dormouse
(Member)
04-19-00 04:29
No 122759
      More oxazoline goodness-drone 342
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Author  Topic:   More oxazoline goodness 
drone 342
Member   posted 10-13-98 12:04 PM          
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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
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Field Availability List

RX Reaction Details 1
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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
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RX Reaction Details 1
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Reaction Details

Reaction Classification Preparation
Reagent water
bromo potassium bromide
Temperature 90 C
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
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RX Reaction Details 1
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Reaction Details

Reaction Classification Preparation
Reagent HOBr
Solvent acetone
Time 30 min
Temperature 20 C
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          
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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
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RX Reaction Details 2
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Reaction Details 1 of 2

Reaction Classification Preparation
Reagent bromine-water potassium bromide solution
Temperature 90 C
Ref. 1 506812; Journal; Read; Reid; JCSOA9; J.Chem.Soc.; 1928; 1490;
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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          
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Synthesis of P2P from either of the dirt cheap precursors Benzene or Propiophenone

Propionyl Chloride [1]
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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]
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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 20C 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 50C. 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 200-220C; yield 84%.


2-Chloro-propiophenone [2]
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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 40C. The solution was washed several times with water and dried over MgSO4. The 2-chloro-propiophenone was purified by distillation under vacuum (bp 108-110C 1 mmHg). The yield was 80% of theory.

2-Chloro-1-phenylpropanol
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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]
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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
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Reflux of the crude epoxide with catalytic LiI to give P2P, which is purified by bisulfite/distillation.


References:
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[1] J. Am. Chem. Soc. 44, 1751-1752 (1922)
[2] Tetrahedron: Asymmetry 5(7), 1249-1268 (1994)