Antibacterial Activities of New (E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoylamide Derivatives

(E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoyl chloride (2) underwent mono‐ and binucleophilic displacement with hydrazines, amines, ureas, and aromatic bifunction amines to give new 2‐propenoyl hydrazines (4 and 5), 2‐propenoylamide (6, 7, 12, 13, 15, 17, 19, 21), and 2‐thiol propenoate (22–24). Some of these products were cyclized to give novel heterocyclic derivatives (8, 10, 14, 16, and 20).     

Efficient Synthesis of Trialkyl (E)‐3‐{3‐Oxo‐2‐3,4‐dihydro‐2‐(1H)‐quinoxalinylidene}‐prop‐1‐ene‐1,2,3‐tricarboxylates

The reaction of dialkyl acetylenedicarboxylates with alkyl 2‐[3‐oxo‐3,4‐dihydro‐2(1H)‐quinoxadinylidene]ethanoates in the presence of triphenylphosphine leads to trialkyl (E)‐3‐{3‐oxo‐2‐3,4‐dihydro‐2‐(1H)‐quinoxalinylidene}‐prop‐1‐ene‐1,2,3‐tricarboxylates in good yields.     

Oxidative Conversion of 3‐Alkoxyfurans to 2‐Hydroxy‐3(2H)‐furanones and 2‐Hydroxy‐2‐butene‐1,4‐diones with 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) or Phenyltrimethylammonium Tribromide (PTAB) in t‐BuOH

2‐Alkoxy‐1,3,4‐triphenylfurans were oxidized to 3‐alkoxy‐2,4,5‐triphenyl‐ 2‐butene‐1,4‐diones with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) in t‐BuOH. In contrast, various 3‐alkoxy‐2,4,5‐triphenylfurans were directly converted to 2‐hydroxy‐3(2H)‐furanone with phenyltrimethylammonium tribromide (PTAB) in t‐BuOH. The oxidative ring opening of 3‐alkoxy‐2,5‐diphenylfurans to cis‐2‐hydroxy‐2‐butene‐1,4‐dione was also accomplished with PTAB in t‐BuOH under the same reaction conditions.     

Synthesis of the Potassium Channel Opener (3S,4R)‐3,4‐Dihydro‐4‐(2,3‐dihydro‐2‐methyl‐3‐oxo‐pyridazin‐6‐Yl)oxy‐3‐hydroxy‐6‐(3‐hydroxyphenyl)sulphonyl‐2,2,3‐trimethyl‐2H‐benzo[b]pyran

The preparation of the potassium channel opener (3S,4R)‐3,4‐dihydro‐4‐(2,3‐dihydro‐2‐methyl‐3‐oxo‐pyridazin‐6‐yl)oxy‐3‐hydroxy‐6‐(3‐hydroxyphenyl)sulphonyl‐2,2,3‐trimethyl‐2H‐benzo[b]pyran (1) as a single enantiomer is reported. Considerable improvements have been implemented with respect to the original synthesis that allow for the preparation of multigram quantities of the final target compound. The optimized synthesis consists of a six‐step linear sequence whose key step is an asymmetric epoxidation protocol through the use of Jacobsen's (S,S)‐(+)‐N,N′‐bis(3,5‐di‐tert‐butylsalicylidene)‐1,2‐cyclohexanediaminomanganese(III) chloride catalyst.     

Efficient Synthesis of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines

A general method for the preparation of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines is described. These heterocycles can be synthesized from their respective anilines with 2‐chloro‐2‐imidazoline or 2‐chloro‐1,4,5,6‐tetrahydropyrimidine, generated in situ from imidazolidin‐2‐one and tetrahydropyrimidin‐2(1H)‐one activated by dimethyl chlorophosphate, in good to excellent yields.     

Convenient Synthesis of Substituted 5‐(Hydroxymethyl)‐8‐methyl‐3‐(4‐phenylquinazolin‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones

Abstract

Interaction of 2‐imino‐2H‐pyrano[2,3‐c]pyridin‐3‐carboxamide with substituted 2‐aminobenzophenones proceeds via recyclization mechanism leading to substituted 3‐(4‐arylquinazolyn‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones. Their reaction with acetic anhydride affords the O‐acylation products.     

Synthesis of (E)‐ and (Z)‐5‐(Bromomethylene)furan‐2(5H)‐one by Bromodecarboxylation of (E)‐2‐(5‐Oxofuran‐2(5H)‐ylidene)acetic Acid

(E)‐ and (Z)‐5‐(bromomethylene)furan‐2(5H)‐one have been prepared starting from the commercially available adduct between furan and maleic anhydride. A bromodecarboxylation reaction is a key step in the synthesis. The reaction gives the (E)‐ or (Z)‐5‐(bromomethylene)furan‐2(5H)‐one as the major product, dependent on the method used in the bromodecarboxylation.     

Novel Synthesis of 5‐Substituted‐3‐phenylindole‐2‐(1,2,4‐triazole) Derivatives

Various substituted 3‐phenylindole 2‐carboxylates (1a–c) were prepared according to the literature methods. These carboxylates (1a–c) on reaction with thiosemicarbazide yielded 5‐substituted‐3‐phenylindol‐2‐(1,2,4‐triazole‐3‐thione) (2a–c) on refluxing in pyridine for 8 h. The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐thioacetic acid] (3a–c) were prepared from 5‐substituted‐3‐phenyl indole‐2‐[1,2,4‐triazole‐3‐thione] (2a–c) on reaction with an appropriate alkylating agent and sodium acetate in acetic acid. Further, (3a–c) were reacted with acetic anhydride to bring about a cyclocondensation reaction to yield 5‐substituted‐3‐phenylindol‐2‐thiazolo(2,3‐b)‐triazole (4a–c). The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐acetic acid] (3a–c) were reacted with o‐phenylenediamino dihydrochloride in ethylene glycol to yield 5‐substituted‐3‐phenylindole‐1,2,4‐triazolo‐3′‐yl‐thiomethyl)benzimidazoles (5a–c).     

Copolymers of 2‐(3‐(6‐tetralino)‐3‐methyl‐1‐cyclobutyl)‐2‐Hydroxyethyl Methacrylate with Acrylonitrile and 4‐Vinylpyridine: Synthesis,Characterization, and Monomer Reactivity Ratios

The copolymerization of 2‐(3‐(6‐tetralino)‐3‐methyl‐1‐cyclobutyl)‐2‐hydroxyethyl methacrylate (TCHEMA), monomer with acrylonitrile and 4‐vinylpyridine were carried out in 1,4‐dioxane solution at 65°C using AIBN as an initiator. The copolymers were characterized by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopic techniques. Thermal properties of the polymers were also studied by thermogravimetric analysis and differential scanning calorimetry. The copolymer compositions were determined by elemental analysis. The monomer reactivity ratios were calculated by the Fineman‐Ross and Kelen‐Tüdös method. Also, the apparent thermal decomposition activation energies were calculated by the Ozawa method with a Shimadzu TGA 50 thermogravimetric analysis thermobalance.     

Facile One‐Pot Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐one Catalyzed by Zn(NH2SO3)2

An efficient synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones (DHPMS) from aromatic aldehydes, β‐keto ester, and urea (or thiourea) in refluxing ethanol using zinc sulfamate as a catalyst is first described here. Compared to the classical Biginelli reaction, this new method consistently has the advantages of good yields (76–96%), short reaction time (2–5 h), no corrosion of equipment, ease of manipulation, and low‐cost catalyst.     

Regioselective Endocyclic Oxidation of Enantiopure 3‐Alkylpiperidines: Synthesis of (3S,5S)‐(‐)‐3‐Ethyl‐5‐Methylpiperidine

An efficient regioselective endocyclic oxidation of enantiopure 3‐alkylpiperidines 1(a–c) with bromine in acetic acid to generate the corresponding 5‐alkylpiperidin‐2‐ones 3(a–c) as main product is described. In addition, starting from 3a or 3b, the synthesis of (3S,5S)‐(‐)‐3‐ethyl‐5‐methylpiperidine 6 · HCl was achieved. Finally, the X‐ray single‐crystal analysis of compound 4 is reported.     

Two‐Step Novel Synthesis of 2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐4,7‐diphenyloxepine‐3‐carbonitrile and 5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐6‐phenyl‐2H‐pyran‐3‐carbonitrile

Starting from indan‐1,3‐dione, a novel two‐step synthesis of the oxepine derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction conditions is described.     

Facile One‐Pot Synthesis of 4‐Hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic Acid 1,1‐Dioxide

We report a convenient synthesis of 4‐hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic acid‐1,1‐dioxide (6a) prepared in a novel one‐pot reaction. The synthesis involves two transformations starting from 2‐methyl‐2H‐1,2‐benzothiazin‐4‐(3H)‐one 1,1‐dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One‐pot synthesis of an important intermediate, saccharin‐N‐methane sulfonic acid (4), is also described.     

Scalable Process for 4‐(2‐Hydroxy‐2‐methyl)‐ethyl‐benzylamine

The preparation of the title compound has been revisited and improved. Starting from inexpensive cuminonitrile, 4‐(2‐hydroxy‐2‐methyl)‐ethyl‐benzylamine is obtained in a scalable two‐step process with an overall yield of 55%.     

Stereoselective Synthesis of (2S, 8S)‐2‐Benzyl Hexahydro‐pyrrodizin‐3‐one Starting from (L)‐Proline Based on Stereoselective Benzylation

Abstract

A pyrrolizidine alkaloid, (2S, 8S)‐2‐benzyl hexahydro‐pyrrodizin‐3‐one, was synthesized from (L)‐proline using diastereoselective benzylation as the key step. The absolute configuration of the target compound was confirmed through 2D H‐H COSY and H‐H NOESY spectra.     

Improved Synthesis of 1‐Hydroxy‐2,2,5,5‐tetramethyl‐3‐imidazoline 3‐Oxide (HTIO)

A simple, efficient, mild, and reproducible method for the synthesis of 1‐hydroxy‐2,2,5,5‐tetramethyl‐3‐imidazoline 3‐oxide is described. The method is based on the condensation of 2‐hydroxyamino‐2‐methylpropanal oxime with 2,2‐diethoxypropane in the presence of an equimolar quantity of acetic acid. Cost‐effectiveness of the condensation procedure could be also achieved by replacing 2,2‐diethoxypropane with less expensive 2,2‐dimethoxypropane.     

Synthesis of C‐Nucleoside Analogues Starting from 1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one

Abstract

1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one (4) was synthesized by the reaction of (methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)ethanal (2) with lithium phenylethynide and following oxidation. Compound 4 and hydrazine hydrate provided the 3(5)‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl‐methyl)‐5(3)‐phenyl‐1H‐pyrazole (5). The reactions of 4 with amidinium salts and a S‐methyl‐isothiouronium salt, respectively, furnished the pyrimidine C‐nucleoside analogues 6a–6c. Treatment of 4 with 2‐aminobenzimidazole afforded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐ylmethyl)‐4‐phenyl‐benzo [4,5]imidazo[1,2‐a]pyrimidine (7a). Compound 4 and sodium azide yielded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐1‐[5(4)‐phenyl‐1H(2H)‐1,2,3‐triazole‐4(5)‐yl]ethanone (8).     

Efficient Synthesis of N‐Oxide Derivatives: Substituted 2‐(2‐(Pyridyl‐N‐oxide)methylsulphinyl)benzimidazoles

Different substituted 2‐chloromethylpyridyl derivatives (6a–d) were oxidized with mCPBA to give the respective 2‐chloromethylpyridine‐N‐oxide derivatives (7a–d) at low temperature, which on condensation with 2‐mercapto‐1H‐benzimidazole (8a–c) in the presence of aprotic solvents give the 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfanyl]‐1H‐benzimidazole (9a–d) in good yield. Finally, 9a–d oxidized with mCPBA in chlorinated solvent gives a mixture of 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfonyl]‐1H‐benzimidazole (3a–d, 10%) and 2‐[[(pyridin‐2‐yl‐1‐oxide) methyl]sulfinyl]‐1H‐benzimidazole (4a–d, 90%) derivatives.     

A Novel Holmium(III) Membrane Sensor Based on N‐(1‐Thien‐2‐Ylmethylene)‐1,3‐Benzothiazol‐2‐Amine

Abstract

A novel plasticized membrane sensor for Ho(III) ions based on N‐(1‐thien‐2‐ylmethylene)‐1,3‐benzothiazol‐2‐amine (TBA) as a neutral carrier was prepared. The best performance was obtained with a membrane composition of 31% PVC, 61% benzyle acetate, 2% sodium tetra phenyl borate and 6% carrier. The electrode exhibits a Nernstian response for Ho(III) ions over a particular concentration range (1.0×10^?5?1.0×10^?2 M) with a slope of 19.7±0.2 mV decade^?1. The limit of the detection is 7.0×10^?6 M. The sensor has a response time of <15 s and a useful working pH range of 4.0–9.5. The proposed sensor discriminates relatively well towards Ho(III) ions with regard to common alkali, alkaline earth, and specially lanthanide ions. It was successfully applied as an indicator electrode in a potentiometric titration of Ho(III) ions with EDTA. It was also applied in determination of fluoride ions in a mouth wash preparation. The proposed sensor was applied for the determination of Ho(III) ion concentration in binary mixtures.