Description
Tris(o-tolyl)phosphine is an organophosphorus compound. This compound is a white, water-insoluble solid that is soluble in organic solvents. In solution, it slowly converts to the phosphine oxide. As a phosphine ligand, it has a wide cone angle of 194°. Consequently, it tends to cyclometalate when treated with metal halides and metal acetates. Complexes of this ligand are common in homogeneous catalysis.
Chemical Properties
white to light yellow crystal powder.
Uses
Tri(o-tolyl)phosphine is used in a ruthenium-catalyzed direct amination of alcohols. It is also used in Suzuki reaction. Further, it is used in the preparation of tri-ortho-phosphinselenide by reacting with selenium as a reagent. In addition to this, it acts as a ligand in coordination chemistry.
Application
Tris(2-methylphenyl)phosphine (Eletriptan Impurity 13) is a phosphine catalyst. It can be used in the rhodium-catalyzed hydrogenation, Suzuki-Miyaura cross-coupling reactions and Heck reactions.
Preparation
Tri(o-tolyl)phosphine can be obtained by the reduction of tris(o-tolyl)phosphine oxide or prepared by the 2-bromotoluene Grignard reaction.
Procedure: To a solution of magnesuim turnings (3.11 g, 128 mmol, 3.5 equiv) in THF (50 mL) was added a small amount of 2-bromotoluene (1 mL) and 1 iodine crystal. The reaction vessel was heated until initiation occurred, where upon a solution of the remaining 2-bromotoluene (20 g, 117 mmol, 3.2 equiv in total) in THF (100 mL) was added. The reaction was set to reflux for 2 hours (colour change to black solution), after which it was cooled to 0 oC and a solution of phosphorus trichloride (5.01 g, 36.5 mmol, 1 equiv) in THF (30 mL) was added dropwise. Upon addition completion the reaction was set to reflux for 18 hours. The reaction was allowed to cool to room temperature, whereupon NH4Cl solution was added with care. The resulting solution was extracted with ether (3 x 100 mL), dried over MgSO4, filtered and concentrated in vacuo. The resulting white solid was recrystalised from ethanol to yield Tri(o-tolyl)phosphine as a white solid. (6.8 g, 62 %)
Reactivity Profile
Tri(o-tolyl)phosphine is suitable for the following reaction types: Cross Couplings, Silylations, Buchwald-Hartwig Cross Coupling Reaction, Heck Reaction, Negishi Coupling, Stille Coupling, Suzuki-Miyaura Coupling.
Flammability and Explosibility
Not classified
reaction suitability
reagent type: ligand
Synthesis
The general procedure for the synthesis of tris(o-methylphenyl)phosphorus from pabuxilib impurities was as follows: 2a (2 mmol) was added to a mixture containing magnesium powder (8 mmol, 4 eq.), trimethylchlorosilane (6 mmol, 3 eq.) and 1,3-dimethyl-2-imidazolidinone (DMI, 8 mL), and the whole mixture was stirred for 2 h at room temperature. After completion of the reaction, saturated aqueous ammonium carbonate solution was added to the reaction mixture and the mixture was extracted with ether (10 mL × 3). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure. The resulting product was analyzed by 31P NMR and was found to be in the ratio of 97:3 for 1a to 2a. After purification by silica gel column chromatography (eluent: hexane/ethyl acetate = 5:1), the target product 1a was obtained in 96% yield (Table 1, entry 1).
Purification Methods
It crystallises from EtOH [Boert et al. J Am Chem Soc 109 7781 1987]. [Beilstein 16 III 835.]
References
[1] Tetrahedron Letters, 2015, vol. 56, # 7, p. 918 - 920
[2] Synthesis, 2011, # 24, p. 4091 - 4098
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 46, p. 15253 - 15256
[4] Angew. Chem., 2018, vol. 130, # 46, p. 15473 - 15476,4
