Methyl trifluoroacetate hydrogenation

Vanadium-catalyzed hydroxylation of benzene and cyclohexane has also been obtained with in situ generation of hydrogen peroxide from H2/O2 in the presence of palladium. A similar process has been settled for methane oxygenation to methyl trifluoroacetate and formic acid. Monoperoxovanadate, as well as copper hydroperoxides, have been indicated as the active species for the activation of the C—H bond of methane. 

Fig. 12. First-order rate coefficients for the hydrolysis of weakly basic esters, as a function of acid concentration. Data for phenyl and methyl trifluoroacetates in HCIO, in 70% dioxan-water at 0°C (from refs. 89 and 90). and for o-nitrophenyl hydrogen oxalate in aqueous HCI at 25.5°C (from ref. 171 corrected for the reaction of the anion using pA", = 0.35).

Trifluoroacetic acid at 300-390 °C produces mainly carbon dioxide, difluoro-methyl trifluoroacetate, carbon monoxide and trifluoroacetyl fluoride. Blake and Pritchard propose that the decomposition proceeds through the elimination of hydrogen fluoride, followed by the formation of difluorocarbene which largely adds to trifluoroacetic acid to form the difluoromethyl ester. The kinetic order is about 0.5 and the overall activation energy for the formation of carbon dioxide and the difluoromethyl ester is about 45 kcal.mole" ... 

CH3F (trace). Pyrolysis of sodium trifluoroacetate alone yields trifluoro-acetyl fluoride and trifluoroacetic anhydride pyrolysis of sodium trifluoroacetate in the presence of sodium hydroxide, however, does appear to give difluorocarbene since tetrafluoroethylene is produced in at least 32% yield. Data from kinetic studies on hydrogen atom abstraction by Me and CFa (generated by photolysis of acetone and hexafluoroacetone, respectively) from methyl trifluoroacetate and methyl fluoroformate have been presented and discussed. ... 

Surprisingly, there are very few examples of successful fV-oxidation of pyrazoles. Simple fV-alkylpyrazoles generally do not react with peracids (B-76MI40402,77JCS(P1)672). The only two positive results are the peracetic acid (hydrogen peroxide in acetic acid) transformation of 1-methylpyrazoIe into 1-methylpyrazole 2-oxide (268) in moderate yield and the peroxy-trifluoroacetic acid (90% hydrogen peroxide in trifluoroacetic acid) transformation of 5-amino-l-methylpyrazoIe into l-methyl-5-nitropyrazoIe 2-oxide (269). 

Attempts to effect ring expansion of methyl 2-azidobenzoate in the presence of other nucleophiles have failed. Thus, photolysis in tetrahydrofuran solution saturated with hydrogen sulfide, or with ammonia, produced methyl 2-aminobenzoate in 54 and 37 % yield, respectively, as the sole identifiable product.197 Photolysis of phenyl azide in ethanolic phenol gave 2-phenoxy-3//-azepine in poor yield (8 %).203,204 2-Mesityl-3//-azepine (10 %) is the surprising, and only tentatively explained, product from the photolysis of phenyl azide in mcsitylene in the presence of trifluoroacetic acid.179... 

A mixture of exo- and endo-isomers of 5-methylbicylo[2.2.1]hept-2-ene is hydrogenated with the aid of five equivalents of triethylsilane and 13.1 equivalents of trifluoroacetic acid to produce a 45% yield of < <7o-2-methylbicylo[2.2.1] heptane (Eq. 71). The same product is formed in 37% yield after only five minutes. The remainder of the reaction products is a mixture of three isomeric secondary exo-methylbicylo[2.2.1]heptyl trifluoroacetates that remains inert to the reaction conditions. Use of triethylsilane-l-d gives the endo-2-methylbicylo-[2.2.1]heptane product with an exo-deuterium at the tertiary carbon position shared with the methyl group. This result reflects the nature of the internal carbocation rearrangements that precede capture by the silane.230... 

Preferential protonation of oxygen in comparison to carbon prevents 4-methyl-enetetrahydropyran from undergoing reduction to 4-methyltetrahydropyran even when held at 70° for 10 hours in the presence of triethylsilane and a 20-fold excess of trifluoroacetic acid.146 However, when the reaction conditions are changed so that a dichloromethane solution of the same substrate is treated with a mixture of four equivalents of triethylsilane and three equivalents of aluminum chloride in the presence of excess hydrogen chloride, a 40% yield of 4-methyltetrahydropyran product is obtained at room temperature after one hour (Eq. 75).136... 

Exceptions to the generally facile ionic hydrogenation of trisubstituted alkenes include the resistance of both 2-methyl-1-nitropropene (R = NO2) and 3,3-dimeth-ylacrylic acid (R = CO2H) to the action of a mixture of triethylsilane and excess trifluoroacetic acid at 50° (Eq. 85).234 The failure to undergo reduction is clearly related to the unfavorable effects caused by the electron-withdrawing substituents on the energies of the required carbocation intermediates. 

Reduction of dienes incorporated into steroid structures may lead to different configurations in the products. For example, treatment of 8(9),14(15)-bisdehydroestrone 42 (R = H) for four hours at room temperature with twenty equivalents of trifluoroacetic acid and two equivalents of triethylsilane leads to an ionic hydrogenation product mixture containing the natural 8/1,9a,14a-estrone 43 as a minor component (11%) and the 8a,9/i, l 4/i-isomcr 44 as the major component (83%) (Eq. 92).241 The related methyl ether (42, R = Me) behaves in a similar fashion.241 The yield of natural isomer 46 formed from the methyl ether of A8(9),i4(i5)-bigdehydroestradiol analog 45 increases from 22 to 34%, and that of... 

Acid- and base-promoted methods have also been used in the syntheses of pyrazoles. Hydrogenation of methyl 2-Cbz(hydrazine)-3-hydroxy-4,4-dimethoxybutanoate 11 followed by cyclization in the presence of trifluoroacetic acid afforded the first asymmetric synthesis of the (4S,5.R)-5-carbomethoxy-4-hydroxy-A2-pyrazoline 12 <00TL8795>. Reaction of 2-nitrobenzyl triphenylphosphonium ylide (13) with aiyl isocyanates afforded 2-aryl-2H-indazoles 14 <00TL9893>. Base-promoted reaction of nitrobenzenes 15 with aryl imines 16 afforded aryl pyrazoles 17 . 

The hexahydro-l//-pyrrolo[2,l-f][l,4]oxazin-l-one 82 (obtained by radical cyclization see Section 11.11.7.3) was transformed into the proline derivative 83 by hydrogenation in the presence of the Pearlman s catalyst and a stoichiometric amount of trifluoroacetic acid (TFA) (Scheme 10). This reaction led with high yield to the disub-stituted proline 83 in an enantiomerically pure form <2003SL1058>. In an analogous approach, the chiral (4/ ,7/ ,8aA)-methyl 6,6-dimethyl-l-oxo-4-phenylhexahydro-l//-pyrrolo[2,l-r-][l,4]oxazine-7-carboxylate 84 was hydrogenated on Pd(OH)2 in the presence of TFA to give enantiomerically pure 5,5-dimethylproline derivatives 85 <2001SL1836> (Scheme 10). 

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