Take Home Lessons from Lecture 3
MECHANISMS
1. Reactions are like crimes, they need motive and opportunity.
A. A reaction has a motive if the products are lower in energy than the starting materials. That is, stronger bonds are made than broken in the reaction, and/or a weaker acid/weaker base is produced, and/or entropy is increased through the creation of a small gaseous fragment. Motive (also called thermodynamic driving force) determines position of equilibrium.
B. A reaction has an opportunity to take place if the mechanism contains no species that are higher in energy than the energies of a resonable fraction of starting material molecules at a given temperature. Opportunity determines rate of a reaction (also called reaction kinetics).
2. Heating up a reaction increases the rate by increasing the number of molecules with enough energy to get over an energy barrier.
3. In mechanisms, arrows are used to indicate movement of electrons.
4. Arrows never indicate movement of atoms directly.
5. Arrows always start at an electron source and end at an electron sink. An electron source is usually a pi bond or lone pair, and an electron sink is an atom that can accept a new bond, often it has a full or partical positive charge.
6. Breaking a bond will occur to avoid overfilling valence at the electron sink atom.
7. A nucleophile contains an electron rich pi bond or lone pair that is the electron source for a bond forming process. Analogous to a Lewis base.
8. An electrophile contains an electron deficient atom that serves as the electron sink in a bond forming process. Analogous to a Lewis acid.
9. Most organic mechanisms are composed of only four different mechanistic elements, so that predicing mechanisms often comes down to a fourway multiple choice for each step.
A. MAKE A NEW BOND BETWEEN A NUCLEOPHILE AND ELECTROPHILE (Use this element when there is a nucleophile present in the solution as well as an electrophile suitable for reaction to occur)
B. BREAK A BOND TO GIVE STABLE MOLECULES OR IONS (Use this element when there is no suitable nucleophile-electrophile or proton transfer reaction, but breaking a bond can create neutral molecules or relatively stable ions, or both.)
C. ADD A PROTON (Use this element when there is no suitable nucleophile-electrophile reaction, but the molecule has a strongly basic functional group or there is a strong acid present.)
D. TAKE A PROTON AWAY (Use this element when there is no suitable nucleophile-electrophile reaction, but the molecule has a strongly acidic proton or there is a strong base present)
10. Pi bonds act as weak nucleophiles with strong electrophiles (including protons).
11. Carbocations (carbon atoms with a positive charge) are common reaction intermediates with starting materials such as alkenes.
A. They are sp2 hybridized, with an empty 2p orbital.
B. They are stablilized by hyperconjugation (adjacent sigma bonds from attached alkyl groups overlap and share electron density with empty 2p orbital) and inductive effect (a carbocation is more electronegative than other carbon atoms [it wants electron density to 'quench' its charge], so attached carbon atoms will share some electron density through sigma bonding network.)
C. Bottom line: carbocations with more alkyl groups attached are more stable (3°>2°>1°>methyl).
D. Carbocations can rearrange if movement of a hydrogen atom or small alkyl group gives a more stable carbocation.
E. When there is a choice, the more stable carbocation will be formed in a reaction, thereby explaining Markovnikov's rule of product regiochemistry.
KEY EXAMPLES: Addition of HX and X2 to alkenes
12. Radical reactions involve intermediates with upaired electrons, and they generally proceed through a radical chain mechanism. For the free radical halogenation of alkanes, more substituted carbons react first and Br2 is more selective than Cl2.
KEY EXAMPLE: Free radical halogenation of alkanes
13. Substitution and elimination reactions are among the most common mechanisms in organic chemistry. When deciding whether a reaction proceeds through SN2, E2, or SN1/E1 evaluate the structure of the electrophile (primary, secondary, tertiary) and the base strength of the nucleophile (strong, medium or very weak, see table) then use the decision map
A. SN2 and E2 are much more common and important than SN1 and E1
B. SN2 is a simultaneous making of a bond and breaking of a bond (backside attack, inversion of stereochemistry).
C. E2 is a simultaneous taking a proton away and breaking a bond (antiperiplanar geometry, Zaitsev's rule).
SUMMARY OF SKILLS YOU MUST MASTER FOR THE MCAT:
1) Understand how to recognize nucleophiles and electrophiles.
2) Understand how to assemble complete mechanisms from the four most common mechanism elements (See 9. above)
3) Draw mechanisms for reactions of alkenes, including an understanding of Markovnikov's rule.
4) Be familiar with the key features of a radical chain process.
5) Predict subsitution vs. elimination mechanisms and products for various combinations of nucleophiles/bases and electrophiles.
