76903-88-3

Basic information

• Product Name: 3,4-Difluorobenzoyl chloride
• Synonyms: 3,4-DIFLUOROBENZOYL CHLORIDE;TIMTEC-BB SBB006722;Benzoyl chloride, 3,4-difluoro- (9CI);3,4-Difluorobenzoyl chloride 98%;3,4-Difluorobenzoylchloride98%;3,4-Difluorobenzoyl;3,4-Difluorobenzoyl chloride, 98% 5ML
• CAS NO: 76903-88-3
• Molecular Formula: C₇H₃ClF₂O
• Molecular Weight: 176.55
• EINECS: 278-570-7
• Product Categories: ACIDHALIDE;Miscellaneous;Acid Halides;Carbonyl Compounds;Organic Building Blocks;Acid Halides;Aryl Fluorinated Building Blocks;Building Blocks;C7;Carbonyl Compounds;Chemical Synthesis;Fluorinated Building Blocks;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;Fluorine series
• Mol File: 76903-88-3.mol
• Article Data: 26

Chemical Properties

• Melting Point: 53-54 °C
• Boiling Point: 61-63 °C (15 mmHg)
• Flash Point: 173 °F
• Appearance: clear yellow liquid
• Density: 1.403 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.39mmHg at 25°C
• Refractive Index: n20/D 1.5114(lit.)
• Sensitive: Moisture Sensitive
• BRN: 4177619
• CAS DataBase Reference: 3,4-Difluorobenzoyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Difluorobenzoyl chloride(76903-88-3)
• EPA Substance Registry System: 3,4-Difluorobenzoyl chloride(76903-88-3)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 76903-88-3(Hazardous Substances Data)

Usage

Chemical Properties

Clear yellow liquid

Uses

3,4-Difluorobenzoyl chloride may be used in chemical synthesis studies.

InChI:InChI:1S/C7H3ClF2O/c8-7(11)4-1-2-5(9)6(10)3-4/h1-3H

Synthetic route

3,4-Difluorobenzoic acid (455-86-7) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide at 70 - 80℃; Substitution;	96.3%
With thionyl chloride Heating;	88%
With thionyl chloride In benzene Heating;	81%

1,2-difluoro-4-(trifluoromethyl)benzene (32137-19-2) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / conc. sulfuric acid / 2 h / 80 °C 2: thionyl chloride / benzene / 2 h / Heating View Scheme

1,2-dichloro-4-(trifluoromethyl)benzene (328-84-7) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: KF / various solvent(s) / 24 h / 265 °C / other temperatures, other solvents 2: 86 percent / conc. sulfuric acid / 2 h / 80 °C 3: thionyl chloride / benzene / 2 h / Heating View Scheme

4-chlorotrichloromethylbenzene (5216-25-1) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: chlorosulfuric acid / 1) 120 deg C, 1 h 2) 150 deg C, 2 h 2: 94 percent / SOCl2 / benzene / 8 h / Heating 3: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 4: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 5: 93 percent / 10percent NaOH / 1 h 6: 81 percent / SOCl2 / benzene / Heating View Scheme

4-chloro-3-(chlorosulfonyl)benzoic acid (2494-79-3) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 94 percent / SOCl2 / benzene / 8 h / Heating 2: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 3: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 4: 93 percent / 10percent NaOH / 1 h 5: 81 percent / SOCl2 / benzene / Heating View Scheme

3-chlorosulfonyl-4-chlorobenzoyl chloride (62574-66-7) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 2: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 3: 93 percent / 10percent NaOH / 1 h 4: 81 percent / SOCl2 / benzene / Heating View Scheme

3,4-difluorobenzoyl fluoride (127269-25-4) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / 10percent NaOH / 1 h 2: 81 percent / SOCl2 / benzene / Heating View Scheme

4-fluoro-3-(fluorosulfonyl)benzoyl fluoride (127986-80-5) → 3,4-difluorobenzoyl chloride (76903-88-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 2: 93 percent / 10percent NaOH / 1 h 3: 81 percent / SOCl2 / benzene / Heating View Scheme

1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]-piperidin-4-amine (1408075-34-2) + 3,4-difluorobenzoyl chloride (76903-88-3) → N-{1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}-3,4-difluorobenzamide

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 3h;	100%

1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid ; hydrochloride (41994-51-8) + 3,4-difluorobenzoyl chloride (76903-88-3) → 2-(3,4-difluorobenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1147550-70-6)

Conditions	Yield
Stage #1: 1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid ; hydrochloride; 3,4-difluorobenzoyl chloride With sodium hydroxide In water; acetone for 1h; pH=> 10; Stage #2: Stage #3: With hydrogenchloride In water	98.8%
Stage #1: 1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid ; hydrochloride With sodium hydroxide In acetone at 20℃; Stage #2: 3,4-difluorobenzoyl chloride With sodium hydroxide In acetone at 20℃; pH=> 10; Stage #3: With hydrogenchloride In water pH=5 - 6;	95%

3,4-difluorobenzoyl chloride (76903-88-3) + acetonitrile (75-05-8) → 3-(3,4-difluorophenyl)-3-oxopropanenitrile (71682-97-8)

Conditions	Yield
Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 3,4-difluorobenzoyl chloride In tetrahydrofuran at 20℃; for 4h;	97%

3,4-difluorobenzoyl chloride (76903-88-3) + N-butylamine (109-73-9) → 2-(3',4'-difluorophenyl)pyridine (387831-85-8)

Conditions	Yield
With dmap; copper(II) ethylacetoacetate; C26H36NP; silver(I) acetate In propan-1-ol at 60℃; for 12h; Reagent/catalyst;	96.2%

3,4-difluorobenzoyl chloride (76903-88-3) + glycine (56-40-6) → 2-(3,4-difluorobenzamido)acetic acid (315707-69-8)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran at 0 - 20℃;	96%
With hydrogenchloride; sodium hydroxide In water

trans-4-(4-quinolyloxy)cyclohexylamine + 3,4-difluorobenzoyl chloride (76903-88-3) → N-[trans-4-(4-quinolyloxy)cyclohexyl]-3,4-difluorobenzamide

Conditions	Yield
With pyridine; triethylamine at 0 - 20℃;	96%

berberrubine chloride (15401-69-1) + 3,4-difluorobenzoyl chloride (76903-88-3) → 9-O-(3,4-diflourobenzoyl)berberrubine chloride (1297302-82-9)

Conditions	Yield
In acetonitrile at 20℃; for 0.5h;	94%

glycine ethyl ester hydrochloride (5680-79-5) + 3,4-difluorobenzoyl chloride (76903-88-3) → methyl N-(3,4-difluorobenzoyl)glycinate

Conditions	Yield
With triethylamine In dichloromethane at 18 - 25℃; for 2h; Cooling with ice;	94%

2-chloroethanamine hydrochloride (870-24-6) + 3,4-difluorobenzoyl chloride (76903-88-3) → N-(2-chloroethyl)-2-(3,4-difluorophenyl)acid amide (1082817-08-0)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere;	93%

3,4-difluorobenzoyl chloride (76903-88-3) + dimedone (126-81-8) → 5,5-dimethyl-3-oxocyclohex-1-en-1-yl 3,4-difluorobenzoate

Conditions	Yield
With pyridine In 1,2-dichloro-ethane at 20℃; for 12h; Inert atmosphere;	93%

3,4-difluorobenzoyl chloride (76903-88-3) + Propargylamine (2450-71-7) → 3,4-difluoro-N-(prop-2-ynyl)benzamide (1250231-35-6)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;	92%
With dmap; triethylamine In dichloromethane at 0 - 20℃;

7-hydroxy-4,6-dimethylcoumarin (1484-98-6) + 3,4-difluorobenzoyl chloride (76903-88-3) → 4,6-dimethyl-2-oxo-2H-chromen-7-yl-3,4-difluorobenzoate

Conditions	Yield
With potassium carbonate for 0.25h;	92%

piperidine-2,6-dione (1121-89-7) + 3,4-difluorobenzoyl chloride (76903-88-3) → 1-(3,4-difluorobenzoyl)piperidine-2,6-dione

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	91.2%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;	91%
With dmap; triethylamine In dichloromethane at 0 - 23℃; Inert atmosphere;
With dmap; triethylamine In dichloromethane at 0 - 23℃; Inert atmosphere; Schlenk technique;

3,4-difluorobenzoyl chloride (76903-88-3) + 3-chloro-6-hydroxy-4,7-dimethyl-2H-chromen-2-one → 3-chloro-4,7-dimethyl-2-oxo-2H-chromen-6-yl 3,4-difluorobenzoate

Conditions	Yield
With potassium carbonate In neat (no solvent) at 20℃; for 0.25h; Milling;	91%

3,4-difluorobenzoyl chloride (76903-88-3) → N-(tert-butyl)-3,4-difluorobenzamide (223444-29-9)

Conditions	Yield
	90%

2-methoxy-ethanol (109-86-4) + potassium thioacyanate (333-20-0) + 3,4-difluorobenzoyl chloride (76903-88-3) → O-(2-methoxyethyl)(3,4-difluorobenzoyl)carbamothioate

Conditions	Yield
Stage #1: potassium thioacyanate; 3,4-difluorobenzoyl chloride In acetone at 55℃; for 1h; Inert atmosphere; Stage #2: 2-methoxy-ethanol In acetone at 55℃; for 12h;	90%

tert-butyl N-[(1s,4s)-4-aminocyclohexyl]carbamate (247570-24-7) + 3,4-difluorobenzoyl chloride (76903-88-3) → (cis-4-{[1-(3,4-difluoro-phenyl)-methanoyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester (771553-05-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 1h;	89%

4-[2-(2-Methyl-piperidin-1-yl)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (887938-43-4) + 3,4-difluorobenzoyl chloride (76903-88-3) → 3,4-difluoro-N-[4-[2-(2-methyl-piperidin-1-yl)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	88.2%

3,4-difluorobenzoyl chloride (76903-88-3) + cis-<2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl>methanol (145782-15-6, 145782-16-7) → 3,4-Difluoro-benzoic acid (2R,4R)-2-biphenyl-4-yl-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethyl ester

Conditions	Yield
With pyridine at 0℃; for 2.5h;	88%

3-aminobenzenemethanol (1877-77-6) + 3,4-difluorobenzoyl chloride (76903-88-3) → 3,4-difluoro-N-(3-hydroxymethyl-phenyl)-benzamide (879871-58-6)

Conditions	Yield
With triethylamine In 1,4-dioxane	88%

methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester (548769-49-9) + 3,4-difluorobenzoyl chloride (76903-88-3) → methyl-phenyl-carbamic acid 5-(3,4-difluoro-benzoylamino)-pyridin-2-yl ester (812639-58-0)

Conditions	Yield
With triethylamine In acetonitrile at 20℃; for 1h;	88%

3,4-difluorobenzoyl chloride (76903-88-3) + methyl {(2R)-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetate (565460-55-1) → methyl [(2R)-1-(3,4-difluorobenzoyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl]-acetate

Conditions	Yield
With 4-pyrrolidin-1-ylpyridine In tetrahydrofuran	88%
With 4-pyrrolidin-1-ylpyridine In tetrahydrofuran	88%

C19H23N5O3 + 3,4-difluorobenzoyl chloride (76903-88-3) → C26H25F2N5O4

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 3h;	88%

4-aminopyridine (504-24-5) + 3,4-difluorobenzoyl chloride (76903-88-3) → 3,4-difluoro-N-(pyridin-4-yl)benzamide

Conditions	Yield
In tetrahydrofuran at 0℃; Inert atmosphere;	88%

3,4-difluorobenzoyl chloride (76903-88-3) + 2-amino-5-chloro-6-fluro[2,1-b][1,3]benzothiazole (101337-92-2) → N-(5-chloro-6-fluoro-benzothiazol-2-yl)-3,4-difluoro-benzamide

Conditions	Yield
With triethylamine In 1,4-dioxane at 50 - 60℃; for 2h;	87.2%

4-oxazol-2-yl-benzoic acid ethyl ester (1139705-32-0) + 3,4-difluorobenzoyl chloride (76903-88-3) → ethyl 4-(5-(3,4-difluorobenzoyl)oxazol-2-yl)benzoate (1492786-00-1)

Conditions

Yield

Stage #1: 4-oxazol-2-yl-benzoic acid ethyl ester With zinc chloride-2,2,6,6-tetramethylpiperidin-1-ide lithium chloride complex In tetrahydrofuran at 50℃; for 2h; Inert atmosphere; Schlenk technique; Stage #2: 3,4-difluorobenzoyl chloride With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 25℃; for 1h; Negishi Coupling; Inert atmosphere; Schlenk technique; regioselective reaction;

87%

3,4-difluorobenzoyl chloride (76903-88-3) + 3,4-difluoro-benzaldehyde oxime (238743-29-8) → (E)-3,4-di-fluorobenzaldehyde O-3,4-difluorobenzoyloxime

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	85%
Stage #1: 3,4-difluorobenzoyl chloride; 3,4-difluoro-benzaldehyde oxime Stage #2: With triethylamine hydrochloride	85%

1,3-diphenyl-1H-pyrazol-5-amine (5356-71-8) + 3,4-difluorobenzoyl chloride (76903-88-3) → N-(1,3-diphenyl-1H-pyrazol-5-yl)-3,4-difluorobenzamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	84%
Stage #1: 1,3-diphenyl-1H-pyrazol-5-amine With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.25h; Stage #2: 3,4-difluorobenzoyl chloride In dichloromethane at 20℃;

3,4-difluorobenzoyl chloride (76903-88-3) → 2,3-difluoro-N-[4-(2-trifluoromethyl-imidazo[1,2-a]pyrid-3-yl)-phenyl]-benzamide

Conditions	Yield
Stage #1: 3-(4-nitrophenyl)-2-(trifluoromethyl)imidazo[1,2-a]pyridine With water; tin(ll) chloride In ethanol; dichloromethane Heating / reflux; Stage #2: 3,4-difluorobenzoyl chloride With N-ethyl-N,N-diisopropylamine In dichloromethane for 4h;	84%

Upstream product

• 871656-84-7 3,4-difluoro-N,N-dimethylbenzamide 
• 127986-80-5 4-fluoro-3-(fluorosulfonyl)benzoyl fluoride 
• 127269-25-4 3,4-difluorobenzoyl fluoride 
• 62574-66-7 3-chlorosulfonyl-4-chlorobenzoyl chloride 
• 2494-79-3 4-chloro-3-(chlorosulfonyl)benzoic acid 
• 5216-25-1 4-chlorotrichloromethylbenzene 
• 328-84-7 1,2-dichloro-4-(trifluoromethyl)benzene 
• 32137-19-2 1,2-difluoro-4-(trifluoromethyl)benzene 
• 455-86-7 3,4-Difluorobenzoic acid 

Downstream Products

• 280779-86-4 Dimethyl 1-(3,4-difluorobenzoyl)-2,2-dioxo-5-methyl-1H,3H-pyrrolo[1,2-c][1,3]thiazole-6,7-dicarboxylate 
• 1026360-58-6 N-(3,5-dimethoxy-2-methoxyacetyl-phenyl)-3,4-difluoro-benzamide 
• 902524-12-3 3-(3',4'-difluorophenyl)isocoumarin 
• 863505-11-7 azetidin-1-yl-(3,4-difluoro-phenyl)-methanone 
• 771553-05-0 (cis-4-{[1-(3,4-difluoro-phenyl)-methanoyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester 
• 866648-45-5 [cis-4-(3,4-difluoro-benzoylamino)-cyclohexylmethyl]-carbamic acid benzyl ester 
• 866648-47-7 {cis-4-[(3,4-difluoro-benzoylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester 

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