Name: 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl
Other Names: X-Phos; Xphos; dicyclohexyl(2′,4′,6′-triisopropyl-[1,1'-biphenyl]-2-yl)phosphane; 2-(Dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl; dicyclohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane
CAS Number: 564483-18-7
Chemical Formula: C₃₃H₄₉P
Molecular weight 476.72 g/mol
InChI InChI=1S/C33H49P/c1-23(2)26-21-30(24(3)4)33(31(22-26)25(5)6)29-19-13-14-20-32(29)34(27-15-9-7-10-16-27)28-17-11-8-12-18-28/h13-14,19-25,27-28H,7-12,15-18H2,1-6H3
Boiling point 569.8±50.0 °C (predicted value)
Flash point 317.7 °C
Water solubility Insoluble/slightly soluble (slightly soluble in benzene)
Storage conditions Store in an inert atmosphere at room temperature.
Sensitivity: Air-sensitive.
Appearance: White powder or crystals.
Color: White.
MDL Number: MFCD04117682
Hazard Symbol: Xi (Irritant)
Risk Terms: R22 (Harmful if ingested); R36/37/38 (Irritation to eyes, respiratory system, and skin)
Safety Terms: S26 (In case of accidental contact with eyes, immediately flush with plenty of water and seek medical advice); S36 (Wear appropriate protective clothing); S37 (Wear appropriate gloves); S39 (Wear safety goggles or face mask)
Customs Code: 2931.90 (Organophosphorus compounds)
I. Properties
2-Dicyclohexylphosphine-2′,4′,6′-triisopropylbiphenyl (XPhos) is a sterically hindered, electron-rich biarylphosphine ligand belonging to the Buchwald ligand family. This compound is a white crystalline powder at room temperature with a melting point of 187-190°C. Its molecular structure contains two dicyclohexylphosphine groups and three isopropyl substituents, a unique structure that endows it with significant steric hindrance and electron-donating capabilities.
This compound is sensitive to air and must be stored under an inert atmosphere (such as nitrogen or argon). It is slightly soluble in common organic solvents such as benzene, exhibits good thermal stability, and has a predicted boiling point as high as 569.8°C. As a trivalent phosphorus compound, it is readily oxidized by oxidants to form the corresponding phosphine oxide; therefore, contact with air and oxidants must be avoided during handling.
II. Applications
XPhos is one of the most important phosphine ligands in modern organic synthesis, primarily used in transition metal-catalyzed cross-coupling reactions:
* Suzuki coupling: used in conjunction with palladium catalysts to achieve efficient coupling of arylboronic acids with aryl halides.
* Heck reaction: used for the arylation of alkenes.
* Negishi coupling: achieves cross-coupling of organozinc reagents with aryl halides.
* Buchwald-Hartwig amination: used for the construction of C-N bonds to synthesize aromatic amine compounds.
Furthermore, this ligand is also used to synthesize novel [1,2,4]triazolo[4,3-a]pyrazine derivatives as a potential selective C-met inhibitor. It also has wide applications in the preparation of functional materials such as photofunctional materials, drug synthesis, and liquid crystal materials.
III. Preparation Method
The industrial synthesis of XPhos typically follows this route:
Grignard reagent coupling method:
Under nitrogen protection, magnesium shavings are mixed with anhydrous tetrahydrofuran, and 1,2-dibromoethane is added to initiate the reaction.
1-Bromo-2,4,6-triisopropylbenzene is added dropwise to prepare the Grignard reagent.
A second batch of magnesium shavings is added, along with o-bromochlorobenzene, and the reaction continues to generate a diaryl Grignard reagent.
The mixture is cooled to room temperature, catalyzed by copper chloride, and then dicyclohexylphosphine chloride is added dropwise.
The mixture is stirred overnight at room temperature. After the reaction is complete, it is quenched with an aqueous sodium bisulfite solution.
The mixture is extracted with ethyl acetate, concentrated, and crystallized at low temperature. The crystals are filtered and dried to obtain a white solid product.
The entire synthesis process requires strict anhydrous and oxygen-free operation. The yield can be further improved by optimizing the reaction conditions.
IV. Safety Information
GHS Classification: Chronic Aquatic Toxicity (Category 4) – May have long-term, persistent harmful effects on aquatic life
Main Hazards:
Health Hazards: Harmful if ingested (R22); Irritating to eyes, respiratory system and skin (R36/37/38)
Environmental Hazards: May have long-term negative effects on aquatic environments
Safe Handling:
Handle in a fume hood to avoid inhalation of dust.
Wear appropriate protective gloves, goggles and clothing (S36/S37/S39).
Avoid release into the environment (P273).
Store in an inert atmosphere, away from oxidizers and heat sources.
Dispose of waste in accordance with local regulations, to an approved waste treatment facility (P501).
First Aid Measures:
Inhalation: Move to fresh air and perform artificial respiration if necessary.
Skin Contact: Wash with soap and plenty of water.
Eye Contact: Rinse immediately with plenty of water and seek medical attention.
Ingestion: Seek immediate medical attention.
Post time: Mar-30-2026
