Purine-Furan and Purine-Thiophene Conjugates

Furyl and thienyl moieties were introduced into a purine structure to elevate its fluorescence properties, while a trityl group was used to increase the amorphous properties of the purine compounds. The title compounds were prepared by a sequence involving a Mitsunobu, a SNAr and a Suzuki–Miyaura reaction and their photophysical properties were studied. Quantum yields in the solution reached up to 88% but only up to 5% in the thin layer.


Introduction
The synthesis and development of novel push-pull purine derivatives with potential as new materials and/or heavy metal sensors are currently in high demand [1].Purines containing fivemembered heterocycles in their structure show fluorescence with good quantum yields in the solution [2,3].In 2017, functionalized purine chromophores were developed using a Stille crosscoupling between 6-bromopurine and distannyl π-linkers of benzodithiophene, thiophene, or dithienylbenzothiadiazole [4].These chromophores showed high thermal stability, long excited state lifetimes and high quantum yields, which will permit the use of such purine derivatives in material chemistry in the future.
We have developed novel purine derivatives, containing a group at N(9) to enhance their amorphous properties [5], for study a fluorescent materials in thin films.Our approach for building push-pull structures is based on the introduction of electron donating piperidinyl groups at C(2) and C (6) of the purine cycle and by extending the conjugation through introduction of a furan or thiophene at C (8).
Various approaches have been used for the introduction of thienyl and furyl substituents at the purine C(8) position.Ozola and co-workers used palladium-catalyzed Stille cross-coupling reactions in the presence of CuO to install the 2-and 3-furanyl rings [6].The Sedlaček group also successfully introduced a 2-thienyl group to the 9-substituted 2,6-diaminopurine using a Stille cross-coupling and a 3-thienyl group using a Suzuki-Miyaura reaction [7].2-Iodothiophene was used for direct cross-coupling at the purine C(8) position in the presence of CuI and Pd(OAc) 2 giving the 8-substitued product in 15% yield [8].

Results and Discussion
The Mitsunobu reaction between 2,6-dichloropurine 1 and 2-hydroxyethyl 3,3,3-triphenylpropanoate 2 led to the C(9)-substituted 2,6-dichloropurine 3 (Scheme 1) which was used as a starting material in subsequent steps.In the S N Ar reaction of 2,6-dichloropurine 3 with piperidine, the most reactive chlorine atom at C(6) was replaced followed by the less active C(2) chlorine.A complete conversion to 2-chloro-6piperidinylpurine derivative was observed by HPLC over a period of 15 min, followed by the slower substitution at C(2) of the purine giving product 4 in 56% yield.In isopropanol, this reaction runs without any significant formation of side-products.
In the SNAr reaction of 2,6-dichloropurine 3 with piperidine, the most reactive chlorine atom at C(6) was replaced followed by the less active C(2) chlorine.A complete conversion to 2-chloro-6-piperidinylpurine derivative was observed by HPLC over a period of 15 min, followed by the slower substitution at C(2) of the purine giving product 4 in 56% yield.In isopropanol, this reaction runs without any significant formation of side-products.
The 8-bromo derivative 5 was obtained by bromination of the 8-position of the purine ring in 71% yield.Subsequently, the Suzuki-Miyaura reaction with the furyl-and thienylboronic acids resulted in the 2,6,8-tri-substituted purine derivatives 6a-c in 50-63% yields (Scheme 2).Fluorescence quantum yields were measured for compounds 6a-c in solution (DCM) and as thin films.The quantum yields were much lower in the films than in solution.Compound 6c exhibited the highest quantum yield (0.88, solution) among the three synthesized compounds.In the case of compounds 6b and 6c, there is a significant drop in fluorescence quantum yields in the thin film in comparison to the solution, from 0.60 and 0.88 to 0.04 and 0.05, respectively (Table 1).Typically, amorphous thin films are characterized by a significant degree of disorder which might result in the concentration induced or aggregation induced fluorescence self-quenching [9][10][11][12][13][14][15][16].Compounds 6a-c exhibited an absorption maximum around 320-350 nm and an emission maximum around 380-450 nm when excited at 320-350 nm (Figure 1).Fluorescence quantum yields were measured for compounds 6a-c in solution (DCM) and as thin films.The quantum yields were much lower in the films than in solution.Compound 6c exhibited the highest quantum yield (0.88, solution) among the three synthesized compounds.In the case of compounds 6b and 6c, there is a significant drop in fluorescence quantum yields in the thin film in comparison to the solution, from 0.60 and 0.88 to 0.04 and 0.05, respectively (Table 1).Typically, amorphous thin films are characterized by a significant degree of disorder which might result in the concentration induced or aggregation induced fluorescence self-quenching [9][10][11][12][13][14][15][16].Compounds 6a-c exhibited an absorption maximum around 320-350 nm and an emission maximum around 380-450 nm when excited at 320-350 nm (Figure 1).

Materials and Methods
1 H-and 13 C-NMR spectra were recorded at 300 MHz, respectively.signals for residual non-deuterated solvents (δ 7.26 for CDCl3 and δ 2.50 for DMSO-d6) and carbon signals (δ 77.1 for CDCl3 and δ 39.5 for DMSO-d6) were used as internal references for 1 H-and 13 C-NMR spectra, respectively (see Supplementary Materials).Coupling constants are reported in Hz.Infrared spectra were recorded using a Perkin Elmer Spectrum BX spectrometer (PerkinElmer, Inc., Hebron, KY, USA).Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60 F254 aluminum plates precoated with a 0.25 mm layer of silica gel.For HPLC analyses Agilent Technologies 1200 Series system (Agilent Technologies, Foster City, CA, USA) was used (XBridge C18 column, 4.6 × 150 mm, particle size 3.5 µ m) with a flow rate of 1 mL/min; eluent system: 0.01% TFA water solution/MeCN (95:5, v/v).The content of MeCN was changed as follows: 20-95-95-20% (0-5-10-12 min).The wavelength of detection was 260 nm.The UV-vis absorption spectra of compounds were using a Perkin-Elmer 35 UV-vis spectrometer.Emission spectra were measured on a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc., Ford, West Sussex, UK).Absolute photoluminescence quantum yields were determined using a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc.) equipped with a 6-inch integrating sphere by LabSphere, using a florescence standard of quinine sulfate in 0.1 M H2SO4 as the reference.

Materials and Methods
1 H-and 13 C-NMR spectra were recorded at 300 and 75.5 MHz, respectively.The proton signals for residual non-deuterated solvents (δ 7.26 for CDCl 3 and δ 2.50 for DMSO-d 6 ) and carbon signals (δ 77.1 for CDCl 3 and δ 39.5 for DMSO-d 6 ) were used as internal references for 1 H-and 13 C-NMR spectra, respectively (see Supplementary Materials).Coupling constants are reported in Hz.Infrared spectra were recorded using a Perkin Elmer Spectrum BX spectrometer (PerkinElmer, Inc., Hebron, KY, USA).Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60 F 254 aluminum plates precoated with a 0.25 mm layer of silica gel.For HPLC analyses Agilent Technologies 1200 Series system (Agilent Technologies, Foster City, CA, USA) was used (XBridge C18 column, 4.6 × 150 mm, particle size 3.5 µm) with a flow rate of 1 mL/min; eluent system: 0.01% TFA water solution/MeCN (95:5, v/v).The content of changed as follows: (0-5-10-12 min).The wavelength of detection was 260 nm.The UV-vis absorption spectra of compounds were acquired using a Perkin-Elmer 35 UV-vis spectrometer.Emission spectra were measured on a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc., Ford, West Sussex, UK).Absolute photoluminescence quantum yields were determined using a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc.) equipped with a 6-inch integrating sphere by LabSphere, using a florescence standard of quinine sulfate in 0.1 M H 2 SO 4 as the reference.

Materials and Methods
1 H-and 13 C-NMR spectra were recorded at 300 and 75.5 MHz, respectively.The proton signals for residual non-deuterated solvents (δ 7.26 for CDCl3 and δ 2.50 for DMSO-d6) and carbon signals (δ 77.1 for CDCl3 and δ 39.5 for DMSO-d6) were used as internal references for 1 H-and 13 C-NMR spectra, respectively (see Supplementary Materials).Coupling constants are reported in Hz.Infrared spectra were recorded using a Perkin Elmer Spectrum BX spectrometer (PerkinElmer, Inc., Hebron, KY, USA).Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60 F254 aluminum plates precoated with a 0.25 mm layer of silica gel.For HPLC analyses Agilent Technologies 1200 Series system (Agilent Technologies, Foster City, CA, USA) was used (XBridge C18 column, 4.6 × 150 mm, particle size 3.5 µ m) with a flow rate of 1 mL/min; eluent system: 0.01% TFA water solution/MeCN (95:5, v/v).The content of MeCN was changed as follows: 20-95-95-20% (0-5-10-12 min).The wavelength of detection was 260 nm.The UV-vis absorption spectra of compounds were acquired using a Perkin-Elmer 35 UV-vis spectrometer.Emission spectra were measured on a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc., Ford, West Sussex, UK).Absolute photoluminescence quantum yields were determined using a QuantaMaster 40 steady state spectrofluorometer (Photon Technology International, Inc.) equipped with a 6-inch integrating sphere by LabSphere, using a florescence standard of quinine sulfate in 0.1 M H2SO4 as the reference.

Table 1 .
Photophysical properties of target compounds

Table 1 .
Photophysical properties of target compounds