Piperazine adduct

The p-DVB-piperazine adducts can also undergo self condensation whereby the macromonomers formed exhibit rather low molecular weights, and are insoluble in the reaction mixture (benzene or THF). They dissolve only upon the addition of an acid or in hot chloroform. Free-radical copolymerization of this macromonomer with styrene was carried out in benzene in the presence of some acetic acid (to obtain a homogeneous reaction mixture) to yields of about 20% M). Here again separation of the unreacted macromonomer is possible, and the polyamine content of the graft copolymer is very close to the amount contained in the reaction mixture. 

Variable-temperature Raman spectra of aqueous solutions containing Cd(OH2)6 show vCdOe bands at 235 cm and 185 cm , assigned to Cg and t2g modes respectively. The IR spectra of cadmium(II) bis(acetylacetonate) and its bis-piperazine adduct show that vCdO decreases on the additional coordination of the V-donor. 2... 

The reaction of 5-methoxy-2(5//)-furanone 168 with amines was also studied (89T6799). The conjugated addition of ethanolamine to the furanone 168 gave the racemic amino lactone 275 (R = CH2CH20H). Similarly, piperazine reacted with two equivalents of 168 to provide the diadduct 276 as a single diastereomer (no traces of the other isomer were detected). With tryptamine, the reaction was nearly quantitative with the the formation the tran -adduct 277 (R = tryptophanyl) (Scheme 72) (89T6799). 

In some cases we may benefit from using an external agent to carry out the desired separation through crystallization. Thus, in the case of isomeric and non-isomeric mixtures of close-boiling acidic or basic materials we may use a suitable base or acid to carry out dissociative extractive crystallization, akin to dissociative extraction referred to in Section 4.2.1. For instance, for a mixture of p- and m-cresol or p-cresol and 2,6-xylenol we may use a base like anhydrous piperazine to obtain a precipitate of relatively pure p-cresol salt of piperazine, which can then be filtered and subjected to recovery of piperazine for recycle. Similarly, we may add a substance which forms an adduct with the desired substance. 

The initiating nucleophile in the vast majority of these studies is the hydroxide anion. However, in principle, any nucleophile can add to the keto or formyl group to give rise to an anionic intermediate, which then could act as an intramolecular nucleophile and effect hydrolysis of the ester. Their relative effectiveness will depend on two factors the relative extent of formation and the nucleophilicity of the adduct. The nucleophiles that have been investigated are hydroxide, cyanide, morpholine and piperazine. The only quantitative comparison available is that of hydroxide, morpholine and piperazine, which are effective in the order of ca. 102 10-3 1 (Bender et al., 1965 Dahlgren and Schell, 1967). For morpholine and piperazine this is as expected on the basis of their relative basicities. However, the expected order of increasing formation of the adducts would be cyanide > nitrogen bases > hydroxide (Hine, 1971). At this time, these results cannot be analysed further, but more work on the systems could enable the structural dependence and reactivity to be elucidated. 

Hutzler, J.M., Steenwyk, R.C., Smith, E.B., Walker, G.S. and Wienkers, L.C. (2004) Mechanism-based inactivation of cytochrome P450 2D6 by l-[(2-ethyl-4-methyl-1 H-imidazol-5-yl) methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine kinetic characterization and evidence for apoprotein adduction. Chemical Research in Toxicology, 17 (2), 174—184. 

Fig. 7 Manual grinding of the ferrocenyl dicarboxylic acid complex [Fe(ip -C5H4COOH)2] with l,4-diazabicyclo[2.2.2]octane, 1,4-phenylenediamine,piperazine, fraMS-l,4-cyclohexa-nediamine and guanidinium carbonate generates quantitatively the corresponding organic-organometallic adducts. The reaction with phenylenediamine highlights that single crystals of the adduct can be grown from solution and used to fully characterize the reaction product...

As shown by mass spectrometry and NMR spectroscopy, these amine derivatives of Cgfl, after work up, are dehydrogenated adducts [81]. After nucleophilic addition, the H atoms brought in by the diamines were oxidatively eliminated. The final adduct formation of the secondary diamines proceeds exclusively at [6,6] bonds. Besides the monoadduct, most of the regioisomeric bisadducts of piperazine or N,N -dimefhylethylenediamine and Cjq could be separated by column chromatography. The structure of the monoadduct and some of these bis-adducts were proven by X-ray crystal-structure analysis [90]. 

Tellurium tetrabromide is amphoteric in fused arsenic tribromide, from which complex bromides such as [(Et)4N]2TeBr6 and ammine adducts such as TeBr4-2PhNMe2 have been obtained. Addition compounds with pyridine, tetramethylthiourea and piperazine have also been reported.38,39 Alkali metal Salts such as TeBr4-2CsCl and the full brominated complexes of the type M2TeBr6 and M2PoBrs are also known. 

One approach utilizes Katritzky s route to tertiary amines to construct the benzhydrylpiperazine (Scheme 7) [42]. This method involves addition of an aryl Grignard reagent to a masked iminium, an adduct formed from the piperazine, an appropriate benzaldehyde, and benzotriazole. In solution, this adduct is in equilibrium with an iminium ion formed by elimination of the benzotriazole, and it is likely that the Grignard reagent adds to this species. Assuming that the iminium ion is the reactive entity, the stereoselectivity appears to rely on two separate events 1) preferential formation of one of the... 

The method ofTsuruta was also extended to the synthesis of macromonomers containing piperazine cycles, and even diaza crown ethers81 84185). Here again the first step involves preparation of 1 1 adducts of p-divinylbenzene and the corresponding heterocyclic compound ... 

Reaction of 2, 3 -ene-3 -phenylselenone 13 [R2 = C(4-CH3OC6H4)(C6H5)2] with 1,2-ethanedi-amine in tetrahydrofuran at about 20 °C gives a mixture of the 2, 3 -ribo-piperazine 20 (28%) and the 2, 3 -[A -(2-aminoethyI)]-ribo-aziridine 21 (54%)106. This shows that the second nucleophilic attack at C-3 by a more basic 2 -secondary amino group is favored over attack of the /(-amino group in the C-2 -substituted adduct. The proximity of the 2 -secondary amino group may also contribute to its facile attack at C-3. A similar reaction of 13 (R2 = H) gives direct access to the fully deprotected nucleosides 20 and 21 (R2 = H) in 34% and 38% yield, respectively. 

Some unusual zwitterionic pyrazines have been prepared by dehydrogenation of 1,4-disubstituted piperazine-2,6-diones. Honzl et al. (476a) prepared theanhydro-2,6-dihydroxy-l, 4-diphenyl-3,5-bis(phenylthio)pyrazinium dihydroxide [s/c] (92) (which yields adducts by dipolar cycloaddition of maleic anhydride or formaldehyde) by the reaction of 1,4-diphenylpiperazine-2,6-dione with benzenesulfonyl chloride in pyridine. Tanaka et al. (476b), from I,4-diphenylpiperazine-2,6-dione with benzoyl chloride, and tosyl chloride in pyridine at reflux, obtained the anhydro - 3 - benzoyl - 2,6 -dihydroxy -1,4 -diphenyl - 5 - (p - toly lthio)pyrazinium dihydroxide [src] (93), together with some of the S-p-tolyl analogue of (92). 

Piperazine reacts with benzyl chloroformate to give l-(benzyloxycarbonyl)-piperazine (1690), with benzyl chloride (1 mol) (and piperazine dihydrochloride) to 1 -benzylpiperazine (1691-1693), with ethyl chloroformate and sodium hydroxide to 1,4-diethoxycarbonylpiperazine, which with sodium benzyl oxide gave 1,4-dibenzyloxycarbonylpiperazine (1694), and with cyanogen to 1,4-bis(C-cyano-C-iminomethyl)piperazine (139) (1695). The piperazine-chlorotrimethylsilane adduct with triethylamine gave l,4-bis(trimethylsilyl)piperazine (1696), and piperazine in... 

Stability constants of mixed ligand complexes containing ATP, tryptophan (Trp) and copper(ii) have been obtained. The reaction of amines with [Cu(Bz-AlaO)2],-H2O (Bz-AlaO = A -benzoyl-DL-alaninato) gives adducts [Cu(Bz-AlaO)2],B (n = 1, B = piperazine, 3-Me-py, 4-Me-py, 2,2 -bipy, 4,4 -bipy, or phen n = 2, B = piperidine or morpholine). The crystal structure of aqua(glycyl)-L-tryptophanatocopper... 

The reaction indeed worked well. Thus, heating to reflux a methanolic solution of piperazine, formaldehyde, acetic acid, and cyclohexyl isocyanide afforded the split-Ugi adduct 79 in 75% yield. Note that in this reaction, the symmetric diamine has been effectively desymmetrized since one nitrogen atom was alkylated while the other was acylated. The piperidine ring in intermediate 77 has to adopt a boat conformation in order for the transacylation to take place smoothly [Scheme 5.23, reaction (a)]. 

Piperazine- and triethylenediamine-monoborane (but not diborane) adducts of BH2F, BHF2, and BF3 are produced by displacement reactions between the diamine and the Me3N-fluoroboranes. H and B n.m.r., and i.r. data were given for these new species. ... 

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