725-89-3

Basic information

• Product Name: 3,5-Bis(trifluoromethyl)benzoic acid
• Synonyms: 3, 5-Bis (trifluoromrthyl) benzoic acid;3,5-Di(trifluoromethyl)benzoic acid , TECH;3,5-Bis(trifluoroMethyl)benzoic acid, 98% 5GR;3,5-Di(trifluoroMethyl)benzoic acid, 90, TECH;3,5-BIS(TRIFLUOROMETHYL)BENZOIC ACID;3,5-DI(TRIFLUOROMETHYL)BENZOIC ACID;MBT-BOA;BIS(3,5-TRIFLUOROMETHYL)BENZOIC ACID
• CAS NO: 725-89-3
• Molecular Formula: C₉H₄F₆O₂
• Molecular Weight: 258.12
• EINECS: 211-970-1
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Benzoic acid;Miscellaneous;Benzotrifluoride Series;C9;Carbonyl Compounds;Carboxylic Acids;Fluorides;Boronic Acid series;Fluorobenzene
• Mol File: 725-89-3.mol
• Article Data: 16

Chemical Properties

• Melting Point: 142-143 °C(lit.)
• Boiling Point: 223.9 °C at 760 mmHg
• Flash Point: 89.2 °C
• Appearance: white to light yellow crystal powder
• Density: 1,42 g/cm3
• Vapor Pressure: 0.0537mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO, Methanol
• PKA: 3.34±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• BRN: 2058600
• CAS DataBase Reference: 3,5-Bis(trifluoromethyl)benzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Bis(trifluoromethyl)benzoic acid(725-89-3)
• EPA Substance Registry System: 3,5-Bis(trifluoromethyl)benzoic acid(725-89-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• RTECS: DG4448020
• HazardClass: IRRITANT
• Hazardous Substances Data: 725-89-3(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

3,5-Bis(trifluoromethyl)benzoic acid is a useful synthetic intermediate, and is a derivative of Benzoic acid (B203900). 3,5-Bis(trifluoromethyl)benzoic acid has also been identified as a major metabolite of a series of 3,5-bis(trifluoromethyl)benzyl ethers in vitro, and is hypothesized to result via oxidation of the benzylic position.

General Description

3,5-Bis(trifluoromethyl)benzoic acid is a significant metabolite formed during metabolism of 3,5-bis(trifluoromethyl)benzyl ether via oxidation.

InChI:InChI=1/C9H4F6O2/c10-8(11,12)5-1-4(7(16)17)2-6(3-5)9(13,14)15/h1-3H,(H,16,17)/p-1

Synthetic route

carbon dioxide (124-38-9) + 3,6-bis(trifluoromethyl)bromobenzene (328-70-1) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With n-butyllithium In diethyl ether at -75℃;	94%
Stage #1: 3,6-bis(trifluoromethyl)bromobenzene With isopropylmagnesium chloride In tetrahydrofuran at -10℃; for 1h; Stage #2: carbon dioxide In tetrahydrofuran at -45℃; under 1034.3 Torr; for 1h;	94%
Stage #1: 3,6-bis(trifluoromethyl)bromobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78 - 20℃;	90.3%
(i) Mg, I2, Et2O, (ii) /BRN= 1900390/; Multistep reaction;

3,5-bis(trifluoromethyl)benzoyl fluoride (401-96-7) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With water In diethyl ether	85%

2-hydroxy-4-phenylbutanenitrile (121054-03-3) + 3,5-bis(trifluoromethyl)benzoic anhydride (155929-90-1) → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + 1-cyano-3-phenylpropyl 3,5-bis(trifluoromethyl)benzoate

Conditions	Yield
Stage #1: 2-hydroxy-4-phenylbutanenitrile; 3,5-bis(trifluoromethyl)benzoic anhydride With triethylamine In dichloromethane at 20℃; for 2h; Stage #2: With hydrogenchloride In water	A n/a B 85%

1,3,5-tris(trifluoromethyl)benzene (729-81-7) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
Stage #1: 1,3,5-tris(trifluoromethyl)benzene With trifluorormethanesulfonic acid In chloroform for 4h; Inert atmosphere; Stage #2: With water In chloroform Inert atmosphere;	82%

3,5-bis(trifluoromethyl)styrene (349-59-7) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With methyl 3,5-bis((1H-1,2,4-triazol-1-yl)methyl)benzoate; oxygen; sodium acetate; nickel dibromide at 120℃; under 760.051 - 912.061 Torr; for 48h; chemoselective reaction;	80%

carbon monoxide (201230-82-2) + 3,5-bis(trifluoromethyl)iodobenzene (328-73-4) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With water; potassium carbonate In acetonitrile at 100℃; under 3750.38 Torr; for 0.0161111h;	79%

(2S,3S,5R,6R)-5-hydroxy-2-methoxy-4-oxo-6-(pivaloyloxymethyl)tetrahydro-2H-pyran-3-yl pivalate (90213-79-9) + 3,5-bis(trifluoromethyl)benzoic anhydride (155929-90-1) → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + (2R,3R,5S,6S)-6-methoxy-4-oxo-5-(pivaloyloxy)-2-(pivaloyloxymethyl)tetrahydro-2H-pyran-3-yl 3,5-bis(trifluoromethyl)benzoate

Conditions	Yield
Stage #1: (2S,3S,5R,6R)-5-hydroxy-2-methoxy-4-oxo-6-(pivaloyloxymethyl)tetrahydro-2H-pyran-3-yl pivalate; 3,5-bis(trifluoromethyl)benzoic anhydride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With hydrogenchloride In water	A n/a B 71.8%

carbon dioxide (124-38-9) + 1,3-bis(trifluoromethyl)benzene (402-31-3) → 2,4-bis(trifluoromethyl)benzoic acid (32890-87-2) + 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With N,N,N',N'',N'''-pentamethyldiethylenetriamine; sec.-butyllithium In tetrahydrofuran at -75℃; for 2h;	A 38% B 14%

3,5-bis(trifluoromethyl)benzoic anhydride (155929-90-1) + D-glucurono-3,6-lactone acetonide (3067-56-9, 20513-98-8, 25159-39-1, 26623-22-3, 29514-28-1, 85080-95-1) → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + 1,2-O-isopropylidene-5-O-(3,5-bis(trifluoromethyl)benzoyl)-α-D-xylo-hexofuranurono-6,3-lactone

Conditions	Yield
Stage #1: 3,5-bis(trifluoromethyl)benzoic anhydride; D-glucurono-3,6-lactone acetonide With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With hydrogenchloride In water	A n/a B 31.6%

carbon dioxide (124-38-9) + 1,3-bis(trifluoromethyl)benzene (402-31-3) → 2,6-bis(trifluoromethyl)benzoic acid (24821-22-5) + 2,4-bis(trifluoromethyl)benzoic acid (32890-87-2) + 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine; n-butyllithium 1.) THF, -78 deg C, 1.5 h, 2.) THF; Yield given; Multistep reaction. Yields of byproduct given;

1,3-bis(trifluoromethyl)benzene (402-31-3) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 94 percent / sulfuric acid; 1,3-dibromo-5,5-dimethylhydantoin / acetic acid / 4 h / 45 °C 2.1: i-PrMgCl / tetrahydrofuran / 1 h / -10 °C 2.2: 94 percent / tetrahydrofuran / 1 h / -45 °C / 1034.3 Torr View Scheme
Multi-step reaction with 2 steps 1: 87 percent / 96percent H2SO4, N,N'-dibromo-5,5-dimethylhydantoin / 24 h / 0 °C 2: 94 percent / BuLi / diethyl ether / -75 °C View Scheme
Multi-step reaction with 2 steps 2: (i) Mg, I2, Et2O, (ii) /BRN= 1900390/ View Scheme

4,4'-dimethoxybenzhydryl 3,5-bis(trifluoromethyl)benzoate → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
In ethanol; dichloromethane at 25℃; Kinetics;

3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride (785-56-8) → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + 1-cyano-3-phenylpropyl 3,5-bis(trifluoromethyl)benzoate

Conditions	Yield
Multi-step reaction with 2 steps 1: phosphoric acid; acetic anhydride / 150 - 190 °C 2: triethylamine / dichloromethane / 2 h / 20 °C View Scheme

3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride (785-56-8) → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + (2R,3R,5S,6S)-6-methoxy-4-oxo-5-(pivaloyloxy)-2-(pivaloyloxymethyl)tetrahydro-2H-pyran-3-yl 3,5-bis(trifluoromethyl)benzoate

Conditions	Yield
Multi-step reaction with 2 steps 1: phosphoric acid; acetic anhydride / 150 - 190 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C View Scheme

3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride (785-56-8) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosphoric acid; acetic anhydride / 150 - 190 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C View Scheme

carbon dioxide (124-38-9) + 1,3-bis(trifluoromethyl)benzene (402-31-3) → 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions

Yield

Stage #1: carbon dioxide; 1,3-bis(trifluoromethyl)benzene With [1,2-bis(dicyclohexylphosphino)ethane]rhodium(I) chloride dimer; Al(3+)*1.5CH3(1-)*1.5C2H5O(1-); tetramethylurea In N,N-dimethyl acetamide at 20 - 145℃; under 760.051 Torr; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether; N,N-dimethyl acetamide; water Catalytic behavior; Inert atmosphere; regioselective reaction;

3,5-bis(trifluoromethyl)benzenemethanol (32707-89-4) → 3,5-Bis(trifluoromethyl)benzaldehyde (401-95-6) + 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; laccase from Trametes versicolor; oxygen In water at 20℃; for 120h; Enzymatic reaction;	A 48 %Spectr. B 21 %Spectr.

(S)-Mandelic acid (17199-29-0) + diruthenium tetra(3,5-bis(trifluoromethyl)) benzoate → 3,5-bistrifluoromethylbenzoic acid (725-89-3) + diruthenium tetra (L-mandelate)

Conditions	Yield
at 55℃; for 2h; Kinetics; Equilibrium constant; Temperature;

diruthenium tetra(3,5-bis(trifluoromethyl)) benzoate + acetic acid (64-19-7) → tetra-μ-acetato-ruthenium(II) + 3,5-bistrifluoromethylbenzoic acid (725-89-3)

Conditions	Yield
at 55℃; for 2h; Kinetics; Equilibrium constant; Temperature;

Upstream product

• 124-38-9 carbon dioxide 
• 402-31-3 1,3-bis(trifluoromethyl)benzene 
• 75462-61-2 3,5-bis(trifluoromethyl)benzylchloride 
• 100-09-4 4-methoxybenzoic acid 
• 99-94-5 p-Toluic acid 
• 455-24-3 4-trifluoromethylbenzoic acid 
• 456-22-4 4-Fluorobenzoic acid 
• 65-85-0 benzoic acid 
• 64-19-7 acetic acid 
• 17199-29-0 (S)-Mandelic acid 
• 201230-82-2 carbon monoxide 
• 328-73-4 3,5-bis(trifluoromethyl)iodobenzene 
• 32707-89-4 3,5-bis(trifluoromethyl)benzenemethanol 
• 349-59-7 3,5-bis(trifluoromethyl)styrene 

Downstream Products

• 551943-85-2 3,5-Bis-trifluoromethyl-benzoic acid (S)-2-phenyl-2-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-ethyl ester 
• 551943-86-3 3,5-Bis-trifluoromethyl-benzoic acid (R)-2-phenyl-2-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-ethyl ester 
• 26107-82-4 3,5-bis-(trifluoromethyl)benzoic acid hydrazide 
• 346417-35-4 1-{(S)-2-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazine 
• 551943-94-3 1-{(S)-2-[(S)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazine 
• 551943-93-2 1-{(R)-2-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazine 
• 551943-95-4 1-{(R)-2-[(S)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazine 
• 346417-69-4 2-(4-{(S)-2-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazin-1-yl)-acetamide 
• 346417-70-7 2-(4-{(S)-2-[(S)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazin-1-yl)-acetamide 
• 346417-71-8 2-(4-{(R)-2-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazin-1-yl)-acetamide 
• 346417-72-9 2-(4-{(R)-2-[(S)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-1-phenyl-ethyl}-piperazin-1-yl)-acetamide 

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