59-26-7Relevant academic research and scientific papers
Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents
An, Ju Hyeon,Kim, Kyu Dong,Lee, Jun Hee
supporting information, p. 2876 - 2894 (2021/02/01)
Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).
Pd-Catalyzed Oxidative Aminocarbonylation of Arylboronic Acids with Unreactive Tertiary Amines via C-N Bond Activation
Kolekar, Yuvraj A.,Bhanage, Bhalchandra M.
, p. 14028 - 14035 (2021/05/29)
An efficient synthesis of tertiary amides from aryl boronic acids and inert tertiary amines through the oxidative carbonylation via C(sp3)-N bond activation is presented. This protocol significantly restricts the homocoupling biarylketone product. It involves the use of a homogeneous PdCl2/CuI catalyst and a heterogeneous Pd/C based catalyst, which promotes C(sp3)-N bond activation of tertiary amines with aryl boronic acids. This process represents a ligand-free, base-free, and recyclable catalyst along with an ideal oxidant like molecular oxygen.
A predictive model for additions to: N -alkyl pyridiniums
Knight, Brian J.,Tolchin, Zachary A.,Smith, Joel M.
supporting information, p. 2693 - 2696 (2021/03/18)
Disclosed in this communication is a thorough study on the dearomative addition of organomagnesium nucleophiles to N-alkyl pyridinium electrophiles. The regiochemical outcomes have observable and predictable trends associated with the substituent patterns on the pyridinium electrophile. Often, the substituent effects can be either additive, giving high selectivities, or ablative, giving competing outcomes. Additionally, the nature of the organometallic nucleophilic component was also investigated for its role in the regioselective outcome. The effects of either reactive component are important to both the overall reactivity and site of nucleophilic addition. The utility of these observed trends is demonstrated in a concise, dearomative synthesis of a tricyclic compound shown to have insecticidal activity. This journal is
Direct Amidation of Esters by Ball Milling**
Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
supporting information, p. 21868 - 21874 (2021/09/02)
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
Palladium nanoparticles on a pyridinium supported ionic liquid phase: a recyclable and low-leaching palladium catalyst for aminocarbonylation reactions
Adamcsik, Bernadett,Nagy, Enik?,Pekker, Péter,Skoda-F?ldes, Rita,Szabó, Péter,Urbán, Béla
, p. 23988 - 23998 (2020/07/14)
A new SILP (Supported Ionic Liquid Phase) palladium catalyst was prepared and characterized by 13C and 29Si CP MAS NMR, DTG, FTIR and TEM. The presence of the grafted pyridinium cations on the surface of the support was found to result in the formation of highly dispersed Pd nanoparticles with their diameter in the range of 1-2 nm. The catalyst was proved to be active not only in the aminocarbonylation of some model compounds but also in the synthesis of active pharmaceutical ingredients. Catalyst recycling and palladium leaching studies were carried out for the first time in aminocarbonylations leading to CX-546(1-(1,4-benzodioxan-6-ylcarbonyl)piperidine), Moclobemide, Nikethamide and a precursor of Finasteride. The latter reaction proves that not only aryl iodides but also an iodoalkene can be converted into the products with the help of the heterogeneous catalyst. The results show that the conditions should be always fine-tuned in the reactions of different substrates to achieve optimal results. Palladium loss was also observed to depend considerably on the nature of the reaction partners. This journal is
Photorelease of Pyridines Using a Metal-Free Photoremovable Protecting Group
Dong, Zaizai,Fang, Xiaohong,Kou, Xiaolong,Tan, Weihong,Tang, Xiao-Jun,Wu, Yayun,Zhang, Zhen,Zhao, Rong,Zhou, Wei
supporting information, p. 18386 - 18389 (2020/08/24)
The photorelease of bioactive molecules has emerged as a valuable tool in biochemistry. Nevertheless, many important bioactive molecules, such as pyridine derivatives, cannot benefit from currently available organic photoremovable protecting groups (PPGs). We found that the inefficient photorelease of pyridines is attributed to intramolecular photoinduced electron transfer (PET) from PPGs to pyridinium ions. To alleviate PET, we rationally designed a strategy to drive the excited state of PPG from S1 to T1 with a heavy atom, and synthesized a new PPG by substitution of the H atom at the 3-position of 7-dietheylamino-coumarin-4-methyl (DEACM) with Br or I. This resulted in an improved photolytic efficiency of the pyridinium ion by hundreds-fold in aqueous solution. The PPG can be applied to various pyridine derivatives. The successful photorelease of a microtubule inhibitor, indibulin, in living cells was demonstrated for the potential application of this strategy in biochemical research.
Pd/PTABS: An Efficient Catalytic System for the Aminocarbonylation of a Sugar-Protected Nucleoside
Bhanage, Bhalchandra M.,Bhilare, Shatrughn,Gaikwad, Vinayak,Gupta, Gaurav,Kapdi, Anant R.,Sanghvi, Yogesh S.,Shah, Jagrut
supporting information, p. 4239 - 4248 (2019/11/14)
A highly efficient and mild protocol for the aminocarbonylation of a nucleoside is developed by employing palladium/(1,3,5-Triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate (Pd/PTABS) as the catalytic system. The developed aminocarbonylation methodology employs CO gas at a relatively low temperature of 60? °C and is suitable for a wide range of amines, including (heteroaryl)benzylic, aliphatic acyclic, alicyclic and secondary amines. This protocol is also utilized for the synthesis of a sangivamycin precursor by carrying out the Pd-catalyzed amination and aminocarbonylation simultaneously. The utility of this protocol is further demonstrated by the synthesis of the drugs moclobemide and nikethamide.
COtab: Expedient and Safe Setup for Pd-Catalyzed Carbonylation Chemistry
Collin, Hugo P.,Reis, Wallace J.,Nielsen, Dennis U.,Lindhardt, Anders T.,Valle, Marcelo S.,Freitas, Rossimiriam P.,Skrydstrup, Troels
supporting information, p. 5775 - 5778 (2019/08/26)
Bench-stable tablets (COtabs) have been developed for the rapid and safe production of carbon monoxide. The tablets can be made in less than 5 min without the use of a glovebox and only require a stock solution of an amine base to liberate a specific quantity of CO in a two-chamber system. The COtabs were tested in five different carbonylation reactions and provided similar yields compared to literature procedures. Finally, a gram-scale reaction was conducted, as well as 13C-isotope labeling of the anticancer drug, olaparib.
Method for preparing nikethamide
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Paragraph 0027-0047, (2018/11/03)
The invention relates to a method for preparing nikethamide. The method for preparing nikethamide comprises the following steps: S1, a certain amount of a solvent and a certain amount of niacin are added into a reaction bottle, mixing and stirring are carried out for 30-40 minutes, and the materials are cooled to the room temperature; S2, a certain amount of organic amine is added dropwisely withstirring in order to slowly increase the temperature of the reaction mixture system; S3, when the temperature of the system is raised to 70-80 DEG C, a certain amount of a by-product inhibitor and a mixed solution A are added dropwisely, and after the dropwise addition is completed, the reaction system is heated for reflux for 30 min; S4, the materials are continued to stir and cooled to the roomtemperature, a certain amount of sodium hydroxide solution is added dropwisely till the pH value of a water layer is about 8-9, an organic layer is separated, the water layer is extracted twice with trichloroethane, the organic layer is combined, concentration and reduced pressure distillation are carried out, and the product nikethamide is collected. The method for preparing nikethamide has the advantages of high product yield, few by-products, and easy treatment; and compared with other methods, the method is more environmentally friendly.
Metal-Free Amidation of Acids with Formamides and T3P
Bannwart, Linda,Abele, Stefan,Tortoioli, Simone
, p. 2069 - 2078 (2016/07/06)
A new, simple and metal-free method for the direct formation of dialkylamides from carboxylic acids employing N,N-dialkylformamides as amine source is described. The one-pot reaction is promoted by propylphosphonic anhydride (T3P) in the presence of 0.5 equivalents of HCl.
