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dormouse
(Member)
04-19-00 04:29
No 122759
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More oxazoline goodness-drone 342
(Rated as: good read)
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Author Topic: More oxazoline goodness drone 342 Member posted 10-13-98 12:04 PM -------------------------------------------------------------------------------- It was brought to my attention by Piglet in a private e-mail, that phenylpropenes can be converted to rather useful halohydrins by means of addition of X2 and H2O. These are useful for a number of reasons. They're an excellent reagent for making beta-hydroxy alpha-methyl fentanyls (I'm still writing up the details, in case you're wondering, but these are by far the most potent fentanyls around), and they ca easily be made into some exotic rigid-bodies PEA's (not to mention racemic ephedrine analogs.) Anyways, the lesson to take away today is that halides, when in the presence of water, add across double bonds to form halohydrins. Reaction ID 168261 Reactant BRN 1679279 propenylbenzene Product BRN 2437331 2-bromo-1-phenyl-propan-1-ol -------------------------Field Availability List RX Reaction Details 1 ------------------------- Reaction Details Reaction Classification Preparation Reagent bromine water Ref. 1 1540971; Journal; Fourneau; Kanao; BSCFAS; Bull.Soc.Chim.Fr.; <4> 35; 1924; 619, 620; Ref. 2 1540970; Journal; Fourneau; Puyal; ASEFAR; An.R.Soc.Esp.Fis.Quim.; 20; 398; CHZEA6; Chem.Zentralbl.; GE; 95; I; 1924; 1364; Reaction ID 795509 Reactant BRN 774229 1-methoxy-4-propenyl-benzene Product BRN 2522397 2-bromo-1-<4-methoxy-phenyl>-propan-1-ol -------------------------Field Availability List RX Reaction Details 1 ------------------------- Reaction Details Reaction Classification Preparation Reagent water bromo potassium bromide Temperature 90 øC Ref. 1 1545717; Journal; Read; Reid; JCSOA9; J.Chem.Soc.; 1928; 1489; Reaction Reaction ID 1763960 Reactant BRN 1361672 trans-propenyl-benzene Product BRN 4292107 C9H11BrO ------------------------- Field Availability List RX Reaction Details 1 ------------------------- Reaction Details Reaction Classification Preparation Reagent HOBr Solvent acetone Time 30 min Temperature 20 øC Note 1 Yield given Ref. 1 5740967; Journal; Marples, B. A.; Saint, C. G.; SYNCAV; Synth.Commun.; EN; 12; 7; 1982; 545-556; When I get the chance, I'll post more on the subsequent reactions for forming rings, etc. -drone #342 drone 342 Member posted 10-13-98 12:30 PM -------------------------------------------------------------------------------- Here's some syntheitc detail on the hlaohydrin of isosafrole: Reactant BRN 82640 5-propenyl-benzo<1,3>dioxole Product BRN 171391 1-benzo<1,3>dioxol-5-yl-2-bromo-propan-1-ol -------------------------Field Availability List RX Reaction Details 2 ------------------------- Reaction Details 1 of 2 Reaction Classification Preparation Reagent bromine-water potassium bromide solution Temperature 90 øC Ref. 1 506812; Journal; Read; Reid; JCSOA9; J.Chem.Soc.; 1928; 1490; ------------------------- Reaction Details 2 of 2 Reaction Classification Preparation Reagent NaBr Solvent acetonitrile Yield 100. (BRN171391) Other conditions electrolysis Ref. 1 5575774; Journal; Torii, Sigeru; Uneyama, Kenji; Ueda, Kyoji; JOCEAH; J.Org.Chem.; EN; 49; 10; 1984; 1830-1832; I looked for some data on this, and I realized how limited this may be in usefullness; while halohydrins can be readily converted into epoxides (and subsequently rearranged into everybody's favorite ketone), and ammonia or methylamine, when properly added, would yield something interesting (if combined with BrCN), it would be far from as stylish as I was hoping. Anyway, it is at least SOMEWHAT intersting. Maybe somebody can help me out here and show why this still is significant. -drone #342 Rhodium Administrator posted 10-14-98 09:24 AM --------------------------------------------------------------------------------Synthesis of P2P from either of the dirt cheap precursors Benzene or Propiophenone Propionyl Chloride [1] ---------------------- Propionyl chloride was prepared not only by the usual methods with phosphorus bichloride or phosphorus pentachloride, but also by the chlorination of propionic acid in the cold with sulfur monochloride present. To 540 g of propionic acid, 245 g of sulfur monochloride was added and chlorine was passed through the mixture while it was stirred for 15 hours. The chlorination proved to be incomplete at this point, since 150 g of unchanged propionic acid was recovered. There was also considerable sulfur monochloride, which was removed from the propionyl chloride by treatment with hydrogen sulfide. The propionyl chloride obtained amounted to 250 g. This product functioned as satisfactorily in the subsequent preparation of propiophenone as that prepared by the phosphorus halide methods. Propiophenone [1] ----------------- Propiophenone was made by Pampel and Schmidt in 1886 by application of the Friedel and Crafts reaction. These investigators state that their yields were good, but give no data. In our preparation it was found necessary to employ vigorous mechanical stirring, and to keep the temperature of the reaction mixture below 20°C until all reagents were added. Where occasional shaking was depended upon, the yields amounted on an average to 40% but, with the above precautions, yields were more than doubled. The following preparation is given as typical of the final procedure.
Two hundred grams of finely divided anhydrous aluminum chloride was suspended in 300 g of dry benzene in a flask equipped so that the mixture could be thoroughly stirred and cooled. A mixture of 126 g of propionyl chloride and 105 g of benzene was run in drop by drop, the entire time of addition being 3 hours. At the end of this time the reaction mixture was kept for 2 hours at 50°C. The contents of the flask were cooled and poured over crushed ice; and, after 50 ml of conc hydrochloric acid had been added, the propiophenone and benzene were removed by distillation with steam. Thus, 152 g of propiophenone was obtained, boiling point 200-220°C; yield 84%. 2-Chloro-propiophenone [2] -------------------------- 55g (0.41 mol) of thionyl chloride was added dropwise to a stirred solution of 50g (0.37 mol) of propiophenone in 250ml of carbon tetrachloride. The temperature of the mixture shold never exceed 40°C. The solution was washed several times with water and dried over MgSO4. The 2-chloro-propiophenone was purified by distillation under vacuum (bp 108-110°C 1 mmHg). The yield was 80% of theory.
2-Chloro-1-phenylpropanol ------------------------- Aluminium isopropoxide is made from Al foil, HgCl2 and IPA. This catalyst is isolated, and added to a solution of 2-Chloro-propiophenone in IPA, and refluxed until the evolution of acetone has ceased. The alcohol is then isolated through vacuum distillation. 1-Phenyl-1,2-epoxypropane [2] ----------------------------- 75 uL of distilled water, 4 ml of DMF and 0.330g (2.4 mmol) of potassium carbonate was added to 0.79 mmol of 2-chloro-propiophenone. The mixture was stirred at room temp for 24 hours, diluted with water and extracted with ether. The etheral solution was washed with a saturated solution of NaCl and dried over MgSO4. The ether was evaporated under vacuum, to yield ~70% of crude epoxide.
Phenyl-2-Propanone ------------------ Reflux of the crude epoxide with catalytic LiI to give P2P, which is purified by bisulfite/distillation. References: ----------- [1] J. Am. Chem. Soc. 44, 1751-1752 (1922) [2] Tetrahedron: Asymmetry 5(7), 1249-1268 (1994)
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