Reaction acid catalysed

CF3CO2H. Colourless liquid, b.p. 72-5 C, fumes in air. Trifluoroacetic acid is the most important halogen-substituted acetic acid. It is a very strong acid (pK = o y) and used extensively for acid catalysed reactions, especially ester cleavage in peptide synthesis. 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

Appreciating the beneficial influences of water and Lewis acids on the Diels-Alder reaction and understanding their origin, one may ask what would be the result of a combination of these two effects. If they would be additive, huge accelerations can be envisaged. But may one really expect this How does water influence the Lewis-acid catalysed reaction, and what is the influence of the Lewis acid on the enforced hydrophobic interaction and the hydrogen bonding effect These are the questions that are addressed in this chapter. 

Scheme 2.2. Lewis-acid catalysed reactions in pure water.

To the best of our knowledge the data in Table 3.2 constitute the first example of enantio selectivity in a chiral Lewis-acid catalysed organic transformation in aqueous solution. Note that for the majority of enantioselective Lewis-acid catalysed reactions, all traces of water have to be removed from the... 

The use of dienophile 5.1 also allows study of the effect of micelles on the Lewis-acid catalysed reaction. These studies are described in Section 5.2.2. and represent the first in-depth study of Lewis-acid catalysis in conjunction with micellar catalysis , a combination that has very recently also found application in synthetic organic chemistry . ... 

The rate of the Lewis-acid catalysed Diels-Alder reaction in water has been compared to that in other solvents. The results demonstrate that the expected beneficial effect of water on the Lewis-acid catalysed reaction is indeed present. However, the water-induced acceleration of the Lewis-add catalysed reaction is not as pronounced as the corresponding effect on the uncatalysed reaction. The two effects that underlie the beneficial influence of water on the uncatalysed Diels-Alder reaction, enforced hydrophobic interactions and enhanced hydrogen bonding of water to the carbonyl moiety of 1 in the activated complex, are likely to be diminished in the Lewis-acid catalysed process. Upon coordination of the Lewis-acid catalyst to the carbonyl group of the dienophile, the catalyst takes over from the hydrogen bonds an important part of the activating influence. Also the influence of enforced hydrophobic interactions is expected to be significantly reduced in the Lewis-acid catalysed Diels-Alder reaction. Obviously, the presence of the hydrophilic Lewis-acid diminished the nonpolar character of 1 in the initial state. 

As expected, the solvent has a significant effect on the endo-exo selectivity of the uncatalysed Diels-Alder reaction between 1 and 2. In contrast, the corresponding effect on the Lewis-acid catalysed reaction is small. There is no beneficial effect of water on the endo-exo selectivity of the catalysed Diels-Alder reaction. The endo-exo selectivity in water is somewhat diminished relative to that in ethanol and acetonitrile. 

Acid-Gatalyzed Synthesis. The acid-catalysed reaction of alkenes with hydrogen sulfide to prepare thiols can be accompHshed using a strong acid (sulfuric or phosphoric acid) catalyst. Thiols can also be prepared continuously over a variety of soHd acid catalysts, such as seoHtes, sulfonic acid-containing resin catalysts, or aluminas (22). The continuous process is utilised commercially to manufacture the more important thiols (23,24). The acid-catalysed reaction is commonly classed as a Markownikoff addition. Examples of two important industrial processes are 2-methyl-2-propanethiol and 2-propanethiol, given in equations 1 and 2, respectively. 

Allylic A" -3-hydroxyls are particularly reactive, although some difficulty arises because this system is prone to acid-catalysed dehydration to the 3,5-diene. A" -3-Methyl ethers are readily prepared by direct, p-toluenesulfonic acid-catalysed reaction with methanol. 

With 77 % aqueous acetic acid, the rates were found to be more affected by added perchloric acid than by sodium perchlorate (but only at higher concentrations than those used by Stanley and Shorter207, which accounts for the failure of these workers to observe acid catalysis, but their observation of kinetic orders in hypochlorous acid of less than one remains unaccounted for). The difference in the effect of the added electrolyte increased with concentration, and the rates of the acid-catalysed reaction reached a maximum in ca. 50 % aqueous acetic acid, passed through a minimum at ca. 90 % aqueous acetic acid and rose very rapidly thereafter. The faster chlorination in 50% acid than in water was, therefore, considered consistent with chlorination by AcOHCl+, which is subject to an increasing solvent effect in the direction of less aqueous media (hence the minimum in 90 % acid), and a third factor operates, viz. that in pure acetic acid the bulk source of chlorine ischlorineacetate rather than HOC1 and causes the rapid rise in rate towards the anhydrous medium. The relative rates of the acid-catalysed (acidity > 0.49 M) chlorination of some aromatics in 76 % aqueous acetic acid at 25 °C were found to be toluene, 69 benzene, 1 chlorobenzene, 0.097 benzoic acid, 0.004. Some of these kinetic observations were confirmed in a study of the chlorination of diphenylmethane in the presence of 0.030 M perchloric acid, second-order rate coefficients were obtained at 25 °C as follows209 0.161 (98 vol. % aqueous acetic acid) ca. 0.078 (75 vol. % acid), and, in the latter solvent in the presence of 0.50 M perchloric acid, diphenylmethane was approximately 30 times more reactive than benzene. 

Kinetic studies of acylation, which are limited almost exclusively to the Lewis acid-catalysed reaction represented by... 

A third mechanism of protodeboronation has been detected in the reaction of benzeneboronic acids with water at pH 2-6.7625. In addition to the acid-catalysed reaction described above, a reaction whose rate depended specifically on the concentration of hydroxide ion was found. In a preliminary investigation with aqueous malonate buffers (pH 6.7) at 90 °C, 2-, 4-, and 2,6-di-methoxybenzeneboronic acids underwent deboronation and followed first-order kinetics. A secondary reaction produced an impurity which catalysed the deboronation, but this was unimportant during the initial portions of the kinetic runs. 

Rows 12-16 in Table 201 show that the acceleration by cadmium ion is not linear with concentration, becoming proportionally less as the concentration is increased. The last entry shows the magnitude of the experimental error in the acid-catalysed portion of the reaction for this result now indicates that cadmium ion has no effect on the acid-catalysed reaction. 

Analysis of the rate coefficients, corrected for this uncatalysed reaction revealed a complex dependence of an acid-catalysed reaction, such that the logarithms of the rate depended on H0 in phosphoric acid, upon log (aH2o-aHcioJ n perchloric acid and upon log (aH20 aH2so4) n sulphuric acid clearly, no satisfactory mechanistic picture is likely to ensue from these data for the acid-catalysed reaction without considerable further investigation. 

Analysis of substituent effects in the reaction revealed random correlations of rate with a values of substituents for the uncatalysed reaction, but for the acid-catalysed reaction, reasonable Hammett plots with p factors of —1.27 (HC104) and -1.12 (H3P04) were obtained (Table 253). 

It is important for acid-catalysed reactions to determine whether the reaction is specifically catalysed by hydrogen ions or whether general acid catalysis takes place. Specific acid catalysis has been conclusively demonstrated for the benzidine rearrangement by three different sorts of kinetic experiments. In the first, it has been shown41 by the standard test for general acid catalysis (by measuring the rate of reaction in a buffered solution at constant pH over a range of concentration... 

Acid catalysed reactions of transition metal complexes. P. J. Staples, Coord. Chem. Rev., 1973,11, 277-342 (181). 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

The first enantioselective synthesis of cis- and trans- 3-hydroxyflavanones is based on the Lewis-acid-catalysed reaction of phenylmethanethiol with chalcone epoxides <96CC2747>. Further support for the intermediacy of epoxides in the Algar-Flynn-Oyamada flavone synthesis has been provided by the isolation of epoxides in the corresponding preparation of 3-hydroxy-2-phenylquinol-4-ones <96JCS(P2)269>. 

Phosphonoformic acid (85) decarboxylated in acid solution, and it was proposed that the uncatalysed reaction involved a simple decarboxylation of the zwitterion. The acid-catalysed reaction showed some kinetic similarity to that of mesitoic acid and an elimination of carbon dioxide as trihydroxymethylcarbonium ion was preferred. Participation of the trans vicinal phosphonyl group in the solvolysis of the halides (86) and (87) has been deduced from rate measurements. In the norbornene derivatives, the relative rates of loss of chloride from (87a) and (87b) were 5 x 10 1. 

Sulphated zirconia catalysts can be acidic or superacidic depending on the method of treatment. A variety of acid-catalysed reactions, referred to earlier in this section, can be carried out with sulphated zirconia. Yadav and Nair (1999) have given a state-of-the art review on this subject. Examples of benzylation of benzene with benzyl chloride / benzyl alcohol, alkylation of o-xylene with. styrene, alkylation of diphenyl oxide with 1-dodecene, isomerization of epoxides to aldehydes, acylation of benzene / chlorobenzene with p-chloro benzoylchloride, etc. are covered in the review. 

Reaction Scheme. The acid catalysed reactions for preparing the hybrid materials in the present study can be illustrated by the simplified scheme shown below ... 

HP As containing heteroatoms such as Si and Ge were also measured and the results are outlined in Table 2. From the table, the activity of silica-supported Keggin HP As is in an order of HPW HSiW > HGeW, which corresponds to the order of the acidity of the bulk Keggin HP As (8). This is not surprising since the direct addition of the ethylene to acetic acid is an acid catalysed reaction. 

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