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).     

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.     

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.     

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 and Characterization of Alkyl and Aryl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amines: X‐Ray Structures of Ethyl and Cyclohexyl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amine

Abstract

We have synthesized and characterized a series of alkyl and aryl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amines through a high‐yield, three‐step procedure starting from 4‐methylquinolin‐2‐ol. Nitration using concentrated nitric/sulfuric acids, followed by chlorination in phosphorus oxychloride, yielded 2‐chloro‐4‐methyl‐6‐nitro‐quinoline. All of the intermediates and aminated products have been characterized by multinuclear (¹H and ¹³C) NMR spectroscopy, elemental analysis, and, in the case of the two title compounds (ethyl and cyclohexyl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amine), a single crystal X‐ray structure was obtained to verify the nature of the new materials.     

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%.     

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.     

Simple and Convenient Synthesis of 4‐Unsubstituted‐3‐(3‐Oxoalkyl)isocoumarins

A simple transformation of 2‐alkylfurans and 2‐formylbenzoic acids into 4‐unsubstituted 3‐(3‐oxoalkyl)isocoumarins is described. It is based on the synthesis of 2‐(2‐carboxybenzyl)furans followed by their acid‐catalyzed recyclization to the target isocoumarins.     

Synthesis,Characterization and Photocrosslinking Properties of Poly(1‐(4‐Methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one)

The phenylmethacrylamide monomer, 1‐(4‐methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one (MPNP) containing a photosensitive group was synthesized by reacting 4‐nitrocinnamoylaniline with methacryloyl chloride in the presence of triethylamine at 0–5°C. The functional monomer, MPNP was polymerized in ethyl methyl ketone (EMK) under nitrogen atmosphere at 70°C using benzoyl peroxide (BPO) as the initiator. The synthesized polymer was characterized by UV, IR, ¹H‐NMR and ¹³C‐NMR spectroscopy. The molecular weight data of the polymer as obtained from gel permeation chromatography suggests a higher tendency for chain termination by radical recombination than disproportionation. The thermal studies of the polymer were obtained from thermogravimetric analysis. The glass transition temperature of the polymer was determined by differential scanning calorimetry. The solubility of the polymer was tested in various organic solvents at room temperature. The photosensitivity of the polymer was investigated in various solvents in the presence and absence of triplet photosensitizers. The effect of the different solvents nature and concentration on the rate of photocrosslinking of the polymer were also examined for using the polymer as negative photoresist materials.     

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.

     

Synthesis and Structure of 2‐Hydroxy‐2‐Methyl‐1,3‐Bis‐(Methyl 3′,4′,6′‐Tri‐O‐Acetyl‐β‐D‐Glucopyranosid‐2‐yl)‐Imidazolidine‐4,5‐Dione

The title compound was synthesized starting from methyl 3,4,6‐tri‐O‐acetyl‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside, oxalyl chloride, and methyl 3,4,6‐tri‐O‐acetyl‐2‐amino‐2‐deoxy‐β‐D‐glucopyranoside. The crystal and molecular structure of the obtained imidazolidine‐4,5‐dione have been determined by X‐ray analysis as well as ¹H and ¹³C NMR spectroscopy.     

Synthesis of Some Novel 2,3,4,8,9‐Pentahydro‐7‐(4‐haloaryl)‐pyrazolo[5,1‐e]benzo[1,5]oxazocines and 2,3(erythro), 7,8‐Tetrahydro‐2‐aryl‐3‐(4‐fluoro‐3‐methylbenzoyl)‐6‐(4‐haloaryl)pyrazolo[5,1‐d] Benzo[1,4]oxazepines via Solid–Liquid PTC

In this communication, a simple and straightforward procedure for the heterocyclization of 1H‐4,5‐dihydro‐3‐(4‐haloaryl)‐5‐substituted phenylpyrazoles (4) with 1‐bromo‐3‐chloropropane and 2,3‐dibromo‐1‐(4‐fluoro‐3‐methylphenyl)‐3‐phe‐ nylpropanone affording 2,3,4,8,9‐pentahydro‐7‐(4‐haloaryl)pyrazolo[5,1‐e]benzo[1,5] oxazocines 5 and regioselective synthesis of 2,3(erythro),7,8‐tetrahydro‐2‐ aryl‐3‐(4‐fluoro‐3‐methylbenzoyl)‐6‐(4‐halophenyl)pyrazolo[5,1‐d]benzo[1,4]oxa‐ zepines 6, respectively, via solid–liquid PTC is reported. All the synthesized compounds have been characterized on the basis of their spectral studies (IR, PMR, and MS) and analytical data.     

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.     

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 Potentially Bioactive Heterocycles: Thermal [3,3]Sigmatropic Rearrangement of 4‐(4′‐Aryloxybut‐2′‐ynyloxy)‐6‐methyl‐2‐pyridone

Synthesis of a number of hitherto unreported 4‐aryloxymethylene‐7‐methyl‐2,3‐dihydropyrano[3,2‐c]pyridine‐5‐ones 4a–h have been achieved in moderate yields by the thermal [3,3]sigmatropic rearrangement of 4‐(4′‐aryloxybut‐2′‐ynyloxy)‐6‐methyl‐2‐pyridone.     

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.     

Organic Base‐Catalyzed Stereoselective Isomerizations of 4‐Hydroxy‐4‐phenyl‐but‐2‐ynoic Acid Methyl Ester to (E)‐ and (Z)‐4‐Oxo‐4‐phenyl‐but‐2‐enoic Acid Methyl Esters

We have developed a 1,4‐diazabicyclo[2.2.2]octane (DABCO)‐catalyzed isomerization of 4‐hydroxy‐4‐phenyl‐but‐2‐ynoic acid methyl ester to (E)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester and an N,N‐diisopropylethylamine‐catalyzed isomerization of the same substrate to (Z)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester.     

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.     

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.