Parallel synthesis of 3-amino-4H-quinolizin-4-ones, fused 3-amino-4H-pyrimidin-4-ones, and fused 3-amino-2H-pyran-2-ones

On the basis of the enaminone methodology, libraries of 3-amino-4H-quinolizin-4-ones, fused 3-amino-4H-pyrimidin-4-ones, and fused 3-amino-2H-pyran-2-ones were synthesized by the solid-phase and by the solution-phase parallel synthesis. The solution-phase approach turned out to be advantageous over the solid-phase approach. The solution-phase synthesis afforded, in most cases, analytically pure products in high yields, whereas the solid-phase approach gave products in poor yields and in low purity.     

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.     

Anwendung der Massenspektrometrie zur Identifizierung isomerer Amino-oxadiazole

The mass spectrometric fragmentation products of the four isomeric monophenyl amino oxadiazoles, 2-amino-5-phenyl-l, 3,4-oxadiazole, 3-amino-5-phenyl-l, 2, 4-oxadiazole, 5-amino-3 phenyl-l, 2, 4-oxadiazole and 3-amino-4-phenyl-1, 2,5-oxadiazole, differ with respect to their fragment composition and abundance in such a way that isomers can easily be distinguished and determined. The most important fragmentation patterns giving characteristic ions for structure identification are discussed.     

Studies on the Thorpe-Ziegler-reaction. A new synthesis of the pyridine part of thiamine]

Thorpe-Ziegler cyclization of N′-cyano-N-(2-cyanoethyl)-acetamidine ( 5a ) yields 4-amino-2-methyl-1,6-dihydro-5-pyrimidinecarbonitrile ( 8a ). The acetamidine 5a is accessible either from the N-cyanoimidate 1 and β-aminopropionitrile ( 3a ) or the N-cyanoamidine 2 and acrylonitrile ( 4 ). The dihydropyrimidine 8a is easily converted to 4-amino-2-methyl-5-pyrimidine-carbonitrile ( 13 ) by dehydrogenation or to 4-amino-5-aminomethyl-2-methylpyrimidine ( 15 ) by hydrogenation-dehydrogenation. Both products are important intermediates in the synthesis of thiamine.     

Regioselective Heteroannelation in 4-Cyanomethyl-3,5-pyridinedicarbonitriles. Synthesis of 6-Alkoxy-3-dialkylamino-1,8-diamino-2,7-naphthyridine-4-carbonitriles

 The title naphthyridines were found to be the sole products obtained after treatment of 2-amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles with alkoxides. The starting pyridine derivatives were prepared by amination of the readily available 2-amino-6-chloro-4-cyanomethyl-3,5-pyridinedicarbonitrile in quantitative yields.     

固相萃取-高效液相色谱法同时测定传统禽肉制品中的9种杂环胺类化合物

建立了固相萃取-高效液相色谱同时测定传统禽肉制品中9种杂环胺类化合物(HAAs)(包括2-氨基-3-甲基咪唑并［4,5-f］喹啉、2-氨基-3,4-二甲基咪唑并［4,5-f］喹啉、2-氨基-3,8-二甲基咪唑并［4,5-f］喹喔啉、2-氨基-3,4,8-三甲基咪唑并［4,5-f］喹喔啉、2-氨基-1-甲基-6-苯基-咪唑并［4,5-b］吡啶、3-氨基-1-甲基-5H-吡啶并［4,3-b］吲哚、3-氨基-1,4-二甲基-5H-吡啶并［4,3-b］吲哚、9H-吡啶并［4,3-b］吲哚、1-甲基-9H-吡啶并［4,3-b］吲哚)含量的分析方法。经过条件优化,肉样选用乙酸乙酯进行提取,提取液经丙基磺酸(PRS)和C18固相萃取小柱净化,采用TSK-gel ODS-80TM色谱柱,以乙腈和0.05 mol/L醋酸-醋酸铵缓冲液(pH 3.4)为流动相进行梯度洗脱分离,紫外-荧光检测器串联方式对目标化合物进行检测。通过波长扫描,确定紫外检测波长为263 nm,荧光激发波长/发射波长随时间切换程序为: 0～21 min, 300 nm/440 nm; 21～23.8 min, 315 nm/410 nm; 23.8～35 min, 265 nm/410 nm。在上述条件下,9种HAAs在35 min内实现基线分离。3个加标水平的平均回收率为60.47%～90.55%(n=6),相对标准偏差(RSD)为0.49%～9.74%(n=6),检出限(以信噪比为3计)为0.1～3.6 μg/kg。该方法简便快速、结果准确、灵敏度高,可作为测定传统禽肉制品中多种杂环胺类化合物的有效方法。     

Photolyse von indazolen,benzisoxazolen und anthranilen in saurer Lösung Vorläufige Mitteilung

Indazoles and anthranils on irradiation with a mercury high-pressure lamp in acidic solution (H₂SO₄/H₂O or H₂SO₄/CH₃OH) yield 2-amino-5-hydroxy(or methoxy)-benzaldehydes (acetophenones, respectively) as major products and 2-amino-3-hydroxy (or methoxy)-benzaldehydes (acetophenones, respectively) as minor products. Photolysis of benzisoxazoles in conc. sulfuric acid results in the formation of 2,5-and 2, 3-dihydroxybenzaldehydes (acetophenones, respectively). 5-Methylindazoles form on irradiation in diluted sulfuric acid 2-amino-5-methyl-benzaldehydes.     

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides: III. Heterocyclization by the action of hydrogen halides

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides reacted with hydrogen halides along two concurrent pathways with formation of furan or pyridine derivatives. The reaction in butan-2-ol afforded 2-amino-4-acyl-(aroyl)-6-halopyridine-3,5-dicarbonitriles, whereas the major products in the reactions with HCl and HBr in aqueous solution were the corresponding 2-(5-amino-2-aryl-2-chloro(bromo)-4-cyano-2,3-dihydrofuran-3-ylidene)malononitriles. The reaction with aqueous hydrogen iodide was accompanied by reductive deiodination and produced 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)malononitriles.     

Synthesis of substituted 2-(2-oxopyrrolidin-1-yl)acetamides

The reaction of chloroacetamide with 2 equiv of γ-aminobutyric acid potassium salts provides a convenient method for the synthesis of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids. Alkylation products of 2-aminoacetic and 3-aminopropanoic acid with chloroacetamide were isolated. Thermal cyclization of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids afforded 2-(2-oxopyrrolidin-1-yl)acetamides.     

Separation and determination of nitrobenzenes by micellar electrokinetic chromatography and high-performance liquid chromatography

A micellar electrokinetic chromatographic method and a high-performance liquid chromatographic method are proposed for the separation and determination of a mixture of 12 nitrobenzenes and their reduction products, namely 4-nitro-1,2-phenylenediamine, 4-nitro-1,3-phenylenediamine, 2-nitro-1,4-phenylenediamine, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 4-amino-2-nitrophenol, 2-amino-5-nitrophenol, 2-amino-4-nitrophenol, 2-nitrophenol, 3-nitrophenol, and 4-nitrophenol. A solution of 50 mM sodium dodecyl sulfate and 10% ethanol in 23 mM sodium borate buffer was used as the electrophoretic medium. Good resolution could be obtained by the addition of tetrahydrofuran to the liquid chromatographic mobile phase. The retention and migration behavior of the nitrobenzenes are discussed.     

Oxidative degradation of 8-nitroquinoline with hydrogen peroxide in acetic acid a possible mechanism through 3,4-epoxide of quinoline ring

The treatment of 8-nitroquinoline with hydrogen peroxide and acetic acid at 60°C afforded 7-nitroindole, 7-nitro-2-oxindole, 2-amino-3-nitrobenzoic acid, 2-amino-3-nitrobenzaldehyde, 3,4-dihydro-3, 4-trans-dihydroxy-8-nitrocarbostyril, 3,4-trans-dihydro-3-hydroxy-4-acetoxy-8-nitrocarbostyril, and 1-(2-amino-3-nitrophenyl)-2-hydroxy-ethanone. The reaction mechanism acceptable in elucidating the formation of these products involves, at the initial step of reaction, an epoxidation of the 3,4-double bond of the 1,2-dihydro adduce of quinoline ring.     

Heterocyclisation of substituted ylidenethiocarbonohydrazides using dimethyl acetylenedicarboxylate

A facile and rapid procedure for the synthesis of dimethyl-2-[3-amino-5-(2-methoxy-2-oxoethylidene)-4-oxothiazolidin-2-ylidenehydrazono]succinate, dimethyl {[2-alkylidenehydrazono)-5-(2-methoxy-2-oxoethylidene)-4-oxothiazolidin-3-yl)amino]succinate and methyl (4-amino-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-yl)acetate affording yields of 61–54 %, 22–18 % and 14–11 %, respectively, via a condensation reaction of dimethyl acetylenedicarboxylate (DMAD) with (substituted ylidene)thiocarbonohydrazides. One of the products was conclusively confirmed by single-crystal X-ray analysis. A mechanism for the formation of the products is presented.     

Synthesis and Oxidation of 1,3-Diamino- and 1-Amino-3-azidoindazoles

The amination of 3-amino- and 3-azidoindazoles by hydroxylamine-O-sulfonic acid in an alkaline medium yields previously unreported 1,3-diamino- and 1-amino-3-azidoindazoles. These products undergo slow autoxidation in chloroform solution to give 4-aminobenzo-1,2,3-triazine. The action of formic or acetic acid on 3-amino-1-benzylideneaminoindazole leads to recyclization and formation of 3-amino-2-benzylindazole, which is also formed in the catalytic hydrogenation of 1-benzylamino-3-nitro- and 1-benzylideneamino-3-nitroindazoles.     

Solution and solid state structure and tautomerism of azo coupled enaminone derivatives of benzoylacetone

The reaction of 4-substituted benzenediazonium tetrafluoroborates with 3-amino-1-phenylbut-2-en-1-one, 4-amino-4-phenylbut-3-en-2-one and their N-aryl derivatives 1a-1g has been used to prepare the respective azo coupling products i.e. compounds 2-5 from enaminone 1a, compounds 6-9 from enaminone 1c, compound 10 from enaminone 1d, compound 11 from enaminone 1e, compounds 12, 13 from enaminone 1f, compounds 14, 15 from enaminone 1b and compound 16 from enaminone 1g. Tautomerism of the azo coupling products prepared has been investigated in CDCl3 solutions by means of 1H, 13C and 15N NMR spectra. Crystal structures of selected products have also been investigated by means of X-ray diffraction.     

Arylierungen von cyclischen Guanidin-Analogen mit α-halogenierten Anthrachinonen: neue Anthrapyrimidine

Arylation Reaction of Cyclic Guanidine-Analogs with α-Halo- anthraquinones: New Anthrapyrimidines 2-Amino-benzimidazole gives on Ullmann-reaction with α-halo-athraquinones such as 1-amino-4-bromoanthraquinone-2-sulfonic acid (la) the new benzimidazo-anthrapyrimidine 2a , whereas 3-amino- triazole gives under the same conditions two products: the 1,2,4-triazoloanthrapyrimidine 7 and l-amino-4-(3-amino-1,2,4- triazolyl)anthraquinone-2-sulfonic acid ( 8 ). The new structures were elucidated by ¹H- and ¹³C-NMR. and X-ray analysis.     

2-氨基-5-硫代-噻二唑啉-β-D-核呋喃糖苷的合成

2-氨基-5-硫代-1,3,4-噻二唑啉和1-O-乙酰-2,3,5-三-O-苯甲酰核呋喃糖通过熔融缩合和Vorbruggen缩合, 所得两个产物经^1H, ^1^3C NMR, 质谱以及X射线结晶学分析, 鉴定为位置异构体2-亚氨基-5-硫代-1,2,4-噻二唑啉-3-β-D-核呋喃糖苷和2-氨基-5-硫代-1,3,4-噻二唑啉-4-β-D-核呋喃糖苷。     

Regioselective Heteroannelation in 4-Cyanomethyl-3,5-pyridinedicarbonitriles. Synthesis of 6-Alkoxy-3-dialkylamino-1,8-diamino-2,7-naphthyridine-4-carbonitriles

Summary.  The title naphthyridines were found to be the sole products obtained after treatment of 2-amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles with alkoxides. The starting pyridine derivatives were prepared by amination of the readily available 2-amino-6-chloro-4-cyanomethyl-3,5-pyridinedicarbonitrile in quantitative yields. Corresponding author. E-mail: atver@mail.univ.kiev.ua Received November 4, 2002; accepted November 22, 2002 Published online May 6, 2003     

Reactions with cyclic amidines II. The behaviour of cyclic amidines toward ethoxycarbonyl and aroyl isothiocyanates

The behaviour of the aminopyrazole derivatives 1a-c, 2-amino-4-phenylthiazole (2) and 2-amino-5-phenyl-1,3,4-thiadiazole (3) toward the action of ethoxycarbonyl and benzoyl iso-thiocyanate is reported. The data clearly demonstrates the dependence of the nature of the products obtained from the reaction of isothiocyanates with cyclic amidines on the nature of the substituents on the heterocyclic ring.     

Efficient and Green Preparation of 2-Amino-4H-chromenes by a Room-Temperature,Na2CO3-Catalyzed,Three-Component Reaction of Malononitrile,Benzaldehydes, and Phloroglucinol or Resorcinol in Aqueous Medium

The preparation of substituted 2-amino-4H-chromenes by a Na₂CO₃-catalyzed reaction of malononitrile, benzaldehydes, and phloroglucinol or resorcinol in aqueous medium and at room temperature is reported. The merits of this procedure include limited use of organic solvents, easy workup technique, and high purity of products. The 2-amino-4H-chromenes were prepared in yields of 54–96%.     

Heterocycles from substituted amides. VIII Oxazole derivatives from reaction of isocyanates with 2-isocyanoacetamides

A facile reaction of 2-isocyanoacetamides 1 with reactive aryl and sulfonyl isocyanates is shown to give 5-amino-2-oxazolecarboxamides 3 in a reaction arising from electrophilic attack of isocyanate with the nucleophilic isocyanide carbon. This reaction, perhaps proceeding through an unstable nitrile ylid intermediate reminiscent of the Cornforth rearrangement, is a first example of ring closure via acylation, involving the activated methylene of an organic isocyanide, without recourse to added base. Isomeric 5-amino-4-oxazolecarboxamides 4 are formed when 5-aminooxazoles 2 react with isocyanates. Since 2 has previously been shown to easily form by thermal isomerization of 1 , methods now exist for the preparation of both 5-amino- 2- and 4-oxazolecarboxamides from the single starting material 1 . In contrast, 1 with acyl isocyanates is shown to give a variety of products, including iminooxazolinediones, 5-amino-2-oxazolecarbox-amide 3 and 2 (1) pyrazinones (tentatively identified), depending on the structure of the isocyanates.