Microwave assisted organic synthesis

1. MORE CHEMISRY
AN ECO-FRIENDLY TECHNOLOGY
NAME – MOUMITA BANERJEE
B.PHARM
3RD YEAR
24201911013

2. (MORE) CHEMISTRY
It can be termed as “E-Chemistry” because it is easy
effective, eco friendly and economic and is believed a step
towards a green chemistry and pharmaceutical
applications.
Microwave induced organic reaction enhancement chemistry is gaining
popularity as a non-conventional technique for rapid organic synthesis.
Important features of this technique are easy access to very high
temperature, good control over energy input over a reaction and rapid
synthesis.
Advantages include requirement of simple, inexpensive instrument, lesser
quantity of solvents and eco friendly technology.

3. MICROWAVE
A microwave is a form of
electromagnetic energy that falls
at the lower frequency and of
the electromagnetic spectrum
and is defined in the 300 to
300,000 (MHz) frequency range.
Within this region of
electromagnetic energy only
molecular rotation is affected
not the molecular structure.

4. MICROWAVE ASSITED ORGANIC SYNTHESIS
“Preparation of a desired
organic compound
from available starting
materials via some
(multi-step) procedure,
involving microwave
irradiation”

5. BENEFITS OF MW-ASSISTED SYNTHESIS
Higher temperatures (superheating / sealed vessels)
Faster reactions, lesser by products, pure compounds
Absolute control over reaction parameters
Selective heating / activation of catalysts
Energy efficient, rapid energy transfer
Easy access to high pressure performance
Does things that can´t be done conventionally
Rapid synthesis results in lesser evaporation of solvents
Recent simplification of MORE technique have increased safety and practical utility.

6. DEMERITS OF MW-ASSISTED SYNTHESIS
Heat Force controlled is difficult.
Water Evaporation.
Closed container is dangerous because it can blast.

7. COMPARISON
CONVENTIONAL HEATING
• Vessel gets heated first
• Both gas and solution phase get heated
• Too high pressure -> Explosion
MICROWAVE HEATING
• Only Solution gets heated

8. Applicable Microwave Instrumentation
Multimode Batch Reactors
MLS Ethos 1600
Domestic MW Oven
Mars-S
Single Mode Instruments
Emrys Liberator
Initiator
Discover

9. SOLVENTS
Energy Transfer Medium Boiling Point Dielectric Constant (20°/25°)
Acetone 56.6 20.70
Acetyl Acetone 140.6 25.70
Acetonitrile 82.0 37.50
Benzene 80.1 2.27
1-Butanol 117.7 17.80
Carbon Disulfide 46.3 2.64
Carbon Tetrachloride 76.7 2.23
Chlorobenzene 132.1 5.62
Chloroform 61.7 4.81
1,2-Dichloroethane 83.5 10.65
Diethyl Ether 34.6 4.34
Diethyl Glycol 244.8 31.70
Dimethyl Formamide 153.0 36.71
Dimethyl Sulfoxide 189.0 46.60

10. SOLVENTS – Cont.
Energy Transfer Medium Boiling Point Dielectric Constant (20°/25°)
1,4-Dioxan 101.1 2.21
Ethanol 78.4 32.40
Ethyl Acetate 77.1 6.02
Ethylene Glycol 124.0 38.66
N-Hexane 68.7 1.89
1-Hexanol 157.5 13.30
Methanol 64.7 32.70
Pyridine 115.5 12.30
Tetrahydrofuran 66.0 7.58
Toluene 110.6 2.38
Water 100.0 78.50
m-Xylene 139.1 2.37
p-Xylene 137.8 4.80

11. REAGENTS
Quinidine
Toluene
DCM
Conc. H2SO4
Na2WO4
H2O2
Aq. KOH, Aq. KMnO4

12. Conditions Appropriate For Microwave Synthesis
SOLVENT
• Different Solvent interact very differently with microwave , because of their diverse
polar and ionic properties.
VOLUME
• Don’t exceed a fall below the vial’s specific volumes.
• Too low volumes  gives incorrect temperature measurement.
• High volumes  does not leave sufficient head space for pressure build up.
CONCENTRATION
• The concentration depends on the type of chemistry that is performed, like higher
concentration gives faster reaction.
PHASE
• All different phases can be used , i.e. solution phase, solid phase, solid supported
reagents, solvent free and Scavenger resins.
STIRRING
• Add always a magnetic stirring bar to the microwave vial.

13. Conditions Appropriate For Microwave Synthesis
INERT ATMOSPHERE
• Inert atmosphere is not initially employed, if needed flush the vial with an inert gas
before capping.
TIME
• Typically ,most reactions require 2-15 min of irradiation.
TEMERATURE
• Maintain the temperature b/w 600C to 2500C.
PRESSURE
• The reaction can be safely performed at pressure of up to 20 bar.
TIME PREDICTION
• Reactions proceed faster using microwave synthesis simply because they are
conducted at higher temperature, like based on Arrhenius equation a ten degree
increase in reaction temperature doubles the reaction speed.
OPTIMIZATION
• Optimizing a microwave synthesis is similar to optimizing a conventional synthesis
like if reaction fails changing the target temp. and reaction time can cause significant
improvement.

14. REACTIONS
HYDROLYSIS
OXIDATION

15. REACTIONS
ESTERIFICATION
DECARBOXYLATION

16. REACTIONS
CYCLOADDITION
N-ALKYLATION

17. ENHANCED MICROWAVE SYNTHESIS
An alternative method for performing microwave
assisted organic reactions, is termed “ENHANCED
MICROWAVE SYNTHESIS”. Externally cooling the
reaction vessel with compressed air and simultaneously
administering microwave irradiation, more energy can
be directly applied to the reaction mixture.
In convention microwave synthesis
(CMS), the initial microwave power is
high, increasing the bulk temperature to
the desired set point very quickly.

18. ENHANCED MICROWAVE SYNTHESIS
EMS has also been beneficial in producing higher release levels
of the desired amides from solid phase resin, as compared with
microwave heating alone.

19. APPLICATIONS
The rapid heating effect has been exploited to create better crystallinity
in intercalation compounds such as ceramics and synthetic zeolites.
In industry its important application is preparation of hydrogen cyanide
and in chlorination plant.
In pharmaceutical powders and pasteurization of food products.
Microwave irradiation is also used in the waste management .
In Polymer synthesis.

20. APPLICATIONS/MODEL REACTIONS
1) Biginelli Multicomponent Reaction
2) Kindler Thioamide Synthesis
3) Heck Couplings
4) Negishi Coupling
5) Suzuki Cross-Coupling
6) Solid Phase Synthesis
7) Diels-Alder Cycloaddition
8) Near Critical Water Chemistry

21. CONCLUSION
MORE chemistry has been identified as a current trend in
organic synthesis. Entry of microwave oven in chemistry
laboratory has made it possible to carry out many organic
transformation with great efficiency and ease of work up.
Development of appropriate technology can lead the
applicability of MORE chemistry for industrial manufacture
of fine chemicals ,thereby improving overall process, cost
effectiveness and reducing pollution of the environment
through the use of solvents free protocols.

22. FUTURE PROSPECTS
MAOS can be beneficial to Pharmaceutical Industry by increasing
the rate with which new chemical entities (NCE) can be
synthesised. As synthesis of NCEs is only one part of the overall
process by which new pharmaceuticals are developed therefore an
increasing rate of MAOS adoption must also be done concurrently
with an overall process assessment.
A huge scope to extend the applicability of microwave technology
includes: Synthesis of new, novel ceramic powders, Fabrication of
glass ceramic coating, modelling of microwave heating, Analysis of
the role of the H field in microwave material interaction etc.

23. REFERENCES
Bagnell, L. S. C. R. Chem. Commun. 1999, 287-288
Borman, S., Chem. Eng. News, 1998, 6, 47
Brain, C. T.;Paul, J. M. Synlett 1999, 1642-1644
Brittany L. Hayes Ph.D., Microwave Synthesis Chemistry at the Speed of Light, 2002, pp. 14,70,34
Brittany L. Hayes Ph.D., Recent Advance in Microwave Assisted Synthesis, 2002, pp. 1-6
Eur. J. Org. Chem., 2005, 3672-3679
Mali, R. S.; Massey, A P. J. Chem. Res. 1998, 230-231
Org. Process Res. Dev. 2003, 707-716
Org. Biomol. Chem. 2004, 2, 154-156
Shaabani, A. J. Chem. Res. 1998, 672-673
Wan, J.S.K. , U.S. Patent No. , 1982, 4, 345, 983

24. THANK YOU
EVERYONE
&
ENJOY!!!