Iodination of vanillin and subsequent Suzuki-Miyaura coupling: two-step synthetic sequence teaching green chemistry principles

Abstract

A two-step synthetic sequence was developed for the undergraduate organic chemistry laboratory using vanillin as the starting material. The multi-step synthesis was designed to replace two traditional experiments teaching electrophilic aromatic substitution and carbon-carbon bond forming chemistries with greener transformations. Vanillin is iodinated using Oxone® and potassium iodide in refluxing water, and students are tasked with determining the position of aromatic substitution using 1 H NMR spectroscopy. The tan, shiny, pleasant-smelling iodovanillin is subsequently used in an aqueous Suzuki-Miyaura reaction with para-methylphenylboronic acid; strategically chosen to afford a second instructive 1 H NMR spectrum. Both conventional heating and microwave conditions can be employed for the palladium-catalyzed reaction. This synthetic sequence, successfully performed over multiple semesters by hundreds of students, models green chemistry principles through the use of a potentially renewable feedstock and safer reagents, the choice of water as a safer reaction solvent, and the employment of a catalytic reaction. Additionally, the sequence minimizes waste in teaching labs through use of an intermediate product.

Environmentally Friendly Organic Chemistry Laboratory Experiments for the Undergraduate Curriculum: A Literature Survey and Assessment

“…Wissinger and co-workers reported a two-step synthesis involving iodination followed by a Suzuki−Miyaura coupling. 33 This experimental sequence adapts previously reported procedures for iodinations 34 as well as the Suzuki−Miyaura coupling suitable for undergraduate laboratories. It offers a greener alternative to electrophilic iodination, which is carried out using oxone and KI instead of molecular I 2 , and the subsequent Suzuki−Miyaura coupling is carried out under aqueous conditions (Scheme 16).…”

“…Wissinger and co-workers reported a two-step synthesis involving iodination followed by a Suzuki–Miyaura coupling . This experimental sequence adapts previously reported procedures for iodinations as well as the Suzuki–Miyaura coupling suitable for undergraduate laboratories.…”

A promise to a sustainable future: 10 years of the Green Chemistry Commitment at Beyond Benign

“…81,82 Besides being promoted by a wide range of resources highlighted herein, this low-barrier incorporation of more sustainable teaching, research, and practices is also supported by the existence of a proactive and engaging community of green chemistry practitioners and educators supported by the GCC program across the globe. 83–103…”

Exploring the Effect of Phosphine Ligand Architecture on a Buchwald–Hartwig Reaction: Ligand Synthesis and Screening of Reaction Conditions

“…Palladium-catalyzed coupling reactions are fundamental methods in synthetic organic chemistry . Introductory-level textbooks have recently begun to include discussion of this area, and many instructional laboratory exercises are now available for showcasing the Suzuki–Miyaura coupling − and related reactions. − In contrast to these C–C σ-bond forming processes, the Pd-catalyzed coupling of amines with organic halides to form C–N σ-bonds, termed the Buchwald–Hartwig amination (BHA), is underrepresented in the instructional literature. Indeed, despite its broad utility, − only three instructional laboratory modules focusing on the BHA reaction have been reported.…”