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Preparation and Antibacterial Activity of Some New 4-(2-Heterylidenehydrazinyl)-7-chloroquinoline Derivatives.

1. Introduction

Quinoline derivatives, which widely occur in nature, especially alkaloids, have become an important skeleton in synthetic chemistry due to their variety of applications in medicinal, bioorganic, and industrial chemistry. Some hydrazone derivatives possessing a quinoline moiety have been well known as having a broad spectrum of biological activities such as antibacterial [1], anticancer [2], antitubercular [3-5], antifungal [6], anti-inflammatory [7], antimalarial [8], and antimicrobial [9, 10]. According to Ferreira et al. [11], hydrazone derivatives, which were prepared from the reaction of 7-chloro-4-hydrazinylquinoline and heteroaromatic aldehydes, showed a good antimycobacterial activity in comparison with some drugs such as ethambutol and rifampicin. Additionally, some hydrazones being born from 2-chloroquinoline-3-carbaldehyde possessed a moderate to good antibacterial activity against both Gram-positive and Gram-negative bacteria [12].

Besides, pyrazole derivatives have been of great interest in medicinal chemistry for their role as potent antiparasitic [13], antimicrobial [14], and antitumor agents [15]. (4-Chlorophenyl)-[1-(4-nitrophenyl)-3-phenylpyrazol-4-yl-methylene]amine [13] compound possesses a good activity against L. infantum with IC50 of 12.4 [micro]M while 5-(3-isobutyl-1-phenyl-1H-pyrazol-4-yl)-2-substituted-1,3,4-oxadiazoles [15] have an anticancer activity against breast and liver cell line with IC50 of around 2-7 [micro]M and 4-13 [micro]M, respectively.

In this article, 7-chloro-4-hydrazinylquinoline 2 was prepared from the reaction of 4,7-dichloroquinoline 1 and hydrazine hydrate and then was utilized as the key intermediate material for the synthesis of some new hydrazones containing 2-chloroquinoline or pyrazole moiety. The new synthesized hydrazones including 4-{2-[(6-substituted-2-chloroquinolin-3-yl)methylidene]hydrazinyl}-7-chloroquinoline 4a-c and 4-(2-{[3-(4-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl]methylene}hydrazinyl)-7-chloro-quinoline 4d-f were evaluated for antimicrobial activities against eight kinds of microorganisms. The chemical structure of the hydrazones was elucidated by IR, NMR, and HRMS spectral analysis and their biological activities were reported for the first time.

2. Materials and Methods

All chemicals were purchased from Merck or Aldrich and solvents were commercial and were used without any further purification.

Melting points were determined with a Gallenkamp digital Melting-point apparatus 5A-6797 and were uncorrected.

The IR absorption spectra were scanned on Shimadzu FTIR 8400S spectrum using potassium bromide (KBr) pellets.

All the [sup.1]H, [sup.13]C-NMR, HSQC, and HMBC spectra were recorded on a Bruker Advance 500 MHz model spectrometer using DMSO-[d.sub.6] as solvents and internal standard. The spinspin coupling constants (J) are given in Hz. Peak multiplicity is reported as s (singlet), d (doublet), dd (double-doublet), t (triplet), q (quartet), m (multiplet), and br (broad).

Mass spectrometric data were recorded on a micrOTOF-QII Bruker.

Thin-layer chromatography (TLC) was performed on silica-gel sheets (silica gel 60 F254, Merck) and visualized in ultraviolet light (254 nm).

The synthesis of the hydrazones containing quinoline heterocycles was performed following the steps shown in Scheme 1.

2-Chloroquinoline-3-carbaldehydes 3a-c were prepared according to the literature [16]. p-Substituted aniline was added to the solution of acetic anhydride in acetic acid, following by being refluxed in 2 hours. Consequently, cooling to room temperature and pouring into ice water were performed to collect N-(4-substituted phenyl)acetamide derivatives, which then reacted to the mixture of dimethylformamide and phosphoryl chloride (Vilsmeier-Haack reagent) to form 2-chloroquinoline-3-carbaldehyde derivatives 3a-c.

1,3-Diarylpyrazole-4-carbaldehydes 3d-f were prepared according to the literature [17]. Phenylhydrazine hydrochloride was slowly added to the mixture of 4'-substituted acetophenones and acetic acid in ethanol. The reaction mixture was stirred and then was poured into water to separate the product 1-(1-phenylethylidene)-2-phenylhydrazine, which was treated with Vilsmeier-Haack reagent at 80-90[degrees]C in 15 hours to form 1,3-diphenylpyrazole-4-carbaldehyde derivatives 3d-f.

Preparation of 7-Chloro-4-hydrazinylquinoline 2. 4,7-Dichloroquinoline (10 g, 5 mmol) was dissolved in ethanol (20 mL) in which hydrazine hydrate (35 mL, 50 mmol) was slowly dropped. The reaction mixture was refluxed for 2 hours. Consequently, this mixture was cooled to room temperature and was kept overnight to separate the solid. The yellow precipitates were filtered and recrystallized from ethanol to give compound 2. Yield: 80%; mp. 224-225[degrees]C (literature [1]: 223-225[degrees]C). IR (v, [cm.sup.-1]): 3255,3258 (-NH- and -N[H.sub.2]), 3055 ([Csp.sup.2]-H), 2931 ([Csp.sup.3]-H), 1600 (C=C) and 1566 (C=N); [sup.1]H-NMR (500 MHz, DMSO-[d.sub.6]) [delta] (ppm), J (Hz): 8.60 ([sup.1]H, br, >NH), 8.39 ([sup.1]H, br, Ar-H), 8.16 ([sup.1]H, d, J = 9.0, Ar-H), 776 ([sup.1]H, s, Ar-H),739([sup.1]H, dd, [J.sub.1] =9.0, [J.sub.2] = 2.0, Ar-H), 6.87([sup.1]H, br, Ar-H) and 4.45 (2H, br, -N[H.sub.2]); [sup.13]C-NMR (125 MHz, DMSO-[d.sub.6]) [delta] (ppm): 152.8, 151.8, 148.8, 133.2, 127.4, 123.8, 115.9 and 98.8 (S1-S3 from Supplementary materials).

Preparation of 4-(2-Heterylidenehydrazinyl)-7-chloroquinoline Compounds 4a-f. Appropriate 2-chloroquinoline-3-carbaldehyde derivatives 3a-c or 1,3-diphenylpyrazole-4-carbaldehyde derivatives 3d-f (1 mmol) were dissolved in absolute ethanol (10 mL) with a few drops of glacial acetic acid. This mixture was stirred for 10 minutes and then compound 2 (0.19 g, 1 mmol) was added in. The reaction mixture was refluxed for 3 hours. At the completion of reaction, the mixture was cooled to room temperature to separate the solid, which was filtered and recrystallized from suitable solvent to give products 4a-f, respectively.

All the synthesized hydrazones were evaluated to in terms of antimicrobial activities against microorganism. The method for these experiences was based on the literature [18, 19].

3. Result and Discussion

7-Chlorohydrazinylquinoline 2 was prepared from the reaction of 4,7-dichloroquinoline 1 and hydrazine hydrate. Its [sup.1]H-NMR spectrum (S2 from Supplementary materials) showed two broad singlet signals of hydrazine group (-NHN[H.sub.2]) at [[delta].sub.H] 8.6 and 4.5. Additionally, there were a doublet signal at [[delta].sub.H] 8.16 with spin-spin coupling of 9.0 Hz attributed to H5 and a double-doublet signal at 7.39 attributed to H6. Meanwhile, H8 gave a singlet signal at [[delta].sub.H] 7.76. Two signals appearing at [[delta].sub.H] 8.39 and 6.87 were attributed to H2 and H3, respectively. Theoretically, H2 and H3 usually appear as doublet signals due to having spin-spin coupling together. However, in our case, the ring system may lead to them becoming hydroxylic protons, and, so, the broad signals were obtained.

Compound 2 was utilized as a precursor for preparation of six new hydrazones according to Scheme 1. The reaction of 4,7-dichloroquinoline 1 with hydrazine hydrate formed 7-chlorohydrazinylquinoline 2, which was treated by 2-chloroquinoline-3-carbaldehyde derivatives 3a-c to form 4-{2-[(6-substituted-2-chloroquinolin-3 -yl)methylidene]hydrazinyl}-7-chloroquinoline compounds 4a-c. Meanwhile, 4-(2-{[3-(4-substituted phenyl)-1-phenyl -1H-pyrazol-4-yl]methylene}hydrazinyl)-7-chloroquinoline compounds 4d-f were produced by the reaction of compound 2 and 1,3-diphenylpyrazole-4-carbaldehyde derivatives 3d-f.

The reaction of 2 and some heteroaromatic 3a-f occurred easily and may be observed clearly by both changing color of reaction solution and the appearance of precipitates in the progress of reaction.

[formula not reproducible]

In IR spectra, the specific vibration of amino group (-N[H.sub.2], double peak) at 3255-3258 [cm.sup.-1] disappeared while the sharpness peak of N-H bonds still appeared around 3200 [cm.sup.-1]; the stretching bands of the C=N bonds were recognized at 1555-1582 [cm.sup.-1]. These data are similar to those of the 7-chloro-4-quinolinylhydrazone compounds described in literature [3].

The physical properties and IR spectral data of the 4a-f compounds were presented in Table 1.

The structures of the hydrazones were further confirmed by the HRMS data. Molecular ion peaks in the mass spectra of the products were in conformity with desired molecular formulas of them (see Tables 2 and 3).

Both the [sup.1]H-NMR (500 MHz, DMSO-[d.sub.6]) and [sup.13]C-NMR (125 MHz, DMSO-[d.sub.6]) spectra of these compounds showed all of the signals matching with the expected structures. The [sup.1]H-NMR spectra of each of the compounds 4a-f showed the singlet signals at [[delta].sub.H] 8.51-8.83 and 11.11-11.70, which were attributed to -CH=N- (H13) and -NH- (Hll), respectively. Furthermore, each of the [sup.13]C spectra presented a signal around 136-139 ppm, which made cross peak with the signal of H13 in the HSQC spectra and so it was attributed to -CH=N- (C13). Besides, singlet signal of the methyl group in molecule of 4b appeared at 2.54 ppm; the signals of the ethyl group in 4c were assigned as quartet at 4.21 ppm (2H, J = 70 Hz) and triplet at 1.44 ppm (3H, J = 70 Hz). The singlet at [[delta].sub.H] 9.01-9.15 in the [sup.1]H-NMR spectra of compounds 4a-c was assigned to proton in the 23th position (H23) while the singlet at [[delta].sub.H] 9.11-9.17 in the [sup.1]H-NMR spectra of compounds 4d-f was assigned to proton of the pyrazole ring (H15). A complete assignment of [sup.1]H and [sup.13]C NMR spectra of the hydrazones was based on analysis of NMR and 2D spectra (the HMBC correlations of 4b and 4e compounds were shown in the structures at Tables 2 and 3) and is presented in Tables 2 and 3.

The configuration of -CH=N- bonds of hydrazone compounds was identified by their NOESY spectral analysis. The supposal configuration of compound 4d was Z due to the correlation between H2 and H22/28, which was shown in its NOESY spectrum. Meanwhile, the NOESY spectrum of compound 4e presented a cross peak of correlation of H13 and H8, which confirmed the E configuration of this compound. There was a remark that the carbon signal of -CH=N- group in Z configuration appears at the higher magnetic field than in E configuration [20]. In our case, the same observation was collected with the carbon signal of -CH=N- group of compound 4d appearing at [[delta].sub.C] 136.4 whereas the others were collected at [[delta].sub.C] 139.0. Furthermore, the [sup.13]C-NMR spectrum of compound 4f showed the signal of -CH=N- group at [[delta].sub.C] 138.9, and, thus, its configuration was supposed to be E. These data were presented in Table 3.

All synthesized compounds were tested for antibacterial and antifungal activities. Four kinds of bacteria including Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 25923), Bacillus subtilis (ATCC 11774), and Staphylococcus aureus (ATCC 11632) and four fungus involving Aspergillus niger (439), Fusarium oxysporum (M42), Candida albicans (ATCC 7754), and Saccharomyces cerevisiae (SH 20) were utilized for these experiments. The results were presented in Table 4.

As the data has shown, the series of 7-chloro-4-[2 -(2-chloroquinolin-3-yl-methylene)hydrazinyl]quinoline compounds 4a-c possess antibacterial and antifungal activities against Bacillus subtilis at the concentration of 25 [micro]g/mL and Aspergillus niger at the concentration of 50 [micro]g/mL, respectively.

Meanwhile, in the other series, there was only 7-chloro -4-(2-((3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene) hydrazinyl)quinoline 4f showing the antifungal activity against Aspergillus niger at the concentration of 25 [micro]g/mL.

4. Conclusion

By a simple and convenient method, 7-chloro-4-hydrazinylquinoline 2 and six aldehydes including 2-chloro-6-substituted quinoline-3-carbaldehydes 3a-c and 1,3-diarylpyrazole-4-carbaldehydes 3d-f were prepared. The reaction of hydrazine 2 with the heteroaromatic aldehydes 3a-f formed six new 4-(2-heterylidenehydrazinyl)-7-chloroquinoline compounds 4a-f. Their chemical structures were elucidated by the analysis of IR, NMR, and HRMS spectral data. It was found that the configuration of hydrazones was E except (Z)-4-{2-[(1,3-diphenyl-1-phenyl-1H-pyrazol-4-yl)methylene]hydrazinyl}-7-chloroquinoline compound 4d. All of them were tested for the antimicrobial activities against eight kinds of bacteria and fungus. The results showed that the hydrazones containing 2-chloroquinoline moiety 4a-c possess good activities in growth inhibition of Bacillus subtilis and Aspergillus niger at the concentration of 25 and 50 [micro]g/mL, respectively. In general, the hydrazones containing 1,3-diarylpyrazole moieties 4d-f had been inactive but compound 4f exhibited high biological activity against Aspergillus niger at the concentration of 25 [micro]g/mL.

https://doi.org/10.1155/2018/4301847

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Supplementary Materials

Supplementary data associated with this article can be found in the attached file. These data include NMR ([sup.1]H, [sup.13]C, HSQC, HMBC, and NOESY), IR, and HRMS spectra of the synthesized compounds (2,3a-f, 4a-f): IR spectrum of compound (2); [sup.1]H NMR spectrum of compound (2); [sup.13]C NMR spectrum of compound (2); [sup.1]H NMR spectrum of compound (3a); [sup.1]H NMR spectrum of compound (3b); [sup.1]H NMR spectrum of compound (3c); [sup.1]H NMR spectrum of compound (3d); [sup.1]H NMR spectrum of compound (3e); [sup.1]H NMR spectrum of compound (3f); IR spectrum of compound (4a); [sup.1]H NMR spectrum of compound (4a); [sup.13]C NMR spectrum of compound (4a); HRMS spectrum of compound (4a); IR spectrum of compound (4b); [sup.1]H NMR spectrum of compound (4b); [sup.13]C NMR spectrum of compound (4b); HSQC spectrum of compound (4b); HMBC spectrum of compound (4b);NOESY spectrum of compound (4b); HRMS spectrum of compound (4b); IR spectrum of compound (4c); [sup.1]H NMR spectrum of compound (4c); [sup.13]C NMR spectrum of compound (4c); HRMS spectrum of compound (4c); IR spectrum of compound (4d); [sup.1]H NMR spectrum of compound (4d); [sup.13]C NMR spectrum of compound (4d); HRMS spectrum of compound (4d); NOESY spectrum of compound (4d); IR spectrum of compound (4e); [sup.1]HNMRspectrum of compound (4e); [sup.13]CNMRspectrum of compound (4e); HSQC spectrum of compound (4e); HMBC spectrum of compound (4e); NOESY spectrum of compound (4e); HRMS spectrum of compound (4e); IR spectrum of compound (4f); [sup.1]H NMR spectrum of compound (4f); [sup.13]C NMR spectrum of compound (4f); HRMS spectrum of compound (4f). (Supplementary Materials)

References

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Trong Duc Le (iD), (1) Ngoc Nam Pham (iD), (2) and Tien Cong Nguyen (iD) (1)

(1) Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City 700000, Vietnam

(2) Department of Organic Chemistry, Ho Chi Minh City University of Science, Vietnam National University, Ho Chi Minh City 700000, Vietnam

Correspondence should be addressed to Tien Cong Nguyen; congnt@hcmup.edu.vn

Received 8 August 2017; Revised 30 October 2017; Accepted 7 November 2017; Published 15 January 2018

Academic Editor: Gabriel Navarrete-Vazquez
Table 1: The physical properties and IR spectral data of the
4a-f compounds.

Comp.    Structure       X or Y             Solvent
                                       recrystallized

4a      [formula not      H           DMF: [H.sub.2]O
        reproducible]
4b      [formula not    C[H.sub.3]    DMF: [H.sub.2]O
        reproducible]
4c      [formula not     OEt               EtOH
        reproducible]
4d      [formula not       H         Dioxane: [H.sub.2]O
        reproducible]
4e      [formula not      Cl           DMF: [H.sub.2]O
        reproducible]
4f      [formula not   N[O.sub.2]       Ac: [H.sub.2]O
        reproducible]

                                  v ([cm.sup.-1])
Comp.         Mp.        Yield
         ([degrees]C)     (%)    C-H     NH    C=C
                                               C=N

4a            236         83     3055   3179   1615
                                               1566
4b            239         83     2895   3179   1615
                                 3055          1566
4c            239         81     2978   3232   1620
                                 3040          1582

4d            236         84     3063   3256   1651
                                               1582
4e            233         85     3063   3241   1613
                                               1575
4f            236         83     3060   3215   1620
                                               1555

More information can be found in Supplementary Materials.

Table 2: [sup.1]H, [sup.13]C-NMR, and HR-MS spectral data of
compounds 4a-c.

                               X = H (4a)

Number      [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                   J (Hz)

2                 8.68 (d)                    152.5
                   J = 4.5
3                 7.62 (d)                    102.9
                   J = 5.0
4                    --                       149.2
5                 8.42 (d)                    124.2
                   J = 9.0
6                 7.67 (dd)                   124.3
              [J.sub.1] = 8.5;
               [J.sub.2] = 1.5
7                    --                       133.4
8                 7.96 (br)                   128.1
9                    --                       147.3
10                   --                       116.1
11                11.70 (5)                    --
13                8.85 (5)                    138.5
14                   --                       125.8
15                   --                       127.1
17                   --                       137.8
18                8.23 (d)                    127.6
                   J = 8.5
19                7.72 (1)                    131.9
                   J = 8.0
20                7.86 (1)                    148.8
                   J = 7.5
20a                  --                        --
20b                  --                        --
21                7.99 (d)                    129.2
                   J = 8.5
22                   --                       148.3
23                9.15 (5)                    134.6
MS                     367.0518 [[M + H].sup.+]
                   ([C.sub.19][H.sub.13][Cl.sub.2]
                       [N.sub.4] + H, 367.0512)

                            X = C[H.sub.3] (4b)

Number      [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                   J (Hz)

2                 8.67 (d)                    152.0
                   J = 5.0
3                 7.60 (d)                    101.8
                   J = 5.5
4                    --                       149.2
5                 8.42 (d)                    123.8
                   J = 9.0
6                 7.66 (dd)                   125.3
              [J.sub.1] = 9.0;
               [J.sub.2] = 2.0
7                    --                       133.9
8                 7.96 (d)                    127.4
                   J = 2.5
9                    --                       145.5
10                   --                       115.6
11                11.67 (s)                    --
13                8.83 (s)                    138.1
14                   --                       126.5
15                   --                       127.1
17                   --                       137.5
18                7.89 (d)                    127.3
                   J = 8.5
19                7.70 (dd)                   133.6
              [J.sub.1] = 8.5;
               [J.sub.2] = 1.5
20                   --                       146.6
20a               2.54 (s)                    21.2
20b                  --                        --
21                7.99 (s)                    127.8
22                   --                       147.4
23                9.02 (s)                    134.3
MS                      381.0674 [[M + H].sup.+]
                    ([C.sub.20][H.sub.15][Cl.sub.2]
                       [N.sub.4] + H, 381.0668)

                   X = O[C.sub.2][H.sub.5] (4c)

Number      [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                   J (Hz)

2                 8.67 (d)                    157.3
                   J = 4.5
3                 7.58 (d)                    101.8
                   J = 4.5
4                    --                       150.0
5                 8.40 (d)                    123.8
                   J = 9.0
6                 7.65 (d)                    124.2
                   J = 8.5
7                    --                       133.7
8                 7.95 (br)                   127.8
9                    --                       145.9
10                   --                       115.3
11                11.67 (s)                    --
13                8.80 (s)                    139.0
14                   --                       125.3
15                   --                       127.5
17                   --                       138.1
18                7.87 (d)                    128.4
                   J = 9.5
19                7.46 (dd)                   130.0
              [J.sub.1] = 9.0;
               [J.sub.2] = 2.5
20                   --                       145.6
20a               4.21 (q)                    63.7
                   J = 7.0
20b               1.44 (t)                    14.5
                   J = 7.0
21                7.61 (s)                    129.1
22                   --                       142.8
23                9.01 (s)                    134.7
MS                     411.0775 [[M + H].sup.+]
                    ([C.sub.21][H.sub.17][Cl.sub.2]
                      [N.sub.4]O + H, 411.0774)

[formula not reproducible]

More information can be found in Supplementary Materials.

Table 3: [sup.1]H, [sup.13]C-NMR, and HR-MS spectral data of
compounds 4d-f.

                             Y = H (4d)

Number     [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                  J (Hz)

2                8.56 (d)                    152.0
                  J = 5.0
3              7.51-7.58 (m)                 101.2
4                   --                       149.2
                 8.33 (d)                    123.9
5                 J = 9.0
6              7.51-7.58 (m)                 124.8
7                   --                       131.6
8                7.90 (s)                    128.6
9                   --                       147.0
10                  --                       115.4
11               11.11 (s)                    --
13               8.51 (s)                    136.4
14                  --                       117.5
15               9.11 (s)                    127.7
18                  --                       151.3
19                  --                       133.8
20, 24           7.79 (d)                    128.5
                  J = 8.0
21, 23         7.51-7.58 (m)                 129.7

22             7.37-7.41 (m)                 132.4
25                  --                       139.1
26, 30           8.03 (d)                    118.7
                  J = 7.5
27, 29         7.51-7.58 (m)                 128.8

28             7.37-7.41 (m)                 127.2
MS                     424.1347 [[M + H].sup.+]
                         ([C.sub.25][H.sub.18]
                       Cl[N.sub.5] + H, 424.1323)

                             Y = Cl (4e)

Number     [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                  J (Hz)

2                8.48 (br)                   152.3
3                7.31 (br)                   101.8
4                   --                       149.2
                 8.36 (d)                    123.0
5                 J = 9.0
6                7.60 (br)                   125.1
7                   --                       131.2
8                7.84 (br)                   128.0
9                   --                       146.5
10                  --                       115.0
11              11.33 (br)                    --
13               8.54 (s)                    139.0
14                  --                       117.5
15               9.14 (s)                    128.7
18                  --                       150.0
19                  --                       133.9
20, 24           7.64 (d)                    128.7
                  J = 8.5
21, 23           7.85 (d)                    129.6
                  J = 8.5
22                  --                       133.4
25                  --                       139.7
26, 30           8.03 (d)                    118.8
                  J = 8.5
27, 29           7.57 (d)                    130.2
                  J = 8.5
28               7.41 (t)                    127.1
                  J = 8.5
MS                     458.0946 [[M+H].sup.+]
                   ([C.sub.25][H.sub.17][Cl.sub.2]
                      [N.sub.5] + H, 458.0934)

                         Y = N[O.sub.2] (4f)

Number     [[delta].sub.H] (ppm)     [[delta].sub.C] (ppm)
                  J (Hz)

2                8.49 (br)                   152.7
3                7.28 (br)                   102.2
4                   --                       147.2
                 8.34 (d)                    123.4
5                 J = 9.0
6                7.58 (br)                   124.8
7                   --                       131.2
8                7.84 (br)                   128.6
9                   --                       146.6
10                  --                       115.0
11              11.26 (br)                    --
13               8.57 (s)                    138.9
14                  --                       117.8
15               9.17 (s)                    127.4
18                  --                       148.8
19                  --                       133.6
20, 24           8.14 (d)                    123.9
                  J = 8.5
21, 23           8.42 (d)                    129.7
                  J = 8.5
22                  --                       132.8
25                  --                       139.0
26, 30           8.05 (d)                    118.9
                  J = 8.5
27, 29           7.60 (d)                    129.5
                  J = 8.5
28               7.44 (t)                    127.4
                  J = 8.5
MS                     469.1179 [[M + H].sup.+]
                   ([C.sub.25][H.sub.17]Cl[N.sub.6]
                       [O.sub.2] + H, 469.1174)

[formula not reproducible]

More information can be found in Supplementary Materials.

Table 4: Antimicrobial activity of hydrazones 4a-f.

       Minimum inhibitory concentration (MIC: [micro]g/mL)

             Bacterial strains        Fungal strains
Samp.
          EC     PA    BS    SA    AN     FO    SC    CA

4a       (-)    (-)    25    (-)   50    (-)    (-)   (-)
4b       (-)    (-)    25    (-)   50    (-)    (-)   (-)
4c       (-)    (-)    25    (-)   50    (-)    (-)   (-)
4d       (-)    (-)    (-)   (-)   (-)   (-)    (-)   (-)
4e       (-)    (-)    (-)   (-)   (-)   (-)    (-)   (-)
4f       (-)    (-)    (-)   (-)   25    (-)    (-)   (-)

(-) means negative; EC, PA, BS, and SA stand for Escherichia coli,
Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus
aureus; AN, FO, SC, and CA stand for Aspergillus niger, Fusarium
oxysporum, Saccharomyces cerevisiae, and Candida albicans.
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Title Annotation:Research Article
Author:Le, Trong Duc; Pham, Ngoc Nam; Nguyen, Tien Cong
Publication:Journal of Chemistry
Date:Jan 1, 2018
Words:4325
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