One-pot synthesis of 3-(2-cyanophenyl)quinazolin-4(3H)-one

Anthranilonitrile reacting with formic acid at room temperature for three days gave 64% of 3-(2-cyanophenyl)quinazolin-4(3H)-one. Under similar conditions anthranilic acid. 4-nitroaniline, and 2,5-dichloroaniline were N-formylated in good yields.Institute of Organic Chemistry and Technology, Silesian Technical University, Krzywoustego, 4, 44–100 Gliwice, Poland; e-mail: wojtex@zeus.polsl.gliwice.pl. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 922–924, July, 2000.     

Atom-Economic Route to Densely Functionalized Thiophenes via Base-Catalyzed Rearrangement of 5-Propargyl-2H-thiopyran-4(3H)-ones

An atom-economic route to densely functionalized thiophenes has been developed via base-catalyzed rearrangement of 5-propargyl-2H-thiopyran-4(3H)-ones involving tandem retro-thio Michael addition, propargyl isomerization, and intramolecular thio-addition to allenes.     

Synthesis and Anti-HIV-1 Activity of 2-[2-(3,5-Dimethylphenoxy)ethylthio]pyrimidin-4(3H)-ones

New 2-[2-(3,5-dimethylphenoxy)ethyl]thio derivatives of pyrimidin-4(3H)-one containing various substituents at positions 5 and 6 of the pyrimidine ring were synthesized. It was shown that alkylation of 2-thiouracils with 1-bromo-2-(3,5-dimethylphenoxy)ethane in DMF takes place exclusively at the sulfur atom. The obtained 6-benzyl and 6-(2,6-difluorobenzyl) derivatives have clearly defined virus-inhibiting properties with respect to type 1 human immunodeficiency virus in vitro and suppress its reproduction by 50% at concentrations of 1.3 and 11.2 mM respectively.     

Reactions of 3-(4-Aryl-2-thiazolyl)- and 3-(2-Benzothiazolyl)-2-iminocoumarins with N-Nucleophiles

The reaction of 3-(4-aryl-2-thiazolyl)- and 3-(2-benzothiazolyl)-2-iminocoumarins with N-nucleophiles was studied. This reaction gives 2-N-substituted 3-(4-aryl-2-thiazolyl)- and 3-(2-benzothiazolyl)iminocourmarins. N-Nucleophiles such as arylamines, heterocyclic amines, and hydrazine derivatives undergo this reaction.     

Reaction of 2-(2-oxoethylidene)furan-3(2H)-ones with isopropylidenehydrazides of aromatic carboxylic acids: Synthesis of 3-hydroxy-3-(2-oxoethyl)-2,3-dihydropyridazin-4(1H)-ones

3-Hydroxy-3-(2-oxoethyl)-6-phenyl-2,3-dihydropyridazin-4(1H)-ones were obtained by the reaction of methyl 3-oxo-5-phenylfuran-2(3H)-ylideneacetate or 2-[2-(4-chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one with benzoic or p-nitrobenzoic isopropylidenehydrazides. Equilibrium C₍₅₎H and C₍₅₎H₂ tautomeric forms were detected in solutions of the 4-chlorophenyl derivatives in DMSO-d₆. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1156–1158, August, 2007.     

Synthesis and reactivity of 3-aralkoxy-4-imino-imidazolidin-2-ones: a novel class of 4-iminohydantoins

Reactions of diethylphosphonoalkyl α-aminonitriles with 1,1′-carbonyl-diimidazole or 1,1′-carbonyl-di-(1,2,4-triazole) and O-substituted hydroxylamines under acidic conditions gave 3-alkoxy-4-imino-imidazolidin-2-ones, whereas in presence of triethylamine 4-alkoxy(aralkoxy)imino-imidazolidin-2-ones were formed.     

Molybdenum-mediated synthesis of quinazolin-4(3H)-ones via cyclocarbonylation using microwave irradiation

A new, efficient and practical synthesis of quinazolin-4(3H)-ones is reported via molybdenum-mediated cyclocarbonylation using microwave irradiation. These methods allow access to a wide range of quinazolin-4(3H)-ones in reasonable yields without the need for gaseous carbon monoxide and palladium catalysts. A range of reactions illustrating the wide scope of this chemistry was carried out and all proceeded in reasonable yields.     

Stripping voltammetric determination of silver(I) at carbon paste electrode modified with 3-amino-2-mercapto quinazolin-4(3H)-one

A differential pulse anodic stripping voltammetric method was developed for the determination of Ag(I) at a 3-amino-2-mercapto quinazolin-4(3H)-one modified carbon paste electrode. The analysis procedure consisted of an open circuit accumulation step in stirred sample solution for 12 min. This was followed by medium exchange to a clean solution where the accumulated Ag(I) was reduced for 15 s in −0.6 V. Subsequently an anodic potential scan was effected from −0.2 to +0.2 V to obtain the voltammetric peak. The detection limit of silver(I) was 0.4 μg L⁻¹ and R.S.D. for 10, 100 and 200 μg L⁻¹ silver(I) were 2.4, 1.8 and 1.3%, respectively. The calibration curve was linear for 0.9-300 μg L⁻¹ silver(I). Many coexisting ions had little or no effect on the determination of silver(I). The procedure was applied to determination of silver(I) in X-ray photographic films and natural waters. In X-ray photographic film samples, the results have compared to those obtained by atomic absorption spectroscopy.     

Facile Synthesis of 2-Alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones

Isothiocyanate 2, obtained from aza-Wittig reaction of iminophosphorane 1 with CS₂, reacted with amine to give 2-thioxo-2,3,5,6,7,8-hexahydrobenzothieno[2,3-d]pyrimidin-4(1H)-ones 4 in the presence of sodium ethoxide. S-Alkylation of 4 produced 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 5 in good yields.     

A Selective Synthesis of 2-Alkylamino-5, 6, 7, 8-tetrahydrobenzothieno[2, 3-d]pyrimidin-4（3H）-ones

2-Alkylamino-5, 6, 7, 8-tetrahydrobenzothieno [2,3-d] pyrimidin-4(3H)-ones 7 were synthesized by a new selective synthetic method, which includes aza-Wittig reaction of iminophosphorane 4 with aromatic isocynate to give carbodiimide 5 and subsequent reaction of 5 with various aliphatic primary amine in the presence of EtO^-Na^ .     

新型2-氨基-呋喃并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及抗肿瘤活性

报道应用aza-Wittig反应,采用易得的原料,在温和的条件下,以78%～90%的产率有效的合成了新型2-氨基-呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物5,其结构经IR,1H NMR,MS和元素分析确认.为进一步得到结构确认,化合物5c经X射线衍射分析证实.运用噻唑蓝(MTT)标准法对化合物5进行了体外抗肿瘤活性的测定,其中5f对肺癌细胞A459的IC50值为18.4μmol/L,显示出潜在良好的抗肿瘤活性.     

Reactions of N,N-Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5H)-ones with CH Acids

Summary.  N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed. Corresponding author. E-mail: kamalkandeel@hotmail.com Received November 5, 2001. Accepted (revised) December 17, 2001     

The Reactions of 6-(tert-Butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with Carbonyl Compounds

The reaction of 6-(tert-butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with acetone and benzaldehyde yields the corresponding hydrazones. In the presence of thionyl chloride the benzaldehyde hydrazone is converted to 3-(tert-butyl)-6-phenyl-1,2,4-triazolo[4,3-b]-1,2,4-triazin-2(1H)-one and this can also be formed via the acylation of the starting hydrazinotriazinone using benzoyl chloride.     

Oxidative alkylamination of 2-methyl-3(2H)-cinnolinone: unexpected dealkylation of the entering alkylamino group

The oxidative alkylamination of 2-methyl-3(2H)-cinnolinone by secondary alkylamines in the presence of KMnO₄ leads to the smooth formation of the expected 4-alkylamino-2-methyl-3(2H)-cinnolinones. The analogous reaction with primary alkylamines is accompanied by the partial or complete N-dealkylation of the entering alkylamino group depending on the temperature. *Dedicated with gratitude to an outstanding heterocyclic chemist, Prof. Henk van der Plas on the occasion of his eightieth jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 602-611, April, 2009.     

Synthesis and Crystal Structure of 2-(4''-Methylphenoxy)-5,8,9-trimethyl-3-phenyl Thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidin-4-(3H)-one Hydrochloride

The title compound 2-(4′-methylphenoxy)-5,8,9-trimethyl-3-phenyl thieno[3′,2′:5,6]pyrido[4,3-d]pyrimidin-4(3H)-one hydrochloride (C26H23Cl4N3O2S, Mr = 583.33) has been deter- mined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 14.8442(11), b = 11.5131(8), c = 17.2010(13) (A), β = 113.7250(10)o, V = 2691.3(3) (A)3, Z = 4, Dc = 1.440 g/cm3, S = 1.094, μ = 0.547 mm-1, F(000) = 1200, the final R = 0.0571 and wR = 0.1458. X-ray analysis reveals that the title compound combines with a molecule of dichloromethane by an intramolecular hydrogen bond. The thienopyridine ring is almost coplanar, and the dihedral angle between the thiophene plane and the pyridine plane is 0.6o.     

Thioureas from 3-aminoquinazolin-4(3H)-one. 2. Unusual alkaline recyclization of 3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones into new 1,3,4-oxadiazoles

3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones obtained by the reactions of 3-(N",N"-dialkylthioureido)quinazolin-4(3H)-ones with alkyl halides undergo unusual recyclization into 5-(2-aminophenyl)-2-dialkylamino-1,3,4-oxadiazoles under the action of aqueous solutions of alkali, hydrazine, and primary aliphatic amines. A plausible mechanism of the recyclization was proposed.     

2-烷(芳)氧基苯并呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物的合成及杀菌活性

应用膦亚胺3与芳基异氰酸酯的氮杂Wittig反应, 生成碳二亚胺4, 4再分别与酚、醇作用, 在碳酸钾或醇钠催化下关环, 以72%～88%的产率合成了2-烷(芳)氧基取代-苯并呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物5和6, 其结构经IR, 1H NMR, MS和元素分析证实. 初步生物活性测试表明该类化合物表现出温和的杀菌活性. 如5f在50 mg/L浓度时, 对黄瓜灰霉菌的抑制率为55%.     

Heteroannulated Quinazoline and Quinazolinone Derivatives from (Z)-2-[1-Benzamido-2-(3,4,5-trimethoxyphenyl)]vinyl-3,1-benzoxazin-4(3H)-one

The title compound 1 was prepared and allowed to react with a series of nitrogen nucleophiles to afford the quinazoline and quinazolinone derivatives 2–12 and tetrazole derivative 13. The IR, ¹H NMR, ¹³C NMR, and mass spectra of all the synthesized compounds were discussed.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Polycyclic N-heterocyclic compounds. Part 58: Rearrangement reactions of fused 3-(2-bromoethyl)pyrimidin-4(3H)-ones with primary amines and antidepressive evaluation of the products

Reaction of fused 3-(2-bromoethyl)pyrimidin-4(3H)-ones with primary alkylamines gave abnormal fused 3-alkyl-4-alkyliminopyrimidines via a new rearrangement, as well as normal substituted 3-(2-alkylaminoethyl) derivatives. Antidepressive evaluation of these compounds was performed by antireserpine action and one compound exhibited the positive activity comparable to imipramine.