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 The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction.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 primary hydrogen−deuterium incoming nucleophile KIEs for the SN2 reactions between para-substituted benzyl chlorides and borohydride ion in DMSO at 30.000 ± 0.002 °C are small (≤1.14) and insensitive to a change in substituent at the α-carbon. The small Hammett ρ (0.51) and ρr (−0.52) values found when the para substituent on the benzene ring of the substrate is altered indicate there is very little charge on the α-carbon in the transition state. The large, constant secondary α-deuterium KIEs of 1.089 ± 0.002 and the large chlorine leaving group KIEs of 1.0076, 1.0074, and 1.0078 found for the p-methyl-, the p-hydrogen-, and the p-chlorobenzyl chloride reactions suggest that the transition states for these reactions are unsymmetric with short H−Cα and long B−Η and Cα−Cl bonds. The decrease in the chlorine leaving group KIE from 1.0076 ± 0.0003 for the p-methylbenzyl chloride reaction to 1.0036 ± 0.0003 for the p-nitrobenzyl chloride reaction indicates the Cα−Cl bond shortens markedly when a strongly e...

Using Incoming Nucleophile Primary Hydrogen−Deuterium Kinetic Isotope Effects To Model the SN2 Transition State

A kinetic study of the nucleophilic substitution reactions of a series of para-substituted phenylbenzyldimethylammonium nitrates with sodium thiophenoxide at 0 °C in N,N-dimethylformamide containin...

Isotope Effects in Nucleophilic Substitution Reactions. I. The Mechanism of the Reaction of Phenylbenzyldimethylammonium Ion with Thiophenoxide Ion

Fourier transform infrared spectroscopy has been used to investigate the behaviour of HCN and alkali metal and tetraethylammonium cyanides in DMF and aqueous DMF. The cyanide ion exists as free ions and ion pairs in pure DMF but as water-solvated and DMF-solvated ions in aqueous DMF. The aqueous DMF solutions can be treated as a pseudo two-phase system with a distribution coefficient of 0.018 between the aqueous and DMF-rich pseudo phases. A kinetic analysis of the cyanide ion – benzyl chloride reaction in DMF and aqueous DMF has shown that the rate constant for the SN2 reaction is markedly decreased with the addition of as little as 2.5% water. This decrease is primarily due to changes in transition state solvation. The SN2 reactions between cyanide ion and benzylmethyl-4-substituted phenylsulphonium perchlorates in 20% aqueous DMF have also been investigated.

Fourier transform infrared spectroscopy studies of cyanide ion solutions of dimethylformamide and aqueous dimethylformamide

Large concentration effects on the magnitude of secondary alpha-deuterium kinetic isotope effects

A very large secondary α-deuterium kinetic isotope effect of 1.179 ± 0.007 (1.086 ± 0.003 per α-deuterium) has been observed for the SN2 reaction of thiophenoxide ion with benzyldimethylphenylammon...

Kenneth Charles Westaway

Papers

Using Incoming Nucleophile Primary Hydrogen−Deuterium Kinetic Isotope Effects To Model the SN2 Transition State

Isotope Effects in Nucleophilic Substitution Reactions. I. The Mechanism of the Reaction of Phenylbenzyldimethylammonium Ion with Thiophenoxide Ion

Fourier transform infrared spectroscopy studies of cyanide ion solutions of dimethylformamide and aqueous dimethylformamide

Large concentration effects on the magnitude of secondary alpha-deuterium kinetic isotope effects

Isotope effects in nucleophilic substitution reactions. II. Secondary α-deuterium kinetic isotope effects: a criterion of mechanism?