Molecular Structure of an Isocytosine Analog: Combined X-ray Structural and Computational Study of 2-Diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone

The structure of 2-diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone has been studied by X-ray crystallography and quantum-chemical calculations. X-ray analysis established that 2-diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone exists exclusively as the lactam tautomer protonated at the N3 ring nitrogen in the solid state. Crystals of 2-diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone are monoclinic (space group P2₁/n); the unit-cell dimensions are: a = 11.0460(8) Å, b = 5.0064(4) Å, c = 22.8358(17) Å, = = 90°, = 90.521(1)°. In the crystal, molecules of 2-diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone are assembled in planar centrosymmetric dimers by strong resonance-assisted N—H···O intermolecular hydrogen bonds from the NH group of one molecule to the C=O of the adjacent molecule (N—H···O distance 2.804 Å). Bond distances and angles are generally similar to those reported for the corresponding tautomer of isocytosine and derivatives. Quantum-chemical calculations on 2-diethylamino-6-methyl-5-n-propyl-4(3H)-pyrimidinone are also reported in order to estimate the relative energies of the possible tautomeric forms; ab initio and DFT results predict the coexistence of the N3 and AH tautomers in the gas phase. There is excellent correspondence between the crystal and the HF/6-311G** or B3LYP/6-31G* calculated structures of the N3 lactam form; the largest deviations between the experimental and computed structures are mostly the effects of strong intermolecular H bonds in the crystal.     

Synthesis and Chemical Conversions of 2-Chloro-3-cyano-4-methylamino-5-nitropyridine

5-Cyano-6-(-dimethylamino)vinyl-1-methyl-4-pyrimidinone was synthesized by the interaction of -cyano--(N-methylamino)crotonamide with N,N-dimethylformamide diethylacetal. Recyclization of the product in alkaline medium leads to 3-cyano-4-methylamino-2-pyridone. Nitration of the latter and transformation of the nitropyridone by boiling in POCl₃ gave 2-chloro-3-cyano-4-methylamino-5-nitropyridine. This is a key compound for various transformations including the synthesis of derivatives of dipyrido[1,2-a:3,2-e]pyrimidine, thieno[2,3-b]pyridine, and (2-pyridylamino)polyene derivatives.     

Synthesis and study of polydentate ligands that contain a pyrimidine ring

The corresponding hydrazones, azo compounds, and 2,4-bis(1H-pyrazol-1-yl)pyrimidines were synthesized by the reaction of 5-ethyl-2-hydrazino-6-methyl-4(3H)-pyrimidinone, 2-(N-p-butylanilino)-4-hydrazino-6-methylpyrimidine, and 4-hydrazino-2-(1H-pyrazol-1-yl)pyrimidines with salicylaldehyde, isatin, -naphthoquinone, phenanthrenequinone, and acetylacetone. The structures of the synthesized compounds are discussed on the basis of a study of their electronic, IR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1682–1687, December, 1980.     

Basis and optimization of the indooxine method to determine oximes

Summary Consideration is given to a spectrophotometric method for determining oximes that involves acid hydrolysis followed by reaction of liberated hydroxylamine with 8-quinolinol to form a dye, indooxine (5-[(8-hydroxy-5-quinolyl)imino]-8-(5H)-quinolone). The various steps of the method, applied to pyruvic oxime (2-oximinopropanoic acid) as representative of -oximino acids, were investigated and optimized, leading to improvements in reproducibility and sensitivity over the existing procedure. Incomplete liberation of hydroxylamine from oximes is due largely to incomplete hydrolysis at equilibrium in acid solution. An additional cause with -oximino acids, as opposed to simple oximes, is decarboxylative dehydration to form the corresponding nitrile. Hydrolysis is more complete and nitrile formation less favored the lower the pH, at least in the pH range 0 to 2.5. The importance of calibration curves and the control of pH, time of hydrolysis and temperature in quantitative application of the method is emphasized. The method can be used quantitatively for determination of a single oxime but only semiquantitatively or qualitatively for determination of total oximes in an unknown mixture of oximes.     

Studies with 2‐arylhydrazononitriles: Further investigations on reactivity of 2‐arylhydrazononitriles towards hydroxylamine

The utilization of arylhydrazononitriles ( 6‐9 ) for synthesis of azoles is demonstrated. Thus, arylazomalononitriles ( 6 ) reacted with hydroxylamine hydrochloride to afford isoxazol‐5‐imine ( 10 ), amidoxime ( 12 ) and bis‐amidoxime ( 13 ) derivatives depending upon both the reaction conditions and molar ratio employed. 2‐Thiazolyl‐2‐arylhydrazononitriles ( 7 ) and cyanoformazans ( 8 ) gave 1,2,3‐triazole derivatives ( 15 ) and ( 17 ) respectively upon treatment with hydroxylamine hydrochloride and concomitant loss of water molecule. Formation of novel 1,2,4‐triazin‐5(4H)‐one derivatives ( 21 ) has efficiently been carried out by treatment of amidoximes ( 18 ) with acetic anhydride in acetic acid.     

Synthesis of new pyrazole and isoxazole derivatives based on products of condensation of β-dicarbonyl compounds with 1,2,3-trihalopropanes

The reaction of 2-(2-halo-3-propenyl)-1,3-dicarbonyl compounds, which are formed in the alkylation of -dicarbonyl compounds with 1,2,3-trihalopropanes in the presence of potassium carbonate in DMSO, with hydrazine and hydroxylamine derivatives was studied. The synthesis of new pyrazole and isoxazole derivatives on the basis of this reaction is described. Some chemical transformations of the 1,2-azoles obtained were investigated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–791, June, 1987.     

Chemistry of heteroanalogs of isoflavones 14. Isoxazole analogs of isoflavones

Isoxazole analogs of isoflavones have been synthesized by the cyclization of -(3-isoxazolyl)-2-hydroxyacetophenones. Their alkylation, acylation, and electrophilic substitution reactions, and reactions with binucleophiles have been studied. 3-(3-Isoxazolyl)-7-methoxychromones are rearranged selectively into 2-aminochromone derivatives by the action of hydroxylamine as a result of a double recyclization and are recyclized into pyrazole derivatives by hydrazine. Preparations with hypolipidemic, anabolic, hypoglycemic, and antiarrhythmic action are found among the derivatives of 3-(3-isoxazolyl)chromones.For Communication 13, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 29–39, January, 1993.     

Synthesis and Structural Features of 1-Acyl-1-nitro-2-furyl(thienyl)ethenes

A one-stage synthesis of 1-acyl-1-nitro-2-furyl(thienyl)ethenes was developed and structural assessment of the products was performed by means of ¹H, IR, and UV spectroscopy and dipole moment measurements. The acetyl derivatives have Z configuration, and the benzoyl derivatives, E configuration. The UV and IR spectra, as well as the rather high dipole moments ( 5-6 D) point to an essential contribution in the structures of dipolar forms.     

2-Polyfluoroalkylchromones. 10. Synthesis of regioisomeric 3-(2-hydroxyaryl)-5-polyfluoroalkyl- and 5-(2-hydroxyaryl)-3-polyfluoroalkylisoxazoles and determination of their structures by 1H, 19F, and 13C NMR spectroscopy

The reactions of 2-hydroxy-2-polyfluoroalkylchroman-4-ones with hydroxylamine yield, through ²-isoxazolines as intermediate products, 3-(2-hydroxyaryl)-5-polyfluoroalkylisoxazoles. Analogous reactions with 2-polyfluoroalkylchromones afford -diketone monooximes, which in an acidic medium undergo cyclodehydration into 5-(2-hydroxyaryl)-3-polyfluoroalkylisoxazoles. The structures of regioisomeric 3- and 5-polyfluoroalkylisoxazoles were determined using ¹H, ¹⁹F, and ¹³C NMR spectroscopy.     

Synthesis of pyrazolo[1,5-a]-pyrimidines by reaction of 3,5-diamino-4-nitropyrazole with acetoacetic ester in the presence of alkaline agents

Two major compounds are formed in the reaction of 3,5-diamino-4-nitropyrazole with acetoacetic ester: 2-amino-5-methyl-3-nitro-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one and 3-amino-5-(-hydroxycrotonyl)amino-4-nitropyrazole. The latter is converted to bicyclic dihydropyrazolo[1,5-a]-pyrimidinone in solutions with heating.State Science Center of the Russian Federation NIOPIK (Scientific Research Institute of Organic Intermediates and Dyes), Moscow 103787Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 73–77, January, 2000.     

A kinetic study of the homogeneous oxidation of hydroxylamine by manganese(III)-bis(salicylaldimine) complexes

Summary The kinetics of the oxidation of hydroxylamine by manganese(III)-bis (salicylaldimine) complexes have been studied over the 5.2–8.4 pH range. The reaction is first order in both hydroxylamine and oxidant, and inversely proportional to [H⁺]. The [complex]: [hydroxylamine] stoichiometric ratio is 11 in both acidic and neutral media, and 21 in an alkaline medium. The second-order rate constant increased in the sequence: [Mn^III(L²)OH₂]-ClO₄·2H₂O > [Mn^III(L¹)OH₂]ClO₄ > [Mn^IIIL¹)OAc]-H₂O. The reactivity of unprotonated hydroxylamine is much higher than that of the protonated form. The reaction rate decreased significantly with addition of chloride ions. A plausible mechanism is proposed.     

Synthesis of aminoacyl derivatives of nucleosides,nucleotides, and polynucleotides

Conclusions The possibility has been shown of extending the method of synthesis of O-aminoacyl derivatives of nucleotides and nucleoside triphosphates to prepare 3(2)-O-peptidyI-micleoside-5-triphosphates.TranslatedfromlzvestiyaAkademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1369–1372, June, 1970.     

Synthesis in the fields of 5-nitrofuryl-2-polyalkenals and 5-nitrofuryl-2-polyalkenones. VII. Synthesis and investigation of the antibacterial properties of derivatives of α,β-unsaturated and polyene aldehydes and ketones of the 5-nitrofuran series

Antibacterial properties and toxicities were determined for 66 compounds of the 5-nitrofuran type to ascertain the connection between structure and biological activity.Unsaturated 5-nitrofuran aldehydes and some of their simplest derivatives (acetals, acylals) have high antibacterial activity and a broad spectrum. However, these compounds cannot be used in medicine because of their appreciable toxicities and low stabilities. One of the ,-unsaturated ketones in this series, 5-nitrofurfurylideneacetone, has a broad antibacterial spectrum combined with lower toxicity. Low-toxicity derivatives of 1-aminohydantoin and 3-amino-2-oxazolid-2-one are among the imino derivatives of high antibacterial activity investigated.For Part VI see [1].     

Synthesis of Substituted Pyridazin-3-ones, 1,2-Oxazin-3-ones,and Furopyrimidines from (Arylmethylidene)furan-2(3<Emphasis Type="Italic">H</Emphasis>)-ones

Reactions of 5-substituted 3-(arylmethylidene)furan-2(3H)-ones with hydrazine hydrate, hydroxylamine, and guanidine involved opening of the furanone ring. Their hydrazinolysis under mild conditions afforded acyclic 4-oxoalkanoic acid hydrazides which underwent heterocyclization to substituted pyridazinones in boiling ethanol. The presence of an alkyl substituent in the 5-position of the initial furanone favored heterocyclization with the formation of pyrazolidinone derivatives. The reactions of 3-(arylmethylidene)furan-2(3H)-ones with hydroxylamine and guanidine also produced new six-membered heterocycles, 2H-1,2-oxazin-3(4H)-ones and 4,6-disubstituted 3,4-dihydrofuro[2,3-d]pyrimidin-2-amines, respectively.     

Syntheses and studies of metaphase-arresting pyrimidinones

Methods are described for the syntheses of chloromethyl hydroxyalkylphenyl and benzyl ethers, and for the synthesis of bromomethyl phenyl ketone analogs. The hydroxy groups were protected as acetates. The halogenomethyl derivatives have been used for N-alkylation of 5-chloro-2(1H)-pyrimidinone. The acetyl groups in the products were removed by aminolysis or by enzymatic (pig liver esterase) hydrolysis. The hydroxy derivatives are chemically labile because of polymerization reactions. Adduct formation (1:1) with sodium hydrogensulfite improved the stability. The products are specific inhibitors of the cell cycle in the metaphase. In vitro data are given from screening in cultivated Chang liver cells.     

Zur Struktur der Tetrahydro-4-phenylspiro([1]benzopyran-2,4′(1′H)-pyrimidin)-2′(3′H)-one bzw.-thione Über Heterocyclen, 49. Mitt

The structures of tetrahydro-4-phenylspiro([1]benzopyran-2,4(1H)-pyrimidin)-2(3H)-ones and-thiones4 a, b resp., are proved by synthesis. 3-(2-methoxy-3,5-dimethylphenyl)-3-phenylpropionic acid11 b is prepared from 3,4-dihydro-6,8-dimethyl-4-phenylcoumarin10. The lithium salt of11 b reacts with isobutenyl-lithium to 1-(2-methoxy-3,5-dimethylphenyl)-5-methyl-1-phenyl-4-hexen-3-on12 a. 12 a is transferred with urea in acid medium and NH₄CNS resp. in a mixture of dihydro-6-[2-(2-methoxy-3,5-dimethylphenyl)-2-phenyläthyl]-4,4-dimethyl-2(1H)-pyrimidinone and-thione13 a, b and tetrahydro-6-[2-(2-methoxy-3,5-dimethylphenyl)-2-phenyläthyliden]-4,4-dimethyl-2(1H)-pyrimidinone and-thione14 a, b resp.14 b leads to13 a, b with H₂O₂. Heating of13 a, 14 a and14 b resp. with pyridin-HCl leads to the spiro compounds4 a, b.     

Zur Struktur der Tetrahydro-4-phenylspiro([1]benzopyran-2,4′(1′H)-pyrimidin)-2′(3′H)-one bzw.-thione über Heterocyclen, 49. Mitt

The structures of tetrahydro-4-phenylspiro([1]benzopyran-2,4(1H)-pyrimidin)-2(3H)-ones and-thiones4 a, b resp., are proved by synthesis. 3-(2-methoxy-3,5-dimethylphenyl)-3-phenylpropionic acid11 b is prepared from 3,4-dihydro-6,8-dimethyl-4-phenylcoumarin10. The lithium salt of11 b reacts with isobutenyl-lithium to 1-(2-methoxy-3,5-dimethylphenyl)-5-methyl-1-phenyl-4-hexen-3-on12 a. 12 a is transferred with urea in acid medium and NH₄CNS resp. in a mixture of dihydro-6-[2-(2-methoxy-3,5-dimethylphenyl)-2-phenyläthyl]-4,4-dimethyl-2(1H)-pyrimidinone and-thione13 a, b and tetrahydro-6-[2-(2-methoxy-3,5-dimethylphenyl)-2-phenyläthyliden]-4,4-dimethyl-2(1H)-pyrimidinone and-thione14 a, b resp.14 b leads to13 a, b with H₂O₂. Heating of13 a, 14 a and14 b resp. with pyridin-HCl leads to the spiro compounds4 a, b.     

Synthesis and Reactions of 1-(3-Chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium Perchlorate

Acid-catalyzed acylation of 3,4-dimethoxyphenylacetone with -chlorobutyryl chloride gave 1-(3-chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium perchlorate. Recyclization of the product with nitrogen nucleophiles (ammonia, primary amines, hydrazine derivatives, hydroxylamine) led through the corresponding isoquinolinium salts to benzo[f]indolizinium, pyridazino[2,1-b]isoquinolinium, and 1,2-oxazino[2,1-b]isoquinolinium salts.     

New example of the dimroth rearrangement. Intramolecular cyclization of acyl derivatives of anthranilic acid nitrile

A new example of the Dimroth rearrangement in which 4-amino-1H-quinazolin-2-one 3(N)-oxide undergoes isomerization to 4-oximino-1H, 3H-quinazolin-2-one was observed. It is shown that the thermal cyclization of N-(2-amidoximophenyl)ureas and carbamates leads to the production of 4-amino-1H-quinazolin-2-one 3(N)-oxides, while their O-carbamoyl derivatives give 4-oximino-1H, 3H-quinazolin-2-one and 5-oxo-²-1,2,4-oxadiazolino[c3,4]-1H,3H-quinazolin-2-one.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1264–1266, September, 1981.     

Synthesis and study of 2-(1-pyrazolyl)pyrimidine derivatives

Alkyl derivatives of 2-(1-pyrazolyl)-4(3H)-pyrimidinone were synthesized and converted to 4-chloro-, 4-arylamino-, and 4-hydrazino-2-(1-pyrazolyl)pyrimidines. The corresponding hydrazones were obtained by reaction of 5-ethyl-2-hydrazino-6-methyl-2-(4-ethyl-3,5-di-n-propylpyrazolyl) pyrimidine with isatin and salicylaldehyde. The UV and IR spectra of the synthesized compounds were studied. It was established that the hydrazones contain intra-molecular hydrogen bonds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1255–1257, September, 1977.