Kaplan Organic Chemistry; Chapter 4 - Analyzing Organic Reactions

DEF: Lewis acid

Electron acceptor; accepts an electron pair to form a covalent bond.

DEF: Lewis base

Electron donor; donates an electron pair to form a covalent bond.

DEF: Brønsted–Lowry acid

Proton donor; donates H+ to a base.

DEF: Brønsted–Lowry base

Proton acceptor; accepts H+ from an acid.

DEF: Amphoteric molecule

Can act as either acid or base; water is a common example.

T/F: Acid–base reaction proceeds only if products are weaker than reactants

True. The conjugate acid and base must be less reactive than original reactants.

T/F: α-Hydrogens are not acidic

False. α-Hydrogens are acidic due to resonance stabilization of enolates.

FB: Strong acid pKa range

Typically below –2; they nearly completely dissociate in aqueous solution.

FB: Example of nucleophile

OH–, RO–, CN–; electron-rich species that attacks electrophiles.

MC: Which species is a Lewis acid?

BCl3; it accepts electrons to form a covalent bond.

MC: Which species is a Lewis base?

NH3; it donates electrons to form a covalent bond.

MC: Rank nucleophilicity in polar protic solvent: F–, Cl–, Br–, I–

I– > Br– > Cl– > F–; larger ions are less solvated and more reactive.

MC: Which carbon is more reactive in SN1: tertiary or primary?

Tertiary; more substituted carbons stabilize carbocations.

MC: Which carbon is more reactive in SN2: tertiary or primary?

Primary; less steric hindrance allows backside attack.

DEF: Oxidation

Increase in oxidation state; often more bonds to oxygen or fewer to hydrogen.

DEF: Reduction

Decrease in oxidation state; often more bonds to hydrogen or fewer to oxygen.

DEF: Oxidizing agent

Accepts electrons and is reduced; often contains metals in high oxidation states or oxygen-rich species.

DEF: Reducing agent

Donates electrons and is oxidized; often metals with low electronegativity or metal hydrides.

DEF: Chemoselectivity

Preferential reaction of one functional group in the presence of others.

DEF: Nucleophile

Electron-rich species with lone pairs or π bonds that attacks electrophiles.

DEF: Electrophile

Electron-deficient species with positive charge or polarized atom that accepts electrons.

DEF: Leaving group

Group that departs with electrons in heterolysis; weak bases make good leaving groups.

T/F: SN1 reactions are stereospecific

False. SN1 reactions produce racemic mixtures due to planar carbocation intermediate.

T/F: SN2 reactions invert configuration at the reactive carbon

True. Backside attack flips stereochemistry.

FB: Four major factors affecting nucleophilicity

Charge, electronegativity, steric hindrance, solvent.

FB: Solvent effect on nucleophilicity in polar protic solvents

Increases down the periodic table; larger anions are less solvated.

FB: Solvent effect on nucleophilicity in polar aprotic solvents

Increases up the periodic table; smaller anions react faster.

MC: Which carbonyl compound is more reactive to nucleophiles, aldehyde or ketone?

Aldehyde; less steric hindrance than ketone.

MC: Rank carboxylic acid derivatives by electrophilicity: amide, ester, anhydride, carboxylic acid

Anhydride > carboxylic acid > ester > amide.

MC: Strong oxidizing agent example

KMnO4; contains metal in high oxidation state bonded to multiple oxygens.

MC: Strong reducing agent example

LiAlH4; provides hydride (H–) to reduce carbonyl compounds.

MC: Which alcohol can be oxidized to carboxylic acid with dichromate?

Primary alcohol; oxidizes first to aldehyde, then carboxylic acid.

FB: Functional groups that act as acids on MCAT

Alcohols, aldehydes/ketones (α-H), carboxylic acids, carboxylic acid derivatives.

FB: Functional groups that act as bases on MCAT

Amines, amides; donate lone pairs to electrophiles.

DEF: α-Hydrogen

Hydrogen attached to carbon adjacent to a carbonyl; acidic due to enolate resonance stabilization.

DEF: Enolate

Conjugate base formed by deprotonating α-hydrogen; strong nucleophile.

MC: Which functional group is most reactive to nucleophilic attack: ester, ketone, or amide?

Ester > Ketone > Amide; matches electrophilicity trend.

MC: Which reaction occurs faster: SN1 at tertiary or SN2 at tertiary?

SN1 at tertiary; SN2 is hindered at tertiary carbons.

FB: First step in acid-base reaction

Protonation or deprotonation of reactant depending on acid/base properties.

FB: First step in nucleophilic substitution

Nucleophile attacks electrophilic carbon while leaving group departs (SN2) or after carbocation formation (SN1).

DEF: Steric hindrance

Bulk of substituents prevents nucleophile or reagent from accessing reactive site.

FB: Protection of carbonyl during reduction

Convert to acetal or ketal; prevents unwanted reaction on carbonyl.

MC: In an SN2 reaction, what must be true of the nucleophile relative to the leaving group?

Nucleophile must be stronger base/reactive than leaving group.

MC: In an SN1 reaction, what determines the rate of reaction?

Formation of carbocation; rate

DEF: Polar solvent requirement for nucleophile–electrophile reactions

Like dissolves like; nucleophiles are polar or charged, so polar solvent required.

FB: Six steps to solve organic chemistry reactions

1. Know nomenclature, 2. Identify functional groups, 3. Identify other reagents, 4. Identify most reactive groups, 5. Determine first step, 6. Consider stereochemistry.

MC: In the reaction of ethyl 5-oxohexanoate with 1,2-ethanediol and p-toluenesulfonic acid, which functional group is protected first?

Ketone; diol forms a protective diether at the ketone carbonyl.

MC: After protecting the ketone in ethyl 5-oxohexanoate, which reagent reduces the ester?

LiAlH4; reduces ester to alcohol without affecting protected ketone.

MC: What happens to the protective diether group during acidic workup?

Removed; regenerates the original ketone.

MC: Oxidation of ethanol with potassium dichromate produces which product?

Ethanoic acid; primary alcohol oxidized fully to carboxylic acid.

MC: Why does ethanol oxidized with PCC stop at aldehyde?

PCC is a mild oxidant; does not further oxidize aldehyde to carboxylic acid.

MC: In peptide bond formation between serine and lysine, which functional group acts as nucleophile?

Amino group of lysine; attacks electrophilic carbonyl of serine.

MC: In peptide bond formation, which functional group leaves?

Hydroxyl group from carboxylic acid; converted to water to become good leaving group.

MC: Why does the hydroxyl on serine not react in peptide bond formation?

Less oxidized than carboxylic acid; more oxidized groups react preferentially.

MC: Which carbon is preferred in SN2 reactions?

Methyl or primary carbon; minimal steric hindrance allows backside attack.

MC: Which carbon is preferred in SN1 reactions?

Tertiary > secondary > primary; carbocation stability dictates rate.

MC: Rank nucleophiles in aprotic solvent: F–, Cl–, Br–, I–

F– > Cl– > Br– > I–; aprotic solvent removes solvation, basicity determines nucleophilicity.

MC: Rank nucleophiles in protic solvent: F–, Cl–, Br–, I–

I– > Br– > Cl– > F–; larger ions less solvated, more nucleophilic.

MC: Which type of alcohol can be oxidized to ketone but not carboxylic acid?

Secondary alcohol; oxidation stops at ketone.

MC: Which type of alcohol can be oxidized to aldehyde or carboxylic acid?

Primary alcohol; strong oxidants push to carboxylic acid.

MC: A tertiary alcohol reacts with CrO3

No reaction; tertiary alcohols have no hydrogen on carbon to oxidize.

MC: Which molecule is more reactive toward nucleophilic attack: aldehyde or carboxylic acid?

Aldehyde; less steric hindrance and high electrophilicity.

MC: Why are amides poor electrophiles?

Nitrogen donates electron density; lowers carbonyl carbon positive character.

MC: Which factors increase electrophilicity?

Positive charge, electron-withdrawing groups, resonance stabilization, poor leaving groups.

MC: Which leaving groups are generally good?

Weak bases like I–, Br–, Cl–; stabilized by resonance or inductive effects.

MC: How does steric hindrance influence SN2 reactions?

Bulky groups prevent backside attack; slows or prevents reaction.

MC: How does steric hindrance influence SN1 reactions?

Minimal effect; carbocation forms first, nucleophile attacks planar intermediate.

MC: For chemoselectivity, which functional group reacts first?

Most oxidized functional group; higher electrophilicity or reactivity.

MC: What is the role of a protecting group?

Temporarily masks reactive functional group; allows selective reaction elsewhere in molecule.

MC: In reduction, which reagent reduces ketones to secondary alcohols?

NaBH4 or LiAlH4; adds hydride to carbonyl carbon.

MC: In reduction, which reagent reduces carboxylic acids to primary alcohols?

LiAlH4; stronger than NaBH4, can reduce carboxylic acids.

MC: In nucleophilic substitution, how must nucleophile strength compare to leaving group?

Must be stronger/more reactive; ensures reaction proceeds.

MC: In nucleophilic substitution, how does substrate concentration affect SN1 vs SN2?

SN1 depends only on substrate; SN2 depends on both substrate and nucleophile concentrations.

MC: In SN2 reaction, which configuration results?

Inversion; backside attack flips stereochemistry.

MC: In SN1 reaction, which configuration results?

Racemic mixture; planar carbocation intermediate allows attack from either side.

MC: Which α-hydrogen is most acidic?

Hydrogen on carbon adjacent to carbonyl; resonance stabilization of enolate anion.

MC: Why are esters more reactive than amides?

Amides have nitrogen donation, stabilizing carbonyl; esters less stabilized, more electrophilic.

MC: Which reagent can stop oxidation at aldehyde stage?

PCC; mild oxidant, prevents further oxidation to carboxylic acid.

MC: Which functional group can form enolate under strong base?

Ketone or aldehyde; deprotonation at α-hydrogen forms enolate.

MC: Why are SN1 reactions faster at tertiary carbons?

Tertiary carbocations stabilized by alkyl groups; lowers activation energy.

MC: Why are SN2 reactions slower at tertiary carbons?

Steric hindrance prevents nucleophile access; high energy barrier.

DEF: Organic chemistry reactions are governed by sets of rules

True. Understanding these rules allows prediction of reaction outcomes rather than relying on memorization.

DEF: A Lewis acid is an electron pair acceptor

True. Lewis acids often have vacant p-orbitals or positive charge.

DEF: A Lewis base is an electron pair donor

True. Lewis bases often have lone pairs and may carry a negative charge.

DEF: Brønsted-Lowry acids donate protons

True. Bases accept protons under this definition.

DEF: Amphoteric molecules can act as acids or bases

True. Water is a common example.

FB: Acid-base reactions will only proceed if the products are ? than the reactants

Weaker; the reaction favors formation of less reactive products.

FB: The α-hydrogen adjacent to a carbonyl is acidic due to ?

Resonance stabilization of the enolate.

DEF: Acids with a pKa below −2 are considered strong acids

True. They usually dissociate completely in aqueous solution.

DEF: Amines are common functional groups that act as bases

True. Nitrogen lone pair allows nucleophilic attack or proton acceptance.

MC: Which of the following is a strong acid?

HCl; pKa < −2 indicates strong dissociation.

MC: Which functional group is acidic at the α-carbon?

Ketone; adjacent hydrogens are acidic due to resonance stabilization.

T/F: Water can act as a base in acidic solution

True. It accepts protons in acidic conditions.

T/F: Alcohols are stronger acids than carboxylic acids

False. Carboxylic acids are more acidic due to resonance stabilization.

DEF: Nucleophiles are electron-rich species that form bonds with electrophiles

True. They often contain lone pairs or π bonds.

DEF: Electrophiles are electron-deficient species that accept electrons

True. Positively polarized atoms or carbocations are electrophilic.

FB: Nucleophilicity is a ? property, while basicity is a ? property

Kinetic; Thermodynamic; nucleophilicity is reaction rate dependent, basicity is equilibrium dependent.

MC: Rank nucleophilicity in a polar protic solvent: F–, Cl–, Br–, I–

I– > Br– > Cl– > F–; larger ions are less solvated and more nucleophilic.

MC: Rank nucleophilicity in a polar aprotic solvent: F–, Cl–, Br–, I–

F– > Cl– > Br– > I–; solvent does not hinder small, basic ions.

DEF: Good leaving groups are the conjugate bases of strong acids

True. Weak bases stabilize extra electrons and leave easily.