140-29-4

Basic information

• Product Name: Benzeneacetonitrile
• Synonyms: phenyl acetyl nitrile;PHENYLACETONITRILE;TOLUNITRILE;(Cyanomethyl)benzene;2-Phenylacetonitrile;aceticacid,phenyl-nitrile;Acetonitrile, phenyl-;acetonitrile,phenyl-
• CAS NO: 140-29-4
• Molecular Formula: C₈H₇N
• Molecular Weight: 117.15
• EINECS: 205-410-5
• Product Categories: Pharmaceutical Intermediates;Organics;Agrochemical
• Mol File: 140-29-4.mol

Chemical Properties

• Melting Point: −24 °C(lit.)
• Boiling Point: 233-234 °C(lit.)
• Flash Point: 215 °F
• Appearance: colourless liquid
• Density: 1.015 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.1 mm Hg ( 20 °C)
• Refractive Index: n20/D 1.524
• Storage Temp.: Store below +30°C.
• Solubility: 0.1g/l
• Water Solubility: insoluble.
• Stability: Stable. Incompatible with strong oxidizing agents. May produce hydrogen cyanide in a fire.
• Merck: 14,1131
• BRN: 385941
• CAS DataBase Reference: Benzeneacetonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: Benzeneacetonitrile(140-29-4)
• EPA Substance Registry System: Benzeneacetonitrile(140-29-4)

Safety Data

• Hazard Codes: T+,T
• Statements: 22-24-26-23/24/25
• Safety Statements: 28-36/37-45-23
• RIDADR: UN 2470 6.1/PG 3
• WGK Germany: 3
• RTECS: AM1400000
• F: 8-9
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 140-29-4(Hazardous Substances Data)

Usage

Uses

1. Organic Synthesis:
Benzeneacetonitrile is used in organic synthesis for various applications, including the production of dyes, perfumes, and pharmaceuticals. It is particularly important as a precursor for penicillin, a widely used antibiotic.
2. Solvent:
Due to its chemical properties, benzeneacetonitrile is also used as a solvent in various industrial processes.
3. Pharmaceutical Industry:
In the pharmaceutical industry, benzeneacetonitrile is used as a chemical intermediate for the synthesis of various drugs, such as amphetamine, phenobarbital, and methyl phenidylacetate.
4. Perfumes and Flavors:
Benzeneacetonitrile is used in the production of perfumes and flavors, adding to the aromatic properties of soaps, detergents, creams, and lotions.

Production Methods

Benzyl cyanide is synthesized by reaction of benzyl chloride with potassium cyanide or sodium cyanide . The nitrile is a natural constituent of plants and is a constituent of foods, particularly citrus fruits, papaya, cabbage, mushrooms, roasted onions, tomatoes, cocoa, tea, roasted peanuts and cauliflower .The benzyl cyanide, at least in part, is formed by breakdown of benzylglucosinolate in the plant material. Benzyl nitrile also is found in tap water, river water, sewage and in cigarette smoke ).

Synthesis Reference(s)

Canadian Journal of Chemistry, 39, p. 1340, 1961 DOI: 10.1139/v61-169Chemistry Letters, 13, p. 1511, 1984Organic Syntheses, Coll. Vol. 1, p. 107, 1941

Air & Water Reactions

Benzeneacetonitrile is moisture sensitive. Insoluble in water.

Reactivity Profile

PHENYLACETONITRILE can react with strong acids, strong bases, strong oxidizing agents and strong reducing agents. Benzeneacetonitrile may react vigorously with sodium hypochlorite. .

Hazard

Highly toxic, absorbed by skin.

Health Hazard

Benzyl cyanide is a highly toxic irritant that may be fatal if inhaled, swallowed or absorbed through the skin. The chemical causes eye, mucous membrane and skin irritation. Benzyl cyanide was applied as a 2% concentration in petroleum to the skin of 27 human volunteers and found to be nonsensitizing.

Health Hazard

Poisonous. May be fatal if inhaled, swallowed, or absorbed through skin. Contact may cause burns to skin and eyes.

Fire Hazard

When heated to decomposition, Benzeneacetonitrile emits very toxic fumes of cyanide and nitrogen oxides. Container may explode in heat of fire. Runoff from fire control water may give off poisonous gases. Avoid sodium hypochlorite.

Safety Profile

Poison by ingestion, inhalation, skin contact, subcutaneous, and intraperitoneal routes. A skin irritant. Explosive reaction with sodium hypochlorite. Used in production of drugs of abuse. When heated to decomposition it emits very toxic fumes of CNand NOx. See also NITRILES

Potential Exposure

(as CN): Benzyl cyanide is used in organic synthesis, especially of penicillin precursors. It is used as a chemical intermediate for amphetamines, phenobarbital; the stimulant, methyl phenidylacetate; esters as perfumes and flavors.

Metabolism

Giacosa isolated phenylaceturic acid from the urine of a dog dosed with benzyl cyanide, while Adeline et al showed that in the dog, benzyl cyanide formed both benzoic acid and a small amount of ethereal sulfate. In rabbits, a large proportion of the cyano group could be accounted for as thiocyanate ion in the urine. There was a sex difference in the conversion with female rabbits excreting 70% of the dose as thiocyanate and males only 50%. However, cyanide was liberated slowly from i.p. or orally administered benzyl cyanide in rats and excreted in the urine as cyanide and thiocyanate, the proportion of the former increasing with the dose . Benzyl cyanide is oxidized by mouse liver microsomes to benzaldehyde and cyanide ion presumably via the intermediate mandelonitrile. The microsomal metabolism of benzyl cyanide and other nitriles was significantly increased when mice were pre treated with ethanol , suggesting that the ethanol-inducible cytochrome P-450 may play an important role in the metabolism of such compounds.

Shipping

UN2470 Phenylacetonitrile, Hazard Class: 6.1; Labels: 6.1—Poisonous materials.

Purification Methods

Any benzyl isocyanide impurity can be removed by shaking vigorously with an equal volume of 50% H2SO4 at 60o, washing with saturated aqueous NaHCO3, then half-saturated NaCl solution, drying and fractionally distilling under reduced pressure. Distillation from CaH2 causes some decomposition of this compound: it is better to use P2O5. Other purification procedures include passage through a column of highly activated alumina, and distillation from Raney nickel. Precautions should be taken because of possible formation of free TOXIC cyanide, use an efficient fume cupboard.[Beilstein 9 IV 1663.]

Incompatibilities

Violent reaction with strong oxidizers; sodium hypochlorite, lithium aluminum hydride. Nitriles may polymerize in the presence of metals and some metal compounds. They are incompatible with acids; mixing nitriles with strong oxidizing acids can lead to extremely violent reactions. Nitriles are generally incompatible with other oxidizing agents such as peroxides and epoxides. The combination of bases and nitriles can produce hydrogen cyanide. Nitriles are hydrolyzed in both aqueous acid and base to give carboxylic acids (or salts of carboxylic acids). These reactions generate heat. Peroxides convert nitriles to amides. Nitriles can react vigorously with reducing agents. Acetonitrile and propionitrile are soluble in water, but nitriles higher than propionitrile have low aqueous solubility. They are also insoluble in aqueous acids.

InChI:InChI=1/C6H6.C2H3N/c1-2-4-6-5-3-1;1-2-3/h1-6H;1H3

Upstream product

• 103-82-2 phenylacetic acid 
• 98-10-2 benzenesulfonamide 
• 793-25-9 1,2-di(phenylacetyl)hydrazine 
• 7223-30-5 3-phenyl-propynoic acid amide 
• 25289-32-1 Phenyl-prop-2-ynoyl azide 
• 14377-99-2 1,2,3-triphenyl-1,3-propanedicarbonitrile 
• 532-28-5 (RS)-mandelonitrile 
• 5873-91-6 phenyldithioacetic acid 
• 22259-83-2 2-chloro-2-phenylacetonitrile 
• 151-50-8 potassium cyanide 
• 7028-48-0 Phenylacetaldehyde oxime 
• 108-24-7 acetic anhydride 
• 3204-68-0 benzyldimethylphenylammonium chloride 
• 143-33-9 sodium cyanide 

Downstream Products

• 106736-67-8 3-hexyl-5-phenyl-3H-[1,2,3]triazol-4-ylamine 
• 876480-59-0 2-benzyl-3-cyano-2-hydroxy-3-phenyl-propionic acid 
• 6720-37-2 3-(3-nitro-phenyl)-2-phenyl-acrylonitrile 
• 16610-80-3 (E)-2,3-diphenylacrylonitrile 
• 955-10-2 3-phenylcumarin 
• 408307-21-1 3-cyano-2-hydroxy-2,3-diphenyl-propionic acid 
• 21151-64-4 N,N'-methylenebis(2-phenylacetamide) 
• 56951-36-1 2-phenyl-4-pyrrolidino-butyronitrile 
• 93013-58-2 8-methoxy-3-phenyl-quinolin-2-ylamine 
• 58323-63-0 4-(morpholin-4-yl)-2-phenylbutanenitrile 
• 6312-29-4 2-phenyl-4-pyridin-2-yl-butyronitrile 
• 102459-85-8 2-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-yl-ethyl)-butyronitrile 
• 6312-30-7 2-phenyl-4-[4]pyridyl-butyronitrile 
• 23581-48-8 2-phenyl-octahydro-quinolizine-2-carbonitrile 

Relevant articles and documents

Microwave-assisted dehydration and chlorination using phosphonium salt

Microwave-assisted reaction using phosphonium salt for dehydration of primary amides and chlorination of hydroxyheteroaromatics was carried out. Copyright Taylor & Francis, Inc.

A convenient preparation of alkyl nitriles by the Mitsunobu procedure

A convenient preparation of alkyl nitriles from alcohols extending the use of the Mitsunobu reaction is described. Acetone cyanohydrin is the acidic component and the source of cyanide ion.

Construction of enantioenriched polysubstituted hexahydropyridazines via a sequential multicatalytic process merging palladium catalysis and aminocatalysis

An efficient multicatalytic strategy for the construction of nitrogen-containing heterocycles has been reported. The powerful combination of organic and metal catalysis in a single vessel allowed the formation of enantioenriched polysubstituted cyclic 6-membered hydrazines bearing a quaternary stereocenter in good yields and selectivities.

Switch of reaction pathway induced by solid support and ultrasound

The influence of activation methods and solid support on the reaction course of benzyl bromide, KCN, and toluene has been investigated. When KCN is not supported on alumina, the reaction under the mechanical agitation follows the aromatic electrophilic substitution pathway, while the reaction under sonication follows nucleophilic substitution. However, when KCN supported on alumina is employed, only the nucleophilic substitution product is obtained under both ultrasound and mechanical agitation. Copyright Taylor & Francis Group, LLC.

A New Synthesis of α-Phenylhomoallylnitriles from β-Nitrostyrene and Allylic Silanes

TiCl4-catalyzed addition of allylic silanes to β-nitrostyrene affords γ,δ-unsaturated nitronates which, on treatment with low valent titanium in situ generated from Ti(IV) and zinc, are smoothly converted to γ,δ-unsaturated nitriles in moderate yields.

Polycationic (Mixed) Core-Shell Dendrimers for Binding and Delivery of Inorganic/Organic Substrates

The convergent synthesis of a series of polycationic aryl ether dendrimers has been accomplished by a convenient procedure involving quantitative quaternarization of aryl(poly)amine core molecules. The series has been expanded to the preparation of the first polycationic, mixed core-shell dendrimer. All these dendrimers consist of an apolar core with a peripheral ionic layer which is surrounded by a less polar layer of dendritic wedges. These cationic, macromolecular species have been investigated for their ability to form assemblies with (anionic) guest molecules. The results obtained from UV/Vis and NMR spectroscopies, and MALDI-TOF-MS demonstrate that all the cationic sites throughout the dendrimer core are involved in ion pair formation with anionic guests giving predefined guest/host ratios up to 24. The large NMR spectroscopic shifts of resonances correlated with the groupings located in the core of the dendrimers, together with the relaxation time data indicate that the anionic guests are associated with the cationic core of these dendrimers. The X-ray molecular structure of the octacationic, tetra-arylsilane model derivative [Si(C6H3{CH2NMe3}2-3,5)4](8+) * 8I(-) shows that the iodide counterions are primarily located near the polycationic sphere. The new polycationic dendrimers have been investigated for their catalytic phase-transfer behavior and substrate delivery over a nanofiltration membrane.

Ionic liquids as catalytic green solvents for nucleophilic displacement reactions

We demonstrate the use of room-temperature ionic liquids as a catalytic, environmentally benign solvent for the cyanide displacement on benzyl chloride, replacing phase-transfer catalyzed biphasic systems and thus eliminating the need for a volatile organic solvent and hazardous catalyst disposal.

The hydrogenation of mandelonitrile over a Pd/C catalyst: Towards a mechanistic understanding

A carbon supported Pd catalyst is used in the liquid phase hydrogenation of the aromatic cyanohydrin mandelonitrile (C6H5CH(OH)CH2CN) to afford the primary amine phenethylamine (C6H5CH2CH2NH2). Employing a batch reactor, the desired primary amine is produced in 87% selectivity at reaction completion. Detection of the by-product 2-amino-1-phenylethanol (C6H5CH(OH)CH2NH2) accounts for the remaining 13% and closes the mass balance. The reaction mechanism is investigated, with a role for both hydrogenation and hydrogenolysis processes established.

BENZYLGLUCOSINOLATE DEGRADATION IN HEAT-TREATED LEPIDIUM SATIVUM SEEDS AND DETECTION OF A THIOCYANATE-FORMING FACTOR

Lepidium sativum seeds were dry heated at 125 deg C for varying periods, and also for 30 min at various temperatures.Autolysates were then analysed for benzylglucosinolate degradation products.Whilst heating for 4 hr 20 min at 125 deg C was sufficient to prevent formation of benzyl thiocyanate, just over 7.5 hr at 125 deg C was required before benzyl isothiocyanate also ceased to be produced.This indicates the presence of a discrete, thiocyanate-forming factor in L. sativum seeds, separate from thioglucosidase.After 7.5 hr at 125 deg C, benzyl cyanide continued to be formed, proving that it can be obtained (in relatively small amounts) directly from the glucosinolate even without the influence of any thioglucosidase.In general, isothiocyanate was the more favoured product of glucosinolate degradation following heat treatment of seeds, until the point of thioglucosidase inactivation was approached when nitrile formation took over.It is suggested that the thiocyanate-forming-factor is an isomerase causing Z-E isomerization of the glucosinolate aglucone, but that only those glucosinolates capable of forming particularly stable cations are then able to undergo E-aglucone rearrangement to thiocyanate. Key Word Index- Lepidium sativum; Cruciferae; cress; glucosinolate degradation; thiocyanate.

HPLC-based kinetics assay facilitates analysis of systems with multiple reaction products and thermal enzyme denaturation

Glucosinolates are plant secondary metabolites abundant in Brassica vegetables that are substrates for the enzyme myrosinase, a thioglucoside hydrolase. Enzyme-mediated hydrolysis of glucosinolates forms several organic products, including isothiocyanates (ITCs) that have been explored for their beneficial effects in humans. Myrosinase has been shown to be tolerant of non-natural glucosinolates, such as 2,2-diphenylethyl glucosinolate, and can facilitate their conversion to non-natural ITCs, some of which are leads for drug development. An HPLC-based method capable of analyzing this transformation for non-natural systems has been described. This current study describes (1) the Michaelis–Menten characterization of 2,2-diphenyethyl glucosinolate and (2) a parallel evaluation of this analogue and the natural analogue glucotropaeolin to evaluate effects of pH and temperature on rates of hydrolysis and product(s) formed. Methods described in this study provide the ability to simultaneously and independently analyze the kinetics of multiple reaction components. An unintended outcome of this work was the development of a modified Lambert W(x) which includes a parameter to account for the thermal denaturation of enzyme. The results of this study demonstrate that the action of Sinapis alba myrosinase on natural and non-natural glucosinolates is consistent under the explored range of experimental conditions and in relation to previous accounts.