Ammonia Mannich reaction

The Mannich Reaction involves the condensation of formaldehyde with ammonia or a primary or secondary amine and with a third compound containing a reactive methylene group these compounds are most frequently those in which the methylene group is activated by a neighbouring keto group. Thus when acetophenone is boiled in ethanolic solution with paraformaldehyde and dimethylamine hydrochloride, condensation occurs readily with the formation of... 

Mannich reaction is the condensation between formaldehyde, ammonia, or a primary or secondary amine (preferably as the hydrochloride), and a compound containing at least one active hydrogen atom... 

The condensation reaction of a CH-acidic compound—e.g. a ketone 3—with formaldehyde 1 and ammonia 2 is called the Mannich reaction, the reaction products 4 are called Mannich bases. The latter are versatile building blocks in organic synthesis, and of particular importance in natural products synthesis. 

With an unsymmetrical ketone as CH-acidic substrate, two regioisomeric products can be formed. A regioselective reaction may in such cases be achieved by employing a preformed iminium salt instead of formaldehyde and ammonia. An iminium salt reagent—the Eschenmoser salt—has also found application in Mannich reactions. ... 

An a-amino acid 3 can be prepared by treating aldehyde 1 with ammonia and hydrogen cyanide and a subsequent hydrolysis of the intermediate a-amino nitrile 2. This so-called Strecker synthesis - is a special case of the Mannich reaction-, it has found application for the synthesis of a-amino acids on an industrial scale. The reaction also works with ketones to yield a, a -disubstituted a-amino acids. 

Alternatively a Mannich-like pathway may be followed (see Mannich reaction), where ammonia reacts with the aldehyde 1 to give an intermediate iminium species, that adds hydrogen cyanide to give the a-amino nitrile 2. The actual mechanistic pathway followed depends on substrate structure and reaction conditions. 

A particularly useful variation of this reaction uses cyanide rather than HCN. a-Amino nitriles can be prepared in one step by the treatment of an aldehyde or ketone with NaCN and NH4CI. This is called the Strecker synthesisand it is a special case of the Mannich reaction (16-15). Since the CN is easily hydrolyzed to the acid, this is a convenient method for the preparation of a-amino acids. The reaction has also been carried out with NH3-I-HCN and with NH4CN. Salts of primary and secondary amines can be used instead of NH to obtain N-substituted and N,N-disubstituted a-amino nitriles. Unlike 16-51, the Strecker synthesis is useful for aromatic as well as aliphatic ketones. As in 16-51, the Me3SiCN method has been used 64 is converted to the product with ammonia or an amine. ... 

In its simplest form, the Mannich reaction consists of the condensation of formaldehyde (or sometimes another aldehyde) with ammonia, in the form of its salt, and another compound containing an active hydrogen. Instead of using ammonia, however, this reaction can be done with primary or secondary amines, or even with amides. An example is illustrated in the condensation of acetophenone, formaldehyde, and a secondary amine salt (the active hydrogens are shown underlined) ... 

Even though the CMR and MBR operate under conditions in which pressure is developed, gaseous reactants or media often can be handled in these systems without problems arising through over-pressure. Mannich reactions with dimethylamine, Baylis-Hillman reactions with formaldehyde, aminoreductone formation with ammonia, all proceeded without difficulty, as did Willgerodt reactions in which gases are formed during the process. 

Diethyl dl-1 -aminobenzylphosphonate has been prepared by a Mannich reaction of diethyl phosphite, benzaldehyde, and ammonia, resolved as its D-mandelate salt, and hydrolysed to give (+)-l-aminobenzylphosphonic acid.27 While the tetraethyl-diamide (33) reacts with benzaldehyde to give the expected phosphonic diamide (34), the corresponding tetramethyl-diamide reacts, with migration of the dimethyl-amino-group, to give (35).28... 

This MCR chemistry began in 1850 when the Strecker reaction S-3CR of ammonia, aldehydes, and hydrogen cyanide was introduced. Since 1912 the Mannich reaction M-3CR of secondary amines, formaldehyde, and (3-protonated ketones is used. 

Primary and secondary nitroalkanes, dinitromethane, and terminal em-dinitroaliphatic compounds like 1,1-dinitroethane, all contain acidic protons and have been used to generate Mannich products. Formaldehyde is commonly used in these reactions although the use of other aliphatic aldehydes has been reported. The nitroalkane component is frequently generated in situ from its methylol derivative, a reaction which also generates formaldehyde. Ammonia, " aliphatic amines, " hydrazine, and even urea have been used as the amine component of Mannich reactions. 

Frankel and Klager have reported using the Mannich reaction for the condensation of 2,2-dinitroalkanols with ammonia and hydrazine. This method was used to synthesize 2,2,6,6-tetranitro-4-azaheptane (100%) and bis(2,2-dinitropropyl)hydrazine (162) (73%) from the reaction of 2,2-dinitropropanol (25) with ammonia and hydrazine hydrate respectively. This work was later extended to using polynitroaliphatic amines and diamines. " ... 

Mannich Reaction The reaction of a compound with a reactive hydrogen with aldehydes (non-enol forming) and ammonia or a primary or secondciry amine to form a Mannich base (ciminomethylated compound). 

MANNICH REACTION. Reaction ol active methylene compounds with formaldehyde and ammonia of primary or secondary amines to give fj-aminocarbonyl compounds. 

Fulop and co-workers [124] have reported the synthesis of some new (ami-noalkyl) naphthols and (aminoalkyl) quinolinols 85 in good yields through a one-pot, microwave-assisted three-component modified Mannich reaction of naphthol or quinolinol with two equivalents of an aldehyde using ammonium carbamate or ammonium hydrogen carbonate as solid ammonia sources. It was observed that aliphatic aldehydes did not lead to the formation of the desired (aminoalkyl) quinolinols 85 (Scheme 64). 

In the Mannich reaction, formaldehyde (or sometimes another aldehyde) is condensed with ammonia, in the form of its salt, and a compound containing an active... 

Mannich reaction The reaction of a ketone with formaldehyde in the presence of an amine or ammonia under acidic conditions to give the 3-aminocarbonyl adduct, which is referred to as a Mannich base. After methylation and heating with silver oxide, the a,(3-unsaturated P-carbonyl compound may be formed. 

A number of years ago Armesto and his colleagues reported the photochemical Mannich reactions of the dienes (92) in the presence of perchloric acid. This reaction brought about conversion into the isoquinolinones (93) efficiently via the photocyclization of the protonated species (94). The mechanism for the transformation was proposed to involve an intramolecular SET process as a key event in the reaction. The present report gives details of quantum yield measurements on a series of derivatives that support this mechanistic postulate. Kojima and coworkers have studied the dicyanobenzene-sensitized reactions of the dienes (95) and (96) in acetonitrile/water/ammonia systems. Products (97) and (98) are... 

The original Mannich reaction is the acid-catalyzed aminomethylation of enohz-able ketones with non-enolizable aldehydes and ammonia, primary amines, or secondary amines, which involves nucleophilic addition of ketone enols to iminium salts generated in situ from the aldehydes and the nitrogen compounds [183]. This three-component coupling reaction provides a powerful tool for carbon-carbon bond formation and introduction of nitrogen functionality. The classical Mannich reaction has some drawbacks in reaction efficiency, regioselectivity, and appli-... 

The Mannich reaction is the prototype of carbon-carbon bond forming reactions that involve the addition of resonance-stabilized carbon nucleophiles to iminium salts and imines. In its original and most widely recognized form, the Mannich reaction consists of three components (i) ammonia, a primary amine, or a secondary amine (ii) a nonenolizable aldehyde, usually formaldehyde and (iii) an active... 

Reactions using highly acidic active methylene compounds (pAa = 9-13) comprise nearly all the early examples of imine condensation reactions, some of which date back to the turn of the century. Reviews by Layer and Harada have summarized many of these reactions and include examples using diethyl malonate, ethyl cyanoacetate, ethyl malonamide, acetoacetic acid, benzoylacetic esters and nitroalkanes. Conditions of these reactions vary they have been performed both in protic and aptotic solvents, neat, and with and without catalysts. Elevated temperatures are generally required. Reactions with malonates have useful applications for the synthesis of 3-amino acids. For example, hydrobenzamide (87), a trimeric form of the benzaldehyde-ammonia Schiff base, and malonic acid condense with concomitant decarboxylation to produce p-phenylalanine (88) in high yield (equation 14). This is one of the few examples of a Mannich reaction in which a primary Mannich base is produced in a direct manner but is apparently limited to aromatic imines. 

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