452-77-7

Basic information

• Product Name: 3-Fluoro-4-methylaniline
• Synonyms: 2-FLUORO-4-AMINO-TOLUENE;3-FLUORO-4-METHYLANILINE;3-FLUORO-4-METHYLBENZENEAMINE;3-FLUORO-P-TOLUIDINE;4-AMINO-2-FLUOROTOLUENE;3-fluoro-4-methyl-benzenamin;3-fluoro-p-toluidin;3-Fluoro-4-methylaniline 98%
• CAS NO: 452-77-7
• Molecular Formula: C₇H₈FN
• Molecular Weight: 125.14
• EINECS: 207-212-4
• Product Categories: Fluorobenzene;Anilines, Aromatic Amines and Nitro Compounds;Aniline;Miscellaneous;Anilines, Amides & Amines;Fluorine Compounds;Amines;Aryl Fluorinated Building Blocks;Building Blocks;C7;C7-C8;Chemical Synthesis;Fluorinated Building Blocks;Nitrogen Compounds;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks
• Mol File: 452-77-7.mol
• Article Data: 12

Chemical Properties

• Melting Point: 30-32 °C
• Boiling Point: 93°C 12mm
• Flash Point: 88 °C
• Appearance: clear pale yellow to brownish liquid after melting
• Density: 1.093 g/mL at 25 °C(lit.)
• Refractive Index: 1.5385-1.5405
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 4.02±0.10(Predicted)
• BRN: 2715987
• CAS DataBase Reference: 3-Fluoro-4-methylaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Fluoro-4-methylaniline(452-77-7)
• EPA Substance Registry System: 3-Fluoro-4-methylaniline(452-77-7)

Safety Data

• Hazard Codes: T,Xi,Xn
• Statements: 36/37/38-23/24/25-20/21/22
• Safety Statements: 45-36/37/39-26-36/37-36
• RIDADR: 2811
• WGK Germany: 3
• RTECS: XU6825000
• HazardClass: 6.1(b)
• PackingGroup: I
• Hazardous Substances Data: 452-77-7(Hazardous Substances Data)

Usage

Chemical Properties

clear pale yellow to brownish liquid after melting

InChI:InChI=1/C7H8FN/c1-5-2-3-6(9)4-7(5)8/h2-4H,9H2,1H3

Synthetic route

2-fluoro-4-nitrotoluene (1427-07-2) → 3-fluoro-4-methyl-phenylamine (452-77-7)

Conditions	Yield
With ammonium chloride; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate; zinc In water at 20℃; for 7h;	93%
With indium (III) iodide; 1,1,3,3-Tetramethyldisiloxane In toluene at 60℃; for 6h; Inert atmosphere; Sealed tube; chemoselective reaction;	74%
With ethanol; platinum Hydrogenation;

1-methyl-2-nitrobenzene (88-72-2) → 3-fluoro-4-methyl-phenylamine (452-77-7)

Conditions	Yield
aluminum nickel In ethanol

4-chloro-2-fluorotoluene (452-75-5) → 3-fluoro-4-methyl-phenylamine (452-77-7)

Conditions	Yield
Stage #1: 4-chloro-2-fluorotoluene With [(k2-P,N-di(1-adamantyl)-2-morpholinophenylphosphine)Pd(Ph)Cl]; sodium t-butanolate In 1,4-dioxane Inert atmosphere; Glovebox; Stage #2: With ammonia In 1,4-dioxane at 24℃; Inert atmosphere; Glovebox;	62%
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; N-[2-(di(1-adamantyl)phosphino)phenyl]morpholine; ammonia; sodium t-butanolate In 1,4-dioxane at 65℃; for 20h; Inert atmosphere; chemoselective reaction;	61%

meta-fluoroaniline (372-19-0) + Methyl fluoride (593-53-3) → 3-fluoro-2-methylaniline (443-86-7) + 3-fluoro-6-methylaniline (367-29-3) + 3-fluoro-4-methyl-phenylamine (452-77-7)

Conditions	Yield
With oxygen; trimethylamine In gaseous matrix at 80℃; Irradiation;	A 56 % Spectr. B 25 % Spectr. C 19 % Spectr.

p-toluidine (106-49-0) → 3,5-difluoro-4-methylaniline + 2,5-difluoro-4-methylaniline + 2-fluoro-4-methylaniline (452-80-2) + 3-fluoro-4-methyl-phenylamine (452-77-7)

Conditions	Yield
With trifluorormethanesulfonic acid; fluorine at 20℃; Title compound not separated from byproducts;

3-fluoro-4-methyl-phenylamine + acetic anhydride (108-24-7) → N-(3-fluoro-4-methylphenyl)acetamide (458-10-6)

3-fluoro-4-methyl-phenylamine (452-77-7) → 2-bromo-5-fluoro 4-methylaniline (202865-78-9)

Conditions	Yield
With bromine; potassium carbonate In dichloromethane at -15℃; for 1h;	100%
With bromine; potassium carbonate In dichloromethane at -15℃; for 1h;	100%
With bromine; potassium carbonate In dichloromethane at -15℃; for 1h;	100%

3-fluoro-4-methyl-phenylamine (452-77-7) + potassium thioacyanate (333-20-0) → 5-fluoro-6-methylbenzo[d]thiazol-2-amine (1155287-47-0)

Conditions	Yield
With acetic acid at 20℃; for 3h;	99%
Stage #1: 3-fluoro-4-methyl-phenylamine; potassium thioacyanate With bromine; acetic acid at 20℃; for 20.33h; Stage #2: With ammonia In water for 2h; pH=8;	98%

3-fluoro-4-methyl-phenylamine (452-77-7) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) → C10H16FNSi

Conditions	Yield
With sulfuric acid at 170 - 175℃; for 1h;	98%

3-fluoro-4-methyl-phenylamine (452-77-7) + C11H8FN → (R)-3-fluoro-N-(2-fluoro-2-(quinolin-2-yl)ethyl)-4-methylaniline

Conditions	Yield
Stage #1: C11H8FN With (S)-3,3'-bis(2,4,6-tri-iso-propylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate at -20℃; for 0.25h; Michael Addition; Sealed tube; Inert atmosphere; Stage #2: 3-fluoro-4-methyl-phenylamine at -20℃; for 120h; Sealed tube; Inert atmosphere; enantioselective reaction;	98%

3-fluoro-4-methyl-phenylamine (452-77-7) → 5-fluoro-2-iodo-4-methyl-phenylamine (1126423-32-2)

Conditions	Yield
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethane at 0 - 20℃; for 17h;	95%
With benzyl dimethyl ammonium dichloroiodate; calcium carbonate In methanol; dichloromethane at 20℃; for 1h;	87%
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethane at 20℃; for 1h;	87%

→ N-(3-fluoro-4-methylphenyl)-3-nitropyridin-2-amine

3-fluoro-4-methyl-phenylamine (452-77-7) + 6-(2-chloro-6-methylphenyl)-2-(enthylsulfonyl)thiazolo[4,5-d]-pyrimidin-7(6H)-one → (6-(2-chloro-6-methylphenyl)-2-(3-fluoro-4-methylphenyl)amino)thiazolo[4,5-d]pyrimidin-7(6H)-one

Conditions	Yield
With acetic acid at 40℃; for 6h;	91%

3-fluoro-4-methyl-phenylamine (452-77-7) → 4-azido-2-fluoro-1-methylbenzene (558441-20-6)

Conditions	Yield
Stage #1: 3-fluoro-4-methyl-phenylamine With hydrogenchloride In water at 20℃; Inert atmosphere; Stage #2: With sodium nitrite In water at 0 - 5℃; for 0.166667h; Inert atmosphere; Stage #3: With sodium azide In water at 20℃; for 2h; Inert atmosphere;	90.8%
With hydrogenchloride; sodium azide; sodium nitrite In water at 0 - 5℃; for 2h;	89%
Stage #1: 3-fluoro-4-methyl-phenylamine With hydrogenchloride; sodium nitrite In water at 0℃; for 1h; Stage #2: With sodium azide In water at 0 - 20℃;	70%
Stage #1: 3-fluoro-4-methyl-phenylamine With hydrogenchloride; sodium nitrite In water at 0℃; Stage #2: With sodium azide In water at 0℃;
With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 0 - 20℃; for 2.5h;

4,6-dimethyl-1H-indole-2-carboxylic acid (383132-27-2) + 3-fluoro-4-methyl-phenylamine (452-77-7) → N-(3-fluoro-4-methylphenyl)-4,6-dimethyl-1H-indole-2-carboxamide (883014-15-1)

Conditions	Yield
Stage #1: 4,6-dimethyl-1H-indole-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 3-fluoro-4-methyl-phenylamine With triethylamine In dichloromethane at 20℃;	89%

3-fluoro-4-methyl-phenylamine (452-77-7) + 5-bromo-2-chloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine → 5-bromo-2-N-(3-fluoro-4-methylphenyl)-4-N-((tetrahydrofuran-2-yl)methyl)pyrimidine-2,4-diamine hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water at 150℃; for 0.333333h; Microwave irradiation;	87%

3-fluoro-4-methyl-phenylamine (452-77-7) + 4-methoxy-1,3-benzenedicarbonyl dichloride (13235-60-4) → N1,N3-bis(3-fluoro-4-methylphenyl)-4-methoxybenzene-1,3-isophthalamide

Conditions	Yield
Stage #1: 3-fluoro-4-methyl-phenylamine; 4-methoxy-1,3-benzenedicarbonyl dichloride In tetrahydrofuran at 20℃; for 1h; Stage #2: With pyridine In tetrahydrofuran Reflux;	86.5%

Upstream product

• 452-75-5 4-chloro-2-fluorotoluene 
• 88-72-2 1-methyl-2-nitrobenzene 
• 106-49-0 p-toluidine 
• 372-19-0 meta-fluoroaniline 
• 593-53-3 Methyl fluoride 
• 1427-07-2 2-fluoro-4-nitrotoluene 

Downstream Products

• 558441-20-6 4-azido-2-fluoro-1-methylbenzene 
• 1227372-41-9 2-amino-4-fluoro-5-methylbenzenesulphonic acid 
• 494789-04-7 (3-fluoro-4-methylphenyl)carbamic acid tert-butyl ester 
• 87126-75-8 3-(3-Fluoro-4-methyl-phenylcarbamoyl)-7-oxa-bicyclo[2.2.1]heptane-2-carboxylic acid 
• 27916-96-7 α-chloro-β-(3-fluoro-p-tolyl)propionitrile 
• 53719-13-4 C,C,C-Trifluoro-N-(3-fluoro-4-methyl-phenyl)-methanesulfonamide 
• 1478-85-9 4-(3-fluoro-4-methyl-phenyl)piperazine 
• 458-10-6 N-(3-fluoro-4-methylphenyl)acetamide 
• 452-78-8 3-fluoro-4-methyl phenol 

Relevant articles and documents

Indium(III)-Catalyzed Reduction of Nitrobenzenes to Anilines: Scope and Limitations

We have demonstrated that a combination of indium(III) iodide and 1,1,3,3-tetramethyldisiloxane (TMDS) effectively catalyzes the chemoselective reduction of nitrobenzenes with a variety of functional groups (halogens, alkyl, alkoxy, hydroxy, ester, amino, amide, cyanide, thiol, and an alkene moiety), producing the corresponding aniline derivatives.

NOVEL CATALYSTS

The present invention provides novel compounds and ligands that are useful in transition metal catalyzed cross-coupling reactions. For example, the compounds and ligands of the present invention are useful in palladium or gold catalyzed cross-coupling reactions.

Highly efficient solvent-free catalytic hydrogenation of solid alkenes and nitro-aromatics using Pd nanoparticles entrapped in aluminum oxy-hydroxide

Solid alkenes and aromatic nitro compounds are readily hydrogenated to the corresponding alkanes without further reduction of other functional group and amino compounds in nearly quantitative yields in the presence of Pd nanoparticles entrapped in aluminum oxy-hydroxide under the solvent-free condition.