Ethyl trifluoroacetate, hydrolysis

The imidazole by-product is relatively inert and does not cause decomposition of the derivatives [69]. As with the use of ethyl trifluoroacetate as an acylating agent, the unfavourable properties of trifluoroacetic acid produced are eliminated [70]. With the addition of hexamethylenediamine the reaction proceeds rapidly at 60—70°C and the yield is about 70%. If dry ammonia is added to the reaction mixture, the reaction proceeds quantitatively. Ammonia probably neutralizes the residues of trifluoroacetic acid produced by the hydrolysis of the ester and in this way eliminates a competitive acylation reaction. 

It is interesting that the carbonyl addition reactions in both ethyl trifluoroacetate ethanolysis (Johnson, 1964) and ethyl trifluorothiol-aoetate hydrolysis involve the same general base catalysis... 

No acid inhibition can be detected in the hydrolysis of ethyl trifluoroacetate (Bender and Heck, 1966) instead the pH-rate profile shows an acid-catalyzed reaction below pH 2-5, a base-catalyzed reaction above pH 5, and a flat valley from pH 2-5-5, due to the uncatalyzed water reaction. Such results would be expected, since the entering OH-group and the leaving OC2H6-group in this reaction are so similar in nature that the symmetrical reaction path should exist. 

Later studies on the solvent isotope effect of the kjk ratio for the hydrolysis of ethyl trifluoroacetate have shown a sizeable effect ... 

To escape this menace, one has to introduce electron-withdrawing substituents into the adduct 221. The intermediates produced upon addition of phenyllithium or lithium acetylides onto ethyl trifluoroacetate remain intact and the sequestered ketone is liberated not before hydrolysis. In this way, 19,19,19- and 20,20,20-trifluororetinal (222a and 222b ) can be readily prepared (Scheme 1-165). 

Groves and Swan tried unsuccessfully to cyclize Af-2-(indol-3-yl)ethyl aminomethylenemalonate (1413) to tetrah ydro-/3-carboline-1 -acetate (1414) by the action of an acid or base. Instead of cyclization, hydrolysis of 1413 occurred to yield tryptamine (52JCS650). Later, Maclaren obtained 3,4-dihydro-/3-carboline when he treated 1413 with trifluoroacetic acid or boron trifluoride (87AJC1617). 

Kinetic studies of the reaction of Z-phenyl cyclopropanecarboxylates (1) with X-benzylamines (2) in acetonitrile at 55 °C have been carried out. The reaction proceeds by a stepwise mechanism in which the rate-determining step is the breakdown of the zwitterionic tetrahedral intermediate, T, with a hydrogen-bonded four-centre type transition state (3). The results of studies of the aminolysis reactions of ethyl Z-phenyl carbonates (4) with benzylamines (2) in acetonitrile at 25 °C were consistent with a four- (5) and a six-centred transition state (6) for the uncatalysed and catalysed path, respectively. The neutral hydrolysis of p-nitrophenyl trifluoroacetate in acetonitrile solvent has been studied by varying the molarities of water from 1.0 to 5.0 at 25 °C. The reaction was found to be third order in water. The kinetic solvent isotope effect was (A h2o/ D2o) = 2.90 0.12. Proton inventories at each molarity of water studied were consistent with an eight-membered cyclic transition state (7) model. 

This sensitivity to substitution of neutral hydrolysis means that the pH-independent reaction gradually becomes more important than the hydroxide reaction at the high pH end of the region, and becomes much more rapidly more important than acid-catalyzed hydrolysis at low pH. Thus from Fig. 13, the acid-catalyzed reaction can be seen to be significant for the hydrolysis of ethyl acetate between pH 4 and 5, and for phenyl acetate about pH 2 but for 2,4-dinitrophenyl acetate the acid-catalyzed reaction is not detectable at pH 1, and is presumably important only in relatively strong acid. It seems certain that this fast neutral hydrolysis is at any rate a partial explanation for the low efficiency of acid catalysis in the hydrolysis of very weakly basic esters, such as the trifluoroacetates and oxalates, in moderately concentrated acid (see p. 145). 

Apart from ethyl acetate, the least reactive ester studied is N,0-diacetyl serinamide, which is hydrolyzed in a pH-independent reaction between pH 7 and 8 with a rate coefficient193 of 2.66 x 10-5 sec-1. Salmi and Suonpaa194 and Palomaa et al. 9S, have measured the rates of neutral hydrolysis of a number of chloroacetate esters, and this work has been extended more recently by Euranto and Cleve196-198, who have measured the activation parameters for the hydrolysis of several compounds. Motfat and Hunt199 have obtained the same data for the hydrolysis of a variety of alkyl and aryl trifluoroacetates, and the data for substituted phenyl acetates191 have been plotted in Fig. 14. Most of the available data are collected in Table 27. 

Alternatively, when 21 was treated with benzaldehyde diethyl acetal-hydrochloric acid, ethyl 3,5 4,6-di-0-benzylidene-L-gulonate (76) was formed in >90% yield. Diacetal 76 was efficiently oxidized to 77 (>90% yield) with dimethyl sulfoxide-trifluoroacetic anhydride, or by way of the nitrate of 76 and triethylamine. Hydrolysis of 77 then afforded ethyl L-xy(o-2-hexulosonate in 86% yield.383... 

Ethyl enol ethers of acyl silanes have been prepared by the palladium-mediated addition of silyl stannanes to alkynyl ethers. Hydrolysis using trifluoroacetic acid gave very high yields of acyl silanes (vide supra, Section m.A.4)82. 

Finally, Winchester, Zappone and Skinner have reported the synthesis of 7,8-dihydro-8-oxa-9-oxopteroic acid (190) as part of a programme to evaluate members of this class of heterocyclic compounds as DHFR inhibitors [112]. In their approach (Scheme 3.36 ), the key intermediate acid (187) was prepared from 2,5-diamino-4,6-dihydroxypyrimidine and ethyl bromopyruvate followed by saponification [113]. Owing to the extreme insolubility of (187) in most solvents, it was converted to the disodium salt (188) and treated with excess trifluoroacetic anhydride to yield the mixed anhydride (189) [114]. Coupling with p-aminobenzoic acid and careful base hydrolysis gave (190), albeit in low... 

Hydrolysis of vinyl chlorides. One step in the Wichterle annelation with l,3-dichloro-cw-2-butene (1,214-215 2, 111-112) involves hydrolysis of an intermediate vinyl chloride to a ketone. This reaction has been conducted with cone. H2SO4. A new method involves reaction with mercury(II) trifluoroacetate, which can result in either a methyl or an ethyl ketone depending on the solvent. For example, hydrolysis of 1 with the mercury salt in CH3NO2, CH2CI2, or HOAc gives only the 1,5-diketone 2 in 90-97% yield hydrolysis in CH3OH gives 3 as the major product in 83% yield. ... 

Due to the instability of the feri-butyl ester, and the resistance of the ethyl ester to transesterification, installation of the methyl ester prior to glycosylation was clearly required. Conversion of tert-butyl enol ester 51b to the methyl ester 51a was achieved in 78% yield over two steps, with hydrolysis of the tert-bvAy ester using trifluoroacetic acid at 0 °C, followed by methylation with trimethylsilyl diazomethane (Scheme 21). Gratrfyingly, when methyl enol ester 51a was... 

Transformation of oxazoline 53 formed the amino alcohol derivatives 54 on opening of the ring with H2SO4. Reduction of 53 with diisobutylaluminium hydride provided A -Ethyl amino alcohol 55. Oxazoline was converted to acetamide 56 by acidic hydrolysis with trifluoroacetic acid. The overall transformation of 53 to 56 represents the regioselective caibohydroxylation of (V-Allylacetamide [83-84] (Scheme 12.13). 

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