5-Butoxy-2-Chlorophenylboronic Acid: Handling & Use Guide

5-Butoxy-2-chlorophenylboronic acid is a bifunctionally substituted arylboronic acid that serves as a versatile organoboron building block in palladium-catalyzed cross-coupling reactions, medicinal chemistry, and materials science research.

Product Name

5-Butoxy-2-chlorophenylboronic acid

SKU

B180635

Molecular Formula

C10H14BClO3

Functional Groups

Boronic acid (–B(OH)₂), chloro substituent (–Cl), butoxy ether (–OC4H9)

Primary Application

Suzuki–Miyaura cross-coupling reactions and related palladium-catalyzed transformations

Storage Condition

Store in a cool, dry place away from moisture and light; recommended 2–8 °C under inert atmosphere

Handling Precaution

Use in a well-ventilated fume hood; avoid inhalation of dust; wear appropriate PPE

Chemical Identity and Structure

5-Butoxy-2-chlorophenylboronic acid (SKU: B180635) is an arylboronic acid bearing three distinct functional handles on a single phenyl ring: a boronic acid group (–B(OH)₂) at the 1-position, a chloro substituent at the 2-position (ortho), and an n-butoxy ether at the 5-position (para relative to chloro). This multifunctionality makes it a highly versatile intermediate in synthetic chemistry.

The electron-donating butoxy group and the electron-withdrawing chloro substituent create a differentiated electronic environment on the aromatic ring, influencing regioselectivity in downstream transformations. The –Cl group can itself serve as a handle for further cross-coupling reactions after the boronic acid has been consumed, enabling sequential functionalization strategies.

The molecular formula is C₁₀H₁₄BClO₃. Like most arylboronic acids, the compound exists as a mixture of the free boronic acid and its cyclic anhydride (boroxine) form depending on temperature and humidity conditions.

Applications in Cross-Coupling and Synthesis

Suzuki–Miyaura Coupling: The boronic acid moiety of 5-Butoxy-2-chlorophenylboronic acid is the primary reactive site in palladium-catalyzed Suzuki–Miyaura coupling reactions. It couples with aryl, vinyl, or heteroaryl halides (or triflates) in the presence of a Pd(0) or Pd(II) catalyst precursor, a base (e.g., K₂CO₃, Cs₂CO₃), and a protic or mixed aqueous–organic solvent system to form biaryl or styryl products.

Sequential Functionalization: The retained aryl–Cl bond after Suzuki coupling at the boronic acid site offers a secondary handle for additional metal-catalyzed reactions (e.g., Buchwald–Hartwig amination, carbonylation), enabling efficient access to complex polysubstituted aromatics from a single starting material.

Medicinal Chemistry: Substituted arylboronic acids with ether and halogen substituents are commonly employed as fragments or coupling partners in the synthesis of pharmaceutical candidates, particularly in programs targeting kinases, proteases, and other enzyme classes where biaryl pharmacophores are prevalent.

Materials Science: Arylboronic acid derivatives can be incorporated into conjugated organic materials, polymers, and supramolecular assemblies via boronate ester formation or cross-coupling polymerization.

Handling, Storage, and Stability Guidelines

Personal Protective Equipment (PPE): Always wear appropriate laboratory PPE including chemical-resistant gloves, safety goggles, and a laboratory coat when handling this compound. Conduct all weighing and solution preparation in a well-ventilated chemical fume hood to minimize dust and vapor inhalation.

Storage: Store B180635 in a tightly sealed container in a cool (recommended 2–8 °C), dry environment, protected from light and moisture. Arylboronic acids are susceptible to hydrolytic and oxidative degradation; therefore, storage under an inert gas (nitrogen or argon) blanket is strongly recommended, particularly for opened containers.

Stability Considerations: Boronic acids can undergo protodeboronation (loss of the –B(OH)₂ group) under strongly acidic or basic aqueous conditions and at elevated temperatures. Oxidation to the corresponding phenol is possible upon prolonged exposure to air and moisture. Verify compound integrity by TLC, HPLC, or NMR prior to use in sensitive synthetic applications.

Disposal: Dispose of all waste in accordance with institutional, local, and national regulations governing organoboron-containing chemical waste. Consult the current Safety Data Sheet (SDS) for detailed first-aid, fire-fighting, and disposal information.

Reaction Protocol: Suzuki–Miyaura Coupling (General Guide)

The following represents a general framework for employing 5-Butoxy-2-chlorophenylboronic acid (B180635) as the boronic acid partner in a Suzuki–Miyaura coupling reaction. Optimize conditions for your specific substrate.

1. Reagents: 5-Butoxy-2-chlorophenylboronic acid (1.0–2.0 equiv), aryl halide or pseudohalide electrophile (1.0 equiv), Pd catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, 2–5 mol%), inorganic base (e.g., K₂CO₃ or Cs₂CO₃, 2–3 equiv).
2. Solvent: DMF/H₂O, dioxane/H₂O, or EtOH/H₂O mixtures are commonly used. The presence of water facilitates transmetalation of the boronic acid.
3. Temperature: Typically 80–110 °C under reflux or in a sealed vial; reaction times range from 2 to 24 hours depending on substrate reactivity.
4. Atmosphere: Perform reactions under an inert atmosphere (N₂ or Ar) to prevent catalyst oxidation and boronic acid degradation.
5. Workup: After completion (monitor by TLC or LCMS), cool to room temperature, dilute with ethyl acetate, wash with brine, dry over MgSO₄ or Na₂SO₄, and concentrate. Purify by column chromatography.

Note: The intact aryl–Cl bond in the product can be exploited in subsequent coupling steps if desired.

Quality, Purity, and Analytical Verification

Purity Assessment: For critical synthetic applications, the purity of arylboronic acids should be confirmed prior to use. Recommended analytical methods include:

• ¹H and ¹¹B NMR Spectroscopy: Confirms structure and detects the presence of boroxine (cyclic anhydride) or protodeboronated byproducts. The ¹¹B NMR chemical shift for a free arylboronic acid typically appears near 28–32 ppm.
• HPLC: Reverse-phase HPLC with UV detection provides quantitative purity assessment.
• TLC: A rapid qualitative check using a UV-active silica plate; boronic acids may appear as distinct spots with appropriate visualization reagents.

Moisture Sensitivity: Weigh the compound quickly and reseal the container immediately under inert gas. Use freshly dried glassware to avoid adventitious moisture affecting the boronic acid or catalytic cycle.

Lot-Specific Documentation: Aladdin Scientific provides a Certificate of Analysis (CoA) for each lot of B180635. Verify the reported purity, melting point (if available), and spectral data against the CoA prior to committing material to a key experiment.

Frequently asked questions

How should I store 5-Butoxy-2-chlorophenylboronic acid to maintain its integrity?

Store B180635 in a tightly sealed vial at 2–8 °C in a cool, dry, and dark environment. After opening, transfer remaining material under an inert atmosphere (N₂ or Ar) and reseal promptly. Moisture and oxygen are the primary degradation agents for arylboronic acids.

Can the aryl chloride group in B180635 also participate in cross-coupling reactions?

Yes. The aryl–Cl bond is retained after Suzuki coupling at the boronic acid site and can subsequently participate in additional palladium-catalyzed reactions such as Suzuki coupling (with a second boronic acid partner), Buchwald–Hartwig amination, or carbonylation. This allows sequential, orthogonal functionalization from a single starting material.

What solvents and bases are recommended for Suzuki coupling with this boronic acid?

Aqueous mixtures are generally recommended: dioxane/H₂O (4:1), DMF/H₂O (9:1), or EtOH/H₂O (3:1) are commonly used solvents. K₂CO₃ (2 M aqueous) or Cs₂CO₃ are suitable bases. The water component facilitates transmetalation of the boronic acid to the palladium center.

How do I confirm the purity of B180635 before a critical reaction?

Review the Certificate of Analysis (CoA) supplied with your lot. For additional confirmation, ¹H NMR and ¹¹B NMR spectroscopy are the most informative techniques; ¹¹B NMR distinguishes free boronic acid (~28–32 ppm) from its boroxine anhydride. HPLC with UV detection provides quantitative purity data.

Is 5-Butoxy-2-chlorophenylboronic acid air- and moisture-sensitive?

Yes, like most arylboronic acids it is susceptible to oxidative degradation (forming the phenol) and hydrolysis upon prolonged exposure to air and moisture. Handle under inert atmosphere where possible, and verify integrity by NMR or HPLC if the compound has been stored for an extended period after opening.

References

1. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
2. Hall, D. G. (Ed.) Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials. Wiley-VCH, 2011.
3. Lennox, A. J. J.; Lloyd-Jones, G. C. Selection of boron reagents for Suzuki–Miyaura coupling. Chem. Soc. Rev. 2014, 43, 412–443. doi:10.1039/C3CS60197H

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