Isoxazolium enolates derived from α,β-unsaturated and 1,3-dicarbonyl compounds. The through-space effect of the enolate moiety on the chemical shift of α-protons

The reaction of 4-phenyl-3,5-dihydroxyisoxazole with α,β-unsaturated cyclic ketones and 1,3-cyclic diketones was studied. β-Substituted α,β-unsaturated ketones give pairs of isomeric isoxazolium enolates. The remarkable influence of the heterocyclic betaine on the proton chemical shifts is discussed. 1,3-Cyclic diketones reacted spontaneously with 4-phenyl-3,5-dihydroxyisoxazole yielding isoxazolium enolate enols and enol ethers.     

Disic acids : A study of a new series of strong organic acids and their condensation products with aldehydes

4-(p-Nitrophenyl)-3,5-dihydroxyisoxazole is a remarkably strong acid which possesses unique chemical reactivity towards carbonyl compounds. It has been shown that these properties are encountered in a series of related 3,5-dihydroxyisoxazole derivatives. It appears that this isoxazole system is very electron deficient, a fact that together with a neighboring group effect is responsible for the exceptional acidity and reactivity. The electron deficiency is also reflected in the deshielding of the aromatic protons. Comparison of the NMR spectra served as a criterion for the electron deficiency of the isoxazole moiety. This new class of acids yield a variety of novel systems. The influence of substitution on the visible spectrum of the aldimonium system obtained with derivatives of benzaldehyde is discussed.     

Birch reduction of (-)-ephedrine. Formation of a new, versatile intermediate for organic synthesis

The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. In addition to the reduction of the aromatic ring, the hydroxy group was reduced as well. The resulting 1,4-cyclohexadienyl group is a potentially versatile intermediate for further synthetic transformations. The ozonolysis of this group was investigated, producing derivatives of beta-keto-delta-methylamino esters and beta-keto aldehydes which could be subsequently converted to heterocycles. The restriction to rotation of the C-N bond in N-benzoyl-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine is described.     

Ozonolysis of 1,4-cyclohexadienes in the presence of methanol and acid. Mechanism and intermediates in the conversion of 1,4-cyclohexadiene derivatives to beta-keto esters

Conditions for the preparation of beta-keto esters directly from 1,4-cyclohexadiene derivatives are described. This procedure is a further step in the application of the synthetic methodology, which consists of the combination of Birch reduction of available benzene derivatives followed by ozonolysis. In this work, the syntheses of derivatives of dimethyl gamma-keto-alpha-aminoadipate and dimethyl beta-keto glutamate from the corresponding 1,4-cyclohexadiene derivatives are described. The latter compounds are prepared from phenylalanine and phenylglycine, respectively. The study of the ozonolysis of simple alkyl derivatives of 1,4-cyclohexadiene in the presence of methanol, both in the presence and absence of acid, helped to establish the mechanism of this reaction. The proximity of the two double bonds, which are cleaved, leads to the intermediate formation of 1,2-dioxolane derivatives that could be identified by NMR spectroscopy. It is shown that regardless of the regioselectivity of the cleavage of the primary ozonide, which is formed, all 1,2-dioxolane derivatives can lead to beta-keto esters. This is due to the equilibrium between these dioxolanes in the presence of methanol and acid.     

Prospects for monolithic nano-LC columns in shotgun proteomics

We report a premier side-by-side comparison of two leading types of monolithic nano-LC column (silica-C(18), polystyrene) in shotgun proteomics experiments. Besides comparing the columns in terms of the number of peptides from a real-life sample (Arabidopsis thaliana chloroplast) that they identified, we compared the monoliths in terms of peak capacity and retention behavior for standard peptides. For proteomics applications where the mobile phase composition is constrained by electrospray ionization considerations (i.e., there is a restricted choice of ion-pairing modifiers), the polystyrene nano-LC column exhibited reduced identification power. The silica monolith column was superior in all measured values and compared very favorably with traditional packed columns. Finally, we investigated the performances of the monoliths at high flow rates in an attempt to demonstrate their advantages for high-throughput identification.     

On the reaction of phenyldisic acids with α,β-unsaturated carbonyl compounds. Reversible non-catalyzed michael addition and ring closure to derivatives of 2H,7H-isoxazolo[3,2-b][1,3]oxazine

4-Aryl-3,5-dihyroxyisoxazoles which are strong organic acids add spontaneously to mesityl oxide to form 4-aryl-2-(1,1-dimethyl-3-oxobutyl)isoxazolidine-3,5-dione. This reaction was found to be reversible and the equilibrium is solvent dependent. These acids add to 2 moles of methyl vinyl ketone. The adducts obtained from mesityl oxide undergo ketalization to form derivatives of 2H,7H-isoxazolo[3,2-b][1,3]oxazine on exposure to alcohols. The rate of this ring closure reaction is dependent on the nature of the alcohol and on the nature of the substituent on the phenyl group which is at position 4 of the isoxazole ring. The mechanisms of the non catalyzed Michael addition and of the ketalization reaction are discussed. The structure of the polymers which are obtained by the reaction of phenyldisic acids with acrolein and crotonaldehyde is also discussed.     

A novel bimolecular disproportionation in purine-N-oxides: A spontaneous autocatalytic and an anhydride induced disproportionation of 8-alkyl-7-hydroxyxanthines

8-Alkyl-7-hydroxyxanthines undergo in aqueous solution, near pH 5, an unusual spontaneous autocatalytic disproportionation. They yield the corresponding 8-alkylxanthines as the reduction product and 6-amino-5-nitrosouracil as the oxidation product. The disproportionation can also be induced by anhydrides at pH 4–12. The alkyl group at position 8 is essential for these reactions. Possible mechanisms are discussed.