Room temperature diazotization and coupling reaction using a DES-ethanol system: A green approach towards the synthesis of monoazo pigments

Article abstract of DOI:10.1039/c9cc01114e

An environmentally benign, one-pot diazotization and coupling reaction using ChCl:tartaric acid DES at room temperature is described. The bulky tartrate ion renders stability to the diazonium salt at room temperature, also evidenced by ¹H NMR.

Full text of DOI:10.1039/c9cc01114e

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DOI: 10.1039/C9CC01114E
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Room temperature diazotization and coupling reaction using DES-
Ethanol system: A green approach towards the synthesis of
monoazo pigments.
Received 00th January 20xx,
Accepted 00th January 20xx
Sujit Suresh Kamble and Ganapati Subray Shankarling*
DOI: 10.1039/x0xx00000x
An environmentally benign, one pot diazotization and coupling reaction media due to their features like Negligible vapour
reaction using ChCl: tartaric acid DES at room temperature is pressure, non-flammability, biodegradability, non-toxicity,
described. The bulky tartrate ion renders stability to the diazonium recyclability and cost-effectiveness, etc.11,26–29 Thus considering
salt at room temperature, also evidenced by 1H NMR. The isolated the drawbacks of conventional methods and the merits of DES,
diazonium salt is stable and active even after 192 h at room herein we demonstrate a simple, one-pot, environmentally
temperature.
benign and industrially feasible protocol for the synthesis of
stable diazonium salts and their subsequent coupling using
ChCl: tartaric acid DES at room temperature for the first time.
To elucidate the catalytic activity of DES, we have coupled 2-
The diazonium salts are very important in synthetic chemistry
as they serve as a building block for the synthesis of azo dyes as
well as various functionally active molecules.1–4 Their synthesis
i.e the diazotization reaction has been extensively explored.5–8
It is well known that the diazonium salts are stable at 0-5 °C and
undergo decomposition with violent explosions at high
temperatures.9,10
chlorobenzene
diazonium
tetrafluoroborate
with
acetoacetanilide (2). Important to be noted that, the
tetrafluoroborate salt was initially synthesized from 2-chloro
aniline (1) following conventional diazotization using NaNO2,
HCl at 0-5 °C followed by chloride exchange by
tetrafluoroborate using NaBF4. To our delight, 2-(2-(2-
chlorophenyl)hydrazono)-3-oxo-N-phenylbutanamide (3) is
obtained in 82% yield within 30 min at room temperature
(Scheme 1).
To alleviate the drawbacks associated with conventional
diazotization reaction, different researchers have reported
various methods and catalysts like ionic liquid promoted diazo
coupling reaction of β-naphthol and aryltriazines,11 clay as a
support and a catalyst,12 ter-Butyl nitrite as a nitrosonium
Cl
Cl
source,13,14 silica sulphuric acid etc. Though these methods
15
NH2
N2 BF4
NaBF4, 0-5°C
HCl-H2O
offer good yields for diazotization and coupling, maintaining low
temperatures, tedious synthesis, and activation of the catalyst,
viability for selected anilines, and commercial non-applicability
are some drawbacks which limit these protocols. Similarly, the
efforts have been taken for the synthesis of stable diazonium
salts16–22 with different counter anions such as fluoroborates,23
trifluoromethanesulfonates,24 naphthalene sulfonates25, etc.
Following this approach, it increases one more step to isolate
the stable diazonium salt prior to coupling. This makes the
process time consuming, labour intensive and less economic
from the industrial viewpoint.
NaNO2
1
diazonium tetrafluoroborate
O
O
DES (ChCl:tartaric
acid), 30 min, r.t.
N
H
2
O
O
Cl
N
NHHN
Last two decades, deep eutectic solvents (DES) have
fascinated researchers as environmentally benign catalysts and
3
Scheme 1 Synthesis of monoazo arylide pigment using sodium
tetrafluoroborate.
Encouraged with these results, we have investigated the
one-pot diazotization and coupling reaction using ChCl: tartaric
acid (ChCl: TA) DES. The in situ diazotization of 2-chloroaniline
a S. S. Kamble, Prof. Ganapati S. Shankarling
Dyestuff Technology Department,
Institute of Chemical Technology,
N. P. Marg, Matunga, Mumbai-400019, India.
Tel.: ++91-22-33612708
E-mail: gsshankarling@gmail.com
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
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N
(1 eq.) with NaNO2 (1 eq.) in ChCl: TA was carried out and
followed by coupling with acetoacetanilide at room
temperature (Scheme 2).
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N
Cl
H
O
DOI: 10.1039/C9CC01114E
OH
N
O
H
Ar
O
NaNO2
O
Ar
Ar-NH2
Ar-N2-ChCl:tartaric acid-N2-Ar
H
N
N
O
O
H
O
DES-ethanol,
r.t.
2
Cl
Cl
2
O
1
N
DES (ChCl:tartaric
acid)
Cl
N
NH2
O
O
OH
Stable diazonium salt
NH HN
NaNO2
O
O
30 min, r.t.
N
H
N
DES-ethanol,
H
2
1d
3d
r.t.
3
Scheme 2 One pot diazotization and coupling reaction at room
temperature.
O
Interestingly, the product was obtained in a good yield of
86% within 30 min. The reaction was further investigated in
different acidic deep eutectic solvents, and mineral as well as
organic acids at room temperature (Table 1).
Table 1. Optimization of the one pot diazotization and coupling reaction
at room temperature under different conditionsa:
Yieldc (%)
O
H
N
N
HN
Ar
4
Scheme 3 Plausible mechanism for one pot diazotization and coupling
reaction using deep eutectic solvents.
Entry
Acid/ DES
N
HO
Ethanol
86
Water
NR
HO
Cl
N
N
Cl
N
Cl
H
N
N
1
2
ChCl: tartaric acid
ChCl: malonic acid
ChCl: oxalic acid
Tartaric acid
Malonic acid
Oxalic acid
N
N
OH
H
O
O
O
H
O
Ar
O
O
Ar
O
H
O
N
Ar
73
NR
O
Ar
O
H
N
O
O
O
3
68
NR
H
Cl
N
O
N
4
62
NR
OH
5
53
NR
Arene diazonium tartrate
Arene diazonium malonate
Arene diazonium oxalate
6
46
NR
7
Adipic acid
54
NR
I
II
III
8b
ChCl, tartaric acid
HCl
67
NR
9
NR
NR
Figure 2 Proposed stability of diazonium salts.
a Reaction conditions, 2-chloroaniline: (1 eq.), acetoacetanilide (1 eq.),
NaNO2: (1 eq.), acid/ DES (0.5 eq.), b: ChCl and tartaric acid as an
individual component, c: isolated yield, room temperature, solvent:
3 vol., NR: No Reaction.
Initially, the one pot diazotization and the coupling reaction
was investigated with ChCl: tartaric acid (ChCl: TA), ChCl:
malonic acid (ChCl: MA), and ChCl: oxalic acid (ChCl: OA) DES in
water and ethanol separately. In ethanol, all the three deep
eutectic solvents offered comparable yields i.e. 86%, 73%, and
68% respectively. Whereas when water is used as a solvent, no
product was obtained (Table 1, Entries 1-3).
Not only has the size of the counterion but also the choice
of solvent also altered the stability of diazonium salt and
consequently the reaction. The decomposition of the diazonium
salt in an aqueous solution of ChCl:TA DES (Table 1, Entry 1) may
be due to the disruption of DES structure into individually
solvated DES components.33 The probable structure of
diazonium salt is suggested by the 1H NMR spectrum (Figure 3).
The ChCl: TA DES is sufficiently acidic to generate the
nitrosonium ion which initiates the diazotization reaction. We
propose that, after the formation of diazonium salt, the DES
stabilizes the diazonium salt as depicted in Scheme 3. Thus
isolated diazonium salt was characterized by 1H NMR
spectroscopy (Figure 3).
It is known that diazonium salts are stable at room
temperature with bulky anion30–32. The stability of different
diazonium salts in ChCl:TA, ChCl:MA, and ChCl:OA DES is
proposed in figure 2. In the case of ChCl:TA, the formation and
stability of diazonium salt is attributed to the presence of bulky
tartrate counter ion (Figure 2-I). Four hydrogen bonding sites of
two carboxylic groups take part in bonding with two diazonium
cations and two of hydroxyl groups are bonded with choline
chloride rendering stability to the diazonium salt. While in the
case of ChCl:MA and ChCl:OA small size and less number of
hydrogen bonding sites lower the stability of diazonium salt and
subsequently lower the reaction yield (Figure 2-II and III).
Figure 3 1H NMR of diazonium salt of 2-chloro aniline
Next, the reaction was studied using organic acids in water
and ethanol as solvents (Table 1, Entries 4-7). The reaction
yields were 54 to 62% using different organic acids. We then
investigated the role of DES in diazotization reaction and the
stability of diazonium salt. To investigate the role of cholinium
ion in the stability of diazonium salt, the reaction was carried
out using a mixture of tartaric acid and NaCl instead of ChCl:TA
DES. The diazonium salt got decomposed by stirring at room
temperature underlying the role choline cation along with
tartaric acid. Figure 4 shows the decomposed diazonium salt
2 | J. Name., 2012, 00, 1-3
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when synthesized using a mixture of tartaric acid and NaCl (a) The versatility of the developed protocol with diffVeierwenArtticalme Oinnlienes
DOI: 10.1039/C9CC01114E
and couplers was studied further (Scheme 4).
and stable diazonium salt synthesized using ChCl:TA DES (b).
O
O
O
O
N
N
NH
H
3
R
HN
4
R'
O
O
N
NH2
N
N
N
NaNO2
N
NH
5
Figure 4 Diazotization reaction using a) tartaric acid and NaCl, b) ChCl:TA
DES.
DES-EtOH,
room
temperature
R
R
6
The reaction was carried out in the presence of mineral acid
too (Table 1, Entry 9). In another study, we carried out a
reaction using a mixture of tartaric acid and ChCl as individual
components dissolved in alcohol just before the reaction was
carried out, results showed the formation of coupled product in
67%. And an attempt to isolate the diazonium salt was not
successful, which validates the necessity of DES for isolation of
diazonium salt and subsequent coupling.
1
OH
O
7
NH
N
R
As ChCl: tartaric acid DES was found to be the best amongst
the other, the reaction was further optimized by varying the DES
concentration. (Table 2). Comparatively less yield was observed
in solvent-free conditions using 1 eq. of DES (Table 2, Entry 6)
which may be due to the high viscosity of ChCl:TA DES which
hinders the mixing of substituents. To overcome this issue, DES:
Ethanol (1:1) mixture was used for further study.
Scheme 4 One pot diazotization and coupling reaction of aniline with
different coupling components at room temperature.
The optimized protocol (Table 2, entry 3) was successfully
employed for the synthesis of various monoazo pigments by
coupling diazonium salt with acetoacetanilide derivatives, 3-
methyl-1-phenyl pyrazolone, and β-naphthol (Figure 5). (More
derivatives are listed in supporting information.)
O
Table 2 Optimization of the one pot diazotization and coupling reaction
in different DES concentartions.a
O
O
O
NO2
O
N
O
N
NO2
N
Yield (%)c
NH HN
Entry
Conc. of DES (eq.)
Time (min)
NH HN
NH HN
3r
3a
3p
C.I. PY 1
O
1
2
0.2
0.3
0.5
0.7
1.0
1.0b
-
40
25
54
79
85
81
82
32
NR
O2N
71%
81%
75%
O
O
O
O
O
3
25
O
Cl
4
25
N
N
Cl
N
NH HN
NH HN
NH HN
5
25
3f
3e
3d
6
7d
25
77%
82%
O
86%
120
O
a Reaction conditions, 2-chloroaniline: (1 eq.), acetoacetanilide (1 eq.),
NaNO2: (1 eq.), room temperature, solvent: 1 vol., b: solvent-free, c:
isolated yield, d: in absence of DES, NR: No reaction.
It is observed that the diazonium salt is quite stable even
after 192 h. It offers substantial product yields underlining the
high stability of salt. The results are depicted in table 3.
Table 3 Stability study of the diazonium salt
O
N
N
Cl
N
N
N
NH
N
N
N
NH
N
NH
6d
6c
80%
6f
O2N
Cl
80%
C.I. P Y 60
85%
O
N
O
N
N
Cl
N
N
N
N
H
N
N
NH
N
NH
6g
HN
6o
O
O
73%
78%
S
6n
HO
Cl
O
O
C.I. P Y 10
78%
Reaction after
Time for
Yieldb
(%)
86
O
Entry
O
NH
O
NH
time (h)
reaction (min)
O
O2N
NH
N
N
N
1
2
3
4
5
Immediate
4
4
NO2
8l
C.I. P R-1 or Parared
8t
81%
24
48
84
8a
79%
66%
4
79
C.I. P R-3
96
10
15
73
192
72
Figure 5. Synthesis of various monoazo pigments of various anilines at
room temperature using DES.
a Reaction conditions, 2-chloroaniline: (1 eq.), acetoacetanilide (1 eq.),
NaNO2: (1 eq.), room temperature, solvent: DES: Ethanol (1:1) vol.,
b: isolated yield.
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J. Name., 2013, 00, 1-3 | 3
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In conclusion, we have developed
a
simple and 18
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View Article Online
DOI: 10.1039/C9CC01114E
environmentally benign protocol for the one-pot diazotization
and coupling reaction at room temperature in the presence of
1
ChCl: tartaric acid DES. H NMR study suggests the formation 19
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“There are no conflicts to declare”.
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