A novel traceless route to synthesize 3,5-disubstituted-1,2,4-triazoles on PEG6000

A novel traceless route to 3,5-disubstituted-1,2,4-triazoles has been described, which allows the incorporation of two elements of diversity. This method provided a library of 3,5-disubstituted-1,2,4-triazoles with high yields and purity.     

N- and C-sulfenylation of 1-(1,2-oxazol-3 (and 5)-yl)-3-alkylureas with organic sulfenyl chlorides

Condensation of chlorocarbonylsulfenyl chloride 1 with 1-(5-(1,1-dimethylethyl)-1,2-oxazol-3-yl)-3-methylurea 4a has been found to give isomeric 2,4-disubstituted-1,2,4-thiazolidine-3,5-diones 5 and 6 . Assignments are confirmed by the X-ray structure data of 6 . Sulfenylation with alkoxycarbonylsulfenyl chlorides 7 and trichloromethylsulfenyl chloride 10 of 4 occurs exclusively on N-1 rather than N-3 of the urea moiety. With the isomeric 1-[3-(1,1-dimethylethyl)-1,2-oxazol-5-yl]-3-methylurea 14 and ethoxycarbonylsulfenyl chloride 7b , C-sulfenylated derivatives 15 and 16 are formed in low yield.     

Towards the total synthesis of tangutorine by intramolecular Diels-Alder reaction

The syntheses of 3,5-disubstituted-2-sulfolenes, and their participation in Pictet-Spengler reactions to give precursors of tangutorine, are described.     

A Convenient Synthesis of 3,5-Disubstituted 2-Acetylindoles

An easy synthesis of 3,5-disubstituted-2-actylindoles by the HC1 cyclization of the corresponding phenylhydrazones is described.     

The synthesis of some dialkyl 4-(3-substituted amino)phenyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates

Dialkyl 4-(3-aminophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 1 were transformed into alkyl 4-(3-(((2-benzoylamino-2-methoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 4 and with 2,2-disubstituted-1-dimethylaminoethenes 7 into dimethyl 4-(3-(((2,2-diacyl- or 2-acyl-2-alkoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 8 and their ethyl methyl analogues 9.     

TBAI/TBHP-Catalyzed Synthesis of [1,2,4]Triazolo[4,3-a]pyridines and 3,5-Diaryl-1,2,4-oxadiazoles via Oxidative Cleavage of C=C Double Bond

Russian Journal of Organic Chemistry - A simple and efficient protocol has been described for the synthesis of [1,2,4]triazolo[4,3-a]pyri­dines and 3,5-disubstituted-1,2,4-oxadiazoles by...     

SmCl3-catalyzed C-acylation of 1,3-dicarbonyl compounds and malononitrile

A recyclable, convenient, and efficient catalytic system for C-acylation of 1,3-dicarbonyl compounds and malononitrile with acid chlorides has been developed, giving moderate to excellent yields under mild conditions. This is the first catalytic example of such reactions. In addition, by applying this protocol as the key step, 3,5-disubstituted-1H-pyrazole-4-carboxylate can easily be synthesized in high yields in a one-pot procedure.     

Synthesis of 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes

The Michael addition of cyanothioacetamide to nitrostyrenes was investigated. Previously unknown 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes were obtained. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1472–1477, October, 2007.     

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Acylation of N-Boc-N-methylhydrazones followed by TFA treatment affords regioselective access to substituted pyrazoles. Both regioisomers of 1-methyl-3,5-disubstituted-1H-pyrazoles can be selectively obtained. This procedure can also be employed for the regioselective preparation of fully substituted 1H-pyrazoles.     

Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters

A general procedure is described for the preparation of 6-substituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19-77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters).     

Preparation of compounds in the new dipyrrolo[3,4-b:3′,4′-e]-pyridine series from 1-benzylidene-2,3-dioxopyrrolidines. A variation of the hantzsch synthesis

Treatment of easily prepared l-substituted-4-benzylidene-2,3-dioxopyrrolidines with ammonium formate produces 1,2,4,6,7,8-hexahydro-2,6-disubstituted-8-aryldipyrrolo [3,4-b:3′,4′-e]pyridine-3,5-diones (II), usually in yields of 50 to 60%. Aromatization of the dihydropyridine ring of the hexahydroderivatives II yields corresponding 1,2,6,7-tetrahydro-2,6-disubstituted-8-aryldipyrrolo[3,4-b:3′,4′-e]pyridine-3,5-diones (III). These compounds appear to be the first to incorporate the dipyrrolo[3,4-b:3′,4′-e]pyridine ring system.     

Synthesis of 1,3-disubstituted-2-amino-5-hydroxyindoles by reductive aromatization

Reductive aromatization and demethylation of 1,3-disubstituted-2-amino-5-oxo-7a-methyl-5,7a-dihydroindoles with zinc, pyridine and a trace of water yields 1,3-disubstituted-2-amino-5-hydroxyindoles. Simple derivatives of the 5-hydroxy substituent are described.     

Synthesis of New 3-Methylthio-4, 5, 6, 7-tetrahydro Benzo[c]thiophene-4-ones

A new route to 1,3-disubstituted-4, 5, 6, 7-tetrahydro benzo[c]thiophene-4-one is described starting from 1, 3-cyclohexanedione.     

Efficient in Situ Synthesis of 3,5-Disubstituted-1,2,4-triazoles Under Microwave-Assisted Conditions

Based on an efficient in situ metal/ligand reaction, a serial of 3,5-disubstituted-1,2,4-triazoles were synthesized via cycloaddition of organonitriles and ammonia under microwave conditions. This synthetic protocol provides a concise and high-yield access to 3,5-disubstituted-1,2,4-triazoles in organic synthesis. Moreover, the tautomerism of the product was also investigated.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.]     

Facile room-temperature assembly of the 1,2,4-oxadiazole core from readily available amidoximes and carboxylic acids

A one-pot ambient-temperature procedure for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles from amidoximes and carboxylic acids under superbase-promoted conditions is reported.     

Synthesis of 2,5-disubstituted-3-cyanoindoles

An efficient synthesis of 2,5-disubstituted-3-cyanoindoles is described. This approach utilizes a highly selective iodination together with the modified Madelung reaction to generate an intermediate which can be readily transformed to more fully elaborated 2,5-disubstituted-3-cyanoindole templates that were previously difficult to access. Detailed examples and utility of this approach are presented herein.     

Synthesis of 2-(4H-1,2,6-thiadiazin-4-ylidene)malononitriles

The base-free TiCl₄-mediated condensation of 3,5-disubstituted-4H-1,2,6-thiadiazin-4-ones 8 with malononitrile affords 20 difficult to access (3,5-disubstituted-4H-1,2,6-thiadiazin-4-ylidene)malononitriles 7. The reaction tolerates 3,5-diaryl, diphenoxy, dimethoxy and diphenylthio substituted thiadiazinones, but not diamino, monohydroxy or dihalo substituents. Nevertheless, asymmetrically substituted 3-halo-5-phenyl- and 3-chloro-5-methoxy-4H-1,2,6-thiadiazin-4-ones convert into the corresponding ylidenemalononitriles in good yield. Furthermore, the condensation works well with ethyl cyanoacetate and diethyl malonate, but not with Meldrum's acid, dimedone or nitromethane. Finally, 2-(3-chloro-5-phenyl-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (7q) reacts with aniline to give 4,7-diphenyl-6-(phenylimino)-6,7-dihydropyrrolo[2,3-c][1,2,6]thiadiazine-5-carbonitrile (12) in moderate yield demonstrating the potential use of these ylidenes to prepare novel 6–5 fused 4H-1,2,6-thiadiazines.     

Investigation of the reactions of 2-hydrazino-benzimidazoles with β-diketones: Synthesis of 2-(3,5-disubstituted- 1H-pyrazol-1-yl)benzimidazoles

Reaction of 2-hydrazinobenzimidazoles with β-diketones in neutral and acidic media revealed that 2-(3,5-disubstituted-1H-pyrazol-1-yi)benzimidazoles are formed in the former case, whereas hydrazones are obtained in acidic medium. Further the alkylation of > NH of the title compound was investigated. Characterisation of these products have been done by elemental analysis, ir, pmr, ¹⁹F nmr, ¹³C nmr and mass spectral studies.     

A Practical and Efficient Synthesis of 2,5-Disubstituted-3,5-dihydro-imidazol-4-ones from Oxazolones

An alternative procedure for the synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-4-ones from substituted oxazolones was evaluated. The initial oxazolone ring-opening reaction was examined with a variety of ammonia source compounds followed by the subsequent 3,5-dihydro-imidazol-4-one cyclization reaction, which was carried out with either an organic or inorganic base in aprotic solvents. In this article, we report the results of an efficient and straightforward procedure for the synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-4-ones that gives satisfactory yield and quality.     

Stereocontrolled Conversion of 3,5-Dioxopyrrolizidine Into (Z)- and (E)- 5-Acetonylpyrrolizidin-3-ones

Stereocontrolled synthesis of (Z)-5-acetonyl-pyrrolizidin-3-one (4) and (E)-isomer 5 from 3,5-dioxopyrrolizidine 1 is described.