38642-74-9Relevant articles and documents
Synthesis method of 2-cyanophenothiazine
-
Paragraph 0056; 0058, (2021/10/30)
The invention discloses a synthesis method of 2-cyanophenothiazine. The method comprises the following steps of: step 1, taking 4-halo-3-nitrobenzonitrile as a raw material, and performing a reaction in the presence of sulfide to obtain 3-amino-4-sulfydryl cyanophenyl; and 2, in the presence of nickel salt, ligand and alkali, making the 3-amino-4-sulfydryl cyanophenyl react with a compound C to generate 2-cyanophenothiazine. The 4-halo-3-nitrobenzonitrile which is low in price and easy to obtain serves as a raw material, and the synthesis of 2-cyanophenothiazine is achieved through few two steps. The reagent used in the reaction process is cheap and easy to obtain; and the reaction process is short in step; and the method has the advantages of simple and convenient operation, high yield, safe operation and no pollution, and is suitable for industrial production.
Nickel-Catalyzed Cyanation of Aryl Thioethers
Delcaillau, Tristan,Woenckhaus-Alvarez, Adrian,Morandi, Bill
supporting information, p. 7018 - 7022 (2021/09/13)
A nickel-catalyzed cyanation of aryl thioethers using Zn(CN)2 as a cyanide source has been developed to access functionalized aryl nitriles. The ligand dcype (1,2-bis(dicyclohexylphosphino)ethane) in combination with the base KOAc (potassium acetate) is essential for achieving this transformation efficiently. This reaction involves both a C-S bond activation and a C-C bond formation. The scalability, low catalyst and reagents loadings, and high functional group tolerance have enabled both late-stage derivatization and polymer recycling, demonstrating the reaction's utility across organic chemistry.
Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
supporting information, p. 3723 - 3728 (2021/04/07)
We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.
Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species
Dong, Yanan,Li, Yuehui,Yang, Peiju,Zhao, Shizhen
, (2020/08/19)
Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO2/NH3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.
An Inhibitor of the Interaction of Survivin with Smac in Mitochondria Promotes Apoptosis
Park, Seong-Hyun,Shin, Insu,Park, Sang-Hyun,Kim, Nam Doo,Shin, Injae
supporting information, p. 4035 - 4041 (2019/08/02)
Herein we report the first small molecule that disrupts the survivin-Smac interaction taking place in mitochondria. The inhibitor, PZ-6-QN, was identified by initially screening a phenothiazine library using a fluorescence anisotropy assay and then conducting a structure–activity relationship study. Mutagenesis and molecular docking studies suggest that PZ-6-QN binds to survivin similarly to the known Smac peptide, AVPI. The results of the effort also show that PZ-6-QN exhibits good anticancer activity against various cancer cells. Moreover, cell-based mechanistic studies provide evidence for the proposal that PZ-6-QN enters mitochondria to inhibit the survivin-Smac interaction and promotes release of Smac and cytochrome c from mitochondria into the cytosol, a process that induces apoptosis in cancer cells. Overall, the present study suggests that PZ-6-QN can serve as a novel chemical probe for study of processes associated with the mitochondrial survivin-Smac interaction and it will aid the discovery of novel anticancer agents.
Efficient and regioselective synthesis of phenothiazine via ferric citrate catalyzed C-S/C-N cross-coupling
Das, Tonmoy Chitta,Quadri, Syed Aziz Imam,Farooqui, Mazahar
supporting information, p. 16 - 24 (2019/05/04)
Efficient C-S and C-N cross-coupling reactions have been developed for regioselective, scalable and environmentally benign synthesis of substituted phenothiazine derivatives. Cross-coupling reactions were demonstrated on various challenging substrates using non-toxic, highly economical, readily available ferric citrate as a catalyst to get desired product with high regioselectivity. Atom economy is the added advantage of this protocol since additional N-protection step before coupling and eventual deprotection of the same to obtain the desired product arenot required. To the best of our knowledge, this is the first report on the use of inexpensive ferric citrate as a catalyst without involving any ligand for the synthesis of regioselectively substituted phenothiazine.
A 2 - cyano phenothiazine preparation method (by machine translation)
-
Paragraph 0005; 0027-0058, (2018/09/02)
The invention relates to a preparation method of 2-cyanophenothiazine. Dehydration reaction is firstly performed, thereby avoiding the complex technical step of performing dehydration refinement after the 2-cyanophenothiazine crude product is generated, and effectively reducing the product decomposition; meanwhile, the 2-cyanophenothiazine generation reaction is performed after dehydration to obviously reduce the recrystallization frequency in the refinement process, so that the recrystallization is only needed once, thereby greatly reducing the loss of the materials and energy sources, lowering the preparation cost and enhancing the reaction yield; and thus, the yield of the preparation method can reach 90.3% or above. Besides, the purity of the product is very high and can reach 99.5% or above, and the content of the impurity amide is less than 0.1%. In addition, the catalyst used by the method can effectively accelerate the reaction, shorten the reaction time and lower the reaction temperature, thereby enhancing the energy utilization ratio and further lowering the cost of the whole preparation process.
Environment-friendly industrial preparation method for 2-cyanophenothiazine
-
Paragraph 0054-0062; 0096-0099, (2017/09/01)
The invention provides an environment-friendly industrial preparation method for 2-cyanophenothiazine. The method includes the steps of: a) with 2-chlorophenothiazine and cuprous cyanide as raw materials, a high-boiling-point organic solvent as a solvent and an alkali metal halide as a catalyst, performing a high-temperature reaction; b) before a reflux reaction, performing azeotropic water removal to the reaction system including the raw materials, solvent and catalyst under protection of an inert gas; c) after azeotropic water removal, carrying out the reflux reaction; d) after the reflux reaction is completed, reducing the temperature, performing post-treatment and extraction to a reaction product to obtain a crude product, and purifying the crude product to obtain the 2-cyanophenothiazine. For controlling amide impurities, the azeotropic water removal is employed, so that a complex process of treatment with phosphorus oxychloride is avoided, and meanwhile, generation of a highly toxic gas, hydrocyanic acid, due to usage of acyl chloride or concentrated sulfuric acid for dehydration is avoided. The method is beneficial to large-scale industrial production. A recycled first organic solvent can be reused, so that production cost is reduced.
A Facile Synthesis of Cyanophenothiazines
Marivingt-Mounir, Cecile,Mettey, Yvette,Vierfond, Jean-Michel
, p. 843 - 845 (2007/10/03)
A one-pot synthesis of 1, 3 and 4-cyanophenothiazines and a two-step approach to 2-cyanoisomer have been developed. The condensation of 2-aminobenzenethiol and 2,3 or 3,4-dihalogenobenzonitriles followed by Smiles rearrangement or by intramolecular aromatic substitution gave the desired ring systmes.
A NOVEL SYNTHETIC ROUTE TO CYANOPHENOTHIAZINES. FIRST EXAMPLE OF SMILES REARRANGEMENT FROM HALOGENOBENZONITRILES
Mettey, Yvette,Vierfond, Jean-Michel
, p. 987 - 993 (2007/10/02)
The reaction of halogenobenzonitriles with 2-aminobenzenethiol gave, by a Smiles rearrangement 2-mercaptocyanodiphenylamines which are cyclised to cyanophenothiazines via a disulfide intermediate.A mechanism is proposed.
