34067-83-9Relevant articles and documents
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.
A practical and sustainable protocol for direct amidation of unactivated esters under transition-metal-free and solvent-free conditions
Chen, Cheng,Cheng, Hua,Du, Min-Chen,Qian, Liang,Qin, Xin,Sang, Wei,Yao, Wei-Zhong,Yuan, Ye,Zhang, Rui
supporting information, p. 3972 - 3982 (2021/06/17)
In this paper, a NaOtBu-mediated synthesis approach was developed for direct amidation of unactivated esters with amines under transition-metal-free and solvent-free conditions, affording a series of amides in good to excellent yields at room temperature. In particular, an environmentally friendly and practical workup procedure, which circumvents the use of organic solvents and chromatography in most cases, was disclosed. Moreover, the gram-scale production of representative products3a,3wand3auwas efficiently realized by applying operationally simple, sustainable and practical procedures. Furthermore, this approach was also applicable to the synthesis of valuable molecules such as moclobemide (a powerful antidepressant), benodanil and fenfuram (two commercial agricultural fungicides). These results demonstrate that this protocol has the potential to streamline amide synthesis in industry. Meanwhile, quantitative green metrics of all the target products were evaluated, implying that the present protocol is advantageous over the reported ones in terms of environmental friendliness and sustainability. Finally, additional experiments and computational calculations were carried out to elucidate the mechanistic insight of this transformation, and one plausible mechanism was provided on the basis of these results and the related literature reports.
A metal-free picolinamide assisted electrochemical ortho-trifluoromethylation of arylamines
Wang, Kai,Hou, Jiahao,Wei, Tingting,Zhang, Changjun,Bai, Renren,Xie, Yuanyuan
supporting information, (2020/12/21)
An eco-friendly and effective electrochemical process was developed for the ortho-trifluoromethylation of arylamines using CF3SO2Na as the trifluoromethyl source, affording the desired products in moderate to good yields with high regioselectivity under mild reaction conditions. Importantly, the requirement for both transition metals and oxidants utilized in previous methods were avoided. A radical mechanism was proposed on the basis of various control experiments.
Synthesis of pyrazinamide analogues and their antitubercular bioactivity
Wati, First A.,Adyarini, Prisna U.,Fatmawati, Sri,Santoso, Mardi
, p. 2157 - 2163 (2020/10/02)
The Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapons Convention and releases toxic sulfur oxide when react with carboxylic acid. We successfully synthesized series of pyrazinamide analogues using the Yamaguchi reaction. The synthesis involved reaction of pyrazine-2-carboxylic acid with various aliphatic and aromatic amines in the presence of Yamaguchi reagent and 4-dimethylaminopyridine. The yield of the pyrazine-2-carboxamides and the reaction time depended on the type of the amine (aliphatic vs aromatic), substitution pattern, and number of substituents on the aromatic amines. N-(4-chlorophenyl)pyrazine-2-carboxamides can be prepared by this method in 81% yield; N-(2-ethylhexyl)pyrazine-2-carboxamide and N-(4-fluorobenzyl)pyrazine-2-carboxamide showed the best activity against Mycobacterium tuberculosis H37Rv (6.25 μg/mL). This result could lead to find more active pyrazinamide analogues.
Iron-catalyzed: Ortho trifluoromethylation of anilines via picolinamide assisted photoinduced C-H functionalization
Xia, Chengcai,Wang, Kai,Wang, Guodong,Duan, Guiyun
supporting information, p. 2214 - 2218 (2018/04/05)
A convenient, oxidant-free protocol was developed for the ortho trifluoromethylation of aniline via picolinamide assisted Fe-promoted C-H functionalization under ultraviolet irradiation. In this transformation acetone essentially acted as both a solvent to dissolve reactants and a low-cost radical initiator to efficiently generate a CF3 radical from Langlois' reagent. A broad substrate scope was tolerated and picolinamide bearing strong electron withdrawing groups also could be transformed into the corresponding products with acceptable yields. Furthermore, the value of this method has been highlighted via the efficient synthesis of the nonsteroidal anti-inflammatory drug floctafenine.
Copper-Catalyzed Electrochemical C-H Amination of Arenes with Secondary Amines
Yang, Qi-Liang,Wang, Xiang-Yang,Lu, Jia-Yan,Zhang, Li-Pu,Fang, Ping,Mei, Tian-Sheng
supporting information, p. 11487 - 11494 (2018/09/13)
Electrochemical oxidation represents an environmentally friendly solution to conventional methods that require caustic stoichiometric chemical oxidants. However, C-H functionalizations merging transition-metal catalysis and electrochemical techniques are, to date, largely confined to the use of precious metals and divided cells. Herein, we report the first examples of copper-catalyzed electrochemical C-H aminations of arenes at room temperature using undivided electrochemical cells, thereby providing a practical solution for the construction of arylamines. The use of n-Bu4NI as a redox mediator is crucial for this transformation. On the basis of mechanistic studies including kinetic profiles, isotope effects, cyclic voltammetric analyses, and radical inhibition experiments, the reaction appears to proceed via a single-electron-transfer (SET) process, and a high valent Cu(III) species is likely involved. These findings provide a new avenue for transition-metal-catalyzed electrochemical C-H functionalization reactions using redox mediators.
Synthesis of N -Aryl Amides by Ligand-Free Copper-Catalyzed ipso -Amidation of Arylboronic Acids with Nitriles
Qiao, Yan,Li, Gaoqiang,Liu, Sha,Yangkai, Yujie,Tu, Jingxuan,Xu, Feng
supporting information, p. 1834 - 1838 (2017/04/06)
A facile copper-catalyzed ipso-amidation of arylboronic acids with nitriles has been developed. The method provides a highly efficient and economical synthesis of N-aryl amides with a broad substrate scope.
Copper-catalyzed carboxamide-directed ortho amination of anilines with alkylamines at room temperature
Li, Qiong,Zhang, Shu-Yu,He, Gang,Ai, Zhaoyan,Nack, William A.,Chen, Gong
supporting information, p. 1764 - 1767 (2014/04/17)
In this report, a highly efficient method for the room temperature installation of alkyl amino motifs onto the ortho position of anilines via Cu-catalyzed carboxamide-directed amination with alkylamines is described. This method offers a practical solution for the rapid synthesis of complex arylamines from simple starting materials and enables new planning strategies for the construction of arylamine-containing pharmacophores. A single electron transfer (SET)-mediated mechanism is proposed.
Preparation of pyrazine carboxamides: A reaction involving N-heterocyclic carbene (NHC) intermediates
Naredla, Rajasekhar Reddy,Dash, Barada P.,Klumpp, Douglas A.
supporting information, p. 4806 - 4809 (2013/10/08)
In the reactions of 2,3-pyrazinedicarboxylic anhydride with amines and anilines, pyrazine carboxamides are formed in good to excellent yields. A mechanism is proposed involving ring opening of the anhydride and decarboxylation of the heterocyclic ring. Based on other similar heterocyclic decarboxylations, this suggests the involvement of an N-heterocyclic carbene intermediate leading to the product.
Effect of halogen bonding interaction on supramolecular assembly of halogen-substituted phenylpyrazinamides
Khavasi, Hamid Reza,Tehrani, Alireza Azhdari
, p. 3222 - 3235 (2013/06/27)
A series of halogen-substituted phenylpyrazinamides have been synthesized and crystallographically characterized in order to investigate the effect of halogen bonding interaction on supramolecular assembly of N-phenylpyrazine-2- carboxamide derivatives. The notable feature in crystal structures of meta- and para-iodinated, brominated and chlorinated compounds is that there is a tendency to form a halogen bonding synthon between adjacent halophenyl and prazine/halophenyl rings. Influence of these halogen bonding interactions on supramolecular assemblies have been discussed with the help of geometrical analysis and theoretical calculations. The X...N halogen bonding distances are 2.2-7.7% shorter than the sum of the van der Waals radii of the nitrogen and halogen atoms. Also, theoretical methods show the N...X halogen bonding energies within a range of -9.43 to -23.67 kJ mol-1. Our studies show that the selection of halogen atom as well as the position of substitution on phenylpyrazinamide compound may be important for crystal design based on halogen bonding.
