Synthesis and derivatization of angular 3-chloro-3-chlorosulfenyl naphtho[1,2-b]pyran(4H)-4-ones with evaluation of antiviral activity

Angular 2,3-dihydronaphtho[1,2-b]pyran(4H)-4-ones 1a,b react with an excess of thionyl chloride to give the α-chlorosulfenyl chlorides 2a,b, which are reduced by iodide ion to give the corresponding 1,3,4-oxadithiino derivatives 3a,b. However, the aducts 4a,b and 5a,b were obtained by reduced 2a,b with iodide ion in the presence of 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene, respectively. Direct oxidation of 2a,b afford 3,3-dichloronaphthopyran-4-ones 6a,b, whilst conversion to the sulfenamides 7a,b prior to oxidation provides 3-chloronaphthopyranones 8a,b. While α-chloro β-oxo sulfenyl chlorides 2a,b undergo straight forward substitution with 1-methylpiperazine and with potassium cyanide to give 9a,b and 10a,b, respectively. Some of the prepared products were selected and tested for their antiviral activity against herpes simplex virus type-1 (HSV-1). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with test compounds. Compound 5a showed moderate effect against HSV-1.     

Facile synthesis of some novel 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4] thiazin-2-yl}-2H-chromen-2-one derivatives

A protocol for chemoselective one pot synthesis of 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4]thiazin-2-yl}-2H-chromen-2-ones 4 and 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4]thiazin-2-yl}-2H-chromen-2-ones 6 under refluxing conditions has been developed. Starting from 4-bromomethylcoumarin and Schiff base, which is derived from o-aminothiophenol and substituted aromatic aldehydes, the intermediate sulfide spontaneously underwent intramolecular carbanion addition across the azomethine carbon.     

Syntheses and optical,electrochemical, and photovoltaic properties of polymers with 6-(2-thienyl)-4H-thieno[2,3-b]indole with a variety of electron-deficient units

Conjugated polymers were synthesized and used for polymer solar cells with new electron-rich units, 6-(2-thienyl)-4H-thieno[2,3-b]indole (2-TTI). 2-TTI was coupled with electron-pulling units, including benzothiadiazole and benzimidazole derivatives, to provide push–pull types of conjugated polymers (poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2-methyl-5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2-(trifluoromethyl)-2H-benzimidazole) (PTTIDOCF3), poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole) (PTTIDOBT), poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2,2-dimethyl-4,7-di(thiophen-2-yl)-2H-benzimidazole) (PTTIMBI), and poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2,2-dimethyl-5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2H-benzimidazole) (PTTIDOMBI)). The synthesized conjugated polymers provided deep highest occupied molecular orbital energy levels for higher open-circuit voltages (V_OC). The device composed of PTTIDOMBI and [6,6]-Phenyl C₇₁ butyric acid methyl ester PC₇₁BM (1:2) with chloronaphthalene additive showed a V_OC of 0.72 V, a short-circuit current (J_SC) of 9.16 mA/cm², and a fill factor of 0.43; this gave a power conversion efficiency (PCE) of 2.84%. The PTTIDOMBI provided better morphology for enhanced charge transport, and this led to the higher J_SC and PCE of the organic solar cells. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47624.     

Synthesis of some new 3-mercapto-5-substituted-1,2,4-triazine-s-triazoles for evaluation as antimicrobial agents

The synthesis of several S- and N-substituted derivatives of 5-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-s-triazole-3-thiol, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)-oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-briazole, 2-[(5,6-diphenyl-1, 2,4-triazin-3-yl)oxymethyl]-5H,6,7-dihydro-s-triazolo-[3,2-b]-1,3-thiazine, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-triazol-5-one and 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-6-phenylthiazolo-[3,2-b]-s-triazole is reported. All the novel compounds have been screened for antimicrobial activity and one of them showed noteworthy activity.     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

Aryl and Arylalkyl Substituted 3-Hydroxypyridin-2(1H)-ones: Synthesis and Evaluation as Inhibitors of Influenza A Endonuclease

Seasonal influenza infections are associated with an estimated 250–500 000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have prompted research on inhibitors that target the cap-snatching endonuclease activity of the polymerase acidic protein (PA). Baloxavir marboxil (Xofluza®), recently approved for clinical use, inhibits cap-snatching endonuclease. Resistance to Xofluza® has been reported in both in vitro systems and in the clinic. An X-ray crystallographic screening campaign of a fragment library targeting IAV endonuclease identified 5-chloro-3-hydroxypyridin-2(1H)-one as a bimetal chelating agent at the active site. We have reported the structure–activity relationships for 3-hydroxypyridin-2(1H)-ones and 3-hydroxyquinolin-2(1H)-ones as endonuclease inhibitors. These studies identified two distinct binding modes associated with inhibition of this enzyme that are influenced by the presence of substituents at the 5- and 6-positions of 3-hydroxypyridin-2(1H)-ones. Herein we report the structure–activity relationships associated with various para-substituted 5-phenyl derivatives of 6-(p-fluorophenyl)-3-hydroxypyridin-2(1H)-ones and the effect of using naphthyl, benzyl, and naphthylmethyl groups as alternatives to the p-fluorophenyl substituent on their activity as endonuclease inhibitors.     

Facile synthesis of novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2] oxazolo[4′,5′:5,6]pyrano[2,3-d][1,3,2]diazaphosphinines

A number of 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]oxazolo[4′,5′: 5,6]pyrano[2,3-d][1,3,2]diazaphosphinines 4–11 were synthesized via an interaction of tetraphosphorus decasulfide and Lawesson’s reagent under different conditions with 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile (3). The reaction mechanisms for these products were discussed. Structures of the newly synthesized products were established on the basis of elemental analysis and spectral data.     

Retracted: Palladium‐Catalyzed Decarboxylative Selective Acylation of 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives with α‐Oxo Carboxylic acids via Preferential Cyclic Imine‐N‐Directed Aryl C−H Activation

The benzoxazine scaffolds are of much interest as they are found in a large array of natural products and pharmaceutical drugs with diverse activities. We have developed a palladium‐catalyzed decarboxylative selective mono‐ and bis‐acylation of 4H‐benzo[d][1,3]oxazin‐4‐one derivatives with α‐oxo carboxylic acids via preferential cyclic imine‐N‐directed C−H activation. 2‐Aryl‐4H‐benzo[d][1,3]oxazin‐4‐one was acylated with a variety of substituted phenylglyoxylic acids to produce the corresponding products. It was observed that electron‐donating groups (CH₃, OCH₃) at any position of the aromatic ring of phenylglyoxylic acid provided good to excellent yields, whereas phenylglyoxylic acids containing electron‐withdrawing groups (COCH₃, CN, NO₂) gave the products in moderate yields. Interestingly when the reaction was performed with silver triflate (AgOTf) in place of silver nitrate (AgNO₃) in the presence of 4 equivalents of glyoxylic acid, the bis‐acylated product was obtained together with a small amount of mono‐acylated product. This is the first report of acylation of 2‐aryl‐4H‐benzo[d][1,3]oxazin‐4‐ones via C−H activation. The notable features of this reaction are acylation with more challenging heteroarene‐oxo carboxylic acids and alkyl oxo carboxylic acids. This new protocol provides an easy and efficient access to a variety of o‐acyl‐4H‐benzo[d][1,3]oxazin‐4‐one derivatives which are of pharmaceutical importance.

     

A convenient and efficient method for the synthesis of benzo- and naphthothiazolediones

A series of benzo- and naphthothiazolediones have been synthesized by the reactions of N-substituted thioureas with π-deficient quinones. The products were obtained by the reaction of N-aroylphenylthioureas with 2,3,5,6-tetracholoro-1,4-benzoquinone, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 2,3-dichloro-1,4-naphthoquinone.     

Thiation of new 5-(2-aryl-2-oxoethyl)-2,4-dioxo-1, 3-thiazolidines

Abstract

The hitherto unknown 5-(2-aryl-2-oxoethyl)-3-substituted-2,4-dioxo-1,3-thiazolidines 2 and 5-(2-aryl-2-oxoethylidene)-3-aryl-2,4-dioxo-1,3-thiazolidines 4 have been prepared from their 2-thioxo- homologues 1 and 3, respectively, via treatment with CrO₃. Compound 4 has also been obtained by treating 1 and/or 2 with bromine at different experimental conditions. Thiation of 2 and/or 4, gave a mixture of 3,5-di-substituted-2,3-dihydro-2-oxothieno[2,3-d]thiazoles 5 and the respective 2-thioxo derivatives 6. Reactions of hydrazine hydrate with 1c, d, were carried out at room temperature as well as under reflux, affording di-(3-oxo-6-aryl-4,5-dihydropyridazin)disulfides 7c, d and di-(3-oxo-6-arylpyridazin)disulfides 8c, d, respectively, together with 4-arylthiosemi carbazides 9c, d, under both conditions. Structures of the above products have been elucidated based on their microanalytical and spectroscopic data. Compound 2e exhibited pronounced antischistosomal activity.     

Facile and convenient synthesis of 2,4-disubstituted and 2,3,4-trisubstituted 1,3-thiazoles

An efficient route for the synthesis of (E)-2-(2-(2-nitrobenzylidene)-hydrazinyl)-4-phenylthiazol-3-ium bromide, (E)-2-(2(substituted benzylidene)hydrazinyl)-4-phenylthiazoles and (E)-4-(4-bromophenyl)-2-(cycloalkylidenehydrazono)-3-phenyl-2,3-dihydrothiazoles by reaction of 1-aryl-2-bromoethanones with 2-(1-substituted methylidene)hydrazinecarbothioamides and cycloalkylidene-N-phenyl-hydrazinecarbothioamides. The structure of the products has been confirmed by using IR, NMR, mass spectrometry and single-crystal X-ray analyses.     

One-Pot Synthesis of Spiro[chromeno[2,3-c]pyrazole-4,3′-indoline]-diones Using Sulfonic Acid Functionalized Nanoporous Silica SBA-Pr-SO3H and Study of Their Antimicrobial Properties

A novel and clean one-pot synthesis of spiro[chromeno[2,3-c]pyrazole-4,3′-indoline]-2′,5(6H)-diones via cyclocondensation reaction of isatins, 1,3-cyclohexadiones, and pyrazolone in aqueous media using SBA-Pr-SO₃H (sulfonic acid-functionalized mesoporous silica) as an efficient heterogeneous solid acid catalyst was reported. The antimicrobial activities of synthesized compounds have been tested.     

Synthesis and antimicrobial evaluation of some pyrazolo-thiazolyl alkoxy-1H-isoindole-1, 3(2H)-dione derivatives

1,3-Thiazolidine-2,4-dione 2 has been synthesized by the cyclisation reaction of thiourea and chloroacetic acid in the presence of ethanol. The reaction of compound 2 with substituted aromatic aldehyde afforded the corresponding derivatives of substituted 5-benzylidene-1,3-thiazolidinone-2,4-dione 3a–d, which upon reflux with ω-bromoalkoxyphthalimide gave 2-{[-5-(substituted benzylidine)-2,4-dioxo-1,3-thiazolidine-3-yl]alkoxy} -1H-isoindole-1,3(2H)-dione 4a–i. Further, compounds 4a–i were treated with phenyl hydrazine and 2,4 dinitro phenyl hydrazine in the DMF to yield the title compound 2-[5-oxo-2,3-substituted diphenyl-2H-pyrazolo[3,4-d][1,3]thiazol-6(5H)-yl)alkoxy]-1H-isoindole-1,3(2H)-dione 5a–r. Structures of newly synthesized compounds were established based on elemental analysis, IR, ¹H NMR and mass spectral data. Synthesized compounds have been assayed for their antibacterial activities against B. subtilis, K. pneumoniae, P. aeruginosa and S. aureus and antifungal activities against A. fumigatus and C. albicans.     

Electrocatalytic tandem Knoevenagel–Michael addition of barbituric acids to isatins: Facile and efficient way to substituted 5,5′-(2-oxo-2,3-dihydro-1H-indole-3,3-diyl)bis(pyrimidine-2,4,6-(1H,3H,5H)-trione) scaffold

Electrocatalytic transformation of isatins and barbituric acids in ethanol in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of substituted 5,5′-(2-oxo-2,3-dihydro-1H-indole-3,3-diyl)bis(pyrimidine-2,4,6(1H,3H,5H)-triones) in 89–95% substance yields and 890–950% current yields. The developed efficient electrocatalytic approach to medicinally relevant 5,5′-(2-oxo-2,3-dihydro-1H-indole-3,3-diyl)bis(pyrimidine-2,4,6(1H,3H,5H)-trione) scaffold is 10 times faster than general chemical method, is beneficial from the viewpoint of diversity-oriented large-scale processes and represents novel example of facile environmentally benign synthetic concept for electrocatalytic tandem reaction strategy.     

Oxidation of aroylthioureas during their reactions with 2,3-diphenylcyclopropenone resulting in (E/Z)-3-(aroylthioureido)-2-phenylcinnamic acids

Isolated (E/Z)-3-(aroylthioureido)-2-phenylcinnamic acids have been obtained from the reactions of N-substituted-aroylthioureas with 2,3-diphenylcyclopropenone in acetic acid. The abnormal behavior of the reaction was described as due to nucleophilic addition of N ³ followed by hydrolysis, ring opening and oxidation processes.     

Preparation of novel 2-(2-oxo-2H-chromen-4-yl)-3- arylthiazolidin-4-one derivatives using an efficient ionic liquid catalyst

An eco-friendly procedure for synthesis of 2-(2-oxo-2H-chromen-4-yl)-3-arylthiazolidin-4-one derivatives by three-component reaction of 2-oxo-2H-chromene-4-carbaldehydes, aromatic amines and thioglycolic acid, with tetramethylbutane-1,4-diammonium acetate as a low-cost ionic liquid catalyst under reflux condition is described. The use of an ionic liquid as a catalyst has the advantages of high yields, short reaction time and environmentally friendly reaction media.     

A 3-D silver(I) polymer with 5,6-dihydro-1,4-dithiin-2,3-dicarboxylate ligand,showing an unusual 6-connected (412.63)2(49.66) topology

The in situ reaction of AgClO₄·6H₂O with 5,6-dihydro-1,4-dithiin-2,3-dicarboxylic anhydride in the presence of lithium hydroxide afforded a photoluminescent three-dimensional (3-D) Ag^I coordination polymer, [Ag₂(L)]_∞ (1), which exhibited an unusual trinodal 6-connected (4¹².6³)₂(4⁹.6⁶) topological net (L = 5,6-dihydro-1,4-dithiin-2,3-dicarboxylate). Moreover, the luminescent/thermal properties of 1 have also been briefly investigated.     

Two-component,one-pot synthesis of pyrimido[1,2-b] [1,2,4,5]tetrazines

Derivatives containing the cyclohepta4′,5′thieno[2′,3′:4,5]pyrimido[1,2-b][1,2,4,5]-tetrazin-6-one system were prepared from the reaction of 3-amino-2-thioxo-1,2,3,5,6,7,8,9-octahydro-4H-cyclohepta[4,5]thieno[2,3-d]pyrimidin-4-one (5) or its 2-methylthio derivative 6 with hydrazonoyl chlorides 9. The mechanism of the studied reactions has been discussed and the biological activity of the isolated products has been evaluated.     

Recyclization of 2-iminocoumarin-3-carbonitriles with 2-aminothiobenzamide: a new synthetic route to substituted 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones

The reaction of 2-aminothiobenzamide with either 2-iminocoumarin-3-carbonitrile or 2-iminocoumarin-3-thiocarboxamides has been studied. It has been established that in both cases, 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones are formed as the result of a two-step procedure. The reactions of 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones with arylamines and alkylating agents have been studied.     

Copper-Catalyzed Diazidation of Allenes: Access to 3-(Azidomethyl)-2H-Azirines

A class of 3-(azidomethyl)-2H-azirine has been obtained through a copper-catalyzed diazidation of allenes and a subsequent azirination involving vinyl azides. A variety of functional groups in the allenes are well tolerated, providing a series of 3-(azidomethyl)-2H-azirine motifs in 51%-93% yields (26 examples).