DFT study of the gas-phase thermal decomposition kinetics of 2-ethoxypyridine into 2-pyridone

DFT Study of the Gas-Phase ThermalDecomposition Kinetics of2-Ethoxypyridine into 2-Pyridone

EDGAR MARQUEZ,1 TANIA CORDOVA,2 GABRIEL CHUCHANI3

1Departamento de Quımica, Escuela de Ciencias, Universidad de Oriente Nucleo Sucre,Cumana, Venezuela2Department of Medicinal Chemistry, College of Pharmacy, University of Florida,P.O Box. 100485, Gainesville, FL 326103Centro de Quımica, Instituto Venezolano de Investigaciones Cientıficas (I.V.I.C.),Apartado 21827, Caracas 1020.A, Venezuela

Received 24 September 2010; accepted 8 January 2011Published online 4 April 2011 in Wiley Online Library (wileyonlinelibrary.com).DOI 10.1002/qua.23072

ABSTRACT: The mechanism of the gas-phase elimination kinetics of 2-ethoxypyridine has been studied through the electronic structure calculations usingdensity functional methods: B3LYP/6-31G(d,p), B3LYP/6-31þþG(d,p), B3PW91/6-31G(d,p), B3PW91/6-31þþG(d,p), MPW1PW91/6-31G(d,p), MPW1PW91/6-31þþG(d,p), PBEPBE/6-31G(d,p), PBEPBE/6-31þþG(d,p), PBE1PBE1/6-31G(d,p), andPBE1PBE1/6-31þþG(d,p). The elimination reaction of 2-ethoxypyridine occursthrough a six-centered transition state geometry involving the pyridine nitrogen,the substituted carbon of the aromatic ring, the ethoxy oxygen, two carbons of theethoxy group, and a hydrogen atom, which migrates from the ethoxy group to thenitrogen to give 2-pyridone and ethylene. The reaction mechanism appears to occurwith the participation of p-electrons, similar to alkyl vinyl ether elimination reaction,with simultaneous ethylene formation and hydrogen migration to the pyridinenitrogen producing 2-pyridone. VC 2011 Wiley Periodicals, Inc. Int J Quantum Chem112: 724–730, 2012

Key words: 2-ethoxypyridine; mechanism; gas-phase elimination; DFT calculations

Correspondence to: G. Chuchani; e-mail: [email protected] grant sponsor: Consejo de Desarrollo Cientıfico y

Humanıstico.Contract grant number: PG-03-00-6499-2006.

International Journal of Quantum Chemistry, Vol 112, 724–730 (2012)VC 2011 Wiley Periodicals, Inc.

1. Introduction

An interesting work of a homogeneous unim-olecular gas-phase pyrolysis reaction is the

reported conversion of 2-ethoxypyridine into 2-pyridone [1]. Kinetic data, especially the value oflog A ¼ 12.22, led to believe a typical processundergoing a semiconcerted six-membered cyclictransition state (TS) type of mechanism asdescribed in reaction (1).

ð1Þ

The mechanistic consideration of reaction (1)was derived by the analogy of the nitrogen withcarboxylate ester pyrolysis [reaction (2)] whereX ¼ Y ¼ O [2, 3]. This kinetic study regarded thistype of reaction to be the first in which aromaticp-electrons participate.

ð2Þ

It has been established that heteroaromatic com-pounds are divided in two broad groups: p-exces-sive and p-deficient, depending on whether theheteroatom acts as an electron donor or an electronacceptor [4]. In this respect, pyridine is known tobe p-deficient and deactivated to electrophilicattack. It has been suggested that the pyrolysis of 2-ethoxypyridine in the gas phase could alsoundergo an alkyl vinyl ether type of elimination [5]as depicted in reaction (3). The present work isaimed at examining the potential energy surface(PES) of 2-ethoxypyridine at the DFT level oftheory to obtain the kinetic and thermodynamicparameters for the reasonable mechanism of 2-ethoxypyridine elimination in the gas phase.

ð3Þ

2. Computational Methods andModels

Electronic structure calculations of the PES of2-ethoxypyridine were carried out using densityfunctional theory methods at B3LYP/6-31G(d,p),B3LYP/6-31þþG(d,p), B3PW91/6-31G(d,p), B3PW91/6-31þþG(d,p), MPW1PW91/6-31G(d,p), MPW1PW91/6-31þþG(d,p), PBEPBE/6-31G(d,p), PBEPBE/6-31þþG(d,p), PBE1PBE1/6-31G(d,p), and PBE1PBE1/6-31þþG(d,p) levels. These methods are implemented inGaussian 03 [6]. The stationary point structures ofreactant and products were obtained using thedefault options in Gaussian for convergence andverified by vibrational analysis. The TS structurewas localized using the quadratic synchronoustransit method and confirmed by normal-modeanalysis by having a single imaginary frequency.Intrinsic reaction coordinate (IRC) calculationswere carried out to study the minimum energypath and verify that the TS produce the reactantand products in the reverse and forward calcula-tion directions, respectively. Zero-point vibra-tional energies (ZPVE), temperature corrections(E(T)), and absolute entropies (S(T)) wereobtained from frequency calculations at the sametheory level used in the optimizations. The idealgas model was used for temperature correctionsand absolute entropies from the harmonic fre-quencies and moments of inertia by standardmethods [7]. Scaling factors for frequencies andzero point energies were taken from the literature[8, 9]. Average experimental temperature andpressure values were used in the frequency calcu-lations. First-order rate coefficients k(T) for thereactions under study were estimated using theclassical TS theory (TST) [10] assuming that thetransmission coefficient is equal to 1 as expressedin the equation:

kðTÞ ¼ rðkBT=hÞ expð�DG‡=RTÞ

Where DG‡ is the Gibbs free energy changebetween the reactant and the TS, and kB and h arethe Boltzmann and Plank constants, respectively,and r is the symmetry number.

DG‡ was calculated using the following relations:

DG‡ ¼ DH‡ � TDS

DH‡ ¼ V‡ þ DZPVEþ DEðTÞ

GAS-PHASE ELIMINATION KINETICS OF 2-ETHOXYPYRIDINE

VOL. 112, NO. 3 DOI 10.1002/qua INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 725

where V‡ is the potential energy barrier andDZPVE and DE(T) are the differences of ZPVEand temperature corrections between the TS andthe reactant, respectively.

3. Results and Discussion

3.1. KINETIC AND THERMODYNAMICPARAMETERS

The thermal elimination of 2-ethoxypyridine togive 2-pyridone and ethylene was studied usingDFT methods with the proposed mechanism inreaction (1). Calculations of thermodynamic andkinetic parameters are reported in Table I. Thecalculation results of these compounds are ingood agreement with experimental values atMPW1PW91/6-31Gþþ(d,p) and PBE1PBE1/6-31Gþþ(d,p) levels of theory. The B3LYP andB3PW91 functionals also gave good agreementwhen using 6-31G(d,p) basis set, yet the results

deteriorate when the basis set 6-31Gþþ(d,p) isused. As a better description should be obtainedwhen using bigger basis set including diffuse andpolarized functions, we have selected theMPW1PW91/6-31þþG(d,p) method for the geo-metries of the species involved in the reaction.These geometries were used in NBO charges andbond order calculations as described later. The ex-perimental entropy of activation �26 implying theloss of degrees of freedom in the TS is in accordwith cyclic six-centered geometry. Calculatedentropies deviate from the experimental value,due to the use of the harmonic approximationand the presence of low frequency modes.

3.2. TS AND MECHANISM

The optimized structures for reactants, TS,and products for the elimination reaction of 2-ethoxypyridine from calculations at MPW1PW91/6-31Gþþ(d,p) level of theory are shown in Figure1. The TS geometry accompanied with a cartoondrawing is provided in Scheme 1 showing atom

TABLE IThermodynamic and Arrhenius parameters for gas-phase decomposition of 2-ethoxypyridine at 418.848C.

Methods 104 k1 (s�1) Ea (kJ/mol) Log A (s�1) DH= (kJ/mol) DS= (J/mol K) DG= (kJ/mol)

Experimental 2.93 195.9 12.22 190.2 �26.29 208.3B3LYP/6-31G(d,p) 38.5 196.2 13.28 190.3 �3.90 193.1B3LYP/6-31þþG(d,p) 104.2 189.8 13.34 184.1 �4.68 187.3B3PW91/6-31G(d,p) 43.3 194.8 13.34 189.1 �4.67 192.3B3PW91/6-31þþG(d,p) 957.0 189.9 13.31 184.1 �5.36 187.8MPW1PW91/6-31G(d,p) 15.9 200.8 13.36 195.0 �4.45 198.1MPW1PW91/6-31þþG(d,p) 357.5 195.7 13.32 189.2 �5.13 193.5PBEPBE/6-31G(d,p) 68936.7 166.6 13.40 160.6 �3.67 163.2PBEPBE /6-31þþG(d,p) 14837 161.0 13.32 155.3 �5.07 158.8PBE1PBE1/6-31G(d,p) 16.9 200.6 13.37 194.8 �4.23 197.8PBE1PBE1/6-31Gþþ(d,p) 39.1 195.4 13.33 189.6 �4.92 192.9

FIGURE 1. Optimized structures for reactant, R, transition state, TS, and product, P, in the gas phase decomposi-tion of 2-ethoxypyridine at MWPW91/6-31þþG (d, p) calculations. [Color figure can be viewed in the online issue,which is available at wileyonlinelibrary.com.]

MARQUEZ, CORDOVA, AND CHUCHANI

726 INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY DOI 10.1002/qua VOL. 112, NO. 3

numbering for clarity in the discussion of the TSstructural parameters, charges, and bond orderanalysis that follow.

Geometrical parameters of the optimized reac-tant, TS, and products are shown in Table II. TheTS structure located elimination reaction of 2-ethoxypyridone is a six-centered cyclic geometrycomprising atoms O1, C2, C3, H4, N5, and C6

shown in Scheme 1. The O1AC2 bond is elongatedfrom 1.43 A in the reactant to 1.90 A in the TS;conversely, the C2AC3 bond is shortened from1.52 A in the reactant to 1.40 A in the TS indicat-ing the double bond formation; the C3AH4 isstretched from 1.09 to 1.40 A in the TS, and thedistance H4AN5 is significantly smaller, from 2.75to 1.27 A in the TS, as hydrogen H4 is transferredto the pyridine nitrogen. Changes in N5AC6 andC6AO1 distances are also observed indicating thebond order changes involved in product forma-tion. The reaction proceeds with elimination ofethylene along with a hydrogen migration inretro-ene fashion. Dihedral angles show the TS isnot a planar configuration. The imaginary fre-quency that characterizes the TS is mainly associ-

ated with the hydrogen transfer from C3 to thepyridine nitrogen N5. IRC calculations were per-formed to verify the TS leads to the products andthe reactant in the forward and reverse directionsrespectively. IRC is given in Figure 2. Further analy-sis of the reaction and the TS structure was carriedout by means of NBO calculations; NBO chargesand bond indexes are discussed in the next sections.

3.3. BOND ORDER ANALYSIS

The changes in electron density distributionoccurring in the reaction pathway can be followedby NBO analysis. The NBO charges are shown inTable III. Charges estimated with the NBOmethod for the 2-ethoxypyridine elimination reac-tion show an increase in electron density at theoxygen atom O1 (from about �0.54 in the reactantto �0.61 in the TS). The hydrogen that is trans-ferred to the pyridine nitrogen, H4, becomes morepositive (from 0.25 to about 0.40 in the TS). C2 inthe ethoxy group in the reactant becomes morenegative in the TS, showing a change in chargefrom �0.12 to �0.17, and also C3 becomes morenegative, from �0.72 to �0.80. Carbon C6

increases in positive charge from 0.55 to 0.60 inthe TS, whereas nitrogen N5 increases in electrondensity from �0.53 to �0.58.

Bond orders are used to study the reaction pro-gress along the minimum energy path connectingthe reactant and the products [11–13]. Wibergbond indexes [14] were computed using the natu-ral bond orbital NBO program [15] implementedin Gaussian 03W. These indexes allow estimatingbond orders from population analysis. Bondbreaking and making process involved in the

SCHEME 1. [Color figure can be viewed in the onlineissue, which is available at wileyonlinelibrary.com.]

TABLE IIStructural parameters of reactant (R), transition state (TS), and products (P) for gas-phase decomposition of2-ethoxypyridine obtained from MWPW91/6-3111G (d, p) calculations.

O1AC2 C2AC3 C3AH4 H4AN5 N5AC6 C6AO1

Interatomic Lengths (A)R 1.433 1.5152 1.091 2.749 1.324 1.346TS 1.905 1.406 1.403 1.269 1.363 1.282P 3.396 1.334 2.668 1.017 1.410 1.231

O1AC2AC3AH4 C2AC3AH4AN5 C3AH4AN5AC6 H4AN5AC6AO1 N5AC6AO1AC2 C6AO1AC2AC3

Angles (�)TS �2.909 28.495 �13.438 �29.620 40.328 �22.132

Imaginary frequency (cm�1)1388.13



reaction mechanism are monitored by means ofthe synchronicity (Sy) concept proposed byMoyano et al. [16] defined by the expression:

Sy ¼ 1�Xni¼1

jdBi� dBavj=dBav

" #=2n� 2;

n is the number of bonds directly involved in thereaction.

The calculated bond index is Bi, and the rela-tive variation of the bond index is obtained from:

dBi ¼ ½BTSi � BR

i �=½BPi � BR

i �

where the superscripts R, TS, P, represent reac-tant, TS, and product, respectively.

The average value is calculated from:

dBave ¼ 1=nXni¼1

dBi

Wiberg bonds indexes Bi were calculated forthose bonds involved in 2-ethoxypyridine elimina-tion reaction, that is, O1AC2, C2AC3, C3AH4,H4AN5, N5AC6, and C6AO1. Changes in otherbonds are smaller and were not considered in theanalysis. The synchronicity parameter had beenused to explain if a concerted reaction proceeds ina synchronic fashion where all events have the sameprogress along the reaction coordinate (Sy ¼ 1) orif the reaction is not synchronic (Sy¼ 0).

The examination of calculated bond ordersgiven as Wiberg indexes shows intermediate pro-gress along all reaction coordinates except for theC2AC3 double bond formation which shows37% development. The hydrogen transfer to the

FIGURE 2. IRC profile for gas-phase decomposition of 2-ethoxypyridine obtained at MWPW91/6-31þþG(d,p) theorylevel. The strong line and rots represent specific points at which the energy has been calculated. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]

TABLE IIINBO charges for reactant (R), transition state (TS), and products (P), at MWPW91/6-3111G (d, p) calculations.

O1 C2 C3 H4 N5 C6

R �0.535 �0.118 �0.717 0.247 �0.532 0.546TS �0.605 �0.167 �0.804 0.399 �0.576 0.598P �0.643 �0.450 �0.450 0.450 �0.597 0.624



pyridine nitrogen represented by the breaking ofC3AH4 bond and the formation of H4AN5 bondis advanced about 51 and 55%, respectively.Similarly, the breaking of O1AC2 bond show53% progress in the TS. The elimination reactionof 3-ethoxypyridine is molecular concertedprocess and occurs nearly to synchronic fashion(Sy ¼ 0.94).

The N5AC6 bond order in the reactant BRi ¼

1.395; this bond possess less double bond charac-ter as part of the aromatic system, however,N5AC6 bond p-electrons are involved in the elimi-nation reaction. The lone pair at the nitrogen actsas Lewis base to abstract the proton simultane-ously with the breaking of O1AC2 bond. Thechanges in bond order suggest the events takeplace in concerted fashion. The reaction mecha-nism proponed in reaction (1) appears to be simi-lar to alkyl vinyl ether in reaction (3), except thehydrogen is transferred to basic nitrogen.

4. Conclusions

The unimolecular gas-phase elimination of 2-ethoxypyridine have been studied by densityfunctional methods to characterize the reactionpath leading to the products observed. The TS isa six-centered structure comprising the pyridinenitrogen, the aromatic carbon bearing the ethoxysubstituent, the ethoxy oxygen, the two carbonsin the ethoxy group, and the hydrogen that istransferred to the pyridine nitrogen. The reactionis characterized as concerted and almostsynchronic (Sy ¼ 0.94); all but one, the ethylenedouble bond formation, reaction coordinateshave similar progress, about 50%, in the TS.Calculated enthalpy and energy of activation arein good agreement with experimental values atMPW1PW91/6-31þþG(d,p) and PBE1PBE1/6-

31þþ(d, p) levels of theory. NBO charges andbond orders support the participation of p-elec-tron of the aromatic system in the eliminationreaction which appears to proceeds in similarfashion to alkyl vinyl ether eliminations.

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TABLE IVWiberg bond index of reactant (R), transition state (TS) and products (P) for gas-phase decomposition of2-ethoxypyridine obtained at MWPW91/6-3111G (d, p) calculations.

O1AC2 C2AC3 C3AH4 H4AN5 N5AC6 C6AO1 Sy

BRi 0.867 1.029 0.920 0.003 1.395 1.029

BTSi 0.414 1.398 0.392 0.382 1.205 1.315 0.94

BPi 0.007 2.023 0.009 0.748 1.051 1.611

%Ev 52.67 37.12 57.95 50.87 55.23 49.14



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DFT study of the gas-phase thermal decomposition kinetics of 2-ethoxypyridine into 2-pyridone

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