Exam 3

Question 1

Regiocontrol

Answer 1

The ability to control where a functional group adds to a compound.

Regiocontrol ≈ Regiospecificity

Question 2

Nucleophilic Acid

Answer 2

An acid whose conjugate base is a strong nucleophile.

Question 3

Non-Nucleophilic Acid

Answer 3

An acid whose conjugate acid is a weak nucleophile.

Question 4

William Ether Synthesis

Answer 4

An SN2 mechanism for synthesizing an ether in which an alkoxide serves as the nucleophile.

RO^– = Alkoxide

Question 5

Examples of Nucleophilic Acids

Answer 5

• HCl (Hydrochloric Acid)
• HBr (Hydrobromic Acid)
• HI (Hydroiodic Acid)

Question 6

Examples of Non-Nucleophilic Acids

Answer 6

• HNO₃ (Nitric Acid)
• H₂SO₄ (Sulfuric Acid)
• H₃PO₄ (Phosphoric Acid)

Question 7

Why is the conjugate base of a non-nucleophilic acid a poor nucleophile?

Answer 7

The conjugate base is resonance stabilized.

The negative charge of the conjugate base is delocalized about the compound by way of resonance.

Question 8

Oxacycloalkane Formation Kinetics

Answer 8

K₃ > K₅ > K₆ > > > K₄ > > > K₇ > K₈

Question 9

Why does oxacyclopropane form extremely quickly?

Answer 9

The proximity of the nucleophilic Oxygen and the electrophilic Carbon compensate for the tremendous ring strain of the three-membered ring.

Question 10

Why do oxacyclopentane and oxacyclohexane form quickly?

Answer 10

The compounds experience minimal ring strain at their bonds, which compensates for the distance between the nucleophilic Oxygen and the electrophilic Carbon.

Oxacyclohexane has zero ring strain due to having bonds with the ideal 109.5° angle.

Question 11

Why does oxacyclobutane form slowly?

Answer 11

The distance between the nucleophilic Oxygen and the electrophilic Carbon does NOT compensate for the great ring strain of the four-membered ring.

Question 12

Why do oxacycloheptane and oxacyclooctane form extremely slowly?

Answer 12

The nucleophilic Oxygen and the electrophilic Carbon are at a great distance from one another, which adds to the instability caused by ring strain within the compounds.

Question 13

Why do oxacyclopropanes frequently undergo ring-opening reactions?

Answer 13

Ring-openings reactions relieve the great ring strain of these compounds.

Question 14

Nucleophilic Attack on Oxacyclopropane

Answer 14

Stereospecific Reaction

Question 15

Stereospecific Reaction

Answer 15

A reaction in which a unique stereoisomer forms a unique stereochemical product.

The cis-configuration and the trans-configuration of a compound will yield different stereochemical products

Question 16

Regiospecific

Answer 16

A reaction in which the addition of a functional group to a compound can only occur at a specific region of the compound.

Regiospecificity ≈ Regiocontrol

Question 17

Why does reacting an alcohol with a non-nucleophilic acid result in an E1 mechanism?

Answer 17

The conjugate base of a non-nucleophilic acid is an extremely poor nucleophile since it is resonance-stabilized. A substitution reaction is not possible due to the poor nucleophilicity of the non-nucleophilic base, so an elimination mechanism must be favored.

The non-nucleophilic conjugate base is a weak base, so it cannot perform an E2 reaction.

Question 18

Why does reacting an alcohol with a non-nucleophilic acid create an internal alkene?

Answer 18

Formation of an internal alkene is favored because the most stable intermediate and the most stable resultant compound are created.

• Hyperconjugation causes the internal alkene intermediate to be the most stable carbocation.
• The internal alkene is most stable due to sp²–sp³ bonding character.

Question 19

Thermodynamic Favorability of Internal Alkene over Terminal Alkene

Answer 19

The internal alkene results is more sp²–sp³ carbon bonding than the terminal alkene.

Question 20

Electronic Favorability of Internal Alkene over Terminal Alkene

Answer 20

The internal alkene intermediate has a higher number of electron-donating groups than the terminal alkene.

A higher number of electron-donating groups results in greater hyperconjugation stabilization.

Question 21

Internal Alkene Product

Answer 21

Zaitsev Product

Question 22

Terminal Alkene Product

Answer 22

Hoffman Product

Question 23

How can the Hoffman product be favored over the Zaitsev product during elimination?

Answer 23

Using a hindered base for the elimination mechanism restricts the accessibility of hydrogen atoms bonded to internal carbons.

Question 24

Why do alkene addition reactions occur despite being antientropic?

Answer 24

During addition of an alkene, one π bond (from the substrate) and one σ bond (from the reagent) are broken and two σ bonds are formed (in the product).

The thermodynamic benefit of σ-bond formation exceeds the entropic loss of the addition reaction.

Question 25

7 Mechanisms for Alcohol Synthesis

Question 26

Alcohol Synthesis via SN2

Question 27

Alcohol Synthesis via SN1

Question 28

Alcohol Synthesis via Reduction

Question 29

Alcohol Synthesis from Oxacycloalkane

Question 30

What is the *driving force* of nucleophilic attack of an oxacyclopropane?

Answer 30

Relief of *ring strain* that occurs as the oxacyclopropane *ring-opens*

Question 31

Vicinal Compound

Answer 31

Compound containing a functional group bonded to *adjacent* carbon atoms.

Question 32

Geminal Compound

Answer 32

Compound containing a functional group bonded bonded twice to the *same* carbon atom.

Question 33

Vic-Diol

Answer 33

Alcohol compound containing hydroxyl groups bonded to *adjacent* carbon atoms.

Question 34

Gem-Diol

Answer 34

Alcohol compound containing two hydroxyl groups bonded to the *same* carbon atom.

Question 35

SN2 Synthesis of Vic-Diol

Answer 35

1) Attack an *oxacycloalkane* with a *strong nucleophile* at the least hindered carbon of the cyclic ring (i.e. the nucleophile attacks the *least hindered* C—O bond). 2) Protonate the *oxide ion* with a polar-protic solvent/reagent to form a second alcohol group. ## Footnote This synthesis mechanism yields a ***trans vic-diol***.

Question 36

Mechanisms for Vic-Diol Synthesis

Answer 36

* SN2 Synthesis from Epoxide (*Trans*) * Osmium Tetroxide Synthesis from Alkene (*Cis*)

Question 37

Why is *2-butene* more stable than *1-butene*?

Answer 37

* The greater inductive-donating (i.e. hyperconjugation) experienced by *2-butene* stabilizes the electron-dense double bond. * The Zaitsev intermediate (i.e. carbocation is placed on the most substituted carbon) is created during synthesis of *2-butene*.