1583144135 13673 Chapter 5 Q PDF

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188

Chapter 5

Stereochemistry

Figure 5.13 The shape of molecules and the sense of smell

brain olfactory nerve cell airflow

mucus receptor on an olfactory hair cyclooctane bound to a receptor site

lining of the olfactory bulb in the nasal passage

olfactory hairs

nasal passage

Cyclooctane and other molecules similar in shape bind to a particular olfactory receptor on the nerve cells that lie at the top of the nasal passage. Binding results in a nerve impulse that travels to the brain, which interprets impulses from particular receptors as specific odors.

(S)-carvone is responsible for the odor of caraway, whereas (R)-carvone is responsible for the odor of spearmint.

CH3

CH3

O

O

H C

CH3

H2C (S)-carvone

CH3 C

H CH2

(R)-carvone

caraway seeds (S)-Carvone has the odor of caraway.

spearmint leaves (R)-Carvone has the odor of spearmint.

These examples demonstrate that understanding the three-dimensional structure of a molecule is very important in organic chemistry.

KEY CONCEPTS Stereochemistry Isomers Are Different Compounds with the Same Molecular Formula (5.2, 5.11). [1] Constitutional isomers—isomers that differ in the way the atoms are connected to each other. They have: • different IUPAC names • the same or different functional groups • different physical and chemical properties [2] Stereoisomers—isomers that differ only in the way atoms are oriented in space. They have the same functional group and the same IUPAC name except for prefixes such as cis, trans, R, and S. • Enantiomers—stereoisomers that are nonsuperimposable mirror images of each other (5.4). • Diastereomers—stereoisomers that are not mirror images of each other (5.7).

Key Concepts

189

Some Basic Principles • When a compound and its mirror image are superimposable, they are identical achiral compounds. When a compound has a plane of symmetry in one conformation, the compound is achiral (5.3). • When a compound and its mirror image are not superimposable, they are different chiral compounds called enantiomers. A chiral compound has no plane of symmetry in any conformation (5.3). • A tetrahedral stereogenic center is a carbon atom bonded to four different groups (5.4, 5.5). • For n stereogenic centers, the maximum number of stereoisomers is 2n (5.7). plane of symmetry

C

H H

CH 3

CH3

CH 3 C

plane of symmetry

[* = stereogenic center]

*C H H

CH 3CH2

no stereogenic centers

CH3

H Cl

Cl H

1 stereogenic center

*C

CH3

CH 3 C*

Cl H

H Cl

2 stereogenic centers

*C

CH3 C*

Cl H

2 stereogenic centers

Chiral compounds contain stereogenic centers. A plane of symmetry makes these compounds achiral.

Optical Activity Is the Ability of a Compound to Rotate Plane-Polarized Light (5.12). • An optically active solution contains a chiral compound. • An optically inactive solution contains one of the following: • an achiral compound with no stereogenic centers • a meso compound—an achiral compound with two or more stereogenic centers • a racemic mixture—an equal amount of two enantiomers

The Prefixes R and S Compared with d and l The prefixes R and S are labels used in nomenclature. Rules on assigning R,S are found in Section 5.6. • An enantiomer has every stereogenic center opposite in configuration. If a compound with two stereogenic centers has the R,R configuration, its enantiomer has the S,S configuration. • A diastereomer of this same compound has either the R,S or S,R configuration; one stereogenic center has the same configuration and one is opposite. The prefixes d (or +) and l (or –) tell the direction a compound rotates plane-polarized light (5.12). • Dextrorotatory (d or +) compounds rotate polarized light clockwise. • Levorotatory ( l or –) compounds rotate polarized light counterclockwise. • There is no relation between whether a compound is R or S and whether it is d or l.

The Physical Properties of Isomers Compared (5.12) Type of isomer

Physical properties

Constitutional isomers Enantiomers Diastereomers Racemic mixture

Different Identical except for the direction polarized light is rotated Different Possibly different from either enantiomer

Equations • Specific rotation (5.12C):

• Enantiomeric excess (5.12D):

specific rotation

ee

=

= =

[α]

=

α = observed rotation (°) l = length of sample tube (dm) c = concentration (g/mL)

α l ×c

% of one enantiomer – % of the other enantiomer [α] mixture [α] pure enantiomer

×

100%

dm = decimeter 1 dm = 10 cm

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PROBLEMS Constitutional Isomers versus Stereoisomers 5.35 Label each pair of compounds as constitutional isomers, stereoisomers, or not isomers of each other. CH 3 O

a.

H CH 3

and

c.

and O

b.

H

O

and

d.

and

O

Mirror Images and Chirality 5.36 Draw the mirror image of each compound, and label the compound as chiral or achiral.

a.

C

CH2OH H

CH3

OH

COOH

CH3

b.

C HSCH 2

c.

H NH2

d.

O

H

Br

e. OHC

OH OH

cysteine (an amino acid)

threose (a simple sugar)

5.37 Determine if each compound is identical to or an enantiomer of A. CH3

CHO C CH3

a.

OH H

C HO

CH3

b.

H CHO

C OHC

HO

c.

H OH

CH3

H C

CHO

A

5.38 Indicate a plane of symmetry for each molecule that contains one. Some molecules require rotation around a carbon–carbon bond to see the plane of symmetry. CH3CH2

a.

C

Cl H

H

HO H HO H

Cl

b.

C CH2CH3

HOOC

C

C

C

H

CH 3CH 2

COOH

c.

H Cl

C

Cl

d.

C

e.

CH 2CH 3

HO H

Finding and Drawing Stereogenic Centers 5.39 Locate the stereogenic center(s) in each compound. A molecule may have zero, one, or more stereogenic centers. a. b. c. d.

CH3CH2CH2CH2CH2CH3 CH3CH2OCH(CH3)CH2CH3 (CH3)2CHCH(OH)CH(CH3)2 (CH3)2CHCH2CH(CH3)CH2CH(CH3)CH(CH3)CH2CH3

OH

OH

Cl

OH

f.

i. OH

OH

OH

OH

H

e. CH3 C CH 2CH 3

g.

j. HO O

O

D

HO

h.

5.40 Draw the eight constitutional isomers having molecular formula C5H11Cl. Label any stereogenic centers.

OH OH

Problems 5.41 Draw both enantiomers for each biologically active compound.

191

O COOH

a.

b.

NH2

ketoprofen (analgesic and anti-inflammatory agent)

amphetamine (a powerful central nervous stimulant)

5.42 Draw the lowest molecular weight chiral compound that contains only C, H, and O and fits each description: (a) an acyclic alcohol; (b) a ketone; (c) a cyclic ether.

Nomenclature 5.43 Which group in each pair is assigned the higher priority in R,S nomenclature? d. – CH2Cl, – CH2CH2CH2Br a. – OH, – NH2 e. – CHO, – COOH b. – CD3, – CH3 f. – CH2NH2, – NHCH3 c. – CH(CH3)2, – CH2OH 5.44 Rank the following groups in order of decreasing priority. a. – F, – NH2, – CH3, – OH b. – CH3, – CH2CH3, – CH2CH2CH3, – (CH2)3CH3 c. – NH2, – CH2NH2, – CH3, – CH2NHCH3 5.45 Label each stereogenic center as R or S. I H a.

C CH3CH2

c.

H CH3

C

NH 2

b. CH3

H

CH 3

e.

CH 3 D

T

Cl

C

d. Br

CH 2CH 3

H HO

CH(CH 3) 2 C

C

H

5.46 Draw the structure for each compound. a. (3R)-3-methylhexane b. (4R,5S)-4,5-diethyloctane

CH 3 HO

C

g.

CH3 SH

HOOC

f.

C

ICH2

d. – COOH, – CH2OH, – H, – CHO e. – Cl, – CH3, – SH, – OH f. – C –– CH, – CH(CH3)2, – CH2CH3, – CH –– CH2

C

NH 2 H

Cl

h.

CH3

Cl

c. (3R,5S,6R)-5-ethyl-3,6-dimethylnonane d. (3S,6S)-6-isopropyl-3-methyldecane

5.47 Give the IUPAC name for each compound, including the R,S designation for each stereogenic center. H

a.

b.

c.

5.48 Draw the two enantiomers for the amino acid leucine, HOOCCH(NH2)CH2CH(CH3)2, and label each enantiomer as R or S. Only the S isomer exists in nature, and it has a bitter taste. Its enantiomer, however, is sweet. 5.49 Label the stereogenic center(s) in each drug as R or S. L-Dopa is used to treat Parkinson’s disease (Chapter 1). Ketamine is an anesthetic. Enalapril belongs to a class of drugs called ACE inhibitors, which are used to lower blood pressure. CH 3

COOH

a.

H NH 2

HO OH

L-dopa

CH3CH2O2C

NH Cl

b.

c.

N H

N

O enalapril Trade name: Vasotec

O ketamine

CO2H

5.50 Methylphenidate (trade name: Ritalin) is prescribed for attention deficit hyperactivity disorder (ADHD). Ritalin is a mixture of R,R and S,S isomers, even though only the R,R isomer is active in treating ADHD. (The single R,R enantiomer, called dexmethylphenidate, is now sold under the trade name Focalin.) Draw the structure of the R,R and S,S isomers of methylphenidate. H N

CO 2 CH 3

meth ylphenidate

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Chapter 5

Stereochemistry

5.51 The shrub ma huang (Section 5.4A) contains two biologically active stereoisomers—ephedrine and pseudoephedrine—with two stereogenic centers as shown in the given structure. Ephedrine is one component of a once popular combination drug used by body builders to increase energy and alertness, while pseudoephedrine is a nasal decongestant. C1

OH NHCH 3 C2

isolated from ma huang

a. b. c. d.

Draw the structure of naturally occurring (–)-ephedrine, which has the 1R,2S configuration. Draw the structure of naturally occurring (+)-pseudoephedrine, which has the 1S,2S configuration. How are ephedrine and pseudoephedrine related? Draw all other stereoisomers of ephedrine and pseudoephedrine and give the R,S designation for all stereogenic centers. e. How is each compound drawn in part (d) related to ephedrine?

Compounds with More Than One Stereogenic Center 5.52 Locate the stereogenic centers in each drug. O NH2

OH C C H

H N

a.

O

c.

b.

S

O

N

O

HO

O

O

O

COOH amoxicillin (an antibiotic)

N CH3

O heroin (an opiate)

norethindrone (oral contraceptive component)

5.53 What is the maximum number of stereoisomers possible for each compound? O

a. CH3CH(OH)CH(OH)CH2CH3

OH OH

c. HO

b. CH3CH2CH2CH(CH3)2

HO

OH

5.54 Draw all possible stereoisomers for each compound. Label pairs of enantiomers and diastereomers. Label any meso compound. a. CH3CH(OH)CH(OH)CH2CH3 c. CH3CH(Cl)CH2CH(Br)CH3 b. CH3CH(OH)CH2CH2CH(OH)CH3 d. CH3CH(Br)CH(Br)CH(Br)CH3 5.55 Draw the enantiomer and a diastereomer for each compound. HOCH2

a.

H HO

CH 3 C

C

CH3

NH2

b.

H OH

c. H I

I H

d. CH 2CH3

OH

5.56 Draw all possible stereoisomers for each cycloalkane. Label pairs of enantiomers and diastereomers. Label any meso compound. CH3

Cl

CH3

b.

a.

c. Br

CH3 CH3

5.57 Draw all possible constitutional and stereoisomers for a compound of molecular formula C6H12 having a cyclobutane ring and two methyl groups as substituents. Label each compound as chiral or achiral. 5.58 Explain each statement by referring to compounds A–E. OH

OH

Cl

HO Cl A

a. b. c. d. e.

B

A has a mirror image but no enantiomer. B has an enantiomer and no diastereomer. C has both an enantiomer and a diastereomer. D has a diastereomer but no enantiomer. E has a diastereomer but no enantiomer.

C

OH

OH D

E

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Problems

Comparing Compounds: Enantiomers, Diastereomers, and Constitutional Isomers 5.59 How is each compound related to the simple sugar D-erythrose? Is it an enantiomer, diastereomer, or identical? OHC H HO

OHC

OH H C

C

a.

CH 2OH C

HO

C

H

CH 2OH

HOCH 2

b.

H OH

HO H

OHC

CHO

C

C C

OH H

c.

OHC

H OH

d.

C

C

HO H

H HO

CH2 OH

H OH C

C CH 2OH

D -erythrose

5.60 Consider Newman projections (A–D) for four-carbon carbohydrates. How is each pair of compounds related: (a) A and B; (b) A and C; (c) A and D; (d) C and D? Choose from identical molecules, enantiomers, or diastereomers. HO

CH2OH

H

CHO

CHO

CHO H

H

OH

H

H

HO

OH

CHO H

OH H

CH2OH

HO

H

OH

CH2OH

CH2OH

OH

A

B

C

D

5.61 How is compound A related to compounds B–E? Choose from enantiomers, diastereomers, constitutional isomers, or identical molecules. NH2

NH2

NH2

NH2

NH2 A

B

C

D

E

5.62 How are the compounds in each pair related to each other? Are they identical, enantiomers, diastereomers, constitutional isomers, or not isomers of each other? CH3

CH3

and

a.

H Br

C C

and H Br

Br H

C

C

CH3

H

CH3

b.

g.

H Br

CH3

CH 3

h.

and

OH and

OH

HO H

CH3

c. H HO

C

and H HO

OH H

C

H

CH3

OHC

CHO C

H

HO

C

i.

and

H OH CH3

H

d.

j.

and

BrCH2

Cl

e.

C

and

HOCH2 C H BrCH2

CH2OH CH3

Cl

k.

and

H

and

CH3 H

CH3 Cl

f.

C

I

Cl Br H

and H

C

HO CH3 Br

I

l. H

C

and CH2Br

CH3

CH2OH C

Br H

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Physical Properties of Isomers 5.63 Drawn are four isomeric dimethylcyclopropanes.

A

B

C

a. How are the compounds in each pair related (enantiomers, diastereomers, constitutional isomers): A and B; A and C; B and C; C and D? b. Label each compound as chiral or achiral. c. Which compounds, alone, would be optically active? d. Which compounds have a plane of symmetry? e. How do the boiling points of the compounds in each pair compare: A and B; B and C; C and D? f. Which of the compounds are meso compounds? g. Would an equal mixture of compounds C and D be optically active? What about an equal mixture of B and C?

D

5.64 The [α] of pure quinine, an antimalarial drug, is –165. a. Calculate the ee of a solution with the following [α] values: –50, –83, and –120. b. For each ee, calculate the percent of each enantiomer present. c. What is [α] for the enantiomer of quinine? H N d. If a solution contains 80% quinine and 20% of its enantiomer, what is the ee of the solution? HO e. What is [α] for the solution described in part (d)? H CH3O N quinine (antimalarial drug)

5.65 Amygdalin, a compound isolated from the pits of apricots, peaches, and wild cherries, is sometimes called laetrile. Although it has no known therapeutic value, amygdalin has been used as an unsanctioned anticancer drug both within and outside of the United States. One hydrolysis product formed from amygdalin is mandelic acid, used in treating common skin problems caused by photo-aging and acne. OH HO

OH

O

HO

O

O

HCl, H 2O

O

OH HO

COOH

only one of the products formed

CN

OH

mandelic acid

OH amygdalin

a. How many stereogenic centers are present in amygdalin? What is the maximum number of stereoisomers possible? b. Draw both enantiomers of mandelic acid and label each stereogenic center as R or S. c. Pure (R)-mandelic acid has a specific rotation of –154. If a sample contains 60% of the R isomer and 40% of its enantiomer, what is [α] of this solution? d. Calculate the ee of a solution of mandelic acid having [α] = +50. What is the percentage of each enantiomer present?

General Problems 5.66 Artemisinin and mefloquine are widely used antimalarial drugs. CF3

H

N

O O O H

H H N

H

O

HO O

H

artemisinin

CF3

H mefloquine

a. b. c. d. e.

Locate the stereogenic centers in both drugs. Label each stereogenic center in mefloquine as R or S. What is the maximum number of stereoisomers possible for artemisinin? How are the N atoms in mefloquine hybridized? Can two molecules of artemisinin intermolecularly hydrogen bond to each other? f. What product is formed...