Theoretical Study On Thermodynamic Properties Of Organonitrogen And Organosulfur Compounds

In recent years,the organic synthesis reactions of organonitrogen and organosulfur compounds as substrates have attracted the interests of many experimental chemists and become a research hotspot.Among them,organonitrogen compounds mainly include various types of hydrazine derivatives（R₁R₂N-NR₃R₄）such as cycloalkyl hydrazine,aryl hydrazine,heterocyclic hydrazine and hydrazides as well as the azide compounds（R-N₃）including cycloalkyl azides,heterocyclic azides and alkyl azides,which are commonly used to introduce a nitrogen source into a compound to synthesize bioactive substances in biochemistry,medicinal chemistry and other fields,etc.In organosulfur compounds,thiol（R-SH）is widely used in protein chemistry and carbohydrate chemistry.In various synthetic applications of these compounds,the activation of chemical bonds is a key step in which organic product containing nitrogen（N）or sulfur（S）can be obtained by the dissociation of N-N bond（hydrazine）,C-N bond（azide）and S-H bond（thiol）.We systematically studied and analyzed the activation and dissociation of X-N bond in organonitrogen compounds and S-H bond in thiol compounds from the point of view of thermodynamics by using the methods of quantum chemistry,including bond dissociation energy（BDE）which is one of the thermodynamic constants used to measure the strength of X-N bonds and the equilibrium constant p K_aused to represent the ability of S-H bond to dissociate hydrogen ions（H⁺）in thiol compounds.The reliable and useful theoretical studies for understanding the dissociation of X-N and S-H bonds provided by the above theoretical studies can be better applied to practical scientific research by chemical experimenters.Concretely,for organonitrogen compounds,we firstly used different high-level ab initio methods of two series（Gn series and CBS series）to calculate the experimental N-N and C-N BDEs of organonitrogen compounds with no more than 8nonhydrogen atoms.In view of the very good self-consistency between the calculation results of various high-level ab initio methods and the errors between calculated and experimental BDE values,the average values of calculated results by high-level ab initio methods are used as the standard reference values for the bond dissociation energies of N-N and C-N bond.Secondly,a variety of different density functional theory（DFT）methods including classical B3LYP method and some new methods that have emerged in recent years（after 2010）are used to calculate the experimental N-N and C-N BDEs of organonitrogen compounds in which more than 8 non-hydrogen atoms are contained.According to the values of average deviation（MD）,mean absolute deviation（MAD）and root mean square error（RMSE）obtained by comparing the calculated results of DFT methods with standard values,finding the DFT methods for respectively calculating the N-N bond and C-N BDEs with the highest precision.Finally,the bond dissociation energy of N-N bond in different types of hydrazine derivatives and C-N bond in azide compounds were systematically studied by the optimal DFT method.Furthermore,the effects of different factors such as substituent effect,position effect,frontier orbital energy and ring tension on the dissociation energy of N-N bond and C-N bond were analyzed.For organic thiol compounds,we firstly calculated the p K_avalues of 58 thiol compounds by using different DFT methods combined with two solvation models of PCM-Bondi and SMS_{s SAS}.Based on the MD,MAD and RMSE values obtained by comparing with the corresponding experimental p K_avalues,looking for the best combination of method and solvation model for accurately calculating the p K_aof thiol compounds.Subsequently,the substituent effects on p K_avalues of various types of thiol compound R-SH are studied by using the selected optimal combination,wherein R includes alkyl,cycloalkyl,alkenyl,aryl,heterocyclyl,alkynyl and fluorinated hydrocarbyl,and then the substituent effects were further explained by analysis of NBO and frontier orbital.The details are as follows:1.The strength of N-N bond in hydrazine derivatives was measured by using thermodynamic bond dissociation enthalpy,and the corresponding structure-activity relationship was also studied.We firstly calculated the N-N BDEs of 13 organonitrogen compounds by using 8 high-level ab initio methods including G3,G3B3,G4,G4MP2,CBS-QB3,ROCBS-QB3,CBS-Q and CBS-APNO.The calculated results show that there is a very good self-consistency between the 8 theoretical methods,furthermore,quite differences between the experimental and average calculated values are found in individual compounds.Therefore,we take the average results s of these 8 methods as the follow-up standard reference values.Subsequently,we selected 25 DFT methods to calculate the N-N BDE values of 58 organonitrogen compounds for evaluating different density functional theory（DFT）methods,where the M05-2X method can provide the most accurate results with the smallest RMSE value of 8.9 k J/mol.Finally,the N-N BDE values of cycloalkyl hydrazine,N-heterocyclic hydrazine,aryl hydrazine and hydrazide compounds were predicted by using the M05-2X method,and the corresponding substituent effects were studied in detail.In addition,in order to further understand the nature of the N-N BDE change pattern,we simultaneously analyzed the natural bond orbit（NBO）and the frontier orbital energy.2.In the theoretical study of C-N BDE in azide compounds,the average BDE results calculated by 7 high-level ab initio methods（G3,G3B3,G4,G4MP2 of Gn series and CBS-QB3,CBS-4M,CBS-APNO of CBS series）are regarded as the corresponding standard reference values.And an optima DFT method of w B97 was found for calculating the C-N bond dissociation energy of azide compound by further screening and evaluation.The theoretical calculation of the C-N BDEs of three types of azide compounds including cycloalkyl azide,heterocyclic azide and azide methane was carried out by w B97 method.The calculated results show that for the cycloalkyl azide,the increase of the number of carbon atoms on the ring can reduce the C-N BDE values;for saturated heterocyclic azide,the smallest oxygen-containing three-membered heterocyclic ring provides the maximum C-N BDE value,the-N₃group in the same type of unsaturated heterocyclic azide has a better position effect;and there is a significant substituent effect in azide methane,i.e.,electron-withdrawing groups（EWGs）can decrease the molecular stability and thus make the corresponding C-N BDE values smaller,while the electron donating groups（EDGs）exhibit a significantly opposite substitution effect.After NBO analysis,we further explained the change pattern of C-N BDE values.3.The dissociation equilibrium constant p K_aof thiol compounds in aqueous solution is very important for understanding the properties and reactivities of thiols,especially in terms of protein chemistry and carbohydrate chemistry.To elucidate the structure-activity relationship in thiol compound and the substituent effects on the p K_avalues,we calculated p K_a’s of 58 thiol compounds by using different DFT methods with two types of solvation models including PCM-Bondi and SMD_{s SAS}.Based on the calculated results,the M06-2X method combined with SMD_{s SAS}model gives the highest accuracy with a smallest RMSE value of 0.77 p K unit.Therefore,this combined model was used for systematically studying the p K_a’s of different thiols R-SH,where R=alkyl,cycloalkyl,alkenyl,aryl,heterocyclyl,alkynyl and fluorinated hydrocarbyl.Moreover,according to the calculated p K_avalues,the substituent effects on the p K_a’s and the structure-activity relationship in the thiol compounds were investigated,the results indicate that there are significantly obvious substituent effects on heterocyclic,alkynyl and fluorinated hydrocarbyl thiols.To further understand the substituent effects on p K_a,we also performed a detailed analysis of the relevant NBO and frontier orbital energies.In addition,the good linear relationships between p K_a’swith substituent constantσ_p⁺,the natural charge of the S atom were observed in different types of thiols.