772-49-6

Usage

Chemical Properties

Colorless to light yellow liquid

Uses

1-Chloro-3-(trifluoromethoxy)benzene is used as pharmaceutical intermediate.

InChI:InChI=1/C7H4ClF3O/c8-5-2-1-3-6(4-5)12-7(9,10)11/h1-4H

Upstream product

• 456-55-3 1-trifluoromethoxybenzene 
• 373-91-1 hypofluorous acid trifluoromethyl ester 
• 108-90-7 chlorobenzene 
• 618-32-6 Benzoyl bromide 
• 1035797-66-0 benzoic acid trifluoromethyl ester 
• 1006904-72-8 silver(I) trifluoromethoxide 
• 108-42-9 3-chloro-aniline 
• 927-84-4 bis(trifluoromethyl)peroxide 

Downstream Products

• 456-55-3 1-trifluoromethoxybenzene 
• 1014-81-9 3-(trifluoromethoxy)benzoic acid 

Relevant academic research and scientific papers

Radical C?H Trifluoromethoxylation of (Hetero)arenes with Bis(trifluoromethyl)peroxide

Trifluoromethoxylated (hetero)arenes are of great interest for several disciplines, especially in agro- and medicinal chemistry. Radical C?H trifluoromethoxylation of (hetero)arenes represents an attractive approach to prepare such compounds, but the high cost and low atom economy of existing .OCF3 radical sources make them unsuitable for the large-scale synthesis of trifluoromethoxylated building blocks. Herein, we introduce bis(trifluoromethyl)peroxide (BTMP, CF3OOCF3) as a practical and efficient trifluoromethoxylating reagent that is easily accessible from inexpensive bulk chemicals. Using either visible light photoredox or TEMPO catalysis, trifluoromethoxylated arenes could be prepared in good yields under mild conditions directly from unactivated aromatics. Moreover, TEMPO catalysis allowed for the one-step synthesis of valuable pyridine derivatives, which have been previously prepared via multi-step approaches.

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the residence time up to 16 times in comparison t

Silver-Mediated Trifluoromethoxylation of (Hetero)aryldiazonium Tetrafluoroborates

Here we report a silver-mediated trifluoromethoxylation of (hetero)aryldiazonium tetrafluoroborates by converting an aromatic amino group into an OCF3 group. This method, which can be considered to be a trifluoromethoxylation variation of the classic Sandmeyer-type reaction, uses readily available aryl and heteroaromatic amines as starting materials and AgOCF3 as trifluoromethoxylating reagents. The broad substrate scope and simple, mild reaction condition made this transformation a valuable method in constructing aryl-OCF3 bonds.

DIFLUOROMETHOXYLATION AND TRIFLUOROMETHOXYLATION COMPOSITIONS AND METHODS FOR SYNTHESIZING SAME

The present invention provides a compound having the structure (I), a processing of making the compound; and a process of using the compound as a reagent for the difluoromethoxylation and trifluoromethoxylation of arenes or heteroarenes.

Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent

Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source. The synthetic potency of TFBz is demonstrated by trifluoromethoxylation-halogenation of arynes, nucleophilic substitution of alkyl (pseudo)halides, cross-coupling with aryl stannanes, and asymmetric difunctionalization of alkenes. The unprecedented trifluoromethoxylation-halogenation of arynes proceeds smoothly at room temperature with the aid of a crown ether-complexed potassium cation, which significantly stabilizes the trifluoromethoxide anion derived from TFBz.

Redox-Active Reagents for Photocatalytic Generation of the OCF3 Radical and (Hetero)Aryl C?H Trifluoromethoxylation

The trifluoromethoxy (OCF3) radical is of great importance in organic chemistry. Yet, the catalytic and selective generation of this radical at room temperature and pressure remains a longstanding challenge. Herein, the design and development of a redox-active cationic reagent (1) that enables the formation of the OCF3 radical in a controllable, selective, and catalytic fashion under visible-light photocatalytic conditions is reported. More importantly, the reagent allows catalytic, intermolecular C?H trifluoromethoxylation of a broad array of (hetero)arenes and biorelevant compounds. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1 resulting in exclusive liberation of the OCF3 radical. Addition of this radical to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of trifluoromethoxylation.

Radical Trifluoromethoxylation of Arenes Triggered by a Visible-Light-Mediated N?O Bond Redox Fragmentation

A simple trifluoromethoxylation method enables non-directed functionalization of C?H bonds on a range of substrates, providing access to aryl trifluoromethyl ethers. This light-driven process is distinctly different from conventional procedures and occurs through an OCF3 radical mechanism mediated by a photoredox catalyst, which triggers an N?O bond fragmentation. The pyridinium-based trifluoromethoxylation reagent is bench-stable and provides access to synthetic diversity in lead compounds in an operationally simple manner.

Catalytic C?H Trifluoromethoxylation of Arenes and Heteroarenes

The intermolecular C?H trifluoromethoxylation of arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a novel trifluoromethoxylating reagent and redox-active catalysts for the direct (hetero)aryl C?H trifluoromethoxylation. Our approach is operationally simple, proceeds at room temperature, uses easy-to-handle reagents, requires only 0.03 mol % of redox-active catalysts, does not need specialized reaction apparatus, and tolerates a wide variety of functional groups and complex structures such as sugars and natural product derivatives. Importantly, both ground-state and photoexcited redox-active catalysts are effective. Detailed computational and experimental studies suggest a unique reaction pathway where photoexcitation of the trifluoromethoxylating reagent releases the OCF3 radical that is trapped by (hetero)arenes. The resulting cyclohexadienyl radicals are oxidized by redox-active catalysts and deprotonated to form the desired products of trifluoromethoxylation.

Fluorodecarboxylation for the Synthesis of Trifluoromethyl Aryl Ethers

The synthesis of mono-, di-, and trifluoromethyl aryl ethers by fluorodecarboxylation of the corresponding carboxylic acids is reported. AgF2induces decarboxylation of aryloxydifluoroacetic acids, and AgF, either generated in situ or added separately, serves as a source of fluorine to generate the fluorodecarboxylation products. The addition of 2,6-difluoropyridine increased the reactivity of AgF2, thereby increasing the range of functional groups and electronic properties of the aryl groups that are tolerated. The reaction conditions used for the formation of trifluoromethyl aryl ethers also served to form difluoromethyl and monofluoromethyl aryl ethers.

Direct trifluoro-methoxylation of aromatics with perfluoro-methyl- hypofluorite

The reactivity of CF3OF (FTM) has been widely studied especially in halogenated olefinic systems and its use in pharmaceutical synthesis as a mild radical and electrophilic fluorinating agent is well documented. On the other hand, the chemical behavior of the perfluoro-methyl-hypofluorite with aromatic substrates is much less studied. Up to now few and scattered data regarding its use as electrophilic fluorinating agent of variously substituted aromatic compounds are found in the literature. In this work the reactivity of CF3OF with simple electron rich and electron poor aromatics (α,α,α-trifluoro-toluene, toluene, benzene, chloro-benzene, methoxybenzene) has been investigated. The possibility of selectively bind the trifluoro-methoxy group (via radical mechanism) or the fluorine atom (via electrophilic addition) by varying the reaction conditions has been explored. In particular we have observed that the trifluoro-methoxy free radical substitution can be the main synthetic pathway if the reaction is promoted by an independent and steady source of CF3O radical.