Novel Diels-Alder reaction of 4-nitro-1(2H)-isoquinolones

A novel Diels-Alder (DA) reaction with 4-nitro-1(2H)-isoquinolones acting as the dienophile afforded 5(6H)-phenanthridone derivatives. The DA reaction of 4-nitro-1(2H)-isoquinolone with 1-methoxy-1,3-butadiene gave biologically active 5(6H)-phenanthridone possessing in a high yield. Regioselectivity of 4-nitro-1(2H)-isoquinolones with 1-methoxy-3-silyloxy-1,3-butadiene was calculated using molecular orbital (MO) calculations.     

Synthesis of isoquinoline derivatives by Diels-Alder reactions of 2(1H)-pyridones having an electron-withdrawing group with methoxy-1,3-butadienes

Diels-Alder (DA) reactions of 2(1H)-pyridones having an electron-withdrawing group at the 4-position with 2,3-dimethoxy- and 2-methoxy-1,3-butadienes gave isoquinoline derivatives. Furthermore, an isoquinoline alkaloid (6,7-dimethoxy-2-methyl-1(2H)-isoquinolone) was synthesized by elimination of hydrogen cyanide and dehydrogenation of the DA-adduct having a cyano group at the 4a-position.     

Nucleophilic substitution and ring closure reactions of 4-chloro-3-nitro-2-quinolones

4-Chloro-3-nitro-2-quinolones 3 obtained from the 4-hydroxy quinolones 1 by nitration and chlorination, reacted with sodium azide to the 4-azido derivatives 4 which cyclized on thermolysis to yield the furoxanes 5 . Nucleophilic substitution reactions of 3 led to the 4-amino-, 4-fluoro- and 4-alkoxy-3-nitroquinolones 7, 8 and 9 , respectively. With thiols either 4-thio-3-nitro- 10 or 3,4-dithioquinolones 11 were obtained depending on the basic catalyst.     

Synthesis and structure of 3-amino-4-hetaryl-1-(2H)-isoquinolones

A one-step preparative method of synthesis of 3-amino-4-hetaryl-1(2H)-isoquinolones by reaction of 5-nitro-2-chlorobenzamides with -azahetarylacetonitriles in the presence of base has been developed. It has been shown that benzimidazo[1,2-b]isoquinolones may be obtained in this way.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1104–1106, August, 1991.     

Rhodium(III)-Catalyzed Intramolecular Annulation through CH Activation: Total Synthesis of (±)-Antofine, (±)-Septicine, (±)-Tylophorine, and Rosettacin

Annulation: The efficient synthesis of 3-hydroxyalkyl isoquinolones and 6-hydroxyalkyl 2-pyridones is enabled through the intramolecular annulation of alkyne-tethered hydroxamic esters (see scheme, Cp*=pentamethylcyclopentadienyl). The reaction features high regioselectivity, broad substrate scope, and excellent functional-group tolerance, proceeds under mild reaction conditions with low catalyst loading, and obviates the need for an external oxidant.     

High functionalization of 5-nitro-1H-imidazole derivatives: the TDAE approach

We report herein the synthesis of substituted 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)phenyl]-1-arylethanols, ethyl 3-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)-phenyl]-2-hydroxypropanoate and 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)benzyl]-2-hydroxy-acenaphthylen-1(2H)-one from the reactions of 4-[4-(chloromethyl)phenyl]-1,2-dimethyl-5-nitro-1H-imidazole with various aromatic carbonyl and a-carbonyl ester derivatives using tetrakis(dimethylamino)ethylene (TDAE) methodology.     

4(3H)-Quinazolinones containing heterocyclic group in position 3

The corresponding 2,3-substituted 4(3H)-quinazolinones were obtained in the reactions of 2-methyl- and 2-phenyl-4-oxo-3,1-benzoxazines with 1-amino-1,2,4-triazole, 4-amino-2,3-dimethyl-1-phenyl-5-pyrazolone, 2-amino-5-ethyl-1,3,4-thiadiazole, 3-amino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazole, 1-amino-3-cyano-4,6-dimethyl-2-pyridone, and 1-amino-3-cyano-6-phenyl-4-trifluoromethyl-2-pyridone. The formation of N-benzolyanthranilamides in the reactions of 2-phenyl-4-oxo-3,1-benzoxazine with 2-amino-5-ethyl-1,3,4-thiadiazole and 1-amino-3-cyano-6-phenyl-4-trifluoromethyl-2-pyridones was exceptional. The structures of two of the products have been confirmed by X-ray crystallography.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 936–943, July, 2000.     

Cycloaddition of 2(1H)-pyridones having a methoxycarbonyl group to 1,3-butadiene derivatives

The cycloaddition of 4-methoxycarbonyl-2(1H)-pyridones to silyloxydienes gave isoquinolone derivatives in reasonable yields. Furthermore, the cycloaddition of 6-methoxycarbonyl-2(1H)-pyridones to 2,3-dimethyl-1,3-butadiene produced cycloadducts (isoquinolone and quinolone derivatives) and double cycloadducts (phenanthridone derivatives). The activation energies using Gaussian 98 with RHF/3-21G level of 4- and 6-methoxycarbonyl-2(1H)-pyridones coincided with the experimental facts.     

Flexible strategy for differentially 3,5-disubstituted 4-oxypyridin-2(1H)-ones based on site-selective Pd-catalyzed cross-coupling reactions

3,5-Dihalogeno-4-methoxy-N-methylpyridin-2(1H)-ones have been shown to undergo single Suzuki coupling reactions in a site-selective fashion. Monoarylations occur at the C-5 position preferentially, thus leaving the remaining C-3 halide free for further functionalization, to finally access differentially 3,5-disubstituted 2-pyridones. This two-step strategy has been applied to the elaboration of the 3-acyl-5-aryl-4-oxy-2-pyridone subunit that is prevalent in numerous bioactive natural products. [reaction: see text].     

Diels-alder reaction of 2(1H)-pyridones acting as dienes

Diels-Alder reactions between N-phenylmaleimide, acting as the dienophile, and 2(1H)-pyridones having a methoxy or a chloro substituent, were carried out, under atmospheric and high pressure conditions, to give the corresponding isoquinuclidine derivatives. Stereoselectivity of the Diels-Alder reactions was studied using molecular orbital calculations.     

Oxazolo[3,2-a]pyridinium salts

The first synthesis of the aromatic oxazolo[3,2-a]pyridinium ring system has been accomplished by the cyclization of 1-acetonyl- or 1-phenacyl-2-pyridones. Through use of the analogous quinolones and 2-(p-bromophenacyl)-1-isoquinolone, benzologs of the new system have been prepared.     

Novel and versatile reactions of trifluoroamine oxide: a new route to polyfluorinated ethers

A series of pyrimidine methyl and polyfluoroalkyl ethers were synthesized from the reactions of trifluoroamine oxide (1) with several 5-substituted uracils in the presence of tetrabutylammonium hydroxide and methanol, 2,2,2-trifluoroethanol (6), or 1H,1H-pentafluoropropanol (7). With 5-(trifluoromethyl)uracil (2), the new ethers formed were 5-fluoro-5-(trifluoromethyl)-6-methoxypyrimidine-2,4-dione (8), 5-fluoro-5-(trifluoromethyl)-6-(trifluoroethoxy)pyrimidine-2,4-dione (9), and 5-fluoro-5-(trifluoromethyl)-6-(1H,1H- pentafluoropropoxy)pyrimidine-2,4-dione (10). With 5-chlorouracil (3), the new ethers 5-chloro-5-fluoro-6-methoxypyrimidine-2,4-dione (11), 5-chloro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (12), and 5-chloro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (13) were obtained. With 5-fluorouracil (4), the new ethers 5,5-difluoro-6-methoxypyrimidine-2,4-dione (14), 5,5-difluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (15) and 5,5 difluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (16) were found. By reaction of 5-nitrouracil (5), the new ethers 5-nitro-5-fluoro-6 methoxypyrimidine-2,4-dione (17), 5-nitro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (18), and 5-nitro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (19) were obtained. Each of the new compounds was characterized by using IR, 19F and 1H NMR, and mass spectroscopy, and elemental analysis. A single-crystal X-ray diffraction study of 8 was helpful in confirming compound structure.     

Reactions of ketene silyl acetals with imine-complexes of titanium tetrachloride. New and convenient routes to 5,6-dihydro-2-pyridones and 5-amino-2-alkenoates

The reactions of vinylketene silyl acetals (VKSAs) with imine complexes of TiCl₄ give the corresponding 5,6-dihydro-2-pyridones and/or 5-amino-2-alkenoates in good to excellent yields. It is suggested that an addition-cyclization mechanism is operative for the formation of 5,6-dihydro-2-pyridones in this formal cyclocondensation reaction.     

The diene synthesis reaction and substitutive addition with 2-pyridones and their thio analogs (review)

The literature on the reactions of 2-pyridones and their thio analogs with unsaturated compounds taking place by a mechanism of diene synthesis or of substitutive addition, depending on the structure of the initial components, has been systematized. The basic synthetic directions of the use of these reactions and also the stereochemistry of the diene synthesis with 2-pyridones and 2-thiopyridones are considered.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 3–20, January, 1984.     

Synthesis of Some Halogen- and Nitro-substituted Nicotinic Acids and Their Fragmentation Under Electron Impact

Features of electrophilic and nucleophilic substitution under chlorination and nitration reactions conditions have been investigated for 6-hydroxy- and 6-methyl-substituted derivatives of 3-cyano-4-methyl-2(1H)-pyridones. The polychloro- and nitro-substituted 3-cyano-4-methylpyridines obtained were used as synthons in the synthesis of some polyhalo- and nitro-substituted nicotinic acids and their amides. The fragmentation pathways of the synthesized compounds under electron impact have been studied.     

Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)-quinolones acting as dienophiles

Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives were carried out to give the phenanthridone derivatives under both atmospheric and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)-quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined using molecular orbital (MO) calculation.     

Synthetic, spectral, and antimicrobial aspects of biologically relevant coordination compounds of dioxomolybdenum(VI) and oxovanadium(V)

Heterocyclic ketimines, 5-nitro-3-(indolin-2-one)hydrazinecarbothioamide (L¹H), 5-nitro-3-(indolin-2-one)hydrazinecarboxamide (L²H), 6-nitro-3-(indolin-2-one)hydrazinecarbo-thioamide (L³H), and 6-nitro-3-(indolin-2-one) hydrazinecarboxamide (L⁴H), were prepared by the condensation of thiosemicarbazide and semicarbazide hydrochloride (in the presence of sodium acetate) in ethanol with the respective ketones. The dioxomolybdenum(VI) complexes and oxovanadium(V) complexes have been prepared by mixing dioxobis(2,4-pentanedinato)molybdenum(VI) in 1: 2 molar ratios and vanadium oxytrichloride in 1: 1 and 1: 2 molar ratios with monobasic bidentate ketimines. The resulting complexes have been characterized by elemental analysis, conductance measurements, and spectral studies, including IR, ¹H NMR, and UV spectra. The ketimines and their corresponding metal complexes have been tested on a number of pathogenic bacteria and fungi in order to assess their growth inhibition potency at different concentrations. The article was submitted by the authors in English.     

Regioselective synthesis of two types of highly substituted 2-pyridones through similar multicomponent reactions

The refluxing of a mixture of ethylcyanoacetate, aromatic aldehydes, and primary monoamines in ethanol produces highly substituted 2-amino-6-pyridones such as 2-amino-1-(alkyl)-5-cyano-6-oxo-4-(aryl)-1,6-dihydropyridine-3-ethylcarboxylates in one-pot. On the other hand the refluxing of a mixture of ethylcyanoacetate, aromatic aldehydes, and primary diamines (1,2-ethylenediamine/1,3-propylenediamine) in ethanol furnishes symmetrical zwitterionic 2-pyridones such as 1-(2-amino-ethyl/3-amino-propyl)-6-hydroxy-2-oxo-4-(aryl)-1,2-dihydropyridine-3,5-dicarbonitriles. The result shows that primary diamines and monoamines react differently in the reactions, which provides new mechanistic insight into the regioselective synthesis of these biologically important compounds.     

Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.     

Synthesis and reactivity of N-acyl-5- (1-hydroxyalkyl)-2,3-dihydro-4-pyridones

[structure: see text]. The Nozaki-Hiyama-Kishi reaction was used to prepare the 5-(1-hydroxyalkyl)-2,3-dihydro-4-pyridones 3. Reduction, oxidation, and substitution reactions of 3 were examined.