Microwave-Enhanced Organic Syntheses for the Undergraduate Laboratory: Diels−Alder Cycloaddition, Wittig Reaction, and Williamson Ether Synthesis

Abstract

Microwave heating enhanced the rate of three reactions typically performed in our undergraduate organic chemistry laboratory: a Diels−Alder cycloaddition, a Wittig salt formation, and a Williamson ether synthesis. Ninety-minute refluxes were shortened to 10 min using a laboratory-grade microwave oven. In addition, yields improved for the Wittig salt and ether preparations. The Diels-Alder cycloaddition of N-phenylmaleimide and 1,3-cyclohexadiene in absolute ethanol in a closed vessel and 130 °C gave 84−90% yields. Formation of the Wittig salt, benzyltriphenylphosphonium chloride, from triphenylphosphine and benzyl chloride gave yields greater than 90% when heated in acetonitrile at 200 °C Yields doubled in the Williamson ether synthesis of 2-ethoxynaphthalene, from 2-naphthol, methanolic potassium hydroxide, and iodoethane with microwave heating at 130 °C.

Greening the organic chemistry laboratory: a comparison of microwave-assisted and classical nucleophilic aromatic substitution reactions

“…Furthermore, the present study serves as an excellent introduction to microwave-induced organic reaction enhancement (MORE) which has been shown to be very useful in affecting the pathway of a reaction, the products formed and, especially, reaction times. As such, MORE techniques are appearing more often in the chemical literature (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In one study (39), the authors report that the time and yield of their own previously developed synthesis of 2-chloromethylbenzothiazole from ortho-aminothiophenol and polyphosphoric acid, which gives a reasonable yield of 62% after 8 h of reflux at 180°C, improves to a 90% yield with only 10 min of microwave irradiation.…”

Some Like It Hot: Experimentally Determining ΔΔH⧧, ΔΔS⧧, and ΔΔG⧧ between Kinetic and Thermodynamic Diels–Alder Pathways Using Microwave-Assisted Synthesis

“…Incorporation of microwave-assisted synthetic techniques is becoming increasingly popular across multiple disciplines of research and chemistry education. − Numerous undergraduate experiments using commercial reactors have been developed, including Friedel–Crafts acylations, aldol condensations and conjugate additions, , Wolff–Kishner reductions, carbonyl-based additions and substitutions, ,,,, and synthesis of fluorescent inorganic materials . Domestic microwave ovens have been successfully used as a cost-effective synthetic tool in the undergraduate lab − but suffer from poor efficiency and reproducibility.…”

“…Cycloadditions are one class of reactions in which focused microwave irradiation can be used to achieve quantitative yields in minutes. − More specifically, the Diels–Alder cycloaddition is a concerted, thermally allowed [4 + 2] process yielding a product that contains a new or additional 6-membered ring. Numerous microwave-assisted Diels–Alder procedures are present in literature, − including adaptations designed for use in the undergraduate laboratory. ,,,,,− Conventional Diels–Alder reactions occur through interaction of the highest occupied molecular orbital (HOMO) of a diene and the lowest unoccupied molecular orbital (LUMO) of a dienophile. The rates of Diels–Alder reactions are system dependent, as completion times range from a few seconds to many days under ambient conditions.…”

Process Development of the Weiss–Cook Reaction for the Preparation of cis-1,5-Dimethylbicyclo[3.3.0]octane-3,7-dione in the Undergraduate Organic Laboratory

“…Often, these reactions are carried out in the undergraduate organic chemistry laboratory to help solifidy and support the concepts learned in lecture. Classical transformations such as Wittig, Grignard, and Diels–Alder reactions have been successfully carried out and incorporated in the second-year organic chemistry curriculum. Performing these reactions in the laboratory allows for extensive investigation of new laboratory techniques, proposed reaction mechanisms, and structure elucidations.…”