3-Dimethylaminopropiophenone

Interest continues in the preparation of pyrimido-fused diazepines. In this context, a number of new 6-amino and 6,8-diamino-4-aryl-2,3-dihydropyrimido[4,5- >][l,4]diazepines were synthesised by the highly regioselective condensation of 4,5,6-triaminopyrimidine and 2,4,5,6-tetraaminopyrimidine respectively with 3-dimethylaminopropiophenones <00JHC401>. 

An unexpected product was obtained when the o-phenylene diamine 437 was reacted with an excess of the Mannich base, -substituted 3-dimethylaminopropiophenone hydrochloride. A product, whose relative stereochemistry was determined by NMR, was shown to have structure 438 (Equation 66) <2000EJ01973>. 

PyraZolines. l,3-Diphenyl-2-pyia2olines (7) (Table 2) aie obtainable from appiopiiately substituted phenyUiydiazines by the Knoii reaction with either P-chloro- or P-dimethylaminopropiophenones (30,31). They are employed for brightening synthetic fibers such as polyamides, cellulose acetates, and polyacrylonitriles. 

Treatment of 6-dimethylaminomethyleneaminopyrimidine 446 with / -dimethylaminopropiophenone hydrochloride [ArCO(CH2)2NMe2-HCl] in hot DMF gave the corresponding 6-aroylpyrido[2,3- pytimidine derivatives 448, while cyclization of 447 under the same conditions led to the loss of the C-2 methyl group to form the analogues 449 <1999JHC501>. 

PP-Dimethylacrylic acid, 460 Dimethylamine hydrochloride, 414, 416 Dimethylaminomethylindole, 1012,1013 P-Dimethylaminopropiophenone hydrochloride, 910, 911... 

Condensation of the active methyl group in acetophenone with formaldehyde and dimethylamine (in the form of its hydrochloride) is an example of the Mannich reaction (e.g. the synthesis of dimethylaminopropiophenone, Expt 6.147). The probable mechanism of the reaction involves the intermediate formation of the hydroxymethyldimethylamine which eliminates water to form the reactive species (1). This condenses with the a-carbon atom of acetophenone reacting in its enol form. 

The quaternary salts produced by the Mannich reaction undergo a number of conversions useful in synthesis. For example, although stable at room temperature they eliminate an amine hydrochloride on heating to yield an a,/J unsaturated ketone (e.g. the conversion of dimethylaminopropiophenone to phenyl vinyl ketone, Expt 6.147). 

To a mixture of 21.4g (0.1 mol) of dimethylaminopropiophenone hydrochloride and 13.0g (0.2 mol) 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 solidifies and crystals form in the aqueous layer. Collect the solid [crude 3-benzoylpropionitrile, 10.5 g (66%)] by suction filtration and recrystallise it from benzene-light petroleum (b.p. 40-60 °C) the product separates as almost colourless blades, m.p. 76 °C. 

Conversion to phenyl vinyl ketone. Place an intimate mixture of 21.4 g (0.1 mol) of //-dimethylaminopropiophenone hydrochloride and 0.2 g of hydroquinone in a 100-ml round-bottomed flask. Attach a Claisen still-head fitted with a stout capillary air leak and condenser arranged for distillation under reduced pressure place a few crystals of hydroquinone in the receiving flask. Pyrolyse the amine hydrochloride by heating the flask in an electric mantle at 2 mmHg (oil immersion pump), and collect the crude ketone which distils between 70 and 90 °C. On redistillation 7g (51%) of pure phenyl vinyl ketone, b.p. 72-73 °C/3 mmHg (115 °C/18 mmHg), are obtained. Characterise... 

About 600 g of p-dimethylaminopropiophenone hydrochloride were converted to the corresponding free base by the action of 1.5 N aqueous sodium hydroxide. Free base was dissolved in 2 L of THF, and the resulting solution added in dropwise fashion to a solution of 4 moles of diborane in 4 L of THF. The reaction mixture was stirred overnight. An additional mole of diborane in... 

P-Dimethylaminopropiophenone hydrochloride Hydrogen chloride 4-Trifluoromethylphenol Cyanogen bromide... 

The Grignard solution (prepared from 53 g bromtoluene and 7.2 g magnesium in 300 ml of ether) was added dropwise to a solution of 35 g p-dimethylaminopropiophenone in 50 ml ether. The mixture was refluxed for 3 hours. Then the liquid phase was added to 500 parts of ice and 100 parts concentrated hydrochloric acid. l-Phenyl-l-p-tolyl-3-dimethylaminopropanol-l was crystallized. M.P. of hydrochloride of l-phenyl-l-p-tolyl-3-dimethylaminopropanol-1 185°C. 

---