Mannich bases acid ester

Reactions of enamine (20) with Mannich bases, with esters of a, -unsaturated acids and with acrylonitrile take place under more severe conditions as compared to the similar reactions of cyclohexane enamines. 

Maltol — see Pyran-4-one, 3-hydroxy-2-methyl-Maltol, ethyl — see Pyran-4-one, 3-ethoxy-2-methyl-Maltol, methyl — see Pyran-4-one, 3-methoxy-2-methyl-Mandelic acid ethyl ester, 1, 310-311 Manganaindene reactions, 1, 671 Mannich bases dehydro... 

The replacement of a Mannich base amino group by SH derivatives leads to thiocthers (275), thiocaibamic acid esters (276), and sulfones (277) (Fig. 105 and Table... 

L. L., Denisova, Z. A.,. Markina, V. V., and Bogdanova, H. N Repellent properties of Mannich bases derived from hydroxy- and aminobcnzoic acid esters, Med. Parazitol. Parazit. Bolezni, 52,69, 1983 Chem. Ab.str., 99. 135492, 1983. 

The Mannich bases investigated are acctoacetic and malonic acid derivatives, Y-carboxyglutamic acid included. - Compounds having the lactone structure give preferably decarboxylation of the ester groups not involved in the lactone ring. - ... 

L. A., Dremova, V. P., and Markina, V. V., Repellent effect of Mannich bases derived from lactic acid esters, Med. Parazilol. Par-azil. Bolezni. 44, 1987 Chem. Ahsir, 107, 192961. 1987. 

Acdve methylene compounds ranging in acidity from -keto esters, malonates and nitroalkanes pK = 9-13) to ketones (pATa = 16-20) can be used in the Mannich reaction. The lack of examples using simple unactivated esters (p/iTa = 25) appears to be due to their weaker acidity or to transamination and/or hydrolysis side reactions. Enolizable aldehydes have also been used in certain instances however, side products arising from subsequent aldol condensation of the resulting -amino aldehyde often occur. Best results are achieved with a-branched aldehydes, which produce Mannich bases without enolizable protons. 

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. 

As Table 8 illustrates, the venerable Japp-Klingemann variation of the Fischer indolization continues to attract interest. Entry 1 features a three-component Japp-Klingemann indolization involving diazonium salts, acid chlorides, and amines or alcohols and involving the intermediacy of a-hydrazono carboxylic acid esters and amides prior to indole ring formation [385]. Entry 2 describes a preparation of 5-indolyl-Mannich bases and, hence, an expedient source of 5-(chloromethyl)indoles (acetyl... 

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