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1、11. Reactions of Alkyl Halides: Nucleophilic Substitutions and EliminationsBased on McMurrys Organic Chemistry, 6th edition1Based on McMurry, Organic Chemistry, 6th edition, (c) 2003 Alkyl Halides React with Nucleophiles and BasesnAlkyl halides are polarized at the carbon-halide bond, making the car
2、bon electrophilicnNucleophiles will replace the halide in C-X bonds of many alkyl halides(reaction as Lewis acid)nNucleophiles that are Brnsted bases produce elimination211.1 The Discovery of the Walden InversionnIn 1896, Walden showed that (-)-malic acid could be converted to (+)-malic acid by a se
3、ries of chemical steps with achiral reagents nThis established that optical rotation was directly related to chirality and that it changes with chemical alterationnReaction of (-)-malic acid with PCl5 gives (+)- chlorosuccinic acidnFurther reaction with wet silver oxide gives (+)- malic acidnThe rea
4、ction series starting with (+) malic acid gives (-) acid3Reactions of the Walden Inversion4Significance of the Walden InversionnThe reactions alter the array at the chirality center nThe reactions involve substitution at that center nTherefore, nucleophilic substitution can invert the configuration
5、at a chirality center nThe presence of carboxyl groups in malic acid led to some dispute as to the nature of the reactions in Waldens cycle511.2 Stereochemistry of Nucleophilic SubstitutionnIsolate step so we know what occurred (Kenyon and Phillips, 1929) using 1-phenyl-2-propanol nOnly the second a
6、nd fifth steps are reactions at carbon nSo inversion certainly occurs in the substitution step6Hughes Proof of InversionnReact S-2-iodo-octane with radioactive iodide nObserve, initially that racemization of mixture is twice as fast as incorporation of label so it must be with inversion nRacemizatio
7、n in one reaction step would occur at same rate as incorporation7The Nature of SubstitutionnSubstitution, by definition, requires that a “leaving group“, which is also a Lewis base, departs from the reacting molecule.nA nucleophile is a reactant that can be expected to participate effectively in a s
8、ubstitution reaction.8Substitution Mechanismsn SN1nTwo steps with carbocation intermediatenOccurs in 3, allyl, benzyln SN2nTwo steps combine - without intermediatenOccurs in primary, secondary9Reactant and Transition-state Energy Levels Higher reactant energy level (red curve) = faster reaction (sma
9、ller G).Higher transition- state energy level (red curve) = slower reaction (larger G).10Two Stereochemical Modes of Substitution nSubstitution with inversion:nSubstitution with retention:1111.3 Kinetics of Nucleophilic SubstitutionnRate (V) is change in concentration with time nDepends on concentra
10、tion(s), temperature, inherent nature of reaction (barrier on energy surface) nA rate law describes relationship between the concentration of reactants and conversion to products nA rate constant (k) is the proportionality factor between concentration and rateExample: for S converting to PV = dS/dt
11、= k S12Reaction KineticsnThe study of rates of reactions is called kinetics nRates decrease as concentrations decrease but the rate constant does not nRate units: concentration/time such as L/(mol x s) nThe rate law is a result of the mechanism nThe order of a reaction is sum of the exponents of the
12、 concentrations in the rate law the example is second order1311.4 The SN2 ReactionnReaction is with inversion at reacting centernFollows second order reaction kineticsnIngold nomenclature to describe characteristic step:nS=substitutionnN (subscript) = nucleophilic n2 = both nucleophile and substrate
13、 in characteristic step (bimolecular)14SN2 ProcessnThe reaction involves a transition state in which both reactants are together15SN2 Transition StatenThe transition state of an SN2 reaction has a planar arrangement of the carbon atom and the remaining three groups1611.5 Characteristics of the SN2 R
14、eactionnSensitive to steric effectsnMethyl halides are most reactivenPrimary are next most reactivenSecondary might reactnTertiary are unreactive by this pathnNo reaction at C=C (vinyl halides)17Reactant and Transition-state Energy Levels Affect RateHigher reactant energy level (red curve) = faster
15、reaction (smaller G).Higher transition- state energy level (red curve) = slower reaction (larger G).18Steric Effects on SN2 ReactionsThe carbon atom in (a) bromomethane is readily accessible resulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane (primary), (c) 2-bromopropane (secondar
16、y), and (d) 2-bromo-2-methylpropane (tertiary) are successively more hindered, resulting in successively slower SN2 reactions. 19Steric Hindrance Raises Transition State EnergynSteric effects destabilize transition statesnSevere steric effects can also destabilize ground stateVery hindered20Order of Reactivity in SN2nThe more alkyl groups connected to the reacting carbon, the slower the reaction21The
