CHAPTER 9: ALCOHOLS AND ETHERS - Chemistry 21 · CHAPTER 9: ALCOHOLS AND ETHERS NOMENCLATURE AND...
Transcript of CHAPTER 9: ALCOHOLS AND ETHERS - Chemistry 21 · CHAPTER 9: ALCOHOLS AND ETHERS NOMENCLATURE AND...
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CHAPTER 9: ALCOHOLS AND ETHERS
NOMENCLATURE AND EXAMPLES
ALCOHOLS
COMMON ALCOHOLS
Ethanol Methanol Isopropanol Glycerin
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NAMING ALCOHOLS
1.! Number the parent chain so the –OH group is the lowest number possible. Ending is –ol.
2.! With cyclic alcohols, the –OH group is understood to be position #1 (does not need to be indicated).
ETHERS
COMMON ETHERS Anesthetics
Diethyl Ether first to produce deep anesthesia in 1846
Enflurane Anesthetic in 1970’s
and 80’s
Sevoflurane Current anesthetic
Solvents
Diethyl ether Tetrahydrofuran (THF) 1,4-dioxane (Dioxane) Daughter was sedated with sevoflurane in 2012
OO
O
O
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NAMING ETHERS
1)! SIMPLE ETHERS
Name each alkyl group alphabetically, and add “ether” as a separate word.
MTBE (used as a gasoline anti-knock additive starting in 2003) gives water an unpleasant taste at very low concentrations. It is not carcinogenic, and can be degraded by bacteria. However, it is partially banned in US.
“MTBE is the 2nd most frequently detected VOC in domestic and public wells despite its relatively short production and use history.”1 However, most concentrations are much lower than EPA recommendations.
2)! MORE COMPLEX ETHERS
Name the simpler alkyl group as an “alkoxy” group, and consider it a substituent. Name the compound in a regular manner (ether is not the parent group).
1 https://water.usgs.gov/nawqa/vocs/national_assessment/report/chapter5.html (Aug, 2017)
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SYNTHESIS OF ALCOHOLS AND ETHERS
SYNTHESIS APPLICATION
ALCOHOL CATEGORIES
Primary alcohol 1˚ ROH
Secondary alcohol 2˚ ROH
Tertiary alcohol 3˚ ROH
SYNTHESIS OF ALCOHOLS / ETHERS WITH CURRENT METHODS
Primary Alcohols
Tertiary Alcohols
Secondary Alcohols
Certain Ethers
C
OH
C C
OH
C
C C C
OH
C
C
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WILLIAMSON ETHER SYNTHESIS
GENERAL REACTION
RETROSYNTHESIS (BACKWARDS THINKING)
Synthesize butyl methyl ether with the Williamson Ether Synthesis.
Synthesize the following ether with the Williamson Ether Synthesis.
a. NaHCH3 O H
b. CH3Br
OH
a. NaH b. CH3CH2Cl
Alexander Williamson (1850)
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EXAMPLES
Give the major organic product of each reaction.
Reactants
Rate
(k1 / k2)2 1 9.5 × 102 2.2 × 105 5 × 107
2 H.D. Belitz, W. Grosch, P. Schierberle, Food Chemistry, 3rd edition, 2004, pp. 111
OHa. NaH
b. CH3CH2CH2I
Cl
a. NaH
b.CH3CH2OH
OR
O
O
O
RO
O
O
ORO
O
O
O
O
OR
O
OO
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REACTIONS OF ALCOHOLS
STRATEGY #1
DEHYDRATION
GENERAL REACTION
MECHANISM WITH 2˚ AND 3˚ ROH
CATALYTIC ACID
OH
con. H3PO4
Δ
Con. H2SO4 or H3PO4
heat (!)
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MECHANISM WITH 1˚ ROH
PRODUCT MIXTURES
APPLICATION3
3 G. Buchi, William D. Macleod, Synthesis of Patchouli Alcohol, J. Am. Chem. Soc., 1962, 84 (16), pp 3205–3206.
OH con. H2SO4heat
OH
con. H2SO4170 ˚C
OH con. H3PO4
Δ
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REACTION ENERGY DIAGRAM
1)! REACTION TO STUDY + MECHANISM
2)! BOND ENERGIES TO ESTIMATE !H
3)! ENERGY DIAGRAM
METHODS USED TO DRIVE THE REACTION
con. H2SO4heat
H C
H
C
H
H
H OH
con. H2SO4
heatH C
H
C
H
H
H OH
H C
H
C
H
H OH H+
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REARRANGEMENTS
HYDRIDE SHIFTS
1)! MECHANISM
2)! MOTIVATION FOR HYDRIDE SHIFTS
OH con. H2SO4
heat
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3)! EXAMPLE
A rearrangement occurs in this reaction. What products are likely to form from the rearrangement?
ALKYL SHIFTS
OHcon. H2SO4
Δ
OH
85% H3PO480 ˚C
OH
con. H2SO4
heat
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ALCOHOL REACTION STRATEGY #2
ROH REACTION WITH HX
GENERAL REACTION
MECHANISM WITH 2˚ OR 3˚ ROH
MECHANISM WITH 1˚ ROH
FYI: Normally HCl is used with ZnCl2 to accelerate the reaction. The Lucas Test Reagent (in lab) contains 160 g ZnCl2 in 100 mL concentrated HCl.
R OH R XNu
R Nu
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EXAMPLES
Give the expected major product for each reaction, considering plausible rearrangements.
BIOLOGICAL METHYLATIONS
Biosynthesis of morphine:
Biological methylations often use “SAM” (S-Adenosylmethionine), which is created by the reaction of methionine (an amino acid) with ATP. For example, the biosynthesis of adrenaline (“fight or flight”):
OH
HBr
OHHBr
OH
HCl
OH
HCl
OH
CH2CH3CH2CH3 HI
morphine
HO
CO2
NH3
tyrosine (an amino acid)
NH
HO
HO
HO
N
H3CO
HO
HO
CH3
OHO
OH
NCH3
HO
HO
NH2
OH
noradrenaline(norepinephrine)
N
NN
N
NH2
O
OHOH
SCH3
ONH3
O
(S)-AdenosylmethionineHO
HO
HN
OH
adrenaline(epinephrine)
CH3
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ROH REACTION WITH PBr3
GENERAL REACTION
MECHANISM + STEREOCHEM
ROH REACTION WITH SOCl2
GENERAL REACTION
MECHANISM + STEREOCHEM
OH
ClS
Cl
O
OS
H
Cl
O OS
Cl
O
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SUMMARY AND PROBLEMS
SUMMARY
PBr3 Reaction SOCl2 Reaction Tosylate Reaction
SN2 (Inversion) SN2 (Inversion) Not SN2 (no inversion)
PROBLEMS
1)! SUBSTITUTION WITH NO INVERSION
2)! SUBSTITUTION WITH INVERSION
H3C OH H3C BrPBr3 H3C OH H3C Cl
SOCl2 H3C OH H3C OTsTsCl
py.
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3)! OTHER EXAMPLES
Give the major product for first two reactions, then devise a synthesis for the last reaction.
EPOXIDES
REACTION WITH STRONG NUCLEOPHILES
GENERAL REACTION
Nu– : OH–, OR–, SH–, CN–,
OHa. PBr3b. KOCH2CH3
OCH3
OH
a. TsCl, py.
b. NaCN
O
OH
O
SH
O NaOCH3CH3OH
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STEREOSELECTIVITY
CASCADE EPOXIDATIONS
Gymnocin B is the largest contiguous polyether ring system. It can be isolated from the red tide dinoflagellate Karenia mikimotoi.4
4 Solomons, Organic Chemistry, 12th edition, 2016, p 370.
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The biosynthesis of all steroids involves a cascade reaction of squalene, initiated by opening an epoxide.
REACTION WITH WEAK NUCLEOPHILES
GENERAL REACTION
Nu: X–, H2O, ROH
REGIOSELECTIVITY
Product distribution5
5 Jones, M., Fleming, S.A., Organic Chemistry, 4th ed., Norton, 2010, pp. 457
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REMOVAL OF CARCINOGENS6
Aflatoxins are among the most carcinogenic substances known. They are produced by certain molds (Aspergillus flavus and Aspergillus parasiticus), and are regularly found in improperly stored foods like corn, millet, peanuts, rice, sesame seeds, and wheat.
Adult humans have a high tolerance to aflatoxins, but children are susceptible. Aflatoxins are removed from the body by epoxidation followed by reaction with glutathione.
Polycyclic aromatic hydrocarbons (PAH’s) have been linked to several cancers. They can be found in smoke from solid fuels like wood, coal, and cigarettes, but are also found in the smoke from combusted diesel.
Their carcinogenic mechanisms vary. One mechanism is that enzymatic epoxidation of PAH’s creates intermediates that are reactive to the nucleophiles on DNA. Once attached to DNA, the PAH’s interfere with correct DNA replication, leading to mutations.
6 Solomons, G., Fryhle, C.B., Organic Chemistry, 8th ed., Wiley, 2004, pp. 521
O
O
O
O O
H
H
Aflatoxin B1 (fungus)
O
O
O
O O
H
H
Ocytochrome P-450
O
O
O
O O
H
H
H3NHN
NH
O
OO
OS
O
O
HOGlutathione
Two of the most carcinogenic substances knownH3N
HN
NH
O
OO
OSH
O
O
Glutathione
A polycyclic aromatic hydrocarbon
Cytochrome P-450
enzymeO
HO
OH
HO
OH
HO
DNADNA Nuc