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.     

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.     

Asymmetric Synthesis of (2S)‐1‐(3,4‐Dihydroxyphenoxy)‐3‐(3,′4′‐Dimethoxyphenoxy) Ethylamino‐2‐propanol hydrochloride (RO363)

Enantiomerically pure (S)‐RO363 was synthesized by using (R,R) Salen Co(III) complex for the resolution of terminal epoxide. The hydrolytic kinetic resolution process was carried out at room temperature in excellent enantioselectivity. The method can be applied for large‐scale preparation of (S) RO363.     

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%.     

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 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.     

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.     

Novel Copolymers of N‐(4‐Bromophenyl)‐2‐Methacrylamide with 2‐Acrylamido‐2‐Methyl‐1‐Propanesulfonic Acid

The new acrylamide monomer, N‐(4‐Bromophenyl)‐2‐methacrylamide (BrPMAAm) has been synthesized by reacting 4‐Bromoaniline with methacryloyl chloride in the presence of triethylamine(NR₃) at 0–5°C. The radical‐initiated copolymerization of (BrPMAAm), with 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid (AMPS) has been carried out in dimethylformamide (DMF) solution at 70±1°C using 2,2′‐azobisisobutyronitrile (AIBN) as an initiator with different monomer‐to‐monomer ratios in the feed. The copolymers were characterized by FTIR, ¹H‐ and ¹³C‐NMR spectroscopy. The copolymer composition was evaluated by nitrogen content (N for AMPS‐units) in polymers led to the determination of reactivity ratios. The monomer reactivity ratios for BrPMAAm (M₁)‐AMPS (M₂) pair were computed using the Fineman‐Ross (F‐R), Kelen‐Tüdös (KT) and Extended Kelen‐Tüdös (EKT) methods. These parameters were also estimated using a non‐linear computational fitting procedure, known as reactivity ratios error in variable model (RREVM). The mean sequence lengths determination indicated that the copolymer was statistically in nature. By TGA and DSC analyses, the thermal properties of the polymers have been studied. The antimicrobial effects of polymers were also tested on various bacteria, and yeast.     

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.     

Synthesis of 3,3′‐Di(2‐Pyridyl)‐1,1′‐Bi‐2‐Naphthol Derivatives

Abstract

A new kind of (S)‐3,3′‐dipyridyl BINOLs (3a–d) with C ₂‐symmetry were synthesized in 79–84% yields by Suzuki coupling of the diboronic acid dipinacol ester (S)‐1 containing a (S)‐binaphthyl group with bromopyridine derivatives (2a–d) followed by hydrolysis.     

Novel Synthetic Route of (2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic Acid

(2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic acid, a key intermediate of Fidarestat, was synthesized from natural chiral pool D‐mannitol. Its structure was confirmed by optical analyses, elemental analyses, and IR, ¹H NMR, and ESI‐MS spectra.     

Synthesis of 2‐(5‐Substituted‐1,3,4‐thiadiazolo‐2‐ylimino)‐4‐thiazolidinones under Microwave Irradiation

Fifteen 2‐(5‐substituted‐1,3,4‐thiadiazolo‐2‐ylimino)‐4‐thiazolidinones were efficiently synthesized from the reaction of ammonium thiocyanate with 2‐chloro‐N‐(5‐substutited‐1,3,4‐thiadiazolo‐2‐yl)acetamides under microwave irradiation. The target compounds were obtained in better yields (75–98%) and shorter time (5 min) than with conventional heating.     

Improved Syntheses of 5‐Hydroxy‐2‐Pyridones (2,5‐Dihydroxypyridines)

Improved syntheses of 5-hydroxy-2-pyridone, 6-chloro-5-hydroxy-2-pyridone, 2,5-dihydroxynicotinic acid, and three methyl-substituted 5-hydroxy-2-pyridones are reported.     

Amino Acids as a Chiral Pool: Synthesis of (S)‐and (R)‐2‐N‐Carbomethoxy‐5‐aminoindane from (S)‐ and (R)‐Phenylalanines

Enantioselective syntheses of (R)‐and (S)‐2‐N‐carbomethoxy‐5‐aminoindanes from (R)‐ and (S)‐phenylalanines, respectively, are described. A Friedel–Crafts reaction employing N‐carbomethoxy phenylalanine leads to chiral 2‐N‐carbomethoxy‐1‐indanone, which is diastereoselectively reduced to 1‐hydroxy‐2‐N‐carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives a 6‐nitroindane intermediate, which upon hydrogenation affords (R)‐or (S)‐2‐N‐carbomethoxy‐5‐aminoindane.     

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.     

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.     

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).     

Alternative,High‐Yield Synthesis of (E)‐4‐Oxonon‐2‐enoic Acid from 2‐Methoxyfuran

Alkylation of 2‐methoxyfuran, followed by in situ TPP‐sensitized photooxygenation of 2‐methoxy‐5‐pentylfuran in the presence of Me₂S, gave methyl (Z)‐4‐oxonon‐2‐enoate. Hydrolysis of methyl (Z)‐4‐oxonon‐2‐enoate afforded (E)‐4‐oxonon‐2‐enoic acid in three steps and in 79% overall yield.