Aromaticity and Conformational Flexibility of Five-Membered

Struct Chem (2016) 27:101–109 DOI 10.1007/s11224-015-0707-4

ORIGINAL RESEARCH

Aromaticity and conformational ﬂexibility of ﬁve-membered monoheterocycles: pyrrole-like and thiophene-like structures

1 1,2 3 4,5 Irina V. Omelchenko • Oleg V. Shishkin • Leonid Gorb • Jerzy Leszczynski

Received: 13 November 2015 / Accepted: 18 November 2015 / Published online: 7 December 2015 Ó Springer Science+Business Media New York 2015

Abstract Aromaticity and conformational flexibility of Keywords Aromaticity Á Five-membered heterocycles Á the series of five-membered monoheterocycles with group Aromaticity indices Á Aromatic ring flexibility 14–16 heteroatoms, having one or two lone pairs, were studied with ab initio methods using NICS, ASE and I5 indices. For non-planar molecules like phosphole, aro- Introduction maticity of their planar transition states was also studied, and a special modification of ASE index was proposed to Five-membered aromatic heterocycles have been widely that end. It was found that the presence of two lone pairs is investigated because of their importance for biochemistry, generally preferable for aromaticity of all heterocycles medicine, technology and other aspects of life and industry except CPD and silolyl dianions. Heterocycles with group [1]. Aromaticity is a central concept in the chemistry of 16 heteroatoms have consistently lower aromaticity com- heterocycles; it is the main ground for classification and for pared to other groups. A lot of structures should be clas- rationalization of their properties and reactivity [2, 3]. Most sified as moderate aromatic and non-aromatic. Energies of of the popular quantitative indices of aromaticity were out-of-plane deformation do not correlate with other indi- developed and tested on the basis of both six- and five- ces studied, but reveal the same qualitative trends. Gener- membered heterocycles [4–7]. Degree of aromaticity of a ally, aromaticity of five-membered monoheterocycles great number of different five-membered heterocycles was depends strongly on both heteroatom type and number of carefully calculated and recalculated within the bounds of lone pairs on it. discussion about multidimensionality of aromaticity concept by Katritzky et al. [8–14]. It was concluded finally that for large number of different molecules under study there is Oleg V. Shishkin: Deceased. no statistically significant correlation between different aromaticity indices; however, any of them can be used for a & Irina V. Omelchenko rough classification of molecules into aromatic, non-aro- [email protected] matic and antiaromatic species [12].

1 Effect of heteroatom on aromaticity could be examined SSI ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkiv 61001, Ukraine by replacement of one (CH) group in carbocycle by iso- electronic heteroatomic group. It should considerably 2 V.N.Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv 61077, Ukraine change p-electron delocalization in the ring, primarily due to different electronegativity and atomic radii of carbon 3 Badger Technical Services, LLC, Vicksburg, MS, USA 4 atom and heteroatom [15]. For six-membered monohete- US Army ERDC, 3532 Manor Dr, Vicksburg, MS 39180, rocycles, it was found that aromaticity diminishes with the USA increasing heteroatom number, but all monoheterocyclic 5 Department of Chemistry and Biochemistry, Interdisciplinary analogues of benzene are highly aromatic [16]. Center for Nanotoxicity, Jackson State University, P.O. Box 17910, 1325 Lynch Street, Jackson, MS 39217, Cyclopentadienyl (CPD) anion is fully aromatic ﬁve- USA membered analogue of benzene with 6 p-electron system. 123 102 Struct Chem (2016) 27:101–109

However, aromaticity of known five-membered mono- analogues with 3rd row heteroatoms, with similar but a bit heterocycles varies in a much more wide range than of six- smaller degree of aromaticity [29, 30]. This is in consistent membered monoheterocycles. Even for well-studied with theoretical data on six-membered monoheterocycles molecules that have aromatic system formally analogous to [16]. Recent review about selenaheterocycles [31] shows benzene, it is very different. Pyrrole and thiophene are its similarity to thiophene. Arsole molecule was found to known to be highly aromatic, but furan is considered rather be non-planar and non-aromatic as well as phosphole, with as a non-aromatic molecule [15]. aromatic planar transition state, but inversion barrier of As A lower stability of other monoheterocyclic analogues atom is higher [21]. Germolyl anion is less stable and less of CPD anion hinders the experimental studies of their aromatic than silolyl anion, while its dianion is aromatic aromaticity [15]. Here the computational chemistry tech- again [32, 33]. niques come into play. Among such rare heterocycles, the One can note that listed molecules considered being phosphole is possibly the most studied one. Being formally monoheterocyclic analogues of CPD anion are not exactly similar to the highly aromatic planar pyrrole, the unsub- of the same type of electronic configuration of the five- stituted phosphole molecule was found to be non-aromatic membered ring. Pyrrole, phosphole and arsole, together and non-planar [17–20]. It was shown that a huge inversion with CPD, silolyl and germolyl anions, have only one lone barrier of tricoordinated phosphorous atom forces it to have pair (LP) on heteroatom that either involved or not into p- pyramidal geometry. That prevents conjugation of phos- system of the ring. Monoheterocycles with group 16 het- phorous lone pair with p-system of the ring [20]. Inversion eroatoms, pyrrolide and phospholide anions, as well as barriers grow significantly when moving down from N to silolyl and germolyl dianions, have two lone pairs, with Bi for group 15 tricoordinated atoms [21], while aromatic one of them involved (or not) into p-delocalization [15]. stabilization energy remains approximately the same [22]. The second type of heterocycles has notable electron Aromaticity of the planar transition state of phosphole was redundancy that can affect aromaticity. In the present work, predicted to be rather high [20]. we attempt to compare aromaticity of five-membered Another five-membered ring of great interest is silolyl monoheterocycles of both types (Scheme 1) within the anion, the CPD anion derivative with one carbon atom uniform approach and methods. That can help to locate substituted by Si atom. Chemistry of silaaromatic com- systematic changes depending on the heteroatom type. It pounds was considerably developed in the last decades, and also can be useful for comparison of the effect of het- the role of quantum chemical prediction for such unsta- eroatom on aromaticity of five- and six-membered mono- ble molecules is great [23]. For silolyl anion, the situation heterocycles with the same heteroatoms [16]. Since for six- with aromatic stabilization was found to be very similar to membered cycles the out-of-plane deformation energy was phosphole. Planar conformation of the molecule is a tran- found to be a good estimate of aromaticity or antiaro- sition state that has a significant degree of aromaticity [24]. maticity [34–36], applicability of this index for five- The equilibrium geometry of this anion is non-planar membered monoheterocycles was also comprehensively - because of the high inversion barrier of [SiC2H] moiety; tested. therefore, it is non-aromatic [23]. For both phosphole and silolyl anion, elimination of the ‘‘inversion problem’’ by removing of the proton from Methods of calculation heteroatom leads to significant increase in aromaticity. Silolyl dianions are known to be planar and highly aro- The structures of all molecules under consideration have matic [23–25]. Phopholide anion is highly aromatic too been optimized using the Møller-Plesset second-order [19, 20, 26]. Some anions of pyrrole derivatives are more perturbation theory [37] with Dunning’s correlation-con- aromatic than neutral forms, which indicates the presence sistent triple-zeta basis set [38] (MP2/cc-pVTZ method). of the same steric strain in pyrrole [27]. However, the Character of the stationary points on the potential energy inversion barrier of the nitrogen atom is much smaller than surface was checked by calculations of Hessian at the same aromatic stabilization energy of the planar ring [21]. It is interesting that the presence of electron-donating sub- 34 stituents increases aromaticity and decreases heteroatom X with one LP X with two LP's pyramidality in both phosphole [19, 28] and silolyl dianion CH-+NH OH C2-N - O [23], which forms intermediate structures between parent 2 5 non-aromatic CPD-like rings and their aromatic anionic SiH-+PH SH X Si2- P- S 1 states. GeH- AsH SeH+ Ge2- As- Se Heterocycles with heavier 4th row heteroatoms are less studied and generally considered to be very similar to their Scheme 1 Initial classification of the heterocycles under study 123 Struct Chem (2016) 27:101–109 103 level of theory; no imaginary eigenvalues for equilibrium order saddle point possibly due to the strong vibration geometries were found. For molecules that are non-planar coupling of lower modes; therefore, energy obtained during in the equilibrium state, also planar transition states were the partial geometry optimization with fixed planar con- TS located, with sole negative eigenvalues of Hessian matrix figuration of the [CC2H] moiety was taken for ASE for each, which corresponds to the X heteroatom inversion. estimation. The most stable conformations of rings were Aromaticity was estimated with several well-known taken throughout. All ASE calculations reported here indices [39] of structural (Bird’s I5 index [5]), magnetic include the zero-point energy (ZPE) correction. (NICS [6]) and energetic (ASE [40]) nature. All indices Conformational flexibility of rings was studied at the were calculated using the same level of theory. Bond same level of theory by scan of each of symmetry-inde- orders for Bird’s index calculation were obtained from pendent endocyclic torsion angles in the range ±30° with Wiberg indices [41] calculated in the frame of NBO 5° steps. All remaining geometrical parameters were opti- analysis [42]. Nucleus-independent chemical shifts were mized at every point of the scan. For each molecule, the calculated as the zz-component of the magnetic shielding angle with the smallest deformation energy E(def)30 (dif- tensor at the point located by 1 A˚ above the geometrical ference in energy between planar and twisted on 308 center of the ring (NICS(1)zz) for obtaining more reliable geometries) was chosen. Detailed description of the pro- data [6]. For non-planar structures, a root-mean-square cedure was provided in our earlier works [34, 43, 44]. average plane of all five non-hydrogen atoms was used as While E(def)30 value is proper only for planar aromatic the (xy) plane, and NICS(1) values both above and below it rings, we tried to estimate deformation energy also for non- were calculated. It was found that NICS(1) values mea- planar rings, by averaging of the values of scan on ?308 sured on the same side of the ring with H atom of X(EH) and -308. group are consistently higher (up to 5 ppm), possibly due Degree of pyramidality, P, was calculated as to contribution of the electrons of E–H bond; therefore, P = 360° - V, where V is the sum of valence angles NICS(1) values measured on the opposite side were used. centered on corresponding atom. Hence, P is zero for Aromatic stabilization energies (ASEs) were calculated atoms having planar configuration. using the homodesmotic reaction shown in Scheme 2.This All calculations have been performed using the Gaus- scheme provides the most reliable results for a wide range sian 09 [45] and NBO5.0 [46] program packages. of aromatic, non-aromatic and antiaromatic five-membered rings [40]. For all heterocycles that contain a hydrogen atom bonded with heteroatom, a special modification of Results and discussion this reaction was developed. Values obtained with this modification are denoted here as ASETS. It specifies using Five-membered monoheterocycles with one lone of the energies of transition states with planar heteroatom pair on heteroatom configuration for all structures C4H4X, C4H6X and C4H8X in Scheme 2 rather than their equilibrium state energies. Generally, aromaticity indices obtained for molecules with That scheme allows to eliminate energetic contribution of group 14 and 15 heteroatoms are in consistent with pre- inversion barrier into ASE result and to estimate pure vious findings: In the equilibrium non-planar state (see aromatic stabilization even for transition states of the Fig. 1), phosphole [19], as well as with silolyl and ger- molecules. For all partially and fully hydrogenated hete- molyl anions [12, 32], demonstrates low aromaticity rocycles, transition states that correspond to heteroatom degree, while CPD anion and pyrrole are highly aromatic inversion were located and checked by Hessian calculation. [15]. Protonated forms of the furan, thiophene and sele- - Only for cyclopentyl anion C5H9 , we failed to locate first- nophene did not attract much attention of researchers yet, but broader outlook including these molecules shows that

+ + 2 X X

2 + + X Fig. 1 Typical non-planar equilibrium structure of ﬁve-membered Scheme 2 Homodesmotic scheme for ASE calculation ring with heavier heteroatom 123 104 Struct Chem (2016) 27:101–109

? all heavy analogues of CPD anion, with one lone pair, are the group for all cycles except C4H4OH that is almost non-aromatic. The aromaticity degree drops down the planar but non-aromatic. Generally, this consistency group, and at the same time, it diminishes with increasing reflects interplay between p-conjugation and inversion heteroatom number along the row (Table 1). Aromaticity energies: While the former is assumed to lower slightly ? indices show roughly the same trends. The C4H4OH down the group, the later grows rapidly. This is discussed cation falls out of this trend because of its low structural in next section. ? aromaticity (I5 = 3), while bond orders in C4H4SH and ? C4H4SeH cations are much more uniform (I5 = 26 and Transition states and inversion barriers of five- 21). It should be noted that I5 value of CPD anion membered monoheterocycles with one lone pair (I5 = 100) formally equal to benzene (I6 = 100) does not mean indeed the equal aromaticity of these molecules but Inversion barrier grows significantly with the increasing the is a consequence of the definition of the Bird index: Ref- heteroatom number within the group as well as within the erence structures for I5 and I6 are different (see the com- row. For phosphole and arsole, they are negligibly lower prehensive paper of Kotelevskii and Prezhdo [7]). NICS than obtained earlier by Pelzer et al. [21] at the same level and ASE indices per contra show lower aromaticity of of theory; for silolyl and germolyl anions, values are twice protonated thiophene and selenophene, even up to small lower than calculated previously by Schleyer et al. with energetic destabilization of these aromatic structures. If B3LYP/6-31?G(d,p) method [32]. The later two hetero- ? one excludes C4H4OH structure from the dataset, high cycles have the lowest inversion barriers that are compa- correlation coefficients between indices can be found rable with the energy of thermal motion. Molecules with ([0.90), similarly to six-membered monoheterocycles [16]. group 15 heteroatoms have moderate barriers. It is known However, those values are mainly due to a clear dividing of that at room temperature phosphole undergoes inversion all molecules on two groups, aromatic and non-aromatic, [20]. Heterocycles with heavier group 16 heteroatoms while there are no such correlations inside each group. This should hardly undergo inversion. In spite of correlation of phenomenon was discussed in detail by Cyranski et al. inversion energy with the degree of aromaticity, one should [12]. remember that it is result of balance of two factors: The In compliance with these trends, silolyl anion should first is aromatic stabilization, and the second is steric strain demonstrate the higher aromaticity among all structures of tricoordinated heteroatom that has no relation with with heavier atoms, and it does indeed: Its aromaticity is aromaticity. 59 % relative to CPD anion (cf. 69 % for planar pyrrole) According to different estimates, aromaticity of phosp- according to structural criteria, 72 % according to NICS hole [22] and silolyl anion [24] should be significant for the index, but only 39 % according to ASE (the percentage planar transition states of these structures. Results of cal- was obtained by dividing the aromaticity index on the culation show that NICS and I5 indices for all molecules in corresponding index of CPD anion and multiplying the planar transition states are notably higher than those in quotient on 100 %). However, it is the highest ASE value non-planar states; heterocycles with group 14 and 15 het- in this series of molecules after CPD anion and pyrrole. It eroatoms are highly aromatic, heterocycles with group 16 cannot be classified as non-aromatic structure still but heteroatoms are less aromatic, and aromaticity of proto- should be considered not highly aromatic. It is interesting nated pyrrole is almost identical for planar and non-planar that the degree of pyramidality of heteroatom grows within geometries and corresponds to a non-aromatic structure. That is consistent with negligibly low inversion barrier of ? C4H4OH (1.3 kcal/mol). At the time, ASE values corre- Table 1 Aromaticity indices and heteroatom pyramidalities (P) of spond to non-aromatic and even antiaromatic structures (up five-membered monoheterocycles with one lone pair on heteroatom to -31.6 kcal/mol). At the first glance, one can point out NICS(1)zz, ppm I5 ASE, kcal/mol P, ° the case of discrepancy of magnetic and structural indices - with energetic index. However, the origin of discrepancy is C5H5 -35.6 100 24.5 0 - obviously the steric strain in the most heterocycles. Hence, C4H5Si -25.7 59 9.7 32 - it should be emphasized that classical ASE is reliable only C4H5Ge -15.8 32 6.7 59 for equilibrium geometries in that case. To eliminate this C4H4NH -33.9 69 21.4 0 steric strain contribution, we calculated modified ASETS C4H4PH -16.9 33 3.6 65 index that reflects pure energy of aromatic stabilization for C4H4AsH -11.6 23 1.8 78 planar structures but has nothing common with the total C H OH? -20.8 3 3.6 16 4 4 energetic stabilization of the molecules. Procedure is C H SH? -14.3 26 -0.8 68 4 4 described above in ‘‘Methods.’’ ASETS values are fully C H SeH? -10.1 21 -1.6 78 4 4 consistent with other aromaticity indices. For CPD anion 123 Struct Chem (2016) 27:101–109 105 and pyrrole molecule, the energy gain is low (3–4 kcal/- planar aromatic states, but in general, their degree of aro- mol) but positive still. Molecules with heavier group 14 maticity remains moderate. Furan demonstrates the lowest and 15 heteroatoms have stabilization energies of structural aromaticity and moderate value of aromatic 84–104 % as compared to CPD anion, while ASETS for stabilization energy; however, its NICS value is high and molecules with heavier group 16 heteroatoms is almost corresponds to a fully aromatic structure. Furan reveals twice lower and stabilization of protonated furan molecule chemical reactivity similar to dienes but not typical for is the lowest. It should be noted that stabilization energies aromatic molecules [15] and so is usually classified as non- in all three groups have a maximum on the molecule with aromatic, despite the high NICS indices. In both groups, the 3rd row heteroatom. (NICS index demonstrates the molecules with the 3rd row heteroatoms demonstrate same only for group 16 heteroatoms, while I5 index—for maximal values of ASE, similarly to transition states of group 15 and group 16.) Among six-membered mono- corresponding molecules discussed in previous section. heterocycles, the similar behavior was found only for group The most controversial case is aromaticity of dianions 16 heteroatoms [16]. It is remarkable that aromatic stabi- with group 14 heteroatoms. One can note extremely high lization energy does not diminish with the increasing the values of NICS and I5 indices of CPD and silolyl dianions heteroatom number; quite the contrary, aromatic p-delo- that are higher than ones of CPD anion. At the time, ASE calization in the rings with heavier heteroatoms is more values are very low (\50 % of CPD anion). Adding of the favorable than in the rings with the 2nd row atoms. extra lone pair is energetically unfavorable for aromatic systems of these dianions: ASE is almost twice lower than Five-membered monoheterocycles with two lone ASETS for the corresponding monoanions (Table 2), while pairs other aromaticity indices are similar. This effect is the most pronounced in the case of carbocyclic CPD dianion and the Most of heterocycles with heteroatom bringing two lone less pronounced in germolyl dianion; ASE grows down the pairs are highly aromatic (85–105 % of CPD anion aro- group. maticity according to NICS, 45–92 % according to I5 and 46–100 % according to ASE). The discrepancy between Energies of out-of-plane deformations different indices in that case is much higher as compared to previously discussed structures. NICS values pre- It was found in many earlier studies that strongly bent dictable diminish within the group, except the case of aromatic rings in cyclophanes [47–49] and pyrenophanes group 16 heteroatoms, similarly to six-membered hetero- [50, 51] retain relatively high degree of aromaticity. cycles [16]. I5 values show the same trend except the Energies of the out-of-plane deformation E(def) were tes- unexpectedly low value for silolyl dianion as compared to ted and found to be a reasonable aromaticity measure for germolyl dianion. As for ASE, we can point out that an series of highly aromatic molecules, particularly six- extra lone pair is the most energetically favorable factor for membered monoheterocycles [16] and substituted benzene heterocycles with group 15 and 16 heteroatoms. Pyrrolide derivatives [43, 52]. For different classes of molecules, anion has the same value of ASE as pyrrole; phospholide different correlations between deformation energies and and arsolide anions demonstrate ASE values similar to other aromaticity indices were found, that is generally ASETS value of the planar aromatic states of phosphole and typical for any index [12]. The problem appears when arsole (Tables 2, 3). Furan, thiophene and selenophene are trying to estimate deformation energy for rings with low slightly more aromatic than their protonated forms even in aromaticity, where dependence of the total energy on the

Table 2 Aromaticity indices of NICS(1) , ppm I ASE, kcal/mol ASETS, kcal/mol IB, kcal/mol the planar transition states and zz 5 inversion barriers (IB) of ﬁve- - C5H5 -35.6 100 24.5 28.9 (\0) membered monoheterocycles - with one lone pair on C4H5Si TS -31.1 79 7.2 30.2 3.2 - heteroatom C4H5Ge TS -31.2 80 0.3 28.8 6.7

C4H4NH -33.9 69 21.4 24.4 (\0)

C4H4PH TS -33.5 80 -9.2 29.5 13.7

C4H4AsH TS -32.2 74 -19.7 26.2 22.5 ? C4H4OH TS -23.0 6 3.3 7.4 1.3 ? C4H4SH TS -29.8 51 -22.4 16.0 23.4 ? C4H4SeH TS -27.3 43 -31.6 14.1 32.1 For ASETS estimation, see ‘‘Methods’’ section

123 106 Struct Chem (2016) 27:101–109

Table 3 Aromaticity indices of ﬁve-membered monoheterocycles deformation energy is about 2.5 kcal/mol that should cor- with two lone pairs on heteroatom respond to non-aromatic structure. However, it was shown

NICS(1)zz, ppm I5 ASE, kcal/mol that silolyl anion has the moderate degree of aromaticity. In general, the conformational flexibility does not cor- 2- C5H4 -37.4 90 11.3 relate with any aromaticity index for five-membered 2- C4H4Si -32.4 73 12.2 monoheterocycles. However, some interrelation could be 2- C4H4Ge -32.1 75 16.6 found. Firstly, heterocycles with lighter heteroatoms - C4H4N -36.5 92 21.4 demonstrate generally lower flexibility, with the ‘‘softest’’ - C4H4P -34.8 84 24.6 angle that involves heteroatom (1-2-3-4 or 2-3-4-5). For all - C4H4As -33.5 79 23.4 groups, the flexibility grows with increasing heteroatom C4H4O -30.3 45 15.1 number. That generally corresponds to NICS estimation, C4H4S -32.7 67 19.3 with certain exceptions, namely silolyl anion and furan. C4H4Se -30.2 61 17.2 Flexibility of protonated furan is higher than one of pyrrole and CPD anion that matches NICS and ASE estimations of their aromaticity. Also, flexibility of dianions with group 14 heteroatoms is higher than that of anions with group 15 torsion angle is far from harmonic near the energy minima heteroatoms that correspond to ASE changes. But rings [52]. In the case of five-membered monoheterocycles, with group 16 heteroatoms also demonstrate high defor- series of non-planar molecules is an intricate case indeed. mation energies that do not match their moderate degree of Apart from potential energy surface (PES) anharmonicity, aromaticity. the Cs symmetry causes inequality of deformation energies High flexibility of transition states of molecules with calculated during PES scanning in the two opposite heavier heteroatoms is the result of their high inversion directions. Also the starting geometry is non-planar. Get- barriers. In the case of arsole and protonated thiophene and ting round those difficulties, we calculated E(def) on ± 308 selenophene, the peak on the PES near planar ring con- for each of endocyclic torsion angle and used the lowest formation is very sharp and high, while increasing the mean value as estimation of deformation energy. Corre- energy with increasing of the torsion angle value up to 30° sponding angles and energies are given in Table 4. PES is moderate and smooth. anharmonicity near the planar geometry was ignored here. For transition states of heterocycles, E(def) values are Comparison of aromaticity of different types of five- simply a sum of E(def) value in equilibrium geometry and membered monoheterocycles with the same the inversion barrier value. heteroatoms For most rings, the ‘‘softest’’ torsion angle in heterocycles with heavier heteroatoms is 2-3-4-5 that corresponds Figures 2, 3 and 4 represent values or aromaticity indices to the hydrocarbon part of the ring. Therefore, deforma- of different types of the structures with the same heteroa- tions that involve heavy heteroatom are not energetically tom: molecules with one lone pair on the heteroatom, the favorable. The only exception is silolyl anion for which the same molecules in the planar configuration and molecules 5-1-2-3 angle involving Si atom is the softest. That anion with two lone pairs on heteroatom. Heterocycles are also reveals unexpectedly high flexibility: Value of arranged with lines in groups by heteroatoms, each type of

Table 4 Energies of E(def)30 Angle E(def)30 Angle E(def)30 Angle deformation on ± 308 for ﬁve- membered monoheterocycles - - 2- C5H5 14.5 1234 C5H5 14.5 1234 C5H4 11.8 1234 (kcal/mol) - - 2- C4H5Si 2.5 5123 C4H5Si TS 1.9 5123 C4H4Si 9.0 2345 - - 2- C4H5Ge 7.3 2345 C4H5Ge TS 0.8 2345 C4H4Ge 8.6 2345 - C4H4NH 14.0 5123 C4H4NH 14.0 5123 C4H4N 14.9 1234 - C4H4PH 8.6 2345 C4H4PH TS -4.7 2345 C4H4P 11.0 2345 - C4H4AsH 7.4 2345 C4H4AsH TS -14.6 2345 C4H4As 9.9 2345 ? ? C4H4OH 9.4 5123 C4H4OH TS 8.9 5123 C4H4O 15.5 1234 ? ? C4H4SH 8.4 2345 C4H4SH TS -14.1 2345 C4H4S 11.3 2345 ? ? C4H4SeH 7.3 2345 C4H4SeH TS -23.7 2345 C4H4Se 9.9 2345 The torsion angles that correspond to the minimum deformation energies are marked. Atom numbering can be found in ‘‘Introduction’’ section

123 Struct Chem (2016) 27:101–109 107

Fig. 4 I5 values for different types of ﬁve-membered heterocycles, Fig. 2 ASE values for different types of ﬁve-membered heterocycles, sorted by heteroatom. The legend is given in Fig. 2 sorted by heteroatom. For molecules in planar transition states, ASETS is given for ASE NICS index reveals the maximal difference between the high and low aromatic and low aromatic rings. On the

contrary, estimation by ASE and I5 indices rates a great number of heterocycles as having an intermediate aromaticity degree. Also NICS index is consistently higher for all heterocycles with two LPs that can be a consequence of the general electron redundancy of the ring.

Summary

Five-membered monoheterocycles with groups 14–16 heteroatoms could be classified on two groups by the number of lone pairs on the heteroatom. Among molecules with sole LP, only CPD anion and pyrrole can be classified as aromatic, while silolyl anion has moderate aromaticity and others are non-aromatic. The steric strain of the rings is Fig. 3 NICS(1)zz values for different types of five-membered the main factor that violates aromaticity of heterocycles heterocycles, sorted by heteroatom. The legend is given in Fig. 2 with a heavier atom: Analysis of planar transition states of these molecules revealed their high degree of aromaticity. structure denoted by it’s own mark on the plot (see legend However, that does not concern rings with group 16 het- in Fig. 2). eroatoms that remain non-aromatic even in planar It can be found that aromaticity of five-membered conformation. monoheterocycles strongly depends on both heteroatom The presence of the second LP is favorable for aro- type and p-system structure. At the time, different indices maticity of the most molecules under study, primarily with are not consistent. Some consistency can be found only for group 15–16 heteroatoms. Only CPD and silolyl dianions heterocycles with one LP in equilibrium geometry, because reveal low aromatic stabilization energies, but high values of the strong difference between aromatic and non-aro- of NICS and I5 indices. Interestingly, adding of the second matic structures. However, indices of ‘‘aromatic’’ type LP to the structure is more favorable for molecules with structures are not far from ‘‘non-aromatic’’ type ones; see heavier heteroatoms: Changes of aromaticity within the low ASE values for dianions with group 14 atoms or I5 group in many cases reveal maximum that corresponds to values for all molecules with group 16 atoms. Generally, the 3rd row heteroatom. the later group reveals minimal aromaticity among all other Energies of out-of-plane deformation are rather low as structures. compared to the six-membered heterocycles from our

123 108 Struct Chem (2016) 27:101–109 previous study [16]. They generally do not correlate with 17. Nyula´szi L (1995) Effects of substituents on the aromatization of aromaticity indices, but qualitatively reveal the similar phosphole. J Phys Chem 99:586–591. doi:10.1021/j100002a021 18. Nyula´szi L (2000) Aromatic compounds with planar tricoordinate trends. phosphorus. Tetrahedron 56:79–84. doi:10.1016/S0040-4020 (99)00775-9 19. Nyula´szi L (2001) Aromaticity of phosphorus heterocycles. Chem Rev 101:1229–1246. doi:10.1021/cr990321x References 20. Nyula´szi L, Benko} Z (2009) Aromatic phosphorus heterocycles. Top Heterocycl Chem 19:27–81. doi:10.1007/978-3-540-68343-8_2 1. Pozharskii AF, Soldatenkov AT, Katritzky AR (2011) Hetero- 21. Pelzer S, Wichmann K, Wesendrup R, Schwerdtfeger P (2002) cycles in life and society: an introduction to heterocyclic chem- Trends in inversion barriers IV. The group 15 analogous of istry. Biochem Appl. doi:10.1002/9781119998372.fmatter pyrrole. J Phys Chem A 106:6387–6394. doi:10.1021/jp0203494 2. Balaban AT, Oniciu DC, Katritzky AR (2004) Aromaticity as a 22. Dransfeld A, Nyula´szi L, Schleyer PvR (1998) The aromaticity of cornerstone of heterocyclic chemistry. Chem Rev 104:2777– polyphosphaphospholes decreases with the pyramidality of the 2812. doi:10.1021/cr0306790 tricoordinate phosphorus. Inorg Chem 37:4413–4420. doi:10. 3. Simkin BY, Minkin VI, Glukhovtsev MN (1993) The concept of 1021/ic971385y aromaticity in heterocyclic chemistry. Adv Heterocycl Chem 23. Apeloig Y, Karni M (2009) Theoretical aspects and quantum 56:303–428 mechanical calculations of silaaromatic compounds. PATAI’S 4. Bird CW (1997) Absolute hardness as a convenient criterion of Chem Funct Groups. doi:10.1002/9780470682531 heteroaromaticity. Tetrahedron 53:3319–3324. doi:10.1016/S00 24. Goldfuss B, Schleyer PvR (1995) The Silolyl anion C4H4SiH-is 40-4020(97)00041-0 aromatic and the lithium silolide C4H4SiHLi even more so. 5. Bird CW (1992) Heteroaromaticity, 5, a unified aromaticity Organometallics 14:1553–1555. doi:10.1021/om00004a004 index. Tetrahedron 48:335–340. doi:10.1016/S0040-4020(01)88 25. Goldfuss B, Schleyer PvR, Hampel F (1996) Aromaticity in silole 145-X dianions: structural, energetic, and magnetic aspects. Organo- 6. Fallah-Bagher-Shaidaei H, Wannere CS, Corminboeuf C, Puchta metallics 15:1755–1757. doi:10.1021/om9503306 R, Schleyer PvR (2006) Which NICS aromaticity index for planar 26. Modelli A, Hajgato´ B, Nixon JF, Nyula´szi L (2004) Anionic pi rings is best? Org Lett 8:863–866. doi:10.1021/ol0529546 states of six-membered aromatic phosphorus heterocycles as 7. Kotelevskii SI, Prezhdo OV (2001) Aromaticity indices revisited: studied by electron transmission spectroscopy and ab initio refinement and application to certain five-membered ring hete- methods. J Phys Chem A 108:7440–7447. doi:10.1021/jp0480596 rocycles. Tetrahedron 57:5715–5729. doi:10.1016/S0040-4020 27. Krygowski TM, Szatylowicz H, Stasyuk OA, Dominikowska J, (01)00485-9 Palusiak M (2014) Aromaticity from the viewpoint of molecular 8. Katritzky AR, Barczynski P, Musumarra G, Pisano D, Szafran M geometry: application to planar systems. Chem Rev 114:6383– (1989) Aromaticity as a quantitative concept. 1. A statistical 6422. doi:10.1021/cr400252h demonstration of the orthogonality of classical and magnetic 28. Glukhovtsev MN, Dransfeld A, Schleyer PvR (1996) Why pen- aromaticity in five- and six-membered heterocycles. J Am Chem taphosphole, P 5 H, Is planar in contrast to phosphole, (CH) 4 PH. Soc 111:7–15. doi:10.1021/ja00183a002 J Phys Chem 100:13447–13454. doi:10.1021/jp9600827 9. Schleyer PvR, Jiao H, Goldfuss B, Freeman PK (1995) Aro- 29. Lee VY, Sekiguchi A (2010) Heavy Analogs of Aromatic maticity and antiaromaticity in five-membered C4H4X ring sys- Compounds. Organometallic compounds of low-coordinate Si, tems:‘‘classical’’ and ‘‘magnetic’’ concepts may not be Ge, Sn and Pb. doi:10.1002/9780470669266 ‘‘orthogonal’’. Angew Chem Int Ed Engl 34:337–340. doi:10. 30. Lee VY, Takanashi K, Kato R, Matsuno T, Ichinohe M, Seki- 1002/anie.199503371 guchi A (2007) Heavy analogues of the 6p-electron anionic ring 10. Nyula´szi L, Va´rnai P, Veszpre´mi T (1995) About the aromaticity systems: cyclopentadienide ion and cyclobutadiene dianion. of five-membered heterocycles. J Mol Struct (Thoechem) J Organomet Chem 692:2800–2810. doi:10.1016/j.jorganchem. 358:55–61. doi:10.1016/0166-1280(95)04338-1 2007.01.011 11. Katritzky AR, Karelson M, Sild S, Krygowski TM, Jug K (1998) 31. Młochowski J, Giurg M (2009) New trends in chemistry and Aromaticity as a quantitative concept. 7. Aromaticity reaffirmed application of aromatic and related selenaheterocycles. Top as a multidimensional characteristic. J Org Chem 63:5228–5231. Heterocycl Chem 19:288–340. doi:10.1007/7081_2008_7 doi:10.1021/jo970939b 32. Goldfuss B, Schleyer PvR (1997) Aromaticity in group 14 met- 12. Cyran´ski MK, Krygowski TM, Katritzky AR, Schleyer PvR alloles: structural, energetic, and magnetic criteria. Organome- (2002) To what extent can aromaticity be defined uniquely? J Org tallics 16:1543–1552. doi:10.1021/om960994v Chem 67:1333–1338. doi:10.1021/jo016255s 33. Lee VY, Sekiguchi A, Ichinohe M, Fukaya N (2000) Stable aromatic 13. Cyran´ski MK, Schleyer PvR, Krygowski TM, Jiao H, Hohlne- compounds containing heavier Group 14 elements. J Organomet icher G (2003) Facts and artifacts about aromatic stability esti- Chem 611:228–235. doi:10.1016/S0022-328X(00)00438-1 mation. Tetrahedron 59:1657–1665. doi:10.1016/S0040-4020(03) 34. Shishkin OV, Pichugin KY, Gorb L, Leszczynski J (2002) 00137-6 Structural non-rigidity of six-membered aromatic rings. J Mol 14. Alonso M, Herradoń B (2010) A universal scale of aromaticity Struct 616:159–166. doi:10.1016/S0022-2860(02)00328-9 for pi-organic compounds. J Comput Chem 31:917–928. doi:10. 35. Borbulevych OY, Shishkin OV (1998) Conformational flexibility 1002/jcc.21377 of antiaromatic 1,4 heterocyclic analogues of 1,4-cyclohexadiene. 15. Katritzky AR, Pozharskii AF (2010) Handbook of heterocyclic J Mol Struct 446:11–14. doi:10.1016/S0022-2860(97)00307-4 chemistry. In: Handbook of heterocyclic chemistry, 2nd ed. 36. Omelchenko IV, Shishkin OV, Gorb L, Hill FC, Leszczynski J Elsevier, Oxford, pp 1–138, 239–472 (2013) Substituent effects and aromaticity of six-membered 16. Omelchenko IV, Shishkin OV, Gorb L, Leszczynski J, Fias S, heterocycles. Struct Chem 24:725–733. doi:10.1007/s11224-012- Bultinck P (2011) Aromaticity in heterocyclic analogues of 0124-x benzene: comprehensive analysis of structural aspects, electron 37. Møller C, Plesset MS (1934) Note on an approximation treatment delocalization and magnetic characteristics. Phys Chem Chem for many-electron systems. Phys Rev 46:618–622. doi:10.1103/ Phys 13:20536–20548. doi:10.1039/c1cp20905a PhysRev.46.618

123 Struct Chem (2016) 27:101–109 109

38. Kendall RA, Dunning TH, Harrison RJ (1992) Electron affinities Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth of the first-row atoms revisited. Systematic basis sets and wave GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas functions. J Chem Phys 96:6796. doi:10.1063/1.462569 O¨ , Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 39. Minkin VI, Glukhovtsev MN, Simkin BY (1994) Aromaticity 09, Revision D.01 and antiaromaticity: electronic and structural aspects. Wiley, 46. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Boh- New York, pp 1–313 mann JA, Morales CM, Weinhold F (2001) NBO 5.0 40. Cyran´ski MK (2005) Energetic aspects of cyclic pi-electron 47. Jenneskens LW, Louwen JN, De Wolf WH, Bickelhaupt F (1990) delocalization: evaluation of the methods of estimating aromatic [4]Paracyclophane: MNDO and STO-3G molecular structure and stabilization energies. Chem Rev 105:3773–3811. doi:10.1021/ strain energy. J Phys Org Chem 3:295–300. doi:10.1002/poc. cr0300845 610030505 41. Wiberg KB (1968) Application of the pople-santry-segal CNDO 48. Jenneskens LW, De Kanter FJJ, Kraakman PA, Turkenburg method to the cyclopropylcarbinyl and cyclobutyl cation and to LAM, Koolhaas WE, de Wolf WH, Bickelhaupt F, Tobe Y, bicyclobutane. Tetrahedron 24:1083–1096. doi:10.1016/0040- Kakiuchi K, Odaira Y (1985) [5]Paracyclophane. J Am Chem 4020(68)88057-3 Soc 107:3716–3717. doi:10.1021/ja00298a051 42. Foster JP, Weinhold F (1980) Natural hybrid orbitals. J Am Chem 49. Jenneskens LW, Havenith RW, Soncini A, Fowler PW (2011) Soc 102:7211–7218. doi:10.1021/ja00544a007 Aromaticity of strongly bent benzene rings: persistence of a diat- 43. Shishkin OV, Omelchenko IV, Krasovska MV, Zubatyuk RI, ropic ring current and its shielding cone in [5]paracyclophane. Phys Gorb L, Leszczynski J (2006) Aromaticity of monosubstituted Chem Chem Phys 13:16861–16866. doi:10.1039/c1cp21950b derivatives of benzene. The application of out-of-plane ring 50. Bodwell GJ, Miller DO, Vermeij RJ (2001) Nonplanar aromatic deformation energy for a quantitative description of aromaticity. compounds. 6. [2]Paracyclo[2](2,7)pyrenophane. A novel strained J Mol Struct 791:158–164. doi:10.1016/j.molstruc.2006.01.019 cyclophane and a first step on the road to a ‘‘Vo¨gtle’’ Belt. Org 44. Shishkin OV (1995) Conformational flexibility of dihydropy- Lett 3:2093–2096. doi:10.1021/ol016053i rimidinone and tetrahydropyrimidine-2,4-dione rings in DNA 51. Bodwell GJ, Bridson JN, Cyran´ski MK, Kennedy JWJ, Kry- bases. J Chem Soc Chem Commun. doi:10.1039/c39950001539 gowski TM, Mannion MR, Miller DO (2003) Nonplanar aromatic 45. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, compounds. 8. Synthesis, crystal structures, and aromaticity Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson investigations of the 1, n-dioxa[n](2,7)pyrenophanes. How does GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, bending affect the cyclic pi-electron delocalization of the pyrene Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, system? J Organ Chem 68:2089–2098. doi:10.1021/jo0206059 Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao 52. Omelchenko IV, Shishkin OV, Gorb L, Hill FC, Leszczynski J O, Nakai H, Vreven T, Montgomery Jr. JA, Peralta JE, Ogliaro F, (2012) Properties, aromaticity, and substituents effects in poly Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, nitro- and amino-substituted benzenes. Struct Chem Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, 23:1585–1597. doi:10.1007/s11224-012-9971-8 Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C,

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