120511-72-0

Basic information

• Product Name: 3,5-Bis(2-cyanoprop-2-yl)toluene
• Synonyms: PENTAMETHYL-1,3-BENZENEDIACETONITRILE;2,2'-(5-METHYL-1,3-PHENYLENE)DI(2-METHYLPROPANENITRILE);2,2'-(5-methyl-1,3-phenylene)di(2-methylpropionitrile);A,A,A',A',5-PENTAMETHYL-1,3 BENZENEDIACETONITRILE;5-PENTAMETHYL-1,3-BENZENEDIACETONITRILE;3,5-Bis(2-cyanoprop-2-yl)toluene;3,5-DI[(2,2-DIMETHYL)CYANOMETHYL]TOLUENE;3,5-Bis (2-cyanoisopropyl ) toluene
• CAS NO: 120511-72-0
• Molecular Formula: C15H18N2
• Molecular Weight: 226.32
• EINECS: 1806241-263-5
• Product Categories: INTERMEDIATESOFANASTROZOLE;Anastrozole;Nitriles;(intermediate of anastrozole);Intermediate of Anastrozole;Anastrazole;Aromatics;Inhibitors;Intermediates & Fine Chemicals;Isotope Labelled Compounds;Pharmaceuticals
• Mol File: 120511-72-0.mol
• Article Data: 49

Chemical Properties

• Melting Point: 127-130°C
• Boiling Point: 339.089 °C at 760 mmHg
• Flash Point: 146.304 °C
• Appearance: White crystalline powder
• Density: 1.002 g/cm³
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• CAS DataBase Reference: 3,5-Bis(2-cyanoprop-2-yl)toluene(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Bis(2-cyanoprop-2-yl)toluene(120511-72-0)
• EPA Substance Registry System: 3,5-Bis(2-cyanoprop-2-yl)toluene(120511-72-0)

Safety Data

• Hazardous Substances Data: 120511-72-0(Hazardous Substances Data)

Usage

Chemical Properties

3,5-Bis(2-cyanoprop-2-yl)toluene is White Solid

Uses

Different sources of media describe the Uses of 120511-72-0 differently. You can refer to the following data:
1. 3,5-Bis(2-cyanoprop-2-yl)toluene is a labelled intermediate in the synthesis of Anastrozole, an aromatase inhibitor. Used as an antineoplastic.
2. α,α,α’,α’-Tetramethyl-5-methyl-1,3-benzenediacetonitrile (Anastrozole EP Impurity H) is an intermediate in the synthesis of Anastrozole (A637425), an aromatase inhibitor. Used as an antineoplastic.
3. An intermediate in the synthesis of Anastrozole (A637425), an aromatase inhibitor. Used as an antineoplastic.

Synthetic route

(3-cyanomethyl-5-methyl-phenyl)-acetonitrile (120511-74-2) + methyl iodide (74-88-4) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;	88%
With sodium hydride	79%
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 3 - 3.5h;	70.3%

(3-cyanomethyl-5-methyl-phenyl)-acetonitrile (120511-74-2) + methyl p-toluene sulfonate (80-48-8) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere;	86%

3,5-dibromotoluene (1611-92-3) + potassium 2-cyano-2-methyl-propanoate (851233-80-2) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,3,5-trimethyl-benzene at 20 - 140℃; for 3.16667h; Inert atmosphere; Sealed tube; chemoselective reaction;	84%

2-cyano-2-methylpropanoic acid (22426-30-8) + 1,3-diiodo-5-methylbenzene (49617-79-0) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With 1,10-Phenanthroline; copper (I) acetate; caesium carbonate In dimethyl sulfoxide at 140℃; for 10h; Reagent/catalyst; Inert atmosphere; Large scale;	83.9%

2-cyano-2-methylpropanoic acid (22426-30-8) + 3,5-dibromotoluene (1611-92-3) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With [2,2]bipyridinyl; copper(l) iodide In N,N-dimethyl-formamide at 150℃; for 12h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	81.1%

2-cyano-2-methylpropanoic acid (22426-30-8) + 3,5-bis(trifluoromethanesulfonate)toluene → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
With copper(l) iodide; bathophenanthroline; potassium tert-butylate In 5,5-dimethyl-1,3-cyclohexadiene for 48h; Inert atmosphere; Reflux;	78.8%

anastrozol (120511-73-1) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) + 2-(3-((1H-1,2,4-triazol-1-yl)methyl)-5-isopropylphenyl)-2-methylpropanenitrile

Conditions	Yield
With tetraethylammonium perchlorate; triethylamine In dimethyl sulfoxide at 20℃; for 9h; Electrolysis; Green chemistry;	A 47% B 26%

methyl iodide (74-88-4) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0)

Conditions	Yield
Stage #1: (3-cyanomethyl-5-methyl-phenyl)-acetonitrile With potassium tert-butylate In N,N-dimethyl-formamide at 15 - 20℃; for 4 - 5h; Stage #2: methyl iodide In N,N-dimethyl-formamide for 1h;

2-[3-bromomethyl-5-(cyanodimethylmethyl)phenyl]-2-methylpropanenitrile (120511-84-4) + sodium triazole (41253-21-8) → 3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) + α,α,α',α'-tetramethyl-5-(4H-1,2,4-triazol-4ylmethyl)-1,3-benzene-diacetonitrile (120511-92-4) + anastrozol (120511-73-1)

Conditions	Yield
In N,N-dimethyl-formamide at -10 - -5℃; for 0.75h; Product distribution / selectivity;

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) → 2-[3-bromomethyl-5-(cyanodimethylmethyl)phenyl]-2-methylpropanenitrile (120511-84-4)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 2 - 2.5h; Heating / reflux;	87%
With N-Bromosuccinimide In dichloromethane for 4h; Product distribution / selectivity; UV-irradiation; Heating / reflux;	85%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In acetonitrile at 75 - 80℃; for 3h; Solvent; Reagent/catalyst;	85%

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) → 3,5-bis(2-cyanopropan-2-yl)benzoic acid (1085181-50-5)

Conditions	Yield
With chromium(VI) oxide; sulfuric acid; acetic acid at 0℃;	78%

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) + sodium triazole (41253-21-8) → anastrozol (120511-73-1)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In N-methyl-acetamide; tetrachloromethane; water
Stage #1: 3,5-bis(2-cyanoprop-2-yl)toluene; sodium triazole In N,N-dimethyl-formamide at 45 - 50℃; for 4h; Stage #2: With hydrogenchloride In water at 50℃; pH=1 - 2; Stage #3: With ammonia In water at 0 - 5℃; pH=8 - 9;

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) + acetic anhydride (108-24-7) → C19H22N2O4 (872967-71-0)

Conditions	Yield
Stage #1: 3,5-bis(2-cyanoprop-2-yl)toluene; acetic anhydride With sulfuric acid; chromium(VI) oxide at -10 - 0℃; for 2.5 - 2.75h; Stage #2: With water

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) → 4-amino-1-[3,5-bis(1-cyano-1-methylethyl)benzyl]-4H-1,2,4-triazolium bromide

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / 2,2'-azobis(isobutyronitrile) / cyclohexane / 4 h / 25 - 85 °C 2: isopropyl alcohol / 5 h / 80 - 85 °C View Scheme
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; acetic acid; 2,2'-azobis(isobutyronitrile) / acetonitrile / 6.5 h / 65 °C / Reflux; Industrial scale 2: 3 h / Reflux; Industrial scale View Scheme

3,5-bis(2-cyanoprop-2-yl)toluene (120511-72-0) → anastrozol (120511-73-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / 2,2'-azobis(isobutyronitrile) / cyclohexane / 4 h / 25 - 85 °C 2.1: isopropyl alcohol / 5 h / 80 - 85 °C 3.1: hydrogenchloride; sodium nitrite / water / 8 h / -5 - 20 °C 3.2: 4 h / 5 - 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; acetic acid; 2,2'-azobis(isobutyronitrile) / acetonitrile / 6.5 h / 65 °C / Reflux; Industrial scale 2.1: 3 h / Reflux; Industrial scale 3.1: hydrogenchloride; sodium nitrite / acetonitrile; water / 4 h / 15 - 22 °C / Industrial scale 3.2: 0.5 h / 20 °C / Industrial scale 3.3: 12 h / 12 °C / Industrial scale View Scheme

Upstream product

• 74-88-4 methyl iodide 
• 120511-74-2 (3-cyanomethyl-5-methyl-phenyl)-acetonitrile 
• 80-48-8 methyl p-toluene sulfonate 
• 22426-30-8 2-cyano-2-methylpropanoic acid 
• 49617-79-0 1,3-diiodo-5-methylbenzene 
• 1611-92-3 3,5-dibromotoluene 
• 302-72-7 rac-Ala-OH 
• 98-88-4 benzoyl chloride 
• 51127-13-0 2-phenyl-4-methyl-4H-oxazolin-5-one 
• 7244-67-9 methyl N-benzoylalaninate 
• 64-17-5 ethanol 
• 4452-17-9 N-benzoyl-α,β-dehydroalanine 
• 138079-74-0 C₁₂H₁₃NO₄S 
• 120511-73-1 anastrozol 

Downstream Products

• 120511-84-4 2-[3-bromomethyl-5-(cyanodimethylmethyl)phenyl]-2-methylpropanenitrile 
• 1085181-50-5 3,5-bis(2-cyanopropan-2-yl)benzoic acid 
• 120511-73-1 anastrozol 
• 872967-71-0 C₁₉H₂₂N₂O₄ 

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