2-{[4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy}pyridin
[CAS# 1166997-30-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Benzylpyridine
• Name: 2-{[4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy}pyridin
• Molecular Formula: C₁₇H₂₀BNO₃
• Molecular Weight: 297.16
• CAS Registry Number: 1166997-30-3
• SMILES: CC1(C)COB(c2ccc(COc3ccccn3)cc2)OC1

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 433.3±30.0 ºC 760 mmHg (Calc.)^*
• Flash point: 215.8±24.6 ºC (Calc.)^*
• Index of refraction: 1.549 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

2-{[4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy}pyridine is an organoboron compound incorporating a boron-containing heterocycle (1,3,2-dioxaborinane), a benzyl ether linker, and a pyridine ring. The structure represents a hybrid scaffold that is functionally relevant in organic synthesis, particularly in the context of Suzuki–Miyaura cross-coupling reactions, where arylboronates serve as nucleophilic partners for the formation of carbon–carbon bonds.

The core of this molecule is the 1,3,2-dioxaborinane ring, a six-membered boron-containing heterocycle stabilized by two alkoxy substituents. The 5,5-dimethyl substitution on the dioxaborinane ring increases steric protection and enhances stability by reducing the rate of hydrolysis of the boronic ester moiety. This makes such boronates valuable intermediates in cross-coupling chemistry because they are more shelf-stable than their boronic acid counterparts while retaining high reactivity under palladium-catalyzed conditions.

The attachment of this boron-containing unit to the para-position of a benzyl moiety provides additional synthetic flexibility. Benzyl groups are commonly used as protective groups for alcohols and carboxylic acids and can also participate in functionalization reactions. In this structure, the benzyl group is further functionalized via an ether linkage to a pyridine ring at the 2-position. This oxygen bridge introduces a degree of conformational rigidity while maintaining electronic communication between the heteroaromatic and arylboronate components.

Pyridine, being an electron-deficient nitrogen-containing heterocycle, plays a significant role in pharmaceutical and agrochemical design. Its inclusion in this molecule adds potential coordination capabilities, especially with transition metals, and allows for interactions with biological targets via hydrogen bonding or π-π stacking. The 2-position substitution in pyridine is synthetically valuable, as it often allows for regioselective derivatization and fine-tuning of electronic properties.

The discovery and development of compounds like 2-{[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy}pyridine are grounded in the broader efforts to create boron-containing molecules that are compatible with metal-catalyzed cross-coupling reactions and biologically relevant scaffolds. Boronic esters and their derivatives became prominent after the advancement of Suzuki–Miyaura cross-coupling chemistry, for which Akira Suzuki was awarded the Nobel Prize in Chemistry in 2010. This class of reactions is widely utilized in the pharmaceutical industry for the synthesis of biaryl compounds, complex molecules, and drug candidates.

Synthetically, the compound is typically prepared by first forming the boronate ester through the reaction of a boronic acid or trifluoroborate with diols such as pinacol or neopentyl glycol. In this case, the dioxaborinane ring can be synthesized via condensation of a boronic acid with 2,2-dimethyl-1,3-propanediol. The resulting ester is then coupled to a benzyl halide that has been pre-functionalized with a pyridin-2-yloxy group, or vice versa, using a Williamson ether synthesis under basic conditions.

Applications of such molecules are primarily focused on synthetic utility. In medicinal chemistry, the modular nature of this compound enables rapid generation of analogs by varying the aryl or heteroaryl partners in cross-coupling reactions. It can be used as a building block in the design of kinase inhibitors, receptor antagonists, and imaging agents where the boronate group allows efficient incorporation into larger molecular frameworks. Additionally, the boron center in such compounds can be exploited in sensing, as boronic acids and esters form reversible covalent complexes with diols and carbohydrates, useful in chemical biology and diagnostic applications.

In conclusion, 2-{[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy}pyridine represents a chemically stable and synthetically versatile intermediate combining a boronate ester moiety with a heteroaryl ether linkage. Its design reflects the growing importance of boron chemistry in constructing complex, functionally diverse organic molecules.