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Article

An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity

by
Samar A. Abubshait
Chemistry Department, Girls College of Science, P.O. Box 838, Dammam-31113, Saudi Arabia
Molecules 2007, 12(1), 25-42; https://doi.org/10.3390/12010025
Submission received: 29 October 2006 / Revised: 9 December 2006 / Accepted: 18 December 2006 / Published: 10 January 2007
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Abstract

:
Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl3 for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl3 was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene- or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, 1H-NMR, 13C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.

Introduction

In recent years a substantial number of 6-aryl-3-(2H)-pyridazinones have been reported to possess antimicrobial [1,2], potent analgesic [3], anti-inflammatory [3,4,5,6,7], antifeedant [8], herbicidal [9], antihypertensive [10,11,12] and antiplatelet activities [13,14,15], anticancer effects [16] and other anticipated biological [17] and pharmacological properties [18,19]. In particular, a large number of indolylpyridazinone derivatives are well known as antimicrobial agents [1,20], intermediates for drugs and agrochemicals [21,22], antiphlogistics [23], antipyretics [24], inflammation inhibitors [25], blood platelet aggregation inhibitors, cardiovascular and antihypertensive agents [26]. As part of our program aimed at utilizing β-aroylpropionic acid derivatives containing the indole moiety as starting materials for the synthesis of pyridazine and pyridazinone derivatives, these reports of interesting biological activities prompted us to synthesize a new series of 6-anthracenepyridazinones containing indolyl moieties through the nucleophilic addition of indole to 6-anthracene-4-oxo-2-butenoic acid, followed by cyclocondensation of the resulting adduct to give the corresponding dihydropyridazinone and to screen some of these new compounds for antibacterial activity.

Results and Discussion

4-Anthracen-9-yl-4-oxo-but-2-enoic acid (1) was prepared following a reported procedure [1,27]. Reaction of 1 with indole in dry benzene gave 4-anthracen-9-yl-2-(1H-indol-3-yl)-4-oxo-butyric acid (2). Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide in dry benzene [28,29,30,31] gave 6-anthracen-9-yl-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one, 6-anthracen-9-yl-4-(1H-indol-3-yl)-2-phenyl-4,5-dihydro-2H-pyridazin-3-one, 3-anthracen-9-yl-5-(1H-indol-3-yl)-6-oxo-5,6-dihydro-4H-pyridazine-1-carboxylic acid amide and 3-anthracen-9-yl-5-(1H-indol-3-yl)-6-oxo-5,6-dihydro-4H-pyridazine-1-carbothioic acid amides 3a-d, respectively (Scheme 1). Physical properties, mass spectral data and elemental analyses for the synthesized compounds 1-3d are given in Table 1.
Molecules 12 00025 g001 550
Scheme 1.
Scheme 1.
Molecules 12 00025 g001
Table
Table 1. Physical properties, mass spectral data and elemental analyses for compounds 1-3.
Table 1. Physical properties, mass spectral data and elemental analyses for compounds 1-3.
Compound
No		M.P. (°C)
Cryst. solvent		Mol. Formula
Mol. weight		M.W. from MSAnalysis % Calc./ Found
CHNS
1215-217
Ethanol		C18H12O3
276.29		276.0878.25
78.20		4.38
4.35		----------
2223
Benzene		C26H19NO3
393.43		393.1479.37
79.35		4.87
4.82		3.56
3.53		-----
3a122
Benzene		C26H19N3O
389.45		389.1580.18
80.20		4.92
4.72		10.79
10.59		-----
3b270
Benzene		C32H23N3O
465.54		465.1882.56
82.58		4.98
4.94		9.03
9.06		-----
3c145
Benzene		C27H20N4O2
432.47		432.16 74.98
75.01		4.66
4.70		12.96
13.00		-----
3d160
Benzene		C27H20N4OS
448.54		448.1472.30
72.37		4.49
4.53		12.49
12.52		7.15
7.20
Reaction of pyridazinone 3a with POCl3 for 30 min gave the chloropyridazine derivative 4a [32], which reacted with carbohydrate hydrazones of ribose, glucose, galactose and lactose in ethanol to give hydrazonopyradazine derivatives 5a-d [6,12]. Mixing chloropyridazine 4a with aliphatic or aromatic amines, namely methylamine, ethylamine, aniline, sulphanilinic acid, α-naphthylamine or diphenylamine in dry benzene gave pyridazine derivatives 6a-f [7,12,33]. In addition, 4a reacted with anthranilic acid in dry benzene to give 7 (Scheme 2) [1,30,32]. Physical properties, mass spectral data and elemental analyses for all newly synthesized compounds 4a-7 are listed in Table 2.
Molecules 12 00025 g002 550
Scheme 2.
Scheme 2.
Molecules 12 00025 g002
Table
Table 2. Physical properties, mass spectral data and elemental analyses for compounds 4-7.
Table 2. Physical properties, mass spectral data and elemental analyses for compounds 4-7.
Compound
No		M.P. (°C)
Cryst. solvent		Mol. Formula
Mol. Weight		M.W. from MSAnalysis % Calc./ Found
CHNS
4a200
Benzene		C26H16ClN3
405.88		405.1076.94
76.99		3.97
3.94		10.35
10.33		-----
4b152
Benzene		C18H11ClN2
290.75		290.0674.36
74.40		3.81
3.85		9.64
9.66		----
5a360
Ethanol		C31H27N5O4
533.58		533.5669.78
69.82		5.10
5.15		13.13
13.17		-----
5b315
Ethanol		C32H29N5O5
563.60		563.6068.19
68.23		5.19
5.23		12.43
12.40		-----
5c348
Ethanol		C32H29N5O5
563.60		563.60 68.19
68.14		5.19
5.23		12.43
12.44		-----
5d138-140
Ethanol		C38H39N5O10
725.74		725.2462.89
62.93		5.42
5.46		9.65
9,63		-----
6a147
Benzene		C27H20N4
400.47		400.1780.98
80.95		5.03
5.08		13.99
14.02		-----
6b210
Benzene		C28H22N4
414.50		414.1881.13
81.20		5.35
5.40		13.52
13.56		-----
6c156
Benzene		C32H22N4
462.54		462.5483.09
83.12		4.79
4.74		12.11
12.09		-----
6d286
Benzene		C32H22N4O3S
542.61		542.1470.83
70.79		4.09
4.00		10.33
10.00		5.91
5.94
6e199
Benzene		C36H24N4
512.60		512.2284.35
84.40		4.72
4.76		10.93
10.95		-----
6f236
Benzene		C38H26N4
538.64		538.2284.73
84.77		4.87
4.82		10.40
10.46		-----
7130
Benzene		C33H20N4O
488.54		488.1681.13
81.16		4.13
4.17		11.47
11.50		-----
Surprisingly, when the reaction of 3a with POCl3 was carried out for 3 hr an unexpected product, 6-anthracen-9-yl-6-chloropyridazine (4b), was obtained via dearylation and substitution of the hydroxyl group by chlorine [20] (Scheme 2). The structure of 4b was proven by the similarity of its melting point to that of an authentic sample which was independently prepared by the reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with hydrazine hydrate in dry benzene and treatment of the resulting pyridazinone 8 with POCl3 for 30 min to give 4b (Scheme 3) [1,5,7,30,31]. Reaction of chloropyridazine 4b with hydrazine hydrate in boiling benzene [34] gave the hydrazinopyridazine derivative 9, whose structure was inferred from its infrared spectrum. The structure of 9 was further confirmed by its reaction with acetyl acetone in boiling methanol that gave 3-anthracen-9-yl-6-(3,5-dimethylpyrazol-1-yl) pyridazine (10) [5,6,14,32]. As a point of interest, it was observed that reaction of 4b with methylamine at 140 °C afforded 11. On the other hand, when compound 11 was reacted with excess CH3I in methanol the quaternary ammonium iodide derivative 12 was formed (Scheme 3). Physical properties, mass spectral data and elemental analyses for all newly synthesized compounds 8-12 are given in Table 3.
Molecules 12 00025 g003 550
Scheme 3.
Scheme 3.
Molecules 12 00025 g003
Table
Table 3. Physical properties, mass spectral data and elemental analyses for compounds 8-12.
Table 3. Physical properties, mass spectral data and elemental analyses for compounds 8-12.
Compound
No		M.P. (°C)
Cryst. solvent		Mol. Formula
Mol. Weight		M.W. from MSAnalysis % Calc./ Found
CHNS
8165
Benzene		C18H12N2O
272.30		272.3079.39
79.42		4.44
4.40		10.29
10.32		-----
9230
Benzene		C18H14N4
286.33		286.1275.50
75.50		4.93
4.90		19.57
19.59		-----
10210
Methanol		C23H18N4
350.42		350.1578.83
78.88		5.18
5.15		15.99
16.02		-----
11126
Methanol		C19H15N3
285.34		285.1279.98
80.02		5.30
5.28		14.73
14.77		-----
12150
Methanol		C21H20N3I
441.31		314.1757.15
57.10		4.57
4.52		9.52
9.58		-----
The reaction of pyridazinone 3a with benzene/4-toluenesulfonyl chloride and anhydrous K2CO3 in dry acetone at reflux for 24 hr gave 6-anthracen-9-yl-4-(1H-indol-3-yl)-2-(benzenesulfonyl or 4-toluenesulfonyl)-4,5-dihydro-2H-pyridazin-3-ones 13a and 13b, respectively. Pyridazinone 3a also reacted with same aliphatic and aromatic aldehydes namely formaldehyde, acetaldehyde, benzaldehyde, 2-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, 2-methoxybenzaldehyde, 4-methoxybenzaldehyde, 2,4-dimethoxybenzaldehyde, 2-hydroxynapthaldehyde and furfuraldehyde to give pyridazinone derivatives 14a-j, respectively (Scheme 4). Physical properties, mass spectral data and elemental analyses for all new compounds 13a-14j are given in Table 4.
Molecules 12 00025 g004 550
Scheme 4.
Scheme 4.
Molecules 12 00025 g004
Table
Table 4. Physical properties, mass spectral data and elemental analyses for compounds 13-14.
Table 4. Physical properties, mass spectral data and elemental analyses for compounds 13-14.
Compound
No		M.P. (°C)
Cryst. solvent		Mol. Formula
Mol. Weight		M.W. from MS Analysis % Calc./ Found
CHNS
13a154
Benzene		C32H23N3O3S
526.61		529.1572.57
72.50		4.38
4.41		7.93
7.90		6.05
6.00
13b177
Benzene		C33H25N3O3S
543.64		543.1672.91
72.95		4.64
4.68		7.73
7.77		5.90
5.93
14a260
Benzene		C27H19N3O
401.46		401.1580.78
80.74		4.77
4.79		10.47
10.41		-----
14b288
Benzene		C28H21N3O
415.49		415.1780.94
80.89		5.09
5.13		10.11
10.07		-----
14c360
Benzene		C33H23N3O
477.56		477.1883.00
83.03		4.85
4.88		8.80
8.85		-----
14d350
Benzene		C33H23N3O2
493.55		493.1880.31
80.40		4.70
4.73		8.51
8.53		-----
14e264
Benzene		C33H23N3O2
493.55		493.1880.31
80.37		4.70
4.75		8.51
8.55		-----
14f196
Benzene		C34H25N3O2
507.58		507.1980.45
80.49		4.96
4.92		8.28
8.22		-----
14g202
Benzene		C34H25N3O2
507.58		507.1980.45
80.49		4.96
5.10		8.28
8.26		-----
14h94
Benzene		C35H27N3O3
537.61		537.6178.19
78.22		5.06
5.10		7.82
7.85		-----
14i230
Benzene		C37H25N3O2
543.61		543.1981.75
81.80		4.64
4.68		7.73
7.70		-----
14j328
Benzene		C31H21N3O2
467.16		467.1679.64
79.66		4.53
4.55		8.99
9.11		-----

Biological Screening

The activities of some of the prepared compounds against representative Gram positive and negative bacteria were tested by the disk diffusion method [1,8,35]. The results are listed in Table 5. From the data it is clear that compounds 6b, 14i possess high activity against both types of bacteria, while compound 6c displays low activity. Compounds 1 and 6b possess high activity, compounds 2, 3a-3d, 4a, 5a, 5d, 14g, 14i possess moderate activity and compounds 6c and 13a possess less activity against Gram positive strains. As far as Gram negative microorganisms are concerned, compound 14i showed high activity, while compounds 1, 2, 3a, 3b, 3d, 4a, 5a, 5d, 6b, 13a and 14g all displayed moderate activity and 3c and 6c possess less activity against such microorganisms.
Table
Table 5. Antibacterial activity of select compounds*
Table 5. Antibacterial activity of select compounds*
Compound
No		Gram positive bacteriaGram negative bacteria
Staph. aureusStaph. epidermisE. coliPr. vulgaris
1+++++++++
2++++++++
3a++++++++
3b+++++++++
3c++++++
3d+++++++
4a+++++++
5a+++++++
5d++++++++
6b++++++++++
6c+++++
13a+++++++
14g++++++++
14i++++++++++
* Solvent: DMF, [c] = 250 μg mL-1. Ratings: + = less active (inhibition zone 1-5 mm); ++ = moderately active (inhibition zone 5-10 mm), +++ = more active (inhibition zone 10-15 mm); ++++ = highly active (inhibition zone 15-20 mm); reference substance for Gram positive and Gram negative bacteria: ampicillin.

Conclusions

A novel synthesis of some new indolylpyridazinone derivatives by cyclocondensation of indolylbutyric acid 2 with hydrazine hydrate and its derivatives to give pyridazinone derivatives 3a-d is described. The reactions of pyridazinone 3a with PCl5/POCl3, arylsulphonyl chloride derivatives and aliphatic or aromatic aldehydes were studied, as were the behaviors of chloropyridazine derivatives towards hydrazine hydrate, carbohydrate hydrazones and aliphatic or aromatic amines. The structures of all new synthesized compounds were established from their spectral data and elemental analysis. Additionally, the antimicrobial activity of selected compounds against Gram positive and negative bacteria is reported.

Acknowledgements

I thank Dr. Malka Mehsen in Girls College of Science, Dammam, Saudi Arabia for performing the biological tests

Experimental

General

Melting points were determined on Reichert hot stage microscope and are uncorrected. IR spectra were measured with a Nicolet Magna 520 instrument, using potassium bromide disks; results are given in cm‑1. 1H-NMR and 13C-NMR spectra were recorded at 200 and 90.56 MHz, respectively, in DMSO-d6 on a JEOL JNM-GX270 spectrometer. The chemical shifts are reported in parts per million (ppm) downfield from internal tetramethylsilane (TMS). Electron impact MS spectra were obtained on a JEOL JMS-HX 100 instrument at 70 eV. Elemental microanalysis was done on a Carlo Erba analyzer model 110. Suitable crystals were grown by slow crystallization from methanol, ethanol and benzene.

4-Anthracen-9-yl-4-oxo-but-2-enoic acid (1)

Compound 1 was prepared following the literature procedure [1,20,27]. It was obtained in 85% yield as white crystals; IR (cm-1): 1608 (C=C), 1662 (ketone C=O), 1699 (acid C=O), 3054, 2970, 2927, 2869 (C-H), 4200-3400 (acid OH); 1H-NMR: 7.20-8.50 (m, 11H, Ar-H and vinyl), 11 (br, 1H, COOH); 13C-NMR: 127-144 (16C, Ar and vinyl), 170, 188.10 (2C, acid and ketone C=O). Its physical properties, mass spectral data and elemental analysis are given in Table 1.

4-Anthracen-9-yl-2-(1H-indol-3-yl)-4-oxo-butyric acid (2).

Indole (10 mmol) was added to a solution of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1, 10 mmol) in dry benzene (10 mL) and the reaction mixture was refluxed for 6 hr. The solid that separated on cooling was recrystallized from benzene to give compound 2 as white crystals, yield 80%; IR (cm-1): 1618 (C=C), 1674 (ketone C=O), 1708 (acid C=O), 3030, 3070, 2926, 2853 (C-H), 3414 (indole N-H); 1H-NMR: 3.40 (d, 2H, CH2), 4.04 (t, 1H, CH), 6.51 (s, 1H, indole CH), 7.02-7.91 (m, 13H, Ar-H), 10.08 (br, 1H, NH), 11.10 (br, 1H, COOH); 13C-NMR: 40-41 (2C, CH2-CH), 112.50-136.50 (21C, Ar), 123 (1C, indole C-NH), 175.30, 198.90 (2C, acid and ketone C=O). Physical properties, mass spectral data and elemental analysis for compound 2 are given in Table 1.

General method for the preparation of 3a-d:

Hydrazine hydrate derivatives (10 mmol) were added to a solution of 2 (10 mmol) in dry benzene (5 mL) and the resulting reaction mixture was refluxed for 6 hr. The solid that separated on cooling was recystallized from benzene to give compounds 3a-d. Their physical properties, mass spectral data and elemental analysis are given in Table 1.

6-Anthracen-9-yl-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (3a).

Obtained from hydrazine hydrate and 2 as white needles, yield 81%; IR (cm-1): 1604 (C=C),1635 (C=N), 1671 (pyridazinone C=O), 3080, 3010, 3054, 2957 (C-H), 3100-3272 (-OH), 3411-3375 (pyridazinone and indole N-H); 1H-NMR: 3.35 (d, 2H, CH2), 4.36 (t, 1H, CH), 6.81 (s, 1H, indole CH), 6.90-7.91 (m, 13H, Ar-H), 10.9-12.40 (br, 2H, pyridazinone and indole NH); 13C-NMR: 33.80-40.10 (2C, CH2-CH), 111.20-136 (21C, Ar), 123 (1C, indole C-NH), 153.34 (1C, C=N-N), 170 (1C, C=O).

6-Anthracen-9-yl-4-(1H-indol-3-yl)-2-phenyl-4,5-dihydro-2H-pyridazin-3-one (3b).

Obtained from phenyl hydrazine and 2 as white crystals, yield 79%; IR (cm-1): 1605 (C=C), 1640 (C=N), 1674 (pyridazinone C=O), 3054, 3070, 2923, 2869 (C-H), 3400-3411 (indole N-H); 1H-NMR: 3.35 (d, 2H, CH2), 4.05 (t, 1H, CH), 6.80-7.82 (m, 19H, Ar-H), 11.02 (br, 1H, indole NH); 13C-NMR: 33.80-40.10 (2C, CH2-CH), 111.20-136 (26C, Ar), 123 (1C, indole C-NH), 141.20 (1C, C-N-N), 153.34 (1C, C=N-N), 170 (1C, pyridazinone C=O).

3-Anthracen-9-yl-5-(1H-indol-3-yl)-6-oxo-5,6-dihydro-4H-pyridazine-1-carboxylic acid amide (3c).

Obtained from semicarbazide and 2 as a white solid, yield 75%; IR (cm-1): 1605 (C=C), 1638 (C=N), 1650 (amide C=O), 1678 (pyridazinone C=O), 3070, 3054, 2926(C-H), 3320-3410 (indole and amide N-H, NH2); 1H-NMR: 3.34(d, 2H, CH2), 4.05(t, 1H, CH), 4.50(br, 2H, NH2), 6.81-7.80(m, 14H, Ar-H), 11.02(br, 1H, indole NH); 13C-NMR: 33.80-41.07 (2C, CH2-CH), 112.11-136 (21C, Ar), 123.80 (1C, indole C-NH), 157.36 (1C, C=N-N), 175,189 (2C, pyridazinone and amide C=O).

3-Anthracen-9-yl-5-(1H-indol-3-yl)-6-oxo-5,6-dihydro-4H-pyridazine-1-carbothioic acid amide (3d).

Obtained from thiosemicarbazide and 2 as white needles, yield 87%; IR (cm-1): 1270 (C=S), 1604 (C=C), 1640 (C=N), 1704 (pyridazinone C=O), 3057, 3030, 2959(C-H), 3350-3453 (indole and carbothioic acid amide N-H, NH2); 1H-NMR: 3.34 (d, 2H, CH2), 4.05 (t, 1H, CH), 4.50 (br, 2H, NH2), 7.04-8.30 (m, 14H, Ar-H), 11.02 (br, 1H, indole NH); 13C-NMR: 33.80-41.07 (2C, CH2-CH), 111.56-133.41 (21C, Ar), 122.83 (1C, indole C-NH), 155 (1C, C=N-N), 177 (1C, pyridazinone C=O), 183 (1C, C=S).

3-(6-Anthracen-9-yl-3-chloropyridazin-4-yl)-1H-indole (4a).

POCl3 (5 mL) was added to 3a (10 mmol) and the reaction mixture was heated on oil bath for 30 min, set aside to cool and then poured onto crushed ice (60 g), filtered, washed well with water and recrystallized from benzene to give 4a as a brown solid, yield 81%; IR (cm-1): 756 (C-Cl), 1605 (C=C), 1640 (C=N), 3057, 3047, 2923, 2869 (C-H), 3391 (indole N-H); 1H-NMR: 7.30-8.30 (m, 15H, Ar-H), 10.90 (br, 1H, indole NH); 13C-NMR: 111.10-135 (23C, Ar), 123 (1C, indole C-NH), 152 (1C, N-N=C-Cl), 160 (1C, C=N-N). Physical properties, mass spectral data and elemental analysis for compound 4a are given in Table 2.

3-Anthracen-9-yl-6-chloropyridazine (4b).

Method A: POCl3 (5 mL) was added to 3a (10 mmol) and the reaction mixture was heated on oil bath for 3hr, then set-aside poured on to 60 g crushed ice, filtered, washed well with water and recrystallized from benzene to give 4b as a brown solid, yield 81%.
Method B: POCl3 (5 mL) was added to 8 (10 mmol) and the reaction mixture was heated on oil bath for 30 min, then set-aside poured on to 60 g crushed ice, filtered, washed well with water and recrystallized from benzene to give 4b as a brown solid, yield 87%; IR (cm-1): 752 (C-Cl), 1605 (C=C), 1648 (C=N), 3057, 3028 (C-H); 1H-NMR: 7.32-8.28 (m, 11H, Ar-H); 13C-NMR: 111-132 (16C, Ar), 151 (1C, N-N=C-Cl), 158 (1C, C=N-N). Physical properties, mass spectral data and elemental analysis for compound 4b are given in Table 2.

General procedure for the reaction of chloropyridazine 4a with carbohydrate hydrazones.

The appropriate carbohydrate hydrazone (1 mmol) was added to a mixture of 4a (1 mmol) in ethanol (5 mL) and the reaction mixture was refluxed for 6 hr. The solid that separated on cooling was recystallized from ethanol to give compounds 5a-d. Physical properties, mass spectral data and elemental analysis for compounds 5a-d are given in Table 2.

(2R,3S,4S)-5-{[6-Anthracen-9-yl-4-(1H-indol-3-yl)pyridazin-3-yl]hydrazono}pentane-1,2,3,4,-tetraol (5a).

Ribose hydrazone gave compound 5a as an orange solid, yield 57%; IR (cm-1): 1605 (C=C), 1615 (N=N), 1657 (C=N), 3060, 2967, 2926, 2869 (C-H), 3430-3250 (indole and hydrazone N-H, NH-N=C), 3750-3250 (O-H); 1H-NMR: 3.32-3.50 (m, 3H, aliphatic CH-OH), 3.68 (d, 2H, aliphatic CH2-OH), 3.90 (s, 1H, NH-N), 4.85 (br, 4H, OH), 7- 8.27 (m, 15H, Ar-H), 7.53 (s, 1H, CH=N), 10.90 (br, 1H, indole NH); 13C-NMR: 60.9-74.60 (4C, aliphatic C-O), 111-138.70 (23C, Ar), 122.60 (1C, indole C-NH), 148-154 (2C, C=N-N), 159.20 (1C, N-C=N).

(2R,3R,4R,5S)-6-{[6-Anthracen-9-yl-4-(1H-indol-3-yl)pyridazin-3-yl]-hydrazono}-hexane-1,2,3,4,5-pentaol (5b).

Glucose hydrazone gave compound 5b as a yellow solid, yield 52%; IR (cm-1): 1600 (C=C), 1637 (C=N), 3060, 2960, 2925 (C-H), 3414-3197 (indole and hydrazone N-H), 3625-3620 (O-H); 1H-NMR: 3.30-3.44 (m, 4H, aliphatic CH-OH), 3.68 (m, 2H, aliphatic CH2-OH), 3.90 (s, 1H, NH-N), 4.85 (br, 5H, OH), 6.80-8.50 (m, 15H, Ar-H), 7.53 (s, 1H, CH=N), 10.90 (br, 1H, indole NH); 13C-NMR: 62.10-73.90 (5C, aliphatic C-O), 111-148.70 (23C, Ar), 122.80 (1C, indole C-NH), 148.60-154.7 (2C, C=N-N), 164 (1C, N-C=N).

(2R,3S,4R,5S)-6-{[6-Anthracen-9-yl-4-(1H-indol-3-yl)pyridazin-3-yl]hydrazono}-hexane-1,2,3,4,5-pentaol (5c).

Galactose hydrazone gave compound 5c as a white solid, yield 55%; IR (cm-1): 1565 (HN-N=C), 1605 (C=C), 1640 (C=N), 3057, 2960, 2923, 2890 (C-H), 3460-3412 (indole and hydrazone N-H), 3629-3400 (O-H); 1H-NMR: 2.50-3.48 (m, 4H, aliphatic CH-OH), 3.60 (m, 2H, aliphatic CH2-OH), 3.91 (s, 1H, NH-N), 4.85 (br, 5H, OH), 7.00-8.10 (m, 15H, Ar-H), 7.51 (s, 1H, CH=N), 10.91 (br, 1H, indole NH); 13C-NMR: 61.10-73.90 (5C, aliphatic C-O), 111-148.70 (23C, Ar), 122 (1C, indole C-NH), 148.60-154.70 (2C, C=N-N), 159.20 (1C, N-C=N).

6-{[6-Anthracen-9-yl-4-(1H-indol-3-yl)pyridazin-3-yl]hydrazono}-3-(3,4,5-trihydroxy-6-hydroxy-methyltetrahydropyran-2-yloxy)-hexane-1,2,4,5-tetraol (5d).

Lactose hydrazone gave compound 5d as a white solid, yield 58%; IR (cm-1): 1570 (HN-N=C), 1605 (C=C), 1638 (C=N), 3057, 2960, 2923(C-H), 3412-3412 (indole and hydrazone N-H), 3635-3390 (O-H); 1H-NMR: 2.99-3.76(m, 9H, aliphatic CH-OH), 3.66-3.68 (m,4H, aliphatic CH2-OH), 3.90 (s, 1H, NH-N), 4.85 (br, 8H, OH), 7.00-8.50 (m, 15H, Ar-H), 7.50 (s, 1H, CH=N), 10.90 (br, 1H, indole, NH); 13C-NMR: 62.50-72.10 (10C, aliphatic C-O), 96.50 (1C, O-C-O), 111-148.70 (23C, Ar), 122 (1C, indole C-NH), 148.60-154.70 (2C, C=N-N), 159.20 (1C, N-C=N).

General reaction of chloropyridazine 4a with aliphatic or aromatic amines

The aliphatic or aromatic amine (1 mmol) was added to a mixture of 4a (1 mmol) in dry benzene (5 mL) and the reaction mixture was heated in oil bath for 6 hr. The solid that separated on cooling was recrystallized from benzene to give compounds 6a-f. Their physical properties, mass spectral data and elemental analysis are given in Table 2.

[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-yl]-methylamine (6a).

Methylamine gave 6a as a white solid, yield 67%; IR (cm-1): 1619 (C=C), 1637 (C=N), 3054, 3030, 2957, 2923 (C-H), 3413-3406 (indole and secondary amine N-H); 1H-NMR: 0.83 (s, 3H, CH3), 3.89 (br, 1H, secondary amine NH), 7.05-7.90 (m, 15H, Ar-H), 11.12 (br, 1H, indole NH); 13C-NMR: 37.50 (1C, N-CH3), 111-136 (23C, Ar), 123 (1C, indole C-NH), 148.60 (1C, N-C=N), 159.2 (1C, C=N-N).

[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-yl]-ethylamine (6b).

Ethylamine gave 6b as a brown solid, yield 52%; IR (cm-1): 1617 (C=C), 1635 (C=N), 3054, 2967, 2925, 2869 (C-H), 3429-3410 (indole N-H and secondary amine N-H); 1H-NMR: 0.85 (t, 3H, CH3), 1.60 (m, 2H, CH2), 3.89 (br, 1H, secondary amine NH), 7.05-8.00 (m, 15H, Ar-H), 11.10 (br, 1H, indole NH); 13C-NMR: 16.20 (1C, CH3), 44.20 (1C, N-CH2), 111-136 (23C, Ar), 123.41 (1C, indole C-NH), 151.10 (1C, C=N-N), 160.10 (1C, N-C=N).

[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-yl]-phenylamine (6c).

Aniline gave 6c as white needles, yield 72%; IR (cm-1): 1617 (C=C), 1638 (C=N), 3057, 2982, 2973, 2869 (C-H), 3429-3400 (indole N-H and secondary amine N-H); 1H-NMR: 3.89 (br, 1H, secondary amine NH), 6.80-8.30 (m, 20H, Ar-H), 11.10 (br, 1H, indole NH); 13C-NMR: 111-148 (29C, Ar), 123 (1C, indole C-NH), 150.10 (1C, C=N-N), 160.5 (1C, N-C=N).

4-[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-ylamino] benzenesulfonic acid (6d).

Sulphanilic acid gave 6d as a gray solid, yield 51%; IR (cm-1): 1160, 1423 (SO2), 1601 (C=C), 1631 (C=N), 3057, 2960, 2920 (C-H), 3390 (indole and secondary amine N-H), 3200-3100 (O-H); 1H-NMR: 3.89 (br, 1H, secondary amine NH), 6.00-8.50 (m, 19H, Ar-H), 11.10 (br, 1H, indole NH), 14.90 (br, 1H, SO3H); 13C-NMR: 111-148.70 (27C, Ar), 133.50 (1C, C-S), 124 (1C, indole C-NH), 148.60 (1C, C=N-N), 150.50 (1C, -NH-Ph), 159 (1C, N-C=N).

[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-yl]-naphthalen-1-yl amine (6e).

α-Naphthylamine gave 6e as a light brown solid, yield 58%; IR (cm-1): 1616 (C=C), 1640 (C=N), 3054, 2999, 2973 (C-H), 3429-3401 (indole and secondary amine N-H); 1H-NMR: 3.89 (br, 1H, secondary amine NH), 6.70-8.27 (m, 22H, Ar-H), 11.10 (br, 1H, indole NH); 13C-NMR: 109.40-141.60 (33C, Ar), 122 (1C, indole C-NH), 148.60 (1C, C=N-N), 161.20 (1C, N-C=N).

[6-Anthracen-9-yl-4-(1H-indol-3-yl)-pyridazin-3-yl] diphenylamine (6f).

Diphenylamine gave 6f as a dark brown solid, yield 51%; IR: 1617 (C=C), 1635 (C=N), 3057, 2982, 2973 (C-H), 3410 (indole N-H); 1H-NMR: 6.72-8.50 (m, 25H, Ar-H), 11.10 (br, 1H, indole NH); 13C-NMR: 111-136 (33C, Ar), 122.50 (1C, indole C-NH), 142.90 (2C, N-C), 150 (1C, C=N-N), 160 (1C, N-C=N).

2-Anthracen-9-yl-4-(1H-indol-3-yl)-1,9-a,10-triaza-anthracen-9-one (7).

Anthranilic acid (1 mmol) was added to a mixture of 4a (1 mmol) in dry benzene (5 mL) and the reaction mixture was refluxed for 6 hr. The solid that separated on cooling was recystallized from benzene to give 7 as a brown solid, yield 65%; IR: 1600 (C=C), 1638 (C=N), 1665 (C=O), 3050, 2959, 2925, 2869 (C-H), 3410-3290 (indole N-H); 1H-NMR: 7.10-8.60 (m, 19H, Ar-H), 12 (br, 1H, indole NH); 13C-NMR: 111-147.70 (29C, Ar), 122 (1C, indole C-NH), 155.50 (1C, C=N-N), 160 (1C, N-C=N), 170 (1C, N-C=O).

6-Anthracen-9-yl-2H-pyridazin-3-one (8).

Hydrazine hydrate (1 mmol) was added to a solution of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1, 1 mmol) in dry benzene (10 mL) and the reaction mixture was refluxed for 6 hr. The solid that separated after concentration and cooling was recrystallized from benzene to give 8 as white needles, yield 85%; IR (cm-1): 1604 (C=C), 1630 (C=N), 1670 (C=O), 3070, 3030, 2957 (C-H), 3411-3357 (indole N-H); 1H-NMR: 6.50-8.60 (m, 11H, Ar-H), 10.20 (br, 1H, pyridazinone NH); 13C-NMR: 111-135.70 (16C, Ar), 155 (1C, C=N-N), 168 (1C, C=O).

6-Anthracen-9-yl-pyridazin-3-yl) hydrazine (9).

Hydrazine hydrate (1 mmol) was added to a solution of 4b (1 mmol) in dry benzene (10 mL) and the reaction mixture was refluxed for hr. The solid that separated was recrystallized from dry benzene to give 9 as buff crystals, yield 70%; IR (cm-1): 1605 (C=C), 1181 (C=N), 3054, 3015, 2958 (C-H), 3327-3139 (hydrazine NHNH2); 1H-NMR: 3.89-10 (br, 3H, NH-NH2), 6.59-8.30 (m, 11H, Ar-H); 13C-NMR: 111-137 (16C, Ar), 158 (1C, C=N-N), 160 (1C, N-C=NHNH2).

3-Anthracen-9-yl-6-(3,5-dimethylpyrazol-1-yl)pyridazine (10).

Acetylacetone (1 mmol) was added to a mixture of 9 (1 mmol) in methanol (10 mL) and the reaction mixture was refluxed for 5 hr. The solid that separated after cooling was recrystallized from methanol to give 10 as yellow crystals, yield 62%; IR (cm-1): 1604 (C=C), 1635 (C=N), 3050, 2959, 2925, 2869 (C-H); 1H-NMR: 2.93 (s, 6H, 2CH3), 6.50-8.270 (m, 12H, Ar-H); 13C-NMR: 14.20 (2C, 2CH3), 111-135 (17C, Ar), 148 (2C, C=N), 155 (1C, C=N-N), 160 (1C, N-C=N).

6-Anthracen-9-yl-3-methylamino-pyridazine (11).

Methylamine (1 mmol) was added to a mixture of 4b (1 mmol) and the reaction mixture was heated for 4 hr on an oil-bath at 140 °C; then cooled and triturated with methanol. The solid that separated was recrystallized from methanol to give 11 as white crystals, yield 56%; IR (cm-1): 1604 (C=C), 1635 (C=N), 3050, 2959, 2925, 2869 (C-H), 3412-3412 (indole and hydrazone N-H); 1H-NMR: 2.50 (d, 3H, CH3), 6.30-8.32 (m, 11H, Ar-H), 4.20 (br, 1H, amine NH); 13C-NMR: 35.30 (1C, CH3), 113-135 (16C, Ar), 155.60 (1C, C=N-N), 159 (1C, N-C=N).

(6-Anthracen-9-yl-pyridazin-3-yl)trimethylammonium iodide (12).

Excess methyl iodide (5 mL) was added to a mixture of 11 (1 mmol) in methanol (10 mL) and the reaction mixture was refluxed for 8 hr. After evaporation of all the solvent, the solid residue was recrystallized from methanol to give 12 as white crystals, yield 85%; IR (cm-1): 1604 (C=C), 1635 (C=N), 3050, 2959, 2925, 2869 (C-H), 3412-3412 (N-N); 1H-NMR: 2.89 (s, 9H, 3CH3), 7.39-8.30 (m, 11H, Ar-H); 13C-NMR: 52 (3C, N-CH3), 125.30-135.10 (16C, Ar), 148 (1C, C=N-N), 159 (1C, N-C=N).

6-Anthracen-9-yl-2-benzenesulfonyl-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (13a).

Benzenesulfonyl chloride (1 mmol) was added to a mixture of 3a (1 mmol), anhydrous K2CO3 (1 mmol) in dry acetone (5 mL) and the reaction mixture was refluxed for 24 hr. The solid that separated on cooling was recystallized from benzene to give 13a as a white solid, yield 75%; IR (cm-1): 1337-1175 (SO2), 1616 (C=C), 1637 (C=N), 1670 (pyridazinone C=O), 3054, 2957, 2923, 2869 (C-H), 3406 (indole N-H); 1H-NMR: 2.14 (d, 2H, CH2), 3.50 (t, 1H, CH), 6.90-7.69 (m, 19H, Ar-H), 11.02 (br, 1H, indole NH); 13C-NMR: 35.80 (1C, CH2), 43.80 (1C, CH), 111-140.20 (27C, Ar), 123 (1C, indole C-NH), 157 (1C, C=N-N), 176 (1C, pyridazinone C=O).

6-Anthracen-9-yl-4-(1H-indol-3-yl)-2-(toluene-4-sulfonyl)-4,5-dihydro-2H-pyridazin- 3-one (13b).

4-Toluenesulfonyl chloride (1 mmol) was added to a mixture of 3a (1 mmol), anhydrous K2CO3 (1 mmol) in dry acetone (5 mL) and the reaction mixture was refluxed for 24 hr. The solid that separated on cooling was recystallized from benzene to give 13b as a white solid, yield 73%; IR (cm-1): 1337-1173 (SO2), 1616 (C=C), 1637 (C=N), 1670 (pyridazinone C=O), 3054, 2957, 2923, 2869 (C-H), 3406 (indole N-H); 1H-NMR: 2.10 (s, 3H, CH3), 2.30 (t, 1H, CH2), 3.70 (t, 1H, CH), 6.80-8.43 (m, 19H, Ar-H), 10.02 (br, 1H, indole NH); 13C-NMR: 20.90 (1C, CH3), 34.20 (1C, CH2), 43.90 (1C, CH-CO), 111-142 (27C, Ar), 123 (1C, indole C-NH,), 157 (1C, C=N-N), 178 (1C, pyridazinone C=O).

General reaction of pyridazinone 3a with some aliphatic or aromatic aldehydes

Aliphatic or aromatic aldehyde (1 mmol) was added to a mixture of 3a (1 mmol), NaOH (10%) in ethanol (5 mL) and the reaction mixture was refluxed for 6 hr. The solid that separated on cooling was recystallized from benzene to give 14a-j. Their physical properties, mass spectral data and elemental analysis are given in Table 4.

6-Anthracen-9-yl-4-(1H-indol-3-yl)5-methylene-4,5-dihydro-2H-pyridazin-3-one (14a).

Formaldehyde gave 14a as an orange solid, yield 53%; IR (cm-1): 1615 (C=C), 1637 (C=N), 1671 (pyridazinone C=O), 3054, 2957, 2925, 2869 (C-H), 3400-3413 (pyridazinone and indole N-H); 1H-NMR: 3.36 (s, 2H, CH2), 4.40 (s, 1H, pyridazinone CH), 7.04-8.50 (m, 14H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 51 (1C, pyridazinone CH), 111-142 (23C, Ar and vinyl), 122 (1C, indole C-NH), 155 (1C, C=N-N), 170 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-ethylidene-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14b).

Acetaldehyde gave 14b as an orange solid, yield 58%; IR (cm-1): 1617 (C=C), 1637 (C=N), 1667 (pyridazinone C=O), 3054, 2957, 2925, 2869 (C-H), 3400-3414 (pyridazinone and indole N-H); 1H-NMR: 1.70 (d, 3H, CH3), 3.36 (m, 1H, vinyl CH), 4.40 (s, 1H, pyridazinone CH), 6.67-8.22 (m, 14H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 12- 52.50 (2C, pyridazinone CH3, CH), 111-140 (23C, Ar and vinyl), 122.80 (1C, indole C-NH), 155.60 (1C, C=N-N), 170 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-benzylidene-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14c).

Benzaldehyde gave 14c as an orange solid, yield 62%; IR (cm-1): 1616 (C=C), 1637 (C=N), 1671 (pyridazinone C=O), 3054, 2957, 2925, 2869(C-H), 3400-3412 (pyridazinone and indole N-H); 1H-NMR: 3.36 (s, 1H, vinyl CH), 4.40 (s, 1H, pyridazinone CH), 7.20-8.20 (m, 19H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52.40 (1C, pyridazinone CH), 111-137 (29C, Ar and vinyl), 122 (1C, indole C-NH,), 155.60 (1C, C=N-N), 168 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-(2-hydroxybenzylidene)-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14d).

2-Hydroxybenzaldehyde gave 14d as a brown solid, yield 60%; IR (cm-1): 1619 (C=C), 1637 (C=N), 1681 (pyridazinone C=O), 3059, 2959, 2927, 2870 (C-H), 3250-3500 (O-H), 3400-3411 (pyridazinone and indole N-H); 1H-NMR: 3.37 (s, 1H, vinyl CH), 4.40 (s, 1H, pyridazinone CH), 6.62-8.52 (m, 18H, Ar-H), 5.50 (br, 1H, OH), 11.01 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52 (1C, pyridazinone CH), 111-136.10 (28C, Ar and vinyl), 122.80 (1C, indole C-NH), 155.60 (1C, C=N-N), 156(1C, -C-OH), 168 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-(4-hydroxybenzylidene)-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14e).

4-Hydroxybenzaldehyde gave 14e as a buff solid, yield 72%; IR (cm-1): 1595 (C=C), 1640 (C=N), 1674 (pyridazinone C=O), 3054, 2957, 2925, 2869 (C-H), 3250-3500 (O-H), 3400-3414 (pyridazinone and indole N-H); 1H-NMR: 3.37 (s, 1H, vinyl CH), 4.40 (s, 1H, pyridazinone CH), 5.67 (br, 1H, OH), 6.44-8.17 (m, 18H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 53 (1C, pyridazinone CH), 111-136 (28C, Ar and vinyl), 122.80 (1C, indole C-NH), 155.60 (1C, C=N-N), 157.50 (1C, C-OH), 168 (1C, pyridazinone C=O).

6-Anthracen-9-yl-4-(1H-indol-3-yl)-5-(2-methoxybenzylidene)-4,5-dihydro-2H-pyridazin-3-one (14f).

2-Methoxybenzaldehyde gave 14f as a brown solid, yield 50%; IR (cm-1): 1590 (C=C), 1641 (C=N), 1671 (pyridazinone C=O), 3059, 2958, 2935, 2835 (C-H), 3410-3424 (pyridazinone and indole N-H); 1H-NMR: 3.36 (s, 1H, vinyl CH), 3.70(s, 3H, -OCH3), 4.40 (s, 1H, pyridazinone CH), 6.58-8.28 (m, 18H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52.40 (1C, pyridazinone CH), 56 (1C, O-CH3), 111-138 (28C, Ar and vinyl), 122.80 (1C, indole C-NH,), 155.60 (1C, C=N-N), 159.70 (1C, C-OCH3), 168 (1C, pyridazinone C=O,).

6-Anthracen-9-yl-4-(1H-indol-3-yl)-5-(4-methoxybenzylidene)-4,5-dihydro-2H-pyridazin-3-one (14g).

4-Methoxybenzaldehyde gave 14g as a brown solid, yield 72%; IR (cm-1): 1613 (C=C), 1637 (C=N), 1669 (pyridazinone C=O), 3054, 2957, 2925, 2869 (C-H), 3400-3412 (pyridazinone and indole N-H); 1H-NMR: 3.37 (s, 1H, vinyl CH), 3.74 (s, 3H, OCH3), 4.37 (s, 1H, pyridazinone CH), 6.86-7.80 (m, 18H, Ar-H), 10.02, 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52 (1C, pyridazinone CH,), 56 (1C, OCH3), 111-136 (28C, Ar and vinyl), 122.80 (1C, indole C-NH), 155.60 (1C, C=N-N), 161 (1C, C-OCH3), 168 (1C, pyridazinone C=O,).

6-Anthracen-9-yl-5-(2,4-dimethoxybenzylidene)-4-(1H-indol-3-yl-4,5-dihydro-2H-pyridazin-3-one (14h).

2,4-Dimethoxybenzaldehyde gave 14h as an orange solid, yield 51%; IR (cm-1): 1601 (C=C), 1636 (C=N), 1669 (pyridazinone C=O), 3059, 2958, 2923, 2855 (C-H), 3410-3424 (pyridazinone and indole N-H); 1H-NMR: 3.36 (s, 1H, CH), 3.75 (s, 6H, -OCH3), 4.40 (s, 1H, pyridazinone CH), 6.48-7.98 (m, 17H, Ar-H), 10.52 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52 (1C, pyridazinone CH), 56.27 (2C, O-CH3), 98-151 (27C, Ar and vinyl), 122 (1C, indole C-NH,), 155.60 (1C, C=N-N), 160-162 (2C, C-O-CH3), 168 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-(2-hydroxynaphthalen-1-yl-methylene)-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14i).

2-Hydroxynaphthaldehyde gave 14i as a brown solid, yield 58%; IR (cm-1): 1619 (C=C), 1637 (C=N), 1681 (pyridazinone C=O), 3059, 2959, 2927, 2870 (C-H), 3250-3500 (O-H), 3400-3411 (pyridazinone and indole N-H); 1H-NMR: 3.85 (s, 1H, vinyl CH), 4.40 (s, 1H, pyridazinone CH), 6.47-7.95 (m, 20H, Ar-H), 5.62 (br, 1H, OH), 10.21 (br, 2H, pyridazinone and indole NH); 13C-NMR: 52.40 (1C, pyridazinone CH), 111-137 (32C, Ar and vinyl), 122.80 (1C, indole C-NH), 155.60 (1C, C=N-N), 156 (1C, -C-OH), 170 (1C, pyridazinone C=O).

6-Anthracen-9-yl-5-furan-2-yl-methylene-4-(1H-indol-3-yl)-4,5-dihydro-2H-pyridazin-3-one (14j).

Furfuraldehyde gave 14j as a brown solid, yield 59%; IR (cm-1): 1616 (C=C), 1637 (C=N), 1670 (pyridazinone C=O), 3054, 2957, 2925, 2869 (C-H), 3400-3412 (pyridazinone and indole N-H), 1200 (C-O-C); 1H NMR: 3.39 (s, 1H, vinyl CH), 4.37 (s, 1H, pyridazinone CH), 6.30-8.55 (m, 17H, Ar-H), 11.02 (br, 2H, pyridazinone and indole NH); 13C-NMR: 51 (1C, pyridazinone CH, ), 111-136 (25C, Ar and vinyl), 122.80 (1C, indole C-NH), 145-155.3 (2C, furan O-C), 155.60 (1C, C=N-N), 168 (1C, pyridazinone C=O).

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Abubshait, S.A. An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity. Molecules 2007, 12, 25-42. https://doi.org/10.3390/12010025

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Abubshait SA. An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity. Molecules. 2007; 12(1):25-42. https://doi.org/10.3390/12010025

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Abubshait, Samar A. 2007. "An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity" Molecules 12, no. 1: 25-42. https://doi.org/10.3390/12010025

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