Chapter 11 Carboxylic Acid Derivatives

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Chapter 11Carboxylic Acid Derivatives


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Acid Derivatives

• All acid derivatives can be converted to the
  carboxylic acid by acidic or basic hydrolysis.
• Esters and amides are common in nature.

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Naming Esters

• IUPAC Nomenclature
• As usual the long chain will contain the carbonyl
  carbon. Drop the e then add oate suffix. The
  remaining carbon chain is named as substituent
  and used as a prefix.
• Common Nomenclature
• Esters are named from the common name of the acid
  used to form them. Drop the oic acid from the
  common acid name and att the suffix ate. The
  other carbon group is named as a substituent.

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Naming Esters

• IUPAC Nomenclature
• As usual the long chain will contain the carbonyl
  carbon. Drop the e then add oate suffix. The
  remaining carbon chain is named as substituent
  and used as a prefix.
• Common Nomenclature
• Esters are named from the common name of the acid
  used to form them. Drop the oic acid from the
  common acid name and att the suffix ate. The
  other carbon group is named as a substituent.

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Name These
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Name These
(Common)
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Name These
isobutyl acetate (Common)
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Name These
isobutyl acetate (Common)
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Name These
isobutyl acetate (Common) 2-methylpropyl
ethanoate (IUPAC)
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Name These
isobutyl acetate (Common) 2-methylpropyl
ethanoate (IUPAC)
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Cyclic Esters

• Reaction of -OH and -COOH on same molecule
  produces a cyclic ester, lactone.
• To name, add word lactone to the IUPAC acid name
  or replace the -ic acid of common name with
  -olactone.

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Cyclic Esters

• Reaction of -OH and -COOH on same molecule
  produces a cyclic ester, lactone.
• To name, add word lactone to the IUPAC acid name
  or replace the -ic acid of common name with
  -olactone.

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Amides

• Product of the reaction of a carboxylic acid and
  ammonia or an amine.
• Not basic because the lone pair on nitrogen is
  delocalized by resonance.

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Classes of Amides

• 1? amide has one C-N bond (two N-H).
• 2? amide or N-substituted amide has two C-N bonds
  (one N-H).
• 3? amide or N,N-disubstituted amide has three C-N
  bonds (no N-H).
  

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Naming Amides

• For 1? amide, drop -ic or -oic acid from the
  carboxylic acid name, add -amide.
• For 2? and 3? amides, the alkyl groups bonded to
  nitrogen are named with N- to indicate their
  position.

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Naming Amides

• For 1? amide, drop -ic or -oic acid from the
  carboxylic acid name, add -amide.
• For 2? and 3? amides, the alkyl groups bonded to
  nitrogen are named with N- to indicate their
  position.

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Cyclic Amides

• Reaction of -NH2 and -COOH on same molecule
  produces a cyclic amide, lactam.
• To name, add word lactam to the IUPAC acid name
  or replace the -ic acid of common name with
  -olactam.

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Cyclic Amides

• Reaction of -NH2 and -COOH on same molecule
  produces a cyclic amide, lactam.
• To name, add word lactam to the IUPAC acid name
  or replace the -ic acid of common name with
  -olactam.

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Nitriles

• -C?N can be hydrolyzed to carboxylic acid, so
  nitriles are acid derivatives.
• Nitrogen is sp hybridized, lone pair tightly
  held, so not very basic (pKb about 24).

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Naming Nitriles

• For IUPAC names, add -nitrile to the alkane name.
• Common names come from the carboxylic acid.
  Replace -ic acid with -onitrile.

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Naming Nitriles

• For IUPAC names, add -nitrile to the alkane name.
• Common names come from the carboxylic acid.
  Replace -ic acid with -onitrile.

5-bromohexanenitrile ?-bromocapronitrile
Cyclohexanecarbonitrile

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Acid Halides

• More reactive than acids the halogen withdraws
  e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.

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Acid Halides

• More reactive than acids the halogen withdraws
  e- density from carbonyl.
• Named by replacing -ic acid with -yl halide.

3-bromobutanoyl bromide ?-bromobutyryl bromide

benzoyl chloride
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Acid Anhydrides

• Two molecules of acid combine with the loss of
  water to form the anhydride.
• Anhydrides are more reactive than acids, but less
  reactive than acid chlorides.
• A carboxylate ion is the leaving group in
  nucleophilic acyl substitution reactions.

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Naming Anhydrides

• The word acid is replaced with anhydride.
• For a mixed anhydride, name both acids.
• Diacids may form anhydrides if a 5- or 6-membered
  ring is the product.

gt
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Naming Anhydrides

• The word acid is replaced with anhydride.
• For a mixed anhydride, name both acids.
• Diacids may form anhydrides if a 5- or 6-membered
  ring is the product.

ethanoic anhydride acetic anhydride
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Multifunctional Compounds

• The functional group with the highest priority
  determines the parent name.
• Acid gt ester gt amide gt nitrile gt aldehyde gt
  ketone gt alcohol gt amine gt alkene gt alkyne.

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Multifunctional Compounds

• The functional group with the highest priority
  determines the parent name.
• Acid gt ester gt amide gt nitrile gt aldehyde gt
  ketone gt alcohol gt amine gt alkene gt alkyne.

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Boiling Points
Even 3? amides have strong attractions.
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Melting Points

• Amides have very high melting points.
• Melting points increase with increasing number of
  N-H bonds.

m.p. -61?C
m.p. 28?C
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Solubility

• Acid chlorides and anhydrides are too reactive to
  be used with water or alcohol.
• Esters, 3? amides, and nitriles are good polar
  aprotic solvents.
• Solvents commonly used in organic reactions
• Ethyl acetate
• Dimethylformamide (DMF)
• Acetonitrile
  

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Interconversion ofAcid Derivatives

• Nucleophile adds to the carbonyl to form a
  tetrahedral intermediate.
• Leaving group leaves and CO regenerates.

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Reactivity

• Reactivity decreases as leaving group becomes
  more basic.

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Interconversion of Derivatives

• More reactive derivatives can be converted to
  less reactive derivatives.

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Acid Chloride to Anhydride

• Acid or carboxylate ion attacks the CO.
• Tetrahedral intermediate forms.
• Chloride ion leaves, CO is restored, H is
  abstracted.
  

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Acid Chloride to Ester

• Alcohol attacks the CO.
• Tetrahedral intermediate forms.
• Chloride ion leaves, CO is restored, H is
  abstracted.
  

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Acid Chloride to Amide

• Ammonia yields a 1? amide
• A 1? amine yields a 2? amide
• A 2? amine yields a 3? amide

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Anhydride to Ester

• Alcohol attacks one CO of anhydride.
• Tetrahedral intermediate forms.
• Carboxylate ion leaves, CO is restored, H is
  abstracted.
  

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Anhydride to Amide

• Ammonia yields a 1? amide
• A 1? amine yields a 2? amide
• A 2? amine yields a 3? amide

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Ester to Amide

• Nucleophile must be NH3 or 1? amine.
• Prolonged heating required.

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Leaving Groups

• A strong base is not usually a leaving group
  unless its in an exothermic step.

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Transesterification

• One alkoxy group can be replaced by another with
  acid or base catalyst.
• Use large excess of preferred alcohol.

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TRANSESTERIFICATION OF COCAINE
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Hydrolysis of Acid Chlorides and Anhydrides

• Hydrolysis occurs quickly, even in moist air with
  no acid or base catalyst.
• Reagents must be protected from moisture.

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Acid Hydrolysis of Esters

• Reverse of Fischer esterification.
• Reaches equilibrium.
• Use a large excess of water.

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Saponification

• Base-catalyzed hydrolysis of ester.
• Saponification means soap-making.
• Soaps are made by heating NaOH with a fat
  (triester of glycerol) to produce the sodium salt
  of a fatty acid - a soap.
• One example of a soap is sodium stearate, Na
  -OOC(CH2)16CH3.
  

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Hydrolysis of Amides

• Prolonged heating in 6 M HCl or 40 aqueous NaOH
  is required.

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Hydrolysis of Nitriles

• Under mild conditions, nitriles hydrolyze to an
  amide.
• Heating with aqueous acid or base will hydrolyze
  a nitrile to an acid.

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Reduction to Alcohols

• Lithium aluminum hydride reduces acids, acid
  chlorides, and esters to primary alcohols.

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Acid Chloride Synthesis

• Use thionyl chloride, SOCl2, or oxalyl chloride,
  (COCl)2.
• Other products are gases.

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Acid Chloride Reactions (1)
acid
ester
amide
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Lab Synthesis of Anhydrides

• React acid chloride with carboxylic acid or
  carboxylate ion.

• Heat dicarboxylic acids to form cyclic
  anhydrides.

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Anhydride Reactions
acid
ester
amide
AlCl3
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Anhydride vs. Acid Chloride

• Acetic anhydride is cheaper, gives a better yield
  than acetyl chloride.
• Use acetic formic anhydride to produce formate
  esters and formamides.

• Use cyclic anhydrides to produce a difunctional
  molecule.

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Synthesis of Esters
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Synthesis of Amides
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Reactions of Amides
acid and amine
amine
1 amine
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CHAPTER 11 REVIEW
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Name

• a. Ethyl ethanoate
• b. Propyl propanoate
• c. Ethyl propanoate
• d. Propyl ethanoate
• e. Propyl butanoate

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Answer

• a. Ethyl ethanoate
• b. Propyl propanoate
• c. Ethyl propanoate
• d. Propyl ethanoate
• e. Propyl butanoate

• The longest chain is three carbons. Propyl is
  the alkoxy group.

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Name

• a. 3-Hydroxybutanoic acid lactone
• b. 4-Hydroxybutanoic acid lactone
• c. 4-Hydroxypentanoic acid lactone
• d. 5-Hydroxypentanoic acid lactone

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Answer

• a. 3-Hydroxybutanoic acid lactone
• b. 4-Hydroxybutanoic acid lactone
• c. 4-Hydroxypentanoic acid lactone
• d. 5-Hydroxypentanoic acid lactone

• A lactone is a cyclic ester. The hydroxy is on
  the fifth carbon.

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Name

• a. Pentanamide
• b. Butanamide
• c. N-Ethylethanamide
• d. N-Ethylpropanamide
• e. N-Methylethanamide

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Answer

• a. Pentanamide
• b. Butanamide
• c. N-Ethylethanamide
• d. N-Ethylpropanamide
• e. N-Methylethanamide

• Ethyl is attached to the nitrogen. The longest
  chain is three carbons.

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21.4 Name

• a. 3-Aminobutanoic acid lactam
• b. 4-Aminobutanoic acid lactam
• c. 4-Aminopentanoic acid lactam
• d. 5-Aminopentanoic acid lactam

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Answer

• a. 3-Aminobutanoic acid lactam
• b. 4-Aminobutanoic acid lactam
• c. 4-Aminopentanoic acid lactam
• d. 5-Aminopentanoic acid lactam

• A lactam is a cyclic amide. The amino group is on
  the fifth carbon.

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Name

• a. Pentanenitrile
• b. Butanenitrile
• c. Propanenitrile
• d. 2-Methylbutanenitrile
• e. 3-Methylbutanenitrile

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Answer

• a. Pentanenitrile
• b. Butanenitrile
• c. Propanenitrile
• d. 2-Methylbutanenitrile
• e. 3-Methylbutanenitrile

The longest chain has four carbons. The methyl
is on the third carbon.
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Name

• a. 1-Chloroethanoyl chloride
• b. 2-Chloroethanoyl chloride
• c. 1-Chloropropanoyl chloride
• d. 2-Chloropropanoyl chloride

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Answer

• a. 1-Chloroethanoyl chloride
• b. 2-Chloroethanoyl chloride
• c. 1-Chloropropanoyl chloride
• d. 2-Chloropropanoyl chloride

The longest chain has three carbons. Chlorines
are on the second carbon and the carbonyl carbon.
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Name

• a. Ethanoic methanoic anhydride
• b. Methanoic propanoic anhydride
• c. Ethanoic anhydride
• d. Ethanoic propanoic anhydride
• e. Propanoic anhydride

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Answer

• a. Ethanoic methanoic anhydride
• b. Methanoic propanoic anhydride
• c. Ethanoic anhydride
• d. Ethanoic propanoic anhydride
• e. Propanoic anhydride

• The three-carbon chain is on the left. A
  two-carbon chain is on the right.

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• a. Ethanoic methanoic anhydride
• b. Methanoic propanoic anhydride
• c. Ethanoic anhydride
• d. Ethanoic propanoic anhydride

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Answer

• a. Ethanoic methanoic anhydride
• b. Methanoic propanoic anhydride
• c. Ethanoic anhydride
• d. Ethanoic propanoic anhydride

An acid halide reacts with a carboxylic acid to
form an anhydride.
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• a. Methyl ethanoate
• b. Methyl propanoate
• c. Ethyl ethanoate
• d. Ethyl propanoate

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Answer

• a. Methyl ethanoate
• b. Methyl propanoate
• c. Ethyl ethanoate
• d. Ethyl propanoate

An acid halide reacts with an alcohol to form an
ester.
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• a. N-Methylethanamide
• b. N-Methylpropanamide
• c. N,N-Dimethylethanamide
• d. N,N-Dimethylpropanamide

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Answer

• a. N-Methylethanamide
• b. N-Methylpropanamide
• c. N,N-Dimethylethanamide
• d. N,N-Dimethylpropanamide

• An acid halide reacts with an amine to form an
  amide.

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• a. Ethanoic acid ethanol
• b. Propanoic acid methyl ethanoate
• c. Ethanoic acid ethyl ethanoate
• d. Propanoic acid methyl propanoate
• e. Ethanoic acid ethyl propanoate

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Answer

• a. Ethanoic acid ethanol
• b. Propanoic acid methyl ethanoate
• c. Ethanoic acid ethyl ethanoate
• d. Propanoic acid methyl propanoate
• e. Ethanoic acid ethyl propanoate

• An anhydride reacts with an alcohol to give a
  carboxylic acid and an ester.

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• a. N,N-Diethylpropanamide propanoic acid
• b. N-Ethylpropanamide propanoic acid
• c. N-Ethylethanamide ethanoic acid
• d. N,N-Diethylethanamide ethanoic acid

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Answer

• a. N,N-Diethylpropanamide propanoic acid
• b. N-Ethylpropanamide propanoic acid
• c. N-Ethylethanamide ethanoic acid
• d. N,N-Diethylethanamide ethanoic acid

An anhydride reacts with an amide to form an
amide and a carboxylic acid.
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• a. N-Propyl propanamide methanol
• b. N-Propyl ethanamide ethanol
• c. N-Ethyl propanamide methanol
• d. N-Ethyl ethanamide ethanol
• e. N-Ethyl ethanamide propanol

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Answer

• a. N-Propyl propanamide methanol
• b. N-Propyl ethanamide ethanol
• c. N-Ethyl propanamide methanol
• d. N-Ethyl ethanamide ethanol
• e. N-Ethyl ethanamide propanol

• An ester reacts with an amine to produce an amide
  and an alcohol.

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• a. Propanal ammonia
• b. Ethanoic acid ammonia
• c. Propanoic acid methylamine
• d. Ethanoic acid methylamine

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Answer

• a. Propanal ammonia
• b. Ethanoic acid ammonia
• c. Propanoic acid methylamine
• d. Ethanoic acid methylamine

An amide is hydrolyzed under acidic conditions to
form a carboxylic acid and an amine.
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• a. Propylamine
• b. Propanamide
• c. Propanoic acid
• d. Butanoic acid
• e. No reaction

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Answer

• a. Propylamine
• b. Propanamide
• c. Propanoic acid
• d. Butanoic acid
• e. No reaction

• A nitrile is hydrolyzed to a carboxylic acid in
  the presence of acid and heat.

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• a. Methanol ethanol
• b. Methanol propanol
• c. Ethanol propanol
• d. Ethanol

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Answer

• a. Methanol ethanol
• b. Methanol propanol
• c. Ethanol propanol
• d. Ethanol
• An ester is reduced to two alcohols.

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• a. Ethyl methyl amine
• b. Ethyl propyl amine
• c. Methyl propyl amine
• d. Methyl amine propanoic acid
• e. Ethyl amine propanoic acid

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Answer

• a. Ethyl methyl amine
• b. Ethyl propyl amine
• c. Methyl propyl amine
• d. Methyl amine propanoic acid
• e. Ethyl amine propanoic acid

• An amide is reduced to an amine with lithium
  aluminum hydride.

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• a. 2-Methyl-2-butanol
• b. 3-Methyl-3-pentanol
• c. 1-Butanol
• d. 3-Methyl-2-butanol
• e. 3-Ethyl-3-pentanol

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Answer

• a. 2-Methyl-2-butanol
• b. 3-Methyl-3-pentanol
• c. 1-Butanol
• d. 3-Methyl-2-butanol
• e. 3-Ethyl-3-pentanol

• Two methyl groups add to the carbon of the
  carbonyl. Hydrolysis yields the tertiary alcohol.

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• a. 2-Methyl-2-butanol ethanol
• b. 2-Methyl-2-butanol methanol
• c. 2-Butanone ethanol
• d. 2-Methyl-2-butanol ethanol

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Answer

• a. 2-Methyl-2-butanol ethanol
• b. 2-Methyl-2-butanol methanol
• c. 2-Butanone ethanol
• d. 2-Methyl-2-butanol ethanol

• The reaction of an ester with a Grignard reagent
  forms a tertiary alcohol and an alcohol.

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End of Chapter 11