Thermodynamic H-Abstraction Abilities of Nitrogen Centered Radical Cations as Potential Hydrogen Atom Transfer Catalysts in Y-H Bond Functionalization.

Y-H bond functionalization has always been the focus of research interest in the area of organic synthesis. Direct hydrogen atom transfer (HAT) from the Y-H bond is one of the most efficient and practical methods to activate the Y-H bond. Recently, nitrogen centered radical cations were broadly utilized as H-abstraction catalysts to activate Y-H bonds via the HAT process. As a type of HAT catalyst, the H-affinity of nitrogen centered radical cations is a significant thermodynamic parameter to quantitatively evaluate the thermodynamic H-abstraction potentials of nitrogen centered radical cations. In this work, the pK a values of 120 protonated N-containing compounds in acetonitrile (AN) are predicted, and the H-affinities of 120 nitrogen centered radical cations in AN are derived from the reduction potentials of nitrogen centered radical cations and pK a of protonated N-containing compounds using Hess' law. This work focuses on the H-abstraction abilities of 120 nitrogen centered radical cations in AN to enrich the molecule library of novel HAT catalysts or H-abstractors and provides valuable thermodynamic guidelines for the application of nitrogen centered radical cations in Y-H bond functionalization.

Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

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

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., ΔGH2R(YH2) and ΔGH2A(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 ΔGH2R(YH2) and ΔGH2A(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.

Thermodynamic Evaluations of Amines as Hydrides or Two Hydrogen Ions Reductants and Imines as Protons or Two Hydrogen Ions Acceptors, as Well as Their Application in Hydrogenation Reactions.

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

The Application of Sulfonyl Hydrazides in Electrosynthesis: A Review of Recent Studies.

Sulfonyl hydrazides are viewed as alternatives to sulfinic acids and their salts or sulfonyl halides, which are broadly used in organic synthesis or work as active pharmaceutical substances. Generally, sulfonyl hydrazides are considered good building blocks and show powerful value in a diverse range of reactions to construct C-S bonds or C-C bonds, and even C-N bonds as sulfur, carbon, or nitrogen sources, respectively. As a profound synthetic tool, the electrosynthesis method was recently used to achieve efficient and green applications of sulfonyl hydrazides. Interestingly, many unique and novel electrochemical syntheses using sulfonyl hydrazides as radical precursors have been developed, including cascade reactions, functionalization of heterocycles, as well as a continuous flow method combining with electrochemical synthesis since 2017. Accordingly, it is necessary to specifically summarize the recent developments of electrosynthesis with only sulfonyl hydrazides as radical precursors to more deeply understand and better design novel electrochemical synthesis reactions. Herein, electrosynthesis research using sulfonyl hydrazides as radical precursors since 2017 is reviewed in detail based on the chemical structures of products and reaction mechanisms.

Theoretical Study for Evaluating and Discovering Organic Hydride Compounds as Potential Novel Methylation Reagents.

Methylation reaction is a fundamental chemical reaction that plays an important role in the modification of drug molecules, DNA, as well as proteins. This work focuses on seeking potential novel methylation reagents through a systematic investigation of the thermodynamics and reactivity of methyl-substituted organic hydride radical cations (XH•+s). In this work, 45 classical and important XH•+s were designed to investigate the relationship between their structure and reactivity, to find excellent or potential methylation reagents. The Gibbs free energy and activation free energy of XH•+ to release the methyl radical in MeCN at 298.15 and 355 K are calculated with the density functional theory (DFT) method to quantitatively measure the reactivity of XH•+ as a methylation reagent in this work. The relationships between structures and reactivities on XH•+s as methylation reagents are well examined. Since we have calculated the Gibbs free energy and activation free energy of trifluoromethyl-substituted organic hydride compound radical cations (X'H•+) releasing trifluoromethyl radicals in MeCN with the DFT method in our previous work, accordingly, the relationship of thermodynamics and reactivity between X'H•+ releasing trifluoromethyl radical and XH•+ releasing methyl radical is discussed in detail. Excitingly, 4 XH•+s (1H•+, 3H•+∼4H•+, and 44H•+) are found to be excellent methyl radical reagents, while 9 XH•+s (5H•+, 6H•+, 9H•+, 10H•+, 12H•+, 13H•+, 15H•+, 43H•+, and 45H•+) are found to be potential methyl radical reagents in chemical synthesis. The molecular library and reactivity database of novel methylation reagents could be established for synthetic chemists to query and use. Our work may offer a theoretical basis and reference experience for screening different substituted organic hydride compounds (YRHs) as alkylation reagents.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

Epimerization of C5 of an N-hydroxypyrrolidine in the synthesis of swainsonine related iminosugars.

Epimerization of C5 of an N-hydroxypyrrolidine ring by regioselective oxidation to a nitrone followed by diastereoselective reduction provides a new approach to the synthesis of swainsonine and related compounds. The only protection in the synthesis of the potent mannosidase inhibitor DIM (1,4-dideoxy-1,4-imino-d-mannitol) was the acetonation of d-mannose.