α‐Chymotrypsin–catalyzed direct C (Sp3)–H functionalization reactions for synthesis of azaarene derivatives in water

α‐Chymotrypsin from the bovine pancreas has been shown for the first time to display catalytic nonnatural catalytic ability toward the C (sp³)–H functionalization reaction of 2‐methylquinoline and aromatic aldehydes in water. α‐Chymotrypsin exhibited favorable catalytic activity with good adaptability to different substrates. The activity of the enzyme could be improved by adjusting the solvent, temperature, molar ratio of substrates, and protein loading. The products were obtained in moderate to excellent yields (51%‐93%) in 24 samples. This process afforded a potential biocatalytic approach as an alternative to chemical synthesis for azaarene derivatives.     

Chemo-, regio- and stereospecific addition of adenine and 8-azaadenine to α,β-acetylenic γ-hydroxy nitriles: a short-cut to novel acyclic adenosine analogues

Adenine (9H-purin-6-amine) adds readily to available α,β-acetylenic γ-hydroxy nitriles under mild conditions (molar ratio 1:1, K₂CO₃, DMF, rt, 10 min) to afford chemo-, regio- and stereospecifically (Z)-3-(6-amino-9H-purin-9-yl)-4-hydroxy-4-alkyl-2-alkenenitriles, novel functionalized acyclic nucleoside analogues (95-98% yield). Under similar conditions (K₂CO₃, DMF, rt, 1 h), 8-azaadenine (3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine) reacts with 4-hydroxy-4-methyl-2-pentynenitrile nonselectively at the 7-, 8- and 9-positions to give the corresponding adducts in a 1:10.5:9 ratio, the total yield being 81%. Chemo-, regio- and stereospecific addition of 8-azaadenine to the above α,β-acetylenic γ-hydroxy nitriles leading to (Z)-3-(7-amino-2H-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-4-hydroxy-4-alkyl-2-alkenenitriles in 44-90% yield is attained when the reaction is carried out without solvent in the presence of Et₃N (30 mol %), the molar ratio of 8-azaadenine:α,β-acetylenic nitriles being 1:2.0 (rt, 12-38 h).     

A novel synthesis of new 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile derivatives

New 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitriles are synthesized in good yields, via cyclocondensation of 5-amino-1-(2-oxo-2-arylethyl)-3-(arylamino)-1H-pyrazole-4-carbonitriles, which are prepared by the reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitriles and α-bromoacetophenone derivatives in the presence of K₂CO₃ using acetone as the solvent.     

On triazoles. I. The reaction of N-cyanocarbonimidodithioic acid diesters with hydrazines

The reaction of N-cyanocarbonimidodithioic acid di(alkyl and aralkyl)esters with different alkyl-, aralkyl- and arylhydrazines to yield 1-substituted-3-R-thio-5-amino-1H-1,2,4-triazoles ( 3 ) and 2-substituted-3-R-thio-5-amino-2H-1,2,4-triazoles ( 4 ) was studied. Isolation of the different types of isomeric pairs of 3 and 4 helped to prove the structure of products obtained which made possible correction of some confusion in the literature. The 3 (R = H) tautomeric structure of the non-substituted derivatives was supported by comparison of their uv and cmr spectra with those of the alkylated and aralkylated derivatives 3 and 4 , respectively, again correcting confusion in the literature. An hplc determination of the ratio of products 3 and 4 formed in the above reactions with different hydrazines made it possible to prove the mechanism of the reaction.     

Cu‐Catalyzed Aerobic Oxidative Cyclizations of 3‐N‐Hydroxyamino‐1,2‐propadienes with Alcohols,Thiols, and Amines To Form α‐O‐, S‐, and N‐Substituted 4‐Methylquinoline Derivatives

A one‐pot, two‐step synthesis of α‐O‐, S‐, and N‐substituted 4‐methylquinoline derivatives through Cu‐catalyzed aerobic oxidations of N‐hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N‐hydroxyaminoallenes with NuH (Nu=OH, OR, NHR, and SR) to form 3‐substituted 2‐en‐1‐ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical‐type mechanism rather than a typical nitrone‐intermediate route. The utility of this new Cu‐catalyzed reaction is shown by its applicability to the synthesis of several 2‐amino‐4‐methylquinoline derivatives, which are known to be key precursors to several bioactive molecules.     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

Structural reassignment of the dehydration product of 2′-Hydroxywarfarin

The base catalyzed condensation reaction between 4-hydroxycoumarin and o-hydroxybenzal-acetone yields 6-methyl-6,12-methano-6H,12H,13H-[1]benzopyran[4,3-d][1,3]benzodioxocin-13-one as the product rather than 6-oxo-7-(2-oxopropyl)-6H, 7H-[1]benzopyrano[4,3-b][1]-benzopyran as had been previously postulated.     

One-pot,three-component,catalyst-free synthesis of novel derivatives of pyrido-[2,3-d]pyrimidines under ultrasonic irradiations

Novel derivatives of pyrido-[2,3-d] pyrimidines were synthesized via an efficient and catalyst- free, one-pot, three-component reaction of 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile, 6-amino-(ethylthio)pyrimidine-4(3H)-one, and arylaldehydes under ultrasonic irradiations. This practical method furnished the desired pyridopyrimidines in high yields (79–89%) and short reaction times (25–40 min).     

Choline chloride based eutectic solvent for the efficient synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives via multicomponent reaction under mild conditions

Synthesis of 2-amino-4H-chromen-4-ylphosphonate derivatives has been accomplished by the one-pot three-component reaction of salicylaldehyde, malononitrile/ethylcyanoacetate and dialkyl phosphites in the presence of reusable deep eutectic solvent (DES) under mild conditions. The advantages of this method are mild reaction conditions, simple work-up procedure, use of DES as a green solvent and an economical protocol for the preparation of important biologically active phosphorus-containing compounds.     

2-Amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones. Preparation via a one-pot synthesis of 1-(ω-carboxyalkyl)-4-carbethoxy-2,3-dioxopyrrolidines

1-(ω-Carboxyalkyl)-4-carboethoxy-2,3-dioxopyrrolidines were prepared by a one-pot synthesis from β-alanine or γ-aminobutyric acid, ethyl acrylate and diethyl oxalate. In a second one-pot process these products were hydrolyzed, decarboxylated and condensed with aromatic aldehydes under the influence of hydrochloric acid to yield 1-(ω-carboxyalkyl)-4-arylidene-2,3-dioxo-pyrolidines, which yielded 2-amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)-ones upon treatment with guanidine. It was shown that 3,4-dihydro derivatives of certain 2-amino-4-aryl-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones, formed initially in the guanidine reaction, readily undergo conversion to 5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones.     

Synthesis of new 3<Emphasis Type="Italic">H</Emphasis>-pyrrole derivatives from 3-aryl-2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

8-Amino-3-aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles reacted with acetic anhydride to give different products, depending on the solvent. The reaction in tetrahydrofuran gave the corresponding N-acyl derivatives at the imino group, whereas in pyridine 5-amino-2-morpholin-4-yl-3-(1-aryl-1-oxopropan-2-yl)-3H-pyrrole-3,4-dicarbonitriles were formed as a result of opening of the furan ring.     

Further studies on the structural determination of esters of 4-Oxo-4H-1-heiizopyran-2-carboxylic acids using the paramagnetic shift reagent eu(FOD)3

The effect of Eu(fod)₃ on the signals of benzylic ruethvlene protons in the pmr spectra of 4-oxo-4H-1-benzopyran derivatives is described. Assignments were confirmed by decoupling experiments. The technique provides a method for distinguishing between structural isomers.     

Simple,Catalyst-Free,One-Pot Procedure for the Synthesis of 2-Amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one Derivatives

A one-pot, three-component reaction of 4-hydroxyquinolin-2(1H)-one, malononitrile, and various aldehydes for the synthesis of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives is reported. The reaction is performed without any catalysts in a mixed solvent of water and ethanol to give products in good yields. The present method provided a clean, simple, and economical alternative for the synthesis of potential biologically active pyranoquinoline derivatives.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

New HA 14-1 analogues: synthesis of 2-amino-4-cyano-4H-chromenes

The synthesis of 2-amino-4-cyano-4H-chromene derivatives as new HA 14-1 analogues by a simple and efficient method is reported. In addition, the reaction of 2-amino-2H-chromene-3-carbonitriles, salicylaldehydes and amines results in the formation of new chromeno[2,3-d]pyrimidine derivatives.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1- b ]quinazolin-9-one Derivatives

 A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives.     

Synthesis and Functionalization of 3-Ethylquinoxalin-2(1<Emphasis Type="Italic">H</Emphasis>)-one

A new and effective procedure was developed for the synthesis of 3-ethylquinoxalin-2(1H)-one from o-phenylenediamine and ethyl 2-oxobutanoate. The latter was prepared by the Grignard reaction of diethyl oxalate with ethylmagnesium bromide or iodide. The ethyl group in 3-ethylquinoxalin-2(1H)-one can readily be converted into various functional groups: α-bromoethyl, α-thiocyanato, α-azidoethyl, α-phenylaminoethyl, acetyl, and bromoacetyl. The reaction of 3-(bromoacetyl)quinoxalin-2(1H)-one with thiourea and hydrazine-1,2-dicarbothioamide gives the corresponding 3-(2-amino-4-thiazolyl) derivatives.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 609–616.Original Russian Text Copyright © 2005 by Mamedov, Kalinin, Gubaidullin, Isaikina, Litvinov.     

A facile ZrO<Subscript>2</Subscript> nanoparticles catalyzed synthesis of 2-amino-5-arylpyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>]quinolinediones

In this investigation, an efficient and ecofriendly multicomponent reaction is described for the green synthesis of 2-amino-5-arylpyrimido[4,5-b]quinolinedione derivatives using ZrO₂ (NPs). In this protocol, the reaction of 2,6-diaminopyrimidin-4(1H)-one, arylaldehyde and 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione in the presence of ZrO₂ (NPs) in ethylene glycol at 120 °C produced the desired products in excellent yields (90–98 %) and short reaction times (8–60 min.). Use of recyclable catalyst, green solvent, easy workup and excellent yields are the notable features of this method.     

3-Iodo-4-chalcogen-2H-benzopyran as a convenient precursor for the sonogashira cross-coupling: synthesis of 3-alkynyl-4-chalcogen-2H-benzopyrans

3-Iodo-4-chalcogen-2H-benzopyran derivatives underwent a direct Sonogashira cross-coupling reaction with several terminal alkynes in the presence of a catalytic amount of Pd(PPh₃)₂Cl₂ with CuI as a co-catalyst, using Et₃N as base and solvent. This cross-coupling reaction proceeded cleanly under mild conditions and was performed with propargylic alcohols, propargylic ethers, as well as alkyl and aryl alkynes, furnishing the correspondent 3-alkynyl-4-chalcogen-2H-benzopyrans in good yields.     

Microwave-assisted synthesis and antifungal activity of some new 1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazole derivatives

A number of 3-aryl-4-arylmethylideneamino-4,5-dihydro-1H-1,2,4-triazol-5-ones were synthesized by reaction of the corresponding aromatic aldehydes with 4-amino-3-aryl-1H-1,2,4-triazol-5-ones in anhydrous ethanol under microwave irradiation. The newly synthesized 1H-1,2,4-triazole derivatives were tested for antimicrobial activity. They showed no antibacterial activity but slight mycostatic activity against some Candida species. Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 12, pp. 1843–1847. The text was submitted by the authors in English.     

Choline hydroxide: An efficient and biodegradable catalyst for the synthesis of 2-amino-3-nitro-4H-chromene derivatives in an aqueous medium

Abstract

An expedient, eco-friendly and efficient procedure for the synthesis of novel 2-amino-3-nitro-4H-chromene derivatives has been developed through the reaction of various 2-hydroxybenzaldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine in the presence of the basic ionic liquid catalyst (choline hydroxide (ChOH)) at room temperature an aqueous medium. The advantageous of this method is a biodegradable and recyclable catalyst, mild, environmentally friendly and high products yields (83-96%) in short reaction times.