Synthesis of Bromo Acid by Solvent and CatalystFree Reaction

Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Synthesis of Bromo Acid by Solvent and Catalyst-

Free Reaction
Professor Shrikant Boharupi1,
1
Department of Pharmaceutical Chemistry
Sayali Tejam2,
Pratiksha Thakur2,
Sejal Patil2,
Purvaja Choudhary2,
Ashish Tiwari2,
2
NCRD’s Sterling Institute of Pharmacy, Sector-10, Nerul (E), Seawoods, Navi Mumbai, Maharashtra 40070
Abstract:- Chemistry is an extremely significant field of  Objectives:

study. In the pharmaceutical industry chemistry plays an The main objectives of our research project are:
important role in formulating the drug. Nowadays ,
when a drug is to be synthesized everyone is looking  To design a catalyst-free and solvent-free system to
towards the simple and non-tedious chemical reaction synthesize 3-bromo benzoic acid
which can be done by using less use of materials, In the  To implement and promote green chemistry
past decades, the approach of making organic reactions  To find out the novelty of the synthesized method
sustainable and innovative , various new methodologies  To understand the chemistry of the desired product
by making it solvents or catalysts-free and applying  Selection of the correct reaction method by trial-and-
alternative energy sources such as microwaves, error systems
sonication, conventional and room temperature heating
conditions, mechanochemical mixing, and high-speed  Catalyst Free Organic Synthesis:
ball milling are becoming popular. All are approaching Catalysts usually promote faster chemical reactions
towards the Green Chemistry method which provides and for some reactions the desired selectivity
“Green” paths for different synthetic routes using non- (regioselectivity or chemo selectivity) can be obtained using
hazardous solvents and environmental- friendly specific selective sites of them. Conventional
chemicals. By application of this approach the synthesis catalysts/additives are usually associated with higher costs,
of bromo acids has been done using the sonication toxicity, and non-reusability and thereby generating more
process. wastes. From the green chemistry perspectives, significant
efforts have been made to improve overall applicability of
Keywords: Bromo Acid, Sonication, Green Chemistry, IR catalytic substances from suitable modifications and/or
Spectroscopy. innovation of new kinds of catalysts with multiple benefits.
However, the most useful way for designing an organic
I. INTRODUCTION reaction protocol without the aid of a catalyst. Catalyst-free
synthetic processes provide benefits to get rid of toxicity and
A solvent-free reaction may be carried out by using the wastes related with using these catalysts. Hence, designing
reactants alone or incorporating them with other safe of catalyst-free synthetic processes to improvise toward safe,
catalyst to attain high degree of stereoselectivity in the cost-effective, waste-free, simple, and sustainable
product, to reduce the by-product and to maximize the rate environment. It is often observed that suitably selected
of reaction. Solvent-less technology has many advantages starting materials can undergo self-catalysis in suitable
from the viewpoint of both academy and industry. Two of solvents (preferably in aqueous or aqueous ethanolic
twelve principles of “Green Chemistry” are “use of safer medium) in many conditions and/or the solvents can also
solvent and reactions condition” and to “prevent waste” and yield catalytic benefits to certain reaction processes from
both these principles are directly met by eliminating a their unique inherent properties. Reactions can also be
reaction medium. Solvent-free and/or solvent-less protocol promoted by using simple conventional heating in the
is frequently exhibiting remarkable rate of acceleration due presence or absence of solvent(s), and by the applications of
to the increased reaction conditions with some of them microwave irradiation, ultrasound irradiation and
occurring under ambient situation i.e., at room temperature, mechanochemical mixings.
microwave irradiation, ball milling etc.
 Solvent Free Organic Synthesis:
Solvent-free synthesis is an alternative method to
traditional solution-based synthesis. Solvent-free synthesis
has various advantages over the traditional method of
IJISRT23APR653 www.ijisrt.com 599

ISSN No:-2456-2165
synthesis and that it is a type of green chemistry where little Sonication chemistry enhances or promotes chemical
or no solvents are used and environmentally friendly reactions and mass transfer and offers the advantage for
chemicals are used. The advantages of solvent-free reactions shorter reaction cycles, cheaper reagents, and less physical
are: conditions. Existing literature on sonication chemical
reacting systems is chemistry-intensive. Applications of this
 Economic (cost saving, save money on solvent) novel method provides a means of reaction in
 Not necessary to collect, purify, recycle, and remove environmentally friendly and pollution prevention which
solvent after completion of reaction. seem almost unlimited and is rapidly growing area.
 Due to more availability of reactants, the reaction rate is
generally high.  Experimental Details:
 Environmentally friendly
 Decreased of energy consumption  Requirements: Conical flask, Glass rod, Spatula, Beaker,
 Large reduction in batch size volume (reactor size) and Butter paper, Weighing machine, funnel, Whatmann
capital investment. filter paper, Sonicator
 Chemicals: Benzoic acid LR, Benzoic acid extra pure,
 Sonicator: Bromine liquid, KBrO3, Acetic acid, Ethanol, NaOH,
Sonication is the process of applying sound energy to conc. HNO3, AgNO3 solution, Na metal
agitate particles in a liquid. Ultrasonic frequencies greater
than 20 kHz is used; therefore the process is also known as II. PRINCIPLE
ultrasonication. Sonication can be done using either an
ultrasonic bath or an ultrasonic probe (sonicator) which The reaction of benzoic acid to m-bromobenzoic acid/
converts an electrical signal into a physical vibration to 3-bromo benzoic acid occurs through electrophilic
break substances apart. This interference can mix solutions, substitution reaction means the replacement of any of the
accelerate the dissolution of a solid into a liquid, such as atoms of a parent compound by an electrophile.
sugar into water, and remove dissolved gas from liquids. Electrophiles are electron loving species i.e.; they always
attack at the region of maximum electron density. If we
 Sonication Process: draw the structure of benzoic acid, we will find that the pi
During sonication, cycles of pressure form thousands electrons of carbonyl group of COOH is in conjugation
of microscopic vacuum bubbles in the solution. The bubbles (alternate single and double bonds) with the pi electrons of
collapse into the solution in a process known as cavitation. the benzene ring. As a result, the pi electrons are delocalized
This causes powerful waves of vibration that release an (they move from their original positions) resulting into a
extensive energy force in the cavitation field, which disrupts number of structures which are in equilibrium with each
molecular interactions such as interactions between other. In each of these structures, either the ortho carbon or
molecules of water, separates clumps of particles, and the para carbon acquires a positive charge. It is only the
facilitates mixing. The energy from sound waves creates meta carbon that does not acquire positive charge. That is,
resistance in the solution, which creates heat. To stop a electron density always remains maximum at the meta
sample from heating up and degrading, keep it on ice before, position. So, it is quite natural that electrophile will always
during and after sonication. attack at the meta position. Therefore, electrophilic
substitution in benzoic acid always occurs at the meta
position.
Fig 1 Sonication Process
 Green Aspects of Sonication Process:

Ultrasound- Assisted organic synthesis is applied in  General Reaction of Converting α- Carboxylic Acid to
many organic synthetic routes with advantages such as- Bromo Derivative
 High efficiency  Hell-Volhard-Zelinsky Reaction:

 Low waste Treatment of carboxylic acid with bromine and a
 Low energy requirements catalytic amount of phosphorus leads to the selective α-
 Ability to disperse reagent in small particles and bromination.
accelerate reactions

ISSN No:-2456-2165
 Synthesis of m-bromo benzoic acid/ 3-bromo benzoic
acid takes place by reaction benzoic acid with Br2 and
FeBr3 as a catalyst.
 As discuss earlier, the substitution of bromine at the
meta position occurs via electrophilic reaction.
 The role of FeBr3 is to give the meta substituted bromo
benzoic acid.
 Mechanism of the Hell-Volhard-Zelinsky Reaction:
Phosphorus reacts with bromine to give phosphorus  Hazards of Bromine use:
tribromide, and this converts the carboxylic acid into an acyl  May be harmful if swallowed.
bromide.  Causes severe skin burns and eye damage.
 Fatal if inhaled.
 Precaution Taken During Handling of Bromine:

 Do not breathe fume/gas/mist/vapours/spray.
 Avoid release to the environment.
 Wear protective gloves/protective clothing/eye
protection/face protection.
 Wear respiratory protection.
An acyl bromide can readily exist in the enol form, and
this tautomer is rapidly brominated at the α-carbon. The  Scheme 1:
mono brominated compound is much less nucleophilic, so 1.5 gm of Benzoic Acid LR + 5 ml of Bromine was
the reaction stops at this stage. This acyl intermediate taken in a beaker and the reaction was carried out in an open
compound can undergo bromide exchange with unreacted system. The beaker was placed in a Sonicator. Time Cycle
carboxylic acid via the anhydride, which allows the catalytic for the reaction to completion was 1 hr 20 min. At 30 min,
cycle to continue until the conversion is complete. white small crystals were started to form at inside the walls
of the beaker and water was added almost 2/4 th of the
beaker and heated for 15 min on Sonicator. After completion
of cycle, white solid crystals were formed and allowed to
settle down and filtered. Solid crystals were separated and
dried in hot air oven for 30 min at 80℃. Pale orange
coloured product was obtained. Qualitative tests were
performed on the crystals for detection of functional groups.
 General Reaction of Converting Benzoic Acid to 3-

Bromo Benzoic Acid:

ISSN No:-2456-2165
Table 1 Preliminary Tests and Physical Evaluation for Scheme 1
 Elemental Analysis:
It is a qualitative analysis of an unknown organic sample consists of detection of chemical composition i.e., Elements present
the organic sample. Carbon and hydrogen are main constituents. In addition to this samples contain sulphur, nitrogen, halogens
which can be detected by sodium fusion test, which is also known as Lessaignen’s test.
 Lessaignen’s Test:
In this test the elements in the organic sample are converted into ionizable inorganic substances so that ionic tests can be
done for their detection.
Table 2 Lessaignen’s Test

ISSN No:-2456-2165
 Detection of Functional Group:
Table 3 Tests for Carboxylic Groups
 Conclusion:
As the required elemental group i.e., Bromine is not detected from the performed tests, this scheme fails to give the bromo
derivative of benzoic acid.
 Scheme 2:
2 gm of Benzoic Acid + 5 ml of Bromine + 10 ml of ethanol in beaker was taken and placed on Sonicator. Time cycle
required for completion of reaction is 1 hr 10 min. As crystals were not seen in the beaker addition of 15ml of distilled water + 5
ml of ethanol was done to see whether the crystals are forming or not Again, placed on Sonicator for 30 min. No crystals were
obtained.
 Conclusion:
As not product was obtained, this scheme fails.
Fig 2 Scheme 2

ISSN No:-2456-2165
 Scheme 3:
1.5 gm of benzoic acid + 5 ml of bromine was taken in a conical flask and closed with the cotton plug to avoid escape of
bromine vapours. Conical flask was kept on Sonicator. Time cycle required for completion of reaction was 5 hr 30 min.
Intermittent shaking of flask was taken place during the process. After completion of process the product obtained was filtered and
separated. Solid crystals were separated and dried in hot air oven for 30 min at 80℃. Qualitative tests were performed on the
crystals for detection of functional groups.
 Lessaignen’s Test:
In this test the elements in the organic sample are converted into ionizable inorganic substances so that ionic tests can be
done for their detection.

ISSN No:-2456-2165
Table 5 Lessaignen’s Test
 Detection of Functional Group:
Table 6 Tests for Carboxylic Groups

ISSN No:-2456-2165
 Conclusion: series of absorptions, frequently overlapping each other,
From the above tests performed it is concluded that the mainly due to all kinds of bending or stretching vibrations.
groups required in the desired product is confirmed. So this In group frequency region, the peaks corresponding to
scheme passes for the bromo derivative of benzoic acid. different functional groups can be observed. According to
corresponding peaks, functional group can be determined.
For more conformation of product FTIR is done for the Each atom of the molecule is connected by bond and each
compound. bond requires different IR region so characteristic peaks are
observed. This region of IR spectrum is called as finger print
 Infrared Spectroscopy: region of the molecule. It can be determined by
Infrared spectroscopy is widely used in industry as characteristic peaks. Small differences in structure &
well as in research. IR is most useful in providing constitution of molecule can result in significant changes in
information about the presence or absence of specific the peaks in this region. Hence this region helps to identify
functional groups. Entire IR region is divided into group an unknown compound. The position and magnitudes of
frequency region and fingerprint region. Range of group peaks in the spectrum is compared with profiles of pure
frequency is 4000-1500 cm-1 while that of finger print compounds stored Identification is done based on position of
region is 1500-400 cm-1usually contains a very complicated absorption bands in the spectrum.
 FTIR Spectra:
Fig 3 FTIR Spectra
 IR Interpretation:
Fig 4 Spectrum Graph

ISSN No:-2456-2165
Table 7 IR Interpretation
From the above IR Spectrum graph, we have got the IR frequency of 705.52 cm-1 which is of Meta Disubstituted
Aromatic Compound.
By above IR interpretation data, it is now clear that the IR spectra of the groups containing in the product obtained is
confirm. Therefore, we concluded that the 3-bromo benzoic acid is obtained.
 Scheme 4:
10.6 ml of Acetic Acid + 4g of KBrO3 + 6 ml of Bromine was taken in a conical flask and closed with the cotton plug to
avoid escape of bromine vapours. This conical flask was placed on sonicator. Time cycle for completion of the reaction was 7 hrs
Intermittent shaking of flask was taken place during the process. After completion of process the product obtained was filtered and
separated. Solid crystals were separated and dried in hot air oven for 30 min at 80℃ Qualitative tests were performed on the
crystals for detection of functional groups.

ISSN No:-2456-2165
 Lessaigne’s Test:
Table 9 Lessaigne’s Test
 Conclusion:
As bromine is not confirm through this test, this scheme fails to give the desired Product.

ISSN No:-2456-2165
III. RESULT & DISCUSSION REFERENCES
From the 4 schemes performed, only 3rd scheme was [1]. Ouellette, Robert J. (2014). Organic Chemistry ||
successful for giving the desired product i.e., 3-bromo Electrophilic Aromatic Substitution., (), 417-451.
benzoic acid. After confirmation physical & chemical Available form: https://doi.org/10.1016/B978-0-12-
properties of 3- bromo benzoic acid was determined and 800780-8.00013-9
reported. [2]. Dagani MJ, Barda HJ, Benya TJ, Sanders DC.
Bromine compounds. Ullmann's encyclopedia of
 Compound: industrial chemistry. 2000 Jun 15. Available from:
https://onlinelibrary.wiley.com/doi/abs/10.1002/1435
6007.a04_405
[3]. Martínez RF, Cravotto G, Cintas P. Organic
Sonochemistry: A Chemist’s Timely Perspective on
Mechanisms and Reactivity. the Journal of Organic
Chemistry. 2021 Jun 22;86(20):13833-56. Available
from: https://dx.doi.org/10.1021%2Facs.joc.1c00805
[4]. Puri S, Kaur B, Parmar A, Kumar H. Applications of
ultrasound in organic synthesis-a green approach.
Current Organic Chemistry. 2013 Aug
1;17(16):1790-828. Available from:
http://dx.doi.org/10.2174/13852728113179990018
[5]. Crawford DE. Solvent-free sonochemistry:
 Name - 3-bromo benzoic acid Sonochemical organic synthesis in the absence of a
 Synonyms - m-bromo benzoic acid liquid medium. Beilstein journal of organic
 Molecular Formula - C7H5BrO2 chemistry. 2017 Sep 4;13(1):1850-6. Available
 Molecular Weight - 201.017 From: https://doi.org/10.3762/bjoc.13.179
 Melting Point- 155 – 158 °C [6]. Dr. Dietmar Kennepohl FCIC (Professor of
 Appearance (Form) - Powder or crystals Chemistry, Athabasca University), Prof. Steven
 Appearance (Colour) - White to yellow Farmer (Sonoma State University), Layne Morsch
(University of Illinois Springfield).Alpha
 Solubility - Insoluble in water Soluble in methanol
Bromination of Carboxylic Acids [Internet]. 2021
[cited 2022 May 7]. Available from:
 Application
https://chem.libretexts.org/@go/page/36415
 As test solute in the determination of acidity constants by
[7]. Dr.K.R.Mahadik, Dr.S.H.Bhosale:A Handbook of
capillary zone electrophoresis.
Practical Chemistry Inorganic and Organic
 As internal standard to study the retention mechanisms Chemistry. Nirali Prakashan Publishers &
of an unmodified and a hydroxylated polystyrene- Distributers, Thirteen Edition, May 2016
divinylbenzene polymer by solid-phase extraction. [8]. Donald L. Pavia, Gary M. Lampman, George S. Kriz,
 In synthesis of N-(1,1-dimethyl-2-hydroxyethyl)-3- James R. Vyvyan: Introduction to Spectroscopy.
bromobenzamide. Cengage Learning, Fifth Edition,2015
[9]. MERCK | INDIA – SIGMA-ALDRICH, 3-
IV. CONCLUSION Bromobenzoicacid. Available from: https://www.
Sigmaaldrich.Com/IN/ en/product/aldrich/186295
Various schemes were performed reacting the various [10]. PubChem [Internet]. Bethesda (MD): National
reagents at different volumes and different techniques. From Library of Medicine (US), National Center for
the above results, the scheme 3 was only successful to give Biotechnology Information; 2004-. PubChem
the product 3-bromo benzoic acid. Once the product was Compound Summary for CID 11456, 3-
obtained, firstly the preliminary tests and functional group Bromobenzoic acid; [cited 2022 May 7]. Available
detection test was done to confirm the groups present in the from: https://pubchem.ncbi.nlm.nih.gov/compound/
structure. For final confirmation Infrared Spectroscopy was 3-Bromobenzoic-acid
done on the product by which we came to conclusion that [11]. APPLICATIONS OF IR SPECTROSCOPY: Pharma
the desired product was obtained. As our main aim was to Tutor, 22 March 2010 Available From: https://www.
synthesize product by solvent and catalyst free, scheme 3 is pharmatutor.org/pharma-analysis/analytical-aspects-
best fit for these results and successful. The schemes of-infra-redspectroscopy-ir/application-ir-
performed follow the principles given in the green chemistry spectrophotometry
and the techniques used was by sonication. By the trial-and-
error system, new method of synthesizing the product is
formed which is novel and there is no evidence of this in any
literature. The conclusion of this project is that the 3-bromo
benzoic acid is synthesize by solvent and catalyst free
reaction which is Novel and a Green Method.

Synthesis of Bromo Acid by Solvent and CatalystFree Reaction

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Synthesis of Bromo Acid by Solvent and CatalystFree Reaction

Uploaded by

Copyright:

Available Formats

Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology

Synthesis of Bromo Acid by Solvent and Catalyst-

Abstract:- Chemistry is an extremely significant field of  Objectives:

IJISRT23APR653 www.ijisrt.com 599

Fig 1 Sonication Process

 Green Aspects of Sonication Process:

 High efficiency  Hell-Volhard-Zelinsky Reaction:

IJISRT23APR653 www.ijisrt.com 600

 Precaution Taken During Handling of Bromine:

 General Reaction of Converting Benzoic Acid to 3-

IJISRT23APR653 www.ijisrt.com 601

Table 2 Lessaignen’s Test

IJISRT23APR653 www.ijisrt.com 602

Table 3 Tests for Carboxylic Groups

IJISRT23APR653 www.ijisrt.com 603

IJISRT23APR653 www.ijisrt.com 604

 Detection of Functional Group:

Table 6 Tests for Carboxylic Groups

IJISRT23APR653 www.ijisrt.com 605

Fig 3 FTIR Spectra

Fig 4 Spectrum Graph

IJISRT23APR653 www.ijisrt.com 606

IJISRT23APR653 www.ijisrt.com 607

Table 9 Lessaigne’s Test

IJISRT23APR653 www.ijisrt.com 608

IJISRT23APR653 www.ijisrt.com 609

You might also like