Amination reactions ketones

Other carbonyl compounds are within the scope of the reaction ketones give amides, and aldehydes yield nitriles and formyl derivatives of amines ... 

Extension of the hydration reaction to hydrogen peroxide has shown that stable peroxides are formed from enamines and the imonium salts derived from secondary amines and ketones (506,507). 

An aldehyde or ketone reacts with a primary amine, RNH.2, to yield an imine, in which the carbonyl oxygen atom has been replaced by the =N-R group of the amine. Reaction of the same aldehyde or ketone with a secondary amine, R2NH, yields an enamine, in which the oxygen atom has been replaced by the -NR2 group of the amine and the double bond has moved to a position between the former carbonyl carbon and the neighboring carbon. 

Protophilic solvents are substances such as liquid ammonia, amines and ketones which possess a high affinity for protons. The overall reaction taking place can be represented as ... 

Extensive study by several groups showed that Ar—X (X = I, Ts, Br, and Cl) can undergo coupling reactions with amine and ketones in the presence of a... 

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. 

One route is by reductive amination of ketone (10) available by Friedel-Crafts reaction from acid (11) which we can make by an FGA strategy (Chapter T 24). 

In a total synthesis of inhibitors of this kind, the following methods have so far been employed successfully (a) reaction of a cyclohexenyl halide with an amine, (b) coupling of an amine with an epoxide, and (c) condensation of an amine with ketone and reduction of the resulting Schiff base (reductive alkylation of an amino sugar). 

The reductive alkylation of a primary amine with ketone leads to the formation of a stable imine. In the presence of hydrogen and a hydrogenation catalyst, the imine is reduced to a secondary amine. Similarly, a diamine reacts stepwise to form dialkylated secondary amines. However, several side reactions are possible for these reactions as outlined by Greenfield (12). The general scheme depicting the reaction between primary amine or diamine to yield secondary amine through a Schiff base is shown in Figure 17.1. 

The nitrogen analogs of ketones and aldehydes are called imines, azomethines, or Schiff bases, but imine is the preferred name and we use it here. These compounds can be prepared by condensation of primary amines with ketones or aldehydes.102 The equilibrium constants are unfavorable, so the reaction is usually driven forward by removal of water. 

On the other hand, Kobayashi has developed a Bronsted acid-combined catalyst for aqueous Mannich-type reactions. Three-component Mannich-type reactions of aldehydes, amines, and ketones (e.g., benzaldehyde, p-anisidinc. and cyclohexanone) were efficiently... 

The synthesis of amines by the in-situ reductive amination of ketones is termed the Leuckart-Wallach reaction. Recently, an asymmetric transfer hydrogenation version of this reaction has been realized [85]. Whilst many catalysts tested give significant amounts of the alcohol, a few produced almost quantitative levels of the chiral amine, in high enantiomeric excess. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

Quite recently, not only Lewis adds, but also Bronsted adds were found to be effedive catalysts for the three-component Mannich-type reactions in water with the aid of a surfadant. For example, Akiyama and co-workers1301 have reported that a combination of HBF4 and SDS is effedive for the readions of aldehydes, amines, and silyl enolates. We have found that dodecylbenzenesulfonic add (DBSA), a Bronsted add with a surfadant moiety, also catalyzes the reactions in water.1311 Furthermore, DBSA can be used for the dired Mannich-type reactions of aldehydes, amines, and ketones, without using silyl enolates as nucleophilic components (Eq. 8).1321... 

Michler s ketone (6.155) and related carbonyl compounds can be used to obtain colour salts directly by reaction with a reactive intermediate such as an aromatic amine (the ketone synthesis), as in the case of crystal violet (6.164 Cl Basic Violet 3) shown in Scheme 6.31. 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

The steroid may be bifunctionalized with any of the functional groups participating in the Ugi reaction, i.e., isonitrile, amine, aldehyde (ketone), and carboxylic acid, and having two different functionalities on one steroid building block even increases the possibilities. 

For the general condensation reaction of secondary amines with ketones to yield enamines, pyrrolidine, piperidine, or morpholine is generally used. The rate of enamine formation depends on the basicity of the secondary amine and the steric environment of the carbonyl group [12a, b, 29], Pyrrolidine, which is more basic, usually reacts faster than morpholine. The investigation of piperazine, a disecondary amine, has only been reported recently by Benzing [45, 46] and Sandler [41]. Surprisingly, the reaction of excess -butyraldehyde with piperazine in tetrahydrofuran at — 20°C to 0°C gave mainly AM-butenyl-piperazine [41] (see Eq. 13). 

ECL emission has been also observed in the mixed ECL systems involving PAHs with reaction partners like aromatic amines or ketones forming radical cations D + or radical anions A-, respectively.114127 Such approach solves the problems caused by the instability of ECL reactants but lowers distinctly the free energy available for the formation of an excited state. Usually, the energy released in electron transfer between A- + D + ions is insufficient to populate emissive 11A or D states directly and the annihilation of the radical ions usually generates only nonemissive3 A or 3 D triplets that produce light via triplet-triplet annihilation. Consequently ECL efficiencies in the mixed ECL systems are usually very low. Only in some cases, when radiative electron transfer between A + D+ species is operative, relatively intense [A D + ] exciplex emission can be observed. 

Be(Pc) and Mg(Pc) are obtained by the condensation reaction of phthalonitrile in the presence of metallic Be and Mg respectively.197,198 They form very stable complexes with water. Mg(Pc)(OH2) is square pyramidal and the magnesium atom is displaced out of the N4 plane by 0.5 A with an Mg—distance of 2.04 A. They lose the water on sublimation. Amines, alcohols, ketones, thiols and sulfides also coordinate to Mg(Pc). Ca(Pc) and Ba(Pc) are obtained from phthalonitrile and the metal oxide.197,199... 

Originally reported in 1961,8 the TMSN3-modified Ugi reaction involves condensation of an appropriately substituted aldehyde or ketone with a primary or secondary amine. Reaction of the Schiff base with an... 

Reductive amination of ketones using p-anisidine and the Hantzsch ester for transfer hydrogenation is a low-yielding reaction in toluene at room temperature, but thiourea is an efficient catalyst, and yields of up to 94% are reported at 50 °C.334 A mechanism involving thiourea hydrogen bonding to the intermediate imine is supported by ab initio calculations. 

N,N-disubstituted amines can be produced by reaction of 2° amines with ketones followed by reduction. 

To start with the a-amination of ketones, the Jorgensen group reported a highly enantioselective addition of ketones, 1, to azodicarboxylates, 3, as N=N component [5], The l amino acid L-proline was found to be a highly efficient catalyst. In a first screening using a model reaction (Scheme 7.2) it was found that diethyl... 

Condensation Reactions. Many triam inotriarylmethane dyes can be produced by condensation of Michlers ketone (9) with aromatic amines. The ketone must generally be activated with phosgene or phosphorus oxychloride, whereby a reactive blue chloro compound (10) is formed from the intermediate geminal dichloride. With V-phcnyl-1 -naphthylaminc, for example, (13) reacts to form Victoria blue B (11). 

Nitroalkenes (see 30) are easily made from nitro-alkanes and aldehydes and take part as dieno-philes in Diels-Alder reactions (chapter 17). The products can, as usual, be converted into amines or ketones. The stimulant fencamfamin 39 disconnects to the obvious Diels-Alder adduct 41 from cyelopentadiene 42 and the nitro-alkene 43. 

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