Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200400655

Controlled microwave heating in modern organic synthesis.

Microwave assisted organic synthesis-a review

Microwave irradiation has been successfully applied in organic chemistry. Spectacular accelerations, higher yields under milder reaction conditions and higher product purities have all been reported. Indeed, a number of authors have described success in reactions that do not occur by conventional heating and even modifications of selectivity (chemo-, regio- and stereoselectivity). The effect of microwave irradiation in organic synthesis is a combination of thermal effects, arising from the heating rate, superheating or “hot spots” and the selective absorption of radiation by polar substances. Such phenomena are not usually accessible by classical heating and the existence of non-thermal effects of highly polarizing radiation—the “specific microwave effect”—is still a controversial topic. An overview of the thermal effects and the current state of non-thermal microwave effects is presented in this critical review along with a view on how these phenomena can be effectively used in organic synthesis.

Microwaves in organic synthesis. thermal and non-thermal microwave effects

Microwave assisted organic reactions

CuI‐Catalyzed Alkyne–Azide “Click” Cycloadditions from a Mechanistic and Synthetic Perspective

The use of microwave ovens for rapid organic synthesis

This work demonstrates that organic compounds can be synthesized up to 1240 times faster in sealed Teflon vessels in a microwave oven than by conventional (reflux) techniques. It is shown that all ...

The rapid synthesis of organic compounds in microwave ovens

The reactant and transition-state structures for several s N 2 reactions between different nucleophiles and methyl and ethyl chloride and fluoride have been calculated at the H F / 6 1 3 + G * level. The secondary a-deuterium kinetic isotope effects for these reactions were calculated with Sim's BEBOVIB-IV program. The results demonstrate that the magnitude of these isotope effects is determined by an inverse stretching vibration contribution and a normal bending vibration contribution to the isotope effect. The stretching vibration contribution to the isotope effect is essentially constant for each substrate while the bending vibration contribution varies with the nucleophile and the looseness of the s N 2 transition state. Thus, the out-of-plane bending vibration model for relating the magnitude of secondary a-deuterium kinetic isotope effects to transition-state structure is correct. The bending vibration contribution to the isotope effect is greater in the ethyl substrate reactions than in the methyl substrate reactions. As a result, larger isotope effects and looser transition states are found for the s N 2 reactions of larger substrates. Looser transition states and larger isotope effects are also observed for the s N 2 reactions with softer nucleophiles.

A Theoretical Study of the Relationship between Secondary .alpha.-Deuterium Kinetic Isotope Effects and the Structure of SN2 Transition States

This study shows that chemical reactions in polar solvents can be carried out rapidly and conveniently using microwave heating in sealed Teflon containers. Reactions of organic and or ganometallic compounds are reported, and rate enhancements of up to 1,240 times have been observed. The acceleration of reactions (compared to normal reflux conditions)oc curs because the increased pressure developed in the reaction vessels causes superheating of the solvent. The rate of absorption of microwave radiation is affected by the polarity and the volume of the reaction mixture. The heating rate is also influenced by the presence of ions in solution.The yields of relatively slow reactions can be increased by programming the power levels of the microwave oven. This technique allows the reactions to be carried out more safely and to be scaled up to some extent. Microwave heating results in considerable energy savings compared with conventional heating methods. The energy efficiency can be further increased by power pr...

Microwaves in Organic and Organometallic Synthesis

Publisher Summary This chapter focuses on the use of kinetic isotope effects (KIEs) as a method of determining the mechanism and transition state structures of SN2 reactions. A primary KIE is found when the bond to the isotopically labeled atom is breaking or forming in the transition state of the slow step of the reaction. Three basic relationships indicate how the magnitude of a primary KIE varies with transition state structure in SN2 reactions. Because the smallest α-carbon KIE reported for an SN2 reaction is 80% of the largest-observed KIE, the qualitative conclusion would be that all these SN2 reactions have symmetric or almost symmetric transition states. A secondary KIE is observed when the bond to the isotopically substituted atom is not being broken or formed in the transition state of the rate-determining step of the reaction. KIEs still remain one of the most convincing probes of transition state structure and reaction mechanism, especially when applied at several positions in a reaction.

Kenneth Charles Westaway

Papers

The use of microwave ovens for rapid organic synthesis

The rapid synthesis of organic compounds in microwave ovens

A Theoretical Study of the Relationship between Secondary .alpha.-Deuterium Kinetic Isotope Effects and the Structure of SN2 Transition States

Microwaves in Organic and Organometallic Synthesis

Using kinetic isotope effects to determine the structure of the transition states of SN2 reactions