Organic Chemistry II Final Review

Kinetic Product = ?

Thermodynamic Product = ?

-Kinetic product is the one that forms at the fastest rate (from lowest energy transition state, look at carbocation)

-Thermodynamic product is the most stable final product (look at substitution around double bond)

Diels Alder Reaction

-reagent?

-accelerated by ___ on diene and ___ on dienophile

-endo or exo?

-heat

-accelerated by EDG on diene and EWG on dienophile

-in bicyclic products, always get the endo product where bridge points away from the substituents

EDG or EWG?

a) -NR C=O R2

b) -CN

c) -NR1R2

d) -NO2

e) Br

a) EDG

b) EWG

c) EDG

d) EWG

e) EWG but directs ortho, para

What effect does it have on ortho, meta, para positions?

-Electron donating group

-Electron withdrawing group

-EDG: slight negative on ortho, para (direct electrophiles ortho, para)

-EWG: slight positive on ortho, para (direct meta)

Huckel's criteria for Aromatic Compounds (4)

1. Cyclic

2. Have one p-orbital on each ring atom

3. planar

4. Have 4n + 2 electrons in p-orbitals where n is a whole number

Cl2, FeCl3

Br2, FeBr3

Add Cl or Br to aromatic ring (Chlorination or Bromination)

(Mechanism: Cl+, FeCl4-, electrophilic addition, byproducts: HCl, FeCl3)

HNO3, H2SO4

Add NO2 to aromatic ring (Nitration)

(Mechanism: NO2+, electrophilic addition)

SO3, H2SO4

Add SO3H to aromatic ring (Sulfonation)

R C=O Cl

AlCl3

Friedel Crafts Acylation

RCl

AlCl3

Friedel Crafts Alkylation

N2H4, KOH

Wolff-Kishner reduction, reduce ketone to CH2 group

H2, Ni

Reduction of Nitro to Amino Group (NO2 --> NH2)

Draw Benzene, Pyridine, Pyrrole, Furan, Thiophene

Look online.

1. R-Mg-X (Grignard)

2. HCl, H2O

Grignard, Attack the carbonyl carbon and add new C-C bond, protonation of oxygen to form alcohol after

1. R-X + 2 Li

2. HCl, H2O

Organolithium reaction, attack carbonyl carbon and add new C-C bonds, protonation of oxygen to form alcohol after

Starting: R-Br

1) PPh3

2) nBuLi

3) R2C=O

Wittig Reagent (R2C = PPh3), reacts with carbonyl carbon

1,2) React with R1-X to make R-PPh3

3) PPh3 replaced by R1=CR2 (R1 added where =O was)

R-NH2 + aldehyde or ketone + H+(cat)

Nitrogen Nucleophiles to Aldehydes and Ketones

Primary Amine = Imine (C=O converts to C-NR, deprotonation turns to C=NR)

Secondary Amine = Enamine (same except deprotonation happens on hydrogen on alpha carbon next to carbonyl)

ROH (alcohol) + Aldehyde

Addition of Oxygen Nucleophiles to Aldehyes and Ketones, (Alcohols are too weak to attack carbonyl group by themselves, acid catalyst used to attach onto carbonyl oxygen) (Mechanism: Protonation, R-OH attacks, Hemiacetal, water leaves, R-OH attacks again, acetal)

End Result: R-OH + C=O to RO-C-OR (acetal)

1. 1,2 Diols + Aldehyde or Ketone, H+ (cat)

2. HCl, H2O

1. Protecting Group for C=O

2. Deprotection

Chromic Acid H2CrO4

Strong Oxidation (primary OH--> COOH, aldehyde --> COOH, secondary OH --> ketone)

PCC

Mild Oxidation (Primary OH --> aldehyde, and secondary alcohol --> ketone, no rxn with aldehyde)

H2/Pt or H2/Ni

Catalytic Reduction (reduces both C=C (to C-C) and C=O (to OH)- only aldehydes, not COOH)

H2/Rh

Selectively reduces C=C bonds

NaBH4/ EtOH

Reduction, Reduces ketones and aldehydes to OH

1) LiAlH4 2) H+, H2O

Superreducer, Reduces everything to OH (not C=C bonds)

R- Aldehyde + NaOH, H2O

Aldol Product (ketone + alcohol) --> Dehydration Product

(Mechanism: alpha carbon of aldehyde deprotonated by OH-, attacks another aldehyde, alkoxide turns to OH b/c of H2O, remove hydrogen in between C=O and C-OH, enolate eliminates hydroxide anion creating a carbon double bond)

Starting Compound: Two Ketones or Aldehydes or Mix, one alpha hydrogen, 3 or 4 atoms separating alpha carbon of one carbonyl carbon from another

Intramolecular Aldol Reaction

Starting: R-Aldehyde or Ketone

Reagent: 1) LDA 2) Aldehyde-R 3) H2O

Directed Aldol Reaction (Favor formation of enolate on less substituted carbon)

Starting: Enolate (LDA and R-Aldehyde or Ketone)

Reagent: R-X

Reaction of Lithium (LDA) Enolates with Alkyl Halides (SN2, R adds onto negative charge on enolate)

alpha, beta unsaturated aldehyde, ketone

1. What nucleophiles attack at C=O?

2. What nucleophiles attack at beta carbon?

1. R-Li and R-MgBr strong enough to interact with carbonyl carbon

2. Enolates, Gilman Reagents, and Amines interact with beta carbon

Starting: Enolate (LDA and R-Aldehyde or Ketone)

Reagent: Alpha-beta unsaturated ketone

Michael Reaction: generate 1,5-diketone

(in pic: Nu is enolate)

a) 1,3-diketone with at least one alpha-hydrogen in between two ketones

b) alpha-beta unsaturated ketone

c) moderate base like NaOH

Robinson Annulation: Base-catalyzed Michael reaction, intramolecular base-catalyzed aldol reaction and dehydration for final product

Starting: alpha beta unsaturated compound

1) (R)2CuLi, -78 C

2) H2O

Gilman Reagent with alpha-beta unsaturated carbonyl compound

(Details: add just ONE R to beta carbon)

Starting: alpha beta unsaturated compound

Reagent: R1R2NH (ex. (CH3)2NH)

Reaction of Amines with alpha-beta unsaturated carbonyl compound

(Details: NR1R2 added to beta carbon)

Chemical Shifts of important protons (ppm)

1) Aldehyde

2) Carboxylic Acid

3) Aromatic Protons

IR stretches

4) C=O

5) OH

1) 9.5-10.1

2) 10-13

3) 6.5-8

4) 1700

5) 2400-2400

Factors Contributing to Acidity of the Carboxylic Acid

a) Electronegativity

b) Number of Substituents

c) Location of Subtituent

a) more electronegative (Br=EWG) = more acidic

b) number of EWGs up = more acidic

c) closer EWG is to carboxylic acid group = more acidic

Starting Material = Aromatic Ring

KMnO4

Oxidation of Benzylic Carbons (carbon bonded directly to a benzene ring)

Starting: R-Li or R-MgBr

1) CO2 2) HCl, H2O

R-Carboxylic Acid

Carboxylic Acid + Alcohol

H+ (cat)

Fischer Esterification- Ester

(Mechanism: Protonation of Carbonyl Oxygen, Attack by ROH, Water Leaves, Formation of Ester) (Replace H with R on OH of COOH)

1. Carboxylic Acids undergo ____ with nucleophiles.

2. Ketones and Aldehydes undergo ____ with nucleophiles.

1. Addition then elimination

2. Addition then protonation

Reactivity Order of Carboxylic Acid Derivatives

Acid Chloride > Anhydride > Ester > Amide

Convert Carboxylic Acid to Acid Chloride

SOCl2 (Thionyl Chloride), pyridine

Acid Chloride + Carboxylate Salt, pyridine = ?

Anhydride, pyridine

Acid Chloride + R-OH, H+ = ?

Ester (Fischer esterification)

Acid Chloride + Amine, pyridine = ?

Amide

Convert Carboxylic Acid to Anhydride

R C=O Cl

Convert:

1) Anhydride to Ester

2) Anhydride to Amide

1) Alcohol, pyridine

2) Amine, pyridine

Convert Ester to Amide

Amine, pyridine

Convert Carboxylic Acid to Amide Directly

Amine, DCC

Starting: Ester

Reagents: 1) NaOH, H2O 2) HCl

Hydrolysis of Esters in Basic Conditions (OH-)

Convert Ester to Carboxylic Acid

(Mechanism: OH- attacks carbonyl carbon, elimination of OR-, deprotonation by OR-, protonation by HCl)

Starting: Ester

Reagents: H+ cat, H2O

Hydrolysis of Esters in Acidic Conditions

Convert Ester to Carboxylic Acid

(Mechanism: protonation of carbonyl oxygen, addition of H2O, protonation of OR, HOR leaves)

Starting: Amide

Reagents: H+ cat, H2O OR

NaOH, H2O

Hydrolysis of Amides in Basic or Acid Conditions

Convert Amides to Carboxylic Acid

(Mechanism Acid: Protonation of Carbonyl Oxygen, Addition of H2O, Protonation of NHR, NH2R leaves, Deprotonation to form COOH)

(Mechanism Basic: OH- attacks carbonyl caron, NHR leaving group, deprotonation by NHR)

Polyesters are formed from ____ and _____.

alcohol

carboxylic acid, acid chloride, or anhydride

Polycarbonates are formed from _____ and ______.

Phosgene Cl C=O Cl and 2 ROH or diol (HO-R-OH)

Polyamides are formed from ____ and _____.

amine

carboxylic acid, acid chloride, anhydride, or ester

Starting Chemical Synthesis of Polypeptide

Bead-Ch2Cl

Attach COOH to the Bead?

K2CO3 (deprotonates COOH, and attaches to Bead-Ch2Cl, displacing Cl)

1. Amine Protecting Group

2. Removal of Amine Protecting Group

3. Coupling Reaction (activation of COOH)

1. BOC

2. TFA (RNHBoc --> RNH2)

3. DCC

HF

cleavage of peptide from bead, bead-CH2-F

Starting: Ester

1) R-MgBr (2 equiv.)

2) HCl, H2O

Reaction of Esters with Grignard and Organolithium Reagents

(Effect: Ester (R C=O OR), C=O --> C-OH, OR' leaves and replaced by two R from R-MgBr)

Starting: Acid Chloride

1) (R)2CuLi -78 C

2) H2O

Reaction of Acid Chlorides with Gilman Reagents

(Effect: Cl replaced by one R from (R)2CuLi)

Starting: Ester

1) LiAlH4

2) HCl, H2O

Reduction of Esters and Amides by Hydride Reagents

RC=OOR --> RCOH

1) DIBALH, -78 C

2) H2O

Conversion of Ester to Aldehyde

Starting: Amide

1) LiAlH4

2) HCl, H2O

Reduction of Amides with LiAlH4 converts Amide to amine (gets rid of =O)