Propiophenone, 3- -, hydrochloride

Add 5 ml. (5 g.) of acetophenone, 1-25 g. of finely powdered paraformaldehyde, and 3 5 g. of dry dimethylamine hydrochloride to 8 ml. of absolute ethanol, and then boil the mixture under reflux for 1-5 hours. Filter the solution (which is now almost entirely clear) through a preheated filter-funnel, and cool the filtrate in ice-water with stirring. The white crystals filter oflF the crystals at the pump and recrystallise from a small quantity of ethanol m.p. 155-156°. Yield, 2 5 g. 

Benzoylpropionitrile. To a mixture of 21 4 g. of p dimethylamino propiophenone hydrochloride, 13 0 g. of potassium cyanide in a 500 ml. flask, add 260 ml. of boiling water heat the heterogeneous mixture under reflux for 30 minutes. Part of the dimethylamine, which is eliminated in the reaction, distils collect this in dilute hydrochloric acid. Cool the reaction mixture in ice the oil sohdifies and crystals form from the aqueous layer. Collect the solid (crude p benzoylpropiouitrile, 10-5 g.) by suction filtration and recrystallise it from benzene - light petroleum (b.p. 40-60°) it separates as almost colourless blades, m.p. 76°. 

N-pyrrolidino)-propiophenone hydrochloride thus prepared melted at about 163°C to 164°C after recrystallization from acetone. 

A reaction mixture was prepared containing 4 grams of p-(4-carboethoxy-4-phenylpiperidino)-propiophenone hydrochloride, 100 ml of methanol and about... 

Dimethylamino)propiophenone hydrochloride 715 Acetophenone (60 g, 58.5 ml, 0.5mole), dimethylammonium chloride (52.7 g, 0.65 mole), and paraformaldehyde (19.8 g, 0.66 mole) are placed in a round-bottomed flask (capacity 500 ml). A mixture of concentrated hydrochloric acid (d 1.19 1 ml) and 95% ethanol (80 ml) is added and the whole is boiled under reflux for 2 h. If the yellowish solution produced is turbid it is filtered through a heated filter and, whilst still hot, diluted with acetone (400 ml). The solution is allowed to cool slowly to room temperature and placed in a refrigerator overnight. The crystals formed are filtered off, washed with acetone (25 ml), and dried for 2.5 h at 40-50° this crude product is obtained in 68-72% yield (72-77 g) and melts at 138-141°. It is somewhat hygroscopic and if dried for a further 4 h melts at 152-153°. It can be recrystallized by dissolution in 95% ethanol (85-90 ml) and slow addition of acetone (450 ml) recovery is then about 90%, the m.p. being 155-156°. 

When 3-(dimethylamino)propiophenone hydrochloride is boiled for 0.5 hour with aqueous potassium cyanide solution, 4-oxo-4-phenylbutyronitrile is formed in 67% yield, dimethylamine being split off 806... 

The Mannich reaction consists in the condensation of formaldehyde with ammonia or a primary or a secondary amine and a compound containing at least one hydrogen atom of pronounced reactivity the active hydrogen atom may be derived from a methylene group activated by a neighbouring keto group, or from a nitroparaffin, or it may be the o- or p-hydrogen atoms in phenols. Thus when acetophenone is boiled in alcoholic solution with formaldehyde and dimethylamine hydrochloride, the Mannich base 3-dimethylamino-propiophenone hydrochloride (I) is readily formed ... 

N=CvJ COCH2CH3 Preparation by diazotization of 3-amino-2- methoxy-propiophenone hydrochloride, followed... 

Preparation by diazotization of 4-amino-2-methoxy-propiophenone hydrochloride (SM), followed by treatment of the diazonium salt obtained with cuprous cyanide (41%) [6927]. SM was prepared by hydrolysis of 4-acetamido-2-methoxypropiophenone with boiling 2% hydrochloric acid for 1 h. 

The reaction of a dibromochalcone with hydroxylamine hydrochloride in pyridine gave three products with the expected 2-isoxazoline product as the predominate compound. A ring bromination product and an isoxazole were also isolated (70UC796). The reaction of hydroxylamine with /S-thiosulfates of propiophenone at reflux produced 3-phenyl-2-isoxazo-line (455). At room temperature a bis-Michael product (456) was produced. The reaction with N -phenylhydroxylamine yielded a mono-Michael type product (457) (74CPB1990). 

In an alternative route described in U.S. Patent 3,028,429 propiophenone may be reacted with an alkyl nitrite to give isonitrosopropiophenone which is then hydrogenated and finally converted to the hydrochloride. 

A solution of 44 grams of 2-bromo-4 -benzyloxypropiophenone and 44 grams of 2-(4-meth-oxyphenyDethylamine in 270 ml of ethanol was refluxed for 3 hours. Then the ethanol was distilled off in vacuo and the concentrate mixed with ether. The resulting crystallizate was Sucked off after which the filtrate was mixed with an excess of 2 N hydrochloric acid. As a result of this the hydrochloride of 4 -benzyloxy-2-[2-(4-methoxyphenyl)ethylamino]-propiophenone slowly crystallized. This substance was also Sucked off, washed with water and alcohol, and dried in vacuo. After recrystallization from dilute alcohol the yield was 25.5 grams of a product with a melting point of 217 to 218°C. 

The resulting residue, which consisted of the hydrochloride of 4 -hydroxy-2-[2-(4-methoxyphenyl)ethylamino]propiophenone, was mixed with 30 ml of a 48% hydrobromic acid solution and the mixture was boiled until no methylbromide developed any more, which was the case after approximately... 

In 1981, Hirao and others reported that the chiral borane-amine complex 25a, derived from (S)-prolinol and 1 equivalent of BH3 THF, enantioselec-tively reduced propiophenone to afford (R )-l -phenyl-1 -propanol (26) in 44% ee9 (Scheme 4.3h). The chiral complex 25b was even better than 25a, affording the same secondary alcohol in 60% ee. Two years after the initial disclosure, Hirao et al. uncovered a new catalyst system that improved the previous experimental conditions dramatically10 (Scheme 4.3i). When the chiral aminoalcohol 27, prepared from (S)-valine methyl ester hydrochloride and phenylmagnesium bromide, was used along with 2 equivalents of BH3 THF, the enantioselectivity of the alcohol 26 jumped to 94% ee. In addition, the reaction time was shortened to 2 hours. 

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