Rules of the Day CH320M/328M

1. It is important to categorize the nucleophile/base with respect to nucleophile and base strength. Click here for a table of nucleophiles grouped by nucleophile and base strength and a mechanism decision map.

A) Methyl and primary haloalkanes react with the SN2 mechasnism for all nucleophiles in the table except for tBuOK. tBuOK is a srong base that is so stereically hindered it cannot undergo an SN2 reaction, so even primary haloalkanes will undergo an E2 reaction with tBuOK.

B). For secondary haloalkanes, the strong bases labeled in the table react predominantly via the E2 mechanism. Most other nucleophiles react via the SN2 mechanism, except for the "very weak bases" listed in the table that react via the SN1/E1 pathway.

C). Tertiary haloalkanes react via E2 (never SN2) except when the "very weak bases" listed in the table are used, then they go SN1/E1.

2. For highly substituted haloalkanes you must look for the correct conformation in which the H and X are antiperiplanar in order to identify whether the product alkene is E or Z.

3. For E2 reactions using cyclohexane derivatives, both the H and X (leaving group) must be axial in order for there to be the required anti-periplanar geometry for a reaction to occur.

4. For SN2 reactions using cyclohexane derivatives, the X must be in the axial position. If it is equatorial, the nucleophile cannot approach from the back of the C-X bond due to a "steric blockade" by the rest of the ring.

5. The point of Organic Chemistry is the synthesis of more complex molecules from simpler ones. Often, this requires multiple steps.

6. When doing synthesis problems (enhanced edition):

A) You must have your entire roadmap learned so you can recite the NIRRS parameters for each reagent, i.e. Nature of overall transformation ("locations" on the roadmap), the Intermediate or transition state (carbocation, anti-periplanar etc.), the Reagents and how to designate them, as well as any Regiochemistry (Markovnikov, etc.) and any appropriate Stereochemistry (syn, anti, InVERSiON, scrambled, etc).

B) Work backwards (learn to RECOGNIZE the appropriate reagents and starting materials by looking at the products) from the final product. DO NOT try to work forward from the starting materials. Please trust me on this.

C) Count carbons in the starting material(s) and product(s) to see if any carbon-carbon bonds need to be broken or made, thereby zeroing in on key steps. This will be far more important next semester, so you should get used to doing this now.

D) Pretty much all synthesis problems in OChem 1 involve traveling "north or south" on the so-called "I-35" reactions (alkanes SA, haloalkanes NB/SM, alkenes ATX, vicinal dihaloalkanes Waco, alkynes DFW) at least part way at some point during the synthesis. This is not a promise or a rule, just an observation.

7. Polar protic solvents (have polar bonds with H atoms that can take part in hydrogen bonding) solvate both cations and anions.This has two consequences:1) Well solvated anions are less nucleophilic so polar protic sovlents inhibit nucleophile strength and the rate of SN2 reactions. 2) Polar protic solvents promote SN1/E1 reactions by stabilizing the intermediate carbocation and leaving group anion thus lowering the overall energy barrier.

8. The general rule of solvation is "like dissovles like", so polar, hydrogen bonding solvents dissolve polar, charged, or hydrogen bonding molecules and non-polar hydrocarbons dissolve nonpolar hydrocarbons. Non-polar material does not dissolve in polar solvents because the polar molecules stick to each other too well.

9. Alcohols are realtively weak acids with pKa's in the 15-19 range. Thiols are more acidic, with pKa's in the 8-12 range since the larger S atom can more easily accomodate the negative charge.

HOMEWORK:

Read: Sections 10.1 - 10.4.

Take the Daily Quiz 18 before 10 PM tomorrow. Click here to access the quiz.These quizzes are designed to review the important material from today's lecture. Together, they will count as 5% of your final grade.

Finish working on Gradescope Homework Problem Set 9 due Tuesday November 12. Click here to access the Gradescope Homework Problem Set 9. Note there are Aktiv Learning and Gradescope Questions for Problem Set 9, and you MUST DO BOTH.