Michael Addition Of Ethyl Acetoacetate Research Articles

Michael addition of ethyl acetoacetate on dibenzylideneacetone derivatives: Synthesis, spectroscopy, antimicrobial and in silico studies

A series of trisubstituted cyclohexenones incorporating a styryl framework were synthesized by Michael addition reaction of ethyl acetoacetate onto dibenzylideneacetone derivatives. The reaction was carried out in ethanol in the presence of piperidine as a basic catalyst. The cyclocondensation starts with a 1,4-Michael addition of ethyl acetoacetate on only one ethylenic bond of the Michael acceptors, followed by an intramolecular cyclization of the Michael adduct to form the corresponding cyclohexenones. The structures of the synthesized products were established based on the IR, (1H & 13C) NMR, and HRMS spectral data. The in vitro evaluation of the antimicrobial effect of the synthesized compounds was tested against B. subtilis, S. aureus, C. albicans, and P. mirabilis strains. In silico studies, including molecular docking, ADMET predictions, and molecular dynamics simulations, were additionally performed to correlate observed and computed outcomes of the biological screening, providing further insights into the compounds' potential efficacy.

Synthesis of nonracemic polysubstituted cyclohexanes through cascade reactions of (2R,3S)-2-Acetyl-3-aryl-4-nitrobutanoates, adducts of Ni(II)-catalyzed michael addition

Stereoselective synthesis of ethyl-4,6-diaryl-2-hydroxy-2-methyl-5-nitro-3-formylcyclohexanecarboxylates was described. The formation of the asymmetric site of the required configuration is achieved by an enantioselective Michael addition of ethyl acetoacetate to nitroalkenes in the presence of a chiral Ni(II) complex with (R,R)-N,N′-dibenzylcyclohexane-1,2-diamine. Further reaction of the products obtained with cinnamic aldehyde led to the formation of polysubstituted cyclohexanes.

Synthesis of Novel Fluorescent Cyclohexenone Derivatives and their Partitioning Study in Ionic Micellar Media

An approach is demonstrated toward the synthesis of four novel cyclohexenone derivatives (CDs) via a convenient route of Michael addition of ethyl acetoacetate. The molecular structures of CDs were confirmed by means of FT-IR, (1)H NMR, EIMS, UV and also by X-ray single crystal structure analysis. CDs are strongly fluorescent compounds and their fluorescent spectra exhibits intense violet fluorescence. To model the binding to biological membranes the behavior of CDs in micellar solutions of a cationic surfactant, cetyltrimethylammonium bromide (CTAB) and an anionic surfactant, sodium dodecylsulfate (SDS) has also been examined. The characteristics of partition and binding interactions of CDs with CTAB and SDS were investigated by UV-Visible and fluorescence spectroscopic techniques. Higher values of all mentioned interactions in case of CTAB, compared to SDS, indicate that there are greater interactions between the CDs and CTAB than with SDS.

A study of the sequential Michael addition-ring closure reaction of ethyl acetoacetate with chalcone: influence of quaternary ammonium cations as phase transfer catalysts

The Michael addition of ethyl acetoacetate 1 to chalcone 2 under Solid/Liquid Phase Transfer Catalysis (SL-PTC), solvent free, afforded Michael adduct 3 and an annulated compound 4 in good yield. The cyclic compound 4 was obtained in the majority via an annulation process of the Michael adduct 3. The proportion of 4 in the ratio of 3/4 was dependant on the structure of the quaternary ammonium cation. The results were interpreted on the basis of the organophilicity and accessibility of the catalysts as well as by invoking a 6-membered ring transition state for the formation of 4 due to the chelation level with Q+.

Enantioselective Synthesis and Absolute Stereochemistry of Both the Enantiomers of trans‐Magnolione, a Fragrance Structurally Related to trans‐Methyl Jasmonate.

Abstract Both enantiomers of the trans stereoisomer of magnolione 4 have been prepared by asymmetric Michael addition of ethyl acetoacetate to 2-pentylcyclopentenone, followed by hydrolysis/decarboxylation. The Michael reaction occurs under solid/liquid phase transfer catalysis in the presence of N -methylanthracenylquininium (or quinidinium) chloride. Enantiomeric excesses up to 76% are obtained. The trans structure of the compounds has been fully established by a careful NMR analysis, while the absolute configuration has been assigned as (2 S ,3 S ) for (+)- 4 by the analysis of the CD spectrum.

Enantioselective synthesis and absolute stereochemistry of both the enantiomers of trans-magnolione, a fragrance structurally related to trans-methyl jasmonate

Both enantiomers of the trans stereoisomer of magnolione 4 have been prepared by asymmetric Michael addition of ethyl acetoacetate to 2-pentylcyclopentenone, followed by hydrolysis/decarboxylation. The Michael reaction occurs under solid/liquid phase transfer catalysis in the presence of N-methylanthracenylquininium (or quinidinium) chloride. Enantiomeric excesses up to 76% are obtained. The trans structure of the compounds has been fully established by a careful NMR analysis, while the absolute configuration has been assigned as (2 S,3 S) for (+)- 4 by the analysis of the CD spectrum.

ChemInform Abstract: Michael Addition of Ethyl Acetoacetate to α,β‐Unsaturated Oximes in the Presence of FeCl3: A Novel Synthetic Route to Substituted Nicotinic Acid Derivatives.

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Michael addition of ethyl acetoacetate to α,β-unsaturated oximes in the presence of FeCl 3: a novel synthetic route to substituted nicotinic acid derivatives

The FeCl 3-catalyzed reaction of α,β-unsaturated oximes with ethyl acetoacetate resulted in Michael addition followed by ring closure to produce substituted nicotinic acid derivatives in a very efficient way.

Microwave Assisted Michael Addition of Cycloalkenones and Substituted Enones on the Surface of Alumina in Dry Media

The Michael addition of ethyl acetoacetate, acetyl acetone and ethyl cyanoacetate to cycloalkenones and β -substituted enones and enal has been accomplished efficiently on the surface of alumina under microwave irradiation in dry media.

Electrophilic substitution in indoles. Part 19. Facile syntheses of the 2a,5a-diazacyclopenta[j,k]fluorene, indolo[2,3-a]quinolizinone and aspidosperma alkaloid ring systems from N-acyltryptamines

Reaction of tryptamine with diketene gave N-[2-(1H-indol-3-yl)ethyl]-3-oxobutyramide (80%) which with phosphoryl chloride in dichloromethane gave (9bS*, 9cS*)-1,2,9b,9c-tetrahydro-5-methyl-2a,5a-diazacyclopenta[j,k]fluoren-3-one 13(73%). Hydrogenation gave the 4,5-dihydro and perhydro derivatives. Michael addition of ethyl acetoacetate to benzyl acrylate gave 5-benzyl 1-ethyl 2-acetylpentanedioate (57%) which was hydrogenolysed to 4-ethoxycarbonyl-5-oxohexanoic acid (100%), the mixed anhydride of which condensed with tryptamine to give 4-ethoxycarbonyl-N-[2-(1H-indol-3-yl)ethyl]-5-oxohexanamide 19(78%). The latter, with trifluoracetic acid anhydride gave (±)-cis and trans 1-(ethoxycarbonyl)-2,3,6,7-tetrahydro-12b-methyl-12H-indolo[2,3-a]quinolizin-4(1H)-one (21 and 22)(95%). N-[2-(1-Methylindol-3-yl)ethyl]piperidin-2-one 31 was synthesised in three stages. The anion of 31 with diketene gave (a)N-[2-(1-methylindol-3-yl)ethyl]-3-(1,3-dioxobutyl)piperidin-2-one, 29 and (b) in a three-stage process, N-[2-(1-methylindol-3-yl)ethyl]-3-(1-oxo-2-methoxycarbonylethyl)piperidin-2-one 30. Treatment of the dione 29 with excess of trifluoroacetic acid anhydride gave (2S*, 3R*, 12R*)-3-acetyl-5-deethyl-5,19-didehydro-1-methyl-4-oxoaspidospermidine, 34. Reduction of 34 with sodium cyanoborohydride gave the 20,21-dihydro derivative 35 and two (±)-diastereoisomeric alcohols 36 and 37. Cyclisation of the ester 30 with trifluoracetic acid anhydride gave (2S*, 3S*, 12R*)-5-deethyl-5,19-didehydro-3-methoxycarbonyl-1-methyl-4-oxoaspidospermidine 39.

ChemInform Abstract: Synthesis of Bridged Steroids with a Bicyclo(3.3.1)nonane Ring A System.

Abstract A synthesis of new groups of bicyclic steroids with a bicyclo [3.3.1.] nonane ring A system is described. The insertion of an additional ring is performed by means of the Michael addition of ethyl acetoacetate to 17β-propionoxyandrosta-1,4,6-triene-3-one (1) , followed by an aldol condensation of intermediate 17β- propionoxy-1 -(1'Ξ-carboxyethylo-2'-oxo-propano)-androsta-4,6-diene-3-one (2) to give 17β-propionate of 1α(l'), 3α (3')-(1'Ξ-carboxyethylo-2'-oxopropano)-androsta-4,6-diene-3β , 17β -diol (3) . Among derivatives of 3 an oxaadamantane steroid (1-oxatricyclo [3.3.1.13,7]nonane ring A system); 17β-propionate of 1 α (1'), 3 α (3')-pro-pano-2'5 α-epoxyandrosta-3β , 1.7 β -diol (8) was obtained from 5a , 6a , and 7a . The synthesis of 8 provides the example of an intramolecular addition of a hydroxyl group to a double bond in a neutral medium. Hydrogenating conditions and a favorable stereochemistry seem necessary for this reaction.

Synthesis of bridged steroids with a bicyclo [3.3.1.] nonane ring a system.

A synthesis of new groups of bicyclic steroids with a bicyclo [3.3.1.] nonane ring A system is described. The insertion of an additional ring is performed by means of the Michael addition of ethyl acetoacetate to 17β-propionoxyandrosta-1,4,6-triene-3-one (1) , followed by an aldol condensation of intermediate 17β- propionoxy-1 -(1'Ξ-carboxyethylo-2'-oxo-propano)-androsta-4,6-diene-3-one (2) to give 17β-propionate of 1α(l'), 3α (3')-(1'Ξ-carboxyethylo-2'-oxopropano)-androsta-4,6-diene-3β , 17β -diol (3) . Among derivatives of 3 an oxaadamantane steroid (1-oxatricyclo [3.3.1.13,7]nonane ring A system); 17β-propionate of 1 α (1'), 3 α (3')-pro-pano-2'5 α-epoxyandrosta-3β , 1.7 β -diol (8) was obtained from 5a , 6a , and 7a . The synthesis of 8 provides the example of an intramolecular addition of a hydroxyl group to a double bond in a neutral medium. Hydrogenating conditions and a favorable stereochemistry seem necessary for this reaction.

Mechanism of Michael addition of ethyl acetoacetate to chalcone catalyzed by activated Ba(OH)2

Preliminary studies of the mechanism of Michael addition of ethyl acetoacetate to chalcone are presented. Different products may be obtained with good yields (≧80%) and selectivities (≃100%), under different reaction conditions. A mechanism based on the geometric characteristics of the active site of activated barium hydroxide (C-200) is proposed.

ChemInform Abstract: INVESTIGATIONS OF SUBSTITUTED BENZOFURAN‐3‐CARBOXYLATES, BENZO(1,2‐B‐4,5‐B′)DIFURANS AND BENZO(1,2‐B‐4,3‐B′)DIFURANS

AbstractAus den p‐Benzochinonen (Ia)‐(Ic) erhält man bei der Umsetzung mit Acetessigester (II) Mischungen der beiden Benzofurane (III) und (IV).

Investigations of substituted benzofuran‐3‐carboxylates, benzo[1,2‐b:4,5‐b']difurans and benzo[1,2‐b:4,3‐b']difurans

AbstractThe Michael addition of ethyl acetoacetate to benzoquinone, toluquinone, and chlorobenzo‐quinone leads to formation of substituted 5‐hydroxybenzofuran‐3‐earboxylates and linear benzo‐[1,2‐b:4,5‐b']difurans. The previously reported structural proof for the benzodifurans obtained from chlorobenzoquinone and toluquinone, although correct in the conclusion, is shown to be invalid. Proof of the linear benzodifuran structures was obtained by comparison of the uv spectra with authentic angular benzo[1,2‐b:4,3‐b']difurans.