Synthesis of Dihalo‐Substituted Analogues of Tröger’s Base from ortho‐ and meta‐Substituted Anilines

Abstract

For the first time, ortho-and meta-halo-substituted anilines were successfully condensed with formaldehyde to dihalosubstituted analogues of Tröger's base. By using paraformaldehyde and TFA, yields of 2−85% of these potential supramolecular building blocks were obtained. Even the inconceivable achievement of condensing anilines unsubstituted in para-position to analogues of Tröger's base was successful. Adding our present results to our previous, makes it now pos-

Synthesis of 5,6,11,12-tetrahydrodibenzo[b,f][1,5]diazocines and a demonstration of their reactivity to afford methano strap-modified Tröger’s base analogues

“…This has been largely achieved by the use of functionalised anilines, 6,[11][12][13][14] together with other suitable aromatic amines such as amino-acridines, 15 phenanthrolines, 16,17 pyrroles, 18 thiophenes 19 and porphyrins. 20,21 In recent years the long-held belief that Tröger's base analogues could not be prepared from anilines bearing electron-withdrawing groups has been proven to be incorrect, with the synthesis of halo [22][23][24][25] and nitro-functionalised [26][27][28][29][30] Tröger's bases. Several reviews detail the major accomplishments over the past few decades with regards to Tröger's base and related chemistry.…”

Halogenation of Tröger’s base analogues

“…The site of bromination, exclusively at the 4-and/or 10-sites, i.e., at the ortho position relative to the nitrogens of the diazocine bridge, is consistent with the nitrogen atoms functioning in the same manner as the nitrogen of N,N-dimethylaniline, albeit with reduced reactivity. Whilst the reaction is not a synthetically viable route to the halogenated products (5 can be prepared from the reaction 2-bromo-4-methylaniline and parafomaldehyde in TFA in a yield of 85% 36 ), it demonstrates for the first time that it is possible to halogenate a substituted Tröger's base framework and thereby provides an alternate means of preparing functionalised analogues of Tröger's base. Importantly, the formation of 6, albeit currently in low yields, offers direct access to non-symmetric compounds, i.e., compounds in which the two aryl rings are differentially substituted.…”

“…For example, the use of 3-bromo-4-methylaniline and 3-chloro-4-methylaniline afforded the 1,7-dihalo Tröger's base isomers in yields of 24% and 23%, respectively, as one of three isomers, 36 and under slightly different conditions the 1,7-dibromo-2,8-dimethyl isomer was obtained in 38% yield.…”

“…3 A wide range of functionalised analogues have been prepared from appropriately substituted amino-aryls and these compounds have been used in applications such as molecular recognition, [4][5][6][7][8][9][10][11] DNA binding studies [12][13][14][15][16] and catalysis. [17][18][19][20] In the last few years halogenated Tröger's base analogues have been prepared from haloanilines [21][22][23][24] and proven to be extremely valuable in the synthesis of other analogues as the halogens act as "handles" for further functionalisation. [25][26][27][28] As part of a preliminary study aimed at alternate ways of accessing functionalised Tröger's base analogues, a methodology to brominate and chlorinate four Tröger's base compounds, as racemic mixtures, (Figure 1) was investigated.…”

NMR Spectral Correlations in Some Tröger’s Bases

“…Didier and Sergeyev synthesized a few symmetrical amino and amino ethyl Tröger's base derivatives via Pd catalyzed C-C and C-N bond formation [18]. Tröger's base derivatives are also used as catalysts for organic synthesis-construction of new supramolecular hosts [19,20], complexation [21], diastereoselective self-assembly of double standard helicates [21,23], molecular tweezers [24,25], scaffolds [26,27] and HPLC chromophoric solid phase supporters [28][29][30]. The synthesis of pure optically active Ru(II) complexes with a chiral Tröger's base ligands and their interaction towards DNA was investigated by Classens et al, [31].…”