MCAT Organic Chemistry - Analyzing Organic Reactions

acid–base reaction

an acid and a base react, resulting in the formation of the conjugate base of the acid and the conjugate acid of the base; proceeds so long as the reactants are more reactive, or stronger, than the products that they form

Lewis acid

electron acceptor; electrophiles; vacant p-orbitals into which they can accept an electron pair, or are positively polarized atoms

Lewis base

electron donor; nucleophiles; lone pair of electrons that can be donated, and are often anions, carrying a negative charge

coordinate covalent bonds

covalent bonds in which both electrons in the bond came from the same starting atom (the Lewis base)

Brønsted–Lowry acid

a species that can donate a proton (H+)

Brønsted–Lowry base

species that can accept a proton

amphoteric

ability to act as either Brønsted−Lowry acids or bases

ex. water

acid dissociation constant (K_a)

measures the strength of an acid in solution

pKa

measure of acid strength; smaller numbers are more acidic; acids with a pKa below −2 are considered strong acids

pK_a= - log K_a

α-carbon

carbon adjacent to carbonyl group

α-hydrogens

connected to the α-carbon, very acidic since carbonyl-containing carbanions is stabilized by resonance

acidic functional groups

alcohols, aldehydes and ketones (at the α-carbon), carboxylic acids, and most carboxylic acid derivatives

basic functional groups

amines and amides

Nucleophiles

“nucleus-loving” species with either lone pairs or π bonds that can form new bonds to electrophilesnu

carbon, hydrogen, oxygen, or nitrogen (CHON) with a minus sign or lone pair

nucleophilicity

based on relative rates of reaction with a common electrophile; kinetic property

increases with negative charge

decreases with electonegativity

decreases with steric hinderance

protic solvents hinder

polar protic solvent

hinder nucleophilicity by protonating the nucleophile or through hydrogen bonding

I^- → Br^- → Cl^- → F^-

polar aprotic solvents,

F^- → Cl^- → Br^- → I^-

nonpolar solvents

can’t use nucleophile–electrophile reactions because reactants are polar and wouldn’t dissolve

strong nucleophiles

HO– , RO– , CN–

fair nucleophiles

N₃^-, NH₃, RCO₂^-

weak nucleophiles

H2O, ROH, RCOOH

nucleophilic functional groups

amine

Electrophiles

“electron-loving” species with a positive charge or positively polarized atom that accepts an electron pair when forming new bonds

electrophilicity

based on relative rates of reaction with a common nucleophile; kinetic property

increases with positive charge

improved by good leaving groups

Leaving groups

molecular fragments that retain the electrons after heterolysis

must be able to stabilise the electrons - weak bases, resonance, inductive effects

ex. conjugate bases of strong acids

Heterolytic reactions

the opposite of coordinate covalent bond formation: a bond is broken and both electrons are given to one of the two products

Nucleophilic substitution reactions

a nucleophile forms a bond with a substrate carbon and a leaving group leaves

Unimolecular nucleophilic substitution (SN1) reactions

rate-limiting step in which the leaving group leaves, generating a positively charged carbocation; the nucleophile then attacks the carbocation, resulting in the substitution product

rate = k[R−L], where R−L is an alkyl group containing a leaving group (first order)

racemic mixture.

Bimolecular nucleophilic substitution (SN2) reactions

the nucleophile attacks the compound at the same time as the leaving group leaves

rate = k[Nu:][R−L] (second order)

concerted reaction

takes one step

backside attack

nucleophile attacks electrophile from opposite direction of leaving group, leading to stereotopic Walden inversion

stereospecific reaction

the configuration of the reactant determines the configuration of the product due to the reaction mechanism

oxidation–reduction (redox) reactions

the oxidation states of the reactants change

Oxidation state

indicator of the hypothetical charge that an atom would have if all bonds were completely ionic

Hydrogen = +1

Oxygen = -2

ion = charge

relative oxidation of functional groups

most oxidation

carbon dioxide

carboxylic acids, anhydrides, esters, amides

aldehydes, ketones, imines

alcohols, alkyl halides, amines

alkanes

Oxidation

increase in oxidation state; loss of electrons; increasing the number of bonds to oxygen or other heteroatoms

Reduction

decrease in oxidation state; gain in electrons; increasing the number of bonds to hydrogen

oxidizing agent

element or compound that accepts an electron from another species; gets reduced

have a high affinity for electrons (such as O₂, O₃, and Cl₂) or unusually high oxidation states (Mn⁷⁺ in permanganate and Cr⁶⁺ in chromate).

Oxidation of primary alcohols

one level to become aldehydes using specific reagents such as pyridinium chlorochromate (PCC)

further oxidized to form carboxylic acids with strong oxidising agents chromium trioxide (CrO₃) or sodium or potassium dichromate (Na₂Cr₂O₇ or K₂Cr₂O₇)

Oxidation of primary alcohols

turn into ketones

reducing agents

sodium, magnesium, aluminum, and zinc - low electronegativities and ionization energies

transition metals can often take on many different oxidation states.

Metal hydrides - NaH, CaH2, LiAlH4, and NaBH4

Reduction of aldehydes and ketones

primary and secondary alochols, respectively

Reduction of amides

turns into amines using LiAlH₄

Reduction of carboxylic acids

turn to primary alcohols using LiAlH₄

Reduction of esters

turn into a pair of primary alcohols LiAlH₄

chemoselectivity

the preferential reaction of one functional group in the presence of other functional groups

redox agent chemoselectivity

highest priority group, most oxidized carbon

ex. carboxylic acid > aldehyde > ketone > alcohol/amine

nucleophile-electrophile chemoselectivity

highest priority group; more electronegative groups around

ex. carboxylic acid > aldehyde > ketone > alcohol/amine

carbon of a carbonyl

positive polarity due to the electronegativity of the oxygen

the α-hydrogens are much more acidic than in a regular C−H bond due to the resonance stabilization of the enol form

enolate then becomes a strong nucleophile, and alkylation can result if good electrophiles are available

substrate carbon in substitution reactions

SN1 reactions - tertiary > secondary > primary - carbocation stability

SN2 reactions - methyl > primary carbons > secondary x tertiary - steric hindrance

Steric hindrance/protection

the prevention of reactions at a particular location within a molecule due to the size of substituent groups; bulky groups make it impossible for the nucleophile to reach the most reactive electrophile, making the nucleophile more likely to attack another region

protecting group

group causing steric hindrance

ex. aldehyde or ketone converted to a nonreactive acetal or ketal