Diethyl Acetylenedicarboxylate Research Articles

SYNTHESIS OF NEW 1,3-THIAZOLE DERIVATIVES; USING 1-(4-CARBAMOYLPHENYL)-3-METHYLTHIOUREA AND 1-METHYL-3-(QUINOLIN-8-YL) THIOUREA AS STARTING MATERIALS

ABSTRACT A series of novel 1,3-thiazoles have been synthesized in good yields, using dialkyl acetylenedicarboxylate, benzamide and quinoline derivatives of thiourea in ethanol. Keywords: Thiourea, dimethyl acetylene dicarboxylate, diethyl acetylene dicarboxylate, thiazoline. e-mail: etavakoly@yahoo.com 1. INTRODUCTION Since the past few decades, heterocyclic chemistry has been one of the most important disciplines in organic synthesis and pharmaceutical chemistry 1 . A large numbers of these compounds have emerged as active pharmaceutical ingredients in several drugs for their potential anti-inflammatory 2,3 , anti-tumor 4 , anti-hyperlipidemic 5 , anti-hypertensive 6 , anti-HIV infections 7 , and several other biological properties 8,9 .One of the most important groups of five-membered heterocycles including S and N atoms, are thiazolole compounds. Thiazole heterocycle is a component of many natural products and synthetic compounds exhibiting a wide range of biological activity 10-13 . The pharmacological activities and their coordination properties are important features to prepare metal complexes with potential therapeutical activity or as model of metal-enzyme

ChemInform Abstract: Facile Synthesis of 4‐Quinolone Derivatives via One‐Pot Cascade Reaction under Transition‐Metal‐Free Conditions.

Abstract A practical and efficient strategy has been described for the preparation of 4-quinolone derivatives. Using commercially available diethyl acetylenedicarboxylate and aromatic amines as starting materials, the synthetic protocol has been achieved and afforded the product via hydroamination at room temperature followed by PPA-catalyzed intramolecular ring closure. The products can be easily obtained in high yields. Conditions and mechanism of the reaction have also been investigated. This protocol is environmentally friendly and transition-metal-free, with advantages including short reaction time, convenient operation, and mild reaction conditions.

ChemInform Abstract: Hydroamination Reactions of Alkynes with ortho‐Substituted Anilines in Ball Mills: Synthesis of Benzannulated N‐Heterocycles by a Cascade Reaction.

AbstractOrtho‐substituted anilines (I) undergo hydroamination reactions with diethyl acetylenedicarboxylate in a planetary ball mill.

ChemInform Abstract: ZnO Nanoparticles as an Efficient Catalyst for the Selective Synthesis of 4‐Hydroxychromenes via the Reaction of Salicylaldehydes with Dimethyl or Diethyl Acetylenedicarboxylate in [bmim]BF4.

ZnO nanoparticles as a highly effective heterogeneous base catalyst selectively catalyzes the reaction between salicylaldehydes and dialkyl acetylenedicarboxylates in ionic liquid [bmim]BF4 to obtain 4-hydroxy-4H-chromenes in high to excellent yields. The advantages of this method include the selectivity of reaction, one-pot procedure, mild reaction conditions, operational simplicity, and use of inexpensive and non-toxic catalyst. .

Mechanistic investigation of the reaction of thiourea with dialkyl acetylenedicarboxylates: a theoretical study

In this work, mechanistic investigation of the addition–cyclization reaction between thiourea (TU) and dialkyl acetylenedicarboxylate (DAAD) was made theoretically with the B3LYP method using a 6-311++G(2d,2p) basis set. In order to investigate the effect of substituted alkyl groups, the reaction was evaluated in the presence of dimethyl acetylenedicarboxylate, diethyl acetylenedicarboxylate and di-tert-butyl acetylenedicarboxylate. To evaluate the effect of structure and dielectric constant of the solvent, all structures were optimized in different solvent phases such as dichloromethane and acetone at the B3LYP/6-311++G(2d,2p) level of theory. Different orientations of alkyl groups make different kinetic paths. Results indicated that the reaction mechanism did not change with different orientations of COOMe, COOEt or COOtBu groups, but caused significant changes in the potential energy surfaces of the reaction coordinate. The reaction product (alkyl E-2-(2-imino-4-oxo-1,3-thiazolane-5-yliden) acetates) can be converted to different tautomeric forms in two proton transfer processes. So, in order to investigate the effect of different substituted alkyl groups, intermolecular proton transfer in the product was investigated both in gas phase and in the presence of methanol, ethanol and tert-butanol molecules as a bridge to facilitate the proton transfer process.

Facile synthesis of 4-quinolone derivatives via one-pot cascade reaction under transition-metal-free conditions

A practical and efficient strategy has been described for the preparation of 4-quinolone derivatives. Using commercially available diethyl acetylenedicarboxylate and aromatic amines as starting materials, the synthetic protocol has been achieved and afforded the product via hydroamination at room temperature followed by PPA-catalyzed intramolecular ring closure. The products can be easily obtained in high yields. Conditions and mechanism of the reaction have also been investigated. This protocol is environmentally friendly and transition-metal-free, with advantages including short reaction time, convenient operation, and mild reaction conditions.

Synthesis and the hypoglycemic activity of pyrazolidene-3-carboxylic acids and their derivatives exo-functionalized with the hydrazinilidene-1,3-thiazolidine fragment

It has been shown that 4- formylpyrazole-3-carboxylic acids and their ethyl esters interact selectively with thiosemicarbazide and its N4-aryl-derivatives in boiling acetic acid with formation of the corresponding 4-pyrazolylthiosemicarbazones with the yields of 76-91%. It has been found that heating of 4-pyrazolylthiosemicarbazones with diethyl acetylenedicarboxylate in boiling ethanol for 3 hours leads to formation of 1,3-thiazolidine-containing polyfunctional pyrazole derivatives with yields of 73-95%. Formation of compounds of this type indicates that the process occurs according to the scheme of the primary attack of a highly electrophilic triple bond of acetylenedicarboxylate by the nucleophilic atom of sulfur of the thiosemicarbazone fragment with subsequent intramolecular condensation, which leads to formation of the 4-oxo-1,3-thiazolidine-5-ilidene cycle. The structure of the 1,3-thiazolidinilidenehydrazonepyrazoles synthesized has been proven by a complex of spectral methods; the most informative of them are 13C NMR spectra with signals of carbon atoms of the thiazolidine cycle: C4 (159-161 ppm), C2 (162-165 ppm), C5 (163-165 ppm), as well as of the exo-cyclic ethoxycarbonylethylidene fragment: HC= (114-118 ppm); and of C(O) O (165 ppm). It has been determined that the compounds synthesized cause the hypoglycemic dose-dependent effect in mice, which is much more potent than the same effect of the reference medicine – pioglitazone.

Hydroamination reactions of alkynes with ortho-substituted anilines in ball mills: synthesis of benzannulated N-heterocycles by a cascade reaction.

It was demonstrated that ortho-substituted anilines are prone to undergo hydroamination reactions with diethyl acetylenedicarboxylate in a planetary ball mill. A sequential coupling of the intermolecular hydroamination reaction with intramolecular ring closure was utilized for the syntheses of benzooxazines, quinoxalines, and benzothiazines from readily available building blocks, that is, electrophilic alkynes and anilines with OH, NH, or SH groups in the ortho position. For the heterocycle formation, it was shown that several stress conditions were able to initiate the reaction in the solid state. Processing in a ball mill seemed to be advantageous over comminution with mortar and pestle with respect to process control. In the latter case, significant postreaction modification occurred during solid-state analysis. Cryogenic milling proved to have an adverse effect on the molecular transformation of the reagents.

Chemoenzymatic synthesis of a 1,2,3-triazolo- δ-lactone derivative

Abstract The stereoselective synthesis of a 1,2,3-triazolo-δ-lactone (+)-6 derived from a homoallyl alcohol (S)-(-)-1 backbone was accomplished. 2-Thienyl-substituted allyl alcohol rac-1 was efficiently resolved through enzymatic method with high ee (95%) and known stereochemistry. An enantiomerically enriched azidoalcohol (+)-4 derived from a homoallyl alcohol was subjected to the Huisgen 1,3-dipolar cycloaddition reaction with diethyl acetylenedicarboxylate, followed by intramolecular cyclization of the corresponding cycloadduct (+)-5, to yield the 1,2,3-triazolo-δ-lactone derivative.

ChemInform Abstract: Uncapped SnO2 Quantum Dot Catalyzed Cascade Assembling of Four Components: A Rapid and Green Approach to the Pyrano[2,3‐c]pyrazole and Spiro‐2‐oxindole Derivatives.

AbstractNumerous combinations of ethyl acetoacetate (I), diethyl acetylenedicarboxylate (IX) or the methyl carboxylate derivative of (IX) with hydrazine or aryl hydrazines (V), malononitrile (III) or methyl cyanoacetate (VII) and aldehydes (II) or analogues thereof are applied to the reaction.

Facile, Diversity-Oriented, Normal-Electron-Demand Diels–Alder Reactions of 6-Amino-2H-pyran-2-ones with Diethyl Acetylene­dicarboxylate, 1,4-Naphthoquinone, and N-Phenylmaleimide

A series of 6-amino-4-methoxyphenyl-2 H -pyran-2-ones, having an electron-rich diene system, capable of undergoing normal-electron-demand (NED) Diels–Alder reaction, were synthesized. The Diels–Alder reaction of these pyrones with electron-deficient dienophiles – diethyl acetylene dicarboxylate, 1,4-naphthoquinone, and N -phenylmaleimide – followed three different pathways and gave structurally diverse products, aminobenzenes, aminoanthraquinones, and aminopolycyclic diimides, respectively. The amino group at the 6-position activated substantially the pyrone ring towards NED Diels–Alder reaction and the reaction has a potential to generate great structural diversity.

ZnO nanoparticles as an efficient catalyst for the selective synthesis of 4-hydroxychromenes via the reaction of salicylaldehydes with dimethyl or diethyl acetylenedicarboxylate in [bmim]BF4

ZnO nanoparticles as a highly effective heterogeneous base catalyst selectively catalyzes the reaction between salicylaldehydes and dialkyl acetylenedicarboxylates in ionic liquid [bmim]BF4 to obtain 4-hydroxy-4H-chromenes in high to excellent yields. The advantages of this method include the selectivity of reaction, one-pot procedure, mild reaction conditions, operational simplicity, and use of inexpensive and non-toxic catalyst. .

Catalyst‐Free One‐Pot Synthesis of Ketene Imines under Ultrasound Irradiation

AbstractAn efficient and simple procedure for the synthesis of ketene imines via a one‐pot three‐component reaction of cyclohexyl isocyanide, diethyl acetylenedicarboxylate, and 1,4‐dihydropyridines under ultrasonic irradiation is described. The remarkable advantages are the simplicity of the experimental procedures, high yields, and short reaction times.

3,4,5-Trisubstituted Furan-2(5H)-one Derivatives: Efficient one-pot Synthesis and Evaluation of Cytotoxic Activity.

A series of 3,4,5-trisubstituted 2(5H)-furanone derivatives was synthesized through one-pot reaction of amines, aldehydes and diethyl acetylenedicarboxylate. Silica sulfuric acid efficiently catalyzes the 3-component reaction to afford the corresponding 2(5H)-furanones in high yields. The synthesized compounds were tested against HEPG2, MCF7 and CACO tumor cell lines. The cytotoxic activity for the tested compounds showed that: ethyl 2-(4-fluorophenyl)-5-oxo-4-(phenylamino)-2,5-dihydrofuran-3-carboxylate exhibited significant antitumor activity against HEPG2 and MCF7 cell lines (IC50 values 0.002 and 0.002 µM, respectively) more than reference drug (IC50 0.007, 0.005 µM).

ChemInform Abstract: Recyclable, Graphite‐Catalyzed, Four‐Component Synthesis of Functionalized Pyrroles.

Abstract A facile, convenient, and multicomponent coupling strategy for the synthesis of highly functionalized pyrroles is developed using graphite as a catalyst, but devoid of moisture-sensitive metal catalysts and corrosive acidic reagents. This method involves four-component coupling reactions of ethyl acetoacetate compound or diethyl acetylene dicarboxylate, amines, aromatic aldehydes, and nitromethane without an inert atmosphere. This approach provides easy access to highly substituted pyrroles in good yields via one-pot tandem reaction. The method is very simple, straightforward, and environmentally friendly compared to the existing methods. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Iridium(I) complexes bearing the (S,S)-iPr-pybox ligand in the asymmetric transfer hydrogenation of acetophenone

The complex [Ir(η2-EtO2CCCCO2Et)2{κ3-N,N,N-(S,S)-iPr-pybox}][PF6] ((S,S)-iPr-pybox=2,6-bis[4′-(S)-isopropyloxazolin-2′-yl]pyridine) (2) has been synthesized from the complex [Ir(η2-C2H4)2{κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (1) by substitution of both ethylene ligands by two diethyl acetylenedicarboxylate ligands. Iridium(III) complexes have been obtained from the complexes [Ir(η2-C2H4)2{κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (1) and [Ir(η2-RCCR)2{κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (R=CO2Et (2), CO2Me (3)) by oxidative addition reactions. Thus, the addition of PhICl2 and Br2 to the iridium(I) complex 1 provides the iridium(III) complexes [IrCl2(η2-C2H4){κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (4) and [IrBr(η1-CH2CH2Br)(η2-C2H4){κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (5), respectively. The structure of the complex 5 has been determined by single-crystal X-ray diffraction analysis. The treatment of complexes 3 and 2 with I2 and allyl chloride results in the stereoselective formation of the iridium(III) complexes [IrI2(η2-MeO2CCCCO2Me){κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (6) and [IrCl(η1-CH2CHCH2)(η2-EtO2CCCCO2Et){κ3-N,N,N-(S,S)-iPr-pybox}][PF6] (7), respectively. The catalytic activity of the iridium(I) complexes 2 and 3 in transfer hydrogenation of acetophenone has been examined.

ChemInform Abstract: Ultrasound‐Assisted Synthesis of Highly Functionalized Cyclopentadienes via an Isocyanide‐Based Three‐Component Reaction.

This report provides a description of an efficient and simple procedure for the synthesis of substituted cyclopentadienes via a one-pot three-component reaction of cyclohexyl isocyanide, diethyl acetylenedicarboxylate and (arylmethylidene)malononitriles in H2O under ultrasonic irradiation. The remarkable advantages are the simplicity of the experimental procedures, high yields, short reaction times, and avoidance of organic solvents.

Recyclable, Graphite-Catalyzed, Four-Component Synthesis of Functionalized Pyrroles

A facile, convenient, and multicomponent coupling strategy for the synthesis of highly functionalized pyrroles is developed using graphite as a catalyst, but devoid of moisture-sensitive metal catalysts and corrosive acidic reagents. This method involves four-component coupling reactions of ethyl acetoacetate compound or diethyl acetylene dicarboxylate, amines, aromatic aldehydes, and nitromethane without an inert atmosphere. This approach provides easy access to highly substituted pyrroles in good yields via one-pot tandem reaction. The method is very simple, straightforward, and environmentally friendly compared to the existing methods. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Synthesis of Novel Highly Functionalized 4-Thiazolidinone Derivatives from 4-Phenyl-3-thiosemicarbazones

We present herein the synthesis in good yields of two series of highly functionalized thiazolidinone derivatives from the reactions of various 4-phenyl-3-thio-semicarbazones with ethyl 2-bromoacetate and diethyl acetylenedicarboxylate, respectively.

Si-OSO3H catalyzed one-pot three-component synthesis of 1,3-oxazines

A simple and an efficient method for the synthesis of six membered nitrogen containing heterocyclic compounds—1,3-oxazines from diethyl acetylene dicarboxylate, substituted anilines or amines and formaldehyde is reported. A versatile, economical and eco-friendly heterogeneous reagent silica sulfuric acid (Si-OSO3H) is used as a catalyst for this reaction.