3-Pentanone aldol condensation

Primary amines form Schiff bases, (CH3 )2C=NR. Ammonia induces an aldol condensation followed by 1,4-addition of ammonia to produce diacetone amine (from mesityl oxide), 4-amino-4-methyl-2-pentanone [625-04-7] (CH2)2C(NH2)CH2COCH2, and triacetone amine (from phorone),... 

Diacetone Alcohol. Diacetone alcohol (DAA) (4-hydroxy-4-methyl-2-pentanone) is a colorless, mild smelling Hquid which is completely miscible with water and most organic solvents. It is the simplest aldol condensation product of acetone, and because of its keto-alcohol functionahes it has special utility in the coatings industry where it is used to dissolve cellulose acetate to give solutions with high tolerance for water (115). 

During a preparation of the complex [Ni(NCS)2 P(CH2CH2CN)3 2] in acetone solution, a yellow-orange compound was obtained which was characterized as [Ni(C6H1202)2][Ni(NCS)4- P(CH2CH2CN)3 2] (152) (Cdiacetone alcohol ). This reaction, which involves an aldol condensation of two acetone molecules, was found to be not reproducible. 11858,1185b... 

Stereoselective aldol condensation. Heathcock and Buse have previously employed 2-methyl-2-trimethylsiloxy-3-pentanone (1) in a highly stereoselective route to 3-hydroxy-2-methylcarboxylic acids (8, 295). Aldol condensation of the lithium enolate derived from 1 with a chiral aldehyde yields ery//iro-aldols, which are cleaved with periodic acid to -hydroxy carboxylic acids. However, when 1 is condensed with a chiral aldehyde such as 2, two eryt/iro-products (3 and 4) are produced. Heathcock and co-workers now report that the 1,2-diastereoselectivity of these aldol condensations can be enhanced by use of the ketone 5. Reaction of racemic 5 with racemic aldehyde 2 furnishes a single (racemic) adduct 6. 

Cp 2La CH(SiMe3)2 reacts with 3-pentanone to form the solvated enolate, Cp 2La —O—C(Et)=CHMe Et2CO (equation 9a), while with acetone it forms a chelate (equation 9b) after intramolecular aldol condensation. The reaction of the precursor bistrimethylsi-lyhnethyl organometallic with hydroxyketone, preformed from the pentanone, yields the enolate ketone solvate. This difference between acetone and 3-pentanone presumably reflects the difference in strain in the condensation product because the ethyl groups in 3-pentanone are rather much bigger than the methyl groups in acetone. 

Pittman et al. [29] described the simultaneous aldol condensation and the hydrogenation of the condensation product in a one-pot process with a perfluorinated aliphatic ether polymer with pendant sulfonic acid groups as the acid catalyst and Pd as the hydrogenation catalyst. Taking acetone and hydrogen as the educt components the aim was to obtain 4-methyl-2-pentanone for given reaction conditions. 

The apparent lack of an induction period in methylene chloride would appear to eliminate (1) and (3) as causes of this effect. Acetone, on the other hand, can contain a number of impurities which are not easily removed by distillation (12)- For example, an aldol condensation can be induced under mildly acidic or basic conditions to 4-hydroxy-4-methyl-2-pentanone. 

There are certainly cases when we want a crossed-aldol condensation between two reactive partners that have an enolizable position, as in 3-pentanone with cyclopentanone. If 3-pentanone and benzaldehyde, which has no enolizable protons, can lead to three products, what will happen in this new case If an aldol condensation occurs under thermodynamic conditions. 3-pentanone reacts with sodium ethoxide to give enolate 120. This enolate can condense with either unenolized 3-pentanone (to produce 126) or with unenolized cyclopentanone (to produce 128). Both of these ketones are symmetrical, and there is no opportunity for additional enolates, which would further complicate the reaction (see below). The pAa of 3-pentanone and cyclopentanone are not... 

Thus, a short-range strategy for the synthesis of 4-hydroxy-l-phenyl-pentanone-2 (I) will lead to the two carbonyl compounds methyl benzyl ketone and acetaldehyde as synthesis precursors (Figure 1). Having reached this conclusion it is absolutely necessary to consider whether those two precursors will react by the anticipated aldol condensation to the target compound (I). A closer inspection based on insight into chemical reactivity has to decide that this reaction will not proceed unequivocally to the desired product (I). Rather, a mixture of compounds will be obtained including the... 

Probably, the most studied aldol condensation reaction is the dimerization of acetone to give 4-hydroxy-4-methyl-2-pentanone (diacetone alcohol). The reaction can be carried out in the liquid phase at 273 K on M/MgO catalysts, where M stands for Na+, Cr +, Mn +, Al +, Fe +, Co +, Ni +, Cu +, or Zn + cations... 

It is important to put the thermodynamic aldol condensation into perspective. The actual product as well as the yield depends on the solvent, the base used, and the nature of the carbonyl substrate. When both a kinetic and a thermodynamic enolate are present, the equilibrium may favor the thermodynamic enolate, but steric hindrance makes its reaction much slower. In such a case, the kinetic enolate product may be the isolated product. When 2-pentanone (32) is refluxed with NaOMe in methanol and then treated with 20% sulfuric acid, for example, conjugated ketone 42 is the only isolated product, but in only 8% yield. This clearly makes the reaction confusing to understand. It is presented only to show that this reaction is an equilibrium-driven process and that the equilibrium may be shifted between kinetic and thermodynamic enolates by several factors. For the purposes of doing homework, assume that thermodynamic conditions lead to the thermodynamic aldol as the major product and that kinetic control conditions lead to the kinetic aldol as the major product. 

A stereoselective aldol condensation is known as Mukaiyama reaction." It consists in the reaction of an silyl enol ether of 3-pentanone with an aldehyde (2-methyl-butanal) in presence of TiCl to yield an aldol product, Manicone, an alarm pheromone (Scheme 32)." ... 

Ketones can undergo the aldol reaction too, and the mechanism is similar to that for the aldol condensation of aldehydes. We will use acetone as an example (Fig. 19.72). In base, the enolate is formed first, and adds to the electrophilic carbonyl compoimd. Protonation by water yields a molecule once known as diacetone alcohol, 4-hydroxy-4-methyl-2-pentanone. 

In the real world of practical organic synthesis, one rarely needs to do a simple aldol condensation between two identical aldehydes or two identical ketones. Far more common is the necessity to do a crossed aldol between two different aldehydes, two different ketones, or an aldehyde and a ketone. As noted earlier, there are difficulties in doing crossed aldol reactions. Suppose, for example, that we want to condense 2-pentanone with benzaldehyde. Benzaldehyde has no a hydrogen, so no enolate can be formed from it. Some version of the Claisen-Schmidt reaction (p. 984) seems feasible. But 2-pentanone can form two enolates, and the first problem to solve is the specific formation of one or the other enolate (Fig. 19.127). 

So far, we have discussed only aldehydes as substrates in the aldol condensation. What about ketones Treatment of acetone with base does indeed lead to some 4-hydroxy-4-methyl-2-pentanone, but the conversion is poor because of an unfavorable equilibrium with starting material. 

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