Convenient Syntheses of Perdeuterioacrylonitrile and β,β-Dideuterioacrylonitrile

Perdeuterioacrylonitrile can be prepared conveniently from succinonitrile in a two-step process. Succinonitrile is exchanged with D₂O to obtain perdeuteriosuccinonitrile, which is then pyrolyzed at ～550°C to obtain perdeuterioacrylonitrile and DCN. CDBCN and CzDsCN are by-products of this reaction. A chemical procedure for separating perdeuterioacrylonitrile from these materials was developed. This involved formation of the Diels-Alder adduct of cyclopentadiene with perdeuterioacrylonitrile, followed by pyrolysis of the purified adduct at -330°C. Cyclopentadiene was removed from the resulting pyrolyzate by reaction with maleic anhydride. Purified perdeuterioacrylonitrile exchanged with H₂O to yield β,β-dideuterioacrylonitrile in good yield and good isotopic purity.     

Convenient Syntheses of Aroylamino Acids and α-amino ketones

C-Acylamino acid, especially aroylamino acid is a key and still currently interest compound for the pharmaceutical intermediate in which β-arylserine prepared by the reduction in an example would be physiologically important.     

Direct and Convenient Method of Regioselective Benzylation of Methyl α‐D‐Glucopyranoside

A facile and convenient method for the direct preparation of methyl 2,3,6‐tri‐O‐benzyl‐α‐D‐glucopyranoside (2) by the regioselective benzylation of methyl α‐D‐glucopyranoside (1) with benzyl bromide in the presence of mild bases K₂CO₃ and KOH (1∶1) without solvents is reported.     

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.     

A Novel,Convenient Synthesis of the 3‐O‐β‐D‐ and 4′‐O‐β‐D‐Glucopyranosides of trans‐Resveratrol

Abstract

trans‐Resveratrol‐3‐O‐β‐D‐glucupyranoside (trans‐piceid, 2) and trans‐resveratrol‐4′‐O‐β‐D‐glucupyranoside (trans‐resveratroloside 3) are the naturally occurring O‐glucoside conjugates of the polyphenolic stilbenoid trans‐resveratrol 1. Recently, attention has been drawn towards the interesting biological properties of the glucoside conjugates 2 and 3 as well as those of the aglycone 1. The fact that only limited quantities can be obtained by extraction from natural sources has prompted the development of novel syntheses of 2 and 3, based on a convergent Heck‐coupling strategy, which now conveniently allows for the preparation of multi‐milligram to gram quantities of each.     

A Convenient and Efficient Preparation of 2‐Acetyl‐4,5‐difluorothiophene

A convenient, five‐step preparation of 2‐acetyl‐4,5‐difluorothiophene from 2,3‐dibromothiophene is described.     

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 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.     

Two Efficient Syntheses of Protected 4‐Deoxy‐D‐lyxo‐hexose (4‐Desoxy‐D‐mannose)

The formation of four differently protected 4‐deoxy‐D‐lyxo‐hexose derivatives 7, 8, 12, and 14 is described. In the first procedure, a nucleophilic displacement of the allylic mesylate 4 by hydride was combined with a highly stereoselective osmylation of olefin 6 to afford diol 7. In the second radical procedure, tributyl tin hydride was substituted by the cheap and environmentally friendly hypophosphorous acid as a hydrogen donor in the reduction of xanthate 13 to 4‐deoxy lyxo‐hexose 14.     

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.     

A Convenient One‐Pot Preparation of Stable Equivalents of Cyclobutane‐1,2‐dione and Cyclobutanetrione

A very short, high‐yielding, one‐pot procedure has been developed for the preparation of half‐protected cyclobutane‐1,2‐dione. This compound is much more stable than cyclobutane‐1,2‐dione itself and allowed further transformation to give diprotected cyclobutanetrione equivalents.     

Improved Syntheses of N‐Desmethylcitalopram and N,N‐Didesmethylcitalopram

An improved and efficient synthesis of N‐desmethylcitalopram (2) and N,N‐didesmethylcitalopram (3) is presented. The method involved N‐demethylation of citalopram (1) using 1‐chloroethyl chloroformate to give 2 in 87% yield. Synthesis of 3 was accomplished by alkylation of 8 with 1‐(3‐bromopropyl)‐2,2,5,5‐tetramethyl‐1‐aza‐2,5‐disilacyclopentane (9).     

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.     

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.     

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 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.     

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.     

Syntheses of Acyclo‐C‐nucleoside Analogs from 2,3:4,5‐Di‐O‐isopropylidene‐D‐xylose

Treatment of 1,2‐dideoxy‐4,5:6,7‐di‐O‐isopropylidene‐D‐xylo‐hept‐1‐yn‐3‐uloses 4a,b with hydrazine hydrate and amidines yielded the 3‐(1,2:3,4‐di‐O‐isopropylidene‐D‐xylo‐1,2,3,4‐tetrahydroxy‐butyl)‐5‐phenyl‐1H(2H)‐pyrazole 5 and the substituted 4‐(1,2:3,4‐di‐O‐isopropylidene‐D‐xylo‐1,2,3,4‐tetrahydroxy‐butyl)pyrimidines 7a–f, respectively. Reaction of 4a,b with 2‐amino‐benzimidazol afforded the 2‐(1,2:3,4‐di‐O‐isopropylidene‐D‐xylo‐1,2,3,4‐tetrahydroxy‐butyl)benzo[4,5]imidazo[1,2‐a]pyrimidines 9a,b. Compound 4a and 5‐amino‐pyrazole‐4‐carbonic acid derivatives yielded the 5‐(1,2:3,4‐di‐O‐isopropylidene‐D‐xylo‐1,2,3,4‐tetrahydroxy‐butyl)pyrazolo[1,5‐a]pyrimidines 11a–d. Deprotection of pyrazole 5, pyrimidine 7a, and pyrazolo[1,5‐a]pyrimidine 11b yielded the acyclo‐C‐nucleosides 6, 8, and 12, respectively.     

Convenient Preparation of Optically Pure 3‐Aryloxy‐pyrrolidines

Chiral 3‐methanesulfonyl‐1‐Boc‐pyrrolidine and piperidine were reacted with sodium phenolates, resulting in a mixture of displacement and elimination products. Following carbamate deprotection and pH adjustment, the 3‐pyrroline and tetrahydropyridine by‐products resulting from elimination were easily removed through aqueous partitioning and/or concentration. Although the pyrrolidines were formed with a high degree of optical purity, slight racemization was observed for the piperidine case because elevated temperatures were required to effect displacement.     

Convenient Synthesis of tert‐Butyl Esters of Indole‐5‐carboxylic Acid and Related Heterocyclic Carboxylic Acids

The tert‐butyl esters of indole‐5‐carboxylic acid and related compounds such as benzofuran‐ and benzothiophene‐5‐carboxylic acid were readily accessed by reacting the appropriate carboxylic acids with tert‐butyl trichloroacetimidate. To obtain the tert‐butyl esters of the 5‐carboxylic acids of 1H‐benzotriazole and 1H‐benzimidazole, position 1 of these heterocycles had to be protected by acetylation prior to reaction with tert‐butyl trichloroacetimidate. Cleavage of the acetyl residue of the obtained intermediates by dilute aqueous NaOH in ethanol led to the desired tert‐butyl 1H‐benzotriazole‐and 1H‐benzimidazole‐5‐carboxylates.