7-Chloro-4-hydrazinylquinoline and seven 4-(2-arylidenehydrazinyl)-7-
chloroquinoline compounds were synthesized. The structure of the seven compounds were
determined by IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Three new compounds
(3a, 3f-g) and four other compounds (3b-d, 3e) are similar in characteristic of IR, NMR
spectra: in the IR spectra, absorption band of the N–H bonds appeared at 3120–3194 cm
and absorption band of the C=N bonds appeared at 1568–1589 cm-1 while the 1H-NMR
spectra showed signal of imine protons at 8.24 – 8.31 ppm and in the 13C-NMR spectra,
signal of C=N at 149.3–163.7 ppm.
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TRƯỜNG ĐẠI HỌC SƯ PHẠM TP HỒ CHÍ MINH
TẠP CHÍ KHOA HỌC
HO CHI MINH CITY UNIVERSITY OF EDUCATION
JOURNAL OF SCIENCE
ISSN:
1859-3100
KHOA HỌC TỰ NHIÊN VÀ CÔNG NGHỆ
Tập 14, Số 3 (2017): 5-11
NATURAL SCIENCES AND TECHNOLOGY
Vol. 14, No. 3 (2017): 5-11
Email: tapchikhoahoc@hcmue.edu.vn; Website:
5
SYNTHESIS AND STRUCTURAL STUDY OF SOME
4-(2-ARYLIDENEHYDRAZINYL)-7-CHLOROQUINOLINE COMPOUNDS
Le Trong Duc1, Nguyen Tien Cong1*, Nguyen Quang Tung2
1Ho Chi Minh City University of Education
2Hanoi University of Industry
Received: 14/02/2017; Revised: 03/3/2017; Accepted: 24/3/2017
ABSTRACT
7-Chloro-4-hydrazinylquinoline and seven hydrazone derivatives were synthesized from 4,7-
dichloroquinoline. The structures of the compounds were determined by IR, 1H-NMR, 13C-NMR
and HR-MS spectral data
Keywords: 4-(2-arylidenehydrazinyl)-7-chloroquinoline, 7-chloro-4-hydrazinylquinoline,
4,7-dichloroquinoline.
TÓM TẮT
Tổng hợp và xác định cấu trúc một số hợp chất
4-(2-arylidenehydrazinyl)-7-chloroquinoline
7-Chloro-4-hydrazinylquinoline và bảy dẫn xuất dạng hydrazone của nó (trong đó có 3 hợp
chất mới) đã được tổng hợp từ 4,7-dichloroquinoline. Cấu trúc của các chất tổng hợp được đã
được xác nhận bởi các phổ IR, 1H-NMR, 13C-NMR và phổ khối lượng độ phân giải cao.
Từ khóa: 4-(2-arylidenehydrazinyl)-7-chloroquinoline, 7-chloro-4-hydrazinylquinoline, 4,7-
dichloroquinoline.
1. Introduction
Hydrazones containing quinoline heterocycle have been of great interest in medicinal
chemistry for their role as anticancer, antibacterial, antifungal, anti-tubercular agents [1-7].
It has been evidenced from literature survey that the bioactivity of these compounds were
affected by the presence or absence of chlorine substituent at the 7th position in quinoline
heterocycle as well as the properties of some substituents in molecule of these hydrazones
[4,5]. Although synthesis and bioactive of some hydrazones synthesized from 4,7-
dichloroquinoline were reported, spectral data of many compounds were not published. In
our research on 4-(2-arylidenehydrazinyl)-7-chloroquinoline compounds, we reported here
the result of synthesis of the seven compounds and some features about spectral data
including IR, 1H-NMR, 13C-NMR spectra and MS of them.
* Email: congnt@hcmue.edu.vn
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Tập 14, Số 3 (2017): 5-11
6
2. Experimental
The synthetic route for the preparation of 4-(2-arylidenehydrazinyl)-7-
chloroquinoline compounds is presented in Scheme 1.
R = 4-(CH3)2NC6H4 (3a), 4-ClC6H4 (3b), 4-FC6H4 (3c), 2-FC6H4 (3d), 3CH3O-4-HOC6H3
(3e), 3CH3O-4-HO-5IC6H2 (3f), C6H5CH=CH (3g).
Scheme 1. Pathway for synthesis
Synthesis of 7-chloro-4-hydrazinylquinoline (2): compound (2) was synthesized
following the previously reported procedure [1,6]. The solution of hydrazine hydrate (80%,
35 mL, 50 mmol) in ethanol absolute (30 mL) was droped down slowly to the solution of
4,7-dichloroquinoline (10 g, 5 mmol) in ethanol absolute (20 mL). After the mixture was
refluxed for 2 hours and then was maintained at room temperature overnight, the yellow
precipitates were filtered and recrystallized from ethanol to give 4.66 g crystal (yield 80%,
mp. 224oC matching with [1]).
Synthesis of 4-(2-arylidenehydrazinyl)-7-chloroquinoline compounds (3a-g): The
(3a-g) compounds were synthesized according to the procedure for synthesis of 4-(2-
benzylidenehydrazinyl)-7-chloroquinoline described in reference [1]: The (2) compound
(0.19 g, 1.0 mmol) was dissolved in 10 mL of anhydrous ethanol. To this solution, a
solution of appropriate aromatic aldehyde (1.0 mmol) and a few drops of acid acetic glacial
in 10 mL ethanol absolute was slowly added while stirring. The mixture was refluxed for
3.0 hours. After standing overnight, the precipitate obtained was filtered off and
recrystallized from suitable solvent to give the corresponding hydrazone.
IR spectra (IR) of all compounds were measured in KBr discs on a Shimadzu FTIR-
8400S spectrophotometer at Faculty of Chemistry, Ho Chi Minh City University of
Education and on Shimadzu FTIR Affinity - 1S at Faculty of Chemistry, University of
Science – Ha Noi National University.
1H-NMR spectra (500 MHz) and 13C-NMR spectra (125 MHz) were recorded on a
Bruker Avance 500 MHz using DMSO-d6 as solvent and tetramethylsilane as an internal
standard at Faculty of Chemistry, University of Science – Ha Noi National University
HR-MS spectra were taken on a Bruker micrOTOF-Q 10187 at University of Science
– Ho Chi Minh National University.
3. Result and discussion
7-Chloro-4-hydrazinylquinoline (2) was synthesized from 4,7-dichloroquinoline
according to known method [1,6]. Melting point of the product is in accordance with the
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Le Trong Duc et al.
7
melting point of 7-chloro-4-hydrazinylquinoline described in [1]. All IR, 1H-NMR, 13C-
NMR spectral data of the product are conformed with the structure of the title compound.
IR: 3255 and 3258 cm-1 ( N H of –NH2), 3117 cm
-1 ( N H of –NH–), 3055 cm
-1 ( 2C p Hs ),
2931 cm-1 ( 3C p Hs ), 1600 cm
-1 ( C C ), 1566 cm
-1 ( C N ).
1H-NMR: δ 8.60 (1H, br, NH), δ
8.39 (1H, br, Ar-H), δ 8.16 (1H, d, J = 9.0 Hz, Ar-H), δ 7.76 (1H, br, Ar-H), δ 7.39 (1H, d-
d, J1 = 9.0 Hz, J2 = 2.0 Hz, Ar-H), δ 4.45 (2H, br, NH2). 13C-NMR: δ 152.8, 151.8, 148.8,
133.2, 127.4, 123.8, 116.0, 115.8, 98.8. A search of the SciFinder (December 14, 2016)
showed that the sufficient spectral data of 7-chloro-4-hydrazinylquinoline compound had
not been found in the references.
In reaction of aromatic aldehydes with (2) compound to obtain desired hydrazone
compounds (3a-g), aldehydes are activated by acid acetic. The reaction occurs easily and
may be observed clearly by both changing color of reaction solution and the appearance of
precipitate during and after the progress of reaction.
Table 1. Melting point, yield, IR spectral data and molecular weight of (3a-g) compounds
Com. R
Solvent
recrystal-
ized
Mp. (oC) Yield (%)
ν (cm-1) [M+H]+
[M+ Calcd.] C-H NH OH
C=C
C=N
3a
DMF :
H2O
237 80 2978 3194 1604 1573
325.1241
[324.1142]
3b
EtOH:
H2O
226
[6]: 225–226 82 3078 3191
1602
1576
316.0415
[315.0330]
3c
EtOH 245 [6]: 245–246 79 3086 3194
1600
1570
300.0747
[299.0626]
3d
EtOH 234 [6]: 234–236 79 3085 3194
1601
1568
300.0711
[299.0626]
3e
EtOH:
H2O
224 [7]: 273
– 275 81
2924
3070
3150
3472
1610
1589
328.0875
[327.0775]
3f
DMF :
H2O
233 84 2980 3068
3120
3490
1608
1579
453.9837
[452.9741]
3g
EtOH 231 85 3080 3260 1610 1578
308.0988
[307.0876]
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Tập 14, Số 3 (2017): 5-11
8
Although the synthesis of the (3b-d) compounds were reported in [6], (3e) was
reported in [7], but spectral data (IR, 1H-NMR, 13C-NMR) of these compounds were not
mentioned completely. Both synthesis and spectral data of three other compounds
including (3a) and (3f-g) have not been reported in any references.
In IR spectra of the hydrazones, the specific vibration of amino group (–NH2, double
peak) at 3255 – 3258 cm-1 was disappeared and the sharpness peak of N–H bonds still
appear. IR spectra of the (3a-g) compounds showed stretching bands of the N–H bonds
(around 3200 cm-1) and C=N bonds (at 1568–1589 cm-1), which are similar to that of the 7-
chloro-4-quinolinylhydrazone compounds described in [6]. In the IR spectra, except the
stretching bands of the N–H bonds, (3e) and (3f) compounds also have the peak of the
vibration of O-H group at 3471 – 3645 cm-1. In some compounds that have not the –OH
group in the structure (3a-d, 3g), there are some differences from the stretching bands of
N–H bonds. In the (3g) compound, the longer conjunction in the molecule of (3g) than the
others may be the reason of appearance of the vibration of N–H bonds at higher frequency
(nearby 3260 cm-1).
Compounds (3b-d) have the melting point matching with some references but (3e) is
not. The result of [2] show that the melting point of (3e) from 273 to 275 oC. This
difference can be explain by the solvent used for recrystallization. Each solvent has their
way to forming crystal so that the structure of (3e) may not tight and it show the melting
point lower than that one presented in [7].
Table 2. Signals in the 1H-NMR of hydrazones (3a-g) (δ, ppm and J, Hz)
N
HN N C
H
R
Cl
1
2
3
45
6
7
8
9
10
11 12 13
Vị
trí
X -
4-N(CH3)2
(3a)
4-Cl
(3b)
4-F
(3c)
2-F
(3d)
3-OCH3-4-
OH (3e)
3-OCH3-4-
OH-5-I
(3f)
(3g)
2 8.54 (br) 8.60 (br) 8.60 (br) 8.62 (br) 8.56 (br) 7.86 (br)
8.57 (d)
J = 5.5
3 7.31 (br) 7.42 (br) 7.41 (br)
7.43 (d)
J = 5.0
7.37 (br) 7.41 (br)
7.25 (d)
J = 5.5
5
8.36 (d)
J = 8.0
8.39 (br)
8.38 (d)
J = 9.0
8.38 (d)
J = 9.0
8.37 (d)
J = 8.0
8.43 (d)
J = 9.0
8.37 (d)
J = 9.0
6 7.55 (br)
7.61 (d-
br)
7.60 (br)
7.63 (d-
br)
7.57 (br)
7.62 (d-br)
J = 9.0
7.60
(dd)
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Le Trong Duc et al.
9
J = 7.5 J = 8.5 J1 = 9.0
J2 = 2.5
8 7.87 (br) 7.92 (br) 7.91 (br) 7.93 (br) 7.88 (br) 7.95 (br)
7.90 (d)
J = 2.5
11 10.95 (br)
11.34
(br)
11.26 (br)
11.39
(br)
11.06 (br) 11.78 (br)
11.15
(s)
13 8.29 (s) 8.39 (s) 8.40 (s) 8.62 (s) 8.30 (s) 8.31 (s)
8.24 (d)
J = 9.0
15
7.61 (d)
J =8.5
7.83 (d)
J = 8.5
7.86 (m) 7.31 (m)
7.15 (dd)
J1 = 8.0
J2 = 1.5
7.68 (d)
J = 1.5
7.64 (d)
J = 7.5
16
6.78 (d)
J =8.5
7.53 (d)
J = 8.5
7.31 (dd)
J1 = 8.5; J2
= 9.0
7.47 (dt)
J1 = J2 =
8.0; J3 =
4.5
6.86 (d)
J = 8.0
-
7,41
(dd)
J1 = 7.5
J2 = 7.5
17 - - -
7.08 (t)
J1 = J2 =
8.0
- -
7.33 (t)
J = 7.5
18
6.78 (d)
J =8.5
7.53 (d)
J = 8.5
7.31 (dd)
J1 = 8.5; J2
= 8.8
7.31 (m) - -
7.41
(dd)
J1 = 7.5
J2 = 7.5
19
7.61 (d)
J =8.5
7.83 (d)
J = 8.5
7.86 (m) -
7.41 (d)
J = 1.5
7.45 (d)
J = 2.0
7.64 (d)
J = 7.5
Note: H13a: δ 7.13 (dd), J1 = 16.0 Hz, J2 = 9.0 Hz; H13b: δ 7.05 (d), J1 = 16.0 Hz.
In the 1H-NMR spectra, except the signal of NH group appeared at high field (around
11.0 ppm) and the singlet signals of the methyl group of (3a), (3e) and (3f) compounds
appeared at low field (3a gives the signal of the –N(CH3)2 group at 2.99 ppm; (3e) and (3f)
give the signals of the –OCH3 groups at 3.88 ppm and 3.92 ppm, respectively), most of
signals appeared in the aromatic area. H15 with H19 and H16 with H18 in the (3a-c) and (3g)
molecules were pairs of equivalent protons so they appeared with intensity of 2H in the
spectra. The presence of singlet signal at 9.46 ppm in the 1H-NMR spectrum of (3e) and
singlet signal at 10.07 ppm in the 1H-NMR spectrum of (3f) was attributed to protons of
the hydroxyl groups. Besides, in the 1H-NMR spectrum of (3g) compound, spin–spin
splitting between olefinic protons (H13a and H13b) with the coupling constants J = 16.0 Hz
indicates that this compound exists in a E isomer. We assigned signals according to the
structure of the hydrazone compounds and showing the result in Table 2.
In the 13C-NMR spectra of all the (3a-g) compounds also appeared fully signals as
expected. However, these compounds do not dissolve well in solvent which used for taking
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Tập 14, Số 3 (2017): 5-11
10
spectra so the signals appeared in the spectra with low resolution. (3c) and (3d) compounds
have fluorine substituent so some signals of carbon atom in the aromatic area of these
compounds appear as doublets because of spin–spin splitting between 19F and 13C with the
suitable coupling constants J. In the 13C-NMR spectrum of (3a) compound, the methyl
group has the same chemical shift with the methyl groups of DMSO-d6 solvent and these
signals were assigned at 40.0 ppm. All of compounds showed the signals matching with
the expected structure. The signals in the 13C-NMR spectra were presented in Table 3.
The results showed that all of seven hydrazine compounds (3a-g) have the signal of
imine protons (–N=CH–) at 8.24 – 8.31 ppm which are in agreement with the chemical
shift of imine protons in 7-chloro-4-quinolinylhydrazone molecules described in [6].
Table 3. Signals in the 13C-NMR of hydrazones (δ, ppm)
(see the structure at Table 2)
Compounds C=C, C=N
CH2
CH3
3a
100.7, 111.9, 115.5, 122.1, 123.9, 124.5, 127.6, 128.1,
133.6, 144.5, 147.1, 149.4, 151.2, 152.0
40.0
3b
114.3, 116.0, 116.1, 122.6, 124.4, 125.5, 126.1, 128.7,
129.3, 132.7, 133.8, 134.2, 142.4, 152.5
-
3c
99.5, 101.4, (115.8, 115.9; J = 86), (123.9, 124.0, J =
30.5), 124.1, 124.9, 127.7, 128.8, (133.7, 133.8, J = 30.0);
(142.2, 142.3, J = 30.0), 147.1, 152.0, 161.8, 163.7.
-
3d
101.5, 115.5, (115.9, 116.0, J = 82.5), (122.2, 122.3; J =
39), 123.8, (124.9, 125.1, J = 85.5), 126.1, 127.7, (131.1,
131.2, J = 31.5), 133.8, (135.9, 135.9, J = 10.0); 146.8,
149.2, 152.0, 159.3, 161.3.
-
3e
101.0, 105.8, 109.1, 115.5, 121.4, 124.0, 124.7, 126.2,
127.6, 129.3, 133.8, 144.0, 147.2, 148.1, 148.5, 152.0.
55,6
3f
84.6, 101.0, 109.2, 124.6, 125.3, 125.6, 127.8, 130.0,
131.7, 135.1, 139.8, 145.2, 147.4, 147.9, 148.2, 149.3.
56,1
3g
101.6, 117.1, 124.4, 125.3, 126.1, 127.4, 128.1, 129.0,
129.3, 131.7, 134.3, 137.6, 146.4, 147.1, 149.7, 152.4.
-
4. Conclusion
7-Chloro-4-hydrazinylquinoline and seven 4-(2-arylidenehydrazinyl)-7-
chloroquinoline compounds were synthesized. The structure of the seven compounds were
determined by IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Three new compounds
(3a, 3f-g) and four other compounds (3b-d, 3e) are similar in characteristic of IR, NMR
spectra: in the IR spectra, absorption band of the N–H bonds appeared at 3120–3194 cm-1
TẠP CHÍ KHOA HỌC - Trường ĐHSP TPHCM Le Trong Duc et al.
11
and absorption band of the C=N bonds appeared at 1568–1589 cm-1 while the 1H-NMR
spectra showed signal of imine protons at 8.24 – 8.31 ppm and in the 13C-NMR spectra,
signal of C=N at 149.3–163.7 ppm.
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