2,5-Dimethoxypyridine-4-boronic acid
[CAS# 1630193-77-9]

Identification

• Classification: Chemical reagent >> Organic reagent >> Boric acid
• Name: 2,5-Dimethoxypyridine-4-boronic acid
• Molecular Formula: C₇H₁₀BNO₄
• Molecular Weight: 182.97
• CAS Registry Number: 1630193-77-9
• EC Number: 863-756-8
• SMILES: B(C1=CC(=NC=C1OC)OC)(O)O

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 381.4±52.0 ºC 760 mmHg (Calc.)^*
• Flash point: 184.5±30.7 ºC (Calc.)^*
• Index of refraction: 1.517 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Danger
• Hazard Statements: H302-H315-H319-H331-H335-H361fd-H412
• Precautionary Statements: P203-P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P316-P318-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H331
Skin irritation	Skin Irrit.	2	H315
Germ cell mutagenicity	Muta.	2	H341
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

2,5-Dimethoxypyridine-4-boronic acid is a heterocyclic organoboron compound in which a pyridine ring is substituted with methoxy groups at the 2- and 5-positions and a boronic acid functionality at the 4-position. The combination of electron-donating methoxy groups and the boronic acid moiety imparts unique chemical reactivity, making the compound valuable as a building block in organic synthesis, particularly in cross-coupling reactions. Boronic acids are well-established intermediates for constructing carbon–carbon and carbon–heteroatom bonds due to their stability and versatility under mild reaction conditions.

The synthesis of 2,5-dimethoxypyridine-4-boronic acid generally involves the selective borylation of a 2,5-dimethoxypyridine precursor. Transition metal-catalyzed processes, such as palladium- or iridium-catalyzed borylation, are commonly employed to install the boronic acid group at the 4-position with high regioselectivity. Protection of methoxy groups is typically unnecessary due to their stability under borylation conditions, simplifying the synthetic procedure. The product is usually isolated as a crystalline solid and purified through recrystallization or chromatography.

In organic synthesis, this compound serves as a key intermediate for Suzuki–Miyaura cross-coupling reactions, enabling the formation of substituted pyridines with diverse functional groups. The boronic acid group reacts with aryl or vinyl halides under palladium catalysis to construct new carbon–carbon bonds efficiently. The presence of methoxy substituents modulates the electronic properties of the pyridine ring, influencing reaction rates, selectivity, and the overall reactivity of the molecule in multi-step synthetic sequences.

In medicinal chemistry, derivatives derived from 2,5-dimethoxypyridine-4-boronic acid are explored as pharmacologically active compounds, including enzyme inhibitors and receptor ligands. The pyridine nitrogen can act as a hydrogen-bond acceptor or coordinate with metal centers in biological systems, while the methoxy groups provide additional hydrogen-bonding interactions and influence lipophilicity and solubility. Through cross-coupling or further functionalization, the boronic acid can be transformed into diverse molecular frameworks suitable for biological evaluation.

The compound is also of interest in chemical methodology and materials science. Its boronic acid functionality enables exploration of selective transformations, including oxidative couplings, condensation reactions, and the preparation of boronate esters for downstream applications. In materials research, boronic acid derivatives have been employed for the development of sensors, supramolecular assemblies, and polymeric frameworks, exploiting their capacity to form reversible covalent bonds with diols and other nucleophiles.

Physically, 2,5-dimethoxypyridine-4-boronic acid is typically obtained as a solid with moderate solubility in polar organic solvents such as dimethylformamide, methanol, and ethanol. It is stable under ambient laboratory conditions but should be stored away from strong acids, bases, and oxidizing agents that may degrade the boronic acid or affect the methoxy substituents. Proper handling ensures the compound remains suitable for synthetic, biological, and materials applications.

Overall, 2,5-dimethoxypyridine-4-boronic acid is a versatile heterocyclic boronic acid featuring methoxy-substituted pyridine and a reactive boronic acid moiety. Its combination of functional groups allows selective transformations and cross-coupling reactions, making it a valuable building block for the synthesis of substituted pyridines, bioactive molecules, and functional materials in organic and medicinal chemistry.

References

2024. Structure-based design and synthesis of novel FXIa inhibitors targeting the S2' subsite for enhanced antithrombotic efficacy. Molecular Diversity.
DOI: 10.1007/s11030-024-11024-2