Volume 93

2015

An NRC Research Press Journal

Une revue deNRC Research PressCanadian Journal of

Chemistry

Revue canadienne de

chimie

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ARTICLE

Substituent effect on N–H bond dissociation enthalpies ofcarbamates: a theoretical studyRupinder preet Kaur, Damanjit Kaur, and Ritika Sharma

Abstract: The present investigation deals with the study of the N–H bond dissociation enthalpies (BDEs) of the Y-substituted(NH2-C(=X)Y-R) and N-substituted ((R)(H)NC(=X)YH) carbamates (X, Y = O, S, Se; R = H, CH3, F, Cl, NH2), which have been evaluatedusing ab initio and density functional methods. The variations in N−H BDEs of these Y-substituted and N-substituted carbamatesas the effect of substituent have been understood in terms of molecule stabilization energy (ME) and radical stabilization energy(RE), which have been calculated using the isodesmic reactions. The natural bond orbital analysis indicated that the electrode-localization of the lone pairs of heteroatoms in the molecules and radicals affect the ME and RE values depending upon the typeand site of substitution (whether N- or Y-). The variations in N−H BDEs depend upon the combined effect of molecule stabilizationand radical stabilization by the various substituents.

Key words: carbamates, substituent effect, molecule stabilization energy, radical stabilization energy, natural bond orbital,electron delocalization.

Résumé : La présente étude s’intéresse aux enthalpies de dissociation des liaisons (EDL) N−H de carbamates Y-substitués(NH2-C(=X)Y-R) et N-substitués ((R)(H)NC(=X)YH) (X, Y = O, S, Se; R = H, CH3, F, Cl, NH2), lesquels ont été évalués a l’aide de méthodesab initio et de la fonctionnelle de la densité. Les variations des EDL N–H de ces carbamates, conséquences de l’effet de substituant,ont été appréhendées du point de vue de l’énergie de stabilisation moléculaire (ESM) et de l’énergie de stabilisation radicalaire(ESR) qui ont été calculées a partir des réactions isodesmiques. L’analyse des orbitales naturelles de liaison a montré que ladélocalisation électronique des paires isolées d’hétéroatomes dans les molécules et les radicaux affectait les valeurs de l’ESM etde l’ESR, en fonction du type et du site de substitution (N- ou Y-). Les variations des EDL N−H dépendent des effets combinés desstabilisations moléculaire et radicalaire par divers substituants. [Traduit par la Rédaction]

Mots-clés : carbamates, effet de substituant, énergie de stabilisation moléculaire, énergie de stabilisation radicalaire, orbitalenaturelle de liaison, délocalisation électronique.

IntroductionIn reactions involving radical intermediates, no quantity is

more important than the homolytic bond dissociation energy(BDE).1 Thermodynamics of reactions involving the free radical isgoverned by enthalpy change accompanying the formation ofthe free radical, i.e., BDE.2 The BDEs act as database for reflectingthe intrinsic or instantaneous strength of the bond as well as thestability of the radicals obtained after cleavage. These are one ofthe important properties of molecules for considering their de-composition and chemical reactivities and for estimating theirheat of formation.3 The accurate prediction of BDEs has numer-ous applications, including the identification of sites for potentialfree radical attack in peptides, the assessment of the effectivenessof antioxidants, and the study of chain-transfer processes (such aslong-chain branching) in free radical polymerization.4–7 Most ofthe organic and biochemical reactions involve abstraction of thehydrogen atom that includes combustion, polymerization, atmo-spheric, and interstellar chemical pathways. The oxidation of ri-bonucleosides and deoxyribonucleosides by certain antibiotics,metal complexes, and redox active metalloenzymes has been sug-gested to occur through hydrogen abstraction.8–10 Hydrogen atomabstraction by the adenosyl radical is the key activation step incoenzyme B-12 mediated processes,11 whereas hydrogen atom ab-straction reactions involving peptide radicals are associated with

various physiological disorders12,13 such as arteriosclerosis,14 dia-betes, aging,15,16 and Alzheimer’s disease.17–19

The N−H bond is a key functional group in organic and biolog-ical chemistry. The class of compounds containing N–H bonds hasattracted a large number of researchers due to their presence inpharmaceutical agents,20–24 building blocks of biomolecules,synthetic commercial products and toxic substances, and25–27

antioxidants and as22,28–30 complexing agents,31 herbicides, andsurfactants.22,30,32 Nitrogen-centered radicals are of synthetic im-portance33 where they have been used in a number of cyclizationprocesses34 and homolytic amination reactions of aromatic mol-ecules. The N−H bond cleavage is also reported in the protontransfer enzymatic reactions catalyzed by acetylcholinestrase. Ni-trogen derivatives of amides, lactams, carbamates, and imideshave been shown to be effective initiators for the metal-catalyzedliving radical polymerization of methacrylates.35

Determination of N−H BDEs of carbamates is important frombiological, synthetic, medicinal as well as industrial perspec-tive, as they exhibit complex chemical and biological activi-ties as synthetic intermediates, protecting groups, chelatingagents, and free radical scavengers and being constituents ofinsecticides, pesticides, fungicides, antiviral, antifungal, anti-bacterial, antiparasitic, antiproliferative, antidermatophytic,antitumor agents, chemotherapeutic drugs, antioxidants, andindustrial chemicals.36–43

Received 18 July 2014. Accepted 3 October 2014.

R. Kaur and R. Sharma. Guru Nanak Dev University College, Verka, Distt, Amritsar 143001, India.D. Kaur. Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.Corresponding author: Rupinder preet Kaur (e-mail: rupinderpreet@gmail.com).

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Can. J. Chem. 93: 279–288 (2015) dx.doi.org/10.1139/cjc-2014-0326 Published at www.nrcresearchpress.com/cjc on 20 October 2014.

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The strength of a bond is sensitive to the number of atoms/groups attached to the atom involved in bond dissociation. Asubstituent influences the bond strength of a molecule in a quan-titative sense. The strength of the N–H bond is sensitive to thenumber of atoms attached to the nitrogen.44,45 Substituents pres-ent on the radical because of their steric or electronic natureinfluence both the kinetic and thermodynamic stability of theradical.46 Substituents through their steric effects can play asignificant role in the kinetic stabilization, whereas loweringof energy of the ground state plays an important role in the ther-modynamic stabilization of the radical. It is therefore the intrinsicproperty that is principally influenced by the ability of the sub-stituents to delocalize the unpaired electron.47 This can reducethe reactivity by reducing the spin densities on radical center. Themeasure of stability of nitrogen-centered radicals is provided bythe N−H homolytic BDE.

The effect of the substituent on the intrinsic structure, reactiv-ity, and energetics of carbamates has been analyzed by studyingthe BDE in NH2C(=X)Y-R and (R)(H)NC(=X)YH (X, Y = O, S, Se; R = H,F, Cl, CH3, NH2) molecules.

Computational detailsAll of the calculations reported in the present study were car-

ried out using the Gaussian 98 program suite.48 Full geometryoptimizations were performed on each species without anysymmetry constraint at the B3LYP/6-31+G* and MP2/6-31+G*theoretical levels. Each optimized structure was characterized byfrequency calculations to be a minimum without any imaginaryvibrational frequency. The geometries optimized at the B3LYP/6-31+G* level have been used to calculate single point energies at the6-31+G* and 6-311++G** basis sets using restricted open-shell for-malism. The CBS-Q composite level has also been used to calculatethe BDEs. The calculations have been performed using the Gauss-ian 09 program suite.

BDE is calculated as the enthalpy change of the following reac-tion in the gas phase at 298 K and 1 atm of pressure:

A-B �g� ¡ A �g� � B �g�

The BDE at 298 K was calculated by using the thermochemicalscheme supplied by Gaussian as in the following equation:BDE298(R1−R2) = [�fH298(R1) + �fH298(R2)] − �fH298(R1−R2), in whichR1–R2 is the neutral molecule and R1 and R2 are the correspond-ing radicals.49 By following the comprehensive paper of Merricket al., zero-point energies are scaled by a factor of 0.9153 at HF/6-31+G*, and these scaled zero-point vibration energy values areused for applying corrections to energies evaluated at the MP2/6-31+G* theoretical level and by 0.9806 at the B3LYP levels.50 Vibra-tional frequencies for calculating vibrational enthalpy are scaledby 0.8945 at HF/6-31+G*, and these scaled values are used for theMP2/6-31+G* theoretical level and by 0.9989 for the B3LYP level.51

The electronic energy of atomic hydrogen atom in DFT calcu-lations is basis set dependent, as can be observed from Jursicand Martin’s data (−0.50027 hartree for the 6-31G basis set,−0.50216 hartree for the 6-311G basis set, and −0.50226 hartree forthe 6-311++G basis set).52 Pople et al. suggested a high-level correc-tion for bound unpaired electrons and corrected the electronicenergy of the hydrogen atom to 0.50000 hartree in the G2 method.53

DiLabio and Pratt suggested that for the hydrogen atom being aunique one-electron system, a similar correction should be ap-plied in DFT calculations for the evaluation of BDE by fixing theelectronic energy of hydrogen to −0.50000 hartree.54 This hasbeen found to decrease the deviation of calculated BDEs fromexperimental data. The electronic energy of the hydrogen atom isfixed as 0.50000 hartree in the present studies.

Results

Geometries of Y-substituted and N-substituted carbamatesThe different conformations for Y-substituted (NH2-C(=X)Y-R)

and N-substituted ((R)(H)NC(=X)YH) carbamates (X, Y = O, S, Se; R =H, CH3, F, Cl, NH2) have been optimized at the B3LYP/6-31+G* andMP2/6-31+G* theoretical levels. Scheme 1a depicts the two energyminima corresponding to syn (Si) and anti (Ai) orientations ofNH2C(=X)Y-R that differ in relative position of R (Y–R bond) withrespect to the C=X group. Scheme 1b depicts four energy min-ima, SiSj, AiSj, SiAj, and AiAj, corresponding to orientations of(R)(H)NC(=X)YH that depict the relative position of N–R and Y–Hbonds with respect to C=X bond. In our earlier reports,55 we ob-served the syn orientation to be more stable than anti in the caseof carbamic acid and its higher chalcogenide (sulfur, selenium)analogs in the absence of any substituent. The higher stability ofsyn orientation has been assigned to stronger conjugative inter-actions involving the lone pair of electrons on N, X, and Y and theC=X bond. The substituents can alter the relative stability of synand anti conformers through inductive effect, variation in theconjugative interactions, and in addition the steric interactions.With the presence of substituents fluorine, chlorine, and NH2 at Y,the anti orientation is more stable than syn (with the exception ofchlorine (X = S, Y = O) and NH2 (X = S, Y = O)) but with R = CH3, thesyn conformation is relatively more stable for all X, Y = O, S, Se, ascan be seen from Table 1. Of the four optimized orientations foreach nitrogen-substituted molecule, the orientation SiAj is themost stable when R = F, Cl, NH2 but with R = CH3 (X, Y = O, X = S,Y = O, S, Se) the SiSj and with R = CH3 (X, Y = Se) the AiAj orienta-tions are the most stable one.

Scheme 1. (a) Different possible conformations for Y substitution.(b) Different possible conformations for nitrogen substitution. Here,“i” indicates the orientation of Y-R with respect to the C=X groupand “j” indicates the orientation of R-N with respect to the C=Xgroup. The dihedral angles for syn (S) and anti (A) conformation are0.0 and 180.0, respectively.

Y3

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N–H BDEs of H2NC(=X)Y-R (X, Y = O, S, Se) and(R)(H)NC(=X)YH (X, Y = O, S, Se) molecules

The radicals corresponding to the most stable conformations of(R)(H)NC(=X)YH and H2NC(=X)Y-R (X, Y = O, S, Se; R = H, F, Cl, CH3,NH2) molecules have also been optimized at the B3LYP/6-31+G*and MP2/6-31+G* theoretical levels. The N−H BDEs of thesemolecules have been evaluated using the ROB3LYP/6-31+G*//B3LYP/6-31+G* (L1), ROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* (L2),UMP2/6-311++G(d,p)//MP2/6–31+G* (L3), and CBS-Q (L4) theoreticallevels and are reported in Tables 2 and 3. The BDEs obtained usingDFT method ROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* are higherthan the values obtained with the MP2/6-311++G(d,p)//MP2/6-31+G* method. The N−H BDE of H2N-C(=O)OH (113.42 kcal/mol atthe L2 theoretical level) is higher than that of NH3 (107.3 kcal/molat the L2 theoretical level) but for H2N-C(=X)OH (X = S, Se), the N−H

BDE is 4.16 and 11.40 kcal/mol, respectively, lower than that ofNH3. The comparison of BDEs for NH2C(=X)-OH (X = O, S, Se) mol-ecules at the L2 theoretical level with those in the respectiveamides shows that the N−H BDE for X = O is lower (by 1.08 kcal/mol), while the BDEs with X = S, Se are higher (1.58 and 3.23 kcal/mol, respectively) relative to the corresponding N−H BDEs ofamides at the L2 theoretical level.56 The N−H BDE in carbamic acidand its thio- and seleno- analogs decreases in the order of X asO > S > Se for each Y = O, S, Se and in the order of Y as O > S > Sefor each X = O, S, Se. The variation in N−H BDE is higher in the caseof charge in chalcogen at position X than in the case of change atposition Y. The trends in N−H BDEs in the order of X and Y remainunchanged with the presence of substituents at nitrogen and Y.

The data in Table 2 reflect the decrease in N−H BDEs of nitrogen-substituted carbamates with the presence of substituents fluorine,

Table 1. The most stable conformation of the Y-substituted NH2C(=X)Y-R and nitrogen-substituted(R)(H)NC(=X)YH (X, Y = O, S, Se; R = H, CH3, F, Cl, NH2) molecules under study at the MP2/6-31+G*theoretical level.

Molecule Molecule

R at Y position X YMost stableconformation R at N position X Y

Most stableconformation

H O O Si H O O SiO S Si O S SiO Se Si O Se SiS O Si S O SiS S Si S S SiS Se Si S Se SiSe O Si Se O SiSe S Si Se S SiSe Se Si Se Se Si

F O O Ai F O O SiAjO S Ai O S SiAjO Se Ai O Se SiAjS O Ai S O SiAjS S Ai S S SiAjS Se Ai S Se SiAjSe O Ai Se O SiAjSe S Ai Se S SiAjSe Se Ai Se Se AiAj

Cl O O Ai Cl O O SiAjO S Ai O S SiAjO Se Ai O Se SiSjS O Si S O SiAjS S Si S S SiAjS Se Ai S Se SiAjSe O Ai Se O SiAjSe S Ai Se S SiAjSe Se Ai Se Se SiAj

CH3 O O Si CH3 O O SiSjO S Si O S SiAjO Se Si O Se SiAjS O Si S O SiSjS S Si S S SiSjS Se Si S Se SiSjSe O Si Se O SiAjSe S Si Se S AiSj

NH2 O O Si NH2 O O SiAjO S Ai O S SiAjO Se Ai O Se SiAjS O Ai S O SiAjS S Ai S S SiAjS Se Ai S Se SiAjSe O Ai Se O SiAjSe S Ai Se S SiSjSe Se Ai Se Se AiAj

Note: “i” indicates the orientation of Y-R with respect to the C=X group and “j” indicates the orientation of R-Nwith respect to the C=X group.

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Table 2. N−H bond dissociation enthalpies (kcal/mol) for (R)(H)NC(=X)YH (X, Y = O, S, Se; R = H, F, Cl,CH3, NH2) at the ROB3LYP/6-31+G*//B3LYP/6-31+G* (L1), ROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* (L2), andUMP2/6-311++G(d,p)// MP2/6-31+G(d,p) (L3) theoretical levels.

L1 L2 L3

R X Y = O Y = S Y = Se Y = O Y = S Y = Se Y = O Y = S Y = Se

H O 109.46 107.20 106.94 113.42 113.36 111.79 112.08 111.22 110.58S 98.79 94.80 92.94 103.14 97.22 92.77 98.38 94.67 92.39Se 94.67 90.16 87.32 95.90 90.17 86.13 92.07 84.04 83.75

F O 91.67 89.92 89.36 103.60 92.99 92.14 94.14 94.84 94.16S 81.76 88.82 80.69 84.97 91.52 82.69 84.90 83.75 79.81Se 81.92 75.58 74.05 78.16 75.99 75.78 75.07 73.99 77.32

Cl O 94.48 94.04 89.50 97.51 94.03 93.04 98.16 97.06 97.60S 87.79 85.06 82.88 90.47 87.58 83.59 91.72 86.03 79.96Se 82.20 79.96 76.92 83.60 80.73 77.50 77.60 75.60 76.27

CH3 O 104.39 100.94 98.68 107.05 103.93 103.17 106.86 103.71 103.22S 97.54 94.33 94.60 100.13 96.40 97.15 104.30 91.90 94.07Se 93.56 88.68 85.58 92.44 88.65 85.22 79.71 82.31 84.14

NH2 O 78.17 75.85 76.36 80.62 78.36 79.81 79.71 78.55 80.04S 76.36 72.74 72.31 78.61 74.87 74.24 78.04 77.80Se 76.56 72.38 70.43 78.54 74.23 72.49 78.49 83.49 81.02

Table 3. N−H bond dissociation enthalpies (kcal/mol) for Y-substituted carbamates H2NC(=X)Y-R (X,Y = O, S, Se; R = H, F, Cl, CH3, NH2) at the ROB3LYP/6-31+G*//B3LYP/6-31+G* (L1), ROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* (L2), and UMP2/6-311++G(d,p)// MP2/6-31+G(d,p) (L3) theoretical levels.

L1 L2 L3

R X Y = O Y = S Y = Se Y = O Y = S Y = Se Y = O Y = S Y = Se

H O 109.46 107.20 106.94 113.42 113.36 111.79 112.08 111.22 110.58S 98.79 94.80 92.94 103.14 97.22 92.77 98.38 94.67 92.39Se 94.67 90.16 87.32 95.90 90.17 86.13 92.07 84.04 83.75

F O 114.07 109.40 112.92 127.37 115.59 116.62 127.18 115.58 134.30S 103.49 108.32 96.64 106.45 103.70 97.20 97.48 100.47 109.77Se 99.32 94.09 91.91 101.49 94.59 101.49 107.04 124.90 95.14

Cl O 108.51 108.61 111.39 111.41 107.26 110.87S 96.55 99.01 97.13 99.08 101.46 97.72 92.01 100.21 97.62Se 91.64 94.09 92.46 95.17 94.09 91.75 82.14 90.34 118.88

CH3 O 109.60 106.92 105.75 112.24 109.86 108.35 115.93 109.80 101.97S 95.54 96.24 93.29 97.69 97.82 92.37 92.41 93.26 97.53Se 86.82 89.03 87.97 92.47 88.81 87.98 88.48 87.82 88.45

NH2 O 109.73 111.49 112.27 114.30 112.24 112.60S 95.61 95.50 95.31 97.60 95.63 95.75 92.17 94.95 121.06Se 89.38 92.20 91.79 89.37 91.95 90.82 82.81 85.26 91.66

Fig. 1. Trends in N−H bond dissociation enthalpies (BDE) of(R)(H)NC(=X)YH (X = O, S, Se; Y = O, S, Se; R = H, CH3, NH2, Cl, F) atthe ROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* theoretical level.

Fig. 2. Trends in N−H bond dissociation enthalpies (BDE) ofH2NC(=X)Y-R (X = O, S, Se; Y = O, S, Se; R = H, F, Cl, CH3, NH2) at theROB3LYP/6-311++G(d,p)//B3LYP/6-31+G* theoretical level.

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chlorine, CH3, and NH2 at nitrogen relative to H2NC(=X)YH (X,Y = O, S, Se). The largest decrease in N−H BDE with substitution atnitrogen is indicated in the case of R=NH2. As can be observedfrom the table, the variation in N−H BDE as the result of substitu-tion is higher with change in X from oxygen to sulfur or selenium.The variations in N−H BDEs with the presence of substituents atposition Y are relatively smaller in comparison with the varia-tions with substituents at nitrogen (see Tables 2 and 3). There is

an increase in N−H BDE with the presence of highly electrone-gative substituent fluorine at Y but the increase in BDE with thesubstituents NH2 and Cl is reflected only for molecules with X,Y = S, Se in H2NC(=X)YR molecules (Table 3). The decrease inN−H BDE results in H2NC(=X)YR (R = Cl, NH2 with X = O, S, Seand with Y = O) molecules. There is negligible to small variationin N−H BDEs in H2NC(=X)YCH3 (X, Y = O, S, Se) relative toH2NC(=X)YH.

Table 4. Molecule stabilization effect (ME) (kcal/mol), radical stabilization effect (RE) (kcal/mol), and total stabilizationeffect (RSE) (kcal/mol) for nitrogen-substituted carbamic acid (R)(H)NC(=X)YH (X, Y = O, S, Se; R = F, Cl, CH3, NH2) at theROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

�BDE Y = O Y = S Y = Se

R X Y = O Y = S Y = Se ME RE TSE ME RE TSE ME RE TSE

F O 17.79 17.28 17.58 −11.16 7.10 18.26 −8.97 8.36 17.32 −7.04 10.54 17.58S 17.03 6.79 12.25 −13.72 6.70 17.02 −6.49 −0.11 6.38 −4.71 7.53 12.24Se 12.75 14.58 13.27 −9.92 2.83 12.75 −5.70 8.88 14.58 −4.35 8.92 13.27

Cl O 14.98 13.16 17.44 −0.98 5.17 14.97 −8.59 4.67 13.26 −6.00 11.18 17.18S 11.00 9.74 10.06 −8.46 2.54 10.99 −6.68 3.07 9.75 −4.95 5.49 10.44Se 12.47 10.20 10.40 −5.67 6.97 12.64 −4.68 5.51 10.19 −2.40 8.00 10.40

CH3 O 5.07 6.26 8.26 0.02 5.10 5.08 −0.84 5.47 6.31 0.06 8.34 8.28S 1.25 0.47 −1.66 0.88 2.13 1.25 0.88 1.36 0.48 1.92 0.27 −1.65Se 1.11 1.48 1.74 9.51 4.34 −5.16 2.14 3.65 1.51 3.62 5.60 1.98

NH2 O 31.29 31.35 30.58 −0.81 30.49 31.30 0.38 31.48 31.10 3.09 33.31 30.21S 22.43 22.06 20.63 0.59 23.79 23.20 1.37 24.28 22.91 2.79 25.54 22.75Se 18.11 17.78 16.89 2.88 20.99 18.11 3.45 19.26 16.02 4.64 21.53 16.89

��te: �BDE = BDEH2NC(=X)YH − BDE(R)(H)NC(=X)YH.

Table 5. Molecule stabilization effect (ME) (kcal/mol), radical stabilization effect (RE) (kcal/mol), and total stabilizationeffect (TSE) (kcal/mol) for H2N-C(=X)YR (X, Y = O, S, Se; R = H, F, Cl, CH3, NH2) molecules at the ROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

�BDE Y = O Y = S Y = Se

R X Y = O Y = S Y = Se ME RE TSE ME RE TSE ME RE TSE

F O −4.61 −2.20 −5.98 −1.44 −5.79 −4.35 6.88 4.72 −2.16 6.61 0.62 −5.99S −5.70 −13.52 −3.70 4.50 −0.21 −4.71 12.09 −1.42 −13.51 10.53 6.83 −3.70Se −4.65 −3.93 −4.59 9.48 4.84 −4.64 13.56 9.62 −3.94 14.26 9.67 −4.59

Cl O 0.95 −1.41 − −5.36 −4.41 0.95 4.03 4.24 −1.36 − − −S 2.24 −4.21 −4.19 −2.02 0.20 2.22 8.84 4.64 −4.20 8.12 3.93 −4.19Se 3.03 −3.93 −5.14 3.39 6.24 2.85 10.82 7.64 −3.18 12.37 7.22 −5.15

CH3 O −0.14 0.28 1.19 2.00 2.84 0.84 3.32 3.66 0.34 2.36 3.23 1.20S 3.25 −1.44 −0.35 1.50 4.98 3.48 4.08 2.66 −1.42 2.36 2.01 −0.35Se 7.85 1.13 −0.65 2.72 9.01 7.83 5.20 6.32 1.12 3.79 3.15 −0.64

NH2 O −0.27 −4.29 − −1.11 −1.37 −0.26 6.74 2.49 −4.25S 3.18 −0.70 −2.37 −1.62 1.55 3.17 9.38 8.68 −0.70 7.59 5.22 −2.37Se 5.29 −2.04 −4.47 1.01 6.30 5.29 10.32 8.29 −2.03 10.88 6.42 −3.46

��te: �BDE = BDENH2C(=X)YH − BDENH2C(=X)Y−R.

Fig. 3. Trends in molecular stabilization energies (ME) of(R)(H)NC(=X)YH (X = O, S, Se; Y = O, S, Se; R = H, CH3, NH2, Cl, F) atthe ROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

Fig. 4. Trends in molecular stabilization energies (ME) ofH2NC(=X)Y-R (X = O, S, Se; Y = O, S, Se; R = H, CH3, NH2, Cl, F) at theROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

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The substituents at position Y in the molecules are at position �to the N−H bond; therefore, their effect on N−H BDE is expected tobe small. However, the significant variation in N−H BDE due to thepresence of the highly electronegative fluorine substituent at theY position suggests the importance of substituents at the � posi-tion also. As can be seen from the Table 2, the N−H BDEs in(R)(H)NC(=X)YH (X = O; Y = O, S, Se) decrease in the orderH > CH3 > Cl > F > NH2, while with (X = S; Y = O, S, Se), thesedecrease in the order H > CH3 > Cl > F > NH2 and for (X = Se; Y = O,S, Se) decrease follows the order H > CH3 > Cl > F > NH2. In Figs. 1and 2, plots indicating the trends in N−H BDEs with substitutionof (R)(H)NC(=X)YH and NH2C(=X)YR (X = O, S, Se; Y = O, S, Se)molecules by fluorine, chlorine, CH3, and NH2 substituents aredepicted. These plots reflect that the substituent effect is morepronounced in nitrogen-substituted relative to the Y-substitutedmolecules and the substituent effect is not operative throughinductive effect only. In contrast with NH2C(=X)YR molecules, thetrend with respect to various substituents does not differ much inthe case of (R)(H)NC(=X)YH molecules for all of the possibilities ofX = O, S, Se; Y = O, S, Se. The variation in N−H BDE as the result ofsubstitution is evaluated as

�BDE � BDE�NH2C(�X)YH� � BDE�NH2C(�X)YR or (R)(H)NC(�X)YH�

The values for �BDE for (R)(H)NC(=X)YH and H2NC(=X)YR (X = O, S,Se; Y = O, S, Se) molecules are given in Tables 4 and 5, respectively.The data in Tables 4 and 5 show that the highest �BDE in(R)(H)NC(=X)Y (X = O, S, Se; Y = O, S, Se) is reflected by R = NH2,while in the case of H2NC(=X)YR (X = O, S, Se; Y = O, S, Se), thevariation is largest for R = F.

Substituent effect on the stability of the molecule andradical

Since the variation in BDE is the result of the effect of thesubstituent on the relative stability of the molecule and the radi-cal, to understand the role of substitution on the stability of thetwo species, the molecule stabilization energy (ME) and radicalstabilization energy (RE) have been evaluated. The ME and RE for(R)(H)NC(=X)YH are evaluated as the enthalpy changes associatedwith the isodesmic reactions 1 and 2, respectively:

(1)

(2)

The ME and RE values for (R)(H)NC(=X)YH (X, Y = O, S, Se; R = H, F,Cl, CH3, NH2) are reported in Table 4 at the ROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level. Positive ME values, as definedhere, denote greater stability of the molecule relative to H2NC(=X)YHand contribute to an increase in BDE. Positive RE values indi-cate greater stability of the radical relative to the unsubstitutedreference radical species NH.C(=X)YH and contribute to a de-crease in BDE. The stabilization of molecules and their respec-tive radicals can be rationalized in terms of electronic andsteric factors. The electronic factors result from the change inelectron delocalization, change in ionic and covalent characterof bonds, and additional noncovalent interactions like the hy-drogen bond if any.

Table 4 lists the ME and RE values for (R)(H)NC(=X)YH (X, Y = O,S, Se; R = H, F, Cl and NH2) molecules and their respective radicals.

ME values for (R)(H)NC(=X)YH molecules with R = F, Cl are nega-tive, suggesting destabilization of the molecules with substitu-tion, while with R = CH3, NH2; X, Y = O, S, Se, positive ME values(with two exceptions) reflect stabilization of the molecule by suchsubstitutions. The range of ME values in (R)(H)NC(=X)YH mole-cules when X = O, S, Se and Y = O is from −13.72 to 9.51 kcal/mol.The ME values range from −8.97 to 3.45 kcal/mol when X = O, S, Seand Y = S and from −7.04 to 4.64 kcal/mol when X = O, S, Se and Y =Se. The strongest destabilization effect is reflected by substitutionof fluorine at the nitrogen in (R)(H)NC(=X)YH molecules.

The positive RE values for the radicals (R)N·C(=X)YH (X, Y = O, S,Se; R = F, Cl, CH3, NH2) indicate a stabilizing effect of the substitu-ent on the stability of the radical and it tends to lower the BDE.The magnitude of the RE value is higher than |ME| in nearly 70% ofthe radicals under study. The largest RE values are evaluated forR = NH2 for all X and Y. The RE values of (R)N·C(=X)YH radicalswhen X = O, S, Se and Y = O range from 2.13 to 30.39 kcal/mol. TheRE values range from −0.11 to 31.48 kcal/mol when X = O, S, Se andY = S and from 0.27 to 33.31 kcal/mol when X = O, S, Se and Y = Se.

The ME and RE in H2NC(=X)Y-R molecules are evaluated employ-ing the following isodesmic reactions:

(3)

Fig. 5. Trends in relative stabilization energies (RE) of(R)(H)NC(=X)YH (X = O, S, Se; Y = O, S, Se; R = H, CH3, NH2, Cl, F) atthe ROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

Fig. 6. Trends in relative stabilization energies (RE) of H2NC(=X)Y-R(X = O, S, Se; Y = O, S, Se; R = H, CH3, NH2, Cl, F) at the ROB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level.

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(4)

The ME and RE values for the H2N-C(=X)YR molecules are recordedin Table 5. As can be seen from the table, the ME values arepositive for X = S, Se and Y = O, S, Se in H2N-C(=X)YR moleculeswith R = F, Cl, CH3, NH2 with two exceptions, while negative MEvalues result in the case of X = O and Y = O with all four substitu-ents. The molecular stabilization resulting from these substitu-ents present at Y in H2N-C(=X)YR with X = S, Se and Y = O, S, Seshows the effect in the increase in N−H BDE of the substituent.The presence of substituents at position Y of the radicals H2N-C(=X)YR stabilizes the respective radical with respect to the un-substituted counterpart with the exception of R = F, Cl, NH2 withX = O and Y = O. The magnitude of RE values is less than |ME| in alarge number of cases. The RE values are lower in comparisonwith respective values for nitrogen-substituted radicals. The REvalues of HN·C(=X)YR radicals when X = O, S, Se and Y = O rangefrom −5.79 to 10.55 kcal/mol. The RE values range from −1.42 to

9.62 kcal/mol when X = O, S, Se and Y = S and from 0.62 to9.67 kcal/mol when X = O, S, Se and Y = Se. The trends of variationin ME and RE values of (R)(H)NC(=X)YH and H2NC(=X)Y-R (X, Y = O,S, Se; R = H, F, Cl, CH3, NH2) molecules are depicted in Figs. 3–6.

As the positive ME tends to enhance the BDE, while positive REfavors a decrease in BDE, the total stabilization effect (RE − ME)gives the expected change in BDE. The comparison of the totalstabilization effect with �BDE (as defined earlier) shows a perfectmatch between the two in most of the cases with three exceptionswhere only small deviations have been observed. The �BDE valuesare higher in the case of nitrogen-substituted carbamates than ofY-substituted carbamates.

Discussion

Electron delocalization and MEOur earlier results on the stability of carbamic acid indicated

the role of extended conjugation resulting from electron delocal-ization of lone pairs of electrons present on nitrogen, X, and Y.55

The substituents at the nitrogen or Y position can alter the elec-tron delocalization. To explore the variation in electron delocal-

Table 6. Important lone pair occupancies � on different atoms in (R)(H)NC(=X)YH and H2NC(=X)YR (X = O, S, Se; Y = O, (S), [Se]; R = F, Cl, CH3, NH2)molecules at the MP2/6-31+G* theoretical level.

(R)(H)NC(=O)YH H2NC(=O)YR (R)(H)NC(=S)YH H2NC(=S)YR (R)(H)NC(=Se)YH H2NC(=Se)YR

R �(O) �(Y) �(N) �(O) �(Y) �(N) �(S) �(Y) �(N) �(S) �(Y) �(N) �(Se) �(Y) �(N) �(Se) �(Y) �(N)

H 1.87 1.90 1.83 1.87 1.90 1.83 1.88 1.88 1.76 1.88 1.88 1.76 1.90 1.88 1.81 1.90 1.88 1.81(1.87) (1.91) (1.82) (1.87) (1.91) (1.82) (1.89) (1.88) (1.85) (1.89) (1.88) (1.85) (1.91) (1.87) (1.74) (1.91) (1.87) (1.74)[1.87] [1.93] [1.80] [1.87] [1.93] [1.80] [1.88] [1.90] [1.75] [1.88] [1.90] [1.75] [1.90] [1.88] [1.74] [1.90] [1.88] [1.74]

F 1.87 1.87 1.90 1.84 1.92 1.79 1.87 1.85 1.87 1.82 1.90 1.73 1.88 1.84 1.86 1.88 1.91 1.75(1.87) (1.87) (1.90) (1.86) (1.90) (1.78) (1.88) (1.83) (1.87) (1.85) (1.86) (1.73) (1.90) (1.82) (1.86) (1.85) (1.84) (1.71)[1.87] [1.89] [1.90] [1.86] [1.91] [1.78] [1.88] [1.85] [1.87] [1.85] [1.87] [1.72] [1.89] [1.83] [1.86] [1.84] [1.85] [1.70]

Cl 1.87 1.88 1.87 1.85 1.92 1.81 1.87 1.86 1.81 1.86 1.90 1.78 1.89 1.86 1.76 1.86 1.89 1.73(1.87) (1.89) (1.86) (1.86) (1.91) (1.79) (1.88) (1.85) (1.82) (1.85) (1.88) (1.73) (1.89) (1.85) (1.75) (1.85) (1.86) (1.71)[1.86] [1.92] [1.85] [1.86] [1.92] [1.78] [1.87] [1.87] [1.77] [1.84] [1.89] [1.75] [1.89] [1.86] [1.78] [1.84] [1.87] [1.70]

CH3 1.88 1.90 1.79 1.87 1.87 1.84 1.88 1.88 1.72 1.89 1.85 1.78 1.90 1.87 1.71 1.90 1.85 1.75(1.87) (1.91) (1.77) (1.88) (1.88) (1.83) (1.89) (1.89) (1.71) (1.89) (1.85) (1.78) (1.91) (1.86) (1.69) (1.90) (1.84) (1.74)[1.87] [1.92] [1.77] [1.87] [1.91] [1.81] [1.88] [1.90] [1.71] [1.88] [1.87] [1.75] [1.90] [1.89] [1.69] [1.90] [1.86] [1.74]

NH2 1.87 1.90 1.79 1.87 1.89 1.83 1.88 1.88 1.73 1.88 1.89 1.75 1.90 1.88 1.72 1.89 1.88 1.73(1.87) (1.91) (1.78) (1.88) (1.90) (1.79) (1.88) (1.87) (1.73) (1.88) (1.87) (1.73) (1.91) (1.88) (1.71) (1.90) (1.86) (1.71)[1.86] [1.91] [1.80] [1.88] [1.89] [1.73] [1.88] [1.89] [1.72] [1.90] [1.87] [1.71] [1.89] [1.88] [1.70]

Table 7. Lone pair occupancies � on X and N of (R)·NC(=X)YH (X, Y = O, (S), [Se]; R = H, F, Cl, CH3, NH2)radicals at the MP2/6-31+G* theoretical level.

(R)·NC(=O)YH (R)·NC(=S)YH (R)·NC(=Se)YH

�1(N) �1(N) �1(N)

R � � �2(N) � � � �2(S) � � � �2(Se) �

F 0.99 0.99 0.95 0.98 0.98 0.98 0.98 0.96 0.95(0.99) (0.99) (0.97) (0.98) (0.98) (0.98) (0.98) (0.96) (0.95)[0.99] [0.99] [0.95] [0.98] [0.98] [0.98] [0.98] [0.96] [0.95]

Cl 0.99 0.98 0.95 0.98 0.98 0.98 0.97 0.95 0.96(0.99) (0.99) (0.95) (0.98) (0.97) (0.98) (0.98) (0.96) (0.95)[0.99] [0.99] [0.95] [0.98] [0.98] [0.97] [0.97] [0.96] [0.94]

CH3 0.97 0.95 0.94 0.96 0.96 0.95 0.95 0.89 0.96(0.97) (0.95) (0.94) (0.96) (0.96) (0.95) (0.95) (0.92) (0.95)[0.97] [0.95] [0.94] [0.95] [0.95] [0.93] [0.94] [0.92] [0.97]

NH2 0.98 0.97 0.89 0.97 0.97 0.97 0.97 0.89 0.84(0.98) (0.97) (0.88) (0.97) (0.97) (0.97) (0.97) (0.92) (0.82)[0.98] [0.97] [0.88] [0.96] [0.96] [0.97] [0.96] [0.92] [0.93]

NO2 0.96 0.97 0.96 0.96 0.97 0.97 0.97 0.91 0.91(0.96) (0.97) (0.96) (0.97) (0.97) (0.97) (0.97) (0.90) (0.90)[0.95] [0.97] [0.96] [0.97] [0.97] [0.97] [0.96] [0.90] [0.89]

OH 0.99 0.99 0.94 0.98 0.98 0.98 0.98 0.96 0.93(0.99) (0.99) (0.94) (0.98) (0.97) (0.98) (0.98) (0.96) (0.89)[0.98] [0.98] [0.92] [0.98] [0.98] [0.95]

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ization as a result of nitrogen and Y substitution, NBO analysis ofall of the molecules under study has been carried out at the MP2/6-31+G* theoretical level.57 Important lone pair occupancies ofnitrogen- and Y-substituted carbamates are listed in Table 6 andsecond-order stabilization energy E(2) values for different electrondelocalizations are reported in the supplementary data (Tables S1–S6) (see Supplementary material section). The E(2) values for nN ¡

*C−X, nN ¡ *C−X, nX ¡ *C−N, and nY ¡ *C−X orbital interactionsreflect the importance of conjugative interactions in the carbamicacid molecule and its thio and seleno analogs. The nN ¡ *C−X andnY ¡ *C−X interactions involve a shift of electron density to thesame acceptor orbital; with the change in X from oxygen to sele-nium through sulfur, there is increase in E(2) values for both thetypes of interactions. The trend can be rationalized in terms oflarger size and polarizability of the chalcogen atom.

The electron delocalization can also be depicted from the lonepair occupancies �(N) in Table 6. As can be seen from the table, thelone pair of electrons present at the nitrogen is the most delocal-ized. The �(N) increases in the order of X as O > S > Se in thenitrogen-substituted molecules. There is decrease in �(N) with CH3

and NH2 as substituent, while there is relative increase in �(N)with R = F, Cl, suggesting an increase in electron delocalizationwith R = CH3 and NH2 and a decrease in electron delocalization ofthe lone pair of electrons present at the nitrogen in the latter.

There is negligible to small change in �(X) with substitutionat the nitrogen but �(Y) undergoes a decrease in the case of R = F, Cl.These variations along with ME values explain that ME variationsarise as a result of change in conjugative interactions. The lonepair occupancies of the H2NC(=X)YR molecules also reflect thevariation in conjugative interactions arising as a result of substi-tution at position Y. In spite of the presence of substituents atposition Y, the lone pair occupancy of nitrogen is decreased fur-ther. In the case of R = F, X = S, and Y = O, S, Se, the lone pairspresent at the sulfur are also further delocalized, thereby stabiliz-ing the molecule. In the case of X = Se, Y = O, S, Se, and R = F, all ofthe lone pairs of electrons present at X, Y, and nitrogen undergo adecrease, thereby resulting in the highest ME values in these mol-ecules.

Electron delocalization and REThe E(2) values from NBO analysis (Tables S7–S12) of radicals

(R)N·C(=X)YH (X, Y = O, S, Se; R = H, F, Cl, CH3, NH2) suggest that onradical formation, nN ¡ *C−O/*C−O delocalization decreases or isabsent, which is understandable in terms of the presence of anunpaired electron at the nitrogen restricting the delocalization ofthe lone pair of electrons of the nitrogen. The E(2) values for nX ¡

*C−N and nX ¡ *C−Y electron delocalization in the radicals(R)N·C(=X)YH (X,Y = O, S, Se) reflect only small variation withsubstituents. This is supported by the lone pair occupancies listedin Tables 7 and 8. In the radicals of molecules (R)(H)NC(=X)YH (X =S, Se; Y = O, S, Se), the orbital interactions nX ¡ *C−Y,nN ¡ *C−S,and nY ¡ *C−X are absent, while nY ¡ *C−N becomes operativewith the exception of R = NH2. The molecular orbitals in the NBOanalysis suggest the formation of a C–N bond in (R)N·C(=X)YH(X = S, Se; Y = O, S, Se) that is absent in the case of (R)N·C(=X)YHradicals with X = O.

The energy of unpaired electron at the nitrogen matches theenergy of the C−O molecular orbital, thereby indicating theprobability of stabilization of the radical center through interac-tion of the unpaired electron with the electron, thereby result-ing in positive RE values for RN·C(=O)H radicals. Indeed, the C2–O1bond is strengthened upon radical formation. In the case of(R)N·C(=X)YH (X = S, Se; Y = O, S, Se) radicals, the molecular orbitalanalysis indicates the shift of the radical center to X and thepresence of a C–N bond in place of a C–X bond in the respec-tive molecules. The geometrical parameters also support the in-ference. T

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b�(C

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286 Can. J. Chem. Vol. 93, 2015

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In the case of HN·C(=O)YR radicals, there is a considerable de-crease in nN ¡ *C−X delocalization on radical formation in all ofthese substituted carbamates, as indicated by the E(2) values, whilean increase in E(2) values of nY ¡ *C−X delocalization is observedon radical formation. The new orbital interaction nY ¡ *C−N

arises on radical formation in Y-substituted molecules also. Otherorbital interactions undergo only small variations. This is re-flected by the lone pair occupancies.

The occupancies of some important � and � spin orbitals of theradicals are reported in Tables 7 and 8. The analysis of occupanciesof � and � spin orbitals of the radicals indicate that the unpairedelectron resides at the nitrogen atom with X = O but is at X in thecase of X = S or Se. Thus, the positive RE values in (R)N·C(=X)YH (X =S, Se; Y = O, S, Se) can be rationalized in terms of difference instability of the C–N bond and C–X bond. The extraordinarilyhigh RE value of R = NH2 in the case of X, Y = O, S, Se results as thelone pair of electrons present on the substituent nitrogen interactwith the unpaired radical center on the nitrogen in RN(·)C(=O)YH,thereby stabilizing the radical considerably.

The decrease in N−H BDE of R(H)NC(=X)YH with X, Y = O, S, Seand R = F, Cl arises with respect to unsubstituted H2NC(=X)YHbecause of decreasing molecular stability and increasing radicalstability With R = CH3, NH2, it is mainly the increase in radicalstability that causes the decrease in N−H BDE.

On the contrary, with the substitution at Y, the variations inN−H BDEs are smaller with respect to unsubstituted H2NC(=X)YH.With Y = S, Se and X = O, S, Se and Y = O and X = S, Se, both ME andRE values are positive but the magnitude of RE is lower than thatof ME in most of the cases, hence causing an increase in BDE.

ConclusionsBDE is considered to be representative of bond strength. The

present study highlights the role of substituents on the rela-tive stability of a molecule and the corresponding radical in(R)(H)NC(=X)YH and NH2C(=X)Y-R molecules. The following factorsare observed to contribute towards the N−H BDEs: (i) variation inelectron delocalization as the result of stabilization in themolecules and radicals, (ii) change in hybridization upon radicalformation, (iii) reorganization of the geometry upon radical for-mation, (iv) unpaired electron delocalization through conjugativeand inductive effects, and (v) shift of the radical center.

Important observations in the present study are:

(1) In nitrogen-substituted or Y-substituted carbamates, the N−HBDE decreases in the order of X as O > S > Se for each value ofY. The N−H BDEs follow the same trend with change in Y fromO to S and Se but the magnitude is comparatively smaller incomparison with that with X.

(2) The effect of substituent on N−H BDE is more pronouncedwhen the substituent is present at the nitrogen in R(H)NC(=X)YHmolecules. The change in N−H BDE does not follow any trendwith electronegativity of the substituent, indicating the roleof several factors rather than only the inductive effect.

(3) The molecule stabilization energy as the result of substitutionat the nitrogen can be rationalized in terms of variation inelectron delocalization of the lone pairs of electrons presentat X, Y, and nitrogen.

(4) The change in molecular stabilization using isodesmic reac-tions (ME) suggests destabilization in molecules R(H)NC(=X)YH(X, Y = O, S, Se; R = F, Cl), while stabilization results in mole-cules R(H)NC(=X)YH (X, Y = O, S, Se; R = CH3, NH2). The REvalues reflect stabilization of radicals for each X, Y, and R.Thus, the decrease in BDE in the case of R = CH3, NH2 is duetoenhanced radical stabilization, while for R = F, Cl, both MEand RE contribute to the decrease in BDE.

(5) For H2NC(=X)YR molecules, stabilization resulted with all thefour substituents when X, Y = S, Se X = O Y = S, Se but MEvalues are lower in magnitude in comparison with the values

in the case of R(H)NC(=X)YH molecules. The RE values for theradicals (H)·NC(=X)YR (X, Y = O, S, Se; R = F, Cl, CH3, NH2) alsoreflect stabilization. As the combined effect of ME and RE, theBDE values are increased for R = F, Cl with few exceptions.

(6) The NBO analysis helped in rationalizing the ME and RE val-ues in terms of change in electron delocalization, shift in theradical center, and stabilization resulting as interaction of anunpaired electron with the substituent.

Supplementary materialSupplementary material is available with the article through the

journal Web site at http://nrcresearchpress.com/doi/suppl/10.1139/cjc-2014-0326. Supplementary information includes second-orderdelocalization energies E(2) (in kcal/mol) for the orbital interac-tions in (R)(H)NC(=X)YH and H2NC(=X)YR (X, Y = O, S, Se; R = H, F,Cl, CH3, NH2) molecules and their radicals at the MP2/6-31+G*theoretical level in Tables S1–S12. Figures S1–S3 incude the moststable comformations of (R)(H)NC(=X)YH and H2NC(=X)YR (X, Y =O, S, Se; R = H, F, Cl, CH3, NH2) molecules.

AcknowledgementThe authors are very thankful to the Council of Scientific and

Industrial Research, New Delhi, for financial assistance.

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