Methyl transfer reactivity of pentachloromethylplatinate(IV) anion with a series of N-nucleophiles

Article abstract of DOI:10.1016/j.jorganchem.2018.10.020

Reactivity of K₂[Pt^IVCH₃Cl₅] toward a series of substituted N,N-dimethylanilines 1a-1g, N,N-diisopropylaniline 1h and 2,6-substituted pyridines 2a-2b was investigated in 60% (vol.) aqueous acetone solutions. The reactions result in corresponding N-methylammonium or N-methylpyridinium products, 3 or 4, with high selectivity for the substrates 1a-1g and 2b, and follow an overall 2nd order kinetics, 1st order in both the Pt^IV complex and the amines. The reactivity is discussed in terms of the amine electronic properties and steric bulk. For the series of N,N-dimethylanilines 1a-1g, Me₂NC₆H₄R (R = H, m-Cl, p-Cl, m-Me, p-Me, p-MeO, p-Me₂N), a high quality linear correlation was found between logarithm of the reaction second order rate constant, log(k₂), and pK_a of the anilines. At the same time, the reactivity of the bulkier N,N-diisopropylaniline substrate 1h is about 3 orders of magnitude lower than predicted using this correlation. Finally, the pyridines 2a-2b are 3–4 orders of magnitude less reactive than N,N-dimethylanilines of similar pK_a. Interestingly, the reactivity of K₂[Pt^IVCH₃Cl₅] toward N,N-dimethylanilines is of the same order of magnitude or slightly greater than that of a standard organic methylating agent, dimethylsulfate Me₂SO₄. A computational (DFT) modeling of the title reaction is consistent with the formation of five-coordinate Pt^IVMe electrophile, [Pt^IVCH₃Cl₄]^-, which is involved in S_N2 attack at its methyl group carbon by nucleophilic amines.

Full text of DOI:10.1016/j.jorganchem.2018.10.020

Accepted Manuscript
Methyl transfer reactivity of pentachloromethylplatinate(IV) anion with a series of N-
nucleophiles
Daniel J. Adams, Brian Johns, Andrei N. Vedernikov
PII:
S0022-328X(18)30866-0
DOI:
https://doi.org/10.1016/j.jorganchem.2018.10.020
JOM 20605
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 4 October 2018
Revised Date: 22 October 2018
Accepted Date: 23 October 2018
Please cite this article as: D.J. Adams, B. Johns, A.N. Vedernikov, Methyl transfer reactivity of
pentachloromethylplatinate(IV) anion with a series of N-nucleophiles, Journal of Organometallic
Chemistry (2018), doi: https://doi.org/10.1016/j.jorganchem.2018.10.020.
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ACCEPTED MANUSCRIPT
Methyl transfer reactivity of pentachloromethylplatinate(IV) anion with a
series of N-nucleophiles
This work is dedicated to Prof. Richard J. Puddephatt on the occasion of his 75th birthday
Daniel J. Adams, Brian Johns, Andrei N. Vedernikov* ; E-mail: avederni@umd.edu
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742,
USA
Abstract
Reactivity of K2[PtIVCH3Cl5] toward a series of substituted N,N-dimethylanilines 1a-1g, N,N-
diisopropylaniline 1h and 2,6-substituted pyridines 2a-2b was investigated in 60% (vol.)
aqueous acetone solutions. The reactions result in corresponding N-methylammonium or N-
methylpyridinium products, 3 or 4, with high selectivity for the substrates 1a-1g and 2b, and
follow an overall 2nd order kinetics, 1st order in both the PtIV complex and the amines. The
reactivity is discussed in terms of the amine electronic properties and steric bulk. For the series
of N,N-dimethylanilines 1a-1g, Me2NC6H4R (R = H, m-Cl, p-Cl, m-Me, p-Me, p-MeO, p-
Me2N), a high quality linear correlation was found between logarithm of the reaction second
order rate constant, log(k2), and pKa of the anilines. At the same time, the reactivity of the bulkier
N,N-diisopropylaniline substrate 1h is about 3 orders of magnitude lower than predicted using
this correlation. Finally, the pyridines 2a-2b are 3-4 orders of magnitude less reactive than N,N-
dimethylanilines of similar pKa. Interestingly, the reactivity of K2[PtIVCH3Cl5] toward N,N-
dimethylanilines is of the same order of magnitude or slightly greater than that of a standard
organic methylating agent, dimethylsulfate Me2SO4. A computational (DFT) modeling of the
title reaction is consistent with the formation of five-coordinate PtIVMe electrophile,
[PtIVCH3Cl4]-, which is involved in SN2 attack at its methyl group carbon by nucleophilic
amines.
Keywords: pentachloromethylplatinate(IV), anilines, pyridines, methyl transfer, kinetics,
aqueous acetone

ACCEPTED MANUSCRIPT
1. Introduction
Chloro complexes of platinum(II), such as PtIICl2(H2O)2, were the first homogeneous transition
metal complexes used for catalytic oxidative CH functionalization of methane to form CH3X
derivatives (Scheme 1, X = Cl, OH) [1-2]. These complexes are especially attractive as catalysts
because they allow for alkane functionalization under aerobic conditions and for the use of O2 as
terminal oxidant when combined with specific redox-mediators [3-5].
Scheme 1. Methane CH functionalization catalyzed by PtIICl2(H2O)2 in the Shilov system.
The mechanism of the Shilov reaction was studied in detail and the intermediacy of PtIV
chloro methyl complexes such as [PtIVCH3Cl5]2- was demonstrated [2, 6]. The relatively stable
potassium pentachloromethylplatinate(IV) was used to conduct kinetics studies of bimolecular
nucleophilic substitution at the methyl ligand of [PtIVCH3Cl5]2- with chloride (eq 1), water, as
well as some other nucleophiles [6].
[PtIVCH3Cl5]2- + Cl- ‰ CH3Cl + [PtIICl4]2- + Cl-
( 1 )
Similar studies were carried out using an analogous PtIV 2-chloroethyl complex [7].
While important for drawing conclusions about plausible mechanism of the Shilov reaction,
these works also open up a horizon for possible application of alkyl transfer from the
electrophilic [PtIV(Alkyl)Cl5]2- to other nucleophilic species and, potentially, catalytic formation
of methane derivatives CH3X, different from alcohols or alkylchlorides, in modified Shilov
systems. To be successful with the latter goal, one needs to know how reactive nucleophiles of
other types can be with respect to [PtIV(Alkyl)Cl5]2-. Notably, amines have never been studied in
methyl transfer reactions with [PtIVCH3Cl5]2-.
With this idea in mind, in this work we have carried out a kinetics study of methyl
transfer from pentachloromethylplatinate(IV) to a series of N-nucleophiles, substituted N,N-
dialkylanilines 1 and pyridines 2 (Chart 1) in 60% (vol.) aqueous acetone solutions at 22 oC (eq
2):
( 2 )
2

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Chart 1. Amine nucleophiles 1 and 2 studied in this work and products of their N-
methylation, 3 and 4 (eq 2).
The reaction (eq 2) progress was monitored by means of 1H NMR spectroscopy. Triflate
salts derived from N,N,N-trimethylarylammonium cations 3a-3h and N-methylpyridinium
cations 4a-4b, have been prepared independently and their 1H NMR spectra were matched to the
NMR spectra of the reaction (eq 2) products.
Recently Goldberg et al. reported methyl transfer reactions involving a RhIII diiodo
methyl complex (POP)RhIII(CH3)I2 and various alkylamines [8], where formation of electrophilic
cationic (POP)RhIII(CH3)I(ammine)+ species occurs first as a result of an amine for iodo ligand
substitution. The resulting cationic species are sufficiently electrophilic to be attacked, at the rate
determining step, by second equivalent of the amine to form products of the amine methylation.
Overall, the methyl transfer reaction between (POP)RhIII(CH3)I2 and alkylamines is second order
in alkylamines.
In contrast to the above report, in this work we find that the reaction (eq 2) rate is 1st
order in both the amine and [PtIVCH3Cl5]2-, and the reaction is, overall, 2nd order. We also find
that for all N,N-dimethylanilines 1a-1g studied here, there is a high quality linear correlation
between logarithm of their second order rate constant, log(k2), and the amines pKa values. A
significant deviation from this dependence is only found here for N,N-diisopropylaniline 1h and
it is discussed in terms of the amine steric bulk.
2. Experimental details
2.1. General procedures
All reagents for which the synthesis is not given were purchased from Aldrich, Acros or
Alfa-Aesar and were used without further purification except where stated. Deuterated solvents
were purchased from Cambridge Isotope Laboratories (D2O, acetone-d6 and DMSO-d6). 1H (600
MHz) and 13C NMR (125 MHz) spectra were recorded on a Bruker DRX-500 or Bruker AVIII-
600MHz spectrometer. Chemical shifts are reported in parts per million (ppm) (δ) and referenced
to residual solvent resonance peaks. Mixed solvent samples are referenced to acetone-d6 residual
signal. Multiplicities are reported as follows: s (singlet), d (doublet), t (triplet), q (quartet), quin
(quintet), sept (septet), m (multiplet). K2[PtIVCH3Cl5] containing KCl as a major impurity was
prepared according to published procedure [6]. Anilines 1a, 1b, 1d, 1f, 1g and 1h along with
3

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pyridines 2a, 2b were purchased from Sigma Aldrich. Anilines 1c and 1e were synthesized in
accordance with the published procedures [9, 10]. Methylammonium salts 3a-g and 4a, 4b were
synthesized as triflates according to published procedures [11-17].
2.2. Synthetic procedures
2.2.1. Preparation of K2[PtCl5CH3] [6]
K2PtCl4 (426 mg, 1.02 mmol) was dissolved in water and MeI (64.0 µL, 1.02 mmol) was
added via microliter syringe. The solution was stirred at rt for 2h until PtI2 stopped precipitating.
AgCl (152 mg, 1.06 mmol) was added and the mixture was stirred for 20 min. The mixture was
filtered and water removed at reduced pressure to give the K2PtCl5CH3 product in 73% crude
yield. The KCl impurity could not be removed; however this did not affect the kinetics
experiments. The KCl-contaminated product contained, typically, ~46% K2PtCl5CH3 by mass
(about 7 : 1 KCl : K2PtCl5CH3 molar ratio), as confirmed by 1H NMR using 1,4-dioxane as an
internal standard. 1H NMR (600 Hz, 22°C, 60% acetone-d6 in D2O) δ: 2.95 (s, 3H; 2JPtH = 77
Hz).
2.2.2. Preparation of anilines 1
4-chloro-N,N-dimethylaniline 1c [9]
1H NMR (60% acetone-d6 in D2O): δ 7.06 (d, 2 H), 6.63 (d, 2 H), 2.93 (s, 6 H).
3,N.N-trimethylaniline 1e [10]
1H NMR (60% acetone-d6 in D2O): δ 7.17 (m, 1 H), 6.60 (m, 3 H), 2.97 (s, 6 H), 2.36 (s, 3 H).
2.2.3. Preparation of ammonium triflates 3(OTf) and 4(OTf)
N,N,N,-Trimethylanilinium triflate 3a(OTf) [11]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.88 (d, 2H), 7.59 (t, 2H), 7.52 (t, 1H), 3.68
(s, 9H).
3-Chloro-N,N,N-trimethylanilinium triflate 3b(OTf) [12]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 8.05 (s, 1H), 7.99 (d, 1H), 7.66 (t, 1H), 7.57
(d, 1H), 3.78 (s, 9H).
4-Chloro-N,N,N-trimethylanilinium triflate 3c(OTf) [13]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 8.00 (d, 2H), 7.61 (d, 2H), 3.74 (s, 9H).
4,N,N,N-Tetramethylanilinium triflate 3d(OTf) [14]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.75 (d, 2H), 7.38 (d, 2H), 3.64 (s, 9H),
3.02 (s, 3H).
3,N,N,N-Tetramethylanilinium triflate 3e(OTf) [15]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.71 (s, 1H), 7.65 (d, 1H), 7.45 (t, 1H), 7.32
(d, 1H), 3.64 (s, 9H), 2.35 (s, 3H).
4-Methoxy-N,N,N-trimethylanilinium triflate 3f(OTf) [16]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.82 (d, 2H), 7.07 (d, 2H), 3.77 (s, 3H),
3.63 (s, 9H).
4-Dimethylamino-N,N,N-trimethylanilinium 3g(OTf) [15]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.63 (d, 2H), 6.77 (d, 2H), 3.56 (s, 9H),
2.88 (s, 6H).
4

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N,N-diisopropyl-N-methylanilinium triflate 3h(OTf)
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.71 (d, 2H), 7.59 (t, 2H), 7.54 (t, 1H), 4.54
(sept, 2H), 3.40 (s, 3H), 1.24 (dd, 12H). 1H NMR (600 Hz, 22 °C, DMSO-d6) δ: 7.80 (d, 2H),
7.63 (t, 2H), 7.59 (t, 1H), 4.53 (sept, 2H), 3.39 (s, 3H), 1.18 (dd, 12H). 13C NMR (125 Hz, 22°C,
DMSO-d6) δ: 139.5, 130.5, 130.1, 123.8, 65.8, 40.9, 17.4, 17.1.
1,2,6-Trimethylpyridinium triflate 4a(OTf) [17]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 8.18 (t, 1H), 7.74 (d, 2H), 4.08 (s, 3H), 2.77
(s, 6H).
1,2,4,6-Tetramethylpyrdinium triflate 4b(OTf) [17]
1H NMR (600 Hz, 22 °C, 60% acetone-d6 in D2O) δ: 7.56 (s, 2H), 4.01 (s, 3H), 2.72 (s, 6H), 2.45
(s, 3H).
2.3. Kinetics study
A stock solution of each nucleophile was prepared by adding 1.5 mL of 60% (vol.) acetone-d6 in
D2O to the appropriate amount of nucleophile via micro syringe. 600 µL of the stock solution
was combined with ~2 mg of solid K2PtClCH3 and quickly transferred to a 5 mm NMR tube and
placed into an NMR probe. The reaction progress was followed by 1H NMR. The peak at 2.95
ppm which corresponds to the methyl group of K2PtCl5CH3 and the peak corresponding to the
signal of the methyl group of ammonium product were integrated and the values obtained were
used to generate pseudo first order kinetics plots for each nucleophile.
Each run was performed under pseudo first order conditions. To find the pseudo-first
order rate constant, kobs, for each run, ꢀ from equation 3 was plotted against time, where
[ꢁꢂ(ꢃꢄꢅꢆꢂ)ꢇ∞] represents the concentration of the methylammonium species at the end of the
reaction (t = infinity). To get an accurate value for [ꢁꢂ(ꢃꢄꢅꢆꢂ)ꢇ∞] at t = infinity, the mixtures
were left for 72 h and a final data point was taken for each. The second order rate constant k2 was
produced using equation 4.
ꢐ
[
]
ꢉꢊꢋ(ꢌꢍꢎꢏꢋ) ꢑ
ꢀ = ꢈꢆ([
)
ꢐ
( 3 )
( 4 )
ꢐ
] [
]
ꢊꢋ(ꢌꢍꢎꢏꢋ) ꢑ ꢒ ꢊꢋ(ꢌꢍꢎꢏꢋ)
ꢓꢔ = ꢓꢕꢖꢗ/[ꢃꢄꢅꢆꢂ]
2.4. Computational study
Theoretical calculations in this work have been performed using density functional theory
(DFT) method [18], specifically functional PBE [19], and LACVP relativistic basis set with two
polarization functions, as implemented in the Jaguar program package [20]. Full geometry
optimization has been performed without constraints on symmetry in gas phase. For all transition
states solvation Gibbs energies Gsolv in water as solvent were found using single point
calculations utilizing Poisson-Boltzmann continuum solvation model (PBF) [20]. For water as a
o
solute Gsolv was found using saturated vapor pressure of water at 25 C [21]. Geometry
optimization for PtIVCH3 species, K2PtCl5CH3, 5 and 6, in water have also been carried out in
water as solvent. For all species under investigation frequency analysis has been carried out. All
energy minima have been checked for the absence of imaginary frequencies. All transition states
possessed just one imaginary frequency. Using method of Intrinsic Reaction Coordinate,
5

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reactants, products and the corresponding transition states were proven to be connected by a
single minimal energy reaction path. For gas-phase geometry-optimized species the total gas
phase Gibbs free energy (Gtot) at 298 K were produced in Hartrees (1 Hartree = 627.51
kcal/mol). The standard reaction Gibbs energies, ∆Grxn, in kcal/mol were calculated as follows:
∆Grxn = 627.51·[Σ(Gtot)products - Σ(Gtot)reactants gas phase + Σ(Gsolv)products - Σ(Gsolv)reactants +
]
∆nRTln(RT/P), where ∆n is the change in the number of moles in a balanced reaction equation
when going from reactants to products. The standard state for all solutes is 1 M concentration
and 55.5 M concentration for H2O solvent.
3. Results and Discussion
3.1. Reaction (eq 2) selectivity in methylammonium products 3 (4) and its rate law
1H NMR spectroscopy was used to monitor concentrations of the reactant, [PtIVCH3Cl5]2-,
exhibiting the signal of its methyl ligand at 2.95 ppm, and the products, methylammonium
cations 3 or methylpyridinium cations 4, for which the integral intensity of their N-methyl group
signals was measured. Formation of CH3OH and CH3Cl due to competitive reaction of
[PtIVCH3Cl5]2- with water and chloride anions, respectively [6], was also monitored. The exact
amount of MeCl could not be determined due to its distribution between solution and gas phases.
In general, the observed rate constant for the disappearance of [PtIVCH3Cl5]2-, kobs(PtIVMe), is
expected to be somewhat higher, as compared to the rate constant of formation of
methylammonium cations, kobs(MeN+), due to competitive reaction of [PtIVCH3Cl5]2- with water
and chloride anions originating from KCl present in our samples of K2[PtIVCH3Cl5] as a major
impurity in about 7 : 1 KCl : K2PtCl5CH3 molar ratio. In fact, in the case of N,N-dimethylaniline
1a taken in 38-fold excess, both observed rates constants were almost identical within
experimental error (Fig. 1a, 1b). This suggests realization of a selective methyl transfer to the
amine in this case. Direct integration of MeOH and MeCl signals allows to find the upper
estimate for the selectivity in 3a of 99% whereas the yield of 3a determined in the end of the
reaction is its more accurate measure, 96% (Tables 1 and S1).
For reactions involving other anilines 1b-1g taken, typically, in 20-100 fold excess with
respect to K2[PtIVCH3Cl5], the reaction selectivity in methylammonium products 3, determined
as yield of 3 in the end of reaction, ranged from 79% to 99% (Tables 1 and S1). For 2,4,6-
trimethylpyridine 2b the best observed selectivity in 4b was also high, 87%, whereas for the less
reactive 2,6-dimethylpyridine 2a and N,N-diisopropylaniline 1h the reaction selectivity in the
corresponding ammonium products was only 36% and 28%, respectively.
The reactions (eq 2) between K2[PtIVCH3Cl5] and amines 1 or 2 were run using anilines 1
or pyridines 2 taken in large excess, under pseudo-first order conditions. Typically, 0.40 – 8.4
mM solutions of K2[PtIVCH3Cl5] were used and the reactions were monitored for about 3 half-
lives. In all of these cases the reactions followed pseudo-first order kinetics behavior (Fig. S1-
S16). The reaction order in [amine] was analyzed using the parent compound of the anilines
series, N,N-dimethylaniline 1a. By varying concentration of the aniline 1a in the range of 10 –
40 mM, a linear relationship was found between the observed pseudo-first order rate constant of
the reaction, kobs, and aniline concentration (Fig. 2). A similar dependence was also observed for
6

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2,4,6-trimethylpyridine 2b [22]. Hence, we conclude that the reaction (eq 2) is first order in the
amine and first order in K2[PtIVCH3Cl5].
1.8
1.6
1.4
1.8
1.6
1.4
1.2
1
1.2
1
0.8
0.6
0.4
0.2
0
y = 0.0008x + 0.0361
R² = 0.9905
0.8
0.6
0.4
0.2
0
y = 0.0008x - 0.0025
R² = 0.9976
Time, s
Time, s
0
1000
2000
0
1000
2000
(a) kobs(PtIVMe), s-1 = (8.3±0.4)×10-4
(b) kobs(MeN+), s-1 = (8.0±0.2)×10-4
Fig. 1. Kinetic plots for reaction between K2[PtIVCH3Cl5] and N,N-dimethylaniline 1a (eq 2)
used in 38-fold excess, [PtIVMe]0 = 0.77 mM, [1a]0 = 29.0 mM: a) ln(Co/C) plot produced by
monitoring [PtIVCH3Cl5]2- signal at 2.95 ppm and b) ln[C∞/(C∞-C)] plot produced by monitoring
+
the NMe3 group signal of 3a at 3.68 ppm.
7

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Table 1. Second order rate constants for methyl transfer from [PtIVCH3Cl5]2- to various amines
(eq 2) measured in 60% (vol.) aqueous acetone solutions at 22 oC, yield of 3 or 4 a in the end of
reaction and the amines pKa values.
c
Amine
1a (R = H)
1b (R = m-Cl)
1c (R = p-Cl)
1d (R = p-Me)
1e (R = m-Me)
1f (R = p-MeO)
1g (R = p-Me2N)
1h
k2, M-1 s-1 b
(2.6±0.3)×10-2
(2.11±0.02)×10-3
(4.71±0.02)×10-3
(5.15±0.07)×10-2
(2.85±0.02)×10-2
(8.4±0.3)×10-2
0.174±0.002 d
Yield of 3 (4), % a
pKa
1
2
96
79
95
95
96
98
99
28
36
87
5.12 [23]
3.83 [21]
4.39 [21]
5.63 [24]
5.34 [24]
5.85 [24]
6.4 [25] d
7.4 [26]
3
4
5
6
7
(6.7±0.2)×10-4
(1.85±0.08)×10-5
(6.1±0.1)×10-4
8
9
6.73 [27]
7.48 [28]
2a
10
2b
a Determined in the end of reaction as 100% ×[3] (or [4])/[K2PtCl5Me]0 with all concentrations
derived from 1H NMR integration; b average of two to four runs; c aqueous solutions, 25 oC; d
statistically corrected for the number of NMe2 groups.
1.40E-03
1.20E-03
y = 0.0264x + 0.0001
1.00E-03
R² = 0.9695
8.00E-04
6.00E-04
[1a], M
4.00E-04
0.01
0.02
0.03
0.04
Fig. 2. Dependence of the observed pseudo-first order constant, kobs, for reaction between
[PtIVCH3Cl5]2- and N,N-dimethylaniline, 1a, and the aniline concentration in 60% (vol.) aqueous
acetone at 22 oC.
8

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3.2. Reactivity of anilines 1
The signal of the reactant [PtIVCH3Cl5]2- in 1H NMR spectra of K2[PtIVCH3Cl5] in 60%
(vol.) aqueous acetone was observed at 2.95 ppm. The position of the signal did not change when
the reagent was combined with anilines 1 or pyridines 2. No new 1H NMR signals associated
with PtIVMe fragment were observed in the presence of the anilines 1a-1f, 1h, or pyridines 2, so
suggesting that no adducts of these amines and ‘PtIVCH3’ formed in detectable amounts via
amine for chloro ligand substitution. A very weak, ~5% of the intensity of the signal at 2.95
ppm, additional signal of ‘PtIVCH3’ at 2.58 ppm was observed in reaction mixtures containing p-
N,N,N’,N’-tetramethylphenylenediamine and 1g in 16 : 1 ratio. This signal may result from a
reaction of [PtIVCH3Cl5]2- with Pt-coordinating impurities present in our sample of 1g (vide
infra). In this case both ‘PtIVCH3’ signals disappeared at the same rate. Overall, based on
available observations, we can conclude that the steric and/or electronic properties of the amines
1a-1h and 2 are sufficient to make ligand substitution at the PtIV center slow enough and/or
thermodynamically unfavorable under the reaction conditions employed in our work. Hence, the
second order rate constants k2 found for 1a-1h and 2a-2b may be used as a correct measure of
nucleophilicity of these amines with respect to electrophilic [PtIVCH3Cl5]2- or a derived aqua
complex [PtIVMeCl4(H2O)]- (vide infra) [6] (eq 5).
[PtIVCH3Cl5]2- + H2O ‰ [PtIVMeCl4(H2O)]- + Cl-
Keq
( 5 )
In the latter case, since ~7 : 1 KCl : K2PtCl5CH3 mixtures were used in all of our
experiments, the KCl impurity may be expected to produce some inhibiting effect on the
formation of the aqua complex [PtIVMeCl4(H2O)]- and the reaction (2) rates. At the same time,
since the value of the equilibrium constant Keq for the reaction (5) is close to 1 [6] and the
solutions of K2[PtIVCH3Cl5] used in this work are very dilute, such effect should be negligible.
The second order rate constants for reaction of anilines 1 and pyridines 2 with
K2[PtIVCH3Cl5] are summarized in Table 1. Their inspection shows that the reactivity of the
studied pyridines 2a-2b is inferior, as compared to N,N-dimethylaniline substrates 1a-1g. The
reactivities of these two groups of substrates are analyzed separately.
It is a common practice to use the pKa values of nucleophiles of the same structural type
as an approximate measure of their nucleophilicity [29]. Our analysis of the rate constants k2 of
N,N-dimethylanilines 1a-1g shows that, indeed, there is a high-quality linear correlation between
log(k2) and pKa values of the amines (Fig. 3, eq 6):
log(k2) = 0.76pKa - 5.55
( 6 )
The high quality of the correlation suggests that the electronic effects of the substituents
present in the aniline core responsible for the change in the basicity of the amines are also
responsible for the change in the amines nucleophilicity in methylation reaction (eq 2) with
[PtIVCH3Cl5]2-.
Considering the rate constants k2 given in Table 1, it is also interesting to compare the
electrophilicity of the K2[PtIVCH3Cl5] and that of some standard methylating agents used in
organic chemistry. For N,N-dimethylaniline 1a as a nucleophile in reaction (eq 2), its k2 value,
0.026 M-1 s-1, is about an order of magnitude larger that second order rate constant 0.0021 M-1 s-1
reported for methylation of this amine with dimethylsulfate, (CH3)2SO4, in sulfolane as a solvent
at 30 oC [30]. Similarly, a comparison of reactivity of p-N,N,N’,N’-tetramethylphenylendiamine
1g toward K2[PtIVCH3Cl5] (eq 2) and dimethylsulfate (sulfolane, 30 oC) shows that the second
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order rate constant for the former reaction, 0.174 M-1 s-1, is about 3 times greater than the rate
constant for the second process, 0.059 M-1 s-1 [30]. Hence, K2[PtIVCH3Cl5] is approximately as
electrophilic as (CH3)2SO4.
Among all the anilines 1 studied in reaction (eq 2), the N,N-diisopropylaniline 1h is the
least reactive with its log(k2) value deviating by 3.3 orders of magnitude from the linear
correlation (eq 6) established for 1a-1g. The most likely origin of this deviation / diminished
nucleophilicity is the steric bulk of two isopropyl groups at the nucleophilic nitrogen center that
interfere with its approach to the PtIVCH3 electrophile
3.3. Reaction of K2[PtIVCH3Cl5] with the aniline 1g
The aniline 1g is the most reactive, most nucleophilic and most reducing [25] among the anilines
studied in this work. As compared to other anilines 1a-1f, this compound is readily oxidized in
aqueous solutions when exposed to air, so that its solutions may contain some small amounts of
derived impurities. Because of this sensitivity to O2, all the work with this amine was carried out
under argon atmosphere. Notably, no signals of the compound could be observed in its 1H NMR
spectra in 60% (vol.) aqueous acetone solutions, although a clean 1H NMR spectrum of 1h could
be produced in CDCl3. Upon combination of 1g and K2[PtIVCH3Cl5] in aqueous acetone, the
solution color immediately turned light blue and, as the methyl transfer reaction (eq 2)
progressed, four sharp signals attributed to the reaction product 3g appeared and continued to
grow, two singlets at 3.57 ppm (9H, Me3N+) and 2.89 ppm (6H, Me2N), and two AX doublets of
the aromatic protons at 6.77 and 7.63 ppm. The blue color observed in our reaction mixtures is
likely associated with the formation of the amine cation radical reported earlier for this
compound and produced by catalytic oxidation of aqueous 1g with H2O2 [25]. In spite of these
observations that may suggest a possible change in the mechanism of the methyl transfer from
[PtIVCH3Cl5]2- to the amine, the reaction (eq 2) rate constant does not deviate from the trend (eq
6) established for all N,N-dimethyl anilines studied here. Hence, the dominant reaction path for
this amine is likely to involve an SN2 mechanism.
3.4. Reactivity of pyridines 2a-2b
As it was mentioned earlier and is shown in Fig. 3, pyridines 2a-2b are the least reactive
among the nucleophiles explored here. Their low nucleophilicity may be attributed, in particular,
to the steric bulk created by two methyl groups in the positions 2 and 6 of the pyridine ring. In
turn, the 33-fold increase in nucleophilicity of 2b, in response to the electronic effect of the
methyl group para- to the pyridine nitrogen, as compared to 2,6-dimethylpyridine 2a, is much
greater than the effect of the para-methyl substituent in N,N-dimethyl-para-toluidine 1d, as
compared to the parent N,N-dimethylaniline 1a. In the latter case, an about 2-fold nucleophilicity
increase is observed for 1d, as compared to 1a. A fewer number of bonds separating nucleophilic
nitrogen atom and the methyl substituent in 2b vs. 1d may, in part, be responsible for the
difference.
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-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
-4.0
-4.5
-5.0
p-NMe2
p-OMe
p-Me
H
m-Me
p-Cl
iPr2NPh
m-Cl
y = 0.756x - 5.5495
R² = 0.9938
2,4,6-Me3-py
2,6-Me2-py
pKa
3
4
5
6
7
8
Fig. 3. The reactivity of amines 1, 2, log(k2), with respect to [PtIVCH3Cl5]2- (eq 2) in 60% (vol.)
aqueous acetone at 22 oC as a function of the amines pKa.
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3.5. Computational (DFT) analysis of reaction between [PtIVCH3Cl5]2- and anilines 1
Previously [6] two possible methyl transfer pathways were considered for the systems
comprised of aqueous [PtIVCH3Cl5]2- and water or chloride anion as nucleophiles, one involving
5-coordinate PtIV transient species [PtIVCH3Cl4]-, 5, (Scheme 2) and another involving the
derived aqua complex [PtIVCH3Cl4(H2O)]-, 6. Two corresponding pathways shown in Scheme 2
for the case of N,N-dimethylaniline 1a as a nucleophile are pathways 2 and 3, respectively. For
the completeness of the analysis, one more reaction path, pathway 1, is also added to the Scheme
2 that includes the starting 6-coordinate complex [PtIVCH3Cl5]2-.
Scheme 2. Methyl transfer from various PtIVCH3 species to PhNMe2, 1a, in aqueous media.
Numbers in blue font are the DFT-calculated Gibbs energies for the corresponding aqueous
solutions under standard conditions (1 M solutions, 25 oC).
The three pathways in Scheme 2 have been analyzed computationally (DFT) in this work
using modeling of pure water as a solvent. The 5-coordinate transient 5 was found to be 12.1
kcal/mol higher in energy than [PtIVCH3Cl5]2-, and the corresponding reaction pathway 2 leads to
a relatively low energy ‘classic’ SN2-type reaction transition state TS5 (Fig. 4a) with the overall
Gibbs energy of 24.5 kcal/mol. For the 6-coordinate complex [PtIVCH3Cl5]2- (pathway 1), no
individual transition state could be found. In this case, our transition state search converges to a
combination of a ‘free’ non-coordinated chloride anion and the TS5. Hence, the reaction path 1
does not include a mechanism that would be kinetically more competitive, as compared to
pathway 2. Finally, the 6-coordinate transient aqua complex [PtIVCH3Cl4(H2O)]-, 6, is 1.1
kcal/mol higher in energy than [PtIVCH3Cl5]2-, a good match to an experimental estimate of ~0
kcal/mol Gibbs energy change for the aqua-for-chloro ligand substitution in [PtIVCH3Cl5]2- [6].
Remarkably, the reaction pathway 3 leads to the transition state TS6 (Fig. 4b) which, similar to
pathway 1, corresponds to a loss of the ligand trans- to the methyl happening well before the C-
Pt/C-N bond breaking / making event. But, in contrast to pathway 1, in the transition state TS6
the former H2O ligand remains hydrogen-bonded to two adjacent chloro ligands of the leaving
group [PtIICl4]2- with the two shortest Cl…HO distances of 2.48 Å each. Comparing other key
parameters of the transition states TS5 and TS6, one can conclude that they are very close, with
the Pt-C and (Pt)C-N distances being essentially the same in both species. Hence, TS6 may be
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viewed as a hydrogen bond - stabilized version of the TS5 where an explicit water molecule
helps to better account for the transition state interaction with the solvent. The calculated Gibbs
energy for TS6 is 20.6 kcal/mol, a good match to the experimental value of 19.4 kcal/mol.
Hence, we can conclude that: i) the methyl transfer from [PtIVCH3Cl5]2- to the aniline 1a
proceeds via the 5-coordinate PtIVCH3 transient 5 and ii) a proper account for the solvation /
hydrogen bonding between reacting solutes and water solvent is important for achieving better
match of experimental and calculated reaction activation energies.
a)
b)
Fig. 4. Structures of the SN2-type reaction transition states in Scheme 2: a) the TS5 located for
the pathway 2, b) the TS6 found for the pathway 3.
3. Conclusions
The reaction of K2[PtIVCH3Cl5], N,N-dimethylamines and 2,6-disubstituted pyridines
studied here (eq 2) follows a ‘simple’ second order reaction kinetics with first order in both the
amines and K2[PtIVCH3Cl5]. Remarkably, K2[PtIVCH3Cl5] complex is about as reactive as a
methyl transfer agent as a typical organic methylating agent, dimethylsulfate. In turn, among the
substrates studied, the N,N-dimethylanilines 1a-1g react at about 100-1000 times faster rates
than 2,6-dimethylpyridines 2a and 2b or N,N-diisopropylaniline 2h, thanks, most likely, to the
greater steric bulk of the alkyl substituents near the nucleophilic nitrogen atom in the latter three
substrates. A high quality linear free energy relationship was found between logarithm of second
order rate constants for the methyl transfer reaction (eq 2) and pKa of the dimethylanilines 1a-1g.
A computational (DFT) analysis of the reaction (eq 2) is consistent with the realization of SN2
mechanism where 5-coordinate PtIV transient electrophile [PtIVCH3Cl4]- is attacked by the
amines.
Acknowledgements
This work was supported by the National Science Foundation (CHE-1464772, CHE-1800089).
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TOC
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
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N,N‐dimethylanilines can be selectively methylated using K2[PtIVCH3Cl5]
K2[PtIVCH3Cl5] is at least as reactive as a methylating agent as (CH3)2SO4
Reactivity of substituted N,N‐dimethylanilines is a linear function of their pKa
N,N‐diisopropylpyridine and 2,6‐dimethylpyridines are about 1000 times less reactive