Synthesis of 4-alkyl-substituted 1,2,3,4-tetrahydropyrimidin-2-ones by the Biginelli reaction

p-Toluenesulfinic acid is an effective catalyst for condensation of acetoacetic ester with urea and aliphatic or aromatic aldehydes, leading to formation of 4-substituted 6-methyl-5-ethoxycarbonyl-1,2,3,4-tetrahydropyrimidin-2-ones.M. V. Lomonosov State Academy of Fine Chemical Technology, Moscow 117571, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 979–982, July, 1998.     

A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH, eliminate CHCl₃ to give the target compounds.     

New approach to 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones via base-induced chloroform elimination from 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A four-step method for the synthesis of 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with sodium enolates of α-arylsulfonylketones followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-arylsulfonyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of strong bases, eliminate CHCl₃ to give the target compounds.     

4-Functionally Substituted 3-Heterylpyrazoles: XIII. 3-Aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydropyrimidin-2-ones(thiones)

Cyclocondesation of 3-aryl(heteryl)pyrazole-4-carbaldehydes with ethyl acetoacetate and urea (thiourea) in the presence of FeCl₃ · 6H₂O afforded 3-aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydropyrimidin-2-ones(thiones).__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 97–98.Original Russian Text Copyright © 2005 by Bratenko, Chornous, Vovk.     

Suzuki-Miyaura cross-coupling of 2-aryl-6,8-dibromo-1,2,3,4-tetrahydroquinolin-4-ones and subsequent dehydrogenation and oxidative aromatization of the resulting 2,6,8-triaryl-1,2,3,4-tetrahydroquinolin-4-ones

Dichlorobis(triphenylphosphine)palladium(II)/tricyclohexylphosphine-catalyzed Suzuki-Miyaura cross-coupling of the 2-aryl-6,8-dibromo-1,2,3,4-tetrahydroquinolin-4-ones with arylboronic acids afforded the corresponding 2,6,8-triaryl-1,2,3,4-tetrahydroquinolin-4-ones, exclusively. The latter was subjected to thallium(III) p-tolylsulfonate (TTS) in dimethoxyethane under reflux or to molecular iodine in methanol at reflux to afford the 2,6,8-triarylquinolin-4-(1H)-ones and 2,6,8-triaryl-4-methoxyquinoline derivatives, respectively.     

Voltammetric oxidation of 2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxamides: substituent effects

Electrochemical oxidation of a series of 20 substituted 2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxamides (THPMs) in acetonitrile has been studied using voltammetric methods at a glassy carbon electrode to investigate the influence of the substituents on the 4- and 5-positions of the heterocyclic ring. Analysis of the results shows that the electronic nature and steric hindrance of the substituents, especially their orientations toward the heterocyclic ring, determine their effects on the oxidation potential. Analysis of the computational results obtained at the DFT-B3LYP/6-31++G** level of theory suggests a mechanism in which the first electron removal occurs from either the N(1) of the heterocyclic ring or N(17) of the amide substitution. This process is followed by a fast proton removal resulting in the formation of stable allylic and/or benzylic radicals which then undergo further oxidation to the 2-oxo-1,2-dihydropyrimidin-5-carboxamides (DHPMs).     

Nucleophile-mediated ring expansion of 4-chloromethyl- and 4-mesyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones: effect of the leaving group and the substituent at C6

A five-step synthesis of 4-chloromethyl- and 4-mesyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones has been developed. The reaction of N-[(2-benzoyloxy-1-tosyl)ethyl]urea with sodium enolates of α-tosylketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones, which were transformed into the 4-chloromethyl- or 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as sodium cyanide, sodium diethyl malonate, sodium thiophenolate, or potassium phthalimide, afforded the corresponding 4,7-disubstituted 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones as a result of ring expansion. The effect of the leaving group and the substitution at the position C6 on the reactivity of the pyrimidines is discussed.     

1,2,3,5-Tetrahydro-4H-1,5-benzodiazepin-4-ones and 1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-ones from the reaction of hydrazoic acid on 1,2,3,4-tetrahydroquinolin-4-ones

The Schmidt reaction on 1,2,3,4-telrahydroquinolin-4-ones (1) gave 1,2,3,5-telrahydro-l,5-benzodiazepin-4-ones (II) and 1,2,3,4-tetrahydro-1,4-benzodiazepin-5)-ones(III). The ratio of II and III is dependent upon substituents present on the nitrogen ring atom of the quinolinones.     

2-Thioxo-1,3-thiazepan-4-ones,a novel class of cyclic dithiourethanes with a 7-membered ring system

Reaction of isothiocyanates 1 with γ-thiobutyrolactone ( 2 ) in alkaline medium yielded 4-thiocarbamoylthiobutyric acids 3 after acidification, which could be cyclized to the 2-thioxo-1,3-thiazepan-4-ones 6 . Additional reactions were observed with the formation of 6t from p-phenylenediisothiocyanate ( 1s ) and with the formation of 6w from benzyl isothiocyanate ( 1t ). 3-Acetylamino-γ-thiobutyrolactone ( 7 ) could also be used in this reaction yielding the butyric acid derivatives 3u-3w . Cyclization yielded the 1,3-thiazepane derivatives 6x, y which rearranged under ring contraction to the 1,3-thiazinanes 8a, b .     

Synthesis of 2,4-Dioxo-1,2,3,4-tetrahydropyrimidin-5-yl Methacrylates

2,4-Dioxo-1,2,3,4-tetrahydropyrimidin-5yl methacrylates were synthesized for the first time by reaction of 5-hydroxyuracil derivatives with methacrylic anhydride. 5-Hydroxyuracil derivatives are involved in this reaction in the dioxo form.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 141–143.Original Russian Text Copyright © 2005 by Krivonogov, Chernyshenko, Kozlova, Yakovleva, Spirikhin, Abdrakhmanov, Plechev, Sivkova, Battalov.     

One-pot, Simple, and Convenient Synthesis of 2-Thioxo-2,3-dihydroquinazolin-4(1 H )-ones

A simple and convenient method for the synthesis of diverse 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones was developed as one-pot reaction of anthranilic acid esters, primary amines, and bis(benzotriazolyl)methanethione in presence of the amidine base DBU.     

New approach to the synthesis of 1,2,3,4-tetrahydroquinolin-4-ones

The reaction of aromatic amines with complexes of N,N-dimethylacrylamide and N,N-dimethylmethacrylamide with trifluoromethanesulfonic anhydride leads to the formation of tetrahydro-4-quinolones and 3-methyltetrahydro-4-quinolones respectively. M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 503–508, April, 1997.     

高氯酸镁催化合成1,2,3,4-四氢嘧啶-2-酮

在高氯酸镁催化作用下,由醛、1,3-二羰基化合物、脲(硫脲)合成了一系列1,2,3,4-四氢嘧啶-2-酮,此合成方法反应温和、产率高,并且高氯酸镁具有能重复使用的优点.     

Isolation of 1,2,3,4-tetrahydrobenzo[f]quinolin-2-ones on the reaction of 2-arylidenenaphthylamines with 4-hydroxycoumarin. IV

The reaction of 2-arylidenenaphtylamines with 4-hydroxycoumarin results in Hoffman-Martius type rearrangement yielding 2H-benzo[f][1]benzopyrano[4,3-b]quinolin-2-ones I and the compounds II. This work describes the structure elucidation of the compounds II. The structure was confirmed using ir, nmr and X-ray spectroscopy.     

Mass spectra of trisubstituted 1,2,3,4-tetrahydro-1,5-benzodiazocin-2-ones

The mass spectra of 1,5-benzodiazocin-2-ones are characterized by multiline character due to the large number of pathways of fragmentation of the molecular ions. In a number of cases the same signal in the high m/e region corresponds to ions with different compositions. The principal fragmentation pathways were determined by high-resolution mass spectrometry. The possible structures of the fragment ions and the mechanisms of their formation are discussed. The mass spectra of model compounds were also investigated for this purpose.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 529–536, April, 1977.     

Facile Synthesis of Some New Pyrazole-Based 2-Thioxo-4-thiazolidinone

5-Ethoxymethylene-2-thioxo-4-thiazolidinone (1) reacts with hydrazine hydrate at room temperature to afford 5-(hydrazinylmethylene)-2-thioxo-4-thiazolidinone (3). Compound 3 condensed with different aromatic aldehydes 6a–d in ethanol in the presence of a few drops of piperidine to give the corresponding Schiff’s bases 7a–d. On the other hand, compound 3 reacts with o-hydroxybenzaldehyde derivatives 8a and 8b in refluxing ethanol catalyzed by a few drops of piperidine to yield 1H-inadzolyl-2-thioxo-4-thiazolidinones 9a and 9b. Reaction of compound 3 with α-ketoesters 10a and 10b or α-diketones 10c–e in refluxing glacial acetic acid furnished the pyrazolyl-2-thioxo-4-thiazolidinone derivatives 11a–e. Also, compound 3 reacts with some different enaminones 12a–f in refluxing glacial acetic acid to afford the new pyrazolyl-2-thioxo-4-thiazolidinone derivatives 13a–f. Pyrazoles 15a–d was obtained via reaction of compound 3 with chalcones 14a–d in dimethylformamide (DMF). The structures of all the newly synthesized products were confirmed on the basis of their elemental and spectral data, and a plausible mechanism has been postulated to account for their formation.     

Chemically-enabled synthesis of 1,2,3,4-tetrahydroisoquinolin-1-ones

We have developed a number of efficient protocols for the facile synthesis of 1,2,3,4-tetrahydroisoquinolin-1-ones. This synthetic methodology allowed concise and efficient exploration of the SAR in all areas of the molecule. A number of these methods proved to be versatile, efficient and amenable to parallel synthesis.     

Quantum-chemical Studies of Pyrimidin-4-ones. 2. Stability in the Gas Phase of Tautomers of Pyrimidin-2,4-dione, 2-Thioxo-, 2-Selenoxo-, 2-Amino-, and 2-Acetylaminopyrimidin-4-ones, and Their 6-Methyl- and 6-Phenyl Derivatives

The relative stability in the gas phase and the most probable reaction centers for electrophilic attack for the tautomers of pyrimidin-2,4-dione, 2-thioxo-, 2-selenoxo-, 2-amino-, and 2-acetylaminopyrimidin-4-ones, and their 6-methyl- and 6-phenyl derivatives have been investigated on the basis of the results of quantum-chemical calculations, using the semi-empirical PM3 method, without taking solvent effects into account.     

Acylation of 2-thioxoquinazol-4-ones: Formation of 2-acylthioquinazol-4-ones

The acylation of 2-thioxoquinazol-4-ones by various acylating agents was studied. The main products are 2-benzoylthioquinazol-4-ones. Minor amounts of the N₍₃₎-acylation products are formed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1095–1097, August, 1987.