The Application of Microwaves, Ultrasounds, and Their Combination in the Synthesis of Nitrogen-Containing Bicyclic Heterocycles

Abstract

The use of alternative energy sources, such as microwaves (MW) or ultrasounds (US), and their mutual cross-combination have been widely described in the literature in the development of new synthetic methodologies in organic and medicinal chemistry. In this review, our attention is focused on representative examples, reported in the literature in the year range 2013–2023 of selected N-containing bicyclic heterocycles, with the aim to highlight the advantages of microwave- and ultrasound-assisted organic synthesis.

Ultrasonic or Microwave Modified Continuous Flow Chemistry for the Synthesis of Tetrahydrocannabinol: Observing Effects of Various Solvents and Acids

“…To our knowledge, this is the first time that sonochemistry has been merged with flow chemistry for the synthesis of THC. The use of ultrasound as an unconventional energy source has been widely described in the literature in the development of new synthetic methodologies in organic and medicinal chemistry. − …”

“…Due to the difficulty that microwave chemistry can present in scale up of batch environments, microwave-flow can possibly solve those issues as depicted in Figure c,d. Combining a sonicator with flow reactors can be advantageous in creating reactive microenvironments during the circulation around the sonicating field, and expediting reaction kinetics creates a greener way of producing products than in standard bench reactions. − …”

Microwave‐Assisted Synthesis of Fluorinated 5‐Membered Nitrogen Heterocycles

“…[79] The 8-acetyl-7-hydroxy-4-methylcoumarin ( 47) and substituted 1-(1,3-diphenyl-1H-pyrazole-4-carboxaldehyde (48) ware dissolved in ethanol having a small amount of piperidine in a glass vial. This solution was then heated by MW (100 W) for 13 min to give the fluorinated chalcones (49). The use of MW increases the yield from 58 % to 87 % in 13 min against the 24 h in conventional heating.…”

“…[41][42][43] MW-assisted synthesis takes advantage of the dielectric volumetric heating potential of microwaves, leading to faster and more selective reactions, due to the homogeneous heat distribution. [44] There are several books, journal reviews, and monographs dedicated to MW-assisted synthesis [45][46][47][48][49][50] giving in-depth coverage of the subject matter. There have recently been a few reviews published in the literature on the use of microwaves in the synthesis of N-heterocyclic compounds; [51][52][53][54][55] however, there is a lack of publications on the use of microwaves in the synthesis of fluorinated 5-membered N-heterocycles.…”