Chapter 12: Ethers, Epoxides, Glycols, and Sulfides Flashcards
What is an ether?
A molecule with an oxygen atom bounded to two R groups
What is a sulfide?
A molecule with a sulfur atom bounded to two R groups
What is the basicity of ethers and sulfides?
Ethers are very weak bases because of how electronegative oxygen is, it does not easily give up electrons to a proton.
Sulfides are even weaker bases because of the element effect where S-H is much weaker than O-H because of orbital mismatch
Bronsted Basicity versus Lewis Basicity of Ethers
Ethers will act as bronsted bases by attacking a proton from an acid in the 1s orbital
Ethers will act as lewis bases by attacking a low energy p orbital of a lewis acid
Describe the synthesis of ethers through substitution of an alcohol and an alkyl halide
A tertiary alcohol is deprotonated and stabilizes negative charge. The oxygen acts as a nucleophile and backside attacks a primary alkyl halide carbon to gain another R group
Describe the synthesis of ethers through alkoxymercuration-reduction of alkenes
Alkene reacts with Hg(OAc)2 and an ROH solvent. OAc attacks H on ROH. The Hg(OAc) goes on the least substituted carbon while the R-O adds to the most substituted.
The Hg(OAc) is treated with NaBH4 to form hydrogen
Describe the synthesis of ethers through alcohol dehydration
A protonated alcohol will be attacked by another alcohol, causing the water to fall off. The resulting molecule has a proton on the oxygen that is taken by another alcohol (forming the protonated alcohol) leaving behind a stable ether. This is an Sn2 reaction where everything is concerted.
What if the alcohol is tertiary when dehydrating it to an ether?
The alcohol is protonated and the water breaks away leaving a carbocation. The carbocation is attacked by another primary alcohol to form an ether.
What is the oxidation process of alkenes to epoxides?
mCPBA is used to add a cyclopropanol ring where an carbon double bond was through a syn addition
Describe the intramolecular mechanism for halohydrins to form epoxides
A halohydrin contains an OH and a halogen. The OH will get deprotonated, and will attack the partial positive carbon attached to the halogen, forming a ring and kicking out the halogen.
This is opposite side substitution, so in order for this to occur, the oxygen and the halogen must be anti to each other so the O can get in there and bond to the C
For chairs, the favored conformation is axial so that sufficient backside attack to close the ring can occur
Describe how ethers can cleave with a primary alkyl group (ex I-H)
For a primary ether, the oxygen atom in the ether will attack the hydrogen on HI and a positive charge will form. The negative I will attack the carbon connected to the oxygen and the lone pair will go back to the oxygen, and I-R will form. This is an Sn2 Reaction.
For a tertiary ether, the oxygen atom will attack the hydrogen to form a positive charge on the oxygen, and the alcohol created will dissociate forming a carbocation. The I then comes in and attacks the carbocation. This is an Sn1 reaction.
Describe ring opening under basic conditions
Epoxides can be opened with a nucleophile (basic conditions). The nucleophile will come in and attack a carbon attached to the oxygen, usually the one with less substituents. This break the ring and adds a lone pair to oxygen. The oxygen will then get protonated into OH from the original protonated nucleophile.
Describe ring opening under acidic conditions
The oxygen atom is protonated which creates a positive charge on the oxygen. This causes the oxygen to stretch toward the carbon with fewer substituents. Solvent molecules will react with carbon with more substituents, breaking that bond to the oxygen and forming the product.
This causes inversion of stereochemistry where OH and solvent molecule are trans
Describe how epoxides can be turned into alcohols using Grignard Reagents
Grignard Reagent (R-MgBr)
The nucleophile carbon from R- attacks carbon in epoxide and break open ring, leaving behind MgBr. The oxygen is then protonated to form an alcohol.
This whole process extends an alcohol (R-OH –> R-Br –> R-MgBr) by two carbons from the epoxide
What are Lithium Organocuprate Reagents?
They are nucleophilic molecules that are selective due to R-Li being a mild source of carbon nucleophiles that open ring epoxides.
R-Li + CuCl 2x –> Li+ + R-Cu-R-
Where mild carbon nucleophile R attacks lower substituted carbon in backside attack and Cu-R leaves
What is a glycol?
A molecule that contains OH groups on adjacent carbons
OH OH
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C—-C
Describe how alkenes can be oxidized into glycols
Alkene reacts with OsO4 which is a very reactive molecule that attaches an O to each carbon breaking the double bond, and the Os is attacked by water and leaves and the oxygen on the carbons are protonated with NaHSO3
This is syn addition where the OH groups are both added on the same plane and push the rest downwards
OsO4 is very expensive and toxic, and so amine oxides can be used to recycle the Os by acting and a stoichiometric agent
Describe how glycols are cleaved with H5IO6
The C-C bond between the OH groups can be cleaved with H5IO6 acid to form a double bond oxygen to the carbon with the constituents left on the carbon (ketones, aldehydes, etc)
Not all glycols undergo cleavage if they can not form the cyclic ring with the H5IO6 such as those in chairs where the constituents are not both facing upwards
What are oxonium salts?
When a protonated ether has its proton replaced with an alkyl group, it becomes an oxonium salt
Used when a nucleophile needs a strong alkylating agent willing to give up alkyl group. Nuc can come in and do an Sn2 reaction with oxonium salts
What are intramolecular Reactions?
Occur between groups within the same molecule—MUCH faster than intermolecular reactions
A good example is adding sulfur in hydrocarbon tail of alkyl halide and the sulfur reactions with the carbon next to the halogen to form a sulfur ring and kick out the halogen, and that the water can then come in and attack the carbon attached to the sulfur to form the alcohol
