Mannich condensation reaction

Primary nitramines react with amines in the presence of an aldehyde to form 1,3-amino-nitramines in a reaction analogous to the Mannich condensation. In these reactions the amine and aldehyde component combine to form an intermediate imine which is then attacked by the nitramine nucleophile. 

The products obtained from these condensations are predictable for simple mono-functional substrates primary amines usually form compounds where two equivalents of primary nitramine are incorporated into the product (Equation 5.19), whereas simple secondary amines can only combine with one equivalent of nitramine (Equation 5.20). The bis-nitramine (185) is formed from the reaction of methylamine with two mole equivalents each of methyl-nitramine and formaldehyde. 

Mannich condensations involving polyamines or polynitramines are more complex, and in the case of linear dinitramines, leads to very interesting and diverse chemistry, enabling the synthesis of many cyclic nitramine products. The reaction of methylenedinitramine (168) with various primary amines in the presence of formaldehyde leads to l,5-dinitro-l,3,5,7-tetraazacyclooctanes the 3,7-dimethyl analogue (186) is isolated when methylamine is used.  

3-Dinitraminopropane (174) reacts with a range of primary amines in the presence of formaldehyde to yield l,5-dinitro-l,3,5-triazacyclooctanes like (187) (R = methyl), (188) (R = ethyl), and (189) (R = ixo-propyl). When ammonia is used as the amine component in these reactions the bicycle (192) is formed. Reaction of the bicycle (192) with nitrous acid and absolute nitric acid leads to C-N bond cleavage with the formation of (190) and (191), respectively.  

Ethylenedinitramine (EDNA) (2) condenses with ammonia in the presence of formaldehyde to form the triazacycloheptane bicycle (193). ° The chemistry of the bicycle (193) is very diverse and is only partly summarized in this discussion.  

---

Figure 16.3 Conceptual illustration of two peptides before (left) and after (right) a chemical reaction with formaldehyde. The amino acids are represented as circles. In this particular peptide, a tyrosine (Y) is located within the epitope (shaded circles). An arginine (R) is located elsewhere in the peptide. Formaldehyde results in the formation of a covalent bond between the two residues, due to a Mannich condensation reaction, as shown on the right. The new configuration prevents antibodies from binding to the epitope on the left. 

Tyrosine may be targeted specifically for modification through its phenolate anion by acylation, through electrophilic reactions such as the addition of iodine or diazonium ions, and by Mannich condensation reactions. The electrophilic substitution reactions on tyrosine s ring all occur at the ortho position to the —OH group (Figure 1.11). Most of these reactions proceed effectively only when tyrosine s ring is ionized to the phenolate anion form. 

Mannich condensation reaction See Mannich reaction. man-ik, kan-don sa-shon re,ak-shon ... 

Mannich reaction org chem Condensation of a primary or secondary amine or ammonia (usually as the hydrochloride) with formaldehyde and a compound containing at least one reactive hydrogen atom, for example, acetophenone. Also known as Mannich condensation reaction. man-ik re,ak-shon mannite See mannitol. ma,nlt ... 

Dimethylolnitramine (252) readily participates in Mannich condensation reactions treatment of a aqueous solution of (252) with methylamine, ethylenediamine and Knudsen s base (254) (generated from fresh solutions of ammonia and formaldehyde) yields (253), (255) and (239) (DPT) respectively. The cyclic ether (258) is formed from the careful dehydration of dimethylolnitramine (252) under vacuum. ... 

The Mannich condensation reaction of phenylglyoxal monophenylhydrazone 83 and aminal 84 gave rise to product 85 which was cyclizcd to the morpholinotriazine derivative 86 <01ZN(B)533>. 

Mannich condensation reaction can occur between nitroalkanes and aldehydes with amines, r-nitroalkane does not have a-hydrogen atoms and can not have the Mannich condensation reaction. 

Though ashless dispersants made by Mannich condensation reaction, functionalized ethylene-propylene dispersants, and succinate ester dispersants can be used in ATF formulations, succin-imide dispersants are more commonly nsed. The dispersants used in ATFs have similar chanistries as those described in engine oil applications, except in most cases the molecular weights of the polyisobutyl hydrocarbon chain of the dispersants used in ATFs are lower. Furthermore, the dispersant molecules are reacted with boric acid and caped with additional antiwear chemistries. 

Sadly, this simple mechanism cannot be correct because, when the P-hydroxy ketone is made in other ways, it is not converted into Mannich product under the reaction conditions. What else can happen Amines are nucleophiles and react rapidly with carbonyl compounds in acid to give iminium ions (p. 795). It is this imini-um ion that is the real participant in the Mannich condensation reaction. Formaldehyde is more reactive than the ketone, so the iminium ion is preferentially... 

A combination of resorcinarene, formaldehyde and secondary amines results to tertiary amines or tetrakis-aminoalkylated resorcinarenes through a Mannich condensation reaction. When primary amines are used, the resulting secondary amine 2 reacts intramolecularly with one of the phenolic hydroxyl groups and a second equivalent of formaldehyde, forming tetrabenzoxazines 3 (Fig. 11.3) [20-23]. 

When aminoethanol starting compounds are used in the Mannich condensation reaction with resorcinarenes, the 2-aminoethanol does not lead to the formation of benzodihydro-l,3-oxazines. Under the same reaction conditions instead these reactants give 1,3-oxazolidines 4 (Fig. 11.5) in which the second formaldehyde molecule reacts with the hydroxyl group of aminoethanol instead of the phenolic hydroxyl group [20]. 

Complementing our work on pure A-alkyl ammonium resorcinarene salts, Szumna and coworkers have prepared a series of zwitter-ionic resorcinarene molecules from amino acids through Mannich condensation reactions [63, 64, 65, 66]. These... 

Dissection of the reaction sequence results in a tandem Knoevenagel condensation/A-carbamoyl-Mannich/condensation reaction sequence, which was first exploited by Biginelli in 1891. The resulting dihydropyrimidone scaffold is represented in many medicinal products, which are now produced by this efficient. 

---