645-59-0

Basic information

• Product Name: 3-PHENYLPROPIONITRILE
• Synonyms: (2-Cyanoethyl)benzene;3-Phenylpropanenitrile;3-Phenylpropiononitrile;benzenepropanenitrile;Benzenepropionitrile;beta-Phenylethyl cyanide;Hydrocinnamique nitrile;hydrocinnamiquenitrile
• CAS NO: 645-59-0
• Molecular Formula: C₉H₉N
• Molecular Weight: 131.17
• EINECS: 211-447-8
• Product Categories: Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 645-59-0.mol

Chemical Properties

• Melting Point: −2-−1 °C(lit.)
• Boiling Point: 113 °C9 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to light yellow/Liquid
• Density: 1.001 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.521(lit.)
• Storage Temp.: Store below +30°C.
• Solubility: 1.68g/l (calculated)
• BRN: 636348
• CAS DataBase Reference: 3-PHENYLPROPIONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-PHENYLPROPIONITRILE(645-59-0)
• EPA Substance Registry System: 3-PHENYLPROPIONITRILE(645-59-0)

Safety Data

• Hazard Codes: T,C
• Statements: 23/24/25-36-34
• Safety Statements: 36/37/39-45-27-26
• RIDADR: UN 3276 6.1/PG 3
• WGK Germany: 3
• RTECS: MW5604750
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 645-59-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Phenylpropionitrile is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique structure allows it to be a key component in the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
3-Phenylpropionitrile is used as a precursor in the production of agrochemicals, specifically as a glucosinolate enzymic hydrolysis product with potential antibacterial activities against plant pathogenic bacteria. This application helps in the development of more effective and targeted pesticides to protect crops from diseases.
Used in Enzyme Research:
3-Phenylpropionitrile has been utilized in studies to investigate the free enzyme activity of nitrilase AtNIT1. This research contributes to the understanding of enzyme mechanisms and their potential applications in various industries, including pharmaceuticals and biotechnology.

Preparation

To a stirred solution of 3-phenylpropanamide (50 mg, 0.34 mmol) in acetonitrile (0.8 mL) at room temperature were successively added formic acid (0.2 mL) and paraformaldehyde (50 mg, 1.67 mmol). The reaction mixture was then refluxed for 12 h, and the solution obtained was cooled to room temperature. Work-up A: The crude mixture was concentrated under reduced pressure, and the residue was subjected to flash chromatography on silica gel (230–240 mesh) eluting with hexane/ethyl acetate (7:3) to yield 3-phenylpropanonitrile (37 mg, 85%). Work-up B: The reaction mixture was diluted with ethyl acetate (10 mL) and washed successively with saturated sodium hydrogen carbonate solution (5 mL) and water (5 mL). The combined aqueous layers were extracted with ethyl acetate (2 × 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude 3-phenylpropanonitrile was purified as described above (Work-up A).

Synthesis Reference(s)

Journal of the American Chemical Society, 98, p. 4685, 1976 DOI: 10.1021/ja00431a078Chemical and Pharmaceutical Bulletin, 10, p. 427, 1962 DOI: 10.1248/cpb.10.427

InChI:InChI=1/C9H9N/c10-8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7H2

Upstream product

• 4360-47-8 cinnamonitrile 
• 1197-50-8 3-phenylpropanal oxime 
• 108-24-7 acetic anhydride 
• 151-50-8 potassium cyanide 
• 103-63-9 1-phenyl-2-bromoethane 
• 107-13-1 acrylonitrile 
• 501-52-0 3-Phenylpropionic acid 
• 542-76-7 3-Chloropropionitrile 
• 71-43-2 benzene 
• 4360-60-5 2-phenethyl-[1,3]dioxolane 
• 20496-01-9 4-chloro-n-butyric anhydride 
• 588-73-8 (Z)-β-bromostyrene 
• 588-72-7 [(E)-2-bromoethenyl]benzene 
• 935-02-4 3-Phenyl-2-propynonitrile 

Downstream Products

• 854677-36-4 4-[4-(2-cyano-ethyl)-phenyl]-4-oxo-butyric acid 
• 20869-98-1 1-(5,7-dihydroxy-2,2-dimethyl-chroman-8-yl)-3-phenyl-propan-1-one 
• 20870-00-2 1-(5,7-dihydroxy-2,2-dimethyl-chroman-6-yl)-3-phenyl-propan-1-one 
• 26038-62-0 2-phenethyl-4,5-dihydro-1H-imidazole 
• 158613-21-9 3-(4-acetylphenyl)propanenitrile 
• 59238-97-0 1-(2,4-dihydroxy-6-methyl-phenyl)-3-phenyl-propan-1-one 
• 5396-91-8 1,5-diphenyl-3-pentanone 
• 1088-08-0 2',4',6'-trihydroxydihydrochalcone 
• 83247-38-5 2',6'-Dihydroxy-4'-methoxy-3'-methyl-2-phenylpropiophenon 
• 2038-57-5 3-Phenylpropan-1-amine 
• 70155-33-8 1-(2,4,6-trihydroxy-3-methyl)phenyl-3-phenyl-1-propanone 
• 1083-30-3 dihydrochalcone 
• 53596-71-7 2',4'-dihydroxy-α,β-dihydrochalcone 
• 104-53-0 3-phenyl-propionaldehyde 

Relevant articles and documents

Bridging the gap between electrochemical and organometallic activation: Benzyl chloride reduction at silver cathodes

Integration of voltammetry, surface-enhanced Raman spectroscopy (SERS), and density functional theory (DFT) has allowed unraveling the mechanistic origin of the exceptional electrocatalytic properties of silver cathodes during the reduction of benzyl chloride. At inert electrodes the initial reduction proceeds through a concerted direct electron transfer yielding a benzyl radical as the first intermediate. Conversely, at silver electrodes it involves an uphill preadsorption of benzyl chloride onto the silver cathode. Reduction of this adduct affords a species tentatively described as a distorted benzyl radical anion stabilized by the silver surface. This transient species rapidly evolves to yield ultimately a benzyl radical bound onto the silver surface, the latter being reduced into a benzyl-silver anionic adduct which eventually dissociates into a free benzyl anion at more negative potentials. Within this framework, the exceptional electrocatalytic properties of silver cathodes stem from the fact that they drastically modify the mechanism of the 2e-reduction pathway through a direct consequence of the electrophilicity of silver cathode surfaces toward organic halides. This mechanism contrasts drastically with any of those tentatively invoked previously, and bridges classical electroreduction mechanisms and oxidative additions similar to those occurring during organometallic homogeneous activation of organic halides by low-valent transition-metal complexes.

Enantioselective hydrogenation of diaryl-substituted α,β-unsaturated nitriles

α,β-Unsaturated nitriles can be hydrogenated with enantioselectivities up to 88% ee using chiral ruthenium-diphenylphosphino bisaryl and bisheteroaryl complexes such as ruthenium(II)-BINAP and ruthenium(II)-BINP. Mechanistic investigations indicate that conversion is accelerated by electron-rich ligands and that an additional coordinative group needs be present in order to promote conversion. The chiral products are useful building blocks for the synthesis of histamine H2 agonists of the arpromidine type.

From Stoichiometric Reagents to Catalytic Partners: Selenonium Salts as Alkylating Agents for Nucleophilic Displacement Reactions in Water

The ability of chalcogenium salts to transfer an electrophilic moiety to a given nucleophile is well known. However, up to date, these reagents have been used in stoichiometric quantities, producing a substantial amount of waste as byproducts of the reaction. In this report, we disclose further investigation of selenonium salts as S-adenosyl-L-methionine (SAM) surrogates for the alkylation of nucleophiles in aqueous solutions. Most importantly, we were able to convert the stoichiometric process to a catalytic system employing as little as 10 mol % of selenides to accelerate the reaction between benzyl bromide and other alkylating agents with sodium cyanide in water. Probe experiments including 77Se NMR and HRMS of the reaction mixture have unequivocally shown the presence of the selenonium salt in the reaction mixture. (Figure presented.).

Palladium-catalyzed synthesis of nitriles from N-phthaloyl hydrazones

The Pd-catalyzed transformation of N-phthaloyl hydrazones into nitriles involving the cleavage of an N-N bond is reported. The use of N-heterocyclic carbene as a ligand is essential for the success of the reaction. N-Phthaloyl hydrazones prepared from aromatic aldehydes or cyclobutanones are applicable to this transformation, which gives aryl or alkenyl nitriles, respectively.

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.

Reduction of Electron-Deficient Alkenes Enabled by a Photoinduced Hydrogen Atom Transfer

Direct hydrogen atom transfer from a photoredox-generated Hantzsch ester radical cation to electron-deficient alkenes has enabled the development of an efficient formal hydrogenation under mild, operationally simple conditions. The HAT-driven mechanism is supported by experimental and computational studies. The reaction is applied to a variety of cinnamate derivatives and related structures, irrespective of the presence of electron-donating or electron-withdrawing substituents in the aromatic ring and with good functional group compatibility. (Figure presented.).

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.).

A Titanium-Catalyzed Reductive α-Desulfonylation

A titanium(III)-catalyzed desulfonylation gives access to functionalized alkyl nitrile building blocks from α-sulfonyl nitriles, circumventing traditional base-mediated α-alkylation conditions and strong single electron donors. The reaction tolerates numerous functional groups including free alcohols, esters, amides, and it can be applied also to the α-desulfonylation of ketones. In addition, a one-pot desulfonylative alkylation is demonstrated. Preliminary mechanistic studies indicate a catalyst-dependent mechanism involving a homolytic C?S cleavage.

Selective oxidation of alcohols to nitriles with high-efficient Co-[Bmim]Br/C catalyst system

An efficient method for catalyzing the ammoxidation of aromatic alcohols to aromatic nitriles was developed, in which a new heterogeneous catalyst based on transition metal elements was employed, the new catalyst was named Co-[Bmim]Br/C-700 and then characterized by X-ray photo-electronic spectroscopy, transmission electron microscope and X-ray diffraction. The reaction was carried out by two consecutive dehydrogenations under the catalysis of Co-[Bmim]Br/C-700, which catalytically oxidized the alcohol to the aldehyde, and then the aldehyde was subjected to ammoxidation to the nitrile. The catalyst system was suitable for a wide range of substrates and nitriles obtained in high yields, especially, the conversion rate of benzyl alcohol, 4-methoxybenzyl alcohol, 4-chlorobenzyl alcohol and 4-nitrobenzyl alcohol reached 100%. The substitution of ammonia and oxygen for toxic cyanide to participate in the reaction accords with the theory of green chemistry.

Arylketones as Aryl Donors in Palladium-Catalyzed Suzuki-Miyaura Couplings

Herein, we report the arylation, alkylation, and alkenylation of aryl ketones via a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. The use of the pyridine-oxazoline ligand is the key to the cleavage of the unstrained C-C bond. The late-stage arylation of aryl ketones derived from drugs and natural products demonstrated the synthetic utility of this protocol.