Synthesis of pyrano[4,3-b ]quinolizine derivatives from 6-aryl or styryl-4-methylsulfanyl-2-oxo-2 H -pyrans and their fluorescence

New fluorescent compounds 1,11-dihydro-11-imino-1-oxo-3-phenylpyrano[4,3-b ]quinolizines were synthesized in good yields by the reaction of 6-aryl-3-cyano-4-methylsulfanyl-2 H -pyrones and 4-methylsulfanyl-2,5-dioxo-2,5-dihydro-1 H -pyrrole-3-carbonitrile with 2-pyridylacetates. These fused quinolizine derivatives exhibited fluorescence in solid and solution states.


Results and Discussion
It has been reported that the reactions of 6-aryl or styryl-4-methylsulfanyl-2-oxo-2H-pyrans with aryl acetyl compounds yield pyrano [3,4-c]pyridine and pyrano [3,4-c]pyrone derivatives.3b,d Although pyrano [3,4-c]pyrone compounds (Type B) do not exhibit fluorescence in solid states, pyrano [3,4-c]pyridine compounds (Type A) having an intramolecular H-bonded structure because of a C=O----H-O-C system exhibit strong fluorescence (Figure1).The increase in their fluorescence is attributed to the strong packing caused by the molecular flatness resulting from the intramolecular H-bonded structure of the C=O----H-O system.This indicates the possibility of the development of fluorescence in other fused 2H-pyrone derivatives with an intramolecular H-bonded structure of the C=O----H-O system type.Polycyclic pyrone derivatives are expected to exhibit fluorescence and are synthesized by the reaction of 6-aryl or styryl-4-methylsulfanyl-2-oxo-2H-pyrans with active methylene compounds.

Table 2. Reaction of 2H-pyrones (1e, f) with active methylene compound (2b) in the presence of a base
The UV-vis absorption and fluorescence emission spectra of 3a-g, 4a, b, and 5a, b were analyzed in solution (dichloromethane and ethanol) and solid states, respectively, at room temperature.The spectroscopic properties-absorption maxima (λ max ), molar absorptivities (ε), fluorescence maxima (Em max), and relative fluorescent intensities (RI)-are listed in Table 3.In solid states, the RI was measured against the standard of Alq 3 [tris(8hydroxyquinolinato)aluminum]. 5 As expected, polycyclic pyrone derivatives with an intramolecular H-bonded structure resulting from a C=N-H----O=C system exhibited fluorescence.Some of them emitted a greater bathochromical shift than the pyrone derivatives used as precursors.However, polycyclic pyrone derivatives without an intramolecular H-bonded structure also exhibited fluorescence.As a result, it is considered that the optimal structures for emitting between pyrone and polycyclic pyrone derivatives have great differences.From our earlier study, the flatness of the structure resulting from a C=O----H-O-C system appears to influence both the Em max and RI in pyrone derivatives; whereas, it does not necessarily influence them in polycyclic pyrone derivatives.Moreover, with respect to the substitution effect, the introduction of electro-donating or electrowithdrawing groups influences the emissions of pyrone derivatives, whereas their contribution is very low in polycyclic pyrone derivatives with the intramolecular H-bonded structure due to a C=N-H----O=C system.On the other hand, polycyclic pyrone derivatives without the intramolecular H-bonded structure are influenced by the substitution effect.Research regarding this effect is currently being conducted.

Experimental Section
General Procedures.Identifications of compounds and measurements of properties were carried out by general procedures using the following equipment.All melting points were determined in a capillary tube and uncorrected.Infrared (IR) spectra were recorded in potassium bromide pellets on JASCO 810 or Shimazu IR-460 spectrometer and ultraviolets (UV) absorption spectra were determined in 95% ethanol on a Hitachi 323 spectrometer.Fluorescence spectra were determined on Shimazu RF-5300.Nuclear magnetic resonance (NMR) spectra were obtained on Gemini 300NMR(300MHz), 500NMR(500MHz) and a JEOL-GX-400 (400MHz) spectrometers with tetramethylsilane as an internal standard.Mass spectra (MS) were recorded on JOEL DX-303 and JMS-T100LP mass spectrometers.Microanalyses were performed on a Perkin Elmer 2002 at Nagasaki University.All chemicals were reagent grade and used without further purification unless otherwise specified.

Method of Measurement of Fluorescence (a)
In the solid state.A powder sample of subject compound is heaped in the tray.After covering the sample with quartz plate, this part was fixed in fluorescence spectrometer.After fixing the fluorescent wavelength, the excitation spectrum was determined by the scanning with the fluorescent wavelength.Similarly, fluorescent spectrum was obtained after scanning with the excitation wavelength.After obtaining these results, the excitation wavelength was decided and the fluorescence spectrum was measured.The fluorescent relative intensity was determined by using Alq 3 as standard sample.Fluorescence of standard sample and all subject compounds were measured on 345 nm excitation.(b) In solution.The concentration of measuring samples in the excitation wavelength region was adjusted under 0.05 on the molar absorption.

e
Relative intensity of fluorescence in solid states, using Alq 3 as the standard compound.The Em max of 3a-f ranged from 486-512 nm in dichloromethane, except for 3c, and 549-565 nm in solid states.Compared with 2H-pyrones (1a-c), 3a, b, d, and e exhibited bathochromical shifts near the red fluorescent compounds in solid states.In ethanol, these compounds did not emit any light.With regard to Em max and RI, the obvious substitution effects at position 5 of the pyrano[4,3-b]quinolizine ring and position 4 of the aryl ring were not observed.The ε values of these compounds were almost equal to those of their precursors.The 6-(4dimethylamino)styryl compound (3g) was dark red in color; however, it did not exhibit fluorescence in the solution or solid state.In dichloromethane, 3a, b, d, and e exhibited significantly larger Stokes shifts (SS), indicating that the S 1 states of these compounds are stabilized by a solvent polarization field.Fused pyrones-dicarbonyl derivatives 4a, b and decarboxylated derivatives 5a, b-were also analyzed for fluorescent emissions.The Em max of 4a, b exhibited hypsochromic shifts compared with 3d, e in dichloromethane and solid states.The RIs of 4a, b were stronger than those of 3d, e in solid states.This suggested that a change in the structure at position 11 of the pyrano[4,3-b]quinolizine ring influenced both the Em max and RI.However, the light emitting region of 5a, b shifted upward by approximately 20 nm compared with that of 4a, b in solid states, and the RIs of 5a, b were weaker than those of 4a, b in solid states, indicating that the substitution effects on the Em max and RI occurred because of the introduction of a carboxyl group at position 5 of the pyrano[4,3-b]quinolizine ring.The substitution effect at the position 4 of the aryl ring was not observed.In ethanol, 4a, b and 5a, b also did not emit any light, as was the case with 3a-f.The F value, the difference between the Em values in the solid and solution states, varied from 41 nm to 84 nm in all compounds.

Table 1 .
Reaction of 2H-pyrones (1a-d) with active methylene compounds (2a, b) in the presence of a base

Table 3 .
UV and fluorescence spectra of pyrano[4,3-b]quinolizine derivatives in dichloromethane and in solid states a Measurement in ethanol.b Stokes Shift, Em-Ex in solution.c ∆F = Em(solid)-Em(solution).d Stokes Shift, Em-Ex in solid states.