80-48-8

Basic information

• Product Name: Methyl p-toluenesulfonate
• Synonyms: 4-methyl-benzenesulfonicacimethylester;Benzenesulfonicacid,4-methyl-,methylester;Methyl 4-methylbenzenesulfonate;Methyl ester of 4-methylbenzenesulfonic acid;Methyl para-toluenesulfonate;Methyl p-methylbenzenesulfonate;Methyl toluene-4-sulfonate;methyl4-methylbenzenesulfonate
• CAS NO: 80-48-8
• Molecular Formula: C₈H₁₀O₃S
• Molecular Weight: 186.23
• EINECS: 201-283-5
• Product Categories: Organic Building Blocks;Sulfur Compounds;Tosylates;Building Blocks;Chemical Synthesis;Organic Building Blocks;Sulfur Compounds
• Mol File: 80-48-8.mol
• Article Data: 68

Chemical Properties

• Melting Point: 25-28 °C(lit.)
• Boiling Point: 144-145 °C5 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: White to yellow/Liquid or Low Melting Solid
• Density: 1.234 g/mL at 25 °C(lit.)
• Vapor Density: 6.45 (vs air)
• Vapor Pressure: 1 mm Hg ( 20 °C)
• Refractive Index: n20/D 1.5172(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• Water Solubility: Insoluble
• Sensitive: Moisture Sensitive
• BRN: 609209
• CAS DataBase Reference: Methyl p-toluenesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl p-toluenesulfonate(80-48-8)
• EPA Substance Registry System: Methyl p-toluenesulfonate(80-48-8)

Safety Data

• Hazard Codes: C,Xn
• Statements: 22-34-43-40-36/37/38
• Safety Statements: 26-36/37/39-45-24
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• RTECS: XT7000000
• F: 21
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 80-48-8(Hazardous Substances Data)

Usage

Chemical Properties

white to slightly yellow low melting solid. Soluble in alcohol, ether, benzene, insoluble in water. Hygroscopic.

Uses

Different sources of media describe the Uses of 80-48-8 differently. You can refer to the following data:
1. Methyl p-Toluenesulfonate can be used in the manufacture of dyes and organic synthesis, and also is the raw materials of methylation.
2. Methyl p-toluenesulfonate is used as a methylating agent in organic synthesis. It acts as a catalyst for alkyd resins. It is also employed in selective 1-substitution reaction of tetrazole. Further, it is used in the preparation of dyes.

Preparation

Methyl p-toluenesulfonate was synthesized by the reaction of p-toluenesulfonyl chloride with methanol. Mix p-toluenesulfonyl chloride and methanol, slowly add 25% sodium hydroxide solution, control the temperature below 25 °C, stop adding alkali when the pH is 9, continue stirring for 2 hours, and leave overnight. The lower layer of reactant was taken, the upper layer was extracted with benzene, the extract was recovered with benzene and then combined with the lower layer, washed with water and 5% potassium carbonate solution in turn, dried and distilled under reduced pressure to obtain the finished product of methyl p-toluenesulfonate.

Synthesis Reference(s)

Chemical and Pharmaceutical Bulletin, 29, p. 623, 1981 DOI: 10.1248/cpb.29.623Synthetic Communications, 15, p. 1057, 1985 DOI: 10.1080/00397918508076842

General Description

Methyl p-toluenesulfonate is sulfonate ester present as potentially genotoxic impurity in drug substances. Kinetics of reactions of methyl p-toluenesulfonate with N,N-dimethylaniline has been investigated. It participates in selective 1-substitution reaction of tetrazole.

Hazard

Toxic by ingestion and inhalation, strongirritant to skin and eyes.

Safety Profile

Poison by ingestion and subcutaneous routes. An eye and severe skin irritant. A vesicant and skin sensitizer. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits toxic fumes of SOx.

Purification Methods

The ester is purified by distillation in vacuo and could be crystallised from pet ether or Et2O/pet ether at low temperature. It is a powerful methylating agent, is TOXIC andis a skin irritant, so it is better to purify it by repeated distillation. [IR: Schreiber Anal Chem 21 1168 1949, Buehler et al. J Org Chem 2 167 1937, Roos et al. Org Synth Coll Vol I 145 1948, Beilstein 11 IV 247.]

InChI:InChI=1/C8H10O3S/c1-7-3-5-8(6-4-7)12(9,10)11-2/h3-6H,1-2H3

Upstream product

• 493-02-7 trans-Decalin 
• 80-11-5 N-methyl-N-nitrosotoluene-p-sulfonamide 
• 100-66-3 methoxybenzene 
• 98-95-3 nitrobenzene 
• 108-90-7 chlorobenzene 
• 67-56-1 methanol 
• 98-59-9 p-toluenesulfonyl chloride 
• 124-41-4 sodium methylate 
• 16836-95-6 silver(I) 4-methylbenzenesulfonate 
• 74-88-4 methyl iodide 
• 599-91-7 propyl tosylate 
• 756-79-6 dimethyl methane phosphonate 
• 80-40-0 ethyl ester of p-toluenesulfonic acid 
• 536-57-2 p-toluene sulfinic acid 

Downstream Products

• 123127-12-8 8,8-dimethyl-3endo-phenacyl-nortropanium; toluene-4-sulfonate 
• 109-02-4 4-methyl-morpholine 
• 109438-78-0 1-ethyl-1-methyl-piperidinium; toluene-4-sulfonate 
• 694-85-9 1-methyl-2-pyridone 
• 38542-71-1 N-methylpyridinium p-toluenesulfonate 
• 116998-58-4 1-methyl-pyrimidinium; toluene-4-sulfonate 
• 7327-42-6 1-Methyl-4-vinylpyridinium p-Toluenesulfonate 
• 53920-49-3 N-methoxypyridinium p-toluenesulfonate 
• 7403-46-5 2-chloro-1-methylpyridinium p-toluenesulfonate 
• 16183-05-4 2,3,4-trimethyl-thiazolium; toluene-4-sulfonate 
• 25985-99-3 N-methoxy-2-methylpyridinium tosylate 
• 1703-18-0 1-methoxy-4-pyridone 
• 4594-71-2 N-methylisocarbostyril 
• 53890-40-7 N-Methyl-isoquinoline tosylate 

Relevant articles and documents

Ring contraction of N-acetyl-2-aryl-1,2,3,4-tetrahydro-4-quinolones with [hydroxy(tosyloxy)iodo]benzene to trans methyl N-acetyl-2-aryl-2,3-dihydroindol- 3-carboxylates

The ring contraction of N-acetyl-2-aryl-1,2,3,4-tetrahydro-4-quinolones with [hydroxy(tosyloxy)iodo]benzene to trans methyl N-acetyl-2-aryl-2,3- dihydroindol-3-carboxylates in trimethylorthoformate in good yield is described.

Grob-type fragmentation of 5-oxabicyclo[2.1.1]hexane system: A strategy for synthesis of annulated and 2,2,5-trisubstituted tetrahydrofurans

Acid mediated, efficient Grob-type fragmentation reaction facilitated by vicinal ketal and ester moieties in variety of 5-oxabicyclo[2.1.1]hexanes leading to the corresponding annulated and 2,2,5-trisubstituted tetrahydrofurans is reported. Among the Br?nsted and Lewis acids tested, BF 3·OEt2 appears to give the best results, furnishing near quantitative yield (>99%) of tetrahydrofuran tricarboxylate derivatives under mild reaction condition. In case of unsymmetrical monosubstituted 5-oxabicyclo[2.1.1]hexanes two regioisomeric products are obtained. A strategy to transform one of the ester groups of the title compounds to protected hydroxymethyl moiety was evolved, which allows access to differentially protected 2-hydroxymethyl THF derivatives upon fragmentation. Employing TiCl4/R or S-BINOL as chiral Lewis acid, an enantioselective fragmentation (up to 66% ee) was described for the meso bis-furan derivative.

A Scalable Metal-, Azide-, and Halogen-Free Method for the Preparation of Triazoles

A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

A simple method for the synthesis of sulfonic esters

An efficient and simple approach for the direct synthesis of aryl and heteroaryl sulfonic esters was developed using DMS and DES as alkoxysulfonylation reagents. The reaction is operationally simple and scalable. This protocol does not require solvent, expensive catalysts, base, ligand additives or other reagents. A wide range of sulfonic esters were synthesized in moderate to good chemical yields. This method has the advantage of low cost, facile and tolerated a wide range of substrates.