2040-90-6

Basic information

• Product Name: 2-Chloro-6-fluorophenol
• Synonyms: 2-CHLORO-6-FLUOROPHENOL;Chlorofluorophenol3;2-Chloro-6-fluorophenol, 97+%;6-CHLORO-2-FLUORO PHENOL;2-Chloro-6-flurophenol;2-Chloro-6-fluorophe;2-Chloro-6-fluorophenol, 98%, 98%
• CAS NO: 2040-90-6
• Molecular Formula: C₆H₄ClFO
• Molecular Weight: 146.55
• EINECS: 433-890-8
• Product Categories: Fluorobenzene;Phenol&Thiophenol&Mercaptan;Organic Building Blocks;Oxygen Compounds;Phenols
• Mol File: 2040-90-6.mol
• Article Data: 8

Chemical Properties

• Melting Point: 62-65 °C(lit.)
• Boiling Point: 160.6 °C at 760 mmHg
• Flash Point: 50.9 °C
• Appearance: /
• Density: 1.408 g/cm³
• Vapor Pressure: 1.82mmHg at 25°C
• Refractive Index: 1.547
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: soluble in Methanol
• PKA: 7.23±0.10(Predicted)
• BRN: 1936441
• CAS DataBase Reference: 2-Chloro-6-fluorophenol(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-fluorophenol(2040-90-6)
• EPA Substance Registry System: 2-Chloro-6-fluorophenol(2040-90-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 1759
• WGK Germany: 3
• HazardClass: IRRITANT, IRRITANT-HARMFUL
• PackingGroup: II
• Hazardous Substances Data: 2040-90-6(Hazardous Substances Data)

Usage

Chemical Properties

Solid

InChI:InChI=1/C6H4ClFO/c7-4-2-1-3-5(8)6(4)9/h1-3,9H

Synthetic route

2-chloro-6-fluorophenyl isopropylcarbamate (899427-23-7) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; ethanol at 20℃; for 2h;	98%

(2-chloro-6-fluorophenyl)(isopropoxy)dimethylsilane (1228447-85-5) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With tetrabutyl ammonium fluoride; dihydrogen peroxide; potassium hydrogencarbonate In tetrahydrofuran; methanol; water at 20℃; for 16h; Inert atmosphere;	94%

2-fluorophenol (367-12-4) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With 1,3-dichloro-5,5-dimethylhydantoin; diisopropylamine hydrochloride In toluene at 0℃; for 4h; Darkness; regioselective reaction;	91%
With tetrachloromethane; chlorine
With chlorine In tetrachloromethane
Multi-step reaction with 5 steps 1.1: TMEDA / diethyl ether; pentane / 0.5 h / 20 °C 2.1: n-butyllithium; TMEDA / diethyl ether; pentane / 1 h / -78 °C 2.2: C2Cl6 / diethyl ether; pentane / 1 h / -78 °C 3.1: 0.210 g / aq. HCl / methanol / -78 - 20 °C 4.1: 98 percent / aq. NaOH / ethanol; tetrahydrofuran / 2 h / 20 °C View Scheme
With diisobutylamine; sulfuryl dichloride In toluene at 20℃;

2-(2-fluoro-6-chlorophenyl)oxypyridine → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Stage #1: 2-(2-fluoro-6-chlorophenyl)oxypyridine With methyl trifluoromethanesulfonate In toluene at 100℃; for 2h; Inert atmosphere; Stage #2: With sodium ethanolate for 1h; Reflux; Inert atmosphere;	78%

2-monochlorophenol (95-57-8) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With acetic acid; Selectfluor; eosin y In water at 20℃; for 6h; Irradiation; Green chemistry;	77%
Multi-step reaction with 3 steps 1.1: copper(l) iodide; 2-Picolinic acid; potassium phosphate / dimethyl sulfoxide / 24 h / 80 °C / Inert atmosphere 2.1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethyl acetate / 5 h / 80 °C 3.1: methyl trifluoromethanesulfonate / toluene / 2 h / 100 °C / Inert atmosphere 3.2: 1 h / Reflux; Inert atmosphere View Scheme

1-chloro-3-fluoro-2-methoxybenzene (53145-38-3) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With pyridine hydrochloride
With boron tribromide In dichloromethane at -78 - 20℃; for 16h;

2-fluorophenyl isopropylcarbamate (199585-08-5) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: TMEDA / diethyl ether; pentane / 0.5 h / 20 °C 2.1: n-butyllithium; TMEDA / diethyl ether; pentane / 1 h / -78 °C 2.2: C2Cl6 / diethyl ether; pentane / 1 h / -78 °C 3.1: 0.210 g / aq. HCl / methanol / -78 - 20 °C 4.1: 98 percent / aq. NaOH / ethanol; tetrahydrofuran / 2 h / 20 °C View Scheme

C13H20FNO2Si → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium; TMEDA / diethyl ether; pentane / 1 h / -78 °C 1.2: C2Cl6 / diethyl ether; pentane / 1 h / -78 °C 2.1: 0.210 g / aq. HCl / methanol / -78 - 20 °C 3.1: 98 percent / aq. NaOH / ethanol; tetrahydrofuran / 2 h / 20 °C View Scheme

C13H19ClFNO2Si → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.210 g / aq. HCl / methanol / -78 - 20 °C 2: 98 percent / aq. NaOH / ethanol; tetrahydrofuran / 2 h / 20 °C View Scheme

2,2,6-trichloro-6-fluoro-1,1-cyclohexane-diol (145706-45-2) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Å molecular sieve In pyridine

C12H19ClFNSi → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
With tetrabutyl ammonium fluoride; dihydrogen peroxide; potassium hydrogencarbonate In tetrahydrofuran; methanol; water at 20℃; for 16h; Inert atmosphere;	277 mg

2-(2-chlorophenoxy)pyridine (4783-70-4) → 2-chloro-6-fluorophenol (2040-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethyl acetate / 5 h / 80 °C 2.1: methyl trifluoromethanesulfonate / toluene / 2 h / 100 °C / Inert atmosphere 2.2: 1 h / Reflux; Inert atmosphere View Scheme

trifluoromethylsulfonic anhydride (358-23-6) + 2-chloro-6-fluorophenol (2040-90-6) → 2-chloro-6-fluorophenyl trifluoromethanesulfonate (1443684-70-5)

Conditions	Yield
With pyridine at 0 - 20℃;	100%
With pyridine In dichloromethane at 0 - 20℃; for 3h;
With pyridine In dichloromethane at 0℃; for 3h;	1.25 g
With pyridine In dichloromethane at 0℃; for 3h;

2-chloro-6-fluorophenol (2040-90-6) + 4-chlorobenzoyl chloride (586-75-4) → C13H7BrClFO2 (1443037-89-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	97%

2-chloro-6-fluorophenol (2040-90-6) + 4-methyl-benzoyl chloride (874-60-2) → 2-chloro-6-fluorophenyl 4-methylbenzoate (1443037-91-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	96%
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	96%
With triethylamine In dichloromethane at 0℃; for 5h;	96%
With sodium hydroxide at 0℃; for 3h;

2-chloro-6-fluorophenol (2040-90-6) + 4-chloro-benzoyl chloride (122-01-0) → 4-chloro-benzoic acid 2-chloro-6-fluoro-phenyl ester (1443037-88-4)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	95%
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	95%
With triethylamine In dichloromethane at 0℃; for 5h;	95%
With sodium hydroxide In water at 0 - 5℃;	85%
With sodium hydroxide at 0 - 5℃;	82%

2-chloro-6-fluorophenol (2040-90-6) + methyl iodide (74-88-4) → 1-chloro-3-fluoro-2-methoxybenzene (53145-38-3)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 3h;	94%

2-chloro-6-fluorophenol (2040-90-6) + 4-fluorobenzoyl chloride (403-43-0) → 2-chloro-6-fluorophenyl 4-fluorobenzoate (1443037-87-3)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	94%
With triethylamine In dichloromethane at 0℃; for 5h;	94%
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	92%
With sodium hydroxide at 0℃; for 3h;

2-chloro-6-fluorophenol (2040-90-6) + 4-iodobenzoic acid chloride (1711-02-0) → 2-chloro-6-fluorophenyl 4-iodobenzoate (1443037-90-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	93%
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	93%
With sodium hydroxide at 0℃; for 3h;

2-chloro-6-fluorophenol (2040-90-6) + benzyl bromide (100-39-0) → 2-chloro-6-fluorophenyl phenylmethyl ether (938180-34-8)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide for 12h;	92%
With potassium carbonate In acetone at 65℃; for 16h;

2-chloro-6-fluorophenol (2040-90-6) + tert-butyldimethylsilyl chloride (18162-48-6) → (2-chloro-6-fluorophenoxy)(tert-butyl)dimethylsilane (1434722-77-6)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 25℃;	90%

2-chloro-6-fluorophenol (2040-90-6) + (S)-2-(6-(hydroxymethyl)-4-((3-(trifluoromethyl)phenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)ethan-1-ol → (S)-2-(6-((2-chloro-6-fluorophenoxy)methyl)-4-((3-(trifluoromethyl)phenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)ethan-1-ol

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 20℃; for 1h;	89%
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 20℃; for 1h;	89%

2-chloro-6-fluorophenol (2040-90-6) → sodium 2-chloro-6-fluorophenolate

Conditions	Yield
With sodium hydroxide In methanol Inert atmosphere; Schlenk technique;	87%

3-bromo-2-chloropyridine (52200-48-3) + 2-chloro-6-fluorophenol (2040-90-6) → 3-bromo-2-(2-chloro-6-fluorophenoxy)pyridine (1167991-82-3)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 140℃;	80%
With caesium carbonate In dimethyl sulfoxide at 120℃;

2-iodo-propane (75-30-9) + 2-chloro-6-fluorophenol (2040-90-6) → 1-chloro-3-fluoro-2-isopropoxybenzene

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h;	78%

2-chloro-6-fluorophenol (2040-90-6) + N-(3-(bromomethyl)phenyl)-N-ethyl-3-(trifluoromethyl)benzenesulfonamide → N-(3-((2-chloro-6-fluorophenoxy)methyl)phenyl)-N-ethyl-3-(trifluoromethyl)benzenesulfonamide

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 4h;	74%

2-chloro-6-fluorophenol (2040-90-6) + (S)-(2-methyl-4-((3-(trifluoromethyl)phenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methanol → (S)-6-((2-chloro-6-fluorophenoxy)methyl)-2-methyl-4-((3-(trifluoromethyl)phenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 20℃; for 1h;	73%
With di-isopropyl azodicarboxylate; triphenylphosphine at 20℃; for 1h;	73%

Ethyl 2-butynoate (4341-76-8) + 2-chloro-6-fluorophenol (2040-90-6) → (E)-3-(2-chloro-6-fluoro-phenoxy)-but-2-enoic acid ethyl ester (1191997-67-7)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran Reflux;	71%

2-chloro-6-fluorophenol (2040-90-6) + (1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-indol-6-yl)methanol → 6-((2-chloro-6-fluorophenoxy)methyl)-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-indole

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 20℃; Mitsunobu Displacement;	69%

2-chloro-6-fluorophenol (2040-90-6) + 1-((3-(trifluoromethyl)phenyl)sulfonyl)indoline-6-carboxylic acid → 2-chloro-6-fluorophenyl 1-((3-(trifluoromethyl)phenyl)sulfonyl)indoline-6-carboxylate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 60℃;	67%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 60℃;	18 mg

2-chloro-6-fluorophenol (2040-90-6) + 2-bromoethanol (540-51-2) → 2-(2-chloro-6-fluorophenoxy)ethanol

Conditions	Yield
With sodium hydroxide at 90℃; for 16h;	64.5%

2-chloro-6-fluorophenol (2040-90-6) + ethyl iodide (75-03-6) → 1-chloro-2-ethoxy-3-fluorobenzene

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 16h;	63%

2-chloro-6-fluorophenol (2040-90-6) + N-ethyl-N-(3-(1-hydroxyethyl)phenyl)-3-(trifluoromethyl)benzenesulfonamide → N-(3-(1-(2-chloro-6-fluorophenoxy)ethyl)phenyl)-N-ethyl-3-(trifluoromethyl)benzenesulfonamide

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 2h;	62%

2-chloro-6-fluorophenol (2040-90-6) → C6H3ClFNO3

Conditions	Yield
With sulfuric acid; potassium nitrate at 0℃; for 0.25h;	61%

2-chloro-6-fluorophenol (2040-90-6) + (1-((3-(trifluoromethyl)phenyl)sulfonyl)indolin-6-yl)methanol → 6-((2-chloro-6-fluorophenoxy)methyl)-1-((3-(trifluoromethyl)phenyl)sulfonyl)indoline

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 20℃; Mitsunobu Displacement;	44%

2-chloro-6-fluorophenol (2040-90-6) + 2-(tert-butoxycarbonylamino)ethyl methanesulfonate (96628-67-0) → tert-butyl (2-(2-chloro-6-fluorophenoxy)ethyl)carbamate

Conditions	Yield
Stage #1: 2-chloro-6-fluorophenol With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: 2-(tert-butoxycarbonylamino)ethyl methanesulfonate In N,N-dimethyl-formamide at 100℃; for 16h;	42%

2-chloro-6-fluorophenol (2040-90-6) + (S)-isopropyl 2-(5-(2-bromoethoxy)-4'-(4,4-dimethylpiperidin-1-yl)-6'-methyl-[2,3'-bipyridin]-5'-yl)-2-(tert-butoxy)acetate → (S)-isopropyl 2-(tert-butoxy)-2-(5-(2-(2-chloro-6-fluorophenoxy)ethoxy)-4'-(4,4-dimethylpiperidin-1-yl)-6'-methyl-[2,3'-bipyridin]-5'-yl)acetate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;	41.5%

Upstream product

• 367-12-4 2-fluorophenol 
• 899427-23-7 2-chloro-6-fluorophenyl isopropylcarbamate 
• 4783-70-4 2-(2-chlorophenoxy)pyridine 
• 95-57-8 2-monochlorophenol 
• 1228447-85-5 (2-chloro-6-fluorophenyl)(isopropoxy)dimethylsilane 
• 145706-45-2 2,2,6-trichloro-6-fluoro-1,1-cyclohexane-diol 
• 199585-08-5 2-fluorophenyl isopropylcarbamate 
• 53145-38-3 1-chloro-3-fluoro-2-methoxybenzene 

Downstream Products

• 53145-35-0 α-bis-(2-Fluor-6-chlorphenoxy)essigsaeure 
• 938180-34-8 2-chloro-6-fluorophenyl phenylmethyl ether 
• 1268486-37-8 C₁₃H₇ClF₂O₂ 
• 1191997-67-7 (E)-3-(2-chloro-6-fluoro-phenoxy)-but-2-enoic acid ethyl ester 
• 1136961-91-5 1-chloro-2-(difluoromethoxy)-3-fluorobenzene 
• 1058702-84-3 C₁₆H₂₁ClFNO₃ 
• 1036713-47-9 2-chloro-6-fluoro-1,4-benzoquinone 
• 53145-38-3 1-chloro-3-fluoro-2-methoxybenzene 
• 28177-48-2 2,6-difluorophenol 
• 108-95-2 phenol 

Relevant articles and documents

Phenol compound ortho-position direct fluorination method

The invention relates to a phenol compound ortho-position direct fluorination method which comprises the following steps: reacting a phenol compound shown in a formula (1A) with a fluorination reagentin a solvent under the action of a photocatalyst and a light source at room temperature, and separating and purifying a reaction mixture after the reaction to obtain a fluorinated phenol compound shown in a formula (2A). The advantages are as follows: the method for directly fluorinating phenol by organic photocatalysis is simple in operation process; raw materials are commercialized and easy toobtain; the photocatalyst is low in price, easy to obtain and environmentally friendly; the reaction condition is mild; the site selectivity is high; the reaction is efficient; and a fluorinated phenol derivative can be prepared only through one step.

Synthesis of 2 - fluoro phenol compounds

The present invention provides a method for synthetizing a 2-fluoro phenol compound shown in a formula IV. The phenol compound shown in the formula I is prepared into a 2-pyridine oxygroup arene compound shown in a formula II through an Ullmann reaction, the 2-pyridine oxygroup arene compound shown in the formula II is mixed with a palladium catalyst, a fluorinating reagent, an additive and an organic solvent, the mixture is stirred under the temperature of 30-160 DEG C to perform a fluorination reaction to obtain an ortho-position fluoridated 2-pyridine oxygroup arene compound shown in a formula III, and the ortho-position fluoridated 2-pyridine oxygroup arene compound shown in the formula III is prepared into the 2-fluoro phenol compound shown in the formula IV through the action of alkali. The method provided by the present invention has the advantages of mild reaction conditions, simplicity in operations, good substrate adaptability, high fluorination selectivity and the like. The 2-fluoro phenol compound is shown in the figure below.

The trifluoromethoxy group as a fluorine twin in the Diels-Alder reactions of halogenated quinones

We describe here a study devoted to the comparison of the relative influence of chlorine, fluorine, and trifluoromethoxy substituents on the regiochemical outcome of the Diels-Alder reaction. For this purpose, we examined the behavior of mixed 'halogenated' quinones bearing these groups in their cycloadditions with simple dienes. Contrary to the expectation based on its known electronic properties, the trifluoromethoxy group behaves very much more like a fluorine than a chlorine atom in such reactions. On the basis on an endo transition state demonstrated here for these additions, we tentatively suggest that non-bonded interactions are the main factor controlling the regiochemistry.