Synthesis of 4-substituted 3,5-dinitro-1,4-dihydropyridines by the self-condensation of β-formyl-β-nitroenamine.

3,5-Dinitro-1,4-dihydropyridines (DNDHPs) are readily constructed by the acid-promoted self-condensation of β-formyl-β-nitroenamines. In the DNDHPs, one molecule of the nitroenamine serves as a C3N1 building block and the other serves as a C2 block. This synthetic method does not require any special reagents and conditions.

One-step synthesis of differently bis-functionalized isoxazoles by cycloaddition of carbamoylnitrile oxide with β-keto esters.

A new protocol for synthesizing different functionalized isoxazoles is provided. Carbamoylnitrile oxide generated from nitroisoxazolone underwent inverse electron-demand 1,3-dipolar cycloaddition with 1,3-dicarbonyl compounds in the presence of magnesium acetate that formed magnesium enolate in situ. Although electron-deficient trifluoroacetoacetate did not undergo this cycloaddition under the same conditions, conversion to sodium enolate furnish the corresponding bis-functionalized trifluoromethylisoxazole.

Inverse electron-demand 1,3-dipolar cycloaddition of nitrile oxide with common nitriles leading to 3-functionalized 1,2,4-oxadiazoles.

A carbamoyl-substituted nitrile oxide was generated upon treatment of easily available 2-methyl-4-nitro-3-isoxazolin-5(2H)-one with THF (not dried); the reaction proceeded efficiently even in the absence of any special reagents and reaction conditions. The nitrile oxide caused 1,3-dipolar cycloaddition with common aliphatic nitriles or electron-rich aromatic nitriles to afford 3-functionalized 1,2,4-oxadiazoles, which are expected to serve as precursors for the preparation of a variety of functional materials by the chemical transformation of the carbamoyl group. While conventional preparative methods for 1,2,4-oxadiazoles involve the cycloaddition of an electron-rich nitrile oxide with an electron-deficient nitrile or a nitrile activated by a Lewis acid, our method employs the complementary combination of an electron-rich nitrile and an electron-deficient nitrile oxide- the inverse electron-demand 1,3-cycloaddition.

An anomalous hydration/dehydration sequence for the mild generation of a nitrile oxide.

A nitrile oxide containing a carbamoyl group is readily generated upon the treatment of 2-methyl-4-nitro-3-isoxazolin-5(2H)-one with water under mild reaction conditions, even in the absence of special reagents. The obtained nitrile oxide undergoes cycloaddition with dipolarophiles, alkynes and alkenes, to afford the corresponding isoxazol(in)es, which are useful intermediates in the synthesis of polyfunctionalized compounds. A plausible mechanism underlying the formation of the nitrile oxide is proposed, which involves an anomalous hydration/dehydration sequence.

Base induced chemical conversion of 3-carbamoyl-2-isoxazolines.

3-Carbamoyl-2-isoxazolines, prepared by cycloaddition of functionalized nitrile oxide, serve as masked 3-unsubstituted isoxazolines to afford 2-isoxazoline-3-carboxylic acid, beta-cyanoalcohol, alpha,beta-unsaturated nitrile, and alpha,beta-unsaturated amide upon heating in the alkaline solution. The present reaction is also applicable to synthesis of 3,4-difunctionalized isoxazoles and beta-hydroxy-gamma-lactone.

Formylnitroenamines: useful building blocks for nitrated pyridones and aminopyridines with functional groups.

beta-formyl-beta-nitroenamines possess both an electrophilic formyl group and a nucleophilic amino group and, therefore, serve as C3N1 building blocks having a nitro group to afford nitropyridones and aminonitropyridines with a functional group at the 3-position. Upon treatment with malonic acid derivatives or beta-keto esters, nitropyridones were obtained, whereas reactions with functionalized acetonitriles afford aminonitropyridines, via a formal transfer of an alkyl group from the ring nitrogen to the imino group. These procedures provide practical and useful methods for preparation of heterocycles with a nitro group.

Dimerization of acetoacetamide leading to 5-carbamoyl-4,6-dimethyl-2-pyridone.

The dimerization of acetoacetamide easily proceeds at room temperature in a dimethyl sulfoxide solution to afford 5-carbamoyl-4,6-dimethyl-2-pyridone.

A convenient method for synthesizing modified 4-nitrophenols.

[reaction: see text] Beta-nitroenamine having a formyl group behaves as the synthetic equivalent of unstable nitromalonaldehyde upon treatment with ketones under basic conditions and leads to 2,6-disubstituted 4-nitrophenols. The present method is safer than the conventional one using sodium nitromalonaldehyde and enables the preparation of hitherto unknown nitrophenols.

New synthetic equivalent of nitromalonaldehyde treatable in organic media.

beta-Nitroenamines having a formyl group at the beta-position behave as the synthetic equivalent of unstable nitromalonaldehyde, which is a useful synthon for syntheses of versatile nitro compounds. High solubility of the nitroenamines into general organic solvents enables us to conduct reactions in the organic media accompanied by easy experimental manipulations and considerable safety. When nitroenamines are treated with 1,2-bifunctional nucleophiles such as hydrazines, hydroxylamine and glycine ester, nitrated pyrazoles, isoxazole and pyrrole-2-carboxylate were readily prepared.

Synthesis of unnatural 1-methyl-2-quinolone derivatives.

Unnatural 1-methyl-2-quinolone derivatives were synthesized by regioselective C-C bond formation. When 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was treated with enamines, nucleophilic addition readily occurred at the 4-position, and succeeding hydrolysis of enamine moiety followed by elimination of nitrous acid furnished 4-acylmethyl-1-methyl-6,8-dinitro-2-quinolones. The same products could be prepared by the reaction of TNQ with ketones in the presence of triethylamine.

Substituent effects of beta-diketiminate ligands on the structure and physicochemical properties of copper(II) complexes.

Substituent effects of beta-diketiminate ligands on the structure and physicochemical properties of the copper(II) complexes have been systematically investigated by using 3-iminopropenylamine derivatives R1LR3H, R3-N=CH-C(R1)=CH-NH-R3, where R1 is Me, H, CN, or NO2, and R3 is Ph, Mes (mesityl), Dep (2,6-diethylphenyl), Dipp (2,6-diisopropylphenyl), or Dtbp (3,5-di-tert-butylphenyl). When the ligands with R3=Ph or Dtbp were treated with CuII(OAc)2, bis(beta-diketiminate) copper(II) complexes exhibiting distorted tetrahedral geometries were obtained, the crystal structures of which were nearly the same as each other regardless of the alpha-substituent (R1); dihedral angles between the two beta-diketiminate coordination planes are 62.5 +/- 1.

Transacylation of alpha-aryl-beta-keto esters.

The acyl group of an alpha-aryl-beta-keto ester was readily transferred to N-, O-, and S-nucleophiles. The transacylation from arylated diethyl 3-oxoglutarate to amines led to unsymmetrical malonic acid amide esters in high yields. The present reaction proceeded under mild conditions without formation of detectable byproducts.

Facile synthesis of functionalized 4-aminopyridines.

The title compounds are readily available by ring transformation of nitropyrimidione with active methylene compounds in the presence of ammonium acetate.