Research on aminomethylene derivatives of azoles

It is shown that, in contrast to hippuric acid, thiohippuric acid reacts with dimethylformamide in the presence of phosphorus oxychloride to give three compounds, viz., 2-phenyl-4-dimethylaminomethylene-5-thiazolone, 2-phenyl-4-dimethylamino-methyleneoxazole-5-thione, and 2-phenyl-4-formyl-5-chlorothiazole. The pathways of their formation are discussed. The structures of the compounds obtained and some transformations of 2-phenyl-4-formyl-5-chlorothiazole were studied. 2-Phenyl-4-formyl-5-hydroxy(mercapto) thiazoles and their methyl derivatives, as well as 2-phenyl-4-dimethylaminomethylenethiazole-5-thione, were synthesized from the latter.See [1] for Communication 23.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 36–39, January, 1980.     

Synthesis and reactions of 2-(4-pyridyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinazoline

7,7-Dimethyl- and 7-phenyl-2-(4-pyridyl)-5-oxo-5,6,7,8-tetrahydroquinazolines were synthesized in the reactions of 2-formyl-5,5-dimethyl- and 5-phenyl-1,3-cyclohexanediones, respectively, with 4-amidinopyridine. The oxime, thiosemicarbazone, 4-quinazolyl-, nicotinoyl-, isonicotinoyl-, and 2-hydroxybenzoylhydrazones of 2-(4-pyridyl)-5-oxo-7,7-dimethyl-5,6,7,8-tetrahydroquinazoline were obtained. The reduction of this ketone by sodium borohydride leads to the 5-hydroxy derivative.     

Formation of pyrrole derivatives through aminolysis of 2-azetidinone derivatives

A mixture of 3-(α,β-epoxyisopropyl)-1-phenyl-2-azetidinone and benzylamine was heated in a sealed tube at 120–130° yielding 4-anilinomethyl-1-benzyl-3-hydroxy-3-methyl-2-pyrrolidinone as a mixture of diastereoisomers. By this method, 4-anilinomethyl-3-hydroxy-3-methyl-1-phenyl-2-pyrrolidinone and 4-anilinomethyl-3-hydroxy-3-methyl-1-(3,4-dimethoxyphenethyl)-2-pyrrolidinone were obtained by using aniline and 3,4-dimethoxyphenethylamine, respectively, instead of benzylamine. The reaction of 4-formyl-1-phenyl-2-azetidinone with 3,4-dimethoxyphenethylamine afforded 4-anilino-1-(3,4-dimethoxyphenethyl)-2,3-dihydro-2-oxopyrrole. In a similar fashion, the 1-n-butyl and 1-isobutyl analogues were obtained by the use of n-butylamine and isobutylamine, respectively, instead of 3,4-dimethoxyphenethylamine.     

Bioactive aromatic derivatives from endophytic fungus, Cytospora sp

Two new benzyl gamma-butyrolactone analogues, (R)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (1) and its 6-acetate (2), and a new naphthalenone derivative (8), together with eight additional known aromatic derivatives, (S)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (3), (S)-5-benzyl-dihydrofuran-2(3H)-one (4), 5-phenyl-4-oxopentanoic acid (5), gamma-oxo-benzenepentanoic acid methyl ester (6), 3-(2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furyl)propionic acid (7), (3R)-5-methylmellein (9), integracins A (10) and B (11) were isolated from Cytospora sp., an endophytic fungus isolated from Ilex canariensis from Gomera. The structures of these compounds were elucidated by detailed spectroscopic analysis, comparison with reported data, and chemical interconversion. The absolute configurations of the new compounds (1, 2, 8) were established on the basis of optical rotation or CD spectra analysis. Preliminary studies showed antimicrobial activity of these compounds against the fungi Microbotryum violaceum, Botrytis cinerea and Septoria tritici, the alga Chlorella fusca, and the bacterium Bacillus megaterium.     

Crystal structures and photoisomerization behaviors of five novel pyrazolone derivatives containing furoyl group

Five novel pyrazolone derivatives containing a furoyl group, 1-phenyl-3-furoyl-4-(4-chlorobenzal)-5-pyrazolone thiosemicarbazone (PF4ClBP-TSC) (1)/methylthiosemicarbazone (PF4ClBP-MTSC) (2)/ethylthiosemicarbazone (PF4ClBP-ETSC) (3), 1-phenyl-3-furoyl-4-(2-chlorobenzal)/(3-chlorobenzal)-5-pyrazolone methylthiosemicarbazone (PF2ClBP-MTSC) (4)/(PF3ClBP-MTSC) (5), have been synthesized and characterized by elemental analysis, IR, ¹H NMR spectra, and the molecular structures of 2 and 5 were determined by X-ray single crystal diffraction. Photoisomerization properties have been studied by UV–vis and fluorescence spectra. Based on theoretical calculation and crystal structural analysis, the compounds undergo photoisomerization from the enol form to the keto form through an intermolecular proton transfer upon UV light irradiation. Moreover, the photoisomerization rate decreases with the increase of volume of substituent groups on 4-position of thiosemicarbazide and the steric hindrance of Cl atom on benzal of 4-positon on the pyrazolone ring.     

Heterocyclic compounds from 3,3-dimercapto-1 -aryl-2-propen-1-ones. Note 2. Condensation with o-aminothophenol and o-aminophenol

The condensation of 3,3-dimercapto-1-phenyl-2-propen-1-one with o-aminothiophenol and o-aminophenol in hot xylene gave 2-phenacylbenzothiazole ( 3 ) and 2-phenacylbenzoxazole ( 5 ). When the reaction with o-aminophenol was carried out in hot benzene, 2-beuzoylthioacctamidophenol ( 4 ) was obtained, which, heated in hot xylene gave 5. Ethyl benzoylacetale by reaction with o-aminothiophenol gave 3 , whereas by reaction with o-aminophenol gave no heterocyclic compound. However, we were able to isolate 2-benzoylacetamidophenol ( 6 ), ethyl β-phenyl-β-(o-hydroxy)phenyliminopropionate ( 7 ), and 2-[β-(o-hydroxy)anilino] cinnamoylamidophenol ( 8 ). Ir and nmr spectra of synthesized compounds point out the existence of tautomers.     

5-Phenyl-2-(pyrazol-4-yl)-1,3,4-thiadiazoles

By recyclization of 2-R-6-ethyl-7-hydroxy(methoxy)-3-(5-phenyl-1,3,4-thiadiazol-2-yl)chromones when treated with hydrazine hydrate and phenylhydrazine, we synthesized 5-phenyl-2-(3-R-5-R1-1H-pyrazol-4-yl)-1H-1,3,4-thiadiazoles and 2-(3-R-5-R1-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1H-1,3,4-thiadiazoles. We confirmed the structure of the latter from ¹H NMR spectra.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 781–787, May, 2005.     

Investigation of the IR,PMR, UV,and mass spectra of betaines of the azole series

It was established by a complex spectral method that 5-formyl-4-(1-pyridinia)thiazole 2-oxide and 1-phenyl-5-formyl-(1-pyridinia)imidazole 2-oxide have betaine structures.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 255–257, February, 1978.     

Crystal Structure of the Polymer Copper(II) Complex with 1-Phenyl-3-Methyl-4-Formyl-5-Hydroxypyrazole Hetarylhydrazone

A new coordination polymer of Cu(II) based on 1-phenyl-3-methyl-4-formyl-5-hydroxypyrazole 4,6-dimethylpyrimidylhydrazone is synthesized. The polymer is studied by X-ray diffraction analysis (CIF file CCDC no. 1565772). It is shown that the polymer is formed due to the coordination of the nitrogen atom of the pyrazolone fragment to the copper(II) ion of the adjacent monomeric fragment.     

Synthesis of functionally substituted isoxazole and isothiazole derivatives

Acylation of benzene and toluene with 5-phenyl- and 5-(p-tolyl)isoxazole-3-carbonyl chlorides gave 5-phenyl(or p-tolyl)isoxazol-3-yl phenyl(or p-tolyl)ketones which were reduced to the corresponding alcohols with sodium tetrahydridoborate in propan-2-ol. Selective reduction of the carboxy group in 4,5-dichloroisothiazole-3-carboxylic acid was achieved by the action of BH₃, and the aldehyde group in 4-formyl-2-methoxyphenyl 5-arylisoxazole-3-carboxylates and 4,5-dichloroisothiazole-3-carboxylates was reduced to hydroxymethyl group with sodium triacetoxyhydridoborate in benzene. Acylation of the resulting hydroxymethyl derivatives with 5-arylisoxazole- and 4,5-dichloroisothiazole-3-carbonyl chlorides afforded the corresponding esters containing two azole fragments in their molecules.     

Tautomerism and Acid-Base Properties of Formyl Derivatives of 1-Phenyl-3-methyl-4,5-dihydropyrazol-5-one and Its Thio Analog

A single-crystal X-ray diffraction study showed that 1-phenyl-3-methyl-4-formyl-4,5-dihydropyrazol-5-one occurs in the solid phase as two conformers of the NH tautomer. The acidity and basicity constants of 1-phenyl-3-methyl-4-formyl-4,5-dihydropyrazol-5-one and its analog, -5-thione, in 50% aqueous dioxane were measured. PM3 calculations qualitatively explan the differences in the tautomerism and acid-base properties of 4-formylpyrazolone (-pyrazolethione) and the corresponding compounds without the formyl substituent.     

Synthesis of unsaturated ketones and derivatives of 2-pyrazoline containing an indole nucleus

The crotonic condensation of 3-acetylindole, its N-methyl derivative, 3-formyl-1-methylindole, and 3-formyl-6-nitroindole with various aldehydes and methyl ketones in an alkaline medium has yielded a number of unsaturated ketones, some of which have been characterized as their 2, 4-dinitrophenylhydrazones. The reaction of some of these unsaturated ketones with phenylhydrazine has yielded derivatives of 1-phenyl-2-pyrazoline, which possess luminescent properties.     

Application of photoelectron spectroscopy to biologically active molecules and their constituent parts. II. 1,4-Benzodiazepines

The Hel photoelectron (PE) spectra of 5-phenyl-7-chloro-2H-1,4-benzodiazepin-2-one ( 1 ), its 1-methyl derivative ( 2 ), 3-hydroxy derivative ( 3 ), 1-methyl-3-hydroxy derivative ( 4 ), 3-(S)-methyl derivative ( 5 ), and 1-methyl-3-(S)-methyl derivative ( 6 ) have been recorded. The electronic structure of these compounds is discussed on the basis of the observed ionization energies, and of the semiempirical CNDO/2 calculations on model compounds 1a-6a , which have a hydrogen instead of the phenyl group in the 5-position. As a result the character of the seven highest occupied orbitals in 1–6 have been assigned.     

Benzoid-quinoid tautomerism of azomethines and their structural analogs

A number of organomercury derivatives of N-alkyland N-arylimines of 2-and 3-hydroxy-(mercapto) formylbenzo[b]furans and 2- and 3-hydroxy(mercapto)formylbenzo[b]thiophenes were synthesized. A conclusion regarding the position of the C₆H₅Hg group in these compounds was drawn from the vibrational and electronic absorption spectra.     

7-Azaindole derivatives

A study is made of new synthetic routes, based on accessible 3-formyl-7-azaindoles, to 3-substituted 7-azaindole. 2-Phenyl-4-(1-phenyl-4-methyl-7-azaindolyl-3-rnethylene)-1, 3-oxazol-5-one is synthesized, and it is converted to 1-phenyl-4-methyl-7-azatryptophane, 1-phenyl-4-methyl-7-azaindolyl-3-acetic acid,1-phenyl-3-(,-dihydroxypropyl)-4-methyl-7-azaindole, and 1-phenyl-4-methyl-7-azaindolyl-3-pyrotartaric acid.For Part XVIII see [1].     

A study of 8-mercaptoquinoline (thiooxine) and its derivatives

The absorption spectra of 5-fluoro-8-mercaptoquinoline in aqueous solutions at various pH values have been studied. The _max values of the 5-fluoro-8-mercaptoquinolinium ion and also of the 5-fluoro-8-mercaptoquinolate ion, and the apparent molar absorption coefficient of the hydrated form have been determined. In the hydrated form, a molecule of water is connected by hydrogen bonds both with the nitrogen and with the mercapto group. The presence of the fluorine atom in positions 5 of the molecule of the 8-mercaptoquinoline increases the acidic properties of the mercapto group and decreases the basic properties of the nitrogen, in comparison with those in 8-mercaptoquinoline. The dissociation constants of 5-fluoro-8-mercaptoquinoline are pK_SH=7.49 ± 0.02 (thermodynamic) and pK_NH= 1.97 ±0.02 (concentration). The isoelectric point is at pH 4.70.For part XXXVIII, see [4].     

Synthesis and spectral luminescence properties of stilbene derivatives containing 2-pyrazolinyl and 1,3-oxazolyl groupings

A number of trans-stilbene derivatives containing 2-pyrazolinyl and 1,3-oxazolyl groupings were synthesized by PO olefination from 1-(4-formylphenyl)-3-aryl-5-phenyl-2-pyrazolines and 2-(4-bromomethylphenyl)-5-phenyl-1,3-oxazole. The products fluoresce intensely in the green or yellow-green region (quantum yields 0.4–0.57). The intense long-wave absorption band of the investigated compounds is due to an electron transition that is localized primarily in the stilbene fragment of their molecules that includes, as a substituent, the amine nitrogen atom of the pyrazoline ring; the less intense shortwave band corresponds to localization of the electronic excitation in the hydrazone grouping.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 656–661, May, 1977.     

Synthesis,properties, and X-ray diffraction study of 4-trifluoromethyl-6-phenyl-2-chloro-3-cyanopyridine

4-Trifluoromethyl-6-phenyl-2-chloro-3-cyanopyridine was synthesized, and its molecular-crystal structure was established. The chlorine atom was replaced by amino, mercapto, thiocyanato, and azido groups. The possibility of the direct amination of 4-trifluoromethyl-6-phenyl-3-cyano-2-pyridone by the action of hexamethylphosphoric triamide (HMPT) was demonstrated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1233–1237, September, 1987.     

Mass spectrometric studies on 4-aryl-1-cyclopropyl-1,2-dihydropyridinyl derivatives: an examination of a novel fragmentation pathway

Examination of the electrospray ionization product ion spectra of 1,2-dihydropyridinyl and 4-aryl-1,2-dihydropyridinyl derivatives bearing a 1-cyclopropyl or 1-trans-2-phenylcyclopropyl group has led to the characterization of unexpected fragment ions. For example, the base peak at m/z 156 present in the product ion spectrum of trans-1-(2-phenylcyclopropyl)-4-phenyl-1,2-dihydropyridine proved not to be the expected 4-phenylpyridinium species but rather the isomeric 3-phenyl-5-azoniafulvenyl species. The results of studies with a series of structural and isotopically labeled analogs require a novel fragmentation pathway to account for the formation of this and related fragment ions. One possible pathway is based on an initial 1,5-sigmatropic shift of a cyclopropylmethylene hydrogen atom that is accompanied by opening of the cyclopropyl ring. The resulting eniminium intermediates then fragment to yield the 5-azoniafulvenyl species.     

One-pot multi-component synthesis of novel ethyl-2-(3-((2-(4-(4-aryl)thiazol-2-yl)hydrazono)methyl)-4-hydroxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate derivatives and evaluation of their in vitro antimicrobial activity

A novel series of ethyl-2-(3-((2-(4-(4-aryl)thiazol-2-yl)hydrazono)methyl)-4-hydroxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate derivatives ( 4a-f and 5a-f ) were synthesized by employing one-pot multi-component approach involving ethyl 2-(3-formyl-4-oxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate, thiosemicarbazide and various phenacyl bromides/3-(2-bromoacetyl)-2H-chromen-2-one/2-(2-bromoacetyl)-3H-benzo[f]chromen-3-onein ethanol in the presence of catalytic amount of acetic acid. The structures of all the synthesized compounds were confirmed with spectral analysis, ie, IR, 1H NMR, 13C NMR and mass spectrometry, and all the compounds were screened for their in vitro antimicrobial activity.