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Synthesis and Characterization of Various Alkyl, Aryl and Hetero Aryl Substituted Hydrazines and Study of their Biological Activity

Volume 33, Number 2

Poonam Goklani

Department of Chemistry, Govt. Dungar College, Bikaner, India.

Corresponding Author E-mail: anil362@gmail.com

DOI : http://dx.doi.org/10.13005/ojc/330262

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ABSTRACT:

Due to the presence of N-N linkage hydrazines are well-known for their diverse biological activity.N-N linkage has been used as a key structural motif in various bioactive agents. A series of aryl, alkyl and hetero aryl substituted hydrazine derivatives has been synthesized, for this  diazotization of alkyl, aryl amines has been done, followed by reduction with stannous chloride or sodium sulfite. All synthesized compounds were characterized by elemental   analysis, IR, 1H-NMR, Mass spectra  and  their  biological  activity has  been  studied.

KEYWORDS:

Hydrazine derivatives; N-N linkage; Biological activity; Diazotization

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Goklani P. Synthesis and Characterization of Various Alkyl, Aryl and Hetero Aryl Substituted Hydrazines and Study of their Biological Activity. Orient J Chem 2017;33(2).

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Goklani P. Synthesis and Characterization of Various Alkyl, Aryl and Hetero Aryl Substituted Hydrazines and Study of their Biological Activity. Orient J Chem 2017;33(2). Available from: http://www.orientjchem.org/?p=31346

Introduction

Among the nitrogen-nitrogen bond containing chemical the hydrazines are well-known for their diverse biological activity and as therapeutic agents in medicines. Many hydrazine derivatives are known to exhibit significant biological activity and several compounds with hydrazine moiety were shown to be effective for treatment of tuberculosis, Parkinson’s disease and hypertension1.Hydrazinesshowsneuroprotective, antitumor antidepressant and antimicrobial properties2,3,4,5.

The hydrazine moiety has been used for modification of peptides6.Azapeptides hydrazine based peptidomimetics, were found to be potent against hepapititas, AIDS & SARS7,8,9.Hydrazines  derivatives  occur  naturally in tobacco and mushrooms,p-tolylhydrazine(bioactive molecule) isolated as a degradation  product  fromthe  mushroom Agaricusbisporus, was found  to  be  highly   active  compared to 5-flourouracil in vitro anticancer studies 10.

Diacylhydrazines have been identified as one of the most important types of insect regulators11-13. Several commercial compounds, such as tebufenozide, methoxyfenozide, chromafenozide,andhalofenozide, are all classified as diacylhydrazines, and all of these insecticides affect the ecdysonereceptor complex, leading to precocious lethal molting, especially in caterpillars 14,15.Diacylhydrazines have attracted significant attention because of their high insecticidal selectivity,simple structure, and low toxicity to vertebrates 13.

Aryl hydrazides   and  hydrazine  compounds  shows  anticancer   activity  against  5  cancer  cell  lines  namely  A-549, SK-N-SH, HEP-2, PC-3 and MCF-7. Gallic acid hydrazide found to be most active,having high scores, indicating highest binding propensity  towards the thymidylate  synthase16.

Materials and Methods

All the reactions were carried out with A. R. grade chemicals. The C. P. grade chemicals, whenever used, were purified by standard methods. All m.p. were determined on a Yanaco micro-melting point apparatus andwere uncorrected. Elemental  analysis  was  get  done at  CDRI Luckhnow. IR  spectra were  taken  on a  Perkin  Elmer  System  2000  FT-IR  Spectrophotometer, in  KBr  pellets. EI-mass  spectra  were recorded on a VG  Biotech Quattro 5022 spectrometer.  1H-NMR spectra  were  recorded  on a  Bruker  AMX-500 in  CDCl3  and chemical shifts are given in ppm  with  TMS as  internal standard .Silica gel was used  for CC and silica gel  60 F-254 for  TLC  preparation. TLC optical rotations were measured using a Jasco DIP -370 Polarimeter in   CHCl3.

Synthesis of Compounds

Alkyl,aryl and hetero aryl substituted hydrazine derivatives were synthesized.17-19

Scheme 1: Synthesis of Hydrazine Derivatives

Scheme 1: Synthesis of  Hydrazine Derivatives

 



Click here to View Scheme

 

Analysis

Table 1: physical  characteristics  and   analytical  data  of  the  compounds  investigated

Compound Colour Molecular mass g/lmole Elemental Analysis Melting Point oC Molecular formula
C% H% N% O%
1 Yellow Powder 160 60 5 35 172.50 C8H8N4
2 Orange-red needle shaped crystal 153 47.05 4.5 27.4 20.9 156 C6H7N3O2
3 Clear Liquid 136 70.5 8.8 20.5 22,  B.P.74 C8H12N2

 

Table 2:  IR spectral  data  of  the  compounds investigated  in cm-1

Compound

 VN-H VN-N VC-H VC-C VC-N

VC=N
      1 3304, 3411 1373 3000, 2976 1540, 1465 1289 1596, 1668
       2 3322, 3202 1377 3087 1532, 1501 1341, 1315 1600, 1559
        3 3405 1395 3020, 2850 1610, 1118 1310

 

Table 3: NMR and Mass spectral data of the compounds investigated Table 3: NMR and Mass spectral data of the compounds investigated

Click here to View table

 

Biological Activity

All the synthesized compounds  have  been  tested  for  theirbiological  activity.

Compound 1 shows antihypertensive  activity. It  can be  used  to  treat  high  blood  pressure, which  helps  in  preventing   strokes, heart  attacks  and  kidney  problem. For thisNon-invasive (Tail cuff method) has  been used.

Compound  2  shows  anticancer  activity  against  SK-N-SH (CNS) cancer cells.Thisactivity  of  the  compounds  have  been  test  by  MTT  essay.

Compound 3  shows  antidepressant  activity. It is a non-selective  momoamine  oxidase (MAO)  inhibitor commonly  used  to  treat  depression and panic disorder.It  is  checked  by  the behavioral despair test (porsolt –forced swimming  test).

Results and Discussion

Compounds were synthesized from their respective amines. Synthesized  compounds  shows  antihypertensive , antidepressant  and anticarcinogenic activity.Compound  2  shows  anticancer  activity against SK-N-SH cancer cell  line with  IC50= 29µg/ml.

Aknowledgements

The author is thankful to Dr. Anil Gupta for their guidance in the research work and grateful to Govt. Dungar College Bikaner for providing facilities to carry out the work.

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