Phosphorus oxychloride, quenching

A solution of 1.1 g of the cyanohydrin in 6 ml of pyridine is treated with 0.6 ml of phosphorus oxychloride and allowed to stand at room temperature overnight. The reaction mixture is quenched with ice and water and the resulting crystalline precipitate is collected, washed with water and dried to yield 1.05 g. Recrystallization from aqueous pyridine affords 0.88 g (83%) of 20-cyano-21-hydroxy-3,3-ethylenedioxypregna-5,17(20)-dien-l l-one acetate mp 197-200°. 

A mixture of 10 g of the above piperazine carboxylate ester, 8 g of phosphorus pentoxide and 20 ml of phosphorus oxychloride is heated under reflux for about 1 day, diluted with 100 ml each of chloroform and benzene and quenched with 200 g of ice. The mixture is made basic with 10% sodium hydroxide. Theorganic layer is Isolated and extracted with 150 ml of dilute hydrochloric acid. The product is precipitated from the aqueous layer by addition of 10% sodium hydroxide, extracted with benzene and dried over potassium carbonate. Recrystallization from benzene-petroleum ether gives 2[Pg.77]

The entire product from the previous reaction (calculated to contain about 46 mmol of 6) is combined with phosphorus oxychloride (8.53 mL, 91.6 mmol). The viscous mixture is mechanically stirred (note 2) at 0°C, and DMF (5.31 mL, 68.7 mmol) is added portionwise over 1 h. The reaction mixture is stirred for an additional 20 h at 25°C, and then quenched by addition of ice (200 g). The very acidic aqueous solution is washed with ethyl ether (3 x 75 mL) to remove 4 carried over from the previous reaction, after which the pH is adjusted to 6.0 with 19 N aqueous NaOH. Sodium acetate (40 g) is also added, and the solution is extracted with EtOAc (3 x 75 mL). The combined organic phases are washed with saturated aqueous... 

To 0.3 ml DMF was added 0.33 ml phosphorus oxychloride at 0 °C and the mixture stirred 10 minutes at ambient temperature. A solution of the product from Step 1 (0.63 mmol) dissolved in 0.1ml DMF was added and the mixture stirred 3 hours. Thereafter, the reaction was quenched with ice (5 g), the pH raised to 9 by addition of 28% NaOH, the mixture refluxed 10 minutes, cooled, and extracted 3 times with 5 ml EtOAc. The extracts were dried, concentrated, and the product isolated in 97% yield, mp = 150-151 °C after re-crystallization from EtOAc. Elemental analysis data supplied. 

Perigaud reported the synthesis of the /f-phosphonamidate of AZT (169). It was synthesized by the successive coupling of AZT to bis(diisopropylamino) chlorophosphine and in situ hydrolysis in the presence of tetrazole and water. Phosphorodiamides (170-179) have also been reported as prodrugs for antiviral nucleosides. These were prepared by quenching the reaction between phosphorus oxychloride and the nucleoside with an excess of amine in methanol or dioxane. 

A stirred mixture of 1-naphthol and 2 moles of the same reagent treated dropwise with 2 moles of phosphorus oxychloride and reaction continued for 7 hours at 60°C afforded after work-up by quenching with ice-cold water an 88% yield of 1-naphthyl N-methylcarbamate (ref.31). 

Coumarin was synthesised by the addition of 2-hydroxybenzaldehyde to a stirred mixture of phosphorus oxychloride and N,N-dimethylacetamide at ambient temperature followed by heating at 60-70°C to give the 2-dimethylaminobenzopyrylium salt which was isolated in 98% yield after quenching the reaction mixture in ice and treatment with perchloric acid. Hydrolysis of this at 100°C with 20% sodium carbonate solution until dimethylamine ceased to be evolved afforded coumarin quantitatively (ref.69). 

Figure 9. Photomicrographs of quench slurry, a, b thionyl chloride precipitation, c, d phosphorus oxychloride based precipitation...

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