Aldehydes amidation reactions

The addition of phenylisocyanate to aldehyde-derived enamines resulted in the formation of aminobutyrolactams (438,439). As aminal derivatives these produets can be hydrolyzed to the linear aldehyde amides and thus furnish a route to derivatives of the synthetically valuable malonaldehyde-acid system. With this class of reactions, a second acylation on nitrogen becomes possible and the six-membered cyclization products have been reported (440). Closely related to the reactions of enamines with isocyanates is the condensation of cyclohexanone with urea in base (441). 

Reaction with water to yield a carboxylic acid Reaction with an alcohol to yield an ester Reaction with ammonia or an amine to yield an amide Reaction with a hydride reducing agent to yield an aldehyde or an alcohol... 

Examples of the protection of alkynes, carboxylic acids, alcohols, phenols, aldehydes, amides, amines, esters, ketones, and alkenes are also indexed on p. xvii. Section (designated with an A 15A, 30A, etc.) with protecting group reactions are located at the end of pertinent chapters. 

Among the compounds capable of forming enolates, the alkylation of ketones has been most widely studied and applied synthetically. Similar reactions of esters, amides, and nitriles have also been developed. Alkylation of aldehyde enolates is not very common. One reason is that aldehydes are rapidly converted to aldol addition products by base. (See Chapter 2 for a discussion of this reaction.) Only when the enolate can be rapidly and quantitatively formed is aldol formation avoided. Success has been reported using potassium amide in liquid ammonia67 and potassium hydride in tetrahydrofuran.68 Alkylation via enamines or enamine anions provides a more general method for alkylation of aldehydes. These reactions are discussed in Section 1.3. 

Note also the stereochemistry. In some cases, two new stereogenic centers are formed. The hydroxyl group and any C(2) substituent on the enolate can be in a syn or anti relationship. For many aldol addition reactions, the stereochemical outcome of the reaction can be predicted and analyzed on the basis of the detailed mechanism of the reaction. Entry 1 is a mixed ketone-aldehyde aldol addition carried out by kinetic formation of the less-substituted ketone enolate. Entries 2 to 4 are similar reactions but with more highly substituted reactants. Entries 5 and 6 involve boron enolates, which are discussed in Section 2.1.2.2. Entry 7 shows the formation of a boron enolate of an amide reactions of this type are considered in Section 2.1.3. Entries 8 to 10 show titanium, tin, and zirconium enolates and are discussed in Section 2.1.2.3. 

Considerable interest remains in catalyzed hydrogen-transfer reactions using as donor solvents alcohols, glycols, aldehydes, amides, acids, ethers, cyclic amines, and even aromatic hydrocarbons such as alkylben-... 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

Uses Solvent for liquids, gases, vinyl resins, wire enamels polyacrylic fibers gas carrier catalyst in carboxylation reactions organic synthesis (manufacture of aldehydes, amides, amines, esters, heterocyclics). 

Ortholithiated oxazoline 62 is best transmetallated to its magnesium analogue before reaction with aldehydes. As with the equivalent amide reaction, treatment with 4.5 M HCl then cyclizes the products to lactones (Scheme 31) °. ... 

G.A. Olah, M. Nojima, I. Kerekes, Synthetic methods and reactions. I. Seleniuum tetrafluoride and its pyridine complex. Convenient fluorinating agents for fluorination of ketones, aldehydes, amides, alcohols, carboxylic acids, and anhydrides, J. Am. Chem. Soc. 96 (1974) 925-927. 

The utility of the method was demonstrated with a variety of electron-rich and electron-poor aryl aldehydes, but the method was not suitable for aliphatic aldehydes. No racemization was observed in the copper-catalyzed oxidative amidation reaction when an optically active amine, (S)-valine methyl ester, was employed. 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

The UDC concept can be further extended by application of ethyl glyoxylate (a convertible aldehyde ). Simple reaction of 48 in the Ugi MCR with /V-Boc anthranilic acids, /V-Boc-rt-amino acids, mono-A-Boc diamines, and niono-A-Boc phenylenediamines, followed by acid treatment and in some cases proton scavenging, affords 1,4-benzodiazepines 49, diketopiperazines 50, ketopiperazines 51, and dihydroquinoxalinones 52, respectively.25 Note that products differ from those obtained from convertible isocyanides in that they contain an additional exocyclic amide... 

Many enzymes are both active and stable in carbon dioxide and have been used to conduct a number of reactions. Several different types of reactions have been examined, including hydrolysis (Lee et al., 1993 Randolph et al., 1985 Zheng and Tsao, 1996), oxidation (Hammond et al., 1985 Randolph et al., 1988), and esterification/transesterification (Kamihira et al., 1987 Nakamura et al., 1986 Rantakyla and Aaltonen, 1994), but there are other types of reactions that would make worthwhile investigations in carbon dioxide. These include preparation of amides, reduction of ketones, preparation of cyanohydrins from aldehydes, aldol reactions, hydroxylation reactions, and Baeyer-Villiger oxidation. 

Electronically excited carbonyl chromophores in ketones, aldehydes, amides, imides, or electron-deficient aromatic compounds may act as electron acceptors (A) versus alkenes, amines, carboxylates, carboxamides, and thioethers (D, donors). In addition, PET processes can also occur from aromatic rings with electron-donating groups to chloroacetamides. These reactions can be versatile procedures for the synthesis of nitrogen-containing heterocyclic compounds with six-membered (or larger) rings [2],... 

Carbonylation reactions of aryl chlorides may be accomplished by two different approaches. Coordination of the arene ring to a tricarbonylchromium unit facilitates oxidative addition, and carbonylation may consequently be accomplished382. Alternatively, Pd(dippp)2 (47) has proven to be a catalyst capable of converting chloroarenes to aldehydes, amides, esters or acids in good yields. This catalyst may be generated in situ, by the addition of Pd(OAc)2 and dippp. Both electron-withdrawing and electron-donating... 

By far one of the most important reactions through the S l mechanism is formation of a C—C bond by the reaction of aryl halides with carbanions derived from hydrocarbons, ketones, esters, amides, nitriles and even, with some limitations, from aldehydes. The reactions of cyanide ions and carbonyl complexes of Co and Fe also form a new C—C bond. 

Classification and Organization of Reactions Forming Difunctional Compounds. This chapter considers all possible difunctional compounds formed from the groups acetylene, carboxylic acid, alcohol, thiol, aldehyde, amide, amine, ester, ether, epoxide, thioether, halide, ketone, nitrile, and olefin. Reactions that form difunctional compounds are classified into sections on the basis of the two functional groups of the product. The relative positions... 

Strubing D, Neumann H, Jacobi von Wangelin A et al (2006) An easy and general protocol for multi-component coupling reactions of aldehydes, amides, and dienophiles. Tetrahedron 62 10962-10967... 

With primary or secondary amides, reaction with LiAlH4 is wasteful in that hydrogen gas is evolved and reduction usually proceeds through to the amine. Nevertheless, it has been shown that r-butylamides, refluxed with an excess of LiAlD4 for 15 h in diethyl ether, give very good yields of deuteriated aldehydes, RCDO. O ... 

Reaction between Two Different Ketones. This is seldom attempted with hydroxide or alkoxide bases in protic solvents since similar considerations apply to those discussed for aldehydes. This reaction is commonly done with amide bases in aprotic solvents, but with somewhat more difficulty than with aldehydes. 

In the early amidation approach, 2 may be assembled by condensation of aldehyde-amide 4 with 5-fluorooxindole 3. The aldehyde-amide would arise from a Knorr pyrrole reaction involving oxime 5 (derived from t-butyl acetoacetate) and (3-ketoamide 6, which can, in turn, be synthesized from diketene 7 and A,iV-diethylethylenediamine 8. 

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