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.     

4-(3-nitrophenyl)-2-pieohne

The preparation of 4-(3-nitrophenyl)-2-pieoline (3) was accomplished in one step by the Zecher-Krohnke ring-closure reaction. Compound 3 is the starling material for 2-lormyl-4-(3-arninophenyl)pyridine thiosemicarbazone (4-APPT), a promising antineoplastie agent.     

Pd-catalyzed synthesis of 3-(diarylmethylene)-2-oxindoles and 3-(arylmethylene)-2-oxindoles

An efficient method for the stereoselective synthesis of 3-(diarylmethylene)-2-oxindoles and 3-(arylmethylene)-2-oxindoles via carbopalladation is described. In this approach, an Ugi-4-component reaction (4-CR) adduct was used as the starting material. A one-pot sequence involving intermolecular carbopalladation C-H activation/C-C bond formation efficiently afforded the oxindole derivatives.     

2-(Acylmethylmercapto)-3-amino- and 2-(acylmethylmercapto)-3-acetamidopyridines

The reaction of 2-mercapto-3-acetamido-5-(or 6-)chloropyridines with phenacyl bromide and substituted phenacyl bromides yielded 2-(phenacylmercapto)-3-acetamidopyridines, while the reaction of the former with -chloroacetoacetic ester yielded 2-(carbethoxyacyl-methylmercapto)-3-acetamidopyridlnes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1391–1394, October, 1971.     

Reaktionen von 3-(Dimethylamino)-2H-azirinen mit 1,3-Benzoxazol-2(3H)-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thione The reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione ( 5 ), which can be considered as NH-acidic heterocycle (pK_aca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2-(isopropylthio)-1,3-benzoxazole ( 12 ), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.     

Umsetzung von 3-(Dimethylamino)-2H-azirinen mit 1,3-Oxazolidin-2-thion zu 3-(2-Hydroxyethyl)-2-thiohydantoinen

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Oxazolidine-2-thione to 3-(2-Hydroxyethyl)-2- thiohydantoins The reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-oxazolidine-2-thione ( 6 ), in MeCN at room temperature, yields, after hydrolytic workup, 3-(2-hydroxyethyl)-2-thiohydantoins 7 (Scheme 2). In the case of the spirocyclic 1c , crystallization of the crude reaction mixture leads to spiro [cyclopentane-1, 7′(7′aH)-imidazo [4, 3-b] oxazole] -5′-thione 8c . The mechanism is discussed.     

6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉的合成

以6-溴-3-(氯苯基甲基)-2-甲氧基喹啉(2)为起始原料,经过偶合对接反应合成了新型喹啉类抗结核药物TMC-207的衍生物6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉,其结构经1H NMR和HR-MS确证.最佳反应条件:2 10 mmol,Et_3N 5 mL,KI 0.17 g,乙腈150 mL,于80 ℃反应6 h,收率73%.     

(R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}- 1H-苯并咪唑的合成

以2,3-二甲基吡啶为起始原料, 经过11步反应, 不对称合成了质子泵抑制剂的关键中间体: (R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}-1H-苯并咪唑. 研究了用手性高效液相色谱拆分对映体、测定产品光学纯度的方法, 结果表明目标产品的ee值达到99%. 通过IR, UV, MS以及1H NMR分析对重要中间体和目标产品进行了结构鉴定.     

The autoxidation of 2-(2-aminophenyl)-3- methylindole

Fischer indolisation of 2-aminophenyl ethyl ketone phenylhydrazone using glacial acetic acid saturated with hydrogen chloride as catalyst affords 3-methylindolo(l′:2′-3:4)2-methylquinazoline and 2-(2-aminophenyl)-3-methylindole. The latter compound is autoxidised to 2-(2-amino-phenyl)-3-hydroxy-3-methyl-3H-indole, a reaction which is shown to be dependent upon the presence of the primary amino group at the 2-position of the 2-phenyl substituent and which is much slower than the corresponding autoxidation of 2-(2-hydroxyphenyl)-3-methylindole to 3-hydroxy-2-(2-hydroxyphenyl)-3-methyl-3H-indole previously reported.Nitration of isopropyl phenyl ketone occurs preferentially at the ortho- rather than the meta- positions of the benzene nucleus.     

Synthesis of 2-(2-Naphthyl)quinolines from Z-3-(2-Naphthyl)-3-chloro-2-propenal

By reaction of Z-3-(2-naphthyl)-3-chloro-2-propenal and aromatic amines 1-(2-naphthyl)-3-iminoaryl-1-propenylarylamines were prepared which at heating in the glacial acetic acid afforded the corresponding 2-(2-naphthyl)quinolines.     

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins were prepared by reaction of substituted salicylaldehydes and hetarylacetonitriles. Alkylation and acylation of 3-hetaryl-7-hydroxycoumarins were studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 432–434, September–October, 2005.     

N-dealkylation of 2-(tert-butyl)-3-hydroxy-3-(4-chlorophenyl)isoindolinone and n-(tert-alkyl)-2-aroylbenzamides in concentrated sulfuric acid

It has been established that 2-(tert-butyl)-3-hydroxy-3-(4-chlorophenyl)isoindolinone and N-(tert-Alkyl)-2-aroylbenzamides are dealkylated in concentrated sulfuric acid to give 3-hydroxy-3-arylisoindolinones. The reaction is realizable. only when there is a tert-alkyl group attached to the nitrogen atom. The reaction mechanism is discussed on the basis of data on the change with time in the electronic spectra of the investigated compounds in concentrated sulfuric acid and a comparison with the spectra of model structures.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 763–765, June, 1977.     

Synthesis of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles

Abstract  

An efficient synthesis method for the preparation of a series of new (Z)- and (E)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles was developed. The reaction of (Z)- and (E)-3-styrylchromones with hydrazine hydrate afforded the corresponding (Z)- and (E)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles, except for nitro derivatives, where both (Z)- and (E)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations is discussed and the stereochemistries of all products were established by NMR experiments.     

Synthesis and Alkylation of 4-(2-Chlorophenyl)-3-cyano-6-hydroxy-5-(2-thienoyl)-6-trifluoromethylpiperidin-2-thione

4-(2-Chlorophenyl)-3-cyano-6-hydroxy-5-(2-thienoyl)-6-trifluoromethylpiperidin-2-thione, which was used for the synthesis of 2-allylthio-4-(2-chlorophenyl)-3-cyano-6-hydroxy-5-(2-thienoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine, was obtained by the reaction of 2-thienoyltrifluoroacetone with 2-chlorophenylphenylmethylenecyanothioacetamide or with a mixture of 2-chlorobenzaldehyde and cyanothioacetamide in the presence of N-methylmorpholine. The molecular and crystal structure of the piperidinthione have been established by X-ray crystallography.     

Reaction of 2-(2-Azahetaryl)-4-chloro-3-oxobutyronitriles with Substituted Benzaldehyde Hydrazones. Unexpected Formation of 4-Arylideneamino-2-(1-R-benzimidazol-2-yl)-3-oxobutyronitriles

The reaction of 2-(2-azahetaryl)-3-oxo-4-chlorobutyronitriles with substituted benzaldehyde hydrazones gives 4-arylideneamino-2-(1-R-benzimidazol-2-yl)-3-oxobutyronitriles, the structures of which were proved using spectroscopic data, the results of elemental analysis, and through their chemical reactions. It was found that the reaction course depends on the basicity of the heterocyclic fragment in the starting nitrile. A likely mechanism for the process is proposed.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

3-(2-methylthiopyridin-3-yl)-3-oxopropionic esters

A reaction of alkyl bromoacetates with substituted 3-cyano-2-methylthiopyridines in the presence of zinc dust furnishes 3-amino-3-(2-methylthiopyridin-3-yl)propenoic esters. Their hydrolysis under mild conditions leads to 3-(2-methylthiopyridin-3-yl)-3-oxopropionic esters. The latter were used in the synthesis of pyridine-substituted pyrazolones.     

Synthesis of ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates

An approach to the synthesis of substituted ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates was developed based on the reaction of ethyl cyanoacetate, carbon disulfide, and ethyl 4-chloroacetoacetate. The reaction regioselectively involved the ester group, rather than the nitrile one like in the case when malononitrile or cyanacetamide were used.     

Silica Gel Catalyzed Stereoselective Conversion of Dialkyl 2-(3-acetyl-4-hydroxy-1-naphthyl)-3-(triphenylphosphoranylidene) butanedioates to Dialkyl 2-(3-acetyl-4-hydroxy-1-naphthyl)-2-butenedioates in Solvent-Free Conditions

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, by 1-hydroxy-2-acetonaphthone leads to vinyltriphenylphosphonium salts, which undergo aromatic electrophilic substitution reaction with conjugate base to produce dialkyl 2-(3-acetyl-4-hydroxy-1-naphthyl)-3-(triphenylphosphoranylidene) butanedioates. Silica gel was found to catalyze conversion of dialkyl 2-(3-acetyl-4-hydroxy-1-naphthyl)-3-(triphenylphosphoranylidene) butanedioates to dialkyl 2-(3-acetyl-4-hydroxy-1-naphthyl)-2-butenedioates in solvent-free conditions at 90°;C in fairly good yields.     

Lithiation of 2-Alkyl-3-amino- and 2-Alkyl-3-(methylamino)-4(3H)-quinazolinones(1)

3-Amino-2-methyl-4(3H)-quinazolinone has been doubly lithiated, on nitrogen and in the 2-methyl group, with n-butyllithium. The lithium reagent thus obtained reacts with a variety of electrophiles (D(2)O, benzophenone, cyclohexanone, cyclopentanone, acetophenone, benzaldehyde, tetraisopropylthiuram disulfide (TITD)) to give the corresponding 2-substituted derivatives in very good yields. Reactions of the dilithio reagent with 2 molar equiv of methyl iodide or phenyl isocyanate give disubstituted derivatives. Double lithiation of the 2-ethyl and 2-propyl analogues have been achieved using LDA, and subsequent reactions with most electophiles are then similar. In the reaction of the dianion of the 2-ethyl compound with TITD, deamination from position 3 takes place with the formation of the 2-substituted derivative. In reactions with prochiral ketones, the dianion of the 2-ethyl compound gives very high diastereoselectivity. Lithiation and subsequent reactions of 3-(methylamino) analogues take place in a similar manner, thus providing access to a range of substituted 3-(methylamino)-2-alkyl-4(3H)-quinazolinones by a general procedure. Lithiation of 3-(dimethylamino)-2-ethyl-4(3H)-quinazolinone did not take place under similar conditions. Lithiation of 3-amino-2-unsubstituted-4(3H)-quinazolinone was also unsuccessful.