Quantum chemical study of the mechanism of the palladium-catalysed C−H acetoxylation of benzene

Abstract

In this work, the mechanism of the palladium-catalysed acetoxylation of benzene C-H has been studied theoretically in detail. Based on experimental studies, a four-step mechanism for this reaction had been proposed, that is, C−H activation of benzene is the rate-determining step which forms an intermediate (k₁ pathway) which is subsequently oxidized to produce a high-valent Pd intermediate (k₂ pathway). Using quantum chemical calculations, all pathways were investigated, and the activation energy, activation enthalpy and activation Gibbs free energy for all steps were calculated and compared with each other. It was determined that the RDS proceeds through a square complex instead of a T-shaped complex. The activation energy related to the k₂ pathway is higher than that of the RDS, and therefore, a new mechanism is proposed.

Keywords

Palladium density functional theory C−H acetoxylation activation energy

Introduction

At present, it is well known that palladium has greatly improved the synthesis of organic compounds, which is why Heck, Negishi and Suzuki received the 2010 Nobel Prize in Chemistry.^1–3 Many reactions that seemed to be impractical in the past were made possible using palladium.⁴ Therefore, understanding the mechanism of palladium-catalysed reactions is of paramount importance.^5,6

In recent years, Pd-catalysed C−H functionalization has been widely used to synthesize valuable organic compounds.^7–10 There are efficient methods for direct functionalization of C−H bonds, but many of these require a directing group (DG) to increase the reactivity and selectivity of the reaction.¹¹ These reactions are well known mechanistically.^12,13 On the other hand, non-directed Pd-catalysed C−H functionalization reactions have been less developed and mechanistically not fully understood (Scheme 1).^14–16

Scheme 1.

Non-directed C–H functionalization.

In recent years, Cook and colleagues^17,18 and Emmert and colleagues^19,20 have studied extensively the non-directed C−H acetoxylation of arenes. In particular, they investigated the role of pyridine (Pyr) as a supporting ligand in increasing the reaction efficiency using catalyst systems such as Pd(OAc)₂(Pyr)₂ and proposed the following mechanism (Scheme 2).¹⁷

Scheme 2.

Mechanism of palladium-catalysed C−H acetoxylation of benzene.

The mechanism commences with precatalyst I (Pd(OAc)₂(Pyr)₂), which undergoes reversible pyridine dissociation to produce monopyridine species II. The rate-determining step (RDS) is related to C–H activation of benzene at complex II which forms intermediate III. Oxidation of this intermediate by PhI(OAc)₂ forms a high-valent Pd intermediate IV. The combination of PhI(OAc)₂ as oxidant and Pd(OAc)₂ as catalyst was reported in 1996.²¹ Intermediate IV undergoes reductive elimination to produce PhOAc and regenerate species II.

The development of appropriate molecular models is of special importance in understanding the mechanistic behaviour of catalyst systems such as Pd(OAc)₂(Pyr)₂. The most important method for designing such models is quantum chemical calculations.²² In this work, we investigated the mechanism of the palladium-catalysed C−H acetoxylation of benzene using the quantum mechanical approach.

Computational method

All quantum chemical calculations have been done using the GAUSSIAN 09 package²³ at B3LYP^24–26 hybrid density functional level and 6-31G(d, p) basis set.²⁷ For Pd and I atoms, the LANL2DZ basis set,²⁸ with effective core potential (ECP) functions, was used. Standard convergence criteria for geometry optimization were used. For all configurations, all degrees of freedom were optimized. The transition states obtained were confirmed to have only one imaginary frequency of the Hessian. Zero-point corrections were used to calculate activation energies. The solvent can have a significant effect on chemical systems and reactions explicitly or implicitly. The polarized continuum model (PCM) method was used to consider the implicit role of the solvent.^29,30 All calculations were done in acetic acid (HOAc) as an implicit solvent.

Results and discussion

We started studying this reaction from the equilibrium between species I and II. In the study of species II, we concluded that this species has two different configurations. One configuration has a T-shaped structure that we call it IIT, and another configuration has a square structure called IIS (Figure 1). OAc is a bidentate ligand and in configuration IIS, one of the OAc ligands is coordinated to palladium via two oxygen atoms. Because the trans effect of the Pyr ring is greater than that of the OAc ligand, the CO bond length trans to the Pyr (2.13 Å) is longer than that of the OAc (2.10 Å), and the substitution of CO with benzene in the next step will occur trans to the Pyr ring (Figure 1).

Figure 1.

Optimized structures of IT, IS, IIT and IIS.

Relative energies for the different species are presented in Table 1. In this table, $Δ E$ , $Δ H$ and $Δ G$ are relative electronic plus zero point energy, enthalpy and Gibbs free energy, respectively. Using Table 1, configuration IIS is more stable than IIT by 52.50 kJ mol^–1.

Table 1.

Relative energies (kJ mol^–1) for all species in equilibrium (K) and RDS (k₁).

Species	$Δ E$	$Δ H$	$Δ G$
	Equilibrium (K)
IT	0.00	0.00	0.00
IIS + Pyr	57.9	56.2	7.3
IS	1.7	1.5	2.8
IIT + Pyr	110.4	109.4	59.5
	RDS (IIS pathway)
IIS + BZ	0.00	0.00	0.00
IISBZ	6.1	9.5	44.4
TS_RDS.S	79.4	80.3	132.1
IIIS	33.7	35.3	86.0
	RDS (IIT pathway)
IIT + BZ	0.00	0.00	0.00
IITBZ	–25.0	–23.5	28.3
TS_RDS.T	28.1	28.0	82.0
IIIT	10.5	12.7	59.2

According to the two configurations IIT and IIS, there are two structures for species I referred to as IT and IS, respectively (from now on, letters T and S represent different species in the pathways related to IIT and IIS, respectively). Contrary to the configurations IIT and IIS, these two structures (IT and IS) do not differ much in energy (Table 1). Figure 1 shows the optimized structures of species IT, IS, IIT and IIS. The values of the equilibrium constant $(K = e^{- Δ G / RT})$ related to configurations IIT and IIS are equal to $4.5 \times 10^{- 11}$ and 0.16, respectively.

C–H activation of species II to generate species III is the RDS. In order to optimize the transition states of RDS (k₁ pathway), the IIT and IIS molecules in the vicinity of benzene should be optimized (IITBZ and IISBZ in equation (1)). For species III, corresponding to IIT and IIS, two structures IIIT and IIIS are obtained. The optimized structures of IITBZ, IISBZ, IIIT and IIIS are presented in Figures 2 and 3.

Figure 2.

Optimized structures of IISBZT, TS_RDS,S and IIIS and molecular graph of TS_RDS,S.

Figure 3.

Optimized structures of IITBZT, TS_RDS,T and IIIT.

Considering reactant IISBZ (IITBZ) and product IIIS (IIIT), the transition state of the RDS is obtained which we call TS_RDS,S (TS_RDS,T). Figures 2 and 3 present the optimized structures of TS_RDS,S and TS_RDS,T, respectively. Using Figure 2, the Pd-C and O-H bond lengths decrease (increase) from 5.09 and 2.54 Å (2.00 and 1.02 Å) for IISBZ (IIIS) to 2.16 and 1.31 Å for TS_RDS,S, respectively.

In TS_RDS,S, a six-membered transition state has been formed. Due to the fact that during this step, a proton transfer to oxygen occurs, the role of hydrogen bonds in forming the six-membered transition state is very important. For further investigation, quantum theory of atoms in molecules (QTAIMs)³¹ computations were performed on TS_RDS,S using the AIMALL package.³² The values of the electron density (ρ(r)), its Laplacian $(\nabla^{2} ρ (r))$ , total energy density $(H_{b})$ , electronic kinetic energy density $(G_{b})$ and electronic potential energy density $(V_{b})$ were considered. The molecular graph including critical points and bond paths is shown in Figure 2. According to this figure, the $O 22 \dots H 36 \dots C 30$ interactions with $\nabla^{2} ρ < 0$ , $H_{b} < 0$ and $- G_{b} / V_{b} < 0.5$ are related to strong hydrogen bonds. In addition, a ring critical point is formed by intermolecular hydrogen bonds. The values of the electron density at the ring critical point $(ρ_{RCP})$ and its Laplacian $(\nabla^{2} ρ_{RCP})$ for the six-membered ring (O22-H36-C30-Pd8-O23-C21) are 0.019167 a.u. and 0.085352 a.u., respectively.

Relative energies for the different structures in the RDS are shown in Table 1. The activation energy $(E_{a})$ , activation enthalpy $(Δ H^{‡})$ and activation Gibbs free energy $(Δ G^{‡})$ for $k'_{1}$ pathway related to IIS (IIT) are 73.4 (53.0), 70.8 (51.5) and 87.7 (53.7) kJ mol^–1, respectively (Table 1). The total rate constant for RDS is equal to $k_{1} = k'_{1} \times K_{1}$ , so the total activation energy, the total activation enthalpy and total activation Gibbs free energy for the RDS related to IIS (IIT) are 79.4 (28.1), 80.3 (30.5) and 132.1 (82.0) kJ mol^–1, respectively (Table 2). Due to the formation of hydrogen bonding, IIIS is more stable than IIIT by 29.3 kJ mol^–1. Although the activation parameters related to IIT are lower than those of IIS, with respect to the previous equilibrium (K = 0.16), it can be concluded that species IIS makes a major contribution to the RDS.

Table 2.

Relative energies (kJ mol^–1) for all species in k₂ and k₃ pathways.

Species	$Δ E$	$Δ H$	$Δ G$
	k₂ step
IIIS + PhI(OAc)₂	0.00	0.00	0.00
IIIsPhI(OAc)₂	–16.3	–13.6	35.9
TS_path2	101.5	106.2	138.6
IVPhI	–145.9	–142.9	–102.2
IV + PhI	–140.3	–141.2	–132.7
	k₂ step (proposed)
TS_k2	29.9	29.0	84.6
VPhIHOAc	-150.0	-149.9	-104.2
V + PhI + HOAc	-123.9	-124.7	-175.0
	k₃ step
V	0.00	0.00	0.00
TS_k3	54.1	53.4	59.0
IISPhOAc	-195.3	-195.3	-203.7
IIS + PhOAc	-206.3	-209.0	-258.6

In step next step, a 2e oxidation of intermediate III forms species IV (equation (2))

IIIS + {PhI (OAc)}_{2} \overset{K_{2}}{⇌} I {IISPhI (OAc)}_{2} \overset{K_{2}^{'}}{\to} IVPhI ⇄ IV + PhI

(2)

First, species IIIS and IV have been optimized in the vicinity of PhI(OAc)₂ and PhI, respectively (IIISPhI(OAc)₂ and IVPhI in Figure 4). Considering reactant IIISPhI(OAc)₂ and product IVPhI, the transition state of $k'_{2}$ step is obtained which we call TS_path2.

Figure 4.

Optimized structures of IIIPhI(OAc)₂, TS_path2 and IVPhI.

Figure 4 shows the optimized geometries of TS_path2, IIISPhI(OAc)₂ and IVPhI. In this figure, the Pd-I bond length increases (decreases) from 4.72 (6.32) Å for IIISPhI(OAc)₂ (IVPhI) to 4.93 Å for TS_path2 and the Pd-O bond length increases (decreases) from 2.10 (3.36) Å for IIISPhI(OAc)₂ (IVPhI) to 2.63 Å for TS_path2. According to Table 2, $E_{a}$ , $Δ H^{‡}$ and $Δ G^{‡}$ for $k'_{2}$ pathway are 117.8, 119.9 and 102.8 kJ mol^–1, respectively. The total rate constant for k₂ step is equal to $k_{2} = k'_{2} \times K_{2}$ , so the total $E_{a}$ , $Δ H^{‡}$ and $Δ G^{‡}$ for step 2 are 101.5, 106.2 and 138.6 kJ mol^–1, respectively (Table 2). It is observed that the activation energies of this step are greater than those of the RDS. Therefore, a new mechanism for this step should be proposed.

Our studies have shown that in this step, instead of the octahedral complex IV, another octahedral complex is formed (species V in Figures 5 and 6) in which one of the OAc ligands is coordinated to palladium through its two oxygen atoms, and HOAc is then released as a reaction product (equation (3))

IIIS + {PhI (OAc)}_{2} \overset{K_{2}}{⇌} I {IISPhI (OAc)}_{2} \overset{K_{2}^{″}}{\to} VPhIHOAc ⇌ V + PhI + HOAc

(3)

Figure 5.

Optimized structures of IIIPhI(OAc)₂, TS_k2 and VPhIHOAc.

Figure 6.

Optimized structures of V, TS_k3 and VPhIHOAc.

The transition state of step $k_{2}^{″}$ (TS_k2) is obtained through reactant IIISPhI(OAc)₂ and product VPhIHOAc and is presented in Figure 5. The Pd-I bond length increases (decreases) from 4.72 (7.17) Å for IIISPhI(OAc)₂ (VPhIHOAc) to 5.76 Å for TS_k2 and the Pd-O bond length increases (decreases) from 3.03 (4.22) Å for IIISPhI(OAc)₂ (VPhIHOAc) to 3.74 Å for TS_k2.

$E_{a}$ , $Δ H^{‡}$ and $Δ G^{‡}$ for the $k_{2}^{″}$ pathway are 46.2, 42.6 and 48.7 kJ mol^–1, respectively. The total rate constant for proposed k₂ step is equal to $k_{2} = k_{2}^{″} \times K_{2}$ ; therefore, the total $E_{a}$ , $Δ H^{‡}$ and $\Delta {G^{{\rm \ddagger }}}$ are 29.9, 29.0 and 84.6 kJ mol^–1, respectively (Table 3). The activation parameters related to proposed mechanism at this step are lower than those of the RDS. In addition, product VPhIHOAc is more stable than product IVPhI.

Table 3.

Absolute energies (a. u.) for all calculated species.

Species	E	H	G
IS	–1080.1036160	–1080.0801820	–1080.1596770
IIS	–831.8748590	–831.8572330	–831.9231980
Pyr	–248.2073410	–248.2021270	–248.2347440
IT	–1080.1042770	–1080.0807680	–1080.1607320
IIT	–831.8548440	–831.8369180	–831.9033110
BZ	–232.1595110	–232.1541770	–232.1869760
IISBZ	–1064.0320600	–1064.0077950	–1064.0932510
TS_RDS,S	–1064.0040890	–1063.9808020	–1064.0598260
IIIS	–1064.0215080	–1063.9979460	–1064.0774030
BZ	–232.1595110	–232.1541770	–232.1869760
IITBZ	–1064.0238610	–1064.0000480	–1064.0795130
TS_RDS,T	–1064.0036580	–1063.9804150	–1064.0590600
IIIT	–1064.0103370	–1063.9862450	–1064.0677510
PhI(OAc)₂	–699.7000280	–699.6823680	–699.7472580
IIISPhI(OAc)₂	1763.727746	–1763.6855150	–1763.8109870
TS_path2	–1763.6828430	–1763.6398320	–1763.7718020
IVPhI	–1763.7771590	–1763.7347830	–1763.8636330
IV	–1520.8332970	–1520.7992650	–1520.9017450
PhI	–242.9417220	–242.9348730	–242.9735090
PhI(OAc)₂	–699.7000280	–699.6823680	–699.7472580
TS_k2	–1763.7101290	–1763.6692660	–1763.7924066
VPhIHOAc	–1763.7787130	–1763.7374460	–1763.8643730
HOAC	–229.0349270	–229.0293990	–229.0622090
V	–1291.7921150	–1291.7635910	–1291.8556750
TS_k3	–1291.7715030	–1291.7432410	–1291.8331880
IISPhOAc	–1291.8665720	–1291.8380540	–1291.9333170
PhOAc	–459.9959110	–459.9860440	–460.0310850

Based on the proposed mechanism, C–O bond formation involves reductive elimination from species V which releases PhOAc and regenerates IIS at the final stage

V \overset{k_{3}^{'}}{\to} IISPnOAc \overset{K_{3}}{⇌} IIS + PhOAc

(4)

The transition state of step $k'_{3}$ (TS_k3) was optimized by using reactant V and product IISPhOAc (Figure 6). The C–O bond length increases (decreases) from 2.91 (1.40) Å for V (IISPhOAc) to 2.09 Å for TS_k3 and the O-Pd-C angle increases (decreases) from 91.7° (8.2°) for V (IISPhOAc) to 57.9° for TS_k3. Using Table 3, $E_{a}$ , $Δ H^{‡}$ and $Δ G^{‡}$ for this step are 54.1, 53.4 and 59.0 kJ mol^–1, respectively. The activation energies for this step are also lower than those of the RDS, which indicates the correctness of the proposed mechanism. The absolute energies of all calculated species are given in Table 3 to allow comparison between them.

Conclusion

The mechanism of the palladium-catalysed C−H acetoxylation of benzene was investigated at B3LYP density functional level in the solution phase. This mechanism consists of four steps: (1) reversible pyridine dissociation of catalyst system (Pd(OAc)₂(Pyr)₂ or (I) into monopyridine species II; (2) C–H activation at the RDS (k₁ pathway) and formation of intermediate III; (3) oxidation of III and formation of high-valent Pd intermediate IV (k₂ pathway); (4) reductive elimination of IV (k₃ pathway).

The activation energy, activation enthalpy and activation Gibbs free energy for all pathways were calculated. It was found that the RDS proceeds through a square complex instead of a T-shaped complex. The activation parameters related to k₁ pathway (RDS) are lower than those of the k₂ pathway. A new mechanism is proposed for the k₂ and k₃ pathways, and it was shown that these pathways have lower activation energies than the RDS.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and/or publication of this article.

Author biographies

Nazanin Beyzaie is a Graduate Student at Ferdowsi University of Mashhad. She concentrates on mechanism of the palladium-catalysed C-H acetoxylation.

Sayyed Faramarz Tayyari is a Professor of Chemistry at Ferdowsi University of Mashhad. His research interests include spectroscopy and quantum chemistry.

Mohammad Vakili is a Professor of Chemistry at Ferdowsi University of Mashhad. His research interests include spectroscopy and quantum chemistry.

Safar Ali Beyramabadi is an Assistant Professor of Chemistry at Islamic Azad University - Mashhad Branch. His research interests include inorganic computational chemistry.

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