Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

One‐Pot Synthesis of 1,4‐Dihydro‐2‐thioxo‐2H‐3,1‐benzoxazine‐4‐acetic Acid Derivatives by the Reaction of 2‐Isothiocyanatophenyl Ketones with Lithium Enolates of Acetates and Tertiary Acetamides

The one‐pot synthesis of 4‐aryl‐1,4‐dihydro‐2‐thioxo‐2H‐3,1‐benzoxazine‐4‐acetic acid derivatives 2 was achieved in good yields by the reaction of aryl(2‐isothiocyanatophenyl)methanones 1 with lithium enolates of acetates and tertiary acetamides. (2E)‐1‐(2‐Isothiocyanatophenyl)‐3‐phenylprop‐2‐en‐1‐one ( 3 ) gave 1,4‐dihydro‐4‐[(1E)‐2‐phenylethenyl]‐2‐thioxo‐2H‐3,1‐benzoxazine‐4‐acetic acid derivatives 4 in good yields as well.     

Synthese und Reaktivität von 2‐Brom‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol Molekülstruktur von Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl)

Synthesis and Reactivity of 2‐Bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborole Molecular Structure of Bis(1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborol‐2‐yl The reaction of a slurry of calcium hydride in toluene with N,N′‐diethyl‐o‐phenylenediamine ( 1 ) and boron tribromide affords 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol ( 2 ) as a colorless oil. Compound 2 is converted into 2‐cyano‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 3 ) by treatment with silver cyanide in acetonitrile. Reaction of 2 with an equimolar amount of methyllithium affords 1,3‐diethyl‐2‐methyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 4 ). 1,3,2‐Benzodiazaborole is smoothly reduced by a potassium‐sodium alloy to yield bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl] ( 7 ), which crystallizes from n‐pentane as colorless needles. Compound 7 is also obtained from the reaction of 2 and LiSnMe₃ instead of the expected 2‐trimethylstannyl‐1,3,2‐benzodiazaborole. N,N′‐Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐ yl)‐1,2‐diamino‐ethane ( 6 ) results from the reaction of 2 with Li(en)C≡CH as the only boron containing product. Compounds 2 – 4 , 6 and 7 are characterized by means of elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}‐, ¹³C{¹H}‐NMR, MS). The molecular structure of 7 was elucidated by X‐ray diffraction analysis.     

Synthesis of 1‐nonanoyl/octadecanoyl‐4‐substituted thiosemicarbazides and substituted 1,2,4‐trizoles as biological active compounds

4‐Alkyl/aryl‐5‐nonanoyl/octadecanoyl‐2,4‐dihydro‐3H‐1,2,4‐triazoline‐3‐thiones were synthesized as potential antimicrobial agents. The course of synthesis included the reaction of nonanoyl/octadecanoyl hydrazines with selected alkyl/aryl isothiocyanates. The prepared thiosemicarbazides gave by cyclization the required 1,2,4‐triazoles. A number of synthesized compounds were subjected to in vitro testing against two gram‐positive, two gram‐negative bacteria and two fungi.     

Studies on the Flash Vacuum Thermolysis of Thiones of Selected N‐, O‐, and S‐Heterocycles

Thermal decomposition of thiones of selected N‐, O‐ and S‐heterocycles under flash vacuum thermolysis conditions was investigated. In the case of six‐membered 4H‐3,1‐benzoxathiin‐4‐thione 6 , the course of the reaction depended on the substitution pattern at C(2) (Scheme 3). Thus, the 2‐unsubstituted derivative 6a led to the unstable product 2 , which upon treatment with MeOH was converted quantitatively into methyl 2‐mercaptobenzoate ( 7 ). The analogous thermolysis of the 2,2‐dimethyl derivative 6b yielded 2‐methyl‐4H‐1‐benzothiopyran‐4‐thione ( 8 ) as a sole product. In the case of thiophthalide derivatives 15 , a thermal rearrangement in the gas phase leading to the corresponding benzo[c]thiophen‐1(3H)‐ones 16 in high yields was observed (Scheme 6). Unexpectedly, thionation of 1,3‐oxathiolan‐5‐one 17 with Lawesson's reagent under standard conditions led to 1,2‐dithietane derivative 19 , which, after the gas‐phase thermolysis, underwent a ring enlargement to yield 3H‐1,2‐dithiole 20 (Scheme 7). The six‐membered 4H‐1,3‐benzothiazine‐4‐thione 21 was shown to give three products: phenanthro[9,10‐c]‐1,2‐dithiete ( 22 ), 3H‐1,3‐benzodithiole‐3‐thione ( 23 ), and N‐(3H‐1,2‐benzodithiol‐3‐ylidene)prop‐2‐en‐1‐amine ( 24 ) (Scheme 8). The latter is the product of the initial reaction, whereas 22 and 23 are postulated to be formed as secondary products of the conversion of the intermediate 6‐(thioxomethylene)cyclohexa‐2,4‐diene‐1‐thione ( 26 ) (Schemes 9 and 10).     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

Syntheses,Characterization, and Antibacterial Activities of Four New Schiff Base Compounds Derived from 1‐Phenyl‐3‐methyl‐4‐benzoyl‐2‐pyrazolin‐5‐one

Four new Schiff bases were designed and synthesized. 5‐Methyl‐4‐(4‐aminophenylamino‐phenyl‐methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 1 ) and 5‐methyl‐4‐(2‐aminophenylamino‐phenyl‐methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 2 ) were synthesized by interaction of 1‐phenyl‐3‐methyl‐4‐benzoyl‐2‐pyrazolin‐5‐one (PMBP) with o‐ and p‐phenylenediamine, respectively; 4,4′‐(1,2‐phenylenebis(azanediyl)bis(phenylmethanylylidene))bis(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one) (compound 3 ) and 5‐methyl‐4‐(phenyl(2‐((3‐phenylallylidene)amino)phenylamino)methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 4 ) were synthesized by interaction of compound 2 with PMBP and cinnamaldehyde in an ethanolic medium, respectively. The molecular structures of the title compounds were first characterized by single‐crystal X‐ray diffraction, mass spectrometry, and elemental analysis. The title compounds were tested for antibacterial activity (Escherichia coli, Staphylococcus aureus, and Bacillus subtilis) by disk diffusion method.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

A novel photoisomerzation of 1,2‐benzothiazine 1,1‐dioxides to 1,3‐benzothiazine 1,1‐dioxides

A novel facile photoconversion of 4‐hydroxy‐1,2‐bezothiazine 1,1‐dioxides ( 3a‐e ) into 4‐oxo‐1,3‐2H‐benzothiazine 1,1‐dioxides ( 4a‐e ) and 4‐hydroxy‐2‐methyl‐N‐(pyridin‐2‐yl)‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide (PRX) into N‐methyl saccharin ( 2 ) upon 254 nm irradiation in methanol or acetonitrile is reported. The structures of the products have been elucidated by spectroscopic methods and single crystal X‐ray structure determination for 4a and 4d .     

Ultrasound‐Promoted Catalyst‐Free Synthesis of 2,2′‐(1,4‐Phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] Derivatives

A convenient approach to 2,2′‐(1,4‐phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] derivatives 4 was explored employing the one‐pot condensation of anthranilic acids (=2‐aminobenzoic acids) 1 with terephthalaldehyde (=benzene‐1,4‐dicarboxaldehyde; 2 ) under ultrasound‐irradiation conditions (Scheme 1). The reactions proceeded smoothly in the presence of excess Ac₂O in the absence of any other catalyst and solvent to afford the respective products in high yields.     

Reaction of Primary Alkylamines,Heterocumulenes, and Isatoic Anhydride,Catalyzed by Magnetic Fe3O4 Nanoparticles in H2O

An efficient protocol for the one‐pot reaction of isatoic anhydride (=1,2‐dihydro‐4H‐3,1‐benzoxazine‐2,4‐dione), primary alkylamines, and heterocumulenes (isothiocyanates and isocyanates) in H₂O catalyzed by magnetically recoverable Fe₃O₄ nanoparticles is described.     

Synthesis of Optically Active 1‐(1‐Phenylethyl)‐1H‐imidazoles Derived from 1‐Phenylethylamine

The three‐component reaction of (R)‐ or (S)‐1‐phenylethylamine ( 6 ), formaldehyde, and an α‐(hydroxyimino) ketone 5 , i.e., 3‐(hydroxyimino)butan‐2‐one ( 5a ) or 2‐(hydroxyimino)‐1,2‐diphenylethanone ( 5b ), yields the corresponding enantiomerically pure 1‐(1‐phenylethyl)‐1H‐imidazole 3‐oxide 7 in high yield (Schemes 2 and 3). The reactions are carried out either in MeOH or in AcOH. Smooth transformations of the N‐oxides into optically active 1‐(1‐phenylethyl)‐1H‐imidazoles 10 and 2,3‐dihydro‐1‐(1‐phenylethyl)‐1H‐imidazole‐2‐thiones 11 are achieved by treatment of 7 with Raney‐Ni and 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 12 ), respectively (Scheme 4).     

Synthesiss of novel 3‐(2‐thienyl)‐1,2‐diazepino[3,4‐b]quinoxalines with algicidal activity

The reaction of the quinoxaline N‐oxide 1 with thiophene‐2‐carbaldehyde gave 6‐chloro‐2‐[1‐methyl‐2‐(2‐thienylmethylene)hydrazino]quinoxaline 4‐oxide 5 , whose reaction with 2‐chloroacrylonitrile afforded 8‐chloro‐2,3‐dihydro‐4‐hydroxy‐1‐methyl‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]quinoxaline‐5‐carbonitrile 6 . The reaction of compound 6 with various alcohols in the presence of a base effected alcoholysis to provide the 5‐alkoxy‐8‐chloro‐2,3,4,6‐tetrahydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 7a‐d . The reaction of compounds 7a and 7b with diethyl azodicarboxylate effected dehydrogenation to give the 5‐alkoxy‐8‐chloro‐4,6‐dihydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 8a and 8b , respectively. Compounds 8a and 8b were found to show good algicidal activities against Selenastrum capricornutum and Nitzchia closterium.     

N‐(X‐Chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide (with X = 2 and 4)

The structures of N‐(2‐chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide and N‐(4‐chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide, both C₁₆H₁₃ClN₂O₄S, are stabilized by extensive intramolecular hydrogen bonds. The 4‐chloro derivative forms dimeric pairs of molecules lying about inversion centres as a result of intermolecular N—H...O hydrogen bonds, forming 14‐membered rings representing an R₂²(14) motif; the 2‐chloro derivative is devoid of any such intermolecular hydrogen bonds. The heterocyclic thiazine rings in both structures adopt half‐chair conformations.     

Strategy to Construct Stair‐Shaped Partially Reduced Naphtho[1,2‐b]pyrano[2,3‐d]oxepines and Dinaphtho[1,2‐b,d]oxepines

A concise and efficient base‐induced synthesis of stair‐shaped, 4‐methylthio‐2‐oxo‐5,6‐dihydro‐2H‐naphtho[1,2‐b]pyran[2,3‐d]oxepine‐3‐carbonitriles ( 3 ) has been delineated by the reaction of 3,4‐dihydronaphtho[1,2‐b]oxepin‐5(2H)‐one ( 1 ) and methyl 2‐cyano‐3,3‐dimethylthioacrylate in DMSO using powdered KOH as a base at room temperature. Amination of 3 has been achieved by reaction with secondary amine in ethanol at reflux temperature to yield 4‐sec‐amino‐2‐oxo‐5,6‐dihydro‐2H‐naphtho[1,2‐b]pyran[2,3‐d]oxepine‐3‐carbonitriles ( 4 ). Reaction of 3 with aryl methyl ketone ( 5 ) in DMSO at room temperature using powdered KOH as a base produced stair‐shaped 5‐aryl‐7,8‐dihydro‐1,4‐dioxa‐2,3‐dioxodinaphtho[1,2‐b,d]oxepine ( 6 ) in good yields. However, reaction of 6‐aryl‐2H‐pyran‐2‐one‐3‐carbonitrile ( 8 ) with 3,4‐dihydronaphtho[1,2‐b]oxepin‐5(2H)‐one ( 1 ) did not give similar product, but in lieu 4‐aryl‐5,6‐dihydronaphtho[1,2‐b]oxepino[4,5‐b]pyran‐2‐ylidene)acetonitrile ( 9 ) was isolated and characterized.     

An efficient and facile ultrasonic‐accelerated one‐pot synthesis of N‐acetyl‐2‐aryl‐1, 2‐dihydro‐(4H)‐3,1‐benzoxazin‐4‐ones

An application of ultrasonic irradiation in the one‐pot synthesis of N‐acetyl‐2‐aryl‐1,2‐dihydro‐(4H)‐3,1‐benzoxazin‐4‐ones from the condensation reaction between aromatic aldehydes and anthranilic acid in the presence of excess amount of acetic anhydride has been explored. The reactions proceed smoothly under mild and solvent‐free conditions at room temperature in the absence of any catalyst to afford the products in good to excellent yields. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:106–113, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20663     

Reaction of ω‐carbonyl substituted 1,3,3‐trimethyl‐2‐methyleneindolines with phosphorus(III) halides

The phosphorylation of N‐benzoyl‐2‐(1,3,3‐trimethyl‐2‐methyleneindoline)acetamide ( 2 ) and ω‐(3‐dimethylamino)benzoyl‐1,3,3‐trimethyl‐2‐methyleneindoline ( 6 ) with phosphorus(III) halides resulted in the formation of 2,3‐dihydro‐4H‐1,5,2‐oxazaphosphinin‐4‐one and 1,2‐dihydro‐3H‐phosphindol‐3‐one systems, respectively. The properties of the obtained compounds were studied. Further cyclization of 1,2‐dihydro‐3H‐phosphindol‐3‐one into dihydrophosphindolo[3,2‐c]pyrazole was carried out. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:23–28, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10060     

Reactions of a,ß‐unsaturated N‐benzenesulfonyl Imine – N‐[(2E)‐3‐phenyl‐2‐propen‐1‐ylidene]benzenesulfonamide with Methyllithium

α,β‐Unsaturated N‐benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2‐addition adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2‐addition product, benzenesulfonamide derivative 3 and 2H‐1,2‐benzothiazine 1,1‐dioxide derivatives 4 and 5 were isolated.     

Synthesis and spectral properties of 2‐methylthio‐3H‐7‐[(o‐; m‐ and p‐substituted)phenoxy]‐4‐(p‐substituted‐phenyl)‐[1,5]benzodiazepines

A series of eleven new 2‐methylthio‐3H‐7‐[(o‐; m‐ and p‐substituted) phenoxy]‐4‐(p‐substituted‐phenyl)‐[1,5]benzodiazepines, which have potentially useful pharmacological activities, has been synthesized by condensing the 4‐[(o‐; m‐ and p‐R₁)phenoxy]‐1,2‐phenylendiamines with 3,3‐dimercapto‐1‐(p‐R₂‐phenyl)‐2‐propen‐1‐one. Afterward the lH‐[1,5]benzodiazepine‐2‐thiones obtained were treated with sodium hydride and methyl iodide. The structure of all products was corroborated by ir, ¹H nmr, ¹³C nmr and ms.     

Selenium heterocycles XLIV. Syntheses of 8,9‐dihydro‐1,2,3‐thiadiazolo[4,5‐a]‐4,7‐dihydroxynaphthalene and 1,2,3‐selenadiazolo[4,5‐a]‐4,7‐dimethoxynaphthalene

The reaction of thionyl chloride with the semicarbazone 2 gave 4,5‐dihydro‐6,9‐dihydroxynaphtho‐[1,2‐d][1,2,3]thiadiazole ( 3 ) instead of 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]thiadiazole ( 4 ). Selenium dioxide oxidation of compound 2 gave 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 5 ). Oxidation of compound 5 with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone afforded 6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 6 ).