Aldol reactions Alumina

Several approaches based on nitro-aldol for the synthesis of amino sugars have been reported Alumina-catalyzed reaction of methyl 3- nitropropanoate with O-benzyl-o-lactaldehyde gives the o-ribo-nitro-aldol fanti, and isomeri in 63% yield, which is converted into L-dannosamine fsee Secdon 3 3 Jager and coworkers have reported a short synthesis of L-acosamine based on the stereoselective nitro-aldol reaction of 2-O-benzyl-L-lactaldehyde with 3-nitropropanal dimethyl acetal as shovm in Scheme 3 10 The stereoselecdve nitro-aldol reacdon is carried ont by the silyl nitronate approach as discussed in Secdon 3 3... 

The Cannizzaro reaction, that is, the base-catalysed disproportionation of a carbonyl compound to an alcohol and a carboxylic acid, has gained some importance as an economically viable alternative to the reduction with borohydrides. However, the reaction is restricted to carbonyl compounds without any a-hydrogen, which do not undergo competing aldol reactions. Thus, mainly aromatic aldehydes are used for this kind of transformation. The protocols developed for microwave applications typically involve solvent-free conditions using alumina as the solid support. Under these conditions, a significant acceleration of the reaction was achieved. 

The aldol reaction of 184 with crotonaldehyde 35 was rather unsatifactory as a mixture of aldol 185 and dienone 186 was formed. The aldol could be converted into the enone with basic alumina but the yield was only 61%. An alternative was needed. 

The reaction of ethanol with ammonia on zeolite catalysts leads to ethylamine. If, however, the reaction is carried out in the presence of oxygen, then pyridine is formed [53]. MFI type catalysts H-ZSM-5 and B-MFI are particularly suitable for this purpose. Thus, a mixture of ethanol, NH3, H2O and O2 (molar ratio 3 1 6 9) reacts on B-MFI at 330 °C and WHSV 0.17 h 1 to yield pyridine with 48 % selectivity at 24 % conversion. At 360 °C the conversion is 81% but there is increased ethylene formation at the expense of pyridine. Further by-products include diethyl ether, acetaldehyde, ethylamine, picolines, acetonitrile and CO2. When applying H-mordenite, HY or silica-alumina under similar conditions pyridine yields are very low and ethylene is the main product. The one-dimensional zeolite H-Nu-10 (TON) turned out to be another pyridine-forming catalyst 54]. A mechanism starting with partial oxidation of ethanol to acetaldehyde followed by aldolization, reaction with ammonia, cyclization and aromatization can be envisaged. An intriguing question is why pyridine is the main product and not methylpyridines (picolines). It has been suggested in this connection that zeolite radical sites induced Ci-species formation. 

High yields of hydroxythioxanthones are readily obtained with good regioselectivity when a mixture of alumina and methanesulfonic acid is used to effect the reaction between thiosalicylic acid and phenols <04S2900> and a one-pot conjugate addition - aldol reaction sequence provides benzo[6]thioxanthene-6,l 1-diones from naphthoquinone and 2-acylthiophenols (Scheme 24) <04BCJ2095>. 

The cross-aldol reaction is actively studied with the aim of improved control of the stereoselectivity.58 The use of silyl enol ethers for a condensation with aldehydes constitutes important progress, but catalysis by Lewis acids can be unsatisfactory for acid labile substrates, and the predominant anti stereoselectivity is not always optimal. An attempt was made to solve this problem by running the reaction sonochemically in the presence of alumina, without any solvent.59 products are absent, and the anti-isomer forms predominantly (Eq. 16). 

Application of ultrasound to a number of alumina catalysed aldol reactions has also been found to be beneficial. Initial reports stated that self-condensation of ketones was enhanced by a factor of two over the acid catalysed dimerisation [211]. 

Recent work has shown that they, and the more reactive 2-hydroxytetrahydro-pyridines, can be obtained by photochemical addition of enamino-aldehydes (165) to olefins. The photochemical [2 + 2] cycloaddition proceeds with complete regiospecificity, presumably by the formation of a cyclobutane system, followed by a hetero-retro-aldol reaction and formation of a new enamino-aldehyde, which re-cyclizes to (166). Further treatment with acid provides a useful method for synthesis of benzo[a]quinolizidine alkaloids (167). The last two steps may be completed in one treatment of (166) with BFa EtjO on alumina. 

The diastereoselectivity is observed in the Henry reaction using optical active niti o compounds or a-heteroatom substituted aldehydes. Lor example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-niti opropionate in the presence of neubal alumina leads to a mixture of three niti o-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

In contrast, transmetalation of the lithium enolate at —40 C by treatment with one equivalent of copper cyanide generated a species 10b (M = Cu ) that reacted with acetaldehyde to selectively provide a 25 75 mixture of diastereomers 11 and 12 (R = CH3) which are separable by chromatography on alumina. Other diastereomers were not observed. Similar transmetalation of 10a (M = Li0) with excess diethylaluminum chloride, followed by reaction with acetaldehyde, produced a mixture of the same two diastereomers, but with a reversed ratio (80 20). Similar results were obtained upon aldol additions to other aldehydes (see the following table)49. 

Aldol condensation reactions have also been conducted. A good example is provided by Climent et al. (1998) for making a-n-amyl cinnamaldehyde (Jasmin aldehyde) by condensing benzaldehyde with n-heptaldehyde, in the presence of mesoporous MCM-41 aluminosilicates. Mesoporous silica-aluminas with a narrow range of pore diameter such as MCM-41 also... 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

Acetone purified by these means, or the analytical reagent grade, may have the water content reduced by storage over a Type 4A molecular sieve. Silica gel or alumina should not be used as an aldol type reaction is initiated with the formation of water as a by-product. Pure acetone has b.p. 56.2 °C/760mmHg and is highly flammable. 

The acidifying effect of the nitro group is so profound that very mild bases can be used to catalyse the reaction. This enables selective removal of the proton next to the nitro group and helps to avoid side-reactions involving aldol condensations of the carbonyl component, Common examples include amines, quaternary ammonium hydroxides, and fluorides, Even basic alumina is sufficient to catalyse virtually quantitative addition of this benzylic nitroalkane to cyclohexenone at room temperature ... 

It has previously been reported that hydrotalcite catalyzes the aldol condensation of acetone (25). Polyoxometalates are known to dehydrate alcohols due to their acidic nature (IS ). In order to compare the relative basicity of polyoxometalate-pillared hydrotalcites to that of hydrotalcite itself, a variety of hydrotalcites were screened for 2-propanol conversion (Table II). This reaction is known to give propylene when the catalyst contains acidic sites (such as alumina) and acetone when the catalyst contains basic sites (such as magnesium oxide). 

Alumina is probably the most commonly used adsorbent. It has the advantages of being white, insoluble, reasonably chemically inert, a good adsorbent for many compounds, and readily available. Ordinary alumina often contains some sodium carbonate or sodium bicarbonate, and in many cases this is a disadvantage since the base may promote aldol condensations, hydrolysis of esters and lactones, and similar reactions. The basic impurities may be removed by washing the alumina... 

Non-activated y grade alumina for chromatography is sufficiently basic to promote hydrogen abstraction to rather acidic carbon acids (pKa<15) [19]. In such a way, numerous anionic condensations are described, for example, an aldolization [Eq. (10)] [20] leading to aurone, a basic compound in flower pigmentation, a Knoevenhagel reaction [Eq. (11) ] [21 ], or a case of a Henry reaction [Eq. (12)] [22]. 

Varma has run many types of reactions on nontoxic supports, such as alumina, silica, and clay, using microwaves.45 (For more on the use of microwaves, see Chap. 15.) The method offers selectivity under safe, fast, mild reaction conditions in open vessels. The supports can be recycled. The reactions include oxidations, reductions, nitrations, aldol condensations, and others. Solvents were used in the workups. Other workers have devised a condensation (8.3) of aromatic aldehydes with malonic acid (without a support) that uses no solvents at all.46 The workup consisted of pouring the glassy reaction mixture from the Erlenmeyer flask into ice water, filtering off the solid, and drying it. The conventional procedure for this reaction requires heating at 120°C for 3 h to give the product in 96% yield. 

A number of methods may be used for self-condensation of ketones to give a, -unsaturated ketones. Cyclic ketones are especially prone to aldol condensation, and the product from cyclopentanone (equation 29) is frequently encountered as a by-product in reactions that involve exposure of cyclopentanone to acid or base. In the example shown in equation (29), the aldol addition reaction is carried out with gaseous HCl, leading to an intermediate 0-chloro ketone that is dehydrochlorinated by treatment with base. It has recently been shown that basic alumina is an effective catalyst for the aldol condensation of ketones. ... 

The aldol condensation of benzaldehyde with acetophenone has been used to compare hydrated hydrotalcites with many solids claimed to be strong solid bases-KF and KNO3 supported on alumina, X zeolites containing excess Cs or Mg, and lanthanum oxide. Only hydrated HDT and KF/AI2O3 could be used to perform this reaction at 273 K-HDT with 100% selectivity for chalcone and KF with lower selectivity, because of secondary Michael addition of the chalcone to acetophenone. The other solids were inactive, but could induce comparable conversions at 423 K. 

Aldol condensation. The ultrasound-promoted reaction between silyl enol ethers and aldehydes on alumina surface is anfi-selective. 

The derivation of rate equations for simultaneous hydrogenation of TMP-aldol and formaldehyde was based on a plausible surface reaction mechanism. According to the mechanism, the aldol, formaldehyde and hydrogen undergo competitive adsorption on the nickel-alumina surface. Adsorbed hydrogen atoms add to the carbonyl bonds of the aldol and formaldehyde. These irreversible reaction steps are presumed to be rate-determining, whereas the product desorption is regarded as rapid. Consequently, the reaction mechanism is written as follows ... 

Alumina forms more and heavier coke than MgO but the latter deactivates faster. This is explained by the fact that on MgO primary aldol condensation reactions and formation of coke precursors species take place on the same basic sites. In contrast, alumina forms predominantly aromatic coke involving Bronsted OH groups that are inactive for aldol condensation reactions. The initial deactivation rate of acetone oligomerization on MgyAlOx oxides is essentially related to the surface basic properties. This is because the activity decline is significantly higher when coke poisons very active basic Mg-0 pairs than when eliminates moderately active acidic Al-O pairs. 

On the other hand, a single amphoteric oxide such as alumina, which is a Lewis acid solid, catalyzes aldol condensations rapidly at room temperatures (61). For reactions carried out either in the gas (62) or in the liquid phase (41),... 

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