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
• Article Data: 1

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

2,4-Disulfamyl-5-trifluoromethylaniline is a carbonic anhydrase inhibitor, used as a potential anti-tumor and antiglaucoma drug. Metabolite of hydroflumethazide, 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

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

Downstream Products

• 73-48-3 bendroflumethiazide 
• 137-26-8 Thiram 
• 1087345-31-0 (R)-bendroflumethiazide 
• 748-18-5 3-(3-fluoro-phenyl)-1,1-dioxo-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 
• 393-21-5 6-Trifluormethyl-7-sulfamoyl-3-carboxy-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothia-diazin 
• 3872-12-6 3-(4-nitro-phenyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 
• 748-19-6 3-(4-chloro-phenyl)-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 
• 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 
• 14471-80-8 3-(2-methyl-benzyl)-1,1-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonic acid amide 

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