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.     

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).     

Bromination of 4‐Dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐ones

Bromination of 4‐dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐one and 4‐dichloromethyl‐3,4‐dimethylcyclohexa‐2,5‐dien‐1‐one has been studied. The reaction conditions required for the formation of mono‐, di‐, and tribrominated products have been optimized.     

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.     

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.     

Structure of 2,4,4,5,5‐pentamethyl‐2‐imidazoline‐1‐oxyl‐3‐oxide

The crystal and molecular structures of the stable nitroxide radical 2,4,4,5,5pentamethyl2imidazoline1oxyl3oxide was determined. The N—O bond lengths are 1.279(2) and 1.280(2), respectively. The O^-—N⁺=C—N— O fragment is nearly planar with carbon atoms of the ethyl fragment that deviated from the O—N⁺=C—N—O plane by –0.204(5) and +0.176(5). The minimum intermolecular distance between the oxygen atoms of NO groups is 4.094.     

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.     

Facile Synthesis of 2‐Alkylthio‐3‐alkyl‐5‐phenylmethylidene‐4H‐imidazol‐4‐ones

2‐Alkylthio‐3‐alkyl‐5‐phenylmethylidene‐4H‐imidazol‐4‐ones 6 were synthesized by N‐alkylation and S‐alkylation of 2‐thioxo‐5‐phenylmethylidene‐4‐imidazolidinone 5, which was obtained via cyclization of vinyl isothiocyanate 4 with excess ammonium hydroxide (28% NH₃ in water).     

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.     

Facile Synthesis of 2‐Alkylthio‐5,5‐dimethyl‐4H‐imidazol‐4‐ones

The isothiocyanate 3, obtained from aza‐Wittig reaction of iminophosphorane 2 with CS₂, reacts with phenylhydrazine to give thiosemicarbazide 4. Reactions of 4 with alkyl halides in the presence of K₂CO₃ directly provided 2‐alkylthio‐4H‐imidazol‐4‐ones 6 in good yields.     

Microwave‐Promoted Efficient Synthesis of 3‐(5‐Arylfuran‐2‐yl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles

A simple, rapid, and efficient method for the synthesis of substituted 1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles under microwave irradiation conditions is reported, and a series of 3‐(5′‐aryl‐2′‐furyl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles was synthesized via this method.     

Synthesis of Novel Anellated Pyranosides as Precursors of C‐Nucleoside Analogues Using Isopropyl 6‐O‐Acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose

Abstract

Isopropyl 6‐O‐acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose (3) was converted to the corresponding 3‐[bis(methylthio)methylene] derivative 4 with a push–pull activated C–C double bond. Treatment of 4 with hydrazine and methylhydrazine afforded the pyrano[3,4‐c]pyrazol‐5‐ylmethyl acetates 5a and 5b, respectively. Desulfurization of compound 4 with sodium boron hydride yielded the 3‐[(methylthio)methylene]hexopyranosid‐2‐ulose 7. Compound 7 was reacted with amines to furnish 3‐aminomethylene‐hexopyranosid‐2‐uloses 8, 9. Reaction of 7 with hydrazine hydrate, hydrazines, hydroxylamine, and benzamidine afforded the pyrazolo, isoxazalo, and pyrimido anellated pyranosides (10–13).     

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 O‐β‐D‐Glucopyranosides of 7‐Hydroxy‐3‐(imidazol‐2‐yl)‐4H‐chromen‐4‐ones

The 7‐hydroxy‐3‐formyl‐4H‐chromen‐4‐one 1 reacted with various cyclic 1,2‐dicarbonyl compounds in the presence of ammonium acetate to furnish 7‐hydroxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 2a–f, which on glucosylation with α‐acetobromoglucose affords 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 3a–f. 7‐O‐β‐D‐Glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 4a–f were prepared by deacetylation with anhydrous zinc acetate in absolute methanol. The structure of these new O‐β‐D‐glucosides was established on the basis of chemical, elemental, and spectral analysis. These compounds were evaluated for their in vitro biological activity.

     

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.     

Fe(III) Ion‐Selective Membrane Electrode Based on 4‐Amino‐6‐methyl‐3‐methylmercapto‐1,2,4‐triazin‐5‐one

Abstract

An original highly selective and sensitive PVC membrane sensor, working as a Fe(III) ion selective electrode and using 4‐amino‐6‐methyl‐3‐methylmercapto‐1,2,4‐triazin‐5‐one (AMMTO) as an ionophore, has been developed. This cetain sensor demonstrated the following performance; a linear dynamic range between 1.0×10^?6 and 1.0×10^?1 M with a near Nernstian slope of 19.4±0.5 mV per decade; a detection limit of 6.8×10^?7 M; characteristically, the best performance was obtained with a membrane composition of 30% poly(vinyl chloride), 65.5% nitrophenyl octyl ether, 2% sodium tetraphenyl borate and 2.5% AMMTO. Furthermore, the potentiometric response of the developed electrode is independent of the solution pH in the range of 2.2–4.8. The sensor possesses the advantages of short conditioning time, fast response time (<15 s) and, especially, great selectivity towards transition and heavy metal ions and some mono, di‐ and trivalent cations. The electrode can be used for at least 9 weeks without any considerable potential divergence. It was effectively used as an indicator electrode in the potentiometric titration of Fe(III) ions with EDTA and the direct determination of Fe³⁺ in different water samples.     

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.     

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.     

The Structure of N‐(1‐Deoxy‐β‐D‐fructopyranos‐1‐yl)‐L‐proline Monohydrate (“D‐Fructose‐L‐proline”) and N‐(1,6‐Dideoxy‐α‐L‐fructofuranos‐1‐yl)‐L‐proline (“L‐Rhamnulose‐L‐proline”)

Nano n-propylsulfonated γ-Fe₂O₃ was found to be a highly efficient, reusable heterogeneous catalyst for the conversion of a range of monosaccharides and some of their derivatives to the corresponding O-isopropylidene derivatives in good to excellent yields by refluxing the reaction mixture in dry acetone. The magnetic property of the catalyst enabled its separation from the reaction mixture by a simple process of filtration along with the aid of an external magnet. The efficiency of the catalyst was found to be largely unaffected for at least up to six cycles of reuse, thus proving the new methodology to be environmentally rewarding besides being simple and facile in operation.