Aldol reaction base-catalysed

Called the aldol reaction, base-catalysed dimerization i a gene reaction for all aldehydes and kcUmes with an r hydrogen atom. If the sMe hyde or ketwie does not have an a hydri en atom, however, aldol coiukt-... 

The mecluLnism of this base-catalysed reaction probably involves the intermediate formation of an aldol ... 

A probable mechanism of these base-catalysed aldol reactions may be written in gena-al terms as follows ... 

The solid base catalysed aldol condensation of acetone was performed over a CsOH/Si02 catalyst using a H2 carrier gas. The products observed were diacetone alcohol, mesityl oxide, phorone, iso-phorone and the hydrogenated product, methyl isobutyl ketone. Deuterium tracer experiments were performed to gain an insight into the reaction mechanism. A mechanism is proposed. 

The aldol reaction is easily rationalized, with acetyl-CoA providing an enolate anion nucleophile that adds to the carbonyl of oxaloacetate - easily rationalized, but surprising. Oxaloacetate is more acidic than acetyl-CoA, in that there are two carbonyl groups flanking the methylene. If one were to consider a potential base-catalysed reaction between these two susbstrates, then logic suggests that oxaloacetate would be preferentially converted into... 

Aldol condensation reaction may be either acid or base catalysed. However, base catalysis is more common. The product of this reaction is called an aldol, i.e. aid from aldehyde and ol from alcohol. The product is either a P-hydroxyaldehyde or P-hydroxyketone, depending on the starting material. For example, two acetaldehyde (ethanal) molecules condense together in the presence of an aqueous base (NaOH), to produce 3-hydroxybutanal (a P-hydroxyaldehyde). 

Aldol condensations were originally carried out in the liquid phase and catalysed homogeneously by acids or bases this way of operation is still predominant. Solid-catalysed aldol reactions can also be performed in the liquid phase (in trickle or submerged beds of catalyst), but in many cases vapour phase systems are preferred the factors determining the choice are the boiling points and the stability of the reactants at elevated temperatures. At higher temperatures, the formation of a, j3-unsaturated aldehydes or ketones [reactions (B) and (C)] is preferred to aldol (ketol) formation [reaction (A)]. A side reaction, which may become important in some cases, is the self-condensation of the more reactive carbonyl compound if a mixed condensation of two different aldehydes or ketones is occurring. The Cannizzaro reaction of some aldehydes or polymerisation to polyols or other resin-like products can also accompany the main reaction. 

In the work concerning the mechanism of solid-catalysed aldol reactions, the analogy between the homogeneous and heterogeneous mechanisms is usually assumed [370,372—375]. The mechanism of base-catalysed condensations, which has received much attention (cf. ref. 371), may be pictured in general as... 

The Cannizzaro reaction, that is, the base-catalysed disproportionation of a carbonyl compound to an alcohol and a carboxylic acid, has gained some importance as an economically viable alternative to the reduction with borohydrides. However, the reaction is restricted to carbonyl compounds without any a-hydrogen, which do not undergo competing aldol reactions. Thus, mainly aromatic aldehydes are used for this kind of transformation. The protocols developed for microwave applications typically involve solvent-free conditions using alumina as the solid support. Under these conditions, a significant acceleration of the reaction was achieved. 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

Chiral iminopyridines catalyse nitro aldol reactions with good ees in the pres- ence of copper(II) acetate, without the need for exclusion of air or moisture.143 A (g) phenylalanine-derived Schiff base - also complexed to copper(II) - is also effective, with the advantage that product configuration is easily reversed (by using the enantiomeric phenylalanine).144... 

The aldol and Claisen reactions both achieve carbon-carbon bond formation and in typical base-catalysed chemical reactions depend on the generation of a resonance-stabilized enolate anion from a suitable carbonyl system (Figure 2.7). Whether an aldol-type or Claisen-type product is formed depends on the nature of X and its potential as a leaving group. Thus, chemically, two molecules... 

The base-catalysed Aldol reaction is shown in Equation 3.11 [3, 4], and a mechanism to account for the global process in Scheme 3.1. At low concentrations of acetaldehyde, reverse of the proton-abstraction steps is fast compared with the forward bimolecular enolate capture (k [CH3CHO] <rate limiting. Under these conditions, the kinetics are second order in [CH3CHO] and show specific base catalysis, i.e. the reaction is first order in [HCY ] and, even though B is involved in the mechanism, it does not appear in the rate law [5]. According to this mechanism, therefore, the overall rate law is given by Equation 3.12 ... 

Scheme 3.1 A mechanism for the base-catalysed Aldol reaction.

The presence of H3 0+ or HO may alter drastically the observed reaction rate either because they catalyse the reaction (acid or base catalysis, see Section 3.2.3 for the Aldol reaction, and Chapter 11) or because of ionic strength effects. Proper pH control in an aqueous solution will require a buffer system which is described by the appropriate version of the Henderson-Hasselbach equation, according to whether the acid or base is the charged species ... 

Modern Aldol Reactions contains several pertinent reviews (i) catalytic enantiose-lective aldols with chiral Lewis bases 97 (ii) the aldol-Tishchenko reaction 98 (iii) titanium—enolate aldols 99 (iv) crossed aldols mediated by boron and silicon enolates 100 (v) amine-catalysed aldols 101 and (vi) aldols catalysed by antibodies.102... 

The base catalysed reaction of 3-azidochroman-4-one with simple aldehydes affords the aldol product, but reaction of the enolate with acetone is slower than loss of N2 from the azido function and... 

A widely studied example of this kind is the synthesis of methyl isobutyl ketone (MIBK, used as a solvent for inks and lacquers) from acetone. The former was previously prepared from the latter through a catalytic three-step process base-catalysed production of 4-hydroxy-4-methylpentan-2-one, acid dehydration into mesityloxide (MO), then hydrogenation of MO on a Pd catalyst. Since acetone aldolization occurs through acid catalysis as shown over a H-MFI zeolite at 433 K (MO is the main reaction product, the aldolization product being rapidly dehy-drated[5]), it is possible, by associating with the acid catalyst a hydrogenation phase,... 

The elimination is even easier in acid solution and acid-catalysed aldol reactions commonly give unsaturated products instead of aldols. In this simple example with a symmetrical cyclic ketone, the enone is formed in good yield in acid or base. We shall use the acid-catalysed reaction to illustrate the mechanism. First the ketone is enolized under acid catalysis as you saw in Chapter 21. 

None of these intermediates is detected or isolated in practice—simple treatment of the ketone with acid gives the enone in good yield. A base-catalysed reaction gives the same product via the aldol-ElcB elimination mechanism. 

Base-catalysed aldol reactions may give the aldol product, or may give the V dehydrated enone or enalby an ElcB mechanism... 

Base-catalysed conjugate addition of nitropropane to methyl vinyl ketone occurred smoothly to give the nitroketone. Formation of the salt with sodium methoxide was followed by oxidative cleavage of the C-N linkage with ozone. The product was a 1,4-diketone which was isolated without further aldol reaction by this route. 

Base-catalysed reactions such as the Knoevenagel, Michael and aldol reactions continue to be of importance in industrial routes to synthetic chemicals and are often inherently clean, with water (or nothing) as the by-product. Traditional homogeneous methods of catalysis often require upwards of 40 mol% catalyst (such as piperidine) with the attendant difficulties in recovery and reuse of the catalyst. They often offer extremely poor selectivity to the desired products, either due to competing processes (side reactions) or further reaction of the first-formed product. 

Examples are reactions initiated by the protonation, as for example carbenium ion formation from — for example—olefins (Bronsted acidic centres) or deprotonation reactions like base-catalysed aldol condensation. 

The aldol products from the base-catalysed reaction between aliphatic aldehydes and formaldehyde react with 2-tetralone under acidic conditions to give 2,2-dialkyl-2,3-dihydro-3Ef-naphtho[2,l-b]pyrans 22 <07SL3127>. 

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