75344-77-3

Usage

Uses

Used in Pharmaceutical Industry:
4-BROMO-3,5-DIMETHYL-BENZONITRILE is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. Its unique structure allows it to be a key building block in the development of new drugs, contributing to the advancement of medicinal chemistry.
Used in Organic Chemistry:
4-BROMO-3,5-DIMETHYL-BENZONITRILE serves as a versatile building block in organic chemistry reactions. Its presence in the synthesis of agrochemicals and fine chemicals highlights its importance in creating a wide range of chemical products with diverse applications.
Used in Chemical Research:
As a compound with distinct structural features, 4-BROMO-3,5-DIMETHYL-BENZONITRILE is utilized in chemical research to explore new reaction pathways, understand molecular interactions, and develop innovative synthetic methods. Its role in research contributes to the broader understanding of chemical processes and the discovery of new compounds with potential applications.

InChI:InChI=1/C9H8BrN/c1-6-3-8(5-11)4-7(2)9(6)10/h3-4H,1-2H3

Synthetic route

4-bromo-3,5-dimethylbenzaldehyde oxime (400822-49-3) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
With carbon disulfide; sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In toluene at 20℃; for 20h;	75%

2-bromo-5-(bromomethyl)-1,3-dimethylbenzene (35510-00-0) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
With ammonium hydroxide; iodine In acetonitrile at 60℃; for 4h; Solvent; Temperature; Inert atmosphere;	73.5%

4-bromo-3,5-dimethylbenzaldehyde (400822-47-1) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + 4-bromo-3,5-dimethylbenzaldehyde oxime (400822-49-3)

Conditions	Yield
With pyridine; hydroxylamine hydrochloride In toluene for 2h; Heating;	A 39% B 56%

4-bromo-3,5-dimethylbenzamide (864825-81-0) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
With phosphorus pentachloride

1,4-dibromo-2,6-dimethylbenzene (100189-84-2) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: nBuLi / diethyl ether; hexane / 0.75 h / -78 °C 1.2: 79 percent / diethyl ether; hexane / -78 - 20 °C 2.1: 39 percent / hydroxylamine hydrochloride; pyridine / toluene / 2 h / Heating View Scheme
Multi-step reaction with 3 steps 1.1: nBuLi / diethyl ether; hexane / 0.75 h / -78 °C 1.2: 79 percent / diethyl ether; hexane / -78 - 20 °C 2.1: 56 percent / hydroxylamine hydrochloride; pyridine / toluene / 2 h / Heating 3.1: 75 percent / CS2; aq. NaOH; (nBu)4NHSO4 / toluene / 20 h / 20 °C View Scheme

4-bromo-3,5-dimethylbenzaldehyde (400822-47-1) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 56 percent / hydroxylamine hydrochloride; pyridine / toluene / 2 h / Heating 2: 75 percent / CS2; aq. NaOH; (nBu)4NHSO4 / toluene / 20 h / 20 °C View Scheme

4-bromo-3,5-dimethylbenzoic acid (7697-32-7) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / Behandeln des erhaltenen Saeurechlorids mit wss. Ammoniak 2: phosphorus (V)-chloride View Scheme

zinc(II) cyanide (557-21-1) + 4-bromo-3,5-dimethylphenyl trifluoromethanesulfonate (864825-79-6) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl acetamide; acetonitrile at 50 - 88℃;

2,4,6-trimethylphenyl bromide (576-83-0) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 2 h / 85 °C 2: ammonium hydroxide; iodine / acetonitrile / 4 h / 60 °C / Inert atmosphere View Scheme

zinc(II) cyanide (557-21-1) + 2-Bromo-m-xylene (576-22-7) → 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + 3-bromo-2,4-dimethylbenzonitrile

Conditions	Yield
With 3-(trifluoromethyl)quinoline; palladium diacetate; silver fluoride; N-acetylglycine at 80℃; for 18h; Overall yield = 65 %;

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 4-bromo-3,5-dimethylbenzoic acid (7697-32-7)

Conditions	Yield
With potassium hydroxide In ethanol for 22h; Reflux;	98%
With water; sodium hydroxide In ethanol at 120℃; for 12h; Sealed tube;
With water; sodium hydroxide at 95℃; for 17h;

isopropylboronic acid (80041-89-0) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 4-isopropyl-3,5-dimethylbenzonitrile

Conditions	Yield
With potassium phosphate monohydrate; bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; C20H34O3P2 In toluene at 100℃; Suzuki-Miyaura Coupling; Inert atmosphere;	96%

2-(3,4,5-trifluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (827614-70-0) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3',4',5'-trifluoro-2,6-dimethyl-[1,1'-biphenyl]-4-carbonitrile

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; Inert atmosphere;	89.2%

mesitylboronic acid (5980-97-2) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3,5-dimethyl-4-(2,4',6'-trimethylphenyl)-benzonitrile (76410-97-4)

Conditions	Yield
With BI-DIME; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 12h; Suzuki-Miyaura Coupling; Inert atmosphere;	88%

potassium tert-butyl N-[(difluoroboranyl)methyl]carbamate + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → (4-cyano-2,6-dimethylbenzyl)carbamic acid tert-butyl ester (1618647-92-9)

Conditions	Yield
With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); caesium carbonate In 1,4-dioxane; water at 110℃; for 16h; Inert atmosphere;	86%

4-(diphenylamino)phenylboronic pinacol ester (267221-88-5) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → C27H22N2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; for 24h; Inert atmosphere;	84%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + 9-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-9H-3,9'-dicarbazole → C39H27N3

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; for 24h; Inert atmosphere;	79%

9-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-9H-carbazole (785051-54-9) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → C27H20N2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; for 18h; Inert atmosphere;	78.1%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Conditions	Yield
Stage #1: 4-bromo-3,5-dimethyl benzonitrile With n-butyllithium In tetrahydrofuran; hexane at -100℃; for 1.41667h; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -100 - 20℃;	77%
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / -100 °C / Inert atmosphere 1.2: 12 h / -100 - 23 °C / Inert atmosphere 2.1: hydrogenchloride / water; tetrahydrofuran; hexane / 1 h / 23 °C / pH 2 / Inert atmosphere View Scheme

10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-10H-phenoxazine + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → C27H20N2O

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; for 24h; Inert atmosphere;	77%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + ethyl (S)-3-((tert-butoxycarbonyl)amino)-3-(2-fluoro-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate → ethyl (S)-3-((tert-butoxycarbonyl)amino)-3-(4'-cyano-4-fluoro-2',5,6'-trimethyl-[1,1'-biphenyl]-3-yl)propanoate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 110℃; for 2h; Inert atmosphere;	70%

10-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10H-phenoxazine + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → C27H20N2O

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 85℃; for 24h; Inert atmosphere;	69%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + bis(pinacol)diborane (73183-34-3) → 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	65%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	65%
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In dimethyl sulfoxide at 90 - 100℃; for 24h; Inert atmosphere;	57%
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In dimethyl sulfoxide at 90 - 100℃; for 24h; Inert atmosphere;	57%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester (93267-04-0) → methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate (1227311-10-5)

Conditions	Yield
Stage #1: N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester With iodine; zinc In N,N-dimethyl-formamide at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 4-bromo-3,5-dimethyl benzonitrile With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0) In N,N-dimethyl-formamide at 50℃; Temperature;	50%
Stage #1: N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester With iodine; zinc In N,N-dimethyl acetamide at 21 - 29℃; Inert atmosphere; Stage #2: 4-bromo-3,5-dimethyl benzonitrile; tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine In N,N-dimethyl acetamide at 35 - 70℃; Product distribution / selectivity; Inert atmosphere;

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 3,5-dimethyl-4-formylbenzonitrile (157870-16-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane for 1h; Cooling with ether-dry ice;	47%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3,5-dimethyl-4-hydroxybenzonitrile (4198-90-7)

Conditions	Yield
With oxygen; triethylamine; sodium iodide In acetonitrile at 32℃; for 24h; Schlenk technique; UV-irradiation;	42%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) + 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene (349666-24-6) → 3,5-dimethyl-4-(pyren-1-yl)benzonitrile

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In toluene for 20h; Suzuki cross-coupling; Heating;	28%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 4-bromo-3,5-bis(bromomethyl)benzonitrile

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In dichloromethane at 20℃; for 24h; Inert atmosphere; Schlenk technique; Glovebox;	25%

5-(tributylstannyl)-[1,2,4]triazolo[1,5-a]pyridine (1332076-55-7) + 4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3,5-dimethyl-4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 120℃; for 0.333333h; Stille Cross-Coupling (Migita-Kosugi-Stille Coupling); Inert atmosphere; Sealed tube; Microwave irradiation;	20%

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 4-bromo-N-hydroxy-3,5-dimethyl-benzamidine (1458656-36-4)

Conditions	Yield
With hydroxylamine hydrochloride; triethylamine In ethanol for 4h; Reflux;

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3-(4-bromo-3,5-dimethyl-phenyl)-5-methyl-[1,2,4]oxadiazole (1458656-37-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; triethylamine / ethanol / 4 h / Reflux 2: 2,4,6-trimethyl-pyridine / 4 h / 20 - 120 °C View Scheme

4-bromo-3,5-dimethyl benzonitrile (75344-77-3) → 3-(4-bromo-3,5-dimethyl-phenyl)-5-(2-hydroxy-prop-2-yl)-[1,2,4]oxadiazole (1458656-41-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; triethylamine / ethanol / 4 h / Reflux 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 2.2: 20 - 110 °C View Scheme

Upstream product

• 557-21-1 zinc(II) cyanide 
• 576-22-7 2-Bromo-m-xylene 
• 576-83-0 2,4,6-trimethylphenyl bromide 
• 35510-00-0 2-bromo-5-(bromomethyl)-1,3-dimethylbenzene 
• 864825-79-6 4-bromo-3,5-dimethylphenyl trifluoromethanesulfonate 
• 7697-32-7 4-bromo-3,5-dimethylbenzoic acid 
• 400822-47-1 4-bromo-3,5-dimethylbenzaldehyde 
• 100189-84-2 2,5-dibromo-1,3-dimethylbenzene 
• 400822-49-3 4-bromo-3,5-dimethylbenzaldehyde oxime 
• 864825-81-0 4-bromo-3,5-dimethylbenzamide 

Downstream Products

• 1227311-10-5 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate 
• 90877-62-6 4-isopropyl-3,5-dimethylbenzonitrile 
• 1458655-70-3 1-(5-(4-bromo-3,5-dimethylphenyl)-2H-tetrazol-2-yl)-2-methylpropan-2-ol 
• 1458655-71-4 2-(5-(4-bromo-3,5-dimethylphenyl)-2H-tetrazol-2-yl)-2-methylpropan-1-ol 
• 1458655-63-4 5-(4-bromo-3,5-dimethyl-phenyl)-2-methyl-2H-tetrazole 
• 1458655-64-5 5-(4-bromo-3,5-dimethyl-phenyl)-1-methyl-1H-tetrazole 
• 1458653-92-3 methyl 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate 
• 1458655-62-3 5-(4-bromo-3,5-dimethyl-phenyl)-1H-tetrazole 
• 1458656-41-1 3-(4-bromo-3,5-dimethyl-phenyl)-5-(2-hydroxy-prop-2-yl)-[1,2,4]oxadiazole 
• 1458656-37-5 3-(4-bromo-3,5-dimethyl-phenyl)-5-methyl-[1,2,4]oxadiazole 
• 1458656-36-4 4-bromo-N-hydroxy-3,5-dimethyl-benzamidine 
• 4198-90-7 3,5-dimethyl-4-hydroxybenzonitrile 

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