2-Amino-4-bromo-3-fluorobenzoic acid:Exports & Compliance White Paper 2026

I. Executive Summary

2-Amino-4-bromo-3-fluorobenzoic acid (CAS 1416013-62-1) is a heavily substituted anthranilic acid. Its carboxyl group at C1, amine at C2, fluorine at C3 and bromine at C4 give a single small molecule carrying four orthogonal handles: a carboxylic acid for amide formation, an ortho-aminobenzoic acid unit for cyclocondensation, an aryl bromide for palladium-catalysed cross-coupling, and a fluorine substituent that tunes acidity, conformation and metabolic stability. That density of functionality is why it appears in anthranilamide diamide insecticide programmes and in quinazolinone medicinal chemistry.

This article is written from a contract development and manufacturing perspective. The compound itself has no approved therapeutic or pesticidal indication; it is supplied as a research and development intermediate, labelled research use only and not for human or veterinary use, and not as a finished consumer or formulated product. Commercial work therefore centres on custom synthesis, regioselective halogenation, process research and scale-up, analytical method development and validation, research-use-only versus GMP campaigns, and technology transfer to pharmaceutical, agrochemical and contract research partners.

Four issues decide qualification. Regioselectivity is the first, because a wrongly placed bromine gives an isomer that behaves very differently downstream. The second is decarboxylation: anthranilic acids lose carbon dioxide on heating or under strongly acidic conditions, so process and storage temperature matter. The third is elemental impurity control under ICH Q3D for palladium, iron and copper. The fourth is fluorinated-substance screening, where customers increasingly ask whether a single aromatic carbon-fluorine bond brings the molecule inside per- and polyfluoroalkyl substance restrictions.

II. Product Deep Dive: Molecular Mechanisms and Production Evolution

2.1 Physicochemical Properties and Mechanisms

Anthranilic acids are amphoteric and extensively hydrogen-bonded: the ortho amine and carboxyl group form an intramolecular interaction that reduces amine nucleophilicity, raises acid strength relative to unsubstituted benzoic acid and stabilises the zwitterionic solid. Substitution sharpens those effects. The fluorine at C3 withdraws inductively and blocks a metabolically labile position, the bromine at C4 sits para to the carboxyl group where it is well placed for oxidative addition in Suzuki, Sonogashira and Buchwald-Hartwig chemistry, and together the halogens make the ring electron-poor enough for nucleophilic aromatic substitution under forcing conditions.

• Orthogonal reactivity of the four handles: The acid is activated and coupled to amines to give anthranilamides, the ortho aminobenzoic acid unit condenses to benzoxazinones and quinazolinones, and the aryl bromide is reserved as a late-stage coupling point. The practical consequence is that a medicinal chemistry team can hold one intermediate and diversify in several directions without redesigning the route.
• Decarboxylation and thermal sensitivity: Anthranilic acids decarboxylate far more readily than benzoic acid because the ortho amine assists carbon dioxide loss through a cyclic transition state. Drying at high jacket temperature and prolonged acid reflux are therefore the operations most likely to generate the des-carboxy impurity, and process design must keep a margin below the onset temperature measured by differential scanning calorimetry.

2.2 Synthesis and Manufacturing Technologies

Routes fall into three families. The most direct is regioselective electrophilic bromination of a 2-amino-3-fluorobenzoic acid or its ester with N-bromosuccinimide or bromine, relying on the amine to direct substitution to the position para to itself; the amine is often acylated first to moderate its reactivity and suppress dibromination. The second family uses directed ortho metalation or halogen-lithium exchange on a protected anthranilic derivative to install the halogen with positional certainty. The third builds the substitution pattern from a halogenated fluorotoluene or fluoronitrobenzene by oxidation or reduction chemistry.

• Regioselective halogenation and protecting-group strategy: The choice is between speed and certainty. Direct bromination is short and cheap but produces isomeric and dibrominated by-products that must be rejected by crystallisation; protecting the amine as an acetamide or carbamate improves selectivity and simplifies work-up at the cost of two extra steps. Development work usually compares both on isolated yield, isomer rejection and waste load before committing.
• Metal-catalysed steps and impurity purging: Where coupling or cyanation steps are involved, spent palladium and copper must be removed by scavenging resins, thiol or charcoal treatment and polish filtration, then reported against ICH Q3D limits. Residual bromide, fluoride, regioisomeric acids and the des-carboxy impurity are tracked by liquid chromatography, and final isolation uses a crystallisation that rejects isomers rather than a chromatographic step wherever the campaign is expected to scale.

2.3 Core Application Matrix

• Anthranilamide diamide insecticide research: The compound is a recognised entry point to anthranilamide diamides, the class of ryanodine receptor modulators used in modern crop protection. The acid is coupled to an anthranilamide core and the aryl bromide is then used for diversification. Material is supplied research-use-only or as a qualified intermediate; the compound itself is not an approved active substance.
• Pharmaceutical building block for fused heterocycles: Anthranilic acids convert to benzoxazinones and thence to quinazolinones and quinazolines, scaffolds that recur in kinase inhibitor programmes, and the fluorine and bromine allow property tuning and late-stage coupling. These customers buy grams to kilograms, expect full structural confirmation, and require impurity and elemental data suitable for inclusion in a regulatory filing.
• Cross-coupling platform and reference-standard supply: The aryl bromide is also bought as a platform substrate for Suzuki, Sonogashira and Buchwald-Hartwig method development, for building screening libraries, and as an analytical or impurity standard for method validation. Small volumes, high documentation intensity and a strong preference for lot continuity characterise this channel.

III. Global Market Supply-Demand Landscape and Export Trends

3.1 Demand Drivers and Market Shifts

Demand is programme-driven and lumpy. Agrochemical discovery around diamide chemistry and continued pharmaceutical interest in halogenated heteroaromatic and quinazolinone scaffolds generate campaigns that can move from grams to tens of kilograms in a year and then stop. Two shifts shape the market: sponsors increasingly outsource regioselective halogenation rather than run cryogenic metalation themselves, and they increasingly demand that the supplier be able to continue the same route into qualified GMP supply rather than handing over a laboratory procedure.

3.2 Capacity Distribution and Export Flows

There is no dedicated commodity capacity for this substance; it is made in multi-purpose kilogram labs and pilot plants. Chinese suppliers in Zhejiang, Jiangsu and Shandong combine electrophilic halogenation, fluorinated aromatic feedstock and fast quotation; Indian CDMOs in Gujarat, Hyderabad and Bengaluru provide route development, analytical validation and documented GMP transition; European and Japanese specialists contribute fluorination and halogenation expertise, high-purity finishing and regulatory writing. Shipments are small, high-value air-freight consignments moving to research and development locations and pilot plants in Europe and North America.

3.3 Market Bifurcation and Pricing Dynamics

Pricing bifurcates by service tier rather than by molecule. Catalogue research-use-only material is quoted per gram with a basic certificate of analysis, whereas a development programme covering route selection, isomer control, analytical validation, thermal safety testing and a GMP campaign is quoted as a project with milestones. Because the dominant cost is analytical and process-development labour, buyers achieve better outcomes by funding route and method development early and by agreeing isomer and metal specifications before the first campaign.

IV. In-depth Analysis of Global Compliance and Regulatory Barriers

Compliance is two-layered. As a traded chemical the substance must satisfy inventory, registration and classification rules; as an intermediate for crop protection or pharmaceutical customers it must also satisfy the quality-system expectations of the sponsor's filing.

4.1 European Market: REACH, CLP, and Sector-Specific Directives

• REACH registration, intermediate status and fluorinated-substance screening: Registration obligations depend on tonnage and on whether the substance is placed on the market as an isolated intermediate under strictly controlled conditions, which may allow a reduced dossier; buyers should verify the number, tonnage band and registrant in the ECHA database or buy through an EU-established Only Representative. On fluorine, the compound carries a single aromatic carbon-fluorine bond and no perfluorinated methyl or methylene carbon, so it falls outside the per- and polyfluoroalkyl substance definition used in the current universal restriction proposal, but customers increasingly request a written statement plus total-fluorine or adsorbable organic halide data.
• CLP classification and sector product rules: Importers must self-classify and notify to the C and L Inventory, with irritation and aquatic hazard endpoints assessed for halogenated aromatic acids, and the outcome reflected in the safety data sheet and label. Finished crop protection products are separately governed by Regulation (EC) No 1107/2009, under which the active substance, not the intermediate, must be approved; the intermediate supplier supports that process with impurity and specification data rather than claiming any approval.

4.2 North American Market: TSCA, EPA, and FDA Regulations

• TSCA inventory, research and development exemption and FIFRA boundaries: Commercial import into the United States requires the substance to be listed on the TSCA Inventory; where it is not listed, small quantities imported solely for research and development may fall under the research and development exemption with its conditions, while larger volumes require a pre-manufacture notice. Crop protection actives are separately regulated by the EPA under FIFRA, and an intermediate is not itself registered.
• ICH quality expectations for the customer's filing: Pharmaceutical customers expect the supplier to operate under ICH Q7 for intermediate manufacture, to describe route selection and control under ICH Q11, to assess mutagenic impurities under ICH M7, and to report elemental impurities against ICH Q3D limits for the drug product. Support for a drug master file or equivalent CMC package, with specifications, validated methods and change control, is the practical deliverable.

4.3 The Critical Hurdle: Quality Control and Safety Limits

V. Green Trade Barriers and ESG in Manufacturing

ESG review of halogenated aromatic chemistry concentrates on halogenated waste, precious-metal recovery, solvent intensity and the governance of end use, with customers asking for evidence rather than assertions.

5.1 Carbon Footprint and Circular Economy

Halogenated aromatic synthesis is solvent- and energy-intensive: cryogenic metalation where used, multiple crystallisations and halogenated solvent loads all raise the E-factor. Credible suppliers report solvent consumption and recovery per kilogram, energy intensity and Scope 1, 2 and 3 figures, because sponsors include purchased goods in their own Scope 3 inventories. The most material environmental issue is the halogenated waste stream: brominated and fluorinated liquors and spent carbon carry an adsorbable organic halide load, and incineration capacity is constrained by halogen limits, so solvent recovery and dedicated halogenated waste treatment matter more than marginal energy savings.

5.2 Sustainable Sourcing and Traceability

Traceability combines governance with quality. Buyers and suppliers should apply documented Know-Your-Customer and end-use declaration procedures, confirm that material is destined for legitimate research or manufacturing, and state research-use-only status in quotation, label and contract. ISO 9001 and ISO 14001 certification, auditable batch records, sample retention and data integrity are the evidence customers request, palladium recovery should be documented rather than asserted, and chain-of-custody documents should name the manufacturing site so that a plant transfer triggers requalification.

VI. Supply Chain Resilience and Export Logistics

Volumes are small and value density is high, so logistics protect sample integrity and thermal history rather than minimising freight cost.

6.1 Packaging Standards and Moisture/Contamination Control

• Light, heat and moisture protection: The solid should be packed in a sealed polyethylene liner inside a foil-laminated bag or opaque drum with desiccant, kept cool and dry, and protected from light, because the aminobenzoic acid chromophore discolours and the acid can decarboxylate if held hot. Storage and drying limits should be set from thermal data, and containers should carry tamper-evident closures with the lot number matched to the certificate of analysis.
• Retained samples and sub-lot discipline: Because each campaign is short and customers requalify frequently, suppliers should retain a sample from every batch stored under the same conditions as the shipped material and ship in numbered sub-lots. That turns any later question about isomer level or colour into a measurable comparison rather than a dispute.

6.2 Dangerous Goods Identification and Transit Protocols

Transport classification must be established from measured data for the specific grade by a dangerous goods safety adviser and stated in Section 14 of the safety data sheet; many halogenated aromatic acids are shipped as non-regulated solids, but irritant or environmentally hazardous classification is possible and marine pollutant status must be checked for sea freight. Road movements follow ADR, sea movements the IMDG Code and air movements the IATA Dangerous Goods Regulations. Shipments should be temperature-monitored on long routes, and delivered with certificate of analysis, safety data sheet and customs documents matched to one lot number.

VII. Enterprise Global Expansion Strategy Guide

Winning on this intermediate means behaving as a development partner. Three priorities follow.

1. Prove regiochemistry and metal control: Identify every isomer produced by the halogenation step, set limits, and validate a chromatographic method that resolves them; report palladium, iron and copper against ICH Q3D. Presenting isomer and metal data unprompted is the fastest way onto a sponsor's shortlist.
2. Offer a clean research-use-only to GMP pathway: Define two service tiers with explicit deliverables, keep research-use-only and GMP campaigns segregated, and invest in thermal safety testing, technology transfer, batch records and change control. Sponsors pay for a route that survives inspection, not for a laboratory recipe.
3. Answer the fluorine question early: Prepare a written position explaining that the molecule contains a single aromatic carbon-fluorine bond and no perfluorinated methyl or methylene carbon, supported by structure, total-fluorine or adsorbable organic halide data where requested, and pair it with halogenated waste and palladium recovery evidence.

VIII. Conclusion

CAS 1416013-62-1 is a functional-dense anthranilic acid whose value lies in the programmes it feeds: anthranilamide diamide crop protection chemistry and halogenated quinazolinone pharmaceutical scaffolds. It has no approved therapeutic or pesticidal indication of its own and is supplied as a research-use-only or qualified intermediate, never as a consumer or formulated product.

For 2026 the differentiators are concrete: demonstrated regiochemical control, thermal safety data that prevents decarboxylation, elemental impurity reporting under ICH Q3D, verified REACH and TSCA position, a clear statement on fluorinated-substance scope, and disciplined end-use screening. Suppliers who deliver these will be retained as development partners when a programme scales.

IX. Industry Resource Connection and Supplier Ecosystem

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This white paper is exclusively compiled by the Guidechem Intelligence Team based on global customs data, regulatory databases, and industry research. Guidechem is a leading global B2B chemical platform, dedicated to connecting global buyers with verified, high-quality manufacturers.

Guidechem Global 2-Amino-4-bromo-3-fluorobenzoic acid Supplier Ecosystem List

Relying on Guidechem's extensive global database, we have mapped the core participants in the current global 2-Amino-4-bromo-3-fluorobenzoic acid supply chain:

• China halogenated aromatic custom-synthesis cluster: Multi-purpose plants in Zhejiang, Jiangsu and Shandong combine electrophilic halogenation, fluorinated aromatic feedstock and fast quotation, supplying research-use-only and pilot-scale quantities to global discovery teams.
• India route development and GMP transition hub: CDMOs in Gujarat, Hyderabad and Bengaluru provide regioselective halogenation development, analytical validation, impurity identification and documented transition into qualified GMP intermediate campaigns.
• Europe and Japan fluorination and high-purity specialists: European and Japanese houses contribute fluorochemical expertise, high-purity finishing, thermal safety testing and regulatory writing, typically at premium prices for clinical and reference-standard work.