Aminomethylation intramolecular

Formation, transamination, and mutual transitions of aminomethyl derivatives of phosphines, representing nucleophilic substitution at the carbon atom in the P—C—O(N) fragment, take place under milder conditions than similar reactions of alcohols and amines. The reason is likely the participation of a phosphino group in intramolecular interactions (86MI1). 

The intramolecular photochemistry of 9-[2-(7V-substituted aminomethyl)-l-naph-thyl]phenanthrenes has also been studied101 (equation 40). The pyrroline derivatives are obtained by the addition of the N—H to the C-9 carbon atom of phenanthrene ring. Reasonable yields for the highly regioselective products are obtained by irradiation in benzene solution. 

Fig. 4 Halotelluronium species stabilized by intramolecular chelation formed by oxidative addition of halogens to A,A-dimethyl-2-(aminomethyl)phenyl phenyltelluride (17).

In one route, tidopidine (1) was assembled via Sn2 displacement of 2-chlorobenzyl chloride (9) with 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (8). " The nucleophile 8 was synthesized by heating 2-thiophen-2-yl-ethylamine (6) with 1,3-dioxolane in the presence of concentrated hydrochloric acid. 1,3-Dioxolone gave better yields than with formaldehyde, paraformaldehyde and 1,3,5-ttioxane. The interesting transformation 6 —> 8 first involved the formation of the corresponding Mannich base 7, which then underwent a Pictet-Spengler type reaction to afford the ring-closure product 8. It was of interest to note that a possible intramolecular aminomethylation did not take place. 

Pyrrole and indole rings can also be constructed by intramolecular addition of nitrogen to a multiple bond activated by metal ion complexation. Thus, 1-aminomethyl-l-alkynyl carbinols (obtained by reduction of cyanohydrins of acetylenic ketones) are cyclized to pyrroles by palladium(II) salts. In this reaction the palladium(II)-complexed alkyne functions as the electrophile with aromatization involving elimination of palladium(II) and water (Scheme 42) (81TL4277). 

Further constraint of the aminomethyl chain has been performed by incorporating it into 5,6,7,8-tetrahydronaphthoic acids 19 and 20 (Scheme 7) 5961 731 X-ray diffraction and NMR analysis of the TV-acetyl-jV -isopropylamide 21 revealed that the compound induces a turn structure without the formation of an intramolecular hydrogen bond. However, molecular modeling studies indicate that this amino acid derivative prefers a partially extended conformation 71,72 ... 

In the course of the catalytic hydrogenation of a,us dinitriles over Raney nickel, by-products are obtained from C-N and C-C bond formation. The mechanism of the formation of these compounds was investigated. Cyclic and linear secondary amines can result from the same secondary imine through a transimination process involving a ring-chain tautomerism. Stereochemical results for 2-aminomethyl-cyclopentylamine (AMCPA) are in accordance with a specific cyclisation pathway favored by an intramolecular hydrogen bond giving rise to the cis isomer from aminocapro-nitrile, unfavored in the case of adiponitrile which leads to the trans AMCPA as the major isomer. 

A library of di- and trisubstituted 5-amino-l 77-1-benzazepine derivatives was assembled through attachment of a preformed 1-benzazepine unit to an aminomethylated polystyrene resin. The initial solution phase synthesis of the 1-benzazepine moiety was based on an intramolecular Dieckmann cyclization (type d) followed by a ketone to primary amino group transformation via reduction ( NaBH3CN) of an imine intermediate <2007JC0487>. 

The aziridine ring may also be opened in an electrophilic fashion. For example, the aziridine nucleus of the functionalized allyl silane 113 undergoes intramolecular ring opening in the presence of boron trifluoride etherate to give the aminomethyl vinyl cyclohexane 114 in 90% yield as a 2.7 1 mixture of cis and tram isomers [95TL3793]. 

The 1-aminomethyl derivative of pyrimidine nucleoside 343 undergoes cyclization in the presence of a mixture of triethylamine and pyridine at 90 °C with concomitant demesylation to yield 344 but a variety of other bases and conditions failed to produce the required intramolecular nucleophilic attack <2006JOC299>. 

V-Benzyl-/V-(but-3-yny l)aminomethyl]-5-chloro-3-methoxy-1-phenylpyra-zin-2( I //)-one (45) underwent an intramolecular Diels-Alder reaction to afford 2-benzyl-8-chloro-6-methoxy-l,2,3,4-tetrahydro-2,7-naphthyridine (46) (PhBr, reflux 78 %).602... 

Benzimidazole reacts with formaldehyde and secondary amines in a Mannich reaction to give 1-aminomethyl products. Intramolecular Mannich reactions at ring nitrogen can produce bicyclic products, for example, 131 in Scheme 23 <2005JHC173>. 

Except in a few cases,cyclic Mannich ba.scs derived from alkenes arc produced by the reaction of unsaturated amino derivatives with formaldehyde. Intramolecular aminomethylation (Fig. 65) takes place with aminoalkenes (184, X = H path a) or with analogous silyl allyl derivatives (184, X = SiMc , path b) ... 

Aminomcthyl derivatives are usually described as unstable intermediates affording more stable C-aminomethyl products by deaminomethylation (sec above). However, the synthesis of ebumane alkaloids involves as a key step the formation of a mcthylol derivative of the a-dicarboxyester 455 (Fig. 173), which then leads to the tcu-ahydro-pyranc ring 456 by intramolecular 0-aminoalkylation reaction with the immonium ion present in the molecule. 

Amino groups are well established as intramolecular donors for silicon centers [1]. Due to the enhanced nucleophilicity of hydrazines the intramolecular coordination ability of the terminal nitrogen center in the 2-(trimethylhydrazino)phenyl substituent (PTMH) is expected to be stronger than in the 2-(dimethyl-aminomethyl)phenyl substituent (DMBA). 

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