Reaction Of Enaminones Research Articles

Syntheses, spectroscopic characterization, and electrical properties of important semiconducting organic compound

This work proposes the synthesis of new azomethine by the reaction of enaminone with an appropriate aldehyde. The new compound was identified by NMR (1H and 13C), and others techniques such as: UV–Vis spectroscopy, Fourier Transform Infra-red spectroscopy (FT-IR) and X-ray diffraction (XRD).The optical data shows the synthesized azomethine exhibit low band gaps. (Eg =2.87 eV). Electrical conductivity study indicates that conductivity of product is in the range of ∼ 10−6 S/cm. . So, it is evaluated that the sample is a typical organic semiconductor as its conductivity increases with increasing temperature and the electronic parameters such as activation energy and room-temperature conductivity are in the regime of semiconductors. It is also found that the dielectric constant and the dielectric loss values increase with temperature and decrease with frequencies.Furthermore, the results obtained in this pioneering study are thoughtfully discussed in the context of existing literature. This study is opening doors to potential applications in chemistry.

A facile and robust approach for synthesis and structural characterization of an unprecedented ring system of 4H-pyrazolo[3,4-f]indolizine-4,9(2H)-dione derivatives

A facile and efficient route for the synthesis of novel 4H-pyrazolo [3,4-f]indolizine-4,9(2H)-dione derivatives was investigated and confirmed as a robust method. 2-Acetyl pyrrole was reacted with dimethylformamide dimethyl acetal (DMF-DMA) to afford the enaminone, (3-(dimethylamino)-1-(1H-pyrrol-2-yl)prop-2-en-1-one). The latter obtained enaminone was treated with C-ethoxycarbonyl-N-arylhydrazonoyl chloride derivatives in mild reaction conditions to give unprecedented 4H-pyrazolo [3,4-f]indolizine-4,9(2H)-dione derivatives. The structures of novel pyrazolo-indolizine derivatives were confirmed by NMR spectra, mass spectrometry, elemental analyses, as well as single-crystal X-ray diffraction. Also, 4H-pyrazolo [3,4-f]indolizine-4,9(2H)-dione derivatives were confirmed chemically via the reaction of enaminone with C-methoxycarbonyl-N-arylhydrazonoyl chlorides. By this protocol, a wide range of pyrazolo-indolizine-4,9-dione with different substitutions could be prepared in a straightforward manner under mild reaction conditions in good to excellent yields.

B2pin2-Mediated Cascade Cyclization/Aromatization Reaction: Facial Access to Functionalized Indolizines.

Herein, a B2pin2-mediated radical cascade cyclization/aromatization reaction of enaminone with pyridine is described. This strategy provides a practical way for the construction of valuable functionalized indolizines under metal-, external oxidant-, and base-free conditions, which could be compatible with various kinds of functional groups, such as halogen, π-system, heterocycle, ferrocenyl, etc. A preliminary mechanism investigation indicated that the pyridine-boryl radical formed in situ triggered the reaction to occur.

Synthesis, Structural Determination, and Antioxidant Activities of Acyclic and Substituted Heterocyclic Phosphonates Linearly Linked 4-hydroxy-2(1H)-quinolinone.

The chemical reactivity of 3-[(E)-3-(dimethylamino)-2-propenoyl]-4-hydroxy-1-methy-2(1H)-quinolinone (1) towards some phosphorus reagents was studied. The enaminone 1 was cyclized into pyranoquinolinylphosphonate 2 via treatment with diethyl phosphite in basic medium. However, its reaction with triethoxy phosphonoacetate gave the substituted oxopyranylphosphonate 3. Using the same reaction conditions, both thioxopyridinylphosphonate 4 and oxopyranylphosphonate 5 were produced via a reaction of enaminone 1 with both diethyl 2-amino-2-thioxoethylphosphonate and diethyl vinylphosphonate, respectively, in low yields. In addition, the two novel oxopyridinylphosphonates 6 and 7 were obtained by treatment of enaminone 1 with a diethyl cyanomethylphosphonate reagent. Two oaxathiaphosphininyl derivatives, 8 and 9, were obtained by treatment of the enaminone 1 with O, O-diethyl dithiophosphoric acid under different reaction conditions. Diazaphosphininyl 11 and oxazaphosphininyl 12 derivatives were obtained in excellent yields using a P-phenylphosphonic diamide reagent under different reaction conditions. The treatment of the enaminone 1 with phosphorus pentasulfide produced the non-phosphorylated product thioxothiopyranoquinolinone 13. Finally, the enaminone was turned into oxathiaphosphininyl 14 using Lawesson’s reagent. The possible reaction mechanisms of the formation of these products were discussed. The structures of newly isolated products were established by elemental analysis and spectral tools. The compounds were evaluated for their antioxidant activities.

Reactions of Enaminones with p‐Quinone Methides: Access to 4H‐Chromene and 4H‐Chromen‐4‐one Derivatives

AbstractA one‐pot approach for the synthesis of oxygen‐containing heterocycles such as 4H‐chromenes and 4H‐chromen‐4‐ones has been established through the reaction of enaminones with p‐quinone methides (p‐QMs). This transformation basically involves an acid‐catalyzed 1,6‐conjugate addition of enaminones to p‐QMs followed by annulation. In the case of reaction between 2‐hydroxyphenyl‐substituted p‐quinone methides and N,N‐dimethyl enaminones, 4H‐chromene derivatives were obtained in moderate to excellent yields. Similarly, the reaction between simple p‐quinone methides and 2‐hydroxyphenyl‐substituted N,N‐dimethyl enaminones led to 4H‐chromen‐4‐one derivatives in good yields.

Selective Synthesis of Azoloyl NH-1,2,3-Triazoles and Azolyl Diazoketones: Experimental and Computational Insights.

Here, we report that the reaction of enaminones, from a class of azole series, with sulfonyl azides leads to a difficult-to-separate mixture of two pairs of compounds: (1) 4-azoloyl-NH-1,2,3-triazoles with sulfonamides and (2) azolyl diazoketones with N-sulfonamidines, as a result of the implementation of two competing reactions. On one hand, the electron-donating methyl or methoxy group in the aryl para-position of arylsulfonyl azides favors the production of NH-1,2,3-triazoles together with sulfonamides. On the other hand, the use of highly electrophilic 4-nitrophenylsulfonyl azide promotes the formation of diazoketones and sulfonamidines. It is shown that the direction of each reaction is not only controlled by the nature of the initial enaminones and sulfonyl azides but also depends on the tested solvent. The problem of removing sulfonamides and amidines from the desired products was solved for the first time using new water-soluble enaminones. Based on the experimental and computational studies, the factors contributing to the selective course of alternative reactions were identified, and methods for the synthesis of azoloyl-NH-1,2,3-triazoles and azolyl diazoketones were developed. Density functional theory (DFT) results have shown that the 1,3-dipolar cycloaddition is totally driven toward one single regioisomer with a high asynchronous bond formation, and the introduction of an electron-deficient group in sulfonyl azides induces faster cycloaddition. Additionally, DFT calculations were used to gain further mechanistic insights on the reaction studied here.

Performance efficiency of MIPOH polymers as organic filler on cellulose pulp waste to form cellulosic paper sheets with biological evaluation and computational studies

In this elucidation, we synthesized novel molecularly imprinted polymers (MIPOH1-4) that were used as organic fillers on bagasse pulp to form cellulosic paper sheets, the formation of MIPOH1-4 from the reaction of enaminone 3 with methyl methacrylate monomer in the presence of ethylene glycol dimethyl acrylate and 2,2’-azobisisobutyronitrile. The obtained MIPOH1-4 was confirmed via FT-IR and SEM with different pore sizes. And we noticed that the increase of template 3 increases the hydrogen bond between monomer and template and gave sponge surface of MIPOH4. Furthermore, the computational energies of the template with different monomers utilize DFT/B3LYP/6-31G (d) level to know the stability of polymers and hydrogen bonding between them. So that we applied that in paper manufacture through the adsorption of MIPOH4 as an organic filler on bagasse pulp to form novel cellulosic paper sheets with different concentrations and these sheets which characteristic through FT-IR, SEM, sizing test, tensile strength, and elucidation their antimicrobial activity with theoretical and docking studies. The MIPOH4 and cellulosic paper sheets showed the thermal stability and high tendency of sizability of these paper sheets and concluded the interaction between cellulose fibers of pulp with MIPOH polymer with physical hydrogen bonding.

Stereoselective Synthesis of Cyclohepta[b]indoles by Visible‐Light‐Induced [2+2]‐Cycloaddition/retro‐Mannich‐type Reactions

AbstractA novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible‐light‐induced, photocatalyzed [2+2]‐cycloaddition/ retro‐Mannich‐type reaction of enaminones. Experimental and computational studies suggested that the reaction is a photoredox process initiated by single‐electron oxidation of an enaminone moiety, which undergoes subsequent cyclobutane formation and rapidly fragmentation in a radical‐cation state to form cyclohepta[b]indoles.

Stereoselective Synthesis of Cyclohepta[b]indoles by Visible-Light-Induced [2+2]-Cycloaddition/retro-Mannich-type Reactions.

A novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones. Experimental and computational studies suggested that the reaction is a photoredox process initiated by single-electron oxidation of an enaminone moiety, which undergoes subsequent cyclobutane formation and rapidly fragmentation in a radical-cation state to form cyclohepta[b]indoles.

A Novel and Efficient Isocyanide-Catalyzed Addition Reaction of Enaminones to Isatin Derivatives for Oxindoles Synthesis

A mild, efficient and novel pseudo three-component condensation reaction approach has been designed for straightforward synthesis of 3,3’-bis-substitued-2-oxindole derivatives. The products were prepared through one-pot and pseudo three-component condensation reactions of anilinolactones, isatin derivatives, and cyclohexyl isocyanide in acetonitrile solvent. The key features of this approach include using cyclohexyl isocyanide, which unpredictably has not participated in the condensation reaction and instead of that, plays a fascinating catalytic role. The 3,3’-bis-substitued-2-oxindoles have been afforded in excellent isolated yields, with high purity, straightforward work-up procedure and short reaction times.

Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons.

A series of heterocyclic compounds with a sulfonamide moiety were synthesized from reaction of enaminone 4 with active methylene compounds, glycine derivatives, 1,4-benzoquinone, hydroxylamine hydrochloride, hydrazonyl halides and dimethylacetylenedicarboxylate. The newly synthesized sulfonamide derivatives were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, elemental analysis and alternative synthetic routes. The reactions products were evaluated for their antiproliferative activity against a panel of three different human cancerous cell lines, MCF-7 (breast), HepG-2 (liver) and HCT-116 (colon) and the results were deployed to derive the structure-activity relationships (SAR). Various test compounds were potent antiproliferative to cancerous cells; reaching very low micromolar levels, as in case of 21 which showed IC50 value of 6.2μM against HepG-2 cell. In addition, treatment of cancerous cells with the synthesized compounds induced cell apoptosis and G2/M phase arrest evidenced by flow cytometric analysis. Furthermore, the activity of the synthesized compounds against TOP I and II were documented by DNA relaxation assays. Data revealed that compound 24 significantly interfered with TOP I- and II-mediated DNA relaxation, nicking and decatenation, with IC50 values 27.8 and 33.6μM, respectively. Moreover, the molecular docking studies supported the results from enzymatic assays, where compound 24 was intercalated between nucleotides flanking the DNA cleavage site via pi-pi stacking and hydrophobic interactions. In conclusion, aromatic heterocycles linked to sulfonamides are excellent molecular frameworks amenable for optimization as dual TOP I and II poisons to control various human malignancies.

A novel trans-amination process in 3-arylamino- 5,5-dimethylcyclohex-2-en-1-one with nucleophiles and antimicrobial activity of selected products

Reaction of dimedone with arylamines afforded the respective enaminones. Some N-acetyl derivatives were prepared. The reaction of enaminones with hydroxylamine was found to be dependent on the nature of the arylamine moiety and the molar ratio of hydroxylamine to give the mono-, di- or tri-oximes. Cyclization of the trioxime by acetic anhydride gave dihydrobenzo[c][1,2,5]oxadiazol-4(5H)-one-5-O-acetyloxime. Coupling of the synthesized enaminones with benzene diazonium chloride gave 2,4-bis-phenylhydrazones or a mixture of 2-mono hydrazones and bis-hydrazones depending on the nature of the arylamine moiety. Trans-amination of the arylamine of the bis hydrazones with hydroxylamine gave the same1,3-bis oxime derivative. The structures of the synthesized compounds were confirmed by IR, 1HNMR, 13C NMR spectra. The antimicrobial activity of some selected products showed promising results.

Synthesis of 8,10-disubstituted-triazoloperimidines from (E)-3-(dimethylamino)-1-(8- phenyl-8H-[1,2,4]triazolo[4,3-a]perimidin-10-yl)prop-2-en-1-one and Their Antimicrobial Activity

Aim and Objective: Enaminones belay to be extremely stable compounds and constitute a versatile group of salutary precursors for the synthesis of enormous classes of organic compounds. So, in this context, we synthesized a new enaminone, namely, (E)-3-(dimethylamino)-1-(8-phenyl-8H-[1,2,4]triazolo[4,3- a]perimidin-10-yl)prop-2-en-1-one (enaminone 2). Materials and Methods: The reaction of enaminone 2 with different types of hydrazonoyl chlorides or hydrazine hydrate afforded new substituted pyrazoles. Also, the reaction of enaminone with 6-amino-2- thioxopyrimidin-4-one in acetic acid under reflux produced 2-thioxopyridopyrimidinone derivative. The latter thione derivative reacts with hydrazonoyl chlorides to give pyridotriazolopyrimidines. 5-(8-Phenyl-8H- [1,2,4]triazolo[4,3-a]perimidin-10-yl)isoxazole was produced from the reaction of enaminone 2 with hydroxylamine. Results & Conclusion: The structure of all the novel perimidine derivatives was confirmed on the basis of spectral data and elemental analyses. The enaminone and the newly synthesized compounds were tested for their antimicrobial activity, and the results obtained revealed that some derivatives are more potent than the reference drugs used.

Copper-catalyzed direct oxidative C(sp2)-H α-sulfenylation of enaminones with disulfides or thiophenols: Synthesis of polyfunctionalized aminothioalkenes

A copper(II)-catalyzed protocol for the construction of aminothioalkenes has been achieved that is based on the reaction of enaminones with disulfides/thiophenols in the presence of tert-butyl hydroperoxide (TBHP) to give good to excellent yields. This study provides a new strategy for the formation of C(sp2)−S bonds via direct α-sulfenylation of C(sp2)−H bonds.

Convenient Synthesis and Biological Activity of 4-minomethylene 1-phenylpyrazolidine-3,5-diones

Reaction of (Z)-4-((dimethylamino)methylene)-1-phenylpyrazolidine-3,5-dione (1) with different nucleophiles is described. Treatment of enaminone 1 with phenylhydrazine led to 3-oxo-N’,2-diphenyl-2,3-dihydro-1H-pyrazole-4-carbohydrazide 7. New enaminone derivatives 2–6 and 12–14 were conveniently obtained in high yields via nucleophilic substitution of the dimethylamino group in enaminone 1 when reacted with o-aminophenol, o-aminothiophenol, ethanolamine, cysteamine hydrochloride, piperidine, morpholine, 2-aminopyridine and glycine. Reaction of enaminone 1 with diaza-nucleophiles, such as hydrazine hydrate, ethylenediamine and o-phenylenediamine, afforded the corresponding bis-enaminones 9–11. Anti-inflammatory and antimicrobial activities of some new products were evaluated. Compounds 1, 2, 4, 7, 12a, and 12b showed high anti- inflammatory activity compared with indomethacin as the reference, while the highest antimicrobial effect was observed in the case of compound 3.

Design, synthesis, structure elucidation, and biological activities of 3-(substituted amino)-1-(pyridin-4-yl)propenones and 5-isonicotinoyl-1,2,3,4-tetrahydropyrimidine–adamantane hybrids

Novel molecular hybrids of 5-isonicotinoyl-1,2,3,4-tetrahydropyrimidine–adamantane have been synthesized in excellent yields by the reaction of enaminones, 1-adamantanamine, and formaldehyde. Enaminones (Z)-3-alkyl/aralkyl/aryl-1-(pyridin-4-yl)prop-2-en-1-ones have been synthesised by the reaction of 4-acetylpyridine with N,N-dimethylformamide dimethyl acetal and its bioassay test showed good anti-inflammatory property, but no zone of growth inhibition against Bacillus subtilis (MTCC Code-121), Staphylococcus aureus (MTCC Code-9886), Escherichia coli (MTCC Code-1302), and Salmonella enterica (MTCC Code-3232) bacterial strains. The structures of the synthesized compounds have been established with the help of spectral and analytical data. X-ray analysis of a representative candidate of the series 5-isonicotinoyl-1,2,3,4-tetrahydropyrimidine–adamantane was done for the final confirmation of the structure.

ChemInform Abstract: A Simple One‐Pot Synthesis of Quinoline‐4‐carboxylic Acids by the Pfitzinger Reaction of Isatin with Enaminones in Water.

Abstract A simple one-pot method for synthesizing quinoline-4-carboxylic acids ( 3 ) by the reaction of enaminones ( 1 ) and isatin ( 2 ) using the Pfitzinger reaction conditions is described. Additionally, a plausible mechanism for this transformation is presented.

A simple one-pot synthesis of quinoline-4-carboxylic acids by the Pfitzinger reaction of isatin with enaminones in water

A simple one-pot method for synthesizing quinoline-4-carboxylic acids (3) by the reaction of enaminones (1) and isatin (2) using the Pfitzinger reaction conditions is described. Additionally, a plausible mechanism for this transformation is presented.

ChemInform Abstract: Multicomponent, One‐Pot and Expeditious Synthesis of Highly Substituted New Spiro[indolo‐3,10′‐indeno[1,2‐b]quinolin]‐2,4,11′‐triones under Micellar Catalytic Effect of CTAB in Water.

AbstractThe title compounds (IV) (51 examples) are efficiently obtained by reaction of enaminones, various 5‐substituted isatins, and indane‐1,3‐dione in water.

Induction of intrinsic apoptosis pathway in colon cancer HCT-116 cells by novel 2-substituted-5,6,7,8-tetrahydronaphthalene derivatives

2-Acetyl tetralin (1) reacted with N,N-dimethylformamide dimethylacetal (DMF-DMA) to afford the enaminone 3. The reaction of 3 with piperidine and morpholine afforded the trans enaminone 5a,b, respectively. Compound 3 was treated with primary aromatic amines to give secondary enaminones 6a–e. The enaminone 3 reacted with acetylglycine and hippuric acid to yield pyranones 10a, b, respectively. The reaction of enaminone 3 with 1,4-benzoquinone and 1,4-naphthoquinone gave benzofuranyl tetralin derivatives 14a,b, respectively. Also, when 3 reacted with 5-amino-3-phenyl-1H-pyrazole 15a and 5-amino-1,2,3-triazole 15b, it afforded the new pyrazolo[1,5-a]pyrimidine 17a and 1,2,3-triazolo[1,5-a]pyrimidine 17b, respectively. While the reaction of 3 with pyrimidines 18a, b resulted in the formation of pyrido[2,3-d]pyrimidine derivatives 20a, b, respectively. Investigations of the cytotoxic effect of those compounds against different human cell lines indicated that some compounds showed high selective cytotoxicity against colon cancer HCT-116 cells. Some of these compounds led to DNA damaging and fragmentation that was associated with the induction of apoptosis via mitochondrial pathway. This pathway is initiated by the impairment of mitochondrial transmembrane potential (Δψm) and in response to that the mitochondria released cytochrome c increased, that in turn activated caspase-9 and caspase-3 and induced apoptosis. Compounds 17b and 20b were promising anti-cancer agents that induced intrinsic apoptosis pathway in colon cancer cells.