Piperazine dialkyl

IV-acetyl pyrrolidines and -piperidines to the corresponding diones or ketones were similarly effected [405, 406], as were conversions of diacetyl and dibenzyl piperazines to diketo componnds by the same system (Table 5.1) [407]. Methylene groups adjacent to the N atom in tertiary polycyclic amines were oxidised by RuO /aq. NaCIO j/CCl (Fig. 5.5) [408]. A large-scale oxidation of l,4-bis(2-phenylethyl) piperazine to the dione was made by RnO /aq. Na(10 )/Et0Ac [409], and RuO /aq. Na(IO )/CCl converted dialkyl or diaryl A A -dimethyladenosines to the corresponding monoamido derivatives (Fig. 5.4) [410]. 

Peptide-resin assembly was performed by Fmoc solid-phase methodology. All peptide-amphiphiles were synthesized as C-terminal amides to prevent piperazine-2,5-dione formation. 62 Peptide-resins were characterized by Edman degradation sequence analysis as described previously for embedded (non-covalent) sequencing. 67 Peptide-resins were then lipidated with the appropriate (Cn)2-Glu-C2-OH tail to give the dialkyl peptide-amphiphile-resin. 

Most such processes have involved treatment with an alkyl halide or with an (activated) aryl or heteroaryl halide in the presence of a base but many other reagents have been used as well. Naturally, piperazines can undergo mono- or dialkylation, broadly according to the amount of reagent, but sometimes prior protection of one NH grouping may be necessary to avoid any dialkylation. The following classified examples illustrate recently reported alkylation processes ... 

Piperazinecarbaldehyde (1-formylpyrazine) gave successively l-cinnamyl-4-piperazinecarbaldehyde (183) (PhCH=CHCH2Br, K2C03, PhMe, 110°C, 23 h 45% note protection from dialkylation), 1-cinnamylpiperazine (184) (HC1, 95°C, 3 h 55% deprotection), and l-cinnamyl-4-[2-(2,6-dimethoxyphenoxy)ethyl]piperazine (185) [BrCH2CH2OC6H3(OMe)2-2,6, K2C03, AcOEt, reflux, 6 h 35%].707... 

Piperazine (196) and 2-methylaziridine (199) gave a mixture of l-(2-amino-propyl)piperazine (200), 1-(2-amino-l-methylethyl)piperazine (201), and a trace of dialkylated material (a kinetic study with products identified spectrally H20, trace HC1, 35-80°C).1343... 

Other chlorinations have been effected with phosphorus pentachloride alone as follows piperazine-2,5-dione in carbon tetrachloride to 2,5-dichloro-3,6-dihydropyrazine (847, 849) [but at 250°/24hours to tetrachloropyrazine (850, 851)] 2[Pg.102]

Honzl (853) has described the preparation of alkyl(or aryl)-2-oxo-l, 2-dihydropyrazines by reaction of A,A -dialkyl(or aryl)piperazine-2,5-diones with phosphorus pentachloride. For example, 1,4-dicyclohexyl(or diethyl)piperazine-2,5-dione (85, R = cyclohexyl, Et) with phosphorus pentachloride in 1,2-dichloroethane gave... 

Condensations of chloroacetyl chloride (and similar compounds) with substituted ethylenediamines to give 1,4-disubstituted piperazin-2-ones have been described, and a number of 4-alkyl(or aralkyl)- -arylpiperazin-2-ones has been prepared either by catalytic debenzylation or pyrolytic debenzylation (or demethylation) of I,l-dialkyl(or l,l-diaralkyl)-3-oxo-4-arylpiperazinium halides (1609). 3-Ethoxy-carbonylmethylene-6-methylpiperazin-2-one has been synthesized by the reaction of diethyl acetylenedicarboxylate with propylenediamine (1610), and treatment of diethyl fumarate with propylenediamine has been shown to give 3-ethoxycarbonyl-methyl-6-methylpiperazin-2-one, also prepared from the diethyl ester of N- 2 -hydroxyiminopropyl)aspartic acid (84) (1611). 

Piperazine-2,6-diones have been prepared as follows. A group of 3,3-dialkyl-piperazine-2,6-diones were obtained by treating 7V-(l-cyanoalkyl)glycine esters... 

The fact that demethylation of DEC gives rise to inactive metabolites prompted Wise et al. [18] to synthesize some l-dialkyl-4-diethylcarbamoylpiperaz-inium salts (10) which would resist a DEC-like demethylation in znvo. A few piperazine-N-oxides (11) have also been prepared [19] however, none of these compounds exhibited antifilarial activity better than DEC. 

Polymerization of 1-alkyl aziridines is often accompanied by the formation of a dimer, 1,4-dialkyl piperazine ... 

In this category, there are no multiple bonds between the ring atoms. The compounds react largely like their aliphatic analogues, e.g. oxane (tetrahydropyran) and dioxane behave like dialkyl ethers, thiane and 1,4-dithiane like dialkyl sulfides, and piperidine and piperazine like secondary aliphatic amines. 

I, 4-dialkyl-, 1,4-dibenzyl, and l-benzyl-4-alkyl-2-(4, 5 -dihydro-l H-imidazol-2 -yl) piperazines and isosteric analogues of imidazoline. Journal of Medicinal Chemistry 42(9) 1587-1603. 

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