Propylene Oxide

[75-56-9] C3H6O (MW 58.09) (monomer for polymerization; electrophile; chiral building block) Alternate Names: 1,2-epoxypropane; methyloxirane. Physical Data: mp −112 °C; bp 34 °C; d 0.859 g cm−3; [α]D20 +14.6° for the (R)-enantiomer, corrected to 100% ee. Solubility: sol H2O (405 g L−1); miscible with organic solvents. Form Supplied in: colorless liquid; commercially available as a racemic mixture and as the enantiomers. Drying: distillation from calcium hydride or calcium. Upon cooling, a hydrate C3H6O·(H2O)16 of mp −3 °C is precipitated from the moist oxirane as white crystals.2 Analysis of Reagent Purity: 13C NMR (CDCl3): δ 47.1, 46.8 (C-1, C-2), 17.2 (C-3) ppm; determination of ee by complexation gas chromatography on nickel(II) bis[3-heptafluorobutanoyl-(1R)-camphorate] in squalane, separation factor α 1.24 at 50 °C;3 other suitable chiral stationary phases are nickel(II) bis[2-heptafluorobutanoyl-(S)-4-methylthujan-3-onate] and manganese(II) bis[3-heptafluorobutanoyl-(1R)-camphorate].4 Preparative Methods: (R)-propylene oxide is prepared (eq 1) in three steps: diazotization of (S)-alanine with Sodium Nitrite in hydrochloric acid; to give (S)-2-chloropropanoic acid; reduction to 2-chloropropan-1-ol with Lithium Aluminum Hydride; and cyclization by distillation from Potassium Hydroxide pellets.4, 5 (1) The (S)-enantiomer is prepared from (S)‐Ethyl Lactate via (S)-propane-1,2-diol, and cyclization of a mixture of (S)-2-acetoxy-1-bromopropane and (R)-2-bromo-1-acetoxypropane (eq 2).6, 7 (2) Alternatively, conversion of (S)-ethyl lactate into the mesylate is followed by reduction of the ester group with Aluminum Hydride/THF and ring closure with aqueous KOH.8 Another route to (S)-propylene oxide involves protection of the (secondary) hydroxyl group of (S)-ethyl lactate with Ethyl Vinyl Ether, followed by reduction of the ester group with LiAlH4, conversion of the primary hydroxyl group into the tosylate, acidic deprotection of the secondary hydroxyl group, and cyclization with aqueous KOH.9 By means of a combined microbial/chemical synthesis, (R)-propylene oxide is obtained from glucose with ee >99%.10 Metal-mediated access to both enantiomers is provided by either chromatographic or kinetic resolution of racemic propylene oxide, and also by asymmetric epoxidation of propylene.11 Handling, Storage, and Precautions: a suspected carcinogen for humans; it is inflammable and explosive; because of its high volatility, cooling to 0 °C before use is recommended. Use in a fume hood.