Aldol condensation, minimization

Aldol condensation and subsequent heavies formation are minimized by using a low concentration of the copper reoxidant. 

In some reactions, oc,a-diarylation can also occur, but generally in low yields (>15%). a-Diarylation is caused by ionization in the basic medium of the monoarylated product. In order to minimize the diarylation, a nucleophile/substrate ratio of 3-5 is recommended. Use of an excess of t-BuOK (10-20%) is also convenient to avoid the possibility of aldol condensation of the ketones. 

Show the structure of the product of the aldol condensation of heptanal under vigorous conditions. How would you minimize the formation of this product in the synthesis of Flosal ... 

Aldol condensation is catalyzed by base, but not by the cobalt catalyst. This allows the pathway from aldehyde to alcohol to be studied separately with aldehyde as starting material and under conditions that preclude aldol condensation. For example, condensation is minimal in the absence of a base or with an aldehyde whose carbon skeleton has a branch adjacent to the aldehyde group. 

This reaction, which is an aldol condensation followed by a hydrolysis, is catalyzed by citrate synthase. Oxaloacetate first condenses with acetyl CoA to form citryl CoA, which is then hydrolyzed to citrate and CoA. The hydrolysis of citryl CoA, a high-energy thioester intermediate, drives the overall reaction far in the direction of the synthesis of citrate. In essence, the hydrolysis of the thioester powers the synthesis of a new molecule from two precursors. Because this reaction initiates the cycle, it is very important that side reactions be minimized. Let us briefly consider the how citrate synthase prevents wasteful processes such as the hydrolysis of acetyl CoA. 

Before the introduction of metal-ammonia solutions for the reduction of a,p-unsaturated carbonyl compounds,sodium, sodium amalgam, or zinc in protic media were most commonly employed for this purpose. Some early examples of their use include the conversion of carvone to dihydrocarvone with zinc in acid or alkaline medium, and of cholest-4-en-3-one to cholestanone with sodium in alcohol. These earlier methods are complicated by a variety of side reactions, such as over-reduction, dimerization, skeletal rearrangements, acid- or base-catalyzed isomerizations and aldol condensations, most of which can be significantly minimized by metal-ammonia reduction. 

Monohydroboration of 1-alkynes followed by oxidation gives the corresponding aldehydes in high yields.-" Oxidation of the vinyl carbon-boron bond produces the enol, which then tautomerizes to the carbonyl group. To minimize aldol condensation of the aldehyde formed during oxidation, the reaction should be carried out at pH 8 or in buffered medium. " ... 

No method has yet been devised for bringing about formation of a single product from a nonenzymic Lobry de Bruyn-Alberda van Ekenstein transformation. However, this feat should be possible, since the reactions involved are reversible. Yields can be improved by choosing catalysts which limit side-reactions. Thus, a low concentration of hydroxide ion minimizes the aldol condensation, the seriousness of which, as a side reaction, is sufficient reason for avoiding even moderate concentrations of hydroxide ion. It is interesting to note that lime-water and anhydrous pyridine, which have been the most used as catalysts in sugar preparations by these reactions, both meet this requirement. The hydroxide-ion concentrations of the former solution have usually been low, and the calcium... 

Non-activated carbon-carbon double bonds react catalytically and rapidly with H2 and CO at 80°C and a few atmospheres pressure (<1 mPa). The milder conditions are attractive for the synthesis of aldehydes without high pressure equipment and for minimizing competitive but undesirable reactions. Among the latter are partial hydrogenation to alcohols which form acetals, aldol condensation products, ketone formation and hydrogenation to alkane. 

Aliphatic nitro compounds cannot as a rule be prepared in the same way as the aromatic nitro compounds. The more rapid oxidation of aliphatic hydrocarbons by nitric acid is the main interfering factor, so that conditions must be chosen which minimize oxidation and promote nitration. The oxidation reactions are of such complexity in these cases that no attempt will be made to formulate them. Only a summary of the conditions favoring nitration will be given. The use of a solvent such as ether for carrying out the reaction is often successful. Also dilute nitric acid has been used, and alkyl (generally ethyl) nitrate. In the Friedel-Crafts reaction with ethyl nitrate, aluminium chloride is used as catalyst. In aliphatic nitrations with ethyl nitrate, alkalis such as metal alkoxides (NaOC Hs) are found to be best. The use of alkalis brings out the similarity of this reaction to aldol condensations which are also favored by alkalis. An example of aliphatic nitration, in comparison with an aromatic one may be given ... 

In the case of the formulation of mixed resins for adhesives for which extensive formulation experience does not exist, the gel theory approach is also particularly useful. Le us examine, as an example, what would be the degree of conversion at the gel point of a resin based on the reaction of resorcinol (R) with acetaldehyde (A) and formaldehyde (F) in relative molar proportions of, respectively, R A F = 1 1 0.5. The two aldehydes can react and do react with resorcinol while under the conditions used they are considered as not being able to react with each other (aldol condensation is indeed minimal under the conditions used to prepare adhesive resins). In short to avoid any gelling of our prereacted resin in the reactor, during manufacture, we want to know at what degree of conversion we can advance reaction of the resin without gelling it. 

Enolate alkylation can be difficult to carry out with simple aldehydes and ketones. It is not always possible to limit the reaction to monoalkylation, and aldol condensation competes with alkylation, especially with aldehydes. The formation of regioisomeric alkylation products is an issue with unsymmetrical ketones but can be minimized by selecting reaction conditions that favor either kinetic or thermodynamic control of enolate formation. The kinetic enolate of 2-methylcyclohexanone, for example, was prepared by deprotonation with lithium diisopropylamide then treated with benzyl bromide to give predominantly 2-benzyl-6-methylcyclohexanone,... 

From 1974 onwards, Rh-based hydroformylation became industrial. The use of a catalyst metal that is about 1000-times more expensive than cobalt was driven by several reasons. First, Rh-hydroformylation is more active and thus requires much lower process pressures (lower energy consumption in compression units) and smaller reactors. Second, Rh-hydroformylation shows a very high selectivity to the aldehyde product with only minimal hydrogenation activity being observed. This is of particular importance for propylene hydroformylation where butyl alcohol is not the principle market use. In contrast, for the desired end-use of w-butyraldehyde in the form of its aldol condensation product 2-ethylhexanol a pure aldehyde feed is required as hemiacetals (formed by reaction of aldehyde and alcohol) complicate product purification and add to operating costs. 

Stereoselective aldol condensation is observed using tris(diethylamino)sul-phonium enolates, and shows a high eryt/tro-selectivity independent of the geometry of the starting silyl enol ether. The stereoselectivity is suggested to be the result of minimal interaction with the cation, reaction proceding via an extended transition state (Scheme 42). 

The reaction was performed mostly in methanol and led to some asymmetric induction due to the chirality of the catalysts. Water was also used, providing quantitative aldol condensation, although no optical activity could be obtained in this case (Buonora et al, 1995). The influence of pH on this system was measured in order to minimize undesired dehydration of aldol... 

How does the alkylation of an enamine compare with the alkylation of an enolate Enamine alkylation is far superior, because it minimizes double or multiple alkylation Under the conditions of the process, the iminium salt formed after the first alkylation is relatively stable and unable to react with additional haloalkane. Enamines can also be used to prepare alkylated aldehydes, as shown here. (We shall see in the next section that aldehyde enolates undergo a new reaction called the aldol condensation and, therefore, cannot be alkylated readily.)... 

These problems could be minimized by the use of bulky and readily enolizable malonates and a sterically hindered organocatalyst such as 145. Accordingly, substrate 144, bearing a nucleophilic malonate and an electrophilic aldehyde group, was utilized for the cascade Michael-aldol condensation process (Scheme 1.54) [90]. The process is catalyzed efficiently by readily available (S)-diphenylprolinol triethylsilyl ether 145 to give synthetically useful, highly functionalized chiral cyclopentenes. 

Examples include acetaldehyde, CH CHO paraldehyde, (CH CHO) glyoxal, OCH—CHO and furfural. The reaction is usually kept on the acid side to minimize aldol formation. Furfural resins, however, are prepared with alkaline catalysts because furfural self-condenses under acid conditions to form a gel. 

Dumas et al. noted the good yields and syn diastereoselectivities obtained in a high-pressure aldol reaction of bis-silyl ketene acetals 154 with benzaldehyde (155) (Scheme 7.39). The syn aldol 156 was obtained with a diastereoselectivity that was significantly correlated with the steric bulkiness of the R-substituent in the acetals 154. The preference for syn bis-silyl aldols 156 has been attributed to the reaction pathway that involves compact transition states in which steric interactions between the R substituent of 154 and the phenyl group of benzaldehyde are minimized. The authors also studied the condensation of unsaturated bis-silyl ketene acetal as a model for the synthesis of retinoid compounds. ... 

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