離去基團(tuán)非及中間體性質(zhì)對(duì)取代苯甲酸苯酯氨解反應(yīng)影響

(理論化學(xué)與分子模擬教育部重點(diǎn)實(shí)驗(yàn)室分子構(gòu)效關(guān)系湖南省普通高校重點(diǎn)實(shí)驗(yàn)室湖南科技大學(xué)化學(xué)化工學(xué)院湘潭摘要X-Y-取代苯基酯(X-C6H4COOC6H4-Y)的氨解反應(yīng)是一個(gè)親核加成-X評(píng)價(jià)Um等對(duì)離去基團(tuán)(Y-C6H4O-)、非離去基團(tuán)(X-C6H4-)及中間體(T±)的性質(zhì)對(duì)氨解反應(yīng)速率影響的研究結(jié)果，分別用取代基X的Hammett常數(shù)XY-C6H4OH的pKa和取代基XYPEI表征上述結(jié)構(gòu)因素，并用其對(duì)logkN建立多元線性回歸模型，得到了良好的相關(guān)結(jié)果。進(jìn)一步分析得出，Y-C6H4OH的pKa對(duì)logkN(90.46%)，而取代基X的Hammett常數(shù)X影響最小。關(guān)鍵詞取代苯甲酸苯酯氨解反應(yīng)速率電子效應(yīng)極化效應(yīng)指數(shù)InfluenceofthePropertiesofLeavingGroup,Non-leavingGroupandIntermediateontheAminolysisReactionofSubstitutedPhenylBenzoates Cao(KeyLaboratoryofTheoreticalChemistryandMolecularSimulationofMinistryofEducation,KeyLaboratoryofQSAR/QSPRofHunanProvincialUniversity,SchoolofChemistryandChemicalEngineering,HunanUniversityofScienceandTechnology;Xiangtan411201)AbstractTheaminolysisreactionofY-substitutedphenylX-substitutedbenzoates(X-C6H4COOC6H4-Y)isanucleophilicaddition-eliminationprocess.InordertoquantitativelyevaluatetheinfluenceofstructuralfactorsofsubstituentsXandYontheapparentsecond-orderrateconstants(kN)ofaminolysisofthetitlecompoundsreportedbyUmetc,HammettconstantXofsubstituentX,pKaofY-C6H4OHandpolarizabilityeffectindex(PEI)ofsubstituentsXandYwereusedtocharacterizetheabovementionedstructuralinformationandbuildmultiplelinearregressionmodelagainstlogkN.Goodcorrelationresultshadbeenobtained.FurtherinvestigationindicatedthatthepKaofY-C6H4OHhasthemostimportanteffectonlogkN(itscontributionpercentageis90.46%),whileHammettconstantXofsubstituentXhastheleastinfluenceonlogkN.KeywordsSubstitutedphenylbenzoates,Aminolysis,Reactionrate,Electroniceffect,Polarizability酯類化合物1C2)的親核取代反應(yīng)在有機(jī)合成和生物化學(xué)中具有重要意義12]ato36]自上世紀(jì)0Um2[7,8]、非離去基團(tuán)1[810]、親電中心(C=O、=S、=O、=1]、親核試劑胺145]對(duì)酯的氨解atro26m等[764CC64與哌啶親核取代反應(yīng)的研究指出，64C64Y首先與哌啶生成兩性中間體)，然后在非離去基團(tuán)64-)與離去C642個(gè),,O +HN

X

O

X=NO2,Cl,H,Me,

+-YY=3-COMe,3-Cl,4-COMe,4-CHO,4-NO2,3,4- Scheme1MechanismofaminolysisofY-substitutedphenylX-substitutedbenzoateswithUm通過大量實(shí)驗(yàn)測(cè)定了不同取代基X和Y時(shí)X-C6H4COOC6H4-Y的氨解反應(yīng)速率常數(shù)——表觀二級(jí)速率常數(shù)kN[7],kN與圖1中各步反應(yīng)速率常數(shù)之間有如下關(guān)系:kNk1k2k1k2 圖式 為便于理解該速率常數(shù)，在此對(duì)文獻(xiàn)的實(shí)驗(yàn)過程做一簡(jiǎn)要概述。所有反應(yīng)均在哌啶過量的情況下，也即準(zhǔn)一級(jí)反應(yīng)條件下進(jìn)行。哌啶的濃度在(1～200)×10-3mol/L2×10-5mol/L，子(Y-C6H4O-)。在檢測(cè)器的選用方面，慢反應(yīng)(t>10s)采用紫外-可見分光光度計(jì)，快反應(yīng)(t≤10s)采用停流分光光度計(jì) vkobsd kobsdkN

X、Y的立體效應(yīng)可以忽略。從電子效應(yīng)來看，取代基X、Y與苯環(huán)直接相連，它們的電子效應(yīng)對(duì)酯羰基碳的親電性及離去基團(tuán)的離去能力有較大影響，從而影響親核取代反應(yīng)的速率。結(jié)合反應(yīng)機(jī)理(圖式1)及式(1)可知，影響兩T±的形成及分解方向的主要因素有(1)X的吸電子效應(yīng)(Hammett常數(shù)X[17]描述)越6 6 力越強(qiáng)，Y-CHO-(pK度量)，T±Y-CHO-k增大。但是，XHammett常數(shù)XY-C6H4OH的pKalogk6 6 T±PEI[18,19]T±的穩(wěn)定性，并考察它對(duì)圖式1反應(yīng)的影響。根據(jù)文獻(xiàn)[19]的方法，PEI可表示為：PEIPEIX+PEIYiPEIi

根據(jù)上述分析，取代基X、Y1所示酯氨解反應(yīng)速率的主要原因。為定量研定量相關(guān)模型，并對(duì)各參數(shù)之間的相關(guān)性及各參數(shù)對(duì)kN的貢獻(xiàn)進(jìn)行了研究。logkN=9.4991+0.9277X–1.1826pKa–

R2=0.9882, pR2=0.9856,sP=0.21,p證的統(tǒng)計(jì)量，RPsP表示對(duì)測(cè)試集進(jìn)行預(yù)測(cè)的統(tǒng)計(jì)量。結(jié)果表明，模型的相關(guān)系數(shù)高，標(biāo)準(zhǔn)偏差低，而且交叉驗(yàn)證和預(yù)測(cè)結(jié)果均表明該模型具有良好的穩(wěn)定性和預(yù)測(cè)能力。由式(6)logkN1。1中還列出了用式(6)logkN實(shí)驗(yàn)值的另外6logkN進(jìn)行了預(yù)測(cè)結(jié)果。Tab.1Theapparentsecond-orderconstants(kN,L/mol·s)forthereactionsofY-substitutedphenylX-substitutedbenzoateswithpiperidine,andtheelectroniceffectparametersofsubstituentsXandYXYkNY-C6H4OH的X、Y的10090-1-120090-1-130080-0-0421070115050326H0090-1-17H0080-0-08H0070-009H5070000-090-2-20-090-2-20-070-0-01-0700032-05011807000251050220-090-1-275-05011207000H0090-2-2H191050220-080-1-10090-1-13-07000-090--2-080--0-070-0--090--2--080--1--070--0a標(biāo)“*”的化合物構(gòu)成測(cè)試集b“-1logkNFig1PlotofthecalculatedlogkNvstheexperimental2Tab.2Thecorrelationsbetweeneachpairof101-0-01應(yīng)。但當(dāng)本文將Y作為一個(gè)參數(shù)加入到式(6)Y的電率的影響已被包含到pKa中，故再加入Y作參數(shù)不會(huì)對(duì)結(jié)果有明顯改善。3個(gè)因素中哪一個(gè)對(duì)反應(yīng)的影響更大呢?我們用文獻(xiàn)[21,22]的方法考察了各參數(shù)對(duì)反應(yīng)速率的貢獻(xiàn)率f(i):i

logkN31kNpKa，即Y-C6H4O-的離去能力;PEI，也即中間體T±的穩(wěn)定性;X的電子效應(yīng)X貢獻(xiàn)最小.3式(6)logkNTab.3Thecontributionfractionofeachparameterinequation(6)to1907T±1反應(yīng)的進(jìn)行，其中離去基團(tuán)的共軛酸氨解反應(yīng)速率,最有效的方法是增強(qiáng)離去基團(tuán)中的取代基Y的吸電子能力。上述結(jié)果可為X-C6H4COOC6H4-Y類型的酯氨解反應(yīng)速率的預(yù)測(cè)和控制提供有價(jià)值的理論參考，并且有望被推廣到酯EACastroChemRev,1999,99:HKOh,JEPark,DDSungJOrgChem,2004,69:EACastro,FJGilJAmChemSoc,1977,99:EACastro,CLSantanderJOrgChem,1985,50:EACastro,PMunoz,JGSantosJOrgChem,1999,64:EACastro,MAliaga,JGSantosJOrgChem,2005,70:IHUm,JYLee,SHKoetalJOrgChem,2006,71:IHUm,YMPark,MFujioetalJOrgChem,2007,72:IHUm,KHKim,HRParketalJOrgChem,2004,69:IHUm,JSMin,JAAhnetalJOrgChem,2000,65:IHUm,EYKim,HRParketalJOrgChem,2006,71:IHUm,KAkhtar,YHShinetalJOrgChem,2007,72:IHUm,SJHwang,MHBaeketalJOrgChem,2006,71:IHUm,SELee,HJKwonJOrgChem,2002,67:IHUm,SMChun,OMChaeetalJOrgChem,2004,69:RWTaftJAmChemSoc,1952,74:LPHammettJAmChemSoc,1937,59:CZCao,ZLLiJChemInfComputSci,1998,38:CZCao,YBLinJChem