35303-76-5

Basic information

• Product Name: 4-(2-Aminoethyl)benzenesulfonamide
• Synonyms: P-(2-AMINOETHYL)BENZENESULFONAMIDE;OTAVA-BB BB7020410047;TIMTEC-BB SBB003544;4-(2-AMINOETHYL)BENZENESULFONAMIDE;4-(2-AMINOETHYL)BENZENE SULFONMIDE;4-(2-AMINOETHYL)BENZENE SULPHONAMIDE;LABOTEST-BB LT00080735;4-(2-Ethylamino) Benzene Sulfonamide
• CAS NO: 35303-76-5
• Molecular Formula: C₈H₁₂N₂O₂S
• Molecular Weight: 200.26
• EINECS: 252-501-0
• Product Categories: SULFONAMIDE;Benzene derivates;(intermediate of glibenclamide,glipizide,gliquido;Organic Building Blocks;Sulfonamides/Sulfinamides;Sulfur Compounds
• Mol File: 35303-76-5.mol
• Article Data: 4

Chemical Properties

• Melting Point: 150-152 °C(lit.)
• Boiling Point: 387.4 °C at 760 mmHg
• Flash Point: 188.1 °C
• Appearance: white to yellowish crystalline powder powder
• Density: 1.2581 (rough estimate)
• Vapor Pressure: 3.31E-06mmHg at 25°C
• Refractive Index: 1.5690 (estimate)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.16±0.10(Predicted)
• Water Solubility: 15.5g/L at 20℃
• CAS DataBase Reference: 4-(2-Aminoethyl)benzenesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(2-Aminoethyl)benzenesulfonamide(35303-76-5)
• EPA Substance Registry System: 4-(2-Aminoethyl)benzenesulfonamide(35303-76-5)

Safety Data

• Hazard Codes: C,Xi,Xn
• Statements: 34-22-36/37/38-20/21/22
• Safety Statements: 45-36/37/39-26-36-24/25
• RIDADR: UN3259
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 35303-76-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 35303-76-5 differently. You can refer to the following data:
1. 4-(2-Aminoethyl)benzenesulfonamide is used as the starting material in the synthesis of Des(5-methylpyrazinecarbonyl) trans-4-Methyl Glipizide (D292605); a degradation product of Glimepiride (G410150) which is a sulfonylurea hypoglycemic agent and an antidiabetic. 4-(2-Aminoethyl)benzenesulfonamide is also used as a reagent in the synthesis of deorphaning pyrrolopyrazines as potent multi-target antimalarial agents.
2. 4-(2-Aminoethyl)benzenesulfonamide was used to develop a model system to study the implementation of a microfluid chip required for Fourier transform measurements of biochemical interactions.

Chemical Properties

white to yellowish crystalline powder

General Description

The human hepatocellular carcinoma (HCC) cells were treated with its inhibitor 4-(2-aminoethyl)benzenesulfonamide.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C8H12N2O2S/c9-6-5-7-1-3-8(4-2-7)13(10,11)12/h1-4H,5-6,9H2,(H2,10,11,12)

Synthetic route

4-cyanomethyl-benzenesulfonic acid amide (3665-08-5) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
With sodium methylate; nickel In methanol at 45℃; Electrochemical reaction;	86%

4-(β-acetylaminoethyl)phenylsulfonamide (41472-49-5) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
With sodium hydroxide; water for 3h; Reflux;	78%
With hydrogenchloride

4-(2-carboxyethyl)-benzenesulfonamide (90610-69-8) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
With pyridine; thionyl chloride; chloroform Behandeln des Reaktionsprodukts mit Natriumazid in wss. Aceton und Erwaermen des erhaltenen Azids in Benzol;

4-sulfamoyl-trans-cinnamic acid (147723-92-0) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous NaOH-solution; sodium-amalgam 2: thionyl chloride; chloroform; pyridine / Behandeln des Reaktionsprodukts mit Natriumazid in wss. Aceton und Erwaermen des erhaltenen Azids in Benzol View Scheme

methyl-N-(benzyl-methyl)-formamide (877-95-2) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: chlorosulfuric acid 2: aqueous ammonia 3: aqueous hydrochloric acid View Scheme

sulfonyl chloride (35450-53-4) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous ammonia 2: aqueous hydrochloric acid View Scheme

4-ethylpyrazole-1-carboxylic acid chloride (67514-65-2) + cyclopentyl isocyanate (4747-71-1) → 4-[2-(4-ethylpyrazole-1-carbonamide)-ethyl]-benzenesulphonamide + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

3,5-dimethyl-4-chloropyrazole-1-carboxylic acid chloride (67514-73-2) → 4-[2-(3,5-dimethyl-4-chloropyrazole-1-carbonamide)-ethyl]-benzenesulphonamide + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

phenethylamine (64-04-0) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / tetrahydrofuran / 4 h / 20 °C / Cooling with ice 2: chlorosulfonic acid / 2 h / 20 °C / Cooling with ice 3: ammonium hydroxide / acetone / 20 °C View Scheme

2,2,2-trifluoro-N-(2-phenylethyl)acetamide (458-85-5) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 2 h / 20 °C / Cooling with ice 2: ammonium hydroxide / acetone / 20 °C View Scheme

4-[2-(2,2,2-trifluoroacetamido)ethyl]benzenesulfonyl chloride (223253-87-0) → 4-(2-aminoethyl)benzenesulfonamide (35303-76-5)

Conditions	Yield
With ammonium hydroxide In acetone at 20℃;	21.6 g

ethyl [3-(benzoylamino)-2-oxopyridin-1(2H)-yl]acetate (1000693-06-0) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → N-[1-(2'-{2''-[4'''-(aminosulfonyl)phenyl]ethylamino}-2'-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl]benzamide (1177500-05-8)

Conditions	Yield
at 120℃; for 1h;	100%

N-methyl-2-imidazolcarboxaldehyde (13750-81-7) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-(bis((1-methyl-1H-imidazol-2-yl)methyl)amino)ethyl) benzenesulfonamide (1228927-49-8)

Conditions	Yield
Stage #1: N-methyl-2-imidazolcarboxaldehyde; 4-(2-aminoethyl)benzenesulfonamide With acetic acid In 1,2-dichloro-ethane at 75℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 0 - 20℃; Inert atmosphere;	100%

tert-butyl 2,2′-(2-(2-formyl-1H-imidazol-1-yl)-acetylazanediyl)diacetate (1228647-94-6) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → tert-butyl 2,2′-(2,2′-(4-sulfamoylphenethylazanediyl)bis-(methylene)bis(1H-imidazole-2,1-diyl-acetylazanediyl))diacetate (1228647-95-7)

Conditions	Yield
Stage #1: tert-butyl 2,2′-(2-(2-formyl-1H-imidazol-1-yl)-acetylazanediyl)diacetate; 4-(2-aminoethyl)benzenesulfonamide With acetic acid In 1,2-dichloro-ethane at 75℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 0 - 20℃; Inert atmosphere;	100%

Boc-Glu (2419-94-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → C26H37N5O8S2 (1558622-20-0)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 0 - 20℃; for 73h;	100%

(S)-4-(3-((S)-6-(bis((1-(2-tert-butoxy-2-oxo-ethyl)-1H-imidazol-2-yl)methyl)amino)-1-tert-butoxy-1-oxo-hexane-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → (S)-tert-butyl-6-(bis((1-(2-tert-butoxy-2-oxo-ethyl)-1H-imidazol-2-yl)methyl)amino)-2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoyl-phenethyl-amino)pentan-2-yl)ureido)hexanoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 40℃;	100%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 40℃;	100%

succinic acid anhydride (108-30-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-oxo-4-((4-sulfamoylphenethyl)amino)butanoic acid (401819-70-3)

Conditions	Yield
In tetrahydrofuran at 60℃; for 7h;	100%
In tetrahydrofuran at 60℃; for 7h;	100%

Tetrabromophthalic anhydride (632-79-1) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-(4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl)ethyl)benzenesulfonamide (1454891-19-0)

Conditions	Yield
With acetic acid at 130℃; for 1.5h; Inert atmosphere;	99%
With acetic acid for 12h; Reflux;

tetrachlorophthalic anhydride (117-08-8) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)ethyl)benzenesulfonamide (1449762-39-3)

Conditions	Yield
With acetic acid at 130℃; for 1.5h; Inert atmosphere;	98%
With acetic acid for 12h; Reflux;

pyridine-2-carbaldehyde (1121-60-4) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-(bis(pyridin-2-ylmethyl)amino)ethyl)benzenesulfonamide (1170318-30-5)

Conditions	Yield
Stage #1: pyridine-2-carbaldehyde; 4-(2-aminoethyl)benzenesulfonamide With acetic acid In 1,2-dichloro-ethane at 75℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 0 - 20℃; Inert atmosphere;	97%

4-(2-aminoethyl)benzenesulfonamide (35303-76-5) + (S)-tert-butyl (1-(1H-benzo[d][1,2,3]triazol-1-yl)-1-oxo-3-phenylpropan-2-yl)carbamate (514214-66-5) → (S)-benzyl (1-oxo-3-phenyl-1-((4-sulfamoylphenethyl)amino)propan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	97%

di-tert-butyl dicarbonate (24424-99-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → tert-butyl (4-sulfamoyl phenethyl)carbamate (258262-54-3)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 4h;	97%
In N,N-dimethyl-formamide at 20℃; for 4h;	95%
In N,N-dimethyl-formamide at 20℃;	86%
With triethylamine In tetrahydrofuran at 25℃; for 2h;
In N,N-dimethyl-formamide at 20℃; for 5h;

2-(carboxymethyl)-5-methoxybenzoic acid (52962-25-1) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-[2-(3,4-dihydro-7-methoxy-1,3-dioxo-2(1H)-isoquinolinyl)ethyl]benzenesulfonamide (586415-13-6)

Conditions	Yield
In water at 160℃; for 8h; Solvent; Temperature; Autoclave; Green chemistry;	96%
for 0.333333h; Heating;	90%

2-bromophenylacetyl chloride (55116-09-1) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-[2-(2-bromophenyl)acetamidoethyl]benzenesulfonamide (1446750-92-0)

Conditions	Yield
With triethylamine In acetonitrile at 0 - 5℃;	95%

4-Phenylbenzaldehyde (3218-36-8) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-{2-[(biphenyl-4-ylmethylene)amino]ethyl}benzenesulfonamide

Conditions	Yield
In methanol at 0℃; for 0.05h;	95%
In methanol

benzyl [2‑(1H‑benzo[d][1,2,3]triazol‑1‑yl)‑2‑oxoethyl]carbamate (173459-80-8) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl (2-oxo-2-((4-sulfamoylphenethyl)amino)ethyl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	95%

succinic acid anhydride (108-30-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-(2,5-dioxopyrrolidin-1-yl)ethyl)benzenesulfonamide

Conditions	Yield
With sodium acetate; acetic anhydride; acetic acid for 12h; Reflux;	95%

C29H31N5O4 + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl ((S)-1-(((2S,3S)-3-methyl-1-oxo-1-((4-sulfamoylphenethyl)amino)pentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	95%

C29H31N5O4 + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl ((S)-4-methyl-1-oxo-1-(((S)-1-oxo-3-phenyl-1-((4-sulfamoylphenethyl)amino)propan-2-yl)amino)pentan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	95%

C24H29N5O4S2 + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl ((S)-4-(methylthio)-1-(((S)-4-(methylthio)-1-oxo-1-((4-sulfamoylphenethyl)amino)butan-2-yl)amino)-1-oxobutan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	95%

C29H31N5O4 + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → tert-butyl ((S)-1-oxo-1-(((S)-1-oxo-3-phenyl-1-((4-sulfamoylphenethyl)amino)propan-2-yl)amino)-3-phenylpropan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	95%

C19H20N4O3 (1173817-60-1) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate

Conditions	Yield
In dichloromethane at 70℃; for 0.5h; Microwave irradiation;	95%

acide chromone carboxylique-2 (4940-39-0) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-oxo-N-(4-sulfamoylphenethyl)-4H-chromene-2-carboxamide

Conditions	Yield
Stage #1: acide chromone carboxylique-2 With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 80 - 90℃; for 1.2h; Stage #2: 4-(2-aminoethyl)benzenesulfonamide In N,N-dimethyl-formamide for 1h; Heating;	95%

10-methyl-7-oxa-5-thia-3,6,11b-triazabenzo[c]fluorene 5,5-dioxide (1206768-85-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-hydroxy-5-methylphenyl)-3-[2-(4-sulfamoylphenyl)ethylamino]-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide

Conditions	Yield
In tetrahydrofuran for 6h; Reflux;	94.3%
In tetrahydrofuran for 5h; Reflux;	92%

methyl 5-methyl-1,2,4-oxadiazole-3-carboxylate (19703-94-7) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → p-[β-(5-methyl-1,2,4-oxadiazole-3-carbonylamino)ethyl]-benzenesulfonamide (49586-60-9)

Conditions	Yield
In N-methyl-acetamide	94%

4,6-dihydroxy-2-mercaptopyrimidine (504-17-6) + orthoformic acid triethyl ester (122-51-0) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-(2-{[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino}ethyl)benzenesulfonamide (1345551-71-4)

Conditions	Yield
In iso-butanol for 3h; Reflux;	94%

4-bromosalicylaldehyde (22532-62-3) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 4-{2-[(4-bromo-2-hydroxybenzylidene)amino]ethyl}benzenesulfonamide

Conditions	Yield
In methanol at 0℃; for 0.05h;	94%
In methanol

2-(4-fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (18600-51-6) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 2-(4-fluorobenzamido)-N-(4-sulfamoylphenethyl)benzamide

Conditions	Yield
In acetic acid Reflux;	94%

3-chloro-1,2,4-benzotriazine 1-oxide (67692-91-5) + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → 3-(4-sulfamoylphenethylamino)benzo[e][1,2,4]triazine 1-oxide

Conditions	Yield
In 1,2-dimethoxyethane Reflux;	94%
In 1,2-dimethoxyethane Inert atmosphere; Reflux;	94%

C21H23N5O4S + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl (R)-(2-((4-(methylthio)-1-oxo-1-((4-sulfamoylphenethyl)amino)butan-2-yl)amino)-2-oxoethyl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	94%

C33H31N5O4S + 4-(2-aminoethyl)benzenesulfonamide (35303-76-5) → benzyl ((S)-1-(((R)-3-(benzylthio)-1-oxo-1-((4-sulfamoylphenethyl)amino)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	94%

Upstream product

• 41472-49-5 4-(β-acetylaminoethyl)phenylsulfonamide 
• 90610-69-8 4-(2-carboxyethyl)-benzenesulfonamide 
• 877-95-2 methyl-N-(benzyl-methyl)-formamide 
• 223253-87-0 4-[2-(2,2,2-trifluoroacetamido)ethyl]benzenesulfonyl chloride 
• 458-85-5 2,2,2-trifluoro-N-(2-phenylethyl)acetamide 
• 64-04-0 phenethylamine 
• 67514-73-2 3,5-dimethyl-4-chloropyrazole-1-carboxylic acid chloride 
• 67514-65-2 4-ethylpyrazole-1-carboxylic acid chloride 
• 4747-71-1 cyclopentyl isocyanate 
• 35450-53-4 sulfonyl chloride 
• 147723-92-0 4-sulfamoyl-trans-cinnamic acid 
• 3665-08-5 4-cyanomethyl-benzenesulfonic acid amide 

Downstream Products

• 52068-94-7 2-Methylamino-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide 
• 52069-01-9 2-Ethylamino-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide 
• 52069-05-3 5-Chloro-2-ethylamino-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide 
• 52068-99-2 5-Chloro-2-methylamino-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide 
• 22782-27-0 4-[2-(3-Methyl-3-p-tolyl-ureido)-ethyl]-benzenesulfonamide 
• 22781-80-2 4-{2-[3-(3,4-Dimethyl-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22781-65-3 4-{2-[3-(4-Isopropyl-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22782-24-7 4-{2-[3-(4-Chloro-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22950-19-2 4-{2-[3-(3-Chloro-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22782-19-0 4-{2-[3-(2-Chloro-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22781-54-0 4-{2-[3-(3-Methoxy-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22781-52-8 4-{2-[3-(4-Methoxy-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 
• 22764-83-6 4-{2-[3-(4-Chloro-phenyl)-3-ethyl-ureido]-ethyl}-benzenesulfonamide 
• 22764-87-0 4-{2-[3-(4-Ethoxy-phenyl)-3-methyl-ureido]-ethyl}-benzenesulfonamide 

Relevant articles and documents

Synthesis method of glibenclamide

The invention discloses a synthesis method of glibenclamide, which includes the steps of: 1) protection of amino groups with trichloroacetic anhydride; 2) sulfonation; 3) sulfo-amidation; 4) amidation: performing a reaction to 5-chloro-2-methoxybenzoic acid with N,N-carbonyl diimidazole and performing a reaction to the product with a compound (III) under effect of a second acid-binding agent; 5) addition: adding the second acid-binding agent and crown ether, in catalytic amount, to perform an addition reaction to a compound (IV) with cyclohexyl isocyanate to prepare the glibenclamide. The method is high in yields in all steps, wherein residue of impurities is effectively reduced during processes of protection, deprotection, acid treatment, alkali treatment and water-adding separation of the substrate. According to the method, a phase-transfer catalyst is matched with the second acid-binding agent, so that compatibility between the isocyanate and the compound (IV) is effectively increased, and the nucleophilic reaction is carried out more completely. The produced product is higher in purity.

Novel synthesis of mafenide and other amino sulfonamides by electrochemical reduction of cyano sulfonamides

Both aliphatic and aromatic amino sulfonamides such as mafenide (1a) were synthesized in good yields (80-86%) by direct electrochemical hydrogenation of the corresponding nitriles in an undivided cell containing a Ni cathode, a Pt anode, and Raney Ni as catalyst (Table 1). The reaction can be performed without external supply of pressurized gas by in situ generation of H2. Slightly elevated temperatures (45°) and low current densities (10 mA/cm2) are favorable conditions for this type of electrochemical nitrile hydrogenation. Our synthetic protocol does not require high-pressure equipment or chemical hazards, is environmentally very friendly, and more economical than traditional methods. The concentration of adsorbed H. radicals on the catalyst surface can be easily controlled by adjusting the electric potential, which may lead to improved product selectivity and, at the same time, reduces the risk of explosion and fire.