Ethyl formate, hydrolysis

Metwally et al. [28] also studied the resin-catalyzed hydrolysis of ethyl formate in acetone-water mixtures at different temperatures. The experimental results indicated a linear dependence of the logarithm of rate constant on the reciprocal of the dielectric constant (Fig. 2). The decrease of dielectric constant may lower the concentration of the highly polar transition state and thereby decrease the rate [28]. 

Figure 2 Log kr for the resin catalyzed hydrolysis of ethyl formate as a function of the reciprocal of the dielectric constant.

J mol ). This is additional evidence in favor of rate limitation by inner diffusion. However, the same reaction in the presence of Dowex-50, which has a more open three-dimensional network, gave an activation energy of 44800 J mol , and closely similar values were obtained for the hydrolysis of ethyl acetate [29] and dimethyl seb-acate [30]. The activation energy for the hydrolysis of ethyl acetate on a macroreticular sulphonated cationic exchanger [93] is 3566 J mol . For the hydrolysis of ethyl formate in a binary system, the isocomposition activation energy (Ec) [28,92] tends to decrease as the solvent content increases, while for solutions of the same dielectric constant, the iso-dielectric activation energy (Ed) increases as the dielectric constant of the solvent increases (Table 6). 

Table 6 Iso-Dielectric Activation Energy Ed) for the Hydrolysis of Ethyl Formate in Acetone-Water Systems [28]...

Block one side of the ketone by introducing a removable group. Alkylation takes place on the other side the blocking group is then removed. A common reaction for this purpose is formylation with ethyl formate (10-119) this generally blocks the less hindered side. The formyl group is easily removed by alkaline hydrolysis (12-41). 

The lower spectrum shows an ester group (triplet at 1.2 ppm, quartet at 4.2 ppm) and a singlet at 8.1 ppm, the latter indicating the presence of a formyl group. Peak 1 results from ethyl formate, formed by adventitious hydrolysis of the acetal 4. The middle and top spectra correspond to the two acetals (see equation) the assignment is very simple. 

Consider the esterification of ethyl alcohol with formic acid to give ethyl formate (and water) in a mixed alcohol-water solvent, such that the alcohol and water are present in large excess. Assume that this is pseudo-first-order in both esterification (forward) and hydrolysis (reverse) directions ... 

Serine has been prepared by the Strecker method from glycol-aldehyde 1 and from ethoxyacetaldehyde,2 3 by the condensation of ethyl formate with ethyl hippurate followed by reduction and hydrolysis,4 5 from the reaction product of chloromethyl ether with ethyl sodium phthalimidomalonate,6 and by amination of a-bromo-/3-methoxypropionic acid with subsequent demethyla-tion.7... 

Yet a further increase in potency is observed when the para-isobutyl group is replaced by a benzene ring. One published synthesis for that compound is quite analogous to the malonate route to the parent drug. The acetyl biphenyl (50-1) is thus converted to the corresponding arylacetic acid by reaction with sulfur and morpholine, followed by hydrolysis of the first-obtained thiomorpholide. This is then esterified and converted to malonate anion (50-2) with sodium ethoxide and ethyl formate. The anion is quenched with methyl iodide hydrolysis of the esters followed by decarboxylation yields the NSAID flubiprofen (50-3) [51]. 

A small amount (5-10 ml.) of lower-boiling material usually comes over before the ethanol this is probably ethyl formate, produced by hydrolysis of the ethyl orthoformate. 

This is also consistent with the results obtained from the basic hydrolysis of formamide imidate salt 63 (33) for which there is evidence (cf 53) that this compound exists in the syn conformation. This salt gave a =1 1 mixture of ethyl formate and N,N-dimethylformamide. 

In a review of nucleophile isotope effects in chemistry, the hydrolysis of formates was discussed.10 The effect of dioxane on the acid-catalysed hydrolysis of ethyl formate was studied by carrying out the reaction in 0-80% (v/v) dioxane at different temperatures ranging from 20 to 40 °C. It was proposed that up to 1.5 mol of water are associated with the activated complex.11 Kinetic studies of the alkaline hydrolysis of ethyl decanoate12 in DMF-H2O solutions and of ethyl isovalerate13 in aqueous acetone were reported. 

Predicting Hydrolysis Rate Difference Based on Substituents Sizes PROBLEM Based on Taft steric parameters, how much faster than ethyl acetate would you expect ethyl formate to hydrolyze ... 

SOLUTION Ethyl formate (12.12, R = H) should hydrolyze faster than ethyl acetate (12.12, R = CH3) because steric hindrance about the carbonyl is lower in ethyl formate. The question is How much faster The only equation provided in this section on Taft parameters is Equation 12.17, and that is where we will begin. In this case, we are solving for the ratio of the hydrolysis rate constants, kR/kcu, . / ( n is known and equals +1.24 according to Table 12.4. Ethyl formate hydrolyzes 17.4 times faster than ethyl acetate. 

The synthesis of this starting material 73 X = SMe also uses interesting strategy. The first step was a Diels-Alder reaction between a cyelopentadiene 77 and the dienophile 62 used by Nicolaou in his taxol synthesis. The diene was made from the anion of cyclopentadiene 74 and ethyl formate,18 and the enolate 76 transformed into the enol acetate 77. Diels-Alder addition of 62 and hydrolysis of the enol ester gave the adduct19 78. 

Ethyl formate Acid hydrolysis x, 9 1938, 1964 Conflicting observations... 

The titanium complex is diamagnetic which, if the titanium is present as Tin, indicates a strong exchange interaction. It reacts with C02 forming THF.Ti(OOCH)2MgCl15, which yields formic acid on hydrolysis and ethyl formate with C2H5I. This indicates that the hydrogen is bound to the carbon atom of the co-ordinated C02 molecule as in (7) or (8). The formation of C—H bonds implies the presence of reactive metal-hydride intermediates.76... 

In the forward direction the ester is formed, and in the reverse direction it is hydrolyzed. For esterification, the alcohol can be used as a solvent as described for methyl acetate synthesis [26]. For ester hydrolysis, water can be used as a solvent, as described for hydrolysis of methyl formate, ethyl formate, methyl acetate and ethyl acetate [28]. Usually, the solvent is taken in large excess and it can be assumed in good approximation that its concentration is constant. For constant alcohol... 

Hydrolysis of ethyl formate follows the reverse path of the Fischer esterification. This part of the mechanism is left to you as an exercise. 

Ergosteryl tosylate, 239 Esters, conformation, 25 —, hydrolysis, 18,24-26 Ethers, cleavage, 50 —, oxidation, 52 Ethoxycarbonylhydrazine, 337 Ethyl formate, 181 Ethyleneimines, 117 Ethylidenetriphenyiphosphorane, 153... 

Example 4.18. Hydrolysis of ethyl orthoformate to ethyl formate. 

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