88333-03-3Relevant articles and documents
Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides
Leech, Matthew C.,Petti, Alessia,Tanbouza, Nour,Mastrodonato, Andrea,Goodall, Iain C. A.,Ollevier, Thierry,Dobbs, Adrian P.,Lam, Kevin
, p. 9371 - 9375 (2021/12/09)
A new electrochemical method for the preparation of isocyanides from easily accessible aminotetrazole derivatives has been developed, which tolerates an unprecedented range of functional groups. The use of chemical, rather than electrochemical, oxidation to afford isocyanides was also demonstrated, which provides access to these compounds for those without electrosynthesis equipment. The practicality of scale-up using flow electrochemistry has been demonstrated, in addition to the possibility of using electrochemically generated isocyanides in further reactions.
One-Pot Synthesis of Thiocarbamates
Barther, Dennis,Malliaridou, Triantafillia,Meier, Michael A. R.,Moatsou, Dafni,Waibel, Kevin A.
supporting information, p. 4508 - 4516 (2021/08/30)
An efficient isocyanide-based synthesis of S-thiocarbamates was discovered and thoroughly investigated. The new reaction protocol is a one-pot procedure and allows the direct conversion of N-formamides into thiocarbamates by initial dehydration with p-toluene sulfonyl chloride to the respective isocyanide and subsequent addition of a sulfoxide component. Contrary to recent literature, which also uses isocyanides as starting material, but with other sulfur reagents than sulfoxides, in this protocol, no isolation and purification of the isocyanide component is necessary, thus significantly decreasing the environmental impact and increasing the efficiency of the synthesis. The new protocol was applied to synthesize a library of sixteen thiocarbamates, applying four N-formamides and four commercially available sulfoxides. Furthermore, experiments were conducted to investigate the reaction mechanism. Finally, four norbornene-based thiocarbamate monomers were prepared and applied in controlled ring-opening metathesis polymerization (ROMP) reactions. The polymers were characterized by size-exclusion chromatography (SEC) and their properties were investigated utilizing differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
Method for preparing isonitrile compound
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Paragraph 0056-0061, (2021/01/30)
The invention discloses a method for preparing an isonitrile compound, and belongs to the field of organic synthesis. According to the method, sodium chlorodifluoroacetate or potassium bromodifluoroacetate is used as a difluoromethyl source and is condensed with primary amine under the action of alkali to obtain an isocyanide target product, so that isocyanide is generated in situ on the primary amine. The reaction raw materials, alkali and solvent used in the method are simple and easy to obtain, wide in source and convenient to operate, do not need special storage and use conditions, the method has the advantages of safety, low cost, high yield, simple process, environmental friendliness and the like, and has important application value in the fields of medicine, protein and polypeptidepreparation, pesticides, high polymer materials, dyes and the like.
A more sustainable and highly practicable synthesis of aliphatic isocyanides
Waibel,Nickisch,M?hl,Seim,Meier
, p. 933 - 941 (2020/02/21)
Synthesis protocols to convert N-formamides into isocyanides using three different dehydration reagents (i.e. p-toluenesulfonyl chloride (p-TsCl), phosphoryl trichloride (POCl3) and the combination of triphenylphosphane (PPh3) and iodine) were investigated and optimized, while considering the principles of green chemistry. Comparison of the yield and the E-factors of the different synthesis procedures revealed that, in contrast to the typically applied POCl3 or phosgene derivatives, p-TsCl was the reagent of choice for non sterically demanding aliphatic mono- or di-N-formamides (yields up to 98% and lowest E-factor 6.45). Apart from a significantly reduced E-factor, p-TsCl is cheap, offers a simplified reaction protocol and work-up, and is less toxic compared to other dehydration reagents. Thus, this procedure offers easier and greener access to aliphatic isocyanide functionalities.
Isocyanide 2.0
Ahmadian-Moghaddam, Maryam,D?mling, Alexander,Patil, Pravin
supporting information, p. 6902 - 6911 (2020/11/09)
The isocyanide functionality due to its dichotomy between carbenoid and triple bond characters, with a nucleophilic and electrophilic terminal carbon, exhibits unusual reactivity in organic chemistry exemplified for example in the Ugi reaction. Unfortunately, the over proportional use of only a few isocyanides hampers novel discoveries about the fascinating reactivity of this functional group. The synthesis of a broad range of isocyanides with multiple functional groups is lengthy, inefficient, and exposes the chemist to hazardous fumes. Here we present an innovative isocyanide synthesis overcoming these problems by avoiding the aqueous workup which we exemplify by parallel synthesis from a 0.2 mmol scale performed in 96-well microtiter plates up to a 0.5 mol multigram scale. The advantages of our methodology include an increased synthesis speed, very mild conditions giving access to hitherto unknown or highly reactive classes of isocyanides, rapid access to large numbers of functionalized isocyanides, increased yields, high purity, proven scalability over 5 orders of magnitude, increased safety and less reaction waste resulting in a highly reduced environmental footprint. For example, the hitherto believed to be unstable 2-isocyanopyrimidine, 2-acylphenylisocyanides and even o-isocyanobenzaldehyde could be accessed on a preparative scale and their chemistry was explored. Our new isocyanide synthesis will enable easy access to uncharted isocyanide space and will result in many discoveries about the unusual reactivity of this functional group. This journal is
Rapid Discovery of Aspartyl Protease Inhibitors Using an Anchoring Approach
ünver, M. Yagiz,Camacho, Carlos Jamie,D?mling, Alexander,Haupenthal, J?rg,Heine, Andreas,Hirsch, Anna K. H.,Jumde, Varsha R.,Klebe, Gerhard,Konstantinidou, Markella,Magari, Francesca,Sutanto, Fandi
supporting information, (2020/04/10)
Pharmacophore searches that include anchors, fragments contributing above average to receptor binding, combined with one-step syntheses are a powerful approach for the fast discovery of novel bioactive molecules. Here, we are presenting a pipeline for the rapid and efficient discovery of aspartyl protease inhibitors. First, we hypothesized that hydrazine could be a multi-valent warhead to interact with the active site Asp carboxylic acids. We incorporated the hydrazine anchor in a multicomponent reaction and created a large virtual library of hydrazine derivatives synthetically accessible in one-step. Next, we performed anchor-based pharmacophore screening of the libraries and resynthesized top-ranked compounds. The inhibitory potency of the molecules was finally assessed by an enzyme activity assay and the binding mode confirmed by several soaked crystal structures supporting the validity of the hypothesis and approach. The herein reported pipeline of tools will be of general value for the rapid generation of receptor binders beyond Asp proteases.
Synthesis of isocyanides by reacting primary amines with difluorocarbene
Si, Yi-Xin,Zhu, Peng-Fei,Zhang, Song-Lin
supporting information, p. 9086 - 9090 (2020/11/30)
A general, convenient, and friendly route for preparing a versatile building block of isocyanides from primary amines is developed. Difluorocarbene, generated in situ from decarboxylation of chlorodifluoroacetate, reacts efficiently with primary amines to produce isocyanides. Various primary amines are well tolerated, including aryl, heteroaryl, benzyl, and alkyl amines, as well as amine residues in amino acids and peptides. Late-stage functionalization of biologically active amines is demonstrated, showing its practical capacity in drug design and peptide modification.
Multicomponent Ugi Reaction of Indole- N-carboxylic Acids: Expeditious Access to Indole Carboxamide Amino Amides
Zeng, Linwei,Sajiki, Hironao,Cui, Sunliang
, p. 5269 - 5272 (2019/07/03)
A novel multicomponent Ugi-type reaction for the synthesis of indole carboxamide amino amides from aldehydes, amines, isocyanides, and indole-N-carboxylic acids, which were simply prepared from indoles and CO2, is described. This method provides an expeditious and practical access to indole tethered peptide units, along with the achievement of remarkable structural diversity and brevity. Gram-scale reaction was conducted to demonstrate the scalability, and the products could be transformed to new indole derivatives.
[3+2] Anionic Cycloaddition of Isocyanides to Acyclic Enamines and Enaminones: A New, Simple, and Convenient Method for the Synthesis of 2,4-Disubstituted Pyrroles
Bakulev, Vasiliy A.,Efimov, Ilya V.,Luque, Rafael,Matveeva, Maria D.,Voskressensky, Leonid G.
supporting information, (2020/02/27)
We herein demonstrate a new approach for the synthesis of 2,4-disubstituted pyrroles by [3+2] cycloaddition reaction of isocyanides to the activated double bond of various enamines and enaminones. This process paved the way for the synthesis a series of 2,4-disubstituted pyrroles, which are known to be intermediates in the synthesis of biologically active compounds, in good to excellent yields from simple and commercially available starting materials. The process is carried out efficiently using a strong base, tBuOK, at low temperatures (0 °C). The described method is simple, proceeds in one step, does not require additional catalysts and hence, has a wide scope.
Thermolysis-Induced Two- or Multicomponent Tandem Reactions Involving Isocyanides and Sulfenic-Acid-Generating Sulfoxides: Access to Diverse Sulfur-Containing Functional Scaffolds
Wu, Shengfeng,Lei, Xiaofang,Fan, Erkang,Sun, Zhihua
, p. 522 - 525 (2018/02/10)
Direct reaction of isocyanides with some sulfenic-acid-generating sulfoxides led to the effective formation of the corresponding thiocarbamic acid S-esters in good to high yields. A multicomponent reaction involving isocyanide, sulfoxide, and a suitable nucleophile has also been developed, providing ready access to a diverse range of sulfur-containing compounds, including isothioureas, carbonimidothioic acid esters, and carboximidothioic acid esters.
