Green Chemistry Microwave Synthesis 9789350431849, 9789350243176

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GREEN CHEMISTRY Microwave Synthesis Dr. K.R. DESAI Professor & Head, Department of Chemistry, Veer Narmad South Gujarat University, Surat - 395 007

Foreword by

Prof. V.R. KANETKAR Professor & Head, ' Division of Technology, Dyestuff and Intermediates, University Department of Chemical Technology, Matunga, Mumbai.

~ GJIimalaya GpublishingGfIouse MUMBAI • DELHI • NAGPUR • BANGALORE • HYDERABAD

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CONTENTS CHAPTER 1

MICROWA VE SYNTHESIS ~

1- 10

General Introduction

~

History of Microwave

~

If microwave ovens are good enough for the kitchen, Why shouldn't tney be used to speed up chemical reactions in the laboratory?

~

What is the characteristic of microwave heating?

~

What are Microwave and how they work?

~

Fundamental Theory

~

What is the difference between microwave heating and Conventional heating?

CHAPTER

2

MICROWA VE INDUCED ORGANIC REACTION ~

Introduction

~

General Principles

~

Mechanism of the Microwave Dielectric Heating

~

Dielectric Polarization

~

Dipolar Polarization

~

Experimental Consideration

~

Domestic Microwave Ovens

~

Type of Reactions: (A) Non Solid-State Reactions (B) Solid-State Reactions

~

Choice of solvent

~

Reaction Vessels

~

Modified Fischer-Porter Reaction Vessels Microwave assisted organic reactions

(A) Microwave assisted reactions in organic solvents (B) Microwave assisted organic reaction in dry media.

11- 31

CHAPTER

3

MICROWAVE ASSISTED ORGANIC SYNTHESIS (NAME REACTIONS) (1 ) Pericyclic Reactions (2) Vilsmeir-Haack reaction (3) Friedlander condensation (4) Ortho-Ester Clasien Rearrangement. (5) Clasien-Schmidt condensation (6) Gould-Jacob Reaction (7) Fischer Cyclization

(8) Alder-Bong Reaction (9) Fischer-Indole Reaction (10) Michael Addition (11) Meerwein-Ponndrof-Veriely Reduction

(12) Pinacole-Pinacolone Rearrangement (13) Refortmatsky Reaction (14) Bischler-Napieralski Reaction (15) Bucherer-Strecker Synthesis (16) Graebe-Ullamann Synthesis (17) Krapcho Reaction (18) Tipsou-Cohen Reaction (19) Friedal Craft Germylation Reaction (20) Baylis-Hillman Reaction (21) Ferrier Rearrangement (22) Biginelli Reaction (23) Finkelstein Reaction (24) Heisenberg Reaction (25) Willgerodt Reaction (26) Hoffmann Elimination (27) Williamson Ether Synthesis (28) Gabriel Condensation (29) Leuckart Reductive Animation

32 - 67

(30) Knoevenegel Condensation (31) Heck Arylation (32) Pechmann Reaction (33) Akabori Reaction (34) Perkin Reaction (35) Wolf-Kishner Reduction (36) (37) (38) (39)

Henry Reaction Prins Reaction Niementowski Reaction Michaelis-Arbuzov Reaction

(40) Friedal-Craft Acylation (41) Cross-Cannizzaro condensation (42) Beckmann Rearrangement (43) Benzil Benzillic acid Rearrangement (44) Cannizzaro Reaction (45) Doebner Condensation (46) (47) (48) (49) (50) (51) (52) (53) (54)

Paal-Knorr Cyclization Ritter Reaction Stille-Coupling Suzuki Reaction Ugi Reaction Willgerodt Kindler Wittig Olefmation Hunsdiecker Reaction Mannich Reaction

(55) Sanogashira Coupling (56) Miscellenoues Reaction (i) Oxidation (ii) Reduction (iii) Protection (iv) Deprotection (v) Enzymatic Reaction

(vi) (vii) (viii) (ix) (x) (xi) (x) (xi) (xii) (xiii) (xiv) (xv) (xvi) (xvii) (xi) (xii) (xiii) (xiv) (xv) (xvi) (xvii) (xviii) (xix)

Microwave Enhanced Radio chemistry Esterification Ring Expansion u-Vinyl-u-Lactams Catalytic transfer hydrogenation Preparation of oximes. Alkenes Functionalisation Synthesis ofChalconcs Thiadiazole Nitration Acetalization Heterocyclization Tetra hydro Pyrimidines Deoximation of Carbonyl Compounds Protecting and dcprotccting groups Molecular Rearrangement Condensation Alkylation Heterocyclization Synthesis of Hydantoins and thiohydatoins Deoximation Protection of amino group Synthesis of Pyrimidine

CHAPTER 4

MICROWAVE HARDWARE ~

Microwave Equipment

~

Modification of domestic microwave oven

~

Continuous Microwave Reactor

~

Temperature Monitoring and Control

68 -75

CHAPTERS

APPLICATION OF MICROWAVE HEATING ~

Application of Microwave in material Chemistry

76 - 85

~

Catalyst preparation under microwave irradiation

~

Application of Microwave Technology for Nanotechnology

~

Application of Microwave in polymer synthesis

~

Analytical chemistry

~

Digetion

~

MW Extraction

~

MW Drying

~

MW Apparatus and MW Analytical Techniques

~

MW Irradiation in Waste Management

~

Safety Guidelines from microwave systems

~

Recent Microwave Technologies

REFERENCES

86 - 129

"This page is Intentionally Left Blank"

CHAPTER!

MICROWAVE SYNTHESIS ~

INTRODUCTION

~

HISTORY OF MICROWAVE

The organic synthesis is one of the major role of research in chemistry, from plastics to medication it participates in the improvements of everyone's life. Over the past few decades, many significant advances in practical aspects of organic chemistry have included novel synthetic strategies and methods as well as advent of a vast array of analytical techniques. In these environmentally conscious days, the developments in the technology are directed towards environmentally sound and cleaner procedures. Hence, the present day chemists are no longer confined to using only thermal energy for dri ving chemical reactions. With increasing complexity of the problems and the availability if newer methods of activation of chemical reactions, chemist have restored to using wide variety of techniques such as photochemical, electrochemical, sonochemical, microwave and enzymatic methods. The first two methods are as old as chemistry itself, their use by synthetic chemist has gained importance only in the past decade. With easy availability of ultrasound and microwave sources, their use in chemistry has gained momentum recently. The use of microwave (MW) irradiation to carry out chemical synthesis is an upcoming field of research. The interest in this field among the researches is evident from the exponential growth in the number of publications, approximately 1200 so far and number of process patents filed in this area of active research (Figure 1).

Green Chemistry - Microwave Synthesis PUBLICATION ON MICROWAVE ORGANIC CHEMISTRY

1400

:g

1200

o ~ 1000

.2

:ga.

800

'0 Qi

600

E

400

Z

200

.0 ::J

0

1985

1990

1995

2000

2005

Year

Figure 1

The domestic microwave oven was a serendipitous invention. Percy spencer was working for Ray theon-a company heavily involved with radar during World War II when he noticed the heat generated by a radar antenna. In 1947, an appliance called a Radarange appeared on the market for food processing. The first kitchen microwave oven was introduced by Tappan in 1955. Both devices were based on patents developed by Spencer. Sales of in-expensive domestic microwave ovens now represent a multibillion-dollar annual market. The rapid heating of food-stuffs in microwave ovens is routinely used by a significant proportion of mankind. People have recognized other potential applications for this method of heating and scientists, engaged in a number of disciplines, have applied the rapid heating associated with microwave technology to number of useful processes. ~

WHAT IS THE CHARACTERISTIC OF MICROWAVE HEATING? • Source of MW distant from heat • Heat material directly, not container • Low penetration at short wavelengths • Heating may be non-homogeneous • Rapid heating of lossy materials

3

Microwave Synthesis

• Superheating • Heating depends upon size and geometry of material • Selective heating possible • Heating rates may be temperature dependent • No relation between applied energy and temperature available • Arcing is potential problem with volatiles • Enhanced chemistry possible. Chemists have exploited the advantages outlined above extensively, thus applying microwave heating to solve chemical problems. TiJI now the theoretical basis for the type of reactions which can undergo rate enhancement is poorly understood. Thus interpretation of relationship between the dielectric properties of the materials and their heating rates must be explored further so as to get an in depth knowledge of MW heating. );>

WHAT ARE MICROWAVES AND HOW THEY WORK?

The microwave region of the electromagnetic spectrum lies between IR and radio-frequency regions corresponding to wavelengths 1 cm to 1 m (frequencies of 30 GHz to 300 MHz) respectively. In order not to interfere with RADAR transmissions and telecommunications, domestic and industrial microwave heaters are required to operate at either 12.2 cm (2.45 GHz) or 33.3 cm (900 MHz). Microwave heating provides an alternative to conventional conductive heating for introducing energy into reaction. The frequency between 1 to 25 cm is designated for Radar bands longer wave length for telecommunications such as cell phone networks

x- Rays-U.V-VIS-IR

Wavelength

I Frequency

Radiowaves

Microwaves

• Radar Bands • •1cm 10cm 10

3x 10 Hz

9

3x10 Hz

•

I I

I 3X1d Hz ----

Figure 2

10 m

1m

.~-

- - -- ---

_I

4

Green Chemistry - Microwave Synthesis

etc. To prevent interference, some specific frequencies within the microwave spectrum have been internationally agreed for the use in domestic, industrial, scientific and for medical; ailment that are designated as ISM frequencies ranging from 896 to 3390 MHz. Currently, domestic microwave ovens use 2450 MHz (wavelength 12.25 cm) and for larger industrial applications 900 MHz (wavelength 33 cm) is available. The use of other frequencies is permitted if proper shielding of radiation is done so as to prevent any radiation losses. The energy carried by microwave at 2450 MHz is very small nearly 1 llmol of quanta. In contrast to classical photochemistry, many quanta would be necessary to activate a chemical bond. ~

FUNDAMENTAL THEORY

To understand the concept of microwave heating we will brush up some basic concepts of interaction between the electromagnetic radiation and matter. From our knowledge of higher school physics a dielectric material is one which when placed between the two electrodes allows the charge to be stored on the plates and dc conductivity is observed between the plates as in the case of a capacitor. A dielectric material may have either a permanent or induced dipoles. The polarization of dielectric arises from the finite displacement of charges or rotation of dipoles under the influence of applied electric field. At the molecular level polarization involves either the distortion or distribution of the electron cloud within a molecule or it may be physical rotation ofmolecular dipoles. The latter are particularly significant in the context of microwave dielectric heating. The permittivity of a material E is a property, which describes the charge storing ability of a substance irrespective of the sample dimensions. The dielectric constant orrelative permittivity is the permittivity of the material relative to that offree space. It is usually observed that compounds, which have large permanent dipole moments, have large dielectric constant, because the electric polarization depends primarily on the ability of their dipoles to reorient in an applied electric field. In the gas and liquid phases the molecules rotate very rapidly and are normally able to respond to field reverses occurring at 106 times a second or higher, but in case of solids the molecular rotations are generally restricted and therefore the reorientation in the electric field dose not

Microwave Synthesis

5

contribute to the dielectric constant. If the electric field component is reversed more rapidly that is at 10 12 times per second, even the smallest molecules are no longer able to rotate a significant amount before the electric field is reversed and the permittivity necessarily falls. Therefore we can say that the permittivity is frequency dependent. It can be seen that even the solvent which has much lower dielectric constant, can get heated up rapidly due to its lower heat capacity for e.g. I-propanol has lower heat capacity (2.45 Jig K) compared to water (4.18 Jig K). From the chemical point of view this means that the introduction of ions into a solution leads to a marked increase in dielectric heating rates. In the case of semiconducting and semimetallic materials, the conduction loss is dominated by the electronic transport. The temperature profile within the material exposed to microwave radiation depends on geometrical factors related to design of the microwave cavity, the reaction vessels as well as on the size of the sample. The commonly used domestic microwave oven magnetrons have a frequency of 2.45 GHz. Corresponding to a wavelength 12.25 cm while the penetration depth for that frequency of most solvents ranges from a couple of millimeters up. This implies that it may be helpful to perform initial investigative reaction on a small scale offew millimeters where the influence of the microwave field is easier to handle than in larger scale systems. ~

HOW THE MICROWAVE RADIATION INTERACTS WITH THE MATERIAL?

To above physical aspects such as dielectric heating, relaxation time, and penetration depth have been explained so as to make us understand how the microwave radiation interacts with the material; and its consequence leading to microwave dielectric heating. Interaction of different materials with microwave irradiation plays an important role in application and designing of a chemical reaction. These materials can be part of apparatus and oven. Interaction of microwave with different materials can be divided into three classes such as metals which tend to reflect microwaves whereas many material such as quartz, Teflon, glass are practically transparent to microwave and can be penetrated by microwaves. The type is called as dielectric or lossy material which interact with microwaves to different extents such as water, graphite etc. (Figure 3)

6

Green Chemistry - Microwave Synthesis

t

,..-----.

~~

Transparent insulator Low loss of MW intensity

~~ Absorbing insulator High loss of MW intensity

Metal (Opaque) All MW intensity Reflected

Figure 3

Liquids Polar solvents with permanent dipoles such as water, acetic acid, DMSO, dioxan, diglyme, ethylene glycol have high dielectric constant and are good candidates for microwave assisted chemical synthesis. DMF with its high dielectric constant (£ = 36.7, bp = 154) is an efficient microwave energy transferring agent and a convenient solvent because it is claimed that they become superheated even at atm. pressure. This superheating of up to 25°C greater than the boiling point is caused because heating occurs not at the surface, but within the solvent. The solvent heating is so rapid that convection and vaporization cannot dissipate the excess energy sufficiently. The presence of salts in polar solvents can increase the dielectric loss and hence heating effects. Therefore addition of salts to polar solvent can also be used to get maximum heat during a chemical reaction under microwave heating. The non polar solvents, which have no permanent dipole moment, are microwave transparent. When exposed to microwave irradiation they

Microwave Synthesis

7

do not heat of a very little increase in temperature may be observed e. g. benzene, petroleum ether, hexane, carbon tetrachloride, xylene etc. But these solvents can be used as microwave coolants for removing excess heat from microwave cavity. However, small amount of solvents which do couple to microwave when added to these transparent solvents can lead to a dramatic increase in temperature of the mixture, hence very useful for chemical manipulation during chemical reactions.

Solids Dielectric properties are dependent on both the chemical composition and on the physical state of the solid material. For example, impurities, crystal defects, and the chemical nature of the material (whether it is a transition metal compound of a chalcogenide, etc.) can give rise to high _ dielectric constants and losses and results in strong microwave coupling. We may note that microwave frequencies correspond to rotational excitation energies in materials. Thus the incident microwaves may exits rotational modes in a material. The dielectric properties themselves being temperature-dependent, both microwave coupling and the resulting temperature profiles of the sample can be very different for silica (Si0 2), whose dielectric constant and dielectric loss do not show much dispersion, does not get heated up much when exposed to microwaves even after a long duration. But the temperatures of the other two oxides NiO and Cr20 3 escalate after some initial exposure times. In case of NiO the high dielectric loss results in almost a parabolic increase in temperature while increased dielectric loss at high temperature is responsible for the fairly abrupt rise in temperature in Cr20 3 .

»

WHAT IS THE DIFFERENCE BETWEEN MICROWAVE HEATING AND CONVENTIONAL HEATING?

Claimed effects of microwave dielectric heating can be divided in two kinds: thermal effects and non-thermal effects. Thermal effects are those, which caused by different temperature regime which can be created due to microwave dielectric heating. Non-thermal effects are effects, which are caused by effects specifically inherent to the microwaves and are not caused by different temperature regimes. Microwave heating is totally different from conventional heating. In case of conventional heating the heat gradient is from the heating

8

Green Chemistry - Microwave Synthesis

device to the medium while in case of microwave heating the heat is dissipated inside the irradiated medium (mass heating) and heat transfers from the medium to outside. Again in case of conventional heating the heat transfer depends on thermal conductivity, on the temperature difference across the material and on convection currents, therefore the temperature increase is often rather slow. While in microwave heating due to the mass heating effect much faster temperature increase can be obtained depending on microwave power and the loss factor of the material being irradiated (Figure 4).

Sample solvent mixture (absorbs microwave energy)

Sample-solvent mixture

Locasized superheating

~~!~~~,

Vessel wall " " (transparent to microwave energy)

Temperature on the outSide surface is In excess of the boiling point of solvent

B :Microwave heating

A :Conventional heating

Figure 4

Though there is difference in conventional and microwave heating there is a debate among the scientific community as whether Microwave Activation Myth or Reality? ~

HOW MICROWAVE HEATS SOLVENTS ABOVE THEIR NORMAL BOILING POINTS?

Mingos and Baghurst l have observed that liquids superheat under microwave irradiation they have used fluoroptic temperature measurements to establish that organic liquids are superheated by 13-26 D e above their conventional boiling points at atmospheric pressure. Water for example, hits lO5 De instead of lOoDe before boiling, and acetonitrile, another popular solvent, gets to l20 D e, an amazing 38 D e higher than its usual boiling point. Although microwave afford a mass heating, it is known that

Microwave Synthesis

9

the field distribution is not even in the irradiated material; therefore energy is not homogeneously dissipated this results in formation of 'hotspots.' Hotspots occur if generation of heat is faster than heat transfers. Hot spots have actually been observed by Abtal et al 2 in poorly conductive materials (solids of highly viscous liquids), but could possibly occur in liquids also. As such hotspots have been observed at the surface of boiling liquids by IR measurements. In the field of reaction chemistry, however initially it was believed that there was anonthermal microwave effect when Diels-Alderreactions 3 were carried out under homogeneous reaction conditions ( both in nonpolar reaction medium). However when careful temperature control was generated no special rate effects were observed. This was confirmed again when Raner et al. 4 provided the first example of a systematic study to determine and evaluate activation parameters for reaction both heated dielectrically and conventionally. No difference depending on heating mode was observed when they studied isomerization of carvone, the Diels Alder reaction between diethyl maleate and anthracene and the acid catalyzed estrification of2,4,6 trimethylbenzoic acid in isopropyl alcohol. Neither of the researchers found areproducib1e microwave effect (Scheme 1). Thus, it was concluded that most rate enhancement effects were observed during microwave heating because there were inadequate temperature monitoring and control systems.

Isomerization

Caraerol

Caravone

Scheme 1

10

Green Chemistry - Microwave Synthesis

However this did not signal the end of the debate and apparent observation of a "special microwave effect" when dielectric heating was used. A study of the MW heating of oiVwater mixture and emulsions by Barringer and co-workers5 at Ohio State University showed that the rate of heating depended on the dispersion of the two liquids, which was attributed to increase power absorption at the interfaces. Within the field of polymer chemistry there has been clarity regarding whether effects observed were non-thermal or not. Yet, for the epoxyamine kinetics of curing of a polymer under careful temperature conditions no effect was observed by Mijovic et a1. 6 But in a study conducted by Lewis et al. 7 have observed enhancement in the rate of reaction for an imidization reaction between BTDA (Bnezophenone - 3, 3', 4, 4'tetracarboxylic acid anhydride) and DDS (Diaminodiphenylsulphone) under microwave curing than the conventional curing. Microwave heating could be employed to control the isomeric ratio of the products of the sulfonation of naphthalene. This seems a route to make either the kinetically or the thermodynamically controlled reaction. In microwave irradiation thermodynamic product8 was found to be a major one and increased with increase in power of microwave irradiation (Scheme 2).

co

--l.~

_H...:;2,-S_O-,-4

as" (X)so~ +

Thermodynamic product (major)

Scheme 2

In conclusion, though there are claims and counterclaims for microwave heating the debate turns to be never ending. As the subject is interesting it warrants more investigation and therefore more careful comparison between conventional and microwave heating has to be carried out with control reaction. Then only one can conclusively prove the microwave effects and its influence on microwave heating. Anyway microwave heating has come a long way and has established itself in carrying out chemical reaction not only in laboratories but also in industries too. 000

CHAPTER 2

MICROWAVE INDUCED ORGANIC REACTION ~

INTRODUCTION

The rapid heating of foodstuffs in microwave ovens is routinely used by a significant proportion of mankind. However, people have recognized other potential applications for this method of heating and scientists engaged in a number of disciplines have applied the rapid heating associated with microwave technology to a number of useful processes. These include the preparation of samples for analysis 9, application to waste treatment IO, polymer technology 11, drug release/ targeting l2 , ceramics 13 and alkane decomposition. 14 The technique has also found use in a range of decomposition processes including hydrolysis of proteins and peptides. 15 Application to inorganic solid state synthesis has also been shown to have significant advantages. 16 Organic synthesis is an area which can benefit significantly from this technology 17 , with still a large scope of improvement. ~

GENERAL PRINCIPLES

The micro\\ a \ ~ regions of the electromagnetic spectrum lies between 1 cm and I m and in order to avoid interfering with RADAR and telecommunication activities which operate within this region, most domestic and commercial microwave instruments operate at 2.45 GHz. ~

MECHANISM OF THE MICROWAVE DIELECTRIC HEATING

Microwave are conventionally used for spectral analysis of compounds in their gaseous state, but in liquids and solids, molecules are

12

Green Chemistry - Microwave Synthesis

generally not free to rotate independently, the spectra are too broad to be observed. It is to these phase that microwave dielectric loss heating effects are relevant and (need to be distinguished from the spectroscopic effects.) is exploited as non-conventional source of energy. A material can be heated by applying energy to it in the form of high frequency electromagnetic waves. The origin of heating effect produced by the high energy electromagnetic waves arise from the ability of an electric field to exert a force on charged particles. If the particle present in the substance can move freely through it, then a current has been induced. However, if the charge carriers are bound to certain regions, they will move until a counter force balances them and the net result is a dielectric polarisation. Both conduction and dielectric polarisation are sources of microwave heating. I8

»

DIELECTRIC POLARIZATIONS

The source of microwave dielectric heating lies in the ability of an electric field to polarise charges in a material and the inability of this polarisation to follow rapid reversal of an electric field. The total polarisation is the sum of a number of individual components.

N

~

N I H

Agapoor et al. l62 have also reported another method in which neat sample of o-phenelyne diamine is condensed with NH 2CONH 2, NH 2CSNH2 , NH 2CNHNH 2 to give benzimidazole in solvent free reaction under MW activation of 5-6 min with yields between 75-90%.

62

Green Chemistry - Microwave Synthesis H

Qc ~

I

N.>==O ...

N

I

Mi2

0 ~NH2

H

Isoflav-3-ones Verma et al. 163 have developed a convenient method for synthesis of isoflave-2-enes with basic moieties at 2 position. In this heterocyclic system the generation of enamine derivatives in situ and inducing subsequent reactions with o-hydroxy aldehydes in the same port is a key feature with total reaction time of 2 to 8 min. R

o

JX

An

A

H

I :

Ph

OH

Rill

Aryl Piperazines Khadilkar et al. l64 have carried out rapid and efficient synthesis of l-arylpiperazines under microwave irradiation. l-arylpiperazines finding wide applicability in pharmaceuticals were synthesized under microwave irradiation. Substituted aniline and bis (2-chloroethyl)amine hydrochloride without any solvent were irradiated in modified MW oven to give CI rHCI

~CI

+

Microwave Assisted Organic Synthesis (Name Reaction)

63

products within 1-3 min. The yields reported are from 53-73%. Potent serotonin legends like Trifluoromethylphenylpiperazine (TFMPP) and 3- Chlorophenylpiperazine (mCPP) were also prepared by this method. In another method, 165 diethanolamine and substituted anilines were irradiated under microwave irradiation to give I-aryl piperazines. The yields were comparable with the conventional yields and drastic reduction in reaction time was observed.

Bridghead Nitrogen Heterocycles Bridgehead nitrogen heterocycles are easily prepared under MW irradiation in solventless conditions. Rahmouni et al.166.167 have synthesized pyrimidino [1 ,6-a] benzimidazoles and 2,3dihydroimidazoles[ 1,2-c] Pyrimidines under focused MW irradiation of 15 to 30 min, from N-acylimidates and activated 2-benzimidazo1es and Imidazolines ketene aminals respectively.

O=