CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC Organic Chemistry 1 Lecture 8 Instructor: Prof. Duncan Wardrop Time/Day: T & R, 12:30-1:45 p.m. February 04, 2010 1 Self Test Question Which of the following transformations is unlikely to generate the product indicated? OH HCl Cl a. 25 ºC primary alcohols HCl A. a. and HCl are insufficiently x b. OH 25 ºC Cl reactive B. b. SOCl2 O O c. OH Cl C. c. K2CO3 Cl D. d. d. Cl2 hν University of Slide CHEM 232, Spring 2010 2 Illinois at Chicago UIC Lecture 8: February 4 2 Compound “b.” is a primary alcohol, which are insufciently reactive to undergo reaction with hydrogen chloride. Primary alcohols do, however, react with thionyl chloride (SOCl2) to form chlorides and so the transformation shown in “c” will proceed successfully Compound “a” is tertiary alcohol and consequently reacts with HCl. Substitution Reaction hydroxyl group halide R O H + H X R X + H O H alcohol hydrogen alkyl water halide halide Hydroxyl group is being substituted (replaced with) a halide University of Slide CHEM 232, Spring 2010 3 Illinois at Chicago UIC Lecture 8: February 4 3 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC Mechanisms of Substitution Reactions Sections: 4.8-4.11 4 Substitution: How Does it Happen? break bond break bond make bond make bond R O H + H X R X + H O H alcohol hydrogen alkyl halide water halide mechanism: a generally accepted series of elementary steps that show the order of bond breaking and bond making elementary step: a bond making and/or bond breaking step that only involves one transition state University of Slide CHEM 232, Spring 2010 5 Illinois at Chicago UIC Lecture 8: February 4 5 Ingold-Hughes Mechanistic Designators Designates # molecularity Designates type of process Letter Nucleophilic N or E or Electrophilic Example Me Me Substitution, H-Br Me Me nucleophilic, OH Br SN1 Me Me 1st order Rate = k x [t-BuOH] University of Slide CHEM 232, Spring 2010 6 Illinois at Chicago UIC Lecture 8: February 4 6 Nucleophilic Substitution (SN1) Step One Proton Transfer (Protonation) fast & reversible H O H Cl O Cl H H pKa = -3.9 alkyloxonium ion University of Slide CHEM 232, Spring 2010 7 Illinois at Chicago UIC Lecture 8: February 4 7 this is an acid-base reaction; product is an alkoxonium ion exothermic and fast (proton transfer is among the fastest processes in organic chemistry) rate of individual step =k x [alcohol] x [HX]; two reactants = bimolecular (2nd order) oxonium ion is an intermediate in the overall reaction Step One Potential Energy Diagram Step One Proton Transfer (Protonation) transition state: energy maximum along reaction coordinate for one elementary step; usually involves partial bond making and partial bond breaking intermediate: energy minimum along the reaction coordinate; species with a finite lifetime; neither reactant, nor product Hammond Postulate: structure of the transition state “looks” most like its closest energy reactant or intermediate University of Slide CHEM 232, Spring 2010 8 Illinois at Chicago UIC Lecture 8: February 4 8 Mechanism: Nucleophilic Substitution (SN1) Step Two Dissociation (Ionization) slow H Me Me O H2O H Me carbocation (t-butyl cation) University of Slide CHEM 232, Spring 2010 9 Illinois at Chicago UIC Lecture 8: February 4 9 breaking a carbon-oxygen bond slowest (rate determining) step in entire mechanism; endothermic rate=k[oxonium ion]; one reactant = unimolecular (1st order) Step Two Potential Energy Diagram Step Two Dissociation (Ionization) • largest activation energy (Ea) • endothermic, slowest • carbocation intermediate is much higher in energy than an oxonium ion • carbocations do not have a full octet, whereas oxonium ions do • structure of transition state most resembles the closest energy neighbor, the carbocation (Hammond Post.) University of Slide CHEM 232, Spring 2010 10 Illinois at Chicago UIC Lecture 8: February 4 10 Mechanism: Nucleophilic Substitution (SN1) Step Three Carbocation Capture Me Me fast Cl Cl Me carbocation t-butyl chloride (t-butyl cation) Cation = Electrophile Anion = Nucleophile University of Slide CHEM 232, Spring 2010 11 Illinois at Chicago UIC Lecture 8: February 4 11 exothermic and fast; neutral products much lower in NRG small activation energy; negative charge to positive charge transition state looks most like carbocation since they are closest in energy rate = k x [carbocation][halide]; two reactants = bimolecular Step Three Potential Energy Diagram Step Three Carbocation Capture • fast step because small activation energy; positive and negative atoms bond fast • products are much lower in energy since they are neutral; exothermic reaction • transition state looks most like its closest neighbor, the carbocation intermediate (very little C-Cl bond formation at transition state) (Hammond Postulate) University of Slide CHEM 232, Spring 2010 12 Illinois at Chicago UIC Lecture 8: February 4 12 Nucleophiles Add to Electrophiles nucleophile: nucleus loving; Lewis base; electron pair donor; forms bonds with a nucleus that can accept electrons; does not necessarily have to be negatively charged; has available, !lled orbitals! electrophile: electron loving; Lewis acid; electron pair acceptor; forms bonds by accepting electrons from other atoms; does not necessarily have to be positively charged; has available, empty orbitals! Cation is Electrophile Me Me empty 2pz orbital Cl Chloride is Nucleophile Me filled n orbital (: = lone pair) University of Slide CHEM 232, Spring 2010 13 Illinois at Chicago UIC Lecture 8: February 4 13 Complete Mechanism fast & reversible H O H Cl O Cl H H alkyloxonium ion slow Me Me fast Cl Cl Me carbocation H O t-butyl chloride (t-butyl cation) 2 University of Slide CHEM 232, Spring 2010 14 Illinois at Chicago UIC Lecture 8: February 4 14 Complete Potential Energy Diagram • mechanism only valid for 3º & 2º alcohols • reaction is only as fast as its slowest step rate • slowest step (largest Ea) = determining step (RDS) rate determining step (RDS) • here, slowest step is carbocation formation • here, RDS is unimolecular Protonation carbocation formation carbocation capture University of Slide CHEM 232, Spring 2010 15 Illinois at Chicago UIC Lecture 8: February 4 15 Naming the Mechanism: Ingold Notation R O H + H X R X + H O H alcohol hydrogen alkyl halide water halide SN1 1: 1st order S: Substitution N: Nucleophilic (unimolecular) the RDS is the alcohol the halide doing the carbocation functional groups is substitution is a formation; this step is being substituted nucleophile unimolecular (1st with a halide order) University of Slide CHEM 232, Spring 2010 16 Illinois at Chicago UIC Lecture 8: February 4 16 Self Test Question Consider the SN1 mechanism for the formation of 2- bromobutane. Which structure best represents the highest energy transition state in this mechanism? Br a. c. + A. a. O H Br H O H H H δ+ δ− B. b. C. c. δ+ + Br + Br D. d. b. O d. O H H H H δ+ University of Slide CHEM 232, Spring 2010 17 Illinois at Chicago UIC Lecture 8: February 4 17 Structure of Carbocations • carbocations are high energy intermediates; hard, but not impossible to isolate 2pZ • carbon is sp2-hybridized with a single, H unoccupied 2pZ orbital; 6 valence electrons H3C C • planar structure : three bonds to carbon are H at 120º angles from each other and 90º to empty p-orbital; VSEPR • nucleophiles add to either lobe of the empty carbocations can be stabilized by inductive effects and hyperconjugation p-orbital; since it is "at, there is no preference to which side nucleophile adds University of Slide CHEM 232, Spring 2010 18 Illinois at Chicago UIC Lecture 8: February 4 18 Stability of Carbocations 1. Inductive Effects electron withdrawal or electron donation that is transmitted through σ- bonds; polarization of σ-bonds • electron donation through 1º cation σ-bonds toward δ+ carbocation delocalizes δ+ H charge (spreads out) • C-C σ-bonds are more H3C C polarizable, therefore δ+ donate more electron H density through σ-bonds • more C-C σ-bonds = more stable carbocation University of Slide CHEM 232, Spring 2010 19 Illinois at Chicago UIC Lecture 8: February 4 19 Stability of Carbocations 1. Inductive Effects Since C-C σ-bonds are more polarizable than C-H bonds, the additional of more alkyl groups leads to stabilization of the cation 2º cation 3º cation δ+ δ+ δ+ CH3 δ+ CH3 H3C C H3C C H δ+ CH3 δ+ University of Slide CHEM 232, Spring 2010 20 Illinois at Chicago UIC Lecture 8: February 4 20 Stability of Carbocations 2. Hyperconjugation stabilizing interaction that results from the interaction of the electrons in a σ-bond (C–H or C–C bond ) with an adjacent empty (or partially !lled) orbital. Leads to the formation of an extended molecular orbital that increases the stability of the system filled σ orbital • stabilization results from σ-donation to empty p orbital of planar carbocation empty • electron donation through σ-bonds H p orbital toward carbocation delocalizes charge H (spreads out) C C H H • methyl cations cannot be stabilized by hyperconjugation since σ-bonds are H perpendicular to the empty p orbital 1º cation University of Slide CHEM 232, Spring 2010 21 Illinois at Chicago UIC Lecture 8: February 4 21 Stability of Carbocations 2. Hyperconjugation filled empty σ orbital 2pZ orbital empty C-H 2pZ H p orbital bonding y (filled) g H r e C C n E H H Stabilization resulting from H σ hyperconjugation University of Slide CHEM 232, Spring 2010 22 Illinois at Chicago UIC Lecture 8: February 4 22 Stability of Carbocations H H CH3 H H H3C CH2 CH2 CH2 C C C C C C H H H CH2 H CH2 H H H H CH3 H 2º carbocation 3º carbocation 3º carbocation 2 C-H bond 3 C-H bond 3 C-C or C-H bond hyperconjugative hyperconjugative hyperconjugative donors donors donors University of Slide CHEM 232, Spring 2010 23 Illinois at Chicago UIC Lecture 8: February 4 23 i>Clicker Question Rank the following carbocations in order of increasing stability? A.