Piperazin-2-ones 3,6-disubstituted

Aminomethyl-4//-pyrido[ 1,2-a ]pyrimidin-4-ones 387 were obtained in the reaction of 2-chloromethyl derivatives 385 (R1 = H) and cyclic or disubstituted amines in boiling toluene in the presence of triethylamine for 24 hours (86FES926). When 1 mole of piperazine was reacted with... 

Brouwer and Wilbrandt have applied resonance Raman spectroscopy and calculations to questions of structure of amine radical cations [73]. Well-resolved Raman spectra of trialkylamine radical cations that are so short-lived that their electrochemical oxidation waves are irreversible may be obtained at room temperature in solution by photoionization and time-resolved detection. Comparison of the observed spectrum with calculations for various isomers provides a powerful method of answering structural questions. Density-functional calculations prove much easier to apply to open-shell species than Hartree-Fock calculations, which require cumbersome and expensive corrections to introduce suffieient electron correlation to eonsider questions like the charge distribution of disubstituted piperazine (1,4-diazacyclohexane) radical cations. The dimethyl- and diphenyl-substituted piperazine radical cations are delocalized, but charge is localized on one ArN unit of the dianisyl-substituted compound [73dj. 

Disubstituted piperazin-2-ones (83) were first synthesized by the reaction of a-chloro oximes (81) with esters of amino acids, followed by reductive cyclization... 

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). 

A greater array of amine substrates has also been explored for this reaction utilizing the 4-fluorobromobenzene as the fluoroarene. The results (Table 1) show excellent yields (85 - 93 %) for the primary (7) and secondary (8, 9) amines. Although no reaction was observed with aniline, 93 % yield was obtained with N-methylaniline (8). Derivatives prepared from the cyclic amines, morpholine (10) and piperidine (11), were also obtained in excellent yields of 82 - 98 %. A preliminary attempt at a disubstitution reaction using two equiv of piperazine Avith one equiv of 4-bromofluorobenzene gave the disubstituted product (12) in only 35 % yield. However, it is likely that this yield could be improved using an excess of... 

The same group has also described the synthesis of 1,4-disubstituted polyfunctional piperazines 65 through a one-pot Ugi-5-MCR (Scheme 7.27) [60]. In this case, the authors used piperazine (62), which attacked the intermediate 63, and later, the formed intermediate 64 would attack to a second unit of the intermediate 63, forming the final 1,4-disubstituted piperazine 65. Thus, this reaction allowed the use of four points of diversity in the starting materials. 

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