Intramolecular Condensation Reaction Research Articles

KOtBu Assisted Regio‐ and Stereo‐Selective Alkoxy‐Isomerization of Ortho‐Alkynyl Allylic Alcohols: Synthesis of Alkylidene Dihydroisobenzofurans and Indenones

AbstractA transition metal‐free synthesis of alkylidene dihydroisobenzofurans from the ortho‐alkynyl allylic alcohols is reported herein. Notably, a simple base tBuOK is utilized for the 5‐exo‐dig cyclization and double bond isomerization of ortho‐alkynyl allylic alcohols to furnish alkylidene dihydrobenzofurans with Z‐stereoselectivity under shorter reaction times. In addition, the geometry of the double bonds was confirmed by 1D Selective Gradient NOESY and 2D NMR (NOESY) analysis. Furthermore, the effectuality of the ortho‐alkynyl allylic alcohols has been shown by extending to the one‐pot synthesis of indanones via aqueous acid‐mediated hydrolysis (ring‐opening) of in‐situ formed dihydroisobenzofurans followed by intramolecular condensation reaction under acidic conditions

Lignin Structure and Reactivity in the Organosolv Process Studied by NMR Spectroscopy, Mass Spectrometry, and Density Functional Theory.

There is need for well-defined lignin macromolecules for research related to their use in biomaterial and biochemical applications. Lignin biorefining efforts are therefore under investigation to meet these needs. The detailed knowledge of the molecular structure of the native lignin and of the biorefinery lignins is essential for understanding the extraction mechanisms as well as chemical properties of the molecules. The objective of this work was to study the reactivity of lignin during a cyclic organosolv extraction process adopting physical protection strategies. As references, synthetic lignins obtained by mimicking the chemistry of lignin polymerization were used. State-of-the-art nuclear magnetic resonance (NMR) analysis, a powerful tool for the elucidation of lignin inter-unit linkages and functionalities, is complemented with matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF MS), to gain insights into linkage sequences and structural populations. The study unraveled interesting fundamental aspects on lignin polymerization processes, such as identifications of molecular populations with high degrees of structural homogeneity and the emergence of branching points in lignin structure. Furthermore, a previously proposed intramolecular condensation reaction is substantiated and new insights into the selectivity of this reaction are introduced and supported by density functional theory (DFT) calculations, where the important role of intramolecular π-π stacking is emphasized. The combined NMR and MALDI-TOF MS analytical approach, together with computational modeling, is important for deeper fundamental lignin studies and will be further exploited.

Halogen-Bonding-Mediated Radical Reactions: The Unexpected Behavior of Piperazine-Based Dithiooxamide Ligands in the Presence of Diiodine.

N,N'-Dialkylpiperazine-2,3-dithiones (R2pipdt) were recognized as a class of hexa-atomic cyclic dithiooxamide ligands with peculiar charge-transfer donor properties toward soft electron-acceptors such as noble metal cations and diiodine. The latter interaction is nowadays better described as halogen bonding. In the reaction with diiodine, R2pipdt unexpectedly provides the corresponding triiodide salts, differently from the other dithiooxamides, which instead typically achieve ligand·nI2 halogen-bonded adducts. In this paper, we report a combined experimental and theoretical study that allows elucidation of the nature of the cited products and the reasons behind the unpredictable behavior of these ligands. Specifically, low-temperature single-crystal X-ray diffraction measurements on a series of synthetically obtained R2pipdt (R = Me, iPr, Bz)/I3 salts, complemented by neutron diffraction experiments, were able to experimentally highlight the formation of [R2pipdtH]+ cations with a -S-H bond on the dithionic moiety. Differently, with R = Ph, a benzothiazolylium cation, resulting from an intramolecular condensation reaction of the ligand, is obtained. Based on density functional theory (DFT) calculations, a reasonable reaction mechanism where diiodine plays the fundamental role of promoting a halogen-bonding-mediated radical reaction has been proposed. In addition, the comparison of combined experimental and computational results with the corresponding reactions of N,N'-dialkylperhydrodiazepine-2,3-dithione (R2dazdt, a hepta-atomic cyclic dithiooxamide), which provide neutral halogen-bonded adducts, pointed out that the difference in the torsion angle of the free ligands represents the structural key factor in determining the different reactivities of the two systems.

Diesters Compound Intramolecular Condensation and Its Applications

Abstract: Diesters are important synthetic tools for many biologically active compounds. Dieckmann condensation is an important organic reaction. This reaction is generally used in the formation of larger molecules and form new carbon -carbon bond. Condensation reaction is important for the formation of biological molecules. Dieckmann condensation reaction is named after a German chemist Walter Dieckmann. Dieckmann condensation reaction is intramolecular organic reactions of diesters with base and give β-keto esters. Dieckmann condensation is equivalent to intramolecular claisen condensation reaction. In this project we will discuss about the mechanism and applications of dieckmann condensation.

Design of a Fluorogenic Probe Based on Intramolecular Condensation for Specific Detection of HDAC3.

It is crucial to develop fluorogenic probes for selective targeting of HDACs to explore the roles of HDACs in the tumor onset and progression as well as HDAC-related drug development. However, considerable non-specific signals were produced by spontaneous hydrolysis and undesirable intermolecular attack of the unstable caging moiety in the detection of HDACs with previous probes. To improve the detection specificity, we proposed an intramolecular condensation strategy by the replacement of the traditional acetamide moiety with a trans-enamide unit. Upon deacetylation by HDACs, rapid intramolecular condensation reaction between newly formed terminal aldehyde and hydrazine moiety would occur to afford highly fluorescent hydrazone product. Systematic studies demonstrated that the probe exhibited an extraordinary selectivity for HDAC3 over other HDAC isoforms and interfering substances. The stability and specificity of the indicator make it a powerful tool for HDAC3 activity detection and HDAC3-related drug development.

Synthesis and biological activity of novel hydantoin cyclohexyl sulfonamide derivatives as potential antimicrobial agents in agriculture.

Plant disease is one of the most serious problems in agriculture that can damage crops. Chemical fungicides are widely used to control plant diseases, but have led to resistance and a series of environmental problems. It is, therefore, necessary to develop highly effective and eco-friendly antimicrobial compounds with novel structures. A series of novel hydantoin cyclohexyl sulfonamide derivatives were synthesized through an intramolecular condensation reaction. The bioassay results indicated that a majority of the title compounds displayed potent inhibitory activity against Botrytis cinerea, Sclerotinia sclerotiorum and Erwinia carotorora. The in vivo inhibition rate of compound 3h was 91.01% against B. cinerea, which was higher than that of iprodione (84.07%). Compound 3w showed excellent antifungal activity against B. cinerea with a half-maximal effective concentration (EC50 ) of 4.80 μg ml-1 , which is lower than that of iprodione. Compound 3q had an EC50 value of 1.44 μg ml-1 against S. sclerotiorum, which was close to that of iprodione (1.39 μg ml-1 ), and the inhibition rate was also similar to that of iprodione. Compounds 3i and 3w had the best inhibition efficacy against S. sclerotiorum, both on growth of the mycelium and sclerotia and in the greenhouse pot test in vitro. Further study showed that compounds 3h, 3r and 3s have superb antibacterial activity against E. carotorora with EC50 values of 2.65, 4.24 and 4.29 μg ml-1 respectively, and were superior to streptomycin sulfate (5.96 μg ml-1 ). Because of their excellent antifungal and antibacterial activity against B. cinerea, S. sclerotiorum and E. carotorora, these hydantoin cyclohexyl sulfonamide derivatives could be considered as suitable candidates for new antimicrobial agents. © 2021 Society of Chemical Industry.

An Alternative Approach towards C-12 Functionalized Scalaranic Sesterterpenoids Synthesis of 17-Oxo-20-norscalaran-12α,19-O-lactone.

Scalarane sesterterpenoids emerged as interesting bioactive natural products which were isolated extensively from marine sponges and shell-less mollusks. Some representatives were also reported recently from superior plants. Many scalarane sesterterpenoids displayed a wide spectrum of valuable properties, such as antifeedant, antimicrobial, antifungal, antitubercular, antitumor, anti-HIV properties, cytotoxicity and stimulation of nerve growth factor synthesis, as well as anti-inflammatory activity. Due to their important biological properties, many efforts have been undertaken towards the chemical synthesis of natural scalaranes. The main synthetic challenges are connected to their complex polycyclic framework, chiral centers and different functional groups, in particular the oxygenated functional groups at the C-12 position, which are prerequisites of the biological activity of many investigated scalaranes. The current work addresses this problem and the synthesis of 17-oxo-20-norscalaran-12α,19-O-lactone is described. It was performed via the 12α-hydroxy-ent-isocopal-13(14)-en-15-al obtained from (-)-sclareol as an accessible starting material. The tetracyclic lactone framework was built following an addition strategy, which includes the intramolecular Michael addition of a diterpenic acetoacetic ester and an intramolecular aldol condensation reaction as key synthetic steps. The structure and stereochemistry of the target compound have been proven by X-Ray diffraction method.

Consecutive reactions to construct tricarbonyl compounds and synthetic applications thereof.

Lithium anions derived from O-carbonate-protected cyanohydrins undergo conjugate addition to cycloalkenones with the concomitant transfer of the alkoxycarbonyl group to produce tricarbonyl compounds. These products offer numerous possibilities for further elaboration. The synthetic potential of the cascade products was demonstrated by forming bicyclic and tricyclic systems through intramolecular condensation reactions.

Total syntheses of (±)-penicibilaenes A and B via intramolecular aldol condensation

Concise total syntheses of penicibilaenes A and B were achieved via intramolecular aldol condensation and other key reactions.

Spirosilicate Dimers of a Bowl-shaped Diol Generated by Intramolecular Cyclization of an Aliphatic Tetraketone Chain

A bowl-shaped, bicyclic diol compound was synthesized by intramolecular twofold aldol condensation reaction of a decane-2,4,7,9-tetraone derivative. Two hydroxy groups at the concave side of the bicyclic compound provided convergent reaction sites for silylation. Reaction with tetrachlorosilane furnished two spirosilicate-type dimers that were remarkably stable toward hydrolysis as compared to other tetraalkoxysilanes.

Thermal characterization of antimicrobial peptide stigmurin employing thermal analytical techniques

Stigmurin is a peptide with amidated C-terminus (FFSLIPSLVGGLISAFK-NH2) identified in the transcriptome of the scorpion Tityus stigmurus that has shown antimicrobial action against methicillin-resistant pathogens and low antihemolytic activity, and recently proved to be efficient in controlling sepsis. Despite its pharmacological potential, there is no report about thermal studies for the characterization of the amorphous solid. The objective of this work is to characterize stigmurin using thermoanalytical techniques in the solid state in an inert and oxidative atmosphere. Stigmurin presents glass transition temperature at 149 °C. The results of TG–FTIR and pyrolysis suggest that the pathways for decomposition include homolytic breakdown of the side chains of amino acid residues. Decomposition possibly begins at the N-terminus, with formation of the aromatic compounds, amines, nitriles, alcohols, and ethers among others followed by defragmentation reactions (mainly decarboxylation and deamination) and intramolecular condensation reactions. It generates compounds similar to 2,5-diketopiperazine or DKP, and releases water and low molecular mass products (CO2, NH3, CO, HCNO). The decomposition of stigmurin is an endothermic process where the product of decomposition is originated in the liquid state according to DSC-photovisual images. Stigmurin is more stable in nitrogen atmosphere than synthetic air. This approach provides important information about the thermal decomposition of stigmurin, a molecule endowed with potent antimicrobial activity, supplying relevant parameters (temperature, degradation products, etc.) for technological strategies focusing on quality control and development studies of preformulation involving stigmurin and synthetic peptides in general.

Synthesis and properties of novel N,C,N terdentate skeleton based on 1,3-di(pyridin-2-yl)benzene moiety—new tricks for old dogs

Utilization of intermolecular Friedel–Crafts and intramolecular condensation reaction, novel 1,3-di(pyridine-2-yl)benzene(N,C,N terdentate) skeleton with electro-withdrawing group in 6' position of pyridyl and a cyclization between 6' position of pyridyl and 6 position of benzyl ring were firstly designed and synthesized. The structures of these novel N,C,N terdentate were confirmed by NMR, MS and X-ray single crystalanalyses. The photophysical properties of these compounds were briefly explored.

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 of Polycyclic and Cage Siloxanes by Hydrolysis and Intramolecular Condensation of Alkoxysilylated Cyclosiloxanes.

The controlled synthesis of oligosiloxanes with well-defined structures is important for the bottom-up design of siloxane-based nanomaterials. This work reports the synthesis of various polycyclic and cage siloxanes by the hydrolysis and intramolecular condensation of monocyclic tetra- and hexasiloxanes functionalized with various alkoxysilyl groups. An investigation of monoalkoxysilylated cyclosiloxanes revealed that intramolecular condensation occurred preferentially between adjacent alkoxysilyl groups to form new tetrasiloxane rings. The study of dialkoxy- and trialkoxysilylated cyclotetrasiloxanes revealed multistep intramolecular condensation reactions to form cubic octasiloxanes in relatively high yields. Unlike conventional methods starting from organosilane monomers, intramolecular condensation enables the introduction of different organic substituents in controlled arrangements. So-called Janus cubes have been successfully obtained, that is, Ph4 R4 Si8 O12 , in which R=Me, OSiMe3 , and OSiMe2 Vi (Vi=vinyl). These findings will enable the creation of siloxane-based materials with diverse functions.

Click reactions and intramolecular condensation reactions on azido-adamantyl-functionalized tin sulfide clusters

Azide–alkyl decorated organotin sulfide clusters were synthesized and further reacted to form peptide-decorated derivatives in solution via strain-promoted azide–alkyne cycloaddition as the key step.

Slow pyrolysis polygeneration of bamboo (Phyllostachys pubescens): Product yield prediction and biochar formation mechanism

Slow pyrolysis of bamboo was conducted at 400–600 °C and pyrolysis products were characterized with FTIR, BET, XRD, SEM, EDS and GC to establish a pyrolysis product yield prediction model and biochar formation mechanism. Pyrolysis biochar yield was predicted based on content of cellulose, hemicellulose and lignin in biomass with their carbonization index of 0.20, 0.35 and 0.45. The formation mechanism of porous structure in pyrolysis biochar was established based on its physicochemical property evolution and emission characteristics of pyrolysis gas. The main components (cellulose, hemicellulose and lignin) had different pyrolysis or chemical reaction pathways to biochar. Lignin had higher aromatic structure, which resulted higher biochar yield. It was the main biochar precursor during biomass pyrolysis. Cellulose was likely to improve porous structure of pyrolysis biochar due to its high mass loss percentage. Higher pyrolysis temperatures (600 °C) promoted inter- and intra-molecular condensation reactions and aromaticity in biochar.

Rh-catalyzed selective synthesis of 1,5-dimethylhexahydro-1H-inden-4(2H)-one via hydroformylation of (R)-carvone

This work reports domino hydroformylation, hydrogenation and intramolecular keto-aldol condensation reactions for the selective synthesis of 1,5-dimethylhexahydro-1H-inden-4(2H)-one obtained from (R)-carvone and dihydrocarvone under homogeneous hydroformylation condition. The synthesis of the desired product was achieved by using conventional rhodium/1,3-bis(diphenylphosphino)propane (Rh/dppp) catalyst and PPTS (pyridinium p-toluenesulfonate) as an acidic co-catalyst. The reaction conditions were optimized with respect to various reaction parameters like time, temperature, synthesis gas (CO/H2) pressure, solvents, catalyst and co-catalyst loading. The experimental results showed that less planner carbon backbone in dihydrocarvone increases the steric hindrance around the reaction site and responsible for the reactivity difference between (R)-carvone and dihydrocarvone.

Formation of 1-aza-2-silacyclopentanes and unexpected products from the insertion of phenylisocyanate into 2,2-dimethyl-1-(trimethylsilyl)-1-aza-2-silacyclopentane

Abstract Substances like 3-aminopropyltriethoxysilane are often used as adhesive promoters in various formulations for coatings or to adjust the properties of siloxanes and other polymers. Cyclisation of similar substances is also interesting because of the formation of the Si-N bond. 1-Aza-2-silacyclopentanes were synthesised from 3-aminopropylalkoxysilanes by intramolecular condensation reactions and substitution reactions at the silicon atom. The products tend to undergo ring-opening polymerisation. In contrast to literature reports, they can only be isolated as N-substituted derivatives. Phenylisocyanate inserts into the Si-N bonds of cyclic aminosilanes to form seven-membered heterocycles. Furthermore, phenylisocyanate reacts with N-H bonds in the same molecule. Two insertion products were isolated, and their crystal structures were determined.

Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of Rotationally Restricted Aromatic Compounds

By taking inspiration from the fascinating biosynthetic machinery that creates aromatic polyketides, our group investigates analogous reactions catalyzed by small molecules. We are particularly captivated by the prospects of intramolecular aldol condensation reactions to generate different rotationally restricted aromatic compounds. In a first project of our independent research group, a highly stereoselective amine catalyzed synthesis of axially chiral biaryls, tertiary aromatic amides and oligo-1,2-naphthylenes has been developed. In this article, we outline the twists and turns for our escape from the aromatic flatland to structurally intriguing chiral arene scaffolds relevant for various fields of application.

Synthesis of 5H-Dibenzo[c,e]azepine-5,7(6H)-diones from Benzamides via Palladium-Catalyzed Double C-H Bond Activation.

A convenient and efficient method for the synthesis of 5H-dibenzo[c,e]azepine-5,7(6H)-diones from simple and readily available benzamides is described in this work. The palladium-catalyzed homocoupling of benzamides occurred via ortho-selective double C-H bond activation using the simplest amide CONH2 as a directing group. The subsequent intramolecular condensation reaction proceeded smoothly to produce 5H-dibenzo[c,e]azepine-5,7(6H)-diones in satisfactory to excellent yields in one pot.