AlCl3·6H2O-catalyzed Schiff-base reaction between aryl ketones and aromatic acylhydrazines/hydrazines in water

Article abstract of DOI:10.1007/s00706-019-02488-2

Abstract: Schiff-bases have important applications in the field of analysis, biomedicine, as well as material sciences. Hydrazones and acylhydrazones are two representative types of Schiff-bases. In this study, a green synthesis of aromatic hydrazones and

Full text of DOI:10.1007/s00706-019-02488-2

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-019-02488-2
ORIGINAL PAPER
AlCl3·6H2O‑catalyzed Schif‑base reaction between aryl ketones
and aromatic acylhydrazines/hydrazines in water
Zhi Xiang Zhao1 · Ting Li1 · Li Ping Cheng1 · Meng Li1 · Zhi Jian Zhong1 · Wan Pang1
Received: 14 May 2019 / Accepted: 22 July 2019
© Springer-Verlag GmbH Austria, part of Springer Nature 2019
Abstract
Schif-bases have important applications in the feld of analysis, biomedicine, as well as material sciences. Hydrazones and
acylhydrazones are two representative types of Schif-bases. In this study, a green synthesis of aromatic hydrazones and acyl-
hydrazones via Schif-base reaction of aryl ketones and aromatic acylhydrazines/hydrazines had been reported. In the synthesis,
water was used as solvent and AlCl3·6H2O was used as catalyst. The reaction is simple, highly efcient, and eco-friendly.
Graphic abstract
Keywords Green synthesis · Acylhydrazone · Hydrazone · AlCl3·6H2O
Introduction
Schif-base reaction was discovered by Hugo Schif
in 1864 [2], which refers to the reaction between carbon-
yls (aldehydes and ketones) and amines (primary amine,
hydrazine, acylhydrazine, and hydroxylamine) condensed
into imine groups (–C=N–). The formation of C=N bond
belongs to dynamic covalent reactions [3], and Schif-
base’s structure has obvious reversibility with the change
of pH [4], which makes it useful in many felds. Over the
last few decades, Schif-bases had been widely used in
analysis [5, 6], biomedicine [7–9], and material sciences
[10, 11].
Environment-friendly chemical processes and products are
essential in the sustainable development of mankind. Green
chemistry is one of the most attractive concepts in organic
chemistry because of its low pollution and low cost. Envi-
ronmentally friendly solvent is an important research area
of green chemistry with great merits [1]. In this study, a
variety of Schif-bases were prepared with an efcient and
green synthetic method.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-019-02488-2) contains
supplementary material, which is available to authorized users.
Conventionally, Schif-bases can be prepared in organic
solvents [12, 13]. For example, Enthaler et al. [14] and Lu
et al. [15] prepared acylhydrazones by the reaction between
aromatic ketones and acylhydrazines in EtOH and THF,
respectively. Rathelot et al. [16] prepared hydrazones in
organic solvent with AcOH as catalyst in high yield and
short reaction time. However, green synthetic methods for
Schif-bases with water as solvent seem to be more attractive
in terms of cost and environmental protection. AlCl3 had
* Li Ping Cheng
chengliping@sit.edu.cn
Wan Pang
pangwan@sit.edu.cn
1
School of Chemical and Environmental Engineering,
Shanghai Institute of Technology, Shanghai 201418, China
Vol.:(0123456789)
1 3

Z. X. Zhao et al.
Table 1 Examination of reaction conditions
Entry
Catalyst (0.1 equiv)
Time/h
Yield/%
1
2
3
4
5
6
7
CH3COOH
HCl
ZnCl2
ZnBr2
CuCl2·2H2O
FeCl3
12
12
12
12
7
4
2.5
–
–
–
–
56
68
74
AlCl3·6H2O
been reported as an efcient Lewis acid catalyst. However,
it is generally thought to be unstable in aqueous medium
and recommended to be used as catalyst in organic sol-
vents under anhydrous conditions [17]. Fringuelli et al. [18]
discovered that 1 mol% of AlCl3 efectively catalyzed the
azidolysis of α,β-epoxycarboxylic acids in water at pH 4.0.
In this study, a novel, simple, and green method was frst
developed to obtain various aromatic acylhydrazones by
reacting ketones with acylhydrazines and adding 0.1 equiv
AlCl3·6H2O as new catalyst in water. High purity products
were collected by fltration and drying. It is delightful that a
considerable number of aromatic hydrazone compounds had
also been prepared using the same method. Most important
of all, AlCl3·6H2O slowly dissociates in water and the reac-
tions are mild and safe. This methodology has a wider range
of substrate suitability and more simple operation.
achieving this reaction, and the corresponding adduct 3aa
was obtained in 74% yield and faster reaction rate.
Results and discussion
In accordance with the optimized conditions, we then
explored the scope of this Schif-base reaction with various
ketones and acylhydrazines (Table 2). Aryl ketones with a
hydroxyl in the para-position and meta-position had a fast
reaction rate and ordinary yield (3ab, 3ac). Furthermore,
benzoic acid [1-(2-hydroxyphenyl)ethylidene]hydrazide
(3ad) and 4-hydroxybenzoic acid 2-[1-(2-hydroxylphenyl)-
ethylidene]hydrazide (3bd) were obtained in higher yields
but the reaction time is longer. Perhaps it is the formation
of intramolecular hydrogen bond between ortho-hydroxyl
group and carbonyl oxygen that makes carbonyl more active,
and thus facilitates to decompose. Meanwhile, ortho steric
hindrance leads to longer reaction time to exhaust reactant.
Besides, the reaction of 2e bearing a strong electron-with-
drawing nitro group at meta-position of phenyl with benzo-
ylhydrazine leads to the product 3ae in good yield and short
reaction time. Maybe, electron-withdrawing group on the
aromatic ketone is benefcial to the reaction.
To explore and optimize reaction conditions, we begin
our study with the model reaction between benzoylhydra-
zine (1a) and 1-(4-ethoxyphenyl)ethanone (2a) in water. It
is worth mentioned that all the aromatic ketones can easily
soluble in water under heating conditions in this study. It is
reported that weak acid condition can promote the forma-
tion of –C=N– [4], so the reaction was frst carried out in
water with CH3COOH and HCl as catalyst, but no product
was formed. To fnd a suitable catalyst, the reaction was
performed using diferent Lewis acid such as ZnCl2, ZnBr2,
CuCl2·2H2O, FeCl3, and AlCl3·6H2O as catalyst in water
at 60 °C. As shown in Table 1, desired product 3aa was
obtained with 56% yield using CuCl2·2H2O as catalyst.
Although the reaction was done within 7 h, the yield of
product was difcult to improve by changing the reaction
temperature. To our delight, the reaction in the presence of
FeCl3 aforded 3aa in 68% yield. Fortunately, further studies
revealed that the catalyst AlCl3·6H2O was more efective for
Halogen groups such as Br and F, electron-donating
groups such as ethoxyl, methyl, and amino in the phenyl unit
in the ketones were all well tolerated in this reaction. Ben-
zoylhydrazine reacted smoothly with 1-(4-bromophenyl)-
ethanone (2f) and 1-(3,4-difuorophenyl)ethanone (2g) to
furnish the corresponding products in good yields, respec-
tively (Table 2, 3af and 3ag). This trend may be attributed to
the weak electron-withdrawing capability of halogen groups,
which may promote the reaction between carbonyl and ben-
zoylhydrazines. But if with C-F bond adjacent to methyl
1 3

AlCl3·6H2O‑catalyzed Schif‑base reaction between aryl ketones and aromatic…
Table 2 AlCl3·6H2O catalyzed Schif-base reaction of acylhydrazines and ketones in water
Entry
R1
R2
Time/h
Yield/%
References
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3aia
3ba
3bd
3bl
H (1a)
4-Ethoxy (2a)
4-Hydroxy (2b)
3-Hydroxy (2c)
2-Hydroxy (2d)
4-Methyl-3-nitro (2e)
4-Bromo (2f)
3,4-Difuoro (2g)
2-Fluoro (2h)
4-Methyl (2i)
4-Ethoxy (2a)
2-Hydroxy (2d)
4-Amino (2l)
3-Hydroxyl (2c)
4-Amino (2l)
2.5
1
1
74
71
74
95
97
95
80
76
73
90
82
80
86
79
–
[19]
–
[20]
–
[21]
–
–
–
–
[22]
–
H (1a)
H (1a)
H (1a)
5
H (1a)
1.5
1.5
1.5
1
7.5
13
2.5
12
3
H (1a)
H (1a)
H (1a)
H (1a)
4-Hydroxy (1c)
4-Hydroxy (1c)
4-Hydroxy (1c)
Nicotinic hydrazide (1c)
Nicotinic hydrazide (1c)
3cc
3cl
–
[23]
10
aR=ethyl
Table 3 AlCl3·6H2O catalyzed Schif-base reactions of hydrazines and ketones in water
Entry
R3
R4
Time
Yield/%
References
6aa
6ab
6ac
6ad
6ae
6af
6ba
6cc
6da
6dc
6dg
6dh
H (4a)
4-Amino (5a)
4-Hydroxy (5b)
3-Hydroxy (5c)
2-Hydroxy (5d)
3,4-Difuoro (5e)
4-Bromo (5f)
4-Amino (5a)
3-Hydroxy (5c)
4-Amino (5a)
3-Hydroxy (5c)
2-Methyl (5g)
H (5h)
15 min
10 min
1 h
2.5 h
3 h
68
91
91
70
96
85
76
87
66
84
56
72
[24]
[25]
[26]
[27]
–
[25]
–
H (4a)
H (4a)
H (4a)
H (4a)
H (4a)
4 h
4-Chloro (4b)
2,4-Dinitro (4c)
4-Nitro (4d)
4-Nitro (4d)
4-Nitro (4d)
4-Nitro (4d)
1.5 h
1.5 h
10 min
10 min
1.5 h
20 min
–
[29]
[28]
–
[30]
phenyl ketone 2h, both yield and reaction time will decrease.
Maybe less hindered C-F bond has a negative efect on yield
(Table 2, 3ah). In addition, we employed a series of methyl
phenyl ketones with electron-donating groups in phenyl. As
shown in Table 2, the reactions between aryl ketones 2a,
2b, and 2i and benzoylhydrazine aford to corresponding
1 3

Z. X. Zhao et al.
Table 4 Control experiments for the AlCl3.6H2O-Catalyzed formation of C=N bond
Entry
Solvent (10 cm3)
Catalyst (0.1 equiv)
Time/h
Yield/%
1
2
3
4
CH3CH2OH
CH3CH2OH
H2O
AlCl3.6H2O
None
HCl/CH3COOH
AlCl3.6H2O
12
12
12
2.5
29
29
0
H2O
74
products 3aa, 3ab, and 3ai in lower yields, respectively.
Maybe electron-donating groups of aryl ketones are not
conductive to the progress of the reaction. Moreover, ben-
zoylhydrazine bearing electron-donating groups, such as
4-hydroxybenzoylhydrazine, provides corresponding prod-
ucts 3ba and 3bl in high yields, which confrms that the
electron-donating groups of benzoylhydrazines may improve
the nucleophilicity of acylhydrazine.
formation of hydrazones. Interestingly, halogen groups, such
as F and Br, in the aryl unit in the ketones give a good yield
(6ae and 6af); perhaps weak electron-withdrawing halogen
group increases the reactivity of the carbonyl group.
To have a good insight into the reaction mecha-
nism, we carried out a few control experiments for the
AlCl3.6H2O-catalyzed reaction between 1a and 2a. First, the
reaction was performed in CH3CH2OH under refuxing,but
reactants 1a and 2a cannot be exhausted completely after
12 h. The product was collected by silica gel column chro-
matography and the yield was shown in Table 4. It can be
inferred that perhaps AlCl3.6H2O cannot activate carbonyl in
this reaction. If the reaction was performed in water used the
same AlCl3.6H2O as catalyst, the desired product 3aa was
easily obtained in 74% after 2.5 h. To identify whether acidic
condition is important to cause the reaction happens, control
group experiments were also performed in the presence of
HCl or CH3COOH (Table 4), but no product 3aa was formed
in these two reactions. It is reported that AlCl3 dissociates
in water and forms the corresponding aqua ion Al(H2O)63+
[18]. We believe Al(H2O)36+ plays a critical role in this reac-
tion and it is the real catalyst. Maybe it can activate carbonyl
carbon by interacting with the arylketonic oxygen. Thus,
nucleophile aromatic arylhydrazines/hydrazines are easier
to react with arylketones to aford C=N bond.
This green synthetic method inspires us to further expand
its applications to more types of reactions. In the light of the
procedure of forming acylhydrazones, AlCl3·6H2O plays a
key role in forming C=N bond. It is well-known that hydra-
zones, imines and oximes are Schif-bases with a structure of
C=N. We next applied the same conditions to try to synthesize
these three Schif-bases. It is satisfed that it is easier to pre-
pare hydrazones by the reaction of various aromatic ketones
and hydrazines, and the corresponding results are displayed
in Table 3. Compounds 6ac, 6cc, and 6dc bearing a meta-
hydroxy-substituted phenyl ring could be prepared in a high
yield as well as fast reaction rate. Maybe it is due to electron-
withdrawing of meta-hydroxyl group on the benzene ring,
which makes the carbonyl group more susceptible to decompo-
sition. However, 1-(2-hydroxyphenyl)ethanone (5d) leads to a
lower yield and longer reaction time. Maybe electron-donating
and sterically hindered ortho-hydroxyl groups of benzene ring
are not conductive to the formation of hydrazones.
Moreover, we investigated this reaction process by the
reaction of aromatic hydrazines and ketones with electron-
donating substituents including amino (5a) and methyl
(5g). Notably, the aromatic ketones with para-amino and
ortho-methyl produced corresponding hydrazones in lower
yields (6aa, 6ba, 6da, and 6dg). This confrms a rule that
the electron-donating group on the aromatic ketone is not
conductive to the condensation reaction. Besides, the low
yield of compound 6dg is consistent with that of compound
6ad. It is further proved that aromatic ketones with ortho-
position electron-donating group are not conductive to the
Conclusion
In summary, we have developed a new strategy for the ef-
cient and green synthesis of various aromatic acylhydra-
zones and hydrazones via an efcient C=N bond formation
pathway, water was used as the solvent. Various electron-
withdrawing groups and electron-donating groups were well
tolerated. Meanwhile, catalyst AlCl3·6H2O plays a vital role
in this reaction. This green synthesis of aromatic hydrazones
and acylhydrazones will have a broad application prospects.
1 3

AlCl3·6H2O‑catalyzed Schif‑base reaction between aryl ketones and aromatic…
J=7.2 Hz, 2H), 2.55 (s, 3H), 2.41 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=164.55, 153.08, 149.51, 137.81,
134.42, 133.99, 133.42, 132.00, 131.15, 128.73, 128.44,
122.21, 19.82, 14.71 ppm; HRMS (ESI): m/z calcd for
C16H15N3O3 ([M+H]+) 298.1186, found 298.1189.
Experimental
All reagents were purchased from commercial suppliers
without further purifcation. Experiments were monitored
by thin layer chromatography (TLC) and the TLC was per-
formed on pre-coated silica gel plates. The 1H and 13C NMR
spectra were recorded on a Bruker Avance III 500 MHz
spectrometer with DMSO-d6 as the solvent and tetramethyl-
silane (TMS) as an internal standard at room temperature.
Chemical shifts are given in δ relative to TMS, and the cou-
pling constants J values are given in Hertz (Hz). HRMS
were obtained from solariX.
Benzoic acid [1‑(4‑bromophenyl)ethylidene]hydrazide
(3af, C15H13BrN2O) White solid; m.p.: 220–221 °C; yield:
300 mg (95%); 1H NMR (500 MHz, DMSO-d6): δ=10.82
(s, 1H), 7.85 (d, J=40.8 Hz, 4H), 7.61 (dd, J=26.4, 6.2 Hz,
3H), 7.52 (t, J=7.1 Hz, 2H), 2.37 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=164.50, 154.41, 137.80, 134.48,
131.78, 128.87, 128.77, 128.39, 123.36, 40.53, 14.76 ppm;
HRMS (ESI): m/z calcd for C15H13BrN2O ([M + H]+)
317.0284, found 317.0287.
Synthesis of aromatic acylhydrazones
and hydrazones
Benzoic acid [1‑(3,4‑difuorophenyl)ethylidene]hydrazide
(3ag, C15H13F2N2O) White solid; m.p.: 206–207 °C; yield:
219 mg (80%); 1H NMR (500 MHz, DMSO-d6): δ=10.86
(s, 1H), 7.89 (s, 3H), 7.72 (s, 1H), 7.59 (d, J = 6.8 Hz,
1H), 7.52 (t, J=7.3 Hz, 3H), 2.37 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=164.50, 153.38, 150.74, 148.89,
136.30, 134.43, 132.00, 128.74, 128.43, 123.89, 117.94,
117.80, 115.79, 115.64, 14.84 ppm; HRMS (ESI): m/z calcd
for C15H13F2N2O ([M+H]+) 275.0990, found 275.0997.
Acylhydrazines (1 mmol), aromatic ketones (1 mmol), and
AlCl3·6H2O (0.1 mmol) were frst charged to a round-bottom
fask. 10 cm3 water was also added to the fask. Then the
reaction mixture was heated to 60 °C and stirred. TLC was
used to monitor reaction progress. After the reaction was
completed, solids were collected by fltration; the fltrate was
washed by water. The product was drained by vacuum pump
to aford desired compound.
Benzoic acid [1‑(4‑ethoxyphenyl)ethylidene]hydrazide (3aa,
C17H18N2O2) White solid; m.p.: 157–158 °C; yield: 208 mg
(74%); 1H NMR (500 MHz, DMSO-d6): δ=10.72 (s, 1H),
8.05-7.68 (m, 4H), 7.62–7.47 (m, 3H), 6.98 (d, J=6.7 Hz,
2H), 4.14–3.97 (m, 2H), 2.34 (s, 3H), 1.34 (t, J = 6.8 Hz,
3H) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 164.08,
160.20, 156.27, 134.61, 131.85, 130.80, 128.76, 128.42,
128.26, 128.24, 128.14, 114.60, 63.64, 15.06 ppm; HRMS
(ESI): m/z calcd for C17H18N2O2 ([M+H]+) 283.1441, found
283.1441.
Benzoic acid [1‑(2‑fuorophenyl)ethylidene]hydrazide (3ah,
C15H13FN2O) White solid; m.p.: 157–159 °C; yield: 195 mg
(76%); 1H NMR (500 MHz, DMSO-d6): δ=10.83 (s, 1H),
7.95-7.83 (m, 2H), 7.59 (s, 2H), 7.51 (dd, J=17.9, 11.3 Hz,
3H), 7.28 (t, J=9.5 Hz, 2H), 2.38 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=161.41, 159.44, 153.71, 134.40,
132.00, 131.58, 131.51, 130.27, 128.74, 128.45, 127.82,
127.73, 124.90, 116.51, 18.28 ppm; HRMS (ESI): m/z calcd
for C15H13FN2O ([M+H]+) 257.1085, found 257.1090.
Benzoic acid [1‑(4‑methylphenyl)propylidene]hydrazide
(3ai, C17H18N2O) White solid; m.p.: 146–147 °C; yield:
194 mg (73%); 1H NMR (500 MHz, DMSO-d6): δ=10.80
(s, 1H), 7.80 (d, J=54.4 Hz, 4H), 7.63–7.56 (m, 1H), 7.53
(d, J=7.6 Hz, 2H), 7.30–7.15 (m, 2H), 2.91 (q, J=7.6 Hz,
2H), 2.35 (d, J=4.7 Hz, 3H), 1.08 (t, J=7.6 Hz, 3H) ppm;
13C NMR (125 MHz, DMSO-d6): δ = 164.63, 159.76,
139.29, 134.63, 131.81, 129.50, 128.72, 128.38, 127.56,
126.98, 21.30, 20.24, 11.41 ppm; HRMS (ESI): m/z calcd
for C17H18N2O ([M+H]+) 267.1491, found 267.1492.
Benzoic acid [1‑(3‑hydroxyphenyl)ethylidene]hydrazide (3ac,
C15H14N2O2) White solid; m.p.: 180–181 °C; yield: 188 mg
(74%); 1H NMR (500 MHz, DMSO-d6): δ=10.74 (s, 1H),
9.58 (s, 1H), 7.96-7.82 (m, 2H), 7.59 (t, J = 7.3 Hz, 1H),
7.52 (t, J = 7.5 Hz, 2H), 7.35 (s, 1H), 7.24 (d, J = 8.7 Hz,
2H), 6.85 (d, J=7.0 Hz, 1H), 2.34 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=164.35, 157.75, 155.97, 139.93,
134.57, 131.85, 129.80, 128.76, 128.31, 117.94, 117.11,
113.44, 15.06 ppm; HRMS (ESI): m/z calcd for C15H14N2O2
([M+H]+) 255.1128, found 255.1135.
4‑Hydroxybenzoic acid 2‑[1‑(4‑ethoxyphenyl)propylidene]‑
hydrazide (3ba, C17H18N21O3) White solid; m.p.: 225–226 °C;
yield: 268 mg (90%); H NMR (500 MHz, DMSO-d6):
δ = 10.44 (s, 1H), 10.07 (s, 1H), 7.79 (d, J = 8.4 Hz, 4H),
6.96 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 4.07
(q, J = 6.9 Hz, 2H), 2.31 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H)
Benzoic acid [1‑(4‑methyl‑3‑nitrophenyl)ethylidene]‑
hydrazide (3ae, C16H15N31O3) White solid; m.p.: 203–204 °C;
yield: 288 mg (97%); H NMR (500 MHz, DMSO-d6):
δ = 10.91 (s, 1H), 8.42 (d, J = 17.3 Hz, 1H), 8.13–8.02
(m, 1H), 7.90 (s, 2H), 7.59 (d, J = 7.5 Hz, 2H), 7.53 (t,
1 3

Z. X. Zhao et al.
ppm; 13C NMR (125 MHz, DMSO-d6): δ=163.72, 160.84,
160.02, 148.49, 130.96, 130.32, 128.28, 125.09, 115.28,
114.58, 63.62, 15.07, 14.59 ppm; HRMS (ESI): m/z calcd
for C17H18N2O3 ([M+H]+) 299.1390, found 299.1395.
(125 MHz, DMSO-d6): δ=149.27, 146.03, 143.35, 129.02,
127.16, 126.83, 121.72, 114.37, 113.92, 13.30 ppm; HRMS
(ESI): m/z calcd for C14H14ClN3 ([M+H]+) 260.0949, found
260.0951.
4‑Hydroxybenzoic acid 2‑[1‑(4‑aminophenyl)propylidene]‑
hydrazide (3bl, C15H15N2O3) Light yellow solid; m.p.: 272–
274 °C; yield: 215 mg (80%); 1H NMR (500 MHz, DMSO-
d6): δ = 10.33 (s, 1H), 10.05 (s, 1H), 7.87–7.71 (m, 2H),
7.58 (s, 2H), 6.92–6.81 (m, 2H), 6.65–6.53 (m, 2H), 5.48
(s, 2H), 2.25 (s, 3H) ppm; 13C NMR (125 MHz, DMSO-d6):
δ=163.48, 160.70, 156.73, 150.69, 130.15, 128.09, 125.80,
125.30, 115.30, 113.67, 14.45 ppm; HRMS (ESI): m/z calcd
for C15H15N2O3 ([M+H]+) 270.1237, found 270.1237.
1‑(3‑Hydroxyphenyl)ethanone 2‑(2,4‑dinitrophenyl)hydra‑
zone (6cc, C14H12N4O5) Red solid; m.p.: 250–252 °C; yield:
275 mg (87%); 1H NMR (500 MHz, DMSO-d6): δ=10.99
(s, 1H), 9.59 (s, 1H), 8.79 (s, 1H), 8.35 (d, J=12.0 Hz, 1H),
7.93 (d, J=9.5 Hz, 1H), 7.23 (dq, J=15.6, 7.8 Hz, 3H), 6.83
(d, J=5.7 Hz, 1H), 2.33 (s, 3H) ppm; 13C NMR (125 MHz,
DMSO-d6): δ = 157.90, 153.43, 149.58, 144.77, 138.63,
137.67, 130.50, 129.90, 123.29, 117.82, 117.47, 116.69,
113.37, 13.70 ppm; HRMS (ESI): m/z calcd for C14H12N4O5
([M+H]+) 317.0880, found 317.0885.
3‑Pyridinecarboxylic acid [1‑(3‑hydroxyphenyl)propylidene]‑
hydrazide (3cc, C14H13N2O3) White solid; m.p.: 191–192 °C;
1‑(2‑Methylphenyl)ethanone 2‑(4‑nitrophenyl)hydrazone
(6dg, C15H15N3O2) Yellow solid; m.p.: 147–151 °C; yield:
151 mg (56%); 1H NMR (500 MHz, DMSO-d6): δ=10.13
(s, 1H), 8.12 (d, J=9.3 Hz, 2H), 7.35 (d, J=7.9 Hz, 1H),
7.29–7.24 (m, 5H), 2.41 (s, 3H), 2.31 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6): δ=151.97, 149.34, 140.15, 138.88,
135.52, 131.20, 128.62, 128.31, 126.33, 126.15, 112.23,
21.21, 18.08 ppm; HRMS (ESI): m/z calcd for C15H15N3O2
([M+Na]+) 292.1056, found 292.1057.
1
yield: 219 mg (86%); H NMR (500 MHz, DMSO-d6):
δ = 10.94 (s, 1H), 9.59 (s, 1H), 9.06 (s, 1H), 8.79–8.73
(m, 1H), 8.25 (d, J=7.9 Hz, 1H), 7.58–7.53 (m, 1H), 7.36
(s, 1H), 7.25 (d, J = 9.0 Hz, 2H), 6.86 (d, J = 7.3 Hz, 1H)
ppm; 13C NMR (125 MHz, DMSO-d6): δ=162.96, 157.77,
156.37, 152.44, 149.24, 139.79, 136.18, 130.34, 129.82,
123.90, 118.04, 117.29, 113.47, 15.24 ppm; HRMS (ESI):
m/z calcd for C14H13N2O3 ([M + H]+) 256.1081, found
256.1082.
Acknowledgements We thank for fnancial support given by Middle
and Youth Teachers Scientifc and Technological Talents Developing
Fund (No. ZQ 2018-20), Natural Science Foundation of Shanghai (No.
15ZR1440400), Collaborative Innovation Fund (No. XTCX2016-14),
National Youth Fund Project of China (No. 21602135), Shanghai
Municipal Education Commission (Plateau Discipline Construction
Program).
3‑Pyridinecarboxylic acid [1‑(4‑aminophenyl)propylidene]‑
hydrazide (3cl, C14H14N4O) Yellow solid; m.p.: 207–208 °C;
1
yield: 201 mg (79%); H NMR (500 MHz, DMSO-d6):
δ = 10.82 (s, 1H), 9.05 (s, 1H), 8.71 (d, J = 25.8 Hz, 1H),
8.28–8.10 (m, 1H), 7.70–7.31 (m, 3H), 6.62 (s, 2H), 5.53
(s, 2H), 2.29 (s, 3H) ppm; 13C NMR (125 MHz, DMSO-
d6): δ = 162.47, 158.40, 152.24, 151.04, 149.06, 135.98,
130.53, 128.37, 125.37, 123.93, 113.69, 14.79 ppm; HRMS
(ESI): m/z calcd for C14H14N4O ([M+H]+) 255.1240, found
255.1242.
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1 3