Triphenylphosphine oxide, removal

Carbon telrabromide (26.1 g, 78.6 mmol) was added portionwise to a solution of triphenylphosphine (41.3 g, 158 mmol) in CH2CI2 (300 mL), and the resultant deep red solution stirred at rt. for 15 min. Benzaldehyde (2.00 mL, 19.7 mmol) was then added dropwise at 0 °C, and the mixture stirred at rt. for 2 h. Pentane (200 mL) was added to the mixture, and the precipitated triphenylphosphine oxide removed by filtration through a pad of siUca. The filtrate was concentrated under reduced pressure, and the residue purified by column chromatography (petrol) to afford (2,2-dibromovinyl)benzene (2.79 g, 54 %) as a pale yellow oil. 

Rhodium(III) chloride trihydrate (2 g.) is dissolved in 70 ml. of ethanol (95%) in a 500-ml. round-bottomed flask fitted with gas inlet tube, reflux condenser, and gas exit bubbler. A solution of 12 g. of triphenylphosphine (freshly crystallized from ethanol to remove triphenylphosphine oxide) in 350 ml. of hot ethanol is added and the flask purged with nitrogen. The solution is refluxed for about 2 hours, and the crystalline product which forms is collected from the hot solution on a Buchner funnel or sintered-glass filter. The product is washed with small portions of 50 ml. of anhydrous ether yield 6.25 g. (88% based on Rh). This crystalline product is deep red in color. 

The excess triphenylphosphine used in the preparation can be recovered by addition of water to the ethanol filtrates until precipitation begins. After allowing the solutions to stand 2 to 3 days in a stoppered flask, the triphenylphosphine crystallizes out. Recrystallization from ethanol and ethanol-benzene (1 1) removes triphenylphosphine oxide contaminant. 

When this distillation was replaced by a procedure in which the acetonitrile was removed with a rotary evaporator and steam bath, and the product was extracted from the triphenylphosphine oxide with small portions of acetonitrile totaling ca. 250 ml., the checkers obtained an improved yield (79%) of cinnamyl bromide. 

The precipitate of triphenylphosphine oxide is filtered and washed with 50 ml. of pentane. The solvent is removed from the combined filtrate at the rotary evaporator under water aspirator pressure at room temperature. Distillation of the residue through a 2-cm. Vigreux column attached to a short-path distillation apparatus (Note 4) provides 13.0-14.0 g. (75-81%) of geranyl chloride, b.p. 47-49° (0.4 mm.), w2Sd = 1.4794 (Note 5). 

Hydroxy amides undergo cyclodehydration to oxazolines under very mUd conditions with triphenylphosphine and carbon tetrachloride. Carbon tetrabromide can also be used. The formation of the corresponding p-chloro amide is generally not a significant problem. The major disadvantage is that removal of the byproduct triphenylphosphine oxide may be difficult at times. Representative examples are shown in Table 8.14 (Fig. 8.5).n4,i4o,i73-i8i... 

A modification of GSR has been reported by Classon and co-workers.190 The idea remains the same create a covalently bound phosphorus cation and displace with a nucleophile—in this case, a halogen. Both bromine and iodine have been used.190 Three different systems were evaluated (1) chlorodiphenylphophine, iodine-bromine, and imidazole (2) p-(dimethylamino)phenyldiphenylphosphine, iodine-bromine, and imidazole or (3) polymer-bound triphenylphosphine, iodine-bromine, and imidazole. The last two were found to be very similar to just triphenylphosphine itself, and displayed reactivity inferior to the first system. The polymer-bound reagent does allow for easier removal of triphenylphosphine oxide produced in the course of the reaction. As with the original procedure, and consistent with a Sn2 mechanism, inversion of configuration occurred. Again, as with the original method vicinal diols were readily converted into alkenes.191 This... 

Sulfonamides may be directly synthesized from sulfonic acid salts by treatment with triphenylphosphine ditriflate followed by an amine <2004JA1024>. This procedure, that avoids the generation of sulfonic acids, converts sulfonic acid salt 129 to sulfonamide 130 in 81% yield (Equation 92). Problems associated with the removal of triphenylphosphine oxide by-products can be alleviated by performing the reaction with polystyrene-supported phosphine. 

The mixture of reaction product and triphenylphospbine oxide (16), which mixture is gelatinous owing to the alkali metal salt formed, enters an extraction column e, in which the desired reaction product, after acidification with sulfuric acid, is extracted, in counter-current, by hydrocarbons. In a second column, the hydrocarbon extract is washed, also continuously, with aqueous alcohol in order to remove the last residues of triphenylphosphine oxide (16). After concentration, under mild conditions, of the hydrocarbon extract, the all-trans vitamin A acetate (9) formed in the reaction crystallizes out and is separated off. The cis isomer, which does not crystallize, remains in the mother liquor and can be converted, according to one of the above-mentioned techniques, into the all-trans compound. 

Polymer-supported Wittig reagents have recently been developed as an extension to the traditional reagents.29 For example, polystyryldiphenylphosphine has been developed in an attempt to replace the use of triphenylphosphine in the preparation of phosphoranes (see Protocol 1). The hope is that these polymer-bound regents will overcome the practical problem of removing the triphenylphosphine oxide by-product formed in Wittig reactions. Polymer supported phosphonates and Wittig substrates have also been prepared for use in solid phase synthesis and combinatorial chemistry.30... 

The hydroxyl azide mixture from Step 8 (2.0 mol) was dissolved in 1L acetonitrile, triph-enylphosphine (1.83 mol) dissolved in 100 ml THF and 0.92 L acetonitrile added dropwise over 2 hours. The mixture refluxed for 6 hours, concentrated in vacuo to leave a yellow paste, triturated with diethyl ether (0.35 L), and filtered to remove triphenylphosphine oxide. The dark brown oil was dissolved in 500 ml 20% aqueous methyl alcohol, extracted 3 times with 1L hexanes and the product isolated in 96.8% yield. 

The affinity of trivalent phosphorus for oxygen (and sulfur) has been put to use in many reaction systems. For example, triphenylphosphine takes oxygen from N-oxides to form amines and triphenylphosphine oxide, which is a very stable polar compound, and in most cases it is easily removed from the other products. 

Even with immobilized catalysts being developed, removal of ruthenium by-products remains an important challenge. Georg and coworkers found that addition of 50 equiv (relative to ruthenium) of dimethyl sulfoxide or triphenylphosphine oxide brought ruthenium levels in reaction mixtures down from 50 to l-2qgmg-. The ruthenium levels in purified products are similar to those reported by Grubbs, where the metal was removed as trishydroxymethylphosphine complexes, " and those from the Pb(OAc)4 oxidation of ruthenium reported by Paquette. 

A solution of triflic anhydride (1.57 ml, 10 mmol) [84] in dichloroethanc (30 ml) at 0"C is added to a solution of triphenylphosphine oxide (5.55 g, 20 mmol) or equivalent phosphinamide in dichloroethanc. After appearance of a precipitate (usually in less than 15 min), a solution containing n-phcnylenediamine (0.44 g, 4 mmol) and benzoic acid (0.61 g, 5 mmol) in dichloroethanc (10 ml) is added drop wise. After stirring (0.5 h), the solution is washed with 5% sodium bicarbonate solution, dried (MgS04) and evaporated. The residue is passed through a short column packed with silica and eluted with bexanc-cthyl acetate (3 1) to remove excess phosphine oxide. Evaporation gives 2-phcnylbenzimida7.ole (0.66 g, 85%), m.p. 287°C. 

To a stirred solution of 2.77 g (10.9 mmol) of the lactol in 45 mL of dry CH CIj at 25°C, under nitrogen, was added 4.55 g (13.1 mmol) of carbethoxymethyienetriphenylphosphor-ane and 26.6 mg (0.22 mmol) of benzoic acid. After being stirred at room temperature for 26 h, the reaction mixture was poured into ether (200 mL), washed with saturated NaHC03(2 X 50 mL), and dried over MgSO. Solvent was removed in vacuo to afford a yellow oil. Flash column chromatography (50 x 158 mm 29% ethyl acetate-hexanes), to remove triphenylphosphine oxide, followed by MPLC (65 g of SiOj and 60 g of SiOj in series 20% ethyl acetate-hexanes) afforded 2.66 g of pure Z isomer (76%) and 0.33 g of pure E isomer (9%). Z isomer +87.38° (c 1.26, CHClj) E isomer [a]jj +29.10° (c... 

A related triazole synthesis utilizes phosphorous ylids, such as 264. The initially formed triazenes cyclize with elimination of triphenylphosphine oxide. The reaction proceeded sluggishly with phenyl azide, but good results have been obtained with acyl or sulphonyl azides. Tosyl azide and 264 yielded 98% of the 1-tosyl-triazole 265. The tosyl group could be removed by solvolysis in boiling ethanol... 

The first example is the synthesis of pellitorine (152) (Scheme 42), a naturally occurring pesticide58. The terminal double bond in 149 is hydrogenated selectively using dichloro-tris-(triphenylphosphine)-ruthenium(II) as a catalyst. Partial hydrolysis affords the potassium salt of the monoester 150 which is treated with diphenyl diselenide to displace one of the carboxyl groups by the phenylselenenyl group. Oxidative removal of this group leads to 2,4-decadienoate (151) which is converted to pellitorine (152). 

A solution of BOC-sulfamoylaminoalcohol (5.35 mmol), triphenylphosphine (16.05 mmol), and CCI4 (16.05 mmol) in anhydrous acetonitrile (100 mL) was refluxed for 8 h. After cooling to room temperature, the solution was concentrated in vacuo. The residue was triturated with diethyl ether (3 x 150 mL). Triphenylphosphine oxide, which precipitates in the combined organic layers, was removed by filtration. The filtrate was concentrated and the residue purified on silica gel (CH2CI2) to afford ALBOC,2V -(2-chloroethyl) sulfamide with 85% yield. 

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