SYNTHESIS AND FLUORESCENCE CHARACTERISTIC OF 2-N- ANILINOPYRIDINE AND 3-N-ANILINOPYRIDINE

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1 The Malaysian Journal of Analytical Sciences, Vol 11, o 1 (007): 9- SYTHESIS AD FLUOESCECE CHAACTEISTIC OF -- AILIOPYIDIE AD --AILIOPYIDIE oordini Mohd Salleh, Liow Pei Ling, Zanariah Abdullah, Maizathul Akmam A. Bakar* and Zaharah Aiyub Department of Chemistry, Faculty of Science, University of Malaya, 00 Kuala Lumpur Keywords: --Anilinopyridine, --Anilinopyridine, Fluorescence Abstract --Anilinopyridine and --anilinopyridine were obtained when aniline was refluxed with -chloropyridine and - chloropyridine, respectively. The structures of both compounds were confirmed by 1 H M, 1 C M, infra red and mass spectrometries. Fluorescence studies of these compounds were carried out in various solvents and --anilinopyridine showed the highest fluorescence peak at 8 nm, when excited at 9 nm in tetrahydrofuran. --Anilinopyridine showed the highest fluorescence peak in acetonitrile when excited at nm. The fluorescence peak was recorded at 8 nm. Both -anilino pyridines showed a decreased in fluorescence intensity in other solvents such as ethyl acetate and ethanol. Fluorescence peak was also reduced with time in capped and uncapped conditions. For uncapped condition, the presence of oxygen is believed to be responsible in reducing the fluorescence intensity of both compounds studied through quenching effect. Abstrak --Anilinopiridina diperolehi apabila anilina direfluks dengan -kloropiridina, manakala --anilinopiridina diperolehi apabila anilina direfluks dengan -kloropiridina. Struktur kedua-dua sebatian ini dikenalpasti melalui analisis spektrum 1 H M, 1 C M, infra merah dan spektrum jisim. Kajian pendafluoran dilakukan dalam berbagai pelarut di mana -anilinopiridina menunjukkan puncak pendafluran pada 8 nm apabila diuja pada 9 nm dalam tetrahidrofuran. -- Anilinopiridina pula menunjukkan puncak pendafluoran yang tertinggi dalam asetonitril, dengan panjang gelombang penujaan nm. Puncak pendafluoran direkodkan pada 8 nm. Kedua-dua -anilino piridina menunjukkan penurunan keamatan pendafluoran dalam pelarut lain seperti etil asetat dan etanol. Puncak pendafluoran juga menurun dengan masa bagi sampel tertutup dan sampel terbuka. Bagi sampel terbuka, kehadiran oksigen dikaitkan dengan penurunan keamatan melalui kesan pelindapan. Introduction The pyridine ring systems are very widely distributed in nature, especially in the plant kingdom. Many important alkaloids are pyridine derivatives [1]. The pyridine ring plays a key role in several biological processes such as the oxidation/reduction coenzyme nicotine adenine dinucleotide (APP), whereby the vitamin niacin is required for its biosynthesis []. The first pyridine was obtained from the isolation of bone oil and from coal tar in 18 by Anderson []. Korner and Dewar, in 189, suggested the cyclic nature of pyridine as a hexagonal structure having alternate double and single bonds []. Today, the pyridine ring can be synthesized using two main synthetic routes, namely Hantzsch synthesis and Guareshi synthesis. The most important and widely used pyridine synthesis is by using Hantzsch method, which involved the condensation of two molecules of ß-keto ester with an aldehyde and ammonia as shown in Scheme 1. Pyridine and its derivatives undergo electrophilic and nucleophilic substitutions. In an electrophilic substitution reaction, the electrophile reacts preferentially at the lone pair of the nitrogen to generate a pyridinium ion. The pyridium ion being a positively charged ion, is unreactive towards further electrophilic substitution. eutral pyridine can react with various electrophiles at other positions (i.e at carbon atoms), but the reaction is slow. In this work, we were focusing on the nucleophilic substitution reaction of - and -halogenated pyridine as the substrate, and various amines were used as the nucleophiles. 9

2 oordini Mohd Salleh et al.: SYTHESIS AD FLUOESCECE CHAACTEISTIC OF -- ' O CH C CO CH + 'CHO H H CO C CO CH H CO CH HO ' CO CH Scheme 1 The numbering system universally used for pyridine is shown in Figure 1. 1 Figure 1 The work was then further extended to study the fluorescence characteristic of various aminopyridine derivatives prepared. This is due to the fluorescence characteristic of pyridine or other heterocycles are not extensively studied and well reported, eventhough a wide variety of heterocylic compounds are known to be fluorescent [-7]. This paper will report on the preparation of --anilinopyridine and --anilinopyridine and their fluorescence characteristics. Experimental Synthesis --Anilinopyridine -Chloropyridine (1.0 ml) was added to aniline (1.0 ml) and refluxed for 7 hours. The mixture was cooled and evaporated. The slurry was extracted with ether ( x 10 ml) and washed with water and dried over anhydrous sodium sulphate. Evaporation of ether gave dusty pink solid. %, m.p: 119 o - 1 o C, I (cm -1 ): 190, 10, 180 ppm; 1 H M (CDCl ) δ?8.1, d, 1H (H), 7., m, 1 ( H), 7., m, H (H, H, H, H ),.99, m, 1H (H ),.8, d, 1H ( H),., t, H (H, H); M + : requires: Anilinopyridine -Chloropyridine (0.1 ml) was added to aniline (0.1 ml) and refluxed for hours. The mixture was cooled and evaporated. The slurry was extracted with ether ( x 10 ml) and washed with water and dried over anhydrous sodium sulphate. Evaporation of ether gave brownish liquid. 8.%, I (cm -1 ): 190, 10, 180 ppm; 1 H M (CDCl ) δ?8., s, 1H (H), 8., d, 1H (H), 7.0, d, 1H ( H), 7.0, t, 1H (H),7.10, t, H (H & H ),.80, t, 1H (H),.70, t, H (H, H & H ); M + : requires: Spectroscopic analysis All solvents were redistilled before use. Melting points were determined with Electrothermal Melting Point Apparatus and were not corrected. Infrared spectra were recorded using Perkin Elmer 98 Infrared Spectrometer and FTI Perkin Elmer 100 Series. 1 H M spectra were recorded on JEOL JM -LA00FT 0

3 The Malaysian Journal of Analytical Sciences, Vol 11, o 1 (007): 9- M System. Mass spectrum was recorded using GCMS Hewlett-Packard HP 890 Series with mass selective indicator. Fluorescence Studies --Anilinopyridine and --anilinopyridine with the same concentration (.1 X 10 - M) were prepared in ethanol, tetrahydrofuran, ethyl acetate and acetonitrile. The fluorescence measurement was carried out in a quartz cell, using Fluorescence Spectrometer Model F-000 Hitachi at room temperature with the same instrument setting. esults and Discussion --Anilinopyridine (1) and --anilinopyridine () were obtained when commercially available - chloropyridine () and -chloropyridine () was reacted with aniline respectively, as shown in Scheme. The structures of both compounds were confirmed by infrared, 1 H M, 1 C M and mass spectra. H Cl H 1 + HCl -Chloropyridine ( ) --Anilinopyridine ( 1 ) H Cl H 1 + HCl -Chloropyridine () Scheme --Anilinopyridine ( ) The 1 H-M spectrum of compound (1) showed a doublet at δ 8.1, which was due to C of pyridine ring. A doublet at δ 7. was due to H proton. A multiplet was recorded at δ 7., was due to proton resonance at C, C, C and C of the aniline ring. A multiplet peak was observed at δ.99, which was due to proton on C. In aromatic region, a doublet peak was observed at δ.8, which due to C proton, and a triplet at δ., which was due to protons on C and C of pyridine ring. The 1 C-M spectrum showed a relatively low intensity absorption peak at δ 1.88, which was due to quaternary carbon C of the pyridine ring. A medium absorption peaks at δ 18.1 and δ were assigned to carbon C and C of pyridine ring. One absorption peak at δ was due to the C and C of the benzene ring. A peak at δ 19.9 was assigned to C of pyridine ring. Two absorption peaks at δ and δ 108. were assigned to C, C and C of benzene ring. One peak at δ 108. was due to C of pyridine ring. The gas chromatography mass spectrum (GCMS) led to the molecular formula C 11 H 10 and M + was recorded at The fragmentation pattern of, -anilinopyridine is as suggested in Scheme. 1

4 oordini Mohd Salleh et al.: SYTHESIS AD FLUOESCECE CHAACTEISTIC OF -- H - H + m/e 170. m/e 19 H + m/e 79 Scheme The 1 H-M spectrum of compound () on the other hand showed a singlet at δ 8., which was due to proton on C of the pyridine ring. Two doublet peaks were observed at δ 8. and δ 7.0, which were due to protons on C and C of pyridine ring. A triplet peak at δ 7.0, was due to proton on C of pyridine ring. Two triplet peaks were observed at δ 7.10 and δ.80, which were due to protons on C, C and H of the anilino ring. A multiplet was observed at δ.70, which was due to protons on C, C and C of the anilino ring. The 1 C- M spectrum of compound showed peaks of relatively low intensity at δ 18.8 and δ 1.7, which were due to carbon C and C. A peak at δ 17.7 was assigned to C and C1. A peak at δ 1.7, was due to carbon C and C. Absorption peaks recorded at δ 1.11, δ 1.7 and δ were due to carbon C, C and C. A peak observed at δ 11.0 was due to carbon C and C. The gas chromatography mass spectrum (GCMS) led to the molecular formula C 11 H 10 and M + was recorded at The fragmentation pattern of, -anilinopyridine is also same as suggested in Scheme. The fluorescence studies of these two compounds were carried out in tetrahydrofuran, ethanol, ethyl acetate and acetonitrile. The concentrations of these compounds were the same and the measurements were taken at room temperature. Table 1 and show the fluorescence characteristic of --anilinopyridine and --anilinopyridine in various solvents It can be seen form Table 1 that, --anilinopyridine showed the highest fluorescence intensity in tetrahydrofuran, followed by ethyl acetate for both capped and uncapped conditions. The high fluorescence intensity recorded in tetrahydrofuran is maybe due to the formation of a complex with the solvent through hydrogen bonding as suggested in Figure 1.

5 The Malaysian Journal of Analytical Sciences, Vol 11, o 1 (007): 9- Table 1: Fluorescence characteristic of --anilinopyridine in various solvents (.1 X 10 - M) Condition Solvent Excitation Fluorescence Intensity/I wavelength/nm Wavelength/nm Capped Ethanol Acetonitrile Ethyl acetate Tetrahydrofuran Uncapped Ethanol Acetonitrile Ethyl acetate Tetrahydrofuran This complex enhanced the p? p* transition in the excited state, resulting in high fluorescence intensity. However the study on the effect of tetrahydrofuran on the fluorescence of diazines system is still undergoing before any concrete conclusion can be made. H O 18 Figure Tetrahydrofuran Ethyl Acetate Intensity/I Wavelength/nm Figure Fluorescence spectra of --anilinopyridine in tetrahydrofuran and ethyl acetate for capped samples The fluorescence intensity of --anilinopyridine in ethyl acetate was recorded as 1. (18.7 in tetrahydrofuran), when excited at 8 nm, and fluoresced at 8 nm (Figure ). As explained for -anilinopyridine in tetrahydrofuran earlier, it is believed that a hydrogen-complex may also formed when ethyl acetate is used as the solvent, as shown in Figure below.

6 oordini Mohd Salleh et al.: SYTHESIS AD FLUOESCECE CHAACTEISTIC OF -- CH H O COCH CH Figure The lower intensity of --anilinopyridine in ethyl acetate compared to when tetrahydrofuran was used as the solvent is probably due to the complex formed in ethyl acetate is less rigid than the complex formed in tetrahydrofuran. The -CH and O-CH CH group of ethyl acetate may increase the vibrational amplitude of the complex, and the resultant energy absorbed is dissipated as heat. As the result low fluorescence intensity was observed. Table shows the fluorescence characteristic of --anilinopyridine in various solvents. --Anilinopyridine showed maximum fluorescence intensity in acetonitrile and followed by tetrahydrofuran. Table : Fluorescence characteristic of --anilinopyridine in various solvents (.1 X 10 - M) Condition Solvent Excitation Fluorescence Intensity/I wavelength/nm Wavelength/nm Capped Acetonitrile Tetrahydrofuran Ethanol 0.07 Uncapped Acetonitrile 8 0. Tetrahydrofuran Ethanol 0. High fluorescence intensity observed in acetonitrile is probably due to the hydrogen-bonding acceptor of the solvent which stabilized the charge deficient amino group in the excited state and the p? p* transition state is more favorable. As the result high fluorescence intensity was observed. The higher intensity in acetonitrile is also probably due to the dielectric properties of this solvent as well as its polarity. It has been reported [8] that solvent polarity produce a greater stabilization of the p? p* excited state, which results in high fluorescence intensity. Figure shows the fluorescence spectra of --anilinopyridine in tetrahydrofuran and acetonitrile for capped condition. The fluorescence studies of both compounds in various solvents were carried in capped and uncapped conditions, as shown in Table and. In general, the fluorescence intensity of the compounds studied in capped condition is higher than the uncapped condition.

7 The Malaysian Journal of Analytical Sciences, Vol 11, o 1 (007): Tetrahydrofuran Acetonitrile Intensity wavelength, nm Figure : Fluorescence spectrum of --anilinopyridine in tetrahydrofuran and acetonitrile Table : Fluorescence characteristic of --anilinopyridine in acetonitrile with time. Condition Duration/min Excitation Fluorescence Intensity/I wavelength/nm Wavelength/nm Capped Immediately Uncapped Immediately Table : Fluorescence characteristic of --anilinopyridine in ethanol with time. Condition Duration/min Excitation Fluorescence Intensity/I wavelength/nm Wavelength/nm Capped Immediately Uncapped Immediately The low fluorescence intensity for uncapped sample is believed to be due to the unlimited amount of oxygen in the quartz cell, and therefore quenched the fluorescence intensity of the compounds [9]. Oxygen, which has an unusually large diffusion coefficient, and on prolong exposure of the solution to the atmosphere, could result in large quantity of oxygen diffusing into solution [10]. Similar results were obtained with other heterocycles studied [11]. It can also be seen from Table and that the fluorescence intensity of both compounds decreases with time. educed fluorescence intensity observed with time is also believed to be due to the quenching effect of oxygen. Figure and 7 shows the fluorescence spectra of --anilinopyridine and --anilinopyridine with time.

8 oordini Mohd Salleh et al.: SYTHESIS AD FLUOESCECE CHAACTEISTIC OF min 0 min 0 min Intensity 10 min wavelength/nm 00 Figure : Fluorescence peaks of --anilinopyridine with time intensity min 0 min 0 min 10 min wavelengh/nm Figure 7: Fluorescence peaks of --anilinopyridine with time Conclusion --Anilinopyridine showed the highest fluorescence peak in tetrahydrofuran, while - -anilinopyridine showed the highest fluorescence peak in acetonitrile. The fluorescence intensity of capped sample is higher than uncapped sample. Fluorescence peak was also reduced with time for both compounds. Acknowledgments Financial support of this work by the Academy of Science under SAGA grant is gratefully acknowledged. eferences 1. Dehmlow E.V, Dehmlow S.S., (1980), Phase Transfer Catalysis Verlag Chemie, 1980, Vol II.. Badger G.M., The Chemistry of Heterocyclic Compounds. Adelaide, South Australia (191).. Joule J.A., Mills K., Smith G.F., Heterocyclic Chemistry. Chapman and Hall, ew York (199).. Acheson.M., An Introduction to the Chemistry of Heterocyclic Compounds. John Wiley and Sons, ew York (197).. Bridges J.W., Davies D.S, William.T. (19), Biochem J, 98, 1.. Abdullah Z., Bakar M. A. A., Awang Din E. I., Abd. ani.., Mohd Salleh., Leong G. P., Ling L. P. and Aiyub Z., (00), Malays. Jour. of Anal. Science, accepted. 7. Abdullah Z., Mohd Tahir., Abas M.., Low B.K. and Aiyub Z. (00), Molecules, 9, A. Weisstuch and A. C. Testa., (1970), J. Phy. Chem.., 7, Haroutounion S.A and Katnezellenbogen (1988), J.A, Photochem. and Photobio., 7, Haroutounion S.A and Katnezellenbogen J.A (199), Tetrahedron, 1,, Z.Abdullah, M. A. A. Bakar, M. A. Mohd Sharifuddin, Z. Aiyub, (00), Int. Jour. of Chem. Sci., (1), 9-.