138-37-4

Basic information

• Product Name: Mafenide hydrochloride
• Synonyms: masudin;morfanil;p-aminomethylphenylsulfonamidehydrochloride;sulfamylonhydrochloride;sulfbenzaminehydrochloride;MARFANIL;MARFANIL HYDROCHLORIDE;MAFENIDE HYDROCHLORIDE
• CAS NO: 138-37-4
• Molecular Formula: C7H11ClN2O2S
• Molecular Weight: 222.69
• EINECS: 205-325-3
• Mol File: 138-37-4.mol
• Article Data: 0

Chemical Properties

• Melting Point: 261-263 °C(lit.)
• Boiling Point: 382 °C at 760 mmHg
• Flash Point: 184.8 °C
• Appearance: /
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Merck: 13,5671
• CAS DataBase Reference: Mafenide hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Mafenide hydrochloride(138-37-4)
• EPA Substance Registry System: Mafenide hydrochloride(138-37-4)

Safety Data

• Hazard Codes: Xn
• Statements: 42/43
• Safety Statements: 22-36/37-45
• WGK Germany: 2
• RTECS: XT5425000
• Hazardous Substances Data: 138-37-4(Hazardous Substances Data)

Usage

Uses

Antibacterial;Inhibitor of folic acid biosynthesis

Purification Methods

Crystallise the salt from dilute HCl or 95% EtOH and dry it in a vacuum at 100o. It is an antibacterial. [Miller et al. J Am Chem Soc 62 2099 1940, Bergeim & Barker J Am Chem Soc 66 1459 1944.] The sulfate salt has m 254-255o (from aqueous EtOH). [Beilstein 14 III 2223, 14 IV 2799.]

InChI:InChI=1/C7H10N2O2S.2ClH/c8-5-6-1-3-7(4-2-6)12(9,10)11;;/h1-4H,5,8H2,(H2,9,10,11);2*1H

Synthetic route

tert-butyl 2-(2-formyl-1H-imidazol-1-yl)acetate (1226869-60-8) + mafenide hydrochloride (138-37-4) → tert-butyl 2,2′-(2,2′-(4-sulfamoylbenzylazanediyl)bis(methylene)-bis(1H-imidazole-2,1-diyl))diacetate (1228647-88-8)

Conditions	Yield
Stage #1: tert-butyl 2-(2-formyl-1H-imidazol-1-yl)acetate; mafenide hydrochloride 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;	99%

mafenide hydrochloride (138-37-4) + sodium 3,5-bis(bis((ethoxycarbonyl)methyl)aminomethyl)benzoate → {[3-[(bis-ethoxycarbonylmethyl-amino)-methyl]-5-(4-sulfamoyl-benzylcarbamoyl)-benzyl]-ethoxycarbonylmethyl-amino}-acetic acid ethyl ester (662165-89-1)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In chloroform; N,N-dimethyl-formamide at 20℃; for 12h;	98%

2,6-dichloropyrido[3,2-d]pyrimidin-4-ol (1036738-13-2) + mafenide hydrochloride (138-37-4) → 4-[(6-chloro-4-hydroxy-pyrido[3,2-d]pyrimidin-2-ylamino)-methyl]-benzenesulfonamide (1036738-14-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 110 - 120℃; for 3h;	97%

methyl adipoyl chloride (35444-44-1) + mafenide hydrochloride (138-37-4) → 5-(4-Sulfamoyl-benzylcarbamoyl)-pentanoic acid methyl ester (928211-28-3)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 7h;	95%

thiophosgene (463-71-8) + mafenide hydrochloride (138-37-4) → 4-(isothiocyanatomethyl)benzenesulfonamide (51929-73-8)

Conditions	Yield
With concentrated hydrochloric acid In water	95%

benzyl [2‑(1H‑benzo[d][1,2,3]triazol‑1‑yl)‑2‑oxoethyl]carbamate (173459-80-8) + mafenide hydrochloride (138-37-4) → benzyl (2-oxo-2-((4-sulfamoylbenzyl)amino)ethyl)carbamate

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

C21H23N5O4S + mafenide hydrochloride (138-37-4) → benzyl (S)-(4-(methylthio)-1-oxo-1-((2-oxo-2-((4-sulfamoylbenzyl)amino)ethyl)amino)butan-2-yl)carbamate

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

tert-butyl (1-(1H-benzo[d][1,2,3]triazol-1-yl)-1-oxo-3-phenylpropan-2-yl)carbamate + mafenide hydrochloride (138-37-4) → tert-butyl (R)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate

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

mafenide hydrochloride (138-37-4) + O2,O3,O4,O6,S-Pentaacetyl-1-thio-β-D-glucopyranose (6806-56-0, 13639-50-4, 51898-27-2, 62860-10-0, 63783-77-7, 92217-67-9, 92217-68-0, 130796-15-5) → C21H28N2O11S2 (1219708-35-6)

Conditions	Yield
Stage #1: O2,O3,O4,O6,S-Pentaacetyl-1-thio-β-D-glucopyranose With Diethyl 2-bromomalonate In methanol at 20℃; for 0.333333h; Inert atmosphere; Stage #2: mafenide hydrochloride With N-ethyl-N,N-diisopropylamine In methanol at 20℃; Inert atmosphere;	94%

Tetrabromophthalic anhydride (632-79-1) + mafenide hydrochloride (138-37-4) → 4-((4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl)methyl)benzenesulfonamide hydrochloride

Conditions	Yield
With acetic acid at 130℃; for 1.5h; Inert atmosphere;	94%

mafenide hydrochloride (138-37-4) + (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-sulfamoylbenzyl)amino)propan-2-yl)carbamate

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

C24H29N5O4S2 + mafenide hydrochloride (138-37-4) → benzyl ((S)-4-(methylthio)-1-(((S)-4-(methylthio)-1-oxo-1-((4-sulfamoylbenzyl)amino)butan-2-yl)amino)-1-oxobutan-2-yl)carbamate

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

mafenide hydrochloride (138-37-4) + 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1<*>4)-2,3,6-tri-O-acetyl-1-S-acetyl-1-thio-β-D-glucopyranose (20728-70-5) → C33H44N2O19S2 (1219708-38-9)

Conditions	Yield
Stage #1: 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1<*>4)-2,3,6-tri-O-acetyl-1-S-acetyl-1-thio-β-D-glucopyranose With Diethyl 2-bromomalonate In methanol at 20℃; for 0.333333h; Inert atmosphere; Stage #2: mafenide hydrochloride With N-ethyl-N,N-diisopropylamine In methanol at 20℃; Inert atmosphere;	93%

mafenide hydrochloride (138-37-4) + benzyl N-[(1S)-2-(1H-1,2,3-benzotriazol-1-yl)-1-methyl-2-oxoethyl]carbamate (820239-42-7) → (S)-benzyl (1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)carbamate

Conditions	Yield
In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	93%

C33H31N5O4S + mafenide hydrochloride (138-37-4) → benzyl ((S)-1-(((R)-3-(benzylthio)-1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	93%

4-bromo-1,8-naphthalenedicarboxylic anhydride (81-86-7) + mafenide hydrochloride (138-37-4) → C19H13BrN2O4S

Conditions	Yield
With triethylamine at 80℃; for 8h;	92%
With triethylamine In ethanol at 80℃; for 8h; Temperature;	92%

C21H23N5O4S + mafenide hydrochloride (138-37-4) → benzyl (R)-(2-((4-(methylthio)-1-oxo-1-((4-sulfamoylbenzyl)amino)butan-2-yl)amino)-2-oxoethyl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	91%

C28H29N5O4S + mafenide hydrochloride (138-37-4) → benzyl ((S)-4-(methylthio)-1-oxo-1-(((S)-1-oxo-3-phenyl-1-((4-sulfamoylbenzyl)amino)propan-2-yl)amino)butan-2-yl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	91%

C25H21N5O3 + mafenide hydrochloride (138-37-4) → benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate

Conditions	Yield
With triethylamine In dichloromethane at 70℃; for 0.5h; Microwave irradiation;	91%

tetrachlorophthalic anhydride (117-08-8) + mafenide hydrochloride (138-37-4) → 4-((4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)methyl)benzenesulfonamide hydrochloride

Conditions	Yield
With acetic acid at 130℃; for 1.5h; Inert atmosphere;	90%

Cbz-Ala-Met-Bt (1452153-98-8) + mafenide hydrochloride (138-37-4) → benzyl ((S)-1-(((S)-4-(methylthio)-1-oxo-1-((4-sulfamoylbenzyl)amino)butan-2-yl)amino)-1-oxopropan-2-yl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	90%

4-(2-(N,N-diethylamino)acetyl)amino-1,8-naphthalic anhydride + mafenide hydrochloride (138-37-4) → C25H26N4O5S

Conditions	Yield
With triethylamine In ethanol at 85℃; for 3h;	90%

diethylenetriaminepentaacetic dianhydride (23911-26-4) + mafenide hydrochloride (138-37-4) → {{2-[carboxymethyl-(2-{carboxymethyl-[(4-sulfamoyl-benzylcarbamoyl)-methyl]-amino}-ethyl)-amino]-ethyl}-[(4-sulfamoyl-benzylcarbamoyl)-methyl]-amino}-acetic acid

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	89%

C19H20N4O3 (1173817-60-1) + mafenide hydrochloride (138-37-4) → benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)-butan-2-yl)carbamate

Conditions	Yield
With triethylamine In dichloromethane at 70℃; for 0.5h; Microwave irradiation;	89%

mafenide hydrochloride (138-37-4) + methyl (2,3,4-tri-O-acetyl-1-S-acetyl-1-thio-β-D-glucopyranosyl)uronate (314079-40-8) → C20H26N2O11S2 (1219708-37-8)

Conditions	Yield
Stage #1: methyl (2,3,4-tri-O-acetyl-1-S-acetyl-1-thio-β-D-glucopyranosyl)uronate With Diethyl 2-bromomalonate In methanol at 20℃; for 0.333333h; Inert atmosphere; Stage #2: mafenide hydrochloride With N-ethyl-N,N-diisopropylamine In methanol at 20℃; Inert atmosphere;	88%

mafenide hydrochloride (138-37-4) + N-(2-benzylthio-4-chloro-5-methyl-benzenesulfonyl)cyanamide potassium salt → 2-(2-benzylthio-4-chloro-5-methylbenzenesulfonyl)-3-(4-sulfamoylbenzyl)guanidine

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 20h; Reflux;	88%

mafenide hydrochloride (138-37-4) + 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrahydro-8-carboxylic acid (113942-30-6) → 3-methyl-4-oxo-N-(4-sulfamoylbenzyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃; Inert atmosphere;	88%

C27H27N5O4S + mafenide hydrochloride (138-37-4) → benzyl ((S)-1-(((R)-3-(benzylthio)-1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)amino)-1-oxopropan-2-yl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	88%

benzyl N-{(S)-1-[(S)-2-benzotriazol-1-yl-1-methyl-2-oxoethylcarbamoyl]-3-methylsulfanylpropyl}carbamate (886981-43-7) + mafenide hydrochloride (138-37-4) → benzyl ((S)-4-(methylthio)-1-oxo-1-(((S)-1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)amino)butan-2-yl)carbamate

Conditions	Yield
With triethylamine In tetrahydrofuran at 70℃; for 0.5h; Microwave irradiation;	88%

9H-fluoren-9-ylmethyl N-[(1S)-1-benzyl-2-benzotriazol-1-yl-2-oxoethyl]carbamate (860800-19-7) + mafenide hydrochloride (138-37-4) → (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate

Conditions	Yield
With triethylamine In dichloromethane at 70℃; for 0.5h; Microwave irradiation;	88%

Downstream Products

• 24489-26-7 5-methyl-isoxazole-3-carboxylic acid 4-sulfamoyl-benzylamide 
• 796871-26-6 4-{[(4,6-dichloro-1,3,5-triazin-2-yl)amino]methyl}-benzene-1-sulfonamide 
• 50889-01-5 4-nitro-N-(4-sulfamoylbenzyl)-benzamide 
• 1219708-39-0 C₃₃H₄₄N₂O₁₉S₂ 
• 1219708-38-9 C₃₃H₄₄N₂O₁₉S₂ 
• 1219708-37-8 C₂₀H₂₆N₂O₁₁S₂ 
• 1219708-35-6 C₂₁H₂₈N₂O₁₁S₂ 
• 1219708-36-7 C₂₁H₂₈N₂O₁₁S₂ 
• 1202699-05-5 N-({5-[({[4-(aminosulfonyl)phenyl]methyl}amino)carbonyl]-1-cyclohexyl-4.6-dihydroxy-2-oxo-1,2-dihydro-3-pyridinyl}carbonyl)glycine 
• 948054-25-9 4-aminomethyl-N¹-nitrobenzenesulfonamide 
• 1311200-31-3 DL-2-[4-chloro-6-(4-sulfamoylbenzylamino)-1,3,5-triazin-2-ylamino]-3-(3,4-dihydroxyphenyl)propanoic acid 
• 1311200-30-2 3-[4-chloro-6-(4-sulfamoylbenzylamino)-1,3,5-triazin-2-ylamino]propanoic acid 
• 1311200-29-9 DL-2,2'-[6-(4-sulfamoylbenzylamino)-1,3,5-triazine-2,4-diyl]bis(azanediyl)dipropanoic acid 
• 1311200-28-8 dimethyl 2,2'-[6-(4-sulfamoylbenzylamino)-1,3,5-triazine-2,4-diyl]bis(azanediyl)diacetate