168267-41-2

Basic information

• Product Name: 3,4-Difluorophenylboronic acid
• Synonyms: 3,4-Difluorophenylboronic acid ,98%;3,4-Difluorophenylboronic acid,97%;3,4-Difluorophenylbo;3,4-Difluorophenylboronic acid, May contain varying amounts of anhydride, 97%;dihydroxy(3,4-difluorophenyl)borane;3,4-DIFLUOROPHENYLBORONIC ACID FOR SYNTH;Boronic acid, B-(3,4-difluorophenyl)-;AKOS BRN-0090
• CAS NO: 168267-41-2
• Molecular Formula: C₆H₅BF₂O₂
• Molecular Weight: 157.91
• Product Categories: Boronic Acids;Boronic Acids and Derivatives;Boronic Acids;Liquid crystal intermediates;Fluorin-contained phenyl boronic acid series;HALIDE;blocks;BoronicAcids;FluoroCompounds;Substituted Boronic Acids;Boronic Acid;Aryl;Halogenated;Organoborons
• Mol File: 168267-41-2.mol

Chemical Properties

• Melting Point: 289-290 °C
• Boiling Point: 265.4 °C at 760 mmHg
• Flash Point: 114.3 °C
• Appearance: White/Powder
• Density: 1.35 g/cm³
• Vapor Pressure: 0.136mmHg at 25°C
• Refractive Index: 1.493
• Storage Temp.: Refrigerator (+4°C)
• Solubility: soluble in Methanol
• PKA: 7.59±0.10(Predicted)
• BRN: 7369788
• CAS DataBase Reference: 3,4-Difluorophenylboronic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Difluorophenylboronic acid(168267-41-2)
• EPA Substance Registry System: 3,4-Difluorophenylboronic acid(168267-41-2)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 36/37/38-22
• Safety Statements: 37/39-26-36
• WGK Germany: 3
• Hazardous Substances Data: 168267-41-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3,4-Difluorophenylboronic acid is used as a building block for the synthesis of substituted 6-phenylpurine bases and nucleosides. These compounds exhibit significant cytostatic activity in various cell lines, such as CCRF-CEM, HeLa, and L1210, making them promising candidates for the development of new drugs to combat various diseases.
3,4-Difluorophenylboronic acid is also used in the preparation of a potent cell penetrant Legumain inhibitor, 10t. Legumain is a lysosomal cysteine protease that has been implicated in various diseases, including cancer and neurodegenerative disorders. Inhibitors of Legumain, such as 10t, can potentially be used as therapeutic agents to target these diseases.
Used in Chemical Industry:
3,4-Difluorophenylboronic acid serves as an intermediate in the synthesis of liquid crystals. Liquid crystals are materials that exhibit properties between those of conventional liquids and solid crystals. They have a wide range of applications, including display technologies, sensors, and optical devices. The use of 3,4-difluorophenylboronic acid in the synthesis of liquid crystal intermediates contributes to the development of advanced materials with improved performance and functionality.
Used in Suzuki Reaction:
3,4-Difluorophenylboronic acid is a key component in the Suzuki reaction, a widely used method for the formation of carbon-carbon bonds in organic synthesis. The Suzuki-Miyaura cross-coupling reaction involves the reaction of an organoboron compound, such as 3,4-difluorophenylboronic acid, with an organohalide or other electrophilic carbon species in the presence of a palladium catalyst. This reaction is highly versatile and allows for the formation of a variety of complex molecular structures, making it an invaluable tool in the synthesis of pharmaceuticals, agrochemicals, and advanced materials.

InChI:InChI=1/C6H2F4O2/c7-1-2(8)5(11)4(10)6(12)3(1)9/h11-12H

Synthetic route

3,4-difluorophenylmagnesium bromide (90897-92-0) → (3,4-difluorophenyl)boronic acid (168267-41-2)

Conditions	Yield
With Triisopropyl borate In tetrahydrofuran at -40 - 0℃;	41%

C6H3BF5(1-) (1033691-65-4) → (3,4-difluorophenyl)boronic acid (168267-41-2)

Conditions	Yield
In phosphate buffer pH=6.9 - 7.0; Kinetics;

C14H21BF2O2 → (3,4-difluorophenyl)boronic acid (168267-41-2)

Conditions	Yield
With hydrogenchloride; water In tetrahydrofuran pH=5;

3-bromo-5-methylpyridin-2-amine (17282-00-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3-(3,4-difluorophenyl)-5-methylpyridin-2-amine (1340487-51-5)

Conditions	Yield
With sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere;	100%
With sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 100℃; for 1h; Suzuki Coupling; Inert atmosphere;	100%

methyl 2-(4-bromophenyl)-2-pivalamidoacetate + (3,4-difluorophenyl)boronic acid (168267-41-2) → methyl 2-(3',4'-difluoro-[1,1'-biphenyl]-4-yl)-2-pivalamidoacetate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 100℃; for 2h; Suzuki Coupling; Microwave irradiation; Inert atmosphere; Sealed tube;	100%

2,2-Dimethyl-1,3-propanediol (126-30-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → C11H13BF2O2

Conditions	Yield
Stage #1: 2,2-Dimethyl-1,3-propanediol; (3,4-difluorophenyl)boronic acid In diethyl ether at 20℃; for 1h; Stage #2: With calcium chloride at 20℃; for 1h;	100%

4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (107346-32-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 4-amino-8-(3,4-difluorophenyl)-N-propyl-cinnoline-3-carboxamide

Conditions	Yield
	98.7%

para-nitrophenyl bromide (586-78-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3,4-difluoro-4'-nitro-1,1'-biphenyl (954369-63-2)

Conditions	Yield
With sodium carbonate In water at 25℃; for 6.5h; Suzuki Coupling;	98%
With sodium carbonate at 80℃; for 1.16667h; Catalytic behavior; Suzuki Coupling;	97%
With sodium carbonate at 100℃; for 0.75h; Suzuki-Miyaura Coupling;	95%

1-bromo-4-methoxy-benzene (104-92-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3',4'-difluoro-4-methoxy-1,1'-biphenyl

Conditions	Yield
With Ph2P(CH2CH2O)22CH3; triethylamine; palladium dichloride In water at 80℃; for 2h; Suzuki coupling; Inert atmosphere;	98%
With sodium carbonate at 100℃; for 2.5h; Suzuki-Miyaura Coupling;	91%

4-bromobenzenecarbonitrile (623-00-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3',4'-difluoro-(1,1'-biphenyl)-4-carbonitrile (151559-21-6)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane Suzuki Coupling; Reflux; Inert atmosphere;	98%
With sodium carbonate at 80℃; for 1.5h; Catalytic behavior; Suzuki Coupling;	97%
With Ph2P(CH2CH2O)22CH3; triethylamine; palladium dichloride In water at 80℃; for 1h; Suzuki coupling; Inert atmosphere;	96%

(3,4-difluorophenyl)boronic acid (168267-41-2) → 3,3’,4,4’-tetrafluorobiphenyl (136755-64-1)

Conditions	Yield
With air In N,N-dimethyl-formamide at 20℃; for 16h; Green chemistry;	98%
With copper fluorapatite In methanol at 20℃; for 2h; Green chemistry;	93%
With oxygen; potassium carbonate In water at 25℃; for 2h; Green chemistry;	93%

4-bromo-6-fluorobenzonitrile (105942-08-3) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3,3',4'-trifluoro-[1,1'-biphenyl]-4-carbonitrile

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane Suzuki Coupling; Reflux; Inert atmosphere;	98%

4-{3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (1162261-01-9) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 4-{3-[6-(5-dimethylcarbamoyl-3',4'-difluoro-biphenyl-3-yloxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (1162261-04-2)

Conditions	Yield
With caesium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In 1,2-dimethoxyethane at 97℃; for 15h; Suzuki Coupling;	97%

(3,4-difluorophenyl)boronic acid (168267-41-2) + 2-(carboxymethyl)-5-iodobenzoic acid → 4-(carboxymethyl)-3',4'-difluorobiphenyl-3-carboxylic acid (1354742-83-8)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water at 150℃; for 0.5h; Suzuki coupling; Inert atmosphere; Microwave irradiation;	97%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water at 150℃; for 0.5h; Suzuki Coupling; Microwave irradiation;

8-bromo-[1,2,4]triazolo[1,5-a]pyridine-2-ylamine (1124382-72-4) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 8-(3,4-difluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (1329672-80-1)

Conditions	Yield
With sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 20 - 110℃; for 18h;	97%
With sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 110℃; for 18h; Suzuki Coupling;	97%

2,6-dibromo-4-nitroaniline (827-94-1) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 2,6-bis(3,4-difluorophenyl)-4-nitroaniline (1426332-53-7)

Conditions	Yield
With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 0.416667h; Suzuki Coupling;	97%

1-bromo-4-(trans-4-pentylcyclohexyl)benzene (79832-89-6) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3,4-difluoro-4'-(4-pentylcyclohexyl)-1,1'-biphenyl (134412-17-2)

Conditions	Yield
With 5%-palladium/activated carbon; potassium carbonate In ethanol; water at 80℃; for 0.5h; Suzuki Coupling;	97%

8-bromo-N-(2-(methylsulfonyl)ethyl)-1,6-naphthyridine-2-carboxamide (1611473-65-4) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 8-(3,4-difluorophenyl)-N-(2-(methylsulfonyl)ethyl)-1,6-naphthyridine-2-carboxamide (1611473-16-5)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 80℃; for 1h;	97%

iodobenzene (591-50-4) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3,4‐difluoro‐1,1′‐biphenyl (67277-33-2)

Conditions	Yield
With sodium carbonate at 100℃; for 0.666667h; Suzuki-Miyaura Coupling;	97%
With sodium carbonate at 80℃; for 0.833333h; Catalytic behavior; Suzuki Coupling;	97%
With sodium carbonate at 80℃; for 1.41667h; Kinetics; Suzuki Coupling; Green chemistry;	96%

7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide + (3,4-difluorophenyl)boronic acid (168267-41-2) → 7-(3,4-difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 100℃; for 1h; Inert atmosphere;	97%

4-(4-propylcyclohexyl)-1-bromobenzene (86579-53-5) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3',4'-difluoro-4-(4-propylcyclohexyl)-1,1'-biphenyl

Conditions	Yield
With potassium phosphate; [Pd(Ph2PCH2CH(CH3)O)2] In tetrahydrofuran; water at 20℃; for 5h; Suzuki cross-coupling reaction;	96%
With potassium fluoride; [Ph2P(CH2)2NH2]2PdCl2 In tetrahydrofuran; water at 25 - 27℃; for 5h; Suzuki cross-coupling reaction;	96%
With potassium phosphate; cis-bis((diphenylphosphino)acetate-κ2P,O)palladium(II) In tetrahydrofuran at 25 - 27℃; for 5h; Suzuki coupling;	91%

4-chloro-8-(2,6-difluorophenyl)-2-{[2-hydroxy-1-(hydroxy-methyl)ethyl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one (911370-10-0) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 4-(3,4-difluoro-phenyl)-8-(2,6-difluoro-phenyl)-2-(2-hydroxy-1-hydroxymethyl-ethylamino)-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 150℃; for 0.25h; Suzuki cross-coupling; Irradiation; microwave;	96%

4-Bromothiophen-2-aldehyde (18791-75-8) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 4-(3,4-difluorophenyl)thiophene-2-carbaldehyde (1019780-50-7)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene for 16h; Suzuki cross-coupling; Heating;	96%

o-cyanobromobenzene (2042-37-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3',4'-difluoro-[1,1'-biphenyl]-2-carbonitrile (1253696-06-8)

Conditions	Yield
With 5%-palladium/activated carbon; potassium carbonate In ethanol; water at 80℃; for 0.666667h; Suzuki Coupling;	96%
With Ph2P(CH2CH2O)22CH3; triethylamine; palladium dichloride In water at 80℃; for 2h; Suzuki coupling; Inert atmosphere;	95%

2,5-diiodo-p-xylene (1124-08-9) + (3,4-difluorophenyl)boronic acid (168267-41-2) → C20H14F4 (1401514-49-5)

Conditions	Yield
With sodium hydroxide In water for 2h; Reflux;	96%

2,6-dibromoaniline (608-30-0) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 2,6-bis(3,4-difluorophenyl)aniline (1426332-55-9)

Conditions	Yield
With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 1.08333h; Suzuki Coupling;	96%

methyl 3-bromo-4-methylbenzoate (104901-43-1) + (3,4-difluorophenyl)boronic acid (168267-41-2) → methyl 3',4'-difluoro-6-methyl-[1,1'-biphenyl]-3-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere;	96%
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere;	96%

bromobenzene (108-86-1) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3,4‐difluoro‐1,1′‐biphenyl (67277-33-2)

Conditions	Yield
With sodium carbonate at 80℃; for 1.16667h; Catalytic behavior; Suzuki Coupling;	96%
With sodium carbonate at 100℃; for 0.5h; Suzuki-Miyaura Coupling;	95%
With sodium carbonate In water at 25℃; for 7h; Suzuki Coupling;	91%

4-tolyl iodide (624-31-7) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 3',4'-difluoro-4-methyl-1,1'-biphenyl

Conditions	Yield
With sodium carbonate at 80℃; for 1.25h; Catalytic behavior; Suzuki Coupling;	96%
With sodium carbonate at 80℃; for 1.5h; Kinetics; Suzuki Coupling; Green chemistry;	92%

bromochlorobenzene (106-39-8) + (3,4-difluorophenyl)boronic acid (168267-41-2) → C12H7ClF2

Conditions	Yield
With sodium carbonate at 80℃; for 1.16667h; Kinetics; Suzuki Coupling; Green chemistry;	96%
With sodium carbonate at 80℃; for 1.16667h; Catalytic behavior; Suzuki Coupling;	87%

2-methoxy-5-bromopyridine (13472-85-0) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 5-(3,4-difluorophenyl)-2-methoxypyridine

Conditions	Yield
With O4P(3-)*3K(1+)*5H2O; palladium dichloride In water; N,N-dimethyl-formamide at 20℃; for 24h;	96%

2-(4-bromophenyl]pyridine (63996-36-1) + (3,4-difluorophenyl)boronic acid (168267-41-2) → 2-(3',4'-difluoro-[1,1'-biphenyl]-4-yl)pyridine

Conditions	Yield
With palladium diacetate; potassium carbonate In ethanol; water at 80℃;	95.6%

tert-butyl 2-chloro-3-cyano-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate + (3,4-difluorophenyl)boronic acid (168267-41-2) → tert-butyl 3-cyano-2-(3,4-difluorophenyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 110℃; for 12h; Inert atmosphere;	95.04%

Upstream product

• 1033691-65-4 C₆H₃BF₅^(1-) 
• 90897-92-0 3,4-difluorophenylmagnesium bromide 

Downstream Products

• 574007-37-7 tert-butyl 4-(3,4-difluorophenyl)-3,6-dihydro-2H-pyridine-1-carboxylate 
• 859204-27-6 2-[(tert-butoxycarbonyl)amino]-5-(3,4-difluorophenyl)thiophen-3-carboxylic acid methyl ester 
• 860617-52-3 1-cyclopentyl-6-(3,4-difluorophenyl)-1,3-dihydro-2H-benzimidazol-2-one 
• 1192036-03-5 (E)-methyl 6-((3,4-difluorophenyl)(ethoxyimino)methyl)nicotinate 
• 1262486-42-9 2-chloro-6-ethoxy-5-(3,4-difluorophenyl)-3-isobutylpyrazine 
• 1416244-95-5 (+/-)-(2Z)-3-(3,4-difluorophenyl)-2-((dimethylamino)methylene)cyclopentanone 
• 1416242-94-8 (+/-)-4-(3,4-difluorophenyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole 
• 85312-59-0 3,4-difluoro-4'-(trans-4-propylcyclohexyl)-1,1'-biphenyl 
• 134412-17-2 3,4-difluoro-4'-(4-pentylcyclohexyl)-1,1'-biphenyl 
• 1246205-76-4 4-[2-(2-carboxy-ethyl)-3-[6-(3',4'-difluoro-5-methoxymethyl-biphenyl-3-yloxy)-hexyl]-phenoxy]-butyric acid 
• 1234340-14-7 1'-(3,4-difluorophenyl)-5'-phenethylspiro[[1,3]dioxane-2,3'-indolin]-2'-one 
• 1231303-48-2 2-(((1s,4s)-4-((4-(3,4-difluorophenyl)-5-ethoxy-3-phenyl-1H-pyrazol-1-yl)methyl)cyclohexyl)methoxy)acetic acid 

Relevant articles and documents

Preparation and application of SBA-15-supported palladium catalyst for Suzuki reaction in supercritical carbon dioxide

The external and internal surfaces of SBA-15 were modified by (MeO) 3SiPh and a phosphine ligand, (MeO)3SiCH 2CH2CH2SCH2C6H 4PPh2, before and after the template Pluronic P123 copolymer was removed, respectively. Palladium was then tethered within the cavity of the mesoporous material Ph-SBA-15-PPh3via a ligand-exchange reaction to provide a new supported palladium catalyst Ph-SBA-15-PPh 3-Pd. This catalyst was demonstrated to be a robust and active catalyst in Suzuki reaction of a wide range of aryl bromides with arylboronic acids in supercritical carbon dioxide. After the reaction mixtures were treated at 90 °C for 24 h, the crude coupling products were obtained as crystalline solids when the reaction temperature was lowered to room temperature and the carbon dioxide was then slowly released. The pure products can be obtained by simple recrystallization in good to excellent yields. The Ph-SBA-15-PPh 3-Pd catalyst has low leaching loss and can be reused at least 7 times without loss of activity.

Substituent effects on aryltrifluoroborate solvolysis in water: Implications for Suzuki-Miyaura coupling and the design of stable 18F-labeled aryltrifluoroborates for use in PET imaging

(Chemical Equation Presented) Whereas electron withdrawing substituents retard the rate of aryltrifluoroborate solvolysis, electron-donating groups enhance it. Herein is presented a Hammett analysis of the solvolytic lability of aryltrifluoroborates where log(Ksolv) values correlate to a values with a ρ value of approximately -1. This work provides a predictable rubric for tuning the reactivity of boron for several uses including 18F-labeled PET reagents and has mechanistic implications for ArBF3-enhanced ligandless metal-mediated cross coupling reactions with aryltrifluoroborates.

Synthesis and monoamine transporter binding properties of 3α-(substituted phenyl)nortropane-2β-carboxylic acid methyl esters. Norepinephrine transporter selective compounds

3α-(Substituted phenyl)nortropane-2β-carboxylic acid methyl esters (8a-h) showed high affinity for the norepinephrine transporter (NET). The most potent and selective compound was 3α-(3-fluoro-4-methylphenyl) nortropane-2β-carboxylic acid methyl ester (8d), with a Ki of 0.43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development of 8d makes available compounds selective for all three transporters from the same structural class.