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Substituent effects on the proton affinities of selenoamides: A theoretical study
Journal of Molecular Structure: THEOCHEM 805 (2007) 119–125 www.elsevier.com/locate/theochem
Substituent effects on the proton affinities of selenoamides: A theoretical study Damanjit Kaur *, Punita Sharma, Rupinder Preet Kaur, Mandeep Kaur, P.V. Bharatam
1
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India Received 31 March 2006; received in revised form 1 November 2006; accepted 1 November 2006 Available online 7 November 2006
Abstract The proton affinities of nine substituted selenoamides for their chalcogen and nitrogen sites have been evaluated theoretically at the MP2/6-31++G*//MP2/6-31+G* and B3LYP/6-31++G*//B3LYP/6-31+G* levels. Similar calculations have been done for substituted thio- and oxo-amides. The proton affinities for the chalcogen site are slightly higher than the corresponding values for nitrogen sites in all the amides. The proton affinities for both chalcogen and nitrogen site decrease in the order of X as Se > S > O. The electron donating substituents increase the proton affinities while the electron withdrawing substituents decrease the proton affinities. The NBO analysis indicates that nN ! pX–C interactions are dominant in neutral molecule. The role of substituent becomes apparent in the protonated specie where electron delocalization of the type nY ! pX–C and nY ! pC–N also become operative. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Amides; Proton affinities; NBO analysis; NPA; Substituents
1. Introduction The presence of substituents on any functional group can alter the properties of the functional group from very small to significantly large extent. As the variations in the properties stem from the interactions of substituents with the functional group, a number of studies have been performed to understand these interactions. Wiberg et al. analyzed the effect of substituents on carbonyl functional group using ab initio methods on acyl radicals [1]. The changes in electron population, bond order and atomic energies were analyzed as a consequence of the presence of substituents. They concluded that the presence of substituents NH2, OH and F stabilizes the carbonyl group through the interaction of lone pair of electrons on substituents with electron deficient carbonyl carbon and the columbic interactions of dipolar bonds. *
Corresponding author. Tel.: +91 183 2256736; fax: +91 183 258820. E-mail address: [email protected] (D. Kaur). 1 Present address: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and research (NIPER), S.A.S. Nagar (Mohali), 160062 Punjab, India. 0166-1280/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2006.11.001
The CN and CF3 groups possess positive charge at the carbon attached to carbonyl carbon and hence have repulsive interactions with the carbonyl carbon. The effect of substituents on thio carbonyl and carbonyl compounds have been analyzed by Abboud et al. by studying isodesmic reactions [2]. They observed that the presence of CH3, NH2, OH, F, and Cl substituents stabilizes the carbonyl compounds and the effect is more predominant on carbonyl in comparison to that on thiocarbonyl compounds. The p interaction of the lone pair of electrons on substituents with the p bond of carbonyl/thiocarbonyl and r bonds have been suggested as the reasons responsible for the stabilization. The amide functional group [3] is an essential structural unit of peptides and proteins that has attracted attention not only for understanding its thermodynamic properties [4] but also for designing peptide mimetics [5,6]. As a result, a number of experimental and theoretical studies have been involved in understanding of electron delocalization from the nitrogen lone pair towards the carbonyl/thiocarbonyl group in formamide and thioformamide respectively [7,8].
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In our earlier report, we tried to analyze the effect of substituents present on carbonyl carbon in amides and their thio and seleno analogs by analyzing the C–N rotational barriers [9]. The proton affinity of a molecule represents an important fundamental, gas phase thermodynamic property [10–12] that helps in understanding the intrinsic reactivity of isolated molecules without interference of solute solvent interactions [13]. A number of addition/elimination reactions in organic chemistry involving carbonyl compounds are known to be acid catalyzed [14]. The three dimensional structure of peptides and their biological activities are readily influenced by protonation [15]. Perrin has shown that the acid catalyzed proton exchange of peptides in an aqueous environment proceeds via a mechanism in which the imidic and [RC(OH)NR 0 R00 ] is an intermediate [16]. The proton affinity values help in understanding fragmentation patterns in mass spectrometry influenced by protonation and other proton transfer reactions, basicity of molecules and susceptibility toward electrophilic substitution. The effect of substituents on the stability of molecules and their protonated ions is of importance in order to distinguish the intrinsic molecular properties from the effect of surrounding medium [17,18]. Earlier results on proton affinities of amides indicate oxygen as the preferred protonation site rather than nitrogen, which is in contrast to the known results for NH3 and formaldehyde where the basicity for protonation for the former is 204 kcal/mol [19–21] while that of later is 172 kcal/mol [19]. The electron delocalization from nitrogen increases in the order O < S < Se in the molecules of type H2NC(@X)H (X = O, S, Se) as suggested in our earlier reports [9]. Gonezalez et al., in their study on basicity scale for selenocarbonyl compounds observed that these compounds behave as selenium bases in gas phase [22]. The thiocarbonyl and carbonyl compounds are also known to have chalcogen as preferred base center even in the presence of NH2 substituent. Selenocarbonyl derivatives are reported to be more basic than the corresponding thiocarbonyl compounds which in turn are more basic than their carbonyl analogs [23]. In the present studies the proton affinities of X (X = O, S, Se) and N sites in amides of type YC(=X)NH2 with Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH have been evaluated. The study provides gas phase basicities of these molecules and also the means to analyze the role of substituent on the stabilization of the molecules and their protonated species. The orbital interactions between the various orbitals have been analyzed by NBO analysis. 2. Computational details Ab initio MO [24,25] and density functional theory (DFT) [26,27] calculations have been performed using Gaussian 98W package, the windows version of Gaussian 98 suite of programs [28]. Complete optimizations were carried out on selenoamides and their thio- and oxo-analogs using HF, MP2 [29] and B3LYP [30–32] methods and
6-31+G* basis set without any symmetry constraints. When ever more than one stable conformation exists, the energy and parameters of most stable conformation are reported. Since these molecules possess several lone pairs of electrons, inclusion of diffuse functions was used to determine minimum energy conformation. To include electron correlation Optimizations were performed at MP2(FC)/ 6-31+G* and B3LYP/6-31+G* theoretical levels. Frequencies were computed for all the optimized structures in order to characterize each stationary point as a minimum or a transition state and to determine ZPE values. The ZPE values were scaled by a factor of 0.9153 at the HF/6-31+G* and by 0.9806 at the B3LYP/6-31+G* level [33]. Proton affinities were calculated at B3LYP/6-31++G*// B3LYP6-31+G* and MP2/6-311++G*//MP2/6-31+G*. NBO analysis was carried out to understand second order interactions [34,35]. Atomic charges were estimated using NPA method with MP2 densities at MP2/6-31+G* level. 3. Results and discussion The absolute energies of different substituted selenoamides, thioamides, and amides Y(C@X)NH2, Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, SH and their protonated species are given in supporting information in Tables S1–S3. The important geometrical parameters are also available in supporting information Tables S4–S9. The planarity of bonds around nitrogen in all the molecules with few exceptions (e.g., deviation from planarity is observed in Y = NH2; X = O, S, Se, and Y = CH3; X = O, and S) indicates that the lone pair of electrons on nitrogen is delocalized to a large extent thereby stabilizing the molecule. The geometrical parameters and the solvent effect on the C–N rotational barriers for the substituted amides Y(C@X)NH2, Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH and solvent effect on the C–N rotational barriers with neutral species have been reported in our earlier studies. The variation in the geometrical parameters of these neutral molecules as a result of the presence of substituents has been rationalized in terms of (i) the variation in extent of delocalization of lone pair of electrons present on N; (ii) the variation in extent of delocalization of lone pair of electrons on X; (iii) change in hybridization at N and C; (iv) variation in atomic charges and hence in electrostatic interactions. Analysis of data suggested that lone pair of electrons from nitrogen in amide moiety is delocalized to pC–X and is independent of charge present on carbonyl carbon. The effect of protonation at N and X (X = O, S, and Se) on geometrical parameters is important as it reflects the variation in strength of bonds and hybridization. The variation in geometrical parameters is reported in Table 1. The significant elongation of C–N bond with protonation at N is rationalized as a result of loss of p interactions between the carbon and nitrogen due to the lone pair of electrons on N being utilized in forming a bond with proton. The C–N
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Table 1 The variation in important geometrical parameters (in A) of N and X (X = O, S, Se) protonated substituted seleno-, thio- and oxo-amides relative to their respective neutral molecules NH2C(@X)Y at MP2/6-31+G* level Substituent (Y)
Protonation at N Selenoamides
H F Cl Br NO2 CN NH2 CH3 CF3 SH
Protonation at Se, S, and O Thioamides
Amides
Selenoamides
Thioamides
Amides
DC–N
DSe–C
DC–N
DS–C
DC–N
DO–C
DC–N
DSe–C
DC–N
DS–C
DC–N
DO–C
0.159 0.162 0.169 0.168 0.154 0.163 0.160 0.179 0.159 0.178
0.041 0.037 0.027 0.022 0.033 0.034 0.046 0.045 0.038 0.044
0.166 0.164 0.173 0.175 0.132 0.168 0.162 0.182 0.164 0.181
0.044 0.038 0.028 0.025 0.058 0.036 0.036 0.044 0.040 0.035
0.200 0.137 0.195 0.204 0.183 0.192 0.184 0.235 0.197 0.208
0.040 0.024 0.021 0.017 0.026 0.031 0.028 0.042 0.038 0.026
0.040 0.038 0.035 0.034 0.036 0.038 0.041 0.039 0.040 0.026
0.048 0.084 0.083 0.086 0.061 0.055 0.064 0.058 0.059 0.069
0.044 0.002 0.038 0.037 0.040 0.041 0.049 0.045 0.044 0.035
0.056 0.086 0.088 0.090 0.065 0.066 0.092 0.068 0.060 0.084
0.059 0.076 0.042 0.039 0.045 0.049 0.062 0.064 0.054 0.051
0.066 0.083 0.091 0.096 0.076 0.072 0.089 0.074 0.067 0.090
bond elongation increases in the order of X as Se < S < O. The C–N rotational barriers however decrease in the order Se > S > O. It is interesting to note the opposite trends. The rotational barriers are reflective of p character between carbon and nitrogen while on protonation, the C–N bond variation results from variations in electrostatic interactions between the carbon and nitrogen, change in hybridization at nitrogen and carbon in addition to the loss of p bond character. The hybridization at nitrogen changes from sp2 to sp3 as can be observed from angles around nitrogen. The elongation of C–N bond is accompanied by contraction of C–X bond with protonation at nitrogen. The contraction is relatively smaller in X = O in comparison to molecules with X = S or Se. The higher chalcogen being larger in size polarizes easily and tends to stabilize the positive charge that develops on protonation. A small increase in variation of C–N bond distance is caused by the presence of all the substituents except NO2 under study. The variation in DC–N is also accompanied by decrease in DSe–C bond distance. The C–X bond elongation on protonation at X is much smaller in comparison to elongation of C–N bond on protonation at nitrogen. The C–X bond elongation is accompanied by contraction of C–N bond distance reasonably comparable in magnitude to one another. The lone pair on nitrogen stabilizes the X protonated species through extended electron delocalization. 4. NBO analysis To further understand the electronic effects in the presence of substituents, NBO analysis using MP2/6-31+G* geometries has been carried out. Second order delocalization energies E(2), which are quantitative representative of the stabilization energies associated with the electronic delocalization are given in Table 2. As can be seen from the table, there is a significant stabilization energy for nN ! pSe–C delocalization in selenoformamide (E(2) = 120.46 kcal/mol). The similar delocalization energy in thioformamide is 110.97 kcal/mol nN ! pS–C and is still lower
88.54 kcal/mol for nN ! pO–C delocalization in formamide. The increase in size of chalcogens enhances its capacity to accept electronic charge. The NO2 and CN substituents through their extended p conjugation with pC–X bond increase nN ! pC–X delocalization energy. The decrease in the E(2) for nN ! pX–C in NH2 substituted seleno-, thio-, and oxo-amides is the result of two competing lone pairs on different nitrogen atoms for the same pC–X bond. The electron withdrawing substituents, F, Cl, and Br do not affect the E(2) for nN ! pC–X delocalization significantly clearly suggesting that electronegativity of substituents which is expected to affect the charge on carbonyl carbon is not important for nN ! pC–X delocalization. The nX ! rC–N and nX ! rC–Y delocalizations are comparatively weaker. These delocalizations increase in the order of X as Se < S < O. These interactions are affected by inductive and p acceptor ability of the substituents. The nN ! pC–X delocalization is seen only in neutral molecules. With protonation at nitrogen, lone pair of electron becomes unavailable and with protonation at X, the acceptor orbital pC–X bond is absent. The nitrogen lone pair forms p bond with carbonyl carbon after the shift of p charge density towards proton. However the electron delocalization from X and Y tend to stabilize the protonated species. The E(2) values for nX ! pC–N suggest the stabilization resulting from delocalization of one of the lone pair of electrons on X while the other used for protonation. The nX ! pC–N delocalization increases in the order of X as Se < S < O in X protonated amides. The order is the reverse of the trend expected on the basis of size and polarizability of the chalcogen. The substituents with lone pair of electrons tend to stabilize the protonated amides as can be seen from nY ! pX–C and nY ! pC–N delocalization energies present in N-protonated and X-protonated species. The lone pair occupancies of nitrogen shown in Table 3 indicate that it is highly delocalized and the delocalization increases in the order O < S < Se. The NO2 and CN substituents that can have extended p conjugation with C@X bond help in increasing p bonding interactions between
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Table 2 Second order delocalization energy (E(2) in kcal/mol) of seleno-, thio- and oxo-amides YC(@X)NH2, X = Se, [S], (O); Y= H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH at MP2/6-31+G* level Y a
H Hb Hc Fa Fb Fc Cla Clb Clc Bra Brb Brc NO2a NO2b NO2c CNa CNb CNc NH2a NH2b NH2c CH3a CH3b CH3c CF3a CF3b CF3c SHa SHb SHc a b c
nN ! pX–C
nX ! pC–N
nX ! rC–Y
nY ! pX–C
nY ! pC–N
120.46 [110.97] (88.54) – – 120.66 [78.66] (89.11) – – 120.65 [111.43] (93.96) – – 122.25 [113.10] (96.45) – – 131.67 [115.94] (107.72) – – 132.90 [111.51] (96.38) – – 82.41 [78.66] (56.27) – – 122.63 [107.06] (87.16) – – 127.87 [56.34] (100.07) – – 120.01 [107.81] (40.91) – –
– 79.78 [86.92] (97.00) – – 68.63 [80.56] (96.80) – – 69.42 [80.75] (93.19) – – 71.34 [81.14] (92.39) – – 90.28 [103.51](104.81) – – 80.30 [87.18] (96.95) – – 29.36, [8.45] (73.04) – – 67.72 [77.33] (90.87) – – 80.03 [93.71] (99.55) – – 53.79 [61.69] (82.04) –
9.56 [12.89] (26.02) [5.44] (1.95) 10.52 [13.30] (21.64) 29.21 [36.53] (61.49) 7.52 [9.35] (6.29) 27.97, [34.50] (49.95) 24.07 [30.69] 55.59) 7.81 [9.04] (2.11) 19.28, [23.79] (35.92) 28.90 [36.64] (64.16) 8.57 [9.68] (1.61) 21.09 [25.79] (36.49) 29.47 [37.11] (63.75) 8.52 [9.68] (5.72) 26.76 [34.84] (50.02) 11.21 [15.75] (31.53) [7.20] (1.96) 12.50 [15.66] (25.86) 12.92 [16.70] (31.09) 29.36 [5.89] 14.40 [17.66] (27.04) 9.56 [11.88] (23.19) [6.68] (1.04) 9.68 [11.89] (18.26) 13.50 [1.58] (30.92) [10.12] (3.00) 14.19 [17.70] (27.66) 15.09 [32.33] (37.30) 7.81 [8.52] (0.93) 13.43 [16.19] (25.06)
– – – (30.93) – 35.73 [36.68] (44.28) (24.10) – 39.58 [38.74] (42.66) (17.42) – 33.84 [33.34] (34.60) – – – – – – (56.26) – 119.89 [115.28] – – – – – – (22.02) – 64.96 [61.05] (58.96)
– – – – 45.27 [45.89] (52.25) – – 47.64 [47.31] (51.64) – – [39.58] (41.92) [11.12] – – – – – – – – – – – – – – – – 54.03 [61.67] (70.65) –
Neutral species. Protonated at X. Protonated at N.
carbon and nitrogen (amino group) also indicated by NBO analysis lead to decrease in occupancy of lone pair on nitrogen. The lone pair on nitrogen loses its identity as lone pair, becomes a bonding pair in N and X protonated species. In N protonated species it is forming a bond with H+ while in X protonated form, it is being utilized to form p bond with carbonyl carbon. The lone pair occupancies on X support higher delocalization in protonated species that tends to stabilize charge on the species. The lone pair present on Y also shows occupancy less than 2.00. However, the variation in lone pair occupancies on protonation is not very large. Analysis of atomic charges indicates that it is the carbon atom that shows highest variation in the charge on substitution followed by atomic charge on X. Charge variation on N is comparatively smaller with substitution and even with protonation at N. The variation in charge on carbon with substitution is the direct consequence of inductive effect of substituents. The charge distribution in N and X protonated species indicates that the positive charge is not localized at one center rather it is distributed over whole molecule. Our results on C–N rotational barriers in substituted amides indicate that in spite of charge varia-
tion on carbonyl carbon, the C–N p bond character is not affected significantly. 5. Proton affinity The proton affinities of selenoamides and its thio- and oxo-analogs have been evaluated at MP2/6-311++G*// MP2/6-31+G* and B3LYP/6-311++G*//B3LYP/6-31+ G* levels and are listed in Table 4. The proton affinities for chalcogen site at B3LYP/6-311++G*//B3LYP/631+G* are higher than the values evaluated using MP2/ 6-311++G*//MP2/6-31+G* level while vice versa is observed for proton affinities for N site. The experimental value for proton affinity of ammonia is 204 ± 1 kcal/mol and that of formaldehyde is 172 ± 1 kcal/mol. The proton affinities for N centers are lower than the experimental value for NH3 while that of carbonyl oxygen are higher than that of the formaldehyde in all the substituted amides under study. The proton affinities for chalcogen sites and for nitrogen site for these molecules decrease in the order Se > S > O. Our earlier results on the effect of substituents on C–N rotational barriers have shown that nitrogen lone pair is
D. Kaur et al. / Journal of Molecular Structure: THEOCHEM 805 (2007) 119–125
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Table 3 Atomic/group charges and lone pair occupancies in substituents of seleno-, thio- and oxo-amides Y
Atomic/group charges Se [S] (O)
C
N
Y
nSe,
Ha
0.05[0.09] (0.72) 0.41[0.33] (0.69)
Hc
0.44 [0.24] (0.48)
Fa
0.01 [0.05] (0.70)
Fb
0.36 [0.32] (0.69)
0.67 [0.39] (1.28)
Fc
0.42 [0.24] (0.49)
0.30 [0.73] (1.19)
Cla
0.04 [0.01] (0.68)
Clb
0.40 [0.35] (0.69)
Clc
0.45 [0.27] (0.48)
Bra
0.08 [0.04] (0.67)
Brb
0.40 [0.37] (0.70)
Brc
0.47 [0.27] (0.49)
NO2a
0.13 [0.08] (0.63)
0.12 [0.06] (0.80) 0.12 [0.16] (0.77) 0.25 [0.18] (0.70) 0.19 [0.12] (0.77) 0.03 [0.24] (0.70) 0.35 [0.09] (0.63) 0.01 [0.07] (0.94)
NO2b
0.45 [0.52] (0.66)
NO2c
0.65 [0.31] (0.40)
CNa
0.08 [0.02] (0.65)
CNb
0.49 [0.44] (0.66)
CNc
0.56[0.30] (0.41)
NH2a
0.15 [0.16] (0.75)
0.30 [0.02] (0.99) 0.10 [0.37] (0.91) 0.11[0.05] (0.74) 0.13 [0.14] (0.82) 0.25 [0.20] (0.74) 0.17 [0.20] (0.97)
NH2b
0.32 [0.09] (0.72)
0.42 [0.24] (1.01)
NH2c
0.15 [0.18] (0.60)
0.17 [0.48] (0.98)
CH3a
0.08 [0.10] (0.68)
CH3b
0.38[0.29] (0.70)
CH3c
0.39 [0.23] (0.50)
CF3a
0.07 [0.02] (0.74)
CF3b
0.42 [0.43] (0.68)
0.01 [0.03] (0.73) 0.25 [0.00] (0.90) 0.09 [0.31] (0.85) 0.16 [0.10] (0.82) 0.13 [0.18] (0.80)
CF3c
0.56 [0.33] (0.43)
SHa
0.06 [0.06] (0.62)
SHb
0.37 [0.24] (0.71)
SHc
0.33 [0.23] (0.54)
0.82 [0.83] (0.95) 0.79 [0.88] (0.82) 0.87 [0.79] (0.93) 0.85 [0.86] (0.96) 0.84 [0.88] (0.87) 0.88 [0.83] (0.91) 0.84 [0.84] (0.94) 0.81 [0.87] (0.84) 0.87 [0.81] (0.70) 0.84 [0.84] (0.77) 0.82 [0.88] (0.70) 0.87 [0.81] (0.63) 0.82 [0.82] (0.94) 0.78 [0.84] (0.99) 0.86 [0.78] (0.91) 0.77 [0.78] (0.74) 0.76-0.85] (0.80) 0.85 [0.76] (0.90) 0.87 [0.88] (0.96) 0.87 [0.88] (0.89) 0.88 [0.85] (0.92) 0.81 [0.83] (0.95) 0.80 [0.88] (0.84) 0.88 [0.80] (0.94) 0.80 [0.81] (0.93) 0.77 [0.87] (0.81) 0.87 [0.77] (0.92) 0.84 [0.85] (0.98) 0.83 [0.88] (0.86) 0.88 [0.82] (0.92)
0.23 [0.22] (0.15)
Hb
0.23 [0.17] (0.66) 0.03[0.24] (0.72) 0.35 [0.10] (0.64) 0.34 [0.38] (1.19)
1.92 [1.91] (1.90) 1.99[1.99] (1.97) 1.99 [1.99] (1.98) 1.88[1.86] (1.84) 1.98 [1.98] (1.96) 1.98 [1.98] (1.98) 1.88[1.86] (1.84) 1.98[1.98] (1.97) 1.98 [1.98] (1.97) 1.87 [1.85] (1.82) 1.98 [1.98] (1.97) 1.98 [1.98] (1.97) 1.87 [1.85] (1.84) 1.98 [1.97] (1.96) 1.99[1.98] (1.83) 1.82 [1.82] (1.88) 1.99 [1.98] (1.97) 1.99 [1.98] (1.98) 1.92 [1.90] (1.89) 1.99 [1.98] (1.97) 1.98 [1.98] (1.97) 1.92 [1.92] (1.90) 1.99[1.98] (1.97) 1.98 [1.98] (1.97) 1.91 [1.90] (1.89) 1.99 [1.98] (1.97) 1.99 [1.99] (1.98) 1.91 [1.89] (1.87) 1.98 [1.98] (1.97) 1.98 [1.98] (1.97)
a b c
Neutral species. Protonated at X. Protonated at N.
Occupancies
0.27 (0.73) 0.21 (0.65) 0.02 (0.64) 0.34 (0.59)
[0.16] [0.17] [0.25] [0.04]
0.29 [0.28] (0.27) 0.28 [0.28] (0.23) 0.36 [0.37] (0.43) 0.34 [0.36] (0.31) 0.37 [0.33] (0.34) 0.03 [0.01] (0.08) 0.19 [0.15] (0.21) .015 [ 0.19] (0.15) 0.06 [0.04] (0.06) 0.28 [0.25] (0.30) 0.24 [0.29] (0.23) 0.23 [0.24] (0.31) 0.06 [0.18] (0.15) 0.22 [0.15] (0.29) 0.07 [0.07] (0.07) 0.07[0.03] (0.07) 0.03 [0.07] (0.60) 0.01 [0.02] (0.11) 0.07 [0.05] (0.08) 0.04 [0.08] (0.02) 0.04 [0.03] (0.00) 0.13 [0.11] (0.12) 0.10 [0.12] (0.10) 0.00 [0.01] (0.03) 0.11 [0.09] (0.21) 0.05 [0.12] (0.06) 0.23 [0.22] (0.12) 0.41 [0.39] (0.41) 0.39 [0.40] (0.34)
[S], and (O)
nN
nY
1.72 [1.74] (1.80) –
– –
–
–
1.74 [1.75] (1.81) –
–
– 1.73 [1.74] (1.79) – – 1.72 [1.74] (1.79) – – 1.69[1.72] (1.76) –
1.97 [1.97] (1.96) 1.96 [1.96] (1.96) – 1.95 [1.95] (1.95) 1.95 [1.95] (1.95) – 1.99 [1.96] (1.95) 1.95 [1.95] (1.95) – –
–
–
1.68 [1.70] (1.78) –
–
–
–
1.81 [1.82] (1.87) 1.69 (1.75)
– –
–
1.72
1.72 [1.75] (1.80) –
–
–
–
1.70 [1.72] (1.77) –
–
–
–
1.73 [1.75] (1.82) –
–
–
–
–
–
1.98 [1.98] (1.98) 1.98 [1.98] (1.98)
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Table 4 Proton affinities (PA in kcal/mol) of selenoamides, thioamides and amides at MP2/6-311++G*//MP2/6-31+G* and B3LYP/6-311++G*//B3LYP/631+G* levels Substituent (Y) a
H Hb Fa Fb Cla Clb Bra Brb NO2a NO2b CNa CNb NH2a NH2b CH3a CH3b CF3a CF3b SHa SHb a b
MP2/6-311++G*//MP2/6-31+G*
B3LYP/6-311++G*//B3LYP/6-31+G*
YC(@Se)NH2
YC(@S)NH2
YC(@O)NH2
YC(@Se)NH2
YC(@S)NH2
YC(@O)NH2
206.56 199.34 197.95 190.56 201.73 196.16 201.32 197.65 190.06 186.38 191.11 189.73 215.06 203.92 212.53 205.10 195.71 192.57 206.15 203.37
208.59 199.83 197.08 191.13 201.55 196.15 201.54 193.26 189.72 185.07 192.33 189.19 216.97 207.32 205.66 212.61 206.40 191.51 207.67 203.88
202.17 195.71 186.73 186.25 189.39 189.13 189.12 189.69 175.28 175.32 184.74 181.60 212.27 206.56 210.28 204.98 188.06 184.85 200.91 200.45
212.35 195.56 203.67 189.11 207.12 194.05 207.54 195.02 195.83 184.05 197.50 187.68 221.48 205.13 218.67 202.03 202.03 189.66 212.47 201.20
211.94 195.62 200.95 188.22 203.53 192.79 204.22 193.66 193.87 182.20 196.90 186.34 221.21 206.53 212.61 202.53 200.67 188.52 210.95 201.19
205.24 193.86 187.42 182.05 191.37 186.99 191.81 188.20 177.08 172.85 188.35 180.40 217.31 204.63 214.40 204.66 191.58 183.54 204.32 197.83
Protonated at X. Protonated at N.
more delocalized in selenoamides than thioamides which in turn is having more delocalization than that in amides [9]. The NH2 of amide group enhances the basicity of carbonyl chalcogen site by delocalization of its lone pair. The chalcogen site proton affinity values undergo variations of 25.0 kcal/mol at MP2/6-311++G*//MP2/6-31+G* level as a result of the presence of substituents in selenoamides. The corresponding variations in thioamides is 27.8 kcal/ mol and in substituted amide is 36.7 kcal/mol which clearly shows that the role of substituents on proton affinity increases in the order of X as Se < S < O. The Se protonated selenoformamide is more stable by 9.5 kcal/mol than N protonated selenoformamide. This energy difference is 10.7 kcal/mol and 6.4 kcal/mol in thioformamide and formamide respectively. The fact that the X-protonated species is thermodynamically favored does not imply that the N-protonated species can be ruled out in acid catalyzed amide reactions and proton exchange. Although N-protonated isomer is less favored thermodynamically, however the difference in proton affinity of X and N site is not very large. The proton affinity values decrease in the presence of electron-withdrawing substituents while increase in proton affinity values is observed in the presence of electron donating substituents like CH3 and NH2 in all the three chalcogen amides. The NH2 group with the p donor ability stabilizes X protonated species to a significant extent. The NO2 group on the other hand due to its electron withdrawing ability and p conjugation with carbonyl decreases the proton affinity values. Though seleno and thioamides have more basic character for X and N centers than amides
but the variation in basicity with the presence of substituents is more marked in oxo-amides relative to the other two. The Se and S being larger in size and easily polarizable tend to stabilize the positive charge more in comparison to amide. This is also supported by the variation in geometrical parameters in substituted seleno, thio and oxo amides. This stabilization lowers the significance of substituent effect to some extent. 6. Conclusion The proton affinities of selenoamides at MP2/ 6-311++G*//MP2/6-31+G* and B3LYP/6-311++G*// B3LYP/6-31+G* level have been evaluated. Similar evaluations for the thioamides and oxoamides have also been done at the same theoretical levels. The proton affinities of chalcogen sites show an edge over the nitrogen site in all the amides. The proton affinities for both chalcogen and nitrogen site decrease in the order of X as Se > S > O. The difference in values of proton affinities of seleno and thio amides varies from negligible to small extent. The proton affinities of N sites are lower than the values for NH3 while those for chalcogen site are higher than the values in corresponding formaldehydes. The presence of NH2 group enhances the basicity of chalcogen site by losing some of its basicity through electron delocalization. The electron donating substituents like NH2, CH3 increase the proton affinities while electron-withdrawing substituents decrease the proton affinity values. The nN ! pX–C second order delocalization energy is the largest of all the E(2) values in all the amides. The role of substituents becomes
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more apparent in protonated species, the stabilization of protonated species through p conjugation helps in delocalization of positive over whole molecule as indicated by nY ! pX–C and nY ! pC–N delocalizations. The electron donation through inductive effect also stabilizes the protonated specie that results in lowering of proton affinity. Acknowledgement The authors are thankful to Council of Scientific and Industrial Research (CSIR), New Delhi for the financial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/ j.theochem.2006.11.001. References [1] K.B. Wiberg, C.M. Hadad, P.R. Rablen, J. Cioslowski, J. Am. Chem. Soc. 114 (1992) 8644. [2] J.L.M. Abboud, O. Mo, J.L.G. de Laz, M. Yanez, M. Esseffar, W. Bouab, M. El-Mouhtadi, R. Mokhlisse, E. Ballesteros, M. Herreros, H. Homan, C. Lopez-Mardomingo, R. Notario, J. Am. Chem. Soc. 115 (1993) 12408. [3] S. Patai, Patais 1992 Guide to the Chemistry of Functional Groups, John Wiley, New York, 1992. [4] A. Greenberg, J.F. Liebman (Eds.), Structure and Reactivity, vol. 7, VCH Publishers, New York, 1988, p. 139. [5] M. Goodman, S. Ro, 5th ed.Burger’s Medicinal Chemistry and Drug Discovery, vol. 1, John Wiley, New York, 1995. [6] M. Kahn, Tetrahedron 49 (1993) 3433. [7] P.V. Bharatam, P. Uppal, P.S. Bassi, Chem Phys. Lett. 276 (1997) 31. [8] J. Leszczynski, J.S. Kwaitkowski, D. Leszczynska, J. Am. Chem. Soc. 114 (1992) 10089. [9] D. Kaur, P. Sharma, P.V. Bharatam, N. Dogra, J. Mol. Struc. Theochem. 759 (2005) 41. [10] E.M. Arnett, Acc. Chem. Res. 6 (1973) 404. [11] M. Mautner, Acc. Chem. Res. 17 (1984) 186. [12] F. Cacace, Acc. Chem. Res. 21 (1988) 215.
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Substituent effects on the proton affinities of selenoamides: A theoretical study Damanjit Kaur *, Punita Sharma, Rupinder Preet Kaur, Mandeep Kaur, P.V. Bharatam
1
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India Received 31 March 2006; received in revised form 1 November 2006; accepted 1 November 2006 Available online 7 November 2006
Abstract The proton affinities of nine substituted selenoamides for their chalcogen and nitrogen sites have been evaluated theoretically at the MP2/6-31++G*//MP2/6-31+G* and B3LYP/6-31++G*//B3LYP/6-31+G* levels. Similar calculations have been done for substituted thio- and oxo-amides. The proton affinities for the chalcogen site are slightly higher than the corresponding values for nitrogen sites in all the amides. The proton affinities for both chalcogen and nitrogen site decrease in the order of X as Se > S > O. The electron donating substituents increase the proton affinities while the electron withdrawing substituents decrease the proton affinities. The NBO analysis indicates that nN ! pX–C interactions are dominant in neutral molecule. The role of substituent becomes apparent in the protonated specie where electron delocalization of the type nY ! pX–C and nY ! pC–N also become operative. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Amides; Proton affinities; NBO analysis; NPA; Substituents
1. Introduction The presence of substituents on any functional group can alter the properties of the functional group from very small to significantly large extent. As the variations in the properties stem from the interactions of substituents with the functional group, a number of studies have been performed to understand these interactions. Wiberg et al. analyzed the effect of substituents on carbonyl functional group using ab initio methods on acyl radicals [1]. The changes in electron population, bond order and atomic energies were analyzed as a consequence of the presence of substituents. They concluded that the presence of substituents NH2, OH and F stabilizes the carbonyl group through the interaction of lone pair of electrons on substituents with electron deficient carbonyl carbon and the columbic interactions of dipolar bonds. *
Corresponding author. Tel.: +91 183 2256736; fax: +91 183 258820. E-mail address: [email protected] (D. Kaur). 1 Present address: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and research (NIPER), S.A.S. Nagar (Mohali), 160062 Punjab, India. 0166-1280/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2006.11.001
The CN and CF3 groups possess positive charge at the carbon attached to carbonyl carbon and hence have repulsive interactions with the carbonyl carbon. The effect of substituents on thio carbonyl and carbonyl compounds have been analyzed by Abboud et al. by studying isodesmic reactions [2]. They observed that the presence of CH3, NH2, OH, F, and Cl substituents stabilizes the carbonyl compounds and the effect is more predominant on carbonyl in comparison to that on thiocarbonyl compounds. The p interaction of the lone pair of electrons on substituents with the p bond of carbonyl/thiocarbonyl and r bonds have been suggested as the reasons responsible for the stabilization. The amide functional group [3] is an essential structural unit of peptides and proteins that has attracted attention not only for understanding its thermodynamic properties [4] but also for designing peptide mimetics [5,6]. As a result, a number of experimental and theoretical studies have been involved in understanding of electron delocalization from the nitrogen lone pair towards the carbonyl/thiocarbonyl group in formamide and thioformamide respectively [7,8].
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In our earlier report, we tried to analyze the effect of substituents present on carbonyl carbon in amides and their thio and seleno analogs by analyzing the C–N rotational barriers [9]. The proton affinity of a molecule represents an important fundamental, gas phase thermodynamic property [10–12] that helps in understanding the intrinsic reactivity of isolated molecules without interference of solute solvent interactions [13]. A number of addition/elimination reactions in organic chemistry involving carbonyl compounds are known to be acid catalyzed [14]. The three dimensional structure of peptides and their biological activities are readily influenced by protonation [15]. Perrin has shown that the acid catalyzed proton exchange of peptides in an aqueous environment proceeds via a mechanism in which the imidic and [RC(OH)NR 0 R00 ] is an intermediate [16]. The proton affinity values help in understanding fragmentation patterns in mass spectrometry influenced by protonation and other proton transfer reactions, basicity of molecules and susceptibility toward electrophilic substitution. The effect of substituents on the stability of molecules and their protonated ions is of importance in order to distinguish the intrinsic molecular properties from the effect of surrounding medium [17,18]. Earlier results on proton affinities of amides indicate oxygen as the preferred protonation site rather than nitrogen, which is in contrast to the known results for NH3 and formaldehyde where the basicity for protonation for the former is 204 kcal/mol [19–21] while that of later is 172 kcal/mol [19]. The electron delocalization from nitrogen increases in the order O < S < Se in the molecules of type H2NC(@X)H (X = O, S, Se) as suggested in our earlier reports [9]. Gonezalez et al., in their study on basicity scale for selenocarbonyl compounds observed that these compounds behave as selenium bases in gas phase [22]. The thiocarbonyl and carbonyl compounds are also known to have chalcogen as preferred base center even in the presence of NH2 substituent. Selenocarbonyl derivatives are reported to be more basic than the corresponding thiocarbonyl compounds which in turn are more basic than their carbonyl analogs [23]. In the present studies the proton affinities of X (X = O, S, Se) and N sites in amides of type YC(=X)NH2 with Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH have been evaluated. The study provides gas phase basicities of these molecules and also the means to analyze the role of substituent on the stabilization of the molecules and their protonated species. The orbital interactions between the various orbitals have been analyzed by NBO analysis. 2. Computational details Ab initio MO [24,25] and density functional theory (DFT) [26,27] calculations have been performed using Gaussian 98W package, the windows version of Gaussian 98 suite of programs [28]. Complete optimizations were carried out on selenoamides and their thio- and oxo-analogs using HF, MP2 [29] and B3LYP [30–32] methods and
6-31+G* basis set without any symmetry constraints. When ever more than one stable conformation exists, the energy and parameters of most stable conformation are reported. Since these molecules possess several lone pairs of electrons, inclusion of diffuse functions was used to determine minimum energy conformation. To include electron correlation Optimizations were performed at MP2(FC)/ 6-31+G* and B3LYP/6-31+G* theoretical levels. Frequencies were computed for all the optimized structures in order to characterize each stationary point as a minimum or a transition state and to determine ZPE values. The ZPE values were scaled by a factor of 0.9153 at the HF/6-31+G* and by 0.9806 at the B3LYP/6-31+G* level [33]. Proton affinities were calculated at B3LYP/6-31++G*// B3LYP6-31+G* and MP2/6-311++G*//MP2/6-31+G*. NBO analysis was carried out to understand second order interactions [34,35]. Atomic charges were estimated using NPA method with MP2 densities at MP2/6-31+G* level. 3. Results and discussion The absolute energies of different substituted selenoamides, thioamides, and amides Y(C@X)NH2, Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, SH and their protonated species are given in supporting information in Tables S1–S3. The important geometrical parameters are also available in supporting information Tables S4–S9. The planarity of bonds around nitrogen in all the molecules with few exceptions (e.g., deviation from planarity is observed in Y = NH2; X = O, S, Se, and Y = CH3; X = O, and S) indicates that the lone pair of electrons on nitrogen is delocalized to a large extent thereby stabilizing the molecule. The geometrical parameters and the solvent effect on the C–N rotational barriers for the substituted amides Y(C@X)NH2, Y = H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH and solvent effect on the C–N rotational barriers with neutral species have been reported in our earlier studies. The variation in the geometrical parameters of these neutral molecules as a result of the presence of substituents has been rationalized in terms of (i) the variation in extent of delocalization of lone pair of electrons present on N; (ii) the variation in extent of delocalization of lone pair of electrons on X; (iii) change in hybridization at N and C; (iv) variation in atomic charges and hence in electrostatic interactions. Analysis of data suggested that lone pair of electrons from nitrogen in amide moiety is delocalized to pC–X and is independent of charge present on carbonyl carbon. The effect of protonation at N and X (X = O, S, and Se) on geometrical parameters is important as it reflects the variation in strength of bonds and hybridization. The variation in geometrical parameters is reported in Table 1. The significant elongation of C–N bond with protonation at N is rationalized as a result of loss of p interactions between the carbon and nitrogen due to the lone pair of electrons on N being utilized in forming a bond with proton. The C–N
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121
Table 1 The variation in important geometrical parameters (in A) of N and X (X = O, S, Se) protonated substituted seleno-, thio- and oxo-amides relative to their respective neutral molecules NH2C(@X)Y at MP2/6-31+G* level Substituent (Y)
Protonation at N Selenoamides
H F Cl Br NO2 CN NH2 CH3 CF3 SH
Protonation at Se, S, and O Thioamides
Amides
Selenoamides
Thioamides
Amides
DC–N
DSe–C
DC–N
DS–C
DC–N
DO–C
DC–N
DSe–C
DC–N
DS–C
DC–N
DO–C
0.159 0.162 0.169 0.168 0.154 0.163 0.160 0.179 0.159 0.178
0.041 0.037 0.027 0.022 0.033 0.034 0.046 0.045 0.038 0.044
0.166 0.164 0.173 0.175 0.132 0.168 0.162 0.182 0.164 0.181
0.044 0.038 0.028 0.025 0.058 0.036 0.036 0.044 0.040 0.035
0.200 0.137 0.195 0.204 0.183 0.192 0.184 0.235 0.197 0.208
0.040 0.024 0.021 0.017 0.026 0.031 0.028 0.042 0.038 0.026
0.040 0.038 0.035 0.034 0.036 0.038 0.041 0.039 0.040 0.026
0.048 0.084 0.083 0.086 0.061 0.055 0.064 0.058 0.059 0.069
0.044 0.002 0.038 0.037 0.040 0.041 0.049 0.045 0.044 0.035
0.056 0.086 0.088 0.090 0.065 0.066 0.092 0.068 0.060 0.084
0.059 0.076 0.042 0.039 0.045 0.049 0.062 0.064 0.054 0.051
0.066 0.083 0.091 0.096 0.076 0.072 0.089 0.074 0.067 0.090
bond elongation increases in the order of X as Se < S < O. The C–N rotational barriers however decrease in the order Se > S > O. It is interesting to note the opposite trends. The rotational barriers are reflective of p character between carbon and nitrogen while on protonation, the C–N bond variation results from variations in electrostatic interactions between the carbon and nitrogen, change in hybridization at nitrogen and carbon in addition to the loss of p bond character. The hybridization at nitrogen changes from sp2 to sp3 as can be observed from angles around nitrogen. The elongation of C–N bond is accompanied by contraction of C–X bond with protonation at nitrogen. The contraction is relatively smaller in X = O in comparison to molecules with X = S or Se. The higher chalcogen being larger in size polarizes easily and tends to stabilize the positive charge that develops on protonation. A small increase in variation of C–N bond distance is caused by the presence of all the substituents except NO2 under study. The variation in DC–N is also accompanied by decrease in DSe–C bond distance. The C–X bond elongation on protonation at X is much smaller in comparison to elongation of C–N bond on protonation at nitrogen. The C–X bond elongation is accompanied by contraction of C–N bond distance reasonably comparable in magnitude to one another. The lone pair on nitrogen stabilizes the X protonated species through extended electron delocalization. 4. NBO analysis To further understand the electronic effects in the presence of substituents, NBO analysis using MP2/6-31+G* geometries has been carried out. Second order delocalization energies E(2), which are quantitative representative of the stabilization energies associated with the electronic delocalization are given in Table 2. As can be seen from the table, there is a significant stabilization energy for nN ! pSe–C delocalization in selenoformamide (E(2) = 120.46 kcal/mol). The similar delocalization energy in thioformamide is 110.97 kcal/mol nN ! pS–C and is still lower
88.54 kcal/mol for nN ! pO–C delocalization in formamide. The increase in size of chalcogens enhances its capacity to accept electronic charge. The NO2 and CN substituents through their extended p conjugation with pC–X bond increase nN ! pC–X delocalization energy. The decrease in the E(2) for nN ! pX–C in NH2 substituted seleno-, thio-, and oxo-amides is the result of two competing lone pairs on different nitrogen atoms for the same pC–X bond. The electron withdrawing substituents, F, Cl, and Br do not affect the E(2) for nN ! pC–X delocalization significantly clearly suggesting that electronegativity of substituents which is expected to affect the charge on carbonyl carbon is not important for nN ! pC–X delocalization. The nX ! rC–N and nX ! rC–Y delocalizations are comparatively weaker. These delocalizations increase in the order of X as Se < S < O. These interactions are affected by inductive and p acceptor ability of the substituents. The nN ! pC–X delocalization is seen only in neutral molecules. With protonation at nitrogen, lone pair of electron becomes unavailable and with protonation at X, the acceptor orbital pC–X bond is absent. The nitrogen lone pair forms p bond with carbonyl carbon after the shift of p charge density towards proton. However the electron delocalization from X and Y tend to stabilize the protonated species. The E(2) values for nX ! pC–N suggest the stabilization resulting from delocalization of one of the lone pair of electrons on X while the other used for protonation. The nX ! pC–N delocalization increases in the order of X as Se < S < O in X protonated amides. The order is the reverse of the trend expected on the basis of size and polarizability of the chalcogen. The substituents with lone pair of electrons tend to stabilize the protonated amides as can be seen from nY ! pX–C and nY ! pC–N delocalization energies present in N-protonated and X-protonated species. The lone pair occupancies of nitrogen shown in Table 3 indicate that it is highly delocalized and the delocalization increases in the order O < S < Se. The NO2 and CN substituents that can have extended p conjugation with C@X bond help in increasing p bonding interactions between
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Table 2 Second order delocalization energy (E(2) in kcal/mol) of seleno-, thio- and oxo-amides YC(@X)NH2, X = Se, [S], (O); Y= H, F, Cl, Br, NO2, CN, NH2, CH3, CF3, and SH at MP2/6-31+G* level Y a
H Hb Hc Fa Fb Fc Cla Clb Clc Bra Brb Brc NO2a NO2b NO2c CNa CNb CNc NH2a NH2b NH2c CH3a CH3b CH3c CF3a CF3b CF3c SHa SHb SHc a b c
nN ! pX–C
nX ! pC–N
nX ! rC–Y
nY ! pX–C
nY ! pC–N
120.46 [110.97] (88.54) – – 120.66 [78.66] (89.11) – – 120.65 [111.43] (93.96) – – 122.25 [113.10] (96.45) – – 131.67 [115.94] (107.72) – – 132.90 [111.51] (96.38) – – 82.41 [78.66] (56.27) – – 122.63 [107.06] (87.16) – – 127.87 [56.34] (100.07) – – 120.01 [107.81] (40.91) – –
– 79.78 [86.92] (97.00) – – 68.63 [80.56] (96.80) – – 69.42 [80.75] (93.19) – – 71.34 [81.14] (92.39) – – 90.28 [103.51](104.81) – – 80.30 [87.18] (96.95) – – 29.36, [8.45] (73.04) – – 67.72 [77.33] (90.87) – – 80.03 [93.71] (99.55) – – 53.79 [61.69] (82.04) –
9.56 [12.89] (26.02) [5.44] (1.95) 10.52 [13.30] (21.64) 29.21 [36.53] (61.49) 7.52 [9.35] (6.29) 27.97, [34.50] (49.95) 24.07 [30.69] 55.59) 7.81 [9.04] (2.11) 19.28, [23.79] (35.92) 28.90 [36.64] (64.16) 8.57 [9.68] (1.61) 21.09 [25.79] (36.49) 29.47 [37.11] (63.75) 8.52 [9.68] (5.72) 26.76 [34.84] (50.02) 11.21 [15.75] (31.53) [7.20] (1.96) 12.50 [15.66] (25.86) 12.92 [16.70] (31.09) 29.36 [5.89] 14.40 [17.66] (27.04) 9.56 [11.88] (23.19) [6.68] (1.04) 9.68 [11.89] (18.26) 13.50 [1.58] (30.92) [10.12] (3.00) 14.19 [17.70] (27.66) 15.09 [32.33] (37.30) 7.81 [8.52] (0.93) 13.43 [16.19] (25.06)
– – – (30.93) – 35.73 [36.68] (44.28) (24.10) – 39.58 [38.74] (42.66) (17.42) – 33.84 [33.34] (34.60) – – – – – – (56.26) – 119.89 [115.28] – – – – – – (22.02) – 64.96 [61.05] (58.96)
– – – – 45.27 [45.89] (52.25) – – 47.64 [47.31] (51.64) – – [39.58] (41.92) [11.12] – – – – – – – – – – – – – – – – 54.03 [61.67] (70.65) –
Neutral species. Protonated at X. Protonated at N.
carbon and nitrogen (amino group) also indicated by NBO analysis lead to decrease in occupancy of lone pair on nitrogen. The lone pair on nitrogen loses its identity as lone pair, becomes a bonding pair in N and X protonated species. In N protonated species it is forming a bond with H+ while in X protonated form, it is being utilized to form p bond with carbonyl carbon. The lone pair occupancies on X support higher delocalization in protonated species that tends to stabilize charge on the species. The lone pair present on Y also shows occupancy less than 2.00. However, the variation in lone pair occupancies on protonation is not very large. Analysis of atomic charges indicates that it is the carbon atom that shows highest variation in the charge on substitution followed by atomic charge on X. Charge variation on N is comparatively smaller with substitution and even with protonation at N. The variation in charge on carbon with substitution is the direct consequence of inductive effect of substituents. The charge distribution in N and X protonated species indicates that the positive charge is not localized at one center rather it is distributed over whole molecule. Our results on C–N rotational barriers in substituted amides indicate that in spite of charge varia-
tion on carbonyl carbon, the C–N p bond character is not affected significantly. 5. Proton affinity The proton affinities of selenoamides and its thio- and oxo-analogs have been evaluated at MP2/6-311++G*// MP2/6-31+G* and B3LYP/6-311++G*//B3LYP/6-31+ G* levels and are listed in Table 4. The proton affinities for chalcogen site at B3LYP/6-311++G*//B3LYP/631+G* are higher than the values evaluated using MP2/ 6-311++G*//MP2/6-31+G* level while vice versa is observed for proton affinities for N site. The experimental value for proton affinity of ammonia is 204 ± 1 kcal/mol and that of formaldehyde is 172 ± 1 kcal/mol. The proton affinities for N centers are lower than the experimental value for NH3 while that of carbonyl oxygen are higher than that of the formaldehyde in all the substituted amides under study. The proton affinities for chalcogen sites and for nitrogen site for these molecules decrease in the order Se > S > O. Our earlier results on the effect of substituents on C–N rotational barriers have shown that nitrogen lone pair is
D. Kaur et al. / Journal of Molecular Structure: THEOCHEM 805 (2007) 119–125
123
Table 3 Atomic/group charges and lone pair occupancies in substituents of seleno-, thio- and oxo-amides Y
Atomic/group charges Se [S] (O)
C
N
Y
nSe,
Ha
0.05[0.09] (0.72) 0.41[0.33] (0.69)
Hc
0.44 [0.24] (0.48)
Fa
0.01 [0.05] (0.70)
Fb
0.36 [0.32] (0.69)
0.67 [0.39] (1.28)
Fc
0.42 [0.24] (0.49)
0.30 [0.73] (1.19)
Cla
0.04 [0.01] (0.68)
Clb
0.40 [0.35] (0.69)
Clc
0.45 [0.27] (0.48)
Bra
0.08 [0.04] (0.67)
Brb
0.40 [0.37] (0.70)
Brc
0.47 [0.27] (0.49)
NO2a
0.13 [0.08] (0.63)
0.12 [0.06] (0.80) 0.12 [0.16] (0.77) 0.25 [0.18] (0.70) 0.19 [0.12] (0.77) 0.03 [0.24] (0.70) 0.35 [0.09] (0.63) 0.01 [0.07] (0.94)
NO2b
0.45 [0.52] (0.66)
NO2c
0.65 [0.31] (0.40)
CNa
0.08 [0.02] (0.65)
CNb
0.49 [0.44] (0.66)
CNc
0.56[0.30] (0.41)
NH2a
0.15 [0.16] (0.75)
0.30 [0.02] (0.99) 0.10 [0.37] (0.91) 0.11[0.05] (0.74) 0.13 [0.14] (0.82) 0.25 [0.20] (0.74) 0.17 [0.20] (0.97)
NH2b
0.32 [0.09] (0.72)
0.42 [0.24] (1.01)
NH2c
0.15 [0.18] (0.60)
0.17 [0.48] (0.98)
CH3a
0.08 [0.10] (0.68)
CH3b
0.38[0.29] (0.70)
CH3c
0.39 [0.23] (0.50)
CF3a
0.07 [0.02] (0.74)
CF3b
0.42 [0.43] (0.68)
0.01 [0.03] (0.73) 0.25 [0.00] (0.90) 0.09 [0.31] (0.85) 0.16 [0.10] (0.82) 0.13 [0.18] (0.80)
CF3c
0.56 [0.33] (0.43)
SHa
0.06 [0.06] (0.62)
SHb
0.37 [0.24] (0.71)
SHc
0.33 [0.23] (0.54)
0.82 [0.83] (0.95) 0.79 [0.88] (0.82) 0.87 [0.79] (0.93) 0.85 [0.86] (0.96) 0.84 [0.88] (0.87) 0.88 [0.83] (0.91) 0.84 [0.84] (0.94) 0.81 [0.87] (0.84) 0.87 [0.81] (0.70) 0.84 [0.84] (0.77) 0.82 [0.88] (0.70) 0.87 [0.81] (0.63) 0.82 [0.82] (0.94) 0.78 [0.84] (0.99) 0.86 [0.78] (0.91) 0.77 [0.78] (0.74) 0.76-0.85] (0.80) 0.85 [0.76] (0.90) 0.87 [0.88] (0.96) 0.87 [0.88] (0.89) 0.88 [0.85] (0.92) 0.81 [0.83] (0.95) 0.80 [0.88] (0.84) 0.88 [0.80] (0.94) 0.80 [0.81] (0.93) 0.77 [0.87] (0.81) 0.87 [0.77] (0.92) 0.84 [0.85] (0.98) 0.83 [0.88] (0.86) 0.88 [0.82] (0.92)
0.23 [0.22] (0.15)
Hb
0.23 [0.17] (0.66) 0.03[0.24] (0.72) 0.35 [0.10] (0.64) 0.34 [0.38] (1.19)
1.92 [1.91] (1.90) 1.99[1.99] (1.97) 1.99 [1.99] (1.98) 1.88[1.86] (1.84) 1.98 [1.98] (1.96) 1.98 [1.98] (1.98) 1.88[1.86] (1.84) 1.98[1.98] (1.97) 1.98 [1.98] (1.97) 1.87 [1.85] (1.82) 1.98 [1.98] (1.97) 1.98 [1.98] (1.97) 1.87 [1.85] (1.84) 1.98 [1.97] (1.96) 1.99[1.98] (1.83) 1.82 [1.82] (1.88) 1.99 [1.98] (1.97) 1.99 [1.98] (1.98) 1.92 [1.90] (1.89) 1.99 [1.98] (1.97) 1.98 [1.98] (1.97) 1.92 [1.92] (1.90) 1.99[1.98] (1.97) 1.98 [1.98] (1.97) 1.91 [1.90] (1.89) 1.99 [1.98] (1.97) 1.99 [1.99] (1.98) 1.91 [1.89] (1.87) 1.98 [1.98] (1.97) 1.98 [1.98] (1.97)
a b c
Neutral species. Protonated at X. Protonated at N.
Occupancies
0.27 (0.73) 0.21 (0.65) 0.02 (0.64) 0.34 (0.59)
[0.16] [0.17] [0.25] [0.04]
0.29 [0.28] (0.27) 0.28 [0.28] (0.23) 0.36 [0.37] (0.43) 0.34 [0.36] (0.31) 0.37 [0.33] (0.34) 0.03 [0.01] (0.08) 0.19 [0.15] (0.21) .015 [ 0.19] (0.15) 0.06 [0.04] (0.06) 0.28 [0.25] (0.30) 0.24 [0.29] (0.23) 0.23 [0.24] (0.31) 0.06 [0.18] (0.15) 0.22 [0.15] (0.29) 0.07 [0.07] (0.07) 0.07[0.03] (0.07) 0.03 [0.07] (0.60) 0.01 [0.02] (0.11) 0.07 [0.05] (0.08) 0.04 [0.08] (0.02) 0.04 [0.03] (0.00) 0.13 [0.11] (0.12) 0.10 [0.12] (0.10) 0.00 [0.01] (0.03) 0.11 [0.09] (0.21) 0.05 [0.12] (0.06) 0.23 [0.22] (0.12) 0.41 [0.39] (0.41) 0.39 [0.40] (0.34)
[S], and (O)
nN
nY
1.72 [1.74] (1.80) –
– –
–
–
1.74 [1.75] (1.81) –
–
– 1.73 [1.74] (1.79) – – 1.72 [1.74] (1.79) – – 1.69[1.72] (1.76) –
1.97 [1.97] (1.96) 1.96 [1.96] (1.96) – 1.95 [1.95] (1.95) 1.95 [1.95] (1.95) – 1.99 [1.96] (1.95) 1.95 [1.95] (1.95) – –
–
–
1.68 [1.70] (1.78) –
–
–
–
1.81 [1.82] (1.87) 1.69 (1.75)
– –
–
1.72
1.72 [1.75] (1.80) –
–
–
–
1.70 [1.72] (1.77) –
–
–
–
1.73 [1.75] (1.82) –
–
–
–
–
–
1.98 [1.98] (1.98) 1.98 [1.98] (1.98)
124
D. Kaur et al. / Journal of Molecular Structure: THEOCHEM 805 (2007) 119–125
Table 4 Proton affinities (PA in kcal/mol) of selenoamides, thioamides and amides at MP2/6-311++G*//MP2/6-31+G* and B3LYP/6-311++G*//B3LYP/631+G* levels Substituent (Y) a
H Hb Fa Fb Cla Clb Bra Brb NO2a NO2b CNa CNb NH2a NH2b CH3a CH3b CF3a CF3b SHa SHb a b
MP2/6-311++G*//MP2/6-31+G*
B3LYP/6-311++G*//B3LYP/6-31+G*
YC(@Se)NH2
YC(@S)NH2
YC(@O)NH2
YC(@Se)NH2
YC(@S)NH2
YC(@O)NH2
206.56 199.34 197.95 190.56 201.73 196.16 201.32 197.65 190.06 186.38 191.11 189.73 215.06 203.92 212.53 205.10 195.71 192.57 206.15 203.37
208.59 199.83 197.08 191.13 201.55 196.15 201.54 193.26 189.72 185.07 192.33 189.19 216.97 207.32 205.66 212.61 206.40 191.51 207.67 203.88
202.17 195.71 186.73 186.25 189.39 189.13 189.12 189.69 175.28 175.32 184.74 181.60 212.27 206.56 210.28 204.98 188.06 184.85 200.91 200.45
212.35 195.56 203.67 189.11 207.12 194.05 207.54 195.02 195.83 184.05 197.50 187.68 221.48 205.13 218.67 202.03 202.03 189.66 212.47 201.20
211.94 195.62 200.95 188.22 203.53 192.79 204.22 193.66 193.87 182.20 196.90 186.34 221.21 206.53 212.61 202.53 200.67 188.52 210.95 201.19
205.24 193.86 187.42 182.05 191.37 186.99 191.81 188.20 177.08 172.85 188.35 180.40 217.31 204.63 214.40 204.66 191.58 183.54 204.32 197.83
Protonated at X. Protonated at N.
more delocalized in selenoamides than thioamides which in turn is having more delocalization than that in amides [9]. The NH2 of amide group enhances the basicity of carbonyl chalcogen site by delocalization of its lone pair. The chalcogen site proton affinity values undergo variations of 25.0 kcal/mol at MP2/6-311++G*//MP2/6-31+G* level as a result of the presence of substituents in selenoamides. The corresponding variations in thioamides is 27.8 kcal/ mol and in substituted amide is 36.7 kcal/mol which clearly shows that the role of substituents on proton affinity increases in the order of X as Se < S < O. The Se protonated selenoformamide is more stable by 9.5 kcal/mol than N protonated selenoformamide. This energy difference is 10.7 kcal/mol and 6.4 kcal/mol in thioformamide and formamide respectively. The fact that the X-protonated species is thermodynamically favored does not imply that the N-protonated species can be ruled out in acid catalyzed amide reactions and proton exchange. Although N-protonated isomer is less favored thermodynamically, however the difference in proton affinity of X and N site is not very large. The proton affinity values decrease in the presence of electron-withdrawing substituents while increase in proton affinity values is observed in the presence of electron donating substituents like CH3 and NH2 in all the three chalcogen amides. The NH2 group with the p donor ability stabilizes X protonated species to a significant extent. The NO2 group on the other hand due to its electron withdrawing ability and p conjugation with carbonyl decreases the proton affinity values. Though seleno and thioamides have more basic character for X and N centers than amides
but the variation in basicity with the presence of substituents is more marked in oxo-amides relative to the other two. The Se and S being larger in size and easily polarizable tend to stabilize the positive charge more in comparison to amide. This is also supported by the variation in geometrical parameters in substituted seleno, thio and oxo amides. This stabilization lowers the significance of substituent effect to some extent. 6. Conclusion The proton affinities of selenoamides at MP2/ 6-311++G*//MP2/6-31+G* and B3LYP/6-311++G*// B3LYP/6-31+G* level have been evaluated. Similar evaluations for the thioamides and oxoamides have also been done at the same theoretical levels. The proton affinities of chalcogen sites show an edge over the nitrogen site in all the amides. The proton affinities for both chalcogen and nitrogen site decrease in the order of X as Se > S > O. The difference in values of proton affinities of seleno and thio amides varies from negligible to small extent. The proton affinities of N sites are lower than the values for NH3 while those for chalcogen site are higher than the values in corresponding formaldehydes. The presence of NH2 group enhances the basicity of chalcogen site by losing some of its basicity through electron delocalization. The electron donating substituents like NH2, CH3 increase the proton affinities while electron-withdrawing substituents decrease the proton affinity values. The nN ! pX–C second order delocalization energy is the largest of all the E(2) values in all the amides. The role of substituents becomes
D. Kaur et al. / Journal of Molecular Structure: THEOCHEM 805 (2007) 119–125
more apparent in protonated species, the stabilization of protonated species through p conjugation helps in delocalization of positive over whole molecule as indicated by nY ! pX–C and nY ! pC–N delocalizations. The electron donation through inductive effect also stabilizes the protonated specie that results in lowering of proton affinity. Acknowledgement The authors are thankful to Council of Scientific and Industrial Research (CSIR), New Delhi for the financial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/ j.theochem.2006.11.001. References [1] K.B. Wiberg, C.M. Hadad, P.R. Rablen, J. Cioslowski, J. Am. Chem. Soc. 114 (1992) 8644. [2] J.L.M. Abboud, O. Mo, J.L.G. de Laz, M. Yanez, M. Esseffar, W. Bouab, M. El-Mouhtadi, R. Mokhlisse, E. Ballesteros, M. Herreros, H. Homan, C. Lopez-Mardomingo, R. Notario, J. Am. Chem. Soc. 115 (1993) 12408. [3] S. Patai, Patais 1992 Guide to the Chemistry of Functional Groups, John Wiley, New York, 1992. [4] A. Greenberg, J.F. Liebman (Eds.), Structure and Reactivity, vol. 7, VCH Publishers, New York, 1988, p. 139. [5] M. Goodman, S. Ro, 5th ed.Burger’s Medicinal Chemistry and Drug Discovery, vol. 1, John Wiley, New York, 1995. [6] M. Kahn, Tetrahedron 49 (1993) 3433. [7] P.V. Bharatam, P. Uppal, P.S. Bassi, Chem Phys. Lett. 276 (1997) 31. [8] J. Leszczynski, J.S. Kwaitkowski, D. Leszczynska, J. Am. Chem. Soc. 114 (1992) 10089. [9] D. Kaur, P. Sharma, P.V. Bharatam, N. Dogra, J. Mol. Struc. Theochem. 759 (2005) 41. [10] E.M. Arnett, Acc. Chem. Res. 6 (1973) 404. [11] M. Mautner, Acc. Chem. Res. 17 (1984) 186. [12] F. Cacace, Acc. Chem. Res. 21 (1988) 215.
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