Acetone aldol formation from

It may be stated at this point that the presence of a /3-hydroxy-butyrate fat in certain organisms is a matter of general biochemical importance. Usually /3-hydroxybutyric acid and the acetone bodies are derived from n-butyric acid directly. The unambiguous formation of jS-hydroxybutyric acid anhydrides from carbohydrates opens up new vistas its formation from acetaldehyde, and from pyruvic acid, through aldol intermediates can be understood without difficulty. Kirrmann s reaction, to which little attention has been paid, is at the same time an example of an oxygen shift, leading from hydroxyaldehydes to fatty acids. 

Reymond and Chen88 have investigated the same set of antibodies for their ability to catalyze bimolecular aldol condensation reactions. The antibodies were assayed individually at pH 8.0 for the formation of aldol 111 from aldehyde 109 and acetone. None catalyzed the direct reaction, but in the presence of amine 110 three anti-52a and three anti-52b antibodies showed modest activity. In analogy with natural type I aldolase enzymes, the reaction is believed to occur by formation of an enamine from acetone and the amine, followed by rate-determining condensation of the enamine with the aldehyde. As in the previous example, the catalyst, which was characterized in detail, is not very efficient in absolute terms ( cat = 3 x 10-6 s 1 for the anti-52b antibody 72D4), but it is approximately 600 times more effective than amine alone. Moreover, the reactions with the antibody are stereoselective The enamine adds only to the si face of the aldehyde to give... 

The secondary amine of the AEP group is responsible for the supported enamine formation with acetone (aldol reaction), the deprotonation of nitromethane (Henry reaction) and the generation of a potential nucleophile from trimethylsilyl cyanide through hypervalent silicate formation (cyanosilylation reaction). Therefore, the presence of both AEP and UDP groups in close proximity can cooperatively activate the electrophile (through hydrogen bond) and the nucleophile by enamine formation, thus enhancing the reaction rate. 

One of the difficulties in performing aldolization is the reversibility of the reaction, which limits the equilibrium conversion. The thermodynamic equilibrium has been investigated by Craven [2] for the industrially important aldolization of acetone to diacetone alcohol (DA). Because the reaction is exothermic, the yield of aldol obtained from pure acetone decreases with temperature 23.1 % at 273 K, 16.9 % at 283 K, 12.1 % at 293 K and 9.1 % at 303 K. The same conclusions can be drawn from the work of Guthrie [3-6] who reported equilibrium constants in the aqueous phase, in relation to the of the substrates, for a series of aldol condensations at room temperature. For the aldolization of aeetaldehyde at 298 K the values relative to the reaction are AG° = -2.4 kcal mor , A77 = -9.84 kcal mol , and equilibrium constant K = 51 m . The results for a few specific reactions performed in the aqueous phase are reported in Table 1 where Ky and K2 represent the equilibrium constants for the formation of the aldol and for its dehydration, respectively. 

According to these thermodynamic data, significant conversion can be obtained for the condensation of acetone with formaldehyde. Diacetone alcohol can be formed in low yield only and has a lower tendency to dehydrate than the aldols formed from benzaldehyde. The energy balance of the process is so displaced by the formation of water that the unsaturated ketone is usually obtained. The... 

Acetone aldol condensation proceeds on either acidic or basic catalysts. On basic catalysts, the reaction products are mainly a,P-unsaturated ketones [5] whereas on acidic materials formation of aromatics and olefins is favored [6]. In our catalytic tests, the main reaction products were mesityl oxides (MO s) and isophorone (IP). MO is formed from the initial selfcondensation of acetone whereas IP is a secondary product arising from the consecutive aldol condensation between MO and acetone. Over all the samples the reaction rate diminished as a function of time-on-stream as shown in Fig. 1 for the MgjAlOx sample which lost about 60 % of its initial activity after 10 h-run. Initial reaction rates (r ) and product selectivities (S j) were calculated by extrapolating the reaction rates vs. time curves to zero. 

The secondary undesired reactions are the ketonization (11) to acetone and the dehydration to ketene (15). In particular, ketene can react to form ethene by ketene coupling reaction (17), which has a role of coke precursor (Buffoni et al., 2009), while acetone may react through polymerization via aldol condensation, making possible coke formation from reactions (18) and (20). 

It is often said that the property of acidity is manifest only in the presence of a base, and NMR studies of probe molecules became common following studies of amines by Ellis [4] and Maciel [5, 6] and phosphines by Lunsford [7] in the early to mid 80s. More recently, the maturation of variable temperature MAS NMR has permitted the study of reactive probe molecules which are revealing not only in themselves but also in the intermediates and products that they form on the solid acid. We carried out detailed studies of aldol reactions in zeolites beginning with the early 1993 report of the synthesis of crotonaldehyde from acetaldehyde in HZSM-5 [8] and continuing through investigations of acetone, cyclopentanone [9] and propanal [10], The formation of mesityl oxide 1, from dimerization and dehydration of... 

One of the most spectacular and useful template reactions is the Curtis reaction , in which a new chelate ring is formed as the result of an aldol condensation between a methylene ketone or inline and an imine salt. The initial example of this reaction was the formation of a macrocyclic nickel(II) complex from tris(l,2-diaminoethane)nickel(II) perchlorate and acetone (equation 53).182 The reaction has been developed by Curtis and numerous other workers and has been reviewed.183 In mechanistic terms there is some circumstantial evidence to suggest that the nucleophile is an uncoordinated aoetonyl carbanion which adds to a coordinated imine to yield a coordinated amino ketone (equation 54). If such a mechanism operates then the template effect is largely, if not wholly, thermodynamic in nature, as described for imine formation. Such a view is supported by the fact that the free macrocycle salts can be produced by acid catalysis alone. However, this fact does not... 

Functionally and mechanistically reminiscent of the pyruvate lyases, the 2-deoxy-D-ribose 5-phosphate (121) aldolase (RibA EC 4.1.2.4) [363] is involved in the deoxynucleotide metabolism where it catalyzes the addition of acetaldehyde (122) to D-glyceraldehyde 3-phosphate (12) via the transient formation of a lysine Schiff base intermediate (class I). Hence, it is a unique aldolase in that it uses two aldehydic substrates both as the aldol donor and acceptor components. RibA enzymes from several microbial and animal sources have been purified [363-365], and those from Lactobacillus plantarum and E. coli could be induced to crystallization [365-367]. In addition, the E. coli RibA has been cloned [368] and overexpressed. It has a usefully high specific activity [369] of 58 Umg-1 and high affinity for acetaldehyde as the natural aldol donor component (Km = 1.7 mM) [370]. The equilibrium constant for the formation of 121 of 2 x 10M does not strongly favor synthesis. Interestingly, the enzyme s relaxed acceptor specificity allows for substitution of both cosubstrates propional-dehyde 111, acetone 123, or fluoroacetone 124 can replace 122 as the donor [370,371], and a number of aldehydes up to a chain length of 4 non-hydrogen atoms are tolerated as the acceptor moiety (Table 6). 

The concept The possibility of using a simple organic molecule from the chiral pool to act like an enzyme for the catalytic intermolecular aldol reaction has recently been reported by the List and Barbas groups [69-71]. L-proline, (S)-37, was chosen as the simple unmodified catalytic molecule from the chiral pool . The proline-catalyzed reaction of acetone with an aldehyde, 36, at room temperature resulted in the formation of the desired aldol products 38 in satisfactory to very good yields and with enantioselectivity up to >99% ee (Scheme 6.18) [69, 70a],... 

The capability of L-proline - as a simple amino acid from the chiral pool - to act like an enzyme has been shown by List, Lemer und Barbas III [4] for one of the most important organic asymmetric transformations, namely the catalytic aldol reaction [5]. In addition, all the above-mentioned requirements have been fulfilled. In the described experiments the conversion of acetone with an aldehyde resulted in the formation of the desired aldol products in satisfying to very good yields and with enantioselectivities of up to 96% ee (Scheme 1) [4], It is noteworthy that, in a similar manner to enzymatic conversions with aldolases of type I or II, a direct asymmetric aldol reaction was achieved when using L-proline as a catalyst. Accordingly the use of enol derivatives of the ketone component is not necessary, that is, ketones (acting as donors) can be used directly without previous modification [6]. So far, most of the asymmetric catalytic aldol reactions with synthetic catalysts require the utilization of enol derivatives [5]. The first direct catalytic asymmetric aldol reaction in the presence of a chiral heterobimetallic catalyst has recently been reported by the Shibasaki group [7]. 

The deMayo-type photochemistry of 1,3-dioxin-4-ones has been beautifully applied by Winkler et al. to the synthesis of complex natural products. Substrate 133 gave under sensitized irradiation (with acetone as cosolvent) product 134 as single diastereoisomer (Scheme 6.47). The diastereoselectivity results from cyclic stereocontrol exerted by the two stereogenic centers in the spiro-bis-lactone part of the starting material. After installation of the furan, saponification and bond scission in a retro-aldol fashion generated a keto carboxylic add, which produced the natural product ( )-saudin (135) by simultaneous formation of two acetal groups [128]. 

Despite the absence of stereochemical information in the reactive immunogen, the aldolase antibodies promote carbon-carbon bond formation with surprisingly high selectivity. For instance, the enamine formed from acetone adds to the si face of various aldehydes with ee s in excess of 95% [53], In other examples, Robinson annula-tions have been carried out with high enantioselectivity [55], tertiary aldols and other compounds have been successfully resolved [56], and enantiopure intermediates have been prepared for the synthesis of various natural products [57, 58]. 

Houk s first alternative mechanism. Reaction 6.31, posits the direct proton transfer from acetone to acetaldehyde to form an ion pair. This process requires a great deal of energy, 59 kcal mol and even though the subsequent formation of the C-C bond and the ultimate aldol product occur without fur er barrier, this mechanism requires too much energy to be competitive. 

Isatoic anhydride reacts with ethyl -aminocrotonate (9a) or 4-aminopent-3-en-2-one (9b) to give 2-methylquinazolin-4(3//)-one (43-57%), the formation of which can be rationalized as proceeding through the loss of ethyl acetate or acetone from the intermediate 10 by a retro-Claisen or retro-aldol type elimination, respectively. ... 

Besides alkoxides, acetylacetonates are also used as the starting materials for the synthesis of oxides. Titania (anatase) is obtained by decomposition of titanium oxyacetylacetonate (TiO(acac)2) in toluene at 300°C. Similarly solvothermal treatment of Fe(lll) acetylacetonate in toluene yields microcrystalline magnetite. One of the drawbacks of the use of acetylacetonate may be formation of various high boiling point organic by-products via aldol-type condensation of the acetylacetone. Actually more than 50 compounds are detected by gas chromatography-mass spectrometry (GC-MS) analysis of the supernatant of the reaction, some of which are phenolic compounds and are hardly removed from the oxide particles by washing with acetone. ... 

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