Trifluoromethyl ethers

The target compounds (33) were obtained in good yields from a variety of aliphatic, aromatic, and heteroaromatic aldehydes. Owing to mild reaction conditions, other functionalities such as ethers, trifluoromethyl, and heterocycles can be... 

Alkylation. Ben2otrifluoride can also be alkylated, eg, chloromethyl methyl ether—chlorosulfonic acid forms 3-(trifluoromethyl)ben2yl chloride [705-29-3] (303,304), which can also be made from / -xylene by a chlorination—fluorination sequence (305). Exchange cyanation of this product in the presence of phase-transfer catalysts gives 3-(trifluoromethylphenyl)acetonitrile [2338-76-3] (304,305), a key intermediate to the herbicides flurtamone... 

Depending on the ring substituent, trifluoromethoxyben2enes can be made by the sequential chlorination—fluorination of anisole(s) (351—354). A one-step process with commercial potential is the BF (or SbF2)-cataly2ed reaction of phenol with carbon tetrachloride/hydrogen fluoride (355). Aryl trifluoromethyl ethers, which may not be accessible by the above routes,may be made by fluorination of aryl fluoroformates or aryl chlorothioformates with sulfur tetrafluoride (348) or molybdenum hexafluoride (356). 

Herbicides can be grouped according to common stmctural features. Sometimes the assignment is arbitrary when there are a multitude of functional groups, eg, acifluorfen which is a diphenyl ether (phenoxy compound) as well as a trifluoromethyl compound. 

A large variety of newer poly(ether imide)s has been described. Included among these are perfluorinated polymers (96), poly(ester ether imide)s (97), poly(ether imide)s derived from A/,Ar-diamino-l,4,5,8-naphthalenetetracarboxyHcbisimide (98), and poly(arylene ether imide ketone)s (99). In addition, many other heterocyHc groups have been introduced into polyether systems, eg, poly(pyrazole ether)s (100) and poly(aryl ether phenylquinoxaLine)s (101) poly(aryl ether oxazole)s with trifluoromethyl groups (102) and polyethers with other heterolinkages, eg, poly(arylether azine)s (103). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Trifluoromethyl-4-nitrophenol [88-30-2] M 162.1, m 81°, pK si 6.1. Crystd from benzene or from pet ether/ benzene mixture. 

This dialkoxydiphenylsulfurane has been prepared by the reaction of diphenyl sulfide, 2,2,2-trifluoro-l-phenyl-l-(trifluoromethyl)ethyl hypochlorite, and potassium l,l,l,3,3,3-hexafluoro-2-phenyl-2-propanolate and by the reaction of diphenyl sulfide with 1 equivalent of chlorine and 2 equivalents of potassium 1,1,1,3,3,3-hexafluoro-2-phenyl-2-propanolate in diethyl ether. ... 

The reaction of cyclohexane-cw-1,2-dicarboxylic acid with sulfur tetrafluoride affords the correspoding cyclic ether in a 70% yield with very limited formation of the bis(trifluoromethyl) derivative [2IJ] (equation 107)... 

A number ot aryl trifluoromethyl ethers are synthesized by fluormation of aryl chlorothioformates with molybdenum hexafluoride. The reagents are progressively heated from -25 to 130 C, and the products are distilled off. Molybdenum disulfide and carbon disulfide are the by-products [12] (equation 16)... 

Bis(trifluoromethyl)trioxide, CF3OOOCF3, adds to only one equivalent of octafluorocyclopentene to give cis and trans isomers of a mixed tnfluoromethyl ether-tnfluoromethylperoxide (equation 13) A radical rnechamsm is involved [J/, unlike in the electrophilic reacuons of CF3OOCI [32]... 

Similarly, iV,A/ -dimethyl-3,3 -bisindolylmethane (169) has been used in a related experiment, where treatment thereof with trifluoroacetic fflihydride (TFAA) in diethyl ether at room temperature yielded a mixture of products from which the trifluoromethyl-substituted indolo[3,2-b]carbazole 170 was isolated as the major pentacyclic component, accompanied by the hydroxy derivative 171 as well as small amounts of the indolo[2,3-h]carbazole 146 (Scheme 20). The precursor 169 could also be prepared in situ from A-methylindol-3-methanol under... 

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

B) Preparation of S-Trifluoromethyl-2,4-Disulfamylaniline—The 5-trifluoromethylaniline-2,4-disulfonyl chloride obtained in step (A) is taken up in ether and the ether solution dried with magnesium sulfate. The ether is removed from the solution by distillation, the residue is cooled to 0°C, and 60 ml of ice-cooled, concentrated ammonia water is added while stirring. The solution is then heated for one hour on a steam bath and evaporated... 

A solution of 1.0 gram of 10-[3 -(N-acetoxyethylpiperazinyl)-propyl]-2-trifluoromethyl-phenothiazine in 25 ml of 1 N hydrochloric acid is heated at reflux briefly. Neutralization with dilute sodium carbonate solution and extraction with benzene gives the oily base, 10-[3 -(N-(3-hydroxyethylpiperazinyl)-propyl]-2-trifluoromethylphenothiazine. The base is reacted with an excess of an alcoholic hydrogen chloride solution. Trituration with ether separates crystals of the dihydrochloride salt, MP 224° to 226°C, (from U.S. Patent 3,058,979). 

Recently, Baneijee et al. prepared a series of difluoro monomers with pendent trifluoromethyl groups using a Pd(0)-catalyzed cross-coupling reaction (Scheme 6.32).242,243 These monomers were converted to poly(arylene ether)s by nucleophilic displacement of the halogen atoms on the benzene ring with several... 

The diion mechanism c has been reported for at least some of the reae-tions in categories 3 and as well as some ketene dimerizations. For example, the rate of the reaction between l,2-bis(trifluoromethyl)-l,2-dicyanoe-thene and ethyl vinyl ether was strongly influenced by changes in solvent polarity.Some of these reactions are nonstereospecific, but others are stereo-specific. As previously indicated, it is likely that in the latter cases the di-ionic... 

The dimerization of the parent ketene gives the P-lactone. One molecule of ketene reacts across the C=C bond as a donor and the other molecule reacts across the C=0 bond as an acceptor. This is similar to the concerted [2+2] cycloaddition reaction between bis(trifluoromethyl)ketene and ethyl vinyl ether to afford the oxetane (Scheme 26) [127], A lone pair on the carbonyl oxygen in the ketene molecule as a donor activates the C=C bond as the alkoxy group in vinyl ether. 

FIG. 9 Differential capacity C of the interface between 0.1 M LiCl in water and 0.02 M tetrabu-tylammonium tetraphenylborate ( ) or tetrapentylammonium tetrakis[3,5-bis(trifluoromethyl)phe-nyl]borate ( ) in o-nitrophenyl octyl ether as a function of the interfacial potential difference (From Ref 73.)... 

Compound 1 was the first cyclopentane-based NK-1 receptor antagonist development candidate at Merck. It contains five stereocenters a central core possessing three contiguous all-trans stereocenters, a pendent bis(trifluoromethyl)-benzyHc ether, and a nipecotic acid moiety (Figure 7.1). Key to the successful preparation of 1 was construction of the trans, trans-cyclopentyl core and installation of the unsymmetrical secondary-secondary (sec-sec) ether. The preparation of 1 is the focus of this chapter. 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

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