Catalysis acids

Lewis acids act as electron pair acceptors. The proton is an important special case, but many other compounds catalyze organic reactions by acting as electron pair acceptors. The most important Lewis acids in organic reactions are metal cations and covalent compounds of metals. Metal cations that function as Lewis acids include the alkali metal monocations Li+, Na+, K+, di- and trivalent ions such as Mg +, Ca, Zn +, Sc, and Bi + transition metal cations and complexes and lanthanide cations, such as Ce + and Yb. Neutral electrophilic covalent molecules can also act as Lewis acids. The most commonly employed of the covalent compounds include boron trifluoride, aluminum trichloride, titanium tetrachloride, and tin(IV)tetrachloride. Various other derivatives of boron, aluminum, titanium, and tin also are Lewis acid catalysts. 

Neutral compounds such as boron trifluoride and aluminum trichloride form Lewis acid-base complexes by accepting an electron pair from the donor molecule. The same functional groups that act as electron pair donors to metal cations can form complexes with boron trifluoride, aluminum trichloride, titanium tetrachloride, and related compounds. In this case the complex is formed between two neutral species, it too is neutral, but there is a formal positive charge on the donor atom and a formal negative charge on the acceptor atom. 

Complexes of carbonyl oxygen with trivalent boron and aluminum compounds tend to adopt a geometry consistent with directional interaction with one of the oxygen lone pairs. Thus the C—O—M bonds tend to be in the trigonal (120°—140°) range and the boron or aluminum is usually close to the carbonyl plane.The structural specificity that is built into Lewis acid complexes can be used to advantage to achieve stereoselectivity in catalysis. For example, use of chiral ligands in conjunction with Lewis acids is frequently the basis for enantioselective catalysts. 

Titanium(IV) tetrachloride and tin(IV) tetrachloride can form complexes that are similar to those formed by metal ions and those formed by neutral Lewis acids. Complexation can occur with displacement of a chloride from the metal coordination sphere or by an increase in the coordination number at the Lewis acid. 

There are more structural variables to consider in catalysis by Lewis acids than in the case of catalysis by protons. In addition to the hard-soft relationship, steric, geometric, and stereoelectronic factors can come into play. This makes the development of an absolute scale of Lewis acid strength difficult, since the complexation strength depends on the specific characteristics of the base. There are also variations in the strength of the donor-acceptor bonds. Bond strengths calculated for complexes such as H3N+-BF3 (22.0 kcal/mol) and (CH3)3N+-BH3 (41.1 kcal/mol) are substantially 

The principal use of acidity functions has been for the study of reaction mechanisms in acid-catalyzed reactions. We consider acid-catalyzed reactions in which a nucleophile, often water, may be a reactant. Three mechanisms are commonly considered  

A fast preequilibrium protonation of substrate followed by a slow ratedetermining reaction of the protonated substrate. Subsequent steps (such as attack by water) are fast. 

A fast preequilibrium protonation followed by a slow rate-determining attack by nucleophile. 

A slow protonation of substrate followed by fast steps. 

Most acid-catalyzed hydrolyses of carboxylic acid derivatives proceed by the A2 mechanism, as shown for ester hydrolysis  

Sulfated zirconia (SZ) is a well-known solid acid catalyst that has been widely studied in the past 15 years. SZ is a very strong acid catalyst and is active for n-butane isomerisation even at room temperature. Many parameters have been found to impact the catal dic activity of SZ, such as catalyst preparation and pretreatment, which affect the sulfur content, the concentration of Lewis and Bronsted acid sites, and other characteristics. However, the deactivation of SZ during n-butane isomerisation can be severe. 

Kim et studied the fast initial deactivation observed during the first 45 min TOS at 150°C. The SSITKA results, after correction for readsorption, showed an increase in the surface residence time of iso-C4 intermediates and a corresponding decrease in site activity, as well as a 

The first example of acid catalysis appeared in a 1934 patent in which it is claimed that surface catalysts, particularly hydrosilicates of large surface area , known at that time under the trade name Tonsil, Franconit, Granisol, etc. lead to a smooth addition of the olefine to the molecule of the primary aromatic amine . Aniline and cyclohexene were reacted over Tonsil at 230-240°C to give, inter alia, the hydroamination product, N-cyclohexylaniline [47]. 

The hydroamination of alkenes has been performed in the presence of heterogeneous acidic catalysts such as zeolites, amorphous aluminosilicates, phosphates, mesoporous oxides, pillared interlayered clays (PILCs), amorphous oxides, acid-treated sheet silicates or NafioN-H resins. They can be used either under batch conditions or in continuous operation at high temperature (above 200°C) under high pressure (above 100 bar). 

Large-pore zeolites such as Y zeolites are efficient for the hydroamination of several olefins. For example, propene reacts with NH3 over SK-500 (a pelleted lanthanum-exchanged zeolite) or La-Y or H-Y zeolites with 6-15% conversion to give i-PrNHj with high selectivity (95-100%) (Eq. 4.5) [50]. 

Many studies have been devoted to the hydroamination of isobutene with NH, since BASF started the production of FBuNHj in Antwerp in 1986 (6000 t/yr) [60, 61]. These studies were aimed mainly at improving conversion, selectivity, catalyst lifetime and space time yields, using less expensive catalysts than zeolites, decreasing the NHj/isobutene ratio to nearly 1/1, and recycHng of the NHj/isobutene mixtures. 

H-Nafion resins [92] or ammordum hahdes in the presence of a catalyst promoter on an inert support (e.g. NH4l-i-GrGl3 on sihca or NH4I/C) appear less promising catalysts [93]. 

Typic2il examples of acid-catalysis of heteropoly compounds are as follows Dehydration of methanol, - ethanol, - - propanol - - - - - - and butanol, conversion of metanol or dimethyl ether to hydrocarbons, etheration to form methyl /-butyl ether, esterifications of acetic acid by ethanol and pentanol, decomposition of carboxylic acid and formic acid, alkylation of benzene by ethylene and isomerization of butene, o-xylene and hexane.  

The acid catalysis of heteropoly compounds in the solid state is classified into bulk-type and surface-type reations. The former type reactions proceed in the catalyst bulk and the latter only on the surface. Dehydration reactions of alcohols belong to the former and isomerization of butene to the latter. So the classification is closely related to the adsorption property of reactants. The activities for the surface-type reactions are more sensitive to pretreatment. 

The bulk-type catalysis has been proved by several experiments such as i) a transient response analysis of the dehydration of 2-propanol, ii) a phase transition of the pseudo-liquid phase, and iii) the reactivity order of alcohols which was reversed depending on the partial pressure. Unusual pressure dependence as well as direct observation by MAS-NMR of reaction intermediates such as protonated alcohol and alkoxide have been reported for pseudo-liquid phase.  

The acidic properties and, therefore, the acid-catalysis of metal salts sometimes vary in a complex manner, depending on several factors. The absorptivity and homogeneity, as well as the reduction and hydrolysis of polyanions, are particularly influential. When the salts are water-soluble (group A), the catalytic activity for bulk- 

The ratio of the catalytic activity of heteropoly compounds to that of silica-alumina. 

Small to medium pore size zeolites, such as H-clinoptilolite, H-of6etite or H-eri-onite, are efficient for the hydroamination of ethylene [51-54]. Ethylene and NH3 react at 360°C and 50 bar over H-clinoptilolite to give EtNHi only (11.4% conversion). There is a clear shape selectivity since propene and 1-butene as well as higher amines give rise to extremely low conversions [52]. In contrast to H-cIinoptilolite or H-erionite, H-offretite is effective for proprene hydroamination with NH, (7.2% conversion, 90% i-PrNH -i- 8% i-Pr2NH) [55]. Small pore size H-erionite is the best catalyst in terms of lifetime, conversion and selectivity for the synthesis of ethyl-amine [56]. The efficiency of H-clinoptilolite can be improved by acid or base plus acid treatment of natural clinoptilolite (18% conversion, EtNH2/Et2NH 20) [57]. 

In this chapter it will be demonstrated that acid catalysis is due to the increased concentration of the acidic group involved in the reaction, caused by the addition of the acid catalyst. 

In the preceding chapters it has been shown that the behavior of substances like sulfur trioxide, boron trifluoride, aluminum chloride, stannic chloride, and silver perchlorate is analogous to the beha,vior of H-acids in neutralization, in displacement, and in titrations with indicators. Many acid-catalyzed reactions will be discussed here in order to emphasize the fact that acidity depends on the electrophilic nature of the reagent and not on the presence of any particular element. 

The mechanisms of Friedel-Crafts reactions have been studied extensively. The alkylations involve the use of olefins, alkyl halides, alcohols, ethers, and esters. The acylations make use of acids, esters, acid halides, and acid anhydrides. This type of reaction is acid-catalyzed, using such compounds as boron, aluminum, iron, tin, and other metallic halides, as well as sulfuric acid, phosphorus pentoxide, orthophosphoric acid, and hydrogen fluoride. These act as acids in the catalytic activity described because they all have a strong tendency to accept a share in an electron pair as the first step in the reaction. 

Alkyl Halides. Conductance and dielectric-constant measurements indicate the formation of ionic complexes between the catalyst and the alkyl halide  

According to the Lewis concept of acids and bases the catalyst in this reaction behaves as an acid and the halide reacts as a base. Many other metallic halides catalyze this reaction in a similar manner. All of them can be shown to be acids by titrating with indicators in the proper solvent. 

Continuous Friedel-Crafts alkylation in SCCO2 has been demonstrated using a fixed-bed flow reactor and Deloxan , a polysiloxane-based solid acid catalyst.  

The addition of poly(ethylene glycol) (PEG) is effective for Lewis acid-catalyzed reactions in scC02. PEG works as a surfactant in SCCO2 to form emulsions in which the catalyst and substrates are packed, thus leading to an acceleration of the reactions. The CO2-PEG system has been successfully applied to an 

The alkylation of isobutane with 1-butene was carried out over an ultrastable Y-type zeolite (USY) catalyst in scCOi Using supercritical CO2 rather than isobutene/1-butene as the reaction medium allowed the reaction temperature to be lowered. As a result, the Cg alkylate selectivity increased. The effectiveness of SCCO2 in terms of alkylate selectivity and coke precursor removal has also been reported. 

The catalytic activity of metal ions originates in the formation of a donor-acceptor complex between the cation and the reactant, which must act as a Lewis base. The result of the complexation is that the donor atom becomes effectively more electronegative. All functional groups that have unshared electron pairs are 

CHAPTER 4 STUDY AND DESCRIPTION OF ORGANIC REACTION MECHANISMS 

Not unexpectedly, this procedure reveals some dependence on the particular type of base used, so no universal Hq scale can be established. Nevertheless, this technique provides a very useful measure of the relative hydrogen-ion activity of concentrated acid solutions which can be used in the study of reactions that proceed only at high acid concentration. Table 4.8 gives Hq values for some water-sulfuric acid mixtures. 

1 Esterification and ester hydrolysis. A considerable number of commercial esterifications are still carried out with conventional acid catalysis 

2 Rearrangement of oxonium ions. In the acid-catalysed cleavage of cumene hydroperoxide (to phenol and acetone), an important step is aryl transfer from carbon to oxygen in the intermediate oxonium ion  

Alkyl transfers from O to C (Stevens rearrangement), carbenes and methyl carbonium ions have all been postulated to explain the formation of lower olefins from methanol and dimethyl ether over heterogeneous acid catalysts the reaction is autocatalytic, e.g. 

These reactions represent the first steps in the conversion of methanol to hydrocarbon fuels over Mobil s ZSM-5 catalyst further reactions of the olefins are described in section 11.7.2.5. 

3 Formation of carbonium ions from olefins alkenes). Many industrial reactions of olefins involve protonation to give a carbonium ion, which is subject to nucleophilic attack, followed by proton transfer from the product to olefin. The ease of protonation follows the stability of the carbonium ion formed in the sequence tertiary secondary primary. Additional proton exchanges can occur at any stage in the overall process, leading to doublebond shifts in the olefinic feedstock and mixed products in some cases. (At high temperatures, products with terminal substituents may also be detectable). 

As stated already in chapter 2, the hydrolysis of pentosan to pentose and the dehydration of pentose to furfural are both catalyzed by acids. It is, therefore, appropriate to give a brief summary of important features of acid catalysis. 

Aquation of /ra 5 -[CoCl(N3)en2]+, which results in loss of azide, is acid catalysed, but the limiting rate depends on the acid used. A study of rates as functions of added acid and added salts indicates that this limiting rate behaviour can be ascribed to the formation of ion-pairs of varying lability. Relevant to acid catalysis of aquation of azides is the characterisation of the perchlorate of the proposed protonated form in aquation, [Co(N3H)(NHg)5] +. Complexes of HP04 can be considered as equivalent to protonated forms of POi complexes kinetic parameters for aquation of [Co(P04)(NH3)s] and of [Co(P04H)(NH8)5]+ have been obtained.  

Aquation of [Co(NCO)(NH3)5] + is also acid catalysed, indeed rates are proportional to hydrogen ion concentration. The products are [Co(NH3)6] + and carbon dioxide, so here the mechanism involves not cobalt-nitrogen but rather intraligand nitrogen-carbon bond fission.  

Monacelli, G. Mattagno, D. Gattegno, and M. Maltese, Inorg. Chem., 1970, 9, 

---

As an example, experimental kinetic data on the hydrolysis of amides under basic conditions as well as under acid catalysis were correlated with quantitative data on charge distribution and the resonance effect [13]. Thus, the values on the free energy of activation, AG , for the acid catalyzed hydrolysis of amides could be modeled quite well by Eq. (5)... 

This chapter introduces the experimental work described in the following chapters. Some mechanistic aspects of the Diels-Alder reaction and Lewis-acid catalysis thereof are discussed. This chapter presents a critical survey of the literature on solvent ejfects on Diels-Alder reactions, with particular emphasis on the intriguing properties of water in connection with their effect on rate and selectivity. Similarly, the ejfects of water on Lewis acid - Lewis base interactions are discussed. Finally the aims of this thesis are outlined. 

Lewis-acid catalysis of Diels-Alder reactions... 

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. 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

The second important influence of the solvent on Lewis acid - Lewis base equilibria concerns the interactions with the Lewis base. Consequently the Lewis addity and, for hard Lewis bases, especially the hydrogen bond donor capacity of tire solvent are important parameters. The electron pair acceptor capacities, quantified by the acceptor number AN, together with the hydrogen bond donor addities. O, of some selected solvents are listed in Table 1.5. Water is among the solvents with the highest AN and, accordingly, interacts strongly witli Lewis bases. This seriously hampers die efficiency of Lewis-acid catalysis in water. 

A combination of the promoting effects of Lewis acids and water is a logical next step. However, to say the least, water has not been a very popular medium for Lewis-acid catalysed Diels-Alder reactions, which is not surprising since water molecules interact strongly with Lewis-acidic and the Lewis-basic atoms of the reacting system. In 1994, when the research described in this thesis was initiated, only one example of Lewis-acid catalysis of a Diels-Alder reaction in water was published Lubineau and co-workers employed lanthanide triflates as a catalyst for the Diels-Alder reaction of glyoxylate to a relatively unreactive diene . No comparison was made between the process in water and in organic solvents. 

What is the scope of Lewis-acid catalysis of Diels-Alder reactions in water An approach of extending the scope by making use of a temporary secondary coordination site is described in Chapter 4. 

What is the effect of micelles on the aqueous Diels-Alder reaction Can micellar catalysis be combined with Lewis-acid catalysis In Chapter 5 these aspects will discussed. 

In order to be able to provide answers to these questions, a Diels-Alder reaction is required that is subject to Lewis-acid catalysis in aqueous media. Finding such a reaction was not an easy task. Fortunately the literature on other Lewis-acid catalysed organic reactions in water was helpful to some extent... 

Lewis-acid catalysis of organic reactions in aqueous solutions ... 

In organic solvents Lewis-acid catalysis also leads to large accelerations of the Diels-Alder reaction. Table 2.2 shows the rate constants for the Cu -catalysed Diels-Alder reaction between 2.4a and 2.5 in different solvents. 

Surprisingly, the highest catalytic activity is observed in TFE. One mi t envisage this to be a result of the poor interaction between TFE and the copper(II) cation, so that the cation will retain most of its Lewis-acidity. In the other solvents the interaction between their electron-rich hetero atoms and the cation is likely to be stronger, thus diminishing the efficiency of the Lewis-acid catalysis. The observation that Cu(N03)2 is only poorly soluble in TFE and much better in the other solvents used, is in line with this reasoning. 

In summary, the effects of a number of important parameters on the catalysed reaction between 2.4 and 2.5 have been examined, representing the first detailed study of Lewis-acid catalysis of a Diels-Alder reaction in water. Crucial for the success of Lewis-acid catalysis of this reaction is the bidentate character of 2.4. In Chapter 4 attempts to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water beyond the restriction to bidentate substrates will be presented. 

A similar approach is followed in a recent study of the Lewis-acid catalysis of a Michael addition in acetonitrile. See Fukuzumi, S. Okamoto, T. Yasui, K Suenobu, T. Itoh, S. Otera, J. Chem. Lett. 1997, 667. 

Towards Enantioselective Lewis-Acid Catalysis in Water ... 

To our knowledge, the results presented in this chapter provide the first example of enantioselective Lewis-acid catalysis of an organic reaction in water. This discovery opens the possibility of employing the knowledge and techniques from aqueous coordination chemistry in enantioselective catalysis. This work represents an interface of two disciplines hitherto not strongly connected. 

---