Hydroxyacetone, reactions

After cleavage the reaction mass is a mixture of phenol, acetone, and a variety of other products such as cumylphenols, acetophenone, dimethyl-phenylcarbinol, a-methylstyrene, and hydroxyacetone. It may be neutralised with a sodium phenoxide solution (20) or other suitable base or ion-exchange resins. Process water may be added to facilitate removal of any inorganic salts. The product may then go through a separation and a wash stage, or go direcdy to a distillation tower. 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

Similar hydroxylation-oxidations can be carried out using a catalytic amount of osmium tetroxide with A-methylmorpholine oxide-hydrogen peroxide or phenyliodosoacetate." A recent patent describes the use of triethylamine oxide peroxide and osmium tetroxide for the same sequence. Since these reactions are of great importance for the preparation of the di-hydroxyacetone side-chain of corticoids, they will be discussed in a later section. 

Product Acceptors. Many enzyme assays use acceptors, as for instance 2-ethylaminoethanol and other aminated alcohols iihich act as acceptors for the phosphoryl product of the reaction catalyzed by alkaline phosphatase (25) (Fig. 4). Hydroxylamine can act as an acceptor for the hydroxyacetone produced by eno-lase and semicarbazide can act as an acceptor for the pyruvate produced by LD. It is necessary to optimize the concentration of such an acceptor before using it routinely as often what may be a theoretically desirable acceptor is in practice superfluous. 

At even higher temperature, the polysaccharides decompose further by extensive C-C bond breaking. This leads to the formation of C2 4 oxygenates such as glycol aldehyde, acetic acid and hydroxyacetone (CH3-CO-CH2OH). The formation of these products can be rationalized by a series of reactions that include,... 

Furthermore, a base-catalyzed transformation by OH from the reaction medium between glycerate and hydroxypyruvate aldehyde (or hydroxypyruvic acid) could be excluded, while hydroxyacetone and glyceraldehyde interconversion was possible (Scheme 11.11). The existence of two major routes, of which hydroxyacetone and glyceric aldehyde are the primary oxidation products and glycolic and oxalic acid are the end-members, respectively, is now firmly established. Clearly, rapid oxidation of glyceraldehydes favors glyceric acid rather than hydroxyacetone formation. 

This enzyme [EC 1.1.1.101], also known as pahnitoyldi-hydroxyacetone-phosphate reductase, catalyzes the reaction of l-pahnitoylglycerol 3-phosphate and NADP+ to produce pahnitoylglycerone phosphate and NADPH. The enzyme can also utilize as substrates alkylglycerone... 

This enzyme [EC 2.3.1.42], also known as glycerone-phosphate O-acyltransferase, catalyzes the reaction of an acyl-CoA with dihydroxyacetone phosphate (or, glyc-erone phosphate) to produce coenzyme A and an acyldi-hydroxyacetone phosphate (or, an acylglycerone phosphate). The acyl-CoA derivatives of pahnitate, stearate, and oleate can all be utilized as substrates, with highest activity observed with palmitoyl-CoA. 

The determination of 17-ketosteroids is most often determined in the clinical laboratory by the Zimmerman reaction, in which the ether-extracted material is allowed to react with m-nitroaniline to yield a colored product. Thus, any compound with the 17-keto basic structure such as reserpine, morphine, ascorbic acid, or their metabolites will interfere. The Porter-Silber reaction used in the determination of 17,21-dihydroxysteroids is also not specific, and the reaction requires a di-hydroxyacetone side chain. Paraldehyde, chloral hydrate, meprobromate, and potassium iodide have been found to interfere, and patients should be maintained free of these drugs for 24-48 hours before the urine collection (Bll). 

Another dehydration product from glycerol is hydroxyacetone, or acetol (Scheme 4). In one study, several catalysts were tested for this reaction. Of the tested catalysts, however, only copper-chromite appeared to be effective for this transformation. Using this catalyst, 80% selectivity towards hydroxyacetone was achieved at 86% conversion in a reactive distillation experiment carried out under a slight vacuum (98 kPa) at 240... 

Scheme 4 Hydroxyacetone can be obtained from glycerol by dehydration. The reaction has been reported using copper-chromite as catalyst.

FSA makes it possible to use dihydroxyacetone or hydroxyacetone as a donor compound for aldolization reactions this opens up the field for novel carbohydrate compounds such as 1-deoxysugars which otherwise can be obtained by DXS through a different reaction. 

Reaction of the side chain hydroxyacetone in flumethasone (27-4) with periodic acid leads to cleavage of that function to give carboxylic acid (29-1) with the loss of the carbon atom at C-21. Further reaction of the very hindered acid group requires prior activation. Thus, acylation with diphenyl chlorophosphate leads to the mixed anhydride (29-2) this is not isolated, but treated immediately with methyl mercaptan. The product, tibecasone (29-3), is a quite effective topical anti-inflammatory agent [24]. Cleavage of the ester side chain would lead back to the inactive starting acid (29-1). 

Redox initiators have been proposed. The initiation system is composed from iron sulfate, dibenzoyl peroxide, and a reductant. Of the latter, hydroxyacetone, 2-hydroxy-2-phenylacetophenone, ascorbic palmitate, and toluene sulfinic acid are among the most economical. The reaction conditions are such that the cyclic oxida-... 

It was reported that proline catalyzed the direct catalytic asymmetric Mannich reactions of hydroxyacetone, aldehydes, and aniline derivatives [(Eq. (10)] [40-44]. Not only aromatic aldehydes but also aliphatic aldehydes worked well in this reaction, and good to excellent enantioselectivity and moderate to excellent yields were observed. Mannich reactions of glyoxylate imines with aldehydes or ketones were also successfully performed [45,46]. 

A wide range of donor ketones, including acetone, butanone, 2-pentanone, cyclopentanone, cyclohexanone, hydroxyacetone, and fluoroacetone with an equally wide range of acceptor aromatic and aliphatic aldehydes were shown to serve as substrates for the antibody-catalyzed aldol addition reactions (Chart 2, Table 8B2.6). It is interesting to note that the aldol addition reactions of functionalized ketones such as hydroxyacetone occurs regioselectively at the site of functionaliztion to give a-substitutcd-fi-hydroxy ketones. The nature of the electrophilic and nucleophilic substrates utilized in this process as well as the reaction conditions complement those that are used in transition-metal and enzymatic catalysis. 

Asymmetric intramolecular hydrosilylation of a-dimethylsiloxyketones (216), which are prepared from a-hydroxyketones 215, catalyzed by [(S ,S )-R-DuPHOS)Rh(COD)]+CF3 SO3-, (219) proceeds smoothly at 20-25 °C to give siladioxolanes 217. Desilylation of 217 affords 1,2-diols 218 with 65-93% ee in good yields (Scheme 22)231. The best result (93% ee) is obtained for the reaction of a-hydroxyacetone using (S, S)-i-Pr-DuPHOS-Rh+ as the catalyst. The same reactions using (S ,S )-Chiraphos and (S)-binap give 218 (R = Me) with 46 and 20% ee, respectively. 

Use of hydroxyacetone as donor in the asymmetric Mannich reaction led to the formation of optically active syn /i-amino alcohols bearing two stereogenic centers [22, 23], In the presence of 35 mol% L-proline as organocatalyst several types of syn / -amino alcohol syn-35 were successfully synthesized with enantioselectivity up to 99% ee and high diastereomeric ratio. For example, a high yield of 92%, a diaster-eomeric ratio of 20 1, and enantioselectivity >99% ee were observed by List et al. for formation of the syn yfi-amino alcohol 35a (Scheme 5.17) [23]. In addition to hydroxyacetone the methylated derivative methoxyacetone was also applied successfully in this reaction (93% yield, d.r. > 39 1, >99% ee). 

Substrate range As aldol donor hydroxyacetone was investigated for its potential to form the corresponding optically active anti diols 78 as aldol products [92-94a]. As model reaction the conversion of cyclohexyl carboxaldehyde and hydroxyacetone to the aldol product was investigated in the presence of L-proline as catalyst (because this organocatalyst was found to be very efficient in previous reactions see also Section 6.2.1.1) [92]. With this catalyst high diastereoselectivity (d.r. > 20 1), and an excellent enantioselectivity (99% ee) were observed. The yield was in the... 

The reactions also led to high regioselectivity (> 20 1). For alkylated aldehydes unbranched in the a-position, however, low diastereoselectivity (d.r. 1.7 1) and yields of 38% were obtained, although enantioselectivity remained excellent (> 97% ee). Use of aromatic substrates resulted in a d.r. of 1 1 to 1.5 1 only, and the enantioselectivity was in the range 67 to 80% ee [93]. Some representative examples of the L-proline-catalyzed aldol reaction with hydroxyacetone are given in Scheme 6.35. 

Mechanism and transition states The basic principles of the proline-catalyzed direct aldol reaction are summarized in Section 6.2.1.1 [93, 94a], The preferred diastereo- and enantioselectivity were explained in terms of the potential transition states for the aldol reaction using hydroxyacetone shown in Scheme 6.38 [93], Thus, re-facial attack of the aldehyde at the si face of hydroxyacetone leads to the... 

The regioselectivities of the aldol reactions of hydroxyacetone were reversed from those of the proline-catalyzed reactions when small peptide catalyst 6 or 7 containing (S)-proline at the N-terminal was used, as shown in Table 2.5 [20]. 

Table 2.3 (S)-Proline-catalyzed aldol reactions of hydroxyacetone [6, 7].

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