Post on 16-Dec-2015
Goals for the day:
1) Grignard Reaction
2) Ethers (Naming and reactions)
3) Epoxides (naming and reactions)
4) Thiols & sufides (reactions)
Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX
Grignard reagents react with carbonyl compounds to yield alcohols
17.5 Alcohols from Carbonyl Compounds: Grignard Reagents
Grignard reagents act as nucleophilic carbon anions (carbanions = : R) in adding to a carbonyl group
The intermediate alkoxide is then protonated to produce the alcohol
Mechanism of the Addition of a Grignard Reagent
Try to predict the products…
OCH3 MgBr
MgBrOH
Possible depictions are…
OCH3 MgBr
MgBrOH
OH
CH3
O
H H
Try to fill in the mechanism…
OCH3 MgHBr
OH
CH3
1)
2) H3O +
O
CH3O
CH3 MgHBr
H O
H
H
Reactions of Grignard Reagents with Carbonyl Compounds
Yields tertiary alcohols in which two of the carbon substituents come from the Grignard reagent
Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent
Reactions of Esters and Grignard Reagents
Cannot be prepared if there are reactive functional groups in the same molecule, including proton donors
Grignard Reagents and Other Functional Groups in the Same Molecule
Predict the product…
O
OCH3
CH3 MgBr
Remember it goes all the
way to the alcohol &two CH3 groups
are added…
O
OCH3
CH3 MgBr
O
OCH3
CH3
O
CH3
O
CH3
CH3
OH
CH3
CH3
OH
CH3
CH3
Naming Ethers
Ethers contain the R-O-R bond. Basically, you name the two groups
attached to the oxygen (alphabetically) and add the term ether.
O
The smallest ether is dimethyl ether
Ethers as attachments
Methoxy
Ethoxy
isopropoxy
O
CH3
O
O
Pick one to try to name & panel submit
O O
Pick one to try to name & panel submit
O O
Isopropyl pheny ether
Or
Isopropoxy benzene
Secbutyl vinyl ether
Or
1-secbutoxy ethene
R–O–R ~ tetrahedral bond angle Oxygen is sp3-hybridized Oxygen atom gives ethers a slight dipole momentNot very reactive, so they make good solvents (diethyl
ether is the “ether” we use in lab all the time). Not water soluble (although diethyl ether is slightly…
see diagram on the following page)…
Properties of Ethers
This is why you have to “dry” the organic layer in your reactions!
ether layer
water layer
water layer ether layer
add MgSO4
ether layerether layer(dried)
f ilter
Diethyl ether prepared industrially by sulfuric acid–catalyzed dehydration of ethanol – also with other primary alcohols
18.2 Synthesis of Ethers
OH
H+
O2
Works really only if the ether that you want is symmetric….otherwise you can get mixed results..
18.2 Synthesis of Ethers
OH
OH
O
Problem is.....propanol reacts with itself and ethanol reacts with itself…
Need for an unsymmetric ether synthesis
OH
OH
O
O
O
Mechanism of ether formation from alcohols…
Reaction of metal alkoxides and primary alkyl halides and tosylates
Best method for the preparation of unsymmetric ethers
Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH
The Williamson Ether Synthesis
Predict the product...
OH
Na Br
The carbons of the alkyl halide become the “second” group of the ether...
OH
Na BrO
An SN2 process…
OH
Na BrO
O Na + Br
SN2
th
Note that the second step of the reaction is an SN2 process, soworks best for primary alkyl halides (or methyl bromide)
Which is better?(you get phenyl propyl ether either way)…
OH
Na Br
O
BrOH
Na
a)
b)
Path “a” is better because the alkyl halide is primary and will react faster in the SN2 reaction
OH
Na Br
O
BrOH
Na
a)
b)
Cyclic ethers behave like acyclic ethers, except if ring is 3-membered
Two common structures are ethylene oxide and THF
Cyclic Ethers
O
Also called epoxidesEpoxides (Oxiranes)
Treat an alkene with a peroxyacidAbbreviation for this reagent is MCPBA…
Preparation of Epoxides Using a Peroxyacid
What’s the product?
MCPBA
Answer…
MCPBA
O
Addition of HO-X to an alkene gives a halohydrinTreatment of a halohydrin with base gives an epoxide Intramolecular Williamson ether synthesis
Epoxides from Halohydrins
Water adds to epoxides with dilute acid at room temperature
Product is a 1,2-diol (on adjacent C’s: vicinal)Mechanism: acid protonates oxygen and water
adds to opposite side (trans addition)
18.6 Reactions of Epoxides: Ring-Opening
Anhydrous HF, HBr, HCl, or HI combines with an epoxide
Gives trans product
Halohydrins from Epoxides
Regiochemistry of Acid-Catalyzed Opening of Epoxides 1) Nucleophile preferably adds to less hindered site if
primary and secondary C’s 2) Nucleophile adds to a tertiary carbon because of
carbocation character
1)
2)
Steps of Acid-Catalyzed Opening of Epoxides
1) Protonation
2) Attack of the nucleophile from the backside
Note: check for degree of substitution
Strain of the three-membered ring is relieved on ring-opening
Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols
Base-Catalyzed Epoxide Opening
Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain
Acyclic and other larger ring ethers do not react
Addition of Grignards to Ethylene Oxide
Large rings consisting of repeating (-OCH2CH2-) or similar unitsNamed as x-crown-y
x is the total number of atoms in the ringy is the number of oxygen atoms18-crown-6 ether: 18-membered ring containing 6 oxygen
atomsCentral cavity is electronegative and attracts cations
18.7 Crown Ethers
Thiols (RSH), are sulfur analogues of alcoholsNamed with the suffix -thiol SH group is called “mercapto group” (“capturer
of mercury”)
18.8 Thiols and Sulfides
From alkyl halides by displacement with a sulfur nucleophile such as –SH The alkylthiol product can undergo further
reaction with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol
Thiols: Formation and Reaction
Sulfides (RSR), are sulfur analogues of ethersNamed by rules used for ethers, with sulfide in
place of ether for simple compounds and alkylthio in place of alkoxy
Sulfides
Reaction of an alkyl thiol (RSH) with bromine or iodine gives a disulfide (RSSR)
The thiol is oxidized in the process and the halogen is reduced
Cysteine amino acid forms cystine bonds
Oxidation of Thiols to Disulfides
Thiolates (RS) are formed by the reaction of a thiol with a base
Thiolates react with primary or secondary alkyl halide to give sulfides (RSR’)
Thiolates are excellent nucleophiles and react with many electrophiles
Sulfides
Have a wonderful day!
An ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R
Diethyl ether is used industrially as a solventTetrahydrofuran (THF) is a solvent that is a cyclic ether
Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogues of alcohols and ethers
Ethers and Their Relatives