Trifluoroacetic acid cleaving with

Peptide synthesis. The p-methoxybenzyl group is regarded as superior to the benzyl group for S-protection. It is readily cleaved from the final peptide either by sodium in liquid ammonia or by boiling with trifluoroacetic acid or with anhydrous hydrogen fluoride. ... 

In the third method, the amino groups on the support are brought into reaction with an excess of 4,4 -phenylene diisothiocyanate and the residual free isothiocyanate groups are available to couple with the a- and e-amino groups on the peptide (Scheme 5.6). Treatment with trifluoroacetic acid cleaves the first peptide... 

In most of the published Merrifield syntheses the peptides are bound to polystyrene by benzyl ester type of linkages, which in analogy to classical methods can be cleaved by HBr/acetic acid. Already in the incipience period of the methodology, however, trifluoroacetic acid saturated with hydrogen bromide was found more efficient, first, because of the increased acidity of the mixture which in addition does not cause proton catalyzed acetylation and, second, since trifluoroacetic acid is more lipophilic than the acetic one, it solvates much better both the polymer and the peptide to be released. 

The tert butyl group is cleaved as the corresponding carbocation Loss of a proton from tert butyl cation converts it to 2 methylpropene Because of the ease with which a tert butyl group is cleaved as a carbocation other acidic reagents such as trifluoroacetic acid may also be used... 

The (9-isobomyl- and (9-[l-(5-pentamethylcyclopentadienyl)ethyl]-derivatives do not undergo rearrangement, but are very labile in trifluoroacetic acid (100% cleaved in 5 min). The cyclohexyl and isopropyl derivatives are more stable to acid, but undergo some rearrangement. The cyclohexyl group combines minimal rearrangement with ready removal. ... 

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

The change of mechanism with tertiary alkyl esters is valuable in synthetic methodology because it permits certain esters to be hydrolyzed very selectively. The usual situation involves the use of t-butyl esters, which can be cleaved to carboxylic acids by action of acids such as p-toluenesulfonic acid or trifluoroacetic acid under anhydrous conditions where other esters are stable. 

Protect glycine as its Boc derivative and anchor this to the solid support. Remove the protecting group and treat with Boc-protected phenylalanine and DCCI. Remove the Boc group with HCl then treat with FIBr in trifluoroacetic acid to cleave Phe-Gly from the solid support. 

CF3COOH, TFAA, CH2CI2. These conditions afford the trifluoroacetate, thus preventing retritylation, which is sometimes a problem when a trityl group is cleaved with acid. A further advantage of these conditions was that a SEM group was completely stable. When TFAA was not used. 

These esters were prepared from the phenol and the acid chloride, plus DMAP (or from the acid plus trifluoroacetic anhydride). Although the diisopropyl derivative can be cleaved with hot aqueous NaOH, the di-r-butyl derivatives could only be cleaved with NaOMe in a mixture of toluene and HMPA. The related... 

Ethers with a tertiary, benzylic, or allylic group cleave by an S l or FI mechanism because these substrates can produce stable intermediate carbocations. These reactions are often fast and take place at moderate temperatures. fcrf-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. We ll see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

Use of this reagent is however, somewhat limited. You can only use it in solvents which don t react with it (D4-methanol, and D2O are obviously out of the question), or contain a lot of water, i.e., D6-DMSO. Another slight drawback is that the cleaving of the anhydride liberates trifluoroacetic acid,... 

The resin-bound salicylic esters were suspended in N,N-dimethylformamide (DMF) and placed in an Erlenmeyer flask within a domestic microwave cavity. After microwave irradiation for 4—6 min (1 min cycles), the reaction mixture was allowed to cool to ambient temperature and the resin was collected by fdtration and washed with methanol and dichloromethane. The desired compounds were subsequently cleaved with trifluoroacetic acid in dichloromethane. Removal of the solvent by evap-... 

The final conditions were scaled up with no problems chalcone 8a and guanidine (liberated from its hydrochloride with sodium ethoxide) were heated in dimethyl acetamide while bubbling air through the mixture to form pyrimidine 9a. After complete conversion (16 h), the product was cleaved from the support (20% trifluoroacetic acid in DCM). Pure 4-(2-amino-6-phenyl-pyrimidin-4-yl)bcnzamidc 1 was obtained as its trifluoroacetate salt upon evaporation of the filtrate and recrystallisation of the residue from ethanol/water in 56% overall yield based on the solid phase attached 4-carboxybenzaldehyde 6a. 

The Mannich products were cleaved from the resin into tared tubes by reaction with 4mL of 25% trifluoroacetic acid in methylene chloride (v/v) at ambient temperature for 1 min. Each resin was filtered and rinsed with methylene chloride (2mL). The filtrate was concentrated under a stream of nitrogen gas to a brown residue. This material was dissolved in acetonitrile (4mL), and the product was concentrated again under a stream of nitrogen. This procedure was repeated two more times using methanol... 

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