- Formylation of amines through catalyst- and solvent-free transamidation reaction
-
The transamidation between formamide and various amines proceeds under heating, without any catalyst nor solvent, providing thus green and neutral conditions for the formylation of primary and secondary amines. The resulting amide product can be directly transformed, in a one pot sequence, into monomethylamine.
- Lebleu, Thomas,Kotsuki, Hiyoshizo,Maddaluno, Jacques,Legros, Julien
-
-
Read Online
- Mechanism of α-Amino Acids decomposition in the gas phase. Experimental and theoretical study of the elimination kinetics of N-Benzyl Glycine Ethyl Ester
-
The gas-phase elimination kinetics of N-benzylglycine ethyl ester was examined in a static system, seasoned with allyl bromide, and in the presence of the free chain radical suppressor toluene. The working temperature and pressure range were 386.4-426.7 °C and 16.7-40.0 torr, respectively. The reaction showed to be homogeneous, unimolecular, and obeys a first-order rate law. The elimination products are benzylglycine and ethylene. However, the intermediate benzylglycine is unstable under the reaction conditions decomposing into benzyl methylamine and CO2 gas. The variation of the rate coefficients with temperature is expressed by the following Arrhenius equation: log k1 (s-1) = (11.83 ± 0.52) - (190.3 ± 6.9) kJ mol -1 (2.303RT)-1. The theoretical calculation of the kinetic parameters and mechanism of elimination of this ester were performed at B3LYP/6-31G*, B3LYP/6-31+G**, MPW1PW91/6-31G*, and MPW1PW91/6-31+G** levels of theory. The calculation results suggest a molecular mechanism of a concerted nonsynchronous six-membered cyclic transition state process. The analysis of bond order and natural bond orbital charges implies that the bond polarization of C(=O)O-C, in the sense of C(=O)Oδ-...Cδ+, is rate determining. The experimental and theoretical parameters have been found to be in reasonable agreement.
- Tosta, Maria,Oliveros, Jhenny C.,Mora, Jose R.,Cordova, Tania,Chuchani, Gabriel
-
-
Read Online
- New catalyst systems for iron-catalyzed hydrosilane reduction of carboxamides
-
A heptanuclear iron carbonyl cluster, [Fe3(CO) 11(μ-H)]2Fe(DMF)4 (4), is found to be a highly efficient catalyst for the reduction of various carboxamides by 1,2-bis(dimethylsilyl)benzene (BDSB), which makes possible reducing the amount of the catalyst, shortening the reaction time, and lowering the reaction temperatures.
- Tsutsumi, Hironori,Sunada, Yusuke,Nagashima, Hideo
-
-
Read Online
- Methylthio Activating Groups in the Synthesis of Isoquinolines
-
Methylthio activating groups have been found to improve the yields in six different isoquinoline syntheses: in four cases the improvement was from zero, in the unactivated system, to between 54 and 94percent.
- Euerby, Melvin R.,Waigh, Roger D.
-
-
Read Online
- Reactions of N-Halobenzylalkylamines with Sodium Methoxide in Methanol
-
Reactions of N-halobenzylmethylamines 1 and 2 (X = Cl and Br) with MeONa-MeOH have been investigated.Eliminations from 1 were quantitative, producing only benzylidenemethylamines.Reaction of 2 with MeONa-MeOH produced benzylidenemethylamines and benzylmethylamines.The yield of benzylidenemethylamine increased with electron-withdrawing aryl substituents and increased base concentration and became quantitative when pentane was used as a solvent.The results are interpreted as competing bimolecular elimination and nucleophilic substitution by methoxide on bromine.Product studies for reaction of N-halobenzyl-tert-butylamines with MeONa-MeOH and EtSNa-MeOH establish that the substitution reaction is a general reaction pathway available for the N-haloamines.Transition states for eliminations from 1 and 2 are characterized by Hammett ρ and primary deuterium isotope effect values.
- Cho, Bong Rae,Yoon, Jong Chan,Bartsch, Richard A.
-
-
Read Online
- Organolanthanide-catalyzed imine hydrogenation. Scope, selectivity, mechanistic observations, and unusual byproducts
-
In this paper we report the Cp'2LnMe2SiCp''2Ln-catalyzed (Cp' = η5-Me5C5; Cp'' = η5-Me4C5) hydrogenation of acyclic imines to yield the corresponding amines. At 190 psi of H2, the observed turnover frequencies (h-1) (100:1 substrate:catalyst ratio, Cp'2Ln, temperature (°C)) are (1) (N-benzylidene(methyl)amine, Ln = La, 50) 0.03; (Ln = Sm, 90) 1.0; (Ln = Sm + PhSiH3, 90) 2.2; (Ln = Lu, 90) 0.60; (2) (N-benzylideneaniline, Ln = Sm, 90) 0.10; (3) (N-benzylidene(trimethylsilyl)amine, Ln = Sm, 90) 0.40; (4) (N-(α-methylbenzylidene)(methyl)amine, Ln = Sm, 90) 0.20; (5) (N-(α-methylbenzylidene)(benzyl)amine, Ln = Sm, 90) 0.70. The stoichiometric reaction of N-benzylidene(methyl)amine with Cp'2SmCH(SiMe3)2 or (Cp'2SmH)2 yields an orthometalated Cp'2Sm-substrate complex which undergoes either hydrogenolysis/hydrogenation or competing C=N insertion of a second substrate molecule to yield a Cp'2Sm-imine-amido complex with a seven-membered chelate ring. The stoichiometric reaction of 2-methyl-1-pyrroline with Cp'2SmCH(SiMe3)2 or (Cp'2SmH)2 yields a Cp'2Sm-imine-amido complex in which two substrate molecules have been coupled to form a six-membered chelate ring (characterized by X-ray diffraction). The stoichiometric reaction of N-benzylidene(trimethylsilyl)amine with (Cp'2SmH)2 yields a desilylated Cp'2Sm-imine-amido complex with a four-membered Sm(NSiMe3)(CPh)N=CHPh chelate ring (characterized by X-ray diffraction). Additional heating of this product under H2 yields S6-symmetric (Cp'2SmCN)6, which contains an unusual chairlike 18-membered (SmCN)6 ring (characterized by X-ray diffraction).
- Obora, Yasushi,Ohta, Tetsuo,Stern, Charlotte L.,Marks, Tobin J.
-
-
Read Online
- Reactions of N-Chlorobenzylmethylamines with Secondary Amines in Acetonitrile. Effect of Base Strength upon the Imine-Forming Transition State
-
Reactions of N-chlorobenzylmethylamines 1 with R2NH in MeCN have been investigated kinetically.Eliminations from 1 were quantitative and regiospecific, producing only benzylidenemethylamines.For the elimination reaction of 1 with Bu2NH, kH/kD = 8.8, ρ = 0.96, ΔH(excit.) = 7.6 kcal/mol, and ΔS(excit.) = -45.1 eu were determined.The transition state structure is assessed as being highly symmetrical with similar extents of Cβ-H and Nα-Cl bond cleavage, little carbanionic character, and significant ? bond formation.The kH/kD and ρ values first increase and then decrease with enhancing amine base strength.Comparison of these results with those for related olefin-forming eliminations provides insight into the transition state differences between imine- and olefin-forming eliminations.
- Cho, Bong Rae,Namgoong, Sung Keon,Bartsch, Richard A.
-
-
Read Online
- Reduction of amides with NaBH4 in diglyme at 162°C
-
High temperature (162°C) reductions of aromatic amides were studied to extend the useful range of functional group transformations by NaBH4. Primary aromatic amides were reduced to the amines with NaBH4-diglyme at 162°C. Reduction proceeds via fast initial loss of hydrogen, followed by formation of the corresponding nitrile, which is then more slowly reduced to the amine. N-Methylbenzamide is not reduced under these conditions, but it is reduced to benzylmethylamine when LiCl is added to NaBH4-diglyme at 162°C. LiCl addition raised the rate of primary aromatic amide and aromatic nitrile conversions to both the nitrile, first, and the amine. An intermediate was isolated from the reaction of N-benzylformamide with NaBH4-LiCl in diglyme at 162°C. It was examined by 1H NMR, atomic absorption, IR and thermal decomposition. Possible structures are proposed. A mechanism for the reduction of primary aromatic amides is proposed based on the initial evolution of one mole equivalent of hydrogen and formation of the nitrile prior to further reduction to amine.
- Zhu, Hua-Jie,Lu, Kai-Tao,Sun, Guang-Ri,He, Jin-Bao,Li, Hai-Qing,Pittman Jr., Charles U.
-
-
Read Online
- A mild method for cleavage of N-Tos protected amines using mischmetal and TiCl4
-
The para-toluenesulfonyl (Tos) protecting group is removed efficiently and quickly under neutral conditions from the corresponding protected primary and secondary amines using mischmetal in moderate to excellent yields.
- Vellem?e, Eerold,Lebedev, Oleg,M?eorg, Uno
-
-
Read Online
- Chelating bis-carbene rhodium(III) complexes in transfer hydrogenation of ketones and imines
-
Chelating rhodium(III) carbene complexes are accessible via a simple synthesis and are catalytically active for hydrogen transfer from alcohols to ketones and imines.
- Albrecht, Martin,Crabtree, Robert H.,Mata, Jose,Peris, Eduardo
-
-
Read Online
- N-Nitrosobenzylmethylamine is activated to a DNA benzylating agent in rats
-
The ability of rat tissues to activate the esophageal carcinogen, N- nitrosobenzylmethylamine (NBzMA), to a DNA benzylating intermediate was investigated. [3-3H]NBzMA was prepared and given to male F344 rats. Tissues were harvested 4 h after treatment, and DNA was isolated. HPLC analysis with radiochemical detection of chemical and enzymatic hydrolysates of DNA from liver and lung revealed the formation of benzyl adducts. Benzyl alcohol, N2- benzylguanine, 3-benzyladenine, N6-benzyladenine, and 7-benzylguanine were the major radioactive components in the hydrolysates. An unknown adduct was also observed. The adduct distribution was similar to that observed in [3- 3H]benzylnitroseurea ([3-3H]BzNU)treated calf thymus DNA. However, enzymatic hydrolysates of [3-3H]BzNU-treated DNA also contained significant levels of O6-benzyl-2'-deoxyguanosine (O6-BzdG). This radioactive adduct disappeared upon incubation of the DNA with a crude preparation of the repair protein, O6-alkylguanine-DNA alkyltransferase isolated from rat liver. These data provide evidence that O6-BzdG is probably rapidly repaired in vivo. No benzylation of esophageal mucosal DNA was detected. The level of DNA benzylation observed in tissues from [3-3H]NBzMA-treated rats was several orders of magnitude lower than the level of DNA methylation in these same tissues. Therefore, these data indicate that DNA benzylation plays a minor role, if any, in the carcinogenic activity of NBzMA.
- Peterson, Lisa A.
-
-
Read Online
- Deprotection of o-nitrobenzensulfonyl (nosyl) derivatives of amines mediated by a solid-supported thiol
-
A new protocol based on a solid-supported thiol was developed for high yielding deprotection of o-nitrobenzensulfonyl amides derived from primary and secondary amines. The reaction can be carried out at room temperature for 24 hours or accelerated by microwave irradiation, going to completion in six minutes. Georg Thieme Verlag Stuttgart.
- Cardullo, Francesca,Donati, Daniele,Merlo, Giancarlo,Paio, Alfredo,Salaris, Margherita,Taddei, Maurizio
-
-
Read Online
- Development of a microwave-enhanced isotopic labelling procedure based on the Eschweiler-Clarke methylation reaction
-
A number of primary and secondary amines have been rapidly methylated under microwave-enhanced conditions using formic acid-formaldehyde mixtures, providing a route to 2H(D)-containing compounds and the potential for 3H(T), 11C, 13C and 14C labelling.
- Harding, John R.,Jones, John R.,Lu, Shui-Yu,Wood, Robin
-
-
Read Online
- The reaction of benzothiazole sulfenamide with (TMS)3SiH: An example of degenerate-branched chain process
-
The reaction of sulfenamide 3 with (TMS)3SiH initiated by the decomposition of AIBN at 76°C has been studied in some detail. The reaction is a rare example of a radical chain-branching process. The two main products are dialkylamine 4 and the thiosilane 5. It is also established that 2-mercaptobenzothiazole (2) is formed in a substantial yield as one of the by-products. The mechanism of this chain autocatalytic reaction is complex due to a mix of different radical chain reactions and some discussion is provided. The amine obtained in a quantitative yield can arise from two independent routes of attack of (TMS)3Si. radical on sulfenamide 3. The minor route affords thiol 2 that can act as a catalyst for the major route during the reaction course and then gives a salt with secondary amine, which precipitates upon cooling. The origin of autocatalysis is discussed in some detail.
- Varlamov, Vladimir T.,Ferreri, Carla,Chatgilialoglu, Chryssostomos
-
-
Read Online
- Formation of benzylamines from triazene compounds via a 1,2-proton shift
-
A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group. The reaction contains the following steps: intramolecular carbon-carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that the reaction proceeds through a 1,2-proton shift.
- Nishiwaki, Keiji,Ogawa, Takashi,Shigeta, Kazumi,Takahashi, Koichi,Matsuo, Keizo
-
-
Read Online
- Electrolytic N-Alkylation of Amines with Alcohols
-
Electrolysis of the alcohol solution of amines in a one-chamber cell resulted in N-alkylation of the amines with sufficient current efficiencies.Platinum black particles suspended in the reaction mixture enhanced the efficiency due to their catalytic role for hydrogenation of a Schiff base intermediate.
- Ohtani, Bunsho,Nakagawa, Koji,Nishimoto, Sei-ichi,Kagiya, Tsutomu
-
-
Read Online
- Diethylenetriamine-Mediated Direct Cleavage of Unactivated Carbamates and Ureas
-
Diethylenetriamine is effective for the direct cleavage of unactivated carbamates and ureas without additional reagents and catalysts. Various carbamates and ureas were cleaved to afford products in good yield, and the reactions were not affected by air or moisture. Unique chemoselective cleavage of carbamate and urea in the presence of amides was also achieved.
- Noshita, Megumi,Shimizu, Yuhei,Morimoto, Hiroyuki,Ohshima, Takashi
-
-
Read Online
- Carbamate linkers as latent N-methylamines in solid phase synthesis
-
A new linker strategy for solid phase synthesis has been developed. It utilizes LAH reduction of a carbamate connection to Wang resin which results in N-methylamines, a useful functionality in medicinal chemistry.
- Ho, Chih Y.,Kukla, Michael J.
-
-
Read Online
- α-lithiation of 1-Aryl-3,3-dialkyltriazenes and intramolecular conversion to benzylamine and tetrahydrobenzotriazine derivatives
-
An alternative route to benzylamine derivatives is provided by the lithiation of aryltriazenes followed by treatment with an electrophile [Eq. (1)]. The regioselectivity of the reaction can be controlled by means of the substituents X. When the 2- and 6-p
- Nishiwaki, Keiji,Ogawa, Takashi,Matsuo, Keizo
-
-
Read Online
- Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
-
Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC50 value of 5.3 nM and an excellent growth inhibition with GI50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.
- Park, Sun You,Oh, Yong Jin,Lho, Yunmee,Jeong, Ju Hui,Liu, Kwang-Hyeon,Song, Jaeyoung,Kim, Soong-Hyun,Ha, Eunyoung,Seo, Young Ho
-
-
Read Online
- 208. Aminierende reduktive Kupplung aromatischer Aldehyde mit niedervalenten Titan-Reagenzien zu 1,2-Diarylethylendiaminen
-
In a novel McMurry-type one-pot reaction, aromatic aldehydes and secondary amines are coupled to give the N,N,N',N'-tetralkyl-1,2-diarylethylendiamines 1-22 (Table 3).To this end, a lithium dialkylamide is added to an aromatic aldehyde to give the adduct B which is then treated with 1 equiv. of TiCl4 to yield a coloured suspension of a reagent synthetically equivalent to a iminium salt (C/D in Scheme 4).After treatment with a low-valent Ti reagent which is prepared by reduction of TiCl4 with either K or, preferably, Mg, the coupling products are isolated in 23 to 81 percent yield as a 1:1 mixture of the diastereoisomers (meso- and rac-form).These are separated either by chromatography or by crystallization and characterized.
- Betschart, Claudia,Seebach, Dieter
-
-
Read Online
- Naphthalene-catalysed lithiation of phenone imines in the presence of carbonyl compounds: Preparation of 1,2-aminoalcohols
-
The lithiation of different phenone imines 1 with an excess of lithium powder and a catalytic amount (8 mol %) of naphthalene in the presence of several carbonyl compounds 2 in tetrahydrofuran at temperatures ranging between -78 and 20°C leads, after hydrolysis with water, to the corresponding 1,2-aminoalcohols 3 in moderate yields.
- Guijarro, David,Yus, Miguel
-
-
Read Online
- Electronically tuneable orthometalated RuII–NHC complexes as efficient catalysts for C–C and C–N bond formations via borrowing hydrogen strategy
-
The catalytic activities of a series of simple and electronically tuneable cyclometalated RuII–NHC complexes (2a–d) were explored in various C–C/N bond formations following the borrowing hydrogen process. Slight modifications in the ligand backbone were noted to tune the activities of these complexes. Among them, the complex 2d featuring a 1,2,4-triazolylidene donor with a 4-NO2–phenyl substituent displayed the highest activity for the coupling of diverse secondary and primary alcohols with a low catalyst loading of 0.01 mol% and a sub-stoichiometric amount of inexpensive KOH base. The efficacy of this simple system was further showcased in the challenging one-pot unsymmetrical double alkylation of secondary alcohols using different primary alcohols. Moreover, the complex 2d also effectively catalyses the selective mono-N-methylation of various aromatic and aliphatic primary amines using methanol to deliver a range of N-methyl amines. Mechanistically, the β-alkylation reaction follows a borrowing hydrogen pathway which was established by the deuterium labelling experiment in combination with various control experiments. Intriguingly, in situ1H NMR and ESI-MS analyses evidently suggested the involvement of a Ru–H species in the catalytic cycle and further, the kinetic studies revealed a first order dependence of the reaction rate on the catalyst as well as the alcohol concentrations.
- Illam, Praseetha Mathoor,Rit, Arnab
-
-
- A Convenient and Stable Heterogeneous Nickel Catalyst for Hydrodehalogenation of Aryl Halides Using Molecular Hydrogen
-
Hydrodehalogenation is an effective strategy for transforming persistent and potentially toxic organohalides into their more benign congeners. Common methods utilize Pd/C or Raney-nickel as catalysts, which are either expensive or have safety concerns. In this study, a nickel-based catalyst supported on titania (Ni-phen@TiO2-800) is used as a safe alternative to pyrophoric Raney-nickel. The catalyst is prepared in a straightforward fashion by deposition of nickel(II)/1,10-phenanthroline on titania, followed by pyrolysis. The catalytic material, which was characterized by SEM, TEM, XRD, and XPS, consists of nickel nanoparticles covered with N-doped carbon layers. By using design of experiments (DoE), this nanostructured catalyst is found to be proficient for the facile and selective hydrodehalogenation of a diverse range of substrates bearing C?I, C?Br, or C?Cl bonds (>30 examples). The practicality of this catalyst system is demonstrated by the dehalogenation of environmentally hazardous and polyhalogenated substrates atrazine, tetrabromobisphenol A, tetrachlorobenzene, and a polybrominated diphenyl ether (PBDE).
- Anwar, Muhammad,Beller, Matthias,Dastgir, Sarim,Junge, Kathrin,Leonard, David K.,Ryabchuk, Pavel
-
-
- Imine reduction with me2s-bh3
-
Although there exists a variety of different catalysts for hydroboration of organic substrates such as aldehydes, ketones, imines, nitriles etc., recent evidence suggests that tetra-coordinate borohydride species, formed by activation, redistribution, or decomposition of boron reagents, are the true hydride donors. We then proposed that Me2S-BH3 could also act as a hydride donor for the reduction of various imines, as similar compounds have been observed to reduce carbonyl substrates. This boron reagent was shown to be an effective and chemoselective hydroboration reagent for a wide variety of imines.
- Kamal, Mohammad M.,Liu, Zhizhou,Vidovi?, Dragoslav,Zhai, Siyuan
-
-
- Design, Synthesis, and Biological Evaluation of Novel 3-Aminomethylindole Derivatives as Potential Multifunctional Anti-Inflammatory and Neurotrophic Agents
-
The development of multifunctional molecules that are able to simultaneously interact with several pathological components has been considered as a solution to treat the complex pathologies of neurodegenerative diseases. Herein, a series of aminomethylindole derivatives were synthesized, and evaluation of their application for antineuroinflammation and promoting neurite outgrowth was disclosed. Our initial screening showed that most of the compounds potently inhibited lipopolysaccharide (LPS)-stimulated production of NO in microglial cells and potentiated the action of NGF to promote neurite outgrowth of PC12 cells. Interestingly, with outstanding NO/TNF-α production inhibition and neurite outgrowth-promoting activities, compounds 8c and 8g were capable of rescuing cells after injury by H2O2. Their antineuroinflammatory effects were associated with the downregulation of the LPS-induced expression of the inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Western blotting and immunofluorescence assay results indicated that the mechanism of their antineuroinflammatory actions involved suppression of the MAPK/NF-κB signal pathways. Further studies revealed that another important reason for the high comprehensive antineuroinflammatory activity was the anti-COX-2 capabilities of the compounds. All these results suggest that the potential biochemical multifunctional profiles of the aminomethylindole derivatives provide a new sight for the treatment of neurodegenerative diseases.
- Wang, Wei-Wei,Liu, Ting,Lv, Yu-Meng,Zhang, Wu-Yang,Liu, Zhi-Gang,Gao, Jin-Ming,Li, Ding
-
p. 1593 - 1605
(2021/05/31)
-
- Discovery of tert-amine-based RORγt agonists
-
The nuclear receptor retinoic acid receptor-related orphan receptor gamma-t (RORγt) is a transcription factor regulating Th17 cell differentiation and proliferation from naive CD4+ T cells. Since Th17 cells have demonstrated the antitumor efficacy by eliciting remarkable activation of CD8+ T cells, RORγt agonists could be applied as potential small molecule therapeutics for cancer immunotherapy. Based on the previously reported RORγt agonist 1 and its resolved co-crystal structure, a series of new tertiary amines were designed, synthesized and biologically evaluated, yielding optimal moieties with improved chemical properties and biological responses. The combination of these optimal moieties resulted in identification of novel RORγt agonists such as 8b with further elevated RORγt agonism responses at a target-based level as well as in cell-based assays, which provided some structural knowledge for further optimization of RORγt agonists as small molecule therapeutics for cancer immunotherapy.
- Qiu, Ruomeng,Yu, Mingcheng,Gong, Juwen,Tian, Jinlong,Huang, Yafei,Wang, Yonghui,Xie, Qiong
-
-
- Zirconium-hydride-catalyzed site-selective hydroboration of amides for the synthesis of amines: Mechanism, scope, and application
-
Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective. In this respect, catalytic deoxygenative amide reduction has proven to be promising but challenging, as this approach necessitates selective C–O bond cleavage. Herein, we report the selective hydroboration of primary, secondary, and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst, Zr-H, for accessing diverse amines. Various readily reducible functional groups, such as esters, alkynes, and alkenes, were well tolerated. Furthermore, the methodology was extended to the synthesis of bio- and drug-derived amines. Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C–N bond cleavage-reformation process, followed by C–O bond cleavage.
- Han, Bo,Jiao, Haijun,Wu, Lipeng,Zhang, Jiong
-
p. 2059 - 2067
(2021/09/02)
-
- Deoxygenative hydroboration of primary, secondary, and tertiary amides: Catalyst-free synthesis of various substituted amines
-
Transformation of relatively less reactive functional groups under catalyst-free conditions is an interesting aspect and requires a typical protocol. Herein, we report the synthesis of various primary, secondary, and tertiary amines through hydroboration of amides using pinacolborane under catalyst-free and solvent-free conditions. The deoxygenative hydroboration of primary and secondary amides proceeded with excellent conversions. The comparatively less reactive tertiary amides were also converted to the corresponding N,N-diamines in moderate yields under catalyst-free conditions, although alcohols were obtained as a minor product.
- An, Duk Keun,Jaladi, Ashok Kumar,Kim, Hyun Tae,Yi, Jaeeun
-
-
- Hydrogenation of Secondary Amides using Phosphane Oxide and Frustrated Lewis Pair Catalysis
-
The metal-free catalytic hydrogenation of secondary carboxylic acid amides is developed. The reduction is realized by two new catalytic reactions. First, the amide is converted into the imidoyl chloride by triphosgene (CO(OCCl3)2) using novel phosphorus(V) catalysts. Second, the in situ generated imidoyl chlorides are hydrogenated in high yields by an FLP-catalyst. Mechanistic and quantum mechanical calculations support an autoinduced catalytic cycle for the hydrogenation with chloride acting as unusual Lewis base for FLP-mediated H2-activation.
- K?ring, Laura,Sitte, Nikolai A.,Bursch, Markus,Grimme, Stefan,Paradies, Jan
-
p. 14179 - 14183
(2021/09/03)
-
- Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol
-
Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.
- Sarki, Naina,Goyal, Vishakha,Tyagi, Nitin Kumar,Puttaswamy,Narani, Anand,Ray, Anjan,Natte, Kishore
-
p. 1722 - 1729
(2021/04/19)
-
- Degradation of Organic Cations under Alkaline Conditions
-
Understanding the degradation mechanisms of organic cations under basic conditions is extremely important for the development of durable alkaline energy conversion devices. Cations are key functional groups in alkaline anion exchange membranes (AAEMs), and AAEMs are critical components to conduct hydroxide anions in alkaline fuel cells. Previously, we have established a standard protocol to evaluate cation alkaline stability within KOH/CD3OH solution at 80 °C. Herein, we are using the protocol to compare 26 model compounds, including benzylammonium, tetraalkylammonium, spirocyclicammonium, imidazolium, benzimidazolium, triazolium, pyridinium, guanidinium, and phosphonium cations. The goal is not only to evaluate their degradation rate, but also to identify their degradation pathways and lead to the advancement of cations with improved alkaline stabilities.
- You, Wei,Hugar, Kristina M.,Selhorst, Ryan C.,Treichel, Megan,Peltier, Cheyenne R.,Noonan, Kevin J. T.,Coates, Geoffrey W.
-
supporting information
p. 254 - 263
(2020/12/23)
-
- Dimethylamination of Primary Alcohols Using a Homogeneous Iridium Catalyst: A Synthetic Method for N, N-Dimethylamine Derivatives
-
A new catalytic system for N,N-dimethylamination of primary alcohols using aqueous dimethylamine in the absence of additional organic solvents has been developed. The reaction proceeds via borrowing hydrogen processes, which are atom-efficient and environmentally benign. An iridium catalyst bearing an N-heterocyclic carbene (NHC) ligand exhibited high performance, without showing any deactivation under aqueous conditions. In addition, valuable N,N-dimethylamine derivatives, including biologically active and pharmaceutical molecules, were synthesized. The practical application of this methodology was demonstrated by a gram-scale reaction.
- Jeong, Jaeyoung,Fujita, Ken-Ichi
-
p. 4053 - 4060
(2021/03/09)
-
- METHOD FOR PRODUCING m-XYLYLENE DIAMINE
-
PROBLEM TO BE SOLVED: To provide a method for producing m-xylylene diamine that makes it possible to efficiently produce m-xylylene diamine by reducing the formation of by-products even when a reaction temperature is lowered in a hydrogenation reaction step. SOLUTION: In the presence of a catalyst with palladium carried on carbon and in the absence of ammonia and an amine compound (excluding a reaction product), 1,3-dicyanobenzene and hydrogen are reacted at 0°C or higher and 50°C or lower, and hydrogen is added to the 1,3-dicyanobenzene, producing m-xylylene diamine. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0061-0072; 0075; 0078-0079
(2021/08/13)
-
- CO2-tuned highly selective reduction of formamides to the corresponding methylamines
-
We herein describe an efficient, CO2-tuned and highly selective C-O bond cleavage of N-methylated formanilides. With easy-to-handle and commercially available NaBH4 as the reductant, a variety of formanilides could be turned into the desired tertiary amines in moderate to excellent yields. The role of CO2 has been investigated in detail, and the mechanism is proposed on the basis of experiments.
- Chao, Jianbin,Guo, Zhiqiang,Pang, Tengfei,Wei, Xuehong,Xi, Chanjuan,Yan, Leilei
-
supporting information
p. 7534 - 7538
(2021/10/12)
-
- Metal-Ligand Cooperation Facilitates Bond Activation and Catalytic Hydrogenation with Zinc Pincer Complexes
-
A series of PNP zinc pincer complexes capable of bond activation via aromatization/dearomatization metal-ligand cooperation (MLC) were prepared and characterized. Reversible heterolytic N-H and H-H bond activation by MLC is shown, in which hemilability of the phosphorus linkers plays a key role. Utilizing this zinc pincer system, base-free catalytic hydrogenation of imines and ketones is demonstrated. A detailed mechanistic study supported by computation implicates the key role of MLC in facilitating effective catalysis. This approach offers a new strategy for (de)hydrogenation and other catalytic transformations mediated by zinc and other main group metals.
- Rauch, Michael,Kar, Sayan,Kumar, Amit,Avram, Liat,Shimon, Linda J. W.,Milstein, David
-
supporting information
p. 14513 - 14521
(2020/10/13)
-
- Transition metal-free catalytic reduction of primary amides using an abnormal NHC based potassium complex: Integrating nucleophilicity with Lewis acidic activation
-
An abnormal N-heterocyclic carbene (aNHC) based potassium complex was used as a transition metal-free catalyst for reduction of primary amides to corresponding primary amines under ambient conditions. Only 2 mol% loading of the catalyst exhibits a broad substrate scope including aromatic, aliphatic and heterocyclic primary amides with excellent functional group tolerance. This method was applicable for reduction of chiral amides and utilized for the synthesis of pharmaceutically valuable precursors on a gram scale. During mechanistic investigation, several intermediates were isolated and characterized through spectroscopic techniques and one of the catalytic intermediates was characterized through single-crystal XRD. A well-defined catalyst and isolable intermediate along with several stoichiometric experiments, in situ NMR experiments and the DFT study helped us to sketch the mechanistic pathway for this reduction process unravelling the dual role of the catalyst involving nucleophilic activation by aNHC along with Lewis acidic activation by K ions.
- Bhunia, Mrinal,Sahoo, Sumeet Ranjan,Das, Arpan,Ahmed, Jasimuddin,Sreejyothi,Mandal, Swadhin K.
-
p. 1848 - 1854
(2020/03/03)
-
- Silicon hydrogenation reaction method of organic boron and inorganic alkali catalysis amide (by machine translation)
-
The method is characterized in that organic boron and inorganic bases are used as catalysts, silane is used as a reducing agent, primary amide is reduced to primary amine or dehydration dinitrile, the secondary amide is reduced to a secondary amine or aldimine, and the tertiary amide is reduced to tertiary amine. The method has the advantages of simple operation, mild reaction conditions, wide substrate universality, good functional group compatibility and the like, and has the characteristics of good stability, cheap and accessible catalyst, simple and convenient operation, high practicality and the like. (by machine translation)
- -
-
Paragraph 0107-0113
(2020/08/18)
-
- On the Virtue of Indium in Reduction Reactions. A Comparison of Reductions Mediated by Indium and Zinc: Is Indium Metal an Effective Catalyst for Zinc Induced Reductions?
-
Indium(0)-mediated reductions have been reported for the transformation of several functional groups (imines, oximes, nitro groups, isoxazolidines, and conjugated alkenes, among others), prompted by the opportunity of performing the reactions in aqueous media and green conditions. We describe here the comparison of several reactions using indium or the less expensive zinc, carried out in order to evaluate the effective advantages brought about indium metal. We found some reactions for which use of In is mandatory and others where Zn worked equally well or even better. The reduction of hydroxylamines to the corresponding amines was the only reduction for which use of In provided much better results than Zn and was also possible to apply an efficient catalytic version with use of 2–5 mol-% In in the presence of stoichiometric Zn. Applicability of this catalytic reduction to “one-pot” model processes is also demonstrated.
- Matassini, Camilla,Bonanni, Marco,Marradi, Marco,Cicchi, Stefano,Goti, Andrea
-
supporting information
p. 1106 - 1113
(2019/12/24)
-
- Selenoimidazolium Salts as Supramolecular Reagents for Protein Alkylation
-
Se-benzyl selenoimidazolium salts are characterized by remarkable alkyl-transfer potential under physiological conditions. Structure-activity relationship studies show that selective monoalkylation of primary amines depends on supramolecular interactions
- Lim, David,Wen, Xiaojin,Seebeck, Florian P.
-
p. 3515 - 3520
(2020/09/21)
-
- Cobalt-Catalyzed Hydrogenations via Olefin Cobaltate and Hydride Intermediates
-
Redox noninnocent ligands are a promising tool to moderate electron transfer processes within base-metal catalysts. This report introduces bis(imino)acenaphthene (BIAN) cobaltate complexes as hydrogenation catalysts. Sterically hindered trisubstituted alkenes, imines, and quinolines underwent clean hydrogenation under mild conditions (2-10 bar, 20-80 °C) by use of the stable catalyst precursor [(DippBIAN)CoBr2] and the cocatalyst LiEt3BH. Mechanistic studies support a homogeneous catalysis pathway involving alkene and hydrido cobaltates as active catalyst species. Furthermore, considerable reaction acceleration by alkali cations and Lewis acids was observed. The dinuclear hydridocobaltate anion with bridging hydride ligands was isolated and fully characterized.
- Sandl, Sebastian,Maier, Thomas M.,Van Leest, Nicolaas P.,Kr?ncke, Susanne,Chakraborty, Uttam,Demeshko, Serhiy,Koszinowski, Konrad,De Bruin, Bas,Meyer, Franc,Bodensteiner, Michael,Herrmann, Carmen,Wolf, Robert,Von Jacobi Wangelin, Axel
-
p. 7596 - 7606
(2019/08/20)
-
- Amine-Borane Dehydrogenation and Transfer Hydrogenation Catalyzed by α-Diimine Cobaltates
-
Anionic α-diimine cobalt complexes, such as [K(thf)1.5{(DippBIAN)Co(η4-cod)}] (1; Dipp=2,6-diisopropylphenyl, cod=1,5-cyclooctadiene), catalyze the dehydrogenation of several amine-boranes. Based on the excellent catalytic properties, an especially effective transfer hydrogenation protocol for challenging olefins, imines, and N-heteroarenes was developed. NH3BH3 was used as a dihydrogen surrogate, which transferred up to two equivalents of H2 per NH3BH3. Detailed spectroscopic and mechanistic studies are presented, which document the rate determination by acidic protons in the amine-borane.
- Maier, Thomas M.,Sandl, Sebastian,Shenderovich, Ilya G.,Jacobi von Wangelin, Axel,Weigand, Jan J.,Wolf, Robert
-
supporting information
p. 238 - 245
(2019/01/04)
-
- Tris(pyrazolyl)borate Cobalt-Catalyzed Hydrogenation of C=O, C=C, and C=N Bonds: An Assistant Role of a Lewis Base
-
The combination of tris(pyrazolyl)borate cobalt complexes and Lewis base is developed as an efficient catalyst precursor in the homogeneous hydrogenation. A broad substrate scope including carbonyls, alkenes, enamines, and imines is reduced with 60 atm of H2 at 60 °C. Mechanistic studies support the hydrogenation operates through a frustrated Lewis pair (FLP)-like reduction process. These results highlight the development of novel non-noble metal catalytic processes, when combined with the diverse small molecule activation chemistry associated with FLPs.
- Lin, Yang,Zhu, De-Ping,Du, Yi-Ran,Zhang, Rui,Zhang, Suo-Jiang,Xu, Bao-Hua
-
supporting information
p. 2693 - 2698
(2019/04/25)
-
- NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF
-
The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.
- -
-
Paragraph 0249; 0250
(2019/02/13)
-
- Tertiary amine derivative or salt thereof, preparation method and application thereof
-
Belonging to the technical field of chemical medicine, the invention relates to a tertiary amine RORgamma t regulator, in particular to a new tertiary amine compound or salt thereof with RORgamma t inhibition or agonist activity shown as general formula I, a preparation method and a pharmaceutical composition thereof. The tertiary amine compound or a salt thereof provided by the invention can be used for preparation of drugs treating or preventing RORgamma t receptor related diseases.
- -
-
Paragraph 0230; 0233; 0234; 0235
(2019/01/24)
-
- Hydrosilane-Promoted Facile Deprotection of tert-Butyl Groups in Esters, Ethers, Carbonates, and Carbamates
-
Combination of PdCl2 with 1,1,3,3-tetramethyldisiloxane in the presence of activated carbon was found to be an effective catalyst system for the cleavage reaction of C?O bond of O?t-Bu moieties. The present catalytic reaction offers a practical method for the deprotection of tert-butyl esters, tert-butyl ethers, O-Boc, and N-Boc derivatives under mild conditions. The addition of activated carbon in the reaction mixture was proved to be crucial for not only sustaining the catalytic activity but also trapping the palladium species after the reaction. (Figure presented.).
- Ikeda, Takuya,Zhang, Zhenzhong,Motoyama, Yukihiro
-
supporting information
p. 673 - 677
(2019/01/04)
-
- A BEt3-Base catalyst for amide reduction with silane
-
Reported herein is the development of a simple but practical catalytic system for the selective reduction of amides with hydrosilane or hydrosiloxane. Low-cost and readily available triethylborane (1.0 M in THF), in combination with a catalytic amount of an alkali metal base, was found to catalyze the reduction of all three amide classes (tertiary, secondary, and primary amides) to form amines under mild conditions. In addition, the selective transformation of secondary amides to aldimines and primary amides to nitriles can also be achieved by using a proper combination of BEt3 and base. The scope of these BEt3-base-catalyzed amide hydrosilylation reactions has been explored in depth. Preliminary results of mechanistic studies suggest a modified Piers' silane Si-H···B activation mode wherein the hydride abstraction by BEt3 is promoted by the coordination of an alkoxide or hydroxide anion to the Si center.
- Yao, Wubing,Fang, Huaquan,He, Qiaoxing,Peng, Dongjie,Liu, Guixia,Huang, Zheng
-
supporting information
(2019/05/22)
-
- A BEt3-Base Catalyst for Amide Reduction with Silane
-
Reported herein is the development of a simple but practical catalytic system for the selective reduction of amides with hydrosilane or hydrosiloxane. Low-cost and readily available triethylborane (1.0 M in THF), in combination with a catalytic amount of an alkali metal base, was found to catalyze the reduction of all three amide classes (tertiary, secondary, and primary amides) to form amines under mild conditions. In addition, the selective transformation of secondary amides to aldimines and primary amides to nitriles can also be achieved by using a proper combination of BEt3 and base. The scope of these BEt3-base-catalyzed amide hydrosilylation reactions has been explored in depth. Preliminary results of mechanistic studies suggest a modified Piers' silane Si-H···B activation mode wherein the hydride abstraction by BEt3 is promoted by the coordination of an alkoxide or hydroxide anion to the Si center.
- Yao, Wubing,Fang, Huaquan,He, Qiaoxing,Peng, Dongjie,Liu, Guixia,Huang, Zheng
-
p. 6084 - 6093
(2019/05/24)
-
- B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane
-
The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Han, Jiahong,Xu, Xin,Chen, Changjun,Zhao, Haoqiang,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
-
supporting information
p. 2301 - 2308
(2019/01/30)
-
- Hydrosilylative Reduction of Tertiary Amides to Amines Catalyzed by N-(Phosphinoaryl)anilido Complexes of Iron and Cobalt
-
The synthesis and structural characterization of low-coordinate Fe(II) and Co(II) complexes supported by the monoanionic P,N-ligand N-(2-dicyclohexylphosphinophenyl)-2,6-diisopropylanilide are described. A three-coordinate (P,N)Fe-hexamethyldisilazide complex (2), and four-coordinate (P,N)Fe- (3-Fe) and (P,N)Co-alkyl (3-Co) complexes were evaluated as pre-catalysts for the hydrosilylative reduction of amides with PhSiH3 (5 mol % pre-catalyst, 1 equiv. PhSiH3, 80 °C, 1–24 h). The Fe complex 2 proved to be more broadly effective for the reduction of a variety of tertiary amide substrates, and was shown to mediate the reduction of N,N-dibenzylbenzamide at a loading of 1 mol %, to achieve near quantitative formation of tribenzylamine in 1 h (80 °C). Complex 2 also proved effective for the hydrosilylation of tertiary amides under ambient conditions (5 mol % Fe, 24 h), which is a unique example of room temperature amide hydrosilylation mediated by an Fe catalyst without the need for photochemical activation. Given the widespread use of amide reduction protocols in synthesis, the development of efficient Fe-based catalysts that operate under mild conditions is an important target.
- Hale, Dylan J.,Murphy, Luke J.,McDonald, Robert,Ferguson, Michael J.,Turculet, Laura
-
p. 3818 - 3827
(2019/06/17)
-
- Selective Synthesis of Secondary and Tertiary Amines by Reductive N-Alkylation of Nitriles and N-Alkylation of Amines and Ammonium Formate Catalyzed by Ruthenium Complex
-
A new ruthenium catalytic system for the syntheses of secondary and tertiary amines via reductive N-alkylation of nitriles and N-alkylation of primary amines is proposed. Isomeric complexes 8 catalyze transfer hydrogenation and N-alkylation of nitriles in ethanol to give secondary amines. Unsymmetrical secondary amines can be produced by N-alkylation of primary amines with alcohols via the borrowing hydrogen methodology. Aliphatic amines were obtained with excellent yields, while only moderate conversions were observed for anilines. Based on kinetic and mechanistic studies, it is suggested that the rate determining step is the hydrogenation of intermediate imine to amine. Finally, ammonium formate was applied as the amination reagent for alcohols in the presence of ruthenium catalyst 8. Secondary amines were obtained from primary alcohols within 24 hours at 100 °C, and tertiary amines can be produced after prolonged heating. Secondary alcohols can only be converted to secondary amines with moderate yield. Based on mechanistic studies, the process is suggested to proceed through an ammonium alkoxy carbonate intermediate, where carbonate acts as an efficient leaving group.
- Alshakova, Iryna D.,Nikonov, Georgii I.
-
p. 5370 - 5378
(2019/06/14)
-
- Pd/TiO2-Photocatalyzed Self-Condensation of Primary Amines to Afford Secondary Amines at Ambient Temperature
-
Symmetric secondary amines were synthesized by the self-condensation of primary amines over a palladium-loaded titanium dioxide (Pd/TiO2) photocatalyst. The reactions afforded a series of secondary amines in moderate to excellent isolated yields at ambient temperature (30 °C, in cyclopentyl methyl ether). Applicability for one-pot pharmaceutical synthesis was demonstrated by a photocatalytic reaction sequence of self-condensation of an amine followed by N-alkylation of the resulting secondary amine with an alcohol.
- Wang, Lyu-Ming,Kobayashi, Kensuke,Arisawa, Mitsuhiro,Saito, Susumu,Naka, Hiroshi
-
supporting information
p. 341 - 344
(2018/12/11)
-
- Bench-Stable Cobalt Pre-Catalysts for Mild Hydrosilative Reduction of Tertiary Amides to Amines and Beyond
-
The readily synthesized and bench-stable cobalt dichloride complex (dpephos)CoCl2 is employed as a pre-catalyst for a diversity of silane additions to unsaturated organic molecules, including the normally challenging reduction of amides to amines. With regard to hydrosilative reduction of amides even more effective and activator free catalytic systems can be generated from the bench-stable, commercially available Co(acac)2 and Co(OAc)2 with dpephos and PPh3 ligands. These systems operate under mild conditions (100 °C), with many examples of room temperature transformations, presenting a first example of mild cobalt-catalyzed hydrosilylation of amides.
- Nurseiit, Alibek,Janabel, Jaysan,Gudun, Kristina A.,Kassymbek, Aishabibi,Segizbayev, Medet,Seilkhanov, Tulegen M.,Khalimon, Andrey Y.
-
p. 790 - 798
(2019/01/09)
-
- Selective formylation or methylation of amines using carbon dioxide catalysed by a rhodium perimidine-based NHC complex
-
Carbon dioxide can play a vital role as a sustainable feedstock for chemical synthesis. To be viable, the employed protocol should be as mild as possible. Herein we report a methodology to incorporate CO2 into primary, secondary, aromatic or alkyl amines catalysed by a Rh(i) complex bearing a perimidine-based NHC/phosphine pincer ligand. The periminide-based ligand belongs to a class of 6-membered NHC ligand accessed through chelate-assisted double C-H activation. N-Formylation and -methylation of amines were performed using a balloon of CO2, and phenylsilane as the reducing agent. Product selectivity between formylated and methylated products was tuned by changing the solvent, reaction temperature and the quantity of phenylsilane used. Medium to excellent conversions, as well as tolerance to a range of functional groups, were achieved. Stoichiometric reactions with reactants employed in catalysis and time course studies suggested that formylation and methylation reactions of interest begin with hydrosilylation of CO2 followed by reaction with amine substrates.
- Lam, Raphael H.,McQueen, Caitlin M. A.,Pernik, Indrek,McBurney, Roy T.,Hill, Anthony F.,Messerle, Barbara A.
-
supporting information
p. 538 - 549
(2019/02/14)
-
- Manganese catalyzed hydrogenation of carbamates and urea derivatives
-
We report the hydrogenation of carbamates and urea derivatives, two of the most challenging carbonyl compounds to be hydrogenated, catalyzed for the first time by a complex of an earth-abundant metal. The hydrogenation reaction of these CO2-derived compounds, catalyzed by a manganese pincer complex, yields methanol in addition to amine and alcohol, which makes this methodology a sustainable alternative route for the conversion of CO2 to methanol, involving a base-metal catalyst. Moreover, the hydrogenation proceeds under mild pressure (20 bar). Our observations support a hydrogenation mechanism involving the Mn-H complex. A plausible catalytic cycle is proposed based on informative mechanistic experiments.
- Das, Uttam Kumar,Kumar, Amit,Ben-David, Yehoshoa,Iron, Mark A.,Milstein, David
-
supporting information
p. 12962 - 12966
(2019/08/26)
-
- Olefin-Stabilized Cobalt Nanoparticles for C=C, C=O, and C=N Hydrogenations
-
The development of cobalt catalysts that combine easy accessibility and high selectivity constitutes a promising approach to the replacement of noble-metal catalysts in hydrogenation reactions. This report introduces a user-friendly protocol that avoids complex ligands, hazardous reductants, special reaction conditions, and the formation of highly unstable pre-catalysts. Reduction of CoBr2 with LiEt3BH in the presence of alkenes led to the formation of hydrogenation catalysts that effected clean conversions of alkenes, carbonyls, imines, and heteroarenes at mild conditions (3 mol % cat., 2–10 bar H2, 20–80 °C). Poisoning studies and nanoparticle characterization by TEM, EDX, and DLS supported the notion of a heterotopic catalysis mechanism.
- Sandl, Sebastian,Schwarzhuber, Felix,P?llath, Simon,Zweck, Josef,Jacobi von Wangelin, Axel
-
supporting information
p. 3403 - 3407
(2018/02/13)
-
- Remarkably high catalyst efficiency of a disilaruthenacyclic complex for hydrosilane reduction of carbonyl compounds
-
A disilaruthenacyclic complex (1) showed extremely high catalytic activity for hydrosilane reduction of aldehydes and ketones to silyl ethers and secondary and tertiary amides to the corresponding amines. An σ-CAM mechanism was proposed to explain the activity.
- Tahara, Atsushi,Sunada, Yusuke,Takeshita, Takashi,Inoue, Ryoko,Nagashima, Hideo
-
supporting information
p. 11192 - 11195
(2018/10/24)
-
- CLEAVABLE TETRAZINE USED IN BIO-ORTHOGONAL DRUG ACTIVATION
-
Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct CA bound to a Trigger TR, the kit comprising a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine comprising a Construct CA bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of said Construct.
- -
-
Page/Page column 176-179
(2018/02/03)
-
- An Additive-Free, Base-Catalyzed Protodesilylation of Organosilanes
-
We report an additive-free, base-catalyzed C-, N-, O-, and S-Si bond cleavage of various organosilanes in mild conditions. The novel catalyst system exhibits high efficiency and good functional group compatibility, providing the corresponding products in good to excellent yields with low catalyst loadings. Overall, this transition-metal-free process may offer a convenient and general alternative to current employing excess bases, strong acids, or metal-catalyzed systems for the protodesilylation of organosilanes.
- Yao, Wubing,Li, Rongrong,Jiang, Huajiang,Han, Deman
-
p. 2250 - 2255
(2018/02/23)
-
- Direct Reductive N-Functionalization of Aliphatic Nitro Compounds
-
The first general protocol for the direct reductive N-functionalization of aliphatic nitro compounds is presented. The nitro group is partially reduced to a nitrenoid, with a mild and readily available combination of B2pin2 and zinc organyls. Thereby, the formation of an unstable nitroso intermediate is avoided, which has so far severely limited reductive transformations of aliphatic nitro compounds. The reaction is concluded by an electrophilic amination of zinc organyls.
- Rauser, Marian,Ascheberg, Christoph,Niggemann, Meike
-
p. 3970 - 3974
(2018/02/26)
-
- Selective synthesis of mono- and di-methylated amines using methanol and sodium azide as C1 and N1 sources
-
A Ru(ii) complex mediated synthesis of various N,N-dimethyl and N-monomethyl amines from organic azides using methanol as a methylating agent is reported. This methodology was successfully applied for a one-pot reaction of bromide derivatives and sodium azide in methanol. Notably, by controlling the reaction time several N-monomethylated and N,N-dimethylated amines were synthesized selectively. The practical applicability of this tandem process was revealed by preparative scale reactions with different organic azides and synthesis of an anti-vertigo drug betahistine. Several kinetic experiments and DFT studies were carried out to understand the mechanism of this transformation.
- Chakrabarti, Kaushik,Mishra, Anju,Panja, Dibyajyoti,Paul, Bhaskar,Kundu, Sabuj
-
p. 3339 - 3345
(2018/07/29)
-
- Selective Monomethylation of Amines with Methanol as the C1 Source
-
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
- Choi, Geunho,Hong, Soon Hyeok
-
supporting information
p. 6166 - 6170
(2018/04/30)
-
- Synthesis method of N-methylamine compound
-
The invention discloses a synthesis method of an N-methylamine compound. The synthesis method is characterized in that a carbamyl imidazole compound is used as a raw material; a NaBH4/I2 is used for performing backflow in tetrahydrofuran to prepare an N-methyl structure compound. The used reduction system NaBH4/I2 has the advantages of environment-friendly effect, performance stability, high conversion rate and the like. The synthesis method has the beneficial effects that (1) the synthesis method has wide applicability; amine can be used as the raw material; carboxylic acid can also be used as the raw material; (2) the product yield is high and reaches as high as 82 percent; (3) a synthetic agent is simple and can be easily obtained; the cost is low; the process is simple; the reaction conditions are mild; the synthesis method is suitable for industrial production. A concrete reaction formula is shown in the description, wherein R1 and R2 are identical or different atoms or groups, and are respectively and independently selected from one of hydrogen atoms, C1-C20 straight-chain or branch-chain alkane, C5-C10 naphthenic groups, aryl groups and substituted aryl groups; monosubstitution or multi-substitution is performed on aromatic rings of the substituted aryl groups. In addition, KBH4 is also applicable to the reaction.
- -
-
Paragraph 0044-0047
(2018/09/08)
-
- An Efficient Ruthenium Catalyst Bearing Tetradentate Ligand for Hydrogenations of Carbon Dioxide
-
A ruthenium complex with a tetradentate bipyridine ligand was proved to be a highly efficient catalyst for the conversions of CO2. Turnover numbers up to 300 000, 9800, and 2100 were achieved for the hydrogenations of CO2 to formamides, formamides to methanol and amines, and the direct hydrogenation of CO2 to methanol, respectively.
- Zhang, Feng-Hua,Liu, Chong,Li, Wei,Tian, Gui-Long,Xie, Jian-Hua,Zhou, Qi-Lin
-
supporting information
p. 1000 - 1002
(2018/09/21)
-
- N -Monomethylation of amines using paraformaldehyde and H2
-
The selective N-monomethylation of amines is an important topic in fine chemical synthesis. Herein, for the first time, we described a selective N-monomethylation reaction of amines with paraformaldehyde and H2 in the presence of a CuAlOx catalyst. A variety of amines, including primary aromatic amines, benzylamine and cyclohexylamine, as well as secondary amines, have been shown to be compatible with this reaction.
- Wang, Hongli,Huang, Yongji,Dai, Xingchao,Shi, Feng
-
supporting information
p. 5542 - 5545
(2017/07/06)
-
- Method for selectively preparing N-monomethylamine compound
-
The invention discloses a method for selectively preparing an N-monomethylamine compound. The method takes an amine compound, formaldehyde and H2 as reaction raw materials; the raw materials react in a reaction medium in the presence of a compound catalyst at 30 DEG C-180 DEG C for 2h-48h, so as to obtain the N-monomethylamine compound; and the compound catalyst is composed of oxides of at least two of the following metal or oxides of least one of the following metal and at least one metal simple substance: aluminum, copper, nickel, cobalt and iron. According to the method for preparing the N-monomethylamine compound, the conversion ratio and the selectivity of N-monomethylamine are relatively high; the H2 is used as a reducing agent and is clean, cheap and environment-friendly; the catalyst utilized by the method is cheap, simple to prepare and high in catalysis efficiency; and the method has mild preparation and reaction conditions and the catalyst has no corrosiveness, is easy to separate and can be repeatedly used.
- -
-
Paragraph 0032-0033
(2017/08/29)
-
- Switch in Catalyst State: Single Bifunctional Bi-state Catalyst for Two Different Reactions
-
Disclosed here is a molecular switch which responds to acid-base stimuli and serves as a bi-state catalyst for two different reactions. The two states of the switch serve as a highly active and poorly active catalyst for two catalytic reactions (namely a hydrogenation and a dehydrogenative coupling) but in a complementary manner. The system was used in an assisted tandem catalysis set-up involving dehydrogenative coupling of an amine and then hydrogenation of the resulting imine product by switching between the respective states of the catalyst.
- Semwal, Shrivats,Choudhury, Joyanta
-
supporting information
p. 5556 - 5560
(2017/05/05)
-
- Improved Buchner reaction selectivity in the copper-catalyzed reactions of ethyl 3-arylmethylamino-2-diazo-3-oxopropanoates
-
Ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates (diazo amidoacetates) generate generally both cyclohepta[c]pyrrolones (Buchner products) and β-lactams (1,4-insertion products), and show obvious N-substituent-controlled chemoselectivity between the intramolecular Buchner reaction and aliphatic 1,4-C-H insertion under the catalysis of copper salts. The less steric N-alkyl substituents in the amide moiety generally favor the aliphatic 1,4-C-H insertion, while the more steric N-alkyl substituents generally favor the Buchner reaction. Compared with rhodium and ruthenium-catalyzed conditions, the current copper-catalyzed conditions improved the Buchner reaction selectivity of ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates.
- Liu, Jing,Tu, Jianzhuo,Yang, Zhanhui,Pak, Chol-Ung,Xu, Jiaxi
-
p. 4616 - 4626
(2017/07/11)
-
- Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease
-
A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC50 values of 1.2 μM, 3.8 μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our investigation proved that TM-9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease.
- Sang, Zhipei,Wang, Keren,Wang, Huifang,Yu, Lintao,Wang, Huijuan,Ma, Qianwen,Ye, Mengyao,Han, Xue,Liu, Wenmin
-
supporting information
p. 5053 - 5059
(2017/10/18)
-
- Ruthenium-Catalyzed Aminomethylation and Methylation of Phenol Derivatives Utilizing Methanol as the C1 Source
-
A reaction involving ortho-aminomethylation of phenol was developed via ruthenium-catalyzed dehydrogenation of methanol, an environmentally benign C1 building block, without the use of reactive reagents. The reaction was successfully applied to a range of substrates. When naphthol was employed instead of phenol, only methylation was observed. On the basis of various mechanistic studies, we propose that formamide barely participates in the reaction, which mainly occurs through an iminium cation intermediate. The difference in the reactivities of phenol and naphthol is attributable to stronger basicity of naphtholate as a conjugate base owing to its lower aromaticity. Plausible reaction pathways were proposed for both reactions. (Figure presented.).
- Kim, Seoksun,Hong, Soon Hyeok
-
p. 798 - 810
(2017/03/11)
-
- Amidation of unactivated ester derivatives mediated by trifluoroethanol
-
A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
-
p. 3507 - 3518
(2017/04/26)
-
