Analyzing Organic Rxns Flashcards
Lewis acid
e- acceptor in formation of covalent bond
also tend to be electrophiles
Lewis base
e- donor
nucleophiles
usually lone pair
when Lewis acids and bases interact which type of bond is formed?
coordinate covalent
both electrons come from Lewis base
Brønsted-Lowry acid
proton donor
Brønsted-Lowry base
proton acceptor
amphoteric
can act as Brønsted-Lowry base or acid
Equilibrium constant
Ka = ([H+][A-])/[HA]
pKa
pKa = -logKa
acids w pKa below -2 are strong
Acidity as you move down periodic table
bond strength dec and therefore acidity inc
acidity and electroneg
the more electroneg, the higher the acidity
When bond strength is high w high electroneg OR bond strength is low with low electroneg
low bond strength takes precedence
functional groups highest to lowest pKa
alkane ~50>alkene ~43
>hydrogen 42>amine ~35
>alkyne 25>ester 25
>ketone 20-24>aldehyde 17-20
>alcohol 17>water 16
>CA 4>hydronium ion -1.7
Acidic fun groups
aldehydes
alcohols
ketones
CA
CA derivatives
Easier to target w basic or nucleophilic reactants bc they accept a lone pair
Basic fun groups
amines
amides
formation of peptide bonds
N of anime can form coordinate covalent bonds by donating lone pair to a Lewis acid
nucleophiles
“nucleus loving”
lone pairs or pi bonds that can form new bonds to electrophiles
good nucleophiles tend to be good bases
nucleophilicity is a kinetic property as it is depends on rate of rxn
4 factors that determine nucleophilicity
Charge (inc w inc e density)
Electroneg (dec as electroneg inc)
Steric hindrance (bulkier less nucleophilic)
Solvent (protic solvents can hinder nucleophilicity by protonating the nucleophile or via h bonding)
When nucleophilic molecules are in the same row or are the same atom…
the more basic the more reactive
nucleophilicity in polar protic solvents…
inc DOWN the periodic table
nucleophilicity in polar aprotic solvents…
inc UP the periodic table
Protic solvent
can H bond
Aprotic solvent
cannot H bond
Nucleophiles in polar solvents…
dissolve regardless of whether they’re aprotic or protic
Halogen nucleophilicity in protic solvents
I->Br->Cl->F-
Bc protons in solution will be attracted to the nucleophile
Conj bases of strong acids are less affected by protons in solutions and can react w electrophiles
Halogen nucleophilicity in aprotic solvents
F->Cl->Br->I-
bc there are no protons to get in the way of the attacking nucleophile, in aprotic solvents nucleophilicity relates directly to basicity
Nucleophile examples
Anime groups tend to make good nucleophiles
Strong:
HO-
RO-
CN-
N3-
Fair:
NH3
RCO2-
Weak:
H2O
ROH
RCOOH
Electrophiles
-“electron-loving”
- pos charge or positively polarized atom that accepts electron pair when forming new bonds with a nucleophile
- Electrophilicity is a kinetic property tho unlike acidity
- They always act as Lewis acids tho
- Greater degree of positive charge inc electrophilicity, so a carbocation is more electrophilic than a carbonyl carbon
CA derivatives ranked by electrophilicity
Anhydrides
CA
esters
Amides
derivatives of high reactivity can form those of lower but NOT vice versa
Leaving group
Molecular fragments that retain electrons after heterolysis
Heterolytic lysis
- Opposite of coordinate covalent bond formation
- A bond is broken and both e are given to one of the two products
- Best LG will be able to stabilize extra electrons
What make good LG
weak bases
More stable w an extra set of electrons
conj bases of strong acids make good LG
What can better stabilize a LG negative charge?
resonance and inductive effects from EWG
Nucleophilic substitution reactions
A nucleophile forms a bond w a substrate carbon and an LG leaves
SN1
unimolecular sub rxns
2 steps:
1) rate limiting, LG leaves generating carbocation
2) nucleophile then attacks carbocation resulting in substitution product
- the more substituted the carbocation the more stable it is because the alkyl groups act as electron donors, stabilizing the positive charge
- rate = k[R—LG]
- first order, substrate concentration dictates the rate and anything that accelerates the formation of the carbocation will inc the rate of an SN1 rxn
- usually racemic bc of planar intermediate (nu can attack from either side)
SN2
bimolecular nucleophilic substitution rxns
- one step: nu attacks the compound at the same time as the LG leaves
- therefore, a concerted rxn
- single rate limiting step involves two molecules
- nu actively displaces the LG in a backside attack
- nu must be strong and substrate cannot be sterically hindered (less substituted the carbon, the more reactive to SN2 rxns)
- opposite trend for SN1
- rate = k[Nu][R—LG]
- inversion (stereospecific rxn)
oxidation states
CH4 ~> carbon has -4 oxidation state, most reduced
CO2 ~> carbon has +4 oxidation state, most oxidized
Oxidation Levels
0: alkanes
1: alcohols, alkyls halides, and amines
2: aldehydes, ketones, imines
3: CA, anhydrides, esters, and amides
4: CO2
reduction vs oxidation
charge is REDUCED
Oxidation
Is
Loss of electrons
Reduction
Is
Gain of electrons
oxidizing agent
accepting electrons (the thing getting reduced)
reducing agent
electron loser (thing getting oxidized)
- PCC
- CrO3/pyridine
- 1° alcohols to aldehyde
- 2° alcohol to ketone
- H2CrO4
- KMnO4
- w H2O2, aldehyde to CA
- alcohol to CA
- KMnO4
- alkane to CA
- O3 then Zn or CH3SCH3
- alkene to aldehyde/ketone
- O3, then H2O2
- KMnO4, heat, H3O+
- alkene to CA/ketone
- alkyne to 2 CA
mCPBA
- alkene to epoxide
- ketone to ester
- OsO4
- KMnO4, HO-
- alkene to vicinal diol
- NaIO4 or Pb(OAc)4 or HIO4
- diol to aldehyde
LiAlH4/NaBH4
- aldehyde to 1° alc
- ketone to 2° alc
- LiAlH4/ether
- H2O
- amide to 1° amine
- CA to 1° alcohol
- ester to 2 1° alc
Redox reagents tend to act on…
the highest priority functional group.
reactions involving nucleophiles and electrophiles, the reaction tends to occur on…
- the highest priority functional group because it contains the most oxidized carbon
- a nucleophile is looking for a good electrophile and the oxidized carbon will allow the nucleophile to experience a greater partial positive
- aldehydes are generally more reactive towards nucleophiles than ketones bc they have less steric hindrance
why are a-carbons more acidic than regular CH bonds?
- resonance stabilization of the enol form
when it comes to carbocation formation, which carbons are preferred in SN1?
3° and 2°
when is comes to carbocation formation, which carbons are preferred in SN2?
methyl and 1°
steric hindrance
- prevention of reactions at a particular location within a molecule due to the size of substituent groups
- SN2 won’t occur on 3°
- steric protection can be a useful tool in synthesis of desired molecules and the prevention of formation of alternative products
protection during reduction
- when several functional groups present, wise to convert aldehyde or ketone to a nonreactive acetal or ketal
- HO(CH2)2OH and H+ to protect and H2O w H+ to reverse
