2252-51-9

Basic information

• Product Name: 2-Chloro-4-fluorobenzoic acid
• Synonyms: 2-CHLORO-4-FLUOROBENZOIC ACID;TIMTEC-BB SBB003795;RARECHEM AL BO 0405;Benzoic acid, 2-chloro-4-fluoro-;1-chloro-2-fluorobezene;2-Chloro-4-Fluorobenzoic;2-Chloro-4-fluorobenzoic acid 99%;2-Chloro-4-fluorobenzoicacid99%
• CAS NO: 2252-51-9
• Molecular Formula: C₇H₄ClFO₂
• Molecular Weight: 174.56
• EINECS: 218-845-0
• Product Categories: FINE Chemical & INTERMEDIATES;blocks;Carboxes;FluoroCompounds;Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Benzoic acid;Fluorobenzene;Miscellaneous;Acids & Esters;Chlorine Compounds;Fluorine Compounds;C7;Carbonyl Compounds;Carboxylic Acids;Fluorine series
• Mol File: 2252-51-9.mol
• Article Data: 8

Chemical Properties

• Melting Point: 181-183 °C(lit.)
• Boiling Point: 271.9 °C at 760 mmHg
• Flash Point: 118.2 °C
• Appearance: White/Powder or Flakes
• Density: 1.4016 (estimate)
• Vapor Pressure: 0.00308mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: 95% ethanol: soluble50mg/mL, clear to very slightly hazy, colorl
• PKA: 2.90±0.25(Predicted)
• BRN: 1946215
• CAS DataBase Reference: 2-Chloro-4-fluorobenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-4-fluorobenzoic acid(2252-51-9)
• EPA Substance Registry System: 2-Chloro-4-fluorobenzoic acid(2252-51-9)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-37/38-41-36/37/38
• Safety Statements: 26-36/37/39-37/39-36
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 2252-51-9(Hazardous Substances Data)

Usage

Chemical Properties

white powder or flakes

Uses

2-Chloro-4-fluorobenzoic acid was used in the preparation of 2-(2-chloro-4-fluorophenyl)-benzothiazole.

InChI:InChI=1/C7H4ClFO2/c8-6-3-4(9)1-2-5(6)7(10)11/h1-3H,(H,10,11)/p-1

Synthetic route

4-amino-2-chlorobenzoic acid (2457-76-3) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
Stage #1: 4-amino-2-chlorobenzoic acid With dihydrogen peroxide In water at 40 - 50℃; for 3h; Ionic liquid; Stage #2: With potassium fluoride In water at 40 - 50℃; for 3h; Temperature;	97.5%

2-chloro-4-fluorotoluene (452-73-3) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
With di-tert-butyl peroxide; hydrogen bromide; oxygen; cobalt(II) acetate; manganese(II) acetate In acetic acid at 130 - 160℃; under 15514.4 Torr; for 3h;	92%
With potassium dichromate; sulfuric acid

2-chloro-4-fluorobenzaldehyde (84194-36-5) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
With hydrogenchloride; sodium chlorite In water; acetonitrile at 0 - 80℃; for 1h;	90.8%

carbon monoxide (201230-82-2) + 2-chloro-4-fluoro-1-iodobenzene (101335-11-9) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
With water; palladium diacetate; triethylamine; triphenylphosphine In 1,4-dioxane at 110℃; under 11251.1 Torr; for 2h; Flow reactor;	89%

2'-chloro-4'-fluoroacetophenone (700-35-6) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
With sodium hypobromide

3-chlorofluorobenzene (625-98-9) → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / CS2 / Heating 2: aq. sodium hypobromite View Scheme

disodium hydrogenphosphate + phenyl 2-chloro-4-fluorobenzoate (157165-30-5) + 2-chloro-4-fluoro-4'-methylbenzophenone → 2-choro-4-fluorobenzoic acid (2252-51-9)

Conditions	Yield
With sulfuric acid; acetic anhydride; urea In dichloromethane; water

2-choro-4-fluorobenzoic acid (2252-51-9) → 2-chloro-4-fluoro-5-nitrobenzoic acid (114776-15-7)

Conditions	Yield
With sulfuric acid; nitric acid at 0 - 10℃; for 2h;	99%
Stage #1: 2-choro-4-fluorobenzoic acid With zirconium chloride; sulfuric acid; cobalt(II) chloride In ethanol; water at 25℃; for 1h; Stage #2: With nitric acid In ethanol; water at -5 - 8℃; for 1h; Temperature;	97.1%
With sulfuric acid; nitric acid at 20℃; for 1h;	96%

methanol (67-56-1) + 2-choro-4-fluorobenzoic acid (2252-51-9) → methyl 2-chloro-4-fluorobenzoate (85953-29-3)

Conditions	Yield
With chloro-trimethyl-silane at 20℃; for 24h;	99%
With sulfuric acid at 60℃; for 17h;	96%
With thionyl chloride	95%
With sulfuric acid at 60℃; for 10h;	92%
With sulfuric acid

4-Fluorophenol (371-41-5) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 4-fluoro-2-(4-fluorophenoxy)benzoic acid

Conditions	Yield
With pyridine; copper(l) iodide; copper; potassium carbonate In water for 2h; Heating / reflux;	99%
With pyridine; copper(l) iodide; copper; potassium carbonate In water for 2h; Heating / reflux;	99%

2-choro-4-fluorobenzoic acid (2252-51-9) → 2-chloro-4-fluoro-5-iodobenzoic acid (264927-52-8)

Conditions	Yield
With sodium iodate; iodine In sulfuric acid at 20℃; for 8h;	99%

2-choro-4-fluorobenzoic acid (2252-51-9) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → 2-chloro-4-fluoro-N-methoxy-N-methylbenzamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 15℃; for 3h;	98.66%

2-amino-benzthiazole (136-95-8) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 3-fluoro-12H-[1,3]benzothiazolo-[2,3-b]quinazolin-12-one

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.416667h; sonication;	93%
With copper Ullmann condensation; Sonication;

2-choro-4-fluorobenzoic acid (2252-51-9) → N-t-Butyl-2-chloro-4-fluorobenzamide (223444-50-6)

Conditions	Yield
	93%

2-choro-4-fluorobenzoic acid (2252-51-9) + 2-(3-formyl-2-oxoquinolin-1(2H)-yl)acetohydrazide → 1-((5-(2-chloro-4-fluorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-1,2-dihydro-2-oxoquinoline-3-carbaldehyde

Conditions	Yield
With trichlorophosphate at 110 - 120℃; Reflux;	93%

2-choro-4-fluorobenzoic acid (2252-51-9) + benzylamine (100-46-9) → 4-fluoro-N-benzylanthranilic acid (1002965-92-5)

Conditions	Yield
With copper(I) oxide; copper; potassium carbonate In various solvent(s) at 130℃; for 24h;	92%

2-choro-4-fluorobenzoic acid (2252-51-9) → (2-chloro-4-fluorophenyl)methanol (208186-84-9)

Conditions	Yield
With borane-THF In tetrahydrofuran at 0 - 20℃; for 2h;	91.3%

pyrrolidine (123-75-1) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 4-fluoro-2-(1-pyrrolidinyl)benzoic acid

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.25h; Ullmann condensation; ultrasonic irradiation;	89%

2-choro-4-fluorobenzoic acid (2252-51-9) + malonic acid dimethyl ester (108-59-8) → (2-Carboxy-6-fluorophenyl)propanedioic acid dimethyl ester

Conditions	Yield
With NaH; copper(I) bromide In water; mineral oil	89%

2-choro-4-fluorobenzoic acid (2252-51-9) + benzylamine (100-46-9) → 2-chloro-N-benzyl-4-fluorobenzamide (886624-05-1)

Conditions	Yield
Stage #1: 2-choro-4-fluorobenzoic acid With triethylamine; isobutyl chloroformate In dichloromethane for 0.25h; Inert atmosphere; Schlenk technique; Stage #2: benzylamine In dichloromethane at 0℃;	89%

2-choro-4-fluorobenzoic acid (2252-51-9) + (E)-2-(tert-butyldiphenylsilyloxymethyl)-4-hydroxy-2-butenenitrile (639008-45-0) → 2-chloro-4-fluoro-benzoic acid 4-(tert-butyl-diphenyl-silanyloxy)-3-cyano-but-2-enyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In toluene	88%

propylamine (107-10-8) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 4-fluoro-2-(propylamino)benzoic acid

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.416667h; Ullmann condensation; ultrasonic irradiation;	87%

2-choro-4-fluorobenzoic acid (2252-51-9) + 4-chloro-3-[5-(trifluoromethyl)pyridin-2-yl]aniline → 2-chloro-N-{4-chloro-3-[5-(trifluoromethyl)pyridin-2-yl]phenyl}-4-fluorobenzamide

Conditions	Yield
With 2-(7-azobenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	86.4%

piperidine (110-89-4) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 4-fluoro-2-(1-piperidinyl)benzoic acid (865471-09-6)

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.25h; Ullmann condensation; ultrasonic irradiation;	86%

1-(tert-butyl)-2-iodobenzene (62171-59-9) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 3-fluoro-9,9-dimethyl-9,10-dihydrophenanthrene

Conditions	Yield
With tetrabutyl-ammonium chloride; palladium diacetate; potassium carbonate; Tri(p-tolyl)phosphine In N,N-dimethyl-formamide at 140℃; for 12h; Schlenk technique; Inert atmosphere;	86%

2-choro-4-fluorobenzoic acid (2252-51-9) → C7H4ClFO5S (714968-44-2)

Conditions	Yield
With chlorosulfonic acid at 150℃; for 6h;	85%

2-choro-4-fluorobenzoic acid (2252-51-9) + 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (572-09-8) → 1-O-(2-chloro-4-fluorobenzoyl)-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose

Conditions	Yield
With tetraethylammonium bromide; potassium carbonate In dichloromethane at 20℃; Molecular sieve;	85%

2-choro-4-fluorobenzoic acid (2252-51-9) + m-Anisidine (536-90-3) → C14H12FNO3

Conditions	Yield
With copper; potassium carbonate In pentan-1-ol at 20℃; for 5h; Reflux;	85%

(S)-Leu-OMe (2666-93-5) + 2-choro-4-fluorobenzoic acid (2252-51-9) → methyl (2-chloro-4-fluorobenzoyl)-L-leucinate

Conditions	Yield
Stage #1: 2-choro-4-fluorobenzoic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0℃; Stage #2: (S)-Leu-OMe In N,N-dimethyl-formamide at 0 - 20℃;	84%

2-choro-4-fluorobenzoic acid (2252-51-9) + 3,5-dimethylphenyl iodide (22445-41-6) → 3-chloro-5-fluoro-3',5'-dimethyl-1,1'-biphenyl (1344681-42-0)

Conditions	Yield
With palladium diacetate; acetic acid; silver carbonate at 130℃; for 16h; regioselective reaction;	83%

2-choro-4-fluorobenzoic acid (2252-51-9) + acrylic acid methyl ester (292638-85-8) → methyl 2-(4-chloro-6-fluoro-3-oxo-1,3-dihydroisobenzofuran-1-yl)acetate

Conditions	Yield
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; oxygen; potassium hydrogencarbonate; acetic acid In 1,2-dichloro-ethane at 60℃; for 24h; Schlenk technique; Inert atmosphere;	83%

morpholine (110-91-8) + 2-choro-4-fluorobenzoic acid (2252-51-9) → 4-fluoro-2-(4-morpholinyl)benzoic acid

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.25h; Ullmann condensation; ultrasonic irradiation;	82%
With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 90℃; for 2h;	13%
With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 90℃; for 2h;

2-choro-4-fluorobenzoic acid (2252-51-9) + [1,1'-biphenyl]-2,2'-iodonium trifluoromethanesulfonate (189999-35-7) → 2-fluorotriphenylene (439-23-6)

Conditions	Yield
With palladium diacetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 110℃; for 12h;	81%
With palladium diacetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 110℃; for 17h;	81%

Upstream product

• 84194-36-5 2-chloro-4-fluorobenzaldehyde 
• 2457-76-3 4-amino-2-chlorobenzoic acid 
• 201230-82-2 carbon monoxide 
• 101335-11-9 2-chloro-4-fluoro-1-iodobenzene 
• 157165-30-5 phenyl 2-chloro-4-fluorobenzoate 
• 625-98-9 3-chlorofluorobenzene 
• 700-35-6 2'-chloro-4'-fluoroacetophenone 
• 452-73-3 2-chloro-4-fluorotoluene 

Downstream Products

• 365-54-8 4-fluoro-2-phenylamino-benzoic acid 
• 69943-47-1 (2-chloro-4-fluorophenyl)(phenyl)methanone 
• 875479-20-2 2-chloro-4-pyrrolidinobenzophenone 
• 875479-24-6 1-(2-chloro-4-pyrrolidinophenyl)-1-phenylprop-2-yn-1-ol 
• 346608-00-2 2-chloro-4-fluorobenzoic acid 2-pyridinylmethyl ester 
• 625-98-9 3-chlorofluorobenzene 
• 208186-84-9 (2-chloro-4-fluorophenyl)methanol 
• 223444-50-6 N-t-Butyl-2-chloro-4-fluorobenzamide 
• 220603-17-8 (2-Chloro-4-fluoro-phenyl)-(11H-5-oxa-4,10-diaza-dibenzo[a,d]cyclohepten-10-yl)-methanone 
• 1002965-92-5 4-fluoro-N-benzylanthranilic acid 
• 3793-78-0 4-fluoro-2-phenoxy-benzoic acid 
• 456-22-4 4-Fluorobenzoic acid 
• 65-85-0 benzoic acid 
• 714968-44-2 C₇H₄ClFO₅S 

Relevant articles and documents

Stepwise benzylic oxygenation via uranyl-photocatalysis

Stepwise oxygenation at the benzylic position (1°, 2°, 3°) of aromatic molecules was comprehensively established under ambient conditions via uranyl photocatalysis to produce carboxylic acids, ketones, and alcohols, respectively. The accuracy of the stepwise oxygenation was ensured by the tunability of catalytic activity in uranyl photocatalysis, which was adjusted by solvents and additives demonstrated through Stern–Volmer analysis. Hydrogen atom transfer between the benzylic position and the uranyl catalyst facilitated oxygenation, further confirmed by kinetic studies. Considerably improved efficiency of flow operation demonstrated the potential for industrial synthetic application.

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