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
• Article Data: 17

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

Chemical Properties

Pale yellow low melting solid

Uses

3,4-(Methylenedioxy)phenylacetonitrile was used in synthesis of derrubone. It was used as standard to analyze the seized methamphetamine samples showing unique profiles of stable isotopic compositions by isotope ratio mass spectrometry.

General Description

3,4-(Methylenedioxy)phenylacetonitrile undergoes hydrolysis catalyzed by nitrilase ZmNIT2 enzyme from maize.

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

• 153361-93-4 benzo[1,3]dioxol-5-yl-acetaldehyde-oxime 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 495-76-1 piperonol 
• 151-50-8 potassium cyanide 
• 180330-90-9 Benzo[1,3]dioxol-5-yl-chloro-acetonitrile 
• 13435-20-6 tetraethylammoniumcyanide 
• 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 
• 333-20-0 potassium thioacyanate 
• 218144-97-9 N'-(benzo[d][1,3]dioxol-5-ylmethylene)-4-methylbenzenesulfonohydrazide 
• 120-57-0 piperonal 

Downstream Products

• 34140-20-0 6,7-(methylenedioxy)isochroman-3-one 
• 34144-30-4 6,7-methylenedioxy-1,4-dihydro-3(2H)-isoquinolinone 
• 78222-24-9 4,5-methylenedioxy-2-aminomethylphenylacetic acid bisamide 
• 114879-85-5 (chloro-4 phenyl)-2 hydroxy-4 (methylenedioxy-3,4 phenyl)-1 pentane carbonitrile 
• 105702-08-7 (S)-Benzo[1,3]dioxol-5-yl-((R)-2-nitro-cyclohexyl)-acetonitrile 
• 105702-08-7 (R)-Benzo[1,3]dioxol-5-yl-((1S,2R)-2-nitro-cyclohexyl)-acetonitrile 
• 103740-48-3 Benzo[1,3]dioxol-5-yl-[1-(2-benzyloxy-ethyl)-pyrrolidin-(2E)-ylidene]-acetonitrile 
• 85352-32-5 α-phenylthio-1,3-benzodioxole-5-acetonitrile 
• 95-94-3 1,2,4,5-tetrachlorobenzene 
• 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 
• 862574-89-8 1-(2H-1,3-benzodioxol-5-yl)cyclopropane-1-carboxylic acid 
• 1126-62-1 (3,4-dihydroxy-phenyl)-acetonitrile 

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

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.

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.