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

Description

3,5-Bis(2-cyanoprop-2-yl)toluene, also known as α,α,α',α'-Tetramethyl-5-methyl-1,3-benzenediacetonitrile, is an organic compound that serves as a crucial intermediate in the synthesis of Anastrozole, an aromatase inhibitor. It is characterized by its white solid appearance and plays a significant role in the pharmaceutical industry due to its contribution to the production of a vital antineoplastic agent.

Uses

Used in Pharmaceutical Industry:
3,5-Bis(2-cyanoprop-2-yl)toluene is used as a labeled intermediate for the synthesis of Anastrozole (A637425), an aromatase inhibitor. It is utilized for its antineoplastic properties, which are essential in the development and production of cancer-fighting drugs.
As an intermediate in the synthesis of Anastrozole, 3,5-Bis(2-cyanoprop-2-yl)toluene contributes to the creation of a medication that inhibits the aromatase enzyme, thereby reducing the production of estrogen in the body. This inhibition is particularly beneficial in the treatment of hormone receptor-positive breast cancer, as it helps to slow down or stop the growth of cancer cells that rely on estrogen for their development.

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

• 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 
• 98-88-4 benzoyl chloride 
• 302-72-7 rac-Ala-OH 
• 14839-73-7 2-<α-Anilino-isobutyrylamino>-propionsaeure-anilid 
• 51127-13-0 2-phenyl-4-methyl-4H-oxazolin-5-one 
• 7732-18-5 water 
• 64-17-5 ethanol 
• 4452-17-9 N-benzoyl-α,β-dehydroalanine 
• 15985-11-2 D,L-Alanin-trimethylsilylester 
• 138079-74-0 C₁₂H₁₃NO₄S 

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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