Aldol-type Condensation Reactions Research Articles

Biomimetic and Concise Total Syntheses of Prenylated and Bicyclo[2.2.2]diazaoctane-Containing Indole Alkaloids Including Taichunamide A, Notoamide N and Versicolamide B.

Total syntheses of the title prenylated indole alkaloids together with seven others are reported. Biogenetic considerations have been employed in devising the reaction sequences leading to these targets with, in the opening stages, electrochemically-derived indole-3-carboxaldehyde 15 being subject to an aldol-type condensation reaction involving diketopiperazine derivative 19. This led, after prototopic shifts, intramolecular Diels-Alder cycloaddition and hydrolysis/deprotection steps, to the racemic forms of the bicyclo[2.2.2]diazaoctane-containing natural product stephacidin A (2) and its C6 epimer 3. Epoxidation of the last compound afforded, following rearrangement of the primary oxidation products, a mixture of (±)-taichunamide A [(±)-4] and (±)-versicolamide B [(±)-7]. Related protocols allowed for the conversion of (±)-stephacidin A [(±)-2] into (±)-notoamide B [(±)-5]. Analogous aldol condensation, nucleophilic reduction, and epoxidation steps led to the formation of (-)-notoamide E and its conversion into notoamide C as well as the indole fragmentation product amoenamide E. A late-stage chlorination reaction applied to (±)-stephacidin A provided access to the spirocyclic oxindole (±)-notoamide N [(±)-6].

Synthesis of 2-(5-(2-Aminopropyl)-2-hydroxyphenyl)acetic Acid, a Metabolite of the Drug 5-APB

5-(2-Aminopropyl)benzofuran (5-APB), also known as “Benzo Fury,” is a novel psychoactive substance (NPS) belonging to a new class of synthetic phenethylamines. It acts by disrupting serotonergic circuits as a serotonin–norepinephrine–dopamine reuptake inhibitor and is classified as an entactogen, similar to MDMA and MDA. Despite its popularity among users, recent toxicity events have been associated with the consumption of 5-APB and other benzofurans, highlighting the need for a better understanding of their pharmacodynamics and toxicity. One way to achieve this is by developing the synthesis of 5-APB metabolites as biomarkers of exposure. In this study, we present a six-step synthesis for one of the 5-APB metabolites, 2-(5-(2-aminopropyl)-2-hydroxyphenyl)acetic acid (1), involving methylation, formylation, Aldol-type condensation, reduction, and hydrolysis reactions. The compound was obtained in an overall yield of 11%.

Dimension Control in Mixed Linker Metal-Organic Frameworks via Adjusting the Linker Shapes.

In this context, we describe a novel method to control the dimensionality and, further, the morphology in three mixed linker metal-organic frameworks (MOFs) TMU-70, TMU-71, and TMU-49 via altering the linker shapes. The compatibility between the shape of linkers used in the mixed linker framework, specifically linker angles, can directly affect the dimensionality of the resulting networks from 2D to 3D. Using incompatible linkers (one bent and one linear) together with binodal SBU directed the structure to form 2D networks, while 3D networks were obtained through applying linkers with the same shape. Further, the 2D and 3D MOFs were fabricated through the coordination modulation strategy. The impact of various modulators on the size and morphology of the structures has been examined. The 2D MOFs produced only nanorods through application of different capping agents owing to their preferred crystal growth, while the 3D networks led to rod and plate morphologies. Also, the catalytic performance of MOFs in an aldol-type condensation reaction was estimated. High and fast catalytic activity is detected in nanoscale rod-shaped catalysts.

A novel 3D pillar-layered metal-organic framework: Pore-size-dependent catalytic activity and CO2/N2 affinity

The structure–activity relationship plays the main role in the applicability of Metal-organic Frameworks (MOFs) in different areas including catalysis. Regarding to this herein a novel pillar-layered MOF (TMU-52) that is isostructural to our recently reported TMU-25 is introduced. The structure of this framework was analyzed using X-ray crystallography, FT-IR spectroscopy, Thermogravimetric and elemental analyses. According to the similar organic and inorganic backbone, a comparative study was done on catalytic manner of TMU-25 and TMU-52 toward in aldol-type condensation reaction. TMU-52 was designed through replacing the biphenyl core in the pillar linker of TMU-25 with phenyl group as a better candidate heterogeneous catalysis. The selectivity of the TMU-52 was higher owing to its narrower channels. CO2/N2 affinity of these structures was also investigated.

A Green Protocol for the Synthesis of α‐Diazo‐β‐hydroxyesters and One‐Pot Conversion to β‐Keto‐Esters and Imidazo[1,2‐a]pyridine‐3‐carboxylates

AbstractA new solvent cum reagent system comprising of water extract of banana ash and dimethylsulfoxide (WEB‐DMSO) has been engaged for the first time to promote the aldol type condensation reaction of aldehydes with ethyl diazoacetate. The condensation reaction has smoothly undergone producing a range of α‐diazo‐β‐hydroxy esters in good to excellent yields. The solvent system has been reused up to five times without loss of its catalytic activity. Further, two one‐pot sequential reactions have been developed in the same reaction medium. First, the methodology has been extended to synthesize β‐keto esters through Pd catalyzed 1,2‐hydrogen migration. Secondly, β‐keto esters have been converted to imidazo[1,2‐a]pyridine‐3‐carboxylates by using N‐bromosuccinimide and 2‐aminopyridines in a one‐pot fashion.

The LANCA three-component reaction to highly substituted β-ketoenamides - versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives.

The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible.

Synthesis and DSSC application of donor-acceptor stilbenoid dendrimers with triphenylamine as core and benzothiazole as surface unit

Abstract The π-conjugated donor-acceptor stilbenoid dendrimers are successfully synthesized in high yields by either Aldol-type condensation or Wittig reaction with triphenylamine as donor and benzothiazole as acceptor. The molar extinction coefficient increases with increase in the number of the conjugated π-bridges. All the stilbenoid dendrimers exhibit quasi-reversible oxidation reduction signal in cyclic voltammetry. The highly π-conjugated stilbenoid dendrimers exhibit better current generating capacity and light energy harvesting efficiency than the other dendrimers, when used as additives in dye-sensitized solar cells. Stilbenoid dendrimer 7 shows the maximum power conversion efficiency (ɳ) of 5.08%.

Efficient synthesis of chalcone-4′-sulfonyl chlorides and fluorides

A library of 4′-chloro- and 4′-fluorosulfonyl-substituted chalcones was prepared via the aldol-type condensation reactions of 4-acetylbenzene-1-sulfonyl halides with various aromatic aldehydes, either in absolute ethanol or glacial acetic acid, in the presence of dry HCl. This represents the first examples of chalcone sulfonyl halides in which the phenone ring bears one of these functional groups. The reactivity of the chalcone sulfonyl halides were strongly dependent on the styrene ring substituents; sulfonyl chlorides reacted with most nucleophiles (e.g. amines, alcohols), while sulfonyl fluorides reacted only with charged nucleophiles (e.g. phenolates).

Interplay between hydrophobicity and basicity toward the catalytic activity of isoreticular MOF organocatalysts

Four MOF catalysts showing different hydrophobic characters around the basic reaction center showed subtle substrate selectivity in aldol-type condensation reaction.

Application of group V polyoxometalate as an efficient base catalyst: a case study of decaniobate clusters

We demonstrated for the first time that [Nb10O28]6− exhibited base catalytic activity for aldol-type condensation reactions including Knoevenagel and Claisen–Schmidt condensation reactions.

Fluorogenic Labeling of 5-Formylpyrimidine Nucleotides in DNA and RNA.

5-Formylcytosine (5fC) and 5-formyluracil (5fU) are natural nucleobase modifications that are generated by oxidative modification of 5-methylcytosine and thymine (or 5-methyluracil). Herein, we describe chemoselective labeling of 5-formylpyrimidine nucleotides in DNA and RNA by fluorogenic aldol-type condensation reactions with 2,3,3-trimethylindole derivatives. Mild and specific reaction conditions were developed for 5fU and 5fC to produce hemicyanine-like chromophores with distinct photophysical properties. Residue-specific detection was established by fluorescence readout as well as primer-extension assays. The reactions were optimized on DNA oligonucleotides and were equally suitable for the modification of 5fU- and 5fC-modified RNA. This direct labeling approach of 5-formylpyrimidines is expected to help in elucidating the occurrence, enzymatic transformations, and functional roles of these epigenetic/epitranscriptomic nucleobase modifications in DNA and RNA.

Zeolite Catalyzed Aldol Condensation Reactions

The review is based on the description of zeolite structure, uses, synthesis, and catalytic aldol reaction in aldol condensation. An internal aldolcondensation reaction has been achieved over ZSM-5 zeolite with high silica-alumina ratio at 350oC. It therefore follows that zeolite canfunction as a catalyst in aldol type condensation reactions and that weak acid sites as well as a small number of active sites favor the aldolcondensation reaction of carbonyl compounds. However, the mixed condensation product was found to be favored at temperatures above 300oCand the self-condensation of ethanal to crotonaldehyde was favored at temperatures below 300oC. It has also been suggested that both Brønstedand Lewis acids are involved in aldol reactions with Lewis acid sites the most probable catalytic sites. The zeolite group of minerals has founduse in many chemical and allied industries.DOI: http://dx.doi.org/10.3126/ijasbt.v3i1.12291 Int J Appl Sci Biotechnol, Vol. 3(1): 1-8

A general entry to antifeedant sesterterpenoids: total synthesis of (+)-norleucosceptroid A, (-)-norleucosceptroid B, and (-)-leucosceptroid K.

The first asymmetric total synthesis of the antifeedant terpenoids (+)-norleucosceptroid A, (-)-norleucosceptroid B, and (-)-leucosceptroid K has been accomplished. This highly concise synthetic route was guided by our efforts to develop a platform for the collective synthesis of a whole family of antifeedant natural products. The synthesis features a Hauser-Kraus-type annulation followed by an unprecedented, highly efficient intramolecular dilactol aldol-type condensation reaction to produce the 5,6,5 skeleton. The developed synthetic route proceeds for norleucosceptroid A and B in 16 steps (longest linear sequence) from known compounds.

Investigation of K-promoted Cu-Zn-Al, Cu-X-Al and Cu-Zn-X (X = Cr, Mn) catalysts for carbon monoxide hydrogenation to higher alcohols

In this study, we report the effect of Cu/Zn/Al chemical composition and Zn and/or Al substitution by Mn and/or Cr in K-promoted Cu-Zn-Al catalysts for the hydrogenation of CO to higher alcohols. In terms of higher alcohols, the synthesis yielded preferentially primary 2-methyl branched alcohols with up to five carbon atoms, namely 2-methyl-1-propanol and 2-methyl-1-butanol, together with ethanol and propanol. Variation of the Cu/Zn/Al chemical composition showed that the catalyst with a Cu/Zn atomic ratio of 1 and low Al content (K-Cu45Zn45Al10) exhibits the optimum performance in terms of both activity and selectivity to higher alcohols. High Al contents on the other hand favor methanol production at the expense of higher alcohols. It is postulated that due to its acidic nature, alumina reduces the basic sites on the catalyst, thereby retarding the C1→C2 step. Substitution of Zn and/or Al by Mn and/or Cr was found to reduce activity by ∼50%, probably due to the lower exposed copper surface area as indicated by the formation of larger CuO crystals. In terms of selectivity, the most appreciable changes were recorded for the K-Cu45Mn45Al10 catalyst, where a 50% increase in higher alcohol formation was measured, rendering the catalyst the most selective among the investigated materials. Characterization of the catalysts provided some insight on the beneficial influence of Zn substitution by Mn in the K-Cu45Mn45Al10 sample. Inverse correlation between acidity and higher alcohols selectivity was evidenced, in accordance with the general notion that higher alcohol formation requires basic sites and indicates that reduced acidity is needed for the aldol-type condensation reactions. The replacement of Mn by Zn in K-Cu-Mn-Al reduced acidity and thus promoted the production of the desired higher alcohol products.

Cationic β-vinyl substitutedmeso-tetraphenylporphyrins: synthesis and non-covalent interactions with a short poly(dGdC) duplex

Several cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives were synthesized starting from 2-formyl-meso-tetraphenylporphyrin, and the corresponding Zn(II) complex, and different N-alkyl derivatives of 2- and 4-methylpyridine and 2- and 4-methylquinoline. The new compounds were obtained in a one-step process via base catalyzed aldol-type condensation reactions. Electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) spectroscopy were used to investigate the binding mode of the synthesized cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives with a short GC duplex oligonucleotide. Analysis of the obtained mass spectrometry results indicates the probable occurrence of outside binding. UV-vis spectroscopy data also points to non-intercalation. The potential photosensitizing capacity of these compounds was also ascertained from preliminary photophysical studies.

Catalytic Formation of Silyl Enol Ethers and Its Applications for Aldol-Type Condensation and Aminomethylation Reactions

A new catalytic method for the synthesis of silyl enol ethers has been developed from the coupling reaction of ketones with CH2═CHSiMe3 by using a ruthenium hydride catalyst (PCy3)2(CO)RuHCl. The synthetic utility of silyl enol ethers was demonstrated for both Mukaiyama aldol condensation and aminomethylation reactions in forming β-hydroxyketones and β-aminoketones, respectively.

Acetate-Promoted Aldol-Type Reaction: Scope and Reactivity of Acetates and Aldehydes

Potential of acetates and related compounds in glacial acetic acid as a catalyst for aldol-type condensation reactions was examined. Reactions of cycloalkanones or selected heteroaromatics with aldehydes in presence of 10 mol% of various acetates in acetic acid afforded <TEX>${\alpha},{\alpha}$</TEX>'-bis(substituted-benzylidene)cycloalkanones and substituted-benzylidene-mackinazolinones, respectively, in good yields. Among the compounds tested, ammonium acetate is the best and effective especially towards the reactions of mackinazolinone and aliphatic aldehydes to afford 6-alkylidenemackinazolinones.

A facile synthesis of α,α′-bis(substituted-benzylidene)-cycloalkanones and substituted-benzylidene heteroaromatics: utility of NaOAc as a catalyst for aldol-type reaction

Utility of NaOAc in glacial HOAc as a catalyst for aldol-type condensation reactions was examined. Reactions of cycloalkanones and selected heteroaromatics with various aldehydes in the presence of NaOAc in glacial HOAc provided α,α′-bis(substituted-benzylidene)cycloalkanones and substituted-benzylidene heteroaromatics, respectively, in good yields.

Aldol-type condensation reactions of lithium eneselenolates generated from selenoamides with aldehydes

Aldol-type condensation reactions of α-monosubstituted selenoamides with a variety of aldehydes are examined to furnish β-hydroxy selenoamides in good to high yields. The use of selenoamides derived from dibenzylamine exhibits high stereoselectivity. As for the reaction with aliphatic aldehydes selenoamides show better yields and selectivity compared with ordinary amides. Conversion of the resulting β-hydroxy selenoamides to 1,3-amino alcohols is also described.

Water-soluble calixarenes as new inverse phase-transfer catalysts. Their application to aldol-type condensation and Michael addition reactions in water

Aldol-type condensation and Michael addition reactions of activated methyl and methylene compounds in aqueous NaOH solution have been developed without the need for any added organic solvents. The water-soluble calix[ n]arenes, which contain trimethylammoniomethyl groups on the upper rim, were used as inverse phase-transfer catalysts, resulting in the corresponding products in good to excellent yields.