Synthesis, Structural Characterization and Study of Biological Activity of Hydrazine  Derivatives

Poonam Goklani^* and Anil Gupta

P.G. Department of Chemistry, Govt. Dungar College, Bikaner-334001, India

Corresponding Author Email: poomam26wadhwani@gmail.com

DOI : http://dx.doi.org/10.13005/msri/140217

ABSTRACT:

Hydrazide-hydrazone   derivatives   play  vital  role  in  development  of  various pharmacological activities such as anti-tubercular, antiproliferative  and antitumor activities. Some novel biologically active   Hydrazide   derivatives substituted   with  heterocyclic   moiety have  been synthesized.  All the synthesized  compounds  structures   were   confirmed  by   IR,  NMR  and  Mass  spectra. Synthesized  compounds  were  subjected  to  antibacterial  screening in  vitro  and  biological  activity in vivo.

KEYWORDS: Hydrazide derivatives; Pharmacological activity; Heterocyclic-moiety; spectral data

Copy the following to cite this article: Goklani P, Gupta A. Synthesis, Structural Characterization and Study of Biological Activity of Hydrazine Derivatives. Mat.Sci.Res.India;14(2)

Copy the following to cite this URL: Goklani P, Gupta A. Synthesis, Structural Characterization and Study of Biological Activity of Hydrazine Derivatives. Mat.Sci.Res.India;14(2). Available from: http://www.materialsciencejournal.org/?p=5816

Introduction

Hydrazine  derivatives  are  very  useful  compounds. These  are  used   in  pharmaceutical, agrochemicals, polymer  and dye industy.¹ Hydrazines  derivatives  very  tremendously   not  only as  to modification in structure but also as  regard to  their  therapeutic  indication.^2-4 Many of hydrazines having a simple structure are bacteriostatically active compounds which may be used as tuberculostatics, others are monoamine oxidase inhibitors, these are used as antidepressive.⁵ Some group of  hydrazides has a clinically interesting  saluretic  activity. Many  hydrazines  with  general  formula  R₁R₂NNR₃R₄  (R- H, alkyl,  acyl or  aryl substituent) shows  incredible  biological  activity  and  are  used  in  pharmaceutical. Some  examples  can  refer  to tuberculostatic  activity  of  hydrazines.^6,7

Hydrazines derivatives shows  antimicrobial activits.^8,9 N-N’-(carbazol-1-yl-1′,2′,3′,4′-tetrahydrocarbazol-1′-yl)hydrazine  showed antibacterial activity against Escherichia coli, Staphylococeus aureus, Pseudomonas aerugimosa and Bacillus subtilis. These N-N’-carbazolyl hydrazine derivatives has been found to show antifungal activity against Aspergillus niger, Candida albicans.¹⁰ Isoquinolin-1-yl-2-(cycloalk-2-enylidene)hydrazines were prepared by the reaction of

1-hydrazino-3-isoquinoline with appropriate 1,3-diketones. These compounds also show good antibacterial and antifungal activity. Compound with electron rich   groups exhibit antibacterial activity against bacterial species B. cerus.¹¹

Some  hydrazine derivatives  are effective  analgesics and  are used   as cyclooxygenase-2 (COX-2) inhibitors, what is essential for development of non-steroidal anti-inflammatory drugs.¹² Substituted  diphenylhydrazides  are  found to be effective  pharmacophore  for   selective  cyclooxygenase-2   (COX-2)  inhibition, which  is  necessary  in the   design of  novel  anti-inflammattory drugs.¹²

N’-(2-phenoxybenzylidene)-2–phenoxybenzohydrazide, N’-(4-(methylthiobenzylidene)-2-phenoxybenzohydrazide, 2-(2-phenoxybenzylidene)-1-(2-nitrophenyl)hydrazine  and 2-(2-phenoxybenzylidene)-1-(2,4-dinitrophenyl)hydrazine these compounds showed higher inhibitory effect against  inflammation then mefenic acid (analgesic). It has been observed that attachment of phenoxy group in both 2 and 3 position of the phenyl ring can results in better analgesic activity.¹³

Acyl hydrazine derivatives  exhibited  excellent   chemotherapeutic activity.^14-17

Materials and Methods

All the  chemicals  and  solvents  were  of reagent grade. Melting  points were  determined  on a capillary  melting  apparatus  and were  uncorrected. H-NMR  spectra were  recorded on  Bruker AMX-500  in CDCl₃ with  TMS  as  internal  standard. IR  spectra  were  recorded  in  KBr  on a  Perkin  Elmer  System  2000  FT-IR  Spectrophotometer.  For  EI-mass  spectra  we  use a VG  Biotech Quattro 5022 spectrometer.

Some substituted hydrazine derivatives were synthesized  by  the  diazotization method.^18-20

Materials- Various amines, hydrochloric acid, sodium nitrite, sodium carbonate, sodium sulphite, stannous chloride, benzylhydrazine dihydrochloride , n-heptan and  Triethylamine

Synthesis of   Compounds

Compounds 1 and 2- These  were synthesized  by  the  following   method.

Scheme 1

Click on image to enlarge

 

Some  others  have  been  synthesized   by different  methods.

Compound 3– This  compound  is  synthesized  by  the  reaction  of  aryl hydrazide  with  2-propanol  or  acetone  and   then  followed  by   reduction.

Scheme 2

Click on image to enlarge

 

Compound 4– In  this  procedure methyl 5-methylisoxazole-3-carboxylate  reacts  with  benzylhydrazine dihydrochloride  and  n-heptan.  Triethylamine  was  added to  the  suspension   slowly  with a  dropping  funnel.  At  the  end  of  the addition   the  temperature  was  adjusted  to  about  35⁰C  for 5-6 hours.  Then  cooled,  filtered,  washed   with water   and  n-heptane and  product   obtained  as  white  solid.

Scheme 3

Click on image to enlarge

 

Characterization

Chemical and  spectral  data  of  the  compounds are  shown in the following table (table: 1-3)

Table 1:  Physiochemical Characterization Data For Compounds

Compound	Molecular Mass g/mole	Elemental Analysis				Melting point 0C	Molecular Formula
		C%	H%	N%	O%
1.	137	52.55	5.10	30.65	11.67	170-173	C6H7N3O
2.	122	68.85	8.19	22.95	–	143-145	C7H10N2
3.	179	60.33	7.26	23.46	8.93	161	C9H13N3O
4.	231	62.33	5.62	18.18	13.85	105-106	C12H13N3O2

 

Table 2: Mass And  Ir  Spectral  Data Of  The  Compounds

Compound	Mass data m/z	IR Peaks (cm-1)
1.	137	3430,3111,3014,1668,1638,1602,1557, 1493,1336,1222
2.	122	3266,3090,3032,2998,1604,1576,1442, 1368,1312,1214
3.	164	3117,3107,3013,2963,1611,1588,1452, 1391,1322,1307,1228
4.	127	3269,3212,2000,1700,1669,1593,1453, 750,704

 

Table 3: ¹H-NMR and ¹³C-NMR  Spectral Data of the  Compounds

Compounds	NMR Peaks (ppm)
1.	1H NMR δ 8.79(2H, m, H-5.6),  7.75(3H,  m, H-2),  7.73(3H, m, H-3,4),  4.54(2H, d, J=3.7Hz, H-1),  13C NMR δ 163.95(C-1),  150.16(C-2),  140.27(C-3),  121.00(C-4).
2.	1H NMR δ 7.43(2H, dq, J=8.2,1.0Hz, H-4,5),  7.32(2H, m, H-6,8),  7.27(1H,m, H-7),  3.99(2H, dt, J=4.4,1.0 Hz, H-3),  2.80(1H, tt, J=4.4,3.3Hz, H-2), 2.09(2H, d, J=3.4Hz, H-1) 13C NMR δ 133.85(C-1),  129.35(C-2),  128.27(C-3),  128.00(C-4),  53.60(C-5).
3.	1H NMR δ 8.72(2H, dd, J=4.52Hz, H-4), 7.88(2H, dd, J=4.5Hz, H-3), 3.05(1H, dd, J=6.16,6.16Hz,  H-2), 1.14(6H, d, J=6.16Hz,  H-1) 13C NMR δ 164.35( C-1), 150.01(C-2), 134(C-3),  119.46(C-4), 58.06(C-5), 20.28 (C-6)
4.	1H NMR δ 7.316(1H, ddd, J=1.25,1.25Hz, H-1), 7.35(2H, ddd, J=7.71,7.79Hz,  H-2), 7.317( 2H, ddd, J=1.27,7.71Hz), 3.914(2H, m, H-4), 6.55(1H, m, H-5), 2.554(3H,m, H-6)  13C NMR δ 169.9(C-1), 161.1(C-2),  153.8(C-3),  137.5(C-4), 128.9(C-5), 128.6(C-6),  127.79(C-7), 100.7(C-8), 49.3(C-9), 12.0(C-10)

 

Biological Activity

The  biological  activity  of  synthesized  compounds  are as follows.

 Compound  1 and 3  showed  antimycobacterial  activity. This  is checked  by  broth  dilution  method. Compound  1 and 3  shows  antimycobacterial   activity   respectively  at 191µg/ml  and  176µg/ml. 

Compound no. 3 and  4  shows  antidepressant  activity, compounds exert their action by inhibiting the enzyme monoamine oxidase(MAO). Inhibition results in increased levels of norepinephrine, dopamine, tyramine and serotonin in brain neurons and in various other tissues. For  the assessment  of  antidepressant  activity, Forced swim  test  (method)  is used.

Compound 2 doesn’t  shows  any  biological activity.

Results  and  Disscusion

Compounds   were   synthesized  by   amines,  esters  and   arylhydrazides.  These   compounds   shows   anti TB(antimycobacterial)   and  antidepressant  activity.

Aknowledgement

This work  was supported  by  Govt.  Dungar  College  and  S.P. Medical   College  Bikaner.

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