Studies with 1‐functionally substituted alkyl azoles: Novel synthesis of functionally substituted azolylbenzimidazoles and functionally substituted azolyl‐1,2,4‐triazoles

ω‐Azolylacetophenones 1 and 2 react with dimethylformamide dimethylacetal to yield enaminones 7,8 that were converted into azolylazoles via reaction with hydrazine and with hydroxylamine. Compounds 1,2 also coupled with aromatic diazonium salts to yield arylhydrazones and reacted with nitrous acid to yield corresponding oximes.     

The synthesis of some 3‐acylindoles revisited

A study probing the scope of acylation of indoles with dicarboxylic acids in acetic anhydride has been performed, resulting in products incorporating 3‐acylindole‐ or 1‐acylindole motifs depending on the choice of the acid reactant. Synthetically useful results were only obtained from reactions involving malonic acid or Meldrum's acid. Correlations to previous studies have also been made and discussed.     

Studies with 1‐functionally substituted alkylbenzotriazoles: An efficient route for the synthesis of 1‐azolylbenzotriazoles,benzotriazolylazines and benzotriazolylazoloazines

A new approach to the synthesis of pyrazole, isoxazole, pyridine and pyrazolo[1,5‐α]pyrimidine deriva tives is reported. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir and ¹H nmr spectra, and in some cases by ¹³C nmr investigation.     

A novel synthesis of 1‐substituted 2H‐isoquinolin‐3‐ones

The intramolecular cyclization of 2‐acylphenylacetonitriles 1 under strongly acidic conditions easily affords 1‐substituted 2H‐isoquinolin‐3‐ones 2 in excellent yields.     

Convenient synthesis of novel 5‐substituted 3‐methylisoxazole‐4‐sulfonamides

A number of novel sulfonamide derivatives of 5‐substituted‐3‐methylisoxazole were synthesized and characterized, starting from 3,5‐dimethylisoxazole. Key steps include the generation of 3,5‐dimethylisoxazole‐4‐sulfonamides followed by their reactions with N‐(dimethoxymethyl)‐N,N‐dimethylamine or various aromatic and heteroaromatic aldehydes. As a result, a series of novel aryl/heteroaryl‐ and aminovinylsubstituted derivatives of the isoxazole heterocycle were obtained. The scope and limitations of the developed approach are discussed.     

Studies on enaminonitriles: A new synthesis of 1,3‐substituted pyrazole‐4‐carbonitrile

3‐Diethylaminoacrylonitrile ( 1 ) reacts with hydrazonyl halides ( 2a‐d ) to yield 1,3‐disubstituted pyrazole‐4‐carbonitriles 5a‐d. The acetyl 1‐p‐chlorophenylpyrazole‐4‐carbonitrile ( 5a ) condensed with hydrazine hydrate to yield the bishydrazone 10 and with dimethylformamide dimethylacetal to yield 1‐aryl‐3‐(3‐dimethylamino)acryloyl pyrazole‐4‐carbonitrile ( 11 ). This enamine reacts with hydrazine hydrate to yield the pyrazolylpyrazole ( 12 ) and with naphthoquinone to yield the 3‐naphthofuranoyl pyrazole 13. The pyra‐zolyl pyridine derivative 14 was obtained upon treatment of 11 with acetylacetone in the presence of ammonium acetate. Compound 11 was coupled with p‐chlorobenzene diazonium chloride to yield the hydrazone 16 that was coupled further with p‐chlorobenzenediazonium chloride to yield the formazane 18.     

A facile one‐pot synthesis of novel substituted 1,2,3,4‐tetrahydropyrimidines

A facile one‐pot synthesis of 5‐benzoyl‐6‐methylthio‐1,2,3,4‐tetrahydropyrimidines in good yields is reported.     

Studies with 3‐functionally substituted 2‐arylhydrazononitriles: A new route to 3‐substituted‐2‐arylhydrazononitriles, 4‐amino‐pyrazole‐5‐carbonitriles,azadienes and cinnolines

3‐Amino‐3‐phenyl‐2‐phenylazoacrylonitrile 6 is obtained in good yield via reaction of 5 with phenyl magnesium bromide. The compound 6 is readily converted into 4a . The so formed alkanenitrile reacted with phenylmagnesium bromide to yield 8 . Compound 8 could be also obtained from reaction of 9 with phenylmagnesium bromide. The arylhydrazononitriles 8 and 4a reacted with chloroacetonitrile to yield the 4‐aminopyrazoles 12a,b . Compound 12a reacted with acetic anhydride to yield the 15a and with benzoyl chloride to yield the pyrazole 16 which was converted into 15b . Refluxing 10 in acetic acid gave a mixture of the azadiene 21 and the cinnoline 22 is obtained. The azadiene 21 is converted into 22 either thermally or photochemically.     

A novel and simple route for the synthesis of 3,4‐disubstituted pyrroles

A new class of 3,4‐disubstituted pyrroles has been prepared by the reaction of 1‐aroyl‐2‐arylsul‐fonylethenes and 1,2‐diarylsulfonylethenes with tosyl methyl isocyanide.     

A convenient synthesis of substituted 3‐alkoxycarbonyl‐β,γ‐unsaturated esters with predominant Z‐selectivity

The consecutive reaction of bis[2,2,2‐trifluoroethyl]phosphite with sodium hydride, dimethyl maleate, and aldehydes gives 3‐alkoxycarbonyl‐β,γ‐unsaturated esters with predominant Z‐selectivity in 62–94% yields (Z/E = 85–60:15–40). The Z‐ and E‐isomer can be separated conveniently by column chromatography. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:276–279, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10142     

Solvent‐free one‐pot approach for synthesis of substituted 2‐aminochromenes

A solvent‐free one‐pot approach for the preparation of 2‐aminochromenes in the presence of NaHCO₃ by grinding was described. Its advantages are easy work‐up, mild reaction condition, high yield and environmental compatibility.     

Synthesis of novel 3‐ and 5‐substituted indole‐2‐carboxamides

The preparation of several novel 3,5‐substituted‐indole‐2‐carboxamides is described. A 5‐nitro‐indole‐2‐carboxylate was elaborated to the 3‐benzhydryl ester, N‐substituted ester, and carboxylic acid intermedi ates, followed by conversion to the amide and then reduction of the 5‐nitro group to the amine. Indole‐2‐carboxamides with 3‐benzyl and 3‐phenyl substituents were prepared in four steps from either a 3‐bromo indole ester using the Suzuki reaction or from a 3‐keto substituted indole ester. N‐Alkylation of ethyl indole‐2‐carboxylate, followed by amidation and catalytic addition of 9‐hydroxyxanthene gave a 3‐xanthyl‐indole‐2‐carboxamide analog and a spiropyrrolo indole as a side product.     

A facile route for the synthesis of novel γ‐lactams

A selective reduction and its subsequent cyclisation of novel isoxazolidines into γ‐lactams have been examined in presence of Raney ‐ nickel catalyst.     

An intermediate in a new synthesis approach to β‐substituted β‐hydroxy­aspartame

The crystal and molecular structure of 1‐tert‐butyl 4‐ethyl (2′R,3′R,5′R,2S,3S)‐3‐bromo­methyl‐3‐hydroxy‐2‐[(2′‐hydroxy‐2′,6′,6′‐tri­methyl­bi­cyclo­[3.1.1]­hept‐3′‐yl­idene)­amino]­succinate, C₂₁H₃₄BrNO₆, is presented. This compound is an intermediate in the new synthetic route to β‐substituted β‐hydroxy­aspartates, which are blockers of glutamate transport.     

A novel synthesis of some new benzoyl‐substituted heterocycles from 2‐benzoyl‐3‐phenylpent‐2‐ene‐1,5‐dinitrile

2‐Benzoyl‐3‐phenylpent‐2‐ene‐1,5‐dinitrile 1 undergoes bromination with N‐bromosuccinimide (NBS) to afford the bromo derivative 2a . This bromo derivative undergoes reactions with sodium hydrogen sulfide, ethyl thioglycollate, hydroxylamine hydrochloride, hydrazines, cyanoacetamide, cyanacetohydrazide and urea derivatives to afford the thiophene 4 , 4H‐thiopyran 6 , 4H‐1,2‐oxazine 8 , 4H‐pyridazines 10a,b , the pyridine 15 , pyrrolo[1,2‐b]pyridazine 17 and the N‐substituted‐pyrrole derivatives 19a‐c respectively.     

Studies with functionally substituted N‐alkylazoles: The reactivity of 1‐(3,5‐dimethylpyrazol‐1‐yl)‐acetone towards electrophilic reagents

The reaction of 1‐(3,5‐dimethylpyrazol‐1‐yl)acetone 4 with aromatic diazonium salts afforded the corresponding arylhydrazones 5a,b that were converted into pyridazines 6a,b and 8 via condensation with active methylene nitriles and dimethylformamide dimethylacetal, respectively. Condensation of 4 with phenylhydrazine afforded the phenylhydrazone 10 , which could be converted into the indolylpyrazole 11 on treatment with ethanolic hydrochloric acid. Compound 4 also reacted with nitrous acid, benzyl‐idenemalononitrile to yield a variety of substituted new pyrazoles.     

Synthesis and antimicrobial activity of novel 3 substituted 1,5‐dihydro‐2,4,3‐benzodioxaphosphepine 3‐oxides

Novel 3 substituted 1,5‐dihydro‐2,4,3‐benzodioxaphosphepine 3‐oxides ( 5a–h ) were synthesized by reacting 1,2‐benzenedimethanol ( 1 ) with phosphorus tribromide in the presence of triethylamine at 0–30°C and subsequent reaction of the monobromide ( 2 ) with different Grignard reagents ( 3 ) at room temperature. The products ( 4 ) were converted to corresponding oxides 5a–i by oxidation with H₂O₂ at room temperature. The chemical structures of all the products were confirmed by analytical, IR and NMR (¹H, ¹³C, and ³¹P) spectral data. Their antifungal and antibacterial activity is also evaluated. Most of these compounds exhibited moderate antimicrobial activity in the assay. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:572–575, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20154