Ultrasound assisted reactions can enhance chemical synthesis through cavitation effects. Piezoelectric transducers are commonly used to generate ultrasound from 20 kHz to 2 MHz. Cavitation produces localized hot spots exceeding 4000K that can drive homogeneous and heterogeneous reactions. Homogeneous reactions involve single-phase systems and produce radicals from water sonolysis. Heterogeneous reactions involve multi-phase systems and benefit from improved mixing and mass transfer. Many reactions like esterification, hydrolysis, substitution, and addition have been achieved with higher yields and faster reaction times using ultrasound.

1. ULTRASOUND ASSISTED
REACTIONS
PRESENTED BY
MADHURA D
1ST M .Pharm
Pharmaceutical chemistry
Government college of Pharmacy,Bengaluru

2. CONTENTS
1. Ultrasound assisted reactions
2. Principle
3. Sources for ultrasound
4. Homogeneous and heterogeneous reactions
5. Synthetic applications
6. Advantages

3. GREEN CHEMISTRY
 “Green Chemistry is the utilization of a set principles that reduces
or eliminates the use or generation of hazardous substances in
the design, manufacture & application of chemical products”

4. 12 PRINCIPLES OF GREEN CHEMISTRY
1. Prevention
2. Atom economy
3. Less hazardous chemical synthesis
4. Designing safer chemicals
5. Safer solvents and auxiliaries
6. Design for energy efficiency auxiliaries
7. Use of renewable feedstocks
8. Reduce derivatives
9. Catalysis
10. Design for degradation
11. Real time analysis for pollution prevention
12. Inherently safer chemistry for accident prevention.

5. SONOCHEMISTRY
The first commercial application of ultrasound dates back to 1917 with the
echo sounding technique developed by langevin for estimation of the depth
of water.
Sonochemistry is used to describe the chemical & physical processes
occurring in solution through the energy brought by power ultrasound.

7. The effects of ultrasound are the consequence of cavitation phenomenon,
which is the formation, the growth & the collapse of gaseous microbubbles
in liquid phase”
 Different sound frequencies
Human hearing 16 Hz-18Hz
Conventional power ultrasound 20 KHz – 100 KHz
Extended ranges for sonochemistry 20 KHz – 2 MHz
Diagnostic ultrasound 5 MHz – 10 MHz

8. PRINCIPLE
Sound wave travels in compression and relaxation mode which cause
pressure high & low, where the pressure is low it will produce a bubble
which is called as micro bubble. It occurs due to acoustic cavitation.
Micro bubble will grow, at one point it will become highly unstable there it
undergoes implosion. After implosion there will be release of energy and
temperature of 4000k & 1000 Atmospheric pressure.

9. SOURCES FOR ULTRASONIC SOUND
TRANSDUCERS
It’s a device by which electrical or mechanical energy can be converted to
sound energy.
1. Liquid driven transducer
2. Magneto strictive transducer
3. Piezoelectric transducer

10. 1. Liquid driven transducer
These are liquid whistles where a liquid is forced out of an orifice and
across a thin steel blade. Cavitation is generated from two sources: the
vibration of the blade induced by liquid flow and a Venturi effect as the
liquid emerges as a jet.This style of transducer is very effective in mixing
and dispersion but is not used generally for sonochemical reactions
requiring high energy.

11. 2. Magnetostrictive transducers
These are electromechanical devices that use magnetostriction, an effect
found in some ferromagnetic materials, e.g. nickel
Such materials reduce in size when placed in a magnetic field and return to
normal dimensions when the field is removed. This type of transducer is
constructed using laminated nickel as the core of a solenoid.

12. 3. Piezoelectric transducers
These are the most common devices employed for the generation of
ultrasound and they utilize ceramics containing piezoelectric materials such
as barium titanate.
The piezoceramic element commonly used in ultrasonic cleaners and for
probe systems is produced in the form of a disc with a central hole.
 Usually two elements are combined so that their overall mechanical
motion is additive.

13. APPARATUS USED IN SONOCHEMISTRY
1. Ultrasonic cleaning bath
It involves the immersion of standard glass reaction vessels into the bath.
This is important because conventional apparatus can be transferred
directly into the bath and so an inert atmosphere or a static pressure can
be achieved readily and maintained throughout a sono chemical reaction.
It is important to establish the optimum position for the reaction vessel in the
bath both vertically and horizontally.

14. 2. The ultrasonic probe
 In order to increase the amount of ultrasonic power available to a reaction, it
can be attained by introducing the energy directly into the system rather than
rely on its transfer through the water of a tank and the reaction vessel walls.
The simplest method to achieve this is to introduce the ultrasonically vibrating
tip of a sonic probe into the reaction itself.

15. Advantages of probe system over bath system
One can control the ultrasonic power delivered to the reaction in probe
system.
Maximum powers of several hundred watts per square centimeter can be
achieved easily.
ultrasonic streaming from the tip of the probe often is sufficiently powerful to
provide bulk mixing without the need for additional stirring.

16. SONOCHEMISTRY IN CHEMICAL SYNTHESIS
 The physical and chemical effects of ultrasound arise from cavitation.
The ultrasonic frequencies doesn’t even change the rotational and vibrational
frequencies of molecules. Only because of cavitational collapse that releases
sufficient kinetic energy to drive the chemical transformation.
 Ex: in case of water the cavitational implosion leads to production of solvent
radicals these are H• and OH• radical species that can react with each other
to give hydrogen and hydrogen peroxide.
They can also react with other substances to induce secondary reduction and
oxidation reaction.

17. TYPES OF SONOCHEMICAL REACTION
HOMOGENEOUS REACTION
 The sonolysis of water, which produces both strong reductants, and oxidants
is capable of causing secondary oxidation and reduction reaction.
 The OH radicals produced from the sonolysis of water are able to attack
essentially all organic compounds (including Halocarbons, pesticides and
nitro aromatics) and through a series of reactions oxidize them fully.
 The ultrasonic irradiation of organic liquids create the same kinds of
products associated with very high temperature pyrolysis.

18. 1. Hydrolysis of nitrile in acidic or basic conditions
Hydrolysis of nitriles in acidic or basic conditions as hydrolysis of benzonitriles
under thermal or ultrasound using 2 M HCl or 2 M NaOH with improvement of
reaction time from 8h to 45 min.

19. 2. Experimental condition for hydrolysis of benzonitrile under thermal or
ultrasonic activation in acidic or basic condition.
3. Sono chemical solvolysis of 2 Chloro-2 methyl propane in aqueous
ethanol.
 where the ratio of the first order rate constants kult (in the presence of
ultrasound) and knon (under conventional conditions) are compared. The
sono chemical process is more efficient on lowering the temperature.
About a 20- fold increase in reaction rate from 25oC to 10oC.

20. Due to reduction in vapour pressure by the lowering of the reaction
temperature will increase the cavitation bubble collapse energy and hence the
sonochemical effect.

21. HETEROGENEOUS REACTIONS
In heterogeneous liquid–liquid or liquid–solid ionic reactions, mechanical
effects associated with sound waves can affect both rates and yields to an
extent depending on the characteristics of the system, such as surface
tension, density, temperature or nature of the solids.
In the former reactions, cavitational collapse at or near the interface will
cause disruption and mixing, resulting in the formation of fine emulsions.

22. Heterogeneous solid-liquid reactions
1. Type 1: in this solid serves as one of the reagent and is consumed during
reaction. This is used to improve yield, and it is due to the dispersing and
micro streaming effect of ultra sound.
2. Type 2: In this metal functions either as a catalyst or is consumed . The
major effect which is observed when ultrasonic waves propagate. The
erosion of metal follows
• Pb> Mg > Zn > Sn > Cu.
Ex: ArRCHX + NaOCl ArRCHOCl

23. SYNTHETIC APPLICATIONS
1. Esterification: The esterification is generally carried out in the presence of
catalyst like sulphuric acid. Reaction requires longer time, and yields are very
low. A simple procedure for the esterification of a variety of carboxylic acids
with different alcohol at ambient temperature using ultrasound is reported.

24. 2. Saponification: Ester hydrolysis is frequently affected under aggressive
conditions. It can be conducted under milder condition when sonication is
used.
Ex: methyl 1-2,4-dimethylbenzoate on saponification (20KHz) gives 2,4
dimethyl benzoic acid 94% compared to 15% yield by normal process of
heating with aqueous alkali (90 min).

25. Ex: Hydrolysis/solvolysis of tert-butyl chloride in aqueous alcohol has been
studied using sound waves. There is rate enhancement of reaction using a
cleaning bath.

26. 3. Substitution: The Friedel-craft acylation of aromatics is facilitated by
ultrasound.
4. An application of the Friedel- craft reaction is used in the carbon bond
formation. 75% yield is obtained in sono chemical reaction.

27. 4. Addition reaction
1,4 addition to α, β – unsaturated carbonyl compounds is traditionally carried
out by organo copper reagent. The significant improvement in yields, rates
and ease of experimental technique is enhanced by sonication bath.

28. N-Alkylation: Secondary amine can be N-Alkylated under sonication in the
presence of a phase transfer reagent, polyethylene glycol monomethyl ether.
Benzo pyrrole on methylation with methyl iodide in toluene in the presence of
potassium hydroxide and PEG gives the corresponding N-methyl etherin 65%
yield. Under normal condition yield is 60%.

29. Coupling reaction: Sonication is effective in promoting the homocoupling of
organometallic intermediate obtained by reaction of alkyl, aryl or vinyl halides
with lithium wire in THF (ultrasonic bath). No reaction takes place in the
absence of ultrasound.

30. Cannizzaro reaction: under heterogeneous conditions catalyzed by barium
hydroxide is considerably accelerated by low intensity ultrasound. The yield
100% after 10 min where as no reaction is observed without the use of
ultrasound.

31. Aza-Michael addition of nucleophiles to α,β-unsaturated compounds: The
synthesis of N-heterocycles via the aza-Michael addition of nucleophiles to
α,βunsaturated ketones, esters, and nitriles to form carbon–nitrogen bonds.
High yields were obtained in water (98%) as well as in solvent-free conditions
(93%).

32. Barbier -Grignard type reactions: The Barbier -Grignard type reactions are
usually referred as a transformation in which the organometalic reagents
serve as nucleophiles to lead to carbon-carbon bond formations.

33. Ulmann-type coupling reactions: The Ulmann-type coupling reaction
occurs at a lower temperature and shorter time in almost quantitative yield
with probe sonication.

34. Simmons-Smith reaction: Sonochemically activated metals greatly improved
the reaction of CH2X2(X=Br, I) with olefin to produce cyclopropane
derivatives as shown in Figure.

35. Applications of Sonochemistry
Sonochemistry has been used for synthesis of composites for energy storage applications
Ultrasound assisted synthesis has been used for preparation of platinum ruthenium
nanoparticles, gold and platinum nanoparticles etc. for fuel cell electrodes.
Synthesis of Cu2O-Graphene, graphene oxide-Fe2O3 for lithium ion battery electrodes.
 Primary/Binary/Ternary nanocomposites which gave good specific capacitance, power
energy density and cyclic stability applicable for electrode material in Supercapacitors.
 Ultrasound finds its application in biomedical devices like HIFU, for targeted ablation of
cancerous and unwanted tissues in the body making treatments easy and less painful.
Sonoporation: Enhancement in permeation due to acoustic cavitation and thus used for
modifying the permeability of cell plasma membrane. It is mainly used to allow the uptake of
molecules like DNA into the cell.
 Sonolysis: Application in purifying water because of formation of reactive species when
ultrasound reacts with water.

36. Advantages of Sonochemistry
 Ultrasound assisted synthesis aids in preparation of uniformly distributed and
uniformly sized nanocomposites in short time and utilizing less energy as
compared to methods like mechanical attrition, electrodeposition etc. High
reaction rates can be achieved using sonochemistry, resulting in time efficient
synthesis.
 Enhanced properties were observed in the field of kinetics, selectivity, extraction,
dissolution, filtration, crystallinity.
 It acts as a catalyst and thus doesn’t have a need to change or replace on a
regular interval.
 It is environment friendly.

37.  Certain nanoparticles were produced using sonochemical method and
conventional method and the following were the conclusions:
1. Time consuming as its optimum reaction time was 20 min whereas that of
conventional method was 4 hours.
2. Increased yields and average particle size which was due to rapid
micromixing and thus faster reaction.
3. Energy efficient as it saved 92% of the energy.

38. REFERENCES
1. James Clark And Duncan Macquarrie. Handbook of green chemistry and
technology;2002; 372-393.
2. Sonochemistry (Application of ultrasound in chemical Synthesis and
reactions): A Review part I; Az. J. Pharm Sci. Vol. 53, March, 2016.
3. Sonochemistry Advantages and Application -A Review. Research gate
publication.

39. Questions
1. What is sonochemistry, explain the sources of ultrasound with sutiable
diagrams.
2. What are homogenous and heterogeneous reactions in ultrasound
assisted reactions?
3. Explain synthetic applications with suitable examples.