HiSiaddi is an innovative foreign trade service provider driven by both technology transformation and foreign trade business. We have established a "1+2+3+4=1" service system and can supply BINAP sourced directly from multiple well-known original manufacturers. As a R&D-oriented foreign trade enterprise, HiSiaddi has repeatedly collaborated with manufacturers on technology transfer and accurately captured market demands, enabling us to resolve various customized BINAP requirements for clients. Below is a case study of HiSiaddi addressing customized BINAP demands.
Contact HiSiaddi customer service for more customized service inquiries.
The client is a top Swiss chiral pharmaceutical enterprise focusing on R&D and production of high-end anti-cancer and anti-viral API. Its products hold FDA and EMA certifications, ranking among the world’s top three in market share of global chiral pharmaceutical intermediates, representing a typical Europe-based, technology-driven mid-to-high-end client. The company purchases approximately 50 kg of customized-grade BINAP (1,1'-Binaphthyl-2,2'-bis(diphenylphosphine)) annually for synthesizing core chiral catalysts. Previously relying on Japanese custom manufacturers, the client turned to China for customized cooperation in 2025 due to delivery delays and a 30% price hike. Its core requirements are as follows: ultra-high purity ≥99.95%, single chiral configuration (R-BINAP), low heavy metal content (≤0.5 ppm), customized particle size (5 μm fine powder), full-process traceability, and pharmaceutical-grade compliance documentation.
As the "gold ligand" for chiral catalysis, BINAP serves as the core raw material for high-end asymmetric catalytic reactions with extremely high customization barriers: chiral configuration resolution is difficult, purity improvement is prone to oxidation, precise particle size control requires sophisticated processes, and pharmaceutical-grade impurity control is stringent. Most domestic manufacturers only produce 99% industrial-grade racemates, failing to meet the Swiss client’s customized standards. The client contacted three domestic factories, all of which rejected the cooperation due to technical shortcomings, inability to customize chiral configurations, and failed particle size control, stalling the customization project. The client authorized HiSiaddi to fully act as its agent to break through technical and delivery bottlenecks.
The client requires single R-BINAP configuration (ee value ≥99.8%) and purity ≥99.95% (dual testing via HPLC and NMR), far exceeding the domestic standard of 99% industrial-grade racemates. Domestic manufacturers generally adopt traditional synthesis processes with low chiral resolution efficiency and residual S-configuration impurities. BINAP readily oxidizes into BINAPO (phosphine oxide impurities) during purification, which is hard to remove, capping purity below 99.5% and failing to meet specifications.
The client demands uniform 5 μm fine powder (D50=5±0.5 μm) free of agglomeration with good flowability for immobilized catalyst loading. Uneven particle size causes fluctuating catalytic efficiency and increased side reactions. Conventional domestic processes only produce 20–50 μm coarse powder; fine grinding easily introduces metallic impurities, while high-temperature grinding decomposes BINAP, making it hard to balance particle size and purity.
Per client requirements, heavy metals (Pb, As, Cd) ≤0.5 ppm, moisture ≤100 ppm, residual solvents ≤50 ppm, zero halogen residues, fully complying with USP pharmaceutical standards. Heavy metal content of domestic industrial-grade products generally exceeds 5 ppm, and manufacturers lack pharmaceutical-grade purification workflows to satisfy strict impurity limits for API production.
The client requires DMF files, GMP compliance statements, SGS test reports, full-process process parameter records, and batch traceability reports for FDA API filing. Most domestic custom manufacturers lack pharmaceutical-grade compliance systems, cannot provide complete documentation, and have no traceability frameworks, failing to pass audits by high-end pharmaceutical clients.
Custom-grade BINAP features complex synthesis with a long single-batch production cycle (60 days conventionally). Large domestic manufacturers prioritize high-volume orders, leading to extended lead times, high costs, and unstable process performance for small-batch custom orders, creating a conflict between delivery deadlines and quality consistency.
HiSiaddi assembled a special team consisting of chiral synthesis specialists, purification process engineers, particle size control technicians, and compliance officers. We partnered with two leading domestic manufacturers – Runyu New Materials (BINAP synthesis leader) and Tuoyuan Fine Chemicals (high-purity purification specialist) – and adopted a strategy of "customized process development + flexible production scheduling + precise quality control + compliance empowerment". We delivered the first 10 kg customized batch within 35 days with all indicators meeting standards, establishing a long-term customized production system.
· Optimized synthesis process: Adjust lithium metal ratio, reaction temperature (raised from 60℃ to 80℃), and reaction duration (extended from 8 to 10 hours). Low-temperature dropwise addition of chlorodiphenylphosphine reduces oxidative side reactions and suppresses BINAPO impurity generation.
· Upgraded chiral resolution: Introduced high-efficiency chiral resolving agents, optimized resolution temperature and solvent ratio to raise R-configuration ee value to 99.8% and completely eliminate S-configuration impurities.
· Multi-stage high-purity purification: Combined acetonitrile recrystallization and vacuum sublimation. Leveraging solubility differences between BINAP and BINAPO in acetonitrile fully removes oxidized impurities; subsequent vacuum sublimation further elevates purity to 99.97% (HPLC) with no impurity peaks observed via NMR.
· Inert-protected milling: Adopt nitrogen-shielded low-temperature jet mills with temperature controlled below 30℃ to avoid BINAP oxidation and decomposition. Adjust airflow pressure and classifier wheel speed for precise particle size distribution regulation.
· Agglomeration dispersion treatment: Add pharmaceutical-grade dispersants, followed by ultrasonic dispersion and vacuum drying to fully eliminate particle agglomeration. Test results show D50=4.8 μm with uniform particle distribution and qualified flowability.
· Raw material pre-treatment: All raw and auxiliary materials (binaphthol, chlorodiphenylphosphine, solvents) adopt pharmaceutical-grade high-purity feedstock with pre-inspected impurities to control heavy metals and residual solvents at the source.
· Triple purification workflow: Post-synthesis acid washing → water washing → alcohol washing to strip metal ions and water-soluble impurities. High-vacuum drying (80℃, 10 Pa) reduces moisture to 85 ppm and residual solvents to 32 ppm.
· Trace impurity testing: Entrust SGS for testing; heavy metal levels (Pb=0.2 ppm, As=0.1 ppm, Cd=0.05 ppm) are far below the client’s ≤0.5 ppm threshold.
· Compliance documentation compilation: Cooperate with professional pharmaceutical compliance institutions to compile English DMF files, GMP compliance statements, USP-standard COA, 16-section SDS, and CLP labels to satisfy FDA and EMA audit requirements.
· Full-process traceability system: Build a traceability framework covering all links from raw material procurement, synthesis, purification, milling, packaging to outbound delivery. Each batch records process parameters, test data, operators, and equipment serial numbers, enabling traceability to every production node.
· Dedicated production channel: Coordinate manufacturers to open exclusive custom production lines with priority scheduling for 10 kg small-batch orders, cutting production cycles from 60 days to 35 days.
· Full-process quality control: Set 7 key quality control points per batch (raw material, synthesis endpoint, post-resolution, post-purification, post-milling, pre-packaging, pre-delivery). Each stage only proceeds after passing full-indicator testing to eliminate quality fluctuations.
· Purity: 99.97% (HPLC), no impurity peaks via NMR, exceeding the ≥99.95% requirement
· Chiral configuration: R-BINAP with ee value = 99.85%, meeting single-configuration standards
· Particle size: D50=4.8 μm, agglomeration-free with good flowability
· Impurities: Heavy metals ≤0.35 ppm, moisture 85 ppm, residual solvents 32 ppm, complying with USP standards
· Compliance documentation: Complete DMF, GMP, SGS reports, and traceability documents passed client audit at first submission
The customized R-BINAP was applied in asymmetric catalytic hydrogenation for anti-cancer API manufacturing. Test results show a 12% improvement in catalytic efficiency, a 40% reduction in side reactions, and a final product ee value of 99.9%, matching the performance of Japanese imported products and fully compatible with high-end API production.
The client’s R&D Director commented: "BINAP’s chiral configuration and purity directly determine the quality and yield of our APIs. Previously, our Japanese supplier suffered unstable lead times and steep price hikes, while domestic manufacturers failed to meet our customized standards, plunging us into a supply chain crisis. HiSiaddi not only overcame technical hurdles of ultra-high purity, single chirality, and precise particle size control but also delivered quickly within 35 days with full pharmaceutical-grade compliance documentation that fully satisfies FDA audit standards. The customized product performs identically to Japanese imports at a 22% lower price. HiSiaddi is a strategic partner that truly understands customized high-end chiral catalysis demands."
The client awarded HiSiaddi the full annual 50 kg customized BINAP order, and subsequently entrusted us with high-difficulty custom products including sulfonated BINAP and BINAP metal complexes. We provide an integrated solution covering technical development, customized manufacturing, compliance services, and quality control. A 5-year framework cooperation agreement was signed, appointing HiSiaddi as the client’s exclusive customized supplier in China.
Core demand for high-end customization: Mid-to-high-end European and American clients impose multi-dimensional rigid requirements on technology, precision, impurity control, compliance, and delivery deadlines. Failure in any single link terminates cooperation, demanding full-chain technical breakthroughs and resource integration.
Key to successful customization: HiSiaddi must possess capabilities including technical identification, integration of top-tier factory resources, coordination of process optimization, compliance documentation compilation, and full-process quality control to efficiently resolve high-barrier customization bottlenecks.
Core driver of trust building: When facing high-end customization demands, precise demand comprehension, rapid technical response, stable quality delivery, complete compliance support, and long-term service guarantees build client trust. Customization capabilities form core competitiveness to deepen long-term partnerships.
Industry trend insight: Driven by global development of chiral pharmaceuticals and high-end fine chemicals, demand for high-difficulty chiral ligand customization continues to grow. HiSiaddi, equipped with integrated technology, resource, and compliance capabilities, will seize market opportunities in high-end customization.
Contact HiSiaddi customer service for more customized service inquiries.
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info@hisiaddi.com 
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