Aldol Condensation
Aldol condensation is a reaction in organic chemistry where an enol or enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone, followed by dehydration to produce an α,β-unsaturated carbonyl compound. The reaction involves the formation of a carbon-carbon bond and is commonly used in the synthesis of complex organic molecules.
5 Key excerpts on "Aldol Condensation"
eBook - ePub- Graham Patrick(Author)
- 2004(Publication Date)
- Taylor & Francis(Publisher)
...This arises from elimination of a molecule of water from the Aldol reaction product. There are two reasons why this can occur. First of all, the product still has an acidic proton (i.e. there is still a carbonyl group present and an α-hydrogen next to it). This proton is prone to attack from base. Secondly, the dehydration process results in a conjugated product which results in increased stability (Section A4). The mechanism of dehydration is shown in Figure 14. First of all, the acidic proton is removed and a new enolate ion is formed. The electrons in the enolate ion can then move in such a fashion that the hydroxyl Figure 11. Aldol reaction. Figure 12. Mechanism of the Aldol reaction. Figure 13. Formation of 2-butenal. Figure 14. Mechanism of dehydration. group is expelled to give the final product — an α,β-unsaturated aldehyde. In this example, it is possible to vary the conditions such that one gets the Aldol reaction product or the α, β-unsaturated aldehyde, but in some cases only the α, β-unsaturated carbonyl product is obtained, especially when extended conjugation is possible. The Aldol reaction is best carried out with aldehydes. Some ketones will undergo an Aldol reaction, but an equilibrium is set up between the products and starting materials and it is necessary to remove the product as it is being formed in order to pull the reaction through to completion. Crossed Aldol reaction So far we have talked about the Aldol reaction being used to link two molecules of the same aldehyde or ketone, but it is also possible to link two different carbonyl compounds. This is known as a crossed Aldol reaction. For example, benzaldehyde and ethanal can be linked in the presence of sodium hydroxide (Figure 15). In this example, ethanal reacts with sodium hydroxide to form the enolate ion which then reacts with benzaldehyde...
eBook - ePubBiochemistry
An Organic Chemistry Approach
- Michael B. Smith(Author)
- 2020(Publication Date)
- CRC Press(Publisher)
...The reaction of acetone and 4-nitrobenzaldehyde in dimethyl sulfoxide (DMSO) was reported, using proline, for example. 4 The aldol product is 4-hydroxy-4-(4-nitrophenyl)butan-2-one. 4 Sakthivel, K.; Notz, W.; Bui, T.; Barbas III, C.F. Journal of the American Chemical Society 2001, 12 3, 5260–5267. Acid-catalyzed Aldol Condensation reactions are known, which are more pertinent to biological Aldol Condensation reactions. A simple example is the condensation reaction acetophenone and benzaldehyde with sulfuric acid in acetic acid as shown in Figure 6.3. In this example, acetophenone is the only carbonyl partner with α-hydrogen atoms, and in the presence of the acid the enol is formed. In the acidic medium, the α-carbon of the enol reacts with the protonated carbonyl of benzaldehyde, as shown, to give the protonated aldol coupling product. Loss of a proton gives the aldol product 3-hydroxy-1,3-diphenylpropan-1-one. The lesson of this example is that the acidic medium facilitates formation of the enol, and reaction with the other carbonyl partner leads to the aldol product. FIGURE 6.3 Acid-catalyzed Aldol Condensation. 6.4 Enzyme-Mediated Aldol Condensations Enzymes known as aldolases can catalyze both the forward and reverse aldol reactions. Aldolase A (EC 4.1.2.13; bisphosphate aldolase C ; see Section 7.6) is a human enzyme that catalyzes the reversible reaction of fructose-1,6-biphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Aldolase A is found in the developing embryo and is produced in even greater amounts in adult muscle, and deficiency has been associated with myopathy (a muscle tissue disease) and hemolytic anemia (the abnormal breakdown of red blood cells)...
eBook - ePub- Michael North(Author)
- 2017(Publication Date)
- CRC Press(Publisher)
...In these projections, L, M and S represent the largest, medium and smallest groups respectively attached to the carbon adjacent to the carbonyl group. The preferred conformations will be 9.31a,b, since in these conformations the largest substituent on the stereocentre (L) is orthogonal to the carbonyl oxygen and R group. Attack of a nucleophile will occur preferentially on conformer 9.31b, rather than conformer 9.31a, since in the former the nucleophile need only approach close to the small substituent whilst attack on conformer 9.31a would require that the nucleophile approach close to either the medium or large substituents as shown in Scheme 9.23. This is the Felkin–Anh model and it correctly predicts the major diastereomer observed in many non-chelated reactions. An example is shown in Scheme 9.24. Scheme 9.23 Scheme 9.24 9.5.3 The aldol reaction Strictly, the aldol reaction refers to the reaction between the enol or enolate of an aldehyde or ketone and a second aldehyde or ketone as shown in Scheme 9.25. The term is, however, widely used to refer to the reaction of any enolate with an aldehyde or ketone. During an aldol reaction, up to two new stereo-centres may be generated from two starting materials both of which are achiral. Unlike the addition reactions discussed in sections 9.5.1 and 9.5.2, the aldol reaction is reversible, and the observed product is usually that corresponding to thermodynamic control. Scheme 9.25 Scheme 9.26 In the majority of cases, the initial product of an aldol reaction is a six-membered ring cyclic chelate in which the metal counterion to the base is coordinated to both the carbonyl and hydroxyl oxygens of the product. This cyclic chelate adopts a chair conformation, and the most stable product (i.e. the thermodynamically controlled product) is the one in which as many substituents as possible are located in equatorial positions on the six-membered ring. An example of such a reaction is shown in Scheme 9.26...
eBook - ePubApplied Biocatalysis
Volume 1
- Harvey W. Blanch, Douglas S. Clark, Harvey W. Blanch, Douglas S. Clark(Authors)
- 2021(Publication Date)
- CRC Press(Publisher)
...3 Applications of Enzymatic Aldol Reactions in Organic Synthesis Mark David Bednarski Department of Chemistry, University of California at Berkeley, Berkeley, California INTRODUCTION The development of methods for the stereoselective formation of carbon-carbon bonds using the aldol reaction is a current topic of interest in organic synthesis [ 1 – 6 ]. Many successful strategies rely on chiral auxiliaries [ 7 – 15 ], and a few examples exist that use organometallic [ 16 – 19 ] catalysts. The use of enzymes in synthetic organic chemistry is only now being explored [ 20 – 41 ]. This chapter discusses the utility of readily available carbon-carbon bond forming enzymes as catalysts for the asymmetric aldol reaction. ENZYMES THAT FORM CARBON-CARBON BONDS Three general types of enzymes have been applied for the formation of carbon-carbon bonds in organic synthesis: aldolases, synthetases, and transketolases. Aldolases are a class of enzymes that catalyze the stereoselective construction and degradation of carbon-carbon bonds in monosaccharides [ 42 – 46 ]. Synthetases catalyze an irreversible aldol reaction of activated enols such as phosphoenolpyruvate (PEP) with aldoses to form complex monosaccharides [ 47 ]; transketolases catalyze the transfer of a hydroxyketo group of a keto sugar to an aldose [ 48 ]. These enzymes are discussed individually below, with an outline of their use in organic synthesis. d-FRUCTOSE-1,6,-DIPHOSPHATE ALDOLASE (FDP) d-Fructose-1,6-diphosphate (FDP) aldolase from rabbit muscle (E. C. 4.1.2.13) catalyzes the equilibrium condensation of dihydroxyacetone phosphate (1) (DHAP) with d-glyceraldehyde-3-phosphate (2) (G-3-P) to form dfructose-1, 6-biphosphate (3) (FDP) (Scheme 1) [ 42 – 44 ]. The equilibrium constant for this reaction is K = 10 4 M-1 in favor of the formation of FDP. The stereoselectivity of the reaction is absolute; the configuration of the vicinal diols at C-3′ and C-4 is always threo (i.e. d -glycero)...
eBook - ePub- James N. BeMiller(Author)
- 2018(Publication Date)
...Reactions of Maillard browning and related processes, while reactions of monosaccharides with an aldehydic carbonyl group, are covered separately in Chapter 18. Oxidation of the aldehydic group and the anomeric hydroxyl group of aldopyranoses and aldofuranoses Aldonic acids The aldehydic group of aldoses is readily oxidized to a carboxyl/carboxylate (− COOH/ − COO −) group. The products of such an oxidation are carboxylic acids, which when formed from aldoses are called aldonic acids (that is, aldonic acids are monosaccharides in which C1 is a carboxyl group rather than an aldehydic group). The reaction is commonly used for quantitative determination of sugars and for the manufacture of acids, such as D -gluconic acid. Salts of aldonic acids are aldonates, so for example, the sodium salt of D -gluconic acid is sodium D -gluconate. Table 2.1 Important reactions of carbohydrate molecules Group Modified Reactions Carbonyl group (alone) 1. Oxidation to a carboxylic acid group 2. Reduction to a hydroxyl group 3. Additions of nucleophiles a Hydroxyl groups 1. Ester formation 2. Ether formation 3. Cyclic acetal formation 4. Oxidation to a carbonyl group 5. Reduction to a deoxy carbon atom 6. Replacement with amino, thiol, and halogeno groups Both carbonyl and hydroxyl groups 1. Formation of cyclic hemiacetals: pyranose and furanose ring forms 2. Formation of acetals (glycosides) 3. Aldose ⇄ ketose isomerizations Anomeric hydroxyl group 1. Oxidation to lactones 2. Formation of glycosyl halides 3. Formation of glycosylamines ∗ a Chapter 18. Aldoses are called reducing sugars because they effect reduction of reagents that will oxidize their aldehydic group to a carboxylate group (because in the process of the aldehydic group of an aldose being oxidized to the salt of a carboxylic acid group, the oxidizing agent is reduced). A keto group cannot be oxidized...
