Practice school 7th sem

Chapter-1
Introduction
Drug discovery:
Augusta Laurent discovered Benzil, an aromatic organic compound, in the 19th
century. Laurent was a prominent chemist who also synthesized other aromatic compounds,
including anthracene, Table of contents phenanthrene, and phthalic acid. His theories on
radicals and equivalents helped establish the modern approach to organic chemistry. Benzil
is also involved in the benzoic acid rearrangement, an organic reaction that was first
described by Justus von Liebig in 1828. In this reaction, Benzil is treated with hydroxide and
then acid to produce benzilic acid. The benzilic acid rearrangement is a classic reaction in
organic synthesis and is considered the first reported rearrangement reaction.

Benzil

Benzil is an important organic intermediate and organic chemical raw material. It is

synthesized by oxidation of benzoin and widely used in food, medicine, pesticide and other
industries.
There are two methods for synthesizing Benzil by oxidation of benzoin: One is non- There
catalytic oxidation The Benzil is prepared by oxidizing benzoin with an inorganic
compound, or an oregano metallic compound, or a polymer, but there are problems such as
large requirement of oxidant, intense reaction, large amount of by products ,serious pollution
and so on. [1]

Benzil-1, 2-diphenylethane-1,2-dione(C6H5CO)2) is an organic compound consisting of two

phenyl rings, and C-O groups are used as photoinitiators as well as free radicals in polymer
chemistry. Benzil has potential applications in biological metabolism and clinical medicine.
Benzil derivatives exhibit radical scavenging and antibacterial and hypertensive antiprotozoal
[2]
True computational prediction of material properties before experimentation is needed for
finding the new materials for its application. Theoretical computational studies enable us to
go well beyond what is known experimentally and can guide future experimentation. In
continuation of research on Benzil derivatives by the researchers, in this report, we
synthesized that Benzil (1,2-diphenylethane-1,2-dione), the structure, and vibrational
spectrum are reported theoretically by density functional theory. In addition to the above

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studies, other properties like NBO, NLO, and HOMO-LUMO have also been carried out and
explained in this communication.

The design and synthesis of dissymmetric double-Schiff-base ligands containing this TSC
moiety has started during the last decade, but only a short number of research groups in the
world have developed efficient strategies. The accessibility of such asymmetric ligands is
often hampered by several synthetic problems, which is the reason why this field is not much
developed. The problems found in the synthesis include ring-closure reactions or the
obtaining of the corresponding symmetric ligands, as well as ligand mixtures that are very
difficult to purify [18]

Reported that Benzil was prepared from benzoin with ethyl acetate used as solvent, 40%
trichloro is ocyanuric acid (TCCA) as oxidant, the reaction time was as long as 24 h at room
temperature, and the consumption of oxidant was greater.
Other is catalytic oxidation of Benzil by using high efficiency catalyst and molecular oxygen
or air as oxidant. This method has the advantages of low environmental pollution and
conforms to the new concept of green chemistry and clean production. Solvent, 40 mole %
Bi(NO3)2 and 4 mol% Cu(Ac) as catalyst, the only reaction could The be carried out for only
3 h, the reaction condition were 3 h, the reaction conditions were mild and the preparation of
catalyst was simple, but it raised the cost due to large Bi(NO3)2 catalyst dosage.[3]

Reported that air as oxidant, toluene as solvent, Pd/SiO2 as a catalyst to oxidize benzoin to
benzil at 100°C, the reaction only needs 0.75 h, the reaction time was short, but the catalyst
was expensive and the reaction cost was high, which is not conducive to the industrial
production.
There are also studies that combine the use of catalyst and an oxidant. Use dmanganese (II)
Schiff base complexes as catalyst in the presence of acetonitrile as solvent andH2O2 as
oxidant, [4], [5]

Medicinal chemistry:
Benzil (C₁₄H₁₀O₂) is an organic compound classified as a 1, 2-diketone. It is a yellow
crystalline solid, notable for its symmetric structure and high reactivity due to the carbonyl
groups. While benzil itself has limited direct medicinal use, it plays an important role in
medicinal chemistry as a precursor and intermediate in drug development and pharmaceutical

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research. Benzil serves as a crucial synthetic intermediate in medicinal chemistry. Its ability
to participate in diverse chemical reactions makes it essential for the synthesis of various
heterocyclic compounds, metal complexes, and bioactive molecules. Although it is not
directly used as a drug, its derivatives play key roles in the development of pharmaceuticals.
Synonyms:

1. Diphneylethanedione
2. Benzophenone diketone
3. 1,2 diphenylethane- 1,2-dione

IUPAC name: 1,2 diphenylethane- 1,2- dione

Pharmacodynamics:

Benzil is a potent inhibitor of human carboxylesterases, enzymes involved in the hydrolysis

of carboxylesters and many clinically used drugs.

Pharmacokinetics:

1. Absorption: If ingested or absorbed, Benzil could enter the bloodstream, depending on its
solubility in lipids in water.

3. Metabolism: Benzil or its reduced metabolite benzoin can under conjugation with
glucuronic acid or sulfate by UDP- glucuronsytransferases.

2. Protein binding: a common binding protein for many small molecules, Benzil may bind
to albumin in blood due to its hydrophobic and polar characteristics.

4. Route of administration:

 Oral administration: it may have good availability in non-ionized form but could be
subject to first-pass metabolism.

5. Toxicity: Benzil is a toxic chemical that can cause skin, eye, and respiratory

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Adverse reaction: skin irritation, redness, dermatitis, eye irritation, respiratory irritation, and
coughing, short throat, short of breathing in case of high exposure, gastrointestinal irritation,
nausea, vomiting, and hypersensitivity reaction.
6. Use:

 It is used to treat high blood pressure (hypertension).

 Benzil is used as a pharmaceutical intermediate and UV curing resin photosensitizer.
 Benzil is used as a building block for the synthesis of heterocyclic, which have
biological and therapeutic applications

Fig .1 structure of Benzil

parameters Description
Molecular formula (C6H5CO)2
Molecular weight 210.23g.ml
Color Yellow crystalline powder
Odor Characteristics
Melting point 96°C
Boiling point 345°c
Density 1.23g/cm
Solubility Soluble in benzene, ethanol Insoluble in water, methanol

Table no.-1

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Chepter-2

Review of literature

Previous study:

1. Peter J. Michael. (2023) Reported an unexpected direct synthesis of tunable redox –

active Benzil- linked polymers via the benzoin reaction, polymerization of simple dialdehyde
monomers under air- free condition leads directly to insoluble redox- active 1, 2- dione –
linked polymers, eliminating the need for external oxidant. The resulting polymers exhibit
tunable redox properties making them promising material for application in energy storage
and catalysis. Their work contributes significantly to the field of organic material chemistry,
particularly in developing sustainable method for creating redox – active polymers.

2. Patil. L et al., (2013) Published research on the application of Benzil in various organic
reactions, including its role as a precursor in the synthesis of other organic compounds. Most
Benzil is use is as a photoinitiator in polymer chemistry. Its most Benzil is used in the free
radicle curing of polymer networks. Ultraviolet radiation decompose Benzil, generating free
radical species with in the material, promoting the formation cross – links. Benzil is a potent
inhibitor of human carboxylestereses, enzymes involved.

3. Hosseini N.S et al., (2011): Published research on the application of Benzil in various
organic reactions, including its role as a precursor in the synthesis of other organic

compounds. Benzil is simplest aromatic diketones. It is an alpha- diketone imparts a caramel

like a or butter flavor. Dieketone compound take a role in creating various fragrances. Benzil
is used as a precursor to the battle field chemical weapon the anticholinergic deliriant.

4. Jadhav S.S et al., (2008): Studied the synthesis of Benzil derivatives for pharmaceutical
applications. They explored the reactions of Benzil with different reagents to obtain
compounds with potential biological activity has been reported to inhibit bacterial and fungal
growth. They interfere with microbial cell membrane protein function. Some Benzil – based
compound exhibit cytotoxic effects on cancer cell.

5. Banfi M.A et al., (2004): Studied the synthesis of Benzil derivatives for pharmaceutical
applications. They explored the reactions of Benzil with different reagents to obtain

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compounds with potential biological activity. Some Benzil derivatives show anti-oxidants
properties. Which is linked to diabetic complications?

6. Murayama R (2001)- These colleagues isolate and expressed a bacillus cereus gene
encoding benzil reductase, shedding light on the enzymatic reduction of Benzil, these studies
have explored various aspects of benzil, including its synthesis, structural properties, and
application. .

7. David W. C. Macmillan (2000) This experiment provides student with an opportunity to

learn about oxidation reaction the chemistry of carbonyl compounds, and importance of
purification techniques in organic synthesis. While not focused exclusively on benzil, his
work on organ catalysis and diketones highlights methods for synthesizing derivatives of
benzil and exploring its reactivity in asymmetric catalysis.
8. James R. Bolton (1980) The synthesis of Benzil from benzoin from benzoin is a classic
organic chemistry experiment that involves the oxidation of secondary alcohol to a ketone
using an oxidizing agent , Investigated benzil as a model compound in organic
photochemistry to study triplet states and electron transfer mechanisms
9. Biological studies-
Antibacterial and Antifungal Properties: Recent studies have demonstrated benzil's potential
as a scaffold for designing antimicrobial agents (Kumar et al., 2019).Enzyme Inhibition:
Benzil derivatives have shown inhibitory effects on enzymes like tyrosine, making them
potential leads in pharmaceutical research

10. Physical properties-

Benzil is a key molecule in photochemistry due to its fluorescence and phosphorescence.

Research by Phillips et al. (2001) examined its excited-state behavior and applications in
optical materials.

11. Application:

 Photo initiator- benzil is used in photochemical reactions as a photo initiator due to its
ability to absorb UV light as a generate free radicals.

 Organic synthesis: it serves as a precursor in synthesizing heterocyclic compound

such as benzilic acid.

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 Polymer chemistry: benzil derivatives are employed in the preparation of resins and
polymers with specific photochemical properties

 Fluorescence: its diketoe structure contributes to fluorescence application,

12. Reaction and mechanism:

 Benzilic acid rearrangement: benzil reacts with strong basses to from benzilic acid
through a rearrangement mechanism involving nucleophilic attack on the diketone
group.

Mechanism:

13. Biological activity:

 Antimicrobial: some derivatives show activity against bacterial and fungal pathogens.

 Anticancer: modification to benzil structure has resulted in compound with cytotoxic

effect on cancer cells.

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 Antioxidant: exhibit free radicals scavenging activity contributing to its potential in

drug design.

Apparatus: round bottom flask, reflex condenser, heating mental, beaker, dropper,

Buchner funnel, filter paper, vacuum pump, spatula, glass rod, thermometer, water bath.

Chemical: benzoic, conc. Nitric acid, ethanol, sodium hydroxide solution, water

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Chapter-3

Aim & object

Aim: The main aim of present work is to synthesis and chemical evaluation of
pharmaceutical use of Benzil.

Objective:

The main objectives of the present study are:

 To synthesize benzil by using benzoin and nitric acid.

 To calculate the percentage content of Benzil.
 To evaluate of chemical parameter synthesis of Benzil.

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Chapter -4

Plan of work

1.Literature srevay.

2.Collection of material

3.synthesizing benzil.

4. physical and chemical evaluation of synthesis benzil

5.pharmaceutical use

6. praparaing in project report .

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Methodology

sources of material

Synthesis of benzil :

Benzil is synthesized from benzoin through an oxidation reaction that converts the secondary
alcohol in benzoin into a ketone. The reaction is typically carried out in a solvent, such as
methanol or ethanol, and the product is isolated by recrystallization.

Reaction to benzoin from benzil

Procedure :
Dissolve 5g of benzoin in 30ml of concentrated nitric acid. Heat the mixture gently on a
water bath for about 15min. until a yellow precipitate of benzil is formed. Cool the mixture in
an ice bath to promote crystallization. Filter the precipitate using a Buchner funnel and
vacuum filtration. Wash the crystals with distilled water to remove any remaining traces of
acid. Wash the crystals with a solution of sodium bicarbonate to neutralize any residual nitric
acid. Recrystallize the Benzil by dissolving it in hot ethanol and allowing it to cool slowly.
Collect the crystals by vacuum filtration, and try them in a dedicator

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Chemcal evaluation:

Melting point:

Method of preparation melting point:

Materials Needed:

1. Melting point apparatus ( Thiele tube or digital melting point apparatus).

2. Capillary tubes (sealed on one end).

3. Sample to be tested (dry and pure).

4. Thermometer (if using a manual setup).

Procedure:

1. Prepare the Sample

 Finely crush the solid sample using a mortar and pestle to ensure uniformity.
 Pack a small amount of the sample into a capillary tube.
 Tap the closed end of the tube on a hard surface to compact the sample into a 2-3 mm
layer.

2. Set UP the Apparatus

If using a Thiele tube:

Fill the tube with oil and attach the thermometer.

3. Heat the Sample

Start heating slowly, especially near the expected melting point.

Observe the sample closely through the apparatus window or magnifying lens.

4. Record the Melting Point

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The melting point of benzil is 94-95°C. It’s important to note that melting point of a
compound can vary depending on factors such as sample purity and method of determination,

so slight variations in reported values may exist in the literature.

Boiling point:

Method of boiling point:

Apparatus and material needed:

 Liquid sample (water, organic solvent)

 Thermometer (calibrated digital or mercury thermometer)
 Boiling flask or beaker
 Heat source ( Bunsen burner, heating mantle, or water bath)
 Barometer (to measure atmospheric pressure)
 Condenser (if using a distillation setup)
 Stirring rod
 Stopwatch ( for recording boiling time)

Procedure:

Method 1: Simple Boiling Point Determination (Without Distillation Setup)

1. Preparation of Sample:

 Ensure that the liquid you want to measure is pure and free from contaminants.
 Pour the liquid into a clean, dry boiling flask or beaker. If you are working with a
volatile substance, use an appropriate vessel that won’t evaporate too quickly.

2. Setup of Equipment:

 If you are using a boiling flask, attach a thermometer to the flask so that its bulb is
immersed in the liquid but not touching the sides of the flask.

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 Position the boiling flask over a heat source like a Bunsen burner or a heating mantle.
Alternatively, you can use a water bath to provide indirect heating.

3. Heating the Sample:

 Slowly heat the liquid, making sure to observe the temperature rise on the thermometer.
 Stir the liquid gently with a stirring rod to ensure even heating.
 As the temperature approaches the expected boiling point, the liquid will start to form
bubbles at the bottom of the flask. Continue to heat carefully.

4. Observation of Boiling:

 The liquid reaches its boiling point, you will observe the formation of bubbles
throughout the liquid. This indicates that the liquid is boiling.
 Record the temperature at which the first bubble appears and the temperature at which
the liquid is consistently boiling.

5. Verification of Boiling Point:

 Ensure that the temperature remains stable and the liquid is at a rolling boil (bubbles
formed continuously).
 If necessary, adjust the heating rate to avoid superheating (where the liquid is heated
above its boiling point without boiling).

6. Calculation :

The boiling point of Benzil, which is diketone compound with the chemical formula
C14H10O2, is 344-345°C at standard pressure of atmosphere

Solubility:

Hand shaking method of solubility:

The hand-shaking solubility method is a straightforward procedure used to determine the

solubility of a substance in a particular solvent. It is commonly employed in laboratory
settings to assess how much of a solid can dissolve in a liquid under normal conditions. This

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method is based on simple mixing and observation and is typically used for substances that
dissolve in the solvent at room temperature.

Apparatus and Materials Needed:

 Solid sample (the solute)

 Solubility:
Solubility the of Benzil varies depending on the solvent used. In general, it is sparingly
soluble in water, but solution in many organic solvents such as ethanol, acetone, and
chloroform. According to the Merck Index, the solubility of benzil in water at 20°C is
approximately 0.2g/100mL. However, the actual solubility of benzil in water may vary
depending on factors such as temperature
The solubility of Benzil in binary alcohol + 1-octanol solvents is listed in a table in a
scientific article.

Pharmaceutical use:

Benzil is used as a pharmaceutical intermediate and UV curing resin photosensitizer. In

polymer chemistry, it is used as a photoinitiator. Further, it serves as a potent inhibitor of
human carboxylesterases. Benzil is used as a building block for the synthesis of heterocyclic,
which have biological and therapeutic applications. Benzil is used as a reagent in the benzilic
acid rearrangement and in the preparation of diketimines by reacting with amines. Benzil and
its derivatives are used as fluorescence probes.

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Chapter- 5
Result & discussion

Identification Colour:
Test:
Benzil is a yellow crystalline solid at a room temperature. When dissolved in certain solvents
or subjects to certain reactions, it can exhibit a range of colors including yellow, orange, red
and even green. However, its typical color is yellow
Odor: Benzil is a white crystalline solid with a mild, pleasant odor. However, the exact odor
of Benzil can vary depending on factors such as the purity of the compound, the
concentration of the sample, and the individual’s sense of smell.

Powder of Benzil

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Mixture benzoin and nitric acid

Cool the mixture in ice bath

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Filtration of mixture

Conclusion

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The Benzil was synthesized in high yield by the procedure. The product was successfully
characterized by melting point, the reaction proceeds via a series of intermediate steps,
ultimately resulting in the formation of benzil. The yield of the reaction is influenced by
several factors, including the concentration of the reactants, the temperature and reaction
time. The synthesis of benzil from benzoin is a useful and straightforward method for.

Reference

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[1]. Zhang, S. S. (2005). Synthesis of benzil from benzoin: an inquiry- based experiment. Journal of
Chemistry Education, 82(12), 1819.

[2]. Organic Chemistry, 7th Edition by Francis A. Carey and Robert M. Giuliani(ISBN:978-
0077832783)- chapter 22, page 886-814
[3]. Vogel’s Textbook of practical Organic Chemistry, 5th Edition, Pg. 813-814.
[4]. Vogel’s Textbook of practical Organic Chemistry by Brian S. Furniss, Antony J. Hannaford,
Peter W.
[5]. Practical in Organic Chemistry, by Hitesh G. Raval, Sunil L. Baldanis and Dimal A. Shah,
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[6]. Organic Chemistry, 2nd Edition, Jonathan Clayden, Pg. 809-810.
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[8]. McGraw-Hill Dictionary of scientific and Technical Terms, 6E, Copyright 2003 by The
McGraw-Hill
[9] Ippolite, A.S. Kersey, K.R., Salazar, A. R., Tran, L. N., and Cason, R. L. (2011). Characterization
of benzil by NMR spectroscopy and DFT. Journal of Molecular Structure,992, 112-118.
[10] [20]. Organic Chemistry by Jonathan Clayden, Nick Greeves and Stuart Warren. Chapter 31 of
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[12] Maurya MR, Agarwal S, Bader C, Ebel M, Rehder D. Synthesis, characterisation and
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[13] Vollhardt KPC, Schore NE. Organic Chemistry. New York: 2nd ed, Freeman; 1994. pp.
924–929.
[14] Mallat T, Biker A. Oxidation of alcohols with molecular oxygen on solid catalysts.
Chem Rev. 2004; 104:3037–3058.
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