Synthesis of a bifunctional 1,2,3,4-tetrahydroquinoline derivative: 4,4`-(1,4-phenylene)di(1,2,3,4-tetrahydrobenzo[ f ]quinolin-2-ol)

N,N`- di(3-chloro-2-hydroxypropyl)- N,N`- di(2-naphthyl)-1,4-diaminobenzene upon intra-molecular cyclization gives bis-1,2,3,4-tetrahydroquinoline derivative - 4,4`-(1,4-phenylene)di(1,2,3,4-tetrahydrobenzo[ f ]quinolin-2-ol).


Introduction
The chemistry of 1,2,3,4-tetrahydroquinolines is of interest among many investigations during recent years.The growing interest in them can be explained by their biological activities.7][8] Besides pharmaceutical applications, tetrahydroquinoline derivatives are useful as pesticides, 9 antioxidants, 10 corrosion inhibitors, 11 and active components of various dyes. 12In addition, they also have found application in modern recording technologies. 13,14Consequently, synthesis methodologies for preparing tetrahydroquinoline derivatives have attracted considerable interest and several methods offering good results have been reported. 15The nature, number, and relative location of the substituents are the key parameters to consider before choosing a method.Until now, much attention has been paid to the development of synthesis of monofunctional 1,2,3,4-tetrahydroquinolines, but the bifunctional 1,2,3,4-tetrahydroquinoline derivatives have been seldom investigated.

Results and Discussion
7][18] The formation of tetrahydroquinoline core from diphenylamine has been proved to occur via the intermediate N- 19,20 This prompted us to apply these procedures in developing the synthesis of a bifunctional condensed tetrahydroquinoline derivative from N,N`- (3).We expected electrophilic attack of the aliphatic side chains in 2 and 3 on the o-position of the phenyl or naphthyl moieties, thus leading to intramolecular cyclization to two condensed tetrahydroquinoline rings hereby giving compounds 4 or 5 (Scheme 1).
First, the reaction of N,N`-di(2-naphthyl)-1,4-diaminobenzene with epichlorohydrin in the presence of KOH at 25-30 °C was carried out and 2 was obtained in 62 % yield.It should be noted that all our attempts to isolate the desired tetrahydroquinoline derivative under the reaction conditions described in Ref. 16 were unsuccessful.Then, compound 3 was easily obtained by the action of dilute hydrochloric acid on the diepoxy compound 2. The following cyclization of 3 was performed in refluxing 1-hexanol for 7 hours to give a final product.TLC monitoring during the course of the reaction showed two products, one of them (presumably monofunctional) gradually blending in favour of the other (bifunctional).It was found that the reaction time could be reduced up to 3 hours by changing the reaction solvent to more polar o-dichlorobenzene.The product crystallized out after the solvents were removed.Since we could expect two possible tetrahydroquinoline products (4 or 5), depending on the direction of cyclization, the structure was resolved from the spectral data.Thus, the mass spectrum and elemental analysis data are consistent with both probable structures 4 or 5.A consideration of two-dimensional 1 H-1 H COSY data facilitated assignment of resonances to appropriate heteroaromatic protons.In the 1 H NMR spectrum (DMSO-d 6 ) of the isolated product signals are present which can be assumed to the five non-equivalent protons of the formed tetrahydroquinoline ring.The resonances of ArCH 2 protons appeared as two doublets of doublets at 2.91 ppm and 3.34 ppm with J AB = 16.6,J AX = 5.4 and J BX = 7.4 Hz, due to the coupling with CH, while the protons of NCH 2 respectively gave two dd at 3.43 and 3.74 ppm (J AB = 11.6,J AX = 2.1 and J BX = 8.5 Hz).The preservation of a secondary hydroxyl is confirmed by a doublet at 5.19 ppm in 1 H NMR spectrum, also by an absorption band at 3384 cm -1 in the IR spectrum.The direction of intramolecular cyclization can be estimated from the analysis of aromatic part of 1 H NMR spectrum.A sharp singlet at 7.19 ppm is assigned to four protons of psubstituted phenylene, as is in accordance with structure 4, but not two protons as could be expected in the case of structure 5.Moreover, the substitution of 1-H in naphthalene moiety can be clearly confirmed from the data of the appropriate part of 1 H NMR data (Figure 1).The resonance of 3-H in compounds 2 and 3 gives rise to doublet of doublets due to its vicinal coupling to the 4-H (J = 9.0 and 9.2, respectively) and coupling to 1-H (J = 2.4 and 2.3).In a cyclization product the corresponding proton gives only a doublet (J = 9.0) because of missing of a meta-proton, the fact obvious for the structure 4. From all this we can conclude unambiguously, that cyclization occurs at 1-position of the naphthalene ring to give one of the presumable bifunctional compounds -4,4`-(1,4-phenylene)di(1,2,3,4-tetrahydrobenzo[f]quinolin-2-ol) (4).Additionally, the structure of 4 was confirmed by further acetylation it with acetic anhydride to give 6.
It should be noticed, that the same bifunctional compound 4 is formed directly from 1, being refluxed in the excess of epichlorohydrin and acetic acid, but with a very low 9% yield, compared to 45% for the proposed method.

Conclusions
In conclusion, intramolecular cyclization of

Experimental Section
General Procedures.The NMR spectra were taken on a Varian Unity Inova spectrometer (300 MHz for 1 H and 75 Hz for 13 C).The IR spectra were taken for samples in KBr pellets on a Perkin Elmer Spectrum BX II FT-IR System spectrometer.Mass spectra were recorded on Waters (Micromass) 2Q 200.Melting points were determined in capillary tubes on capillary melting point apparatus MEL-TEMP.The course of the reactions was monitored by TLC on Silufol UV-254 plates (acetone/n-hexane: 7/18), which were developed with I 2 or UV light.Silica gel (grade 62, 60-200 mesh, 150 Å, Aldrich) was used for column chromatography.Elemental analyses were performed with an Exeter Analytical CE-440 Elemental Analyzer; their results agreed satisfactorily with the calculated values.