Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI10a_OH.pdf · AFB QO I 2007/08 4 Common Alcohols Methanol, methyl alcohol, wood alcohol common solvent fuel additive antifreeze

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Química Orgânica I

Ciências Farmacêuticas

Bioquímica

Química

AFB QO I 2007/08 2

alcohols

� Adaptado de � Organic Chemistry, 6th Edition; Wade

� Organic Chemistry, 6th Edition; McMurry

� Organic Chemistry, 5th Edition; Vollhardt

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FG -OH

� Alcohols contain an OH group connected to a a saturated C (sp3)

� Phenols contain an OH group connected to a carbon in a benzene ring

� Enols are unstable relative to ketones

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Common Alcohols� Methanol, methyl

alcohol, wood alcohol� common solvent � fuel additive� antifreeze� fuel � produced in large

quantities by hydrogenation of carbon monoxide

� preparation of formaldehyde, HCHO

CO + 2H2 → CH3OHCO + 2HCO + 2H22 →→ CHCH33OHOH

Catalyst: zinc oxide/chromia

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Common Alcohols

http://www.ttmethanol.com/web/methprocess.html#

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Common Alcohols� Ethanol, ethyl alcohol,

grain alcohol, CH3CH2OH, EtOH

� Solvent� Fuel� Beverage� industrial chemical� Most ethanol comes from

fermentation� Synthetic ethanol is

produced by hydrationof ethylene

� (intense research on synthesis)

http://www.ethanol.org http://www.edmunds.com/advice/alternativefuels/articles/109194/article.html

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Sugar alcohols

� Polyalcohols, e.g. Mannitol, Xylitol, Maltitol, Galactitol, Erythritol, Inositol, Ribitol, Dithioerythritol, Dithiothreitol, and Glycerol

� hydrogenated starch hydrolysates

� found in berries, apples, plums...

� produced commercially from carbohydrates such as sucrose, glucose and starch.

http://www.ific.org/publications/factsheets/sugaralcoholfs.cfm

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Sugar alcohols

0.422.41.0Xylitol

0.232.60.6Sorbitol

0.311.60.5Mannitol

0.432.10.9Maltitol

0.22.00.4Lactitol

0.252.00.5Isomalt

0.13–0.33.00.4–0.9HSH

0.144.30.6Glycerol

3.4980.2130.812Erythritol

0.254.01.0Sucrose

3.50.20.7Arabitol

S/kcal/gkcal/gSweetness (S)Name

http://scientificpsychic.com/fitness/carbohydrates1.html

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Erythritol (2R,3S)-butane-1,2,3,4-tetraol)

� natural sugar alcohol

� It occurs naturally in fruits and fermented foods.

� Produced industrially from glucose by fermentation with a yeast, Moniliella pollinis.

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Natural alcohols

� lauryl alcohol

� cetyl alcohol (Cetanol, Ethal, Ethol, Hexadecanol, Hexadecyl alcohol, Palmityl alcohol)

� stearyl alcohol (Octadecyl alchohol)� (lubricants, resins, perfumes and cosmetics)

� behenyl alcohol � (antiviral agent)

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Bombykol

Prostaglandin E1

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Nomenclature of alcohols

� General classifications of alcohols based on substitution on C to which OH is attached

� Methyl (C has 3 H’s), Primary (1°) (C has two H’s, one R), secondary (2°) (C has one H, two R’s), tertiary (3°) (C has no H, 3 R’s)

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IUPAC Rules for Naming Alcohols

� Select the longest carbon chain containing the hydroxyl group, and derive the parent name by replacing the -eending of the corresponding alkane with -ol

� Number the chain from the end nearer the hydroxyl group

� Number substituents according to position on chain, listing the substituents in alphabetical order

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Unsaturated Alcohols

� Hydroxyl group takes precedence. Assign that carbon the lowest number.

� Use alkene or alkyne name.

4-penten-2-ol

pent-4-ene-2-ol

CH2 CHCH2CHCH3

OH

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Naming Priority

� Acids

� Esters

� Aldehydes

� Ketones

� Alcohols

� Amines

� Alkenes

� Alkynes

� Alkanes

� Ethers

� Halides

=>

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Nomenclature

CH2CH2CH2COOH

OH

4-hydroxybutanoic acid

HO OH 1,6-hexanediol

hexane-1,6-diol

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Glycols

� 1,2 diols (vicinal diols) are called glycols.

� Common names for glycols use the name of the alkene from which they were made.

CH2CH2

OH OH

CH2CH2CH3

OH OH

1,2-ethanediol

ethylene glycol

1,2-propanediol

propylene glycol=>

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Many Alcohols Have Common Names

� These are accepted by IUPAC

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Structure of Alcohols

� Hydroxyl (OH) functional group

� Oxygen is sp3 hybridized.

=>

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The O-H bond is shorter than the C-H bonds.

The bond strength of the O-H bond is greater than that of the C-H bonds:

•DHoO-H = 104 kcal mol

-1

•DHoC-H = 98 kcal mol

-1

Structure of alcohols

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Due to the electronegativity difference between oxygen and hydrogen, the O-H bond is polar.

O-H bond

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high boiling points

Hydrogen bonding between alcohol molecules is much stronger than the London forces and dipole-dipole interactions in alkanesand haloalkanes

•O···H-O DHo ~ 5-6 kcal mol-1

•Covalent O-H DHo = 104 kcal mol-1.

An alcohol molecule makes ~ 2 hydrogen bonds to other alcohol molecules on the average.

A water molecule forms hydrogen bonds to ~ 4 other water molecules.

Hydrogen bonding in alcohols

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Properties of Alcohols

� The structure around O of the alcohol is similar to that in water, sp3 hybridized

� Alcohols have much higher boiling points than similar alkanes and alkyl halides

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Alcohols Form Hydrogen Bonds

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alcohols are soluble in water: The –OH groups of alcohols are hydrophilic and enhance solubility.

Alkanes and most alkyl chains are said to be hydrophobic

In order to dissolve, alkanes must interrupt the strong hydrogen bonding between water molecules which is then replaced by weaker dipole induced-dipole forces (∆H > 0).

In addition, long hydrocarbon chains force water molecules to form a cage like (or clathrate) structure about the non-polar chain which greatly reduces the entropy of the water molecules involved (∆S < 0).

Alcohols are popular protic solvents for SN2 reactions.

solubility

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Solubility in Water

Solubility decreases as the size

of the alkyl group increases.

=>

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Properties of Alcohols

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Acidity and Basicity

� Alcohols are weak Brønsted bases, protonated by strong acids to yield oxonium ions, ROH2

+

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Brønsted Acidity Measurements

� The acidity constant, Ka, measure the extent to which a Brønsted acid transfers a proton to water

[A−−−−] [H3O+]

Ka = ————— and pKa = −log Ka[HA]

� Relative acidities are more conveniently presented on a logarithmic scale, pKa, which is directly proportional to the free energy of the equilibrium

� Differences in pKa correspond to differences in free energy

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Relative Acidities of Alcohols

� Simple alcohols are about as acidic as water

� Alkyl groups make an alcohol a weaker acid

� The more easily the alkoxide ion is solvated by water the more its formation is energetically favored; stericeffects are important

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The acidity of an alcohol varies (relative pKa in solution):

Strongest acid Weakest acid

CH3OH < primary < secondary < tertiary

Steric disruption effects control the acidity of alcohols.

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Alkoxides from Alcohols

� Alcohols are weak acids – requires a strong base to form an alkoxide such as NaH, sodium amide NaNH2, and Grignard reagents (RMgX)

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Inductive Effects

� Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)

Inductive EffectGreater inductive effects are seen with a greater number of

electronegative atoms and with closer proximity to the

anion

CH3CH2OH pKa = 15.9

ClCH2CH2OH pKa = 14.3

CF3CH2OH pKa = 12.4

CF3CH2CH2OH pKa = 14.6

CF3CH2CH2CH2OH pKa = 15.4

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The lone electron pairs on oxygen make alcohols basic.

Alcohols may be weakly basic as well as being acidic.

Molecules that can be both acidic and basic are called amphoteric.

Very strong acids are required to protonate alcohols.

alcohols basicity

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Alkoxides from Alcohols

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Spectroscopy rev.

� No UV/vis

� IR

� MS

� H1-NMR

� C13-NMR

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� O—H stretching: 3200-3650 cm–1 (broad)

� C—O stretching: 1025-1200 cm–1 (broad)

� C-H bands around 3000 cm-1.

AFB QO I 2007/08 42Francis A. Carey, Organic Chemistry, Fourth Edition. Copyright © 2000 The McGraw-Hill Companies, Inc. All rights reserved.

2000200035003500 30003000 25002500 1000100015001500 500500

Wave number, cmWave number, cm--11

OO——HH

CC——HH

CC——OO

OHOH

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CC OOHH HH

δδ 3.33.3--4 4 ppmppm δδ 0.50.5--5 5 ppmppm

1H NMR Spectroscopy

� The O-H proton is highly variable in its chemical shift, � normally broad (due to H-bonding) � not coupled to other protons except under special

circumstances. � D2O exchange� The second signal is that for any proton on the oxygen-

bearing carbon; this will occur between 3.5-4.5 ppm and will couple normally to its neighbors (but not usually to the OH).

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01.02.03.04.05.06.07.08.09.010.0

CHCH22CHCH22OHOH

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1313C NMR spectroscopyC NMR spectroscopy

chemical shift of Cchemical shift of C——OH is OH is δδ 6060--80 80 ppmppm

CC——O is about 35O is about 35--50 50 ppmppm less shielded than Cless shielded than C——HH

CHCH33CHCH22CHCH22CHCH33 CHCH33CHCH22CHCH22CHCH22OHOH

δδ 13 13 ppmppm δδ 61.4 61.4 ppmppm

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13C NMR Spectroscopy

Carbons bearing an oxygen are deshielded and normally occur in the 60-80 ppm region; a carbon with more than one oxygen may be further downfield.

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UVUV--VISVIS

Unless there are other Unless there are other chromophoreschromophores in thein the

molecule, alcohols are transparent abovemolecule, alcohols are transparent above

about 200 nm; about 200 nm; λλmaxmax for methanol, forfor methanol, for

example, is 177 nm.example, is 177 nm.

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Mass Spectrometry of AlcoholsMass Spectrometry of Alcohols

molecular ion peak is usually smallmolecular ion peak is usually small

a peak corresponding to loss of Ha peak corresponding to loss of H22OOfrom the molecular ion (M from the molecular ion (M -- 18) is18) isusually presentusually present

peak corresponding to loss of anpeak corresponding to loss of analkyl group to give an oxygenalkyl group to give an oxygen--stabilized stabilized carbocationcarbocation is usuallyis usuallyprominentprominent

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Synthesis

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� alcohols can prepared by SN2 and SN1� hydroxide and water respectively as nucleophiles .

� drawbacks:� Elimination

� Rearrangements

� The use of polar, aprotic solvents alleviates some of these problems.

Synthesis of Alcohols by Nucleophilic Substitution

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Synthesis of Alcohols by Nucleophilic Substitution

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The problem of elimination in SN2 reactions of oxygen nucleophiles with secondary or sterically encumbered, branched primary substrates is the use of acetate as a less basic nucleophile.

Step 1: Acetate formation (SN2 reaction)

Step 2: Conversion to alcohol (hydrolysis)

Synthesis of Alcohols by Nucleophilic Substitution

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Synthesis of Alcohols by Regiospecific Hydration of Alkenes

� Hydroboration/oxidation: syn, non-Markovnikovhydration

� Oxymercuration/reduction: Markovnikov hydration

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Preparation of 1,2-Diols

� Review: Cis 1,2-diols from hydroxylation of an alkenewith OsO4 followed by reduction with NaHSO3

� In Chapter 18: Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides

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Reduction of Aldehydes and Ketones

� Aldehydes gives primary alcohols

� Ketones gives secondary alcohols

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Hydride reducing agents

� Sodium Borohydride, NaBH4, is not sensitive to moisture; it does not reduce other common carbonyl functional groups

� Lithium aluminum hydride, LiAlH4, is more powerful, less specific, and very reactive with water. diethyl ether is most commonly used solvent

NaNa++ ––

BB

HH

HH

HHHH

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Hydride Reducing Agents:

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From mannose to mannitol

OHO

HO

OH

OH

OH

OHHO

HO

OH

OH

O

NaBH4HO

OH

OH

OH

OH O

HO

OH

OH

OH

OH OH

osmotic diuretic agent weak renal vasodilator

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Reduction of Carboxylic Acids and Esters

lithium aluminum hydride is only effective reducing agentlithium aluminum hydride is only effective reducing agent

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Mechanism of hydride reduction

� The reagent adds the equivalent of hydride (H-) to the carbon of C=O

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Catalytic hydrogenation

MeO

H

O

H2

Pt/EthanolMeO

H

OH

H2

Pt/Ethanol

O OH

H2

OONi

OHHO

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Hydrogenation: Selectivity

1) LiAlH4/ether

2) H2O

O OH

neither NaBH4 or LiAlH4neither NaBH4 or LiAlH4reduces isolatedreduces isolateddouble bondsdouble bonds

(90%)(90%)

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Grignard Reagents

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Grignard Reagents

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Grignard Reagents

Ester reaction

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Carboxylic Acids and Grignard Reagents

� Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

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Limitations of Grignard Reagents

� Can't be prepared if there are reactive functional groups in the same molecule, including proton donors

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Mechanism of the Addition of a Grignard Reagent

� Grignard reagents act as nucleophiliccarbon anions in adding to a carbonyl group

� The intermediate alkoxide is then protonated to produce the alcohol

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Epoxides and Grignard Reagents

1)

ether

2) H3O+

MgBrO

OH