53300-46-2

Upstream product

• 62-53-3 aniline 
• 473440-42-5 cyclohexylcarbonyl 2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl)sulfide 
• 108-85-0 1-bromocyclohexane 
• 103-72-0 phenyl isothiocyanate 
• 2719-26-8 N-phenylcyclohexanamide 
• 1268077-11-7 p-bromophenyl cyclohexanedithiocarboxylate 
• 1268077-10-6 p-chlorophenyl cyclohexanedithiocarboxylate 
• 2719-27-9 cyclohexanylcarbonyl chloride 
• 931-50-0 cyclohexylmagnesium bromide 

Downstream Products

• 53883-97-9 C₁₉H₂₀N₂O₂S₂ 
• 104462-82-0 2-cyclohexylbenzoxazole 
• 40115-03-5 2-cyclohexyl-benzothiazole 

Relevant academic research and scientific papers

Contribution of Solvents to Geometrical Preference in the Z/ E Equilibrium of N-Phenylthioacetamide

We studied the Z/E preference of N-phenylthioacetamide (thioacetanilide) derivatives in various solvents by means of 1H NMR spectroscopy, as well as molecular dynamics (MD) and other computational analyses. Our experimental results indicate that the Z/E isomer preference of secondary (NH)thioamides of N-phenylthioacetamides shows substantial solvent dependency, whereas the corresponding amides do not show solvent dependency of the Z/E isomer ratios. Detailed study of the solvent effects based on molecular dynamics simulations revealed that there are two main modes of hydrogen (H)-bond formation between solvent and (NH)thioacetamide, which influence the Z/E isomer preference of (NH)thioamides. DFT calculations of NH-thioamide in the presence of one or two explicit solvent molecules in the continuum solvent model can effectively mimic the solvation by multiple solvent molecules surrounding the thioamide in MD simulations and shed light on the precise nature of the interactions between thioamide and solvent. Orbital interaction analysis showed that, counterintuitively, the Z/E preference of NH-thioacetamides is mainly determined by steric repulsion, while that of sterically congested N-methylthioacetamides is mainly determined by thioamide conjugation.

Photocatalytic Oxidative C-H Thiolation: Synthesis of Benzothiazoles and Sulfenylated Indoles

We report studies on the photocatalytic formation of C-S bonds to form benzothiazoles via an intramolecular cyclization and sulfenylated indoles via an intermolecular reaction. Cyclic voltammetry (CV) and density functional theory studies suggest that benzothiazole formation proceeds via a mechanism that involves an electrophilic sulfur radical, while the indole sulfenylation likely proceeds via a nucleophilic sulfur radical adding into a radical cationic indole. These conditions were successfully extended to several thiobenzamides and indole substrates.

Catalyst- and Supporting-Electrolyte-Free Electrosynthesis of Benzothiazoles and Thiazolopyridines in Continuous Flow

A catalyst- and supporting electrolyte-free method for electrochemical dehydrogenative C?S bond formation in continuous flow has been developed. A broad range of N-arylthioamides have been converted to the corresponding benzothiazoles in good to excellent yields and with high current efficiencies. This transformation is achieved using only electricity and laboratory grade solvent, avoiding degassing or the use of inert atmosphere. This work highlights three advantages of electrochemistry in flow, which is (i) a supporting electrolyte-free reaction, (ii) an easy scale-up of the reaction without the need for a larger reactor and, (iii) the important and effective impact of having a good mixing of the reaction mixture, which can be achieved effectively with the use of flow systems. This clearly improves the reported methods for the synthesis of benzothiazoles.

Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding

Halogen bonding catalysis has recently gained increasing attention as a powerful tool to activate organic molecules. However, the variety of the catalyst structure has been quite limited so far. Herein, we report the first example of the use of an iodoalkyne as a halogen bond donor catalyst. By using an iodoalkyne bearing a pentafluorophenyl group as a catalyst, thioamides were efficiently activated and reacted with 2-aminophenol to generate benzoxazoles in good yield. Mechanistic studies, including 13C NMR spectroscopic analysis and several control experiments, provided concrete evidence that this catalytic activation is based on halogen bonding. Thus, the results obtained in this study demonstrate that iodoalkynes can serve as a new scaffold for future development of halogen bonding catalysis.

Organocatalytic, difluorocarbene-based S-difluoromethylation of thiocarbonyl compounds

Upon treatment with trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA) and a catalytic amount of N,N,N′,N′-tetramethyl-1,8-diaminonaphthalene, secondary thioamides and thiocarbamates undergo selective difluoromethylation on the sulfur atom to give S-difluoromethyl thioimidates and thioiminocarbonates in good yields, respectively. This is the first report on the synthesis of acyclic difluoromethyl thioimidates and thioiminocarbonates. The key for S-difluoromethylation is the organocatalytic generation of difluorocarbene (:CF2) under mild conditions, which prevents decomposition of the substrates. This process provides an efficient approach to pharmaceuticals and agrochemicals bearing a difluoromethylsulfanyl group, starting from widely available thiocarbonyl compounds.

A Robust, Eco-Friendly Access to Secondary Thioamides through the Addition of Organolithium Reagents to Isothiocyanates in Cyclopentyl Methyl Ether (CPME)

The nucleophilic addition of widely available and variously functionalized organolithium reagents to isothiocyanates represents a straightforward, high-yielding, one-pot method to access secondary thioamides. The simple reaction conditions required and the broad scope (>50 cases examples) makes it a robust and reliable method to access both simple and complex thioamides, including enantiopure ones. Noxious and unpleasant-smelling sulfurating agents, usually employed in the literature established methods, are avoided during the whole synthetic procedure thus, rendering the protocol highly attractive, also for sustainability aspects.

Unexpected thioketene derivative formation during thioacyl dithiophosphate synthesis

The scope and limitations of the thioacylation method using thioacyl dithiophosphates were investigated. Thioacyl dithiophosphates are formed in the reaction of acyl dithiophosphates with dithiophosphoric acid. However when the acyl moiety contains two α-substituents then a thioketene derivative is formed thus lowering the yield of expected thioacyl dithiophosphate.

Synthesis of S-thioacyl dithiophosphates, efficient and chemoselective thioacylating agents

Easily available acyl dithiophosphates are not stable and isomerise reversibly to O-thioacyl monothiophosphates, especially when subjected to heating. Much slower but probably irreversible isomerisation to S-thioacyl monothiophosphates occurs. Since equilibrium states are established and S-thioacyl (mono)thiophosphates form slowly, reaction mixtures contain generally both thioacylating and acylating agents, and consequently cannot be used for efficient thioacylation. On the other hand, treatment of a mixture of isomeric anhydrides with an excess of a dithiophosphoric acid leads to exclusive formation of S-thioacyl dithiophosphates. They appear to be excellent thioacylating agents: relatively stable, inert towards water and oxygen and therefore easy to handle. Reactions with nitrogen or sulfur nucleophiles proceed very rapidly under ambient conditions, yielding respective thioacyl derivatives. Isolation of the products is very simple. Due to the low reactivity of S-thioacyl dithiophosphates towards oxygen nucleophiles they can be used for direct thioacylation of multifunctional nucleophiles with unprotected hydroxy groups. Respective thioacyl derivatives cannot readily be obtained using other methods.