Synthesis and characterization of poly(4‐alkyl‐4‐methyl‐2‐azetidinone)s

Poly‐β‐amides (nylons 3) were synthesized via the anionic polymerization of a series of 4‐alkyl‐4‐methyl‐2‐azetidinones where the alkyl group is a methyl, ethyl, propyl, butyl, or pentyl. The “non‐assisted” polymerization was conducted under vacuum, in the bulk, at 160°C, using potassium 2‐pyrrolidonate as catalyst, whereas the “assisted” polymerization was carried in dimethylsulfoxide, at room temperature, using N‐acetylpyrrolidinone‐2 as activator but it gave no polymer with a propyl or bulkier side group. Side reactions occur in all cases. X‐ray spectra showed that poly(4‐alkyl‐4‐methyl‐2‐azetidinone)s are amorphous with propyl, butyl, and pentyl groups, and semi‐crystalline with methyl or ethyl substituents. Both semi‐crystalline polyamides exhibit an extended planar zigzag conformation, with a fiber identity period along the c axis of 4.9 Å. Glass transition temperatures, melting temperatures, and/or decomposition temperatures are also reported. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 761–769, 1999     

Synthesis and herbicidal activity of 2‐alkyl(aryl)‐3‐methylsulfonyl(sulfinyl)pyrano‐ [4,3‐c]pyrazol‐4(2H)‐ones

Useful oxidation reaction of 2‐alkyl(aryl)‐3‐methylthiopyrano[4,3‐c]pyrazol‐4(2H)‐ones, leading to either the corresponding sulfoxides or sulfones, using hydrogen peroxide and acetic acid in 1,2‐dichloroethane, is described. Bioassay results showed that the products have some herbicidal activity. © 2005 Wiley Periodicals, Inc. 16:255–258, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20067     

Synthesis of 4-(4-Methylsulfonylphenyl)-3-phenyl-2(3H)-thiazole Thione Derivatives as New Potential COX-2 Inhibitors

Synthesis of novel 4-（4-methylsulfonylphenyl）-3-phenyl-2（3H）-thiazole thione derivatives with functionalized diarylheterocycle pharmacophore as potential COX-2 inhibitors was described. The title compounds were synthesized by cyclocondensation of corresponding dithiocarbamate and 2-bromo-1-（4-methylsulfonylphenyl）ethanone, followed by dehydration with H2SO4. All of the target compounds were characterized by ^1H NMR, IR and mass spectral data.     

Synthesis of some poly(4‐alkyl‐4‐azaheptamethylene‐D‐glucaramides)

Six 4‐alkyl‐4‐azaheptane‐1,7‐diamines, characterized as their solid bis(D ‐gluconamides), were prepared in a two‐step synthesis: bis(cyanoethylation) of the primary alkylamines (C₈–C₁₈, even‐numbered) followed by an efficient lithium aluminum hydride reduction of the resulting bisnitriles. The azadiamines were then used as monomers in condensation polymerizations with methyl D ‐glucarate 1,4‐lactone in a methanol solution, yielding polyhydroxypolyaminopolyamides isolated directly as white solids with varying hydrophobic/hydrophilic character. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3892–3899, 2000     

Synthesis and catalytic properties of 1‐alkyl‐2‐imidazolineruthenium(II) complexes

New [RuCl₂(imidazoline)(arene)] complexes have been prepared. The complexes were characterized by conventional spectroscopic methods and elemental analyses. Upon reaction with 1,1‐diphenylprop‐2‐ynol they generate catalyst precursors that can perform the cycloisomerization of diallyltosylamide into N‐tosyl‐α‐methylenepyrrolidine. Copyright © 2004 John Wiley & Sons, Ltd.     

Conformational analysis of 2‐alkyl‐4‐methyl‐2,6‐diphenyl‐2H‐thiopyran derivatives: A combined experimental and theoretical study

Some 2‐alkyl‐4‐methyl‐2,6‐diphenyl‐2H‐thiopyrans were synthesized, and the crystal structure of 2‐tert‐butyl‐4‐methyl‐2,6‐diphenyl‐2H‐thiopyran 1 was determined by single‐crystal X‐ray diffraction. X‐ray crystallographic analysis and ab initio HF/6‐31G(d) and B3LYP/6‐31G(d) calculations revealed a favorable nonplanar half‐chair conformation for these compounds in which two ethylene units were rotated relative to each other around the single bond. The most conspicuous feature was the orientation of alkyl and phenyl groups with respect to the S atom. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:142–147, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20192     

Synthesis and nonlinear optical properties of polyester containing 4‐di‐(2′‐hydroxyethoxy)‐4‐diphenyl‐hydrazonomethyl chromophore

The nonlinear optical property of new polyester has been studied via second harmonic generation (SHG). The values of electro‐optic coefficients, d₃₃ and d₃₁, of the poled polymer film were 3.15 × 10 ^?7 and 1.5 × 10^?7 esu, respectively. Thermal behavior of this polyester was studied through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). 4‐di‐(2′‐hydroxyethoxy)‐4‐diphenyl‐hydrazonomethyl was synthesized from the reaction of 3,4‐dihydroxy‐4‐diphenyl‐hydrazonomethyl with 2–chloro–1‐ethanol in a 1:2 mole ratio and subsequently reacted with terephthaloyl chloride (TPC) in the presence of pyridine, as catalyst, to produce the new nonlinear polyester. The chemical structures of the resulting monomers and polymer were characterized by CHN analysis, ¹H‐NMR, FT‐IR, and UV–Vis spectroscopy. Copyright © 2009 John Wiley & Sons, Ltd.     

Packing forces in dichloridobis(3,5‐diphenyl‐1H‐pyrazole‐κN2)cobalt(II) dichloromethane hemisolvate

The title compound, [CoCl₂(C₁₅H₁₂N₂)₂]·0.5CH₂Cl₂, was crystallized from a binary mixture of dichloromethane and hexane and a dimeric supramolecular structure was isolated. The Co^II centre exhibits a distorted tetrahedral geometry, with two independent pyrazole‐based ligands occupying two coordination sites and two chloride ligands occupying the third and fourth coordination sites. The supramolecular structure is supported by complementary hydrogen bonding between the pyrazole NH group and the chloride ligand of an adjacent molecule. This hydrogen‐bonding motif yields a ten‐membered hydrogen‐bonded ring. Density functional theory (DFT) simulations at the PBE/6‐311G level of theory were used to probe the solid‐state structure. These simulations suggest that the chelate undergoes a degree of conformational distortion from the lowest‐energy geometry to allow for optimal hydrogen bonding in the solid state.     

A Convenient Synthesis of 1‐Alkoxy‐2‐alkyl‐1,2‐dihydroisoquinoline‐3,4‐diones Utilizing the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Dimethyl Oxalate

A new and convenient method for the preparation of 1,2‐dihydroisoquinoline‐3,4‐diones with alkoxy and alkyl groups at the 4‐ and 3‐positions, respectively, using an easily operated three‐step sequence starting from 2‐(dialkoxymethyl)phenyl bromides has been developed. Thus, the starting materials are treated with BuLi to generate 2‐(dialkoxymethyl)phenyllithiums, which are allowed to react with (COOMe)₂ to give methyl 2‐(dialkoxymethyl)phenyl‐2‐oxoacetates. These are then transformed into the corresponding secondary amides by the reaction with primary amines. Treatment of these keto amides with a catalytic amount of TsOH?H₂O affords the desired products. In order to demonstrate the synthetic utility of these products, transformation of one of them into the corresponding isoquinoline‐1,3,4(2H)‐trione derivative by the oxidation with PCC was achieved.     

Design and synthesis of novel rofecoxib analogs as potential cyclooxygenase (COX‐2) inhibitors: Replacement of the methylsulfonyl pharmacophore by a sulfonylazide bioisostere

A group of rofecoxib analogs, having a sulfonylazide (SO₂N₃) substituent in place of the methanesulfonyl (SO₂CH₃) pharmacophore at the meta‐position viz 3‐(4‐methyl, 4‐methoxy, or 4‐ethoxyphenyl)‐4‐(3‐sulfonylazidophenyl)‐2(5H)furanone ( 7a‐c ) and para‐position viz 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7d ), 3‐(4‐fluoro, or 4‐chlorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e‐f ) of the C–4 phenyl ring, and 4‐(1‐oxido‐4‐pyridyl)‐3‐phenyl‐2(5H)furanone ( 12 ) were designed and synthesized for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1/COX‐2 enzyme inhibition studies showed that 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7d ) inhibited COX‐1 selectively (COX‐1 IC₅₀ = 0.6659 μM; COX‐2 IC₅₀ > 100 μM) and 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e ) inhibited both enzymes (COX‐1 IC₅₀ = 0.8494 μM; COX‐2 IC₅₀ = 1.7661 μM). A molecular modeling study was performed where 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e ) was docked in the active site of murine COX‐2 isozyme, which showed that the sulfonylazido group inserts deep into the 2°‐pocket of COX‐2 where it undergoes both H‐bonding (Gln¹⁹², Phe⁵¹⁸) and weak electrostatic (Arg⁵¹³) interactions.     

(3+2) Annulation of Amidinothioureas with Binucleophile: Synthesis and Antimicrobial Activity of 3‐Phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole Derivatives

Herein, we report an efficient method for preparation of 3‐phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole by (3+2) annulation of amidinothioureas with binucleophilic hydroxylamine hydrochloride in the presence of mercury (II) chloride. Desired 3‐phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole was prepared in good to moderate yields. On the basis of the literature precedence, the mechanism for the formation of 3‐phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole is proposed. The synthesized compounds were tested for their antimicrobial activity and showed promising inhibition of Gram‐positive bacteria (Staphylococcus aureus) and fungi (Candida albicans).     

Synthesis and complete NMR characterization of 4‐alkyl‐2‐(6‐substituted‐1,3‐benzoxazol‐2‐yl)benzenols

This paper describes the complete assignment of all carbons and hydrogens of several newly synthesized 6‐substituted 2‐(2‐hydroxyaryl)benzoxazoles from 2,2′‐dihydroxydiaryl Schiff bases by the use of two‐dimensional NMR techniques. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of novel spiroazetidinones by selective lactam‐carbonyl cleavage in 1‐aryl/cyclohexyl‐3,3‐diphenyl‐1′‐(diphenylacetyl)spiro[azetidin‐2,3′‐indoline]‐2′,4‐diones

Titled compounds undergo selective N‐C cleavage on treatment with sodium hydroxide in ethanol affording a series of novel isatin‐based spiroazetidinones.     

New efficient approach for the synthesis of 2‐alkyl(aryl) substituted 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones

A new, efficient and easy route for the preparation of a series of 2‐alkyl(aryl) substituted 4‐oxo‐4H‐pyrido‐[1,2‐a]pyrimidines, where alkyl = CH₃; aryl = C₆H₅, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐CH₃C₆H₄, 4‐OCH₃C₆H₄, 4‐NO₂C₆H₄ in 45–80 % yield from the reaction of β‐alkoxyvinyl trichloromethyl ketones with 2‐aminopyridine under mild conditions, is then reported.     

First Stereoselective Synthesis of the Cytotoxic Polyketide (4R)‐1‐(3,5‐Dihydroxyphenyl)‐4‐hydroxypentan‐2‐one

The first stereoselective synthesis of the cytotoxic polyketide (4R)‐1‐(3,5‐dihydroxyphenyl)‐4‐hydroxypentan‐2‐one ( 1 ) was achieved from readily available propylene oxide and 3,5‐dimethoxybenzyl alcohol. The synthesis involves Jacobsen's hydrolytic kinetic resolution (HKR) and Grignard reaction as key steps.     

Revisiting the crystallization of poly(2‐alkyl‐2‐oxazoline)s

Poly(2‐alkyl‐2‐oxazoline)s (PAOx) exhibit different crystallization behavior depending on the length of the alkyl side chain. PAOx having methyl, ethyl, or propyl side chains do not show any bulk crystallization. Crystallization in the heating cycle, that is, cold crystallization, is observed for PAOx with butyl and pentyl side chains. For PAOx with longer alkyl side chains crystallization occurs in the cooling cycle. The different crystallization behavior is attributed to the different polymer chain mobility in line with the glass transition temperature (T_g) dependency on alkyl side chain length. The decrease in chain mobility with decreasing alkyl side chain length hinders the relaxation of the polymer backbone to the thermodynamic equilibrium crystalline structure. Double melting behavior is observed for PButOx and PiPropOx which is explained by the melt‐recrystallization mechanism. Isothermal crystallization experiments of PButOx between 60 and 90 °C and PiPropOx between 90 and 150 °C show that PAOx can crystallize in bulk when enough time is given. The decrease of T_g and the corresponding increase in chain mobility at T > T_g with increasing alkyl side chain length can be attributed to an increasing distance between the polymer backbones and thus decreasing average strength of amide dipole interactions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 721–729     

Substituent effects in the ring‐chain tautomerism of 4‐alkyl‐2‐aryl substituted oxazolidines and tetrahydro‐1,3‐oxazines

The condensation products of 2‐aminoethanol or 3‐aminopropanol (bearing an alkyl substituent on the carbon adjacent to the nitrogen) with substituted benzaldehydes proved to exist in CDCl₃ at 300 K as threecomponent tautomeric mixtures of the diastereomeric five‐ or six‐membered 1,3‐O,N‐heterocyclic ring forms and the corresponding imines. For each equilibrium, the electronic effects of the 2‐aryl substituents were characterized by the Hammett equation. The steric effects of the alkyl groups could be described by Hansch‐type equations for the equilibria involving oxazolidine ring forms. While the alkyl substituents did not cause any significant effect on the ring cis‐chain and the ring trans‐chain equilibria for tetrahydro‐1,3‐oxazines, increasing bulk of the 4‐alkyl group increased the stability of the cyclic tautomers for the analogous oxazolidines.     

A Green Mechanochemical Synthesis of New 3,5‐Dimethyl‐4‐(arylsulfanyl)pyrazoles

A small series of new 3,5‐dimethyl‐4‐(arylsulfanyl)pyrazoles have been synthesized in good to excellent yields by a grinding‐induced, sequential one‐pot three‐component reaction, of an equimolar mixture of 3‐chloro‐2,4‐pentanedione, differently substituted thiophenols, and hydrazine hydrate in the presence of piperidine under solvent‐free conditions.