Microwave assisted synthesis characterization and microbial evaluation of 4-tetrahydro-2H-pyrrolo [2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide derivatives.

 

S.S.Patole1*, Dr.S.S.Rajput2

1Department of Chemistry, S.S.V.P’S College Shindkheda, Dist-Dhule Maharashtra

2Department of Chemistry, S.V.S’SDadasaheb Rawal College,DondaichaMaharashtra

*Corresponding Author E-mail: rajputss65@gmail.com., sandippatole@yahoo.co.in

 

ABSTRACT:

In this work the solid phase microwave assisted synthesis of bis-hetrocyclic chalcones were carried out by reaction of previously synthesized (4-methylphenyl) pyrrolidine-2,5-dione 1 and (4-Chlorophenyl) pyrrolidine-2,5-dione 4 with different substituted benzaldehydes 2a-e in presence of neutral alumina upon microwave irradiation afforded to bis-heterocyclic chalcones 3a-e and 5a-e. This chalcone further treatment withsemicarbazide hydrochloride in presence of neutral alumina solvent free condition upon microwave irradiation leading to ring closure and furnished in to dipyrazoledicorboxamide derivative 6a-e and 7a-e. The structures of all synthesized compounds were determined by using FT- IR and 1HNMR spectroscopy technique. The anti microbial activities of all dipyrazoledicorboxamide derivatives were tested against selective pathogenic microorganisms of gram positive and gram negative bacterial strains similarly antifungal evaluation were determined against pathogenic fungal strains by using disc diffusion method. The zone of inhibition shown by synthesized dicorboxamide derivative were measured in mm and compared with standard antibiotic drug Chloramphenicol and Amphotericine-B. Some compounds dose not shows antibacterial activities some of them are microbially active and the compound 7-(4-chlorophenyl)-3,4-bis(4-methoxyphenyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide 7d exhibited good antifungal activity towards fungal strain Candida Albicans and similarly it display promising antifungal activity against pathogenic fungal species Aspergillus Niger at minimum inhibitory concentration of 100 µgm per disc.

 

KEYWORDS:Pyrrolidine-2,5-dione, Heterocyclic chalcone, Semicarbazide, Dipyrazole,  Dicorboxamide.

 


 

INTRODUCTION:

The nitrogen containing heterocyles are most important among heterocyclic compounds. The substituted pyrazoles are important and well-known class of heterocyclic compounds as they have diverse pharmaceutical and biological applications. The substituted pyrazolines such as pyrazole carboxamides have found to possess inhibition activity of receptors for advanced glycation end product1, they found to possess acaricidal activity2 some derivatives have antidepressant activity3 and antifungal activity4 antibacterial5 the substituted pyrazole moiety act as bradykinin B1 receptor antagonists6 it is also used in treatment of autoimmune disorders7 The pyrazole carboxamides derivatives have anti-inflammatory activity8 analgesic activities9 antioxidant activity10anti-plant pathogenic fungal activity11 diuretic activity12 The cyclic imides such as succinamides have biologically importance13 and have many synthetic applications. The chalcones have diverse biological and synthetic applications14 for synthesizing variety of hetero cyclic compound. All these tremendous applications stimulate us to synthesis dipyrazole dicarboxamide from bis-heterocylic chalcones by using microwave oven in solid phase and solvent free condition which minimizes consumption of energy and elimination waste and pollution

 

MATERIAL AND METHODS:

All chemicals used in the present work are of synthetic grade. The melting points were taken in to open capillaries and are uncorrected. The I.R spectra were recorded on FTIR shimazdu spectrophotometer using KBr disc method. The 1H NMR spectra were recorded on Bruker mx-500 MHz in CDCl3 and DMSO d6. The chemical shift was recorded in δ unit relative to TMS as internal standard. All the compounds synthesized solid phase solvent free condition by using domestic microwave oven in hours. The reactions were monitored by thin layer chromatography by using pre-coated silica gel aluminum plates and mixture of n-hexane: ethyl acetate 5:5 proportion was used as mobile phase. The identification of spots was done by visualizing plate in U.V chamber

 

Experimental:

General procedure for preparation of bis-heterocyclic chalcone:

The bis-hetrocyclic chalcones (3a-e) and (5a-e) was synthesized by reaction of 1 milimole of 1-p-tollylpyrolodine-2, 5-dioneand 1-p-chloropyrolodine-2,5-dione with 2 milimoles of substituted benzaldehyde in presence 1.5 to 2 gm neutral Al2O3 under microwave assisted solvent- free condition at 600 w power for 3 to 4 min. thus colored compound was obtained and recrystalised from ethyl alcohol.

 

General procedure of synthesis of 4-tetrahydro-2H-pyrrolo [2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide derivatives:

The dipyrazoledicorboxamide derivatives (6a-e) and (7a-e) were synthesized by reaction of 2 mmole of semicarbazide hydrochloride with 1 mmole of Bis-chalcone (3a-e) and (5a-e) in presence of 2 grams of neutral alumina in microwave oven as solid phase solvent free condition and irradiated at 450 watt power for 4 to 5 min thus fused mixture obtained and recrystalised it from ethanol.


 

Scheme 1

 

Scheme 2

 

Scheme 3

 

Table 1:Characteristic data of 6a-e and 7a-e

Comp

Aldehyde

M.P (°C)

Yield (%)

Mol. Formula

Found (%) Calcd

 

 

 

 

 

C

H

N

6a

OHC-Ar-OH(o)

153-156

83

C27H25N7O4

63.40

4.93

19.17

 

 

 

 

 

(63.88

4.99

19.78)

6b

OHC-Ar-NO2(m)

210-212

79

C27H23N9O6

56.94

4.07

22.13

 

 

 

 

 

(56.45

4.67

22.45)

6c

OHC-Ar-Cl(o)

139-141

75

C27H23Cl2N7O2

59.13

4.23

17.88

 

 

 

 

 

(59.73

4.56

17.21)

6d

OHC-Ar-CH3(p)

161-163

86

C29H29N7O4

64.55

5.42

18.17

 

 

 

 

 

(64.37

5.68

18.64)

6e

OHC-Ar-OCH3(p)

136-138

77

C29H29N7O2

68.62

5.76

19.32

 

 

 

 

 

(68.17

5.27

19.56)

7a

OHC-Ar-OH(o)

124-126

76

C26H22ClN7O4

58.71

4.17

18.43

 

 

 

 

 

(58.33

4.78

18.79)

7b

OHC-Ar-NO2(m)

95-97

81

C26H20ClN9O6

52.93

3.42

21.37

 

 

 

 

 

(52.43

3.89

`21.88)

7c

OHC-Ar-Cl(o)

141-143

78

C26H20Cl3N7O2

54.90

3.54

17.24

 

 

 

 

 

(54.78

3.67

17.87)

7d

OHC-Ar-OCH3(p)

163-165

71

C28H26ClN7O4

60.05

4.68

17.51

 

 

 

 

 

(60.43

4.81

17.76)

7e

OHC-Ar-CH3(p)

128-131

75

C29H29N7O2

68.62

5.76

19.32

 

 

 

 

 

(68.22

5.26

19.67)

 

 


 

 

(3Z,4Z)-3,4-bis(2-hydroxybenzylidene)-1-p-tolylpyrrolidine-2,5-dione (1a) :

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-OH), 2937(-CH3), 1611(C=C); 1H NMR (500 MHz, DMSO d6, δ ppm): 2.40 (s, 1H, CH3), 5.1(s, 1H, -OH), 7.31-7.17(m, 6H, Ar-H and =CH).

 

(3Z,4Z)-3,4-bis(3-nitrobenzylidene)-1-p-tolylpyrrolidine-2,5-dione (3b):

Yellow solid; FTIR (KBr, cm-1): 2937(-CH3), 1705 (C=O), 1611(C=C) 1345 (Ar-NO2);1H NMR (500 MHz, DMSO d6, δ ppm): 2.40 (s, 1H, CH3), 8.47-6.67(m, 6H,Ar-H and =CH )

 

(3Z,4Z)-3,4-bis(2-chlorobenzylidene)-1-p-tolylpyrrolidine-2,5-dione (3c):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 2937(-CH3), 713 (C-Cl), 1611(C=C); 1H NMR (500 MHz, DMSO d6, δ ppm): 2.40 (s, 1H, CH3), 7.40-7.12 (m, 6H, Ar-H and =CH).

 

(3Z,4Z)-3,4-bis(4-methoxybenzylidene)-1-p-tolylpyrrolidine-2,5-dione (3d):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O)-, 2937(-CH3), 1178 (C-O ether) 1611(C=C); 1H NMR (500 MHz, DMSO d6, δ ppm): 2.40 (s, 1H, CH3), 3.7(s, 3H, -OCH3), 8.22-6.43 (m, 6H, Ar-H and =CH)

 

(3Z,4Z)-3,4-bis(4-methylbenzylidene)-1-p-tolylpyrrolidine-2,5-dione (3e):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 2937(-CH3), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.40 (s, 1H, CH3), 8.22-6.43(m, 6H, Ar-H and =CH).

 

(3Z,4Z)-3,4-bis(2-hydroxybenzylidene)-1-(4-chlorophenyl)pyrrolidine-2,5-dione (5a):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O),, 3368 (-OH), 2937(-CH3), 713 (C-Cl); 1H NMR (500 MHz, DMSO d6, δ ppm): 5.1(s, 1H, -OH), 7.31-7.17(m, 6H,Ar-H and =CH )

 

(3Z,4Z)-3,4-bis(3-nitrobenzylidene)-1-(4-chlorophenyl)pyrrolidine-2,5-dione (5b):

Yellowish white crystals; FTIR (KBr, cm-1): 1705 (C=O),), 2937(-CH3), 1345 (Ar-NO2) 713 (C-Cl); 1H NMR (500 MHz, DMSO d6, δ ppm): 8.57-7.3(m, 6H, Ar-H and =CH)

 

(3Z,4Z)-3,4-bis(2-chlorobenzylidene)-1-(4-chlorophenyl) pyrrolidine-2,5-dione (5c):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 2937(-CH3), 713 (C-Cl); 1H NMR (500 MHz, DMSO d6, δ ppm): 7.40-7.12 (m, 6H, Ar-H and =CH).

 

 

(3Z,4Z)-3,4-bis(4-methoxybenzylidene)-1-(4-chlorophenyl) pyrrolidine-2,5-dione (5d):

Yellow needle shaped crystals; FTIR (KBr, cm-1): 1705 (C=O), 2937(-CH3), 1178 (C-O ether) 713 (C-Cl),1H NMR (500 MHz, DMSO d6, δ ppm): 3.7(s, 3H, -OCH3), 7.6-7.2(m, 6H, Ar-H and =CH).

 

(3Z,4Z)-3,4-bis(4-methylbenzylidene)-1-(4-chlorophenyl)pyrrolidine-2,5-dione (5e):

Pale yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 2937(-CH3), 713 (C-Cl); 1H NMR (500 MHz, DMSO d6, δ ppm): 2.3 (s, 1H, CH3), 7.6-7.2(m, 6H, Ar-H and =CH).

 

3,4-bis(2-hydroxyphenyl)-7-(p-tolyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (6a):

Green solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 3464(-OH), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.3 (s, 3H, CH3), 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 10.1(s, 1H, -OH), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H)       

 

3,4-bis(3-nitrophenyl)-7-(p-tolyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (6b):

Greenish solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 1345(Ar-NO2), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.3 (s, 3H, CH3), 2.6 (d, 1H, CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H), 8.67-7.4 (m, 6H,Ar-H )       

 

3,4-bis(2-chlorophenyl)-7-(p-tolyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (6c):

Brown solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 713(C-Cl), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.3 (s, 3H, CH3), 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H),

 

3,4-bis(4-methoxyphenyl)-7-(p-tolyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (6d):

Brown solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 1188 (O-CH3), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 3.73 (s, 3H,-OCH3), 2.3 (s, 3H, CH3), 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H),

 

3,4,7-tri-p-tolyl-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (6e):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.34 (s, 1H, CH3), 2.6 (d, 1H CH pyrazoline) 3.4 (d, 1H, CH pyrazole), 8.8 (s, 2H, -NH2, carboxamide), 7.8-6.9 (m, 6H, Ar-H)       

 

7-(4-chlorophenyl)-3,4-bis(2-hydroxyphenyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7a):

Pale yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 3464(-OH), 713(C-Cl), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 10.1(s, 1H, -OH), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H))

 

7-(4-chlorophenyl)-3,4-bis(3-nitrophenyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7b):

Light brown solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 713(C-Cl), 1345(Ar-NO2), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H), 8.67-7.4 (m, 6H,Ar-H )       

 

3,4-bis(2-chlorophenyl)-7-(4-chlorophenyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7c):

Light yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 713(C-Cl), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H),

 

7-(4-chlorophenyl)-3,4-bis(4-methoxyphenyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7d):

Yellow solid; FTIR (KBr, cm-1) 1705 (C=O), 3368 (-NH2), 713(C-Cl), 1188 (O-CH3), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 3.73 (s, 3H,-OCH3), 2.6 (d, 1H CH pyrazoline), 3.4 (d, 1H, CH pyrazole), 9.0 (s, 2H, -NH2, carboxamide), 7.6-6.7 (m, 6H, Ar-H),

 

7-(4-chlorophenyl)-3,4-di-p-tolyl-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7e):

Yellow solid; FTIR (KBr, cm-1): 1705 (C=O), 3368 (-NH2), 2937(-CH3), 713(C-Cl), 1611(C=C);1H NMR (500 MHz, DMSO d6, δ ppm): 2.6 (d, 1H CH pyrazoline) 3.4 (d, 1H, CH pyrazole), 8.8 (s, 2H, -NH2, carboxamide), 7.8-6.9 (m, 6H, Ar-H)       

 

RESULTS AND DISCUSSION:

Chemistry:

The solid phase synthesis of chalcones 3a-e and 5a-e were carried out by reaction methyl phenyl succinamide and 4-chlorophenyl succinamide with 2-hydroxy benzaldehyde, 3-nirtro benzaldehyde, 2-chlorobenzaldehyde, 4-methoxy benzaldehyde, 4-methyl benzaldehyde in presence of neutral alumina upon microwave irradiation (scheme 1).The IR spectra of compounds 3a-e and shows frequency at 1700 cm-1 corresponds to presence of carbonyl group. The frequency at 2900 cm-1 indicate to presence C-H starching of methyl group .The1H NMR spectrum in DMSO d6 shows singlet at 2.36 δ this peak indicate presence of methyl group. Similarly IR spectra of compounds 5a-e and shows frequency at 1700 cm-1 corresponds to presence of carbonyl group.

 

The series of synthesized chalcones 3a-e irradiated with semicarbazide hydrochloride in microwave oven in presence of neutral alumina converted in to (7-p-tolyl)-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide 6a-e (scheme 2). The IR spectra of compounds 6a-e shows characteristic frequencies at 1658 cm-1 for presence of amide carbonyl, 3464 cm-1 corresponds to N-H stretching Amide group and 2920 cm-1 indicates the presence Ar-CH3 group. The 1H NMR spectrum in DMSO d6 shows doublet at 4.42 δ this is characteristic peak for –CH of pyrazole ring and another doublet at 2.51 δ is indicates presence of –CH of substituted pyrazole ring.

 

The series of chalcones 6a-e upon irradiation with semicarbazide hydrochloride in microwave oven in presence of neutral alumina afforded to 7-(4-chlorophenyl)- 3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide 7a-e (scheme 3). The IR spectra of compounds 7a-e shows characteristic frequencies at 1670 cm-1 for presence of amide carbonyl, 3450 cm-1 corresponds to N-H stretching Amide group. The 1H NMR spectrum in DMSO d6 shows doublet at 4.19 δ this is characteristic peak for –CH of pyrazole ring and another doublet at 2.41 δ is indicates presence of –CH of substituted pyrazole ring.

 

Antimicrobial activities (6a-e) and (7a-e):

The series of dipyrazole-2,5(7H)-dicarboxamide (6a-e) and (7a-e) were screened for antibacterial activity in vitro against Gram positive bacteria Staphylococcus auras (NCIM 2079) , Bacillus subtilies (NCIM 2250) and Gram negative bacteria pseudomonas aeruginosa (NCIM 2036), Escherichia coli (NCIM 2109) The solution of all compounds (6a-e) and (7a-e) were prepared in DMSO solvent .The assay was carried by taking 100 µgm per disc by using disc diffusion method for this purpose nutrient agar media was employed. The results were obtained in the form of zone of inhibition and noted after period of incubation ( at 370C for 24-28 hrs).The zone of inhibition was measured in mm and compared with std drug Chloramphenicol. Similarly antifungal evaluation was also carried out in vitro against fungi Aspergillus niger (NCIM 545) and Candida albicans (NCIM 3471) in Hi-Media at conc. of 100 µgm per disc. The zone of inhibition was measured in mm and compared with std drug Amphotericine-B. The anti-bacterial and anti-fungal results obtained are mentioned in table 1. And table 2

 

The synthesized derivative shows microbial activities and the zone of inhibition in mm by compounds for anti-bacterial activities shown in fig: 1 and antifungal activity against c.albican is shown in fig: 2 and fig: 3 shown antifungal activities for A.niger. From the compounds (6a-e) and (7a-e) shows bacterial activities and good antifungal activities illustrated in graph: 1 and graph: 2

 


 

Table 2 : Anti-bacterial activity of compounds (6a-e) and (7a-e)

Zone of inhibition measures in mm

Synthesized compounds

Gram positive

Gram Negative

S.aureus

B.subtilis

E.coli

P.aeruginosa

100 µg/ml

100 µg/ml

100 µg/ml

100 µg/ml

6a

-

-

-

-

6b

-

-

-

-

6c

-

-

-

-

6d

-

-

-

-

6e

-

-

-

-

7a

10.92

6.30

6.21

-

7b

8.65

-

7.67

-

7c

7.77

6.44

7.59

-

7d

11.37

6.90

8.42

-

7e

9.97

-

8.36

-

Choramphenicol

32.13

28.30

27.62

14.18

Control (DMSO)

---

---

---

---

 


 

Table 3 : Anti-fungal activity of compounds (6a-e) and (7a-e)

Zone of inhibition measures in mm

Synthesized compounds

Candida aibicans

Aspergillus niger

100 µg/ml

100 µg/ml

6a

-

-

6b

-

-

6c

-

-

6d

-

-

6e

-

-

7a

7.58

-

7b

-

-

7c

-

-

7d

8.69

9.03

7e

6.72

-

Amphotericine B

17.73

10.27

Control (DMSO)

---

---

 

 

Fig.1: Agar plate shows zone of inhibition by 7-(4-chlorophenyl)-3,4-di-p-tolyl-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7d) against fungi C.albicans at 100 µg/ ml

 

 

Fig.2: Agar plate shows zone of inhibition by 7-(4-chlorophenyl)-3,4-di-p-tolyl-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5(7H)-dicarboxamide (7d) against fungi A.niger at 100 µg/ ml

 

 

The synthesized compound shows antibacterial activity against gram positive bacteria S.aureus and B.subtilis and gram negative bacteria E.coli but inactive against P.aeruginosa. The antifungal activity of synthesized derivatives were tested against pathogenic fungal strain Candida albicans and Aspergillus niger the zone of inhibition was compared with std drug Amphotericine–B and the compound 7d shows promising antifungal activity against Aspergillus niger shown in fig 1 and fig 2

 

Graph: 1: Antifungal activities of synthesized dipyrazole dicarboxamide derivatives against pathogenic fungi.

 

CONCLUSION:

The study concluded that synthesis of dipyrazole-2,5(7H)-dicarboxamide derivatives carried out in solid phase solvent free condition upon microwave irradiation in microwave oven with easy workup and high yield. This method of synthesis is environmental friendly because the uses of toxic volatile organic solvents are completely eliminated in this process. The conventional organic synthesis processes are time consuming with lower product yields this green synthesis gives maximum yield in minimum time. The microbial study concluded that dipyrazole-2, 5(7H)-dicarboxamide derivatives shows antibacterial activity against Gram positive bacteria S.aureus, B.subtilis and Gram Negative bacteria E.coli. The dipyrazole-2, 5(7H)-dicarboxamide derivatives inactive against Gram Negative bacteria P.aeruginosa similarly antifungal evolution against pathogenic fungal strains the compound 7-(4-chlorophenyl)-3,4-di-p-tolyl-3,3a,3b,4-tetrahydro-2H-pyrrolo[2,3-c:5,4-c']dipyrazole-2,5 (7H)-dicarboxamide (7d) shows good antifungal activity against fungi C.albicans and shown promising antifungal activity against fungi A.niger.

 

ACKNOWLEDGEMENT:

The authors are thankful to Savitri bai Fule University of Pune for providing spectral analysis facilities and authors are also thankful to Dept of Microbiology R.C.Patel College Shirpur for providing Microbial evaluations facilities.

 

CONFLICT OF INTEREST:

Declared none.

 

REFERENCES:

1.     Young TH, Kim K, Choi GI et al Pyrazole-5-carboxamide, novel inhibitors of receptors for advanced glycation end product (RAGE). European Journal of Medicinal Chemistry.2014; 79:128-142.

2.     Okada I, Okui Y, Takashi Y et al Synthesis and acaricidal activity of pyrazole -5-carboxamide derivatives. Journal of Pesticide Science1991; 16:623-629.

3.     Mathew B, Jerad S, Anbazhangam A et al synthesis periclinical evaluation and antidepressant activity of 5-subtituted phenyl-3-thiophen-2-yl-4, 5 –dihydro-1-H pyrazole -1- carbothiamidesExcli Journal.2014; 13:437-445

4.     Zibing W, Deyu H, Jiqing K et al synthesis and antifungal activity of N-(Substituted pyridnyl-1-methyl phenyl-3-trifluromethyl-1H-pyrazole-4-carboxamide derivatives. Molecule 2012; 17:14205-14218.

5.     Amin BN, Parikh AR, Parikh H et al synthesis and screening of antibacterial antifungal activity of 6-Amino-4-(ary/Heteroaryl)phenyl-3-methyl-2,4-Dihydropyrano[2-3c]pyrazole-5-carboxamide Derivatives. 2014; 3(2):208-212.

6.     Darren D, Garofalo AW, Hawkingson G et al preparation and optimization of a series of 3-carboxamido-5-phenacylaminopyrazole bradykinin B1 receptor antagonists. JOURNAL of Medicinal Chemistry.2007; 50:5161-5167.

7.     Jonsson S, Anderson G, Fex T et al Synthesis and biological evaluation of new 1, 2-dihydro-4-hydroxy-2-oxo-3-quiniline carboxamide for treatment of autoimmune disorders structure activity relationship. Journal of Medicinal Chemistry.2004; 47:2075-2088.

8.     Nagarapu L, Mateti J, Gaikwad HK et al synthesis and anti-inflammatory activity of some novel 3-phenyl-N-3-(4-phenylpiperazine-1yl)propyl-1H-pyrazole-5-Carboxamide derivatives. Bioorganic and Medicinal Chemistry Letters. 2011; 21:4138-4140.

9.     Khalifa NM, Al-Omar, El-Galil AA et al anti-inflammatory and analgesic activities of some novel corboxamides derived from 2-phenyl quinoline candidates. Biomedical Research 2017; 28 (2):869-874.

10.   Kumar CK, Kumar HV, Kumar GR et al 3-Oxoisoindoline-5-Carboxamides synthesis and their antioxidant activity studies. Journal of Pharmaceutical Science and Technology 2010; 2(12):380-390

11.   Xin Y, Wang H, Chen F Synthesis and anti-plant pathogenic fungal activity of novel benzofura-2-carboxamide derivatives. Bulgarian Chemical Chemical Communication. 2016; 49:145-150.

12.   Yar MS, Ansari ZH, Synthesis and vivo diuretic activity of biphenyl benzothiazole-2-carboxamide derivatives. AcetaPoloniae Pharmaceutical-Drug Research. 2009; 66:387-392.

13.   Dhiware RS, Rajput SS Synthesis and antimicrobial activity of five membered cyclic imide derivatives of mono di and tri substituted aromatic amines and napthyl amine. World Journal of Pharmacy and Pharmaceutical Research. 2015; 6:1650-1658.

14.   Rajput SS, Patole SS Synthesis and uses of chalcone in heterocyclic synthesis. World Journal of Pharmacy and Pharmaceutical Research. 2015; 7:1566-1591.

 

 

 

 

 

 

Received on 21.10.2017         Modified on 22.11.2017

Accepted on 18.12.2017         © AJRC All right reserved

Asian J. Research Chem. 2018; 11(1):77-83.

DOI:10.5958/0974-4150.2018.00018.4