO2
7
, Pigment Red 4
HCl
(equiv)
H2O
(mL)
3
T
t
Conversionb
(%)
100
Isolated
yield (%)
>99
Entry
(oC)
rt
(min)
10
1
2
3
4
5
3
3
8
0
3
3
rt
rt
rt
rt
10
100
75
>99
3
120
60
-
-
˗
2
71
1.25
120
85
aReaction conditions: 2-chloro-4-nitroaniline (1.05 equiv), HCl, H2O, NaNO2
(1.10 equiv, in 2 mL of H2O) and granular PTFE (2.5 g), mechanical stirring
(400 rpm), 20 min; 2-naphthol (1 g). bDetermined by 1H NMR.
Table 4 Effects of granular PTFE on the reaction ratesa
OH
NH2
Cl
(1) HCl, NaNO2, H2O,
granular PTFE, rt, 20 min
N
N
Cl
(2) 2-naphthol
NO2
NO2
7
, Pigment Red 4
Amount of
granular PTFE (g)
0.5
10 min, 20 min, 40 min, 60 min,
Entry Amount of 2-naphthol (g)
2-Naphthol:Granular PTFE H2O (mL)
C b (%)
70
C b (%)
71
C b (%)
74
C b (%)
79
1
1
1:0.5
1:1.5
1:2.5
1:5
3
2
1
1.5
2.5
5
3
71
81
100
100
78
76
75
˗
79
91
˗
85
100
˗
100
˗
3
1
3
4
1
3
˗
5
1
10
7.5
12
10
0
1:10
1:1.5
1:1.2
1:1
3
˗
˗
˗
6
5
23
45
45
3
84
100
78
˗
86
˗
100
˗
7
10
10
1
8
85
˗
100
50
75
9
˗
10
1
0
˗
3
˗
˗
˗
aReaction conditions: 2-chloro-4-nitroaniline (1.05 equiv), HCl (3.0 equiv), NaNO2 (1.10 equiv, in 2 mL of H2O), H2O and granular PTFE, mechanical stirring
(400 rpm), 20 min; 2-naphthol (1 g). bConversion, determined by 1H NMR.
In the control experiments, with magnetic stirring and regular were 50% and 75% respectively (Table 4, entries 9 and 10). The
mechanical stirring and no granular PTFE, the conversions at 60 min results for the twice 10-g scale reactions (product scale: 22.7 g)
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 5 of 8
Green Chemistry
Journal Name
ARTICLE
indicate the possibility that this method maybe suitable for the oxygen atom can stabilize the neighboring positVivieewlyArticchleaOrngleinde
industrial scale up of azo pigments.
diazonium salt (Scheme 2, B). This makesDtOhIe: 1d0i.a10z3o9n/iCu8mGCsa0l3t98le2sHs
The success of this reaction is due to the large number of PTFE electrophilic toward the coupling component. We call this the o-
granules that under stirring have large momentums. Thus they can nitro group effect. This effect can also be used to explain the
smash the water-insoluble coupling component and the insoluble classical synthesis with o-nitroaniline as the diazo component
pigment product. Its function is similar to the step in the classical where the coupling reaction took 19 h, whereas p-nitroaniline only
process where coupling component in alkaline solution is converted took 19 min.25,26
into fine particles upon addition of acid. In the large scale
preparations, the radius of the flask is larger and the granular PTFE
have even higher momentums. That is why a higher ratio of 2-
naphthol to granular PTFE can be used in the large scale reactions.
This phenomenon has previously been observed in the aqueous
synthesis of insoluble esters.20
N
H
H2N
O
N
N
O
N
O
O
B
A
: stabilized diazonium salt
: stabilized salt
Scheme 2 o-Nitro group effect.
This method was then used to synthesize 17 industrial organic
pigments and 2 azo compounds (Scheme 3, products 7-25). All of
the reactions were completed within 10 to 60 min. Most of the
reactions were conducted at rt with a few done at 60 °C. All the
products were obtained in quantitative yields after simple filtration
with no further purification. For 12 and 13, 10 equiv of H2SO4 was
used because 3 equiv of HCl gave incomplete reactions.
In the synthesis of 2-naphthol-based pigments, p-nitroaniline and
m-nitroaniline diazo components reacted faster than o-nitroaniline
compounds (Scheme 3, 7-9 vs 10-13). An explanation for this was
not found in the literature10,24 but we believe that the negatively
charged oxygen atom on the o-nitro group plays an important role.
This effect is shown in Scheme 2. The nitro group forms a stabilized
salt (Scheme 2, A) that makes the amino group less nucleophilic
toward the nitrosating agent. In addition, the negatively changed
This o-nitro group effect was not observed for the four
pyrazolone-based pigments (Scheme 3, 14-17). All these reactions
were carried out at rt and were fast (10-20 min). This is probably
because the pyrazolone ring is less hindered and more nucleophilic
than the 2-naphthol ring.
A comparison of the reaction rates for the six acetoacetanilide-
based pigments (Scheme 3, 18-23) shows that the solubility of the
coupling component affects the reaction rate. Higher diazo
component solubilities resulted in higher reaction rates
(acetoacetanilide: 32290 mg/L (10 min), o-acetoacetaniside: 17769
mg/L (60 min), 5-acetoacetlamino benzimdazolone: 125.07 mg/L
(60 min)).23 The syntheses of the heterocycle-based azo compounds
(Scheme 3, 24 and 25) were fast (10 min) and quantitative.
(1) HCl, NaNO2, H2O, granular PTFE, rt, 20 min
Ar-NH2
Azo compound
(2) Coupling component
Coupling component = 2-naphthol, acetoacetanilides, 1,2-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one,
imidazole, barbituric acid
OH
OH
OH
OH
N
N
N
N
N
N
N
N
Cl
NO2
O2N
NO2
rt, 10 min
, Pigment Red 4
rt, 10 min
, Pigment Orange 3
rt, 40 min
60 oC, 60 min
7
8
9
, Sudan I
10
, Pigment Red 3
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 6 of 8
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C8GC03982H
OH
OH
OH
N
N
N
N
N
N
NO2
NO2
NO2
Cl
NO2
60 oC, 60 min
rt, 60 min
rt, 60 min
13
, Pigment Orange 5
c
c
11
12
, Pigment Red 6
, Pigment Orange 2
Cl
Cl
Cl
NO2
N
N
N
N
N
N
O
O
O
N
N
N
N
N
N
rt, 10 min
, Pigment Orange 6
rt, 10 min
, Pigment Yellow 10
rt, 10 min
16
, Pigment Yellow 60
14
15
N
N
N
N
N
N
N
N
O
O
Cl
Cl
rt, 20 min
, Pigment Orange 13
17
O
O
N
O
O
N
O
O
N
O
O
N
N
N
H
N
N
H
N
O
H
H
N
O
N
N
NO2
NO2
NO2
NO2
Cl
Cl
60 oC, 60 min
rt, 10 min
, Pigment Yellow 5
rt, 60 min
20
, Pigment Yellow 203
rt, 10 min
, Pigment Yellow 6
19
18
21
, Pigment Yellow 73
H
N
H
N
O
O
O
O
N
O
O
N
N
H
N
N
H
H
H
N
N
N
NO2
NO2
Cl
60 oC, 60 min
rt, 60 min
23
, Pigment Orange 36
22
, Pigment Orange 62
O
H
N
HN
HN
N
O
N
N
N
N
NO2
NO2
O
rt, 10 min
rt, 10 min
24
25
Scheme 3 Quantitative synthesis of azo compounds in the presence of granular PTFE in one pota, b. Reaction conditions: aniline (1.05 equiv), HCl
a
(3.0 equiv), H2O (3 mL), NaNO2 (1.10 equiv, in 2 mL of H2O) and granular PTFE (2.5 g), mechanical stirring (400 rpm), rt, 20 min; coupling component (1 g). bAll
c
yields are quantitative. Reaction conditions: H2SO4 (10.0 equiv), NaNO2 (1.10 equiv), and granular PTFE, rt, 5 min; 2,4-dinitroaniline or o-nitroaniline (1.05
equiv), 0 oC, 20 min; 2-naphthol (1 g), H2O (2 mL), rt, 60 min.
The recyclability of the reaction media was again explored using granular PTFE and washing water from the filtration was used in the
10 (Scheme 3) as the test compound. As before, the mother liquid, next cycle and an additional 1.0 equiv of HCl was added to each
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 7 of 8
Green Chemistry
Journal Name
ARTICLE
cycle. This procedure was repeated 11 times. Each cycle took 60 the end of the 11th cycle, the volume of the mother liquid and
View Article Online
DOI: 10.1039/C8GC03982H
min to reach completion and all the reactions were quantitative. At washing water was 17 mL.
Table 5 Performance comparison between our method and the current industrial method for the synthesis of Pigment Red 3 (10) starting
from 11 g of 2-naphthol
Surfactant
consumed
(g)
Water consumed
(mL)
HCl consumed
(g)
NaOH consumed
(g)
Yield (%)
This work
15
9.1
27
0
0
>99
93
Current industrial method8
450
10.5
0.22
We have repeated the reaction for preparing Pigment Red 3 (10) aqueous reactions were conducted in 100-mL flasks (except for the
starting from 11 g of 2-naphthol according to the current industrial 22.7-g-scale preparation which used 250-mL flasks). The reactions
method.8 A performance comparison between this method starting were agitated by a modified stirring rod.20,21,22 The size of the
from 1 g of 2-naphthol in each of the 11 cycles and the current granular PTFE was 30 pieces/g.
industrial method for the synthesis of Pigment Red 3 (10) is shown General procedure for the preparations of azo pigments
in Table 5. Obviously our method is superior to the current
For products 1-6, a mixture of the coupling component (1 g),
industrial method in all respects. The industrial method consumes aromatic primary amine (1.05 equiv), HCl (2 equiv), H2O (3 mL),
much more water, HCl and NaOH; it requires the use of sulfonated NaNO2 (1.10 equiv, in 2 mL of H2O) and granular PTFE (2.5 g) was
castor oil (a surfactant); and the yield is lower.
mechanically stirred (400 rpm) at rt. Thin-layer chromatography
With the exception of products 6, 24 and 25, all the other (TLC) indicated the completion of the reaction. After stopping the
products (Table 2, 1-5 and Scheme 3, 7-23) are organic industrial reaction, the products were suspended in water while the granular
pigments. If our process could be adapted industrially, it should PTFE precipitated on the bottom of the flask. The suspended
save large amounts of labor and energy and reduce or eliminate the products were filtered, washed with water (2 mL) and dried to give
use of water, bases, acids and surfactants. This would have a quantitative yield of the product without further purification.
tremendous positive environmental and economic impacts.
For products 7-25, a mixture of aromatic primary amine (1.05
equiv), HCl (3 equiv), H2O (3 mL), NaNO2 (1.10 equiv, in 2 mL of H2O)
and granular PTFE (2.5 g) was mechanically stirred (400 rpm) at rt.
After 20 min, the coupling component (1 g) was added. The
reaction was continued until TLC indicated the completion of the
reaction. After stopping the reaction, the products were suspended
in water while the granular PTFE precipitated on the bottom of the
flask. The suspended products were filtered, washed with water (2
mL) and dried to give a quantitative yield of the product without
further purification.
Conclusions
In conclusion, one-step, one-pot and two-step, one-pot methods
for the synthesis of azo pigments have been developed and applied
to 22 industrial pigments. Compared to the current methods, these
methods are fast, quantitative, pot-efficient and do not require the
use of surfactants or bases to dissolve the coupling components.
The granular PTFE, water and HCl used in the reaction are
recyclable. These reactions can produce up to 22.7 g of product in
the laboratory. If these methods are adapted for the industrial
production of azo compounds, they will be cost efficient,
environmentally friendly, save large amounts of labor, water and
acids and eliminate the use of bases and surfactants. An o-nitro
group effect, which is also applicable to classic synthesis, has been
proposed to explain the differences in reaction rates.
Preparation of Pigment Red 4 (7) in 22.7 g scale
A mixture of 2-chloro-4-nitroaniline (1.05 equiv), HCl (3 equiv),
H2O (45 mL), NaNO2 (1.10 equiv, in 5 mL of H2O) and granular PTFE
(12 g) was mechanically stirred (400 rpm) at rt. After 20 min, 2-
naphthol (10 g) was added. The reaction was continued for 20 min
and TLC was used to confirm the completion of the reaction. After
stopping the reaction, the products were suspended in water while
the granular PTFE precipitated on the bottom of the flask. The
suspended products were filtered, washed with water (5 mL) and
dried to give a quantitative yield of the product without further
purification.
Experimental
General information. All of the chemicals were obtained from
Wastewater and excess HCl recycling in the preparation of
Pigment Yellow 1 (3)
commercial sources. NMR spectra were recorded with a 400-MHz
1
spectrometer for H NMR and a 101-MHz instrument for 13C NMR
A mixture of acetoacetanilide (1 g), 4-methyl-2-nitroaniline (1.05
equiv), HCl (1.5 equiv), H2O (8 mL), NaNO2 (1.10 equiv, in 2 mL of
H2O) and granular PTFE (2.5 g) was mechanically stirred (400 rpm)
at rt. After 45 min, TLC indicated the completion of the reaction.
After stopping the reaction, the products were suspended in water
while the granular PTFE precipitated on the bottom of the flask. The
suspended products were then filtered, washed with water (2 mL)
using TMS as an internal standard. Chemical shifts (δ) are reported
relative to TMS (1H NMR), CDCl3 or DMSO-d6 (13C NMR).
Multiplicities are reported as follows: singlet (s), doublet (d), triplet
(t), quartet (q) and multiplet (m). Infrared analyses (KBr pellet) were
performed by FTIR spectroscopy. High resolution mass spectroscopy
(HRMS) using a quadrupole time of flight mass analyzer with
electrospray ionization was used to analyze reaction products. All
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 8 of 8
ARTICLE
Journal Name
and dried to give a quantitative yield of the product without further
purification. The remaining mother liquid and PTFE from the above 10 W. Herbst and K. Hung, Industrial Organic Pigments, WILEY-
9 E. Merino, Chem. Soc. Rev., 2011, 40, 3835-3853.
View Article Online
DOI: 10.1039/C8GC03982H
reaction and the washing water from the filtration were combined
VCH Verlag GmbH & Co. KGaA, Weinheim, 2004.
and then used in place of the initial H2O in a second cycle. The 11 Q. Yan, Water & Wastewater Engineering, 2003, 29(5), 40-43.
amounts of acetoacetanilide, 4-methyl-2-nitroaniline, NaNO2 and 2- 12 L. Pereira, In Environmental Protection Strategies for
naphthol were the same as for cycle 1 and the amount of added HCl
was reduced to 1.1 equiv. In total, 11 cycles were conducted in this
manner and all the reaction times from cycle 2 to cycle 11 were 30
Sustainable Development, Strategies for Sustainability, ed. A.
Malik and E. Grohmann, Springer Science+Business Media,
New York, 2012, Chapter 4, 111-162.
min with quantitative yields. The combined volume of the mother 13 A. Reife, T. River and H. Freeman, Text. Chem. Color. Am.
liquid and washing water from the 11th cycle was 15.5 mL. Dyest. Rep., 2000, 32(1), 56-60.
Wastewater and excess HCl recycling in the preparation of 14 J. Safari and Z. Zarnegar, RSC Adv., 2015, 5, 17738-17745.
Pigment Red 3 (10)
A mixture of 4-methyl-2-nitroaniline (1.05 equiv), HCl (3 equiv),
15 M. Velasco, C. Kinen, R. Rossi and L. Rossi, Dyes Pigm., 2011,
90, 259-264.
H2O (8 mL), NaNO2 (1.10 equiv, in 2 mL of H2O) and granular PTFE 16 P. Tundo, A. Loris and M. Selva, Green Chem., 2007, 9, 777-
(2.5 g) was mechanically stirred (400 rpm) at rt. After 20 min, 2- 779.
naphthol (1 g) was added. The reaction was continued for 60 min 17 H. Dabbagh, A. Teimouri and A. Chermahini, Dyes Pigm.,
when TLC indicated the completion of the reaction. After stopping 2007, 73, 239-244.
the reaction, the products were suspended in water while the 18 J. Jin, Z. Wen, J. Long, Y. Wang, T. Matsuura and J. Meng,
granular PTFE precipitated on the bottom of the flask. The Synth. Commun., 2000, 30(5), 829-834.
suspended products were filtered, washed with water (2 mL) and 19 B. Fang and P. Yang, CN Pat., 106752063 A, 2017.
dried to give a quantitative yield of the product without further 20 L. Liu, S. Feng and C. Li, ACS Sustainable Chem. Eng., 2016, 4,
purification. The granular PTFE, mother liquid and washing water
6754-6762.
from the filtration were then combined and used in a second cycle. 21 B. Li and C. Li, J. Org. Chem., 2014, 79, 2242-2254.
The amounts of 4-methyl-2-nitroaniline, NaNO2 and 2-naphthol 22 B. Li and C. Li, J. Org. Chem., 2014, 79, 8271-8277.
were the same as for cycle 1 and the amount of added HCl was 23 Tsca screening tools, https://www.epa.gov/tsca-screening-
reduced to 1.0 equiv. Altogether 11 cycles were conducted in this
tools.
same way. All the reactions were complete in 60 min and had 24 H. Zollinger, Color Chemistry: Syntheses, Properties and
quantitative yields. After the 11th cycle, the combined volume of
the mother liquid and washing water was 17 mL.
Applications of Organic Dyes and Pigments, VCH
Verlagsgesellschaft mbH, Weinheim, 1987.
25 S. Thomas, PCT Int. Appl, 2008101842, 2016.
26 G. Shankarling, P. Deshmukh and A. Joglekar, J. Environ.
Chem. Eng., 2017, 5, 3302-3308.
Conflicts of interest
The authors declare no competing financial interest.
Notes and references
1
K. Hunger, Industrial Dyes: Chemistry, Properties,
Applications, WILEY-VCH Verlag GmbH
& Co. KGaA,
Weinheim, 2003.
2
3
4
5
6
7
8
E. Jaffe, Pigments, Organic, John Wiley & Sons, Inc, New York,
2004.
F. Mohamed, M. Bashandy, H. El-Wahab, M. Sheier, M. El-
Molla and A. Bedair, Int. J. Adv. Res., 2014, 2(7), 248-260.
F. Hamon, F. Pilard, F. Barbot and C. Len, Tetrahedron, 2009,
65, 10105-10123.
Y. He, X. Gu, M. Guo and X. Wang, Opt. Mater., 2008, 31, 18-
27.
P. Sharma, N. Rane and V. Gurram, Bioorg. Med. Chem. Lett.,
2004, 14, 4185-4190.
E. Marchevsky, R. Olsina and C. Marone, Talanta, 1985, 32(1),
54-56.
C. Han and X. Song, Yan Liao Sheng Chan Ji Shu (Techniques
in Manufacturing Industrial Pigments), Science Press, Beijing,
2014.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins