654-62-6

Basic information

• Product Name: 4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide
• Synonyms: 4-Amino-6-trifluoromethyl-1,3-benzenedisul-famide;5-AMINO-ALPHA,ALPHA,ALPHA-TRIFLUOROTOLUENE-2,4-DISULFONAMIDE;5-Amino-alpha,alpha,alpha-trifluorotoluene-2,4-disulphonamide;4-AMINO-6-(TRIFLUOROMETHYL)-1,3-BENZENEDISULFONAMIDE;4-AMINO-6-(TRIFLUOROMETHYL)BENZENE-1,3-DISULFONAMIDE;2-AMINO-4-TRIFLUOROMETHYL-1,5-BENZENDISULFONAMIDE;2-AMINO-4-TRIFLUOROMETHYL-1,5-BENZENEDISULFONAMIDE;2-AMINO-4-TRIFLUOROMETHYL-1,5-BENZENEDISULPHONAMIDE
• CAS NO: 654-62-6
• Molecular Formula: C₇H₈F₃N₃O₄S₂
• Molecular Weight: 319.28
• EINECS: 211-506-8
• Product Categories: A-AM;Bioactive Small Molecules;Building Blocks;Cell Biology;Chemical Synthesis;Organic Building Blocks;Sulfonamides/Sulfinamides;Sulfur Compounds
• Mol File: 654-62-6.mol

Chemical Properties

• Melting Point: 241-246 °C
• Boiling Point: 562.8°C at 760 mmHg
• Flash Point: 294.2°C
• Appearance: /
• Density: 1.743g/cm³
• Vapor Pressure: 1.09E-12mmHg at 25°C
• Refractive Index: 1.571
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.14±0.60(Predicted)
• BRN: 1164542
• CAS DataBase Reference: 4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide(654-62-6)
• EPA Substance Registry System: 4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide(654-62-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 654-62-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide is used as a potential anti-tumor and antiglaucoma drug for its carbonic anhydrase inhibitory properties. It helps in managing the growth of tumor cells and reducing intraocular pressure in glaucoma patients.
Used in Metabolism of Diuretics:
4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide is a metabolite of hydroflumethazide, which is a diuretic used to increase urine output and reduce fluid buildup in the body. 4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide plays a role in the metabolism and effectiveness of hydroflumethazide as a diuretic.

InChI:InChI=1/C7H8F3N3O4S2/c8-7(9,10)3-1-4(11)6(19(13,16)17)2-5(3)18(12,14)15/h1-2H,11H2,(H2,12,14,15)(H2,13,16,17)

Synthetic route

bendroflumethiazide (73-48-3, 96782-95-5, 96782-96-6) → 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6)

Conditions	Yield
With sodium hydroxide In water reflux, 2 h; room temperature, 20 h;	68%

5-Amino-α.α.α-trifluor-toluol-2.4-disulfonsaeuredichlorid (1479-95-4) → 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6)

Conditions	Yield
With ammonia

2-amino-4-trifluoromethyl-benzenesulfonic acid (1513-44-6) → 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6)

Conditions	Yield
(i) ClSO3H, (heating), (ii) SOCl2, (iii) aq. NH3; Multistep reaction;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + BARBITURIC ACID (67-52-7) + orthoformic acid triethyl ester (122-51-0) → 4-(trifluoromethyl)-6-{[(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino}benzene-1,3-disulfonamide (1345551-58-7)

Conditions	Yield
In iso-butanol for 3h; Reflux;	96%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + o-phthalic dicarboxaldehyde (643-79-8) → 3-Sulfamoyl-2-trifluoromethyl-11H-isoindolo<1,2-c><1,2,4>benzothiadiazine 5,5-dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃; for 24h;	93%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 2-(2-oxoethyl)benzaldehyde (25705-34-4) → 8-sulfamoyl-9-trifluoromethyl-4b,5-dihydroisoquino<1,2-c><1,2,4>benzothiadiazine 6,6 dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃;	91%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → spiro[2H-1,2,4-benzothiadiazine-7-(aminosulfonyl)-6-(trifluoromethyl)-1,1-dioxide-3(4H),4'-piperidine]-1'-carboxylic acid 1,1-dimethylethyl ester (907624-95-7)

Conditions	Yield
In N,N-dimethyl-formamide for 5 - 7h; Heating / reflux;	91%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 2-benzoylbenzaldehyde (16780-82-8) → 11-Phenyl-3-sulfamoyl-2-trifluoromethyl-11H-isoindolo<1,2-c><1,2,4>benzothiadiazine 5,5-dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃; for 24h;	90%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 4,5-dimethoxy-phthalaldehyde (43073-12-7) → 8,9-Dimethoxy-3-sulfamoyl-2-trifluoromethyl-11H-isoindolo<1,2-c><1,2,4>benzothiadiazine 5,5-dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃; for 24h;	86%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 4,6-dihydroxy-2-mercaptopyrimidine (504-17-6) + orthoformic acid triethyl ester (122-51-0) → 4-{[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino}-6-(trifluoromethyl)benzene-1,3-disulfonamide (1345551-69-0)

Conditions	Yield
In iso-butanol for 3h; Reflux;	85%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + phenylacetaldehyde (122-78-1) → (R)-bendroflumethiazide (1087345-31-0)

Conditions	Yield
With C64H73O4P In dichloromethane at 20℃; for 168h; Inert atmosphere; Molecular sieve; optical yield given as %ee; enantioselective reaction;	80%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + hexanal (66-25-1) → (R)-penflutizide (1087345-32-1)

Conditions	Yield
With C64H73O4P In dichloromethane at 20℃; for 168h; Inert atmosphere; Molecular sieve; optical yield given as %ee; enantioselective reaction;	74%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 2,3-naphthalenedicarboxaldehyde (7149-49-7) → 3-Sulfamoyl-2-trifluoromethyl-13H-benzo<5,6>isoindolo<1,2-c><1,2,4>benzothiadiazine 5,5-dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃; for 24h;	64%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 3-Benzoylpyridine-2-carbaldehyde (167961-86-6) → 11-Phenyl-3-sulfamoyl-2-trifluoromethyl-11H-pyrido<2',3':3,4>pyrrolo<2,1-c><1,2,4>benzothiadiazine 5,5-dioxide

Conditions	Yield
With hydrogenchloride In methanol at 20℃; for 24h;	49%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + Benzaldehyde,3,5-bis[(nitrooxy)methyl] (907625-32-5) → 2H-1,2,4-benzothiadiazine-7-sulfonamide-3-[3,5-bis[(nitrooxy)methyl]phenyl]-3,4-dihydro-6-(trifluoromethyl)-1,1-dioxide

Conditions	Yield
With toluene-4-sulfonic acid In 1,4-dioxane for 5h; Heating / reflux;	45%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 5,5-dimethyl-1,3-dioxane-2-butanol nitrate (907625-40-5) → 3,4-dihydro-3-[4-(nitrooxy)butyl]-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; water Heating / reflux;	38%

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 3,4-diformylfuran (7040-25-7) → 3-(4-Formylfuran-3-yl)-7-sulfamoyl-6-trifluoromethyl-3,4-dihydro-2H-<1,2,4>benzothiadiazine 1,1-dioxide

Conditions	Yield
In methanol at 20℃; for 48h;	34%

1,4-dioxaspiro[4.4]nonane (176-32-9) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 1,1-dioxo-6-trifluoromethyl-1,4-dihydro-2H-1λ6-spiro[benzo[1,2,4]thiadiazine-3,1'-cyclopentane]-7-sulfonic acid amide (2806-04-4)

Conditions	Yield
With sulfuric acid; butan-1-ol
With sulfuric acid In butan-1-ol Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + formaldehyd (50-00-0) → hydroflumenthiazide (135-09-1)

Conditions	Yield
With sulfuric acid
With hydrogenchloride In ethanol
In water
In ethanol for 2h; Heating;
With hydrogenchloride Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + acetaldehyde (75-07-0) → 3-methyl-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (794-76-3)

Conditions	Yield
With sulfuric acid; water
In ethanol Heating;
With hydrogenchloride Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 2,2-dimethoxy-propane (77-76-9) → 3,3-dimethyl-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (3110-35-8)

1,3-dioxolane-2-spirocyclohexane (177-10-6) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 1,1-dioxo-6-trifluoromethyl-1,4-dihydro-2H-1λ6-spiro[benzo[1,2,4]thiadiazine-3,1'-cyclohexane]-7-sulfonic acid amide (1241-88-9)

Conditions	Yield
With sulfuric acid In butan-1-ol Heating;

furfural (98-01-1) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 3-furan-2-yl-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (1763-86-6)

Conditions	Yield
With hydrogenchloride Heating;

3-oxobutyraldehyde (625-34-3) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 1,1-dioxo-3-(2-oxo-propyl)-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (800-95-3)

Conditions	Yield
With hydrogenchloride In N,N-dimethyl-formamide

3-phenyl-propionaldehyde (104-53-0) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 1,1-dioxo-3-phenethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (1691-69-6)

Conditions	Yield
With hydrogenchloride In ethanol Heating;

4-vinylbenzyl chloride (1073-67-2) + 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) → 3-(4-chloro-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (1550-92-1)

Conditions	Yield
(i) aq. H2O2, HCO2H, (ii) /BRN= 1164542/, aq. H2SO4; Multistep reaction;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 1-ethenyl-4-methylbenzene (622-97-9) → 3-(4-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (14471-82-0)

Conditions	Yield
(i) aq. H2O2, HCO2H, (ii) /BRN= 1164542/, aq. H2SO4; Multistep reaction;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 3-methylstyrene (100-80-1) → 3-(3-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (14471-81-9)

Conditions	Yield
(i) aq. H2O2, HCO2H, (ii) /BRN= 1164542/, aq. H2SO4; Multistep reaction;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 8-cyclohexyl-1,4-dioxaspiro[4.5]decane (20818-96-6) → 4'-cyclohexyl-1,1-dioxo-6-trifluoromethyl-1,4-dihydro-2H-1λ6-spiro[benzo[1,2,4]thiadiazine-3,1'-cyclohexane]-7-sulfonic acid amide (3849-89-6)

Conditions	Yield
With sulfuric acid In butan-1-ol Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + 4-Methoxyphenylacetaldehyde (5703-26-4) → 3-(4-methoxy-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (1895-56-3)

Conditions	Yield
With hydrogenchloride Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + pentanal (110-62-3) → 3-butyl-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (2796-29-4)

Conditions	Yield
With hydrogenchloride In ethanol Heating;
With hydrogenchloride Heating;

4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (654-62-6) + para-fluorostyrene (405-99-2) → 3-(4-fluoro-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ6-benzo[1,2,4]thiadiazine-7-sulfonic acid amide (14471-83-1)

Conditions	Yield
(i) aq. H2O2, HCO2H, (ii) /BRN= 1164542/, aq. H2SO4; Multistep reaction;

Upstream product

• 1479-95-4 5-Amino-α.α.α-trifluor-toluol-2.4-disulfonsaeuredichlorid 
• 73-48-3 bendroflumethiazide 
• 1513-44-6 2-amino-4-trifluoromethyl-benzenesulfonic acid 

Downstream Products

• 135-09-1 hydroflumenthiazide 
• 800-95-3 1,1-dioxo-3-(2-oxo-propyl)-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1691-69-6 1,1-dioxo-3-phenethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1550-92-1 3-(4-chloro-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 14471-82-0 3-(4-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 14471-81-9 3-(3-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1895-56-3 3-(4-methoxy-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 14471-83-1 3-(4-fluoro-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 14471-80-8 3-(2-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 14331-39-6 1,1-dioxo-3-(1-phenyl-propyl)-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1691-70-9 1,1-dioxo-3-(1-phenyl-ethyl)-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1550-96-5 3-cyclohex-2-enylmethyl-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 1174-02-3 1,1-dioxo-3-phenethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4,3]thiadiazaborinine-7-sulfonic acid amide 
• 73-48-3 bendroflumethiazide