Benzaldehyde Knoevenagel reaction

Ethylene benzene Benzaldehyde Knoevenagel reaction Gamma ZrP/Si02 Zt(03P0K)2 194 195... 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

An organic base in an ionic liquid was also found to be effective for a Knoevenagel reaction. Glycine was added to the ionic liquid [HMIMjPFs as the base catalyst. The reaction proceeded at room temperature in air without the need for rigorous drying of the ionic liquid. Glycine and the reactants malononitrile and benzaldehyde dissolved readily in the ionic liquid. The product was extracted from the ionic liquid phase with an immiscible co-solvent, toluene 110). 

Use of the Knoevenagel reaction (67OR(l5)204), in which a benzaldehyde reacts with an activated methylene compound in the presence of an amine, goes some way to overcoming the inherent difficulties of the Perkin synthesis of coumarins (see later). In order to obtain the coumarin rather than the usual cinnamic acid, a 2-hydroxy substituent must be present... 

Based on the Knoevenagel reactions discussed above, we have studied the condensation of a series of benzaldehydes 4a-e with ethyl acetoacetate on a series of X, Y and sodium germanium faujasites. 

Benzaldehyde itself could be the electrophile in this Knoevenagel reaction. However, it is also possible that the piperidinium salt derived from benzaldehyde acts as the electrophile. Similarly, several plausible mechanisms can be formulated for the decarboxylation step—they depend, among other things, on the stage at which it may occur. Because of these ambiguities, we do not want to discuss any of the details of these reaction steps. Instead, we want to focus on a mechanistic detail of the first step and that is the question of which species acts as the nucleophile and initiates the C—C bond formation. 

CsX is useful for the simple Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate even a simple NaY is sufficiently basic to form carbamates starting from primary aromatic amines and dialkyl carbonates (35, 36). At contrast CsjO-MCM-41 can also be used for the addition of C02 to epoxides, or for Michael addition of one or two molecules of diethyl malonate on neopentylglycol diacrylate (37, 38) ... 

In contrast with the widespread application of zeolites as solid acid catalysts (see earlier), their use as solid base catalysts received scant attention until fairly recently [121]. This is probably because acid-catalyzed processes are much more common in the oil refining and petrochemical industries. Nonetheless, basic zeolites and related mesoporous molecular sieves can catalyze a variety of reactions, such as Knoevenagel condensations and Michael additions, which are key steps in the manufacture of flavors and fragrances, pharmaceuticals and other specialty chemicals [121]. Indeed, the Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate (Fig. 2.36) has become a standard test reaction for solid base catalysts [121]. 

The Knoevena iel raictioii is a carbonyl condensation reacticm of an ester with an aldehyde or ketone to yield an n,/3-unsaturated product. Show the mechanism of the Knoevenagel reaction of diet hyl malonale with benzaldehyde. 

Problem 26.3 (a) Malonic ester reacts with benzaldehyde in the presence of piperidine (a secondary amine. Sec. 31.12) to yield a product of formula C14H16O4. What is this compound, and how is it formed (This is an example of the Knoevenagel reaction. Check your answer in Problem 21.22 (f), p. 714.) (b) What compound would be obtained if the product of (a) w ere subjected to the sequence of hydrolysis, acidification, and heating (c) What is another way to synthesize the product of (b) ... 

The catalytic activity of proton sponge in the Knoevenagel reaction has been studied227. It was shown that benzaldehyde, in the presence of 2 mol% of 1, reacts with ethyl cyanoacetate and ethyl acetoacetate (equation 22). The condensation is accelerated in polar solvents (especially in DMSO) and does not occur in the case of diethyl malonate, as its CH-acidity is too low (pK = 13.3). 

K2CO3. No side reactions like the Cannizzaro or Knoevenagel reactions are observed on treatment with C-200. In the reaction with benzaldehyde and furfural the products 71 (R = Ph and 2-furyl) are formed nearly quantitatively. Bulky aromatic aldehydes such as pyrene-l-carboxaldehyde and aliphatic aldehydes are also suitable substrates for this process. ( )-acyclic a,/ -unsaturated ketones 74 can be prepared by use of a similar HWE reaction of 2-oxoalkanephosphonates 72 with aliphatic aldehydes 73 under the influence of barium hydroxide C-200 (Scheme 5.14) [36]. The HWE procedure employing activated Ba(OH)2 is applicable to the structurally complex, base-sensitive aldehydes which are susceptible to elimination and/or epimerization under the traditional basic conditions of the HWE reaction using NaH. For instance, when phosphonate 75 and aldehyde 76 are exposed to 0.8 equiv. activated Ba(OH)2 in aqueous THF at 20°C, (//-enone 77 is obtained in 70% yield (Scheme 5.14) [37]. 

Once obtained, these substituted benzaldehydes could be converted into amphetamines by an interesting variant of the Knoevenagel reaction as described in Chapter 9. They could be reacted in a mixture of nitroethane and ammonium acetate to form the appropriately substituted... 

The Knoevenagel reaction between benzaldehydes 22 and malononitrile or ethyl cyanoacetate 74 followed by condensation of the resulting ot,p-unsatu-rated nitriles 75 with dimedone (76) was performed in the presence of SiO2-(CH2)3-NEt2 (Scheme 3.22). ... 

Other applications include the Knoevenagel reaction under microwave irradiation in a solvent-free reaction. With this technique, benzaldehyde reacts in a few minutes with diethyl cyanomethylphosphonate in the presence of carefully controlled amounts of piperidine to give diethyl 1-cyano-... 

Q Outline the full mechanism for the Knoevenagel reaction of benzaldehyde with diethyl malonate. 

The Knoevenagel reaction (Scheme 6.20) involves the reaction of aromatic aldehydes with a variety of molecules CH2XY. The groups X and Y may be the same or different, but are invariably electron withdrawing, so creating an activated methylene group from which the carbanion CHXY is produced. The reaction is usually carried out in pyridine solution, with piperidine as the basic catalyst. The reactions of benzaldehyde with propane-1,3-dinitrile [malononitrile, CH2(CN)2] and diethyl propane-1,3-dioate [diethyl malonate, CH.,(CO,Et)2] are illustrative. In both cases, manipulation of the CH=CX2 group in the product allows the synthesis of other compounds. 

Alkali and alkaline earth carbonates catalyzed the Knoevenagel reaction (6.22) of benzaldehyde with malononitrile.73... 

Having elucidated the optimum conditions for the Knoevenagel reaction in a flow reactor, a range of other reactions using different activated methylene derivatives and aldehydes (Table 14.3) was conducted. In all cases excellent product purities and yields were obtained. The reaction of benzaldehyde and ethyl cyanoacetate was also performed using 3-(dimethylamino)propyl-functionalized silica gel, 3-aminopropyl-functionalised silica gel, 3-(l,3,4,6,7,8-hexahydro-2H-pyrimidojl, 2-l]pyrimidino)propyl-functionalized silica gel and polymer-supported diazabicyclo[2.2.2]octane, whereby excellent conversions were obtained (> 99.0%) in all cases [37]. 

The Knoevenagel reaction is one of the oldest C-C bond forming reactions (see also Section 7.1) [36]. It involves the condensation of a carbonyl component (typically benzaldehyde) with a C-acid (typically ethyl cyanoacetate)-Figure 5. This classical reaction is usually catalyzed by organic bases (primary, secondary, and tertiary amines), ammonia, and ammonium salts [37]. 

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