Fluonnation acids

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

The preparation of fluonnated acid anhydrides can be done by simple methods Phosphorus pentoxide removes a molecular equivalent of water from tnfluoroacetic acid and tnfluoromethanesulfonic acid and forms the mixed anhydride [Si] (equation 53)... 

Carbon dioxide may be eliminated even from the ester of a fluonnated acid by using lithium chlonde-hexamethylphosphonc tnamide complex at reflux temperature The intermediate carbene is formed in 78-90% yield [96, 97] (equation 64)... 

Although fluonnation of peroxoanions [S2] has been examined, the major emphasis in the fluonnation of oxygenated material is the preparation offhioroxy compounds The simplest, trifluoromethyl hypofluorite, can be prepared almost quantitatively by the action of fluorine on carbonyl fluoride (fluorophosgene) in the presence of various catalysts [Si, 84] Addition of fluorine to trifluoroacetic acid [S5] or its sodium salt [S6] gives rise to FjCF(OF)2 Long-chain fluoroxy compounds can also... 

The KF-S reaction presumably involves attack of a fluonnated caibanion on sulfur, whereas the S-Sbp5 reaction may involve electrophilic attack by a cationic sulfur species on the olefin under the strong Lewis acid conditions Electrophilic attack on a fluonnated olefin may also account for formation of a perfluorinated sulfide from reaction of bis(pentafluorophenyl)disulfide with hexafluoropropylene under superacid conditions [IS5] (equation 28)... 

Electrochemical fluonnation ot N,N dialkylammo-substituted carboxylic acids as their methyl esters produces the analogous perfluonnated tertiary amine carboxylic acid derivatives in 18-30% yields as well as cyclic amine ethers [JOO]... 

Carboxylic acids react with xenon difluoride to produce unstable xenon esters The esters decarboxylate to produce free radical intermediates, which undergo fluonnation or reaction with the solvent system Thus aliphatic acids decarboxylate to produce mainly fluoroalkanes or products from abstraction of hydrogen from the solvent Perfluoro acids decarboxylate in the presence of aromatic substrates to give perfluoroalkyl aromatics Aromatic and vinylic acids do not decarboxylate [91] (equation 51)... 

Hydroxybenzoic acids are easily eonverted into hydroxybenzotrifluorides by treatment with sulfur tetrafluoride in a hydrogen fluoride solution under mild conditions [2/5] An exception is salicylic acid, which becomes a resin, however, a 70-75% yield of 2-hydroxybenzotrifluoride can be obtained by carrying out the fluonnation in a mixture of three parts of hydrogen fluoride and one part of benzene [216] (equation 110)... 

Heavily fluonnated aminobenzenes, pyridines, and pyrimidines are diazotized in strong-acid media Solid sodium nitrite added directly to the fluonnated amine dissolved in 80% hydrofluonc acid, anhydrous hydrogen fluoride, or (1 1 wt/wt) 98% sulfuric acid in (86 14 wt/wt) acetic and propionic acids affords the electrophilic fluoroarenediazonium ion Addition of an electron rich aromatic to the resultant diazonium solution gives the fluoroareneazo compound [10 II] (equa tions 9 and 10)... 

Terminally unsaturated fluonnated alkenoic acids can be obtained from poly-fluorocycloalkenes by reaction with potassium hydroxide m rert-butyl alcohol [24] (equation 26) The use of a tertiary alcohol is critical because primary and secondar y alcohols lead to ethers of the cycloalkenes The use of a polar aprotic solvent such as diglyme generates enols of diketones [26] (equation 27) The compound where... 

Pentafluorobenzyl bromide [II] and a partially fluonnated alkyl iodide [12] react with potassium carboxylates An interesting replacement of iodine in a fluonnated alkyl iodide by an acetate group takes place with peroxyacetic acid [13] (equations 10-12)... 

After hydrolysis, fluonnated derivatives of alanine are obtained in both cases because decarboxylation of the substituted malonic acid occurs (equation 109)... 

The discussion of acylation reactions in this chapter is focused on fluonnated carboxylic acid derivatives and their use to build up new fluorine-containing molecules of a general preparative interest Fifteen years ago, fluonnated carboxylic acids and their derivatives were used mainly for technical applications [/] Since then, an ever growing interest for selectively fluonnated molecules for biological applications [2, 3, 4, 5] has challenged many chemists to use bulk chemicals such as tnfluoroacetic acid and chlorodifluoroacetic acid as starting materials for the solution of the inherent synthetic problems [d, 7,, 9]... 

Acylation of various oxygen functions by use of common and commercially available fluonnated carboxylic acid denvatives such as trifluoroacetic anhydride or the corresponding acyl halides have already been discussed sufficiently in the first edition [10] Therefore only exceptional observations will be described in this section In the past 15 years, many denvatizations of various nonfluonnated oxygen compounds by fluoroacylation were made for analytical purposes. Thus Mosher s acid chlorides for example became ready-to-use reagents for the determination of the enantiomeric purity of alcohols and amines by NMR or gas-liquid chromatographic (GLC) techniques [//] (equation 1)... 

In the series of highly advanced enzyme inhibitors, fluonnated substrates are playing an important role [5 6] Many such substrates are synthesized by using fluoroacetic acid derivatives as budding blocks [JO, 51] (equation 25)... 

Perfluoroalkyl or -aryl halides undergo oxidative addition with metal vapors to form nonsolvated fluonnated organometallic halides and this topic has been die subject of a review [289] Pentafluorophenyl halides react with Rieke nickel, cobalt, and iron to give bispentafluorophenylmetal compounds, which can be isolated in good yields as liquid complexes [290] Rieke nickel can also be used to promote the reaction of pentafluorophenyl halides with acid halides [297] (equation 193)... 

The dehydration of highly fluonnated alcohols generally requires phosphorus pentoxide or sulfuric acid, but hexafluoroisobutyl alcohol is easily converted to hexafluoroisobutylene by potassium hydroxide with or without solvent at 20-... 

The decarboxylation reactions of fluonnated carboxylic acids are similar to those of their nonfluonnated counterparts, but predictably many exceptions exist The oxidation of the potassium salts of perfluoro acids with potassium persulfate leads to decarboxylation and coupling [93] (equation 59)... 

In the Schmidt reaction of fluonnated dicarboxyhc acids, the appropnate amides can be obtained in fairly good yield [48] Complications arise from possible cychzation if the fluorine atom is in the 8 position relative to the newly formed amino group [/] Fluonnated aromatic ethers, upon heating in dimethylformamide, undergo Smiles rearrangement to give diarylamines [49, 50] (equation 11)... 

Benzidine rearrangement of fluonnated hydrazobenzenes proceeds with a high yield in the presence of a strong acid [57] (equation 12) Ring contraction occurs when 2-bromoheptafluoronaphthalene is treated with antimony pentafluoride [52] (equation 13)... 

Covalent fluondes of group 3 and group 5 elements (boron, tin, phosphorus, antimony, etc ) are widely used m organic synthesis as strong Lewis acids Boron trifluoride etherate is one of the most common reagents used to catalyze many organic reactions. A representative example is its recent application as a catalyst in the cycloadditions of 2-aza-l,3-dienes with different dienophiles [14] Boron trifluoride etherate and other fluonnated Lewis acids are effective activators of the... 

The lowest wettable surface known = 6 dyne/cm) is a monolayer of perfluoro-launc acid on platinum, whose surface is made up of closely packed CF3 groups [20] Fluonnated graphite, (C2FJ and (CF) , also have surface tensions approachmg 6 dyne/cm [21] Perfluorinated materials, however, are not required tor low surface energies only the outermost surface groups must be perfluorinated [20, 22]... 

The extraordinanly high polaiity of the fluonnated alcohols reflects their strong hydrogen-bonding capability [54] The P values of 10 2 for CF3CH2OH and 11 08 for (CF3)2CHOH compare with 10 6 and 12 1 for 50% formic acid and water, respectively [39]... 

The basicities of amines, ethers, and carbonyl compounds are invariably decreased by fluonnation. 2,2,2-Tnfluoroethylamine (p f = 3.3 [61]) and C 5NH2 = -0.36 [62]) are about 10 times less basic than CH3CH2NH2 and CgH5NH2, respectively, and (CF3)2CHNH2 (p j, = 1 22 [71]) is over 10 times less basic than 1-C3H2NH2. The relative gas-phase acidities in Table 15 illustrate the large effect of fluonnation. Perfluoro-rerf-amines (R )3N and ethers R Rf have no basic character m solution [, 74], and CF3COCF3 is not protonated by superacids [72]. 

The effects of fluonnation on carbanion stability are largely deduced from C-H acidity data (p. 988) [64], a-Halogens stabilize carbanions in the order Br > Cl > F, which IS opposite the inductive electron-withdrawing order and reflects the... 

The chemical resistance of PTFE is almost universal It resists attack by aqua regia, hot fummg nitnc acid, hot caustic, chlorine, chlorosulfonic acid, and all solvents. Despite this broad chemical resistance, PTFE is attacked by molten alkali metals, ammonia solutions of such metals, chlorine trifluoride, and gaseous fluonne at elevated temperature and pressure PTFE swells or dissolves m certam highly fluonnated oils near its melting point. Specific lists of chemicals compatible with PTFE are available [/.8]... 

Almost all of the biomedical research done in the 25 years following the liquid-breathing work was conducted with commercially available fluorocarbons manufactured for various industnal uses by the electrochemical Simons process (fluonnation in a hydrofluoric acid solution) or the cobalt fluoride process (fluori-nation with this solid in a furnace at about 200 C) These processes tended to yield many by-products, partly because they were, to some extent, free radical reactions and partly because it was difficult to easily achieve complete fluonnation Aromatic hydrocarbons gave better products with the cobalt tnfluonde [73] method, whereas saturated hydrocarbons yielded better products with fluonnation using diluted or cooled gaseous fluorine (Lagow) Incompletely fluormated matenal was either... 

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