SN1, SN2, E1, E2

What kind of nucleophile do we use for SN2?

Strong base

i.e. negative charge like OH-

What kind of nucleophile do we use for SN1?

Weak base is okay

i.e. CH3OH is weak bc OH does not have a charge bc it is not an ionic bond as in NaOH

What kind of product do we get for SN2?

Inversion due to backside attack (if we have chiral center)

What kind of product do we get for SN1?

Racemization; mixture of both dash/wedge (if we have chiral center)

What kind of solvents must we use for SN1?

Requires protic to stabilize the carbocation

i.e. water, alcohol, carboxylic acids

What kind of solvents do we use for SN2?

Aprotic solvents (sometimes polar protic is okay)

Acetone, DMF, DMSO, acetonitrile, ether

What type of electrophile reacts the best in SN1?

3>2

bc we want to the most stable carbocation arrangement possible

What type of electrophile reacts the best in SN2?

1>2>3

bc we want to minimize steric hindrance of backside attack

What is the rate law for SN2 reactions?

rate = k [Nu][E]

What is the rate law for SN1 reactions?

rate = k [E]

What is the ideal Leaving group for SN1/SN2 reactions?

F < Cl < Br

What are the two exceptions to Anti-Zaitsev rule?

Durinig E2 reactions:

1. Bulky base- least substituted alkene

2. Cyclohexane- the LG and H must be TRANS to each other (to form concerted anticoplanar mechanism), which may sometimes lead to the least substituted alkene

What is an E2 elimination?

Forms an alkene in an anticoplanar mechanism

HBr + alkene

HCl + alkene

HI + alkene

Markovnikov addn of Br and H. BR on most subbed

Possible CC rearrangement

Acid in Water...

H2SO4/H2O aka H3O+

Markovnikov addn of H and OH. OH on most subbed.

Possible CC rearrangement

Acid in Alcohol...

H+/ROH

Markovnikov addn of H and OR-. OR on most subbed

Possible CC rearrangement

What are the 3 possible carbocation rearrangements?

HBr/H2O

H3O+ .. acid in water

H+/ROH .. acid in alcohol

Br2/CCl4

Cl2/CCl4

Backside attack causing Markovnikon anti addn of Br and Br

Br2/H2O

Cl2/H2O

Markovnikov anti addn of Br and OH. OH on most subbed

Br2/ROH

Markovnikov anti addn of Br and RO-. RO on most subbed

oxymercuration-demurcuration

what are the reactants?

1. Hg(OAc)2, H2O or ROH

2. NABH4

Anti addition of H and OH or OR-

Markovnikov

Hydroboration-oxidation

reactants?

1. BH3, THF (B2H6)

2. H2O2, OH-, H2O

Anti Markovnikov, Syn addn of H and OH

Catalytic hydrogenation

1. H2

2. Pd/C or Pt/C or Ni

Syn addn of H and H

HBr/ROOR

Antimarkovnikov addn of Br and H

Peracid + alkene

1. MCPBA + alkene = epoxide

2. H3O+

Anti addn of OH and OH

Alkene --> 2 alcohols

1. OsO4

2. H2O2

or

1. KMnO4 (cold, dilute)

2. OH-

Syn addn of OH and OH

Oxidative cleavage, oxidizing conditions

1. KMnO4 (hot, concentrated)

2. H3O+

1. O3

2. H2O2

Break double bond, add in carbonyl group. Aldehydes become COOH. Ketones remain ketones

Oxidative cleavage, reducing conditions

1. O3

2. Zn/H2

1. O3

2. (CH3)2S

break double bond, add carbonyl, aldehyde stays aldehyde.

Alkyne

How do we reduce an alkyne ---> alkane

1. H2

2. Pd/C

Alkyne

How do we reduce an alykne ---> cis alkene

1. H2

2. Lindlars

Alkyne

How do we reduce an alkyne ---> trans alkene

1. Na or Li

2. NH3 (l)

What is a Grignard Reagent used for?

To create carbon-carbon bonds to extend carbon chain length! A Grignard is a very strong carbon nucleophile made from organometallic reagents. Grignards CANNOT react with anything protic (i.e. has an H bonded to F, O, N) because it will act as a base and deprotonate the acid and no reaction will occur.

R--X + Mg in ether or THF ---> R---MgX

Grignards can react with....

1. Carbonyls (ketones)

2. Allylic or benzylic halide

3. Epoxides (attaches to least substituted side if not in acid)

What is an acetylide ion and what is it used for?

An acetylide ion is a strong nucleophile that is made by deprotonating an alkyne used to create carbon-carbon bonds to extend carbon chain length!

Alkyne + NaNH2 in NH3 (l) --> acetylide ion

Acetylide can react with

1. Alkyl halide

2. Carbonyl (ketones)

3. Epoxide (adds to least subbed side if not in acid)

To which side do we attack an epoxide in acid? Not in acid?

In acid, epoxides get a (+) charge, which make them carbocation like. We must attack the most substituted side because of stability.

Not in acid, epoxides must be attacked by backside attack at the point with the least steric hindrance, the least substituted side

Hydroboration- oxidation of an alkyne...

Reagents

1. (Sia)2BH, THF

2. H2O2, OH-, H2O

Anti-Markovnikov addn

Tautomerization of enol --> aldehyde (final product)

Addition of H2O to an alkyne can create...

Ketones!

Hydration of Alkyne (Addition of H2O)

Reagents

1. H2SO4 (or H+ in H2O, or H3O+)

2. HgSO4 (alkynes require Hg as a catalyst!)

OH attaches Markovnikov to form an enol product that tautomerizes into a ketone

Alkene + Br2/hv yields...?

You get 2 products:

1. 2 Br added in anti addn to the alkene (exactly as in Br2/CCl4)

2. Allylic Bromination

How do we brominate at the allylic position of an alkene?

We use:

1. NBS

2. hv or heat or ROOR

Free Radical Halogenation

Initiation:

Start the radical party by forming radical from halogen

Propagation:

Radicals recruit more radicals to join the party

Termination:

Radicals join together to form a nonradical product

What are the requirements to be aromatic?

1. Cyclic and Conjugated

2. No sp3 hybridized orbitals

3. Planar (7 or less atoms)

4. Odd number of pairs of pi electrons

What are the requirements of being aromatic?

Must pass rules 1-3 and have even number of pairs of pi electrons

What are the requirements of being nonaromatic?

Does not satisfy at least one or more of rules 1-3

When do you count lone pairs of electrons and when do you not in determining aromaticity?

Count lone pairs of electrons- When they are not near a double bond, the lone electrons are responsible for resonance of the structure, which contributes to the pi system

Do not count lone pairs of electrons- When they are near a double bond, the double bond system provides the pi electrons and we do not count the lone pair as part of the pi system

1. KMnO4, OH-, heat

2. H3O+

or

Na2Cr2O7/H2SO4

is used for...

Benzylic Oxidation

Oxidizes benzylic carbons COMPLETELY to -COOH. If the benzylic carbon is attached to another 50 carbon chain, that chain is gone and it is simply a -COOH. The benzylic carbon MUST have a benzylic hydrogen, or else it will not oxidize to COOH and remain the same.

Clemmenson

1. Zn (Hg)

2. HCl, H2O

Wolff-Kishner

1. H2NNH2

2. OH-, heat

is used for...

Benzylic Reduction

Reduces benzylic aldehydes/ketones completely (removes the carbonyl group and replaces with H). Often, the Benzylic aldehyde/ketone is a product of Friedal-Crafts Acylation and it is useful to reduce it!

Electrophilic Aromatic Substitution

Substituting a benzene's hydrogen for an electrophile.

Therefore, benzene is a very weak nucleophile and it is getting attacked by a strong postively charged electrophile

What is Friedal-Craft Alkylation?

Benzene + RX or ROH with AlCl3/FeBr3/AgNo3 catalyst

Benzene ring with R or OR- group attached to it. Possible Carbocation rearrangment SO BE CAREFUL!

What is Friedal-Craft Acylation?

Benzene + carbonyl electrophile

Benzylic aldehyde/ketone

Electron DONATING groups

Electron rich species that:

stabilize cations (electrophiles) --> less reactive --> weaker

destabilize anions (nucleophiles) --> more reactive --> stronger

NH2, NHR, OH, OR, ---R (methyl groups)

Electron WITHDRAWING groups

Electron poor species that:

stabilize anions (nucleophiles) --> less reactive --> weaker

destabilize cations (electrophiles) --> more reactive --> stronger

Examples:

Halogens, Carbonyls, SO3H, C-triple-N, NO2, N(+)R3

What are the Ortho/para directors (1,3) for EAS?

Activating (electron donating groups) + the halogens

NH2, NHR, OH, OR, ---R, halogens

What are the meta directors for EAS?

Deactivating (electron withdrawing groups) - the halogens

Carbonyls, SO3H, C-triple-N, NO2, N(+)R3

If a benzene has both a donating and withdrawing group on it, which one directs an incoming substituent?

The donating ALWAYS wins! So we direct in ortho/para position.

If you have 2 donating groups on a benzene ring, which one directs an incoming substituent?

The one that is the more donating one wins. How do we know? The one that is the LEAST ELECTRONEGATIVE is the MOST donating to the benzene (nucleophile), causing it to become LESS STABLE, and thus, MORE REACTIVE.

How do we extend carbon chain lengths? i.e. create carbon-carbon bonds

Grignard/organolithium or acetylide ion

List the carboxylic derivatives from most reactive to least reactive...

acid chloride> anhydride> ester > amide > carboxylate

Which of the following would react the fastest with OH- ?

acid chloride would bc it has the best LVG.

Carboxylic Acid derivatives react with H2O/OH- to produce...

carboxylate ion

COOH derivatives react with H3O+ to produce...

carboxylic acid

Williamson Ether synthesis

Alkoxide + primary/secondary halide

To make an alkoxide: alcohol + NaH

Ethers only react with....

XS HBr...

Creates 2 halides

What is Chromic Acid used for?

Stronger than PCC.

Oxidizes secondary alcohols to ketones

Oxidizes aldehydes and alcohols to COOH

What is PCC used for?

Oxidizes primary alcohol to aldehyde

oxidizes secondary alcohol to ketone

What do alcohols usually react with and why?

OH is a poor leaving group, so most of the time, alcohols react with halides to create good LVG.

H-X (SN1 for secondary, tertiary; SN2 for primary)

PBr/pyridine

SOCl2/pyridine

TsCl/pyridine

Alcohol dehydration

H2SO4. Loses water to form an alkene