- Cis-trans stereoisomerism
Problems: 1. Draw the structures for the following two compounds, using wedges and dashes: a. cis-1,3-dimethylcyclobutane; b. trans-1-ethyl-2-methylcyclopentane. 2. For cis-1,3-diethylcyclobutane draw a. a stereoisomer and b. a constitutional isomer.
- Combustion of alkanes and cycloalkanes: we covered these reactions in class: the two products are always CO2 and H2O; you just need to balance the equations.
Problem: Write the products of combustion for each of the following alkanes: a. CH3-CH2-CH2-CH2-CH(CH3)2; b. methylcyclohexane; c. ethylcyclopentane
CHAPTER 5: CONFORMATIONS
- Constitutional isomers and conformational isomers
- Alkane chain conformations: at room temperature, bonds allow for free rotation of the atoms connected by the bond.
- Eclipsed and staggered conformations
- Drawing Newman projections – the dihedral angle
- Determining relative stability of conformational isomers
- Cycloalkane conformations – angle strain: cycloalkanes distort from planarity to alleviate angle strain (except for cyclopropane)
- Drawing cyclohexane chair forms: the axial (a) and equatorial (e) positions. Make sure that in your drawing the (a) and (e) can be distinguished.
- Stability of chair forms
- Mono-and disubstituted cylcohexanes.
CHAPTER 6: CONFIGURATIONAL ISOMERS – STEREOCHEMISTRY
- Two Major Classes of Isomers. Definition of isomers, constitutional isomers, and stereoisomers. You should be able to identify constitutional and stereoisomers.
- Introduction to stereoisomerism. Chiral and Achiral Molecules. Draw the enantiomer of a given chiral molecule.
- Chirality (or Stereogenic) Centers. You should be able to identify/locate all stereogenic centers present in each molecule.
- Enantiomers – what they are, and how do you recognize them?
- Designating Configuration using the Cahn-Ingold-Prelog system. Should be able to label stereogenic centers with R and S. For this, you should be able to apply the rules to assign priority to various substituents.
Problems: Draw all possible stereoisomers for the compound below, label pairs of enantiomers and diastereomers, and label the meso compound! a. CH3-CH(OH)-CH(OH)-CH2-CH3; b. CH3-CH(Cl)-CH2-CH(Br)-CH3. Label compounds as R or S.
- Diastereomers. Calculate the maximum number of stereoisomers for a given molecule (2n, where n is the number of stereogenic centers).
- Symmetry and chirality. Meso Compounds.
- Optical Activity. Definition. How do enantiomers rotate plane-polarized light? Dextrorotatory and levorotatory isomers. Specific rotation and its equation. Racemic mixture: definition, properties, and how does it differ from the meso compound? The Table below was discussed in class. Racemic Mixture Meso Compound
Stereogenic Centers Present Present
Optical Activity None None
Cancellation of Optical Activity Intermolecular (1:1, mol/mol mixture
of the enantiomers) Intramolecular
Can you render it optically active? Yes! E.g., by chiral chromatography, microbial activity Impossible!
CHAPTER 7: INTRODUCTION TO REACTIONS
7.1. Enthalpy or heat of reaction
Steps and species involved in reactions:
Radicals, carbanions, and carbocations
Heat of reaction: exothermic and endothermic reactions. Energy diagrams (do not forget to label the axes: Energy vs. Reaction coordinate)
7.2. Entropy: the state of randomness of a system. The entropy increases, when a gas is released in a reaction, e.g., CH3–CH3 CH2=CH2 + H2. The entropy decreases, when a cycle forms out of an open chain molecule (e.g., X-CH2-CH2 CH2-CH2-Y forms a cyclobutene); the reverse of this reaction, where the cycle cleaves, so that it gains more freedom of motion involves an increase in entropy.
7.3. Gibbs free energy change (Go = Ho – T So) predicts whether a reaction is allowed or not.
Thermodynamics: Equilibrium constant and change in free energy (Go). What does it mean, when Go < 0 and when Go > 0? How can you get this information from an energy diagram?
7.4. Equilibria. Equilibrium constant and free energy changes. You should be able to correlate the magnitude of Keq with Go; Go = -2.303RT*log Keq. Remember that a reaction is spontaneous, when Keq > 1, which translates into Go < 0. 7.5. Reaction Kinetics. Energy diagrams. Be acquainted we the physical measures represented on the two axes. Activation energy (Ea) and the thermal effect (Ho) 7.6. Reading Energy Diagrams. Energy diagram of a one-step reaction and of a two-step reaction. Identification of the rate determining step (rds): the highest energy of its transition state is the highest. Transition state. Kinetics. Rate equations: 1st order and 2nd order.) One-step and two-step mechanisms. Golden rule: one-step reaction is 2nd order, while 2-steps reaction is 1st order. Catalysts. Be able to provide a complete definition and to draw comparative energy diagrams for catalyzed and uncatalyzed reactions. Types of reactions: (i) Redox reactions (generic); (ii) for organic reactions: substitution, elimination, addition, and rearrangement 7.7. Nucleophiles and electrophiles. Ionic reactions. Nucleophiles contain an excess of electrons, which can be donated to another reactant: Charged nucleophiles (OH-, R-O-, SH-, CN-, CH3-COO-, etc.) Neutral nucleophiles (H2O, CH3-OH, NH3, R-NH2, CH3-COOH, etc.) Electrophiles have an empty orbital, where they can accept a pair of electrons 7.8. Reaction mechanisms Note that curved arrows always start from lone pair electrons or from an electron-rich multiple bond! Nucleophilic attack: is performed onto the substrate molecule by a charged or neutral nucleophile. Leaving groups: good leaving groups are: –I > –Br > –Cl; H2O
Poor leaving groups: –F, –OH, –R, –H
CHAPTER 8: SUBSTITUTION REACTIONS
8.1. Alkyl halides. Aryl halides, vinyl halides, and benzylic halides.
Structure of alkyl halides
8.2. Possible mechanisms for substitution reactions: concerted (one-step) vs. sequential (2-steps) mechanisms.
8.3. SN2 Mechanism
One-step process, 2nd order, rate law: r = k•[nucleophile][substrate]
How does the identity of the alkyl group (methyl, 1o, 2o, and 3o) affect the reaction?
Problem: Explain why (CH3)3C-CH2-Br, a 1o alkyl halide, undergoes SN2 reactions very slowly!
8.4. Stereospecificity of SN2 reactions: backside attack with inversion of configuration at a stereogenic center, like flipping the umbrella (Walden inversion): R center S center, and conversely. This applies only when there is a stereogenic (chiral) center in the molecule.
8.5. SN1 Mechanism
Two-step process, 1st order, rate law: r = k•[substrate]
The stereochemistry of SN1: attack from both sides of the sp2 hybridized planar carbocation – racemization. How does the identity of the alkyl group (methyl, 1o, 2o, and 3o) affect the reaction?
How does the structure of the substrate impact this reaction? Explanation resides in the stability of carbocation which forms as the intermediate
8.6. Drawing the Complete Mechanism of an SN1 reaction.
8.7. Drawing the Complete Mechanism of an SN2 reaction.
8.8. Determining which mechanism predominates: When is the Mechanism SN1 or SN2?
Be proficient with the effect of (i) the alkyl halide, (ii) the nucleophile, (iii) the leaving group, and (iv): the solvent effect (polar protic or polar aprotic).
8.9. Introduction to elimination reactions
8.10. Nomenclature of Alkenes: parent chain should contain the double bond, even if not the longest possible carbon chain in the molecule.
8.11. Stereoisomerism of Alkenes: cis/trans and E/Z, respectively
8.12. Alkene Stability:
Increases in the order monosubstituted < disubstituted < trisubstituted < tetrasubstituted.
8.13. Possible Mechanisms for Elimination
8.14. The E2 Mechanism: energy diagram, rate law, effect of substrate – rate increases in the order 1o C < 2o C < 3o C
Regioselectivity of E2 Reactions: Zaitsev and Hofmann elimination products: when smaller base molecules are used, Zaitsev product dominates; upon using bulky, sterically hindered bases, Hofmann product becomes major. (We discussed this in class without mentioning Hofmann’s name. Bulky, sterically hindered bases can only access the outermost hydrogen atoms, cannot get to the carbons inside the chain.)
Stereoselectivity of E2 Reactions: trans elimination product will be major relative to the cis isomer
8.15. The E1 Mechanism: energy diagram, rate law, effect of substrate – reaction rate increases in the order 1o C < 2o C < 3o C
Regioselectivity of E1 Reactions: the Zaitsev elimination product will be major.
Stereoselectivity of E1 Reactions: trans elimination product will be major relative to cis isomer.
8.16. Substitution vs. Elimination: Identifying the reagent
8.17. Substitution vs. Elimination: Identifying the mechanism