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ORIGINAL ARTICLE
Year : 2011  |  Volume : 2  |  Issue : 2  |  Page : 69-72  

Effort toward the single pot synthesis of 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one


1 Department of Pharmacy, GRD (P.G) Institute of Management and Technology, Rajpur, Dehradun;Uttrakhand Technical University, Dehardun, Uttarkhand, India
2 Devsthali Vidyapeeth, College of Pharmacy, Rudrapur, India
3 Department of Pharmacy, GRD (P.G) Institute of Management and Technology, Rajpur, Dehradun, India

Date of Web Publication25-Nov-2011

Correspondence Address:
Mohammad Asif
Department of Pharmacy, GRD (PG) Institute of Management and Technology, 214-Rajpur Road, Dehradun, Uttarkhand - 248 009
India
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Source of Support: GRD (PG) Institute of Management and Technology, Dehradun, India and to SAIF, CDRI, Lucknow, India, Conflict of Interest: None


DOI: 10.4103/0976-9234.90215

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   Abstract 

Background: Many synthetic heterocyclic compounds are known to have different biological activities. Pyridazine and its derivatives are the important six membered heterocyclic compounds containing two N-hetero atoms. The pyridazine moiety is an important structural feature of many biologically active compounds. Pyridazine derivatives show diverse pharmacological properties. Aims and Objectives of the Study: The goal of this study, Pyridazine hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds also. On the basis of its important in reported literature, we synthesized the 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydro pyridazin-3(2H)-one in single step or pot reaction. Results : The important Observations and concrete implications of the study. The result showed that the compound 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl) ethyl]-4,5-dihydropyridazin-3(2H)-one was not prepared by this method. The synthesis of compound has been confirmed by the spectral analysis namely IR, 1H NMR and Mass spectroscopy.

Keywords: Biological activities, heterocyclic, pyridazinone, synthetic compounds


How to cite this article:
Asif M, Singh A, Lakshmayya. Effort toward the single pot synthesis of 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one. J Pharm Negative Results 2011;2:69-72

How to cite this URL:
Asif M, Singh A, Lakshmayya. Effort toward the single pot synthesis of 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one. J Pharm Negative Results [serial online] 2011 [cited 2019 Sep 22];2:69-72. Available from: http://www.pnrjournal.com/text.asp?2011/2/2/69/90215


   Introduction Top


The pyridazine (1,2-diazine) is a six membered ring containing two nitrogen atoms. During the last few decades, much attention has been paid to the synthesis of pyridazin-3(2H)-one derivatives which possess important pharmacological activities. Depending on the type of substituted groups, derivatives of pyridazin-3(2H)-one show very different biological actions, such as analgesic, [1],[2] anti-inflammatory, [3],[4] antibacterial, [5] antifungal, [6] antivirus, [5],[6] antitubercular, [6],[7] antihypertensive, [8],[9],[10] anticancer, [11] antidiabetic, [12] anticonvulsants, [13] etc. properties and various other cardiovascular and nervous system diseases. [14],[15],[16],[17] Various structural modifications were carried out in pyridazinone ring system. These structural changes resulted in some fruitful biological activities of the compounds. [18] Some of these are mentioned. [19],[20]

Pyridazines are inexpensive and easily available and synthesized, and therefore have been examined as biologically active drugs. A slight variation in the substitution pattern on the pyridazine nucleus often causes a marked difference in activities. Therefore, pyridazinone with various substituents are being synthesized and tested for varieties of pharmacological activities in search of better medicinal agents. There are some marketed drugs that containing pyridazinone moiety in there structure. For instance, Emorfazone as analgesic and antiinflammatory, levosandane as cardiotonic etc. are used in medical therapy. In addition, different pyridazinone derivatives are tested for various different biological activities for the treatment of various treatments. Therefore, pyridazinones further drew our attention because of their easy functionalization at various ring positions, which makes them attractive synthetic building blocks for designing and development of novel pyridazinone. The discovery of biological activity in a series of pyridazinone derivatives stimulated the vigorous growth of investigations in this area. Stimulated by these findings, our attention has been focused on the synthesis pyridazinone derivatives[Figure 1],[Figure 2]. [21],[22]
Figure 1: Pyridazinone compound used as NASID

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Figure 2: Some pyridazine compounds used in cardiovascular diseases

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   Materials and Methods Top


Experimental section

Solvent system used throughout the experimental work for running thin layer chromatography (TLC) plates was toluene, ethyl acetate and formic acid (TEF) in the ratio of 5:4:1 for determining time duration of reaction. Infrared (IR) spectra, high-field nuclear magnetic resonance ( 1 HNMR) and mass spectra were recorded by using potassium bromide (KBr) pellet technique on Perkin Elmer IR spectrophotometer, in deuterated chloroform using tetra methyl silane (TMS) as an internal reference standard on Bruker AVANCE II 400 NMR spectrometer.

Synthesis of 6-(Biphenyl-4-yl)-2-[2-(1H-indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one (III): Before synthesis of 6-(Biphenyl-4-yl)-2-[2-(1H-indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one, 6-(Biphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-one (II) was prepared from phenyl benzoyl propionic acid (I). Both compounds were prepared by following below given method. [7],[13]

Synthesis of phenyl benzoyl propionic acid (I)


A mixture of Biphenyl (20 gm) and anhydrous aluminium chloride (0.15 mol) was refluxed under anhydrous condition, followed by addition of succinic anhydride (0.10 mol) in small quantity with continuous stirring for 4 hr. After leaving over night, contents were poured into ice cold hydrochloric acid (2.5% v/v) followed by steam distillation. The aqueous solution was concentrated to obtain crude compound and was re-crystallized from aqueous ethanol. [7],[13]

Synthesis of 6-(Biphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-one (II)

The phenyl benzoyl propionic acid (0.01 mol) was refluxed for 6 hr with hydrazine hydrate (0.01 mol) in methanol (10 ml) containing sodium acetate (50 mg). The content was concentrated and then poured into ice cold water to get the compound. It was re-crystallized from ethanol.



Procedure development for synthesis of 6-(Biphenyl-4-yl)-2-[2-(1H-indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one (III)

These compounds are not formed by method A and method B on the basis of spectral analysis. So, another method will be used for synthesis of this compound in future.

Method A

A mixture of compounds 6-(Biphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-one (0.01 mol), potassium carbonate (0.015 mol) in 40 ml of dimethyl formamide (DMF), indole (0.01 mol), and dibromoethane (0.01 mol) was added, and stirred at 50΀C for 5 hr. The reaction mixture was then poured into ice-water and the precipitate formed was filtered off, washed with water, dried and recrystallized from ethanol.

Method B

A mixture of compounds 6-(1,1'-biphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-one (0.01 mol), indole (0.01 mol), dibromoethane (0.015 mol) and potassium carbonate (0.15 mol) in dry acetone (50 ml) was refluxed for 8 hr. The reaction mixture was filtered hot and the solvent was distilled off from the filtrate. The crude ester thus obtained was purified by re-crystallization from ethanol.


   Results and Discussion Top


IR, 1 HNMR mass spectrum of the compounds

The compounds were characterized on the basis of IR, 1 HNMR and mass spectral data. The spectra showed that compound 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one was not prepared by both the methods.


   Discussion Top


The chemistry of nitrogen hetero atom containing aromatic compounds is becoming more popular as an area of research. Pyridazinone or pyridazine and related compounds have shown diverse biological activities. They bind to physiological targets or receptors, producing many possible mechanisms of actions. Furthermore, some of these derivatives have been reported to exhibit significant biological activities and great interest has arisen in the design and synthesis of new pyridazinone to explore their pharmacological activities. The pyridazine fused with other ring nucleus, which has a useful structure for further molecular exploration for the development of new derivatives with different biological activities, has received much attention in recent years. Several synthetic strategies have been reported for the preparation of pyridazinone derivatives by di-ketoacids with hydrazine or hydrazine derivatives. Most of these are based on modification of the classical reaction and in some cases on more complex multi-step processes, which may involve the use of some expensive and commercially non-available materials. [19],[20] Owing to the versatility of pyridazine and as a continuation of our previous work, we have extended the convenient reaction to include some pyridazinone derivatives containing a fused nucleus.


   Conclusions Top


In continuation to our work as such derivatives, the title compound was synthesized as shown in scheme-I by following sequence of reactions: Friedel craft acylation of biphenyl with succinic anhydride in the presence of anhydrous aluminium chloride yielded phenyl-benzoyl propionic acid, (I) cyclization of phenyl-benzoyl propionic acid to react with hydrazine hydrate to form 6-(biphenyl-4-yl)4,5-dihydropyridazin-3(2H)-one, (II) synthesis of 6-(biphenyl-4-yl)-2-(1H-indol-1-ylmethyl)-4,5-dihydropyridazin-3(2H)-one (III) has not been prepared by both the methods. Recently, much attention has been focused on pyridazine derivatives for their broad-spectrum activities. Pyridazines and their derivatives have been reported having various pharmacological activities.


   Acknowledgment Top


The authors are thankful to GRD (PG) Institute of Management and Technology, Dehradun, India and to SAIF, CDRI, Lucknow, India for providing financial as well as technical support and facilities to carry out this work.

 
   References Top

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