874-87-3

Basic information

• Product Name: 4-(METHYLTHIO)BENZYL CHLORIDE
• Synonyms: P-(METHYLTHIO)BENZYL CHLORIDE;4-(METHYLTHIO)BENZYL CHLORIDE;4-(Chloromethyl)thioanisole;1-(chloromethyl)-4-(methylthio)benzene;P-(METHYLTHIO)BENZYL CHLORIDE (STABILIZED WITH CALCIUM CARBONATE);Einecs 212-870-0;4-(METHYLTHIO)BENZYL;4-Chloromethyl
• CAS NO: 874-87-3
• Molecular Formula: C₈H₉ClS
• Molecular Weight: 172.68
• EINECS: 212-870-0
• Product Categories: Organic Building Blocks;Sulfides/Disulfides;Sulfur Compounds
• Mol File: 874-87-3.mol

Chemical Properties

• Boiling Point: 116°C 8mm
• Flash Point: >230 °F
• Appearance: /
• Density: 1.170 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0179mmHg at 25°C
• Refractive Index: n20/D 1.6020(lit.)
• Storage Temp.: 2-8°C
• Water Solubility: It hydrolyzes in water.
• Sensitive: Moisture Sensitive
• CAS DataBase Reference: 4-(METHYLTHIO)BENZYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(METHYLTHIO)BENZYL CHLORIDE(874-87-3)
• EPA Substance Registry System: 4-(METHYLTHIO)BENZYL CHLORIDE(874-87-3)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 1760 8/PG 2
• WGK Germany: 3
• HazardClass: IRRITANT, STENCH, CORROSIVE
• PackingGroup: II
• Hazardous Substances Data: 874-87-3(Hazardous Substances Data)

Usage

Uses

4-(Methylthio)benzyl chloride is used as pharmaceutical intermediate.

Synthesis Reference(s)

The Journal of Organic Chemistry, 40, p. 1920, 1975 DOI: 10.1021/jo00901a011

InChI:InChI=1/C8H9ClS/c1-10-8-4-2-7(6-9)3-5-8/h2-5H,6H2,1H3

Upstream product

• 3446-90-0 4-(methylthio)benzyl alcohol 
• 100-68-5 methyl-phenyl-thioether 
• 107-30-2 chloromethyl methyl ether 
• 109-87-5 Dimethoxymethane 
• 75-09-2 dichloromethane 
• 13205-48-6 4-(methylthio)benzoic acid 
• 107-06-2 1,2-dichloro-ethane 
• 98-88-4 benzoyl chloride 
• 3795-79-7 methyl 4-(methylthio)benzoate 

Downstream Products

• 38746-92-8 2-[4-(methylsulfanyl)phenyl]acetonitrile 
• 19927-29-8 4-methylsulfanyl-benzyl thiocyanate 
• 107419-13-6 acetylamino-(4-methylsulfanyl-benzyl)-malonic acid diethyl ester 
• 3446-89-7 4-(Methylthio)benzaldehyde 
• 54759-21-6 C₂₀H₁₈O₂S 
• 92191-54-3 4-Methylbenzyl-phenyl-disulfid, 4-Methyl-thiobenzyl-phenylsulfid 
• 99810-15-8 3-chloropropyl p-(methylthio)benzyl sulfide 
• 72138-31-9 2-(p-Thiomethoxyphenyl)-3,3-dimethylmethylenecyclopropane 
• 72138-43-3 2-(p-Thiomethoxyphenyl)isopropylidenecyclopropane 
• 147643-69-4 2-<<<4-(methylthio)phenyl>methyl>amino>-5-fluoronitrobenzene 
• 97889-73-1 1,4,5-Trimethyl-6-(4-methylsulfanyl-benzyl)-1,2,3,6-tetrahydro-pyridine 
• 108836-62-0 1-[3-(4-Methoxy-benzyloxy)-2-(4-methylsulfanyl-benzyloxy)-propyl]-1H-imidazole 
• 58472-47-2 4-methylsulfinylbenzyl chloride 
• 144728-05-2 (4-Chloro-2-nitro-phenyl)-(4-methylsulfanyl-benzyl)-amine 

Relevant articles and documents

Mechanism of solvolysis of substituted benzyl chlorides in aqueous ethanol

The mechanism of solvolyses of activated ortho-, meta- and para-substituted benzyl chlorides in aqueous ethanol has been studied by using the Hammett-Brown and Yukawa-Tsuno treatments as well as by correlating logarithms of solvolysis rate constants with relative stabilities of corresponding benzyl carbocations in water calculated at the IEFPCM-M06–2X/6-311+G(3df,3pd) level of theory. Benzyl chlorides containing strong conjugative electron-donors in the para-position solvolyze by the SN1 mechanism, whereas other activated benzyl chlorides solvolyze by the SN2 mechanism via loose transition states.

Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols

Herein, a method for the nucleophilic substitution (SN) of benzyl alcohols yielding chloro alkanes is introduced that relies on aromatic sulfoxides as Lewis base catalysts (down to 1.5 mol-%) and benzoyl chloride (BzCl) as reagent. A systematic screening of various sulfoxides and other sulfinyl containing Lewis bases afforded (2-methoxyphenyl)methyl sulfoxide as optimal catalyst. In contrast to reported formamide catalysts, sulfoxides also enable the application of plain acetyl chloride (AcCl) as reagent. In addition, it was demonstrated that weakly electrophilic carboxylic acid chlorides like BzCl promote Pummerer rearrangement of sulfoxides already at room temperature. This side-reaction also provided the explanation, why sulfoxide catalyzed SN-reactions of alcohols do not allow the effective production of aliphatic and electron deficient chloro alkanes. Comparison experiments provided further insight into the reaction mechanism.

Photo film derivative and its preparation and use

The invention relates to the field of medicinal chemistry, in particular relates to a spiroketal derivative with a structure in a general formula (I) and a preparation method and an application thereof, and provides a spiroketal derivative or a pharmaceutically acceptable salt, an isomer, a prodrug or a solvate thereof. The structure of the spiroketal derivative is as shown in a general formula I in the specification, wherein R1 is selected from methylsulfonylphenyl, 4-pyridyl or phenyl; and R2 is selected from substituted or non-substituted lower alkyl. The spiroketal derivative with the general formula I provided by the invention has good agonist activity on GPR119, can be used as a GRP119 agonist, and can be further used for preparing medicines for treating diabetes mellitus.

METHOD OF CONVERTING ALCOHOL TO HALIDE

The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.

Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.

Design, synthesis and evaluation of the inhibitory selectivity of novel trans-resveratrol analogues on human recombinant CYP1A1, CYP1A2 and CYP1B1

A series of trans-stilbene derivatives containing 4′-methylthio substituent were synthesized and evaluated for inhibitory activities on human recombinant cytochrome P450(s): CYP1A1, CYP1A2, and CYP1B1. CYP1A2-related metabolism of stilbene derivatives was estimated by using NADPH oxidation assay. Additionally, for CYP1A2 and CYP1B1 molecular docking analysis was carried out to provide information on enzyme-ligand interactions and putative site of metabolism. 3,4,5-Trimethoxy-4′-methylthio-trans-stilbene, an analogue of DMU-212 (3,4,5,4′-tetramethoxy-trans-stilbene) was an effective inhibitor of all CYP1 enzymes. On the other hand, 2,3,4-trimethoxy-4′-methylthio- trans-stilbene, appeared to be the most selective inhibitor of the isozymes CYP1A1 and CYP1B1, displaying extremely low affinity towards CYP1A2. Molecular modeling suggested that the most probable binding poses of the methylthiostilbene derivatives in CYP1A2 active sites are those with the methylthio substituent directed towards the heme iron. Products of CYP1A2-catalyzed oxidation of 2,4,5-trimethoxy-4′-methylthiostilbene and 3,4,5-trimethoxy-4′-methylthiostilbene were identified as monohydroxylated compounds. Other studied derivatives appeared to be poor substrates of CYP1A2. Structure-activity relationship analysis rendered better understanding of the mechanism of action of xenobiotic-metabolizing enzymes crucial at the early stage of carcinogenesis.

NOVEL TETRAHYDRO-1H-PYRIDO [4,3-b] INDOLE DERIVATIVES AS CB1’ RECEPTOR LIGANDS

Compounds of Formulae I, or pharmaceutically acceptable salts thereof: wherein R1, R2 and R3 are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

Synthesis and selective cyclooxygenase-2 (COX-2) inhibitory activity of a series of novel bicyclic pyrazoles

Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3- oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human whole blood (HWB). Several of the compounds were found to be novel and selective COX-2 inhibitors, the most potent and selective being 1-(5-cyclohexyl (2H,3H-pyrazolo[5,1-b]-1,3- oxazolidin-6-yl)-4-(methylsulfonyl)benzene, 7a (IC5o for COX-1>100 μM; for COX-2=1.3 μM).

PYRAZOLOPYRIDINE DERIVATES

New compounds of formula (I) and the salts, solvates and prodrugs thereof, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as p38 kinase inhibitors.

2-THIO-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE IN PHARMACEUTICS

The invention relates to 2-thio-substituted imidazole derivatives of formula (I), wherein the radicals R1, R2, R3 and m have the meanings as cited in the description. The inventive compounds comprise an immunomodulatory action and/or an action that inhibits the release of cytokines and are thus suited for treating diseases associated with a disorder of the immune system.