Condensation reaction aldehydes/ketones

Keywords melt reaction, quantitative, condensation reaction, aldehydes, ketones, phenylhydrazones, phenylhydrazones... 

Tertiary alcohols. Addition of the bipyridine ligand 1 is crucial for the successful condensation reaction involving ketones. For the condensation with aldehydes a beneficial additive is 4-r-butylpyridine which inhibits homocoupling and contributes to the reproducibility of the reaction. ... 

Knoevenagel condensation of aldehydes/ketones with malonitrile and ethyl cyanoacetate. The reactions were carried out under homogeneous and biphasic conditions, including the use of liquid-silica supported IL, with the biphasic system employing cyclohexene as the second phase. Although supported ILs showed a reduced initial activity, in general an excellent recyclability was observed, with the reaction repeated over five times without leaching of the IL into the extractant phase or reduction in activity. 

Scheme 7.4. Mixed Aldol Condensation Reactions of Ketones and Aromatic Aldehydes...

Heteroatom conjugate addition reactions are promoted by superbases. Draper et al. described the synthesis of the estrogen antagonist Sch 57050 (179) [53]. Knoevenagel condensation reaction with ketone 176 and aldehyde 177 in the presence of piperidine... 

Alexei Eugenivich Chichibabin (Kusemino, nr. Poltava, Russia, 17 March 1871 (O.S.)-Paris, 15 August 1945), assistant in the University of Moscow (1900) and professor (1909) in the Technical High-School there, published much work in organic chemistry, notably on tervalent carbon. The Chichibabin amination reaction (1914) involves the formation of 2-aminopyridine by heating pyridine with sodamide in toluene, and hydrolysis of the product with water. The Chichibabin pyridine synthesis involves the condensation of aldehydes, ketones, etc., with ammonia or amines to form substituted pyridines. ... 

Malonic esters can be converted to the enolate anion and condensed with aldehydes, ketones, or acid derivatives. The reaction of malonic acid with an aldehyde using pyridine as a base is called the Knoevenagel condensation. 

The intra-molecular Claisen condensation is called a Dieckmann condensation, and it generates a cyclic compound 58,99,101,118. Malonic esters can be converted to the enolate anion and condensed with aldehydes, ketones, or add derivatives. The reaction of malonic acid with an aldehyde using pyridine as a base is called the Knoevenagel condensation 59, 60, 61, 62, 69, 99,108,110,112, 113,119,124. 

Most of the characteristic reactions of ketones (RR CO) depend upon condensation with substituted amines. The reactions occur between the carbonyl group and the —NHj group of the substituted amine, and hence are also shared by aldehydes RHCO ... 

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acld in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acrtophenone phenylhydrazone (I) gives 2-phenyllndole (I V). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

Condensation. Depending on the reaction conditions, a variety of condensation products are obtained from the reaction of aromatic amines with aldehydes, ketones, acetals, and orthoformates. 

Condensation with Aldehydes and Ketones. Succinic anhydride and succinic esters in the presence of different catalysts react in the gas phase with formaldehyde to give citraconic acid or anhydride and itaconic acid (94—96). Dialkyl acyl succinates are obtained by reaction of dialkyl succinates with C 4 aldehydes over peroxide catalysts (97). 

Succinic esters condense with aldehydes and ketones in the presence of bases, eg, sodium alkoxide or piperidine, to form monoesters of alkybdenesuccinic acids, eg, condensation of diethyl succinate with acetone yields ethyl 2-isopropyhdenesuccinate (eq. 3). This reaction, known as Stobbe condensation, is specific for succinic esters and substituted succinic esters (98,99). 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Methylpyrazine reacts with sodamide in liquid ammonia to generate the anion, which may be alkylated to give higher alkylpyrazines (Scheme 10) (61JOC3379). The alkylpyrazines have found extensive use as fiavouring and aroma agents (see Section 2.14.4). Condensation reactions with esters, aldehydes and ketones are common, e.g. methyl benzoate yields phenacylpyrazine in 95% yield, and reactions of this type are summarized in Scheme 11. 

With l,3-dimethyl-2,l-benzisoxazolium salts, however, considerable reactivity has been reported. Condensation occurs readily with aldehydes, ketones, orthoesters and diazonium salts to yield styryl, cyanine and azo compounds, respectively (78JOC1233). In the presence of triethylamine, dimerization was observed, and the reactions of the cation were considered to involve the intermediacy of the anhydro base (77JOC3929). 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

The Pictet-Spengler reaction is one of the key methods for construction of the isoquinoline skeleton, an important heterocyclic motif found in numerous bioactive natural products. This reaction involves the condensation of a P-arylethyl amine 1 with an aldehyde, ketone, or 1,2-dicarbonyl compound 2 to give the corresponding tetrahydroisoquinoline 3. These reactions are generally catalyzed by protic or Lewis acids, although numerous thermally-mediated examples are found in the literature. Aromatic compounds containing electron-donating substituents are the most reactive substrates for this reaction. 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

Aromatic aldehydes 1 can undergo a condensation reaction to form a-hydroxy ketones 2 (also called benzoins) upon treatment with cyanide anions.This reaction, which is called benzoin condensation, works by that particular procedure with certain aromatic aldehydes and with glyoxals (RCOCHO). 

Ketones, esters, and nitriles can all be alkylated using LDA or related dialkyl-amide bases in THE. Aldehydes, however, rarely give high yields of pure products because their enolate ions undergo carbonyl condensation reactions instead of alkylation. (We ll study this condensation reaction in the next chapter.) Some specific examples of alkylation reactions are shown. 

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. 

The jS-hydroxy aldehydes or ketones formed in aldol reactions can be easily dehydrated to yield a -unsaturated products, or conjugated enones. In fact, it s this loss of water that gives the condensation reaction its name, because water condenses out of the reaction when the enone product forms. 

Esters, like aldehydes and ketones, are weakly acidic. When an ester with an a- hydrogen is treated with 1 equivalent of a base such as sodium ethoxide, a reversible carbonyl condensation reaction occurs to yield a /3-keto ester. For example, ethyl acetate yields ethyl acetoacetate on base treatment. This reaction between two ester molecules is known as the Claisen condensation reaction. (We ll use ethyl esters, abbreviated "Et," for consistency, but other esters will also work.)... 

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an a,j8-unsaturated product. Show the mechanism of the Knoevenagel reaction of diethyl malonate with benzaldchyde. 

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