Synthesis and spectroscopy of the Tröger’s base derived from 2-aminoacridine

The analogs of the Tröger’s base, 7,17-methano-6,7,16,17-tetrahydrodiacridino-[3,4-b :3’,4’-f ]- [1,5]-diazocine was prepared starting from 2-aminoacridine instead of 3-aminoacridine. The new compound, 7,17-methano-6,7,16,17-tetrahydro-diacridino-[2,1-b :2’,1’-f ]-[1,5]-diazocine, has been fully characterized by 1 H-and 13 C-NMR spectroscopies using mono-and bi-dimensional techniques. Other aminoacridine derivatives failed to afford Tröger’s bases


Chemistry
Compound 4 was prepared according to the method of Tatibouët, Demeunynck and Lhomme 15 from 2-aminoacridine, trifluoroacetic acid, and paraformaldehyde under argon for 24 h at room temperature.The compound was obtained only in 45% yield (isomer 2 was obtained in 90 % yield). 1,2e carried out similar reactions with the compounds of Scheme 2. In no case were Tröger's bases identified; only intermediate compounds were isolated, in very low yields.

NMR spectroscopy
We have gathered in Tables 1 and 2 all the information available on compound 4. The protons of the methylene group at position 6 are named 6n (endo) and 6x (exo).We are using the numbering of Tröger's base: NMR spectrum was assigned using first a DEPT experiment to identify the quaternary carbon atoms and then 2-dimensional 13 C-1 H HMQC (one bond)-and HMBC (long distance) correlations. [14]

Conclusions
The formation of Tröger's bases from aminoacridines and their derivatives (acridin-9-ones, acridin-9-thiones) is a reaction of limited scope.Both 2 and 4 are "bent" isomers, which is the normal result in acridines: [16][17][18][19][20] they cyclize towards the peri-position.For the moment, there is no hope of obtaining "linear" compounds such as 2b and 4b, that would be very interesting scaffold structures.

4
The aromatic protons were assigned using double resonance and NOEDIF experiments.The 13 C

Table 2 .
13C NMR data (δ ppm) and13C-1 H correlations of compound 3 in CDCl 3 Boron trifluoride diethyl etherate (1.56 g, 11 mmol) was added slowly via syringe, and the mixture heated under reflux for 24 h.On cooling, a yellow precipitate appeared, which was filtered and washed with water.The product was crystallized from NaOH 1M (100mL).