62115-71-3

Upstream product

• 7035-03-2 2-methoxy-benzeneacetonitrile 
• 616-38-6 carbonic acid dimethyl ester 
• 149-73-5 trimethyl orthoformate 
• 33390-80-6 2-(2-methoxyphenyl)acetamide 
• 27798-60-3 methyl 2-(2-methoxyphenyl)acetate 
• 7677-24-9 trimethylsilyl cyanide 
• 13513-82-1 1-(2-methoxyphenyl)ethanol 
• 67-56-1 methanol 
• 612-15-7 o-methoxystyrene 
• 77287-34-4 formamide 
• 767-91-9 1-ethynyl-2-methoxybenzene 

Downstream Products

• 211230-09-0 (R)-2-(2-methoxyphenyl)propanenitrile 
• 211230-10-3 (S)-2-(2-methoxyphenyl)propanenitrile 
• 1421691-93-1 1-tert-butyl-N-(2-(2-methoxyphenyl)prop-1-en-1-ylidene)-1,1-dimethylsilanamine 
• 81616-80-0 (S)-2-(2-methoxyphenyl)-propionic acid 
• 81616-81-1 (R)-2-(2-methoxyphenyl)-propionic acid 

Relevant academic research and scientific papers

Nickel/Cobalt-Catalyzed Reductive Hydrocyanation of Alkynes with Formamide as the Cyano Source, Dehydrant, Reductant, and Solvent

A Ni/Co co-catalyzed reductive hydrocyanation of various alkynes was developed for the production of saturated nitriles. Hydrocyanic acid is generated in situ from safe and readily available formamide. Formamide played multiple roles as a cyano source, dehydrant, and reductant for the NiII pre-catalyst and vinyl nitriles, along with acting as the co-solvent in this reaction. Detailed mechanistic investigation supported a pathway via hydrocyanation of C≡C bond and the subsequent reduction of C=C bond. Wide substrate scope, the employment of a cheap and stable nickel salt as pre-catalyst, a safe cyano source and convenient experimental operation render this hydrocyanation practical for the laboratory synthesis of saturated nitriles. (Figure presented.).

Rhenium(I)-Catalyzed C-Methylation of Ketones, Indoles, and Arylacetonitriles Using Methanol

A ReCl(CO)5/MeC(CH2PPh2)3 (L2) system was developed for the C-methylation reactions utilizing methanol and base, following the borrowing hydrogen strategy. Diverse ketones, indoles, and arylacetonitriles underwent mono-and dimethylation selectively up to 99% yield. Remarkably, tandem multiple methylations were also achieved by employing this catalytic system.

Methylation with Dimethyl Carbonate/Dimethyl Sulfide Mixtures: An Integrated Process without Addition of Acid/Base and Formation of Residual Salts

Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O-methylated phenols and benzoic acids, and mono-C-methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide‘s neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Br?nsted base.

Ni-Catalyzed hydrocyanation of alkenes with formamide as the cyano source

CN generation from formamide dehydration! A novel Ni-catalyzed hydrocyanation of various alkenes to provide aliphatic nitriles is developed by generating hydrocyanic acid in situ from safe and readily available formamide. Excellent linear or branched regio-selectivity, wide substrate scope, cheap and stable nickel salt as a pre-catalyst, a safe cyano source, slow generation of CN to obviate catalyst deactivation and convenient experimental operation would render this hydrocyanation attactive for laboratory synthesis of aliphatic nitriles.

Preparation method of nitrile compounds with formamide as cyanide source

The invention discloses a preparation method of nitrile compounds. According to the preparation method, formamide used as a cyanide source undergoes a hydrocyanation reaction with various types of olefins under the action of a nickel catalyst to generate various nitrile compounds, wherein a reaction temperature is 60-160 DEG C and reaction time is 6-36 hours. The method overcomes the defects thata traditional olefin hydrocyanation reaction is complex in operation, needs to use a highly toxic cyanide source as a reaction raw material and the like. According to the method, simple, cheap, greenand non-toxic formamide is used as a cyano source, other dehydrating agents (such as phosphorus pentoxide and phosphorus oxychloride) do not need to be added, and cyano anions are generated through spontaneous dehydration of formamide under the catalysis of Lewis acid and undergo a hydrocyanation reaction with olefin in situ to generate nitrile compounds; reaction conditions are simple, operationis easy, and economical performance and high efficiency are realized; meanwhile, the method is applicable to various monosubstituted and disubstituted aliphatic and aromatic olefins, and shows good substrate universality; the nitrile compounds are insensitive to air, moisture and light and high in yield; and the preparation method is simple in product separation and purification and has good application prospects.

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.

Preparation of Indolenines via Nucleophilic Aromatic Substitution

An unusual aromatic substitution to access indolenines is described. 2-(2-Methoxyphenyl)acetonitrile derivatives are reacted with various alkyl and aryl Li reagents to furnish the corresponding indolenine products, constituents of natural products, and cyanine dyes such as indocyanine green. This new method was used to synthesize 41 indolenines with large functional group tolerance, and selected examples were further converted to the corresponding indolenine dyes. Key experiments provide insight into the mechanism of this nucleophilic aromatic substitution.

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.

Facile preparation of α-aryl nitriles by direct cyanation of alcohols with TMSCN under the catalysis of InX3

(Chemical Equation Presented) A convenient and efficient synthesis of α-aryl nitrites was developed by direct cyanation of alcohols with TMSCN under the catalysis of Lewis acid. Using 5-10 mol % of InBr3 as the catalyst, a variety of benzylic alcohols can be converted to the corresponding nitriles in 5-30 min with yields of 46-99%.