Aminomethylating reagents

These compounds are valuable as aminomethylating reagents (see Section 2.20.3.11). In addition, l,3,5-triacryloylhexahydro-l,3,5-triazine, triacryloformal (213), forms the basis of the Basazol range of reactive dyes (65AG(E)312). The schematic reaction is shown in Scheme 118. The colour yield is very high (ca. 90%). 

Although the usual practice still involves mixing the reactants of Mannich synthesis (substrate, amine, and aldehyde) with or without following a particular order of addition, the use of preformed aminomethylating reagents is becoming more and more frequent. Some of them, particularly those deriving from common amines, are available commercially. 

In general, X-aminomethyl reagents have proved their efficacy with the most widely differing substrates. Besides the above reaction, it is worth noting the reactions of tropolones with mcthylene-bis-amines, the and P-aminomethylations -" with... 

The manner of attack on the substrate by the reactive species appears to be strictly related to the nature of the aminomethylating reagent. In an acidic medium, or when a consistent amount of methyleneimmonium ion is present, the electrophilic reaction by the reagent on the substrate takes place (53, Fig. 29). - °° For instance, in C-aminomethylation of the Me group of methyl-nitrooxazoles, kinetically investigated in hydroalcoholic solution, an Sis attack by the methyleneimmonium cation upon the substrate has been postulated. ... 

When the aminomethylating species is an X-aminomethyl reagent, a mechanism involving the hydrogen-bonded complex 54 is generally proposed for carbonyl, - - - phenolic, and other - - substrates. Alternatively, an Sn2 mechanism, involving attack by the carbanion derived from the substrate, has been hypothesized. - - - - ... 

The possibility that the aminomethylating reagent will preferentially replace Ha or Hr in 93 is essentially determined by the presence of asymmetry in the substrate or in... 

The X-aminomethyl reagents 32a-h are reported in Table 5. Several derivatives obtained from aldehydes other than formaldehyde are also included (see the starred references in the table), which thus allow the range of products achievable by Mannich... 

Halogenomethyl, hydroxymethyl and aminomethyl groups readily undergo displacement reactions with nucleophilic reagents. Both side-chain and nuclear substitution products have been obtained (Scheme 57). These two possibilities are exemplified by the reaction of furfuryl chloride with sodium cyanide (Scheme 58). 

A generally applicable reaction scheme naturally cannot be given. The reaction mechanism of one particular carbinolamine with a particular reagent can depend on the reaction conditions in nonpolar solvents, the nondissociated carbinolamine obviously reacts (Sj 2 mechanism). In polar solvents, on the other hand, the mesomeric cation reacts (S l mechanism). Formally all these reactions belong to the general class of aminomethylation. The reaction products can be considered to be Mannich bases. ... 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Khalfan, H., Abuknesha, R., Rand-Weaver, M., Price, R.G., and Robinson, D. (1986) Aminomethyl cou-marin acetic acid A new fluorescent labeling reagent for proteins. Histochem. /. 18, 497-499. 

Similarly, a solid-supported imide has been reported to serve as an acylating reagent under microwave conditions by Nicewonger and coworkers [130], The starting imide was immobilized on aminomethyl polystyrene and in this case benzoyl chloride was chosen to prepare the acylating reagent (Scheme 7.111). Primary amines and piperazines were smoothly acylated at room temperature, but more hindered secondary amines required more time and higher temperatures, and anilines... 

Different reactivity of a-oxyalkyl and boryloxyalkyl fragments was revealed in reactions with amines of weak basicity. For example, in the reaction with diphenylamine or o-aminobenzoic acid with a reagent ratio of 1 1, substitution of the oxymethyl group by the aminomethyl one takes place [Eq. (117)]. The P,B-containing heterocycle is retained (89IZV1340). 

Vainilavicius and co-workers studied the Mannich reaction of oxadiazolethiones in detail and reported several examples pointing to the importance of starting reagent stmctures and the reaction conditions on the course of the reaction <2002M 173, 2003CHE1364>. For example, aminomethylation and acylation of 5-(4,6-diphenyl-2-pyrimidinyl)-... 

FIGURE 5.17 Resins and linkers for synthesis of peptides using Fmoc/tBu chemistry. The linkers are secured to supports by reaction with aminomethyl resins. A protected amino acid is anchored to the support as an ester by reaction with a hydroxyl or chloro group (italicized). The alkoxy and phenyl substituents render the benzyl esters sensitive to the cleavage reagents. 

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