70441-63-3

Basic information

• Product Name: 4-FLUORO-N-ISOPROPYLANILINE
• Synonyms: 4-FLUORO-N-ISOPROPYLANILINE;FI-Aniline;FL-ANILINE;4-Fluor-N-(1-methylethyl)-benzenamin;N-(4-Fluorophenyl)isopropylamine;N-(4-Fluorophenyl)-N-isopropylamine;4-Fluoro-N-(1-Methylethyl)benzenaMine
• CAS NO: 70441-63-3
• Molecular Formula: C₉H₁₂FN
• Molecular Weight: 153.2
• Product Categories: Amines;Aromatics;Intermediates
• Mol File: 70441-63-3.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 214℃
• Flash Point: 83℃
• Appearance: /
• Density: 1.045
• Vapor Pressure: 0.161mmHg at 25°C
• Refractive Index: 1.527
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 5.91±0.32(Predicted)
• CAS DataBase Reference: 4-FLUORO-N-ISOPROPYLANILINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-FLUORO-N-ISOPROPYLANILINE(70441-63-3)
• EPA Substance Registry System: 4-FLUORO-N-ISOPROPYLANILINE(70441-63-3)

Safety Data

• RIDADR: 2810
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 70441-63-3(Hazardous Substances Data)

Usage

Uses

4-Fluoro-N-isopropylaniline is an intermediate used in the synthesis of Flufenacet, a herbicide.

InChI:InChI=1/C9H12FN/c1-7(2)11-9-5-3-8(10)4-6-9/h3-7,11H,1-2H3

Synthetic route

4-Fluoronitrobenzene (350-46-9) + acetone (67-64-1) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With chloroplatinic acid; sodium tetrahydroborate; hydrogen; titanium(IV) oxide In water at 70℃; Temperature; Large scale;	99.2%
With hydrogen at 60℃; under 5250.53 Torr; Autoclave;	93%

4-Fluoronitrobenzene (350-46-9) + 2,2-dimethoxy-propane (77-76-9) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With 3 % platinum on carbon; hydrogen; toluene-4-sulfonic acid In toluene at 70 - 80℃; under 3750.38 - 15001.5 Torr; for 4h; Reagent/catalyst; Temperature; Pressure; Solvent; Autoclave; Large scale;	98%

4-Fluoronitrobenzene (350-46-9) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
Pt on charcoal In water; acetone; toluene	97%
platinum In acetone

diisopropylamine (108-18-9) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With μ-diiodo-di((η5-pentamethylcyclopentadienyl)(iodo)iridium) In 5,5-dimethyl-1,3-cyclohexadiene at 155℃; for 10h; Inert atmosphere;	95%

acetone (67-64-1) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With iridium bromide; formic acid; zinc In water at 30℃; for 20h;	80%
With sodium tetrahydroborate
With sodium tetrahydroborate In neat (no solvent) at 20℃; for 0.5h; Catalytic behavior;	78 %Chromat.

4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With sodium hydroxide; sodium borohydrid In acetic acid; acetone	71%

N-chloroisopropylamine (26245-56-7) + 4-fluorophenylzinc bromide (181705-93-1) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With triethylamine In toluene at 0 - 20℃; for 2h; Reagent/catalyst; Inert atmosphere;	58%

(4-fluorophenyl)lithium (1493-23-8) + N-isopropyl-O-(trimethylsilyl)hydroxylamine (219943-31-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With CuCN In tetrahydrofuran at -50 - 20℃; for 2h; Arylation;	45%

isopropyl bromide (75-26-3) + 4-fluoroaniline (371-40-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 5h; Reflux;	43%

1-Bromo-4-fluorobenzene (460-00-4) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: cobalt(II) bromide; trifluoroacetic acid; 3-chloroprop-1-ene / acetonitrile / 0.05 h / 20 °C 1.2: 20 °C 2.1: triethylamine / toluene / 2 h / 0 - 20 °C / Inert atmosphere View Scheme

C12H16FNO2 (1310991-25-3) → 4-fluoro-N-isopropyl-aniline (70441-63-3)

Conditions	Yield
With potassium hydroxide at 130℃; for 2h;	127 mg

chloroacetyl chloride (79-04-9) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-chloro-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide (66602-64-0)

Conditions	Yield
With triethylamine In toluene at 20℃; for 5.5h; Solvent; Temperature;	98%
With pyridine In toluene	97%
With sodium hydroxide	94%
In toluene at 20 - 90℃; for 2h;	93%

tert-butyl-5-((4'-formylbiphenyl-4-yl)ethynyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (1221257-85-7) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → (E)-tert-butyl 4-(4'-(((4-fluorophenyl)(isopropyl)amino)-methyl)biphenyl-4-yl)-1-hydroxy-2-(hydroxymethyl)but-3-en-2-ylcarbamate (1221257-86-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃;	94%

bromoacetic acid methyl ester (96-32-2) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[N-(4-fluorophenyl)-N-isopropylamino]acetate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 24h; Inert atmosphere; Reflux;	86%

4-fluoro-N-isopropyl-aniline (70441-63-3) + 4-chloro-1-(2,5-difluoro-phenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (176232-40-9) → N-(4-fluorophenyl)-N-isopropyl-4-chloro-1-(2,5-difluorophenyl)-5-phenylpyrazole-3-carboxamide

Conditions	Yield
With 2-chloro-1-methyl-pyridinium iodide; triethylamine In dichloromethane for 3h;	84.2%

(2R,3R)-3-bromo-1,2-epoxy-hexane + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 4-fluoro-N-isopropyl-N-(((2R,3S)-3-propyloxirane-2-yl)methyl)aniline

Conditions	Yield
Stage #1: 4-fluoro-N-isopropyl-aniline With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (2R,3R)-3-bromo-1,2-epoxy-hexane In tetrahydrofuran; hexane at -78 - 20℃; for 16h;	31%

2-Bromoacetyl bromide (598-21-0) + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-bromo-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-88-2)

Conditions	Yield
With triethylamine In dichloromethane Ambient temperature;

4-fluoro-N-isopropyl-aniline (70441-63-3) + 4-ethylsulfanyl-5-methyl-3-oxo-3H-isoxazole-2-carbonyl chloride (1027241-69-5) → 4-ethylsulfanyl-5-methyl-3-oxo-3H-isoxazole-2-carboxylic acid (4-fluoro-phenyl)-isopropyl-amide

Conditions	Yield
With triethylamine In toluene at 20℃; for 0.583333h; Acylation;

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-Fluoro-phenyl)-2-[3-(1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-acetamide

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h 3: 1.) NaH, NaN(TMS)2 / 1.) DMF, THF, 0 deg C, 2.) DMF, THF, RT, 2 h 4: 4N aq. HCl / dioxane / 6 h / Ambient temperature View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide (174180-87-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 18 h 3: 1.) NaH, NaN(TMS)2 / 1.) DMF, THF, 0 deg C, 2.) DMF, THF, RT, 2 h View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-[2,4-Dioxo-5-phenyl-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 16 h View Scheme

C13H12O4S2 + 4-fluoro-N-isopropyl-aniline (70441-63-3) → 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde (1220972-78-0)

Conditions	Yield
In toluene Reflux;

4-fluoro-N-isopropyl-aniline (70441-63-3) + Propiolic acid (471-25-0) → C12H12FNO

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-N-isopropyl-3-phenylpropiolamide

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-N-isopropyl-3-(thiophen-2-yl)propiolamide

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 3-iodo-1-isopropyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere 3: bis-[(trifluoroacetoxy)iodo]benzene; boron trifluoride diethyl etherate / chlorobenzene / 5 h / 80 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 3-iodo-1-isopropyl-4-(thiophen-2-yl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 0 - 20 °C 2: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 3 h / 80 °C / Inert atmosphere 3: bis-[(trifluoroacetoxy)iodo]benzene; boron trifluoride diethyl etherate / chlorobenzene / 6 h / 80 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → 2-acetoxy-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 2 h / 20 - 90 °C 2: toluene / 95 °C View Scheme

4-fluoro-N-isopropyl-aniline (70441-63-3) → N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / 2 h / 20 - 90 °C 2: toluene / 95 °C 3: ethanol / 70 °C View Scheme

Upstream product

• 460-00-4 1-Bromo-4-fluorobenzene 
• 26245-56-7 N-chloroisopropylamine 
• 181705-93-1 4-fluorophenylzinc bromide 
• 350-46-9 4-Fluoronitrobenzene 
• 77-76-9 2,2-dimethoxy-propane 
• 67-64-1 acetone 
• 1310991-25-3 C₁₂H₁₆FNO₂ 
• 75-26-3 isopropyl bromide 
• 371-40-4 4-fluoroaniline 
• 108-18-9 diisopropylamine 
• 1493-23-8 (4-fluorophenyl)lithium 
• 219943-31-4 N-isopropyl-O-(trimethylsilyl)hydroxylamine 

Downstream Products

• 1220972-78-0 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde 
• 1221257-86-8 (E)-tert-butyl 4-(4'-(((4-fluorophenyl)(isopropyl)amino)-methyl)biphenyl-4-yl)-1-hydroxy-2-(hydroxymethyl)but-3-en-2-ylcarbamate 
• 54041-17-7 N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide 
• 142459-58-3 flufenacet 
• 66602-64-0 2-chloro-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide 
• 174180-87-1 2-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 
• 174180-89-3 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 
• 174180-88-2 2-bromo-N-(4-fluoro-phenyl)-N-isopropyl-acetamide 

Relevant articles and documents

Synthetic method N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide

The invention belongs to the technical field of medical intermediates, and particularly relates to a synthesis method N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropylacetamide. To the invention, fluoronitrobenzene is used as a starting material, and hydrogenation is carried out. Condensation gives compound A, compound A is coupled to compound B by amide coupling, compound B is subjected to nucleophilic substitution reaction to give compound C, compound C is exchanged through ester exchange to obtain N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide. The synthesis route of the complete N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide is provided, and the synthesized N - (4 - fluoroaniline) -2 - hydroxyl - N - isopropyl acetamide is high in yield and high in purity.

Flufenacet preparation method

The invention discloses a flufenacet preparation method, which comprises synthesis of 2-methylsulfonyl-5-trifluoromethyl-1,3,4-thiadiazole, synthesis of 2-hydroxy-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide and synthesis of 4'-fluoro-N-isopropyl-2-[5-(trifluridine)-1,3,4-thiadiazole-2-imide]acetamide. The optimal flufenacet preparation method is screened by a large number of experiments, the whole process is reasonable in design, particularly the steps of screening optimal reaction conditions and the optimal amount ratio, reaction temperature, reaction time and the like of reaction raw materials, the reaction yield (capable of reaching 90 percent or more) can be greatly increased, side reaction can be reduced, the reaction rate can be increased, the reaction raw materials can be recycled, the production cost is greatly reduced, and a broad application prospect is achieved.

Nickel(II) complex covalently anchored on core shell structured SiO2@Fe3O4 nanoparticles: A robust and magnetically retrievable catalyst for direct one-pot reductive amination of ketones

A robust and efficient core shell structured magnetically retrievable nickel nanocatalytic system was fabricated via the covalent immobilization of 2-acetyl furan on the surface of an amine functionalized silica coated magnetic nanosupport followed by its metallation with nickel acetate. The newly synthesized magnetic silica based organic-inorganic hybrid nanocatalyst (Ni-ACF@Am-SiO2@Fe3O4) was systematically affirmed using several physico-chemical characterization tools such as FT-IR, XRD, VSM, SEM, TEM, EDS, ED-XRF and AAS. Thereafter, the catalytic performance of this Ni-ACF@Am-SiO2@Fe3O4 nanocatalyst was investigated in the one-pot reductive amination of ketones using NaBH4 as the reductant under neat conditions. The developed core shell magnetic silica based nickel nanocatalyst successfully afforded a structurally diverse range of secondary amines with high turnover frequency (TOF) and excellent conversion percentage. Additionally, it was found that this catalyst could not only be retrieved from the reaction vessel within a fraction of seconds using an external magnet but also be recycled for multiple runs without any discernible loss in its activity that rendered this protocol superior to all the previously established methodologies for the one-pot synthesis of substituted amines. Besides, some of the other fascinating features of this methodology that made it a potential candidate for addressing various economic and environmental concerns were ambient reaction conditions, broad substrate scope, simple workup procedure, shorter reaction time and cost effectiveness.