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.     

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.     

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.     

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).     

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.     

Efficient Diastereoselective Synthesis of Chiral Diferrocenylphosphine‐diamines: X‐ray Crystal Structure of [(η5‐C5H5)Fe{(η5‐C5H3)PPh2CH(CH3) N(CH2)2(CH2)2NCH(CH3)PPh2 (η5‐C5H3)}Fe(η5‐C5H5)]

Abstract

Three novel chiral planar diferrocenylphosphine‐diamines 5 (a–c) were designed and synthesized starting with (s)‐(?)‐N,N‐dimethyl‐1‐ferrocenylethylamine‐1 [(S)‐1]. All new compounds were identified by ¹H NMR and MS. The structure of chiral diferrocenylphosphine‐diamine 5c was determined by X‐ray crystallography. Single crystal X‐ray diffraction analysis reveals that the molecular structure of compound 5c [(η⁵‐C₅H₅)Fe{(η⁵‐C₅H₃)PPh₂CH(CH₃) N(CH₂)₂(CH₂)₂NCH(CH₃)PPh₂‐(η⁵‐C₅H₃)}Fe(η⁵‐C₅H₅)] is enantiomerically pure and crystallizes in the noncentrosymmetric P2(1)2(1)2(1) space group; it maintains “Z” shape and contains a piperazine hexahydrate ring bridge. The piperazine ring adopts a favored chair conformation and the chiral center C₂₃ and C₂₉ substituents in S‐configuration.     

Nonextractive Trace Level Simultaneous Determination of Mercury(II) and Zinc(II) in Environmental Samples with 2‐(5‐Bromo‐2‐pyridylazo)‐5‐diethylaminophenol and Cetylpyridinium Chloride

Abstract

A simple, rapid, selective, and sensitive method for the derivative spectrophotometric determination of Hg(II) and its simultaneous determination in the presence of Zn(II) using 2‐(5‐bromo‐2‐pyridylazo)‐5‐diethylaminophenol in the presence of cetylpyridinium chloride, a cationic surfactant, has been developed. The molar absorption coefficient and analytical sensitivity of the 1∶1 Hg(II) complex at 558 nm (λ_max) are 5.78×10⁴ L mol^?1 cm^?1 and 0.67 ng mL^?1, respectively. The detection limit of Hg(II) is 1.40×10^?2 ng mL^?1, and Beer's law is valid in the concentration range 0.05–2.40 µg mL^?1. Overlapping spectral profiles of Hg(II) and Zn(II) complexes in zero‐order mode interfere in their simultaneous determination. However, 0.10–2.00 µg mL^?1 of Hg(II) and 0.065–0.650 µg mL^?1 of Zn(II), when present together, can be simultaneously determined at zero cross point of the derivative spectrum, without any prior separation. The relative standard deviation for six replicate measurements of solutions containing 0.134 µg mL^?1 of Hg(II) and 0.620 µg mL^?1 of Zn(II) is 1.72 and 1.47%, respectively. The proposed method has successfully been evaluated for trace level simultaneous determination of Hg(II) and Zn(II) in environmental samples.     

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.     

From Tri‐O‐Acetyl‐D‐Glucal to (2R,3R,5R)‐2,3‐Diazido‐5‐Hydroxycyclohexanone Oxime

Abstract

Methyl 3‐azido‐2,3‐dideoxy‐α/β‐D‐arabino‐ and ‐α/β‐D‐ribo‐hexopyranosides were transformed into 6‐iodo analogues via p‐tolylsulfonyl compounds. Elimination of hydrogen iodide from 6‐iodo glycosides provided methyl 4‐O‐acetyl‐3‐azido‐2,3,6‐trideoxy‐α‐ and ‐β‐D‐threo‐hex‐5‐eno‐pyranosides or 3‐azido‐4‐O‐p‐tolylsulfonyl‐2,3,6‐trideoxy‐α‐D‐threo‐ and ‐β‐D‐erythro‐hex‐5‐eno‐pyranosides. Ferrier's carbocyclization of 4‐O‐acetyl‐3‐azido‐2,3,6‐trideoxy‐α‐ and ‐β‐D‐threo‐hex‐5‐eno‐pyranosides gave (2S,3R,5R)‐2‐acetoxy‐3‐azido‐5‐hydroxycyclohexanone, which was converted into oxime. The 2‐OAc group in oxime was substituted by azide ion to yield (2R,3R,5R)‐2,3‐diazido‐5‐hydroxycyclohexanone oxime. The configuration and conformation of all products are widely discussed on the basis of the ¹H and ¹³C NMR.     

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.     

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%.     

Application of Sulfinyl bis(2,4‐dihydroxythiobenzoyl) in the Synthesis of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles

One‐stage synthesis of N‐substituted 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles is described. The compounds were prepared by the reaction of the sulfinyl bis(2,4‐dihydroxythiobenzoyl) (STB) with 4‐substituted 3‐thiosemicarbazides. STB was obtained from 2,4‐dihydroxybenzenecarbodithioic acid and thionyl dichloride. The structure of compounds was confirmed by IR, ¹H NMR, ¹³C NMR, and EI‐MS data.     

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.     

Facile One‐Pot Synthesis of 3‐{2‐[5‐Hydroxy‐4‐(2‐hydroxy‐ethyl)‐3‐methyl‐pyrazol‐1‐yl]‐thiazol‐4‐yl}‐chromen‐2‐ones via a Three‐Component Reaction

Reaction of 3‐(2‐bromo‐acetyl)‐chromen‐2‐one with thiosemicarbazide and 2‐acetylbutyro lactone in anhydrous ethanol gave 3‐{2‐[5‐hydroxy‐4‐(2‐hydroxy‐ethyl)‐3‐methyl‐pyrazol‐1‐yl]‐thiazol‐4‐yl}‐chromen‐2‐one in good yields.     

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.     

Efficient Preparation of ((3‐Chloro‐2‐fluoro‐phenyl)‐[7‐methoxy‐8‐(3‐morpholin‐4‐yl‐propoxy)‐10,11‐dihydro‐5‐oxa‐2,4,11‐triaza‐dibenzo(a,d)cyclohepten‐1‐yl]‐amine) for In‐Vivo Study

An improved route for the preparation of highly functionalized 5,6‐dihydro‐pyrimido[4,5‐b][1,4]oxazepine 1a in multigram quantities was developed. This new methodology was highlighted by the proper methoxy disposition via a regioselective methylation of 2,4,5‐trihydroxy‐benzaldehyde followed by a magnesium sulfate–promoted cyclization.     

Efficient Synthesis of 1‐(5′‐Acylamino‐1′,3′,4′‐thiadiazol‐2′‐yl)‐4‐acyl‐thiosemicarbazides

Acyl chlorides reacted with ammonium thiocyanate and carbonic dihydrazide under phase‐transfer catalysis to first afford 2,2′‐bis(acylaminothiocarbonyl)‐carbonic dihydrazides, which further cyclized in the presence of glacial acetic acid to efficiently give 1‐(5′‐acylamino‐1′,3′,4′‐thiadiazol‐2′‐yl)‐4‐acyl‐thiosemicarbazides in high yield.     

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 New N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines and N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines Esters

Following our efforts towards the synthesis of new potential inhibitors of Xanthine Dehydrogenase (XDH), we describe here a general method for the preparation of N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines and N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycine esters from glycine ethyl ester hydrochloride and various 4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid esters and carbonitriles.     

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.