Organic Chemistry 2 Exam

Williamson Ether Synthesis

• SN2 Reaction (less steric hindrance)

• Does NOT work for 2° & 3° alkyl halides (meaning they can not be bonded to 2 or 3 other carbons)

Step 1: Deprotonate with a base (typically NaH)

Step 2: Alkoxide SN2 Reaction (Nucleophilic attack)

Intramolecular Williamson Ether Reaction

Same rules as before, but for the creation of a ring

Peroxyacid Epoxidation

• 1-step reaction using mCPBA or MMPP

• Solvents: CH2Cl2, CHCl3, Benzene (aprotic)

• The reaction is stereospecific —> syn addition (addition to the same face). Cis = both bonds are the same; trans = bonds are different

Cyclization of Halohydrins

• Same rules as before

Step 1: Add Halogen and water solvents to create a halohydrin

Step 2: Add a base (NaH or NaOH), which creates an SN2 reaction, creating an epoxide

Nucleophiles

• Has a lot of lone pairs/negative charge

• Donate electrons

• Lewis base

• Examples: I-, H2O, -OH, NH3

Electrophiles

• Positively charged

• Seek out electrons

• Lewis acid

• Examples: H+, Fe3+, +CH3

• Some may not have a positive charge, but can accept a pair of electrons

• Examples: FeBr3, BH3, AlCl3

Conjugation

• Double/triple bonds (any atoms)

• Heteroatoms bearing a lone pair in a p orbital

• Carbon bearing a lone pair in a p orbital

• Trigonal carbocations + other six-electron atoms

Aromaticity

• Cyclic

• No sp3

• Conjugated

• Planar

• Aromatic: 4n + 2

• Antiaromatic: 4n

• Nonaromatic: Does not fit either rule

• IMPORTANT: Double bond connected to a molecule INSIDE of a ring or OUTSIDE of a ring cant participate in resonance, so the lone pairs are not counted.

EAS Activated Groups (ORTHO-PARA) —> FOR NAS, THESE ARE DEACTIVATING

• More Nu:

Examples:

• -NR2 (R = anything)

• -OR

• -R (R = alkyl)

EAS Deactivated Groups (META) —> FOR NAS, THESE ARE ACTIVATING

• Less Nu:

• EXCEPTION: -X (X = F, Cl, Br, I) ORTHO PARA

Examples:

• =O-R

• -CN

• -SO3H

• -CF3

• -NO2

Ortho, Meta & Para

Ortho: Position two bonds away from FG of interest

Meta: Position 3 bonds away from FG of interest

Para: Position opposite from FG of interest

*Functional group of interest is usually the electron DONATING group in EAS and the electron WITHDRAWING group in NAS

Halogenation - Bromination (O/P)

The starting product is an H on a benzene ring

• Br2 + FeBr3 —> -Br

Halogination - Chlorination (O/P)

The starting product is an H on a benzene ring

• Cl + AlCl3 —> -Cl

Sulfonylation (M)

The starting product is an H on a benzene ring

• SO3 + H2SO4 —> -SO3H

Nitration (M)

The starting product is an H on a benzene ring on the bottom right

• HNO3 + H2SO4 —> -NO2

Friedel-Crafts Acylation (M)

The starting product is an H on a benzene ring on the top left

AlCl3 + R-C=O-Cl —> R-C=O-

Clemmenson Reduction (O/P)

The starting product has a ketone, which turns into two H’s

Zn (Hg) + Hal (aq) —> two H’s sticking out

• Can turn C=O into CH2 AND NO2 into NH2

Amine Reduction (O/P)

The starting product is an H on a benzene ring

• 1.) HNO3, H2SO4; 2.) H2, Pd/C, EtOH —> NH2

• *H2, Pd/C can also turn an NO2 into an NH2

Nucleophilic Aromatic Substitution

• SNAR —> Aromatic ring here acts as an electrophile and is attacked by the nucleophile

• NOT SN2 (too much steric hindrance)

• Example: Br at the top position of the benzene ring + H20 —> Turns into OH

• Common nucleophiles: NaNH2, NaOH, NaOCH3

Diazoniums

The starting product is a benzene ring with NH2 at the bottom right position

• NaNO2 + HCl —> N+-=-N Cl-

Synthesis with Diazonium

The starting product is a benzene ring with the N+-=-N Cl- at the bottom-right position

• KI —> I

• H2O —> OH

• CuCN —> C-=-N

• Na+B-F4 —> F

Suzuki Catalytic Cycle

Starting products are benzene with X at the top-right position (X = halide) + benzene with B-OH-OH at the top-right position

• Cat. Pd(PPhs)2 + Ligand (PPh3) —> Two benzene rings attached to each other

Heck Reaction

Starting products are benzene with X at the top-right position (X = halide) + alkene with an electron-withdrawing group

• Cat. Pd(PPh3)2 + Base (Et3N) —> Benzene attached with alkene and EWG

C-N Cross Coupling

Starting products are benzene with X at the top-right position (X = halide) + H-NR2 (primary: one carbon/secondary: two carbons)

• Cat. Pd(PPh3)2 + KotBu —> -NR2

ELECTRON DONATING GROUPS (O/P)

Pi donors

• -NH2

• -NR2

• -OH

• -OR

• -H-N-C=O-R

Sigma donors

• -R (e.g. ethane)

• Benzene

ELECTRON WITHDRAWING GROUPS (M)

Weak

• Halogens

Moderate

• Carbonyls

Strong:

• -SO3H

• -CN

• NO2

• NR3