- Nitrile Synthesis via Desulfonylative-Smiles Rearrangement
-
Herein, we designed a simple nitrile synthesis from N-[(2-nitrophenyl)sulfonyl]benzamides via base-promoted intramolecular nucleophilic aromatic substitution. The process features redox-neutral conditions as well as no requirement of toxic cyanide species and transition metals. Our process shows broad scope and various functional group compatibility, affording a variety of (hetero)aromatic nitriles in good to excellent yields.
- Abe, Masahiro,Nitta, Sayasa,Miura, Erina,Kimachi, Tetsutaro,Inamoto, Kiyofumi
-
p. 4460 - 4467
(2022/03/15)
-
- Highly Efficient Oxidative Cyanation of Aldehydes to Nitriles over Se,S,N-tri-Doped Hierarchically Porous Carbon Nanosheets
-
Oxidative cyanation of aldehydes provides a promising strategy for the cyanide-free synthesis of organic nitriles. Design of robust and cost-effective catalysts is the key for this route. Herein, we designed a series of Se,S,N-tri-doped carbon nanosheets with a hierarchical porous structure (denoted as Se,S,N-CNs-x, x represents the pyrolysis temperature). It was found that the obtained Se,S,N-CNs-1000 was very selective and efficient for oxidative cyanation of various aldehydes including those containing other oxidizable groups into the corresponding nitriles using ammonia as the nitrogen resource below 100 °C. Detailed investigations revealed that the excellent performance of Se,S,N-CNs-1000 originated mainly from the graphitic-N species with lower electron density and synergistic effect between the Se, S, N, and C in the catalyst. Besides, the hierarchically porous structure could also promote the reaction. Notably, the unique feature of this metal-free catalyst is that it tolerated other oxidizable groups, and showed no activity on further reaction of the products, thereby resulting in high selectivity. As far as we know, this is the first work for the synthesis of nitriles via oxidative cyanation of aldehydes over heterogeneous metal-free catalysts.
- Hua, Manli,Song, Jinliang,Huang, Xin,Liu, Huizhen,Fan, Honglei,Wang, Weitao,He, Zhenhong,Liu, Zhaotie,Han, Buxing
-
supporting information
p. 21479 - 21485
(2021/08/23)
-
- Method for dehydrating primary amide into nitriles under catalysis of cobalt
-
The invention provides a method for dehydrating primary amide into nitrile. The method comprises the following steps: mixing primary amide (II), silane, sodium triethylborohydride, aminopyridine imine tridentate nitrogen ligand cobalt complex (I) and a reaction solvent under the protection of inert gas, carrying out reacting at 60-100 DEG C for 6-24 hours, and post-treating reaction liquid to obtain a nitrile compound (III). According to the invention, an effective method for preparing nitrile compounds by cobalt-catalyzed primary amide dehydration reaction by using the novel aminopyridine imine tridentate nitrogen ligand cobalt complex catalyst is provided; and compared with existing methods, the method has the advantages of simple operation, mild reaction conditions, wide application range of reaction substrates, high selectivity, stable catalyst, high efficiency, and relatively high practical application value in synthesis.
- -
-
Paragraph 0108-0110
(2021/06/21)
-
- Recyclable and Reusable Pd(OAc)2/XPhos–SO3Na/PEG-400/H2O System for Cyanation of Aryl Chlorides with Potassium Ferrocyanide
-
Pd(OAc)2/XPhos–SO3Na in a mixture of poly(ethylene glycol) (PEG-400) and water is shown to be a highly efficient catalyst for the cyanation of aryl chlorides with potassium ferrocyanide. The reaction proceeded smoothly at 100 or 120?oC with K2CO3 or KOAc as base, delivering a variety of aromatic nitriles in good to excellent yields. The isolation of the crude products is facilely performed by extraction with cyclohexane and more importantly, both expensive Pd(OAc)2 and XPhos–SO3Na in PEG-400/H2O system could be easily recycled and reused at least six times without any apparent loss of catalytic efficiency. Graphical Abstract: Palladium-catalyzed cyanation of aryl chlorides with potassium ferrocyanide leading to aryl nitriles by using Pd(OAc)2/XPhos–SO3Na/PEG-400/H2O as a highly efficient and recyclable catalytic system is described.[Figure not available: see fulltext.]
- Cai, Mingzhong,Huang, Bin,Liu, Rong,Xu, Caifeng
-
-
- Nickel-Catalyzed Cyanation of Aryl Thioethers
-
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.
- Delcaillau, Tristan,Woenckhaus-Alvarez, Adrian,Morandi, Bill
-
supporting information
p. 7018 - 7022
(2021/09/13)
-
- Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
-
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.
- Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
-
supporting information
p. 3723 - 3728
(2021/04/07)
-
- Zinc Oxide/Graphene Oxide as a Robust Active Catalyst for Direct Oxidative Synthesis of Nitriles from Alcohols in Water
-
In this work, without using any linker or chemical modification of graphene oxide, a zinc oxide immobilized graphene oxide-based catalyst was used for the direct aerobic oxidative conversion of alcohols to the nitriles in water. In the first step, graphene oxide was prepared and then zinc ions were electrostatically adsorbed onto the surface of graphene oxide. In the following step, zinc oxide nanoparticles were generated via in-situ growth in presence of NaOH. It was illustrated that graphene oxide layers can control the size of in-situ generated zinc oxide nanoparticles. Various aromatic/aliphatic/heteroaromatic primary alcohols converted to the nitriles in high yields under O2 balloon with ZnO/GO catalyst. This catalyst can be used for 7 successful consecutive runs without significant loss of activity. Graphic Abstract: [Figure not available: see fulltext.]
- Sarvi, Iraj,Zahedi, Ehsan
-
-
- Method for converting aromatic aldehyde into aromatic nitrile by using sulfur powder promoted inorganic ammonium as nitrogen source (by machine translation)
-
The invention discloses a method for converting aromatic aldehyde into aromatic nitrile. The method is conversion of high yield of aromatic aldehyde one-pot reaction of sulfur powder promoted inorganic ammonium as a nitrogen source into aromatic nitrile. The method has the advantages of no need of metal participation, no need of strong oxide, compatibility of reaction to air, easiness in amplification to a gram scale and the like, and overcomes the problems of harsh reaction conditions, complex operation, low functional group compatibility and the like in the prior art. (by machine translation)
- -
-
Paragraph 0042; 0043
(2020/09/12)
-
- Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species
-
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.
- Dong, Yanan,Li, Yuehui,Yang, Peiju,Zhao, Shizhen
-
-
- A convenient reagent for the conversion of aldoximes into nitriles and isonitriles
-
For the dehydroxylation of aldoximes with 4-nitro-1-((trifluoromethyl)sulfonyl)-imidazole (NTSI), slight modifications of reaction conditions resulted in significantly different reaction paths to provide either nitriles or isonitriles. The challenging conversion of aldoximes into isonitriles was achieved under mild conditions.
- Zhang, Wei,Lin, Jin-Hong,Zhang, Pengfei,Xiao, Ji-Chang
-
supporting information
p. 6221 - 6224
(2020/06/29)
-
- Dehydrogenation of Primary Alkyl Azides to Nitriles Catalyzed by Pincer Iridium/Ruthenium Complexes
-
Pincer metal complexes exhibit superior catalytic activity in the dehydrogenation of plain alkanes, but find limited application in the dehydrogenation of functionalized organic molecules. Starting from easily accessible primary alkyl azides, here we report an efficient dehydrogenation of azides to nitriles using pincer iridium or ruthenium complexes as the catalysts. This method offers a route to cyanide-free preparation of nitriles without carbon chain elongation and without the use of strong oxidants. Both benzyl and linear aliphatic azides can be dehydrogenated with tert-butylethylene as the hydrogen acceptor to afford nitriles in moderate to high yields. Various functional groups can be tolerated, and the H?C?C?H bond dehydrogenation does not occur for linear alkyl azide substrates. Furthermore, the pincer Ir catalytic system was found to catalyze the direct azide dehydrogenation without the use of a sacrificial hydrogen acceptor.
- Gan, Lan,Jia, Xiangqing,Fang, Huaquan,Liu, Guixia,Huang, Zheng
-
p. 3661 - 3665
(2020/06/02)
-
- Nickel-Catalyzed Transformation of Alkene-Tethered Oxime Ethers to Nitriles by a Traceless Directing Group Strategy
-
Nickel-catalyzed transformation of alkene-tethered oxime ethers to nitriles using a traceless directing group strategy has been developed. A series of alkene-tethered oxime ethers derived from benzaldehyde and cinnamyl aldehyde derivatives were converted into the corresponding benzonitriles and cinnamonitriles in 46-98% yields using the nickel catalyst system. Control experiments showed that the alkene group tethered to an oxygen atom on the oximes via one methylene unit plays a key role as a traceless directing group during the catalysis.
- Takahashi, Yoshiyuki,Tsuji, Hiroaki,Kawatsura, Motoi
-
p. 2654 - 2665
(2020/02/04)
-
- Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation
-
Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.
- Mills, L. Reginald,Graham, Joshua M.,Patel, Purvish,Rousseaux, Sophie A. L.
-
supporting information
p. 19257 - 19262
(2019/12/02)
-
- Transformation of aromatic bromides into aromatic nitriles with n-BuLi, pivalonitrile, and iodine under metal cyanide-free conditions
-
Various aromatic nitriles could be obtained in good yields by the treatment of aryl bromides with n-butyllithium and then pivalonitrile, followed by the treatment with molecular iodine at 70 °C, without metal cyanides under transition-metal-free conditions. The present reaction proceeds through the radical β-elimination of imino-nitrogen-centered radicals formed from the reactions of imines and N-iodoimines under warming conditions.
- Uchida, Ko,Togo, Hideo
-
-
- Method for preparing nitrile
-
The invention provides a method for preparing nitrile. Aldoxime carboxylic ester is used as a reactant to prepare a nitrile compound. The aldoxime carboxylic ester can be completely converted into corresponding nitrile under common catalysis of ferric salt and phenol within a few minutes. The method for preparing the nitrile has the advantages of gentle reaction conditions, simple and easy-to-getused reagents, cheap and environment-friendly catalyst, wide substrate application range, simple operation, rapid reaction and the like.
- -
-
Paragraph 0015
(2019/06/13)
-
- Iron and Phenol Co-Catalysis for Rapid Synthesis of Nitriles under Mild Conditions
-
A mild, scalable, high yielding, and rapid route to access diverse nitriles from aldehyde oxime esters enabled by iron(III) and phenol co-catalysis has been developed. The reaction was performed at room temperature to give nitriles in excellent yield within minutes. Mechanistic studies show that the reaction may proceed through a radical process in which benzoyl aldehyde oxime is not only a substrate, but also an ancillary ligand to support iron salt in the promotion of the transformation.
- Meng, Hong,Gao, Sen,Luo, Meiming,Zeng, Xiaoming
-
p. 4617 - 4623
(2019/07/15)
-
- Ni-Mediated Generation of "cN" Unit from Formamide and Its Catalysis in the Cyanation Reactions
-
The in situ generation of a "cyano" unit from readily available organic precursors is of high interest in synthetic chemistry. Herein, we report the first example of Ni-mediated dehydration of formamide to form "CN" and its subsequent catalytic applications in the hydrocyanation of alkynes and cyanation of aryl halides. Formamide can serve as a convenient source for the nitrile unit, in that it releases water as the only byproduct.
- Yang, Luo,Liu, Yu-Ting,Park, Yoonsu,Park, Sung-Woo,Chang, Sukbok
-
p. 3360 - 3365
(2019/03/26)
-
- Nickel-catalyzed cyanation of aryl halides and triflates using acetonitrile: Via C-CN bond cleavage assisted by 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine
-
We developed a non-toxic cyanation reaction of various aryl halides and triflates in acetonitrile using a catalyst system of [Ni(MeCN)6](BF4)2, 1,10-phenanthroline, and 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine (Si-Me4-DHP). Si-Me4-DHP was found to function as a reductant for generating nickel(0) species and a silylation reagent to achieve the catalytic cyanation via C-CN bond cleavage.
- Ueda, Yohei,Tsujimoto, Nagataka,Yurino, Taiga,Tsurugi, Hayato,Mashima, Kazushi
-
p. 994 - 999
(2019/02/03)
-
- Preparing method of aromatic nitrile or alkenyl nitrile compound
-
The invention discloses a preparing method of an aromatic nitrile or alkenyl nitrile compound. The preparing method comprises the following step that under protection of inert gas, an aryl or heteroaryl sulphonate compound shown in a formula II or an alkenyl sulphonate compound shown in a formula IV and a cyanation reagent are subjected to a cross-coupling reaction as is shown below in a solvent under the condition of the presence of a nickel complex, metal zinc and an additive to obtain the aromatic nitrile or alkenyl nitrile compound, wherein 4-dimethylamiopryidine (DMAP) is adopted as the additive, and zinc cyanide is adopted as the cyanation reagent. By means of the preparing method, cyanation of aryl sulphonate, heteroaryl sulphonate or alkenyl sulphonate can be simply and efficientlyachieved with a cheap catalysis system; moreover, the functional group compatibility and substrate universality are good, and a better application prospect and higher using value are provided for achieving industrial synthesis of the aromatic nitrile or alkenyl nitrile compound.
- -
-
Paragraph 0130-0132; 0154-0156; 0232-0233
(2019/10/01)
-
- Uniform silver nanoparticles on tunable porous N-doped carbon nanospheres for aerobic oxidative synthesis of aryl nitriles from benzylic alcohols
-
Tunable N-doped carbon nanospheres from sucrose as carbon source and Tris(2-aminoethyl)amine (TAEA) as nitrogen source by a simple and easily reproducible method were prepared. It was demonstrated that the tunable N-doping of carbon spheres could be realized by altering the ratio of TAEA in the raw materials. The content of doped nitrogen, surface area, pore volume and pore size of carbon nanospheres were increased with the increasing of TAEA amount in the hydrothermal process. Prepared N-doped carbon nanospheres act as solid ligand for anchoring of Ag NPs which generated via chemical reduction of Ag ions. Benzylic alcohols and aldehydes were converted into the aryl nitriles by using Ag/N-CS-1 nanospheres as the catalyst and O2 as the oxidant, efficiently. This catalyst was stable and could use for 6 successful runs.
- Hashemi, Alireza Nemati,Eshghi, Hossein,Lamei, Kamran
-
-
- A carboxamide is the cyanogen source of aromatic nitrile to the preparation method of the (by machine translation)
-
The invention discloses a method for preparing aromatic nitrile, is under the action of the nickel catalyst, in order to carboxamide is the cyanogen source, and with various substituents haloarene coupled reactions, preparing aromatic nitrile. The reaction temperature is 100 - 160 °C, the reaction time is 6 - 24 hours. It overcomes the traditional aromatic nitrile of the synthesis method operation of complex steps, requires the use of a toxic, more expensive, functionalization of the cyanogen source as the reaction raw material and the like. Compared with the traditional method, this method is simple to use cheap, green non-toxic of the formamide is cyano sources; without the need of external dehydrating agent, formamide in the nickel catalyst of the catalytic dehydration at the same time, with a nickel catalyst in coordination with the halogenated aromatic hydrocyanation, more economic, high-efficiency, environmental protection; at the same time the method exhibits good substrate universality, to air, moisture, light are not sensitive, high yield, product separation and purification is simple, with wide application. (by machine translation)
- -
-
Paragraph 0015; 0016; 0017; 0018-0024; 0116; 0117-0120
(2019/05/08)
-
- Catalytic Cyanation Using CO2 and NH3
-
Li and co-workers describe the catalytic cyanation of organic halides with CO2 and NH3. In the presence of Cu2O/DABCO as the catalyst, a variety of aromatic bromides and iodides were transformed to the desired nitrile products with broad functional-group tolerance. Both 13C- and/or 15N-labeled nitriles were obtained conveniently with appropriately isotope-labeled CO2 and NH3. Construction of functionalized chemical compounds from small molecules in a highly selective and efficient manner is crucial for sustainable development. The chemical-based manufacturing sector of the future should aim to produce chemicals from very simple and abundant resources, just as nature uses CO2 and N2 to generate sugars, amino acids, and so forth. In practice, however, the utilization of CO2 for the generation of industrial products, such as drugs and related intermediates, still remains a major challenge. Here, we describe the facile cyanide-free production of high-value nitriles with CO2 and NH3 as the sole sources of carbon and nitrogen, respectively. This practical and catalytic methodology provides a unique strategy for the utilization of small molecules for sustainable and cost-effective applications. Selective cyanation of aryl halides was achieved with CO2 and NH3 as the only sources of carbon and nitrogen, respectively. In the presence of Cu catalysts under low pressure (3 atm), a variety of aromatic iodides and bromides were transformed to the desired nitrile products without the use of toxic metal cyanides. Notably, olefins, esters, amides, alcohols, and amino groups were tolerated. Mechanistic studies suggest that Cu(III)-aryl insertion by isocyanate intermediates is involved. [13C,15N]-labeled nitriles were conveniently accessible from the respective isotope-labeled CO2 and NH3 via this methodology.
- Wang, Hua,Dong, Yanan,Zheng, Chaonan,Sandoval, Christian A.,Wang, Xue,Makha, Mohamed,Li, Yuehui
-
supporting information
p. 2883 - 2893
(2019/01/05)
-
- Nickel-Catalyzed Cyanation of Phenol Derivatives with Zn(CN)2 Involving C-O Bond Cleavage
-
An efficient nickel-catalyzed cyanation of aryl sulfonates, fluorosulfonates, and sulfamates with Zn(CN)2 was developed, which provides a facile access to the nitrile products in generally good to excellent yields. The reaction is accomplished by using NiII complex as the precatalyst and DMAP as the additive. The method also displays wide functional group compatibility; for example, keto, methoxy, N,N-dimethylamino, cyano, ester, and pyridyl groups are well-tolerated during the reaction process.
- Gan, Yi,Wang, Gaonan,Xie, Xin,Liu, Yuanhong
-
p. 14036 - 14048
(2018/11/03)
-
- Synthesis method of benzonitrile compounds
-
The invention provides a preparation method of benzonitrile compounds. The preparation method comprises the steps: carrying out a reaction in an organic solvent at 0-50 DEG C for 4-12h under the action of an oxidant by taking phenylacetylene as shown in the formula (I) and a derivative of phenylacetylene as raw materials and nitrite as a nitrogen source, and separating and purifying the obtained reaction liquid to prepare the benzonitrile compound as shown in the formula (II); and the amount-of-substance ratio of the nitrogen source to phenylacetylene as shown in the formula (I) and the derivative of phenylacetylene is (1-3):1. The preparation method is simple and available in raw material, mild in reaction condition, good in functional group tolerance, simple in operation and environment-friendly so as to be a novel method for synthesizing benzonitrile containing various substituent groups.
- -
-
Paragraph 0064; 0065; 0066
(2018/04/02)
-
- Practical CuCl/DABCO/4-HO-TEMPO-catalyzed oxidative synthesis of nitriles from alcohols with air as oxidant
-
A mild and efficient methodology for the direct oxidative synthesis of nitriles from easily available alcohols and aqueous ammonia by employing CuCl/DABCO/4-HO-TEMPO as the catalysts is described. This protocol uses the air as a green oxidant and aqueous ammonia as the nitrogen source at room temperature. A variety of aryl, heterocyclic and allylic alcohols are smoothly converted into the corresponding nitriles in good to excellent yields.
- Hu, Yongke,Chen, Lei,Li, Bindong
-
supporting information
p. 464 - 466
(2017/11/13)
-
- Magnetically recoverable lanthanum hydroxide as an efficient catalyst for Aerobic Oxidative Conversions of primary alcohols to the nitriles
-
Herein we report a novel magnetically recoverable lanthanum hydroxide nanoparticles for oxidative synthesis of nitriles directly from corresponding alcohols with ammonia as nitrogen source. The procedure for the preparation and characterization of La(OH)3/Fe3O4 magnetic nanoparticles were investigated and the scope and generality of the method was explored for a series of structurally diverse primary alcohols with electron-donating and electron-withdrawing groups. The best result was observed when 5?mol% of La with respect to the benzyl alcohol was used at reflux condition under O2 atmosphere. The La(OH)3/Fe3O4 magnetic nanoparticles could be easily isolated from the reaction mixture with an external magnet and reused at least 5 times without significant loss in activity.
- Ziaee, Fariborz,Gholizadeh, Mostafa,Seyedi, Seyed Mohammad
-
-
- Preparation method of aromatic nitrile compound or heteroaromatic nitrile compound
-
The invention discloses a preparation method of an aromatic nitrile compound or a heteroaromatic nitrile compound. The preparation method comprises: under the protection of an inert gas, in a solvent,under the actions of a nickel catalyst, a ligand, metal zinc and an additive, carrying out a reaction on a cyanation reagent and halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon. According to the present invention, by using the inexpensive and easily-available nickel catalyst and the ligand, the halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon,especially the chlorinated aromatic hydrocarbon or chlorinated heteroaromatic hydrocarbon with characteristics of low price, easy obtaining and low reaction activity can mildly and efficiently react with the cyanation reagent with low toxicity to prepare the aromatic nitrile compound or heteroaromatic nitrile compound; and the preparation method has advantages of simple operation, mildness, high efficiency and the like, and further has characteristics of good functional group compatibility, good universality of substrate and the like.
- -
-
Paragraph 0043; 0045; 0061-0063
(2018/11/03)
-
- Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-hydrocyanation with Cross-Coupling
-
We describe a nickel-catalyzed cyanation reaction of aryl (pseudo)halides that employs butyronitrile as a cyanating reagent instead of highly toxic cyanide salts. A dual catalytic cycle merging retro-hydrocyanation and cross-coupling enables the conversion of a broad array of aryl chlorides and aryl/vinyl triflates into their corresponding nitriles. This new reaction provides a strategically distinct approach to the safe preparation of aryl cyanides, which are essential compounds in agrochemistry and medicinal chemistry.
- Yu, Peng,Morandi, Bill
-
supporting information
p. 15693 - 15697
(2017/12/02)
-
- Nickel-Catalyzed C-CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides
-
An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.
- Chatupheeraphat, Adisak,Liao, Hsuan-Hung,Lee, Shao-Chi,Rueping, Magnus
-
supporting information
p. 4255 - 4258
(2017/08/23)
-
- General and Mild Nickel-Catalyzed Cyanation of Aryl/Heteroaryl Chlorides with Zn(CN)2: Key Roles of DMAP
-
A new and general nickel-catalyzed cyanation of hetero(aryl) chlorides using less toxic Zn(CN)2 as the cyanide source has been developed. The reaction relies on the use of inexpensive NiCl2·6H2O/dppf/Zn as the catalytic system and DMAP as the additive, allowing the cyanation to occur under mild reaction conditions (50-80 °C) with wide functional group tolerance. DMAP was found to be crucial for successful transformation, and the reaction likely proceeds via a Ni(0)/Ni(II) catalysis based on mechanistic studies. The method was also successfully extended to aryl bromides and aryl iodides.
- Zhang, Xingjie,Xia, Aiyou,Chen, Haoyi,Liu, Yuanhong
-
supporting information
p. 2118 - 2121
(2017/04/27)
-
- Improving Robustness: In Situ Generation of a Pd(0) Catalyst for the Cyanation of Aryl Bromides
-
Conditions have been developed for the palladium-catalyzed cyanation of aryl bromides utilizing the air-stable XantPhos-PdCl2 precatalyst. By employing a trialkylamine as a reducing agent, the active Pd(0) species is generated in situ, alleviating the need to employ the air-sensitive Pd2(dba)3. Twenty-two substituted benzonitriles have been synthesized using this method.
- Coombs, John R.,Fraunhoffer, Kenneth J.,Simmons, Eric M.,Stevens, Jason M.,Wisniewski, Steven R.,Yu, Miao
-
p. 7040 - 7044
(2017/07/17)
-
- A Homogeneous Method for the Conveniently Scalable Palladium- and Nickel-Catalyzed Cyanation of Aryl Halides
-
Homogeneous conditions for the palladium-catalyzed cyanation of aryl halides were developed. This new system features a broad scope of aryl chlorides and bromides, uses 2-propanol or 1-butanol as solvent, and is readily scalable. The same conditions can also provide simple benzonitriles using the recently developed (TMEDA)NiCl(o-tolyl) precatalyst in conjunction with 1,1′-bis(diphenylphosphino)ferrocene (dppf) as a ligand.
- Burg, Finn,Egger, Julian,Deutsch, Johannes,Guimond, Nicolas
-
p. 1540 - 1545
(2016/08/30)
-
- Utility of Nitrogen Extrusion of Azido Complexes for the Synthesis of Nitriles, Benzoxazoles, and Benzisoxazoles
-
The utility of the nitrogen extrusion reaction of azido complexes, generated in situ from the corresponding aldehydes or ketones with TMSN3 in the presence of ZrCl4 or TfOH, has been described. These azido complexes could undergo three different pathways, depending on the substrates. First, azido methanolate complexes or imine diazonium ions could lead to benzisoxazole products via an intramolecular nucleophilic substitution. Second, imine diazonium ions could also undergo either the elimination of proton to provide nitrile products in good to excellent yields or an aryl migration, followed by an intramolecular nucleophilic addition, to give benzoxazole products in good yields.
- Nimnual, Phongprapan,Tummatorn, Jumreang,Thongsornkleeb, Charnsak,Ruchirawat, Somsak
-
p. 8657 - 8667
(2015/09/15)
-
- Cu-Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO
-
The cyanation of arylboronic acids by using acetonitrile as the "CN" source has been achieved under a Cu(cat.)/TEMPO system (TEMPO=2,2,6,6-tetramethylpiperidine N-oxide). The broad substrate scope includes a variety of electron-rich and electron-poor arylboronic acids, which react well to give the cyanated products in high to excellent yields. Mechanistic studies reveal that TEMPO-CH2CN, generated in situ, is an active cyanating reagent, and shows high reactivity for the formation of the CN- moiety. Moreover, TEMPO acts as a cheap oxidant to enable the reaction to be catalytic in copper. The cyanation of arylboronic acids by using acetonitrile as the "CN" source has been achieved under a Cu(cat.)/TEMPO system. Electron-rich and electron-poor arylboronic acids react well to give the cyanated products in high to excellent yields. Mechanistic studies reveal that TEMPO-CH2CN, generated in situ, is an active cyanating reagent. Moreover, TEMPO, a cheap oxidant, enables the reaction to be catalytic in copper (see scheme; TEMPO=2,2,6,6-tetramethylpiperidine N-oxide).
- Zhu, Yamin,Li, Linyi,Shen, Zengming
-
supporting information
p. 13246 - 13252
(2015/09/15)
-
- Mild palladium-catalyzed cyanation of (hetero)aryl halides and triflates in aqueous media
-
A mild, efficient, and low-temperature palladium-catalyzed cyanation of (hetero)aryl halides and triflates is reported. Previous palladium-catalyzed cyanations of (hetero)aryl halides have required higher temperatures to achieve good catalytic activity. This current reaction allows the cyanation of a general scope of (hetero)aryl halides and triflates at 2-5 mol % catalyst loadings with temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor.
- Cohen, Daniel T.,Buchwald, Stephen L.
-
supporting information
p. 202 - 205
(2015/01/30)
-
- 5-PHENOXY-3H-PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS HIV REVERSE TRANSCRIPTASE INHIBITORS
-
Compounds of Formula (I) are HIV reverse transcriptase inhibitors, wherein R1, R2, RE, L, M and Z are defined herein. The compounds of Formula (I) and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
- -
-
Page/Page column 201
(2014/05/07)
-
- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
-
Compounds of Formula I: are HIV reverse transcriptase inhibitors, wherein R1, R2, RE, L, M and Z are defined herein. The compounds of Formula I and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines
- -
-
Page/Page column
(2014/04/18)
-
- Cu2O-mediated room temperature cyanation of aryl boronic acids/esters and TMSCN
-
A method for the efficient and reliable synthesis of aryl nitriles via the Cu2O-catalyed cross-coupling of aryl boronic acids or esters and TMSCN is presented. A broad range of substrates decorated by electron-rich and deficient, sterically very congested, and labile functionalities were tolerated. Moreover, the reaction can proceed under mild conditions at room temperature. These advantages paired with the use of cheap, readily available, and halogen-free Cu2O as catalysts make the protocol an appealing option for aryl cyanations. A method for the efficient and reliable synthesis of aryl nitriles via the Cu2O-catalyed cross-coupling of aryl boronic acids or esters and TMSCN is presented. The room temperature operation paired with the use of cheap, readily available, and halogen-free Cu2O as catalysts makes the protocol an appealing option for aryl cyanations. Copyright
- Ye, Yong,Wang, Yanhua,Liu, Pengtang,Han, Fushe
-
supporting information
p. 27 - 30
(2013/08/24)
-
- Copper-mediated transformation of organosilanes to nitriles with DMF and ammonium iodide
-
Cyanation of aryl-, diaryldimethyl-, and styrylsilanes was developed for the first time under copper-mediated oxidative conditions using ammonium iodide and DMF as the combined source of nitrogen and carbon atom of the introduced cyano unit, respectively. The reaction was observed to proceed in a two-step process: initial conversion of organosilanes to their iodo intermediates and then cyanation. This method has a broad substrate scope with high functional group tolerance.
- Wang, Zhen,Chang, Sukbok
-
supporting information
p. 1990 - 1993
(2013/06/04)
-
- Copper-mediated sequential cyanation of aryl C-B and arene C-H bonds using ammonium iodide and DMF
-
The cyanation of aromatic boronic acids, boronate esters, and borate salts was developed under copper-mediated oxidative conditions using ammonium iodide and DMF as the source of nitrogen and carbon atom of the cyano unit, respectively. The procedure was successfully extended to the cyanation of electron-rich benzenes, and regioselective introduction of a cyano group at the arene C-H bonds was also achieved. The observation that the reaction proceeds via a two-step process, initial iodination and then cyanation, led us to propose that ammonium iodide plays a dual role to provide iodide and nitrogen atom of the cyano moiety.
- Kim, Jinho,Choi, Jiho,Shin, Kwangmin,Chang, Sukbok
-
supporting information; experimental part
p. 2528 - 2531
(2012/04/04)
-
- Cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by dichloro[bis{1-(dicyclohexylphosphanyl)piperidine}]palladium, a molecular source of nanoparticles, and the reactions involved in the catalyst-deactivation processes
-
Dichloro[bis{1-(dicyclohexylphosphanyl)piperidine}]palladium [(P{(NC 5H10)(C6H11)2}) 2PdCl2] (1) is a highly active and generally applicable C-C cross-coupling catalyst. Apart from its high catalytic activity in Suzuki, Heck, and Negishi reactions, compound 1 also efficiently converted various electronically activated, nonactivated, and deactivated aryl bromides, which may contain fluoride atoms, trifluoromethane groups, nitriles, acetals, ketones, aldehydes, ethers, esters, amides, as well as heterocyclic aryl bromides, such as pyridines and their derivatives, or thiophenes into their respective aromatic nitriles with K4[Fe(CN)6] as a cyanating agent within 24 h in NMP at 140 °C in the presence of only 0.05 mol % catalyst. Catalyst-deactivation processes showed that excess cyanide efficiently affected the molecular mechanisms as well as inhibited the catalysis when nanoparticles were involved, owing to the formation of inactive cyanide complexes, such as [Pd(CN)4]2-, [(CN)3Pd(H)]2-, and [(CN)3Pd(Ar)]2-. Thus, the choice of cyanating agent is crucial for the success of the reaction because there is a sharp balance between the rate of cyanide production, efficient product formation, and catalyst poisoning. For example, whereas no product formation was obtained when cyanation reactions were examined with Zn(CN)2 as the cyanating agent, aromatic nitriles were smoothly formed when hexacyanoferrate(II) was used instead. The reason for this striking difference in reactivity was due to the higher stability of hexacyanoferrate(II), which led to a lower rate of cyanide production, and hence, prevented catalyst-deactivation processes. This pathway was confirmed by the colorimetric detection of cyanides: whereas the conversion of β-solvato-α-cyanocobyrinic acid heptamethyl ester into dicyanocobyrinic acid heptamethyl ester indicated that the cyanide production of Zn(CN)2 proceeded at 25 °C in NMP, reaction temperatures of >100 °C were required for cyanide production with K4[Fe(CN) 6]. Mechanistic investigations demonstrate that palladium nanoparticles were the catalytically active form of compound 1. A balancing act: Compound 1 (see scheme) is a highly active cyanation catalyst. Furthermore, a sharp balance between the rates of cyanide generation, efficient product formation, and catalyst deactivation owing to excess cyanide was observed in deactivation processes. Copyright
- Gerber, Roman,Oberholzer, Miriam,Frech, Christian M.
-
supporting information; experimental part
p. 2978 - 2986
(2012/04/04)
-
- SUBSTITUTED NAPHTHYRIDINES AND THEIR USE AS SYK KINASE INHIBITORS
-
The invention relates to new substituted naphthyridines of formula (1), as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R1 is selected from among -O-R3 or -NR3R4, R3 is C1-6-alkyl which is substituted by R5 and R6 R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, -C1-6-alkylen-O-C1-3-alkyl, C1-3-haloalkyl, R6 is ring X wherein n is either 0 or 1, and Formula (I) is a either a single or a double bond and wherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, -C1-3-alkyl, -C1-3-haloalkyl, -O-C1-3-alkyl, -C1-3-alkanol and halogen, and wherein R4, R2, R7, R8, R9, R10, R11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds.
- -
-
Page/Page column 45
(2011/08/21)
-
- A general rhodium-catalyzed cyanation of aryl and alkenyl boronic acids
-
Give me a cyanide: N-cyano-N-phenyl-p-methylbenzenesulfonamide as a cyanation reagent allows the synthesis of aryl(alkenyl) nitriles in good yield under mild conditions (see scheme; cod=cycloocta-1,5-diene). Combination of the procedure with the direct borylation of arenes and hydroboration of alkynes leads to the straightforward synthesis of various nitriles.
- Anbarasan, Pazhamalai,Neumann, Helfried,Beller, Matthias
-
p. 519 - 522
(2011/03/16)
-
- Cyanation of arenes via iridium-catalyzed borylation
-
We report a method to conduct one-pot meta cyanation of arenes by iridium-catalyzed C-H borylation and copper-mediated cyanation of the resulting arylboronate esters. This process relies on a method to conduct the cyanation of arylboronic esters, and conditions for this new transformation are reported. Conditions for the copper-mediated cyanation of arylboronic acids are also reported. By the resulting sequence of borylation and cyanation, 1,3-disubstituted and 1,2,3-trisubstituted arenes and heteroarenes containing halide, ketone, ester, amide, and protected alcohol functionalities are converted to the corresponding meta-substituted aryl nitriles. The utility of this methodology is demonstrated through the conversion of a protected 2,6-disubstituted phenol to 4-cyano-2,6-dimethylphenol, which is an intermediate in the synthesis of the pharmaceutical etravirine. The utility of the method is further demonstrated by the conversion of 3-chloro-5-methylbenzonitrile, produced through the one-pot C-H borylation and cyanation sequence, to the corresponding 3,5-disubstituted aldehydes, ketones, amides, carboxylic acids, tetrazoles, and benzylamines.
- Liskey, Carl W.,Liao, Xuebin,Hartwig, John F.
-
supporting information; experimental part
p. 11389 - 11391
(2010/10/01)
-
- Synthesis, characterization, and antimicrobial activities of clubbed [1,2,4]-oxadiazoles with fluorobenzimidazoles
-
(Chemical Equation Presented) In this study, a novel series of substituted 4,6-difluoro-2-{2-[3-(substituted-phenyl)-[1,2,4]-oxadiazol-5-yl]-ethyl} -1H-benzo[d]imidazole derivatives were synthesized by condensation of 2,4-difluoro-6-nitrophenyl amine with 3-(substitutedphenyl-[1,2,4]-oxadiazol- 5yl) propionic acid by using 2,4,6-trichlorobenzoyl chloride in the presence of triethyl amine base. The compounds were evaluated for their preliminary in vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa. The antibacterial data of the tested compounds indicated that most of the synthesized compounds showed moderate activity with reference standard Gentamycin.
- Jadhav, Ganesh R.,Shaikh, Mohammad U.,Kale, Rajesh P.,Ghawalkar, Anand R.,Gill, Charansingh H.
-
experimental part
p. 980 - 987
(2009/12/05)
-
- Application of polymer-supported triphenylphosphine and microwave irradiation to the palladium-catalyzed cyanation of aryl triflates
-
A variety of aryl nitriles were prepared in excellent yield from the palladium(II) acetate-catalyzed cross-coupling of aryl triflates and zinc cyanide under microwave irradiation conditions. To facilitate purification, polymer-supported triphenylphosphine was used as the palladium ligand. Comparison to the corresponding thermal conditions revealed much shorter reaction times with comparable yields. Copyright Taylor & Francis Group, LLC.
- Srivastava, Rajiv R.,Zych, Andrew J.,Jenkins, David M.,Wang, Hong-Jun,Chen, Zhen-Jia,Fairfax, David J.
-
p. 431 - 438
(2007/10/03)
-
- Simple and Efficient Copper-Catalyzed One-Pot Conversion of Aldehydes into Nitriles
-
Aromatic, heterocyclic, and tertiary aliphatic nitriles are prepared from the corresponding aldehydes by the ammonium chloride/copper powder/oxygen system in pyridine.This new one-flask procedure affords very high to quantitative yields of pure nitriles.
- Capdevielle, Patrice,Lavigne, Andre,Maumy, Michel
-
p. 451 - 452
(2007/10/02)
-