Synthesis And Quantum Chemical Calculation Of Di-substituted Ethylenediamine

The related di-substituted ethylenediamine in our research work includes the N,N-disubstituted ethylenediamine and N,N'-disubstituted ethylenediamine,according to the substituted position in the molecules.They are both the derivatives of ethylene diamine.Because of the special structures and properties of the di-substituted ethylenediamine,they have been applied widely as the synthetic and pharmaceutical intermediates in the area of organic synthesis,catalysis,drugs and medicines.In our study,the desired products were obtained experimentally and then the quantum chemical calculations were applied to analyze the related reactions.All the calculations were done by the density functional method(DFT)in Gaussian 03 with the B3LYP as the exchange-correlation function and the used basis set was 6-311+G(d).GaussView 5.0.8 was employed to get the input files and analyze the calculation results.Firstly,the modified Delephine reaction was employed to obtain N,N-diisopropyl ethylenediamine(yield is 81.07%),N,N-dimethyl ethylenediamine(yield is less than 37.80%)and ethylenediamine(yield is less than 1%)with N,N-disubstituted ethanolamine as the raw material being chloridized and aminated,of which,ethylenediamine was synthesized in this way to make comparisons with others.And the experimental results showed that the substitution group did have an big effect on the reaction yields,that is,the bigger the steric bulk of the group was,the higher the corresponding yield was then.In order to make further explanation of the experimental results,the DFT method in Gaussian 03 was employed to make quantum chemical calculations of the reaction processes.At the beginning,the structures of the related compounds was optimized and the HOMO,LUMO analysis was made based on the optimized structures,and the results showed that it was possible for N,N-disubstituted chloroethylamine to react with itself.Then,the main reaction of N,N-disubstituted chloroethylamine with hexamine and the side reaction of two N,N-disubstituted chloroethylamine were analyzed further.It showed that the substitution group had a small effect on the main reaction but a big effect on the side reaction,that is,the energy barrier difference was smaller(from 44.81 KJ/mol to 14.78 KJ/mol and then to 11.26 KJ/mol)with the steric space being smaller,which led to the decreasing of the target yield.And it was consistent with the experimental results.At the same time,the PCM model was then used to analyze the solvent effect of this kind of reaction with methanol as the solvent.It showed that all the energy of the related compounds and the related energy barriers decreased with a different extent,but it was still consistent with the conclusions before,that is,the energy barrier difference between main reaction and side reaction decreased in the same order(from 32.85 KJ/mol to 5.57 KJ/mol and then to 0.19 KJ/mol).In conclusions,this experimental method could be applied to synthesize the N,N-disubstituted etylenediamine with high yield,only when the steric bulk of the substitution group was enough big,such as isopropyl group,which was consistent with the experimental and calculation results.And then,the N,N'-disubstituted ethylenediamine was synthesized by the N-alkylation reaction between primary amine and ethylene dicholoride,which has some characteristics of simplicity,wide resources and easiness for industrialization.Firstly,the optimal conditions(n(amine):n(dichloroethane)=5:1,100?,6h,water)were obtained with tert-butyl amine as the model reactant.The optimized conditions were then applied to other primary amines,such as isopropylamine,butylamine,phenylamine and benzylamine and the corresponding yields were tert-butylamine(78%)>benzylamine(74%)phenylamine(70%)isopropylamine(48%)>butylamine(36.7%).It should be noted that the reaction of phenylamine was not completed on the conditions.The optimal conditions for different amines were obtained and it indicated that different amines had their respective optimal conditions.Under these conditions,the corresponding yields were phenylamine(84%)>tert-butylamine(78%)benzylamine(74%)isopropylamine(64.3%)butylamine(56%).Hence,the target yield and optimal conditions were related to the reactivity of primary amine,that is,the target yield of amine with high reactivity was low and its corresponding optimal conditions were milder.In order to explain the experimental results,Gaussian 03 package was used to make NBO,EPS and Scan calculations to analyze the reactivity of amine including its nucleophilicity and accessibility.It showed that the reactivity of related amines decreased in the order:butylamine>isopropylamine>tert-butylamine?benzylamine>phenylamine,consistent with the experimental results.And then the OPT=TS and IRC calculations were applied to analyze the reaction process and it indicated the first SN2 process was the rate-determining step because of its higher barrier value,which could be used to explain the low concentration of intermediate product in the reaction system.Meanwhile,the energy barrier values were used to analyze the relative reactivity,that is,butylamine(122.044KJ/mol)>benzylamine(123.101KJ/mol)>isopropylamine(124.496KJ/mol)>tert-butylamine(128.563KJ/mol)>phenylamine(141.766KJ/mol),which was almost consistent with the experimental results except benzylamine.In additions,water molecules were introduced into the calculation system to explain the catalysis effect of water.The results showed that they could decrease the energy barrier of related rate-determining step with the similar sequence except benzylamine;benzylamine(101.746 KJ/mol)>butylamine(103.258 KJ/mol)>isopropylamine(106.401 KJ/mol)>tert-butylamine(109.906 KJ/mol)>phenylamine(128.310 KJ/mol)and they could stabilize intermediate products and products by lowing their energy.In our research work,the di-substituted ethylenediamines were synthesized experimentally and the reactions were analyzed by quantum chemical calculations,the experimental and theoretical results were compared with each other.By doing that,we could draw some conclusions:1)N,N-disubstituted ethylenediamine was synthesized by the modified Delephine reaction,and the target yield could be high when the steric bulk of substitution group was big,which was explained by the results of quantum chemical calculations;2)N,N'-disubstituted ethylenediamine was synthesized by the N-alkylation reaction of primary amine and ethylene dichloride,and different amines had different yields and optimal conditions,which was explained by the quantum chemical calculations.Our work could be used to synthesize the desired di-substituted ethylenediamine in the laboratory,at the same time,the quantum chemical calculations could be helpful to understand the related reactions and explain the experimental results,which provided a way to predict the experimental results by the theoretical results.