4837-15-4

Upstream product

• 108-88-3 toluene 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 108-39-4 3-methyl-phenol 
• 1864-96-6 3-methylphenyl formate 
• 33104-39-1 Dichlormethyl-m-tolylaether 
• 75-45-6 Chlorodifluoromethane 

Downstream Products

• 4837-19-8 (3-difluoromethoxy)benzoic acid 
• 76903-91-8 3-(difluoromethoxy)benzoyl chloride 

Relevant academic research and scientific papers

Redox-Neutral TEMPO Catalysis: Direct Radical (Hetero)Aryl C?H Di- and Trifluoromethoxylation

Applications of TEMPO. catalysis for the development of redox-neutral transformations are rare. Reported here is the first TEMPO.-catalyzed, redox-neutral C?H di- and trifluoromethoxylation of (hetero)arenes. The reaction exhibits a broad substrate scope, has high functional-group tolerance, and can be employed for the late-stage functionalization of complex druglike molecules. Kinetic measurements, isolation and resubjection of catalytic intermediates, UV/Vis studies, and DFT calculations support the proposed oxidative TEMPO./TEMPO+ redox catalytic cycle. Mechanistic studies also suggest that Li2CO3 plays an important role in preventing catalyst deactivation. These findings will provide new insights into the design and development of novel reactions through redox-neutral TEMPO. catalysis.

Catalytic radical difluoromethoxylation of arenes and heteroarenes

Intermolecular C-H difluoromethoxylation of (hetero)arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a redox-active difluoromethoxylating reagent 1a and photoredox catalysts for the direct C-H difluoromethoxylation of (hetero)arenes. Our approach is operationally simple, proceeds at room temperature, and uses bench-stable reagents. Its synthetic utility is highlighted by mild reaction conditions that tolerate a wide variety of functional groups and biorelevant molecules. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1a forming a neutral radical intermediate that liberates the OCF2H radical exclusively. Addition of this radical to (hetero)arenes gives difluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of difluoromethoxylation.

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.

Difluoromethyl bioisostere: Examining the lipophilic hydrogen bond donor concept

There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085-0.126) were determined using Abraham's solute 1H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water-octanol) values (log P(XCF2H) - log P(XCH3)) spanned from -0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.

Three step procedure for the preparation of aromatic and aliphatic difluoromethyl ethers from phenols and alcohols using a chlorine/fluorine exchange methodology

Difluoromethyl ethers are prepared from phenols in three steps via their respective formate ester derivatives. The formates are first converted to dichloromethyl ethers by treatment with PCl5. These ethers are then induced to undergo chlorine/fluorine exchange to form the respective difluoromethyl ethers. The chlorine/fluorine exchange is carried out by either a room temperature, solvolytic process using THF-5HF or Et3N-3HF as exchange medium, where HF is the ultimate source of fluorine, or by a direct displacement process in sulfolane at 125 C, where KF is the source of fluorine. By one or another of these processes, virtually all phenols, electron-rich and electron-poor, can be converted to their respective difluoromethyl ethers in good yields. Aliphatic alcohols are also able to be converted to their difluoromethyl ether derivatives using the Et3N-3HF exchange medium.

Changes in the activity and selectivity of herbicides by selective fluorine substitution, taking bentranil and classic analogues as examples

The introduction of fluorine atoms into 2-phenyl-4H-3,1-benzoxazin-4-one (bentranil) led to sweeping changes in its herbicidal properties in some cases, and 5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one ('fluorobentranil') was found to be the most active compound. It can be prepared from 2-amino-6-fluoro-benzoic acid or by direct halogen exchange of 5-chloro-2-phenyl-4H-3,1-benzoxazin-4-one. The latter reaction was investigated on a pilot scale, including a high-temperature (350°C) potassium fluoride halogen exchange without solvent. When sulfolane was used as a solvent, a side reaction at 220°C - partial decomposition to a diphenylether - could be prevented by addition of a small amount of a radical scavenger. Other intermediates with a pseudohalogen substitution were obtained by side-chain chlorination of suitable methylsulfanyl benzoic acid precursors and halogen exchange. 'Fluorobentranil' shows good broad-leaf activity and selectivity on rice, cereals and maize. In a second case study, the fluoro-substituted anthranilic acids mentioned above were also found to be appropriate for synthesizing herbicidal sulfonylurea (SU) compounds via Meerwein reaction of their aniline function. Methyl 2-[({[(4-chloro-6-methoxy-2- pyrimidinyl)-amino]carbonyl}amino)sulfonyl]-6-fluorobenzoate is an example of a SU that is compatible with maize, whereas the unsubstituted Classic analogue is not selective.

Substituted 3-fluoroalkoxybenzoyl halides and their preparation

Novel substituted 3-fluoroalkoxybenzoyl halides of the formula STR1 where Hal is fluorine or chlorine, R1 is chlorodifluoromethyl, difluoromethyl, 1,1,2,2-tetrafluoroethyl, 2-bromo-1,1,2-trifluoroethyl, pentafluoroethyl or 1,1,2,3,3,3-hexafluor

4H-3,1-Benzoxazine derivatives

4H-3,1-Benzoxazine derivatives of the formula STR1 where R1, R2 and Y have the meanings given in the specification, and their use for controlling unwanted plant growth in numerous crops, such as cereals, Indian corn, soybeans and cot