Synthesis of some new benzofuran‐based thiophene, 1,3‐oxathiole and 1,3,4‐oxa(thia)diazole derivatives

Treatment of 3‐(3‐methylbenzofuran‐2‐yl)‐3‐oxopropanenitrile ( 1 ) with phenyl isothiocyanate afforded the thioacetanilide derivative 3 , which when reacted with α‐haloketones, α‐halodiketones, and hydrazonoyl chlorides gives thiophene, 1,3‐oxathiole, and 1,3,4‐thiadiazole derivatives 6a,b, 10a,b and 14a–g , respectively. Treatment of 3‐methyl‐2‐benzofurancarboxylic acid hydrazide ( 15 ) with benzaldehyde followed by bromine afforded the 1,3,4‐oxadiazole derivative 18 . Treatment of the acid hydrazide 15 with phenyl isothiocyanate gave the thiosemicarbazide 20 . Compound 20 could be converted into 1,3,4‐oxadiazole, 1,2,4‐triazole‐3‐thione, and 1,3,4‐thiadiazole derivatives 21, 22 , and 23 , respectively. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:294–300, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20298     

The reversible cation-anion isomerisation of 2-imino-2H-pyrido [1,2-b][1,2,4]thia(oxa)diazole hydrobromide

The title compounds exist in pH-dependent equilibrium between cation and ring-opened anion; since pK₂ <pK₁, the hypothetical neutral species is always metastable.     

The vibrational spectra and stability of dipyrrolylmethene hydrobromides and their oxa and thia derivatives

This paper presents the IR spectra of solid alkyl substituted α,α-, α,β-, and β,β-dipyrrolylmethene hydrobromides and their oxa and thia derivatives recorded in KBr pellets over the frequency range 400–4000 cm^?1. The conclusion was drawn that the NH bonds in the pyrrole fragments of α,α-dipyrrolylmethene were identical, as distinct from the α,β and β,β isomers. The influence of functional substitution in the dipyrrolylmethene molecule on the frequencies of NH stretching vibrations was discussed. A satisfactory correlation between NH bond vibrational frequencies and the enthalpies of vaporization of gaseous hydrogen bromide from crystalline samples under heating was observed. This allows the IR data to be used as a criterion of the stability of dipyrrolylmethene salts and their oxa and thia derivatives.     

New type of transannular reactions in azirine-fused medium-size heterocycles: Selective transformations of azirino[2,1-<Emphasis Type="Italic">e</Emphasis>][1,6]benzoxazocines and -benzothiazocines into oxa(thia)zine and oxa(thia)zole derivatives

Opening of the three-membered ring in heterocyclic systems incorporating a dichloroaziridine ring fused to eight-membered O,N-or S,N-heterocycles is accompanied by transannular reactions with participation of the endocyclic oxygen and sulfur atoms. Depending on the conditions, the products are 1,4-benzoxazine (1,4-benzothiazine) or 1,3-benzoxazole (1,3-benzothiazole) derivatives. The discovered transformations were used as a basis of methods for the preparation of new heterocyclic systems, 2,3,4,4a-tetrahydro-1H-pyrido-[3,2-b][1,4]benzoxa(thia)zine derivatives, in domino or consecutive modes, as well as of pyrrolidinyl-substituted 1,3-benzoxa(thia)zoles.     

Synthesis and antimicrobial evaluation of some 1,2,4‐triazole, 1,3,4‐oxa(thia)diazole,and 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives

3‐Methyl‐2‐benzofurancarboxylic acid hydrazide ( 2 ) reacts with carbon disulfide and pota‐ ssium hydroxide to give the corresponding potassium carbodithioate salt 3 . Treatment of the latter salt with hydrochloric acid, hydrazine hydrate, and with phen‐ acyl bromide afforded the corresponding 1,3,4‐oxadia‐ zole‐5‐thione 4 , 4‐amino‐1,2,4‐triazole‐5‐thione 5 , and thiazolidine‐2‐thione 9 derivatives, respectively. The reaction of either 1,3,4‐oxadiazole‐5‐thione 4 or 4‐amino‐1,2,4‐triazole‐5‐thione 5 with phenacyl bromide resulted in the formation of 1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazine derivative 8 . Treatment of compounds 3 or 4 with hydrazonoyl halides 10a–d furn‐ ished the same 1,3,4‐thiadiazol‐2‐ylidene derivatives 11a–d . The 7‐arylhydrazono‐1,2,4‐triazolo[3,4‐ b ]‐1, 3,4‐thiadiazine derivatives 12a–d were obtained either by treatment of 4‐amino‐1,2,4‐triazole‐5‐thione 5 with hydrazonoyl halides 10a–d or by coupling of the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivative 8 with diazonium salts. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:621–627, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20162     

Synthesis and biological activity of 1,3,4-oxa(thia)diazole, 1,2,4-triazole-5-(thio)one and S-substituted derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid

Research on Chemical Intermediates - A series of novel derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid bearing two identical substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole, or...     

Synthesis and comparative study of the heterocyclic rings on liquid crystalline properties of 2,5-aryl-1,3,4-oxa(thia)diazole derivatives containing furan and thiophene units

A series of heterocyclic liquid crystalline compounds containing 1,3,4-oxadiazole/thiadiazole, furan and thiophene units were synthesised and characterised by means of electrospray ionisation-mass spectrometry (ESI-MS), high-resolution mass spectroscopy (HRMS), ¹H nuclear magnetic resonance (NMR) and ¹³C NMR. The thermal behaviours were investigated by differential scanning calorimetry (DSC) and polarised optical microscopy (POM). The effect of the 1,3,4-oxadiazole, 1,3,4-thiadiazole, furan, thiophene and benzene rings on the liquid crystalline properties was discussed briefly in context with the geometrical and electronic factors. The results showed that the tendency to form mesophases follows the sequence: 1,4-disustituted benzene >2,5-disubstituted thiophene >2,5-disustituted furan and 1,3,4-thiadiazole >1,3,4-oxadiazole.     

Pyrazoline derivatives: A convenient synthetic route to new pyrazolo-benzothia-(oxa) or diazepinone derivatives

New pyrazolo-[3,4-b]-[1,5]-benzoazepinone derivatives are reported. One pot reactions of 5-chloro-4-carboxy-1-phenyl (3-substituted) pyrazole derivatives with o-thioaminophenol, o-phenylenediamine, and o-aminophenol derivatives were realized. The influences of the polarizability of the heteroatoms on the reaction rates and chemical yields are discussed. © John Wiley & Sons, Inc.     

Conformational analysis of 14- and 16-membered unsaturated oxa, thia, and selena macrocyclic ligands

Crystallographic results retrieved from the Cambridge Structural Database (CSD) have been used to perform systematic conformational analyses of the free and metal-coordinated ligands 1,4,8,11-tetraoxa/thia/selenacyclotetradecane, 1,5,9,13-tetraoxa/thia/selenacyclohexadecane, and their derivatives. Conformational classifications established using symmetry-modified Jarvis-Patrick cluster analysis have been displayed in torsional space by principal component analysis (PCA) plots. Relative molecular mechanics energies of free macrocycles in the observed conformations are compared with the cluster populations and the effect of metal coordination investigated. While the conformations of the free macrocycles in the solid state are those with low molecular mechanics energies, substantial reorganization is required to produce tetradentate chelating conformers, particularly with S donors. With the latter, several such conformers occur, while one predominates with O donors for both macrocycles, in agreement with molecular mechanics predictions. Factors influencing the conformations adopted are discussed.     

New synthesis of pyrazole and isoxazole derivatives

A convenient synthesis of 5-aryl-1-phenylpyrazoles and 5-arylisoxazoles, from readily available ketimine 1 dimethylformamide dimethylacetal and phenylhydrazine or hydroxylamine, is described.     

Inverted meso-aryl porphyrins with heteroatoms; characterization of thia, selena, and oxa N-confused porphyrins.

Synthesis and characterization of inverted porphyrins containing S, Se, and O are reported. A simple 3 + 1 MacDonald-type condensation using modified tripyrrane containing the N-confused ring and diols afforded various N-confused porphyrins 6a-f in 19-30% yield. The single-crystal X-ray structure of 6b shows a ruffled conformation with tilt angles of 21.11 degrees and 31.23 degrees for the N-confused ring and the adjacent pyrrole ring III, respectively, revealing its severe nonplanarity. Significant changes in C alpha-C beta, C beta-C beta, and C alpha-X bond lengths are observed in 6b relative to free thiophene and pyrrole, suggesting the altered delocalization pathway in the modified N-confused porphyrins. The two molecules in the unit cell show a cyclophane-type noncovalent dimer with a face to face orientation of two N-confused pyrrole rings as a result of the presence of weak N-H...N and C-H...N intermolecular hydrogen bonds involving pyrrole-NH, the N atom of the N-confused ring, and the C atom of the pyrrole ring. A detailed 1H and 13C NMR study by 1D and 2D methods allowed assignments of all the peaks in the free base and protonated forms. NMR studies reveal the presence of three different tautomeric forms in solution for 6c in CDCl3 at low temperature. UV-visible studies reveal absorption band shifts upon heteroatom substitution, and the magnitudes of these shifts are dependent on the nature of the heteroatom. In all cases both monoprotonated and diprotonated species have been identified, and on addition of acid, the first proton goes to the outer N2 atom of the N-confused ring.     

Syntheses, structures and bioactivities of fluorine-containing phenylimino-thia(oxa)zolidine derivatives as agricultural bioregulators

From insight into the structure of trehazolin as trehalase inhibitor, six series of fluorine-containing phenylimino-thiazolidines (oxazolidines) derivatives were designed and prepared through a convenient synthesis of fluoroaryl isothiocyanate and a one-pot facile synthesis in high yield of fluorophenyl aminobenzoxazoles by cyclodesulfurization. The structures of the target compounds were confirmed with using IR, NMR, MS and elemental analysis. Their X-ray crystal analysis suggested that there were novel intermolecular (sp²CF?H₃C) and intramolecular (sp²CF?HN) hydrogen bonds between the fluorine atom on benzene ring and hydrogen atom of methyl group or amino group on five-membered heterocycle. Their fungicidal activities against Rhizoctonia solani and Pyricuraria oryzae at 100 ppm were determined.     

Sulfimidation of thioether groups--a versatile method for modifying and linking thia/oxa crowns

Reaction of the mixed thioether/ether crowns [9]aneO(2)S , [12]aneO(3)S and [18]aneO(4)S(2) with one mol. equivalent of the aminating agent MSH (o-mesitylsulfonylhydroxylamine) in Et(2)O results in the formation of the mono-sulfimidated systems {[9]aneO(2)(S[double bond, length as m-dash]NH(2))}(+), {[12]aneO(3)(S[double bond, length as m-dash]NH(2))}(+) and {[18]aneO(4)S(S[double bond, length as m-dash]NH(2))}(+), while using two mol. equivalents of MSH with gives the disulfimidium cation {[18]aneO(4)(S[double bond, length as m-dash]NH(2))(2)}(2+). All of these species have been isolated in good yields as the [mesSO(3)](-) (mes = 2,4,6-Me(3)C(6)H(2)) salts and can be readily converted to the [BPh(4)](-) salts by metathesis with Na[BPh(4)]. Treatment of or with lithium diisopropylamide (LDA) and N-bromosuccinimide (NBS) at -78 degrees C, followed by addition of a further equivalent of the parent thia/oxa crown, gives monocationic N-bridged sulfimide bicyclic compounds ( and respectively), in which the crowns are linked by the sulfimidic nitrogen. Reaction of with LDA and NBS leads to formation of the {([18]aneO(4)S(2))N}(+) cation which exhibits an intramolecular S-N-S bridge. Crystallographic studies on representative examples of each compound type are described, together with their spectroscopic properties.     

New "green" approaches to the synthesis of pyrazole derivatives

A novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of alpha,beta-unsaturated carbonyl compounds possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation coupled with solvent free reaction conditions. The cycloaddition was studied on three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone). The corresponding 3,5-disubstituted-1H-pyrazoles were obtained in high yields and after short reaction times. In order to simplify and point out the green chemistry features of the method, a further improvement was achieved under the same catalytic conditions with a "one pot" synthesis of these heterocyclic compounds, starting directly from their carbonyl precursors via tosylhydrazones generated in situ. For an exhaustive study, the dielectric properties of the solid reaction mixtures were also measured, in order to obtain input data for the numerical simulation of their heating behaviour in the single mode MW cavity which was used for experimental work. In order to supply a valid methodology and tool for measuring the environmental impact, a comparative study between the synthetic route proposed and the classical synthetic route has been carried out.     

Sulfimidation--a new and versatile strategy for the post ring-closure derivatisation of mixed thia/oxa crowns

Reaction of [18]aneO(5)S with the aminating agent MSH results in the {[18]aneO(5)SNH(2)}+ cation which may be converted through to the linked crown system [({[18]aneO(5)S}(2)N)]+ via deprotonation, bromination and reaction with the parent crown; significantly, despite their positive charge, both systems can coordinate sodium cations to the ether linkages.     

Cyclization of chalcones to isoxazole and pyrazole derivatives

A series of pyrazole and isoxazole derivatives were obtained by the condensation of the chalcones with hydrazine, phenylhydrazine, and hydroxylamine. All compounds were characterized using NMR, IR, and MS techniques.     

Synthesis,characterization, and antitumor activities of two copper(II) complexes with pyrazole derivatives

Two mononuclear copper(II) complexes with pyrazole derivatives, 1,1′-(anthracen-9-ylmethylene)bis(1H-pyrazole) (L¹ ) and 9-(4-(di(1H-pyrazol-1-yl)methyl)phenyl)-9H-carbazole (L² ), of formulae [CuL¹(CH₃CN)₂](ClO₄)₂ (1) and [CuL²(CH₃CN)₂](ClO₄)₂ (2) were prepared. Both complexes were confirmed by IR, MS, ¹H NMR, and elemental analyses. Complex 1 was also characterized by X-ray crystallography, confirming that copper(II) is coordinated by four nitrogen atoms from two L¹ and two oxygen atoms from two perchlorates. Furthermore, all ligands and complexes were tested in vitro for their antitumor activities using mouse melanoma cell line B16-F10, HepG2 human hepatoma cell line, and A549 human lung adenocarcinoma cell line. Both complexes displayed potent cytotoxicity and are promising substrates for further investigations.