140-53-4Relevant academic research and scientific papers
Rapid and Simple Access to α-(Hetero)arylacetonitriles from Gem-Difluoroalkenes
Hu, Dandan,Liu, Jiayue,Ren, Hongjun,Song, Jinyu,Zhang, Jun-Qi,Zhu, Guorong
supporting information, p. 786 - 790 (2022/01/28)
A scalable cyanation of gem-difluoroalkenes to (hetero)arylacetonitrile derivatives was developed. This strategy features mild reaction conditions, excellent yields, wide substrate scope, and broad functional group tolerance. Significantly, in this reacti
Direct C(sp3)-H Cyanation Enabled by a Highly Active Decatungstate Photocatalyst
Kim, Kunsoon,Lee, Seulchan,Hong, Soon Hyeok
supporting information, p. 5501 - 5505 (2021/07/26)
A highly efficient, direct C(sp3)-H cyanation was developed under mild photocatalytic conditions. The method enabled the direct cyanation of various C(sp3)-H substrates with excellent functional group tolerance. Notably, complex natural products and bioactive compounds were efficiently cyanated.
Metal-Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α-Substituted Enantiomerically Enriched Nitriles
Pirola, Margherita,Faverio, Chiara,Orlandi, Manuel,Benaglia, Maurizio
supporting information, p. 10247 - 10250 (2021/06/18)
A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral β-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and α-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral β-cyano esters, α-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).
Lithiation Substitution of Unprotected Benzyltetrazoles
Wong, Jeff Y. F.,Lewandowska, Agnieszka,Trowse, Benjamin R.,Barker, Graeme
, p. 7069 - 7072 (2019/09/30)
1H-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove N-alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles. Metalation with n-BuLi at 0 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.
One-Pot Preparation of C1-Homologated Aliphatic Nitriles from Aldehydes through a Wittig Reaction under Metal-Cyanide-Free Conditions
Ezawa, Masatoshi,Togo, Hideo
, p. 2379 - 2384 (2017/05/01)
A one-pot protocol to obtain C1-homologated aliphatic nitriles was achieved by treating aromatic and aliphatic aldehydes with the (methoxymethyl)triphenylphosphonium ylide followed by hydrolysis of the resulting methyl vinyl ethers with pTsOH (Ts = para-toluenesulfonyl) and treatment with molecular iodine and aqueous ammonia under metal cyanide free conditions. Neopentyl-type nitriles, which could not be obtained by conventional methods that involved conversion of the neopentyl alcohol into a tosylate and treatment with metal cyanide, were successfully obtained by using the present method.
Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "cN" Source
Huang, Yubing,Yu, Yue,Zhu, Zhongzhi,Zhu, Chuanle,Cen, Jinghe,Li, Xianwei,Wu, Wanqing,Jiang, Huanfeng
, p. 7621 - 7627 (2017/07/26)
A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.
Construction of enantioenriched polysubstituted hexahydropyridazines via a sequential multicatalytic process merging palladium catalysis and aminocatalysis
Marques,Giardinetti,Marrot,Coeffard,Moreau,Greck
, p. 2828 - 2832 (2016/03/12)
An efficient multicatalytic strategy for the construction of nitrogen-containing heterocycles has been reported. The powerful combination of organic and metal catalysis in a single vessel allowed the formation of enantioenriched polysubstituted cyclic 6-membered hydrazines bearing a quaternary stereocenter in good yields and selectivities.
Synthesis method of pyrimethamine drug intermediate p-chlorobenzonitrile
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Paragraph 0015; 0016, (2016/11/14)
The invention relates to a synthesis method of a pyrimethamine drug intermediate p-chlorobenzonitrile, which comprises the following steps: adding 1.3 mol of p-benzyl chloride and 0.56 mol of stannous chloride into a reaction vessel which is provided with a stirrer, a thermometer, a reflux condenser and a dropping funnel, controlling the stirring rate at 130-160 rpm, heating the solution to 90-95 DEG C, slowly and dropwisely adding 1.5-1.7 mol of cyanamide within 1-2 hours, continuing stirring to react for 4-5 hours, cooling the solution to 10-15 DEG C, adding 230ml of sodium chloride solution, separating out the water layer, washing the oil layer with a salt solution, washing with acetonitrile, carrying out reduced pressure distillation, and recrystallizing the fraction in ethyl acetate to obtain the crystal p-chlorobenzonitrile, wherein the mass percent of the sodium chloride solution is 15-20%, and the salt solution is any one of potassium bromide and sodium nitrate.
Ametoctradin is a Potent Qo Site Inhibitor of the Mitochondrial Respiration Complex III
Zhu, Xiaolei,Zhang, Mengmeng,Liu, Jingjing,Ge, Jingming,Yang, Guangfu
, p. 3377 - 3386 (2015/04/14)
Ametoctradin is a new Oomycete-specific fungicide under development by BASF. It is a potent inhibitor of the bc1 complex in mitochondrial respiration. However, its detailed action mechanism remains unknown. In the present work, the binding mode of ametoctradin was first uncovered by integrating molecular docking, MD simulations, and MM/PBSA calculations, which showed that ametoctradin should be a Qo site inhibitor of bc1 complex. Subsequently, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized to further understand the substituent effects on the 5- and 6-position of 1,2,4-triazolo[1,5-a]pyrimidine. The calculated binding free energies (ΔGcal) of newly synthesized analogues as Qo site inhibitors correlated very well (R2 = 0.96) with their experimental binding free energies (ΔGexp). Two compounds (4a and 4c) with higher inhibitory activity against porcine SQR than ametoctradin were successfully identified. The structural and mechanistic insights obtained from the present study will provide a valuable clue for future designing of a new promising bc1 inhibitor.
Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles
Lindsay-Scott, Peter J.,Clarke, Aimee,Richardson, Jeffery
, p. 476 - 479 (2015/03/05)
A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.
