2-Piperazino

Zur Herstellung zahlreicher C-Amino-N-hetarene laBt sich die Reaktion zu einem Ein-stufen-Verfahren vereinfachen, bei welchem man die Hydroxy-Verbindung zusammen mit dem Amin, Hexamethyldisilazan und 4-Methyl-benzolsulfonsaure erhitzt. Uberschussiges Hexamethyldisilazan wird vor der (fur jeden einzelnen Fall beschriebenen1) Aufarbeitung abdestilliert. Man erhalt so z. B. 2-Piperazino-chinolin (74%) und 2,4-Bis-[henzylamino]-pyrimidin (84%) . 

Man kann mit diesem Verfahren z.B. aus dem folgenden Bis-carbamidsaure-ester selektiv eine Alkoxycarbonyl-Gruppe abspalten und erhalt so N-(2-Piperazino-ethyl)-carbamid-sdwe-methylester (92%) bzw. -ethylester (90%)2 ... 

The piperazino group of 3-piperazino-l//-pyrimido[l,2-a]quinolin-l-one (149, R = R1 = -CH2CH2NHCH2CH-) and 2-piperazino-4//-pyrimido-[2,l-a]isoquinolin-4-one was N-ethylated with ethyl p-toluenesulfonate in the presence of sodium carbonate in boiling ethanol (95MI1). 

A solution of 1-piperazino ethyl acetate (Q2 mol) in benzene (300 ml) is treated with 3,4.5-trimethoxy cinnamoyl chloride (0,2 mol) in the presence of sodium bicarbonate (0.3 mol). After contacting for one hour at room temperature, the mixture is refluxed for a further hour. The benzene solution is then treated with an aqueous solution of sodium bicarbonate. After evaporation of the solvent, a solid product is obtained which is recrystallized from isopropyl ether. Melting point = 96°C. This base, when treated with hydrochloric acid, gives a hydrochloride having a melting point of 200°C with decomposition. By the action of malaic acid the acid maleate is obtained, having a melting point of 130°C. 

Ethyl-2,3-dioxo-1 -piperazino carbonyl chloride Cefoperazone... 

Bis-[4-methyl-piperazino]-aluminiumhydrid dient der selektiven Reduktion von Carbonsauren, Carbonsau-re-estern und -amiden zu Aldehyden3 (s. S. 146). Chirale Dialkylamino-aluminiumhydride werden zu asymme-trischen Reduktionen vcrwendet4 (s.S. 337). 

Wahrend Bis-[2-methyl-propyl]-aluminiumhydrid (-78 bis -70°, Ather, 8-10 Stdn.) Carbonsauren lediglich mit mittleren Ausbeuten zu Aldehyden reduziert1, erhalt man mit Bis-[4-methyl- piperazino]- aluminiumhydrid2 in siedendemTHF selek-tiv die entsprechenden Aldehyde2. 

Lithium-tri-tert.-butyloxy-hydrido-alanat6 (nur aus Phenylestern) Bis-[4-methyl-piperazino]-alummiumhydrid7... 

Bis-[4-methyl-piperazino]-aluminiumhydrid reduziert Carbonsaure-ester ahn-lich den entsprechenden Carbonsauren (s.S. 146) auch im OberschuB selektiv zu Aldehyden. Mit zwei Mol-Aquivalenten erhalt man u.a. (THF, 6 Stdn., 66°) aus7 ... 

Zum Einsatz von Bis-[4-methyl-piperazino]-aluminiumhydridM bzw. Bis-[3-methyl-butyl-(2)]-boran10 s. Lit. 

Bis- 4-methyl-piperazino]- -hydrid 12 Bis-[2-methyl-propyl]- -hydrid Allgemeines 11 Anwendungsbereich 11 Diathyl- -hydrid 11 Dichlor- -hydrid 10 -hydrid... 

Cyclization of quinoline derivatives 57 in DMSO under the action of Cs2C03 at 85 °C afforded diesters 49 <1995T11125>. No cyclization product could be obtained when a piperazino group was present in 57 (Rz = piperazino). Cyclization in the presence of NaH gave a lower yield. When the potassium salt of 57 was used in the presence of 20 mol% of Cul, the conversion was almost quantitative, but the removal of the last traces of copper was difficult. When allyl ester 57 (R = Et, R1 = allyl, R2 = 4 - 7/-biu o ycarbonyl-l -pipcridinyl) was cyclized in DMSO in the presence of Cul and KOBuc at 50-55 °C for 0.5 h, then 100-105 °C for 6 h, the 3-ester 50 (R = Et, R1 = 4-tert-butoxycarbonyl-l-piperidinyl) was obtained in 32% yield. 

Under microwave heating conditions compound 46 is obtained with reduced reaction time (1.5 h) and better purity. A dramatic improvement was achieved when 46 was treated with N-methyl piperazine in DMF in a sealed glass vessel. After 1 h under microwave irradiation, the N-methyl piperazino derivative 47 was obtained in 68 % yield. 

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