Reactions (EAS) and adjacent ones

Br2/FeBr3 or Cl2/FeCl3

halogenation of benzene

HNO3/H2SO4

nitration of benzene (NO2)

SO3/H2SO4

Sulfonation of Benzene

RCl/AlCl3

Friedel-Crafts Alkylation

ClCOR/AlCl3

Friedel-Crafts Acylation

product of nitration of benzene

NO2

Product of sulfonation of benzene

SO3H

Limitations of Alkylation

1. Cannot alkylate rings with EWG

2. Rxn is hard to control, so will receive multiple alkylations on same molecule

3. Carbocation Rearrangement: may not get desired product

Limitations of acetylation

Can't react with EWG

CO, HCl/AlCl3, CuCl

add aldehyde to a ring

Zn(Hg), HCl

reduces carbonyl to alkane

1. Zn/HCl 2.NaOH

Reduces Nitro group to Amino

Is Ester an EWG or EDG?

EDG

Is alkoxide an EWG or EDG?

Strongly EDG

Is hydroxy an EWG or EDG?

EDG

is Amide an EWG or EDG?

EDG

is Amine an EWG or EDG?

Strongly EDG

is Methyl an EWG or EDG?

Weakly EDG

Is ethyl an EWG or EDG?

Weakly EDG

Is isopropyl an EWG or EDG

Weakly EDG

Is Carbonyl an EWG or EDG?

EWG

Is Sulfonyl an EWG or EDG?

EWG

Is cyano an EWG or EDG?

Strongly EWG

Is Nitro an EWG or EDG?

Strongly EWG

Is haloalkyl an EWG or EDG?

Strongly EWG

Is Ammonium an EWG or EDG?

Strongly EWG

Ph3P=CH2

WITTIG REAGENT

Reacts with either a Ketone or an aldehyde to create a carbon-carbon double bond

"Please make the double bond"

CH3CH2CH2Br in Witting

1st step used to create the Nuc used in Wittig Reaction by letting PPh3 perform backside attack

BuLi

2nd step used in making Nuc for Wittig reaction by deprotonating one of the closest hydrogens to PPH3

Major stero in Wittig Reaction

Trans

Pd(OAC)2 /PPh3, Et3N

Creates a c-c bond with a Halide and Double bond

Na2Cr2O7, H2SO4, Heat

Converts an alkyl group attached to benzene into a carboxylic acid (-COOH), provided the benzylic carbon has at least one hydrogen.

KMnO4, H2O, -OH/ 100C

Converts an alkyl group attached to benzene into a carboxylic acid (-COOH), provided the benzylic carbon has at least one hydrogen.

Note: If done to a cyclic sub, two carboxylic acids with form

SOCl2

convert carboxylic acids into acid chlorides and alcohols into alkyl chlorides.

Good for making Friedel-Crafts

LiAlH4, H3O+

Carboxylic acid to primary Alcohol

NH2NH2, KOH, heat

removes ketone from carbon chain (completely)

NaCN/H+ or -CN/HCN

Aldehyde to Hydroxynitrile

RNH2, H+ primary (1°) amine

ketone to imine

RNH2, H+ Secondary (2°) amine

N-R gets added and the double bond is placed allylic to it

2(CH3CH2OH)/H^+

The carbonyl group (C=O) is converted into a carbon bonded to two ethoxy groups (-OCH₂CH₃).

OHCH2CH2OH, H+

It converts an aldehyde or ketone into a five-membered cyclic acetal, protecting the carbonyl group.

Great to cover an aldehyde when wanting to perform a Grignard on a ketone.

How to get rid of Cyclic Acetal Formation or protecting group?

H3O+

1) LiAlH4

2) H3O+

Reduction: Reduces an aldehyde or ketone to an alcohol

H2, Pd cat.

Changes NO2 to NH2

Na, NH3 (liq.) EtOH

If Electron-donating group (EDG) then Substituted carbon remains sp²

If Electron-withdrawing group (EWG) then Substituted carbon becomes sp³

In NAS how to choose which LG to attack?

Pick LG that is Ortho or Para to EWG

When using Na, NH3 (liq.) EtOH on a compound with EWG and EDG: which one influences the reaction?

Whichever group is stronger

In Diels-Alder, when the dienophile has cis substituents, what stereochemistry do they have in the product?

Cis

In Diels-Alder, when the dienophile has trans substituents, what stereochemistry do they have in the product?

trans

In Diels-Alder, when the diene has IN group substituents, what stereochemistry do they have in the product?

Both IN groups are cis to each other

In Diels-Alder, when the diene has OUT group substituents, what stereochemistry do they have in the product?

Both OUT groups are cis to each other

NaOCH3, NaOH

Typical reagent for Addition-Elimination

(Looks like SN2)

NaNH2, NH3

Typical reagent for Elimination-Addition

Required Elimination-Addition conditions

No activating EWG required; ortho H needed and strong Base

Required Addition-Elimination conditions

Strong EWG ortho/para to leaving group

In NAS which step kicks off the LG?

Elimination

BuLi

Removes a Hydrogen and replaces it with Negative charge