Mackenzie Sawyer 2021

Weak Strong Strong Strong, bulky

Nuc/Weak nuc/weak nuc/strong base base
base base (-)

H2O CN, N3, Cl, Br, OH, OR DBU, DBN,

ROH I, RS, RSH, Et3N, t-but
RCOOH H2S,
RNH2, R3P

Methyl -- SN2 SN2 --

Primary -- SN2 SN2 E2

Secondary SN1 or E1 SN2 E2 E2

Tertiary SN1 or E1 SN1 E2 E2

**if deciding between Sub or Elim:

- if its smaller than ethanol = nucleophile = substitution
- larger than ethanol = base = elimination
**a strong base will be unstable when it has a negative charge
**a weak base will be stable when it has a negative charge
- halogens help to balance the negative charge, so they are weak
SN1 SN2

Rate = Rate =
k[electrophile] k[electrophile][nucleophile]

Nucleophile is Nucleophile is strong

weak or (typically a negative
generally charge)
neutral

Solvent: polar Polar aprotic (DMSO,

PROTIC acetone) that way it can
(alcohols) so it dissolve the substrate
helps stabilize and nuc but doesn’t
the resulting participate in hydrogen
carbocation bonding

Inversion and Inversion ONLY

 retention

Reaction is concerted
(in one step)

Primary = Primary = fastest

slowest Tertiary = slowest
Tertiary = *size of groups
fastest matters too, steric
hindrance

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Ranking Basicity (aka acidity)

- look at conjugate base (remove a hydrogen)
- if a base is stable, it is weak bc it wont want to grab a proton (H+)
- base is not stable, it is strong bc it really wants a proton
Charge
- (+) is more acidic
- (-) is more basic

Atom
- Basicity increases as you go UP periodic table (so acidity decreases going up) o
because you decrease in size as you go up, so shorter bond = stronger bond =
stronger base
o So size of atom w neg: larger = weaker conjugate base = stronger acid - Basicity
increases as you go left on the table, (acidity decreases as you go left) o More
electronegative base = more stable base = weaker base = stronger acid

Resonance
- More resonance = more stable, weaker base = stronger acid

Induction
- Electron withdrawing = electronegative
- EN atom closer to the neg charge = more stable, weaker base = stronger acid -
More electronegative = stabilizes base more so a weaker base thus stronger acid

Orbital hybridization
- More S character = more acidic
- Sp = 50% s = more acidic
- Sp2 = 33% s = acidic
- Sp3 = 25% s = least acidic
Ranking acidity of benzenes with multiple substituents:
- The more deactivated it is, the stronger the acid
- The more activated it is, the weaker the acid bc it doesn’t want a H as bad

H NMR
0-1.5 Saturated

1.5-2.5 Allylic

2.5-4.5 Halogen

4.5-6 Double bond

6-8 Benzene

9-12 Carboxylic acid/aldehyde

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C NMR
0-50 Saturated carbon

25-75 Halogen

50-100 Triple bond

C-O

100-150 Benzene
Double bon

150-200 C=O

178-185 Carboxylic acid

190-200 Aldehyde

205-220 Ketone

IR
Alkane CH 2850-2960

Alkene CH 3020-3100
 Alkyne CH 3300

OH Strong, broad around 3400

C-O Strong at 1050-1150

C-N 1030-1230

CN 2210-2260

C=O 1700

NO2 1540

*the frequency of a given vibration is determined by the mass of the atoms and the stiffness of
their bond.
- lighter atoms vibrate at a higher frequency than heavier ones

Acid Base Extractions

Carboxylic acids: extract with NaOH or NaHCO3
Phenols: extract with NaOH
Amines: extract with HCl
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Lab Tests
Degrees of Unsaturation
2� + 2 + � − � − �
2

Isomers
Constitutional: same formula, different connections
Diastereomers: 1 chiral center changes
- Very different physical properties so are separated easily by boiling points
Enantiomers: both centers change
- Very similar physical properties, may only be distinguished by light polarizability
Epimer: differ at one chiral center
Meso: mirrored

How many stereoisomers does compound have?

2^n
n = number of chiral centers
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Techniques (separation or just analyzing)

Column chromatography purifies, most nonpolar first

TLC less polar substance travels further

Gas chromatography lowest BP first

Recrystallization impure in hot = precipitate

Fractional distillation 2 volatile with close BP

UV-Vis spectroscopy Analyze compounds w conjugated

double bonds

Mass spec Determine compounds mass

pH / pKa
low pH = low pKa = high Ka
pH > pKa = deprotonate
pH < pKa = protonate

“which one has lowest pKa” – look for most acidic aka most stable base
“which one has lowest Ka” – look for most basic aka the least stable base
Base = negative charge (remove a hydrogen from acid)

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EDG EWG

- Activate the ring - Deactivate the ring

- Ortho/para directing - Meta directing
- Lone pairs on the atom adjacent to - Adjacent carbon is bonded to a more
the system EN atom
- Halogens are withdrawing but direct
ortho para!
**The more activating it is the more reactive it is towards EAS
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Lab techniques
Extraction Separates dissolved subs. Based on
differential solubility in aqueous vs
organic solvents

Filtration Separates solids from liquids

Recrystallization Separates solids based on different

solubilities. Temperature is important

Sublimation Separates solids based on their ability

to sublime (go to gas phase)

Centrifugation Separates large things based on mass

and density

Distillation Separates liquids based on BP

Chromatography Separates based on polarity

Electrophoresis Separates biological macromolecules

(DNA/RNA/proteins) based on size
and sometimes charge

- pH = isoelectric point = protein

doesn’t move
- pH > I point = proton deprotonated

Simple distillation Separates liquids that boil below 150*

Vacuum distillation Separates liquids that boil ABOVE 150

(reduces pressure, lowering the BP of
liquids which prevents their
decomposition at high temps)

Fractional distillation Separates liquids that have similar BP

TLC Isolates individual compounds from

complex mixture

Orbitals
 n l Ml ms

Principle Azimuthal Magnetic spin

Electron shell Orbital (s,p,d,f) -l to +l Either +1/2 or -1/2

Which number
orbital

1, 2, 3….+ 0=s S only has 1

1=p P has 3
2=d D has 5
3=f F has 7

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Aromaticity

- cyclic
- every atom must have an AVAILABLE p orbital or be able to participate in resonance -
4n + 2 pi electrons (want odd number of bonds/lone pairs)
o Magic numbers: you want to count 2, 6, 10, 14, 18, 22 electrons (aka 1, 3,5,7,11
pairs)
o Which electrons count and which do not?
▪ If electrons cause it to be sp3 (so already bonded to 3 things w electrons) ▪
Bottom line: each atom on the ring can contribute ONE p orbital (either one
double bond or one lone pair)
- Must be flat (if will look like boat or chair conformation, it is not flat)

Bond angles/Shapes
Electron groups Lone pairs Shape Angles
 2 0 Linear 180

3 0 Trigonal planar 120

1 Bent Less than 120

4 0 tetrahedral 109.5

1 Trigonal pyramid Less than 109.5

2 Bent Even more less

than 109.5

5 0 Trigonal bypyramidal 90, 120

1 See saw

2 T Less than 90

3 linear 180

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Optical activity
- enantiomers have IDENTICAL physical properties except that they rotate plane polarized
light in equal and opposite direction

-
- Optically active = 2 chiral carbons (except meso, they are achiral)

Most acidic hydrogen:

- Will be removed by NaH
- Whatever is attached to very electronegative atoms (oxygen, sulfur, halogens) -
 Hydrogens attached to a positively charged nitrogen, oxygen, sulfur
o The high electronegativity makes them uncomfortable, so they want to diffuse
the positive charge to neighboring atoms by stealing electron density so the
hydrogens are losing electron density thus more positive = more acidic
- A hydrocarbon can be weakly acidic if the conjugate base is a STABLE ion -
More S character of the atom it is bonded to = more acidic hydrogen\ -
Between two carbonyl groups

Highest boiling point:

- IMF: h bonds are the strongest so will have highest BP
- If only carbons and hydrogens, whichever has less branching has higher BP. More
branching = lower BP

Solubility
- Highly acidic acids readily dissolve in base
- Solids dissolved in water become more soluble with increasing temperature - Gases
dissolved in water become less soluble with increasing temperature - Gases dissolved in
organic solvents become more soluble with increasing temperature - Gases increase in
solubility when increase in pressure (Henry’s law)
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Benzene with multiple substituents reactions:

- Friedel crafts cannot occur if the ring has a meta director or nitrogen on it
Halogenation, Sulfonation, Friedel crafts, Nitration, Formylation will react with the
substituent but anything else will be added to another spot on the ring

Kinetic product vs Thermodynamic product:

- Kinetic: Low temperature, low activation energy
o less stable/higher energy final product, comes from most stable carbocation
o Favored at low temp (-40*C or below)
- Thermo: high temp, high Ea
o More stable/lower energy final product
o favored at high temperature (0*C +)
o has the most substituted double bond

Rate of dehydration:
- the bulkier the alcohol, the faster it goes.
- 3* > 2* > 1

Protecting groups:
- Decreases reactivity so that the functional group doesn’t react under synthetic
 conditions
- TMS (trimethylsilyl is a good protecting groups
- Used for alcohols

Reactivity of certain reactions:

- Nucleophilic acyl substitution:
o “What is the easiest to remove and replace with a nucleophile?”
o C=O derivatives reactivity:
▪ Acyl chloride > anhydride > ester/carb acid > amide (aka the weakest
base, the one that is the most stable when it leaves, is the best leaving
group)
Reductions:
LiAlH4: reduces aldehydes, ketones, carboxylic acids, esters, amides, and nitriles
- C=O to -OH
- Amides: just removes the C=O
- Carboxylic acids: removes C=O
NaBH4: reduces aldehydes and ketone to alcohols and reduces acyl chlorides
DIBAL-H: reduces esters and amides and nitriles to aldehydes
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Oxidation
PCC: primary alcohol to aldehyde, secondary alcohol to ketone
H2CrO4: aldehydes, primary alcohols to carboxylic acids
KMnO4: aldehyde, primary alcohol, alkane on benzene to carboxylic acid - With heat: break a
double bond, put an oxygen on each end and convert to ketone or carboxylic acid
Grignard reagents:
- React as negatively charged carbanions
- Attack carboxylic acid derivatives
- They do not behave as nucleophiles in PROTIC solvents so they are in ether or THF
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Reactivity of carbonyls

Aldol addition:
- Product: beta hydroxy ketone or aldehyde
Aldol condensation:

Orbitals bonding energy from least to greatest energy:

Sigma, pi, pi antibonding, sigma antibonding
*sigma bonds are stronger than pi bonds so they have lower bonding energy and higher
antibonding energy

Homolytic bond dissociation energy

- Related to the strength of the bonds being broken and stability of the alkyl radical
formed.
- Less energy is required the weaker the bond and more stable the radical -
Remove hydrogen = radical then the More stable radical = smallest homolytic
dissociation energy
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Multiple substituents:
- More activating = faster EAS
- The strongest donating group gets priority when choosing location
- If choosing between ortho/para, it goes to the one with the least steric strain

Benzene derivatives to memorize

pKa’s for organic compounds
H3O+ -12

Carboxylic acid 5

NH4+ 10

Phenol 10

H2O 16

Spiro Alkanes
Spiro[a.b]parent name

1. Count total number of carbons = parent name

2. Number of carbons to the left = a
3. Number of carbons to the right = b

Spiro[a.b.c]parent name
1. A = to the left
2. B = to the right
3. C = above
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Sugars
- D vs. L (the way they polarize light)
- Look at bottom most OH.
 o Points right = D
o Points left = L
- Most carbs = D
- Most amino acids = L
Radical Halogenation
- Initiation: two radicals on right side
- Propagation: radicals on both sides
- Termination: two radicals on left side

Choosing which will react fastest/slowest with a sn1/sn2 reaction etc

- The more stable the carbocation formed during sn1, the faster it goes -
The less sterically hindered will have a faster sn2 reaction

Identifying the type of reaction

Claisen condensation Enolate + ester

Aldol Condensation Enol + carbonyl compound ->

conjugated diene

Alpha Deuteration All alpha hydrgens replaced with D

atom (D2O)

Fischer esterification Carboxylic acid + alcohol -> ester

Baeyer-Villiger Ketone + peroxy acid -> ester

Wolf Kishner carbonyl compound + H2NNH2 ->

double bonded nitrogen

Williamson ether Alkyl halide + alkoxide -> ether

Heck Reaction Organohalide + alkene -> substituted alkene

Suzuki Reaction Boronic acid + organohalide