Mannich bases from

Primary nitroparaffins react with two moles of formaldehyde and two moles of amines to yield 2-nitro-l,3-propanediamines. With excess formaldehyde, Mannich bases from primary nitroparaffins and primary amines can react further to give nitro-substituted cycHc derivatives, such as tetrahydro-l,3-oxa2iaes or hexahydropyrimidines (38,39). Pyrolysis of salts of Mannich bases, particularly of the boron trifluoride complex (40), yields nitro olefins by loss of the amine moiety. Closely related to the Mannich reaction is the formation of sodium 2-nitrobutane-1-sulfonate [76794-27-9] by warming 1-nitropropane with formaldehyde and sodium sulfite (41). 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Entries 1 and 2 in Scheme 2.11 show the preparation of Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as bis(dimethylamino)methane in entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. 

Harrcl, W. B., Mannich bases from 1.2-di-phcnylindolizine ephedrinc and mclham-phctaminc as amine componeni.s, J. Pharm. S< i.. 59. 275. 1970. 

Suciu, D., Preparation of some Mannich bases from 2-amino- and 2-allylamino-4-methyl-.5-acetylthiazole, 7. Prakt. Chem., 313, 193, 1971. 

Mehta, R. H Synthesis of Mannich bases from coumarin derivatives and screening for their biological aaivity, J. Indian Chem. Sor., 60, 201, 198.3. 

C. W., Synthesis of phenethylamines from phcnylaceionitrilcs obtained by alkylation of cyanide ion with Mannich bases from phenols and ocher bcnzylamincs. Tetrahedron, 29, 1931, 197.3. 

Craig, J. C., Johns, S. R., and Moyle. M., Amine exchange reactions. Mannich bases from primary aliphatic amines and firom amino acids, J. Org. Chem., 28, 2779, 1963. 

Mannich base from Hydrogenation agent (Reference)... 

Katritzky, A. R. and Harris, P. A. Benzotria-zole-assisted synthesis of novel Mannich bases from ketones and diverse aldehydes. Tetrahedron. 46, 987, 1990. 

A Oligomeric phenolic Mannich base from isophorone amine B Bisphenol/epichlorohydrin oligomer... 

This reaction was discovered during preparation of the Mannich base from the ethynyl A-nor steroid 1. Allene 3 is obtained from this reaction as a side product in 31% yield. Allene 3 is also available from 2 by quaternization and L1A1H4 reduction. ... 

Jasor, Y., Luche, M. J., Gaudry, M., Marquet, A. Regioselective synthesis of Mannich bases from unsymmetrical ketones and immonium salts. J. Chem. Soc., Chem. Common. 1974, 253-254. 

The viscosity of the final Mannich polyol depends on the functionalities of the resulting Mannich bases (lower functionalities lead to lower viscosities) and on the molar ratio between the reacted PO/mol of the Mannich base. Figure 15.2 shows the variation of the Mannich polyol viscosities as a function of the molar ratio of the PO/Mannich base (Mannich base from 1 mol of nonyl-phenol, 2 mols of formaldehyde and 2 mols of diethanolamine). One observes that after the addition of one PO mol/mol of Mannich base a maximum of viscosity is obtained and by the addition of 2-5 mols of PO the viscosity decreases continuously. 

Characteristic Unit Mannich base from phenol Mannich base from nonyl phenol... 

The amino group of Mannich bases can also be exchanged against sulfonamides,1128 hydroxylamines,1129 or phenylhydrazine.1130 Interaction of hydrazines and Mannich bases from ketones gives first the hydrazones and then pyrazolines by amine exchange involving cyclization 1131... 

Conversely, indole can be condensed with the Mannich base from nitro-malonic ester, formaldehyde, and ammonium acetate, giving an intermediate that can be worked up to give an overall yield of tryptophan of 77% 815... 

Phenylphenol resulted in 83% yield by reaction of the aminoketonic salt from chloroacetone and pyridine with the Mannich base from acetophenone, formaldehyde and dimethylamine in hot ethanol containing triethylamine (ref. 66). 

Interaction of the Mannich base from 4-methoxyacetophenone, formaldehyde and dimethylamine over 2 hours in refluxing dimethylformamide with the iminoester hydrochloride of ethyl benzoylacetate, initially converted to the amidine with ammonium acetate, afforded 2-amino-6-(4-methoxyphenyl)pyrid-... 

Regioselective synthesis of isomeric Mannich bases from unsymmetrical ketones has been achieved with dimethyl(methylene)ammoniam trifluoroacetate in trifluoroacetic acid to give mainly the more-substituted amino-ketone (13) [and lesser amounts... 

Mannich bases and reactions have found new applications. Preparation of Mannich bases from ar. amines by transamination, transquaternization of quaternized Mannich bases reactions... 

Woods, L.L. (1946) Mannich Bases from Kojic acid and aryl amines. /. Am. Chem. Soc., Vol.68, pp.2744-2745. 

A nonacidic and regioselective route to Mannich bases from ketones and esters involves reaction with DMF acetals at a high temperature to form enamino ketones which are readily reduced by Lithium Aluminium Hydride to the Mannich bases (eq 8). ... 

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