5317-89-5

Basic information

• Product Name: N-(4-Acetylphenyl)methanesulfonamide
• Synonyms: Methanesulfonamide, N-(4-acetylphenyl)-;N-(4-Acetyl-phenyl)-methanesulfon-amide
• CAS NO: 5317-89-5
• Molecular Formula: C₉H₁₁NO₃S
• Molecular Weight: 213.2535
• Mol File: 5317-89-5.mol
• Article Data: 26

Chemical Properties

• Melting Point: 150-152 °C
• Boiling Point: 369.4 °C at 760 mmHg
• Flash Point: 177.2 °C
• Appearance: /
• Density: 1.32 g/cm³
• Vapor Pressure: 1.19E-05mmHg at 25°C
• Refractive Index: 1.573
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 7.16±0.10(Predicted)
• CAS DataBase Reference: N-(4-Acetylphenyl)methanesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-Acetylphenyl)methanesulfonamide(5317-89-5)
• EPA Substance Registry System: N-(4-Acetylphenyl)methanesulfonamide(5317-89-5)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 5317-89-5(Hazardous Substances Data)

Usage

General Description

N-(4-Acetylphenyl)methanesulfonamide, also known as N-(4'-Acetylphenyl)methanesulfonamide or Acetolamide, is a chemical compound with the molecular formula C9H11NO3S. It is a sulfonamide derivative and is often used as a carbonic anhydrase inhibitor in medicinal and pharmaceutical applications. Its chemical structure consists of an acetylphenyl group attached to a methanesulfonamide group, which gives it its carbonic anhydrase inhibiting properties. Acetolamide has been used in the treatment of glaucoma, epilepsy, and altitude sickness, and it has also been utilized as a diuretic. Its ability to inhibit carbonic anhydrase enzymes makes it a valuable compound in various medical and scientific research contexts.

InChI:InChI=1/C9H11NO3S/c1-7(11)8-3-5-9(6-4-8)10-14(2,12)13/h3-6,10H,1-2H3

Synthetic route

4-Aminoacetophenone (99-92-3) + methanesulfonyl chloride (124-63-0) → 4'-(methylsulfonylamino)acetophenone (5317-89-5)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 23h; Inert atmosphere;	100%
With pyridine In dichloromethane at 0 - 20℃; for 16h;	98%
In dichloromethane at 20 - 25℃; for 1h; Large scale;	96%

methanesulfonamide (3144-09-0) + para-bromoacetophenone (99-90-1) → 4'-(methylsulfonylamino)acetophenone (5317-89-5)

Conditions	Yield
With potassium phosphate; copper(l) iodide; dimethylaminoacetic acid In N,N-dimethyl-formamide for 48h; Heating;	96%
With bis(η3-allyl-μ-chloropalladium(II)); potassium carbonate; tert-butyl XPhos In 2-methyltetrahydrofuran at 80℃; for 6h; Inert atmosphere;	95%
With di-tert-butyl(2,2-diphenyl-1-methyl-1-cyclopropyl)phosphine; bis(η3-allyl-μ-chloropalladium(II)); sodium t-butanolate In water at 50℃; for 24h; Inert atmosphere; Green chemistry;	85%

N-(4-acetylphenyl)-N-(methylsulfonyl)methanesulfonamide → 1-[4-amino-3-(methylsulfonyl) phenyl] ethanone + 4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-methanesulfonylphenylamine (5470-49-5) + 4-Aminoacetophenone (99-92-3)

Conditions	Yield
In acetonitrile for 24h; Inert atmosphere; Irradiation;	A 26% B 12% C 5% D 30%

N-phenylmethanesulfonamide (1197-22-4) + acetic anhydride (108-24-7) → 4'-(methylsulfonylamino)acetophenone (5317-89-5)

Conditions	Yield
With aluminium trichloride In 1,2-dichloro-ethane Friedel-Crafts acylation;

4-Aminoacetophenone (99-92-3) + Methanesulfonic anhydride (7143-01-3) → 4'-(methylsulfonylamino)acetophenone (5317-89-5)

Conditions	Yield
With pyridine; sodium hydrogencarbonate In dichloromethane

4'-acetyl-2'-bromomethanesulfonanilide + 2,4-difluorophenol (367-27-1) → 4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide

Conditions	Yield
With pyridine; potassium carbonate; copper(l) chloride at 115℃; for 6h; Reagent/catalyst; Time; Ullmann Condensation; Inert atmosphere; Large scale;	A 35 %Chromat. B 54 %Chromat.

4'-(methylsulfonylamino)acetophenone (5317-89-5) → N-[4-(1-hydrazonoethyl)phenyl]methanesulfonamide

Conditions	Yield
With boron trifluoride diethyl etherate; hydrazine In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere;	99%

4'-(methylsulfonylamino)acetophenone (5317-89-5) → 4'-acetyl-2'-bromomethanesulfonanilide

Conditions	Yield
With bromine; acetic acid In water at 15℃; for 7h; Large scale; regiospecific reaction;	97%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + methyl iodide (74-88-4) → N-(4-acetyl-phenyl)-N-methyl-methanesulfonamide

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	93%

4'-(methylsulfonylamino)acetophenone (5317-89-5) → N-[4-(2-bromoacetyl)phenyl]methanesulfonamide (5577-42-4)

Conditions	Yield
With bromine; acetic acid at 55℃; for 0.25h; regiospecific reaction;	92%
With aluminium trichloride; bromine In chloroform at 0℃; for 0.5h;	81%
With tetra-N-butylammonium tribromide In methanol; dichloromethane at 20℃; for 19h; Inert atmosphere;	60%

4'-(methylsulfonylamino)acetophenone (5317-89-5) → 4'-(methylsulfonylamino)acetophenone oxime

Conditions	Yield
With pyridine; hydroxylamine hydrochloride at 70℃; for 3h;	91%
With hydroxylamine hydrochloride; sodium acetate In ethanol; water

4'-(methylsulfonylamino)acetophenone (5317-89-5) → N-[4-(1-hydroxyimino-ethyl)-phenyl]-methanesulfonamide (401909-82-8)

Conditions	Yield
With pyridine; hydroxylamine hydrochloride	88%
With hydrogenchloride; hydroxylamine; sodium acetate
With pyridine; hydroxylamine hydrochloride at 70℃; for 3h;
With pyridine; hydroxylamine hydrochloride

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d]pyrimidine (1383579-32-5) → N-(4-acetylphenyl)-N-({4-amino-2-(methylthio)furo[2,3-d]pyrimidin-5-yl}methyl)methanesulfonamide (1383579-39-2)

Conditions	Yield
Stage #1: 4'-(methylsulfonylamino)acetophenone With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0℃; for 0.166667h; Mitsunobu reaction; Stage #2: 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d]pyrimidine In tetrahydrofuran at 0 - 20℃; Mitsunobu reaction;	78%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 3,4,5-trimethoxy-benzaldehyde (86-81-7) → N-(4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In ethanol at 20℃;	78%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-chlorobenzaldehyde (104-88-1) → N-(4-(3-(4-chlorophenyl)acryloyl)phenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In ethanol at 20℃;	75%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-nitrobenzaldehdye (555-16-8) → N-(4-(3-(4-nitrophenyl)acryloyl)phenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In ethanol; water at 20℃;	75%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-(methylsulfonyl)phenylhydrazine hydrochloride (17852-67-4) → (E)-N-(4-(1-(2-(4-(methylsulfonyl)phenyl)hydrazono)ethyl)phenyl)methanesulfonamide

Conditions	Yield
In ethanol for 12h; Reflux;	66%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + methanesulfonyl chloride (124-63-0) → N-(4-acetylphenyl)-N-(methylsulfonyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In water for 0.5h;	59%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + ethylene glycol (107-21-1) → N-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)methanesulfonamide

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 18h; Dean-Stark; Reflux;	56%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-fluorobenzaldehyde (459-57-4) → N-{4-[3-(4-fluoro-phenyl)-acryloyl]-phenyl}-methanesulfonamide

Conditions	Yield
With sodium hydroxide In methanol at 25℃; Claisen-Schmidt condensation;	52%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + benzaldehyde (100-52-7) → N-(4-cinnamoylphenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In methanol at 25℃; Claisen-Schmidt condensation;	51%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-methyl-benzaldehyde (104-87-0) → N-[4-(3-p-tolyl-acryloyl)-phenyl]-methanesulfonamide

Conditions	Yield
With sodium hydroxide In methanol at 25℃; Claisen-Schmidt condensation;	45%

4'-(methylsulfonylamino)acetophenone (5317-89-5) → sotalol (3930-20-9, 27948-47-6, 30236-31-8, 30236-32-9)

Conditions	Yield
Stage #1: 4'-(methylsulfonylamino)acetophenone With iodine; dimethyl sulfoxide at 120℃; Stage #2: With isopropylamine In 1,2-dichloro-ethane at 25℃; for 2h; Stage #3: With sodium tetrahydroborate In 1,2-dichloro-ethane at 0℃; for 2h;	45%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 4-methoxy-benzaldehyde (123-11-5) → N-(4-(3-(4-methoxyphenyl)acryloyl)phenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In methanol at 25℃; Claisen-Schmidt condensation;	44%

pyrrolidine (123-75-1) + formaldehyd (50-00-0) + 4'-(methylsulfonylamino)acetophenone (5317-89-5) → 4'-[3-(1-pyrrolidinyl)propionyl]methanesulfonanilide (76467-72-6)

Conditions	Yield
In ethanol; water at 100℃; for 50h;	17%

4'-(methylsulfonylamino)acetophenone (5317-89-5) + 2-imidazolecarbaldehyde (10111-08-7) → (E)‐N‐(4‐(3‐(1H‐imidazol‐2‐yl)acryloyl)phenyl)methanesulfonamide

Conditions	Yield
With sodium hydroxide In ethanol; water at 60℃; for 7h; Michael Addition;	15%

4'-(methylsulfonylamino)acetophenone (5317-89-5) → (4-Methanesulfonylamino-phenyl)-oxo-acetic acid (61560-92-7)

Conditions	Yield
With pyridine; selenium(IV) oxide

4'-(methylsulfonylamino)acetophenone (5317-89-5) + bis(ethylheptylamino)methane (130350-69-5) → N-{4-[3-(Ethyl-heptyl-amino)-propionyl]-phenyl}-methanesulfonamide; hydrochloride

Conditions	Yield
With acetyl chloride 1.) THF, RT, 45 min, 2.) RT, 3 d; Yield given. Multistep reaction;

4'-(methylsulfonylamino)acetophenone (5317-89-5) + benzyl bromide (100-39-0) → N-<4-(1-oxoethyl)phenyl>-N-(phenylmethyl)methanesulfonamide (110698-70-9)

Conditions	Yield
With sodium methylate 1.) methanol, RT, 30 min, 2.) methanol, RT, 28 h; Yield given. Multistep reaction;

4'-(methylsulfonylamino)acetophenone (5317-89-5) → 4-methylsulfonamidophenacyl phenylacetate (919122-30-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / bromine; AlCl3 / CHCl3 / 0.5 h / 0 °C 2: 81 percent / triethylamine / acetonitrile / 1 h / 25 °C View Scheme

Upstream product

• 99-92-3 p-aminobenzophenone 
• 124-63-0 methanesulfonyl chloride 
• 187831-02-3 N-(4-acetylphenyl)-N-(methylsulfonyl)methanesulfonamide 
• 7143-01-3 Methanesulfonic anhydride 
• 3144-09-0 methanesulfonamide 
• 99-90-1 para-bromoacetophenone 
• 367-27-1 2,4-difluorophenol 
• 1197-22-4 N-phenylmethanesulfonamide 
• 108-24-7 acetic anhydride 

Downstream Products

• 5577-42-4 N-[4-(2-bromoacetyl)phenyl]methanesulfonamide 
• 187831-02-3 N-(4-acetylphenyl)-N-(methylsulfonyl)methanesulfonamide 
• 5470-49-5 4-methanesulfonylphenylamine 
• 99-92-3 p-aminobenzophenone 
• 61560-92-7 (4-Methanesulfonylamino-phenyl)-oxo-acetic acid 

Relevant articles and documents

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