COOH --> Esters
H2SO4
COOH --> Methyl Ester
diazomethane (CH2N2)
ROH --> X
PBr3 -or- P/I2
Ketone/Aldehyde/Formaldehyde --> ROH
H2O/H3O+
Acetal Formation
mild acid (TsOH)
Reduce Ketone/CHO with thion
excess PhSH/TsOH
Secondary/Tertiary ROH --> X
HCl/ZnCl2 (Lucas Reagent)
Primary ROH --> X
displacement of the ROH with HCl/ZnCl2
Acylation of Amines (Amide reduction)
Pyridine (base)
alkane ROH --> cycloester
NaOH (Williamson Ether Synthesis)
thiol --> ester like sulfur
1.NaOH 2.CH3I (Sn2)
Cleavage of Ethers
H-X (X=Br, I) (Harsh conditions)
Auto-oxidation by Ethers
excess O2
alkene --> epoxide
peracid (mCPBA, MMPP/CH3/H2O)
ROH--> X
Thionylchloride (SOCl2)/heat
ROH --> X
H-X (only tertiary ROH)
Dehydration-Hydrogentation of ROH
1. H2SO4/heat 2. H2+Pd/C (or Pt)
Removal of ROH
1. TsCl/pyridine 2. LiAlH4/ether 3. H3O+
pitfalls: other carbonyls
Dehydration of ROH
1. H2SO4
secondary and tertiary preferred
Dehydration of ROH
1. with itself
primary ROH --> elimination is slow so this process occurs.
ROH + COOH --> ketone + ester
1. H2SO4
ROH --> Inorganic esters
1. TsCl/pyridine (GLG)
2. H2SO4 (gen. primary R, sulfate, good R+ source)
3. HNO3 (nitrates, explosive)
4. H3PO4 (phosphates, DNA backbone)
Cleavage of vicinal diols
HIO4/perodic acid
alkene --> 2ROH
1. OsO4/H2O2
2. KMnO4/OH-
Pinacol Rearangement
1. H2SO4/heat
R must be alkyl
Bimolecular Dehydration of primary ROH
1. H2SO4/heat
**symmetric ethers
Alkoxymercuration - Demurcuration
1. Hg(OAc)2/ROH
2. NaBH4
Markovnikov addition
Williamson Ether Synthesis (ROH--> ether)
1. NaH 2. R-X (Br2CH2Ch3)
**unsymmetrical ether synthesis
Williamson Ether Synthesis (alkene --> ether)
1. X2/H2O
2. NaH (works through Sn2)
Acid Catalyzed Epoxide Opening
1. Cat. H2SO4/H2O
more substituted sight
Base Promoted Epoxide Opening (Direct Nucleophillic Opening)
1. CH3CH2ONa/CH3CH2OH
sterics govern selectivity
alkene --> X
HBr
alkene --> addition X
1. high conc. Br2
Allylic Bromination
1. low conc. Br2 -or- NBS/hv (to avoid addition)
Diels Alder Reaction
1. cis diene
trans diene = NO RXN
Reagents that do not effect aromatics
1. HBr
2. BH3-THF/NaOH H2O2
3. H2/Pd(-or- C)
4. KMnO4/NaOH/heat + H3O+ (unless benzylic sp3)
Electrophillic Aromatic Substitution
1. Br2/FeBr3
2. I2/HNO3
3. H2SO4/HNO3
4. H2SO4/SO3
Friedel-Craft Alkylation
1. R-X/FeBr3
2. R-X/AlCl3
Protonation of an alkene to make a C+
1. HF
2. H2SO4
Poor nucleophiles so no simple addition like H-Br
Generation C+
1. AlCl3 -or- FeBr3
Add acyl to aromatic
1. HCl/AlCl3
Clemmenson Reduction (remove ketone)
Zn(Hg)/aqHCl
Catterman-Koch Formulation (thoinylchloride --> aldehyde)
1. AlCl3/CuCl
2. benzene (aromatic)
Nucleophillic Aromatic Substitution
1. CH3NH2/heat
sigma complex is negative
Benzyne Mechanism (X --> NH2)
1. NaNH2/heat
50:50 mixture
BIrch Reduction
1.Na -or- Li/NH3/ROH
electron donating on alkene and vice versa
Benzylic Oxidation (benzylic alkane --> COOH)
1.KMnO4/NaOH/heat
2. H3O+
Benzylic Halogenation (Benzylic H --> Br(2))
1. Br2 -or- NBS/heat
chlorination is too difficult to control
Substitution at benzylic position
1. NaCN (Sn2)
2. CH3OH/heat
primary ROH --> CHO (oxidation)
1. PCC/CH2Cl2
2. swern
secondary ROH --> Ketone (oxidation)
1. any [o]
(PCC/CH2Cl2, swern, HCr2O4, HNO3, KMnO4)
alkene --> CHO/Ketone/formaldahyde (ozonolysis)
1. O3
2. S(CH3)2
R= alkyl/H
terminal alkynes --> CHO/Ketone
1. Hg2+/H2SO4/H2O
markovnikov addition
Aldehydes via hydroboration
1. Sia2BH
2. NaOH/H2O2
COOH --> ketones/CHO (addition)
1. 2 eq. RLi
2. H3O+
3.-H2O
only RLi works
Acid chlorides --> CHO (reduction)
1. acid chloride
2. LiAlH4
alternative: LiALH(OtBu)3 + H3O+ (mild reagent)
acid chlorides --> ketones
1. RMgX -or- RLi
alternative: R2CuLi (cuperate)(Gillman Reagent)
Nitriles --> CHO/ketones
1. CH3MgBr/ether
2. H30+
Dithianes --> CHO/ketone
1. H+/HgCl/H2O
Base Promoted Nucleophillic Addition to Carbonyls
1. OH- +H2O
(hydration is the presence of hydroxide)
rate determined by sterics
Base Promoted Nucleophillic Addition to Carbonyls: Cyanohydride Formation
1. KCN -or- NaCN
2. CH3OH
CN --> COOH
1. H30+/heat
CN --> ketone
1. 2 eq. RMgBr
2. H3O+
Carbonyls --> CN (Acid Catalyzed)
1. TsOH
Wolf-Kischner Reduction (of Carbonyls)
1. TsOH
2. KOH/heat
carbonyl --> CN
1. NH2-X/TsOH
Aromatic Substitution
1. excess Br2/NaHCO3 (suck up excess acid
2. excess Cl2/ NaHCO3
3. acid
(NH3 is a very strong deactivator)
Hoffman Elimination
1. excess CH3I
2. AgO/H2O
3. heat
Hoffman selectivity (opp. zaitzevs)
Cope Elimination (tertiary amines)
1.H2O2 -or- peracid
amines --> N2
1. NaNO/HCl
Gabriel Synthesis (make RNH2)
1. KOH
2. R-X
3. H2N-NH2
very acidic hydrogen
Azide Reduction
1. NaN3/DMF
2. LiAlH4
3. H2O
Nitrile Reduction
1. H2/Ni
2. LiAlH4/H2O
aromatic NO2 --> aromatic NH2
1. H2/Ni (or Pd)
2. Sn
3. H2SO4
4. Zn/HCl/ROH
ROH/CHO --> COOH
1. NaCrO7/H2SO4
2. KMnO4
3. HNO3
Benzyllic Oxidation --> COOH
any sp3 carbon
hot KMnO4
alkene --> cleavage in COOH
1. conc. KHnO4
2. [o]
Carbonylation of Organometallics
1. Mg/ether
2. CO2
3. H30+
CN --> COOH
1. HCl/H20/heat
2. NaOH/H2O/heat
CN --> NH2
1. LiAlH4/H2O
COOH --> amide (direct)
1. heat (>100 degrees C)