Ketene Dithioacetals Research Articles

Green Tandem [5C + 1C] Cycloaromatization of α-Alkenoyl Ketene Dithioacetals and Nitroethane in Water: Eco-Friendly Synthesis of Ortho-Acylphenols.

For the first time, an eco-friendly and sustainable tandem [5C + 1C] cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water for the efficient synthesis of ortho-acylphenols was reported. In refluxing water, a range of α-alkenoyl ketene dithioacetals and nitroethane smoothly underwent tandem Michael addition/cyclization/aromatization reactions in the presence of 2.0 equivalents of DBU to provide various ortho-acylphenols in excellent yields. The green approach to ortho-acylphenols not only avoided the use of harmful organic solvents, which could result in serious environmental and safety issues, but also exhibited fascinating features such as good substrate scope, excellent yields, simple purification for desired products, ease of scale-up, and reusable aqueous medium.

Brønsted acid catalyzed annulations of ketene dithioacetals: synthesis of 3-aryl coumarins and indenes.

PTSA-catalyzed divergent synthetic routes toward 3-aryl coumarins and indenes have been developed using ketene dithioacetals. These transformations are transition-metal and oxidant free, proceed under mild conditions, and provide expeditious access to these important structural motifs.

Corrosion Inhibition Performance of Two Ketene Dithioacetal Derivatives for Stainless Steel in Hydrochloric Acid Solution

The methyl 2-(1,3-dithietan-2-ylidene)-3-oxobutanoate (MDYO) and 2-(1,3-dithietan-2-ylidene) cyclohexane-1,3-dione (DYCD) were synthesized and tested at various concentrations as corrosion inhibitors for 316L stainless steel in 1 M HCl using weight loss, electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), surface analysis techniques (SEM/EDX and Raman spectroscopy) and Functional Density Theory (DFT) was also used to calculate quantum parameters. The obtained results indicated that the inhibition efficiency of MDYO and DYCD increases with their concentration, and the highest value of corrosion inhibition efficiency was determined in the range of concentrations investigated (0.01 × 10−3 – 10−3 M). Polarization curves (Tafel extrapolation) showed that both compounds act as mixed-type inhibitors in 1M HCl solutions. Electrochemical impedance spectra (Nyquist plots) are characterized by a capacitive loop observed at high frequencies, and another small inductive loop near low frequencies. The thermodynamic data of adsorption of the two compounds on the stainless steel surface and the activation energies were determined and then discussed. Analysis of experimental results shows that MDYO and DYCD inhibitors adsorb to the metal surface according to the Langmuir model and the mechanism of adsorption of both inhibitors involves physisorption. SEM-EDX results confirm the existence of an inhibitor protective film on the stainless steel surface. The results derived from theoretical calculations supported the experimental observation.

Palladium-catalyzed cross-dehydrogenative-coupling of nitro-substituted internal alkenes with terminal alkenes

The palladium-catalyzed cross-dehydrogenative-coupling (CDC) reaction of internal alkenes (α-nitro ketene dithioacetals) and terminal alkenes (acrylates) was achieved in AcOH/DMSO using air or AgOAc as the sole oxidant. Styrenes were also applied in the CDC reaction of these internal alkenes with AgOAc as the oxidant. Polyfunctionalized 1,3- and 1,4-dienes were obtained in moderate to excellent yields under mild conditions, without prefunctionalization of the substrates. The diene products were readily transformed into the corresponding amines and derivatives.

A new and efficient approach to 2-hydroxybenzophenone derivatives via [5C + 1C] annulation of α-alkenoyl-α-aroyl ketene dithioacetals and nitroalkanes

A new and efficient protocol for the synthesis of 2-hydroxybenzophenone derivatives through [5C+1C] annulation of α-alkenoyl-α-aroyl ketene dithioacetals and nitroalkanes had been developed. In the presence of 1 equivalent of K2CO3 in DMF at 70 °C, a range of α-alkenoyl-α-aroyl ketene dithioacetals smoothly react with nitroalkanes to provide various 2-hydroxy benzophenone derivatives in excellent yields. The protocol featured mild reaction conditions, no the formation of by-products, excellent yield, no involving the problems of both chemoselectivity and regioselectivity and wide substrate scope.

Experimental study and mathematical modelling of the corrosi-on inhibition of mild steel with an organic compound in 1 M HCl

In this paper, synthesized organic compound of the family of ketene dithioacetal was studied as corrosion inhibitors for mild steel in 1.0 M hydrochloric acid by gravimetric measurement. The aim of this work is to study the effect of inhibitor concentration and the temperature on the resistance, corrosion and to compare the experimental results with mathematical models. The structural properties were performed using scanning electron microscopy technique. It has been found that the inhibition efficiency, increases with increasing inhibitor concentration. The adsorption of studied compounds on mild steel surface follows Langmuir’s isotherm. Obtained data were analyzed by suggesting two mathematical models based on linear and quadratic regression, taking into account the influence of concentration and temperature on the inhibition efficiency. Obtained experimental data were in good agreement with those predicated by the quadratic model

Ir(III)‐Catalyzed and Ag2O‐Promoted C−H/C−H Cross‐Coupling/Intramolecular Cyclization of Ketene Dithioacetals with Benzothiophene

AbstractA tandem Ir(III)‐catalyzed and Ag2O‐promoted cross‐dehydrogenative coupling (CDC)/ intramolecular cyclization of ketene dithioacetals with benzothiophene derivatives was developed, affording a series of sulfur‐containing cyclization compounds. Mechanistic investigation demonstrated a radical process may be involving intramolecular cyclization. This tandem reaction described herein could be carried out with a broad range of substrates and wide functional group tolerance.magnified image

Efficient and Direct Selenocyanation of Ketene Dithioacetals Using Malononitrile‐SeO2 Under Transition‐Metal‐Free Conditions

AbstractThe first selenocyanation of ketene dithioacetals is achieved by using selenium dioxide and malononitrile under mild reaction conditions. The major highlights of this method are an easy set‐up, excellent yields, metal free conditions and the use of odorless and inexpensive selenium reagents. Selenocyanated products are successfully transformed into selenated alkenes and nitrogen containing heterocyclic molecules which would be potential candidates with some desired pharmacological activities.

I2‐Catalyzed Tandem Annulation of Ketene Dithioacetals with Sulfonyl Hydrazides for the Synthesis of N‐Aminosulfonamides

AbstractAn iodine‐catalyzed tandem annulation of ketene dithioacetals with sulfonyl hydrazides is established, which gives the N‐aminosulfonamides with pyrazole side chain in moderate yields. A series of aryl, heteroaryl, and alkyl substituted sulfonyl hydrazides are compatible with this reaction.

Visible-Light-Induced Formation of Thiavinyl 1,3-Dipoles: A Metal-Free [3+2] Oxidative Cyclization with Alkynes as Easy Access to Thiophenes.

A visible-light-induced [3+2] oxidative cyclization of various alkynes with easily available ketene dithioacetals as the previously unknown thiavinyl 1,3-dipoles in the presence of an acridine photosensitizer is reported. A series of multisubstituted thiophenes were achieved regioselectively in ≤98% yields under very mild metal-free conditions without other additives. This reaction could tolerate a wide range of substrates and achieve good efficiency in large-scale syntheses. The reaction mechanism and their applications are described in detail to reveal the reactivity of the new 1,3-dipoles and the selectivity of the reactions.

Selectfluor-Promoted Intramolecular N-S Bond Formation of α-Carbamoyl Ketene Dithioacetals in the Presence of Water: Synthesis of Multifunctionalized Isothiazolones.

A practical and efficient protocol toward fully substituted isothiazolones through Selectfluor-mediated intramolecular oxidative annulation of α-carbamoyl ketene dithioacetals has been developed in the presence of H2O and metal-free conditions. Notably, the experimental results reveal that H2O was crucial to the formation of new N-S bonds and the elimination of alkyl group from the sulfur atom. This protocol provides readily prepared substrates and possesses good functional group tolerance, mild reaction conditions, and operational simplicity, which provides potential access to applications in the pharmaceutical chemistry.

Synthesis of novel ketene dithioacetals via one pot reaction: Molecular modelling in-silico Admet studies and antimicrobial activity

A simple and efficient method for the synthesis of fifteen novel ketene dithioacetals (2-(6-amino5-cyano-4-aryl-4H-1,3-dithiin-2-ylidene) malononitrile) via a one-pot three-component reaction of activated methylene group malononitrile with carbon disulfide in the presence of arylidene malononitriles were reported. The effects of LiOH.H2O as a base at different concentrations have been investigated and can provide products in good yields at 40-50ºC temperature (54-89%). All the synthesized ketene dithioacetals compounds (MCB1-MCB15) were checked for favorable pharmacokinetic param¬eters along with toxicities which are based on drug-likeness explained by Lipinski’s rule of five by Med chem designer software correlated with that of pkCSM online tool. Explorations of synthesized ketene dithioacetals compounds for the antimicrobial study were found to be effective towards Staphylococcus aureus (MCB5 and MCB13) with a zone of inhibition at 26mm and 22mm which is compared to that of standard ciprofloxacin (26mm). This made our study to explore the inhibition mechanism with the help of molecular docking studies with possible binding energies (-6.4 to -8.9 kJ/mol) by pyrx 0.8 software to represent a good prediction of interactions between the ligand and protein (2XCT). Further evaluation of druggability and ADMET predictions compounds MCB5 and MCB13 were found to be effective. Based on the in-vitro and in-silico studies a series of ketene dithioacetals compounds may be helpful for further studying SAR and designing more potent antimicrobials.

Transition metal free, green and facile halogenation of ketene dithioacetals using a KX–oxidant system

A facile oxidative halogenation of α-oxo ketene dithioacetals is achieved by using a potassium halide and an oxidant combination under transition metal free conditions at ambient temperature.

Rhodium-catalyzed enone carbonyl directed C–H activation for the synthesis of indanones containing all-carbon quaternary centers

Rhodium(iii)-catalyzed enone carbonyl directed C–H activation/annulation of α-aroyl ketene dithioacetals with diazo compounds has been realized for the synthesis of β-quaternary indanones.

Cyclization of Vinylketene Dithioacetals: A Synthetic Strategy for Substituted Thiophenes

AbstractA synthetic strategy for the synthesis of substituted thiophenes is described by the one‐pot reaction of indoles with ketene dithioacetals under mild reaction conditions. Promoted by triflic acid (TfOH), the reaction of indoles with the easily available α‐acetyl ketene dithioacetals resulted in the formation of vinylketene dithioacetals via condensation instead of the well known nucleophilic addition‐alkylthio elimination process. In thepresence of CuBr2, vinylketene dithioacetals can cyclize into the corresponding substituted thiophenes. This transformation may benefit from the acidic reaction conditions and the steric effects of the 2‐substituted indoles.magnified image

Cyclopentene Synthesis by a Catalytic [3+2] Annulation of Donor‐Acceptor Cyclopropanes with Polarized Alkenes

Abstract[3+2] Annulation of donor‐acceptor cyclopropanes with alkynes represents an efficient route to cyclopentenes. Here, we describe a new cyclopentene synthesis via Lewis acid‐catalyzed ring‐opening addition and intramolecular SNV reaction of donor‐acceptor cyclopropanes with alkenes. The reaction is carried out under the catalysis of Sc(OTf)3 by using polarized alkenes, namely α‐oxo ketene dithioacetals, as 2 C partners.

Cs+/Alcohol Promoted[4C+2C]Annulation: ASynthetic Strategy for Polysubstituted Phenols

AbstractA cesium ion/alcohol promoted [4C+2C]annulation with the easily available diacetyl ketene dithioacetals as 4 C components to give poly‐substituted phenols is reported. It is revealed for the first time that in the presence of cesium ion and alcohol under mild alkaline conditions, the acetyl methyl carbon of ketene dithioacetals can be utilized as a carbon nucleophile. This nucleophile can attack at a carbonyl carbon of a ketone to form a C−C bond to initiate a [4C+2C]annulations, which lead to a poly‐substituted phenol product via intramolecular cyclization followed by aromatization. This reaction provides a new and practical route to the construction of poly‐substituted phenols between the same (two diacetyl ketene dithioacetals) or different ketones (a diacetyl ketene dithioacetal and a ketone) under very mild reaction conditions.

A Route to Indoles via Modified Fischer Indole Intermediates from Sulfonanilides and Ketene Dithioacetal Monoxides

AbstractAn S−N variant of the N−N‐based Fischer indole synthesis has been developed. Treatment of sulfonanilides and ketene dithioacetal monoxides with a powerful acid anhydride provides N‐sulfonyl‐2‐methylsulfanylindoles. The initial interrupted Pummerer reaction would yield the key S−N‐tethered precursor in situ that then undergoes [3,3] sigmatropic rearrangement, after which the endgame to the indole ring follows the Fischer manner.

Brønsted acid promoted C–C bond formation between indolylmethyl electrophiles and ketene dithioacetals: Diastereoselective synthesis of highly functionalized cyclopenta[b]indoles

A Brønsted-acid promoted method for the construction of carbon–carbon bonds between α-substituted indolylmethyl electrophiles and ketene dithioacetals is described. This strategy was utilized to access 2,3-disubstituted cyclopenta[b]indoles via formal [3+2] cycloadditions. Readily available indolyl methanols and α-indolyl-α-amino carbonyl compounds serve as electrophiles upon activation by p-toluenesulfonic acid (PTSA) and react with ketene dithioacetals to result in the formation of two carbon–carbon bonds and a five-membered ring with excellent diastereoselection. The advantages of employing structurally related indolyl precursors to achieve molecular diversity are punctuated by key substitution effects that highlight differences in the mechanisms and guide reaction development.

Annulation of Ketene Dithioacetals and Sulfonyl Hydrazines for the Synthesis of N‐Sulfonyl 5‐Alkylthiopyrazoles

AbstractA facile method for the synthesis of pyrazoles bearing novel N‐sulfonyl and 5‐alkylthio functional substructures has been developed via the reactions of ketene dithioacetals and sulfonyl hydrazines. The reactions are conducted with simple p‐toluenesulfonic acid (p‐TSA) promotion and mild heating under air atmosphere, leading to the synthesis of target products with highly diverse functional substitution.