3508-98-3

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 43, p. 156, 1978 DOI: 10.1021/jo00395a036

Flammability and Explosibility

Notclassified

InChI:InChI=1/C12H15N/c1-2-3-7-12(10-13)11-8-5-4-6-9-11/h4-6,8-9,12H,2-3,7H2,1H3

Upstream product

• 140-29-4 phenylacetonitrile 
• 109-65-9 1-bromo-butane 
• 542-69-8 1-iodo-butane 
• 6393-50-6 α-lithiophenylacetonitrile 
• 591-50-4 iodobenzene 
• 7549-58-8 (dibutoxyphosphoryl)acetonitrile 
• 109-69-3 n-Butyl chloride 
• 96989-36-5 diphenyl n-butyl sulfonium methanesulfonate 
• 71-36-3 butan-1-ol 
• 628-73-9 hexanenitrile 
• 164594-13-2 Phenyl[2-(trimethylsilyl)phenyl]iodonium trifluoromethanesulfonate 
• 27911-12-2 pent-2-en-1-ylbenzene 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 16532-79-9 4-Bromophenylacetonitrile 

Downstream Products

• 5558-94-1 1,1-diphenyl-1-cyanopentane 
• 58971-10-1 2-phenyl-hexylamine 
• 858004-40-7 2-(2-chloro-ethyl)-2-phenyl-hexanenitrile 
• 49538-91-2 2-Phenyl-2-trimethylsilanyl-hexanenitrile 
• 3508-99-4 2-butyl-2-phenyl-hexanenitrile 
• 3623-09-4 opt.-inakt. 2-Aethyl-3-cyan-3-phenyl-heptanal-diaethylacetal 
• 3400-68-8 opt.-inakt. 3-Cyan-3-phenyl-2-propyl-heptanal-diaethylacetal 
• 22180-14-9 3-Phenyl-3-cyan-heptansaeure-t-butylester 
• 3400-72-4 opt.-inakt. 2-Butyl-3-cyan-3-phenyl-heptanal-diaethylacetal 
• 15144-44-2 2-n-Butyl-2-phenyl-5-chlor-pentannitril 
• 15144-52-2 2,6-Di-n-butyl-2,6-diphenyl-pimelinsaeure-dinitril 
• 58422-73-4 α-Peracetoxy-α-phenylhexannitril 
• 18248-71-0 1-Chlor-5-phenyl-5-cyannonan 
• 18248-72-1 5,10-Diphenyl-5,10-dicyan-tetradecan 

Relevant academic research and scientific papers

Mechanisms of Polymer-Supported Catalysis. 4. Alkylation of Phenylacetonitrile with 1-Bromobutane Catalyzed by Aqueous Sodium Hydroxide and Polystyrene-Bound Benzyltrimethylammonium Ions

The rates of reaction of phenylacetonitrile with excess 1-bromobutane catalyzed by excess 50percent aqueous sodium hydroxide and insoluble polystyrene-bound benzyltrimethylammonium ions at 80 deg C depend upon several experimental variables.The rates (1)

THE EFFECT OF POLYMER SWELLING ON ALKYLATION OF PHENYLACETONITRILE BY POLYMER-SUPPORTED PHASE TRANSFER CATALYSIS

Alkylation of phenylacetonitrile by 1-bromobutane with 50percent sodium hydroxide and a polymer-supported phase transfer catalyst proceeds fastest when the phenylacetonitrile is added to the mixture before the 1-bromobutane.

Nickel-Catalyzed Migratory Hydrocyanation of Internal Alkenes: Unexpected Diastereomeric-Ligand-Controlled Regiodivergence

A regiodivergent nickel-catalyzed hydrocyanation of a broad range of internal alkenes involving a chain-walking process is reported. When appropriate diastereomeric biaryl diphosphite ligands are applied, the same starting materials can be converted to either linear or branched nitriles with good yields and high regioselectivities. DFT calculations suggested that the catalyst architecture determines the regioselectivity by modulating electronic and steric interactions. In addition, moderate enantioselectivities were observed when branched nitriles were produced.

Catalyst for α alkylation of nitriles and uses thereof

The invention discloses a nitrile alpha-alkylation reaction catalyst and application thereof. The nitrile alkylation reaction catalyzed by pyridine-pyridine-imidazoline asymmetric pincerlike rutheniumcompounds has a reaction general formula shown in the specification, and in the general formula, a catalyst is a pyridine-pyridine-imidazoline asymmetric pincerlike ruthenium compound, R1 is aryl, and R2 is aryl or alkyl, wherein aryl is phenyl, p-methylphenyl, p-methoxyphenyl, p-chlorophenyl, thiophene and the like, and alkyl is n-butyl, phenylpropyl and the like. The synthesis method comprisesthe following synthesis steps: adding an asymmetric pincerlike ruthenium compound, an alkali, a nitrile compound and an alcohol into a solvent for reaction, and after the reaction is finished, conducting separating and purifying to obtain a corresponding target product. Alcohol is used as an alkylating reagent, generated water is a unique by-product, the method conforms to the ideas of atom economy and environmental friendliness, and meanwhile, the method has the advantages of use of a catalytic amount of alkali, short reaction time, economy and the like.

Ru(II)-PBTNNXN complex bearing functional 2-(pyridin-2-yl)benzo[d]thiazole ligand catalyzed α-alkylation of nitriles with alcohols

Six tridentate NNN ligand precursors derived from 2-(pyridin-2-yl)benzo[d]thiazole(PBT) with different linkers, PBTNNXN (X = NH, NMe, O, S) (1a–1f), have been successfully prepared. The electronic properties of PBTNNXN ligands are well tunable by differing linkers between PBT skeleton and the pyridine ring, and/or by introducing electron-donating/withdrawing groups on the pyridine ring (R = OMe or F). The ligand precursors and representative complexes Ru (PBTNNNHN)Cl2(PPh3) (2a), Ru (PBTNNNMeN)Cl2(PPh3) (2b), and Ru (PBTNNSN)Cl2(PPh3) (2f) have been characterized by NMR spectroscopy, high-resolution mass spectroscopy, and Fourier transform infrared (FT-IR). The molecular structures of 1f, 2a, and 2f have been determined by X-ray diffraction study. The results indicate that PBTNNNHN ligand in the complex presented coplanar with two five-membered chelating rings. It should be noted that 2a featuring a NH group exhibits superior performance compared to those with other linkers (such as NMe, O, or S). A variety of heterocyclic and aromatic nitriles with aromatic and aliphatic alcohols have been explored in α-alkylation for good to excellent yields. Based on kinetic experiments and mechanistic studies, a proposed mechanism was put forward. Ru-H species and benzaldehyde, which was oxidized from benzyl alcohol, were detected in the catalytic cycle.

Sustainable Alkylation of Nitriles with Alcohols by Manganese Catalysis

A general and chemoselective catalytic alkylation of nitriles using a homogeneous nonprecious manganese catalyst is presented. This alkylation reaction uses naturally abundant alcohols and readily available nitriles as coupling partners. The reaction tolerates a wide range of functional groups and heterocyclic moieties, efficiently providing useful cyanoalkylated products with water as the only side product. Importantly, methanol can be used as a C1 source and the chemoselective C-methylation of nitriles is achieved. The mechanistic investigations support the multiple role of the metal-ligand manganese catalyst, the dehydrogenative activation of the alcohol, α-C-H activation of the nitrile, and hydrogenation of the in-situ-formed unsaturated intermediate.

α-Alkylation of Nitriles with Alcohols Catalyzed by NNN′ Pincer Ru(II) Complexes Bearing Bipyridyl Imidazoline Ligands

A series of unsymmetrical NNN′ ruthenium(II) complexes supported by a tridentate bipyridyl imidazoline ligand with variable steric hindrance (2a-c; R1 = tBu, iPr, or Bn) and electronic effect (2d-h; R2 = H, CH3, OCH3, Br, or NO2) were prepared. The molecular structures of ligands 1f and 1g, and Ru complex 2a were further determined by X-ray single-crystal diffraction. The catalytic activity of these eight complexes for α-alkylation of nitriles with alcohols was evaluated, which could be controlled by the substituents on the imidazoline moiety. Ru complex 2h bearing a strong electron-withdrawing group (R2 = NO2) demonstrated the highest catalytic activity, with alkylated nitriles achieved in up to 97% yield.

Enantioseparation of Sulfoxides and Nitriles by Inclusion Crystallization with Chiral Organic Salts Based on l-Phenylalanine

Enantioselective inclusion of aromatic sulfoxides and nitriles was achieved in a host framework created by organic salts comprising achiral benzoic acids and a chiral primary amine (1a) derived from l-phenylalanine. Tuning of the combined achiral acid component successfully changed the chiral recognition ability of the organic salts. The guest molecules were hydrogen-bonded to form three-component inclusion crystals, and the enantiomers of nitriles and sulfoxides were separated with high selectivity up to 92 and 98 % ee. As far as we know, this is the first example of the enantioseparation of non-functionalized aromatic nitriles.

Facile Ruthenium(II)-Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols Enabled by Metal-Ligand Cooperation

A facile ruthenium(II)-catalyzed α-alkylation of arylmethyl nitriles using alcohols is reported. The ruthenium pincer catalyst serves as an efficient catalyst for this atom-economical transformation that undergoes alkylation via borrowing hydrogen pathways, producing water as the only byproduct. Arylmethyl nitriles containing different substituents can be effectively alkylated using diverse primary alcohols. Notably, using ethanol and methanol as alkylating reagents, challenging ethylation and methylation of arylmethyl nitriles were performed. Secondary alcohols do not undergo alkylation reactions. Thus, phenylacetonitrile was chemoselectively alkylated using primary alcohols in the presence of secondary alcohols. Diols provided a mixture of products. When deuterium-labeled alcohol was used, the expected deuterium transposition occurred, providing both α-alkylation and α-deuteration of arylmethyl nitriles. Consumption of nitrile was monitored by GC, which indicated the involvement of first-order kinetics. Plausible mechanistic pathways are suggested on the basis of experimental evidence. The ruthenium catalyst reacts with base and generates an unsaturated intermediate, which further reacts with both nitriles and alcohols. While nitrile is transformed to enamine via [2 + 2] cycloaddition, alcohol is oxidized to aldehyde. The metal bound enamine adduct reacts with aldehyde via Michael addition, resulting in an ene-imine adduct, which perhaps undergoes direct hydrogenation by a Ru dihydride intermediate, produced from alcohol oxidation. However, in situ monitoring of the reaction mixture confirmed the presence of unsaturated vinyl nitrile in the reaction mixture in minor amounts (10%), indicating the possible dissociation of ene-imine adduct during the catalysis, which may further be hydrogenated to provide the α-alkylated nitriles. Overall, the efficient α-alkylation of nitriles using alcohols can be attributed to the amine-amide metal-ligand cooperation that is operative in the ruthenium pincer catalyst, which enables all of the catalytic intermediates to remain in the +2 oxidation state throughout the catalytic cycle.

Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide

Leukemia with a mixed lineage leukemia (MLL) rearrangement, which harbors a variety of MLL fusion proteins, has a poor prognosis despite the latest improved treatment options. Menin has been reported to be a required cofactor for the leukemogenic activity of MLL fusion proteins. Thus, the disruption of the protein-protein interactions between menin and MLL represents a very promising strategy for curing MLL leukemia. Making use of menin-MLL inhibitors with a shape-based scaffold hopping approach, we have discovered that the antidiarrheal loperamide displays previously unreported mild inhibition for the menin-MLL interaction (IC50 = 69 ± 3 μM). In an effort to repurpose this drug, a series of chemical modification analyses was performed, and three of the loperamide-based analogues, DC-YM21, DC-YM25 and DC-YM26 displayed better activities with IC50 values of 0.83 ± 0.13 μM, 0.69 ± 0.07 μM and 0.66 ± 0.05 μM, respectively. Further treatment with DC-YM21 demonstrated potent and selective blockage of proliferation and induction of both cell cycle arrest and differentiation of leukemia cells harboring MLL translocations, which confirmed the specific mechanism of action. In conclusion, molecules of a novel scaffold targeting menin-MLL interactions were reported and they may serve as new potential therapeutic agents for MLL leukemia.