The Isomer-Specific Fluorinated Building Block for Voriconazole, Fluconazole, and Fluoroquinolone Antibiotics: 2,4-Difluorobenzoic Acid (CAS# 1583-58-0)

2,4-Difluorobenzoic acid (CAS# 1583-58-0), also known as 2,4-difluorobenzenecarboxylic acid or 2,4-difluorophenylcarboxylic acid, is a fluorinated aromatic carboxylic acid with the molecular formula C₇H₄F₂O₂ and a molecular weight of 158.10 g/mol. Its molecular structure consists of a benzoic acid core bearing two fluorine atoms at the 2- and 4-positions of the aromatic ring. This specific 2,4-difluoro substitution pattern—distinguishing it from five other difluorobenzoic acid regioisomers with identical molecular formulas—confers unique electronic properties that directly influence its pKa, chromatographic retention time, and synthetic utility, making it the sole acceptable starting material for introducing the 2,4-difluorophenyl moiety into voriconazole, fluconazole, and fluoroquinolone antibiotics.

As a white to light yellow crystalline powder with a melting point of 188–190°C and a boiling point of 239.5±20.0°C, the compound is soluble in water and common organic solvents. It is typically supplied at ≥98% purity (titration) and should be stored in a tightly closed container in a cool, dry, well-ventilated area away from incompatible substances. The compound is classified as an irritant (Xi) with risk codes R36/37/38 and is assigned WGK Germany classification 3.

2,4-Difluorobenzoic acid is a strategically important fluorinated building block that serves as the definitive intermediate in the synthesis of Voriconazole—a triazole antifungal agent used to treat serious fungal infections including invasive aspergillosis and candidemia—as well as Fluconazole and fluoroquinolone antibiotics. Its unique substitution pattern is essential for the correct stereochemistry and biological activity of the final drug substances. Beyond its flagship pharmaceutical applications, the compound functions as a precursor for fluorinated liquid crystals, agrochemical actives, and specialty functional materials. Based on its chemical characteristics and industrial significance, this article systematically analyzes the key properties, core application areas, global market structure, regulatory landscape, and future outlook of this strategically important fluorinated aromatic building block.

Key Properties and Reactivity Profile

2,4-Difluorobenzoic acid (CAS# 1583-58-0) is a regioisomer-specific fluorinated aromatic acid whose value derives from its unique 2,4-substitution pattern.

Key physicochemical parameters include:

• Molecular Formula: C₇H₄F₂O₂
• Molecular Weight: 158.10 g/mol
• CAS Number: 1583-58-0
• EINECS Number: 216-430-9
• MDL Number: MFCD00011670
• Appearance: White to light yellow crystalline powder
• Purity: ≥98% (titration) / ≥99% (HPLC) available
• Melting Point: 188–190°C
• Boiling Point: 239.5±20.0°C at 760 mmHg
• Flash Point: 98.6°C
• Density: 1.432 g/cm³
• LogP: 1.663
• Solubility: Soluble in water
• SMILES: C1=CC(=C(C=C1F)F)C(=O)O
• InChIKey: NJYBIFYEWYWYAN-UHFFFAOYSA-N
• Storage: Store in a tightly closed container in a cool, dry, well-ventilated area away from incompatible substances
• GHS Classification: Warning; H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation)
• WGK Germany: 3 (high hazard to water)
• HS Code: 2916399090

The compound’s reactivity is defined by its carboxylic acid group, which enables amide coupling, esterification, and salt formation, and its 2,4-difluoro substitution pattern, which modulates the electronic environment of the ring and provides the correct regiochemistry for the 2,4-difluorophenyl pharmacophore. The position of fluorine substitution is the primary determinant of both physical properties and chemical reactivity, making simple in-class substitution unreliable. 2,4-Difluorobenzoic acid exhibits a distinct pKa, chromatographic retention time, and synthetic utility compared to its monofluorinated and other difluorinated analogs. Substituting a different isomer compromises synthetic pathways and can yield an inactive product, underscoring the critical importance of regioisomer specificity in pharmaceutical manufacturing.

Core Application Fields and Demand

Market demand for 2,4-difluorobenzoic acid (CAS# 1583-58-0) is concentrated in four primary sectors: pharmaceutical synthesis and drug intermediates (approximately 50–55% of global consumption), agrochemical development (approximately 20–25%), liquid crystal and materials science (approximately 15–20%), and analytical chemistry and research applications (approximately 10–15%). Its unique 2,4-difluoro substitution pattern and role as a definitive intermediate for major antifungal and antibiotic drugs serve as the core drivers of sustained demand growth.

In pharmaceutical synthesis and drug intermediates, 2,4-difluorobenzoic acid is a critical building block for the synthesis of Voriconazole (Vfend®), a triazole antifungal agent developed by Pfizer for the treatment of invasive aspergillosis, candidemia, and other serious fungal infections. The 2,4-difluorophenyl moiety is a critical pharmacophore in Voriconazole, contributing to its broad-spectrum antifungal activity and favorable pharmacokinetic profile. The compound also serves as a key intermediate for Fluconazole (Diflucan®), another widely prescribed triazole antifungal agent, and for fluoroquinolone antibiotics, where the 2,4-difluorophenyl moiety is introduced into the quinolone core. The compound is also used as an analytical standard for HPLC method development, with its distinct retention time enabling fluorobenzoic acid isomer separation. Substituting a different isomer compromises synthetic pathways and can yield an inactive product, making the 2,4-difluoro specificity essential for regulatory and pharmacopeial compliance.

In agrochemical development, 2,4-difluorobenzoic acid is employed as an intermediate in the formulation of herbicides, contributing to more effective weed control while minimizing environmental impact. The compound is also used in the synthesis of pesticides and other crop protection agents, where the fluorinated aromatic scaffold enhances metabolic stability and target selectivity.

In liquid crystal and materials science, 2,4-difluorobenzoic acid is a valuable synthon for the preparation of high-performance liquid crystals, serving as a precursor in the manufacture of fluorinated liquid crystals for display technologies. The compound is also used in the synthesis of functional polymers and specialty materials requiring specific electronic or optical properties.

In analytical chemistry and research, 2,4-difluorobenzoic acid serves as a biochemical reagent for life science research and as a sulfonylation reagent for organic synthesis and drug discovery. Its unique substitution pattern makes it a valuable reference standard for HPLC method development and validation.

Major Market Participants

The global supply system for 2,4-difluorobenzoic acid (CAS# 1583-58-0) features a pattern of “specialized fluorochemical manufacturers, multinational research chemical distributors, and Chinese producers serving distinct market segments.” As a specialized regioisomer-specific fluorinated building block rather than a bulk commodity, the market is characterized by a moderate number of suppliers catering to pharmaceutical R&D, agrochemical development, and materials science applications. Global market research reports on 2,4-difluorobenzoic acid provide comprehensive data on manufacturers, consumers, production situation, supply and demand analysis, price analysis, and import/export situation across Europe, Asia, North America, and other regions, with forecasts extending through 2029.

In the global research and high-purity segment, key international suppliers include Tokyo Chemical Industry (TCI), offering the compound at >98.0% (T) purity under product code D1833, available in 5 g and 25 g quantities with stock in the USA and Japan. Thermo Fisher Scientific (Alfa Aesar) offers the compound at 98% purity under catalog number ALFA13403. Chem-Impex International offers ≥98% (assay by titration) purity with comprehensive documentation including SDS, product specifications, and Certificates of Analysis. AKSci offers 95% purity under product code J94004. These suppliers serve the pharmaceutical, biotechnology, and academic research communities with products that meet rigorous quality specifications.

In the industrial and large-scale production segment, Chinese manufacturers have emerged as significant players in the global supply chain. XinChem is a reliable manufacturer and supplier of high-purity 2,4-difluorobenzoic acid from China, offering the compound with stringent quality standards for use in pharmaceutical synthesis, agrochemical development, and liquid crystal applications. XinChem provides the compound as a white to light yellow crystalline powder with comprehensive quality documentation and flexible packaging options, with risk and safety information available including hazard symbols, risk codes, and safety data. Other Chinese suppliers include Bide Pharmatech (毕得医药) , offering the compound at 98% purity with batch quality inspection reports (NMR, HPLC, GC), Shandong Xuchen Chemical (山东旭晨化工) , offering 99% purity with competitive pricing (1 kg/8 RMB; 100 kg/7 RMB; 1000 kg/6 RMB), and Hubei Kele Fine Chemical (湖北科乐精细化工) , offering 98% HPLC purity in 2 g packaging at 11 RMB. Chinese suppliers offer the compound at various purity grades (typically 98–99%) and packaging options—from grams to multi-kilogram quantities—serving both domestic and export markets with competitive pricing.

Regional Market Dynamics

The global 2,4-difluorobenzoic acid market exhibits distinct regional characteristics, with production concentrated in Asia-Pacific (particularly China) and consumption distributed across North America, Europe, and the Asia-Pacific region, aligned with the pharmaceutical, agrochemical, and materials science industries in these regions.

The Asia-Pacific region has emerged as a significant production hub for 2,4-difluorobenzoic acid, with China hosting numerous manufacturers and suppliers including XinChem. The region’s competitive advantages include lower production costs, established chemical infrastructure, and proximity to rapidly growing pharmaceutical and agrochemical industries. Chinese suppliers offer the compound at various purity grades (typically 98–99%) and packaging options, serving both domestic and export markets. The growing pharmaceutical R&D and API manufacturing sectors in China, Japan, South Korea, and India continue to drive regional consumption growth.

North America remains a key market for high-purity and research-grade 2,4-difluorobenzoic acid, driven by demand from the pharmaceutical industry, biotechnology companies, and academic research institutions. The United States hosts numerous research organizations, pharmaceutical companies, and contract research organizations that require high-quality fluorinated building blocks for drug discovery and development. TCI America, Thermo Fisher Scientific, and Chem-Impex International serve the North American market with extensive distribution networks. The region’s well-established regulatory framework and emphasis on product quality support demand for high-grade research chemicals and pharmaceutical intermediates.

Europe is characterized by stringent regulatory requirements, including REACH registration, and a strong focus on quality and sustainability in pharmaceutical and chemical research. European pharmaceutical companies, agrochemical developers, and research institutions demand high-purity fluorinated building blocks with comprehensive documentation. The region’s advanced pharmaceutical and biotechnology sectors support steady demand for 2,4-difluorobenzoic acid.

Japan represents a specialized market where 2,4-difluorobenzoic acid is supplied by TCI Chemicals and other distributors for pharmaceutical research, agrochemical development, and liquid crystal materials applications.

Regulatory and Safety Considerations

As a research chemical, pharmaceutical intermediate, and fluorinated building block, 2,4-difluorobenzoic acid (CAS# 1583-58-0) is subject to regulatory oversight in major global economies. Compliance with relevant regulations is essential for market access and trade.

GHS classification and handling: 2,4-Difluorobenzoic acid is classified with the signal word ”Warning” . Hazard statements include H315 (Causes skin irritation), H319 (Causes serious eye irritation), and H335 (May cause respiratory irritation). Precautionary statements include P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P264 (Wash face, hands and any exposed skin thoroughly after handling), P271 (Use only outdoors or in a well-ventilated area), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P302+P352 (IF ON SKIN: Wash with plenty of soap and water), P304+P340 (IF INHALED: Remove person to fresh air and keep comfortable for breathing), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing), P312 (Call a POISON CENTER or doctor if you feel unwell), P362+P364 (Take off contaminated clothing and wash it before reuse), P403+P233 (Store in a well-ventilated place; keep container tightly closed), and P501 (Dispose of contents/container to an approved waste disposal plant). The compound is classified as Skin Irrit. 2, Eye Irrit. 2, and STOT SE 3. The WGK Germany classification is 3 (high hazard to water).

Storage and stability: 2,4-Difluorobenzoic acid should be stored in a tightly closed container in a cool, dry, well-ventilated area away from incompatible substances. The compound is stable at room temperature in closed containers under normal storage and handling conditions.

Regulatory compliance: In the European Union, the compound must comply with REACH registration requirements for import and use. Manufacturers and suppliers must provide comprehensive Safety Data Sheets (SDS) and maintain appropriate documentation. In the United States, 2,4-difluorobenzoic acid is intended for research and development use only and is not intended for therapeutic, food, cosmetic, or consumer applications unless explicitly stated otherwise. For pharmaceutical intermediate applications, manufacturers must comply with relevant FDA regulations and quality standards.

Transport information: 2,4-Difluorobenzoic acid is not classified as hazardous material for DOT/IATA transport purposes. Proper packaging, labeling, and documentation are nevertheless required for international shipping. The HS code for the compound is 2916399090 (other aromatic carboxylic acids and their derivatives).

Future Outlook

The market outlook for 2,4-difluorobenzoic acid is positive, supported by several key growth drivers across its major application segments. While the compound remains a relatively specialized fluorinated building block, its role as the definitive intermediate for voriconazole, fluconazole, and fluoroquinolone antibiotics positions it for steady growth in the coming years.

Key growth drivers include:

1. Expansion of the antifungal therapeutics market: The growing global demand for voriconazole and fluconazole—driven by increasing incidence of invasive fungal infections in immunocompromised patients, aging populations, and expanding access to healthcare in developing countries—drives demand for the key intermediate 2,4-difluorobenzoic acid.
2. Growth in fluoroquinolone antibiotic production: The continued global demand for fluoroquinolone antibiotics for the treatment of bacterial infections supports steady consumption of 2,4-difluorobenzoic acid as a key building block.
3. Increasing demand for fluorinated liquid crystals: The expanding market for high-performance liquid crystal displays and specialty fluorinated materials creates new opportunities for the compound in materials science.
4. Expansion of pharmaceutical R&D in Asia: The growth of pharmaceutical R&D and API manufacturing in China and India—driven by increasing investment in generic drug production and innovative drug discovery—supports demand for high-quality pharmaceutical intermediates.
5. Advantages of regioisomer-specific building blocks: The growing emphasis on regioisomer precision in drug design drives demand for 2,4-difluoro-specific building blocks that enable the correct stereochemistry and biological activity of final drug substances.

Challenges and considerations:

• Regulatory compliance: Increasingly stringent pharmaceutical and chemical regulations may require ongoing investment in quality systems and documentation.
• Regioisomer differentiation: The specific 2,4-difluoro substitution pattern must be carefully distinguished from other difluorobenzoic acid regioisomers, necessitating rigorous quality control and analytical verification.
• Competition from alternative building blocks: The market faces competition from other fluorinated benzoic acids and alternative synthetic routes to voriconazole and fluoroquinolone intermediates.
• Limited scale: As a relatively specialized compound, the market for 2,4-difluorobenzoic acid is smaller than that of commodity chemicals.
• Handling requirements: The compound’s irritant classification (H315, H319, H335) requires appropriate safety measures during handling and storage.

To succeed in this evolving market landscape, suppliers must focus on product quality (particularly regioisomeric purity and batch-to-batch consistency), supply chain reliability, regulatory compliance, and responsive customer service. Companies that can offer high-purity products, flexible packaging options, and technical support for pharmaceutical, agrochemical, and materials science applications will be well-positioned to capture growing demand.

Shanghai XinChem Co., Ltd. (XinChem)

As a world-leading supplier of organic chemicals and fluorinated building blocks, Shanghai XinChem Co., Ltd. (XinChem) is dedicated to meeting the innovative needs of the pharmaceutical, agrochemical, and fine chemical industries. Leveraging extensive experience and advanced manufacturing capabilities, XinChem provides high-quality 2,4-Difluorobenzoic Acid (CAS# 1583-58-0) to customers worldwide. As a trusted manufacturer and supplier based in China, XinChem combines competitive pricing, reliable supply, and exceptional service to establish itself as a preferred partner for research institutions, pharmaceutical companies, and industrial manufacturers seeking this versatile regioisomer-specific fluorinated aromatic building block.

1. Technical Advantages

Advanced Synthesis and Purification Processes
XinChem utilizes state-of-the-art manufacturing facilities and rigorous quality control measures to ensure the purity, consistency, and safety of its 2,4-difluorobenzoic acid products. The production process incorporates established synthetic routes—including the selective fluorination of chlorobenzoic acid derivatives and the oxidation of 2,4-difluorotoluene—enabling the delivery of products with purity ≥98% (titration) and ≥99% (HPLC) to meet diverse application requirements. Strict process control ensures consistent regioisomeric purity, minimal impurities, and batch-to-batch reproducibility, providing customers with reliable performance in voriconazole synthesis, fluoroquinolone antibiotic production, and liquid crystal material development.

Full-Chain Quality Control
The production process strictly adheres to international quality standards, with comprehensive quality control covering raw material sourcing, in-process monitoring, and finished product testing. Each batch is accompanied by a detailed Certificate of Analysis (COA) documenting physical and chemical properties, purity data (titration and HPLC), melting point (188–190°C), and impurity profiles. This commitment to quality ensures that XinChem’s 2,4-difluorobenzoic acid meets the stringent requirements of pharmaceutical R&D, agrochemical development, and materials science applications.

2. Product Advantages

High Purity and Consistent Quality
XinChem offers 2,4-difluorobenzoic acid with purity ≥98% (titration) and ≥99% (HPLC), ensuring optimal performance in voriconazole synthesis, fluoroquinolone antibiotic production, and liquid crystal material development. The product’s high purity and regioisomeric specificity minimize the risk of unwanted side reactions and impurities, making it suitable for demanding applications in drug discovery, crop protection, and advanced materials.

Comprehensive Specifications
Key specifications include:

• Molecular Formula: C₇H₄F₂O₂
• Molecular Weight: 158.10 g/mol
• CAS Number: 1583-58-0
• Synonyms: 2,4-Difluorobenzenecarboxylic acid; 2,4-Difluorophenylcarboxylic acid
• MDL Number: MFCD00011670
• Appearance: White to light yellow crystalline powder
• Purity: ≥98% (titration) / ≥99% (HPLC) available
• Melting Point: 188–190°C
• Boiling Point: 239.5±20.0°C at 760 mmHg
• Density: 1.432 g/cm³
• Storage: Store in a tightly closed container in a cool, dry, well-ventilated area away from incompatible substances

Flexible Packaging Solutions
XinChem provides a range of packaging options to accommodate diverse customer needs, from laboratory-scale quantities (1 g, 5 g, 10 g, 25 g, 100 g) to industrial-scale packaging (500 g, 1 kg, 25 kg/drum, 200 kg/drum) and bulk shipments. Customized packaging solutions are available upon request, ensuring safe handling, storage, and transportation.

3. Application Fields

As a versatile regioisomer-specific fluorinated aromatic building block, 2,4-Difluorobenzoic Acid (CAS# 1583-58-0) exhibits wide application value across multiple industries:

Pharmaceutical Synthesis and Drug Intermediates:

• Key intermediate for Voriconazole (Vfend®), a triazole antifungal agent for invasive aspergillosis and candidemia
• Building block for Fluconazole (Diflucan®), a widely prescribed triazole antifungal agent
• Precursor for fluoroquinolone antibiotics with the 2,4-difluorophenyl moiety
• Analytical standard for HPLC method development and fluorobenzoic acid isomer separation

Agrochemical Development:

• Intermediate for herbicides and pesticides with improved efficacy and environmental profiles
• Building block for crop protection agents

Liquid Crystal and Materials Science:

• Valuable synthon for high-performance liquid crystals for display technologies
• Precursor for fluorinated functional materials with specific electronic or optical properties

Analytical Chemistry and Research:

• Biochemical reagent for life science research
• Sulfonylation reagent for organic synthesis and drug discovery

4. Service Support

Technical Expertise and Customized Solutions
XinChem’s team of experienced chemists and application engineers provides full technical support throughout the customer journey—from product selection and specification development to application guidance and troubleshooting. Whether customers require optimization of synthetic routes, guidance on regioisomer selection, or assistance with regulatory documentation, XinChem’s technical experts are ready to help. Custom synthesis and contract manufacturing with flexible scaling from R&D to commercial quantities are available upon request.

Global Logistics and Reliable Supply
With established supply chains serving markets across Europe, North America, Asia-Pacific, and beyond, XinChem ensures timely delivery and consistent product availability. The company’s logistics team manages all aspects of international shipping, including customs clearance and documentation, with appropriate protection from moisture for product stability.

Regulatory Support
XinChem provides comprehensive documentation to support regulatory compliance, including Safety Data Sheets (SDS), Certificates of Analysis (COA), and other required certificates. The company stays current with evolving regulatory requirements in major markets, including REACH, TSCA, and other regional regulations, helping customers navigate the complexities of global trade.

5. Reasons to Choose XinChem

• Professionalism: Extensive experience and deep expertise in fluorinated building block synthesis and supply.
• Quality: Rigorous quality control, high purity (≥98% to ≥99%), regioisomeric specificity, and adherence to international standards.
• Reliability: Stable supply, competitive pricing, and timely delivery.
• Flexibility: Customized solutions to meet diverse customer needs, including custom synthesis and packaging.
• Service: Responsive technical support and comprehensive documentation.

Contact us today to start your partnership with XinChem!

Website: www.xinchem.com

Email: sales1@xinchem.com

WhatsApp: +86 18049800532