Aminomethyl Group

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

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). 

In systems of proper geometry, nucleophiles within a side chain may be well connected for attack on ring atoms. For example, an aminomethyl group at the 5-position of a dibenzazepine-2-one was found to attack the carbonyl group (Section 5.16.3.5.2). Such reactions should be possible in rings of any size. 

Wendler, Taub and Slates have established that the course of rearrangement is independent of the configuration of the 17-aminomethyl group. ... 

Amino group of 7-aminomethyl-2-substituted perhydropyrido[l,2-u]pyr-azines were reacted with 2-bromopyridine and 2-chloropyrimidines to give 7-(hetarylamino)methyl derivatives in the presence of Na2C03 in DMF at 100-120°C for 18h in 13-51% yields (00MIP15). An aminomethyl group of... 

A convenient method for introducing an aminomethyl group into nitroarenes can be accomplished by the use of the anion of phenylthiomethylisocyanide (Eq. 9.40).68... 

Our library synthesis was carried out with a set of 27 tube-shaped solid phase synthesis support, called MicroTubes. These supports are prepared by radiation grafting of polystyrene ( — 350 pmol) onto polypropylene tubes, chemically functionalizing the polystyrene with aminomethyl groups to afford about 55 imol of amine per tube, inserting a reusable Rf ID tag into each tube, and heat-sealing the tube ends to prevent loss of the tag. The chemical conversion of all 36 aminomethyl tubes was carried out simultaneously using standard procedures with rink amide linker, each with —46 pmol of available amine per tube.1 2... 

Contemporaneously with Snieckus, Uemura and coworkers showed that ferrocene 369 bearing an aminomethyl group may also be lithiated enantioselectively by alkyllithi-ums to give 370 in these cases, better results are obtained with the C2-symmetric amine 368 than with (—)-sparteine (Scheme 157). 

Later, Tieke reported the UV- and y-irradiation polymerization of butadiene derivatives crystallized in perovskite-type layer structures [21,22]. He reported the solid-state polymerization of butadienes containing aminomethyl groups as pendant substituents that form layered perovskite halide salts to yield erythro-diisotactic 1,4-trans polymers. Interestingly, Tieke and his coworker determined the crystal structure of the polymerized compounds of some derivatives by X-ray diffraction [23,24]. From comparative X-ray studies of monomeric and polymeric crystals, a contraction of the lattice constant parallel to the polymer chain direction by approximately 8% is evident. Both the carboxylic acid and aminomethyl substituent groups are in an isotactic arrangement, resulting in diisotactic polymer chains. He also referred to the y-radiation polymerization of molecular crystals of the sorbic acid derivatives with a long alkyl chain as the N-substituent [25]. More recently, Schlitter and Beck reported the solid-state polymerization of lithium sorbate [26]. However, the details of topochemical polymerization of 1,3-diene monomers were not revealed until very recently. 

Aminomethyl groups in position 6 (Section IV,D,1 Table XI) yield... 

The aminomethyl group is already protonated (Table 9-4). Protonation on the amino group. 

The direct addition of nitromethane, in a mixture of anhydrous methanol and sodium methoxide, to 9-(3,5-0-isopropylidene-/ -D-fhreo-hexo-furanosyl-2-ulose)adenine (22) gave 9-(2-C-nitromethyl-/ -D-h/xo-hexo-furanosyl)adenine (94) in 75% yield.38 Reduction of 94 in 5 5 1 methanol-water-acetic acid in the presence of 10% palladium-on-charcoal, followed by N-acetylation of the resulting aminomethyl group, afforded, in 62% yield, 9-(2-C-acetamidomethyl-3,5-0-isopropyIidene-/ -D-h/xo-hexofuranosyl)adenine (95). 

Polystyrene does not enable the covalent, reversible attachment of synthetic intermediates unless the support is derivatized with suitable functional groups. The most common groups for the reversible attachment of intermediates are chloromethyl and hydroxymethyl, whereas aminomethyl groups are mainly used as non-cleavable points of attachment for linkers (see Chapter 3). 

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