352-11-4

Basic information

• Product Name: alpha-Chloro-p-fluorotoluene
• Synonyms: Benzene, 1-(chloromethyl)-4-fluoro-;à-chloro-4-fluorotoluene;4-Fluorobenzyl chloride 99%;p-Fluorbenzylchlorid;5) PARA FLUORO BENZYL CHLORIDE;α-Chloro-4-fluorotoluene, 1-Chloromethyl-4-fluorobenzene;4-Fluorophenylmethyl chloride;4-Fluoro-1-(chloromethyl)benzene
• CAS NO: 352-11-4
• Molecular Formula: C₇H₆ClF
• Molecular Weight: 144.57
• EINECS: 206-516-4
• Product Categories: Fluorine series
• Mol File: 352-11-4.mol

Chemical Properties

• Melting Point: -18 °C
• Boiling Point: 82 °C26 mm Hg(lit.)
• Flash Point: 141 °F
• Appearance: Yellow/Powder or Crystals
• Density: 1.207 g/mL at 25 °C(lit.)
• Vapor Pressure: 37.2mmHg at 25°C
• Refractive Index: n20/D 1.513(lit.)
• Storage Temp.: Store below +30°C.
• Solubility: Chloroform (Slightly), Hexanes (Slightly)
• Explosive Limit: 1.30%(V)
• Water Solubility: 417mg/L(temperature not stated)
• Sensitive: Lachrymatory
• BRN: 742272
• CAS DataBase Reference: alpha-Chloro-p-fluorotoluene(CAS DataBase Reference)
• NIST Chemistry Reference: alpha-Chloro-p-fluorotoluene(352-11-4)
• EPA Substance Registry System: alpha-Chloro-p-fluorotoluene(352-11-4)

Safety Data

• Hazard Codes: C
• Statements: 34-22
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 2920 8/PG 2
• WGK Germany: 2
• F: 19
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 352-11-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Alpha-Chloro-p-fluorotoluene is used as a chemical intermediate for the synthesis of various pharmaceutical products. Its unique structure allows for the creation of a wide range of medicinal compounds with diverse therapeutic applications, including antibiotics, anti-inflammatory drugs, and central nervous system agents. The presence of the chlorine and fluorine atoms in its molecular structure facilitates various chemical reactions, making it an essential building block in the development of new drugs.
Used in Agricultural Industry:
In addition to its applications in the pharmaceutical industry, alpha-Chloro-p-fluorotoluene is also utilized as a chemical intermediate in the synthesis of agricultural goods. It plays a crucial role in the production of various agrochemicals, such as pesticides, herbicides, and fungicides, which are essential for maintaining crop health and increasing agricultural productivity. The versatility of alpha-Chloro-p-fluorotoluene in chemical reactions enables the development of novel and effective agrochemicals to combat pests and diseases in the agricultural sector.
Used in Chemical Research:
Due to its unique chemical properties and reactivity, alpha-Chloro-p-fluorotoluene is also employed in various research applications. It serves as a valuable starting material for the synthesis of complex organic molecules and is used in the development of new synthetic methods and reaction pathways. Researchers in the field of organic chemistry often utilize alpha-Chloro-p-fluorotoluene to study the effects of different functional groups on the reactivity and stability of aromatic compounds, contributing to the advancement of chemical knowledge and the discovery of new compounds with potential applications in various industries.

InChI:InChI:1S/C7H6ClF/c8-5-6-1-3-7(9)4-2-6/h1-4H,5H2

Upstream product

• 50-00-0 formaldehyd 
• 462-06-6 fluorobenzene 
• 352-32-9 p-fluorotoluene 
• 459-56-3 4-fluorobenzylic alcohol 
• 29180-23-2 p-fluorobenzyl ion 
• 7647-01-0 hydrogenchloride 
• 56-23-5 tetrachloromethane 
• 5435-44-9 (E)-3-Ureido-but-2-enoic acid ethyl ester 
• 456-22-4 4-Fluorobenzoic acid 
• 61812-54-2 4,4'-(oxybis(methylene))bis(fluorobenzene) 
• 316142-60-6 N-(4-cyanophenyl)-4-fluorobenzamide 
• 13656-36-5 3,5-dichloro-2,4,6-trifluorobenzoic acid 

Downstream Products

• 36288-27-4 1-(4-fluorostyryl)naphthalene 
• 6185-73-5 2-<4-Fluor-phenyl>-1-phenyl-1-<3-trifluormethyl-phenyl>-aethylen 
• 154479-61-5 N-(4-Fluorbenzyl)-piperidon-2 
• 75970-78-4 [1-(4-Fluoro-benzyl)-5-methyl-1H-benzoimidazol-2-yl]-(1-phenethyl-piperidin-4-yl)-amine 
• 75970-79-5 [1-(4-Fluoro-benzyl)-6-methyl-1H-benzoimidazol-2-yl]-(1-phenethyl-piperidin-4-yl)-amine 
• 73735-28-1 6-fluoro-1-<(4-fluorophenyl)methyl>-N-<1-(2-phenylethyl)-4-piperidinyl>-1H-benzimidazol-2-amine 
• 73735-29-2 5-fluoro-1-<(4-fluorophenyl)methyl>-N-<1-(2-phenylethyl)-4-piperidinyl>-1H-benzimidazol-2-amine 
• 83444-25-1 N-(p-fluorobenzyl)aniline 
• 1132-68-9 L-4-fluorophenylalanine 
• 16547-13-0 4-fluoro-N-methyl-N-phenylbenzylamine 
• 3859-77-6 toluene-4-sulfonic acid-(4-fluoro-benzyl ester) 
• 56442-14-9 4-((4'-fluoro)benzyloxy)benzonitrile 
• 4092-92-6 3-(4-fluorophenyl)-2,2-dimethyl-1-propanal 
• 178624-87-8 (±)-1-(4-fluorobenzyl)-3-methylpiperazine 

Relevant articles and documents

p-Fluorobenzaldehyde and p-fluorobenzoic acid by oxidation of p-fluorobenzyl derivatives

Experiments on the oxidation reactions of p-fluorobenzyl alcohol and chloride were carried out. Several oxidizing agents (manganese dioxide, 30% hydrogen peroxide and hypochlorite solutions at different concentrations) were used, and a mixture of p-fluorobenzaldehyde and p-fluorobenzoic acid in different proportions was obtained. In the case of p-fluorobenzyl chloride, some p-fluorobenzyl alcohol was also found in the reaction mixture. The experimental conditions required to obtain an increase in the yield of the aldehyde or acid were also studied.

One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride

Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.

Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof

Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.

α-Diimine-Niobium Complex-Catalyzed Deoxychlorination of Benzyl Ethers with Silicon Tetrachloride

α-Diimine niobium complexes serve as catalysts for deoxygenation of benzyl ethers by silicon tetrachloride (SiCl4) to cleanly give two equivalents of the corresponding benzyl chlorides, where SiCl4 has the dual function of oxygen scavenger and chloride source with the formation of a silyl ether or silica as the only byproduct. The reaction mechanism has two successive trans-etherification steps that are mediated by the niobium catalyst, first forming one equivalent of benzyl chloride along with the corresponding silyl ether intermediate that undergoes the same reaction pathway to give the second equivalent of benzyl chloride and silyl ether.

Synthesis of mono- and difluorobenzyl chlorides by chlorination of mono- and difluorotoluenes with CCl4 and t-BuOCl induced by iron-containing catalysts

Mono- and difluorobenzyl chlorides were synthesized by chlorination of mono- and difluorotoluenes with CCl4?MeOH or t-BuOCl in the presence of iron-containing catalysts.

N -Hydroxyphthalimide/benzoquinone-catalyzed chlorination of hydrocarbon C-H bond using N -chlorosuccinimide

The direct chlorination of C-H bonds has received considerable attention in recent years. In this work, a metal-free protocol for hydrocarbon C-H bond chlorination with commercially available N-chlorosuccinimide (NCS) catalyzed by N-hydroxyphthalimide (NHPI) with 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) functioning as an external radical initiator is presented. Aliphatic and benzylic substituents and also heteroaromatic ones were found to be well tolerated. Both the experiments and theoretical analysis indicate that the reaction goes through a process wherein NHPI functions as a catalyst rather than as an initiator. On the other hand, the hydrogen abstraction of the C-H bond conducted by a PINO species rather than the highly reactive N-centered radicals rationalizes the high chemoselectivity of the monochlorination obtained by this protocol as the latter is reactive towards the C(sp3)-H bonds of the monochlorides. The present results could hold promise for further development of a nitroxy-radical system for the highly selective functionalization of the aliphatic and benzylic hydrocarbon C-H.

Highly selective halogenation of unactivated C(sp3)-H with NaX under co-catalysis of visible light and Ag@AgX

The direct selective halogenation of unactivated C(sp3)-H bonds into C-halogen bonds was achieved using a nano Ag/AgCl catalyst at RT under visible light or LED irradiation in the presence of an aqueous solution of NaX/HX as a halide source, in air. The halogenation of hydrocarbons provided mono-halide substituted products with 95% selectivity and yields higher than 90%, with the chlorination of toluene being 81%, far higher than the 40% conversion using dichlorine. Mechanistic studies demonstrated that the reaction is a free radical process using blue light (450-500 nm), with visible light being the most effective light source. Irradiation is proposed to cause AgCl bonding electrons to become excited and electron transfer from chloride ions induces chlorine radical formation which drives the substitution reaction. The reaction provides a potentially valuable method for the direct chlorination of saturated hydrocarbons.

SNAr catalysis enhanced by an aromatic donor-acceptor interaction; Facile access to chlorinated polyfluoroarenes

Selective catalytic SNAr reaction of polyfluoroaryl C-F bonds with chloride is shown. Stoichiometric TMSCl makes the reaction exergonic and allows catalysis, which involves ground state elevation of chloride, aromatic donor-acceptor interactions, and stabilization of the Meisenheimer complex. Traditional cross-coupling of the products is now possible and demonstrates the utility.

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.

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.