Neighboring amide group participation in ester aminolysis in aprotic solvents

The piperidinolysis of 8-quinolyl-, p-nitrophenyl-, o-, and p-piperidinocarbonylphenyl acetates in acetonitrile and in chlorobenzene was studied at 25°C. The strictly second order kinetic behaviour and the weaks solvent-dependence of the rate of the reaction of o-piperidinocarbonylphenyl acetate indicate anchimeric assistance by the o-amide group, and support the suggestion that amide groups of hydrophobic enzyme active sites may act as general base catalysts.

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8--, --, - - 25°C. - - , .

     

Neighboring group participation in cyclodehydration. A regiospecific isoxazole synthesis

The regiospecific synthesis of isoxazoles 2, 11, 14 , and 15 is explained in terms of neighboring group participation of the ortho nitrogen of the heterocyclic ring in the cyclodehydration step.     

Dialkylaminoacetonitrile derivatives as amide synthons. A one-pot preparation of heteroaryl amides via a strategy of sequential SNAr substitution and oxidation

Dialkylamino acetonitrile derivatives were utilized as alternative to cyanohydrin synthons for preparation of the corresponding heteroaryl dialkyl amides via a strategy of sequential base-mediated coupling and oxidation. The most advantageous oxidant, NiO(2)-H(2)O, can readily oxidize 2-substituted aminoacetonitriles to the corresponding amides under both basic and neutral conditions by forming cyanohydrins in situ.     

Antibody-catalyzed benzoin oxidation as a mechanistic probe for nucleophilic catalysis by an active site lysine

Aldolase antibody 24H6, which was obtained by reactive immunization against a 1,3-diketone hapten, is shown to catalyze additional reactions, including H/D exchange and oxidation reactions. Comparison of the H/D exchange reaction at the alpha-position of a wide range of aldehydes and ketones by 24H6 and by other aldolase antibodies, such as 38C2, pointed at the significantly larger size of the 24H6 active site. This property allowed for the catalysis of the oxidation of substituted benzoins to benzils by potassium ferricyanide. This reaction was used as a mechanistic probe to learn about the initial steps of the 24H6-catalyzed aldol condensation reaction. The Hammett correlation (rho=4.7) of log(k(cat)) versus the substituent constant, sigma, revealed that the reaction involves rapid formation of a Schiff base intermediate from the ketone and an active site lysine residue. The rate-limiting step in this oxidation reaction is the conversion of the Schiff base to an enamine intermediate. In addition, linear correlation (rho=3.13) was found between log(K(M)) and sigma, indicating that electronic rather than steric factors are dominant in the antibody-substrate binding phenomenon and confirming that the reversible formation of a Schiff base intermediate comprises part of the substrate-binding mechanism.     

Hydrogen-bonding-mediated anthranilamide homoduplexes. Increasing stability through preorganization and iterative arrangement of a simple amide binding site

This paper describes the assembly of two new series of self-complementary duplexes by making use of amide units, the simplest assembling units of hydrogen bonding, as binding sites. All the new monomers possess a rigidified anthranilamide skeleton, which is stabilized by intramolecular hydrogen bonding. Amide units are iteratively introduced to one side of the preorganized skeletons to facilitate the formation of intermolecular hydrogen bonding. Compounds 2 and 3 bear two and three CONH(2) units, respectively, while 4, 6, and 7 are incorporated with two, three, and four AcNH units, respectively. For comparison, compound 5, which is similar to 4 but contains one AcNH and one CF(3)CONH unit, is also prepared. X-ray diffraction analysis of 2, 4, and 5 revealed homodimeric motifs in the solid state which are stabilized by two or more intermolecular hydrogen bonds. (1)H NMR investigations in CDCl(3) indicated that all the compounds form hydrogen-bonded homoduplexes. Duplexes 3.3, 6.6, and 7.7 are highly stable in CDCl(3), with a lower K(assoc) limit of 2.3 x 10(5) M(-1). The K(assoc) values of the three duplexes in more polar CDCl(3)/CD(3)CN (9:1, v/v) were determined with the (1)H NMR dilution method. The result opens the way for the development of new polymeric duplexes of well-ordered structures.     

Neighboring group participation in the acetolysis of 1,1,1-triaryl-3-diazo-2-propanones. An unprecedented 1,3 shift of an aryl group via a five-membered transition state.

The acetolysis of diazo ketones 1a,b,c, leads to the corresponding indanones 3a,b,c, and to the rearranged acetates 4a,b,c. The formation of the acetates 4 can be explained in terms of a mechanism involving the same transition state responsible for the ring closure to 3.     

A water-soluble and "self-assembled" polyoxometalate as a recyclable catalyst for oxidation of alcohols in water with hydrogen peroxide

We have demonstrated that a simply prepared water-soluble polyoxometalate, Na12[WZnZn2(H2O)2(ZnW9O34)2], synthesized from readily available zinc and tungsten salts in the presence of nitric acid, is an effective catalyst for selective alcohol oxidation with hydrogen peroxide in biphasic (water-alcohol) reaction media. Experiments have shown that the "self-assembled" catalyst in its mother liquor was as active as the isolated catalyst. The aqueous catalyst solution is easily separated from the water-insoluble products and can be recycled without loss in activity or selectivity.     

Neighbouring group participation in the allylic oxidation of a Δ5-steroid

The allylic oxidation of 3β-acetoxyandrost-5-en-17-one by bromine and silver acetate affords 4β-acetoxy-3β-hydroxyandrost-5-en-17-one rather than the 3β,4β-diacetate. Labelling studies show that this involves the migration of the 3β-acetoxyl group and an overall retention of configuration at C-4.