Orgo 2 EAS

Halogenation Br

Br2, FeBr3

Halogenation Cl

Cl2, AlCl3

Nitration

HNO3 / H2SO4

Sulfonation

H2S04, heat

Friedal Crafts Alcylaltion

O=C < Cl, AlCl3

Friedel Crafts Alcylation Rules

• Avoid having nitro groups and SO3H groups on the ring during this step

• No carbocation rearrangements

Friedel Crafts Alkylcation

/\ Cl and AlCl3

Friedel-Crafts Alkylation Rules

• Avoid having nitro groups and SO3H groups on the ring during this step

• be careful of carbocation rearrangements with linear chains having more than 2 carbons

Wolff Kischner Transformation

NH2MNH2, -OH, Heat

Clemmensen Reduction

Zn (Hg), HCl

Removal of the SO3H group

H3O+ / H2O

Conversion of nitrobenzene to aniline pt 2

H2, Pd/C

Conversion of nitrobenzene to aniline pt 1

SnCl2, HCl

SNAR reaction

OR

SNAR reaction rules

• Works best if the ring contains additional electron-withdrawing groups, particularly NO2 and SO3H

• addition, elimination

formation of diazonium

NaNO2, HCl

Activating groups

• ortho, para directing

• acid

• has e-donating groups directly connected to ring

• includes halogens (F, Cl, etc) but are weak

• includes alkyl groups (methyl, ethyl, isopropyl, etc) but are weak

• NH2, OH, etc

Deactivating groups

• meta directing

• base

• electron-withdrawing groups

• e- donating groups NOT directly connected

• SO3H, NO2, +NH2, +NH2R

two substituents on ring and reinforce each other

third substituent mutually formed position

if substituents present on the ring direct incoming electrophile to different positions

the STRONGER activator wins

avoid overcrowding

sterics

mechanism of SNAR step 1

• sulfur has lone pair and negative charge

• attacks pi bond on ring bearing F

mechanism of SNAR step 2

• resonance of lone pair of e-

• because pi bond got kicked off, that e- resonance kicks off F to restore aromaticity

mechanism of EAS - Friedel Crafts

dont answer

mechanism of EAS Friedel Crafts step 1a

Cl’s lone pair attacks Al on AlCl3

generation of electrophile

mechanism of EAS Friedel Crafts step 1b

+Cl—-AlCl3 leaves to form carbocation

mechanism of EAS Friedel Crafts step 2a

pi bond on ring attacks carbocation on electrophile

EAS reaction

mechanism of EAS Friedel Crafts step 2b

acid attacks H —> H attacks carbocation —> restores pi bond and aromaticity

addition of strong negatively charged nucleophiles

grignard, organolithium reagent, hydride, wittig reaction, preparation of wittig reagent

Grignard

1. \/\ MgBr, Et2O

2. H3O+/H2O

3. recall that the protonated alcohol is formed after aqueous workup

Organolithium Reagent

1. \/\ Li, Et2O

2. H3O+/H2O

Hydride NaBh4

1. NaBH4, MeOH

2. H3O+/H2O

3. will reduce aldehyde or ketone

Hydride LiAlH4

1. LiAlH4

2. H3O+/H2O

3. stronger than NaBH4 hydride

4. If alcohols are present on the substrate, they will be deprotonated with LiAlH4

Wittig reaction

addition followed by immediate elimination

preparation of wittig reagent step 1

PPh3

preparation of wittig reaget step 2

BuLi

addition of nitrogen nucleophiles

primary amines - imine, secondary amine - enamine, reductive amination - amine from imine

primary amines: formation of imines

CH3NH2, catalytic acid

secondary amines: formation of enamines

H3C — NH —CH3, catalytic acid

reductive amination: formation of amine from imine step 1

(+) NH2 — H2C — CH3

reductive amination: formation of amine from imine step 2

NaCNBH3

addition of oxygen nucleophiles

hydrates, hemicacetals, acentals, ketals, acetal hydrolysis

water: formation of hydrates

H2O / HA

alcohols: formation of hemiacetal/hemiketal

CH3OH, HA

alcohols: formation of acetal/product

CH3OH, HA

acetal hydrolysis

H3O+ / H2O

conversion of alkene to markovnikov halide

HBr or HCl

conversion of an alkene to markovnikov alcohol

H3O+ / H2O

conversion of an alkene to an anti-markovnikov alcohol

1. BH3, THF

2. H2O2, NaOH

conversion of alcohol to halide Br

PBr3

coversion of alcohol to halide Cl

SOCl2

conversion of alcohol or halide to alkene by elimination E2

KOtBu

conversion of alcohol or halide to alkene by elimination E1

H2SO4, Heat

conversion of alcohol to ether: williamson synthesis

1. Na or NaH

2. CH3Br

conversion of halide to nucelophillic carbon anion grignard

Mg, Et2O

conversion of halide to nucelophillic carbon anion organolithium

Li, THF

oxidation of alcohol to aldehyde

PCC

oxidation of alcohol to ketone

PCC

oxidarion of primary alcohol to acid

H2CrO4

conversion of carboxylic acid to acid chloride

SOCl2

Grignard Mechanism Step 1

• negatively charged nucleophile will attack at the carbon of the carbonyl

• push the electrons up to oxygen

Grignard mechanism step 2

1. the negatively charged oxygen will attack H-A

2. will go through H3O+ workup
   
   

Grignard mechanism product

OH and R next to each other

hydride mechanism step 1

1. negatively charged LiAlH4 will attack at the carbon on the carbonyl

2. push the electrons up to oxygen

hydride mechanism step 2

1. negatively charged will attack H-A

2. will go through H3O+ workup

hydride mechanism product

OH and H next to each other

Wittig reaction mechanism step 1

1. carbon of the ylide has a negative charge and attacks carbon of the carbonyl

2. oxygen has a strong affinity for phosphorus

3. they form a bond, making a four membered ring

Wittig reaction mechanism step 2

1. the bond of the oxygen farthest from the Ph3P attacks Ph3P

2. that causes the bond of the Ph3P to its neighboring substituent to attack its next neighboring bond

3. four membered ring open

Witting reaction mechanism product

addition of primary amine to form imine mechanism step 1

1. lone pair on nitrogen attack the carbon of the carbonyl

2. pushes the electrons up to oxygen

addition of primary amine to form imine mechanism step 2

negative charged oxygen attacks H-A and gets protonated

addition of primary amine to form imine mechanism step 3

acid attacks H connected to positvely charge nitrogen, which makes nitrogen lose that postive charge

addition of primary amine to form imine mechanism step 4

lone pair on oxygen of OH attacks H-A to create OH2+, a good leaving group

addition of primary amine to form imine mechanism step 5

lone pair on nitrogen helps the OH2+ leave

driving force of reaction

addition of primary amine to form imine mechanism step 6

• acid attacks the H connected to the nitrogen, removing the nitrogen of its positive charge

• two possible structures for the imminum ion

addition of primary amine to form imine mechanism product

addition of secondary amine to form enamine step 1

1. lone pair of nitrogen attacks at the carbon of the carbonyl

2. pushes the electrons UP to oxygen

addition of secondary amine to form enamine step 2

lone pair of negatively charged oxygen attacks H-A to become protonated

addition of secondary amine to form enamine step 3

acid attacks H connected to Nitrogen, removing its positive charge

addition of secondary amine to form enamine step 4

lone pair of OH attacks H-A to become water, good leaving group

addition of secondary amine to form enamine step 5

lone pair of nitrogen helps water leave

addition of secondary amine to form enamine step 6

• acid attacks H two carbons away from nitrogen

• helps nitrogen lose double bond and positive charge

• there are two possible resonance structure for the imminium ion

addition of secondary amine to form enamine product

hemicetal formation mechanism step 1

1. oxygen lone pair attacks H-A to get protonated

2. must protonate carbonyl before adding neutral oxygen nucleophile

hemicetal formation mechanism step 2

• lone pair of OH attacks the carbon at the carbonyl, removing the double bond and postive charge of oxygen in the carbonyl

• two resoance structures for the protonated carbonyl, explains why the carbon is more electrophillic

• we are in acidic conditions, NO oxygen minus in these mechanisms

hemicetal formation mechanism step 3

acid attacks the H attached to O, deprotonating and removing the positive charge of O

hemicetal formation mechanism product

acetal/ketal formation mechanism step 1

• lone pair on oxygen attacks H-A to get protonated

• must protonate carbonul before adding neutral oxygen nucleophile

acetal/ketal formation mechanism step 2

• lone pair on ROH attacks the carbon at the carbonyl, removing the oxygen’s double bond and positive charge

• two resonance structures

• no negative charged oxygens

acetal/ketal formation mechanism step 3

• acid attacks the H connected to the OR to remove its positive charge

• we must neutralize exisitng positive charge before we form the good leaving group

acetal/ketal formation mechanism step 4

• lone pair of OH attacks H-A to become H2O, good leaving group

acetal/ketal formation mechanism step 5

lone pair on OR helped water leave

acetal/ketal formation mechanism step 6

ROH attacks the carbon at the carbonyl once again to remove the double bond and positive charge of OR

acetal/ketal formation mechanism step 7

acid attacks the H connected to the newer OR to remove the its positive charge

acetal/ketal formation mechanism product

OR and OR across from each other

acetal/ketal hydrolysis mechanism step 1

lone pair on OR attacks H-A to protonate and form good leaving

acetal/ketal hydrolysis mechanism step 2

the lone pair on the other OR kicks off the positively charged HOR

acetal/ketal hydrolysis mechanism step 3

HOH attacks the carbon and the carbonyl to remove the double bond and positive charge of OR

acetal/ketal hydrolysis mechanism step 4

acid attacks the H of the HOH and removes the H bond and positive charge of OH

acetal/ketal hydrolysis mechanism step 5

lone pair on OR attacks H-A to get protonated and form good leaving group