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Substituent Effect on the Aromaticity of 1,3-Azole Systems

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Substituent Effect on the Aromaticity of 1,3-Azole Systems Heterocycl. Commun., Vol. 18(1), pp. 11–16, 2012 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/hc-2011-0050 Substituent effect on the aromaticity of 1,3-azole systems Sel ç uk G ü m ü s¸ 1, * and Lemi T ü rker 2 shift (NICS) (Schleyer et al. , 1996 ), which is the computed 1 Department of Chemistry , Faculty of Sciences, value of the negative magnetic shielding at some selected Yuzuncu Yil University, 65080, Kamp ü s, Van , Turkey points in space, generally, in a ring or a cage center. Negative 2 Department of Chemistry , Faculty of Arts and Sciences, NICS values denote aromaticity (-11.5 for benzene, -11.4 for Middle East Technical University, 06531, Ankara , Turkey naphthalene) and positive NICS values denote antiaromaticity (28.8 for cyclobutadiene), whereas small NICS values indi- * Corresponding author cate non-aromaticity (-3.1 for 1,3-cyclopentadiene). NICS e-mail: [email protected] may be a useful indicator of aromaticity that usually corre- lates well with the other energetic, structural and magnetic criteria for aromaticity (Jiao and Schleyer , 1998 ; Schleyer Abstract et al. , 2000 ; Patchkovskii and Thiel , 2002 ; Quinonero et al. , 2002 ). Resonance energies and magnetic susceptibilities are The effects of substituent type and position on the aromaticity measures of the overall aromaticity of a polycyclic molecule, of certain derivatives of oxazole, imidazole and thiazole have but do not provide information about the individual rings. been theoretically investigated by using density functional However, NICS is an effective probe for local aromaticity of theory at the levels of B3LYP/6-31G(d,p) and B3LYP/6- individual rings of polycyclic systems. ++ 31 G(d,p) methods. The second heteroatom substitution Furan, pyrrole and thiophene are the most common fi ve- decreases aromaticity of furan, pyrrole and thiophene. The membered aromatic heterocycles. They show aromatic decreased aromaticity is gained back to some extent by the delocalization involving the unshared electrons located on substitution of strong electron withdrawing groups or atoms respective heteroatom of the ring system. The nitrogen atom of (NO and F). Nucleus-independent chemical shift (NICS) 2 pyrrole is of ideal size to permit extension of the conjugation data have been considered to determine the aromaticity of the around the entire ring leading the maximum aromatic char- systems. The most effective substitution to enhance the aro- acter among the three (Cordell and Boggs , 1981 ). Through maticity has been calculated to be at position 4. The variation the same argument of size alterations, furan and thiophene of the bond lengths of the main skeleton supports the fi ndings become less aromatic than pyrrole. through NICS calculations. The frontier molecular orbital Introduction of a second heteroatom, nitrogen in the pres- energies have also been reported to draw a general correlation ent case, creates azoles. By means of centric perturbation between these energies and the aromaticity of the system. at position 3, oxazole, imidazole and thiazole (1,3-azoles) are structurally obtained from furan, pyrrole and thiophene, Keywords: aromaticity; imidazole; nucleus-independent respectively. It is expected that the introduction of a second chemical shift (NICS); oxazole; thiazole. heteroatom (nitrogen) will reduce the aromaticity of the par- ent heterocyclic structures due to less effective ring current because of some electron localization arising from electrone- Introduction gativity of the nitrogen atom at the perturbed site. The aim of the present article was to investigate the substituent effect on Aromaticity continues to be an actively investigated area of the aromaticity of 1,3-azoles. The effects of type and the posi- chemistry of cyclic structures. It has been shown to be a useful tion of certain substituents on these systems have been theo- quantity in the rationalization of structure, stability and reac- retically studied by means of density functional theory (DFT) tivity of many molecules. The simplest criterion for aromatic calculations focusing a particular interest on NICS values. compounds is that they possess cyclic conjugated π -systems containing the proper number of π -electrons. Although this criterion is robust enough to predict the aromaticity of a host Method of calculation of neutral and charged ring systems, it is not always a clear indicator of aromaticity for more complex systems (Garrat , The geometry optimizations of all the structures were achieved 1986 ; Proft and Geerlings , 2001 ). within the framework of DFT (B3LYP) (Kohn and Sham , Aromaticity is expressed by a set of combinations of prop- 1965 ; Parr and Yang , 1989 ). The exchange term of B3LYP erties in cyclic delocalized systems. In general, aromaticity is consists of hybrid Hartree-Fock and local spin density (LSD) discussed in terms of energetic, structural and magnetic crite- exchange functions with Becke ’ s gradient correlation to LSD ria (Minkin et al. , 1994 ; Schleyer and Jiao , 1996 ; Glukhovtsev , exchange (Becke , 1988 ). The correlation term of B3LYP 1997 ; Krygowski et al. , 2000 ; Schleyer , 2001 ; Cyranski et al. , consists of the Vosko, Wilk, Nusair (VWN3) local correla- 2002 ). In 1996, Schleyer et al. introduced a simple and effi - tion functional (Vosko et al. , 1980 ) and Lee, Yang, Parr (LYP) cient probe for aromaticity: nucleus-independent chemical correlation correction functional (Lee et al. , 1988 ). The BLYP 12 S. G ü m ü s¸ and L. T ü rker method gives a better improvement over the SCF-HF results. ring current. This might be valid for fi ve-membered one het- Its predictions are in qualitative agreement with experiments eroatom containing systems. By contrast, if the heteroatom (Scuseria , 1992 ; Sosa and Lee , 1993 ; Wilson et al. , 2000 ). has already caused some electron population localization on 6-31G(d,p) and 6-31 + + G(d,p) basis sets were used for geom- itself, thus affecting proper ring current destructively, then etry optimizations. the electron withdrawing substituent may counter balance The normal mode analysis for each structure yielded no this localization effect to restore the ring current. Hence, imaginary frequencies for the 3 N -6 vibrational degrees of positional effects of substituents arise. Similar type of argu- freedom, where N is the number of atoms in the system. This ments could be asserted for electron donating substituents indicates that the structure of each molecule corresponds to at which may restore the already disturbed ring current pres- least a local minimum on the potential energy surface. ent in the parent ring system. The most stable isomer for Absolute nuclear magnetic resonance (NMR) shielding each series depends on the type of the substituent and there values (Pulay et al. , 1993 ) were calculated using the Gauge- is no general trend for nitro (NO2 ) and fl uoro (F) deriva- Independent Atomic Orbital method (Hehre et al. , 1986 ) with tives. However, substitution on position 2 creates the most the restricted closed shell formalism employing 6-31G(d,p) stable derivatives in the case of amino (NH2 ) substituted and 6-31 + + G(d,p) basis sets over B3LYP/6-31G(d,p) and heterocyclic systems, which can be attributed to the electron B3LYP/6-31 + + G(d,p) optimized geometries, respectively. donating ability of NH2 into the expectedly most electron NICS values were obtained by calculating absolute NMR defi cient point of the structures. For the NH2 substituted sys- shielding at the ring centers, NICS(0). tems, the stability order is 2 > 4 > 5 in terms of position of the The geometry optimizations and NICS calculations of substitution (Table 1 ). the present systems have been performed by the use of the Gaussian 03 package program (Frisch et al. , 2004 ). NICS The delocalization of a certain number of π -electrons freely Results and discussion in a ring accounts for the aromaticity in that ring which results in better stability. NICS is a measure of aromatic- General ity related to the magnetic properties of the ring under consideration. The effects of centric perturbation of a heteroatom to the cen- The most well-known aromatic compound is benzene tral ring and/or substitution of a heteroatom or a heterocy- where a perfect delocalization of six π -electrons exists. clic group with the hydrogen atoms of well-known aromatic Therefore, in an aromatic ring substitution of a heteroatom compounds have always found application in both theoreti- decreases the aromaticity of the system to some extent due cal and experimental studies. In the present study, 1,3-azoles to the electronegativity difference between carbon and other (oxazole, imidazole and thiazole) and their substituted (NO , 2 atoms. The aromaticity of that ring even decreases more with F, NH ) counterparts have been theoretically investigated 2 the substitution of a second heteroatom, as in the present by performing DFT calculations at the levels of B3LYP/6- case. However, this diminished aromaticity can be restored 31G(d,p) and B3LYP/6-31 + + G(d,p) to determine their sta- back, up to a certain extent, by the substitution of one of the bilities and aromaticities. hydrogen atoms of the system by certain atoms or groups, The structures and numbering of the compounds are given thus improving cyclic delocalization of the ring electrons, in Figure 1 . as explained above in the energetics section. In our case, the effects of substitution of the electronegative nitro group and Energetics the fl uorine atom, as well as the electron donating amino
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