Catalysis/catalytic reactions displacement

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

A classic example of competitive inhibition is the inhibition of succinate dehydrogenase by malonate, a structural analogue of succinate. Competitive inhibitors are usually structural analogues of the substrate, the molecule with which they are competing. They bind to the active site but either do not have a structure that is conducive to enzymatic modification or do not induce the proper orientation of catalytic amino acyl residues required to affect catalysis. Consequently, they displace the substrate from the active site and thereby depress the velocity of the reaction. Increasing [S] will displace the inhibitor. 

The rate of olefin elimination is enhanced by catalytic amounts of Ni compounds, which suppress the growth reaction (in contrast to compounds of Ti, Zr or V) however, they also catalyze double-bond migration and often the catalytic activity rapidly decreases. The catalysis of the displacement reaction is of interest for the preparation of EtjAl or PrjAl from i-BujAl, because no isomerization of the olefin can occur and the conditions (50-100°C, Ni) exclude the growth reaction. ... 

The goal of much activity in synthesis of host-guest complexes is to mimic the selectivity and catalytic activity of enzymes. In Chapter 31, Schneider et al. examine the use of intramolecular inclusion complexes for catalysis of nucleophilic displacement reactions. The main emphasis here is on macrocyclic ammonium ions as hosts. 

The term phase transfer catalysis was coined by Starks to describe the mechanism of catalysis of reactions between water-soluble inorganic salts and water-insoluble organic substrates by lipophilic quaternary ammonium and phosphonium ions Ql). His investigations of nucleophilic displacement reactions, such as that of aqueous sodium cyanide with 1-chlorooctane, and the investigations of Makosza on reactions of aqueous sodium hydroxide with chloroform to generate dichlorocarbene, and with active ketones and nitriles to generate carbanions, pioneered the field in the mid-1960 s. It was nearly fifteen years before many such processes were adopted in industry. Starks now estimates there are about sixty phase transfer catalytic processes in use worldwide, mostly in pharmaceutical and fine chemical manufacturing (32V... 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

The simplest C-C bond formation reaction is the nucleophilic displacement of a halide ion from a haloalkane by the cyanide ion. This was one of the first reactions for which the kinetics under phase-transfer catalysed conditions was investigated and patented [l-3] and is widely used [e.g. 4-12], The reaction has been the subject of a large number of patents and it is frequently used as a standard reaction for the assessment of the effectiveness of the catalyst. Although the majority of reactions are conducted under liquiddiquid two-phase conditions, it has also been conducted under solidrliquid two-phase conditions [13] but, as with many other reactions carried out under such conditions, a trace of water is necessary for optimum success. Triphase catalysis [14] and use of the preformed quaternary ammonium cyanide [e.g. 15] have also been applied to the conversion of haloalkanes into the corresponding nitriles. Polymer-bound chloroalkanes react with sodium cyanide and cyanoalkanes under phase-transfer catalytic conditions [16],... 

The affinity of the polymer-bound catalyst for water and for organic solvent also depends upon the structure of the polymer backbone. Polystyrene is nonpolar and attracts good organic solvents, but without ionic, polyether, or other polar sites, it is completely inactive for catalysis of nucleophilic reactions. The polar sites are necessary to attract reactive anions. If the polymer is hydrophilic, as a dextran, its surface must be made less polar by functionalization with lipophilic groups to permit catalytic activity for most nucleophilic displacement reactions. The % RS and the chemical nature of the polymer backbone affect the hydrophilic/lipophilic balance. The polymer must be able to attract both the reactive anion and the organic substrate into its matrix to catalyze reactions between the two mutually insoluble species. Most polymer-supported phase transfer catalysts are used under conditions where both intrinsic reactivity and intraparticle diffusion affect the observed rates of reaction. The structural variables in the catalyst which control the hydrophilic/lipophilic balance affect both activity and diffusion, and it is often not possible to distinguish clearly between these rate limiting phenomena by variation of active site structure, polymer backbone structure, or % RS. 

One of the oldest techniques for overcoming these problems is the use of biphasic water/organic solvent systems using phase-transfer methods. In 1951, Jarrouse found that the reaction of water-soluble sodium cyanide with water-insoluble, but organic solvent-soluble 1-chlorooctane is dramatically enhanced by adding a catalytic amount of tetra-n-butylammonium chloride [878], This technique was further developed by Makosza et al. [879], Starks et al. [880], and others, and has become known as liquid-liquid phase-transfer catalysis (PTC) for reviews, see references [656-658, 879-882], The mechanism of this method is shown in Fig. 5-18 for the nucleophilic displacement reaction of a haloalkane with sodium cyanide in the presence of a quaternary ammonium chloride as FT catalyst. 

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

Coenzymes - Many enzymes require nonprotein coenzymes for catalytic activity.8 These are cosubstrates, and must be constantly reconverted into their active form for catalysis to continue. This is not a problem for growing microorganisms since the normal metabolic processes ensure an adequate supply of coenzymes. However, with purified, or immobilized enzymes, maintaining a sufficient concentration of coenzyme can pose a major problem. Coenzymes are expensive and it is seldom economically feasible to add them in stoichiometric amounts. This is often undesirable for chemical reasons, e.g., the coenzyme may be unstable, or the eventual build-up of high concentrations of its inactive form may Induce displacement of an equilibrium reaction in the opposite direction to that desired.3 It is therefore necessary to use catalytic amounts of coenzymes and to ensure that the active forms are continuously regenerated. Some coenzymes present little or no problem in this regard since they are automatically reformed under the normal aqueous reaction conditions or in the presence of oxygen. These include biotin, pyrldoxal phosphate (PLP), thiamine pyrophosphate, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).1 ... 

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