Acetone Oxone Dimethyldioxirane

Opening of representative epoxides with 1,2-amino alcohols delivered the amino diols. The product amino diols were then oxidized under Swern conditions. The amino diketones so prepared were not isolated, but were condensed directly with hydroxylamine to give the substituted pyrazines.Pyrazines are important as intermediates for fragrances, 1 pharmaceuticals, 2 and agricultural chemicals. 3 Remarkably, given the importance of other aromatic heterocycles in medicinal chemistry, there are fewer than 100 trialkyl-substituted pyrazines in the SciFinder database. This is due, not to lack of interest on the part of the pharmaceutical community, but to limited methods for their preparation. 4 In the course of other work, we had occasion to briefly explore the coupling of epoxides with 1,2-aminodiols. The coupled products could then be oxidized under Swern conditions and condensed with NH 2 OH to give pyrazines. 5 Herein we report our results. Epoxide OpeningIt is important to note that the hydrogen bonded amino alcohol is much less nucleophilic, perhaps due to intramolecular hydrogen bonding, than is an isolated amine. We initially had difficulty finding conditions for the epoxide opening. We heated cyclohexene oxide and 2-amino-3-phenyl-1-propanol under solvent-free conditions, but after seven days only starting materials were visible by TLC. While LiClO 4 and BF 3 ·OEt 2 failed to activate the epoxide, the addition of a catalytic amount of Yb(OTf) 3 to the reaction 6 facilitated an easy transformation to the amino diol. This is thought to be due to the oxophilicity of the early lanthanides. Further investigations later showed that identical loading of LiBr 7 under solvent-free conditions effected an even faster transformation to the amino diol. When an activated epoxide such as 1b was used (Entries 3 and 4, Table 1), additions were carried out without catalyst. Indeed, if catalysts were added, an increased amount of the undesired regioisomer was observed. Oxidation and Pyrazine FormationWe carried out our initial investigations with 2,2′-bis(cyclohexanol)amine (3e). This amino diol provided a fine platform for the elucidation of oxidation strategies. Amino diol 3e was readily prepared by Taguchi's procedure, 8 combining cyclohexene oxide and aqueous ammonia.* taberdf@udel.edu. Supporting InformationGeneral experimental procedures, experimental details, and spectra for all new compounds. This material is available free of charge via the internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Org Chem. Author manuscript; available in PMC 2012 January 4. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe Jones reagent, 9a Dess-Martin periodinane, 9b and the Swern reaction with trifluoroacetic anhydride 9c each failed to produce the desired amino diketone. The Swern reaction utilizing oxalyl chloride 10 gave some promising results, but incomplete conversion of amino diols (indicated by the presence of amino diol by TLC after workup) proved to be troublesome. When the oxidations ...

A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (−)-citronellal. Three methods for the installation of the propargylic sidechain onto a cyclic enamide are presented.

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A set of 4-(R 2 -imino)-3-mercapto-5-(R 1 )-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.