che2202, chapter 18 learn, 1 ethers and epoxides; thiols and sulfides chapter 18 suggested problems...
TRANSCRIPT
Slide 1Chapter 18
Suggested Problems –
Ethers
*
Names and Properties of Ethers
Simple ethers are named by identifying two organic substituents and adding the word ether
*
Possess nearly the same geometry as water
Bond angles of R–O–R bonds are approximately tetrahedral
Oxygen atom is sp3-hybridized
Relatively stable and unreactive in many aspects
Very useful as solvents in the laboratory
*
Limited to use with primary alcohols
*
Williamson Ether Synthesis
Reaction of metal alkoxides and primary alkyl halides and tosylates in an SN2 reaction
Best method for the preparation of ethers
Alkoxides are prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH
*
CHE2202, Chapter 18 Learn, *
Silver Oxide-Catalyzed Ether Formation
Reaction of alcohols with alkyl halides in the presence of Ag2O forms ethers in one step
*
Competitive E2 elimination with more hindered substrates
*
Williamson Ether Synthesis
*
How are the following ethers prepared using a Williamson synthesis?
a) Methyl propyl ether
Solution:
a)
b)
Methyl propyl ether can be performed in two ways depending on which half is derived from an alcohol and which half is derived from an alkyl halide.
*
Alkoxymercuration of Alkenes
Alkene is treated with an alcohol in the presence of mercuric acetate or trifluoroacetate
Demercuration with NaBH4 yields an ether
Overall Markovnikov addition of alcohol to alkene
Note the similarities between this reaction and the Markovnikov addition of water to alkenes. The mechanism is very similar.
The principal difference is an alcohol replaces water in oxymercuration demercuration of alkenes to form an ether.
*
Worked Example
Rank the following halides in order of their reactivity in Williamson synthesis:
a) Bromoethane, 2-bromopropane, bromobenzene
b) Chloroethane, bromoethane, 1-iodopropene
Cleaved by strong acids
HI, HBr produce an alkyl halide from less hindered component by SN2
Ethers are unreactive to many reagents used in organic chemistry, a property that accounts for their wide use as reaction solvents. However, ethers are cleaved by strong acids.
*
Reactions of Ethers: Acidic Cleavage
Ethers with tertiary, benzylic, or allylic groups cleave by either an SN1 or E1 mechanism
Intermediates are stable carbocations
*
Solution:
A primary alkyl group and a tertiary alkyl group is bonded to the ether oxygen
*
Specific to allyl aryl ethers and allyl vinyl ethers
Caused by heating ally aryl ether to 200-250°C
Leads to an o-allylphenol
Result is alkylation of the phenol in an ortho position
*
A similar rearrangement takes place with allyl vinyl ethers
A g,d-unsaturated ketone or aldehyde results
*
Takes place in a single step through a pericyclic mechanism
Reorganization of bonding electrons occurs in a six-membered, cyclic transition state
Mechanism is consistent with 14C labeling
*
Worked Example
What products are expected from Claisen rearrangement of 2-butenyl phenyl ether?
Solution:
Six bonds will either be broken or formed in the product - Represented by dashed lines in the transition state
*
Cyclic Ethers
Behave like acyclic ethers with the exception of three-membered ring epoxides
Strain of the three-membered ring gives epoxides a unique chemical reactivity
Dioxane and tetrahydrofuran are used as solvents
*
Ethylene oxide is industrially important as an intermediate
Prepared by reaction of ethylene with oxygen at 300 °C over a silver oxide catalyst
-ene ending implies the presence of a double bond in the molecule
The strain of the three-membered ring gives epoxides unique chemical reactivity.
The name, ethylene oxide, is not a systematic one because the –ene ending implies a double bond in the molecule.
The systematic name for ethylene oxide is 1,2-epoxyethane.
*
Also prepared from halohydrins
*
Addition of HO–X to an alkene gives a halohydrin
Treatment of a halohydrin with base gives an epoxide
Intramolecular Williamson ether synthesis
Explain why reaction of cis-2-butene with m-chloroperoxybenzoic acid yields an epoxide different from that obtained by reaction of the trans isomer
Solution:
Epoxidation, in this case, is a syn addition of oxygen to a double bond
*
Reaction of trans-2-butene with m-chloroperoxybenzoic acid yields trans-2,3- epoxybutane
*
Water adds to epoxides with dilute acid at room temperature
Product is a 1,2-diol
Epoxides are more reactive than other ethers because of the ring strain.
1,2-diols are also called vicinal glycols; vicinal means adjacent. A glyclol is a diol
*
Ring-Opening
Also can be opened by reaction with acids other than H3O+
Anhydrous HF, HBr, HCl, or HI combine with an epoxide
Gives a trans product
*
Regiochemistry of acid-catalyzed ring-opening depends on the epoxide’s structure
Nucleophilic attack occurs primarily at the more highly substituted site, when one epoxide carbon atoms is tertiary
A mixture of products is often formed in the ring-opening of an epoxide.
When both epoxide carbon atoms are either primary or secondary, attack of the nucleophile occurs primarily at the less highly substituted site – an SN2-like result.
When one of the epoxide carbona toms is tertiary, however, nucleophilic attack occurs primarily at the more highly substituted site – an SN1-like result.
Thus, 1.2-epoxypropane reacts with HCl to give primarily 1-chloro-2-propanol, but 2-methyl-1,2-epoxypropane gives 2-chloro-2-methyl-1-propanol as the major product.
*
Ring-Opening of 1,2-epoxy-1-methylcyclohexane with HBr
*
Solution:
The rules for acid catalyzed opening of an epoxide are:
*
Base-Catalyzed Epoxide Opening
Epoxide rings can be cleaved by bases and nucleophiles, as well as acids
Strain of the three-membered ring is relieved on ring-opening
Hydroxide cleaves epoxides at elevated temperatures
While an ether oxygen is a poor leaving group in an SN2 reaction, the strain of the three-membered ring causes epoxides to react with hydroxide ion at elevated temperatures.
*
Amines and Grignard reagents can be used for epoxide opening
Ethylene oxide is frequently used
Allows conversion of a Grignard reagent into a primary alcohol
Many different nucleophiles can be used for epoxide opening, including amines (RNH2 or R2NH) and Grignard reagents.
*
Solution:
Addition of a Grignard reagent takes place at the less substituted epoxide carbon
Note the contrast of the site of reaction here which occurs at the less substituted carbon under anionic conditions.
*
y is the number of oxygen atoms
Central cavity is electronegative and attracts cations
*
Crown Ethers
Produce similar effects when used to dissolve an inorganic salt in a hydrocarbon to that of dissolving the salt in a polar aprotic solvent
18-Crown-6 chelates strongly solvates potassium cations
The anion associated with potassium is bare and therefore more nucleophilic
*
15-Crown-5 and 12-crown-4 ethers complex Na+ and Li+, respectively
Make models of these crown ethers, and compare the sizes of the cavities
Solution:
*
–SH group is called mercapto group
Thiols are also called mercaptans.
Like alcohols, thiols are weakly acidic; unlike alcohols they don’t typically form hydrogen bonds (S is not sufficiently electronegative).
*
Thiols
Prepared from alkyl halides by SN2 displacement with a sulfur nucleophile
Alkylthiol product can undergo further reaction with the alkyl halide
Gives symmetrical sulfide, a poorer yield of the thiol
*
Gives an intermediate alkyl isothiourea salt, hydrolyzed by subsequent reaction with an aqueous base
*
Yields disulfides (RSSR’)
Reaction is reversible
Oxidation and reduction are key parts of numerous biological processes
Disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide “bridges” often form cross-links between cysteine amino acid units in protein chains.
*
Sulfur analogues of ethers
Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy
Thiols when treated with a base gives corresponding thiolate ion
*
Sulfides
Thiols can undergo further reaction with the alkyl halide to give a sulfide
Sulfides and ethers differ substantially in their chemistry
Through SN2 mechanism, dialkyl sulfides react rapidly with primary alkyl halides to give sulfonium ions
Because the valence electrons on sulfur are farther from the nucleus and are less tightly held than those on oxygen, sulfur compounds are more nucleophilic than their oxygen analogs.
*
Oxidation of Thiols
Sulfides are easily oxidized by treatment with hydrogen peroxide at room temperature
Yields sulfoxide
Further oxidation of the sulfoxide with a peroxyacid yields a sulfone
Dimethyl sulfoxide is often used as a polar aprotic solvent
*
Infrared Spectroscopy
C–O single-bond stretching 1050 to 1150 cm-1 overlaps many other absorptions
Nuclear magnetic resonance spectroscopy
H on a C next to ether O is shifted downfield to 3.4 to 4.5
In epoxides, these H’s absorb at 2.5 to 3.5 in their 1H NMR spectra
*
*
The electronegative oxygen shifts absorption by hydrogens on adjacent carbons downfield. Typically they occur between 2.5 and 3.5 ppm.
*
Worked Example
The 1H NMR spectrum shown is that of a cyclic ether with the formula C4H8O
Propose a structure
Note there are five chemical shift positions but only four carbons. This means there must be two diastereotopic protons.
There is obviously a methyl and a methylene group. The remaining three signals correspond to methines.
Since there are no aromatic rings based on the number of carbons, draw a straight chain of four carbon atoms.
Since the methyl group is split into a triplet it must be next to the methylene. Thus one or both of the last two carbons must bear an oxygen substituent.
*
Suggested Problems –
Ethers
*
Names and Properties of Ethers
Simple ethers are named by identifying two organic substituents and adding the word ether
*
Possess nearly the same geometry as water
Bond angles of R–O–R bonds are approximately tetrahedral
Oxygen atom is sp3-hybridized
Relatively stable and unreactive in many aspects
Very useful as solvents in the laboratory
*
Limited to use with primary alcohols
*
Williamson Ether Synthesis
Reaction of metal alkoxides and primary alkyl halides and tosylates in an SN2 reaction
Best method for the preparation of ethers
Alkoxides are prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH
*
CHE2202, Chapter 18 Learn, *
Silver Oxide-Catalyzed Ether Formation
Reaction of alcohols with alkyl halides in the presence of Ag2O forms ethers in one step
*
Competitive E2 elimination with more hindered substrates
*
Williamson Ether Synthesis
*
How are the following ethers prepared using a Williamson synthesis?
a) Methyl propyl ether
Solution:
a)
b)
Methyl propyl ether can be performed in two ways depending on which half is derived from an alcohol and which half is derived from an alkyl halide.
*
Alkoxymercuration of Alkenes
Alkene is treated with an alcohol in the presence of mercuric acetate or trifluoroacetate
Demercuration with NaBH4 yields an ether
Overall Markovnikov addition of alcohol to alkene
Note the similarities between this reaction and the Markovnikov addition of water to alkenes. The mechanism is very similar.
The principal difference is an alcohol replaces water in oxymercuration demercuration of alkenes to form an ether.
*
Worked Example
Rank the following halides in order of their reactivity in Williamson synthesis:
a) Bromoethane, 2-bromopropane, bromobenzene
b) Chloroethane, bromoethane, 1-iodopropene
Cleaved by strong acids
HI, HBr produce an alkyl halide from less hindered component by SN2
Ethers are unreactive to many reagents used in organic chemistry, a property that accounts for their wide use as reaction solvents. However, ethers are cleaved by strong acids.
*
Reactions of Ethers: Acidic Cleavage
Ethers with tertiary, benzylic, or allylic groups cleave by either an SN1 or E1 mechanism
Intermediates are stable carbocations
*
Solution:
A primary alkyl group and a tertiary alkyl group is bonded to the ether oxygen
*
Specific to allyl aryl ethers and allyl vinyl ethers
Caused by heating ally aryl ether to 200-250°C
Leads to an o-allylphenol
Result is alkylation of the phenol in an ortho position
*
A similar rearrangement takes place with allyl vinyl ethers
A g,d-unsaturated ketone or aldehyde results
*
Takes place in a single step through a pericyclic mechanism
Reorganization of bonding electrons occurs in a six-membered, cyclic transition state
Mechanism is consistent with 14C labeling
*
Worked Example
What products are expected from Claisen rearrangement of 2-butenyl phenyl ether?
Solution:
Six bonds will either be broken or formed in the product - Represented by dashed lines in the transition state
*
Cyclic Ethers
Behave like acyclic ethers with the exception of three-membered ring epoxides
Strain of the three-membered ring gives epoxides a unique chemical reactivity
Dioxane and tetrahydrofuran are used as solvents
*
Ethylene oxide is industrially important as an intermediate
Prepared by reaction of ethylene with oxygen at 300 °C over a silver oxide catalyst
-ene ending implies the presence of a double bond in the molecule
The strain of the three-membered ring gives epoxides unique chemical reactivity.
The name, ethylene oxide, is not a systematic one because the –ene ending implies a double bond in the molecule.
The systematic name for ethylene oxide is 1,2-epoxyethane.
*
Also prepared from halohydrins
*
Addition of HO–X to an alkene gives a halohydrin
Treatment of a halohydrin with base gives an epoxide
Intramolecular Williamson ether synthesis
Explain why reaction of cis-2-butene with m-chloroperoxybenzoic acid yields an epoxide different from that obtained by reaction of the trans isomer
Solution:
Epoxidation, in this case, is a syn addition of oxygen to a double bond
*
Reaction of trans-2-butene with m-chloroperoxybenzoic acid yields trans-2,3- epoxybutane
*
Water adds to epoxides with dilute acid at room temperature
Product is a 1,2-diol
Epoxides are more reactive than other ethers because of the ring strain.
1,2-diols are also called vicinal glycols; vicinal means adjacent. A glyclol is a diol
*
Ring-Opening
Also can be opened by reaction with acids other than H3O+
Anhydrous HF, HBr, HCl, or HI combine with an epoxide
Gives a trans product
*
Regiochemistry of acid-catalyzed ring-opening depends on the epoxide’s structure
Nucleophilic attack occurs primarily at the more highly substituted site, when one epoxide carbon atoms is tertiary
A mixture of products is often formed in the ring-opening of an epoxide.
When both epoxide carbon atoms are either primary or secondary, attack of the nucleophile occurs primarily at the less highly substituted site – an SN2-like result.
When one of the epoxide carbona toms is tertiary, however, nucleophilic attack occurs primarily at the more highly substituted site – an SN1-like result.
Thus, 1.2-epoxypropane reacts with HCl to give primarily 1-chloro-2-propanol, but 2-methyl-1,2-epoxypropane gives 2-chloro-2-methyl-1-propanol as the major product.
*
Ring-Opening of 1,2-epoxy-1-methylcyclohexane with HBr
*
Solution:
The rules for acid catalyzed opening of an epoxide are:
*
Base-Catalyzed Epoxide Opening
Epoxide rings can be cleaved by bases and nucleophiles, as well as acids
Strain of the three-membered ring is relieved on ring-opening
Hydroxide cleaves epoxides at elevated temperatures
While an ether oxygen is a poor leaving group in an SN2 reaction, the strain of the three-membered ring causes epoxides to react with hydroxide ion at elevated temperatures.
*
Amines and Grignard reagents can be used for epoxide opening
Ethylene oxide is frequently used
Allows conversion of a Grignard reagent into a primary alcohol
Many different nucleophiles can be used for epoxide opening, including amines (RNH2 or R2NH) and Grignard reagents.
*
Solution:
Addition of a Grignard reagent takes place at the less substituted epoxide carbon
Note the contrast of the site of reaction here which occurs at the less substituted carbon under anionic conditions.
*
y is the number of oxygen atoms
Central cavity is electronegative and attracts cations
*
Crown Ethers
Produce similar effects when used to dissolve an inorganic salt in a hydrocarbon to that of dissolving the salt in a polar aprotic solvent
18-Crown-6 chelates strongly solvates potassium cations
The anion associated with potassium is bare and therefore more nucleophilic
*
15-Crown-5 and 12-crown-4 ethers complex Na+ and Li+, respectively
Make models of these crown ethers, and compare the sizes of the cavities
Solution:
*
–SH group is called mercapto group
Thiols are also called mercaptans.
Like alcohols, thiols are weakly acidic; unlike alcohols they don’t typically form hydrogen bonds (S is not sufficiently electronegative).
*
Thiols
Prepared from alkyl halides by SN2 displacement with a sulfur nucleophile
Alkylthiol product can undergo further reaction with the alkyl halide
Gives symmetrical sulfide, a poorer yield of the thiol
*
Gives an intermediate alkyl isothiourea salt, hydrolyzed by subsequent reaction with an aqueous base
*
Yields disulfides (RSSR’)
Reaction is reversible
Oxidation and reduction are key parts of numerous biological processes
Disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide “bridges” often form cross-links between cysteine amino acid units in protein chains.
*
Sulfur analogues of ethers
Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy
Thiols when treated with a base gives corresponding thiolate ion
*
Sulfides
Thiols can undergo further reaction with the alkyl halide to give a sulfide
Sulfides and ethers differ substantially in their chemistry
Through SN2 mechanism, dialkyl sulfides react rapidly with primary alkyl halides to give sulfonium ions
Because the valence electrons on sulfur are farther from the nucleus and are less tightly held than those on oxygen, sulfur compounds are more nucleophilic than their oxygen analogs.
*
Oxidation of Thiols
Sulfides are easily oxidized by treatment with hydrogen peroxide at room temperature
Yields sulfoxide
Further oxidation of the sulfoxide with a peroxyacid yields a sulfone
Dimethyl sulfoxide is often used as a polar aprotic solvent
*
Infrared Spectroscopy
C–O single-bond stretching 1050 to 1150 cm-1 overlaps many other absorptions
Nuclear magnetic resonance spectroscopy
H on a C next to ether O is shifted downfield to 3.4 to 4.5
In epoxides, these H’s absorb at 2.5 to 3.5 in their 1H NMR spectra
*
*
The electronegative oxygen shifts absorption by hydrogens on adjacent carbons downfield. Typically they occur between 2.5 and 3.5 ppm.
*
Worked Example
The 1H NMR spectrum shown is that of a cyclic ether with the formula C4H8O
Propose a structure
Note there are five chemical shift positions but only four carbons. This means there must be two diastereotopic protons.
There is obviously a methyl and a methylene group. The remaining three signals correspond to methines.
Since there are no aromatic rings based on the number of carbons, draw a straight chain of four carbon atoms.
Since the methyl group is split into a triplet it must be next to the methylene. Thus one or both of the last two carbons must bear an oxygen substituent.
*