Integrating Green Chemistry into Teaching Laboratories: Aqueous Suzuki–Miyaura Cross-Coupling Reaction Using a Recyclable Fluorous Precatalyst

Abstract

A method to synthesize biaryls through the Suzuki–Miyaura cross-coupling reaction using a recyclable fluorous precatalyst is described. This laboratory experiment, which demonstrates the safety benefits of green chemistry, is integrated into an upper-division course. Besides simply using the catalyst for a reaction, students can reuse the catalyst which is seldom performed in teaching laboratories. A multioutcome approach was employed for the first reaction where students are provided with different starting materials. Students elucidate the structure of the starting material/product using 1H NMR spectroscopy. Subsequently, the precatalyst is recovered using fluorous solid-phase extraction and reused in the synthesis of a precursor to valsartan. Valsartan is a drug commonly used to treat high blood pressure. Students’ feedback indicates that the laboratory session helped them better understand and apply the principles of green chemistry.

A pesquisa em Ensino de Química Verde: temas e tipologias de estudos

“…O Cluster 3 aborda o esverdeamento de sínteses orgânicas, seja pelo uso de catalisadores metálicos; pelo uso de água como solvente; ativação por micro-ondas; ou condições ambiente de temperatura e pressão. Destacam-se as reações de acoplamento do tipo Suzuki-Miyaura, geralmente catalisadas por metais, realizadas com solvente aquoso ou com ativação por micro-ondas [53][54][55][56][57], de forma similar às reações de Wittig [58,59]. Procedimentos de metátese de olefinas e reações "click", procedimentos agraciados com o prêmio Nobel nos últimos anos, também são discutidos em versões verdes, sendo realizados em condições ambiente e solvente aquoso [60,61].…”

Functionalized graphene oxide by 4-amino-3-hydroxy-1-naphthalenesulfonic acid as a heterogeneous nanocatalyst for the one-pot synthesis of tetraketone and tetrahydrobenzo[b]pyran derivatives under green conditions

“…[4][5][6][7] One of the most important applications of nanotechnology in the field of chemistry is the preparation of nanocatalysts, which have shown a significant impact on green chemistry. [8][9][10][11][12][13][14] Indeed, a variety of inorganic and organic compounds have been reported as homogeneous catalytic species, but they have disadvantages such as difficult separation and recycling, producing large quantities of hazardous waste, high cost, etc. To address these concerns, heterogeneous catalytic systems were introduced as alternatives for the homogeneous catalytic systems.…”

Preparation of Aminals under Continuous Flow Conditions

“…On the other hand, the development of continuous flow methodologies , allows for a more sustainable production of valuable substrates that are advantageous to some processes in comparison to batch mode due to (i) enhanced heat and mass transfer ability; (ii) controlled accuracy; (iii) decreased reaction time; (iv) improved safety of the reaction using extremely dangerous reactive products/intermediates at extreme conditions such as high temperature and pressure and photochemical and electrochemical transformations; (v) high reproducibility; (vi) easy process implementation via a scale-out approach, among others . Considering the emerging importance of flow chemical processes in academia and pharmaceutical and fine chemical industries, it is essential to include this topic at the early stages of chemical education and is also advantageous for more sustainable chemistry (Green Chemistry). − In fact, continuous flow reactions have been described in the context of undergraduate student’s laboratory experiments, namely, in methylation of 2-naphthol by dimethyl carbonate, representative synthetic transformations (amidation, esterification, ester hydrolysis, condensation, Grignard reaction, and bromination), synthesis of 5-hydroxymethylfurfural (HMF), aryl-aldehyde oxidation, photocatalytic thiol-ene reaction, biodiesel production, photopinacol coupling of benzophenone, photooxygenation of citronellol, reaction of diphenyldiazomethane with benzoic acids, and acetylation of ethylene glycol …”