75-75-2

Basic information

• Product Name: Methanesulfonic acid
• Synonyms: SULFOMETHANE;MSA;acidemethanesulfonique;Kyselina methansulfonova;kyselinamethansulfonova;Methylsulphonicacid;Sulphonethane;METHANESULFONIC ACID
• CAS NO: 75-75-2
• Molecular Formula: CH₄O₃S
• Molecular Weight: 96.11
• EINECS: 200-898-6
• Product Categories: HPLC;HPLC Buffer;HPLC Buffers;HPLC Buffers - SolutionChromatography/CE Reagents;Solution;Chromatography/CE Reagents;Eluent concentrates for ICAlphabetic;Ion Chromatography;M;META - METH;Chemical Synthesis;Organic Acids;Synthetic Reagents;Organic AcidsAnalytical Reagents;Products for Amino Acid Hydrolysis;Amino Acid Analysis;Essential Chemicals;Reagent Plus;Routine Reagents;Others;Supported Reagents;Supported Synthesis;Agrochemical Intermediates, Pharmaceutical Intermediates
• Mol File: 75-75-2.mol
• Article Data: 90

Chemical Properties

• Melting Point: 19 °C
• Boiling Point: 167 °C10 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: brown/Solution
• Density: 1.481 g/mL at 25 °C(lit.)
• Vapor Density: 3.3 (vs air)
• Vapor Pressure: 1 mm Hg ( 20 °C)
• Refractive Index: n20/D 1.429(lit.)
• Storage Temp.: 2-8°C
• Solubility: water: soluble1,000 g/L at 20°C
• PKA: -2.6(at 25℃)
• Water Solubility: Miscible with water. Slightly miscible with benzene and toluene. Immiscible with paraffins.
• Sensitive: Light Sensitive & Hygroscopic
• Stability: Stable. Moisture sensitive. Incompatible with amines, bases, water, common metals. Releases a substantial amount of heat when di
• Merck: 14,5954
• BRN: 1446024
• CAS DataBase Reference: Methanesulfonic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Methanesulfonic acid(75-75-2)
• EPA Substance Registry System: Methanesulfonic acid(75-75-2)

Safety Data

• Hazard Codes: C
• Statements: 34-22-21/22-35
• Safety Statements: 26-36-45-1/2-36/37/39
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 1
• RTECS: PB1140000
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 75-75-2(Hazardous Substances Data)

Usage

Uses

Used in Chemical Industry:
Methanesulfonic acid is used as a dehydrating agent, curing accelerator for coating, treating agent for fiber, solvent, catalysis, and esterification as well as polymerization reaction. It is also used as a solvent, alkylation, catalyst of esterification and polymerization.
Used in Pharmaceutical Industry:
Methanesulfonic acid is used in the manufacturing of active pharmaceutical ingredients like telmisartan and eprosartan. It is also involved in the deprotection of peptides and for complete protein and peptide hydrolysis with tryptophan recovery.
Used in Pesticide Industry:
Methanesulfonic acid is a raw material for the production of pesticides.
Used in Electroplating Industry:
Methanesulfonic acid is used in the electroplating industry.
Used in Polymerization:
Methanesulfonic acid has been developed as a polymerization catalyst, offering advantages over sulfuric acid as it is not an oxidizing species.
Used in Organic Reactions:
Methanesulfonic acid is used as a catalyst in organic reactions such as esterification, alkylation, and condensation reactions due to its non-volatile nature and solubility in organic solvents. It is also involved in the production of starch esters, wax oxidate esters, benzoic acid esters, phenolic esters, or alkyl esters.
Used in Batteries:
Methanesulfonic acid finds application in batteries because of its purity and absence of chloride.
Used in Ion Chromatography:
Methanesulfonic acid is useful in ion chromatography.
Used in Methylotrophic Bacteria:
Methanesulfonic acid serves as a source of carbon and energy for some gram-negative methylotrophic bacteria.

Production method

It can be obtained through the nitrate oxidation of thiocyanate methyl. Nitric acid and negative water are heated carefully to 80-88 °C with fractional addition of methyl thiocyanate and the temperature being automatically rose to about 105 ℃. After the reaction becomes mild, the reaction was heated to 120 ° C and reacted for 5 hours to obtain a crude product. The crude product was diluted with exchanged water and adjusted to pH 8-9 by addition of 25% barium hydroxide solution and filtered. The filtrate is condensed to until crystalline precipitation. The crystal is washed by methanol to remove the nitrate to obtain the barium methanesulfonate. It is then added to the exchanged water to boiling, add sulfuric acid for decomposition while it is hot, filter and the filtrate was concentrated under vacuum to no water to obtain the finished product. Another method is that the methyl isothiourea sulfate is successively subject to chlorination, oxidation and hydrolysis to derive the finished product. Methyl isothiourea sulfate was added to the water; and the chlorine is sent into at 20-25 ° C to until phenomenon such as solution color is turned into yellow; oil layer emerges in the bottom of the bottle; the temperature drop and large number of residual chlorine is discharged from the exhaust pipe; this indicates the end point of the reaction. The reaction solution was extracted with chloroform. After drying, the extract was distilled at 60-62 ° C under normal pressure to remove the chloroform, and then further subject to distillation under reduced pressure. Collect the 60-65 °C (2.67 kPa) fraction was to obtain the methanesulfonyl chloride. Add the base drop wise under stirring to 80 ℃ hot water and maintain the heat hydrolysis for about 2h, to until the reaction liquid droplets completely disappear. The reaction solution was concentrated under reduced pressure to a syrupy form, diluted with water, and concentrated under reduced pressure to until no more water was distilled off to obtain methanesulfonic acid.

Preparation

Methanesulfonic acid is produced predominantly by oxidizing methylthiol or dimethyl disulfide using nitric acid, hydrogen peroxide, chlorine or by employing electrochemical processes.

Hazard

Toxic by ingestion, skin irritant, corrosiveto tissue.

Safety Profile

Poison by ingestion and intraperitoneal routes. May be corrosive to skin, eyes, and mucous membranes. Explosive reaction with ethyl vinyl ether. Incompatible with hydrogen fluoride. When heated to decomposition it emits toxic fumes of SOx. See also SULFONATES.

Purification Methods

Dry the acid, either by azeotropic removal of water with *benzene or toluene, or by stirring 20g of P2O5 with 500mL of the acid at 100o for 0.5hours. Then distil it under vacuum and fractionally crystallise it by partial freezing. Sulfuric acid, if present, can be removed by prior addition of Ba(OH)2 to a dilute solution, filtering off the BaSO4 and concentrating under reduced pressure; and is sufficiently pure for most applications. [Beilstein 4 IV 10.]

InChI:InChI=1/2CH4O3S.Fe/c2*1-5(2,3)4;/h2*1H3,(H,2,3,4);/q;;+2/p-2

Synthetic route

methanol (67-56-1) + methanesulfonic phosphoric anhydride, diisopropyl ester (82220-45-9) → methanesulfonic acid (75-75-2) + diisopropyl methyl phosphate (26955-63-5, 129149-78-6)

Conditions	Yield
for 1h; Ambient temperature;	A 100% B 98%

methylthiol (74-93-1) → methanesulfonic acid (75-75-2)

Conditions	Yield
With dihydrogen peroxide; methanesulfonic acid In water at 40 - 110℃; for 10h;	100%
With dihydrogen peroxide In water at 35 - 45℃; for 10h;	100%
With nitric acid at 80℃; for 8h; Concentration; Temperature;	93.75%
With Mg(2+)*O4V(3-)*C19H42N(1+); dihydrogen peroxide In acetonitrile at 20 - 40℃; for 25h; Reagent/catalyst; Temperature;	63.9%

methanol (67-56-1) + methanesulfonic phosphoric anhydride, diethyl ester (4972-37-6) → methanesulfonic acid (75-75-2) + diethyl methyl phosphate (867-17-4)

Conditions	Yield
for 1h; Ambient temperature;	A 91% B 99%

methanesulfonic acid sodium salt (2386-57-4) → methanesulfonic acid (75-75-2)

Conditions	Yield
With hydrogenchloride In water at 40℃; for 3h; Temperature;	98.4%

Methanesulfonic anhydride (7143-01-3) → methanesulfonic acid (75-75-2)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide at 10 - 50℃; under 60006 - 90009 Torr; for 10h; Inert atmosphere;	97%
Product distribution / selectivity;

(1,1-dioxido-4-oxo-3-phenyl-4H-thiochromen-2-yl)methyl methanesulfonate → methanesulfonic acid (75-75-2) + C16H10O3S (1033736-87-6)

Conditions	Yield
In chloroform-d1 for 0.216667h; Photolysis; Inert atmosphere;	A 96% B n/a

methane (34557-54-5) → methanesulfonic acid (75-75-2)

Conditions	Yield
With sulfuric acid; alumina; sulfur trioxide; dihydrogen peroxide In water at 50℃; under 21002.1 - 75007.5 Torr; for 3.5h; Reagent/catalyst; Autoclave;	95%
With Methyl methanesulfonate; sulfur trioxide In fluorosulphonic acid at 50℃; under 75007.5 Torr; for 10h;	93%
With sulfur trioxide at 50℃; under 75007.5 Torr; Autoclave;	91%

Dimethyldisulphide (624-92-0) → methanesulfonic acid (75-75-2)

Conditions	Yield
With nitric acid at 80℃; for 6h; Temperature;	93.8%
With Mg(2+)*O4V(3-)*C19H42N(1+); water; oxygen In acetonitrile at 90℃; under 30003 Torr; for 24h; Reagent/catalyst; Pressure; Temperature; Autoclave;	92%
With oxygen In methanol at 30 - 40℃; for 14h; Irradiation;	65%

1-(methanesulfonoyloxy)-2(1H)-quinolone (1404369-05-6) → methanesulfonic acid (75-75-2) + 2-quinolone (59-31-4, 70254-42-1)

Conditions	Yield
In methanol; water Quantum yield; UV-irradiation; Photolysis;	A 90% B n/a

methane (34557-54-5) → methanesulfonic acid (75-75-2) + Methanesulfonic anhydride (7143-01-3)

Conditions	Yield
With sulfuric acid; sulfur trioxide; dihydrogen peroxide at 50℃; under 75007.5 Torr; Large scale;	A 82% B n/a

methanethiosulfonic acid S-methyl ester (2949-92-0) → formic acid (64-18-6) + methanesulfonic acid (75-75-2) + Dimethoxymethane (109-87-5) + Methyl formate (107-31-3)

Conditions	Yield
With oxygen In methanol Irradiation;	A n/a B 72% C n/a D n/a

methanesulfonyl chloride (124-63-0) → hydrogenchloride (7647-01-0) + methanesulfonic acid (75-75-2)

Conditions	Yield
With water for 5h; Time; Large scale;	A n/a B 70.2%

4-mesyloxy-2-methylbutene (80352-66-5) → methanesulfonic acid (75-75-2) + isoprene (78-79-5)

Conditions	Yield
at 310℃; under 115 Torr; for 0.133333h; Rate constant; Thermodynamic data; var. of initial pressure, temp., Ea, with addition of propene, toluene;	A n/a B 62.3%

4-methanesulfonyloxy-1-butene (40671-34-9) → methanesulfonic acid (75-75-2) + buta-1,3-diene (106-99-0)

Conditions	Yield
at 300.2℃; under 88 Torr; for 0.2h; Rate constant; Thermodynamic data; var. of initial pressure, temp., Ea, with addition of propene, toluene;	A n/a B 47.8%

dimethylsulfide (75-18-3) → methanesulfonic acid (75-75-2) + dimethylsulfone (67-71-0) + S-methyl thioformate (27798-35-2) + dimethyl sulfoxide (67-68-5)

Conditions	Yield
With dihydrogen peroxide; oxygen at 10.85℃; under 750.06 Torr; Product distribution; Kinetics; Further Variations:; Temperatures; Oxidation; Photolysis;	A n/a B n/a C n/a D 46.3%

N-Trichloracetyl-dimesylamin (120622-89-1) → methanesulfonic acid (75-75-2) + dimesylamine (5347-82-0) + N-Mesyl-trichloracetyl-amin

Conditions	Yield
With water In acetonitrile 1.) 40 deg C, 144 h, 2.) 60 deg C, 24 h;	A n/a B n/a C 26%

Dimethyldisulphide (624-92-0) → methanesulfonic acid (75-75-2) + methanethiosulfonic acid S-methyl ester (2949-92-0) + methyl bisulfate (75-93-4) + methyl methanesulfinate (666-15-9)

Conditions	Yield
With oxygen In methanol at 30 - 40℃; for 9.5h; Irradiation; with Pyrex Filter;	A 7.1% B 6.2% C n/a D n/a

1,4-dioxane (123-91-1) + Perbenzoic acid (93-59-4) + chloroform (67-66-3) + bis-methanesulfonyl-bis-methylsulfanyl-methane (408309-55-7) → methanesulfonic acid (75-75-2) + tris-methanesulfonyl-methane (4610-99-5)

methyl thiocyanate (556-64-9) → methanesulfonic acid (75-75-2)

Conditions	Yield
With nitric acid
With nitric acid
With hydrogenchloride; acetic acid at 30 - 40℃; elektrolytische Oxydation;
With calcium chloride

methyl magnesium iodide (917-64-6) → methanesulfonic acid (75-75-2)

Conditions	Yield
With diethyl ether; sulfur dioxide man zersetzt das Reaktionsprodukt mit Wasser und erwaermt die waessr.Loesung mit Brom;

Perbenzoic acid (93-59-4) + chloroform (67-66-3) + tetrathioorthocarbonic acid tetramethyl ester (6156-25-8) → methanesulfonic acid (75-75-2) + tris-methanesulfonyl-methane (4610-99-5)

Dimethyldisulphide (624-92-0) → methanesulfonic acid (75-75-2) + Methanesulfonic anhydride (7143-01-3)

Conditions	Yield
With air; Nitrogen dioxide at 30 - 80℃;

3-aminopropranesulfonic acid (26209-83-6) → methanesulfonic acid (75-75-2)

Conditions	Yield
With nitric acid at 200℃;

trichloromethane sulfonic Acid (27153-10-2) → methanesulfonic acid (75-75-2)

Conditions	Yield
With amalgamated potassium
Durch elektrische Reduktion in neutraler Loesung;
bei der elektrolytischen Reduktion in neutraler Loesung;

N,N'-bis-(4-methanesulfinyl-but-3-enyl)-urea (505053-33-8) + acetic acid (64-19-7) → methanesulfonic acid (75-75-2)

Conditions	Yield
bei der Ozonolyse und folgenden Oxydation mit 30prozentig.H2O2; (-)-N.N'-bis-<4-methanesulfinyl-buten-(3)-yl>-urea;

dimethyl sulfate (77-78-1) → methanesulfonic acid (75-75-2)

Conditions	Yield
With ammonium sulfite Behandeln des erhaltenen Ammonium-methansulfonats mit konz.Schwefelsaeure;
With methanol; sodium sulfite das Natriumsalz ensteht;
With water; sodium sulfite das Natriumsalz;
With Trifluoromethanesulfonyl fluoride

diethyl sulphite (623-81-4) + methyl iodide (74-88-4) → methanesulfonic acid (75-75-2)

Conditions	Yield
With potassium hydroxide

methyl iodide (74-88-4) → methanesulfonic acid (75-75-2)

Conditions	Yield
With alkali sulfite
With acidic alkali sulfite
With ammonium bisulfite; water
With alkali sulfite

methanol (67-56-1) + O,O-diethyl S-methyl phosphorothioate (2404-05-9) → methanesulfonic acid (75-75-2) + diethyl methyl phosphate (867-17-4)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid

propan-1-ol (71-23-8) + O,O-diethyl S-methyl phosphorothioate (2404-05-9) → methanesulfonic acid (75-75-2) + diethyl n-propyl phosphate (814-22-2)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid

methanesulfonic acid (75-75-2) + 2-methyl-3-buten-2-ol (115-18-4) + Δ3-Isopentenyl methyl sulfide (5952-75-0) → isopentenyl methyl prenyl sulfonium methane sulfonate (100669-10-1)

Conditions	Yield
In dichloromethane for 72h; Ambient temperature;	100%

methanesulfonic acid (75-75-2) + Bpoc-Ala-OMaq → CH3SO3H*H-Ala-OMaq

Conditions	Yield
In dichloromethane for 1h; Ambient temperature;	100%

methanesulfonic acid (75-75-2) + N-allyl-N-<4-<(4-amidinophenoxy)carbonyl>-α-methylcinnamoyl>glycine ethyl ester hydrochloride → p-(p-amidinophenoxycarbonyl)-α-methylcinnamic acid N-allyl-N-ethoxycarbonylmethylamide methanesulphonate

Conditions	Yield
In chloroform at 25℃; for 1h;	100%

methanesulfonic acid (75-75-2) + ethanol (64-17-5) + trans-[4-(6-amidinobenzo[b]thiophen-2-carboxamido)cyclohexyloxy]acetic acid trifluoroacetate → ethyl trans-[4-[(6-amidinobenzo[b]thien-2-yl)carbonylamino]cyclohexyloxy]acetate methanesulfonate

Conditions	Yield
for 1h; Esterification; Heating;	100%

methanesulfonic acid (75-75-2) + erlotinib hydrochloride (183319-69-9) → N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, methanesulfonic acid salt

Conditions	Yield
Stage #1: erlotinib hydrochloride With sodium hydroxide In water; ethyl acetate at 60 - 70℃; pH=10 - 11; Stage #2: methanesulfonic acid In ethyl acetate Heating / reflux;	100%
Stage #1: erlotinib hydrochloride With sodium hydroxide In water; ethyl acetate pH=8 - 9; Stage #2: In isopropyl alcohol Stage #3: methanesulfonic acid at 62 - 70℃; for 34h;	93%
Stage #1: erlotinib hydrochloride With sodium hydrogencarbonate In dichloromethane; water Stage #2: In isopropyl alcohol Stage #3: methanesulfonic acid	69%
Stage #1: erlotinib hydrochloride With 50percent NaOH In water; ethyl acetate at 50℃; for 0.25h; Stage #2: methanesulfonic acid at 50℃; for 4h; Further stages.;	111.76 g

methanesulfonic acid (75-75-2) + (R)-benzyl 9-(1-acetylpiperidin-4-yl)-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-ylcarbamate (885609-08-5) → (R)-9-(1-acetylpiperidin-4-yl)-7-amino-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one methanesulfonate

Conditions	Yield
With methoxybenzene In diethyl ether; dichloromethane at 20℃; for 2.5h;	100%

methanesulfonic acid (75-75-2) → methanol (67-56-1)

Conditions	Yield
With zeolite beads at 120 - 385℃; Product distribution / selectivity;	100%

7-{2-[4-(5-fluoro-3a,7a-dihydro-1H-indol-3-yl)-piperidin-1-yl]-ethyl}-4,5-dihydro-1H-pyrrolo[3,2,1-hi]indol-2-one + methanesulfonic acid (75-75-2) → 7-{2-[4-(5-fluoro-3a,7a-dihydro-1H-indol-3-yl)-piperidin-1-yl]-ethyl}-4,5-dihydro-1H-pyrrolo[3,2,1-hi]indol-2-one methanesulfonate

Conditions	Yield
In tetrahydrofuran at 0℃; for 0.5h;	100%

7-{2-[4-(6-fluoro-3a,7a-dihydro-1H-indol-3-yl)-piperidin-1-yl]-ethyl}-4,5-dihydro-1H-pyrrolo[3,2,1-hi]indol-2-one + methanesulfonic acid (75-75-2) → 7-{2-[4-(6-fluoro-3a,7a-dihydro-1H-indol-3-yl)-piperidin-1-yl]-ethyl}-4,5-dihydro-1H-pyrrolo[3,2,1-hi]indol-2-one bismethanesulfonate

Conditions	Yield
In tetrahydrofuran at 0℃; for 0.5h;	100%

TD-6301 (690999-15-6) + methanesulfonic acid (75-75-2) → 4-{N-[7-((3-(S)-1-carbamoyl-1,1-diphenylmethyl)pyrrolidin-1-yl)hept-1-yl]-N-(isopropyl)amino}-1-(4-methoxypyrid-3-ylmethyl)piperidine trimethanesulfonic acid salt

Conditions	Yield
In water; acetonitrile pH=5;	100%
In acetonitrile pH=5;	100%

benzyl 1-[4-(3-cyclohexyl-1-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]-4-piperidinyl(methyl)carbamate + methanesulfonic acid (75-75-2) → 3-Cyclohexyl-1-methyl-6-{4-[4-(methylamino)-1-piperidinyl]phenyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one monomethanesulfonate (553670-59-0)

Conditions	Yield
With hydrogen; 10% palladium on activated carbon In methanol at 20℃;	100%

methanesulfonic acid (75-75-2) + 9-(3-O-benzyl-5-O-(methanesulfonyl)-4-C-[[(methanesulfonyl)oxy]methyl]-2-O-trifluormethanesulfonyl-α-L-threo-pentofuranosyl)-6-N-benzoyladenine (625111-37-7) → 1-(2',3'-epoxide-4-C-methanesulfonyloxymethyl-5-O-methanesulfonyl-2-deoxy-α-L-erythro-pentofuranosyl)-6-benzoyl adenine-9-yl (625111-44-6)

Conditions	Yield
In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 0 - 20℃;	100%

1-isopropylsulfonyl-2-amino-6-(2-(methyl)-5-(2,4-difluorophenyl)-imidazol-4-yl)-benzimidazole + methanesulfonic acid (75-75-2) → 1-isopropylsulfonyl-2-amino-6-(2-(methyl)-5-(2,4-difluorophenyl)-imidazol-4-yl)-benzimidazole methanesulfonate

Conditions	Yield
In methanol; dichloromethane	100%

(S)-1,4-di-(t-butoxycarbonyl)-2-(4-((R)-3-hydroxypyrrolidino)phenyl)piperazine (769944-57-2) + methanesulfonic acid (75-75-2) → (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-(methansulfonyloxy)pyrrolidin-1-yl)phenyl)piperazine (769944-58-3)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 0.333333h;	100%

6-[2-ethoxy-4-(3-methyl-butylamino-methyl)-phenoxy]nicotinamide (676494-41-0) + methanesulfonic acid (75-75-2) → 6-[4-((3-methyl-butylamino)-methyl)-2-ethoxyphenoxy]nicotinamide methanesulfonate salt (676495-42-4)

Conditions	Yield
In tetrahydrofuran	100%

methanesulfonic acid (75-75-2) + [9-(2,2-dimethyl-propyl)-8-oxo-3,6,7,8,9,10-hexahydro-2,3,9-triaza-(R)-cyclohepta[e]inden-7-yl]-carbamic acid benzyl ester (885608-22-0) → 7-(R)-amino-9-(2,2-dimethyl-propyl)-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one bismethanesulfonate

Conditions	Yield
With methoxybenzene In dichloromethane at 20℃; for 2.5h;	100%
With methoxybenzene In diethyl ether; dichloromethane at 20℃; for 3h;	100%
With methoxybenzene In dichloromethane at 20℃; for 2.5h;	100%

methanesulfonic acid (75-75-2) + 4-(7-(R)-benzyloxycarbonylamino-8-oxo-6,7,8,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-9-yl)-piperidine-1-carboxylic acid tert-butyl ester (885608-47-9) → (R)-benzyl 8-oxo-9-(piperidin-4-yl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-ylcarbamate methanesulfonate (885609-06-3)

Conditions	Yield
With methoxybenzene In dichloromethane at 20℃; for 0.5h;	100%
With methoxybenzene In diethyl ether; dichloromethane at 20℃; for 1h;	100%
With methoxybenzene In diethyl ether; dichloromethane at 20℃; for 1h;	100%

tert-butyl 4-(4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamido)piperidine-1-carboxylate (844443-90-9) + methanesulfonic acid (75-75-2) → 4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-yl-amide methanesulphonic salt

Conditions	Yield
In 1,4-dioxane at 80 - 105℃; for 1.5 - 25h; Industry scale;	100%
In 1,4-dioxane at 80 - 105℃; for 1 - 24h; Product distribution / selectivity;	99.4%
In 1,4-dioxane at 80 - 105℃; Product distribution / selectivity;	98.5%

methanesulfonic acid (75-75-2) + N-{4-[(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)(cyano)amino]phenyl}-N'-(5-methyl-pyridin-2-yl)pyrazine-2,3-dicarboxamide (890052-11-6) → N-[4-(2-imino-1,3-oxazolidin-3-yl)phenyl]-N'-(5-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide methanesulfonate

Conditions	Yield
In acetonitrile at 20℃;	100%

methanesulfonic acid (75-75-2) + N-{4-[(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)(cyano)amino]phenyl}-N'-(5-cyanopyridin-2-yl)pyrazine-2,3-dicarboxamide (890052-12-7) → N-(5-cyanopyridin-2-yl)-N'-[4-(2-imino-1,3-oxazolidin-3-yl)phenyl]pyrazine-2,3-dicarboxamide methanesulfonate

Conditions	Yield
In acetonitrile at 20℃;	100%

6-{4-[5-(4-chloro-3-trifluoromethyl-phenylamino)-4H-[1,2,4]triazol-3-yl]-phenoxy}-pyrimidine-2,4-diamine + methanesulfonic acid (75-75-2) → 6-{4-[5-(4-chloro-3-trifluoromethyl-phenylamino)-4H-[1,2,4]triazol-3-yl]-phenoxy}-pyrimidine-2,4-diamine methanesulfonic acid salt

Conditions	Yield
In methanol for 0.5h;	100%

methanesulfonic acid (75-75-2) + perphenazine N-Boc-4-aminobutyrate (503537-30-2) → 4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazineethyl 4-aminobutyryl ester trimesylate

Conditions	Yield
In acetic acid butyl ester; acetonitrile at 40℃; for 16h; Product distribution / selectivity; Inert atmosphere; Industry scale;	100%
In acetonitrile at 40℃; for 5h;	98%
In acetone at 40℃; for 4h; Product distribution / selectivity;	83%

1-{1-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea (936241-19-9) + methanesulfonic acid (75-75-2) → 1-{1-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea mesylate

Conditions	Yield
In dichloromethane at 20℃; for 1h; Product distribution / selectivity;	100%

methanesulfonic acid (75-75-2) + (CH3)3PBH2P(C6H5)2BH3 (122971-97-5) → (CH3)3PBH2P(C6H5)2BH2OSO2CH3 (122953-48-4)

Conditions	Yield
With potassium hydrogencarbonate In dichloromethane MeOSO3 added to a soln. of the borane, KHCO3 added, stirring, mixture passed through a column (silica gel, ethylacetate; concg. (vac.), elem. anal.;	100%

methanesulfonic acid (75-75-2) + (CH3)3PBH2P(C6H5)2BH2P(C6H5)2BH3 (122953-49-5) → (CH3)3PBH2P(C6H5)2BH2P(C6H5)2BH2SO3CH3 (132140-40-0)

Conditions	Yield
With potassium hydrogencarbonate In dichloromethane after 30 min reaction KHCO3 added, stirring; mixture passed through a column (silica gel, ethyl acetate), filtrate concentrated (vac.);	100%

methanesulfonic acid (75-75-2) + (1S,2S)-2-(2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenylamino)cyclopentyl 2-(tert-butoxycarbonylamino)acetate (1073969-87-5) → (1S,2S)-2-(2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenylamino)cyclopentyl 2-aminoacetate methanesulfonate (1073969-68-2)

Conditions	Yield
Stage #1: (1S,2S)-2-(2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenylamino)cyclopentyl 2-(tert-butoxycarbonylamino)acetate With trifluoroacetic acid In dichloromethane at 0℃; for 0.583333h; Stage #2: methanesulfonic acid In dichloromethane	100%

methanesulfonic acid (75-75-2) + 1-tert-butyl 3-ethyl 3-{[(6-methoxy-2-naphthyl)oxy]methyl}azetidine-1,3-dicarboxylate (1078166-64-9) → ethyl 3-{[(6-methoxy-2-naphthyl)oxy]methyl}azetidine-3-carboxylate mesylate

Conditions	Yield
In Isopropyl acetate at 40℃; for 18h;	100%

1-methyl-1H-imidazole (616-47-7) + methanesulfonic acid (75-75-2) → 1-methylimidazolium methylsulfonate (630393-13-4)

Conditions	Yield
at 20℃; for 5.5h; Cooling with ice;	100%
at 0 - 20℃;
at 20℃; Cooling with ice;

Upstream product

• 556-64-9 methyl thiocyanate 
• 16156-50-6 n-hexyl methanesulfonate 
• 124-63-0 methanesulfonyl chloride 
• 66-27-3 Methyl methanesulfonate 
• 108-90-7 chlorobenzene 
• 120622-89-1 N-Trichloracetyl-dimesylamin 
• 1001-62-3 bis(methanesulfonyl)peroxide 
• 75-05-8 acetonitrile 
• 75-18-3 dimethylsulfide 
• 22223-61-6 thionitrous acid S-methyl ester 
• 7446-11-9 sulfur trioxide 
• 108-24-7 acetic anhydride 
• 123-56-8 Succinimide 
• 1255094-23-5 CH₃O₃S^(1-)*C₁₂H₂₂N₄O₂PSSe⁽¹⁺⁾ 

Downstream Products

• 16156-54-0 sec-butyl methanesulfonate 
• 926-06-7 isopropyl methanesulfonate 
• 514-10-3 abietic acid 
• 62-50-0 Ethyl methanesulfonate 
• 19826-89-2 α-methanesulfonyloxy-p-bromoacetophenone 
• 99860-58-9 (1R,2R)-2-amino-3-dichloroacetoxy-1-(4-nitro-phenyl)-propan-1-ol 
• 875224-81-0 5-cyano-2-methyl-6-oxo-4-phenoxymethyl-3,4,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester 
• 67-56-1 methanol 
• 66-27-3 Methyl methanesulfonate 
• 115-10-6 Dimethyl ether 
• 503-40-2 methanedisulfonic acid 
• 124-63-0 methanesulfonyl chloride 
• 7143-01-3 Methanesulfonic anhydride 
• 10595-21-8 1-benzothiazol-2-yl-pyrazolidin-3-one 

Relevant articles and documents

A high-yield approach to the sulfonation of methane to methanesulfonic acid initiated by H2O2 and a metal chloride

Low temperatures and low pressures suffice for the sulfonation of methane with a suitable free-radical initiator and promoter [Eq. (1)]. Since the RhCl3 promoter can be recycled, and the initiator complex is stable and easy to handle, development of this reaction into an industrial process is promising. MSA = methanesulfonic acid.

Direct catalytic sulfonation of methane with SO2 to methanesulfonic acid (MSA) in the presence of molecular O2

Methane is transformed selectively to methanesulfonic acid at low temperature by liquid-phase sulfonation of methane with SO2 and O2 in the presence of Pd- and Cu-salts as the catalysts.

A novel method for the direct sulfonation of CH4 with SO 3 in the presence of KO2 and a promoter

Direct sulfonation of methane with SO3 to methanesulfonic acid (MSA) is accomplished in sulfuric acid in the presence of a small amount of KO2 as the free radical initiator and a metal chloride. Of the several metal chlorides examined, RhCl3 was found to be the most effective promoter. While KO2 alone can activate methane, the conversion of SO3 to MSA increases 2.3-fold when KO2 and RhCl3 are both present in the reaction mixture. The effects of different process parameters such as temperature, SO3 concentration, methane pressure, KO2 concentration, and RhCl3 concentration have been examined on the rate of reaction. The reaction is optimized at a KO2-to-RhCl3 molar ratio of 3.16. Strongly acidic solvents such as H2SO4 or CF3SO 3H are necessary for the reaction. No MSA was formed when the reaction was carried out in DMSO. A mechanism is proposed to explain the activation of CH4 to form MSA. A critical part of the sequence is in situ formation of a metal-peroxo species via the reaction of KO2, acid solvent, and RhCl3.

Direct liquid-phase sulfonation of methane to methanesulfonic acid by SO3 in the presence of a metal peroxide

Activation of methane by metal peroxides: Calcium peroxide serves as an effective radical initiator in the liquid-phase sulfonation of methane to methansulfonic acid (MSA) by SO3 [Eq. (1)]. Under the best reaction conditions a 91% conversion of SO3 to MSA was achieved.

Activation of methane to CH3 +: A selective industrial route to methanesulfonic acid

Direct methane functionalization to value-added products remains a challenge because of the propensity for overoxidation in many reaction environments. Sulfonation has emerged as an attractive approach for achieving the necessary selectivity. Here, we report a practical process for the production of methanesulfonic acid (MSA) from only two reactants: methane and sulfur trioxide. We have achieved >99% selectivity and yield of MSA. The electrophilic initiator based on a sulfonyl peroxide derivative is protonated under superacidic conditions, producing a highly electrophilic oxygen atom capable of activating a C–H bond of methane. Mechanistic studies support the formation of CH3 + as a key intermediate. This method is readily scalable with reactors connected in series for prospective production of up to 20 metric tons per year of MSA.

AgII-Mediated Electrocatalytic Ambient CH4 Functionalization Inspired by HSAB Theory

Although most class (b) transition metals have been studied in regard to CH4 activation, divalent silver (AgII), possibly owing to its reactive nature, is the only class (b) high-valent transition metal center that is not yet reported to exhibit reactivities towards CH4 activation. We now report that electrochemically generated AgII metalloradical readily functionalizes CH4 into methyl bisulfate (CH3OSO3H) at ambient conditions in 98 % H2SO4. Mechanistic investigation experimentally unveils a low activation energy of 13.1 kcal mol?1, a high pseudo-first-order rate constant of CH4 activation up to 2.8×103 h?1 at room temperature and a CH4 pressure of 85 psi, and two competing reaction pathways preferable towards CH4 activation over solvent oxidation. Reaction kinetic data suggest a Faradaic efficiency exceeding 99 % beyond 180 psi CH4 at room temperature for potential chemical production from widely distributed natural gas resources with minimal infrastructure reliance.

Direct sulfonation of methane to methanesulfonic acid by sulfur trioxide catalyzed by cerium(IV) sulfate in the presence of molecular oxygen

Direct sulfonation of methane with SO3 to methanesulfonic acid (MSA) is accomplished in sulfuric acid with almost 100% selectivity in the presence of a catalyst, namely, Ce and Rh salts and molecular oxygen as the catalyst regenerator. In the absence of O2, the catalyst remains effective but the selectivity to MSA decreases to 53% and byproducts, principally CH3OSO3H, are formed. The effects of O 2 pressure, catalyst concentration, temperature, SO3 concentration, and methane pressure have been examined on the rate of SO 3 conversion to MSA. The conversion of SO3 to MSA was the same when CF3SO3H was used as the solvent instead of H2SO4.

Direct sulfonation of methane to methanesulfonic acid with SO2 using Ca salts as promoters

Direct liquid-phase sulfonation of methane to methanesulfonic acid (MSA) with SO2 has been achieved in triflic acid using K2S2O8 as the oxidant and a small amount of a Ca salt as the promoter. The effects of reaction conditions on the conversion of SO2 to MSA were examined. Included were the influence of solvent acidity, reaction duration, reaction temperature, amount of K2S2O8, and composition and amount of promoters. Copyright

PROCESS FOR MANUFACTURING ALKANESULFONIC ACIDS

The present invention relates to an improved process for manufacturing of alkanesulfonic acids.

PROCESS FOR THE PRODUCTION OF ALKANESULFONIC ACIDS

A process for the manufacturing of alkanesulfonic acid by reaction of an alkane with an anhydride in the presence of sulfuric acid and a starter at ambient temperature or higher and under pressure.