Green synthesis of ethyl oxalate benzylidinyl hydrazides

Acylhydrazone compounds play an important role in medicine, materials and other fields. Herein we report the synthesis of ethyl oxalate benzylidinyl hydrazides by the reaction of benzaldehyde derivatives and ethyl oxalate hydrazide under catalyst-free conditions in H₂O near room temperature. This green synthesis method has the advantages of mild reaction conditions, fast reaction rate, non-catalytic, good yield and easy isolation. These synthesized ethyl oxalate benzylidinyl hydrazides can be used as Schiff base metal complexes of small molecule ligands.     

The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂/CH₂(COOEt)₂.     

Application of Sulfonic Acid Functionalized SBA‐15 as a New Nanoporous Acid Catalyst in the Green One‐Pot Synthesis of Spirooxindole‐4H‐pyrans

Sulfonic acid functionalized SBA‐15 (SBA‐Pr‐SO₃H) as a new nanoporous solid acid catalyst was applied in the green one‐pot synthesis of spirooxindole‐4H‐pyrans via condensation of isatins, malononitrile or methyl cyanoacetate or ethyl cyanoacetate, and 4‐hydroxycoumarin in water solvent. SBA‐Pr‐SO₃H was proved to be an efficient heterogeneous nanoporous solid acid catalyst with a pore size of 6 nm that could be easily handled and removed from the reaction mixture by simple filtration and can be recovered and reused for several times without any loss of activity. The significant merits of present methodology are its simplicity, short reaction time, good yields, and environmentally benign mild reaction condition as water was used as a green solvent.     

Facile preparation of aromatic esters from aromatic bromides with ethyl formate or DMF and molecular iodine via aryllithium

Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K₂CO₃ to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K₂CO₃. Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K₂CO₃. The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.     

Synthesis of γ-N-acylamino-β-keto esters and ethyl 5-oxazoleacetates via Ritter reaction and hydration of γ-hydroxy-α,β-alkynoic esters

The classical Ritter reaction on γ-hydroxy-α,β-alkynoic esters produced γ-N-acylamino-β-keto esters or ethyl 5-oxazoleacetates using alkyl or aryl nitriles, respectively. The γ-N-acylamino-β-keto esters resulting from alkyl nitriles are useful intermediates in the synthesis of a variety of building blocks. We also show that these can be converted into ethyl 5-oxazoleacetates using an additional step involving POCl₃.     

Ester der Imidodiphosphorsäure

Imidodiphosphoric Acid Esters Imidodiphosphoryl tetrachloride reacts with aliphatic alcohols (C₁–C₃) as well as with sodium phenolate to form tetraalkylesters or tetraphenylesters of the imidodiphosphoric acid, resp. The tetraalkylesters (alkyl = methyl, ethyl, n-propyl) are also formed by reaction of trichlorphosphazene phosphoryldichloride, Cl₃P?N? POCl₂, with the corresponding alcohols. The purification of the esters can be reached by destillation of their silyl derivatives followed by desilylation. The esters are associated by intermolecular O…?H…?O hydrogen bonds.     

Convenient Synthesis of 2-Aminothiophene Derivatives by Acceleration of Gewald Reaction Under Ultrasonic Aqueous Conditions

Under ultrasound irradiation and in the presence of H₂O/Et₂NH, ethyl cyanoacetate or malononitrile can combine with α-methylene carbonyl compounds and elemental sulfur to efficiently yield 2-aminothiophene derivatives within a few minutes. Products are easily obtained by simple filtration because of their spontaneous precipitation in the reaction mixtures.     

Amide-Bond Syntheses Catalyzed by Penicillin Acylase

The enzymatic synthesis of amide bonds catalyzed by penicillin acylase is investigated both in H₂O solution and in organic solvents containing reverse micelles. The specificity of the reaction is rather high on the side of the acyl component, practically only phenylacetic acid gives sizeable yields. On the contrary, a variety of amino-acid esters, dipeptides, and tripeptides can be used as amino component, e.g., serine methyl ester, methionine ethyl ester, tyrosine ethyl ester, Gly–Asp, Ala–Tyr, Gly–Tyr–Gly etc. However, Many other amino-acid residues do not react, and the possible reasons for this are discussed. Yields varyin rang the 10–80%. A. systematic study to optimize yields by varying the solvent composition is presented for one model reaction. The enzyme is also able to couple certain D-amino-acid residues (e.g. D-methionine ethyl ester or Gly-D -Asp) though at lower rate. Reverse micelles formed by the cationic surfactant cetyltrimethylammonium bromide (CTAB) in CHCl₃/isooctane are used to host penicillin acylase and to perform amide synthesis in which the product is perferentially soluble in the organic solvent mixture. The reaction is studied as a function of pH and certain micellar parameters, e. g. w_o (w_o = [H₂O]/[CTAB]). A new membrane enzyme reactor is utilized to separate the product from the enzyme-containing micelles. The adavantges and the limits of this approach are discussed.     

Polybromoaromatic Compounds: IX. Reactions of Polybromobenzyl Bromides with Enolates Derived from Some Dicarbonyl Compounds

The reaction of polybromobenzyl bromides RC₆Br₄CH₂Br (R = Br, OCH₃) with diethyl malonate sodium salt in ethanol and dimethylformamide leads to formation of diethyl 2-(polybromobenzyl)malonates, whereas in aqueous ethanol ethyl polybromobenzyl malonates are formed. The same polybromobenzyl bromides react with an equimolar amount of ethyl acetoacetate sodium salt or acetylacetone sodium salt to give C-alkylation products; with excess sodium enolates ethyl 3-(polybromophenyl)propionates and 4-(polybromophenyl)-2-butanones are formed, respectively.     

Diastereoselective Aldol Addition Using Boron Trichloride or Alkoxydichloroborane

Under carefully controlled conditions, boron trichloride or alkoxydichloroborane/ethyldiisopropylamine in CH₂Cl₂ can be used to effect diastereoselective aldol additions of ethyl ketones to saturated, α, β-unsaturated, or aromatic aldehydes. The C? C bond formation takes place with relative topicity ul (‘syn,’ configuration of the aldols), in selectivities ranging from 90 to 99% ds (Tables 1–3). Mechanistic aspects of the reaction are discussed.     

Synthesis and Some Reactions of Quinoxalinecarboazides

Chlorination of ethyl(quinoxalin‐2(1H)one)‐3‐carboxylate 1 gave ethyl (2‐chloroquinoxaline)‐3‐carboxylate 2 ;thionation of 1 by P₂S₅ or 2 by thiourea yielded the same product 3 . Reaction of chloro compound 2 or thiocompound 3 with hydrazine hydrate gave pyrazolylquinoxaline 4 . The reaction of ester 1 with thiourea or hydrazine hydrate afforded pyrimido quinoxaline 5 or carbohydrazide 6 ; the reaction of 6 with carbon disulfide in basic medium followed by alkylation afforded oxadiazoloquinoxaline derivatives 7, 8a,b . Carboazide 9 was produced by reaction of 5 with nitrous acid. Compound 9 on heating in an inert solvent, with or without amines, in alcohols or hydrolysis in H₂O undergoes Curtius rearrangments to yield 10‐13 . Reaction of 13 with thiosemicarbazide gave triazoloquinoxaline 14 which on reaction with alkylhalides or hydrazine hydrate yielded 15a‐c while hydrolysis of 13 gave 3‐aminoquinoxalinone 16 which was used as an intermediate to produce 17‐20 .     

Mild preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives with magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under ambient and solvent-free conditions

An efficient, one-pot quantitative procedure for preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives from four-component condensation reaction of hydrazine monohydrate, phthalic anhydride, malononitrile or ethyl cyanoacetate, and aromatic aldehydes in the presence of magnetic Fe₃O₄ nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under mild, ambient, and solvent-free conditions is described. Simple procedure, high yield, short reaction time, and environmentally benign method are advantages of this protocol. The magnetic Fe₃O₄ nanoparticles coated by (3-aminopropyl)-triethoxysilane can be recovered and reused several times without loss of activity.     

Heck arylations of pent-4-enoates or allylmalonate using a palladium/tetraphosphine catalyst

The Heck reaction of aryl halides with functionalised alk-1-enes should be a powerful method for the synthesis of functionalised (E)-1-arylalk-1-ene derivatives. The major problem of this reaction is the palladium-catalysed migration of the carbon-carbon double bond along the alkyl chain when there are no substituents on the C3 carbon of the alk-1-enes. We observed that for the arylation of ethyl pent-4-enoate, ethyl 2-methylpent-4-enoate or dimethyl allylmalonate this migration could be partially or completely controlled using appropriate reaction conditions. The ramification on the alkyl chain and the substituents on the aryl halide have also an important influence on this migration. Moreover, the cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/1/2[PdCl(C₃H₅)]₂ system catalyses this reaction with a wide range of aryl bromides using very high ratio substrate/catalyst in good yields.     

Low-Temperature Reactions of α-Bromopropanoyl Chloride with Lithium Derivative of Ethyl Acetate

The reaction of 2-bromopropanoyl chloride with lithium ethyl acetate generated in situ by the reaction of equimolar amounts of lithium diisopropylamide with ethyl acetate forms, depending on the conditions (temperature, time, reagent ratio), diethyl 2,2′-(3-methyloxirane-2,2-diyl)diacetate, 2,2-dibromo-N,N-diisopropylpropanamide, and ethyl (5-methyl-4-oxo-4,5-dihydrofuran-2-yl)acetate as minor by-products along with the expected acylation product ethyl 4-bromo-3-oxopentanoate. The reaction with 2 or 5 equiv of lithium ethyl acetate (–78°C → –20°C) gave, together with the mentioned α-bromo ester, ethyl (5-methyl-4-oxo-4,5-dihydrofuran-2-yl)acetate formed as a result of transformations of the adduct of the second LiCH₂CO₂Et molecule and ethyl-4-bromo-3-oxopentanoate. The reaction 2-bromopropanoyl chloride with sodium malonic ester involves acylation of enol form of the primary expected acylation product to afford dimethyl |2-bromo-1-[(2-bromopropanoyl)oxy]propylidene-malonate.

     

Significant Heterogeneous Carbonate Salt Catalyzed Acetylation of Alcohols via a Transesterification Process with Carbonate Salt‐activated Alcohol 1H NMR Evidence

Heterogeneous carbonate salt catalyzed acetylation of alcohols via a transesterification process has been developed. Various esters are furnished up to 97% yield. Established procedure is simple and air‐tolerant with readily available reagents. Ethyl acetate and isobutyl acetate are used as not only acetylating agents, but also reaction solvents in transesterification. Aliphatic linear alcohols, allylic alcohols and benzyl alcohols show high reactivities in the presence of 1 or 5 mol% Cs₂CO₃ at 125°C. Cesium carbonate can be recycled by pumping liquid phase out of reactor after reaction. During four cycle runs for reaction of 2‐phenylethanol and ethyl acetate, high yields of phenethyl acetate are provided (>60% yield). Based on experiments and ¹H NMR investigation, bifunctional catalysis is proposed, alcohol activated by carbonate ion is confirmed, and higher activity of catalytic amount than stoichiometric cesium carbonate is interpreted.     

Efficient four‐component synthesis of spiroindole derivatives catalysed by a versatile and reusable nano‐paramagnetic catalyst

A simple, efficient and environmentally benign route was developed for the preparation of spiro(indoline‐3,4‐pyrano[2,3‐c ]pyrazole) derivatives with good yields from condensation of isatins, malononitrile (or ethyl cyanoacetate), hydrazine hydrate and ethyl acetoacetate catalysed by PFu@Fe₃O₄ nanocomposite. The use of easily available catalyst, shorter reaction times, better yields, simplicity of reaction, heterogeneous system and easy work‐up are the advantages of the method presented. Characterization of the catalyst was performed using Fourier transform infrared spectroscopy, X‐ray diffraction and transmission electron microscopy.     

Hydrolysis of new phthalimide-derived esters catalyzed by immobilized lipase

The last step of the production of four phthalimide-derived acids, designed to act as antiasthma drugs, was performed by enzymatic hydrolysis of the respective methyl or ethyl esters. The esters 4-ethyl-[2-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)]-phenoxyacetic methyl ester (PHT-MET), 4-ethyl-[2-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)]-phenoxyacetic ethyl ester, 4-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester, and 2-(1,3-dioxo-1, 3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester were hydrolyzed by immobilized lipase. The enzymatic reaction could be used only to produce the desired 4-substituted compounds. The best result that was found to hydrolysis of PHT-MET, and, therefore, that ester was selected for optimization experiments in a three-phase system. Reactions were performed with solid biocatalyst (Lipozyme® RM IM), organic solvent phase (ethyl acetate), and aqueous phase (saturated Na₂CO₃ solution). To optimize the reaction conditions, an experimental design optimization procedure was used. The variables studied were the amount of enzyme, the temperature, and the volume of the aqueous solution. Time course experiments were then performed for different initial enzyme concentrations (0.5, 0.9, and 1.4 U_H/mL of solvent). The optimized reaction conditions found were 20 mg of Lipozyme (0.9 U_H/mL_solvent) and 5.0 mL of Na₂CO_3(sat) at 40°C for 6 h.     

Alternating ethylene–alkyl acrylate copolymers. I. polymer preparation

High molecular weight alternating ethylene–ethyl acrylate copolymers were prepared by using boron trifluoride to complex the acrylate ester. The polymerizations were run under mild conditions (25–50°C, 6–20 atm ethylene) in dichloromethane or dichloroethane solution with free-radical initiation. At lower ethylene pressures or at less than stoichiometric levels of BF₃, the polymers are acrylate-rich. This is due to ethyl acrylate homopolymerization competing with the copolymerization reaction. The effect of other polymerization variables is also discussed.     

Volume Nonadditivity of Liquid Mixtures: Modifications to Classical Demonstrations

Departures from Raoults law are often found in liquid mixtures resulting in volume nonadditivity. Modifications are proposed for experiments demonstrating volume contraction of water/ethanol and volume expansion of ethyl acetate/carbon disulfide liquid mixtures. A layer of paraffin oil or water is used to prevent mixing of the liquids at an earlier stage then desired. A demonstration of volume expansion in a CS₂/ethyl acetate system is proposed as well. The modifications significantly improve the ease of the demonstrations, which can be made even more impressive by coloring the liquids. A reaction vessel of simple construction is offered for a more vivid demonstration of the phenomenon.     

Synthesis of N,N-bis[2-(2-pyridyl)ethyl]amino steroids and related compounds intended as chiral ligands for copper ions

Compounds with the N,N-bis[2-(2-pyridyl)ethyl]amino structure (RPY2) are useful tridentate ligands for copper(I) ions, which can bind and activate oxygen from the atmosphere. For diastereoselective and enantioselective oxidation reactions, hitherto unknown chiral ligands possessing tripodal structures have been synthesized starting from homochiral steroids. The double Michael addition of primary steroidal amines and aminoalcohols to 2-vinyl pyridine was not very succesful. However, homochiral bidentate ligands with N-[2-(2-pyridyl)ethyl]amino steroid structure could be obtained by this procedure in most cases. New routes (acylation of the bidentate ligands with 2-pyridylacetic acid followed by BH₃·THF reduction, or reductive amination of steroidal ketones, acylation and borane reduction) to the desired tridentate RPY2, also at sterically hindered positions, are described. In the last reaction sequence, ‘mixed’ tridentate ligands can also be obtained. Copper complexation and oxygen activation with these ligands are briefly discussed.