6 alcohols and ethers a notations
TRANSCRIPT
Sec. 6: Alcohols, Ethers 1
Any time a Carbocation is formed Rearrangements can occur.
C
CH3
H3C
CH3
C
H
CH3methanide
migrationCH3C
CH3
C
H
CH3
CH3++
C
C
C
H3CH3C H
H
HHC
H
H
H
Lewisbase
Lewisacid
Why does this happen?
C
CH3
H3C
CH3
CH2
methanide
migration
+
CH3C
CH3
CH2
CH3+
CH3CH2 CH
H
CH2hydride
migration
+
CH3CH2 CH CH2
H+
3°
3°
2°
2°
1°
1°
C
CH3
CH2C
H2C H
C
HH HH
H
+
+
Sec. 6: Alcohols, Ethers 2
Hydride and methanide shifts are very fast (faster than SN1 or E1) which is partially due to hyperconjugation in the carbocation weakening the C-H, or C-C bond:
Primary carbocations are too unstable to be formed by rearrangement.Secondary or tertiary carbocations equilibrate readily, leading to a mixture of products when trapped by a nucleophile.
Sec. 6: Alcohols, Ethers 3
C C
CH3
H3C
CH3
Br
CH3
H
CH3OH
C C
CH3
H3C
CH3
CH3
H
+
+ Br
methanidemigration
C CH3C
CH3
CH3
H
CH3+
CH3OH
-H+
C CH3C
CH3
CH3
H
CH3OCH3
What is the product of the following SN1 reaction?
acidacid
base
weak basepoor nucleophile
base
C C
CH3
H3C
CH3
OCH3
CH3
H
C C
OCH3
H3C
CH3
CH3
CH3
H
C CH2
CH3
H3C
CH3
CH2
C C
CH3
H3C
CH3
CH3O
CH3
H
A) B)
C) D)
H3CO
Mechanism
2o 3o
Sec. 6: Alcohols, Ethers 4
What is the major product formed in the following reaction?
85% H3PO4
60°CC
CH3
H3C
CH3
C
H
CH3
OH
C
H3C
H3C
C
CH3
CH3
C
H2C
H3C
C
CH3
CH3
H
C
CH3
H3C
CH3
CH CH2 C
H3C
H3C
CCH3
H
C
CH3
H3C
CH3
C
H
CH3
A)
C)
B)
E)D)
Also look in Vollhardt Chapter 11-11 (preparation of alkenes by dehydration)
Sec. 6: Alcohols, Ethers 5
What is the Mechanism of the previous reaction?
85% H3PO4
+
+
60°C
C
CH3
H3C
CH3
C
H
CH3
OH
P
O
OH
OH
OH
acid
base
C
CH3
H3C
CH3
C
H
CH3
O
H H
P
O
OH
OH
O+
-H2O
C
CH3
H3C
CH3
C
H
CH3
2°
methanideshift
CC
CH3
C
CH3
CH3
H
H
HH
+
3°
P
O
OH
OH
O
C
H2C
H3C
C
CH3
CH3
H
a
a
b
b
C
H3C
H3C
C
CH3
CH3
major
Zaitsev’sRule
+ H3PO4
Sec. 6: Alcohols, Ethers 6
What is the major product formed in the following reaction?
85% H2SO4C
H
H3C
CH3
C
H
CH3
OH
NaBrC
H
H3C
CH3
C
H
CH3
OH
85% H2SO4
A)
C)
B)
D)
Br
H
Br
H
A)
C)
B)
D)
Sec. 6: Alcohols, Ethers 7
The mechanism of 3-methyl-2-butanol with concentrated H2SO4 and NaBr?
85% H2SO4
+
+
C
H
H3C
CH3
C
H
CH3
OH
acid
base
C
H
H3C
CH3
C
H
CH3
O
H H
+
-H2O
C
H
H3C
CH3
C
H
CH3
2°
hydrideshift
CC
CH3
C
H
CH3
H
H
HH
+
3°
HSO4
Na Br+
Br
CH3C
CH3
C
H
CH3
H
Br
weak base good nucleophile
If no NaBr present the only species present are H2SO4, HSO4¯ and H2O, which are weak bases and poor nucleophiles. E1 reaction
SN1
CH3C
H3C
CCH3
H C
H2C
H3C
C
H
CH3
H
+
major
Sec. 6: Alcohols, Ethers 8
Primary alcohols may undergo rearrangement.
Alkyl and hydride shifts to primary carbons bearing leaving groups can occur without the formation of primary carbocations.
Because this is not a simple primary bromoalkane, steric hindrance interferes with direct attack by the bromide ion. Instead, water leaves at the same time as the methyl group migrates, by passing the formation of a primary carbocation.
Sec. 6: Alcohols, Ethers 9
Making an ether by dehydration of an alcohol
OH
OH
conc. H2SO4O
acid
base
OH
OH2
2°
+
OH
H2O+
+
OH
H2O+
H H
OH
H
H H
+
benzylicvery stable
acid
base
OH
O
-H+
+
H+
1 23
4
1
23
4
+ HSO4
Sec. 6: Alcohols, Ethers 10
Organic and Inorganic Esters from AlcoholsOrganic esters are derivatives of carboxylic acids.Inorganic esters are the analogous derivatives of inorganic acids.
Alcohols react with carboxylic acids to give organic esters.
Esterification is the reaction of alcohols with carboxylic acids in the presence of catalytic amounts of a strong inorganic acid (H2SO4 or HCl) which yields esters and water.This is an equilibrium process which can be shifted in either direction.
Conversion of Alcohols into Alkyl HalidesHydroxyl groups are poor leaving groups, and as such, are often converted to alkyl halides when a good leaving group is needed
Sec. 6: Alcohols, Ethers 11
Haloalkanes can be made from alcohols through inorganic esters.
As an alternative to the acid-catalyzed conversions of alcohols into haloalkanes, a number of inorganic reagents can convert the alcoholic hydroxyl group into a good leaving group under milder conditions.
The reaction of PBr3 with a secondary alcohol yields a bromoalkane and phosphorous acid (all three bromine atoms can be utilized).
Can use if the alcohol is tertiary
Sec. 6: Alcohols, Ethers 12
Iodoalkanes can be prepared using PI3, which, because of its reactivity, is generated from red phosphorous and iodine in the reaction mixture itself.
Chloroalkanes are commonly prepared using thionyl chloride by warming an alcohol in its presence.
An amine such as triethyl amine is usually added to consume the generated HCl.
Sec. 6: Alcohols, Ethers 13
Alkyl sulfonates are versatile substrates for substitution reactions.
Alkyl sulfonates are excellent leaving groups and can be generated by the reaction of an alcohol with the corresponding sulfonyl chloride. Pyridine or a tertiary amine is used to remove the HCl formed.
Alkyl sulfonates are often crystalline solids and can be isolated and purified before further reaction.
What is the major product formed in the following reaction?OH
CH3SO2Cl
pyridine?
NaSCN
acetone
SCN SCN
A) B) C)
Sec. 6: Alcohols, Ethers 14
Ethers as solvents
Ethers are very good solvents because they are fairly unreactive and slightly polar
Cyclic ethers are members of the class of cycloalkanes called heterocycles, in which one or more carbon atoms have been replaced by a heteroatom.
Cyclic polyethers based on the 1,2-ethanediol unit are called crown ethers. The crown ether 18-crown-6 contains 18 total atoms and 6 oxygen atoms.
Note that the inside of the ring is electron rich.
The smaller alkoxyalkanes are water soluble, however solubility decreases with increasing hydrocarbon size.Methoxymethane- completely water solubleEthoxyethane -10% aqueous solution
Sec. 6: Alcohols, Ethers 15
Polyethers solvate metal ions: crown ethers and ionophores.
Crown ethers can render salts soluble in organic solvents by chelating the metal cations. This allows reagents such as KMnO4 to act as an oxidizing agent in the organic solvents.
The size of the central cavity can be tailored to selectively bind cations of differing ionic radii.
Three-dimensional analogs of crown ethers are polyethers called cryptands. These are highly selective in alkali and other metal cation binding.
Sec. 6: Alcohols, Ethers 16
Williamson Ether Synthesis
Synthesis of Ethers
OHNaH
ONaCl
DMSODMSOO
1-butoxybutane
What is the major product produced in the following reaction?
Br OH NaOH
O
HO(CH2)5OH
O
dilute solution
-(O(CH2)5O)-n
A) B) C) D)
The intramolecular reaction is usually much faster than the intermolecular reaction. If necessary, the intermolecular reaction can be suppressed by using a high dilution of the haloalcohol.
Sec. 6: Alcohols, Ethers 17
What is the major product produced in the following reaction?
NaOH
A) B)
HO
D
BrH
HH
O
HD
H
H
O
DH
H
H
Does the following reaction proceed by an A) SN1 or B) SN2 mechanism?
OH OH+
excess
15% aqu. H2SO4
40oCO
2-ethoxy-2-methylpropane
Sec. 6: Alcohols, Ethers 18
What is the major product produced in the following reaction?
HOH
O
(CH3)3COH, H+
?1) BrMgCH2CH3
2) H2O, H+?
OH
OH
Br
O
Br OH
OOH
OH
O
A) B) C)
D)E)
OH2
HOH
O
HO
O
H O
O MgBr
H OH
OH
H O
OH H
Sec. 6: Alcohols, Ethers 19
What is the major product produced in the following reaction?
O
CH2CH3
CH3HH
CH3SNa
SCH3H
H
CH3CH2CH3
HO
HOCH2CH3
CH3
HH SCH3
OHH
H
CH3CH2CH3
H3CS
H3CSCH2CH3
CH3
HH OH
A) B)
C) D)
1)
2) H2O, H+
Ethers are unreactive towards basic nucleophiles because alkoxides are very poor leaving groups. Why would the above reaction occur? What is the driving force for this reaction?
The driving force is the release of strain that occurs in the displacement reaction
Sec. 6: Alcohols, Ethers 20
Hydride and organometallic reagents convert strained ethers into alcohols
LiAlH4 can open the rings of oxacyclopropanes to yield alcohols. (Ordinary ethers do not react.)In asymmetrical systems, the hydride attacks the less substituted side.
Acids catalyze oxacyclopropane ring openingRing opening of oxacyclopropane by acid catalysis proceeds through an initial cyclic alkyloxonium ion.
This acid catalyzed ring opening is both regioselective and stereospecific.
Sec. 6: Alcohols, Ethers 21
What is the major product produced in the following reaction?
O
CH2CH3
CH3HH
H2SO4
CH3OH OCH3H
H
CH3CH2CH3
HO
HOCH2CH3
CH3
HH OCH3
OHH
H
CH3CH2CH3
H3CO
H3COCH2CH3
CH3
HH OH
A) B)
C) D)
In the alkyloxonium ion, more positive charge is located on the tertiary carbon than on the primary carbon. This effect counteracts the effect of steric hindrance and the alcohol attacks the tertiary carbon. Because inversion of configuration occurs during ring opening, free carbocations cannot be involved in the reaction mechanism.
Sec. 6: Alcohols, Ethers 22
Order the intermediates and final product in the reaction of oxacylclopentane (tetrahydrofuran) with excess HBr
Oexcess conc HBr.
HOBr
BrBr
O
H
H2OBr
1)2)
3) 4)
Ethers are unreactive towards basic nucleophiles and are very weak bases and thus are generally good solvents. However ethers will react (ether cleavage) with strong acids in the presence of a good nucleophile, ie HBr, HI or NaBr, NaI in H2SO4.
A) 1, 2, 3, final product 4B) 2, 1, 4, final product 3C) 2, 4, 1, final product 3D) 1, 4, 3, final product 2
Sec. 6: Alcohols, Ethers 23
What is the major product produced in the following reaction?
H
O
LiAlH4 PBr3
A)B)
C)
D) E)
2) H3O+
1)?
/Et2O /Et2O?
/Et2OMg1)
2) H2CO
3) H3O+
?1) NaH
2) CH3Br?
O OBr
O
OH
O
O
O
Sec. 6: Alcohols, Ethers 24
Sulfur Analogs of Alcohols and EthersThe IUPAC system calls the sulfur analogs of alcohols, R-SH, “thiols.” The –SH group in more complicated compounds is referred to as “mercapto.”
The sulfur analogs of ethers are called “sulfides” (common name, thioethers). The RS group is called “alkylthio,” and the RS- group is called “alkanethiolate.”
Thiols are less hydrogen-bonded and more acidic than alcohols. Thiols are more acidic than water and can therefore be easily deprotonated by hydroxide and alkoxide ions:
Sec. 6: Alcohols, Ethers 25
Thiols and sulfides react much like alcohols and ethers
The sulfur in thiols and sulfides is more nucleophilic than the oxygen in the analogous compounds.Thiols and sulfides are readily made through nucleophilic attack by RS¯ or HS¯ on haloalkanes:
A large excess of HS¯ is used to prevent the reaction of the product with the starting halide.
The nucleophilicity of the generated thiolates is much greater than that of hydroxide which eliminates the competing SN2 substitution by hydroxide ion.
Sec. 6: Alcohols, Ethers 26
Sulfides can attack haloalkanes to form sulfonium ions.
Sulfonium ions are subject to nucleophilic attack, the leaving group being a sulfide.
Valence-shell expansion of sulfur accounts for the special reactivity
of thiols and sulfides.Sulfur can expand its valence shell from 8 to 10 or 12 electrons using its available 3d orbitals, allowing oxidation states not available to its oxygen analogs.Oxidation of thiols with strong oxidizing agents (H2O2, KMnO4) gives the corresponding sulfonic acids:
Sulfides can also be oxidized to sulfoxides and then sulfones:
Sec. 6: Alcohols, Ethers 27
Milder oxidizing agents (I2) yield disulfides.These can be reduced back to thiols by alkali metals
Reversible disulfide formation is important in stabilizing the folding of biological enzymes:
Sec. 6: Alcohols, Ethers 28
The polymer chain crosslinking of rubber is called vulcanization.
C H2
CH3
CH3
C H2
CH3
CH3
CH3
H2
C
C H2
CH3
CH3
n
C H2
CH3
CH3
C H2
CH3
CH3
CH3
H2
C
C H2
CH3
CH3
m
S
heat
C H2
CH3
CH3
C H2
CH 3
CH3
CH 3
CH2
H2
C
C H2
CH3
CH3
n
C H2
CH 3
CH3
C H2
CH3
CH3
CH3
CH2
H2 C
C H2
CH 3
CH3
m
S x
x = 1 (sulfide or thioether crosslink)
x > 1 (polysulfide crosslink)
S
NS H
mercaptobenzothiazole(MBT)
S
NS S
xH
a hypothetical intermediate acelerated vulcanization
In older vulcanization processes, the co-polymer was simply heated with elemental sulfur to form sulfide or poly sulfide crosslinks, however this reaction is usually very slow.
Current vulcanization processes use so-called vulcanization accelerators such as MBT