HiSiaddi is an innovative foreign trade service provider driven by both technology commercialization and export business. We have established a "1+2+3+4=1" service system and can supply BINAP sourced directly from well-known original manufacturers worldwide. As a foreign trade enterprise with in-house R&D capabilities, HiSiaddi has repeatedly resolved customized BINAP product requirements through technical cooperation with manufacturers and accurate market insight. Below is a case study of HiSiaddi’s solution for customized BINAP orders.
Please contact HiSiaddi customer service if you require further customized services.
The client is a top Swiss chiral pharmaceutical enterprise specializing in R&D and production of high-end anti-cancer and anti-viral API. Its products are certified by FDA and EMA, ranking among the world’s top three in market share of chiral pharmaceutical intermediates, representing a typical European technology-driven mid-to-high-end customer. The client purchases approximately 50 kg of custom-grade BINAP (1,1'-Binaphthyl-2,2'-bis(diphenylphosphine)) annually for the synthesis of core chiral catalysts. Previously relying on Japanese custom manufacturers, the client turned to China for custom cooperation in 2025 amid delayed delivery and a 30% price hike. Its core requirements include: ultra-high purity ≥99.95%, single chiral configuration (R-BINAP), low heavy metal content (≤0.5 ppm), customized particle size (5 μm micropowder), full-process traceability, and pharmaceutical-grade compliance documents.
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: difficult chiral resolution, easy oxidation during purity upgrading, precision particle size control requirements, and stringent impurity control standards for pharmaceutical grade. Most domestic manufacturers only produce 99% industrial-grade racemates, failing to meet the Swiss client’s customization standards. The client contacted 3 domestic factories but all rejected cooperation due to technical shortcomings, inability to customize chiral configurations, and failed particle size control, halting customization progress. The client entrusted HiSiaddi with full agency to break through technical and delivery bottlenecks.
The client requires exclusive R-BINAP configuration (ee value ≥99.8%) and purity ≥99.95% (dual testing via HPLC and NMR), far exceeding the domestic industrial standard of 99% racemate. Domestic manufacturers generally adopt traditional synthesis processes featuring low chiral resolution efficiency and residual S-configuration impurities. BINAP is prone to oxidation to form BINAPO (phosphine oxide impurities) during purification, which is hard to remove, limiting purity below 99.5% and failing to meet standards.
The client demands uniformly sized 5 μm micropowder (D50=5±0.5 μm) free of agglomeration with good flowability for immobilized catalyst loading. Uneven particle sizes cause 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, complying with USP pharmaceutical standards. Heavy metal content of domestic industrial-grade products generally exceeds 5 ppm, and manufacturers lack pharmaceutical-grade purification processes, unable to meet strict impurity requirements 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 and complete supporting documents, with missing traceability frameworks, failing to pass audits by high-end pharmaceutical clients.
Custom-grade BINAP involves complex synthesis with a standard single-batch production cycle of 60 days. Large domestic manufacturers prioritize mass orders, leading to extended lead times, high costs, and unstable processes for small-batch custom orders, making it difficult to balance delivery schedules and product quality.
HiSiaddi formed a special team consisting of chiral synthesis specialists, purification process engineers, particle size control technicians, and compliance specialists. We collaborated with two leading domestic manufacturers: Runyu New Materials (BINAP synthesis leader) and Tuoyuan Fine Chemicals (high-purity purification specialist). Adopting a strategy of "custom process development + flexible production scheduling + precision quality control + compliance empowerment", we delivered the first 10 kg batch within 35 days with all indicators qualified, establishing a long-term customized production system.
1. Optimized Synthesis Process: Adjust lithium metal ratio, reaction temperature (60°C → 80°C), and reaction duration (8 h → 10 h). Adopt low-temperature dropwise addition of chlorodiphenylphosphine to reduce oxidative side reactions and lower BINAPO impurity generation.
2. Upgraded Chiral Resolution: Introduce high-efficiency chiral resolving agents, optimize resolution temperature and solvent ratio to raise R-configuration ee value to 99.8% and fully eliminate S-configuration impurities.
3. Multi-Stage High-Purity Purification: Combine acetonitrile recrystallization and vacuum sublimation. Leverage solubility differences between BINAP and BINAPO in acetonitrile to thoroughly remove oxidized impurities; further purify via vacuum sublimation to reach HPLC purity of 99.97% with no impurity peaks detected by NMR.
1. Inert Atmosphere Milling: Deploy nitrogen-protected low-temperature jet mill with temperature controlled below 30°C to avoid BINAP oxidation and decomposition. Adjust airflow pressure and classifier wheel speed for precise particle size distribution control.
2. Agglomeration & Dispersion Treatment: Add pharmaceutical-grade dispersants, followed by ultrasonic dispersion and vacuum drying to completely eliminate particle agglomeration. Test results: D50=4.8 μm, uniform particle distribution and qualified flowability.
1. Raw Material Pre-Treatment: All raw materials (binaphthol, chlorodiphenylphosphine, solvents) adopt pharmaceutical-grade high-purity feedstock with pre-testing for impurities to control heavy metals and residual solvents at the source.
2. Triple Purification Process: Post-synthesis acid washing → water washing → alcohol washing to remove metal ions and water-soluble impurities. High-vacuum drying (80°C, 10 Pa) reduces moisture to 85 ppm and residual solvents to 32 ppm.
3. 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 limit.
1. Compile Compliance Documents: Cooperate with professional pharmaceutical compliance institutions to prepare English DMF files, GMP compliance statements, USP-standard COA, 16-section SDS, and CLP labels, satisfying FDA and EMA audit requirements.
2. Full-Process Traceability System: Build a traceability system covering raw material procurement, synthesis, purification, milling, packaging, and outbound delivery. Each batch records process parameters, test data, operators, and equipment serial numbers, enabling traceback to every production stage.
1. Dedicated Production Line: Coordinate manufacturers to open exclusive custom production lines prioritizing 10 kg small-batch orders, cutting production cycles from 60 days to 35 days.
2. Full-Process Quality Control: Set 7 key quality control points per batch (raw material inspection, synthesis endpoint, post-resolution, post-purification, post-milling, pre-packaging, pre-delivery). Only fully qualified products proceed to the next process 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 excellent flowability;
· Impurities: Heavy metals ≤0.35 ppm, moisture 85 ppm, residual solvents 32 ppm, fully compliant with USP standards;
· Compliance Documents: Complete DMF, GMP, SGS reports and traceability files passed client audit in one go.
The customized R-BINAP was applied to asymmetric catalytic hydrogenation for anti-cancer API. Test results show 12% higher catalytic efficiency, 40% fewer side reactions, and product ee value reaching 99.9%, matching the performance of Japanese imported materials 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 API. Previously plagued by unstable lead times and high prices from Japanese suppliers, domestic manufacturers failed to meet our customization standards, triggering a supply chain crisis. HiSiaddi not only overcame technical challenges of ultra-high purity, single chirality and precision particle size, but also delivered rapidly within 35 days with complete pharmaceutical-grade compliance documentation satisfying FDA audits. The customized product performs identically to Japanese imports at a 22% lower price, making HiSiaddi a strategic partner that truly understands high-end chiral ligand customization demands."
The client awarded HiSiaddi full agency rights for its annual 50 kg customized BINAP order. Subsequent high-difficulty customized products including sulfonated BINAP and BINAP metal complexes were also entrusted to HiSiaddi for integrated solutions covering technical development, custom manufacturing, compliance services and quality control. A 5-year framework cooperation agreement was signed, appointing HiSiaddi as its exclusive Chinese custom supplier.
Core demand for high-end customization: Mid-to-high-end European and American clients impose multi-dimensional rigid requirements covering technology, precision, impurity control, compliance and delivery schedules. Failure at any single link terminates cooperation, necessitating full-chain technical breakthrough and resource integration. Key to successful customization: HiSiaddi must possess capabilities including technical identification, integration of top-tier factory resources, coordination for process optimization, compliance document compilation, and full-process quality control to efficiently resolve high-barrier customization bottlenecks. Core of trust building: When facing high-end customization demands, accurate demand comprehension, rapid technical response, stable quality delivery, complete compliance support and long-term service guarantees build client trust, forming core competitiveness through customization capabilities and deepening long-term partnerships. Industry trend insight: With the global development of chiral pharmaceuticals and high-end fine chemicals, demand for high-difficulty chiral ligand customization continues to grow. HiSiaddi, integrating technology, resources and compliance capabilities, will seize opportunities in the high-end customization market.
Please contact HiSiaddi customer service if you require further customized services.
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info@hisiaddi.com 
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