Organylthiochloroacetylenes: IV. Reaction with Thiourea

Alkylthiochloroacetylenes react with thiourea in acetone to form S-(alkylthioethynyl)isothiuronium chlorides and N-[1-(alkylthio)ethylidene]thioureas; phenylthiochloroacetylene reacts with thiourea to give 4-(phenylthio)-2-imino-1,3(3H)-thiazole hydrochloride.     

Synthesis,characterization, and dyeing performance of some azo thienopyridine and thienopyrimidine dyes based on wool and nylon

A string of novel heterocyclic mono azo dyes were synthesized and their utilization in dyeing different fabrics as wool and nylon were discussed. Thienopyridine azo dyes 4 and 6 were prepared by reaction of chloro acetamidederivative 2 with diamino compounds to yield 3 and 5 , followed by reaction with NaNO₂/HCl and coupling with nucleophilic reagent. One-pot reaction of chloro acetamide 2 with ammonium thiocyanat in solvent ethanol gave the unexpected thienopyrimidine derivative 7 , which contain two active sites, the former is primary amine that was able to form diazonium salt that coupled with N,N-dimethylaniline, resorcinol, and/or self-coupling to afford the azo dyes 8-10 , and the latter is active methylene group that underwent coupling with different diazonium salts to give the azo thienopyrimidine derivative dye 11-15 . The dyeing performance of these azo dyes had been investigated in terms of their dyeing behavior and fastness properties on different fabrics. Results showed that the color strength (K/S) values, as well as, washing, rubbing, and resistance to acid, alkali and light showed high efficiency of these heterocyclic mono azo dyes to dye wool rather than nylon fibers.     

Zur Reaktion von cyclischen Ketonen mit Thioharnstoff bzw. Ammonrhodanid Über Heterocyclen, 24. Mitt.

Zusammenfassung Cyclische Ketone reagieren mit Thioharnstoff bzw. Ammonrhodanid je nach den eingehaltenen Bedingungen zu Abkömmlingen des Dihydro-2(1H)-pyrimidinthions bzw. Dihydro-4(3H)-pyrimidinthions.

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Reaction of cyclic ketones with thiourea or ammonia, resp. (Heterocycles XXIV)

Cyclic ketones have been found to react with thiourea or ammonium thiocyanate according to reaction conditions to give derivatives of dihydro-2(1H)-pyrimidinthione or dihydro-4(3H)-pyrimidinthione, resp.

     

Synthesis and spectrophotometric study of 2-[2-(3,5-dibromopyridyl,)azo] -5-dimethylaminobenzoic acid as an analytical reagent: Determination of nickel

2-[2-(3,5-Dibrornopyridyl)azo]-5-dimethyIam;nobenzoic acid (3,5-diBr-PAMB) has been synthesized and its potential for the spectrophotometric determination of metals studied. It reacts sensitively with nickel, cobalt, iron and copper, and is particularly useful for nickel. The apparent molar absorptivity in chloroform is 1.50 × 10⁵ l mol^-1 cm^-1 and the Sandell sensitivity is 0.4 ng Ni cm^-2. Nickel reacts with 3.5-diBr-PAMB at pH 4–10; at pH 4–7 the complex can be extracted into chloroform to give a stable purple solution. The optimal calibration range is 0.04–0.4 ppm Ni. Only Cu, Co, Fe, Pd and V interfere seriously but Pd, Cu and V can be masked by thiourea.     

Fused polycyclic nitrogen-containing heterocycles

The condensation of methyl phenylchloropyruvate with 1-phenyl-3-(2-pyridyl)thiourea and its 3-and 4-picolyl homologs affords the corresponding 4-hydroxythiazolidines, which react with o-phenylenediamine to give one of two possible thiazolo[3,4-a]quinoxalines containing the pyridyl-or picolylimine substituents at position 1. 3a-Hydroxy-3-phenylimino-1-(2-pyridyl)thiazolo[3,4-a]quinoxalin-4-(3H,5H)-one, which is a covalent hydrate of the final product, was isolated as an intermediate in this reaction.     

Synthesis and reactions of some 6-aryl and 2,6-diaryl-4-(4′-antipyrinyl)-2,3,4,5-tetrahydropyridazin-3-ones and screening for their antibacterial activities

Some new pyridazinone derivatives(3) were synthesized through addition of antipyrin to β-aroylacrylic acids (1) followed by cyclization of the adducts. Reactions of 3 with ethyl bromoacetate, benzenesulfonyl chloride, benzoyl chloride and POCl₃ give N-substituted products and monochlorosubstituted pyridazines (4), respectively. The reactions of the latter with thiourea give unexpected dithio-derivatives (5), which react with phenylhydrazine to give pyrazolopyridazino pyridazine derivatives (6). Reactions of 2 with NH₂OH in ethanol and pyridine afford oxime and oxazinone derivatives 7 and 8, respectively. The antibacterial activities of several compounds were screened.     

Azimine. VI. 1-Alkoxycarbony 1-2,3-dialkyl- und -2,3-diaryl-azimine

Azimines VI: 1-Alkoxycarbonyl-2,3-dialkyl- and -2,3-diarylazimines Alkoxycarbonyl-nitrenes 2 – generated in situ by α-elimination from N-[(4-nitrophenyl)-sulfonyloxy]carbamates 4 – were reacted with six aliphatic and aromatic azo compounds to yield 1-alkoxycarbonyl-azimines 11 (R′ = Alkyl). Thus, (2Z)- or (2E)- 1 -alkoxycarbonyl-2,3-diisopropyl-azimines ( 8 or 9 ) were obtained stereospecifically from (E)- or (Z)-1,1′-dimethylazoethane ( 5 or 6 ) and 1-alkoxycarbonyl -2,3-(cis-1,3-cyclopentylene)-azimines ( 10 ) resulted from 2,3-diazabicyclo[2.2.1]-2-heptene ( 7 ), always using both ethoxy- and methoxycarbonyl-nitrene ( 2a and 2b ). With 2a , (E)-azobenzene ( 14 ) was converted only to a single stereoisomer of 1-ethoxycarbonyl-2,3-diphenyl-azimine ( 17 ) and both stereoisomers of azo(p-toluene) ( 15 or 16 ) reacted to give the same stereoisomer of 1-ethoxycarbonyl-2,3-di(p-tolyl)-azimine ( 18 ).     

Synthesis and biological evaluation of new 3,5-di(trifluoromethyl)-1,2,4-triazolesulfonylurea and thiourea derivatives as antidiabetic and antimicrobial agents

Fluorinated 1,2,4-triazoles 3 and benzenesulfonyl urea and thiourea derivatives as well as their cyclic sulfonylthioureas 4–10 were prepared as antimicrobial agents. The chemistry involves the condensation of sulfanilamide derivatives 1 with trifluoroacetic anhydride to give N-di(trifluoroacetyl)sulfonamides 2 which upon reaction with hydrazine hydrate afforded the corresponding triazole derivatives 3. Reaction of triazole derivative 3a with isocyanates and isothiocyanates gave the corresponding ureas 4 and thioureas 5. Cyclization of thiourea derivatives with ethyl bromoacetate, 1,2-diiodoethane, diethyl oxalate and α-bromoacetophenone derivatives yielded the corresponding 4-oxothiazolidines 7, thiazolidines 8, 4,5-dioxothiazolidines 9 and thiazolines 10. Preliminary biological screening of the prepared compounds revealed significant antimicrobial and mild antidiabetic activities.     

Reaktionen von 3-(Dimethylamino)-2H-azirinen mit 1,3-Benzoxazol-2(3H)-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thione The reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione ( 5 ), which can be considered as NH-acidic heterocycle (pK_aca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2-(isopropylthio)-1,3-benzoxazole ( 12 ), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.     

Cascade synthesis of 2-amino-5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole by reaction of 4-chloro-<Emphasis Type="Italic">N</Emphasis>-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide with thiourea

4-Chloro-N-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide reacted with thiourea on heating in DMF in the presence of sodium carbonate to give 5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole-2-amine. A probable reaction scheme includes cyclization of the initial N-dichloroethyl amide to N-sulfonyl-2,3-diaryl-2-chloroaziridine which undergoes isomerization with opening of the three-membered ring to 1-arylsulfonylamino-2-chloro-2-(4-methoxyphenyl)-1-phenylethene. The subsequent heterocyclization in the reaction with thiourea is accompanied by aromatization via elimination of the arenesulfonamide fragment.     

Synthesis,characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione ( 1 ) is synthesized and reacted with chloroacetamide or chloroacetonitrile to give 3-amino-5-ethoxycarbonyl-6-methyl-4(2′-thienyl)-thieno[2,3-b]pyridine-2-carboxamide 3a or its 2-carbonitrile analog 3b , respectively. Cyclocondensation of 3a with triethylorthoformate produced the corresponding pyridothienopyrimidineone 4 , which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative 5 . Compound 5 was used as key intermediate for synthesizing compounds 6 , 9 , 10 , 11 , and 12 upon treatment with some nucleophilic reagents such as thiourea, 5-phenyl-s-triazole-3(1H)-thione, piperidine, morpholine, or hydrazine hydrate, respectively. Reaction of pyridothienopyrimidinethione 6 with N-(4-tolyl)-2-chloroacetamide or ethyl bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines 7 or 8 . The condensation of 3b with triethylorthoformate gave azomethine derivative 13 , which was reacted with hydrazine hydrate to give ethyl 3-amino-3,4-dihydro-4-imino-7-methyl-9-(2′-thienyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate ( 14 ). Compounds 12 and 14 were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds 3a , 5 , 6 , 8 , and 22 were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.     

Synthesis of pyridyl- and quinolyl-substituted 2-aminothiazoles

Five 2-amino-4-(x-pyridyl)- and 2-amino-4-(x-quinolyl)thiazoles have been synthesized by the condensation of thiourea with bromoacetylpyridines and -quinolines. The reaction of pyridyl pyridylmethyl ketones with thiourea and halogens produced four 2-aminothiazoles possessing pyridyl substituents in 4- and 5-positions on the thiazole ring. Treatment of N-(3-pyridyl)- and N-(3-quinoiyl)thiourea with α-bromoketones gave seven new 2-(3-pyridyl)amino- and 2-(3-quinolyl)aminothiazoles. The ultraviolet spectra of the pyridyl- and quinolyl- substituted 2-aminothiazoles were recorded.     

Synthesis,characterization and antibacterial studies of some new tellurated azo compounds

A series of tellurated azo compounds [i.e. (4-HOC₆H₄N=N-Ar)TeBr₃ and (4-HOC₆H₄N=N-Ar)₂TeBr₂, where Ar=5-BrC₆H₃, 5-CH₃C₆H₃ and 5-NO₂C₆H₃] were prepared by the reaction of the corresponding 2-(4-hydroxyphenylazo)aryl mercury chloride with tellurium tetrabromide in 1:1 and 2:1?mole ratio, respectively in dry dioxane as a solvent. The reduction of (4-HOC₆H₄N=N-Ar)TeBr₃ by hydrazine hydrate gave the corresponding ditelluride (i.e., (4-HOC₆H₄N=N-Ar)₂Te₂). Treatment of (4-HOC₆H₄N=N-Ar)₂TeBr₂ with hydrazine hydrate afforded the corresponding tellurides, (4-HOC₆H₄N=N-Ar)₂Te), in good yields. The structures of all newly synthesized compounds were assigned on the basis of their elemental and spectroscopic data. The antibacterial activity of tellurated azo compounds along with mercurated azo compounds was tested with agar diffusion method against the bacteria strains Staphylococcus aureus and Escherichia coli. The antibacterial activities of tellurated azo compounds were in some cases equal or better than those of the reference drug. The mercurated azo compounds were found to be the more antibacterial activity of than those of tellurated azo compounds.     

Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles

Methylglyoxalyl chloride arylhydrazones (III) react with an ethanolic solution of thiourea to give 2-amino-4-methyl-5-arylazothiazoles (XII) instead of the expected 2-acetyl-4-aryl-5-imino-Δ²-1,3,4-thiadiazolines (V) which were obtained from III and potassium thiocyanate. 3-Thiocyanato-2,4-pentanedione (IV) coupled with diazotized anilines to give V. The postulated routes to formation of V and XII from III are given. Nitrosation of V gave the corresponding N-nitroso derivatives (VI) which decomposed upon refluxing in dry xylene to give 2,4-disubstituted-Δ²-1,3,4-thiadiazolin-5-ones (VII). Boiling of either V or VI with hydrochloric acid gave the hydrochloride salt (VIII). The thiadiazolines V gave the respective N-acyl derivatives (IX) and (X) with acetic anhydride and benzoyl chloride in pyridine.     

Use of 3–(2′-formyl-1′-chlorovinyl)coumarin in the syntheses of pyrazol,salicylaldazine and pyrimidine derivatives

3–(Pyrazol-5-yl)coumarin (3) was prepared from condensation of 3–(2′-formyl-l-chlorovinyl)-coumarin (1) with hydrazine hydrate at room temperature, followed by cyclyzation with base. Salicylaldazine was prepared from methoxylation of 1 to give acetal 7 , followed by condensation of 7 with hydrazine hydrate at 80°C: Treatment of acetal 7 with thiourea yielded the corresponding 4-substituted-2-thioxo-2H-pyrimidine[3, 4-b]-coumarin (12).     

Synthesis and characterization of bromo‐, arylazo‐, and heterocyclic‐fused troponoids containing a 1,3‐benzodioxole system

A facile synthesis of a series of novel bromo‐, arylazo‐, and heterocyclic fused troponoid compounds containing 1,3‐benzodioxole system is described. The 7‐bromo‐, 5,7‐dibromo‐, and 5‐arylazo‐substituted 3‐[(2E)‐3‐(1,3‐benzodioxol‐5‐yl)prop‐2‐enoyl]tropolones ( 2 , 3 , and 5 , 6 , 7 ) were obtained by direct bromination or azo‐coupling reactions of 3‐[(2E)‐3‐(1,3‐benzodioxol‐5‐yl)prop‐ 2‐enoyl]tropolone ( 1 ) with bromine, and diazonium salts of aniline derivatives, respectively. 3‐[(2E)‐3‐(1,3‐Benzodioxol‐5‐yl)prop‐2‐enoyl]‐5‐bromotropolone ( 4 ) was obtained from 3‐acetyl‐5‐bromotropolone via one‐pot aldol dehydration reaction with piperonal. Tropolones 2, 3 , and 4 were subjected to nucleophilic cyclization with bifunctional hydroxylamine hydrochloride and phenylhydrazine hydrochloride to give the corresponding isoxazolo‐ and pyrazolo‐fused tropones ( 8 , 9 , 10 , 11 , 12 , 13 ), respectively. J. Heterocyclic Chem., (2012).     

On the preparation of substituted 4H- 1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

The reaction of benzoyl isothiocyanates and methoxycarbonyl isothiocyanate with 4-amino-4,5-dihydro-3-(methylthio)-1,2,4-triazin-5-ones in acetonitrile gave several substituted 4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones VIa-h instead of the expected thioureas. In addition, benzoyl isothiocyanate reacted with 4-amino-3-(methylthio)-5-(trifluoromethyl)-4H-1,2,4-triazole to give the benzoyl thiourea IX and with 4-amino-3-mercapto-5-(trifluoromethyl)-4H-1,2,4-triazole to give the bicyclic compound N-[3-(trifluoromethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-6-yl]benzamide IX .     

Organoaluminum‐mediated polymerization of diazoketones

Polymerization of diazoketones mediated by organoaluminum compounds was investigated. Trialkylaluminum R₃Al (R = iBu, Et, Me) and diisobutylaluminum hydride (DIBAL) polymerized (E)‐1‐diazo‐3‐nonen‐2‐one ( 1 ) to give polymers with M_n = 2000–3500, which contained nearly 33 mol % of azo group (? N?N? ) along with the dominant acylmethylene unit in the main chain. On the other hand, when (E)‐1‐diazo‐4‐phenyl‐3‐buten‐2‐one ( 2 ) was used as a monomer for the organoaluminum‐mediated polymerization, the resulting polymers had ethylidene (? CH[CH₃]? ) units in the main chain along with acylmethylene and azo group, as a result of reductive cleavage of the acyl group during the polymerization. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5209–5214, 2007     

Synthesis of fluoroalkyl-containing 1,2,3-triketone 2-hetarylhydrazones and their reactions with hydrazines

Fluoroalkyl-containing 1,2,3-triketone 2-(2,3-dimethyl-5-oxo-1-phenyl-1,2-dihydropyrazol-4-yl)-, 2-(4-ethoxycarbonylpyrazol-3-yl)-, and 2-(1,2,4-triazol-3-yl)hydrazones were synthesized by the azo coupling reactions of fluorinated 1,3-diketones with the corresponding hetaryldiazonium chlorides. The hetarylhydrazones thus synthesized were subjected to cyclocondensation with hydrazines at the 1,3-dicarbonyl fragment to give 3-fluoroalkyl-4-hetarylazopyrazoles.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2478–2483, November, 2004.     

Synthesis,Reactions, and Antiviral Activity of 1-(1H-Pyrazolo[3,4-b]pyridin-5-yl)ethanone and Pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

1-(3-Amino-6-methyl-4-pyridin-3-yl-1H-pyrazolo[3,4-b]pyridin-5-yl)ethanone (3) was obtained in very pure state and used as a good starting material for the present study. It diazotized to give the corresponding diazonium salt 9 and also reacted with phenyl isothiocyanate to give the corresponding thiourea derivative 4. Compound 4 was used for the preparation of thiazole derivatives 5–8 via the reaction with active halogen-containing compounds. On the other hand, compound 9 coupled with several active –CH₂- containing compounds to afford the corresponding triazine derivatives 10–17. Considering the data from IR, ¹ H NMR, mass spectra, and elemental analyses, the chemical structures of the newly synthesized heterocyclic compounds were elucidated. Cytotoxicity, anti-HSV1, and anti-HAV-MBB activity were evaluated for the newly synthesized heterocyclic compounds.