1939-99-7

Basic information

• Product Name: alpha-Toluenesulfonyl chloride
• Synonyms: Benzenemethanesulfonylchloride;Benzylsulfochloride;Methanesulfonyl chloride, phenyl-;Phenylmethane sulfo chloride;OTAVA-BB BB7020430779;PMS-CL;PHENYLMETHANESULFONYL CHLORIDE;PHENYLMETHYLSULFONYLCHLORIDE
• CAS NO: 1939-99-7
• Molecular Formula: C₇H₇ClO₂S
• Molecular Weight: 190.65
• EINECS: 217-717-1
• Product Categories: Pharmaceutical Intermediates;Benzene derivatives;Benzenesulfonyl chloride;Building Blocks;Chemical Synthesis;Organic Building Blocks;Sulfonyl Halides;Sulfur Compounds
• Mol File: 1939-99-7.mol

Chemical Properties

• Melting Point: 92-94 °C(lit.)
• Boiling Point: 120 °C / 10mmHg
• Flash Point: 128.1 °C
• Appearance: Almost white/Crystalline Powder
• Density: 1.3264 (estimate)
• Vapor Pressure: 0.0041mmHg at 25°C
• Refractive Index: 1.624-1.626
• Storage Temp.: Store below +30°C.
• Solubility: soluble in Toluene
• Water Solubility: decomposes
• Sensitive: Moisture Sensitive
• BRN: 972806
• CAS DataBase Reference: alpha-Toluenesulfonyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: alpha-Toluenesulfonyl chloride(1939-99-7)
• EPA Substance Registry System: alpha-Toluenesulfonyl chloride(1939-99-7)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• F: 10-21
• TSCA: T
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 1939-99-7(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
Alpha-Toluenesulfonyl chloride is used as a protecting group in organic synthesis, particularly for amines and alcohols. It is employed for the temporary protection of these functional groups during the course of a reaction, preventing them from participating in unwanted side reactions. The tosyl group can be easily introduced and later removed under mild conditions, making it a valuable tool in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, alpha-Toluenesulfonyl chloride is used as a reagent for the synthesis of various drugs and drug candidates. Its ability to react with a wide range of organic substrates allows for the creation of diverse chemical structures, which can be further modified to develop new therapeutic agents.
Used in Chemical Research:
Alpha-Toluenesulfonyl chloride is also utilized in academic and industrial research settings for the study of various chemical reactions and mechanisms. Its reactivity with different types of organic compounds makes it a valuable tool for probing the properties of various reaction intermediates and understanding the underlying reaction pathways.
Used in Peptide Synthesis:
In the field of peptide chemistry, alpha-Toluenesulfonyl chloride is used as a coupling agent to facilitate the formation of peptide bonds between amino acid residues. Its ability to activate carboxyl groups for nucleophilic attack by amines makes it a useful reagent for the synthesis of peptides and proteins.
Used in Synthesis of Dyes and Pigments:
Alpha-Toluenesulfonyl chloride is employed in the synthesis of certain dyes and pigments, where its reactivity with organic substrates allows for the creation of a variety of colored compounds with different shades and properties.

Synthesis Reference(s)

The Journal of Organic Chemistry, 16, p. 621, 1951 DOI: 10.1021/jo01144a013Synthesis, p. 1203, 1992 DOI: 10.1055/s-1992-26333

InChI:InChI=1/C7H7ClO2S/c8-11(9,10)6-7-4-2-1-3-5-7/h1-5H,6H2

Upstream product

• 150-60-7 dibenzyl disulphide 
• 16487-46-0 methyl N,N-dichlorocarbamate 
• 538-28-3 S-benzylisothiourea hydrochloride 
• 3012-37-1 benzyl thiocyanate 
• 4431-79-2 bis(benzylthio)methane 
• 100-53-8 phenylmethanethiol 
• 2547-61-7 Trichloromethanesulfonyl chloride 
• 538-74-9 dibenzyl sulfide 
• 3970-13-6 benzyl chloromethyl sulfide 
• 32188-59-3 ethane-1,1-diylbis(benzylsulfane) 
• 26504-28-9 dithiocarbonic acid S,S'-dibenzyl ester 
• 34243-40-8 2,2-bis-(thiobenzyl)propane 
• 98954-22-4 benzyl methoxymethyl sulfide 
• 57267-76-2 sodium α-toluenesulfonate 

Downstream Products

• 312924-71-3 C-phenyl-N-thiazol-2-yl-methanesulfonamide 
• 109600-83-1 4-methyl-7-(toluene-α-sulfonyloxy)-coumarin 
• 7469-39-8 N,O-bis-phenylmethanesulfonyl-L-tyrosine 
• 5434-03-7 phenylmethanesulfon-p-toluidide 
• 536-95-8 Carinamide 
• 56620-21-4 4-chlorophenylphenylmethane sulfonate 
• 110654-37-0 N-(4-nitrophenyl)-1-phenyl-methanesulfonamide 
• 4403-88-7 N-phenylmethanesulfonyl-sulfanilic acid amide 
• 4403-86-5 phenylmethanesulfonyl-sulfanilyl-amine 
• 19127-51-6 N,1-diphenylmethanesulfonamide 
• 32084-04-1 phenyl-methanesulfonic acid-(2-chloro-anilide) 
• 108879-14-7 bis-{2-[(4-amino-2-methyl-pyrimidin-5-ylmethyl)-formyl-amino]-1-(2-phenylmethanesulfonyloxy-ethyl)-trans-propenyl}-disulfide 
• 19299-41-3 N-methyl-1-phenylmethanesulfonamide 
• 15161-08-7 naphthalen-2-yl phenylmethanesulfonate 

Relevant articles and documents

TAPC-promoted synthesis of sulfonyl chlorides from sulfonic acids

A novel and efficient method is described for the preparation of sulfonyl chlorides from sulfonic acids using TAPC as chlorinating agent. Mild reaction conditions, shorter reaction times, high efficiencies, cost-effectiveness, and facile isolation of the desired products make the present methodology a practical alternative and will provide a valuable synthetic tool for various pharmaceutical applications. Georg Thieme Verlag Stuttgart · New York.

An efficient method for the preparation of sulfonyl chlorides: Reaction of disulfides or thiols with sodium hypochlorite pentahydrate (NaOCl·5H2O) crystals

The reaction of disulfides or thiols with sodium hypochlorite pentahydrate in acetic acid efficiently provided the corresponding sulfonyl chlorides in high yields.

Chromoselective Synthesis of Sulfonyl Chlorides and Sulfonamides with Potassium Poly(heptazine imide) Photocatalyst

Among external stimuli used to promote a chemical reaction, photocatalysis possesses a unique one—light. Photons are traceless reagents that provide an exclusive opportunity to alter chemoselectivity of the photocatalytic reaction varying the color of incident light. This strategy may be implemented by using a sensitizer capable to activate a specific reaction pathway depending on the excitation light. Herein, we use potassium poly(heptazine imide) (K-PHI), a type of carbon nitride, to generate selectively three different products from S-arylthioacetates simply varying the excitation light and otherwise identical conditions. Namely, arylchlorides are produced under UV/purple, sulfonyl chlorides with blue/white, and diaryldisulfides at green to red light. A combination of the negatively charged polyanion, highly positive potential of the valence band, presence of intraband states, ability to sensitize singlet oxygen, and multi-electron transfer is shown to enable this chromoselective conversion of thioacetates.

Facile synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazides

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.

Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction

In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.

Design, synthesis and evaluation of sulfonylurea-containing 4-phenoxyquinolines as highly selective c-Met kinase inhibitors

Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of 4-phenoxyquinoline derivatives bearing sulfonylurea moiety were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against tested four cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant potency as compared with foretinib, with the most promising compound 13x (c-Met kinase IC50 = 1.98 nM) demonstrated relatively good selectivity versus 10 other tyrosine kinases and remarkable cytotoxicities against HT460, MKN-45, HT-29 and MDA-MB-231 with IC50 values of 0.055 μM, 0.064 μM, 0.16 μM and 0.49 μM, respectively. The preliminary structure activity relationships indicated that a sulfonylurea moiety as linker as well as mono-EGWs (such as R1 = 4-F) on the terminal phenyl rings contributed to the antitumor activity.

High yielding protocol for direct conversion of thiols to sulfonyl chlorides and sulfonamides

In this paper, a new method for oxidative chlorination of thiols to sulfonyl chlorides and sulfonamides using H2O2 in the presence of TMSCl is reported. The excellent yields, short reaction times, excellent efficiencies, low costs, and easy separation of products are the most important advantages of this method.

Template-Assisted meta-C?H Alkylation and Alkenylation of Arenes

To expand the scope of meta-functionalization, a pyrimidine-based template effective for the formation of β-aryl aldehydes and ketones, using allyl alcohols, by meta-C?H activation of benzylsulfonyl esters is described. In addition, α,β-unsaturated aldehydes were generated by in situ olefination and deprotection of allyl benzyl ethers. These new functionalizations at the meta-position of an arene have also been successfully implemented in benzylphosphonate, phenethyl carbonyl, and phenethylsulfonyl ester scaffolds. Key to these successful new functionalizations is the creation of an electropositive palladium center by accepting the electron cloud from the metal to the energetically low-lying π-orbitals of pyrimidine ring, and it favors coordination of allyl alcohol to the metal center.

Rhodium-Catalyzed meta-C?H Functionalization of Arenes

Rhodium-catalyzed ortho-C?H functionalization is well known in the literature. Described herein is the Xphos-supported rhodium catalysis of meta-C?H olefination of benzylsulfonic acid and phenyl acetic acid frameworks with the assistance of a para-methoxy-substituted cyano phenol as the directing group. Complete mono-selectivity is observed for both scaffolds. A wide range of olefins and functional groups attached to arene are tolerated in this protocol.

Palladium-Catalyzed Remote meta-Selective C-H Bond Silylation and Germanylation

Selective meta-C-H activation of arenes to date has met with a limited number of functionalizations. Expanding the horizon of meta-C-H functionalization, herein we disclose an unprecedented meta-silylation and -germanylation protocol by employing a simple nitrile-based directing template. Longer linkers between the target site and the directing template were successfully explored for meta-silylation (sp2-? and sp2-ζ). Additionally, synthetic utility was demonstrated with several postsynthetic elaborations and with a formal synthesis of TAC101, a promising drug for the treatment of lung cancer.