Trifluoroacetic acid, accelerant

An alternative view of these addition reactions is that the rate-determining step is halide-assisted proton transfer, followed by capture of the carbocation, with or without rearrangement Bromide ion accelerates addition of HBr to 1-, 2-, and 4-octene in 20% trifluoroacetic acid in CH2CI2. In the same system, 3,3-dimethyl-1-butene shows substantial rearrangement Even 1- and 2-octene show some evidence of rearrangement, as detected by hydride shifts. These results can all be accoimted for by a halide-assisted protonation. The key intermediate in this mechanism is an ion sandwich. An estimation of the fate of the 2-octyl cation under these conditions has been made ... 

Direct esr evidence for the intermediacy of radical-cations was obtained on flowing solutions of Co(III) acetate and a variety of substituted benzenes and polynuclear aromatics together in glacial acetic acid or trifluoroacetic acid solution . A p value of —2.4 was reported for a series of toluenes but addition of chloride ions, which greatly accelerated the reaction rate, resulted in p falling to —1.35. Only trace quantities of -CH2OAC adducts were obtained and benzyl acetate is the chief product from toluene, in conformity with the equation given above. 

The Meerwein-Ponndorf-Verley (MPV) reduction is generally mediated by aluminum triiso-propoxide, Al(01Pr)3. In MPV reduction, reversible hydride transfer occurs via a six-membered transition state (Scheme 67). By removing acetone from the reaction system, the reversible reaction proceeds smoothly. The advantages of the reduction are the mildness of the reaction conditions, chemoselectivity, safety, operational simplicity, and its applicability to large-scale synthesis. It is reported that the addition of trifluoroacetic acid, significantly accelerates the reduction (Scheme 68) 304,305 in which case a catalytic amount of Al(0 Pr)3 is enough to complete the reaction. 

The acidic nature of the reagent is important the trifluoroacetic acid liberated in the reaction catalyzes hydrolysis of the intermediate isocyanate, and also ensures that the amine which is formed is protonated and cannot react with the isocyanate to give urea by-products. The reaction can be accelerated by addition of pyridine to an observed pH of about 3.5, and is retarded by added acid or trifluoroacetate ion. In the present procedure pyridine was not employed, since the reaction in its absence proceeds with a satisfactory rate. 

ARS2 (1-10 pmole) was mixed with a 100-fold molar excess of sinap-inic acid in an aqueous solution containing 10% trifluoroacetic acid (TFA). The mixture was placed inside a JMS-LDI 1700 time-of-flight (TOF) MS spectrometer (JEOL, Japan) and irradiated with a nitrogen laser (337 nm, 3 ns pulse). The ions formed by each pulse were accelerated by a 30 kV potential into a 1.7 m evacuated tube. 

Denaturation in solution is known to be faster with 1-propanol than with 2-propanol 60), but in contact with the C 4 RP column a higher rate was observed with 2-propanol. Acetonitrile produced the highest acceleration. Replacement of H3P04 by 0.01 M trifluoroacetic acid did not alter the 2.2 pH, but enhanced by a factor of three the rate of denaturation at 22 °C. Thus, eluent systems containing TFA and... 

Tetramethylenehalonium Ions. 1,4-Halogen participation was first postulated to occur in the acetolysis of 4-iodo- and 4-bromo-l-butyl tosylates.402 In subsequent studies, Peterson and coworkers found anomalous rates in the addition of trifluoroacetic acid to 5-halo-l-hexenes403,404 and 5-halo-1-pentynes.405 406 Such observations were recognized as due to 1,4-halogen participation.341 Also, a study of the solvolysis of 8-chloroalkyl tosylates indicated rate-accelerating 1,4-chlorine participation effects up to 99-fold.407... 

Prakash, Olah, and co-workers256 have prepared Mosher s acid analogs by the hydroxyalkylation of substituted benzenes with ethyl trifluoropyruvate [Eq. (5.95)]. Deactivated aromatics (fluorobenzene, chlorobenzene) required the use of excess triflic acid indicative of superelectrophilic activation.3 5 In contrast to these observations, Shudo and co-workers257 reported the formation gem-diphenyl-substituted ketones in the alkylation of benzene with 1,2-dicarbonyl compounds [Eq. (5.96)]. In weak acidic medium (6% trifluoroacetic acid-94% triflic acid), practically no reaction takes place. With increasing acidity the reaction accelerates and complete conversion is achieved in pure triflic acid, indicating the involvement of diprotonated intermediates. 

The 1,4-photoaddition of aliphatic amines with benzene via photoinduced electron transfer was first reported by Bryce-Smith more than 30 years ago [375-378], In the photoreaction of triethylamine with benzene, the proton transfer from the radical cation of triethylamine to the radical anion of benzene is proposed as a probable pathway (Scheme 113). In the case of tertiary amines, the photoaddition is accelerated by the addition of methanol or acetic acid as a proton source. Similar photoaddition of diethyl ether to benzene takes place assisted by trifluoroacetic acid, where methanol is not affective [379], In these photoreactions, a-hydrogen next to the heteroatom moves to the radical anion of benzene as a proton, followed by radical ccoupling to give 1,4-addition products. Similar photoaddition of amines to the benzene ring has been reported by Ohashi et al. [380,381],... 

Use of trifluoroacetic acid as a co-solvent usually increases the rate of the reaction, but often reduces the yield of products. Acetate anion may accelerate enolization... 

The above refinements of the interpretation of earlier work have been brought about by two important developments, recognition from studies in trifluoroacetic acid that acetic and formic acids are nucleophilic (Peterson et al., 1965) and the use of 2-adamantyl tosylate as a reference point for SnI reactivity (Schleyer et al., 1970). These developments have led to sensitive ways of detecting nucleophilic assistance and have shown that solvolyses of secondary substrates in acetic and formic acids may be significantly nucleophilically assisted (Table 2). Previous arguments were based on less sensitive tests such as the rate-accelerating effect of low concentrations of added nucleophiles, which must be appropriately oriented and desolvated before they are able nucleophilically to assist in the displacement reaction (Peterson et al., 1967). 

The readily prepared and air-stable complex trans 4, catalyzes Diels-Alder reactions between 1,3-dienes and a,]3-unsaturated methyl ketones or enals. Nitro-methane is the best solvent, and rate accelerations are up to a factor of 10 compared to the uncatalyzed reaction and up to 10 compared to catalysis by trifluoroacetic acid (Scheme 10.20) [34]. 

The readily prepared and air-stable complex trans-[Ru(salen)(N0)(H20)](SbF6), when added (1 mol %) to Diels-Alder reactions in nitromethane, leads to acceleration by as much as 10. The presence of water slows the reaction, but does not inhibit it. The Ru catalyst is 1 or 2 orders of magnitude more efficient in catalyzing these reactions than trifluoroacetic acid (Sch. 51) [190]. Asymmetric versions of the Ru methodology have not appeared in the literature but chiral oxo(salen)Mn(V) complexes show some promise the results of the best (of ten compoimds tested) are included in Sch. 51 [191]. 

A very convenient and versatile new reduction method, which has been intensively studied for the reduction of thiophenes (vide infra), makes use of the combination of a trialkylsilane and an acid, usually trifluoroacetic acid (TFA). This so-called ionic hydrogenation provides a novel reduction of furans to tetrahydrofurans (Scheme 3). Although Bolestova et al. find that the conditions are critical in order to avoid polymerization, the yields of tetrahydrofurans can be quite good. The reduction is accelerated by the presence of boron trifluoride etherate but fails with carbonyl-substituted furans, such as methyl pyro-mucate. ... 

MALDI TOP (7) mass spectra were recorded on a Bruker Reflex instrument (Billerica, MA). The rp-HPLC fractions containing PMP labeled oligosaccharides were dried in a SpeedVac concentrator (Farmingdale, NY) and redissolved in water/acetonitrile (75/25, v/v). 2,5-Dihydroxybenzoic acid (DHB) was used as a matrix. Normally, 0.3 uL of a half-saturated solution of DHB in water/acetonitrile/trifluoroacetic acid (70/30/0.1, v/v) was mixed on the sample dish with 0.3 pL of the sample solution. Desorption and ionization was done with a nitrogen laser (337 nm) adjusted to minimum laser attenuation. Mass spectra (10 to 20) were accumulated in linear negative ionization mode with an acceleration voltage of 25 kV. Calibration was done externally with bovine insulin and angiotensin I. 

The rate of acetylation of 0-(hydrox3Tnethyl)cellulose (and other hydroxy compounds) by mixtures of carboxylic acids and their anhydrides has been found to increase greatly in the presence of trifluoroacetic acid. The acceleration is very much less with mono- and tri-chloroacetic acids, presumably because they form unsymmetrical anhydrides which are less effective acylating agents than acyl trifluoroacetates. The exceptional acylating power of the latter anhydrides is shown by their use in the synthesis of alkyl aryl ketones from polyalkylbenzenes, phenyl ethers, furan, and thiophene under mild conditions. The principle has been extended to include acids... 

In the same way, Brdnsted acid catalysts such as trifluoroacetic acid substantially accelerate the Claisen rearrangement of allylphenyl ether. However, the initially formed allylphenols generally react further under the acidic reaction conditions. For instance, crotyl p-tolyl ether (219) in trifluoroacetic acid affords benzofuran 220 as the main reaction product derived from cyclization of the Claisen rearrangement product 221 (equation 151) . ... 

Isomerization of phenols 137 over sUica gel in the solid phase furnishes the corresponding 2,3-dihydro-4-oxo-4//-l-benzopyrane derivatives 138 (equation 60) ° . The cascades of the charge-accelerated rearrangements of the ortl o-(l,l-dimethylpropenyl)phenol 139 catalyzed by Bronsted acid (e.g. trifluoroacetic acid, equation 61) as well as by Lewis acids (anhydrous AICI3 or TiCLj, equations 62 and 63) proceed via the common intermediate 140 . 

Pyrimidines have been reported to undergo accelerated IMDA-cycloelimination reactions when carried out in trifluoroacetic acid as solvent104. 

Trifluoroacetic acid slowly cleaves Cbz groups allowing the selective removal of Boc groups. However, Kiso and co-workers noted a marked acceleration in the presence of thioanisole, and the method is illustrated in Scheme 8.53 by the simultaneous cleavage of a diphenylmethyl ester and a Cbz group in the last step of a synthesis of Acivicin. ... 

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