1- ethyl piperazine

By operating in this manner 10-(2-methyl-3-chloro-propyl)phenothiazine is obtained. A mixture of 10-(2-methyl-3-chloro-propyl)phenothiazine and 1-[2-(2-hydroxyethoxy)ethyl] piperazine is then heated at 110 -120°C for 20 hours. After cooling, the reaction product is dissolved in 200 cc of benzene and the solution washed several times with water. 

Stage 4 Preparation of 1-l2-Phenyi-2-Methoxyl -Ethyi-4-[3-Phenyl-3-Hydroxypropyl] -Piperazine Dihydrochioride - In a double-neck flask equipped with a thermometer and a mechanical stirrer, there is placed in suspension in 800 ml of methanol, 233 grams of 1-[2-phenyl-2-methoxy]-ethyl-4-[2-benzoyl-ethyl]-piperazine dihydrochioride (0.55 mol). It is cooled to approximately 5°C, and 46 grams of NaOH pellets dissolved in 80 ml of HjO are added. When the temperature is about 5°C, one addition of 29,2 grams of sodium borohydride in 40 ml HjO is made. The ice-bath is then removed and stirring continued at ambient temperature for 6 hours. 

A mixture of 0.1 mol of N-mono-1-p-chlorobenzohydrylpiperazine and 0.1 mol of 1-chloro-2-(2-hydroxy-ethoxy)-ethane is heated for 3 hours to 150°C. The mass is then taken up in 100 ml of benzene and 100 ml of a 10% aqueous solution of NaOH decanting takes place, and the benzene solution is washed with water and the solvent is evaporated. Vacuum distilling of the residue yields 1-p-chlorobenzohydryl-4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazine, BP 220 C/0.5 mm Hg. 

Chamical Nama N-3-(2-Trifiuoromethyl-10-phenothia2inyl)-propyl-N -2-[2-(1,3-dioxanyl)]-ethyl-piperazine disuccinate... 

Preparation of N-(3-chlorQpropyl)-N -[2-(1,3-dioxanyl)-ethyl]-piperazine A solution of 30 g... 

The sodium derivative of the 2-trifluoromethylphenothiazine was prepared from 26.7 g (0.1 mol) of 2-trifluoromethylphenothiazine and 2.3 g (0.1 g atom) of sodium in 500 ml of liquid ammonia. After the reaction was completed, the ammonia was driven off and 500 ml of dry toluene were added. A solution of 25 g (0.09 mol) of N-(3-chloropropyl)-N -[2-(1,3-dioxanyl)-ethyl] -piperazine In 200 ml of toluene was added drop by drop to this solution which was then refluxed with stirring for 1B hours. After cooling, the precipitate which had formed was filtered and the filtrate was washed with water, dried and concentrated in vacuo. 33 g of brown oil, the N-3-(2-trifluoromethyl-10-phenothiazinyl)-propyl-N -2-[2-(1,3-dioxanyl)] -ethyl-piperazine, were obtained. 

To this acid was then added 1 g of 4-ethyl-2,3-dioxo-1-piperazinocarbonyl chloride (from the reaction of N-ethylethylenediamine and diethyl oxalate to give 2,3-dioxo-4-ethyl-piperazine which Is then reacted with phosgene) and the resulting mixture was reacted at 15°C to 20°C for 2 hours. After the reaction, a deposited triethylamine hydrochloride was separated by filtration, and the filtrate was incorporated with 0.4 g of n-butanol to deposit crystals. The deposited crystals were collected by filtration to obtain 1.25 g of white crystals of 6-[ D(—l-Ct-(4-ethyl-2,3-dioxo-1 -piperazinocarbonylaminolphenylacetamido] penicillanic acid. Into a solution of these crystals in 30 ml of tetrahydrofuran was dropped a solution of 0.38 g of a sodium salt of 2-ethyl-hexanoic acid in 10 ml of tetrahydrofuran, upon which white crystals were deposited. The deposited crystals were collected by filtration, sufficiently washed with tetrahydrofuran and then dried to obtain 1.25 g of sodium salt of 6-[D(—)-a-(4-ethyl-2,3-di-0X0-1-piperazinocarbonylaminolphenylacetamido] penicillanic acid, melting point 183°C to 185°C (decomposition), yield 90%. 

Phenyl-2-methoxy)ethyl piperazine 3-Phenyl-3-methoxy propylene oxide... 

In a reactor provided with a mechanical stirrer, a reflux refrigerant and a thermometer, there is introduced 393 grams 1-[2-phenyl, 2-methoxy] ethyl piperazine and 22 grams 3-phenyl-3-methoxy propylene oxide in 750 ml of absolute ethanol. 

Stage 2 Preparation of l-[2-Phenyl-2-Methoxy]-Ethyl-Piperazine - 210 grams of 2-phenyl-2-methoxy-ethyl bromide and 260 grams of anhydrous piperazine are heated for 5 to 6 hours to reflux in 600 ml of ethanol, 500 ml of ethanol is then distilled off and finally the solvent is removed in vacuo. The residue is taken up in 250 ml of benzene and the piperazine hydrobromide is filtered off. The benzene is removed in vacuo. The oily residue is taken up by 450 ml of water and acidification is effected up to pH = 1 by concentrated HCI. The aqueous solution is filtered the latter is then made alkaline by 50% aqueous NaOH. The liberated base is decanted, the alkaline aqueous solution is washed twice by 150 ml ether. After distillation of the ether, the previously decanted oil is added to the residue and distillation is effected in vacuo. Thus,135 grams of a colorless viscous oil, becoming carbonated in air, is obtained. 

The excess diethyleneglycol is removed in vacuo and the residue dissolved in water and then in benzene. The benzene extract is washed several times in water, then purified in vacuo. The l-p-chlorobenzhydryl-4-(2 -[2"-(2 "-hydroxyethoxy)-ethoxy]-ethyl)piperazine obtained distills at 250°C/0.01 mm Hg. 

N-[2-(3,l-Dioxanyl)ethyl]piperazine 2-Trifluoromethylphenothiazine Succinic acid... 

Preparation of N-(3-chloropropyl)-N -[2-(l,3-dioxanyl)-ethyl]-piperazine A solution of 30 g (0.15 mol) of N-[2-(l,3-dioxanyl)-ethyl]-piperazine and 11.8 g (0.075 mol) of l-bromo-3-chloropropane in 150 ml of dry benzene was refluxed with stirring for 5 hours. After cooling, the N-[2-(l,3-dioxanyl)-ethyl]-piperazinium bromide which had precipitated was filtered off, the filtrate was concentrated in vacuo and the residual oil was distilled. 14.1 g (68%yield) of N-(3-chloropropyl)-N -[2-l,3-dioxanyl)-ethyl]-piperazine which occurred as a light yellow oil were obtained. Boiling point 152°C to 155°C under 0.07 mm Hg (nD23 = 1.49 40). The disuccinate prepared in acetone and recrystallized from acetone melts at 104°C to 105°C on a hot stage microscope. 

Diphenyl-vinyl-phosphanoxid addiert auch prim, oder sek. Amine, so z.B. Piperazin zu l,4-Bis-[2 diphenylphosphinyl-ethyl]-piperazin (67% Schmp. 279-280°) oder 1,2-Diamino-ethan zu 1,2-Bis-[2-diphenylphosphinyl-ethylamino]-ethan (56% Schmp. 143-145°)412. 

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