Exam Review Schedule: Upcoming exam on Friday; next class will be a review.
Practice Questions: Ample practice questions will be provided until the exam.
Key Concepts in Reactions
Types of Reactions: Understanding SN1, SN2, E1, E2 reactions.
Requirements for Reactions: Each mechanism requires an electrophile (usually an alkyl halide with a good leaving group) and a nucleophile.
A good leaving group, often a halide (Cl, Br, I) or tosylate, is essential for these reactions.
The nucleophile attacks an electron-deficient center, or the base abstracts a proton.
Evaluating Conditions: Conditions determine which mechanism (S_N or E) takes place based on the reactants involved and their arrangements.
Reaction Mechanism Discussion
Mechanisms Required: Need to distinguish between S_N and E reactions based on sets of conditions.
S_N reactions result in the replacement of a leaving group by a nucleophile, while E reactions result in the formation of a double bond by eliminating a leaving group and a proton.
Important Focus Area: Comparing different reactions, especially how to determine if the reaction will proceed via SN1, SN2, E1, or E2.
Problem Analysis: Reaction with Sodium Hydroxide
Problem Example: Evaluating why only a substitution product is obtained with sodium hydroxide on a secondary alkyl halide.
Mechanism Review: Secondary alkyl halides allow for various reactions, both substitutions and eliminations.
Nucleophile and Base: Sodium methoxide (NaOMe) acts as a strong nucleophile/base. NaOMe ≈Na++OMe−.
Sodium hydroxide (NaOH) is a strong base and a strong nucleophile, but its basicity is often exploited in competing elimination reactions.
Anticoplanar Requirement for Elimination: The arrangement is critical; in a ring, if hydrogens are on the same face as the leaving group, elimination cannot occur.
For E2, the eliminated hydrogen and the leaving group must be anti-coplanar (180∘ dihedral angle) for the reaction to occur efficiently. This geometry is crucial, especially in cyclic systems.
S_N2 Specificity: Illustrates backside attack leading to inversion of configuration; elimination is not possible due to lack of anticoplanar hydrogens.
Chair Conformation Questions
Chair Configurations: Understanding axial and equatorial relationships is crucial for determining possibility of reaction mechanisms, especially eliminations.
Anti-coplanar Requirement: If hydrogens are on the same face, they cannot be eliminated. Must evaluate potential chair conformations to confirm.
For elimination (E2) to occur, the hydrogen to be removed and the leaving group must be trans-diaxial in the chair conformation, which corresponds to an anti-coplanar arrangement.
Types of Reactions: Substitution vs. Elimination
Substrate Types: Primary alkyl halides yield SN2 primarily, secondary alkyl halides can yield any type (SN1, SN2, E1, E2), tertiary generally yield E2 for strong nuclei without SN2 possibility.
Weak vs. Strong Conditions: The strength of nucleophiles and bases influences the product formation and the mechanism used:
S_N1 and E1: Associated with weak nucleophiles; carbocations are formed.
These involve a carbocation intermediate, leading to possible rearrangements and racemization (for S_N1) or regioselectivity (for E1). They are favored by polar protic solvents (e.g., water, alcohols) that stabilize the carbocation.
S_N2 and E2: Associated with strong nucleophiles; direct mechanisms.
These are concerted, single-step reactions. SN2 proceeds via a backside attack, causing inversion of configuration. E2 requires an anti-coplanar arrangement. Both are favored by strong nucleophiles/bases. SN2 is often favored by polar aprotic solvents (e.g., DMSO, acetone) which do not solvate the nucleophile as much.
Predicting Products Based on Conditions
Secondary Alkyl Halides: These are versatile, able to undergo any reaction depending on the conditions and the strength of nucleophile/base.
Good nucleophile/bad base: Use conditions favoring substitution (e.g. acetate).
Using a good nucleophile that is also a poor, non-bulky base (e.g., Br−, I−, CH<em>3COO−) tends to favor SN2 over E2 when possible.
Heat in Reactions: Heat tends to favor elimination products due to increased entropy, which influences the reaction direction.
Identify if carbon is primary, secondary, or tertiary.
Assess nucleophile strength (strong or weak).
Strong nucleophiles/bases typically include alkoxides (RO−), hydroxide (HO−), CN−.
Weak nucleophiles/bases often include neutral molecules like water (H2O), alcohols (ROH), or carboxylic acids (RCOOH).
Primary Alkyl Halides: Will yield S_N2 or E2 depending on nucleophile/base strength.
For primary alkyl halides, bulky strong bases can shift preference from S_N2 to E2.
Tertiary Alkyl Halides: Will yield E2 if strong conditions are present; S_N1 and E1 if weak conditions.
Secondary Alkyl Halides: Requires assessing if strong or weak nucleophile/base to determine which combination of reactions will take place.
IUPAC Nomenclature for Alkenes
Basics of Naming: Alkenes (double bonds) are named with the suffix -ene in the parent chain based on the carbon count.
Positioning for Double Bonds: The position of double bonds is prioritized in naming (lower number takes precedence over branches).
E and Z Nomenclature: Used for determining stereochemistry of double bonds based on highest priority groups relative orientation (same = Z, opposite = E).
E and Z configurations are assigned based on the Cahn-Ingold-Prelog (CIP) priority rules for the groups attached to each carbon of the double bond. If the two high-priority groups are on the same side, it is Z (zusammen); if on opposite sides, it is E (entgegen).
Practice Application
Practice Questions Recap: Addressed conditions leading to various product formations:
e.g. S_N2 with small nucleophiles, E2 with larger ones.
Learning through Examples: Engage with each practice question to solidify understanding of reactions and conditions.
Conclusion and Next Steps
Reminder for Upcoming Class: Bring any questions from the slides or practice exams to discuss and review.