Simple and Convenient Synthesis of 21‐Thioalkylether Derivatives of Methyl 16‐Prednisolone Carboxylates

The antedrug approach for corticosteroids has been described as a fundamentally sound approach for the development of safer anti‐inflammatory and anti‐asthmatic therapy. However, the derivatization of prednisolone and its congeners have been considered to be major pitfalls, because their syntheses are complicated by the presence of numerous carboxylate esters and hydroxyl functions in the steroid nucleus. A simple and direct synthesis of 21‐thioalkylether derivatives of methyl 16‐prednisolonecarboxylates is described. The 21‐mesylate of the methyl 16‐prednisolonecarboxylate and 9‐fluoro‐17‐dehydro methyl 16‐prednisolonecarboxylate were reacted with Na‐thioalkoxides to furnish the desired thioethers in good yields. A previously published method for the methanolysis of 16‐cyanoprednisolone to methylcarboxylate has been reexamined, and the conditions are explained clearly. The reaction conditions for all these reactions were critical.     

Convenient Formal Synthesis of (±)‐Paroxetine

A formal total synthesis of antidepressant (±)‐paroxetine employing a solvent‐free Heck reaction is disclosed.     

Simple and Efficient Synthesis of 4,7‐Dimethoxy‐1(H)‐indene

Stirring 4,7‐dimethoxy‐1‐indanol in chloroform at room temperature in the presence of a catalytic amount of p‐toluenesulfonic acid gave 4,7‐dimethoxy‐1(H)‐indene in quantitative yield. Other solvents, including benzene, which was the most frequently used one for this reaction, gave mostly polymeric materials. The new method was also effective for dehydration of other electron‐rich benzylic alcohols.     

Facile and Convenient Synthesis of 1‐Perfluoroalkyl‐1,2,4‐triazoles

Treatment of N‐methylcarbonyl 1, N‐phenylthioamido 2, and N‐cyano 3 iminoethers with perfluoroalkylated hydrazines leads to 1‐perfluoroalkyl‐5‐methyl‐1,2,4‐ triazoles, 4,1‐perfluoroalkyl‐5‐phenylamino‐1,2,4‐triazoles 5, and 1‐perfluoroalkyl‐5‐amino‐1,2,4‐triazoles 6 in good yields. These compounds are screened for their biological activities.     

Efficient and Convenient One‐Pot Synthesis of Phosphoramidates and Phosphates

A simple and efficient one‐pot method is described for the synthesis of phosphoramidates/phosphates in excellent yields from dialkylphosphites and trichloroisocyanuric acid in acetonitrile and subsequent treatment with dialkyl amines/alcohols. The procedure is operationally simple, has reduced reaction times, and uses a one‐pot procedure.     

Convenient Synthesis of 3,5‐Disubstituted Isoxazoles

α,β‐Unsaturated oximes obtained from the corresponding α,β‐unsaturated ketones on treatment with 2 equivalents of manganese dioxide in refluxing chloroform gives 3,5‐disubstituted isoxazoles in good yields.     

Convenient Synthesis of 7,8‐Dimethoxytetralin‐2‐one

7,8‐Dimethoxytetralin‐2‐one (1), an important intermediate for the synthesis of compounds possessing biological activity, was synthesized by simple reaction steps from commercially available starting materials.     

Simple and Convenient One‐Pot Synthesis of Benzimidazoles and Benzoxazoles using N,N‐Dimethylchlorosulfitemethaniminium Chloride as Condensing Agent

N,N‐Dimethylchlorosulfitemethaniminium chloride (SOCl₂‐DMF) has been found to be an efficient reagent for the one‐pot synthesis of benzimidazoles and benzoxazoles in excellent yield by condensation of carboxylic acids with o‐phenylenediamine/2‐amino‐phenol.     

Convenient Synthesis of 5‐Aryl Uracils

A convenient one‐step synthesis of 5‐aryl uracils has been developed. The procedure involves heating ethyl 3‐hydroxy‐2‐arylpropenate with urea at 130°C, followed by base‐catalyzed cyclization. The method is simple and high yielding.     

Convenient and Efficient Synthesis of 1,1‐Bis‐(4‐alkylthiophenyl)‐1‐alkenes via Tandem Friedel–Crafts Acylation and Alkylation of Sulfides and Acyl Chlorides

1,1‐Bis(4‐alkylthiophenyl)‐1‐alkenes were conveniently and efficiently prepared from alkyl phenyl sulfides and acyl chlorides via a tandem Friedel–Crafts acylation and alkylation in the presence of anhydrous aluminum chloride. The scope, limitation, and mechanism of the tandem reaction were also discussed.     

Simple Synthesis of 7‐Formyl‐indole

A simple route to 7‐formyl‐indole (5) is described in which appropriately functionalized o‐nitrotoluenes (1) are converted to 7‐hydroxymethyl‐indole (4) using the Batcho–Leimgruber process. Condensation of 3‐methyl‐2‐nitrobenzyl alcohol (1a) with N,N‐dimethylformamide dimethyl acetal yields the enamine 2a, which upon catalytic hydrogenation affords 4 in 22% yield. When the hydroxyl function in 1 is protected with pivaloyl or tetrahydropyranyl group, the yields of 4 are increased to 39% and 48%, respectively. Finally, 4 is oxidized with pyridinium chlorochromate (PCC) to afford 5 in 86% yield.     

A Simple and Convenient Synthesis of HEPT Analogues via a One‐Pot Reduction–Sulfenylation Reaction

Abstract

The one‐pot reduction–sulfenylation of 5‐alkyl‐6‐chlorouracils (1) with diaryl disulfides (2) and sodium borohydride in methanol was carried out to afford 1‐[(2‐hydroxyethoxy)methyl]‐6‐(phenylthio)thymine HEPT analogues in good to excellent yields.     

A Convenient and Stereospecific Synthesis of (Z)-Benzylidenephthalides

Several 3-benzylidenephthalides have been isolated from natural sources1-2. Some of them are known to possess useful biological activity1 and are also valuable intermediates3 for the synthesis of naturally occurring biologically active compound. Most of the natural 3-benzylidenephthalides exist in the (Z)-configuration. Synthe-tic methods for construction of a 3-benzylidene-phthalide skeleton have been developed4. Some of these methods for synthesizing highly oxygen-functionalized compound…     

Synthesis and study of 4‐(4′‐n‐alkoxybenzoyloxybenzoyl)‐4′′‐n‐butoxyanilides

Thirteen compounds with ester and amide linkages were synthesized and their mesogenic properties evaluated. Methyl to n‐propyl derivatives exhibit nematic phases, n‐butyl to n‐decyl derivatives exhibit smectic and nematic mesophases, whereas n‐dodecyl to n‐octadecyl derivatives exhibit only smectic phases. All the smectic homologues exhibit smectic C phases. Middle members of the homologous series exhibit polymorphism of smectic mesophase. A plot of transition temperatures versus number of carbon atoms in the alkoxy chain reveals an odd–even effect for nematic–isotropic transition temperatures. Nematic–isotropic and smectic–cholesteric thermal stabilities of the prepared compounds (series I) are higher compared to those of previously reported compounds, series A, B and C. The results indicate that a simple reversal of a central linkage has a dramatic effect on the appearance of smectic mesophase in a homologous series. The structures of the synthesized compounds were characterized using elemental analysis, thin‐layer chromatography and spectral data.     

Convenient and Regioselective One‐Pot Solvent‐Free Synthesis of ß‐Hydroxyphosphonates

A simple, efficient, regioselective, and solvent‐free method has been developed for the synthesis of β‐hydroxyphosphonates from epoxides and triethyl phosphite using ZnCl₂ in high yields under mild conditions.     

Efficient and Simple Synthesis of Substituted 3‐Phenyl‐7‐methoxybenzopyrans as Pseudo‐Vitamin‐D3 Analogs

An efficient and simple synthesis of substituted 3‐phenyl‐7‐methoxybenzopyrans as pseudo‐vitamin‐D₃ analogs in good yields under mild reaction conditions is described.     

A Convenient Synthesis of 3, 4′-Bipyridine

3, 4′-Bipyridine was synthesized from 6-methoxy-3, 4′-bipyridine or 6-benzyloxy-3, 4′-bipyridine via 6-chloro-3, 4′-bipyridine. The chloro derivative was catalytically dechlorinated into the corresponding 3, 4′ -bipyridine.     

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.     

Convenient Synthesis of Pyrrole‐ and Indolecarboxylic Acid tert‐Butylesters

Abstract

The tert‐butylesters of pyrrole‐ and indolecarboxylic acids are readily accessed by reacting the appropriate carboxylic acids with N,N‐dimethylformamide di‐tert‐butyl acetal.     

Simple Synthesis of 4‐Substituted 1(2H)‐Isoquinolinones via Electrophilic Trapping of Lithiated Mono‐ and Dianion Precursors

Synthetic routes have been developed to access 4‐substituted 1(2H)‐isoquinolinones from readily available precursors. This is achieved via electrophilic trapping of di‐ and monolithium anions derived from alkyllithium exchange of 4‐bromo‐1(2H)‐isoquinolinones and corresponding 4‐bromo‐1‐methoxyisoquinolines, respectively. Products derived from the latter are then hydrolyzed to the target 4‐substituted 1(2H)‐isoquinolinones. The methodology has potential application to access 4‐substituted 1(2H)‐isoquinolinones with additional substituents in either ring.