INTERNATIONAL JOURNAL OF PHARMACEUTICAL … 1174.pdf · cm-1: 1515 (C = C-NH –N=), 3106 (NH 2. NH...

Research Article CODEN: IJPRNK ISSN: 2277-8713 Anil Kumar, IJPRBS, 2015; Volume 4(6): 94-105 IJPRBS

Available Online at www.ijprbs.com 94

SYNTHESIS AND STUDIES ON POSSIBLE HETERO CYCLIC COMPOUNDS AND THEIR BIOLOGICAL ACTIVITY

ANIL KUMAR

Department of Chemistry Maharaj Singh College, Saharanpur – 247001 (India)

Accepted Date: 27/10/2015; Published Date: 27/12/2015

Abstract: A novel series of sulpha/substituted phenyl azo 1,2 diazole derivatives were synthesized by the condensation of azo moiety of different 1, 3 di ketone and ethyl 3-Oxo butyrate with nicotinic/iso nicotinic acid hydrazide in sufficient quantity of glacial acetic acid. The newly synthesized compounds were characterized and screened for their promising anti-inflammatory activity.

Keywords: 1, 2 diazole. Nicotinic / iso nicotinic acid, Anti-inflammatory activity.

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Anil Kumar, IJPRBS, 2015; Volume 4(6): 94-105



INTRODUCTION

Heterocyclic moieties can be found in a large number of compounds which display biological

activity. The biological activity of the compounds mainly dependent on their molecular

structures (1) Phenyl pyrazoles have attracted considerable attention due to their cockroach

killing activity (2,3). Diazole derivatives are endowed with a number of other biological activities

such as orthopodicides, nematocides, fungicides, anti helminthis and antiprotozoa (4- 8). A few

derivatives are also able to control housefly, spider mites. etc. (9). A series of Pyrazole

derivative, namely N1-4- (Fluorobenzoyl) – 5, 5’ di metyl cyclohexane -4- (sulpha/substituted

phenylazo)- 5, 5’ di metyl cyclohexane – 1, 3 dione with fluorobenzoic acid hydrazide and their

termiticidal activity has been evaluated (10). Radwan, M.A.A. et.al. studied the potential anti-

inflammatory and analgesic activity of 1,2 diazoles (11). Roy et.al. also worked on 1,2,4

Thiazoles and evaluated the activity of newly synthesized compounds (12). In this context,

Arvind et.al.(13) reviewed on biological activities on 1,3,4 Thiazole derivatives. X, Joseph Raj

and N. Rajendran (14) studied corrosion inhibition effect of substituted thiazole on brass.

In view of great biological and medicinal importance of heterocyclic compounds in the light

review of the extensive work done. It was considered worthwhile to synthesize

sulpha/substituted phenylazo – 1, 2 diazoles and 1, 2 diazolin – 5-ones of the 4-

nicotinic/isonicotinic acid hydrazide. Efforts had been made to synthesize some new

compounds by linking two heterocycles moeity for enhancement for their anti-inflammatory

activity. The synthesis of Sulpha /substituted 1, 2 diazole 1, 2 diazolin -5 ones with

nicotinic/isonicotonic acid hydrazide and their anti-inflammatory activity were reported.

EXPERIMENTAL SECTION

Materials: - Solvents are carried of S.D fine chem. and E. Merck grade, were purified and dried

by convential method (15). Sulpha drugs were obtained from Indian Drugs and Pharmaceuticals

Limited, Hyderabad. All other chemicals of S.D. Fine Chem and E. Merck grade have checked for

their purity before use.

The homogeneity and purity of the compounds were checked over thinlayer chromatography

coated with silica Gel – G (thickness 0.5 mm) developing solvent acetone /DMF (3:1) non-

saturated chamber at room temp (20± 10c).

The melting points of the synthesized compounds were determined by capillary method and

were uncorrected. The IR spectra (in KBr) were recorded on JASCO FI-IR spectrophotometer. 1NMR spectra (DMSO/CDCl3) were taken on VRO – 300 MHZ spectrophotometer and chemical

shift expressed as ppm and TMS was used as internal standard.



Experimental method: Scheme of work



Experimental Method

Pentane 2,4 dione, 1,3 diphenylpropane – 1,3 dione, 1- phenylbutane – 1,3 dione; ethyl 3-0xo

butyrate, 2- Sulphonoamidobenzene, N1- 2- acetyl- sulphonamidobenzene, N1-2- guanyl-

sulphonoamidobenzene, N1-2- pyridyl sulphonoamidobenzene and nicotonic/isonicotonic

hydrazide known compounds were prepared for the synthesis of 1,2 diazole and 1,2 diazolin – 5

one derivatives.

Synthesis of 2- methyl phenyl azo pentene hydrazide 2, 4 dione: 2- methyl phenyl diazonium

chloride solution (5ml) is treated with 1,3 diketones (2 ml) and ethyl -3-Oxo butyrate (7ml) in

glacical acetic acid (15 ml) and refluxed for 4 hours; on water bath and cooled Product is

separated out, filtered and recrystallized with ethanol.

Result: Yield = 70% Color =Yellow shining sharp crystals

M.P = 1130 C, M.F = C12 H14N2O2 (Found N = 12.80%, Cal. N = 12.84%)

IR (KBr) vmax cm-1: 1515 (C = C-NH –N=), 3106 (NH2. NH2 associated) , 1629 (C= C), 830 ( C –

CH3)

1H NMR (CDCl3) (δ in ppm): 2.15 (s, 3H, Ar –CH3),2.25 (s, 3H, CO-CH3), 2.45(s.3H, CH-C-CH3),

6.80 – 7.25 (m,4H, Ar-H)

Synthesis of 4 – methoxy azo -1,3 di phenyl propane -1, dione:

Above produce were adopted for this compound.

Result: Yield = 75%, Color = dirty yellow crystals, M.P.= 176 0C,

M.F= C22 H18 N202 (Found N = 7.80% Cal N = 7.82%)

IR (KBr) vmax cm-1: 1515 (C = C-NH-N=), 892 (C-OCH3), 1597 (C=C), 1650 (C =O)

1H NMR (CDCl3) (δ in ppm): 3.65 (s,3H, -OCH3) 6.50 (m, 14H, ArH), 10.0 (s, 1H, C –OH)

Synthesis of 4- Chloro phenyl azo-1-phenyl butane 1,3 dione

Same method was adopted.

Result: Yield = 82%, Color = Orange Red

M.P.= 76 0C, M. F. = C16 H13 N2 O2 Cl (Found N = 10.42%, Cal. N. = 10.43%)

IR (KBr) vmax cm-1: 1527 (C=C-NH-N=), 1653 (C=O), 1592 ( C=C), 3279 (= NH – NH – associated)

833 ( C– Cl)



1H NMR (CDCl3) (δ in ppm): 2.5 (s, 3H, CH3), 6.85 – 7.50 (m ,7H, ArH) 7.60 – 7.85 (m, 2H, C2–H

and C4 – ArH)

Synthesis of 3 Chloro phenyl azo – ethyl - 3oxobutyrate

Result: Yield= 82% Color = SOS, M.P. = 760C

M.F. =C12 H13 N2O3Cl (Found N = 10.41% Cal N = 10.43%)

IR (KBr) vmax cm-1: 1527 ( C = C – NH – N = ), 1709 ( C=O), 1616 (C=C), 2995 (=N-N4), 836 (C-Cl)

1H NMR (CDCl3) (δ in ppm): 1.3 (t, 3H, CH3) 2.3 – 2.5 (3H, C –CH3) 4.2 (q, 2H, CH2)

7.05 – 7.30 (m, Ar-H), 1.49 (s, 2H, C-OH, CH-C)

By adopting same procedure 2 – nitrophenyl, 3- Nitrophenyl, 4- Nitrophenyl, 2- Chloro phenyl,

4- Chlorophenyl, N1-2 Pyrimidyl, N1-2 (4,6 dimethyl) Pyrimidyl, N1- 2 Guanyl,

N1 - 2 Pyridyl, N1-2 thiazoyl etc. Sulphnoamidobenzene azo ethyl butyrate, 3 – oxobutyrates

were synthesized.

Synthesis of N1 nicotinoyl – 3,5 dimethyl (N1 – 2 – Pyrimidyl Sulphonamido benzene azo) – 1,2

diazole: The above synthesised compound (5 gm) are reluxed with nicotinic /isonicotinic acid

drazide (7 ml) in presence of glacial acetic acid (10 ml) to form sulpha /substituted 1,2 diazole

and 1,2 diazole - 5 ones for four hours on

water bath using reflux water condenser. The product is cooled, filtered, washed with ethanol

and recystallised with ethanol.

N1-nicotinoyl – 3,5 dimethyl – 4 – (N1 – Pyrimidyl.) Sulphonamidobenzene azo) – 1,2 diazole:

Result: Yield = 2.63 gm (70%) colour = white Pale yellow M.P. = 2430C

Melecular formula = C21, H11 N8 O3 S (Found N = 24.04%, Cal. N = 24.24%)

R F value = 0.8324

IR (KBr) vmax cm-1: 1580 (N = N), 1655 (C =O Pyridyl), and 1485 (C = N)

1H NMR (CDCl3) (𝜹 in ppm): 2.15 (s, 6H, 2X, CH3)

4.5 (bs, 1H) and 6.9 – 7.8 (m, 10H, ArH )

N1 – 4 nicotinoyl – 3,5 diphenyl – 4 – (2 nitro phenylazo) - 1, 2 diazole



Result: Yield = 2.44 gm (76%), M.P. = 840C color = orange red

Mol. for. = C27 H18 N6 O3 (Found N = 17.65% Cal. N = 17.72%)

Rf value = 0.9160

1H NMR (CDCl3) (𝜹 in ppm): (7.15 – 8.25) (m, 18 H, ArH)

N1 – nicotinoyl - 3 methyl – 4 phenyl – 4 (2Chloro – 4 nitro phenylazo) – 1, 2, diazole.

Result: Yield = 2.39 gm (75%) M.P. = 2730C Colour = Orange Red

M.F. = C22 H15 N6 O3 Cl) (Found N = 18.74% Cal. N = 18.83%)

Rf value = 0.9497

IR (KBr) vmax cm-1: 1580 (N = N), 1520 (C = N) 720 (C -Cl)

N1 – Isonicotinoyl – 3,5 di methyl – 4 – (4 – Chlorophenylazo) 1,2 diazole.

Result: Yield = 3.2 gm (75%) M.P. 2550C Colour = dirty white

Mol. For. = C17 H14 N5 OCl, (Found N =20.51% Cal. N = 20.62%)

Rf value = 0.9053

IR (KBr) vmax cm-1: 1580 (N = N), 1630 (C = O), 840 (C – Cl)

N1 = iso nicotinoyl – 3,5 diphenyl – 4 – (4 – nitrophenylazo) 1, 2 diazole.

Result: Yield = 2.70 gm (70%) M.P. = 2630C. Colour = dirty white

Mol. Formula = C27 H18 N6 O3. (Found N = 17.68%, Cal. N = 17.72%)

Rf value = 0.5745

1H NMR (CDCl3) (𝜹 in ppm): 7.4 – 7.50 (2s, 10 –C- (C6 H5 )2)

7.35 (dd , 2, , meta – N = N, C6 H5N = 6HZ), 7.12 ( dd , 2,O – C(C5H4N), Ortho 3HZ)

8.04 (dd,2, to C = O, J = 9 and 2 HZ) 7.93 (dd. 2, ArH, ortho to NO2, J = 9 and ArH, ortho to C = O,

J = 9 and 2 HZ)



RESULT AND DISCUSSION

Anti-inflammatory activity: -

Some newly synthesized compounds were screened for anti-inflammatory activity. against male

albino rats weighing between 120 – 200 gm, ALD50 dose respectively as compared to standard

indomethacin at 200 μg /ml. Few compounds showed promising anti-inflammatory activity

which are given below in table -

Table: Anti-inflammatory activity of newly synthesized compounds

S. No. Name of Compound. Approxinate Anti-inflammatory

activity % of inhibitation

ALD50 Dose (mg/Kg)

mice P.O.

1- N1- isonicotinoyl - 3.5 di

methyl - 4 - (N1 – 2

Pyrimidyl -

sulphanamido

benzeneazo) 1,2

diazole.

>1000 200 74

2- N1 isonicotinoyl - 3 -

methyl - 5 - phenyl - 4 -

(4 - nitrophenylazo 1,2

diazole.

681 200 79

3- N1 - Nicotinoyl – 3,5

dimethyl - 4 - (4 -

chlorophenylazo 1, 2

diazole.

825 168 77

4- N1 nicotinoyl. 3,5

dimethyl - 4 - (N1 - 2 –

thiazolyl sulphanamido

benzeneazo) 1, 2

diazole

825 173 62



5- N1 isonicotinoyl - 3 -

methyl - 5 - phenyl - 4 -

(4 chloro phenylazo)

1,2 diazole

562 112 53

ACKNOWLEDGEMENT

The author wish to express their sincere thanks to Principal, Maharaj Singh College, Saharanpur

for providing necessary lab facilities and also thankful to Director, C.D.R.I. Lucknow for heling in

spectral studies and biological evaluation of newly synthesized compounds.

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