In the constellation of modern organic synthetic chemistry, 2-Tolylboronic acid (CAS: 16419-60-6) undoubtedly shines brightly. As an important member of the organoboronic acid family, this seemingly simple white crystalline powder plays an irreplaceable role in drug synthesis, materials science, and fine chemicals.
Physicochemical Properties: 2-Tolylboronic acid, also known as o-methylphenylboronic acid or o-tolylboronic acid, has the molecular formula C₇H₉BO₂ and a molecular weight of 135.96. Its structure consists of a benzene ring, an ortho-methyl group, and a boric acid group (-B(OH)₂), a unique structure that endows it with special reactivity.
Classic Grignard Reagent Method
The most commonly used industrial synthetic route involves the reaction of a Grignard reagent with a borate ester:
o-Methylbromobenzene + Mg → o-Methylphenylmagnesium bromide (Grignard reagent)
Grignard reagent + B(OiPr)₃ → Borate ester intermediate
Borate ester + HCl hydrolysis → o-Methylphenylboronic acid
Modern Synthetic Strategies
In recent years, chemists have developed several green synthetic methods:
Palladium-catalyzed boration method: Using diisopropylaminoborane as the boron source, it reacts directly with o-methylbromobenzene under the action of a palladium catalyst, avoiding the harsh conditions required by the Grignard reagent.
Lithium reagent method: Using n-butyllithium for halogen-lithium exchange at -78°C, followed by reaction with trimethyl borate, suitable for substrates sensitive to Grignard reagents.
Practical Cases in Drug Synthesis
Antitumor Drug Intermediates
o-methylphenylboronic acid (o-methylphenylboronic acid) has been used to synthesize human farnesyl pyrophosphate synthase (FPPS) inhibitors, compounds that exhibit significant antitumor activity against multiple myeloma cells. Introducing an o-tolyl group via Suzuki coupling optimizes the drug molecule’s lipophilicity and target binding ability.
Chiral Ligand Construction
In asymmetric Suzuki-Miyaura coupling, o-methylphenylboronic acid serves as a model substrate for evaluating the efficiency of novel chiral monophosphate ligands. The steric hindrance generated by its ortho-substituents provides an ideal probe for testing ligand stereoselectivity.
Sartan Antihypertensive Drug Synthesis
While o-methylphenylboronic acid is more commonly used to synthesize 2-cyano-4′-methylbiphenyl (a key intermediate in sartan drugs), it also plays a crucial role in structure-activity relationship studies of similar structures.
A deeper understanding of the reaction properties of o-methylphenylboronic acid can not only optimize existing synthetic processes but also inspire the design of next-generation catalytic systems and functional materials. In future drug development, materials innovation, and green chemistry practices, this “star molecule” in the Suzuki coupling reaction will undoubtedly continue to shine.
Post time: Feb-25-2026
