D.M. Collard 2007TOPIC 5. ORGANIC REACTIONS: ACIDS AND BASES (Chapter 3)LOBJECTIVES1. Classify types of reaction: -Addition, Substitution, Elimination, Rearrangement2. Define the concept of “Mechanism”3. Discuss the thermodynamics (equilibrium) and kinetics (rate) of organic reactions4. Describe acid-base reactions5. Develop relationships between structure and acidity/basicity6. Take a first look at acid-promoted reactionsD.M. Collard 2007CLASSIFYING REACTIONSReactions are conveniently classified as substitutions, additions, eliminations and rearrangements. These terms describe the overall process, simply comparing the structure of starting materials and products. They do not indicate anything about the pathway (“mechanism”) by which the reaction proceeds. SubstitutionsAdditionsEliminationsRearrangements(often in combinationwith another type of reaction) S:3.1SubstitutionCH3CH2BrOCClH3Cacetone(solvent)pyridine(solvent)NaICH3OH++D.M. Collard 2007AdditionCCH2H2OH2SO4H3CHOH2OH2SO4EliminationCH3CH2SO4CH3HOHD.M. Collard 2007RearrangementCCCH3CH3CCH3HHHH3PO4CCHBrCCHOHCCCCHHSubstnSubstnElimnElimnAddnSubstnSubstnAddnsubstitutionssubstitutionsadditionsA Preview of ReactivityD.M. Collard 2007 Practical Aspects of Running a ReactionStarting material(“substrate”)ReagentsCatalysis(lowers activation energy)Solvent(allows for mixing)Mode of additionBEGINNING ProductByproductsUnreacted reactantsCatalystSolventSEPARATIONPURIFICATIONIDENTIFICATIONEND TimeTemperature(heating/cooling) Environment(avoid O2, H2O?) Stirring% yield = moles of productmoles of limiting reactantx 100 Representations of reactions ...more commonly written as….Reactant(s) Product(s)Substrate(organic startingmaterial)Product (+ byproduct(s))reagent(s)catalyst(s)solvent(s)+H2H2,PtEtOHH2OH2SO4OHSubstrate(organic startingmaterial)reagentD.M. Collard 2007WHAT IS A MECHANISM?A mechanism is a proposal for a step-by-step pathway by which a reaction proceeds. Each step involves bond making and/or breaking. The mechanism takes into account all currently available evidence (kinetics, formation of byproducts, effect of structure on reactivity). Any new data collected must be consistent with the proposed mechanism, or the mechanism itself must be modified to account for the new finding. An understanding of common mechanistic steps can be applied to new combinations of reagents to predict the outcome of a new reaction. As such, development of an understanding of mechanisms will save you frommemorizing a huge amount of material. While you must develop a familiarity with reactions, do not try to pass this course by just memorizing the outcome of reactions!Electrophiles and NucleophilesNucleophileElectron-rich, “nucleus-loving” speciesElectrophileElectron-deficient, “electron-loving” speciesD.M. Collard 2007CURVED ARROWSProb3.20,25,31,36,37,40ABABexamples of 2e-processesNuE+H+S:3.4Polarity and Heterolytic Bond CleavageS:3.3(CH3)3CBrH3CLi(CH3)3CBrCH3LiD.M. Collard 2007Problem 3.20(c). Provide curved arrows to account for the changes in bonding in the following reaction step.Problem 3.31(d). Show the curved arrows to account for the following reaction step.CCHHHHHF CCHHHHHF –HO H3CI HOCH3IProblem: Show the curved arrows to account for the followingreaction step.COCH3H3CHCNCOCH3H3CHCND.M. Collard 2007Problem: What is wrong with each of the following mechanistic steps, suggested by students in previous classes? [consider what the curved arrow is meant to depict, or draw the products of the suggested flow of electrons and comment on why that product is not stable]BrCH3NCH3CH3H3CCHBrHHClClCH3CH3C CH3BrOCH3C CH3ClHOCH3C CH3HClCl HHClProblem: What is wrong with each of the following mechanistic steps suggested by students in previous classes?D.M. Collard 2007DefinitionsBrønsted Acidity: ability to donate a protonBrønsted Acid: proton donorBrønsted Base: proton acceptorH—A + :BStrong acids have weak conjugate basese.g., Acid strength: HBr > H2O Conjugate base strength: Br –< HO–Lewis AcidityLewis Acid: electron pair acceptorLewis Base: electron pair donorPh3P: + BF3ACID-BASE REACTIONSProb3.15,17,19,22-24S:3.2; 3.63.15L pKaand Acid Strength A–H + H2OA+H2O–H acid base conjugate conjugatebase acid since H2O is solvent, [H2O] = 55 M Ka↑ , acid strength ↑ pKa= –logKa Bottom line: pKa↑ , acid strength ↓ KeqO][HA][H]O][H[A23eq+=-K[HA]]O][H[A3a+=-KD.M. Collard 2007THE STRENGTH OF ACIDS AND BASES ¾ HI -10 H2SO4-9 ¾ HBr -9 ¾ HCl -7 (CH3)2C=OH+-2.9 CH3OH2+-2.5 H3O+-1.74 HNO3-1.4 CF3CO2H0.18 ¾►HF 3.2 H2CO33.7Ö CH3CO2H 4.75CH3COCH2COCH39.0Prob3.16,18,2127-29 NH4+9.2 C6H5OH 9.9 HCO3–10.2 CH3NH3+10.6 ► H2O 15.7 Ö CH3CH2OH 16 (CH3)3COH 18 CH3COCH319.2  HC≡CH 25 H235 ► NH338  CH2=CH244 ►CH3CH355 pKavaluesS:3.5Species that can act as either an acid or as a baseCH3NH2 +H2OCH3NH3++HO¯pKa= 38 pKa= 15.7 pKa= 10.6versusCH3NH2+H2OCH3NH¯ + H3O+pKa= 38 pKa= 15.7 pKa= -1.74CH3COOH + H2OCH3COO¯ + H3O+pKa= 5.5 pKa= 15.7 pKa= -1.74versusCH3COOH + H2OCH3COOH2++ HO¯pKa= 5.5 pKa= 15.7D.M. Collard 2007Amine + AcidCH3COOH + CH3NH2CH3COO¯ + CH3NH3+pKa= 5.5 pKa= 38 pKa= 10.6Amino acidsAmino acids in aqueous solutionOOH2NOOHH3NOOH3NOOHH2NOOH3NPredicting Equilibrium ConstantsA–H + B:–A:–+B–Hacid base conjugate conjugatebase acidEquilibrium lies of side of the weaker acid and weaker base (the weaker acid and weaker base will always be on the same side) log Keq= pKa(conjugate acid) – pKa(acid) HCl + NaOH NaCl + H2OpKa= -7 pKa= 15.7 CH3OH + H2SO4CH3OH2+HSO4–pKa= -9 pKa= -4Keq+Keq= Keq=D.M. Collard 2007In order to assess the relative strengths of acids, consider the ability of the acid to donate a proton (ability to break the H-A bond) and for the conjugate base to accommodate negative charge. Stronger acids have weaker conjugate bases...A–H + B:–A:–+ H–BWe have ways to assess the ability of ions (anions and cations) to accommodate negative charge based on: – Inductive effects (substituents donate or withdraw electrondensity via sigma bonds) – Resonance effects (electron donation or withdrawal by pi-bonds) – HybridizationSTRUCTURE-ACIDITY RELATIONSHIPSS:3.7;3.8A;3.12Acidity: Across a Row of the Periodic Table H–CH3H–NH2H–OH H–F pKa48 38 15.7 3.2 conjugate bases CH3 –NH2 –OH