Thermodynamic evaluations of the acceptorless dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles in acetonitrile

Abstract

N-heterocycles are important chemical hydrogen-storage materials, and the acceptorless dehydrogenation and hydrogenation of N-heterocycles as organic hydrogen carriers have been widely studied, with the main focus on the catalyst synthesis and design, investigation of the redox mechanisms, and extension of substrate scope. In this work, the Gibbs free energies of the dehydrogenation of pre-aromatic N-heterocycles (YH₂) and the hydrogenation of aromatic N-heterocycles (Y), i.e., ΔG_H2R(YH₂) and ΔG_H2A(Y), were derived by constructing thermodynamic cycles using Hess' law. The thermodynamic abilities for the acceptorless dehydrogenation and hydrogenation of 78 pre-aromatic N-heterocycles (YH₂) and related 78 aromatic N-heterocycles (Y) were well evaluated and discussed in acetonitrile. Moreover, the applications of the two thermodynamic parameters in identifying pre-aromatic N-heterocycles possessing reversible dehydrogenation and hydrogenation properties and the selection of the pre-aromatic N-heterocyclic hydrogen reductants in catalytic hydrogenation were considered and are discussed in detail. Undoubtedly, this work focuses on two new thermodynamic parameters of pre-aromatic and aromatic N-heterocycles, namely ΔG_H2R(YH₂) and ΔG_H2A(Y), which are important supplements to our previous work to offer precise insights into the chemical hydrogen storage and hydrogenation reactions of pre-aromatic and aromatic N-heterocycles.

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1 Introduction

The acceptorless dehydrogenation and hydrogenation of N-heterocycles are key atom-economical and fundamental methods to afford various imine and amine derivatives with potential bioactivities.^1–11 Additionally, the two kinds of redox reactions, especially the reversible acceptorless dehydrogenation and hydrogenation of N-heterocycles, involve the release and acceptance of H₂, which indicate that N-heterocycles are significant chemical hydrogen-storage materials. In fact, N-heterocycles have already been verified as an important type of chemical hydrogen-storage materials.^12–19 The acceptorless dehydrogenation and hydrogenation of N-heterocycles as organic hydrogen carriers have been broadly studied, mainly focusing on the catalyst synthesis and design, investigation of the redox mechanisms, and extension of substrate scope.^3–19

Since the chemical processes for the acceptorless dehydrogenation and hydrogenation of N-heterocycles involve H₂ release and acceptance, therefore, the thermodynamics of the dehydrogenation and hydrogenation of N-heterocycles are important thermodynamic parameters to evaluate the hydrogen-storage abilities and hydrogenation abilities of N-heterocycles, especially for pre-aromatic N-heterocycles possessing reversible dehydrogenation and hydrogenation abilities.^3–8 This work follows on from our previous study into the thermodynamics of hydrogen transfer for amines.²⁰ This present work focuses on thermodynamic evaluations of the acceptorless dehydrogenation and hydrogenation of a special category of N-heterocycles, namely, pre-aromatic and aromatic N-heterocycles, in acetonitrile.

In our previous research work, we computed the Gibbs free energies of 84 amines (YH₂), including 78 pre-aromatic N-heterocycles and 6 general amines, releasing hydrides and their activation free energies for hydride self-exchange reactions, i.e., ΔG_H⁻R(YH₂) and ΔG^‡(YH₂/YH⁺), using density functional theory (DFT) calculations in acetonitrile.^20a Earlier in 2023, thermodynamic evaluations were conducted of 84 amines releasing two hydrogen ions (H⁻ + H⁺) and the corresponding 84 imines accepting two hydrogen ions (H⁻ + H⁺), including ΔG_H⁻PR(YH₂) and ΔG_H⁻PA(Y).^20b Combined with the above thermodynamic data, in this work, the thermodynamic values upon H₂ release and acceptance for the dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles (Scheme 1) were naturally derived via constructing thermodynamic cycles using Hess' law,²¹ and the thermodynamic abilities of the pre-aromatic N-heterocycles as chemical hydrogen-storage materials were well evaluated and compared. Moreover, application of the thermodynamic data for identifying pre-aromatic N-heterocycles possessing reversible dehydrogenation and hydrogenation abilities^3–8 were investigated and discussed in detail. Undoubtedly, this work focuses on new thermodynamic parameters, which is an important supplement to our previous work to offer precise insights into the chemical hydrogen storage and hydrogenation reactions of pre-aromatic N-heterocycles.^1–19

Scheme 1 Chemical equations for the acceptorless dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles.

2 Results and discussion

In this work, 78 various pre-aromatic N-heterocycles (1H₂–78H₂) were designed to expand the scope of the investigated N-heterocyclic substrates, and 6 general amines (79H₂–84H₂) were designed for comparison with pre-aromatic N-heterocycles. The chemical structures of 84 amines (YH₂), including the 78 pre-aromatic N-heterocycles (1H₂–78H₂) and 6 general amines (79H₂–84H₂), are shown in Scheme 2.

Scheme 2 Chemical structures of 84 amines (YH₂), including the 78 pre-aromatic N-heterocycles (1H₂–78H₂) and 6 general amines (79H₂–84H₂) investigated in this work.

To obtain the Gibbs free energy of YH₂ releasing H₂, the constructed thermodynamic cycle based on the processes of YH₂ releasing two hydrogen ions or H₂ in acetonitrile is shown in Scheme 3. As can be seen from Scheme 3, Step 1 is the chemical process of YH₂ releasing H₂, YH₂ → Y + H₂, and the thermodynamic driving force of YH₂ dehydrogenation could be described by the Gibbs free energy of YH₂ releasing H₂, ΔG_H2R(YH₂). Step 2 is the chemical process of YH₂ releasing two hydrogen ions, YH₂ → Y + H⁻ + H⁺, and the corresponding thermodynamic driving force was defined as the Gibbs free energy of YH₂ releasing two hydrogen ions, ΔG_H⁻PR(YH₂).²⁰ Step 3 is the chemical process of H⁻ reacting with H⁺ to form H₂, H⁻ + H⁺ → H₂, and the related thermodynamic driving force was defined as the Gibbs free energy of one molar H⁻ reacting with one molar H⁺ to generate one molar H₂, ΔG_PA(H⁻). The ΔG_PA(H⁻) value was reported as −76.0 kcal mol⁻¹ in acetonitrile.^22–24 Therefore, the value of ΔG_H2R(YH₂) could be calculated using eqn (1) in Table 1 by establishing a thermodynamic cycle according to Hess' law (Scheme 3),²¹ where ΔG_H2R(YH₂) = ΔG_H⁻PR(YH₂) + ΔG_PA(H⁻) (eqn (1)). For eqn (1), ΔG_H⁻PR(YH₂) values are available from our previous work and are displayed in the fourth column of Table 2. Since the ΔG_H⁻R(YH₂) values were computed using the DFT method with a precision of 1.1 kcal mol⁻¹ in our previous work,^20a and the pK_a values of YH⁺ were predicted using XGBoost with a 0.87 pK_a error,^20a the ΔG_H2R(YH₂) values were derived from ΔG_H⁻R(YH₂) and pK_a(YH⁺), whereby ΔG_H2R(YH₂) = ΔG_H⁻R(YH₂) + 1.37pK_a(YH⁺), and therefore, the precision of the ΔG_H2R(YH₂) values could be estimated within 2.3 kcal mol⁻¹, which was a suitable precision to give practical guidance on the chemical hydrogen storage and hydrogenation reactions, etc.

Scheme 3 Constructed thermodynamic cycle based on the processes of YH₂ releasing two hydrogen ions or H₂ in acetonitrile.

Table 1 Chemical processes, thermodynamic parameters, and data sources or computed equations of step 1–step 4 for YH₂ dehydrogenation and Y hydrogenation in acetonitrile

Chemical processes		Thermodynamic parameters	Sources or computed equations	Equation X
Step 1	YH2 → Y + H2	ΔGH2R(YH2)	ΔGH2R(YH2) = ΔGH^−PR(YH2) + ΔGPA(H^−)	1
Step 2	YH2 → Y + H^− + H^+	ΔGH^−PR(YH2)	Ref. 20	—
Step 3	H^− + H^+ → H2	ΔGPA(H^−)	−76.0 kcal mol^−1 (ref. 22–24)	—
Step 4	Y + H2 → YH2	ΔGH2A(Y)	ΔGH2A(Y) = −ΔGH2R(YH2)	2

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Table 2 ΔG_H⁻PR(YH₂), ΔG_H⁻PA(Y), ΔG_H2R(YH₂), and ΔG_H2A(Y) values of the 84 considered amines (YH₂) and their corresponding imines (Y) in acetonitrile (unit: kcal mol⁻¹)

Compounds	Structures	G	ΔGH^−PR(YH2)^a	ΔGH2R(YH2)^b
			−ΔGH^−PA(Y)^a	−ΔGH2A(Y)^c
a ΔGH^−PR(YH2) and ΔGH^−PA(Y) values are from ref. 20.b ΔGH2R(YH2) = ΔGH^−PR(YH2) + ΔGPA(H^−).c ΔGH2A(Y) = −ΔGH2R(YH2).
1H2		—	68.0	−8.0
2H2		CH3	68.8	−7.2
3H2		^tBu	70.6	−5.4
4H2		Ph	66.5	−9.5
5H2		NH2	63.5	−12.5
6H2		CHO	75.6	−0.4
7H2		CN	75.2	−0.8
8H2		NO	78.9	2.9
9H2		NO2	71.7	−4.3
10H2		CH3	69.7	−6.3
11H2		^tBu	71.8	−4.2
12H2		Ph	70.2	−5.8
13H2		NH2	67.8	−8.2
14H2		CHO	80.6	4.6
15H2		CN	78.7	2.7
16H2		NO	87.3	11.3
17H2		NO2	85.7	9.7
18H2		CH3	67.4	−8.6
19H2		^tBu	72.0	−4.0
20H2		Ph	64.8	−11.2
21H2		NH2	60.2	−15.8
22H2		CHO	72.3	−3.7
23H2		CN	74.1	−1.9
24H2		NO	76.6	0.6
25H2		NO2	84.6	8.6
26H2		—	83.1	7.1
27H2		—	83.3	7.3
28H2		—	83.4	7.4
29H2		—	77.9	1.9
30H2		CH3	75.8	−0.2
31H2		^tBu	79.5	3.5
32H2		Ph	75.9	−0.1
33H2		NH2	69.6	−6.4
34H2		CHO	86.0	10.0
35H2		CN	86.4	10.4
36H2		NO	91.0	15.0
37H2		NO2	81.8	5.8
38H2		CH3	76.7	0.7
39H2		^tBu	81.1	5.1
40H2		Ph	78.8	2.8
41H2		NH2	76.8	0.8
42H2		CHO	89.4	13.4
43H2		CN	87.3	11.3
44H2		NO	98.0	22.0
45H2		NO2	93.2	17.2
46H2		CH3	73.5	−2.5
47H2		^tBu	84.9	8.9
48H2		Ph	74.9	−1.1
49H2		CH3	76.2	0.2
50H2		^tBu	80.1	4.1
51H2		Ph	75.9	−0.1
52H2		NH2	74.7	−1.3
53H2		CHO	79.0	3.0
54H2		CN	80.6	4.6
55H2		NO	80.4	4.4
56H2		NO2	81.2	5.2
57H2		—	67.6	−8.4
58H2		H	87.5	11.5
59H2		CH3	87.5	11.5
60H2		Ph	87.3	11.3
61H2		—	76.3	0.3
62H2		—	87.6	11.6
63H2		—	64.5	−11.5
64H2		—	73.7	−2.3
65H2		—	74.6	−1.4
66H2		—	77.6	1.6
67H2		—	79.6	3.6
68H2		—	78.4	2.4
69H2		—	84.1	8.1
70H2		—	76.6	0.6
71H2		—	80.8	4.8
72H2			77.0	1.0
73H2		—	84.5	8.5
74H2		—	68.6	−7.4
75H2		—	85.5	9.5
76H2		—	78.2	2.2
77H2		—	82.7	6.7
78H2		—	76.9	0.9
79H2		—	86.3	10.3
80H2		—	87.6	11.6
81H2		—	91.2	15.2
82H2		—	93.8	17.8
83H2		—	93.7	17.7
84H2		—	94.3	18.3

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Step 4 in Scheme 2 is the chemical process of Y accepting H₂ to offer YH₂, Y + H₂ → YH₂, and the corresponding thermodynamic driving force could be described as the Gibbs free energy of Y accepting H₂ to generate YH₂, ΔG_H2A(Y). Since the Y hydrogenation and YH₂ dehydrogenation are reverse chemical reactions, the ΔG_H2A(Y) value was the opposite of the ΔG_H2R(YH₂) value,²¹ i.e., ΔG_H2A(Y) = −ΔG_H2R(YH₂) (eqn (2) in Table 1). Herein, the chemical processes, thermodynamic parameters, and data sources or computed equations of step 1–step 4 for YH₂ dehydrogenation and Y hydrogenation in acetonitrile are presented in Table 1, meanwhile, the ΔG_H⁻PR(YH₂), ΔG_H⁻PA(Y), ΔG_H2R(YH₂), and ΔG_H2A(Y) values of the 84 amines (YH₂) dehydrogenation and their relevant imines (Y) hydrogenation in acetonitrile are listed in Table 2.

2.1. Thermodynamic abilities of YH₂ dehydrogenation as organic hydrogen-storage materials

For better comparing the relationship between the thermodynamic abilities and chemical structures, all 84 amines (YH₂) were divided into 4 groups,²⁰ comprising 1,4-dihydropyridine compounds (Y_IH₂, 1H₂–62H₂), 1,2-dihydropyridines (Y_IIH₂, 63H₂–73H₂), 1,2-dihydro-3-substituted-indoline analogs (Y_IIIH, 74H₂–78H₂), and general amines (Y_IVH₂, 79H₂–84H₂) (Scheme 4). Among the 4 groups, Y_IH₂, Y_IIH₂, and Y_IIIH₂ were 1,4-dihydro nitric six-member heterocycles, 1,2-dihydro nitric six-member heterocycles, and 1,2-dihydro nitric five-member heterocycles, respectively, which all belong to pre-aromatic N-heterocycles. As pre-aromatic N-heterocycles, the resulting dehydrogenation products Y (Y_I, Y_II, and Y_III) are aromatic N-heterocycles (Scheme 4) after YH₂ releases H₂, YH₂ → Y + H₂.

Scheme 4 Classifications of the 84 amines (YH₂) and imines (Y) and the corresponding 4 groups of YH₂ and Y, respectively, considered in this work.

According to the definition of ΔG_H2R(YH₂), if the ΔG_H2R(YH₂) value is more negative than 0, ΔG_H2R(YH₂) < 0, the chemical process of YH₂ releasing H₂ is thermodynamically favorable, and YH₂ is recognized as a thermodynamically excellent H₂ donor.²¹ In contrast, if the ΔG_H2R(YH₂) value is greater than 0, ΔG_H2R(YH₂) > 0, the chemical process of YH₂ releasing H₂ is thermodynamically unfavorable, and YH₂ is not a thermodynamically feasible H₂ donor.

As can be seen from Table 2, the ΔG_H2R(YH₂) scale of the 78 pre-aromatic N-heterocycles (1H₂–78H₂) investigated in this work ranged from −15.8 kcal mol⁻¹ to 22.0 kcal mol⁻¹, which spanned a very wide thermodynamic range of 37.8 kcal mol⁻¹. Moreover, among the 78 pre-aromatic N-heterocycles (1H₂–78H₂), 21H₂ from Y_IH₂ was thermodynamically the best hydrogen donor or carrier (−15.8 kcal mol⁻¹), even better than HCO₂H (−5.9 kcal mol⁻¹),²⁵ while 44H₂ from Y_IH₂ was thermodynamically the worst hydrogen donor or carrier (22.0 kcal mol⁻¹). For more refined thermodynamic analysis, the distribution of ΔG_H2R(YH₂) values for the 78 pre-aromatic N-heterocycles (1H₂–78H₂) in every 5 kcal mol⁻¹ is clearly shown in Fig. 1 with YH₂ amounts as the ordinate and ΔG_H2R(YH₂) ranges as the abscissa.

Fig. 1 Distributions of ΔG_H2R(YH₂) ranges for the 78 pre-aromatic N-heterocycles in every 5 kcal mol⁻¹ from −20 kcal mol⁻¹ to 25 kcal mol⁻¹.

From Fig. 1, several interesting conclusions could be drawn as follows. (1) The distribution of YH₂ amounts exhibited an excellent normal distribution, and ΔG_H2R(YH₂) values of pre-aromatic N-heterocycles ranging from 0 to 5 kcal mol⁻¹ were the most common (29.5%). (2) It was found that the ΔG_H2R(YH₂) values of 30 YH₂ were more negative than 0, meaning that 30 YH₂ were thermodynamically feasible H₂ donors, and belonged to potential chemical hydrogen-storage materials. While the ΔG_H2R(YH₂) values of 48 YH₂ were greater than 0, indicating that the 48 YH₂ were thermodynamically unfeasible H₂ donors. (3) It was also discovered that 75 ΔG_H2R(YH₂) values ranged from −15 kcal mol⁻¹ to 15 kcal mol⁻¹, indicating that ∼96% of the thermodynamic driving forces for the pre-aromatic N-heterocycles dehydrogenations were between −15 kcal mol⁻¹ to 15 kcal mol⁻¹, while less than 4% of the thermodynamic driving forces for the pre-aromatic N-heterocycles dehydrogenation were more negative than −15 kcal mol⁻¹ or greater than 15 kcal mol⁻¹. Accordingly, for an unknown pre-aromatic N-heterocycle, the thermodynamic driving force for YH₂ dehydrogenation is generally between −15 kcal mol⁻¹ to 15 kcal mol⁻¹ (∼96% possibilities).

To clearly reveal the relationship between the structural features and thermodynamic abilities, the ΔG_H2R(YH₂) scales of 4 groups of YH₂, along with the ΔG_H2R(XH₂) values of HCO₂H, H₂, 67H₂, 78H₂, and HEH₂ (Hantzsch ester, 27H₂) releasing H₂ in acetonitrile are shown in Scheme 5,^25–27 because HCO₂H,²⁸ H₂,^29–33 67H₂,^34,35 78H₂,^36,37 and HEH₂ (27H₂)^38–40 are the most frequently-used hydrogen reductants (denoted as XH₂) used in the hydrogenation reactions.

Scheme 5 ΔG_H2R(YH₂) scales of 4 groups of YH₂ (Y_IH₂–Y_IVH₂), along with the ΔG_H2R(XH₂) values of HCO₂H, H₂, 67H₂, 78H₂, and HEH₂ releasing H₂ in acetonitrile (kcal mol⁻¹).

From Scheme 5, the following valuable conclusions could be made: (1) the ΔG_H2R(Y_IH₂) scale covered from −15.8 kcal mol⁻¹ to 22.0 kcal mol⁻¹, which spanned the widest thermodynamic range by 37.8 kcal mol⁻¹ among the 4 groups of amines Y_IH₂–Y_IVH₂; (2) according to the ΔG_H2R(YH₂) scales of Y_IIH₂ (−11.5 to 8.5 kcal mol⁻¹), Y_IIIH₂ (−7.4 to 9.5 kcal mol⁻¹), and Y_IVH₂ (10.3–18.3 kcal mol⁻¹), the dehydrogenation abilities decreased in the order of Y_IIH₂ ≈ Y_IIIH₂ > Y_IVH₂; (3) in view of the relations between sets, it was found that the ΔG_H2R(YH₂) values displayed the following regular pattern of {ΔG_H2R(Y_IIH₂) ∪ ΔG_H2R(Y_IIIH₂) ∪ ΔG_H2R(Y_IVH₂)} ⊆ ΔG_H2R(Y_IH₂); (4) for the pre-aromatic N-heterocycles, the ΔG_H2R(YH₂) scales ranged from −15.8 to 22.0 kcal mol⁻¹ for Y_IH₂, from −11.5 to 8.5 kcal mol⁻¹ for Y_IIH₂, and from −7.4 to 9.5 kcal mol⁻¹ for Y_IIIH₂, respectively. Since the ΔG_H2R(YH₂) scales of Y_IH₂, Y_IIH₂, and Y_IIIH₂ crossed negative and positive values (−15.8 to 22.0 kcal mol⁻¹), it was indicated that not all the acceptorless dehydrogenation of pre-aromatic N-heterocycles is a thermodynamically uphill or downhill process under ambient conditions,^3–19 and not all pre-aromatic N-heterocycles are thermodynamically feasible to serve as chemical hydrogen-storage materials. ΔG_H2R(YH₂) is absolutely an important thermodynamic parameter to guide chemists to discover more potentially excellent chemical hydrogen-storage materials.

Initially, we tried to explain the effects of substituents on ΔG_H2R(YH₂), but we failed to draw a meaningful conclusion. For example, an electron-withdrawing group could decrease the hydride-donating ability of YH₂, ΔG_H⁻R(YH₂), while it increased the proton-donating ability of YH⁺, ΔG_PR(YH⁺). Since ΔG_H2R(YH₂) is derived from ΔG_H⁻R(YH₂) and ΔG_PR(YH⁺) essentially, i.e., ΔG_H2R(YH₂) = ΔG_H⁻R(YH₂) + ΔG_PR(YH⁺) + ΔG_PA(H⁻), for YH₂ possessing an electron-withdrawing group, whether the ΔG_H2R(YH₂) value increases or decreases depends on the D-values of ΔG_H⁻R(YH₂) decreasing and ΔG_PR(YH⁺) increasing, i.e., ΔΔG_H⁻R(YH₂) and ΔΔG_PR(YH⁺). In addition, the steric factors from the substituents will have a significant effect on reaction kinetics, and a slight effect on the reaction thermodynamics.

2.2. Thermodynamic abilities of Y hydrogenation to generate YH₂

According to the physical meaning of ΔG_H2A(Y), if the ΔG_H2A(Y) value is more negative than 0, ΔG_H2A(Y) < 0, the Y hydrogenation by H₂ is thermodynamically favorable. The more negative the ΔG_H2A(Y) value, the larger the thermodynamic driving force of Y hydrogenation by H₂. While if the ΔG_H2A(Y) value is greater than 0, ΔG_H2A(Y) > 0, the Y hydrogenation by H₂ is thermodynamically unfavorable, and the larger the ΔG_H2A(Y) value, the smaller the thermodynamic driving force of Y hydrogenation by H₂. From Table 2, among the 84 imines (Y), aromatic N-heterocycle 44 (−22.0 kcal mol⁻¹) had the largest thermodynamic driving force to accept H₂ producing 44H₂, while the aromatic N-heterocycle 21 (15.8 kcal mol⁻¹) had the smallest thermodynamic driving force to obtain H₂ generating 21H₂.

As for the ΔG_H2A(Y) values, we can safely draw some interesting conclusions to inform the hydrogenation reactions of imines, including aromatic N-heterocycles (1–78) and general imines (79–84), from Scheme 6. Specifically: (1) for aromatic N-heterocycles, the ΔG_H2A(Y) scales ranged from −22.0 kcal mol⁻¹ to 15.8 kcal mol⁻¹ for Y_I, from −8.5 to 11.5 kcal mol⁻¹ for Y_II, and from −9.5 kcal mol⁻¹ to 7.4 kcal mol⁻¹ for Y_III, respectively. The ΔG_H2A(Y) scale of aromatic N-heterocycles (Y_I–Y_III) ranged from −22.0 kcal mol⁻¹ to 15.8 kcal mol⁻¹, which covered a very large range of 37.8 kcal mol⁻¹. The ΔG_H2A(Y) scales indicated that the H₂ (0 kcal mol⁻¹),^22–24 even the great hydrogen-reductant HCO₂H (−5.9 kcal mol⁻¹),²⁵ could not hydrogenate all the aromatic imines (Y_I, Y_II, and Y_III) to offer pre-aromatic N-heterocycles (Y_IH₂, Y_IIH₂, and Y_IIIH₂). It also could be deduced that some pre-aromatic N-heterocycles from Y_IH₂, Y_IIH₂, and Y_IIIH₂ were thermodynamically better hydrogen reductants than H₂ in hydrogenation reactions. In practice, 27H₂ (HEH₂),^38–40 67H₂,^34,35 73H₂,⁴¹ 74H₂,⁴² and 78H₂ (ref. 36 and 37) have already been extensively researched in hydrogenating various unsaturated compounds, including aldehydes ketones, alkenes, imines, and heterocycles;^36–42 (2) in contrast, since Y_IV were general imines without aromatic structures, all the ΔG_H2A(Y_IV) values (−18.3 to −10.3 kcal mol⁻¹) were all greater than the ΔG_H2R(H₂) values (0 kcal mol⁻¹), meaning that H₂ could hydrogenate the related general imines (Y_IV) in organic synthesis under suitable catalytic conditions, which has been proved by many published studies in the literature.^43–47 Similarly, HCO₂H (ΔG_H2R(HCO₂H) = −5.9 kcal mol⁻¹),²⁸ 78H₂ (ΔG_H2R(78H₂) = 0.9 kcal mol⁻¹),^36,37 67H₂ (ΔG_H2R(67H₂) = 3.6 kcal mol⁻¹),^34,35 and HEH₂ (ΔG_H2R(HEH₂) = 7.3 kcal mol⁻¹)^38–40 could be applied to hydrogenate Y_IV to prepare general amines Y_IVH₂ in organic synthesis from a thermodynamics viewpoint.

Scheme 6 ΔG_H2A(Y) scales of 4 groups of Y (Y_I–Y_IV), along with the ΔG_H2R(XH₂) values of HCO₂H, H₂, 67H₂, 78H₂, and HEH₂ in acetonitrile (kcal mol⁻¹).

2.3. Thermodynamics for the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles

Many groups have focused on the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles, mainly including discovering better pre-aromatic N-heterocycles carriers and developing novel metal–organic catalysts.^1–19 Since we have obtained so much valuable thermodynamic data of pre-aromatic N-heterocycles dehydrogenation and aromatic N-heterocycles hydrogenation, it seemed meaningful to clarify why the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles could happen, as well as why they possess the typical thermodynamic feature of the corresponding pre-aromatic N-heterocycles.

Theoretically, according to the reaction rule, for the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles, if the Gibbs free energy of a YH₂ dehydrogenation (YH₂ → Y + H₂) is more negative than 0, ΔG_H2R(YH₂) < 0, then the YH₂ dehydrogenation reaction is judged as thermodynamically favorable; while if the Gibbs free energy of the corresponding Y hydrogenation reaction (Y + H₂ → YH₂) is greater than 0, ΔG_H2A(Y) > 0, then the hydrogenation reaction of Y is thermodynamically unfavorable. In contrast, if the Gibbs free energy of a YH₂ dehydrogenation (YH₂ → Y + H₂) is greater than 0, ΔG_H2R(YH₂) > 0, and the dehydrogenation reaction is considered as thermodynamically unfavorable; while if the Gibbs free energy of the corresponding Y hydrogenation (Y + H₂ → YH₂) is more negative than 0, ΔG_H2A(Y) < 0, and the related Y hydrogenation reaction is regarded as thermodynamically favorable. Therefore, it is very curious why the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles could happen, even using the same metal–organic catalyst.^3–9

Examining the previous literature, it is believed that the H₂ plays a very important role in regulating the reversible dehydrogenation and hydrogenation thermodynamics.^3–9 In YH₂ dehydrogenation, the H₂ is released from the reaction system, which greatly affects the dehydrogenation equilibrium.^3–9 Therefore, the Gibbs free energy of YH₂ dehydrogenation could decrease to make the reaction happen if the ΔG_H2R(YH₂) value is not too much greater than 0. Furthermore, in Y hydrogenation, the high H₂ pressure would prompt more H₂ to dissolve in the reaction solvent, which would have a strong influence on the hydrogenation equilibrium.^3–9 Consequently, the Gibbs free energy of Y hydrogenation could decrease to make the reaction occur if the ΔG_H2A(Y) is not too much greater than 0. Herein, this leads to the other key question: what are the restrictions on the ΔG_H2R(YH₂) value for the reversible dehydrogenation and hydrogenation of a pre-aromatic and aromatic N-heterocycle?³

Investigating previous work, the Gibbs solvation energy of H₂ was estimated as 3.4 kcal mol⁻¹ in acetonitrile.⁴⁸ That is, the Gibbs free energy of H₂ release from acetonitrile solution was −3.4 kcal mol⁻¹, and the H₂ release from the dehydrogenation system could decrease the ΔG_H2R(YH₂) by 3.4 kcal mol⁻¹. Therefore, it is reasonable to deduce that if the ΔG_H2R(YH₂) value of a pre-aromatic N-heterocycle is greater than −3.5 kcal mol⁻¹ and more negative than 3.5 kcal mol⁻¹, −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < 3.5 kcal mol⁻¹, the pre-aromatic N-heterocycle could be considered as a potentially reversible chemical organic hydrogen material, which could release H₂ and be regenerated by H₂ too. According to the above judgment criterion, the ΔG_H2R(YH₂) values of general amines (Y_IVH₂) (10.3–18.3 kcal mol⁻¹) are much greater than 3.5 kcal mol⁻¹, and so Y_IVH₂ could not be designed as reversible dehydrogenation and hydrogenation materials, which is proved by published works.^3–9 Moreover, the ΔG_H2R(YH₂) scale of 28 pre-aromatic N-heterocycles from Y_IH₂, Y_IIH₂, and Y_IIIH₂ ranged from −3.5 kcal mol⁻¹ to 3.5 kcal mol⁻¹, while the corresponding 28 pre-aromatic N-heterocycles were identified as reversible dehydrogenation and hydrogenation materials. The 28 pre-aromatic N-heterocycles included 6H₂ (−0.4 kcal mol⁻¹), 7H₂ (−0.8 kcal mol⁻¹), 8H₂ (2.9 kcal mol⁻¹), 15H₂ (2.7 kcal mol⁻¹), 23H₂ (−1.9 kcal mol⁻¹), 24H₂ (0.6 kcal mol⁻¹), 29H₂ (1.9 kcal mol⁻¹), 30H₂ (−0.2 kcal mol⁻¹), 31H₂ (3.5 kcal mol⁻¹), 32H₂ (−0.1 kcal mol⁻¹), 38H₂ (0.7 kcal mol⁻¹), 40H₂ (2.8 kcal mol⁻¹), 41H₂ (0.8 kcal mol⁻¹), 46H₂ (−2.5 kcal mol⁻¹), 48H₂ (−1.1 kcal mol⁻¹), 49H₂ (0.2 kcal mol⁻¹), 51H₂ (−0.1 kcal mol⁻¹), 52H₂ (−1.3 kcal mol⁻¹), 53H₂ (3.0 kcal mol⁻¹), 61H₂ (0.3 kcal mol⁻¹), 64H₂ (−2.3 kcal mol⁻¹), 65H₂ (−1.4 kcal mol⁻¹), 66H₂ (1.6 kcal mol⁻¹), 68H₂ (2.4 kcal mol⁻¹), 70H₂ (0.6 kcal mol⁻¹), 72H₂ (1.0 kcal mol⁻¹), 76H₂ (2.2 kcal mol⁻¹), and 78H₂ (0.9 kcal mol⁻¹), which need further validation and support in experimental work. Examining the chemical structures of the investigated N-heterocycles in previous literature,^3–19 they were not exactly the same pre-aromatic N-heterocycle structure, and most cases involved two H₂ molecules release and acceptance from N-heterocycles, which could not provide direct experimental data to validate the thermodynamic model.

2.4. Application of thermodynamic parameters to the selection of pre-aromatic N-heterocyclic hydrogen reductants for catalytic hydrogenation reactions

It is well known that H₂ is the greenest hydrogenation reagent with 100% atomic economy.^43–47 Besides H₂, the organic hydrogen molecule reductants, most of which are pre-aromatic N-heterocyclics (such as 27H₂, 67H₂, 73H₂, 74H₂, and 78H₂),^36–42 are irreplaceable hydrogen carriers in hydrogenation reactions. Zhou et al. developed dual hydrogenation strategies and utilized catalytic amounts of Hantzsch ester (HEH₂ or 27H₂)⁴⁹ and dihydrophenanthridines (67H₂)⁵⁰ as hydrogen reductants to asymmetrically reduce imines by using H₂ as a real reductant for regeneration of the oxidated Hantzsch esters (HE or 27) under a catalyst of metal complexes (Scheme 7). During their work, the reduction of imines, the oxidation of organic hydrogen reductants (pre-aromatic N-heterocycles), as well as the regeneration of oxidated organic hydrogen reductants (aromatic N-heterocycles) all involved H₂ transfer. Therefore, the Gibbs free energies for amines dehydrogenation and imines hydrogenation are important thermodynamic parameters to evaluate the reducing abilities of amines and the hydrogenation difficulties of imines, which could help us discover thermodynamically excellent organic hydrogen reductants or chemical hydrogen-storage compounds, choose appropriate hydrogen reductants, especially for catalytic amounts of hydrogen reductants during the hydrogenation of unsaturated substrates.

Scheme 7 Dual hydrogenation strategies involving utilizing catalytic amounts of pre-aromatic N-heterocycles as hydrogen reductants to asymmetrically reduce imines by using H₂ as a real reductant for the regeneration of aromatic N-heterocycles.

If an unsaturated substrate (Sub) is hydrogenated to a reduced unsaturated substrate (SubH₂), Sub + H₂ → SubH₂, whose thermodynamic driving force is defined as the Gibbs free energy of an unsaturated substrate (Sub) accepting H₂ to afford SubH₂ (equal to the opposite of Gibbs free energy of SubH₂ releasing H₂ to give Sub, SubH₂ → Sub + H₂), ΔG_H2A(Sub) = −ΔG_H2R(SubH₂), then the larger the thermodynamic driving force for the pre-aromatic N-heterocycle reductant dehydrogenation, the more favorable the Sub hydrogenation by YH₂, i.e., Sub + YH₂ → SubH₂ + Y.²¹

Herein, the applications of thermodynamic parameters on choosing suitable catalytic amounts of pre-aromatic N-heterocycle reductants in hydrogenation reactions are displayed in Scheme 8 to aid a clear discussion.

Scheme 8 Applications of the thermodynamic parameters on choosing suitable catalytic amounts of N-heterocyclic hydrogen reductants in hydrogenation reactions.

It should be noted that not all unsaturated substrates hydrogenation reactions could be designed as organic hydrogen-reductant catalytic reactions. For unsaturated substrates (Sub), if the ΔG_H2R(SubH₂) values are more negative than −3.5 kcal mol⁻¹, due to the regeneration of aromatic N-heterocycles being impossible (ΔG_H2R(YH₂) < −3.5 kcal mol⁻¹), the hydrogenation reactions could not be designed as pre-aromatic N-heterocyclic reductant catalyzed reactions. In contrast, if the ΔG_H2R(SubH₂) values of unsaturated substrates are greater than 3.5 kcal mol⁻¹, whose thermodynamic driving force scale of SubH₂ releasing H₂ is denoted as ΔG_H2R(SubH₂)_min ∼ ΔG_H2R(SubH₂)_max, then pre-aromatic N-heterocycles with ΔG_H2R(YH₂) values more negative than ΔG_H2R(SubH₂)_min and greater than −3.5 kcal mol⁻¹ can be recognized as potential catalytic pre-aromatic N-heterocycle reductants, that is, −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < ΔG_H2R(SubH₂)_min. Specially, if 3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < ΔG_H2R(SubH₂)_min, then the corresponding pre-aromatic N-heterocycles could be designed as thermodynamically good catalytic hydrogen reductants. If 0 < ΔG_H2R(YH₂) < 3.5 kcal mol⁻¹, the corresponding pre-aromatic N-heterocycles could be designed as thermodynamically better catalytic hydrogen reductants. If −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < 0 kcal mol⁻¹, the corresponding pre-aromatic N-heterocycles could be designed as the thermodynamically best catalytic hydrogen reductants. If ΔG_H2R(YH₂) < −3.5 kcal mol⁻¹, the corresponding pre-aromatic N-heterocycles could be considered thermodynamically very excellent reductants, but they could not be regenerated by H₂ and designed as catalytic hydrogen reductants.

Thus, it can be seen that the two new thermodynamic parameters ΔG_H2R(YH₂) and ΔG_H2A(Y) can not only help us evaluate and identify good chemical hydrogen-storage materials, but also choose appropriate hydrogen reductants, especially for catalytic amounts of N-heterocyclic hydrogen reductants during the hydrogenation of unsaturated substrates.

3 Conclusions

In this work, the Gibbs free energies of pre-aromatic N-heterocycles (YH₂) dehydrogenation and corresponding aromatic N-heterocycles (Y) hydrogenation, ΔG_H2R(YH₂) and ΔG_H2A(Y), were derived by constructing thermodynamic cycles using Hess' law. The thermodynamic abilities on the acceptorless dehydrogenation and hydrogenation of 78 pre-aromatic N-heterocycles (YH₂) and related 78 aromatic N-heterocycles (Y) were well evaluated and discussed in acetonitrile. Several valuable conclusions could be drawn as follows:

(1) ΔG_H2R(YH₂) is an important thermodynamic parameter to guide chemists to discover more potentially excellent hydrogen carriers. Not all pre-aromatic N-heterocycles are thermodynamically feasible chemical hydrogen-storage materials. The ΔG_H2R(YH₂) scale of the considered 78 pre-aromatic N-heterocycles ranged from −15.8 kcal mol⁻¹ to 22.0 kcal mol⁻¹, with 30 ΔG_H2R(YH₂) values being more negative than 0, meaning that the related 30 YH₂ were identified as thermodynamically feasible H₂ donors, and belong to potential chemical hydrogen-storage materials. The ΔG_H2R(Y_IH₂) scale (−15.8 to 22.0 kcal mol⁻¹) spanned the widest thermodynamic range by 37.8 kcal mol⁻¹ among Y_IH₂–Y_IVH₂, and the dehydrogenation abilities of Y_IIH₂–Y_IVH₂ decreased in the order of Y_IIH₂ ≈ Y_IIIH₂ > Y_IVH₂.

(2) As for the thermodynamic abilities of Y hydrogenation, the ΔG_H2A(Y) data indicated that for H₂, even the great hydrogen-reductant HCO₂H (−5.9 kcal mol⁻¹), could not hydrogenate all the aromatic imines (Y_I, Y_II, and Y_III) to form pre-aromatic N-heterocycles. Y_IV are general imines without aromatic structures, and all their ΔG_H2A(Y_IV) values (−18.3 to −10.3 kcal mol⁻¹) were greater than ΔG_H2R(H₂) (0 kcal mol⁻¹), meaning that H₂ could hydrogenate the related general imines (Y_IV) in organic synthesis under suitable catalytic conditions.

(3) H₂ plays an important role in regulating reversible dehydrogenation and hydrogenation thermodynamics. The thermodynamic features in the reversible dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles were clarified such that if −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < 3.5 kcal mol⁻¹, the pre-aromatic N-heterocycle is considered as a thermodynamically potential reversible chemical organic hydrogen material, which could release H₂ and be regenerated by H₂ too.

(4) The application of thermodynamic parameters to the selection of pre-aromatic N-heterocyclic hydrogen reductants in catalytic hydrogenation was exhibited in this work. If the ΔG_H2R(SubH₂) values of unsaturated substrates (SubH₂) are greater than 3.5 kcal mol⁻¹, pre-aromatic N-heterocycles with −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < ΔG_H2R(SubH₂)_min could be recognized as thermodynamically potential catalytic reductants. Specially, if 3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < ΔG_H2R(SubH₂)_min, the related pre-aromatic N-heterocycles could be designed as thermodynamically good catalytic hydrogen reductants. If 0 < ΔG_H2R(YH₂) < 3.5 kcal mol⁻¹, the related pre-aromatic N-heterocycles could be designed as thermodynamically better catalytic hydrogen reductants. If −3.5 kcal mol⁻¹ < ΔG_H2R(YH₂) < 0 kcal mol⁻¹, the related pre-aromatic N-heterocycles could be designed as the thermodynamically best catalytic hydrogen reductants.

In summary, this work focused on two new thermodynamic parameters, namely ΔG_H2R(YH₂) and ΔG_H2A(Y), which is an important supplement to our previous work to offer precise insights into the chemical hydrogen storage of pre-aromatic N-heterocycles, and hydrogenation reactions.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

This study was supported by the College Students' Innovative Training Plan Program of Shandong Province (S202210443003), and the Doctoral Scientific Research Foundation of Jining Medical University.

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