Base catalysis ketone

Addition of HCN to unsaturated compounds is often the easiest and most economical method of making organonitnles. An early synthesis of acrylonitrile involved the addition of HCN to acetylene. The addition of HCN to aldehydes and ketones is readily accompHshed with simple base catalysis, as is the addition of HCN to activated olefins (Michael addition). However, the addition of HCN to unactivated olefins and the regioselective addition to dienes is best accompHshed with a transition-metal catalyst, as illustrated by DuPont s adiponitrile process (6—9). 

Solutions of unstable enols of simple ketones and aldehydes can also be generated in water by addition of a solution of the enolate to water. The initial protonation takes place on oxygen, generating the enol, which is then ketonized at a rate that depends on the solution pH. The ketonization exhibits both acid and base catalysis. Acid catalysis involves C-protonation with concerted 0-deprotonation. 

In agreement with expectation for a rate-determining proton transfer, the reaction shows general acid catalysis. Base-catalyzed ketonization occurs by C-protonation of the enolate. 

The most intensively studied oxidizing system is that developed by Pfitzner and Moflatt in which the oxidation is carried out at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and a weak acid such as pyridinium trifluoroacetate or phosphoric acid. The DCC activates the DMSO which in turn reacts with the carbinol to give an oxysulfonium intermediate. This breaks down under mild base catalysis to give the desired ketone and dimethyl sulfide. 

General base catalysis is catalysis by a Br nsted base acting by accepting a proton. The halogenation of ketones, a reaction discussed in Section 5.3, is general base catalyzed. 

In the case of the bis phosphine derivatives of the group 7b metals, the lability of the oxygen atoms was so markedly retarded by substitution that it was necessary to enhance their reactivity by means of base catalysis (15, 14), a process having mechanistic features common wi Tx general base catalysis of the hydration of ketones (eq. 6) (15). 

The enolization of aldehydes and ketones [35] —> [36] is subject to both acid and base catalysis (Bell, 1973 Toullec, 1982 Albery, 1982). Although the kinetics of the reaction were first studied 90 years ago (Lapworth, 1904) and... 

The primary literature now contains a very large body of kinetic data for the catalysis of enolization and ketonization, not only of ketones and aldehydes but also of )3-diketones, )3-keto esters, and dienones, much of which could be treated by the Kurz approach. Also, data exist for third-order enolization, due to combined general acid and base catalysis, that could also be analysed. Such treatment is beyond the scope the present review. However, one study of metal ion catalysis of enolization is discussed later in this section. 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

In general, the product ratio of a mixed aldol condensation will depend upon the individual reaction rates. Most ketones show a pattern similar to butanone in reactions with aromatic aldehydes. Base catalysis favors reaction at a methyl position over a methylene group, whereas acid catalysis gives the opposite preference. 

Polyquinolines (PQ) are obtained by the Friedlander reaction of a bis-o-aminoaromatic aldehyde (or ketone) with an aromatic hisketomethylene reactant [Concilio et al., 2001 Stille, 1981]. The quinoline ring is formed hy a combination of an aldol condensation and imine formation (Eq. 2-221). Polymerization is carried out at 135°C in m-cresol with poly (phosphoric acid) as the catalyst. The reaction also proceeds under base catalysis, but there... 

These data unambiguously establish that a gem diol species is formed in the active site of pepsin when the ketone analogs 6 and 10 are added to the aspartyl protease as shown in Figure 6 and exclude the formation of a covalent intermediate. Our data strongly support the general acid-general base catalysis mechanism for aspartyl proteases that is illustrated schematically in Figure 1. 

Base catalysis is one of the less-well developed areas of heterogeneous catalysis. We have developed novel bases derived from amines via the one-step process outlined above. A range of supported amines have been prepared and evaluated in a series of reactions We have also investigated the nature of the amine groups attached to the surface in comparison with those formed by grafting onto pre-formed silica. While many workers have studied the use of basic catalysts for the Knoevenagel condensation of aldehydes, with three articles on the use of MCM derivatives[ 12], little has been done on the more demanding condensation of ketones. 

Support-bound carbonyl compounds can be converted into alcohols by treatment with suitable carbon nucleophiles. Aldehydes react readily with ketones or other C,H-acidic compounds under acid- or base-catalysis to yield the products of aldol addition (Table 7.2). Some types of C,H-acidic compound, such as 1,3-dicarbonyl compounds, can give the products of aldol condensation directly (Section 5.2.2.2). 

Aldol condensation. With aldehydes, successful with either acid or base catalysis. m With ketones, conditions (strong acid or strong base catalysis) under which dehydration occurs are usually used to shift equilibrium toward the product.. ... 

A much more generally useful process was developed by Robinson to prepare cyclohexenones from ketones and methyl vinyl ketone or its derivatives. Again, because good compilations of the Robinson annulation exist,8 only a few examples are given here. The first step of this process, the Michael addition, is carried out by normal base catalysis, while the second step, the aldol condensation, is best accomplished by the use of a secondary amine to form the enamine of the acyclic ketone, which then cyclizes... 

Apparently, these results implied an inverse relationship between reactivity and selectivity, with the reactivity of the carbocation measured by the inverse of the rate constant for solvolysis. This indeed was not unexpected in the context of a general perception that highly reactive reagents, especially reactive intermediates such as carbocations, carbanions, or carbenes are unselective in their reactions.257 259 Such a relationship is consistent with a natural inference from the Hammond postulate258 and Bell-Evans-Polanyi relationship,260 and is illustrated experimentally by the dependence of the Bronsted exponent for base catalysis of the enolization of ketones upon the reactivity of the ketone,261,262 and other examples21,263 including Richard s careful study of the hydration of a-methoxystyrenes.229... 

Strong bases in dry solvents are usually used in organic synthesis to generate reactive enol anions from ketones. Nevertheless, the kinetic studies discussed here were mostly performed on aqueous solutions. Apart from the relevance of this medium for biochemical reactions and green chemistry, it has the advantage of a well-defined pH-scale permitting quantitative studies of acid and base catalysis. 

The curves for log(kK/s ) and log(kK/s ) of acetophenone are parallel in the range pAT << PH << pAT and the vertical distance between them then equals pAtE = log(kK/s 1) — log /s-1). Most ketones are very weak bases, pAt < 0, so that the parameter does not affect the shape of the pH-rate profiles in the range pH > 1. Base catalysis of ketonization saturates at pH = pAr , while the rate of enolization continues to rise, so that the curves for kE and kK eventually cross at higher pH. At still higher pH, the rate constant kE exceeds that of kK = k o and kobs follows kK. The crossing point, for which kE = kK, lies at pH = pAT = 18.3 for acetophenone (Fig. 3), which is outside the accessible pH range when ionic strength I is limited to 0.1 m, but pA is readily calculated from Equation (2). 

Where R4 is a hydrogen or carbon atom, 10.15 is simply an amidine. However, urea 10.16, thiourea 10.17, or guanidine 10.18 and their derivatives may be used. These nucleophiles may be condensed with ester and nitrile functionalities as well as with aldehydes and ketones. Such condensations to afford pyridimidine derivatives are usually facilitated by acid or base catalysis, although certain combinations of reactive electrophilic and nucleophilic compounds require no catalyst at all. Some examples are shown below. 

Di Cosimo, J. I., Diez, V. K. and Apesteguia, C. R. Base catalysis for the synthesis of a,/ -unsaturated ketones from the vapor-phase aldol condensation of acetone, Appl. Catal., A, 1996, 137, 149-66. 

The gingerols can undergo a retro aldol reaction at the P-hydroxy ketone group to yield zingerone and aliphatic aldehydes, such as hexanal. This reaction can occur by base catalysis or by the action of heat, and with oleoresins it proceeds rapidly at temperatures above 200°C. The process is detrimental not only because of reducing the pungency level, but also from the production of off-flavours by the liberated aldehydes. 

The Timmis reaction makes use of the regioselective condensations of 6-amino-5-nitroso-pyrimidines with aldehydes, ketones, esters, and nitriles under base catalysis. An extension of this principle is seen in the condensation reaction of 6-amino-5-nitroso-(320) and 6-amino-5-phenylazo-1,3-dimethyluracils (321) with dimethyl alkenedicarboxylate and propiolamide, respectively, leading by a Michael addition mechanism to 6,7-bis(methoxycarbonyl)- (322) and 6-carbamoyl-l,3-dimethyllumazine (323) (Scheme 52) <82JHC949>. 

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