4439-02-5

Basic information

• Product Name: 3,4-(Methylenedioxy)phenylacetonitrile
• Synonyms: PIPERONYL CYANIDE;1,3-Benzodioxol-5-ylacetonitrile;3,4-(Methylenedioxy)phenylacetonitrile 1,3-Benzodioxole-5-acetonitrile;A-CYANO-3,4-METHYLENEDIOXYTOLUENE;3,4-METHYLENEDIOXYBENZYL CYANIDE;3,4-(METHYLENEDIOXY)PHENYLACETONITRILE;1,3-BENZODIOXOLE-5-ACETONITRILE;(1,3-Benzodioxol-5-yl)acetonitrile~3,4-(Methylenedioxy)benzyl cyanide~Piperonyl cyanide
• CAS NO: 4439-02-5
• Molecular Formula: C₉H₇NO₂
• Molecular Weight: 161.16
• EINECS: 224-655-9
• Product Categories: Pharmaceutical Intermediates;Aromatic Nitriles
• Mol File: 4439-02-5.mol

Chemical Properties

• Melting Point: 43-45 °C(lit.)
• Boiling Point: 135-140°C 5mm
• Flash Point: >230 °F
• Appearance: Pale yellow low melting solid
• Density: 1.27g/cm³
• Vapor Pressure: 0.00117mmHg at 25°C
• Refractive Index: 1.574
• Storage Temp.: Inert atmosphere,Room Temperature
• Water Solubility: Insoluble in water.
• BRN: 7739
• CAS DataBase Reference: 3,4-(Methylenedioxy)phenylacetonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-(Methylenedioxy)phenylacetonitrile(4439-02-5)
• EPA Substance Registry System: 3,4-(Methylenedioxy)phenylacetonitrile(4439-02-5)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36-36/37
• RIDADR: 3439
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 4439-02-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
3,4-(Methylenedioxy)phenylacetonitrile is used as a key intermediate in the synthesis of derrubone, a compound with potential pharmaceutical applications. Its unique structure allows for the formation of various derivatives, making it a valuable building block in the development of new drugs.
Used in Forensic Analysis:
3,4-(Methylenedioxy)phenylacetonitrile is used as a standard in the analysis of seized methamphetamine samples. It helps in determining the unique profiles of stable isotopic compositions through isotope ratio mass spectrometry, which aids in the identification and characterization of illicit drugs.

InChI:InChI=1/C9H7NO2/c10-4-3-7-1-2-8-9(5-7)12-6-11-8/h1-2,5H,3,6H2

Synthetic route

Benzo[1,3]dioxol-5-yl-chloro-acetonitrile (180330-90-9) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With sodium hydrogen telluride; acetic acid In ethanol; benzene at -20℃; for 0.333333h;	98%

Benzo[1,3]dioxol-5-yl-methylsulfanyl-acetonitrile (84784-39-4) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With acetic acid; zinc at 100℃; for 1h;	90%

3,4-methylenedioxyphenylethylamine (1484-85-1) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; free radical; trichloroisocyanuric acid In dichloromethane at 10℃; for 2.5h;	89%

1,2-(methylenedioxy)-4-bromobenzene (2635-13-4) + sodium cyanoacetate (1071-36-9) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(η3-allyl-μ-chloropalladium(II)) In 1,3,5-trimethyl-benzene at 20 - 140℃; for 5.16667h; Inert atmosphere; Sealed tube; chemoselective reaction;	89%

piperonol (495-76-1) + potassium cyanide (151-50-8) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With tetrachloromethane; 18-crown-6 ether; tributylphosphine In acetonitrile for 24h; Ambient temperature;	84%

ethyl 4-(1,3-benzodioxol-5-yl)-5-methyl-isoxazole-3-carboxylate → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With potassium fluoride In water; N,N-dimethyl-formamide at 125℃; for 16h; Inert atmosphere;	81%

potassium thioacyanate (333-20-0) + N'-(benzo[d][1,3]dioxol-5-ylmethylene)-4-methylbenzenesulfonohydrazide (218144-97-9) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With copper(l) iodide; oxygen; 1,8-diazabicyclo[5.4.0]undec-7-ene; toluene-4-sulfonic acid hydrazide In 1-methyl-pyrrolidin-2-one; acetonitrile at 80℃; under 760.051 Torr; for 7h; Molecular sieve; Green chemistry;	81%

5-(chloromethyl)-1,3-benzodioxole (20850-43-5) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With sodium cyanide	78%

5-chloro-1,3-benzodioxole (7228-38-8) + ethyl 2-cyanoacetate (105-56-6) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
Stage #1: 5-chloro-1,3-benzodioxole; ethyl 2-cyanoacetate With N-(2-methylnaphthalen-1-yl)-N’-(pyridin-2-ylmethyl)oxalamide; copper(I) bromide; sodium t-butanolate In isopropyl alcohol at 105℃; for 24h; Schlenk technique; Inert atmosphere; Stage #2: With water In isopropyl alcohol at 105℃; for 12h; Schlenk technique; Inert atmosphere; Cooling;	71%

5-(2-nitrovinyl)benzo[1,3]dioxole (1485-00-3) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With titanium tetrachloride; tetraethylammonium tosylate In N,N-dimethyl-formamide electroreduction - 4 mA/cm2;	66%

2-(benzo-[d][1,3]dioxol-5-yl)-2-bromoacetonitrile → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With sodium hydrogen telluride; acetic acid In ethanol; benzene at -20℃; for 0.333333h;	54%

5-(chloromethyl)-1,3-benzodioxole (20850-43-5) + sodium cyanide (143-33-9) → 3,4-methylenedioxyphenylacetonitrile (4439-02-5)

Conditions	Yield
With acetone; sodium iodide
With water; mercury(II) cyanide; benzene

Upstream product

• 180330-90-9 Benzo[1,3]dioxol-5-yl-chloro-acetonitrile 
• 253266-72-7 5-(2,2-difluorovinyl)benzo[d][1,3]dioxole 
• 773837-37-9 sodium cyanide 
• 2606-51-1 3,4-Methylenedioxybenzyl bromide 
• 7228-38-8 5-chloro-1,3-benzodioxole 
• 105-56-6 ethyl 2-cyanoacetate 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 333-20-0 potassium thioacyanate 
• 218144-97-9 N'-(benzo[d][1,3]dioxol-5-ylmethylene)-4-methylbenzenesulfonohydrazide 
• 120-57-0 piperonal 
• 2635-13-4 1,2-(methylenedioxy)-4-bromobenzene 
• 1071-36-9 sodium cyanoacetate 
• 5876-51-7 5-iodo-1,3-benzodioxole 
• 86215-81-8 2-(benzo[d][1,3]dioxol-6-yl)-2-hydroxyacetonitrile 

Downstream Products

• 39548-98-6 2-(benzo[d][1,3]dioxol-5-yl)-1-(2,4,6-trihydroxyphenyl)ethanone 
• 55607-36-8 2,4-dihydroxy-6-methoxy-3',4'-methylenedioxy-deoxybenzoin 
• 6443-78-3 2-benzo[1,3]dioxol-5-yl-3c-phenyl-acrylonitrile 
• 142682-02-8 2-benzo[1,3]dioxol-5-yl-3c-(4-dimethylamino-phenyl)-acrylonitrile 
• 1484-85-1 3,4-methylenedioxyphenylethylamine 
• 363-72-4 Pentafluorobenzene 
• 7145-99-5 5-methyl-1,3-benzodioxole 
• 4676-39-5 1-(1,3-benzodioxol-5-yl)-2-propanone 
• 326-59-0 benzo[1,3]dioxol-5-yl-acetic acid methyl ester 

Relevant articles and documents

Rapid and Simple Access to α-(Hetero)arylacetonitriles from Gem-Difluoroalkenes

A scalable cyanation of gem-difluoroalkenes to (hetero)arylacetonitrile derivatives was developed. This strategy features mild reaction conditions, excellent yields, wide substrate scope, and broad functional group tolerance. Significantly, in this reacti

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.).

Assembly of α-(Hetero)aryl Nitriles via Copper-Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides

α-(Hetero)aryl nitriles are important structural motifs for pharmaceutical design. The known methods for direct synthesis of these compounds via coupling with (hetero)aryl halides suffer from narrow reaction scope. Herein, we report that the combination of copper salts and oxalic diamides enables the coupling of a variety of (hetero)aryl halides (Cl, Br) and ethyl cyanoacetate under mild conditions, affording α-(hetero)arylacetonitriles via one-pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with α-alkyl-substituted ethyl cyanoacetates proceeds smoothly at 60 °C, leading to the formation of α-alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls.

Density functional theory calculations, vibration spectral analysis and molecular docking of the antimicrobial agent 6-(1,3-benzodioxol-5-ylmethyl)-5-ethyl-2-{[2-(morpholin-4-yl)ethyl] sulfanyl}pyrimidin-4(3H)-one

Vibrational spectral analysis and quantum chemical computations based on density functional theory have been performed on the antimicrobial agent 6-(1,3-benzodioxol-5-ylmethyl)-5-ethyl-2-{[2-(morpholin-4-yl)ethyl]sulfanyl}pyrimidin-4-(3H)-one. The equilibrium structural geometry, various bonding features and harmonic vibrational wavenumbers of the title compound have been investigated using DFT-B3LYP function at 6-311++G(d,p) basis set. The detailed interpretations of the vibrational spectra have been carried out with the aid of VEDA 4 program. The various intramolecular interactions of the title compound have been exposed by natural bond orbital analysis. The FT-IR and FT-Raman spectra of the title molecule have been recorded and analyzed. Blue-shifting of the C-H wavenumber along with a decrease in the C-H bond length attribute for the formation of the C-H...O hydrogen bonding provide an evidence for a charge transfer interaction. Also, the distribution of natural atomic charges reflects the presence of intramolecular hydrogen bonding. The analysis of the electron density of HOMO and LUMO gives an idea of the delocalization and the low value of energy gap indicates electron transfer within the molecule. Moreover, molecular docking studies revealed the possible binding of the title molecule to different antimicrobial target proteins.

Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "cN" Source

A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.

Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles

A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.

Enantioselective synthesis of amaryllidaceae alkaloids (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine

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Copper-catalyzed cyanation of benzyl chlorides with non-toxic K 4[Fe(CN)6]

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Synthesis of α-Aryl nitriles through palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates

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A Selective and Mild Oxidation of Primary Amines to Nitriles with Trichloroisocyanuric Acid

An efficient and highly selective method for the oxidative conversion of primary amines to the corresponding nitriles using trichloroisocyanuric acid in the presence of catalytic TEMPO under mild reaction conditions is described. Other functional groups such as C,C-double bonds, benzyloxy etc. were found to be unaffected under the reaction conditions. This procedure provides a new entry to the synthesis of various aliphatic, aromatic and heterocyclic nitriles in excellent yield.