P-toluenesulfonylmethyl Isocyanide Research Articles

ChemInform Abstract: Modular Synthesis of Sulfonyl Benzoheteroles by Silver‐Catalyzed Heteroaromatization of Propargylic Alcohols with p‐Toluenesulfonylmethyl Isocyanide (TosMIC): Dual Roles of TosMIC.

A new silver-catalyzed heteroaromatization of propargylic alcohols with p-toluenesulfonylmethyl isocyanide (TosMIC) has been developed that provides an efficient and modular approach to sulfonyl benzoheteroles. For the first time, TosMIC plays a dual role in one reaction: sulfonyl source and ligand. An unprecedented deoxysulfonylation/hydration/condensation reaction pathway is disclosed.

Copper-catalyzed three-component synthesis of benzothiazolethiones from o-iodoanilines, isocyanide, and potassium sulfide.

An efficient copper catalyzed strategy for the synthesis of a variety of benzothiazolethione derivatives has been developed. In the presence of CuCl, the three-component reaction of o-iodoanilines and K2S with p-toluenesulfonylmethyl isocyanide proceeded smoothly to obtain the corresponding benzothiazolethiones in good to excellent isolated yields. Notably, isocyanide functioned as a carbon source and K2S functioned as a sulfur source in this reaction.

Modular synthesis of sulfonyl benzoheteroles by silver-catalyzed heteroaromatization of propargylic alcohols with p-toluenesulfonylmethyl isocyanide (TosMIC): dual roles of TosMIC.

A new silver-catalyzed heteroaromatization of propargylic alcohols with p-toluenesulfonylmethyl isocyanide (TosMIC) has been developed that provides an efficient and modular approach to sulfonyl benzoheteroles. For the first time, TosMIC plays a dual role in one reaction: sulfonyl source and ligand. An unprecedented deoxysulfonylation/hydration/condensation reaction pathway is disclosed.

ChemInform Abstract: An Approach to the Synthesis of 2‐Acylchromeno[3,4‐c]pyrrol‐4(2H)‐one Derivatives via a Sequential Three‐Component Reaction.

An efficient synthesis of 2-acylchromeno[3,4-c]pyrrol-4(2H)-one derivatives by a three-component reaction of salicylaldehydes, β-keto esters, and p-toluenesulfonylmethyl isocyanide is reported.

An Approach to the Synthesis of 2-Acylchromeno[3,4-c]pyrrol-4(2H)-one Derivatives via a Sequential Three-Component Reaction

An efficient synthesis of 2-acylchromeno[3,4-c]pyrrol-4(2H)-one derivatives by a three-component reaction of salicylaldehydes, β-keto esters, and p-toluenesulfonylmethyl isocyanide is reported.

A Novel Synthesis of Multisubstituted Pyrroles via Trisubstituted Olefins and TosMIC Derivatives

A novel synthesis of multisubstituted pyrroles was developed where in trisubstituted olefins were reacted with p-toluenesulfonylmethyl isocyanide (TosMIC) derivatives. The entire process is operationally simplistic and utilizes mild reaction conditions. Additionally a possible mechanism is proposed. Keywords: p-toluenesulfonylmethyl isocyanide(TosMIC), trisubstituted olefins, multisubstituted pyrrole, heterocycles, derivatives

Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. Part 2: Synthesis of novel triplet drugs with the epoxymethano structure (capped homotriplet)

An improved synthetic method for triplet drugs with the 1,3,5-trioxazatriquinane skeleton was developed that used p-toluenesulfonylmethyl isocyanide (TosMIC) instead of 1,3-dithiane. Using the improved method, we synthesized compounds with two identical pharmacophore units and an epoxymethano group, that is, capped homotriplets. Among the synthesized capped homotriplets, KNT-123 showed high selectivity for the μ receptor over the κ receptor, and the μ selectivity was the highest among the reported μ selective nonpeptide ligands. KNT-123 administered subcutaneously induced a dose-dependent analgesic effect in the acetic acid writhing assay, and its potency was 11-fold more potent than that of morphine. KNT-123 may serve as a useful tool for the study of the pharmacological actions mediated specifically via the μ receptor.

Direct sulfonylation of Baylis–Hillman alcohols and diarylmethanols with TosMIC in ionic liquid-[Hmim]HSO 4: an unexpected reaction

A Brønsted acidic ionic liquid-[Hmim]HSO 4 promoted unexpected reaction of Baylis–Hillman alcohols and diarylmethanols with p-toluenesulfonylmethyl isocyanide (TosMIC) affording the corresponding sulfone derivatives instead of N-tosylmethyl amides is reported. After isolation of the product, the ionic liquid [Hmim]HSO 4 was easily recycled for further use.

Theoretical investigation on the reaction mechanism of aryl alcohols and p-Toluenesulfonylmethyl isocyanide catalyzed by InCl3

The reaction mechanism of aryl alcohols and TosMIC (p-Toluenesulfonylmethyl isocyanide) catalyzed by InCl3 has been investigated by density functional theory (DFT). The geometries of reactants, intermediates, transition states, and products have been optimized at the B3LYP/6-31G(d) level. The vibration analysis has been performed to demonstrate the authenticity of transition states. The reaction processes are also confirmed by the changes of charge density at bond-forming critical point which analyzed by the atoms in molecules (AIM) theory. In addition, the nature bond orbital (NBO) analysis is carried out to discuss the bond nature and orbital interactions of the species in the reactions. Compared with that of the reaction without catalyst, the activation energy of that with InCl3 decreases by 339.55kJmol−1. Thus, the present computational results indicate that InCl3 is an effective catalyst.

Novel DABCO-Catalyzed Regio- and Diastereoselective Nucleophilic Substitution of Baylis-Hillman Acetates with TosMIC

An efficient DABCO-mediated regio- and diastereoselective substitution of Baylis-Hillman acetates with p-toluenesulfonylmethyl isocyanide (TosMIC) has been developed via a tandem S N 2'-S N 2' mechanism. The products were obtained in excellent yields (80-92%) and in moderate diastereoselectivity (66-80%).

Synthesis of Benzo[c]thiophene Analogs Containing Benzimidazole, Benzothiazole, and Oxazole

Iodine-mediated cyclization of benzo[c]thiophene aldehyde with 1,2-diphenylamine/2-aminophenylthiol led to the formation of benzimidazole/benzothiazole-incorporated benzo[c]thiophenes. Similarly, reaction of benzo[c]thiophene aldehyde with p-toluenesulfonylmethyl isocyanide (TOSMIC) reagent in the presence of K2CO3 as a base furnished oxazole-containing benzo[c]thiophene analogs.

Synthesis of Polysubstituted Pyrroles

Cross coupling metathesis reactions from two ethylenic compounds 4 and 5 easily led to Michael acceptors 6ab and 7a-b. Reaction of these compounds, or of enone 5, with p-toluenesulfonylmethyl isocyanide (TosMIC) provided the disubstituted pyrroles 9a-c and 10a-b. The analogous reaction of compounds 6a-b and 5, but in presence of Ph3SnCl, provided the trisubstituted pyrroles 11a-c. All of these compounds 9-11 were thus obtained in two steps only. Keywords: Lavendamycin, pyrroles, TosMIC, Michael acceptors, cross metathesis

Heterocyclizations via TosMIC-Based Multicomponent Reactions: A New Approach to One-Pot Facile Synthesis of Substituted Quinoxaline Derivatives

A novel multicomponent reaction involving o-phenylenediamines, aldehydes and p-toluenesulfonylmethyl isocyanide (TosMIC) in the presence of a base leading to the formation of quinoxalines in very good yields is described.

Chromone-3-carboxaldehydes in Passerini Reactions Using TosMIC as the Isonitrile Component

p-Toluenesulfonylmethyl isocyanide (TosMIC) is used as the isonitrile component in Passerini reactions with chromone-3-carboxaldehydes to yield chromenyl-amidoesters in good yields.

Synthesis of Bis- and Trisoxazole Derivatives via Suzuki-Miyaura Cross-Coupling Reaction and van Leusen Oxazole Synthesis

Both C 2- and C 3-symmetric oxazole derivatives are synthesized via the Suzuki-Miyaura cross-coupling and van Leusen oxazole synthesis. Here, bis- and triscarboxaldehydes were obtained via the Suzuki-Miyaura cross-coupling and further treated with p-toluenesulfonylmethyl isocyanide (TosMIC) in the presence of potassium carbonate as a base and methanol as a solvent to deliver the corresponding oxazole derivatives.

Diastereoselective Passerini reactions using p-toluenesulfonylmethyl isocyanide (TosMIC) as the isonitrile component

p-Toluenesulfonylmethyl isocyanide (TosMIC) is used for the first time as the isonitrile component in a diastereoselective Passerini reaction with sugar-derived aldehydes to afford products in moderate to good yields (40–90%) and selectivities (30–90% de’s).

Microwave-assisted synthesis of imidazoles: Reaction of p-toluenesulfonylmethyl isocyanide and polymer-bound imines

A convenient method for the synthesis of 1,5-disubstituted imidazoles has been developed on a polymeric support using base-promoted 1,3-dipolar cycloaddition reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines under microwave irradiation. The immobilized imines were synthesized by the reaction of various primary benzyl amines with 4-formyl-3-methoxyphenoxymethyl polystyrene in the presence of trimethyl orthoformate at room temperature. Cleavage from the polymeric support using trifluoroacetic acid gave the desired 1,5-disubstituted imidazoles with excellent yield and high purity.

Selective Ketone Pyrolysis: New Synthetic Method for Mono‐ and Polycyclic Hydrocarbons

Ring formation with p-toluenesulfonylmethyl isocyanide (TosMIC), and successive CO loss, leads preparatively to hitherto unobtainable or not easily obtained polycyclic hydrocarbons. From the triketone 1, the ketone intermediates 2 and 3 and the hydrocarbon 4 can be isolated.