Kinetic Studies of Hantzsch Ester and Dihydrogen Donors Releasing Two Hydrogen Atoms in Acetonitrile.

In this work, kinetic studies on HEH2, 2-benzylmalononitrile, 2-benzyl-1H-indene-1,3(2H)-dione, 5-benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione, 5-benzyl-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, 2-(9H-fluoren-9-yl)malononitrile, ethyl 2-cyano-2-(9H-fluoren-9-yl)acetate, diethyl 2-(9H-fluoren-9-yl)malonate, and the derivatives (28 XH2) releasing two hydrogen atoms were carried out. The thermokinetic parameters ΔG ⧧° of 28 dihydrogen donors (XH2) and the corresponding hydrogen atom acceptors (XH•) in acetonitrile at 298 K were determined. The abilities of releasing two hydrogen atoms for these organic dihydrogen donors were researched using their thermokinetic parameters ΔG ⧧°(XH2), which can be used not only to compare the H-donating ability of different XH2 qualitatively and quantitatively but also to predict the rates of HAT reactions. Predictions of rate constants for 12 HAT reactions using thermokinetic parameters were determined, and the reliabilities of the predicted results were also examined.

Introduction

The hydrogenation reaction is one of the most widely studied and applied reactions in organic chemistry, a chemical process in which a reducing agent releases two hydrogen atoms or ions to form an unsaturated bond.[1−3] In our previous work, we have elucidated the differences between Hantzsch ester (HEH2) and free H2 gas as reducing agents in thermodynamics, and the related thermodynamic data of HEH2 and free H2 gas releasing two hydrogen atoms or ions have been provided.[4] The thermodynamic parameters on 20 possible elementary steps of Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydrophenanthridine (PDH2) releasing two hydrogen atoms or ions have also been measured or derived from the related thermodynamic data using Hess’ law in acetonitrile.[5] These three organic compounds are dihydrogen donors usually used to reduce olefins, aldehydes, ketones, imines, alkynes, and quinolines and have received wide attention owing to their study and application prospects in academia and industry.[6−12] In addition to these three dihydrogen donors, 2-benzylmalononitrile, 2-(9H-fluoren-9-yl)malononitrile, 2-benzyl-1H-indene-1,3(2H)-dione, 5-benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione, 5-benzyl-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, ethyl 2-cyano-2-(9H-fluoren-9-yl)acetate, diethyl 2-(9H-fluoren-9-yl)malonate, and the derivatives (Scheme ) are also good dihydrogen donors. They are very popular in synthesis, catalysis, medicinal chemistry, and biochemistry.[13−15] Since they are all good reductants in organic synthesis and industrial production, it is necessary and urgent to study their actual dihydrogen-donating abilities in kinetics quantitatively.

Scheme 1

Molecular Structures of XH2 as Two-Hydrogen-Atom Donors Examined in This Work

In this work, 28 organic dihydrogen reductants releasing two hydrogen atoms in hydrogen atom transfer (HAT) reactions (eq ) in acetonitrile are determined, and the thermodynamic and kinetic parameters in the H•–H• donating process are established. The purpose of this work is to elucidate the differences between HEH2 and dihydrogen donors (XH2) shown in Scheme as popular reducing agents in thermodynamics, kinetics, and thermokinetics, and to study their abilities of releasing two hydrogen atoms in HAT reactions qualitatively and quantitatively, although the H-donating abilities of dihydrogen donors have been discussed in our previous work.[4,5] However, the H-donating abilities of these compounds were only studied from a thermodynamics viewpoint. In this work, thermodynamic bond dissociation free energy [ΔG°(XH2)], activation free energy of the self-exchange HAT reaction [ΔG⧧XH], and the thermokinetic parameter [ΔG⧧°(XH2)] are used to compare and analyze the H-donating abilities of these compounds from thermodynamics, kinetics, and actual reaction directions.

Results and Discussion

XH2 shown in Scheme were prepared according to the known synthesis method from the previous literature.[16,19] The structures of XH2 and X were characterized by 1H NMR spectra in the Supporting Information (SI). The nitrogen-centered radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) was selected since it was a relatively stable neutral radical and frequently used as a reactive oxygen species (ROS) model to evaluate the radical-scavenging activity of antioxidants. It was extensively employed in kinetic studies of H-abstraction for many antioxidants.[17] Kinetic studies on two-hydrogen-atom transfer reactions between HEH2 (eq ) and other dihydrogen donors XH2 with DPPH• were carried out by UV–vis stopped-flow spectrophotometry under pseudo-first-order conditions with an excess of XH2 over DPPH• in acetonitrile at 298 K. The absorbance decay of DPPH• at λmax = 518 nm after addition of HEH2 (Figure ) in deaerated anhydrous acetonitrile at 298 K was monitored. The thermodynamic analytic platform (TAP) for the reaction mechanism of HEH2/DPPH• in acetonitrile was analyzed in Scheme , and other XH2/DPPH• are shown in the SI. The absorbance decay of 4H2/DPPH• (eq ) in acetonitrile at λmax = 518 nm (Figure ) was also monitored under a pseudo-first-order kinetic model. According to the TAP of the reaction mechanism, it is clear that the two hydrogen atoms are releasing as H•–H• stepp by stepp, and the first HAT is the rate-determining step. After losing one hydrogen atom (the blue one), the intermediate XH• rapidly loses the other hydrogen atom (the red one), resulting in the stable activated olefin. Thus, the H-donating ability of the dihydrogen donor is determined by how easily the blue hydrogen atom (Scheme ) is lost. The product analysis was proved by 1H NMR in the SI.

Figure 1

Absorbance decay of DPPH• (0.1 mM) in acetonitrile at λmax = 518 nm after addition of HEH2 (2.0 mM) in deaerated anhydrous acetonitrile at 298 K (black line) and the fit (red line) using a pseudo-first-order kinetic model.

Scheme 2

Thermodynamic Analytic Platform (TAP) for the Reaction Mechanism of HEH2 with DPPH• in Acetonitrile

Diagnostic conclusion from TAP: the most likely reaction pathway of HEH2/DPPH• is shown by red arrows: step 1 (rate-determined).

Figure 2

Absorbance decay of DPPH• (0.1 mM) in acetonitrile at λmax = 518 nm after addition of 4H2 (2.0 mM) in deaerated anhydrous acetonitrile at 298 K (black line) and the fit (red line) using the pseudo-first-order kinetic model.

In our previous works,[16,18] a new kinetic model (eq ) was proposed to quantitatively estimate the activation free energy of HAT reaction (eq ) using only one physical parameter for each reactant. The two parameters on the right of eq are thermokinetic parameters of the two-hydrogen-atom donor (XH2) and the free radical (Y•); the definitions of both are listed in eqs and 6 according to the new kinetic model. They can be used to evaluate the actual H-donating ability of hydrogen donor ΔG⧧°(XH2) and the actual H-accepting ability of free radical ΔG⧧°(Y•) accurately and quantitatively. In eqs and 6, ΔG°(XH2) is the bond dissociation free energy of XH-H, the first hydrogen atom release of which is shown in in Scheme . It is the thermodynamic parameter of XH2, usually used to assess the potential H-donating capacity of XH2. ΔG⧧XH is the activation free energy of the self-exchange HAT reaction for XH2 (XH2 + XH• → XH• + XH2). That is the kinetic intrinsic resistance as the thermodynamic driving force of the reaction is zero, which means the kinetic intrinsic resistance barrier of XH2 in the process of releasing the first hydrogen atom (the blue one). It is often called internal resistance energy. Therefore, as long as the thermokinetic parameter of dihydrogen donor is known, it can be used to quantitatively measure the actual H-donating ability of any dihydrogen donor.

In order to obtain the H-donating abilities of these dihydrogen reductants, in this work, the second-order rate constants (k2) and the corresponding activation free energies (ΔG⧧XH) of 28 cross HAT reactions (XH2/DPPH•) in acetonitrile at 298 K were determined, and the detailed results are summarized in Table . In order to calculate the thermokinetic parameters of XH2 and XH• in acetonitrile at 298 K, the molar free energy changes ΔG° of these cross HAT reactions were also provided in Table .

Table 1

Second-Order Rate Constants (k2), Activation Free Energies (ΔG⧧), and Molar Free Energy Changes (ΔG°) of HAT Reactions XH2/DPPH• in Acetonitrile at 298 K

entry	XH2/DPPH•		k2(M−1s−1)a	ΔG⧧(kcal/mol)b	ΔG°(kcal/mol)c
1	HEH2/DPPH•		1.16	17.36	−16.90
2	1(G)H2/DPPH•	p-OCH3	1.10 × 10−1	18.76	−4.70
3		p-CH3	1.94 × 10−1	18.42	−4.90
4		p-H	1.66 × 10−1	18.51	−4.80
5		p-Cl	1.63 × 10−1	18.52	−4.90
6		p-Br	1.87 × 10−1	18.44	−4.80
7		p-CF3	1.26 × 10−1	18.67	−5.60
8		p-NO2	1.68 × 10−1	18.5	−5.40
9	2(G)H2/DPPH•	p-CH3	6.04 × 10	15.02	−8.80
10		p-H	8.70 × 10	14.8	−9.10
11		p-Cl	7.02 × 10	14.93	−9.40
12		p-Br	8.94 × 10	14.78	−9.40
13		p-NO2	8.05 × 10	14.85	−10.00
14	3(G)H2/DPPH•	p-OCH3	1.91	17.06	−10.70
15		p-CH3	1.23 × 10	15.96	−10.80
16		p-H	9.36	16.12	−11.10
17		p-Cl	4.85	16.51	−11.30
18		p-Br	3.24	16.75	−11.40
19		p-NO2	2.08	17.01	−12.10
20	4(G)H2/DPPH•	p-OCH3	2.14 × 102	14.27	−6.30
21		p-CH3	2.07 × 102	14.29	−6.50
22		p-H	1.74 × 102	14.39	−6.90
23		p-Cl	1.21 × 102	14.61	−7.00
24		p-Br	1.13 × 102	14.64	−7.10
25		p-CF3	4.03 × 101	15.26	−7.30
26	5H2/DPPH•		1.04 × 10	16.06	−8.80
27	6H2/DPPH•		5.41	16.45	−7.60
28	7H2/DPPH•		4.87	16.51	−3.50

k2 is obtained from experimental measurements by a stopped-flow method. The uncertainty is smaller than 5%.

ΔG⧧ is derived from the Eyring equation k2 = (kBT/h) exp(–G⧧/RT).

ΔG° is derived from the subtraction of the bond dissociation free energies of two substrates (XH2 and DPPH•): ΔG° = ΔG°(XH2) – ΔG°(DPPHH); the data are obtained from refs (16 and 19b). Reprinted in part with permission from refs (16) and (19b). Copyright 2017 Wiley and 2013 American Chemical Society.

Since the thermokinetic parameter ΔG⧧°(DPPH•) = −29.67 kcal/mol was already obtained in our previous work,[16] the thermokinetic parameters ΔG⧧°(XH2) of these 28 dihydrogen donors could be obtained using eq as ΔG⧧XH are shown in Table . The results were summarized in Table . The ΔG⧧°(XH2) values of these 28 dihydrogen atom donors (XH2) and the ΔG⧧°(XH•) values of the corresponding hydrogen atom acceptors (XH•) in acetonitrile at 298 K can be derived from the corresponding ΔG⧧XH and ΔG°(XH2) values using eqs and 6, respectively. The results were also listed in Table . In order to conveniently calculate ΔG⧧°(XH2) and ΔG⧧°(XH•), the ΔG°(XH2) values in acetonitrile at 298 K which were obtained from ref (19) are also listed in Table .

Table 2

Thermokinetic Parameters of XH2 and XH•, ΔG⧧°(XH2) and ΔG⧧°(XH•), Bond Dissociation Free Energies of XH2, ΔG°(XH2), and Activation Free Energies of Self-Exchange HAT Reactions, ΔG⧧XH, in Acetonitrile at 298 K (kcal/mol)

			DG(kcal/mol)
entry	XH2/XH•		ΔG°(XH2)a	ΔG⧧XH2/XH•b	ΔG⧧°(XH2)c	ΔG⧧°(XH•)d
1	HEH2/HE•		63.80	30.25	47.03	−16.78
2	1(G)H2/1(G)H•	p-OCH3	76.00	20.85	48.43	−27.58
3		p-CH3	75.80	20.37	48.09	−27.72
4		p-H	75.90	20.45	48.18	−27.73
5		p-Cl	75.80	20.57	48.19	−27.62
6		p-Br	75.90	20.31	48.11	−27.80
7		p-CF3	75.10	21.57	48.34	−26.77
8		p-NO2	75.30	21.03	48.17	−27.14
9	2 (G)H2/2(G)H•	p-CH3	71.90	17.47	44.69	−27.22
10		p-H	71.60	17.33	44.47	−27.14
11		p-Cl	71.30	17.89	44.60	−26.71
12		p-Br	71.30	17.59	44.45	−26.86
13		p-NO2	70.70	18.33	44.52	−26.19
14	3(G)H2/3(G)H•	p-OCH3	70.00	23.45	46.73	−23.28
15		p-CH3	69.90	21.35	45.63	−24.28
16		p-H	69.60	21.98	45.79	−23.81
17		p-Cl	69.40	22.95	46.18	−23.23
18		p-Br	69.30	23.53	46.42	−22.89
19		p-NO2	68.60	24.75	46.68	−21.93
20	4(G)H2/4(G)H•	p-OCH3	74.40	13.47	43.94	−30.47
21		p-CH3	74.20	13.71	43.96	−30.25
22		p-H	73.80	14.31	44.06	−29.75
23		p-Cl	73.70	14.85	44.28	−29.43
24		p-Br	73.60	15.01	44.31	−29.30
25		p-CF3	73.40	16.46	44.93	−28.47
26	5H2/5H•		71.90	19.55	45.73	−26.18
27	6H2/6H•		73.10	19.13	46.12	−26.99
28	7H2/7H•		77.20	15.15	46.18	−31.03

ΔG°(XH2) is the bond dissociation free energy of the blue C–H bond.[19] Reprinted in part from ref (19b). Copyright 2013 American Chemical Society.

ΔG⧧XH is the activation free energy of the self-exchange HAT reaction (XH2 + XH• → XH• + XH2), which is derived from eq .

ΔG⧧°(XH2) = 1/2[ΔG⧧XH + ΔG°(XH2)].

ΔG⧧°(XH•) = 1/2[ΔG⧧XH – ΔG°(XH2)].

The Scales of Thermokinetic Parameters of Dihydrogen Donors XH2 and the Corresponding Radicals XH•

From Table , it is clear that the ΔG⧧°(XH2) values of 28 dihydrogen donors (XH2) in acetonitrile at 298 K range from 43.57 kcal/mol for 4(CF3)H2 to 48.43 kcal/mol for 1(OCH3)H2, and the ΔG⧧°(XH•) values of the corresponding hydrogen atom acceptors (XH•) range from −30.47 kcal/mol for 4(OH3)H• to −16.78 kcal/mol for HEH•. In order to make the thermokinetic parameters in Table be convenient for the application, and discover the dependence of ΔG⧧°(XH2) and ΔG⧧°(XH•) on the structures and compare the thermokinetic parameters of XH2 and the corresponding radical intermediates XH• after the loss of one hydrogen atom intuitively, the compounds are sorted according to the value order of thermokinetic parameters in Schemes and 4, respectively.

Scheme 3

Visual Comparison of ΔG⧧°(XH2) among the 28 Well-Known Dihydrogen Donors (XH2) in Acetonitrile at 298 K (kcal/mol)

Scheme 4

Visual Comparison of ΔG⧧°(XH•) among the 28 Well-Known Hydrogen Atom Acceptors (XH•) in Acetonitrile at 298 K (kcal/mol)

From Schemes and 4, it is clear that the effects of the structures of XH2 and XH• on ΔG⧧°(XH2) and ΔG⧧°(XH•) are quite enormous. In Scheme , it is not difficult to see that the order of thermokinetic parameters ΔG⧧°(XH2) of these dihydrogen donors is 4(G)H2 < 2(G)H2 < 3(G)H2 (5H2 < 6H2 < 7H2) < HEH2 < 1(G)H2. As discussed in our previous works, the physical significance of thermokinetic parameter ΔG⧧°(XH2) is used to characterize the actual H-donating ability of XH2 in a HAT reaction during a certain time.[16,18,20,21] The larger the ΔG⧧°(XH2) value is, the weaker the H-donating ability of XH2 is. Therefore, the order of actual H-donating abilities of these dihydrogen donors is 4(G)H2 > 2(G)H2 > 3(G)H2 (5H2 > 6H2 > 7H2) > HEH2 > 1(G)H2. The dihydrogen donors with the strongest H-donating abilities are barbituric acid derivatives 4(G)H2 (5-benzyl-1,3-dimethylpyrimidine-2,4,6-trione), and the dihydrogen donors with the weakest H-donating abilities are malononitrile derivatives 1(G)H2 (2-benzylmalononitrile). As the common dihydrogen reducing agent, the ability to release two hydrogen atoms for the Hantzsch ester is not strong among these compounds. Unlike the other seven dihydrogen donors (1H2–7H2), the first hydrogen leaving in HEH2 is the hydrogen attached to the C–H bond, and the second H leaving is attached to N–H bond. However, the leaving of the first H is the rate-determining step of the dihydrogen transfer reaction, so the hydrogen atom on C–H bond plays a decisive role in the dihydrogen transfer reaction rate and the ability of dihydrogen donating for HEH2. For example, in the synthesis of 1(G)H2, HEH2 is usually used as the reducing agent to reduce activated olefins 1(G). In the synthesis of 5H2, 6H2, and 7H2, the C=C bonds in 5–7 activated olefins form π–π conjugation systems with fluorene groups, which make the C=C bonds difficult to reduce. Therefore, compared with the reduction of olefins 1(G), magnesium perchlorate [Mg(ClO4)2] needs to be added in the reduction of olefins 5–7 when HEH2 is used as the reducing agent (Scheme a). For olefins 2(G) and 3(G), they are difficult to reduce using HHE2 as the reductant, and the stronger reductant sodium borohydride (NaBH4) needs to be added (Scheme b).

Scheme 5

(a) Reduction of C=C Bonds in Olefins 5–7. (b) Reduction of C=C Bonds in Olefins 2 and 3

Thermokinetic parameters ΔG⧧°(XH•) of the active radical intermediates XH• are shown in Scheme . The physical significance of the thermokinetic parameter ΔG⧧°(XH•) is used to characterize the actual H-abstraction ability of XH• in a HAT reaction during a certain time.[16,18,20,21] The greater the negative ΔG⧧°(XH•) value is, the stronger the H-abstraction ability of XH• is. Hence, for these 28 active free-radical intermediates, 4(OH3)H• [ΔG⧧°(XH•) = −30.47 kcal/mol] is the strongest H acceptor and HEH• [ΔG⧧°(XH•) = −16.78 kcal/mol] is the weakest H acceptor. Different from the scales of ΔG⧧°(XH2) for dihydrogen donors, the scales of ΔG⧧°(XH•) for free radicals are quite wide (13.69 kcal/mol). Therefore, the H-abstraction abilities of these radical intermediates vary greatly.

Comparison of Thermokinetic Parameter ΔG⧧°(XH2), Self-Exchange HAT Activation Free Energy ΔG⧧XH, and Bond Dissociation Free Energy ΔG°(XH2) of Dihydrogen Donors XH2

In Scheme , ΔG⧧°(XH2), ΔG⧧XH, and ΔG°(XH2) of these eight dihydrogen donors without substituents are displayed in one scheme. As is well-known, the bond dissociation free energy ΔG°(XH2) is usually used to access the potential H-donating capacity of dihydrogen donor. The bigger the value of ΔG°(XH2) is, the weaker H-donating capacity of XH2 is. It is not difficult to see from Scheme a that the potential H-donating capacities of these eight dihydrogen compounds are in the order of HEH2 > 3H2 > 2H2 > 5H2 > 6H2 > 4H2 > 1H2 > 7H2. Actually, the order of actual H-donating abilities of these eight compounds is provided by thermokinetic parameters ΔG⧧°(XH2) is 4H2 > 2H2 > 5H2 > 3H2 > 6H2 > 7H2 > HEH2 > 1H2 in Scheme c. By comparing Scheme a and 6c, the actual H-donating ability of dihydrogen donor in HAT reactions is inconsistent with the potential H-donating capacity provided by thermodynamic parameter ΔG°(XH2). The reason is that ΔG°(XH2) only evaluates the H-donating capacity of the hydrogen donor from the direction of thermodynamics, without considering the kinetic factor of XH2 in the process of HAT. The activation free energy of the self-exchange HAT reaction ΔG⧧XH, namely the internal kinetic resistance energy of XH2 in HAT reaction, is listed in Scheme b. The bigger the value of ΔG⧧XH is, the bigger the intrinsic kinetic resistance barrier of XH2 in HAT reaction is, and the more difficult hydrogen atom donation in kinetics is. In terms of intrinsic kinetic resistance, the order of H-donating abilities is 4H2 > 7H2 > 2H2 > 6H2 > 5H2 > 1H2 > 3H2 > HEH2. Considering the bond dissociation free energy in thermodynamics and intrinsic kinetic resistance in kinetics of H-donating for XH2, the actual H-donating ability of dihydrogen donor can be explained.

Scheme 6

Visual Comparison of (a) ΔG°(XH2), (b) ΔG≠XH, and (c) ΔG⧧°(XH2) for Eight Dihydrogen Donors (XH2) in Acetonitrile at 298 K (kcal/mol)

For HEH2, although it is the best hydrogen donor in terms of thermodynamics, its actual H-donating ability in HAT reaction is weak due to its maximum intrinsic kinetic resistance for hydrogen donation. For 5H2, 6H2, and 7H2, all three compounds contain fluorene rings. The only differences among them are the groups beside the active hydrogen atoms (the blue hydrogen atoms). The order of the bond dissociation free energies [ΔG°(XH2), 5H2 > 6H2 > 7H2] and intrinsic kinetic resistances (ΔG⧧XH, 7H2 > 6H2 > 5H2) of H-donating of these three compounds are opposite. However, the bond dissociation free energies become the main factor affecting the actual H-donating abilities since these three dihydrogen donors have similar structures and small differences in intrinsic kinetic resistances. For 2H2, 3H2, and 4H2, all three compounds are β-dicarbonyl compounds, but the carbon framework rings containing active hydrogen atoms are different. The orders of ΔG°(XH2) (3H2 > 2H2 > 4H2) and ΔG⧧XH (4H2 > 2H2 > 3H2) of H-donation for these three compounds are also opposite. However, due to the small difference of bond dissociation free energies among these three compounds, the intrinsic kinetic resistances caused by different structures become the main factor affecting the actual H-donating abilities.

Prediction of the Rate Constants and Verification of the Predictions

In order to investigate the reliabilities of these dihydrogen donors’ thermokinetic parameters, HEH2, 3(G)H2, and 4(G)H2 are selected to react with 2,4,6-tert-butylphenol radical (tBu3PhO•), and the HAT reaction rate constants are monitored by a stopped-flow method experimentally. According to the thermokinetic parameters of XH2 in Table and the thermokinetic parameter of tBu3PhO• [ΔG⧧°(tBu3PhO•) = −29.56 kcal/mol] determined in previous work,[16] the second-order rate constants of HAT reactions ktheor. calculated by thermokinetic parameters of each reactants using eq and Eyring equation, the second-order rate constants measured by experiment kexp., and the ktheor./kexp. are listed in Table . Absorbance decay of tBu3PhO• at λmax = 631 nm after addition of XH2 in deaerated anhydrous acetonitrile at 298 K and the fit using the pseudo-first-order kinetic model are listed in the SI. Based on the ratio of ktheor./kexp., the results indicate that the thermokinetic parameters of XH2 in Table are highly reliable and accurate.

Table 3

Comparison of Theoretical kHAT Values of HAT Reactions with the Corresponding Experimental Ones in Acetonitrile at 298 K

entry	XH2/tBu3PhO•	ktheor (M–1 s–1)a	kexp (M–1 s–1)b	ktheor/kexp
1	HEH2/tBu3PhO•	9.60 × 10–1	7.85 × 10–1	1.22
	3(G)H2tBu3PhO•
2	p-OCH3	1.59	1.33	1.20
3	p-CH3	1.02 × 10	8.58	1.19
4	p-Cl	4.03	3.84	1.05
5	p-Br	2.69	2.31	1.16
6	p-NO2	1.73	1.09	1.59
	4(G)H2/tBu3PhO•
7	p-OCH3	1.77 × 102	1.36 × 102	1.30
8	p-CH3	1.71 × 102	1.21 × 102	1.41
9	p-H	1.45 × 102	1.07 × 102	1.36
10	p-Cl	9.97 × 10	7.27 × 10	1.37
11	p-Br	9.48 × 10	6.43 × 10	1.47
12	p-CF3	3.31 × 102	2.40 × 102	1.38

Derived from ΔG⧧°(XH2) values and ΔG⧧°(tBu3PhO•) according to eq .

Derived from experimental measurements using the stopped-flow method.

Conclusions

In this work, the abilities of the Hantzsch ester and other 27 well-known organic dihydrogen donors (XH2) releasing two hydrogen atoms in acetonitrile at 298 K were identified and researched. The second-order rate constants of 28 HAT reactions between XH2 and DPPH• in acetonitrile at 298 K were monitored by a stopped-flow method. The thermokinetic parameters of XH2 and the corresponding radicals XH• were derived according to their definition formulas (eqs –6). The reliabilities of the thermokinetic parameters were also examined. The following conclusions can be made:

(1) For these dihydrogen donors, since the transfer processes of the first hydrogen atoms (the blue ones) are the rate-determining steps, the thermokinetic parameters of the first hydrogen atom transfers can represent the abilities of the dihydrogen donors releasing two hydrogen atoms. So, unlike other dihydrogen donors (1H2–7H2), even though the first hydrogen release for HEH2 is attached to C–H, the second H is attached to N–H, and the release of C–H is the rate-determining step of the dihydrogen transfer reaction, which plays a decisive role in the reaction rate and the ability of hydrogen donation.

(2) Thermokinetic parameters ΔG⧧°(XH2) are used to measure the H-donating abilities of eight series of dihydrogen donors with different structures. The ΔG⧧°(XH2) values range from 43.57 kcal/mol for 4(CF3)H2 to 48.43 kcal/mol for 1(OCH3)H2, and the ΔG⧧°(XH•) values of the corresponding hydrogen atom acceptors (XH•) range from −30.47 kcal/mol for 4(OH3)H• to −16.78 kcal/mol for HEH•. The order of H-donating abilities for these dihydrogen donors is 4(G)H2 > 2(G)H2 > 3(G)H2 (5H2 > 6H2 > 7H2) > HEH2 > 1(G)H2.

(3) In terms of bond dissociation free energies ΔG°(XH2), the order of H-donating abilities of these eight dihydrogen donors is HEH2 > 3H2 > 2H2 > 5H2 > 6H2 > 4H2 > 1H2 > 7H2. In terms of intrinsic kinetic resistance ΔG⧧XH, the order of H-donating abilities is 4H2 > 7H2 > 2H2 > 6H2 > 5H2 > 1H2 > 3H2 > HEH2. The order of actual H-donating abilities of these 8 compounds in HAT reactions provided by thermokinetic parameters ΔG⧧°(XH2) is 4H2 > 2H2 > 5H2 > 3H2 > 6H2 > 7H2 > HEH2 > 1H2.

(4) For HEH2, although it is the best hydrogen donor in terms of thermodynamics, the actual H-donating ability in HAT reaction is weak due to its maximum intrinsic kinetic resistance for hydrogen donation. The H-donating ability of dihydrogen donor is not only related to the bond dissociation free energy ΔG°(XH2) but also to the intrinsic kinetic resistance ΔG⧧XH.