Chapter 12 Flashcards
Synthesis and Retrosynthesis
What is a phenol?
a benzene + alcohol
What is a alkoxide?
deprotonated form of an alcohol
What is needed to form an alkoxide?
strong base
ex. NaH
How is acidity in alcohols determined?
Resonance - more resonance = increased acidity
Induction: presence of electron withdrawing groups increases acidity
Solvation: more poorly solvated (bulky)=acidic
What is the best way to make a 1 prime alcohol?
SN2
What is the best way to make 3 prime alcohols?
SN1
What are the three ways to prepare an alcohol from an alkene and which reagents do they use?
- Acid-catalyzed hydration: Dilute H2SO4
- Oxymercuration: 1)Hg(OAc)2, H2O
2)NaBH4 - Hydroboration: 1) BH3THF
2)H2O2, NaOH
What is the order of oxidation?
alcohol to aldehyde/carbonyl to carboxylic acid
What are the common reducing agents?
- NaBH4
- LiAlH4
What is a diol compound?
compound with two hydroxyl groups
What are the Grignard reagents used to prepare and alcohol?
1)CH3MgBr, Et2O
2)H3O+
(CH3 can be any type of carbon chain)
What protects alcohol groups from modification in a Grignard rxn?
TMS (trimethylsilyl group)
TMSCl
———->
Et3N
What are the options for the substitution of primary alcohols?
1)Simple substitution: primary alcohol +HBr
2)Catalyzed substitution:
primary alcohol + HCl ZnCl2
———>
What are the options for the substitution of primary or secondary alcohols?
1) 2alcohol + TsCl/Pyr +Cl -
- inverts stereochemistry
2)1 alcohol +PBr3—-> OH substituted with Br
3)2* alcohol (SOCl2)/—–> Cl swaps with OH and is inverted
What are the methods for forming an alkene from the elimination of alcohols?
- Acid-Catalyzed Elimination:
3* alcohol (H2SO4)/—>/(delta Heat)
via E1, - Base-catalyzed elimination
TsCl/Pyr + EtONa (strong base) - E2 mechanism
What does the oxidation of 1* alcohol lead to?
Carboxylic acid
What does the oxidation of 2* alcohol lead to?
Ketone
What does the oxidation of 3* alcohol lead to?
Does not happen bc it would lead to 5 bonds to carbon
What are the four types of oxidation reactions?
- Chromium Oxidation
- controlled oxidation
- swern oxidation
- Dess-Martin Oxidation
Details of Chromium oxidation?
Reagents
- CrO3 or Na2Cr2O7
- (very strong oxidizers)
- 2* alcohol to ketone
- 1* alcohol is over oxidized to the acid
Details of controlled oxidation?
- reagent: PCC/CH2Cl2 (pyridinium chlorochromate)
- stops at aldehyde
- prevents over oxidation
Details of stern oxidation?
- Reagents: 1)DMSO, (COCl)2/2)Et3N
- 2* alcohol to ketone
Details of Dess-Martin Oxidation?
Reagents: DMP/CH2Cl2
- 1* alcohol to aldehyde
What is an ether?
an oxygen connected to two hydrocarbon group
What is the oxygen orbital hybridization of an ether?
sp^3
- electronic geometry is tetrahedral
What is the molecular geometry of an ether?
bent (2 lone pairs)
Intermolecular forces of neat ether
- London forces
What is the intermolecular force for ethanol?
hydrogen bonding
Why do alcohols have a greater boiling point than ethers?
alcohols have stronger intermolecular forces than ethers
What are the common ether solvents and what are their benefits?
- Diethyl Ether
- THF
- 1,4-Dioxane
Benefits: - Relatively unreactive
- Low boiling point = easy to remove after a reaction
What is a crown ether?
cyclic polyethers that tightly bind metal ions
Naming: X-Crown-Y
How do ethers interact with metals?
- Oxygen interacts with a metal, often stabilizing the negative charge
- metals bind the center of ring by interacting with oxygens
- hydrocarbons on the outside of the ring mask the positive charge of the metal
How do crown ether produce a stable fluorine?
Crown ethers can produce stable F- to act as a nucleophile in an organic solvents (like benzene) because it overcomes issues of stability and solubility
What ion do each of the crown ethers bind?
1) 12-Crown-4
2) 15 -Crown-5
3) 18- Crown-6
1)Li
2)Na
3)K
What is Williamson Ether Synthesis
- great for symmetrical and asymmetrical ethers
- two step mechanism: Proton transfer and nucleophilic attack
- uses a strong base that deprotonates the alcohol
includes and alcohol and an alkyl halide
What is autooxidation?
- diethyl ether reacts slowly with O2 to form hydro peroxide which reacts violently when heated.
What is an expoxide?
cyclic ether with a single oxygen
What is an oxirane?
an epoxide that is particularly reactive due to ring strain
What are the two common methods for forming epoxides?
1) Peroxy acid addition to an alkene
- trans alkene + MCBPA —->trans epoxide
2) Epoxides via halohydrins
- halohydrin is treated with a strong base Ex. NaOH
Williamson Ether Synthesis Mechanism
(CH3OH) 1)NaH/2)CH3Br —> CH3OCH3
Why are epoxides more reactive than ethers?
ring strain
What are the two kinds of ring-opening reactions?
- reaction with a strong nucleophile
- acid-catalyzed ring opening
Examples of some strong nucleophiles?
RONa, NaCN, NaSH, RMgBr, LAH
When a strong nucleophile reacts with an epoxide ring, which carbon gets the addition of the nucleophile?
the less hindered carbon
What happens to the stereochemistry when the ring is opened?
the stereochemistry is inverted
If the ring has a primary and a secondary carbon which carbon does the nucleophile attach to?
the primary carbon
If the ring has a primary carbon and a tertiary carbon, which carbon does the nucleophile attach to?
the tertiary carbon
If the ring the ring has a secondary and a tertiary carbon, which does the nucleophile attach to?
the tertiary carbon
