Oxidative dehydrogenation of 5-(pyridine-2-yl-methyl)-2-thioxo-4-imidazolidinones in complexation reaction with copper(II) chloride

The treatment of 5-(pyridine-2-yl-methyl)-2-thioxo-4-imidazolidinones with copper(II) chloride dihydrate led to the formation of a dinuclear copper complex L₂Cu₂Cl where L is a dehydrogenated initial organic ligand. X-ray diffraction analysis indicated that the starting 3,5-dihydro-4H-imidazole-4-ones undergo oxidation in the course of the reaction with the formation of an exocyclic double bond at C5 position.     

Pyryliumverbindungen. 45 [1]. 4-Aroyl-fluorene aus 2,4,6-Triaryl-pyryliumsalzen und Indan-1-on via 2-(5-Oxo-pent-2-en-1-yliden)-indan-1-one

Pyrylium Compounds. 45. 4-Aroyl-fluorenes from 2,4,6-Triaryl-pyrylium Salts and Indan-1-one via 2-(5-Oxo-pent-2-en-1-yliden)-indan-1-ones 2,4,6-Triarylpyrylium salts 1 react with indan-1-one in the presence of an appropriate buffer system (e.g. piperidine acetate, triethylamine/acetic acid, triethylamine or sodium acetate) to yield the 2-(1,3,5-triaryl-5-oxo-pent-2-en-1-yliden)-indan-1-ones 2 . For the reaction medium aliphatic alcohols (methanol, ethanol), dipolar aprotic solvents (acetonitrile) or chlorinated hydrocarbons (methylene chloride, chloroform, carbon tetrachloride) can be used. On treating 2 with sodium methanolate in methanol, a cyclization reaction occurs giving rise to the 4-aroyl-1,3-diaryl-fluorenes 3 . As by-products 1,3-diaryl-fluorenes 8 (e.g. 1,3-diphenyl-fluorene) are formed. - I.r., n.m.r. and u.v. spectroscopic data of the novel compounds 2 and 3 are reported.     

Pyryliumverbindungen. 43 [1]. Arylsubstituierte 5-(2-Dialkylamino-thiazol-5-yl)-pentadienone aus 2,4,6-Triaryl-pyryliumsalzen und 2-Dialkylamino-4-arylthiazolen

Pyrylium Compounds. 43. Arylsubstituted 5-(2-Dialkylamino-thiazol-5-yl)-pentadienones from 2,4,6-Triarylpyrylium Salts and 2-Dialkylamino-4-aryl-thiazoles 2,4,6-Triarylpyrylium salts 1 react with 2-dialkylamino-4-aryl-thiazoles 7 (used in substance or prepared in situ from α-thiocyanato-acetophenones 9 ) in the presence of an appropriate acid-binding agent (e.g. piperidine acetate or sodium acetate) to give 5-(2-dialkylamino-4-aryl-thiazol-5-yl)-1,3,5-triaryl-penta-2,4-dien-1-ones 8 . As reaction medium aliphatic alcohols (ethanol, n-propanol), dipolar aprotic solvents (acetonitrile) or chlorinated hydrocarbons (methylene chloride, chloroform) can be used. On the other hand, under the same conditions 2-amino-4-phenyl-thiazole ( 10 ) reacts with salts of type 1 via pyrylium ring transformation yielding 2,4,6-triaryl-1-(4-phenyl-thiazol-2-yl)-pyridinium perchlorates 11 .     

Substitution Reactions of 2-(Aroyl,Methylidene)-thiazolidine-4-on Derivatives

The reaction of 2-(aroyl, methylidene)-3-arylthiazolidine-4-ones 1 with trifluoromethylsulfenyl chloride yields a mixture of geometric (Z, E) isomers of 2(aroyl, trifluorosulfenylmethylen)-3-aryl-thiazolidine-4-ones 2 . The bromination of 1 leads to 2-(aroyl, methylidene)-3-aryl-5-bromothiazolidine-4-ones 3 which on reaction with nitrosobenzene formes nitrones 4 . The structures of the compounds 2 – 4 were determined by means of n.m.r. and i.r. spectroscopy.     

Reactions with 2-thiazolin 5-ones. IV. Action of amines on 4-substituted 2-alkoxy- and 2-benzylmercapto-2-thiazolin-5-ones

Whereas treatment of 2-butyloxy-, 2-pentyloxy- and 2-β-phenylethyloxy-4-arylazo-2-thiazolin-5-ones 1d–h with strong basic amines results in their rearrangement into 1-aryl- Δ²-1,2,4-triazolin-5-one-3-carboxylic acid derivatives 2 , the 2-isobutyloxy, 2-(2-octyloxy)- and the 2-cyclohexyloxy-4-arylazo-2-thiazoline-5-ones 1i–n rearrange upon treatment with the same reagents into Δ²- 1,2,4-triazoline-5-thione-3-carboxylic acid derivatives 3 . On the other hand, 1d–h,1 react with aromatic amines to give 1-aryl-2-alkoxy-1,2,4-triazole-3-carboxylic acid anilides 4a–i , via the loss of hydrogen sulphide. The phenylhydrazides 4j–l are obtained upon treatment of 1g, h,l with phenylhadrazine. Treatment of 4-arylidene-2-benzylmercapto-2-thiazolin-5-ones 6a–c with ammonia results in the formation of the thiohydantoin derivatives 7e, g . However, 6b, c react with phenylhydrazine to yield the phenylhydrazides 8b, c . The reaction of 6a–e with piperidine or morpholine involves to molecules of the reagent to yield 10a–d which are thermally cyclised to the thiazolone derivatives 11a–d .     

Dehydration of 2-(2-Arylethyl)-2-hydroxy-4-oxopentanoic Acids and their hydrazones to form heterocycles

Dehydration of 2-(2-arylethyl)-2-hydroxy-4-oxopentanoic acids 1 with hydrochloric acid/acetic acid, affords 3-(2-arylethyl)-5-hydroxy-5-methyl-2(5H)-furanones 4 . Compounds of type 1 and 4 represent suitable precursors for the formation of pyridazin-3-ones 7 as they smoothly react with hydrazine. A new series of s-triazolo[4,3-b]pyridazin-3-ones 12 and tetrazolo[1,5-b]pyridazines 15 are obtained from the 3-chloropyridazines 11 upon treatment with semicarbazide and sodium azide, respectively. Reaction of 11 with phenyl- acetyl-hydrazine provides 3-benzyl-6-phenyl-8-(2-phenyl-ethyl)-s-triazolo[4,3-b]pyridazine 13 via dehydrative cyclization of the intermediate 14 which was clarified to exhibit tautomeric equilibria between enol–hydrazine form A and keto–hydrazine form B by means of ¹H and ¹³C NMR spectroscopy. Attempts to synthesize 3-alloxy-pyridazines 18 by reacting 11 with sodium alloxide afford N-allyl compounds 17 .     

Bis(3-(2-pyridyl)pyrazol-1-ylmethyl)benzenes: doubly-chelating binucleating ligands and encapsulation of a linear trisilver(I) moiety

The three isomeric bis(3-(2-pyridyl)pyrazol-1-ylmethyl)benzenes (3–5) were prepared by reaction of 3-(2-pyridyl)pyrazole with the appropriate bis(bromomethyl)benzene. Reactions of each isomer with palladium(II) chloride and copper(II) chloride gave high yields of the corresponding binuclear complexes. Reaction of the ortho isomer with silver nitrate gave a complex which was shown by X-ray crystallography to contain a linear array of three silver atoms encapsulated by two molecules of the ligand.     

Regio- and stereoselectivity of 1-(Pyridazin-3-yl)-3-oxidopyridinium Betaines towards 2π- and 4π-conjugated olefins

1-(6-Phenyl) and 1-(6-(4-tolyl)-3-oxidopyridinium betaines ( 1a , b ) react as 1,3-dipoles with conjugated olefines, namely 4-vinylpyridine, ethyl cinnamate and styrene as 2π-1,3-dipolarophiles to give 2,6-cycloadducts [6-substituted-8-azabicyclo[3,2,1]oct-3-en-2-ones ( 3a , b , 4a , b and 5b )] and with butadiene and furan as 4π-dipolarophiles to give 2,4-cycloadducts [7-substituted-7-azabicyclo[4,3,1]deca-3,8-diene-10-one] and 3-6-phenylpyridazin-3-yl)-3-aza-10-oxatricyclo-[5,2,1,1^2,6]undeca-4,8-diene-11-one ( 9a ). Structural and configurational assignments were based on H.n.m.r. spectral analysis.     

Cycloadditions-Eliminierungsreaktionen mit 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-onen (Senföloxiden)

Cycloaddition Elimination Reactions of 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-ones (Mustard Oil Oxides) 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-ones ( 1 ) react with isocyanates, isothiocyanates, and cyanic acid esters by exchange of the COS-part from 1 affording thiadiazole and dithiazole derivatives 4 , 5 , 6 or 12 . The reaction products are able to give further exchange reactions. Ring opening of 2-substituted 4-aryl-5-arylimino-1,2,4-thiadiazolin-3-ones ( 4 ) and -3-thiones ( 6 ) yields thio- and dithiobiurets ( 7 , 8 ) with aryl substituent in 3-position. Oxidation of dithiobiurets, generated from 6 , affords dithiazolidines 9 , which are Dimroth-isomers of 6 .     

Synthesis and antibacterial activity of certain quinoline and quinazoline derivatives containing sulfide and sulfone moieties

Some aryl and/or heterocyclic mercaptans were allowed to react with 8-quinolyl chloroacetate (II), 8-quinolinoxyacetyl chloride (IV) and 3-(2′-chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one (X) in dry benzene and/or sodium hydroxide in absolute ethanol to give corresponding 8-quinolyl-α-mercaptoacetate (V), 8-quinolinoxythioacetate (VI) and 3-(2′-arylmercaptoethyl)-2-methyl-4-(3H)quinazolin-4-ones or 3-(2′-heterocyclicmercaptoethyl)-2-methyl-4(3H)-quinazolin-4-ones (XIa-h). The mercaptans V and XI were subjected to oxidation with hydrogen peroxide/acetic acid mixture (1:2) to afford the corresponding sulfones VII and XII. The structures of the synthesized compounds were elucidated by spectroscopic (IR and ¹H-NMR) and elemental analyses. Some of these compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.     

Radikalreaktionen an N-Heterocyclen. XI [1] Reaktionen von 3-Methyl-pyrazolin-5-onen mit Phenoxyl-Radikalen

Free Radical Reactions of N-Heterocyclic Compounds. XI. Reaction of 3-Methyl-pyrazolin-5-ones with Phenoxy Radicals Pyrazolin-5-ones ( 3a–i ) were oxidized with 2,4,6-trisubstituted phenoxy radicals ( 2a–d ) to the corresponding radicals ( 4a–i ), which dimerised or combined with phenoxy radical ( 2a ) depending on the R¹- and R⁴-substituents in ( 3 ). In the case of 3-methyl-1-phenyl-pyrazolin-5-one ( 3f ) the primary radical combination products were not found, but the corresponding quinone methide ( 17 ) and the o-phenol derivative ( 18 ) were isolated. Products and yields have been investigated as a function of mol ratio substrate: oxidant and solvent. The radical combination products ( 7–10 ) could de-tertbutylated in the presence of aluminium chloride or in the presence of trifluoroarcetic acid, forming heterocyclic substituted phenols ( 21 ) and ( 22 ).     

2,2-(2,2'-4(S)-苯基-4,5-二氢(噁)唑啉基)丙烷金属络合物对硝酮环加成反应的催化作用

研究了手性双噁唑啉配体2,2-（2,2’-4（S）-苯基-4,5-二氢噁唑啉基）丙烷（5）与铜或锌的配合物对二苯基硝酮（8）与3-（（E）-2-丁烯酰基）-1,3-噁唑烷-2-酮（6）和2,3-二氢呋喃（7）两种烯烃的环加成反应的催化效果。研究结果表明,双噁唑啉金属络合物对硝酮的环加成反应有较好的催化作用,表现在反应速度的提高和立体选择性的改变。比较而言,（5）与铜的配合物具有更好的催化作用。使用二氯亚砜作为氯化试剂对双噁唑啉（5）的合成方法进行了合理的改进,使产率由69．7％提高到89％。     

r-5-(α-Halogenbenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-one als Ringtautomere von α-(Arylaminocarbonyloxy)-β-halogen-dihydrochalkonen

r-5-(α-Halogenobenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-ones as Ring Tautomers of α-(N-Arylaminocarbonyloxy)-β-halogeno-dihydrochalcones The reaction of chalcone halogenohydrins ( 1–3 ) with arylisocyanates does not stop at the stage of the α-arylaminocarbonyloxy-β-halogeno-dihydrochalcones ( 7 ), but the cyclic urethanes 4–6 are formed. Compound 7h was synthesized independently. The structure and stereochemistry of 4–6 and 7h were determined by ¹³C n.m.r. spectroscopy.     

Heterocyclic syntheses with malonyl chloride. 15. 7-Chloro-3,4-dihydro-4,5-dioxo-3-aryl(or-alkyl)-2-thio-2H,5H-pyrano[3,4-2-e]-1,3-oxazine from aryl or alkyl isothio-cyanates and their degradation with morpholine and ethanol

Substituted aromatic isothiocyanates with malonyl chloride yield 7-chloro-3-substituted-3,4-dihydro-4,5-dioxo-2-thio-2H,5H-pyrano [3,4-e]-1,3-oxazine ( 1 ). Alkyl isothiocyanates with malonyl chloride yield a mixture of 7-chloro-3-alkyl-2-thio pyranooxazine ( 2 ) and the 2-oxo-analogue ( 3 ). The pyrano oxazine 1 react stepwise with morpholine undergoing replacement of the 7-chloro substituent yielding the 7-morpholino analogue ( 4 ), then the pyrone ring was opened producing 5-morpholino carbonyl-4-oxo-3-substituted phenyl-2-thio-1,3-oxazine-6-ylacetomorpholid ( 5 ). Finally the oxazine ring was opened yielding 2-substituted phenyl carbomyl-3-morpholino-N,N-glutaconoyldimorpholine ( 6 ). Ethanol react with compound 1 at any molar ration causing the opening of the pyrone ring and retain the oxazine ring. Mass spectra. ¹H-n.m.r., u.v. and i.r. spectroscopic data provided information about the fine structures of the products.     

Tetrazolverbindungen. 2. (1-Aryl-1H-tetrazol-5-yl)-acetaldehyd-Derivate aus 1-Aryl-5-(2-dimethylamino-vinyl)-1H-tetrazolen

Tetrazole Compounds. 2. 1-Aryl-1H-tetrazole-5-acetaldehyde Derivatives from 1-Aryl-5-(2-dimethylamino-vinyl)-1H-tetrazoles 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles 2 , easily accessible by the reaction of 3-chloro-propeniminium salts 1 with excess sodium azide in refluxing alcohols, represent enamines of the hitherto unknown 1-aryl-1H-tetrazole-5-acetaldehydes 3 . Attempts to isolate the latter after acid-catalyzed hydrolysis of 2 were unsuccessful. However, generated in situ, they can be trapped by suitable aldehyde reagents. Thus, starting from 1-aryl-5-(2-dimethylamino-vinyl)-1H-tetrazoles 4 , the 4-nitrophenylhydrazones 5a--hyphen;i , 2,4-dinitrophenylhydrazones 5j--hyphen;r , and thiosemicarbazones 6 of the corresponding 1-aryl-1H-tetrazole-5-acetaldehydes 3 were obtained. Analogously, acid-catalyzed hydrolysis of 4 in the presence of 1,2-dianilinoethane resulted in 1-aryl-5-(1,3-diphenyl-2-imidazolidinylmethyl)-1H-tetrazoles 7 . --hyphen; The structure of the aldehyde derivatives 5 , 6 , and 7 was proved by ¹H n.m.r. spectroscopy.     

Zur reversiblen Umwandlung von 3-Diethylamino-5-phenyl-1,2,4-dithiazolium-halometallaten in Metallchelate der 3-(Thio)benzoyl(thio)harnstoffe

About the Reversible Conversion of 3-Diethylamino-5-phenyl-1,2,4-dithiazoliumhalometallates into Metal Chelates of 3-(Thio)benzoyl(thio)ureas Redox reactions of 3-diethylamino-5-phenyl-1, 2,4-dithiazolium halometallates 1a-e and metal chelates (M = Cu^II ( 2 A ), Co^II ( 2 C ), Ni^II ( 2 F )) of 3-thiobenzoylthioureat was studied by cyclic voltammetry. 1 are converted by reduction into 2. The mechanism of the oxidation of 2 A , C , F into 1a , d , e is dependent on the central ion. On formation of 1 a from copper(II) chelates of 3-benzoylthiourea 3 A by means of thionylchloride as well as by electrochemical oxidation 3-benzoylureas 4 A are formed as sideproducts.     

Dithiocarbamate as an efficient intermediate for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones

An effective approach for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones from alkyl dithiocarbamates and chloroacetyl chloride in the presence of NaHCO₃ has been developed. Good to excellent yields of products, simple reaction conditions and general applicability are the most important advantages of this protocol.     

Tetrazolverbindungen. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazole aus 3-Chlor-propen-iminiumsalzen

Tetrazole Compounds. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles from 3-Chloropropeniminium Salts 3-Chloropropeniminium salts 1 react with excess sodium azide in refluxing alcohols to give mainly 1-aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles 3 ; in minor quantities isomeric 5-aryl-1-(2-dialkylamino-vinyl)-1H-tetrazoles 4 are formed. The reaction involves splitting off N₂ and C → N migration of the aryl and dialkylaminovinyl group, respectively. A cross-over experiment indicated that the rearrangement step proceeds intramolecularly. — The i.r., u.v., and n.m.r. spectroscopic data of the novel 1H-tetrazoles 3 as well as the u.v. spectra of some new starting products 1k—v are reported.     

Synthesis and characterization of poly(2-hydroxyethyl methacrylate)-1-naphthylacetic acid adduct

Summary Poly(2-hydroxyethyl methacrylate) (PHEMA) functionalized with chloroacetate groups was obtained by reaction of PHEMA with chloroacetyl chloride using the 5% lithium chloride/N,N-dimethylacetamide system as solvent and pyridine as catalyst. The coupling of bioactive carboxylic acid (1-naphthylacetic acid) to PHEMA functionalized with chloroacetate groups was carried out by reaction with its the potassium salt. The structures of chloroacetylated PHEMA and PHEMA-1-naphthylacetic acid adducts were determined by means FTIR, ¹H-NMR and ¹³C-NMR spectra. The degree of substitution was calculated from the chloride content and ranged from 13.4 to 98.1 mol% depending on the ratio of chloroacetyl chloride to PHEMA. The hydrolysis in the heterogeneous phase of PHEMA-1-naphthylacetic acid adducts showed that the release of the bioactive compound from tablets is dependent on hydrophilic character of adduct as well as on pH value of the medium.     

Synthesis,characterization and antitumour studies of metal chelates of N1-isonicotinoyl-3-methyl-4-(p-hydroxybenzilidene)-2-pyrazolin-5-one

The cobalt(II), nickel(II) and copper(II) complexes of N-Isonicotinoyl-3-methyl-4-(p-hydroxybenzilidene)-2-pyrazolin-5-one (IMHBP) with different counter anions have been prepared and characterized. An octahedral geometry has been assigned to the cobalt(II) and nickel(II) complexes and a square-planar structure to the copper(II) complexes. IMHBP acts as a neutral bidentate ligand in all these complexes by coordinating through the oxygen atoms of the amide group and carbonyl at position-5. The other coordination sites are satisfied by anions alone or anions and water molecules. The ligand and the complexes were screened for their possible antitumour activity. The copper(II) complexes are appreciably active in reducing mice tumours.