Pyridinium ylides in the one-pot synthesis of a new quinoline/indolizine hybrid

1 Introduction

1,3-Dipolar cycloaddition of N-pyridinium ylides and related heteroaromatic ylides [1], e.g. quinolinium or isoquinolinium ylides, with various dipolarophiles is one of the most important methods for the synthesis of various types of indolizine and benzoindolizine [2]. It offers the advantage of removing a few reaction steps [3] and a simple work-up to reach the target molecule [4]. In continuation of our research interest in heteroaromatic N-ylide involving multi-component reactions [5, 6], we report here on the synthesis and the crystal structure determination of a new quinoline/indolizine hybrid obtained via the 1,3-dipolar cycloaddition reaction of dimethyl acetylenedicarboxylate (DMAD) with 1-(quinolin-2-ylmethyl)pyridinium ylide. The crystal structure of the latter as its iodide salt was also determined.

2 Results and discussion

1-(Quinolin-2-ylmethyl)pyridinium iodide (1) undergoes a dehydrohalogenation reaction in the presence of triethylamine in chloroform to give the corresponding pyridinium ylide. The reaction of the latter with DMAD furnished dimethyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylate (2). The structure of which was established with the help of NMR spectroscopy and a single crystal X-ray structure determination. This result clearly showed that, due to the electron-withdrawing ability of the pyridinium moiety, the methylene is acidic, and a 1,3-dipolar cycloaddition reaction of the in situ-generated ylide with DMAD took place. Compound 2 results from the oxidative dehydrogenation (aromatization) of the initially formed cycloadduct in air. The intermediates dihydroindolizine and tetrahydroindolizine were not stable enough to be isolated (Scheme 1).

Scheme 1:

Compound 1 crystallizes in the monoclinic space group P2₁/c with Z = 4 (Fig. 1a; Tables 1 and 2). Compound 2 crystallizes in the orthorhombic system, space group P2₁ab with Z = 4 (Fig. 1b; Tables 1 and 2). The indolizine ring is close to planar with a maximum deviation of –0.044(3) Å at atom C(16). The quinoline ring is almost planar, with a maximum deviation of –0.020(2) Å at atom C(5) and –0.023(2) Å at C(9) and C(4) for both compounds 1 and 2, respectively. The carboxyl group (C(20)/O(3)–O(4)), attached to C(12), forms a dihedral angle of 10.2(1)° with the plane defined by N(2) and atoms C(10)–C(13), while the second carboxyl group (C(18)/O(1)–O(2)) attached at C(11) is rotated by 67.54(8)° out of the same plane. Bond lengths and angles are in the expected range [7, 8]. The C–N bonds (N(2)–C(13) 1.392(2), N(2)–C(10) 1.3967(19), N(2)–C(17) 1.380(2) Å) in compound 2 indicate partial double bond character (Table 2).

Fig. 1:

Ortep plots of the molecular structures of 1 (a) and 2 (b) in the crystal and atomnumbering scheme adopted (displacement ellipsoids at the 50% probability level; H atoms with arbitrary radii; blue: nitrogen, red: oxygen, green: iodide).

3 Conclusion

In summary, the 1,3-dipolar cycloaddition reaction of 1-(quinolin-2-ylmethyl)pyridinium ylide with DMAD as dipolarophile was investigated. Thus, the corresponding substituted indolizine derivative was obtained. Further investigation of this reaction using other reagents is carried out in our laboratory.

4 Experimental section

All chemical reagents and solvents were of analytical grade and were used as received. 1-(Quinolin-2-ylmethyl)pyridinium iodide (1) was synthesized following a literature procedure [9] starting from quinaldine.