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TOPIC 10. REVIEW MOLECULAR STRUCTURE CONCEPTS, MODELS, RULES AND THEORIES Concept Prediction Octet rule Valency, presence of lone pairs Lewis Dot Structures Formal charges electronegativity Electronegativity Polar bonds, molecular dipoles Bonding Covalent bonds between atoms of similar electronegativity Ionic bonds between atoms of different electronegativity D.M. Collard 2007 VSEPR Molecular geometry Hybridization Molecular geometry Resonance Electron distribution, hybrid structures Hyperconjugation σ-bonds as electron donors © D.M. Collard, 2005 RESONANCE THEORY X Y Z Resonance theory helps to explain: Structure i.e., O C R Reactivity i.e., NH2 O C R D.M. Collard 2007 O © D.M. Collard, 2005 HYPERCONJUGATION Hyperconjugation accounts for the enhanced stability of cations, radicals and alkenes with high degrees of substitution. H C C H H H C H C H C H C C H H SYSTEMATIC IUPAC NOMENCLATURE Linear (Unbranched) Alkanes CH4 CH3CH3 CH3CH2CH3 CH3(CH2)2CH3 CH3(CH2)3CH3 CH3(CH2)4CH3 CH3(CH2)5CH3 . . C1 2 3 4 5 6 7 8 9 10 methane ethane propane butane pentane C11 12 13 14 15 16 17 18 19 20 Substituents -CH3 methyl -CH(CH3)CH2CH3 sec-butyl -C6H5 phenyl -CH2CH3 ethyl -CH2CH(CH3)2 isobutyl -CH2C6H5 benzyl -CH(CH3)3 isopropyl -C(CH3)3 tert-butyl Branched Alkanes Longest chain numbered from the end that has the substituents at the lowest possible number. Substituents listed alphabetically (ignoring di, tri, sec, tert) D.M. Collard 2007 © D.M. Collard, 2005 Alkyl Halides R Hal Classes of alkyl halides Alcohols Classes of alcohols 88 kcal/mol 110 kcal/mol R O 0.97 Å 1.43 Å Ethers R H O H R R' N H H Amines Ri Classes of Amines N Rii Riii Ri 177 kcal/mol 1.22 Å Ri C R N H O ketone C R D.M. Collard 2007 Rii O Aldehydes and Ketones aldehyde N Ri © D.M. Collard, 2005 Carboxylic acids Carboxylic esters O O C C R(H) OH Amides Ri R(H) O Nitriles O Ri(H) C R(H) R C N N Rii(H) Functional Molecules Alcohols, R-OH: OH at lowest possible position Alkyl halides, R-Hal: named as halo-substituted alkane Alkenes (and alkynes): Longest chain containing C=C (C≡C), numbered to keep C=C (C≡C) as low as possible D.M. Collard 2007 Aldehydes: Numbered from CHO (C1) Ketones: Numbered to keep C=O as low as possible Ene-Ols #-alken-#-ol (OH at lower position) Ene- Ynes #-alken-#-yne (C=C at lower position) Alkenes: (E) or (Z) Compounds with Stereocenters: (R) or (S) © D.M. Collard, 2005 CHIRALITY: ENANTIOMERS An object which has a non-superimposable mirror image is chiral (the opposite of chiral is “achiral”). Another test for chirality is to assess whether the object itself has a mirror plane of symmetry or point of symmetry (point of inversion). Enantiomers Molecules can be chiral. Pairs of molecules which are non-superimposable mirror images of one another are called enantiomers. Enantiomers are examples of stereoisomers: molecules which differ only in the spatial arrangement of atoms. Molecules with a single carbon atom bearing four different substituents can exist as a pair of enantiomers which differ in the arrangement (“configuration”) of these substituents. The carbon is stereogenic A A The carbon is a stereocenter B C D D C B You must be able to recognize when pairs of molecules are identical (superimposable) or entiomers (non-superimposable mirror images) D.M. Collard 2007 © D.M. Collard, 2005 Designating Configuration Stereocenters are designated as having either R- or S-configurations…. - Assign priorities to the substituents using the Cahn-Ingold-Prelog system (briefly, atoms are ranked in order of atomic weight; if two atoms are identical, the next set of attached atoms is considered). - View the molecule with the lowest priority (4) substituent pointing away from you. - Trace from highest priority (1) to second priority (2), to third (3)…. Clockwise = R Counterclockwise = S e.g., H Cl F Br Optical Rotation The observed rotation is α The observed specific rotation is [α] = a / c·l where c = concentration in g/mL and l = pathlength in dm (10-1 m) The observed rotation, α or [α ] depends on solvent, temperature and wavelength of the polarized light. Generally the sodium D line is used for the light source and the experiment is done at room temperture, 25 °C. The specific rotation is then noted as 25 [α] D (conc./solvent) The specific rotation of an optical pure chiral compound is a “property” like melting point or boiling point The specific rotation of a given sample depends on it “optical purity” D.M. Collard 2007 © D.M. Collard, 2005 STEREOISOMERS WITH MORE THAN ONE STEREOCENTER Diastereomers A X B Y C Z Problem: Draw all the stereoisomers of the molecule below. OH OH CO2H H3C CH CH CO2H CO2H CO2H CO2H For a molecule with n stereocenters, there are a maximum of 2n stereoisomers. Meso Compounds If the sets of substituents on stereogenic centers are identical there will be fewer than 2n stereoisomers. A A B B C C B C A A C B B C A A B C Compounds with stereogenic centers which are not chiral are called meso compounds. Meso compounds possess a point or plane of symmetry D.M. Collard 2007 © D.M. Collard, 2005 CLASSIFYING REACTIONS Reactions 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. Substitutions Additions Eliminations Rearrangements (often in combination with another type of reaction) TWO CLASSES OF NUCLEOPHILIC SUBSTITUTIONS C L Nu C Nu L • Substitution reactions can be performed under different conditions which give rise to dramatically different outcomes. Nucleophilic substitution reactions can be classified as one of two types, based on these experimental observations. • Characteristics which allow this classification are listed on the next slide, and will be studied in greater detail in the next two sections. • In order to develop predictive tools, we need to understand reasons why these observations are important. That is, we need to develop proposals for two different mechanisms which are consistent with the two sets of data and which we can use to predict the outcome of other reactions. D.M. Collard 2007 © D.M. Collard, 2005 Substitution At 1° Substrates: Bimolecular Nucleophilic Substitutions Rate = k[R-L][Nu] Chirality Chiral R-L forms R-Nu with opposite stereochemistry (inversion of stereochemistry, “Walden Inversion”) Effect of Nucleophile Rate: I– > OH– > Br– > Cl– > F– > H2O Effect of Leaving Group Rate: -I > -Br > -Cl >> -F Effect of substrate Rate: methyl > 1° > 2° ( 3° unreactive) Adjacent groups slow the reaction Nu HH L H Nu MeMe L Me D.M. Collard 2007 © D.M. Collard, 2005 Substitution at 3° Substrates: Unimolecular Nucleophilic Substitutions Rate = k[R-L] {independent of concentration of Nu} Chirality Optically active R-L forms racemic R-Nu Effect of substrate Rate: 3° > 2° (1°, methyl not reactive) Effect of Nucleophile Concentration Identity Effect of Leaving Group Rate: -I > -Br > -Cl (F: unreactive) Summary of Factors Effecting SN1 and SN2 Reactions SN1 Substrate: 3°>2°>>1°,methyl - Stability of carbocation intermediate Nu: No effect - Nu not involved in RDS Rate increases by use of polar solvents Enhanced rate of ionization Generally only useful for solvolyses (reactions with H2O, ROH, RCO2H) D.M. Collard 2007 SN2 Substrate: Methyl>1°>2°>>3° - Steric bulk hinders attack of Nu Rate a [nucleophile] Rate depends on type of Nu - Nu involved in RDS Often performed in polar aprotic solvents, e.g., DMF (Me2NCHO), DMSO (Me2SO) to dissolve substrate and ionic reagent, and increase reaction rate © D.M. Collard, 2005 Nucleophilic Substitution Reactions Learn the Reagents!! CN Br SH OMe OTs OH Test yourself: Solomons 6.21 Use Mechanism to Rationalize Outcomes of Reactions HBr O O Δ CH3 Br OH HBr Δ D.M. Collard 2007 2 Br CH3 © D.M. Collard, 2005 Radical bromination of alkanes is only useful when replacing a hydrogen on a 3o carbon, e.g., Br2 hν or when there is only one possible monobrominated product Br2 hν TWO CLASSES OF ELIMINATION REACTIONS E2 Reaction B H L E1 Reaction H L D.M. Collard 2007 © D.M. Collard, 2005 Regiochemistry of Eliminations EtOK EtOH Br Zaitsev’s Rule: _______ substituted (stable) alkene is formed Use of bulky bases can lead to formation of “anti-Zaitsev” products t-BuOK t-BuOH Br Stereochemistry: Anti Elimination Cl H Cl t-Bu H t-Bu H H trans - slow elimination cis - fast elimination Observations CH3 H3C C Br CH3 CH3CH2 Br H3C CH Br or KCN CH3ONa CH3ONa H3C H3C CH Br H3C CH2 CH3ONa KCN H3C C CH3 CH3CH2 OCH3 CH3CH CH2 H3C CH CN H3C CH3 H3C C OK CH3CH2 Br D.M. Collard 2007 CH3 heat H2C CH2 © D.M. Collard, 2005 Competition between SN1, SN2, E1 and E2 Reactions 3° substrates only undergo substitution with weakly basic nucleophiles (ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates generally undergo substitution unless the base itself is sterically crowded (e.g., t-BuO-). substrate nucleophile/base Mechanism 3° ROH, H2O, RCO2H Anionic bases, NH3 SN1 (some E1 on heating) E2 2° Less basic than HO – SN2 1° (e.g.., HS –, RS –, NH3, CN, RCO2–) More basic than HO – ROH, H2O E2 SN1 (some E1 on heating) All except t-BuO– t-Bu-O– SN2 E2 Me all SN2 Rearrangement During Elimination OH H3PO4 Δ not: B: H 2° D.M. Collard 2007 3° © D.M. Collard, 2005 ADDITIONS TO ALKENES Alkenes and Alkynes are Basic and Nucleophilic H Br C C E Regiochemistry H3C C CH2 H H3C Br C CH3 H3C Br H3C Markovnikov’s Rule In the addition of HX to an unsymmetrical alkene, the hydrogen adds to the _____________ substituted carbon and the X groups adds to the _____________ substituted carbon. Mechanistic Markovnikov’s Rule In the ionic addition of HX to an unsymmetrical alkene, protonation gives the more stable carbocation as an intermediate. Anti-Markovnikov Addition The addition of HBr (only), in the presence of peroxides, to unsymmetrical alkene gives the more stable free radical intermediate. Therefore H adds to the more substituted carbon and Br to the less substituted carbon. H3C C CH2 H3C D.M. Collard 2007 H Br peroxide H3C CH CH2Br H3C © D.M. Collard, 2005 Addition and Elimination Reactions of Alkenes Learn the Reagents!! Understanding of mechanism tells you something about regiochemistry (R) and stereochemistry (S). S(syn) S(syn) R(anti-Markov.) Br R(Markov.) OH Br Br OH R(anti-Markov.) S(anti) R(Markov.) e Br S(syn) O OH + CO2 OH O Br O + H H H S(anti) R O OH OH S(syn) S(syn) Test yourself: Solomons 8.21, 8.22 Addition and Elimination Reactions of Alkynes Learn the Reagents!! O 2 O Br OH Br Test yourself: Solomons 8.23, 8.24 D.M. Collard 2007 Br © D.M. Collard, 2005 SYNTHETIC STRATEGIES C C H H C C H Br C C C C H OH C C Work Synthesis Problems! D.M. Collard 2007 © D.M. Collard, 2005 Work More Synthetic Problems!! O OH Keep Going!!! D.M. Collard 2007 © D.M. Collard, 2005 O Here are some more….. Solomons problems: 6.17 (one step substitutions) 7.22, 7.23, 7.32 (one step eliminations, additions) 7.24 (multistep synthesis) 8.25, 8.26 (multistep synthesis) 11.35, 11.42 (one-step and multistep) D.M. Collard 2007 © D.M. Collard, 2005