Synthesis and Evaluation of Hydrazones

Hydrazones are a class of organic compounds with the structure R1R2C=NNH2. They are related to ketones and aldehydes by the replacement of the oxygen with the NNH2 functional group. They are formed usually by the action of hydrazine on ketones or aldehydes.

HYDRAZONES:

Hydrazones are a class of organic compounds with the structure R1R2C=NNH2. They are related to ketones and aldehydes by the replacement of the oxygen with the NNH2 functional group. They are formed usually by the action of hydrazine on ketones or aldehydes.

Structure of the hydrazone functional group

Hydrazones has shown that they possess a wide variety of biological activities viz. antimicrobial, anticonvulsant, antidepressant, anti inflammatory, analgesic, antiplatelet, antimalarial, anticancer, antifungal, antitubercular, antiviral, cardio protective.

CHAPTER-2

AIM

AND

OBJECTIVES

AIM AND OBJECTIVES

To select a topic for the research work from the current problems prevailing in the society.

To collect the multidimensional information in depth about each subtopic involved in the area of research work from different sources.

To plan, acquire execute, evaluate and record the different subtopics of the topic research work in scientific manner.

To work collaboratively in harmonial way with other disciplines of sciences for ensuring the successful completion of research work.

To synthesize crude and recrystallized samples of the compounds by conventional, nonconventional methods.

To purify the compounds by different purification techniques.

To characterize the pure compounds by physical methods and spectral methods.

CHAPTER-3

LITERATURE

SURVEY

LITERATURE SURVEY

The literature survey was done using search engines like Google, Yahoo, Chemfinder and science Finder along with textbooks, reference books compendia, and journals. Science Finder search includes search of the chemical abstract(CA), chemical abstract plus(CA PLUS)and MEDLINE. The search was done using the keywords like esters, hydrazides,hydrazones etc. The outcome of the survey is presented below.

SYNTHETIC REVIEW:

Reaction Schemes:

Synthesis of new hydrazone derivatives and evaluation of their monoamine oxidase inhibitory activity.

Facile and straightforward synthesis of Hydrazone derivatives

Synthesis and biological evaluation of some hydrazone derivatives as new anticandidal and anticancer agents.

Effective methods for the synthesis of hydrazones, quinazolines, and Schiff bases: reaction monitoring using a chemometric approach.

Microwave-Assisted One-Step Synthesis of Fenamic acid Hydrazides from the Corresponding Acids.

A New Procedure for Preparation ofCarboxylic Acid Hydrazides.

Synthesis and Antitumor Evaluation ofMenthone-Derived Pyrimidine-Urea Compounds as Potential PI3K/Akt/mTOR Signaling Pathway Inhibitor.

Preparation Of Hydrazones: Acetophenone Hydrazone

Biological Activity Review:

Hydrazones as Antibacterial agent

Lee et al. synthesized various hydrazones (1,2) as selective inhibitors of staphylococcus aureus β-ketoacyl carrier protein III. 

Hydrazones as Antifungal agent

Hydrazone derivativessynthesized by Ozdemir et al. (2010) after being screened against different Candida spp have been reported to have promising antifungal potential.

Chapter – 4

Materials and Methods

Apparatus:

Reflux condenser 

Bunsen burner 

Tripod stand 

Water bath 

Magnetic stirrer

Hotplate

Ice bath

Beakers 

Round bottom flask 

Separating funnel 

Glass rods 

Spatulas 

Sample bottles 

Thermometers

Capillary tube

Condenser pipes etc

CHEMICALS:

Sodium/potassium dichromate

Concentrated sulphuric acid

Menthol

Ester 

Sodium hydroxide

PABA

Ether 

Ethanol

5% sodium bicarbonate

Hydrazine hydrate

Methanol

Glacial acetic acid

Distilled water

Chloroform

Methyl salicylate

Recrystallizing solvents

Principle:

The scheme involves 2 steps

Step 1 involvescondensation of l-menthone with benzoylhydrazides in the presence of glacial acetic acid.

Step 2 involves reaction between 4-aminobenzohydrazide and l-menthone.

REACTION PROCEDURE:

STEP 1: Synthesis of l-menthone from menthol

SYNTHESIS: 

In a 1-litre round-bottomed flask provided with a mechanical stirrer is placed 120 g (0.4 mole) of crystallized sodium dichromate (or an equivalent amount of potassium dichromate), and to this is added a solution of 100 g(54.3 cc., 0.97 mole) of concentrated sulfuric acid (sp. gr. 1.84) in 600 ml of water. To this mixture 90 g. (0.58 mole) of menthol (crystals, m.p. 41–42°) is added in three or four portions and the mixture stirred. Heat is evolved, and the temperature of the mixture rises to about 55°. As soon as the reaction is complete the temperature falls. The oil is mixed with an equal volume of ether, separated in a separatory funnel, and washed with three 200-ml. portions of 5 % sodium hydroxide solution. The ether is then removed by distillation and the residue distilled under reduced pressure, the menthone being collected at 98–100°/18 mm. If distilled under atmospheric pressure it boils at 204–207°c. The yield is 74–76 g. (83–85 percent of the theoretical amount).

STEP 2: Synthesis of benzoyl hydrazides 

SYNTHESIS:

Place 10 ml of hydrazine hydrate (caution:- corrosive chemical) in a test tube fitted with a short reflux condenser. Add 15ml of methyl salicylate dropwise and heat the mixture gently under reflux for 15mins. Then add just enough methanol through the condenser to produce a clear solution, reflux for further 6 hours, and cool. Filter off the solid of the benzoyl hydrazides.

                                                                 STEP 3: Synthesis of Hydrazones from l-menthone and Benzoyl hydrazide

 SYNTHESIS:

To solution of l-menthone (1.0g, 6.5mmol) in methanol (25ml), the equimolar amount (6.5mmol) of appropriate benzoyl hydrazide and 2 drops of glacial acetic acid were added. The reaction mixture was refluxed for 4hrs, cooled and then was poured into the ice. The solid mass was filtered, dried &purified by recrystallisation from methanol: water (1:1) system.

STEP 4: Synthesis of hydrazide from acid ester

SYNTHESIS:

A mixture of acid ester and an excess of hydrazine hydrate were refluxed for about 16 hrs and cooled. The solid was separated by filtration, dried and recrystallized from ethanol to afford hydrazides were characterized on the basis of physical and spectral data. The purity was checked by single spot TLC.

esisofHydrazones from l-menthone and4-aminobenzohydrazide

SYNTHESIS:

To solution of l-menthone (1.0g,6.5mmol) in methanol (25ml), the equimolar amount (6.5mmol) of appropriate 4-aminobenzohydrazide and 2 drops of glacial acetic acid were added. The reaction mixture was refluxed for 4hrs, cooled and then was poured into the ice. The solid mass filtered, dried and purified by recrystallisation from methanol: water (1:1) system.

CHAPTER 5

RESULTS AND DISCUSSION

Compound profile 

Structure:

IUPAC name:

Molecular formula:

Molecular weight:

Theoretical yield:

Practical yield:

Percentage yield:

Compound profile 

Structure:

IUPAC name:

Molecular formula:

Molecular weight:

Theoretical yield: 

Practical yield:

Percentage yield:

1. TABLE OF CHARACTERIZATION:

COMPOUND NAME                         

MOLECULAR WEIGHT                                         

PHYSICAL STATE                            

COLOR                             

PHYSICAL CONSTANT                                         

RECRYSTALLIZING 

SOLVENT                                              

ELUENT                         

Rf                                        

REFERNCES

[1]M. Moriya (1881). "Contributions from the Laboratory of the University of Tôkiô, Japan. No. IV. On menthol or peppermint camphor". Journal of the Chemical Society, Transactions. 39: 77–83. doi:10.1039/CT8813900077

[2] John Read (1930). "Recent Progress in the Menthone Chemistry". Chemical Reviews. 7 (1): 1–50. doi:10.1021/cr60025a001

[3] Singh, G. (2007). Chemistry of Terpenoids and Carotenoids. Discovery Publishing House. p. 41. ISBN 9788183562799.

[4] ErnstBeckmann (1889). "Untersuchungen in der Campherreihe". LiebigsAnnalen. 250 (3): 322–375. doi:10.1002/jlac.18892500306

[5] Review Article REVIEW OF BIOLOGICAL ACTIVITIES OF HYDRAZONES Volume 23 Issue 4 (2012) 193 Indonesian J. Pharm. Vol. 23 No. 4: 193 – 202 ISSN-p: 0126-1037 

[6] Synthesis of new hydrazone derivatives and evaluation of their monoamine 

oxidase inhibitory activity https://doi.org/10.1016/j.bioorg.2021.105038 Received 6 April 2021; Received in revised form 10 May 2021; Accepted 28 May 2021 Available online 1 June 2021

[7] Facile and straightforward synthesis of Hydrazone derivatives Volume 2022, Article ID 3945810, 6 pages https://doi.org/10.1155/2022/3945810

[8] Synthesis and biological evaluation of some hydrazone derivatives as new

anticandidal and anticancer agents Article history: Received 30 July 2012, Received in revised form 5 October 2012, Accepted 8 October 2012,Available online 16 October 2012