Aldolization of acetaldehyde

Extensions of the proline-catalyzed aldol reaction Recently interesting extensions of the enantioselective proline-catalyzed aldol reaction have been reported. An enan-tioselective proline-catalyzed self-aldolization of acetaldehyde was observed by Barbas and co-workers (Scheme 6.21) [77]. Starting from acetaldehyde, the valuable building block 5 -h ydroxy-( 2E)-hexcnal, (S)-43, was obtained as a product with up to 90% ee, although the yield did not exceed 13%, irrespective of the reaction conditions. This reaction requires a small amount catalyst only (ca. 2.5 mol%). 

Mixed aldol of acetaldehyde and isobutyraldehyde CH3CH(OH)C(CH3)2CHO CH3COCH(CH3)2 12.0... 

Self-aldolization of acetaldehyde provided one-step enantioselective syntheses of (5R)- and (5S)-Hydroxy-(2E)-hexenal using either (R) or (S)-proline as catalysts of the homologation of three acetaldehyde units ee-values of up to 90% were obtained [25]. Using this methodology, a series of triketides was prepared by slow addition of propionaldehyde into acceptor aldehyde and (S)-proline in DMF, and the isolated lactols were converted to the corresponding d-lactones [26]. The product enantiomeric purity was typically moderate because of the isomerization... 

During investigations with RibA it had been realized by serendipity that the initial product 52 from catalyzed self-aldolization of acetaldehyde again serves as a suitable acceptor for the sequential addition of a second donor molecule to... 

Idriss H, Kim KS, Barteau MA (1993) Carbon-carbon bond formation via aldolization of acetaldehyde on single crystal and polycrystalline TiOj surfaces. J Catal 139 119... 

CAS 104-76-7. CH3(CH2)3CHC2H5CH2OH. Properties Colorless liquid. D 0.83 (20C), bp 183.5C, fp -76C, vap press 0.36 (20C), refr index 1.4300 (20C), bulk d 6.9 lb/gal (20C), flash p 178F (81.1C). Miscible with most organic solvents, slightly soluble in water. Combustible. Derivation (a) Oxo process from propylene and synthesis gas (b) aldolization of acetaldehyde or butyraldehyde, followed by hydrogenation (c) from fermentation alcohol. 

This consists in the aMofizstion of butyraldehyde, followed by the dehydration and hydrogenation of the aldoL The butyraldehyde can be obtained cither by the aldolization of acetaldehyde, or by Oxo synthesis of propylene, which is the more widely used method. These different possibilities can be summarized as follows ... 

The aldolization of acetaldehyde on calcined hydrotalcites of different composition has been studied by Kagunya and Jones [21] in a flow reactor at 10 bar and LHSV = 4 at temperatures between 363 and 403 K. MgAl carbonate was the best catalyst conversion reached ca 40 % at 110 °C with a broad range of products with a larger selectivity to Cg isomers. 

Water is removed with especial ease from alcohols whose hydroxyl group is in a /9-position to an oxo, alkoxycarbonyl, nitrile, or nitro group. For example, on aldolization of acetaldehyde the acid present in the reaction medium suffices for dehydration of the product to the unsaturated carbonyl compound, i.e., to crotonaldehyde. One hour s boiling with dilute sulfuric acid suffices for preparation of 3-hepten-2-one from 4-hydroxy-2-heptanone 39... 

Butadiene (bpI o13= — 4-413°C, d4°=0.621 l)(l> has become a major petrochemical product thanks to the development of its copolymers with styrene and acrylonitrile. The earliest processes for manufacturing butadiene started with acetylene and formaldehyde (Germany, the Reppe process), or produced it by the aldolization of acetaldehyde (Germany), or by the dehydration and dehydrogenation of ethanol (USSR, United States Union Carbide),... 

L-/-Leucine catalyses model aldols in moderate to high yields, des, and ees, being superior to leucine, valine, alanine, and proline for the reactions examined. " A simple chiral l°-3° diamine (52, derived fl om L-Meucine) and a tungstate (H4SiWj204o) catalyse direct cross-aldols of acetaldehyde, giving 99% yield in 4h, and ee up to 92%. ... 

Table 2 Aldolization of acetaldehyde-derived enol ethers ...

Class I aldolase-like catalysis of the intermolecular aldol reaction with amines and amino acids in aqueous solution has been studied sporadically throughout the last century. Fischer and Marschall showed in 1931 that alanine and a few primary and secondary amines in neutral, buffered aqueous solutions catalyze the self-aldolization of acetaldehyde to give aldol (11) and crotonaldehyde (12) (Scheme 4.3, Eq. (1)) [41]. In 1941 Langenbeck et al. found that secondary amino acids such as sarcosine also catalyze this reaction [42]. Independently, Westheimer et al. and other groups showed that amines, amino acids, and certain diamines catalyze the retro-aldolization of diacetone alcohol (13) and other aldols (Scheme 4.3, Eq. (2)) [43-47]. More recently Reymond et al. [48] studied the aqueous amine catalysis of cross-aldolizations of acetone with aliphatic aldehydes furnishing aldols 16 (Scheme 4.3, Eq. (3)) and obtained direct kinetic evidence for the involvement of enamine intermediates. 

SCHEME 14 Aldolase- and proline-catalyzed self-aldolization of acetaldehyde. 

The selective intermolecular addition of two different ketones or aldehydes can sometimes be achieved without protection of the enol, because different carbonyl compounds behave differently. For example, attempts to condense acetaldehyde with benzophenone fail. Only self-condensation of acetaldehyde is observed, because the carbonyl group of benzophenone is not sufficiently electrophilic. With acetone instead of benzophenone only fi-hydroxyketones are formed in good yield, if the aldehyde is slowly added to the basic ketone solution. Aldols are not produced. This result can be generalized in the following way aldehydes have more reactive carbonyl groups than ketones, but enolates from ketones have a more nucleophilic carbon atom than enolates from aldehydes (G. Wittig, 1968). 

Mixed aldol condensations can be effective only if we limit the number of reaction pos sibilities It would not be useful for example to treat a solution of acetaldehyde and propanal with base A mixture of four aldol addition products forms under these condi tions Two of the products are those of self addition... 

The base-catalyzed reaction of acetaldehyde with excess formaldehyde [50-00-0] is the commercial route to pentaerythritol [115-77-5]. The aldol condensation of three moles of formaldehyde with one mole of acetaldehyde is foUowed by a crossed Cannizzaro reaction between pentaerythrose, the intermediate product, and formaldehyde to give pentaerythritol (57). The process proceeds to completion without isolation of the intermediate. Pentaerythrose [3818-32-4] has also been made by condensing acetaldehyde and formaldehyde at 45°C using magnesium oxide as a catalyst (58). The vapor-phase reaction of acetaldehyde and formaldehyde at 475°C over a catalyst composed of lanthanum oxide on siHca gel gives acrolein [107-02-8] (59). 

Mercaptals, CH2CH(SR)2, are formed in a like manner by the addition of mercaptans. The formation of acetals by noncatalytic vapor-phase reactions of acetaldehyde and various alcohols at 35°C has been reported (67). Butadiene [106-99-0] can be made by the reaction of acetaldehyde and ethyl alcohol at temperatures above 300°C over a tantala—siUca catalyst (68). Aldol and crotonaldehyde are beheved to be intermediates. Butyl acetate [123-86-4] has been prepared by the catalytic reaction of acetaldehyde with 1-butanol [71-36-3] at 300°C (69). 

Reaction of one mole of acetaldehyde and excess phenol in the presence of a mineral acid catalyst gives l,l-bis(p-hydroxyphenyl)ethane [2081-08-5], acid catalysts, acetaldehyde, and three moles or less of phenol yield soluble resins. Hardenable resins are difficult to produce by alkaline condensation of acetaldehyde and phenol because the acetaldehyde tends to undergo aldol condensation and self-resinification (see Phenolic resins). 

The name aldol was introduced by Wurt2 in 1872 to describe the product resulting from this acid-cataly2ed reaction of acetaldehyde. The addition will occur with base catalysis as well. 

Aldehydes fiad the most widespread use as chemical iatermediates. The production of acetaldehyde, propionaldehyde, and butyraldehyde as precursors of the corresponding alcohols and acids are examples. The aldehydes of low molecular weight are also condensed in an aldol reaction to form derivatives which are important intermediates for the plasticizer industry (see Plasticizers). As mentioned earlier, 2-ethylhexanol, produced from butyraldehyde, is used in the manufacture of di(2-ethylhexyl) phthalate [117-87-7]. Aldehydes are also used as intermediates for the manufacture of solvents (alcohols and ethers), resins, and dyes. Isobutyraldehyde is used as an intermediate for production of primary solvents and mbber antioxidants (see Antioxidaisits). Fatty aldehydes Cg—used in nearly all perfume types and aromas (see Perfumes). Polymers and copolymers of aldehydes exist and are of commercial significance. 

An alternative route for n-hutanol is through the aldol condensation of acetaldehyde (Chapter 7). 

Aldehydes and ketones with an a hydrogen atom undergo a base-catalyzed carbonyl condensation reaction called the aldol reaction. For example, treatment of acetaldehyde with a base such as sodium ethoxide or sodium hydroxide in a protic solvent leads to rapid and reversible formation of 3-hydroxybutanal, known commonly as aldol (aidehyde + alcohol), hence the general name of the reaction. 

What is the structure of the enone obtained from aldol condensation of acetaldehyde ... 

In general, a mixed aldol reaction between two similar aldehyde or ketone partners leads to a mixture of four possible products. For example, base treatment of a mixture of acetaldehyde and propanal gives a complex product mixture containing two "symmetrical" aldol products and two "mixed" aldol products. Clearly, such a reaction is of no practical value. 

The corrosion of metal surfaces and the precipitation of a metal sulfide by an aqueous acid solution can be prevented by an aldol-amine adduct. Aldol (from acetaldehyde) CH3CH(OH)CH2CHO has been utilized as a H2S scavenger that prevents the precipitation of metal sulfides from aqueous acid solutions. However, when the aldol or an aqueous solution of the aldol is stored, the solution separates quickly into two layers, with all of the aldol concentrated in the bottom layer. The bottom layer is not redispersible in the top layer or in water or acid. In addition, the aldol in the bottom layer has very little activity as a sulfide scavenger. Thus the use of aldol as a H2S scavenger in aqueous acid solutions can result in unsatisfactory results [245,247]. However, the aldol can be reacted with an amine, such as monoethanoleamine (=aminoethanol), to form an aldol-amine adduct to overcome these difficulties. The amine utilized to prepare the aldol-amine adduct must be a primary amine. The aldol-amine adduct preferentially reacts with sulfide ions when they are dissolved in the... 

This aldol reaction was employed for an asymmetric synthesis of the azetidinone 9 from the adduct (5) of acetaldehyde and l.5 Azetidinone 9 is a versatile precursor to the antibiotic thienamycin 10. The configurationally stable aldehyde 6, obtained by ozonolysis of the silyl ether of 5, undergoes addition with allylzinc chloride to afford 7, which on transamination is converted to the N-methoxy amide 8. This product is converted in several steps to the desired 9 in 34% overall yield. An interesting feature of this synthesis is the early incorporation of the hydroxyethyl side chain at C6, a step that is difficult to effect after formation of the (3-lactam ring. 

Experiment 11.—A few drops of acetaldehyde, dissolved in about 2 c.c. of water, are heated in a test tube with 0-5 c.c. of dilute sodium hydroxide solution. A yellow colour develops and the acetaldehyde is converted by way of aldol into crotonaldehyde, which can be recognised in the boiling solution by its pungent odour. If acetaldehyde is heated with concentrated alkali solution yellow aldehyde resin is precipitated as a result of further condensation. 

An accessory proposal was Arthur Michael s hypothesis that many reactions proceed by addition, for example, a polymerization of acetaldehyde (CH3CH = O) in the presence of bases (OH) to an aldol (CH3CHOHCH2CHO), with subsequent loss of water to form crotonaldehyde (CH3CH = CHCHO). Michael, educated in America, Germany, and France, made use of Kekule s idea that two molecules may form a "polymolecule" or molecular compound, which, in turn breaks up to yield the final products.33 Lachman expressed fairly standard misgivings about this proposal of an intermediary and transition form "If we are going to explain reactions by means of addition products which we do not or cannot isolate, our explanation loses its definiteness. It becomes simply a possible explanation, and its conclusions are by no means binding."34... 

The formation mechanisms and the nature of chromophores in PET are still a matter of discussion. Postulated chromophores are polyenaldehydes from the aldol condensation of acetaldehyde [73] and polyenes from polyvinyl esters [69], as well as quinones [74, 75], Goodings [73] has proposed aldol condensation as forming poly conjugated species by subsequent reactions of acetaldehyde molecules (Figure 2.16). 

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