Piperazine synthesis

Scheme 6 Use of Lewis acid catalyst for 3-CR 2-imino-piperazine synthesis and representative 3D conformations of the cis- and trans-stereoisomer 39 are shown. Two 3D structures of the cis- and trans-stereoisomer 39 are shown...

Cignarella, G., Occelli, li., Maffli, G., and Testa, E., Bicyclic homologs of piperazine, synthesis of pharmacologically active... 

Deen GR, Lim EK, Mah CH, Heng KM (2012) New cationic linear copolymers and hydrogels of N-vinyl caprolactam and N-acryloyl-N -ethyl piperazine Synthesis, reactivity, influence of external stimuli on the LCST and swelling properties. Ind Eng Chem Res 51 13354 Di Meo C, Capitani D, Mannina L, Brancaleoni E, Galesso D, De Luca G, Crescenzi V (2006) Synthesis and NMR characterization ofnewhyaluronan-basedNO donors. Biomacromolecules 7 1253... 

Synthesis of the CNS depressant/tranquil izer tioperidone (59) begins by alkylation of piperazine derivative with 4-chlorobutyronitrile to give Lithium aluminum hydride... 

According to a hypothesis launched by Larionov et al in the 1960s, some new nitrogen mustard derivatives were developed. They contain metabolites and heterocyclic structures as carriers of the cytotoxic chloroethylamine groups. By this way the synthesis of aliylating metabolites started melphalan (sarcolysine) as L- or DL-phenylalanine derivative prospidine with a tricyclic piperazine moiety and chlorambucil as butyric acid derivative. It was proven that each alkylating metabolite has its own spectrum of selective antitumor activity. 

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

Scheme 9 Synthesis of enantiopure piperazines by reductive coupling of chiral 2,5-diaza-1,5-dienes...

As previously described, in basic conditions the proUne-derived a-sulfonyl amide 141 generates the imine function, which afterwards undergoes addition by a nucleophile, e.g., a nitronate ion see the diastereoselective synthesis of the diamino nitroalkane derivative 172, which is the precursor of the piperazine-2-carboxyUc acid 173, through a Nef reaction [45]. Similarly, the addition of the Uthium enolate of ethyl acetateto the a-sulfonyl amide 174 gave the diamino ester derivative 175, wich was then converted to (-)-l-aminopyrrolizidine 176 (Scheme 27). 

The synthesis of ethylenediamine (EDA) from ethanolamine (EA) with ammonia over acidic t3pes of zeolite catalyst was investigated. Among the zeolites tested in this study, the protonic form of mordenite catalyst that was treated with EDTA (H-EDTA-MOR) showed the highest activity and selectivity for the formation of EA at 603 K, W/F=200 g h mol, and NH3/ =50. The reaction proved to be highly selective for EA over H-EDTA-MOR, with small amounts of ethyleneimine (El) and piperazine (PA) derivatives as the side products. IR spectroscopic data provide evidence that the protonated El is the chemical intermediate for the reaction. The reaction for Uie formation of EDA from EA and ammonia required stronger acidic sites in the mordenite channels for hi er yield and selectivity. 

Acylating Cleavage Investigated in Micro Reactors Organic synthesis 11 [OS 11] Synthesis of piperazine... 

Lopez-Rodriguez ML et al. (1996) Synthesis and structure-activity relationships of a new model of arylpiperazines. 1. 2-[[4-(o-Methoxyphenyl)piperazin-l-yl]methyl]-1, 3-dioxoperhydroimidazo[l,5-alpha]pyridine a selective 5-HTlA receptor agonist. J Med Chem 39(22) 4439-4450... 

Hird NW, Irie K, Nagai K. Solid phase synthesis of 2-aminobutadienes using a piperazine linker. Tetrahedron Lett 1997 38 7111-7114. 

The presence of triethylenetetramine in the hydrothermal synthesis of open-framework zinc phosphates results in a number of frameworks with one- to three-dimensional structures. The structures include one-dimensional ladders, two-dimensional layer structures, and one structure where the tetramine is bound to the zinc center. The structural type was highly sensitive to the relative concentration of the amine and phosphoric acid.411 Piperazine and 2-methylpiperazine can be used as templating molecules in solvothermal syntheses of zinc phosphates. The crystallization processes of the zinc compounds were investigated by real time in situ measurements of synchrotron X-ray powder diffraction patterns.412... 

In a similar fashion, Li and co-workers have described the synthesis of bis-amides 145 by the reaction of 1,4-dibromobutane with the piperazine counterparts 144 (Equation 33) <2003BML1729>. The compounds were tested as analgesics yields were not reported. 

The synthesis of azoniaspirocycles can also be carried out on solid support (Scheme 17) <2005JOC9622>. In the following example the resin-bound piperazine-tethered secondary amine 149 underwent an acylation to give amide 150. This was followed by a spontaneous intramolecular displacement of the bromide to yield the trisubstituted azoniaspiroundecane 151. 

Khazanov, E. Barenholz, Y., Gibson, D., Najraeh, Y. Novel apoptosis-including trans-platinum piperidine and piperazine derivatives Synthesis and biological characterization. J. Med. Chem. 2002, 45, 5189-5195. ... 

Microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis applications. The first example of parallel reactions carried out under microwave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 4.22) [76]. Reactions were carried out in a multimode microwave reactor in individual sealed polypropylene vials using acetonitrile as solvent. Screening of the resulting 2-aminothiazole library in a herpes simplex virus-1 (HSV-1) assay led to three confirmed hits, demonstrating the potential of this method for rapid lead optimization. 

---