Trifluoroacetic acid catalyst

Yen and Chu subsequently also disclosed a related Pictet-Spengler reaction involving tryptophan and ketones for the preparation of 1,1-disubstituted indole alkaloids [417]. In the approach shown in Scheme 6.234, tryptophan was reacted with numerous ketones (12 equivalents) in toluene in the presence of 10 mol% of trifluoroacetic acid catalyst. Using microwave irradiation at 60 °C under open-vessel conditions, the desired products were obtained in high yields. Compared to transformations carried out at room temperature, reaction times were typically reduced from days to minutes. Subsequent treatment with isocyanates or isothiocyanates led to tetrahydro-/8-carbolinehydantoins. 

Diazotization /-Amyl nitrite. i-Amyl nitrite-Trifluoroacetic acid (catalyst). Sulfamic acid. Urea. 

A solution of trifluoroacetic acid in toluene was found to be advantageous for cydization of pyruvate hydrazoncs having nitro substituents[4]. p-Toluene-sulfonic acid or Amberlyst-15 in toluene has also been found to give excellent results in preparation of indole-2-carboxylale esters from pyruvate hydra-zoiies[5,6J. Acidic zeolite catalysts have been used with xylene as a solvent to convert phenylhydraziiies and ketones to indoles both in one-flask procedures and in a flow-through reactor[7]. 

Chemically, 2,2,2-trifluoroethanol behaves as a typical alcohol. It can be converted to trifluoroacetaldehyde [75-90-1] or trifluoroacetic acid [76-05-1] by various oxidi2iag agents such as aqueous chlorine solutions (51) or oxygen ia the preseace of a vanadium pentoxide catalyst (52). Under basic conditions, it adds to tetrafluoroethylene and acetylene to give, respectively, 1,1,2,2-tetrafluoroethyl 2/2/2 -trifluoroethyl ether [406-78-0] (53) and... 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

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... 

Aqueous hydrofluoric acid dissolved in acetonitrile is a good catalyst for intramolecular Diels-Alder reactions [9] This reagent promotes highly stereoselective cyclizations of different triene esters (equation 8) The use of other acids, such as hydrochloric, acetic, and trifluoroacetic acid, results in complete polymerization of the starting trienes [9] (equation 8)... 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

The effect of catalysis by trifluoroacetic acid on chlorination in carbon tetrachloride has also been determined272. For 1,2,4,5-tetramethylbenzene, with low concentrations of catalyst, the order in catalyst is three-halves, but for toluene (which requires a higher concentration) the order is mixed three- and five-halves the indication is, therefore, that a minimum of three catalyst monomers (or one monomer and one dimer) are necessary. Since trifluoroacetic acid is very likely to be dimeric in carbon tetrachloride, the concentration of monomer is pro-... 

Note Kricheldorf et al.268 synthesized the same polyester by a similar procedure using Ti(OPr)4 as polymerization catalyst. The characteristics of the resulting polymer were inherent viscosity 0.22 dL/g (determined at 20°C in 4/1 CH2C12-trifluoroacetic acid at a concentration of 0.2 g/dL). DSC Tg = 164°C. Degree of branching (DB) 0.48 (determined by H NMR). 

Cationic polymerization of cyclosiloxanes is well known but used much less frequently than anionic reactions. The most widely used catalysts include sulfuric acid and its derivatives, alkyl and aryl sulfonic acids and trifluoroacetic acid1 2,1221. Due to their ease of removal, in industrial applications acid catalysts are generally employed on supports such as bentonite clay or Fuller s earth. 

Traditional methods for bromination of toluene with bromine and a catalyst result in relatively low / ara-selectivity. For example, bromine in acetic acid gives rise to approximately a 4 1 mixture of the para- and ort/to-bromotoluenes (ref. 4). The para-selectivity is enhanced in trifluoroacetic acid so that approximately 90 % of the para-isomer is produced, but greater selectivity than this is unusual. 

Acid derivatives that can be converted to amides include thiol acids (RCOSH), thiol esters (RCOSR), ° acyloxyboranes [RCOB(OR )2]. silicic esters [(RCOO)4Si], 1,1,1-trihalo ketones (RCOCXa), a-keto nitriles, acyl azides, and non-enolizable ketones (see the Haller-Bauer reaction 12-31). A polymer-bound acyl derivative was converted to an amide using tributylvinyl tin, trifluoroacetic acid, AsPh3, and a palladium catalyst. The source of amine in this reaction was the polymer itself, which was an amide resin. 

So do anhydrides and many compounds that enolize easily (e.g., malonic ester and aliphatic nitro compounds). The mechanism is usually regarded as proceeding through the enol as in 12-4. If chlorosulfuric acid (CISO2OH) is used as a catalyst, carboxylic acids can be ot-iodinated, as well as chlorinated or brominated. N-Bromosuccinimide in a mixture of sulfuric acid-trifluoroacetic acid can mono-brominate simple carboxylic acids. ... 

Reaction conditions reflux of a mixture of the aromatic compound, N-benzoylimid-azole, and trifluoroacetic acid in a molar ratio of 1 1.2 10. This method for acylating aromatic hydrocarbons works without the use of classical Friedel-Crafts catalysts. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at... 

---