An environmentally friendly approach to the green synthesis of azo dyes with aryltriazenes via ionic liquid promoted C-N bonds formation

Article abstract of DOI:10.1016/j.dyepig.2018.05.073

An efficient and green approach for the synthesis of azo dyes has been developed via the Br?nsted acidic ionic liquid (IL) promoted diazo coupling reaction of naphthols with aryltriazenes. The reaction was carried out with the aryltriazenes as diazotizing

Full text of DOI:10.1016/j.dyepig.2018.05.073

Accepted Manuscript
An environmentally friendly approach to the green synthesis of azo dyes with
aryltriazenes via ionic liquid promoted C-N bonds formation
Yonghong Zhang, Yonghong Liu, Xiaoqian Ma, Xia Ma, Bin Wang, Hongguang Li,
Yan Huang, Chenjiang Liu
PII:
S0143-7208(18)30904-5
10.1016/j.dyepig.2018.05.073
DYPI 6802
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 22 April 2018
Revised Date: 29 May 2018
Accepted Date: 30 May 2018
Please cite this article as: Zhang Y, Liu Y, Ma X, Ma X, Wang B, Li H, Huang Y, Liu C, An
environmentally friendly approach to the green synthesis of azo dyes with aryltriazenes via ionic liquid
promoted C-N bonds formation, Dyes and Pigments (2018), doi: 10.1016/j.dyepig.2018.05.073.
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ACCEPTED MANUSCRIPT
Ar
N
OH
H2O
ILs
N
N
+
N
N
O
Ar
RT., 4 h
OH
ILs as promoter Water as solvent
Mild conditions Gram scale
Transition metal-free
Air benign
HN2
O
O
N
S
N
Me
Simple product isolation process
Drug Late-stage modification
H
N
N
Sulfonamides derivates
OH

ACCEPTED MANUSCRIPT
An environmentally friendly approach to the green synthesis of azo dyes with
aryltriazenes via ionic liquid promoted C-N bonds formation
Yonghong Zhanga,d*, Yonghong Liua, Xiaoqian Maa, Xia Maa, Bin Wangb, Hongguang Lic, Yan Huanga*,
Chenjiang Liua,b,d
*
a
Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous
Region, College of Chemistry and Chemical Engineering of Xinjiang University, Urumqi 830046, China
E-mail addresses: zhzhzyh@126.com; xjuchem_2012@163.com; pxylcj@126.com.
b Physics and Chemistry Detecting Center, Xinjiang University, Urumqi 830046, China
cFaculty of Chemical & Environmental Engineering, Wuyi University, International Healthcare Innovation
Institute (Jiangmen), Jiangmen 529020, China
d Beijing National Laboratory for Molecular Sciences, Beijing100871, China
KEYWORDS: azo dyes, ionic liquids, environmentally friendly, aryltriazenes
ABSTRACT
An efficient and green approach for the synthesis of azo dyes has been developed via the
Brønsted acidic ionic liquid (IL) promoted diazo coupling reaction of naphthols with
aryltriazenes. The reaction was carried out with the aryltriazenes as diazotizing agents, the
Brønsted acidic ionic liquids as the promoter, and water as the green solvent at room temperature
under air and metal-free conditions. Notably, the attractive advantages of the process include
mild conditions with excellent yields, simple product isolation process, large-scale experiment,
late-stage modification of pharmaceutical and recyclability of the promoter. In addition, the
UV-vis spectral characteristics of the azo-dyes were investigated in DMSO.
1. Introduction
1

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Azo compounds are attractive targets for organic synthesis methodology due to their
widespread applications in many areas of technology and medicine [1]. Particularly
attractive are azo dyes, which are utilized as building blocks for dyeing textile fibers [2,
3], pharmaceuticals [4, 5], organic synthesis [5, 6], and optic/photoelectric materials [7,
8]. Because of their value in dyes, pigments and advanced materials, the construction of
azo dye compounds has attracted considerable interests [1, 9-15]. Most of these protocols,
however, involve harsh reaction conditions, such as low temperature, use of instability of
aryl diazonium salts and toxic solvents as well as generate low yields and require long
reaction times [16].
From a sustainable and green chemistry viewpoint, the use of the combination of water
and ionic liquids in organic synthesis has attracted much attention in recent years [17-20].
As a green, inexpensive, non-flammable and nontoxic solvent, water has been widely
used as an alternative to traditional organic solvents in organic transformations due to its
fascinating advantages of low cost, environmental benignity, inherent safety,
biocompatibility, unique physical and chemical properties [21-25]. On the other hand,
ionic liquids (ILs) features many fascinating advantages over traditional reaction media or
catalyst such as their unique physical and chemical properties of nonvolatility, thermal
stability, recyclability, and tunable chemistry [26-28]. Furthermore, acidic functionalized
ionic liquids have been recognized as acceptable reaction catalysts or media, which
combined the catalytic advantages of Brønsted acid and unique properties of ionic liquids
[29-31].
Aryltriazenes, as a very useful and versatile class of compounds with intriguing structural
and chemical properties, have been extensively explored in organic synthesis due to their
superior stability and reactivity [32-36]. Among these transformations, the diazotization
reaction with aryltriazenes represents atom-economic strategy for C–N bond formation
2

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[20, 37-43], compared with that utilized in arylation reaction [44-65]. However, in
general, most of those reactions involving transition metal catalyst, harsh reaction
conditions, volatile acid promoter and organic solvent. Recently, we developed a novel
and green combination of water/ionic liquids/aryltriazenes for the synthesis of azo
compounds [20]. In continuation of our interest in triazene chemistry and green organic
synthesis with ionic liquilds [20, 36, 43], we envisioned that azo dyes could be
synthesized by diazo coupling reaction of aryltriazene with naphthol in aqueous media
under metal-free and mild conditions.
2. Results and discussion
2.1 Optimization of the reaction conditions
We commenced our study using 1-phenyltriazene (1a) and 1-naphthol (2a) as model substrates
(Table 1). Initially, we examined the influence of the promoter Brønsted acidic ionic liquids with
different counter cations and anions (Table1, entries 1-9). The results show that IL9 with
moderate acidity was superior to the others (Table 1, entry 9), as the desired product
(E)-4-(phenyldiazenyl)naphthalen-1-ol (3a) was produced in 97% isolated yield. Since ionic
liquids not only act as promoter but also as a phase transfer catalyst in this reaction. As IL9 has a
4-methylbenzenesulfonate anion, it helps to enhance the solubility of the substrate. Furthermore,
increasing and reducing the amount of IL9 led to a relatively lower yield. Because the increase in
the amount of promoter will lead to poor selectivity and some by-products, reducing the amount
of promoter will also reduce the reaction efficiency. Further study showed that only a trace
amount of product was formed under solvent-free conditions, which might be due to the
insolubility of the substrates and promoter (entry 12). By further screening the amount of
triazene (entry 13), water (entry 14) and the reaction time (entries 15, 16), the optimum
reaction conditions were obtained. The optimal reaction conditions are therefore as follows:
3

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1-phenyltriazene (0.2 mmol), 1-naphthol (0.2 mmol), promoter IL9 (0.2 mmol) in water (1 mL)
at room temperature under air with a reaction time of 4 hours.
Table 1. Optimization of reaction conditions.
Entry[a]
Triazene
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
0.2 mmol
ILs/mmol
IL1 (0.2)
IL2 (0.2)
IL3 (0.2)
IL4 (0.2)
IL5 (0.2)
IL6 (0.2)
IL7 (0.2)
IL8 (0.2)
IL9 (0.2)
Time/h
Solvent
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
Yield/%[b]
1
2
3
4
5
6
7
8
9
4
4
4
4
4
4
4
4
4
79
81
83
80
67
73
76
70
97
4

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10
11
12
13
14
15
16
0.2 mmol
0.2 mmol
0.2 mmol
0.22 mmol
0.2 mmol
0.2 mmol
0.2 mmol
IL9 (0.22)
IL9 (0.16)
IL9 (0.2)
IL9 (0.2)
IL9 (0.2)
IL9 (0.2)
IL9 (0.2)
4
4
4
4
4
3
5
H2O
H2O
94
90
-
Trace
94
H2O
H2O 0.5 mL
H2O
95
91
H2O
98
[a] Conditions: 1a (0.2 mmol), 2a (0.2 mmol), IL (0.2 mmol), H2O (1 mL), at room temperature, 4 h; [b]
Isolated yields.
2.2 Optimization of N-substituted 1-aryltriazenes
Under the optimized conditions, we firstly optimized the N-substituted groups of
1-phenyltriazenes (Table 2). For acyclic substitution, the substrates with various linear and
branched chains, such as diethyl-, dimethyl-, methoxy-methyl-, dipropyl-, diisopropyl- and
dibutyl-amino groups, could produce the desired product in good yields (entries 1-7).
Furthermore, both free alcohol (entry 7) and diversified reactive groups (entries 8, 9) were
tolerated as N-substituents in this transformation. Besides acyclic substituents, cyclic ones were
also scrutinized (entries 10-13) and found that the ring size exhibited almost no obvious
influence on the reaction efficiency (entries 10, 11). The cyclic N-morpholinyl group, which
containing an additional heteroatom, also provided a good yield (entry 12). What’s more, the
compound with two separate cyclohexyl rings on the nitrogen atom was efficient as well (entry
13). Besides the sp3 substituent groups, the sp2 ones could also afforded the desired product in
good yield (entry 14). Consequently, (E)-1-(phenyldiazenyl)pyrrolidine (2a) was chosen as the
optimal as diazotizing agents with pyrrolidinyl as leaving group.
Table 2. Optimization of N-substituted 1-pheyltriazenes.
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OH
IL9, H2O
RT, 4 h
N
R
N
HO
N
+
N
1a
Triazene, 2
3a
Triazene
Allyl
Entry[a]
1
yield[b]
Entry[a]
yield[b]
65%
Triazene
Me
80%
8
9
N
N
N
N
Ph
Ph
Ph
N
Allyl
Ph
Ph
N
Me
Et
Bn
N
2
3
4
5
84%
82%
85%
88%
82%
97%
92%
89%
N
N
N
N
Et
N
Bn
Me
N
10
N
N
N
N
N
N
N
Ph
N
OMe
nPr
11
12
N
N
N
N
Ph
Ph
N
N
N
nPr
nPr
Ph
Ph
Ph
iPr
O
N
N
N
N
nBu
N
Cy
N
6
7
86%
70%
13
14
85%
73%
N
nBu
N
Cy
Ph
N
C2H4OH
N
Ph
N
N
Ph
N
C2H4OH
Ph
N
H
[a] Conditions: 1a (0.2 mmol), 2 (0.2 mmol), IL9 (0.2 mmol), H2O (1 mL), at room temperature, 4 h; [b]
Isolated yields.
2.3 Substrate scope of naphthol and 1-aryltriazenes
Once different N-substituted groups of 1-pheyltriazenes were systematically investigated,
we moved to examine the substrate scope of naphthol and 1-aryltriazenes with different
aryl substitutions (Table 3). First, different naphthols were tested. Both 1-naphthol and
2-naphthol could afford the corresponding azo dyes in excellent yields. Subsequently,
2-naphthol 1b was then selected as ideal coupling partners for the coupling reactions with
various aryltriazenes. 1-Aryltriazenes bearing a broad range of different ortho, meta, and
para substituents were all compatible under the optimized conditions to afford the
corresponding azo products in good to excellent yields. The nature of the substituents on
6

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the benzene rings of aryltriazenes had no obvious effects on the effciency of the reaction.
A series of functional groups, such as methyl (3c
,
3f
3n), tert-butyl (3i), trifluoromethyl (3n), fluoro (3e
3o) were tolerated under the optimal reaction conditions, and the desired products were
,
3h), methoxy (3d
, 3k), iso-propyl
(
(
, 3l), chloro (3g), and carboxyl acid
obtained in 83-99% yields. Bearing a strong electron-withdrawing group like
trifluoromethyl (3n), and carboxyl acid (3p) gave lower yields than other para-substituted
compounds under modified reaction conditions. It is worth mentioning that the substrates
with halogen substitutions at different positions of phenyl ring of triazenes could be well
transformed (3e, 3l, 3g, 3m), which showed that this method has great potential in further
transformation. In addition, the compound containing an active hydrogen group, such as
carboxyl acid (3o), also performed well, which is a big challenge under many common
coupling reactions. Polysubstituted triazene could also afford desired product (3p) in
good yield, which shown that the steric hindrance have seldom effect. Besides
mono-substituted naphthols, multi-substituted naphthol was also studied,
5-amino-1-naphthol can be reacted with 2 equivalent of phenyl triazene to afforded
5-amino-4,8-bis((E)-phenyldiazenyl)naphthalen-1-ol with 33% isolated yield (4a). The
UV-visible absorption spectra of these dyes were measured by a UV-vis spectrometer in
DMSO at a concentration of 1×10-5 molL-1 (Table 3, SI). As expected, these
arylazo-substituted naphthols all have strong light absorptivity in visible range. The
maximum absorption band of each dyes appeares in 400-600 nm with a large molar
absorption coefficient (ε
> 104 Lmol-1cm-1) at the corresponding peaks, which is fully
matches the reported results in the literature [66].
Table 3. Substrate scope of the Brønsted acidic ionic liquid promoted diazenylation of
naphthol with various substituted aryltriazenes.
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[a] Reaction condition: 0.2 mmol of 1 and 0.2 mmol of 2 in the presence of IL9 (0.2 mmol) in H2O (1 mL)
at room temperature for 4 h.
2.4 Pharmaceutical derivatives late-stage diazenylation reaction
To determine the practical utility of this protocol, we undertook a late-stage diazenylation
reaction of drug molecule for the purposes of preparing pharmaceutical derivatives (Scheme 1).
As a useful bacteriostatic antibiotic, sulfamethoxazole was smoothly converted into the
corresponding (E)-N-(5-methylisoxazol-3-yl)-4-(pyrrolidin-1-yldiazenyl)benzenesulfonamide 2q
in quantitative yield. Upon subject this triazene-based drug to our diazenylation protocol,
(E)-4-((2-hydroxynaphthalen-1-yl)diazenyl)-N-(5-methylisoxazol-3-yl)benzenesulfonamide 3q
was obtained in 68% yield. This synthetic method demonstrates the applicability of this
diazenylation protocol for efficient preparation of lead compounds.
Scheme 1. Pharmaceutical derivatives late-stage diazenylation reaction.
2.5 Gram scale experiment
In order to further demonstrate the practicability of this direct diazenylation protocol,
gram-scale operation was carried out under modified reaction conditions. When the
reaction of naphthalen-2-ol 1b and phenyl triazene 2a was enlarged to 7.0 mmol scale, the
desired azo dye 3b was obtained in quantitative yield under these green and easily
9

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handled reaction conditions, in which 50 mol% of the promoter IL9 and 10 mL water was
sufficient (Scheme 2).
Ph
N
OH
N
N
N
IL9
(50 mol%)
N
OH
+
H2O (10 mL), rt, 12 h
1b
2a
(1.23 g, 7 mmol)
(1.01 g, 7 mmol)
3b
(Quantitative)
Scheme 2. Gram scale experiment for the synthesis of (E)-1-(phenyldiazenyl)naphthalen-2-ol.
2.6 Recycling of IL9 in the synthesis azo dye 3b
Stability and recyclability are crucial features for any ILs as a recyclable catalyst and
media. In addition to the obvious environmentally friendly advantages, the use of
recyclable ILs can considerably facilitate product purification. As shown in the
diazenylation of 2-naphthol, our green promoter IL9 is highly stable and is conveniently
recycled and reused for at least six times without any significant loss of activity (Figure 1).
Following each cycle, the product was isolated by direct filtration, and the IL9 was
recovered from the aqueous layer and reused for the next run after drying in vacuo. For
the first cycle, the activity of IL9 remained the same. In the subsequent cycles, the
desired products could be obtained with high yields by extension of the reaction time
from 4 to 6, 8 and 12 h. After that, slight decrease of activity is observed.
100%
80%
60%
40%
20%
0%
1
2
3
4
5
10

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Figure 1. Recycling of IL9 in the synthesis azo dye 3b
.
2.7 Proposed reaction mechanism
According to our previous work [20, 43], a plausible reaction pathway is proposed
(Scheme 4). Initially, triazene 2a was activated by Brønsted acidic IL9 to afford
ammonium salt
N-electrophilic, IL anion/phenyldiazonium cation ion pair
This species could react with nucleophilic naphthol derivatives to provide intermediate
A
. Subsequently, intermediate
A
was then transformed into a soluble
B
by the release of pyrrolidine.
C.
Finally, product 3b was generated by the deprotonation of
C, and promoter IL9 was
regenerated at same time.
Scheme 4. Proposed reaction mechanism
3. Experimental Section
3.1 Typical reaction procedure for the synthesis of azo dyes
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A mixture of Brønsted acidic ionic liquid (0.20 mmol), naphthol (0.20 mmol), aryltriazene (0.20
mmol) and H2O (1 mL) was added to a tube (25 mL), and then the mixture stirred at room
temperature, some substrate bearing strong electron-withdrawing group need elevate temperature
and prolong reaction time to improve yield. Reaction was monitored by TLC plate. After the
reaction was complete, the resulting yellow precipitate isolated by filtration, the damp solid was
washed with water (5 mL × 3) and cold ethanol (2 mL). The filter cake was dried in vacuo, and
then the desired product azo dyes were obtained. If the product was oil, after the reaction was
complete, water (5 mL) was added to the mixture, the mixture was extracted with EtOAc (5 mL
× 3). The combined organic layer was dried over anhydrous MgSO4, then filtrated through celite,
washed with EtOAc (2 mL ×x 3), the mixture was evaporated under vacuum and purified by
flash column chromatography (petroleum ether/ethyl acetate) to afford the desired product.
3.2 Pharmaceutical derivatives late-stage diazenylation reaction
A mixture of IL9 (62.6 mg, 0.20 mmol), 1b (28.8 mg, 0.20 mmol), 2q (66.7 mg, 0.20 mmol) and
H2O (1 mL) was added to a tube (25 mL), and then the mixture stirred at 60 oC for 8 h. After the
reaction was complete, the resulting precipitate isolated by filtration, the damp solid was washed
with water (5 mL x 3) and ethanol (5 mL x 3) respectively, after drying in vacuo afford the
desired
product
(E)-4-((1-hydroxynaphthalen-2-yl)diazenyl)-N-(5-methylisoxazol-3-yl)benzenesulfonamide 3q:
red solid (yield: 68%).
3.3 Gram scale reaction
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(a) IL9 dissolved in water; (b) The mixture of IL9 and 1b; (c) Reaction mixture IL9, 1b and 2a;
(d) Reaction mixture (after reaction); (e) The product isolated by direct filtration; (f) The
recovered IL9 in aqueous.
To a 25 mL round-bottom flask was added IL9 (1.10 g, 3.5 mmol), 1b (1. 01 g, 7.0 mmol), 2a
(1. 23 g, 7.0 mmol) and H2O (10 mL) sequentially, then the mixture was stirred at room
temperature for 12 h. After the reaction was complete, the resulting precipitate isolated by
filtration, the damp solid was recrystallized from EtOH to afford the corresponding product in
quantitative yield.
3.4 Recycling experiments
A mixture of IL9 (62.6 mg, 0.20 mmol), 1b (28.8 mg, 0.20 mmol), 2a (35.0 mg, 0.20 mmol),
and H2O (1 mL) was added to a tube (25 mL), and then the mixture stirred at room temperature
for 1 h. After the reaction was complete, water (5 mL) was added to the mixture, the mixture was
extracted with EtOAc (5 mL×3), and then the separated IL9 from the water layer was reused for
13

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the next reaction after drying in vacuo. The combined organic layer was dried over anhydrous
MgSO4, then filtrated through celite, washed with EtOAc (2 mL x 3), the mixture was
evaporated under vacuum and purified by flash column chromatography (petroleum ether/ethyl
acetate 20:1) to afford the desired product 3b.
3.5 UV–visible absorption spectra
The UV–visible absorption spectra (200-800 nm) of azo dyes was measured by a UV-5300PC
spectrophotometer in DMSO at concentration of 1 × 10-5 mol·L-1 at 25 oC.
4. Conclusions
In summary, we have developed an efficient and green method for the synthesis of azo dyes from
aryltriazene and naphthol. The reaction was carried out with aryltriazenes as azo source, warer as
green solvent, and Brønsted acidic ionic liquid as recyclable promoter at room temperature under
mild conditions. Notably, Late-stage diazenylation of drugs and gram-scale operations were
systematically established under mild conditions. Furthermore, the promoter IL9 could be
conveniently recycled and reused with the same efficacies for at least five cycles. The simple
preparation of the starting material, a novel azo source, a cheap catalyst and the fairly mild
reaction conditions without volatile organic solvents make this process effective and convenient
for organic synthesis and industrial applications.
Acknowledgements
This work is supported by the Natural Science Foundation of Xinjiang Uyghur Autonomous
Region (No. 2017D01C035).
Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in the online version, at
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Highlights
ò
ò
ò
Ionic liquid promoted diazo coupling reaction for the synthesis of azo dyes
This green method featuring mild conditions, high yields and simple isolation process
Drug modification and scale-up process demonstrate the practicability of the protocol