STUDY GUIDE 2

Determine which ones of the following compounds are chiral. Determine the R-S
configuration of the chiral species.

Cl H
OH Me
OH Cl

Cl CH 3
Br Cl
H F Br
H 3C

Fill the missing arrow in forward or backward direction for the following reactions.

O Na + R H R Na + OH

O O H
Li + +
Na

O O
+ NH 4 + NH 3
F 3C O F 3C OH

OH O Na
+ NaH + H2

F + HBr HF + Br
For the following compound, draw all possible stereoisomers. Indicate the relation
between each possible pairs?

Br Cl

Which one of the following molecule is more basic? Explain the reason in details

Which one of the following molecule is more acidic? Explain the reason in details.

For the following pairs, indicate which one of the structures is more acidic (hydrogens
labeled) and clearly explain your reasoning.

OH OH

OMe NO 2

O O O
H
H
OR
 KOH or (2 ) KOH
(1 )
6.25 Listed below areEtOH,
several
∆ hypothetical nucleophilic substitution reactions.
EtOH, ∆ None is synthetically useful because the product
indicated is not formed at an appreciable rate. In each case provide an explanation for the failure of the reaction to take place as
indicated. Styrene Styrene

(a) Your task is to prepare isopropyl methyl ether

6.27
HO OH CH
3 by one of the following reactions. Which reaction would give the better yield?

Explain your answer. OH

(b) HO H
I OCH3
ONa OCH3
Order
(1
(c)) theHO
following
CH3 ONa
compounds inor the
(2 )
increasing order of acidity.
OH CH3 I

Isopropyl methyl ether Isopropyl methyl ether

(d ) NO C O Br O F O
6.28 Starting with
Br an appropriate alkyl halideCN
and using any other needed reagents, outline
F syntheses of each of the following. When
alternative possibilities existOH F
for a synthesis, you should be careful to choose gives the better yield. HBr
(e) NH3 CH3OCH3 CH3NH2 OH
CH(f3OH
) OH the one that
F OH
(a) Butyl sec-butyl ether
F O
F (j) cis-4-Isopropylcyclohexanol
(f) NH3 CH3OH2
(b) CH3NH3 H2O (k) H CN
O
536 CHAPTER
S 11 ALCOHOLS AND ETHERS: Synthesis and Reactions
6.26 Your task is to prepare styrene by one of the following reactions. Which reaction would you choose to give the better yield of
styrene?
(c) Explain
Methyl your ether
neopentyl answer. (l) trans-1-Iodo-4-methylcyclohexane
(g) (S)-2-Pentanol
11.26
(d) Methyl phenyl
Write ether formulas for each of(h)
structural the(R)-2-Iodo-4-methylpentane
following: Br
(e)
(a) (Z)-But-2-en-1-ol (d)
(i) 1-Ethylcyclobutanol (g) 2-Ethoxypentane (j) 2-Ethoxyethanol
CNBr
(b) KOH (e) KOH (h) Ethyl phenyl ether
(1 ) (R)-Butane-1,2,4-triol or 2-Chlorohex-3-yn-1-ol
(2 )
EtOH, ∆ EtOH, ∆
(c) (1R,2R)-Cyclopentane-1,2-diol (f) Tetrahydrofuran (i) Diisopropyl ether
Styrene Styrene
REACTIONS AND SYNTHESIS
GENERAL
6.27 Your SN1,is StoN2,
task AND isopropyl
prepare ELIMINATION ether by one of the following reactions. Which reaction would give the better yield?
11.27 Provide the alkene needed to methyl
synthesize each of the following by oxymercuration–demercuration.
Explain
6.29 your product
Which answer. (or products) would you expect to obtain from each of the following reactions? In each part give the mechanism
OH OH OH 287
(SN1, SN
I 2, E1, or E2) by which eachOCH
product is formed and predict the relative amount of each product (i.e.,PROBLEMS
would the product be the
(a) 3
(b) ONa (c)OCH3 (d)
only
(1 ) product, the major product, a minor product, etc.?).
CH3 ONa or (2 ) CH3 I OH
EtO
– Cl
Br
Isopropyl methyl ether Isopropyl methyl ether
(a) Provide the alkene needed to synthesize each of the following by hydroboration–oxidation.
11.28 EtOH, 50 C
(f) t-Bu syntheses of each of the following. When
6.28 Starting with an appropriate alkyl halide and using any other needed reagents, outline OH MeOH, 25 °C
Br t -BuOK
alternative possibilities exist for a synthesis, you should be careful to choose the one that gives the better yield.
(a) (b) (b) 50 C (f ) (c) MeO (d)
(a) Butyl sec-butyl OH
t -BuOH,
ether O OH (g) 3-Chloropentane
(j) cis-4-Isopropylcyclohexanol
MeOH, 5 0 °C
(b) (k) H CN CH CO OH
11.29
(c) Starting with each MeOof the following, outline a practical synthesis of 1-butanol:
–
O 3 2
MeOH, 50 C (h) 3-Chloropentane
(a) 1-Butene
S Br (b) 1-Chlorobutane (c) 2-Chlorobutane CH3 CO2 H, 5 0(d)
C 1-Butyne
11.30 Showneopentyl
(c) Methyl how youethermight prepare 2-bromobutane from (l) trans-1-Iodo-4-methylcyclohexane
HO
t -BuOK (g) (S)-2-Pentanol (i) (R)-2-bromobutane
(d)(d
(a)
)
Methyl phenyl ether
2-Butanol t -BuOH, 50 C (b) 1-Butanol
(h) (c)
(R)-2-Iodo-4-methylpentane 1-Butene
2 5 °C
(d) 1-Butyne
Br 25 C
(e) (i) (j) (S)-3-Bromo-3-methylhexane each of the following
11.31 Starting with
CN 2-methylpropene (isobutylene) and using any other needed reagents, outline a synthesis ofMeOH
(T tritium, D deuterium):Cl I
I (k) (S)-2-Bromooctane
t-Bu
(a) (e) OH acetone, 50 °C T
(b) (c) T MeOH, 5 0 C
(d) O
D
GENERAL
11.32 Show
N1, Syou
N2, AND
mightELIMINATION
6.30Show
Write carry
conformational out thefor
structures following transformations:
the substitution products of the following deuterium-labeled compounds:
OH (or products) would you
6.29 Which product Cl expect to obtain from each of the following reactions? In each part give the mechanism
(a)
(SN1, SN2, E1, or E2)
Clby which each product is formed and predict (d)relative amount of each product (i.e., would the product be the
Clthe
only product, the major product, a minor product, etc.?). H
H I H I OH
(a) D MeOH Cl (c) MeOH
D OH
(b) H (e) Br

Cl Cl
H I CH3
(c) (b) D MeOH Br (d) H MeOH, H2 O

D
11.33 What Hcompounds would you expect to be formed when each of the following ethers is refluxed with excess concentrated
hydrobromic acid? O
6.31 Although ethyl bromide and isobutyl bromide are both primary halides, O ethyl bromide undergoes SN2 reactions more than
O faster than isobutyl bromide does.
10 times O When each compound is treated with a strong base/nucleophile ( EtO ), isobutyl bromide
(a) (b) (c) (d)
gives a greater yield of elimination products than substitution products, whereas with ethyl bromide this behavior isO reversed. What factor
accounts for these results? (THF)
(1,4-dioxane)
11.34
6.32Considering A–L
Consider the to represent
reaction the major
of I with CH3 CHproducts
2 Cl.
formed in each of the following reactions, provide a structure for each of A
through L. If more than one product can reasonably be conceived from a given reaction, include those as well. 5 1
(a) Would you expect the reaction to be SN1 or SN2? The rateL
constant for the reaction at 60 C is 5 10 L mol s 1.
(b) What is the reaction rate if [I ] 0.1 mol L and [CH3 CH2 Cl] 0.1 mol L 1?
1

(c) If [I ] 0.1 mol L 1 and [CH3 CH2 Cl] 0.2 mol L 1? Br

A B
(d) If [I ] 0.2 mol L 1 and [CH3 CH2 Cl]K 0.1 mol L
SOCl2 ,
1
? HBr

(e) If [I ] 0.2 mol L 1 and [CH3 CH2 Cl] 0.2 mol pyr L 1? NaH
O
6.33 Which reagent in each pair listed here would be the more reactive nucleophile
'
CH ¬S¬Cl
in a polar aprotic solvent?
 Br
11.33 What compounds would you expect to be formed when each ofKOH
the following ethers is refluxed with excess concentrated
KOH or (2 )
(1 )
hydrobromic acid? EtOH, ∆ EtOH, ∆
O O
O Styrene O Styrene
(a) (b) (c) (d)
O
(THF)Which reaction would give the better yield?
6.27 Your task is to prepare isopropyl methyl ether by one of the following reactions.
(1,4-dioxane)
Explain your answer.
11.34 Considering A–L to represent the major products formed in each of the following reactions, provide a structure for each of A
throughIL. If more than one product
OCHcan
3 reasonably be conceived
ONa from a given reaction,
OCH3 include those as well.
(1 ) CH3 ONa or (2 ) L CH3 I

Isopropyl methyl ether Isopropyl methylBrether

K HBr A B
6.28 Starting with an appropriate alkyl halide and using any
SOCl 2 , other needed reagents, outline syntheses of each of the following. When
alternative possibilities exist for a synthesis, you shouldpyr NaH
be careful to choose the one that gives the better yield.
(f ) O
(a) Butyl sec-butyl ether O ' (j) cis-4-Isopropylcyclohexanol
(b) CH3 ¬S¬Cl (k) H CN
'
PBr3 O O CH3 ONa
536 CHAPTER 11 J AND ETHERS: Synthesis andOH
ALCOHOLS Reactionspyr C D
S
(c) Methyl neopentyl ether SO2 Cl (l) trans-1-Iodo-4-methylcyclohexane
(g)Si (S)-2-Pentanol
¬ Cl
11.26
(d) Methyl phenyl
Write ether formulas for each of(h)
structural the(R)-2-Iodo-4-methylpentane
following:
(e) (Z)-But-2-en-1-ol (TBSCl) pyr
(a) CN
(d)
(i) 1-Ethylcyclobutanol H2 SO4, (g) 2-Ethoxypentane
KI
(j) 2-Ethoxyethanol
NaF
(b) (R)-Butane-1,2,4-triol I H
(e) 2-Chlorohex-3-yn-1-ol
140 °C E F
(h) Ethyl phenyl ether
(c) (1R,2R)-Cyclopentane-1,2-diol (f) Tetrahydrofuran (i) Diisopropyl ether
G
REACTIONS AND SYNTHESIS
GENERAL SN1, SN2, AND ELIMINATION
11.27 Provide the alkene needed to synthesize each of the following by oxymercuration–demercuration.
6.29 Which product (or products) would you expect to obtain from each of the following reactions? In each part give the mechanism
OH OH OH 287
(SN1, SN2, E1, or E2) by which each product is formed and predict the relative amount of each product (i.e.,PROBLEMS
would the product be the
(a) (b)
only product, the major product, a minor product, etc.?). (c) (d)
OH
EtO
– Cl
Br
(a) Provide the alkene
11.28 needed to50synthesize
EtOH, C each of the following by hydroboration–oxidation.
(f) t-Bu
OH MeOH, 25 °C
Br t -BuOK
(a) (b) OH (b) 50 C
t -BuOH, (c) MeO (d)
OH (g) 3-Chloropentane MeOH, 5 0 °C
OH
11.29
(c) Starting with each
MeOof the following, outline a practical synthesis of 1-butanol:
–
CH3 CO2
MeOH, 50 C (h) 3-Chloropentane
(a) 1-Butene Br (b) 1-Chlorobutane (c) 2-Chlorobutane CH3 CO2 H, 5 0(d)
C 1-Butyne
11.30 Show how you might prepare 2-bromobutane from HO
t -BuOK (i) (R)-2-bromobutane
(d ) 2 5 °C
(a) 2-Butanol Br t -BuOH, 50 C (b) 1-Butanol (c) 1-Butene (d) 1-Butyne
25 C
11.31 Starting with 2-methylpropene (isobutylene) and using any other needed (j) (S)-3-Bromo-3-methylhexane
reagents, outline a synthesis ofMeOHeach of the following
(T tritium, D deuterium):Cl I
I (k) (S)-2-Bromooctane
t-Bu
(a) (e) OH acetone, 50 °C T
(b) (c) T MeOH, 50 C
(d) O
D
11.32
6.30Show how
Write you might carry
conformational out thefor
structures following transformations:
the substitution products of the following deuterium-labeled compounds:
OH Cl
(a) Cl Cl (d)
H
H I H I OH
(a) D MeOH Cl (c) MeOH
D OH
(b) H (e) Br

Cl Cl
H I CH3
(c) (b) D MeOH Br (d) H MeOH, H2 O

D
11.33 What Hcompounds would you expect to be formed when each of the following ethers is refluxed with excess concentrated
hydrobromic acid? O
6.31 Although ethyl bromide and isobutyl bromide are both primary halides, O ethyl bromide undergoes SN2 reactions more than
O faster than isobutyl bromide does.
10 times O When each compound is treated with a strong base/nucleophile (EtO ), isobutyl bromide
(a) (b) (c) (d)
gives a greater yield of elimination products than substitution products, whereas with ethyl bromide this behavior isO
reversed. What factor
accounts for these results? (THF)
(1,4-dioxane)
11.34
6.32Considering A–L
Consider the to represent
reaction the major
of I with CH3 CHproducts
2 Cl.
formed in each of the following reactions, provide a structure for each of A
through L. If more than one product can reasonably be conceived from a given reaction, include those as well. 5 1
(a) Would you expect the reaction to be SN1 or SN2? The rateL
constant for the reaction at 60 C is 5 10 L mol s 1.
(b) What is the reaction rate if [I ] 0.1 mol L 1 and [CH3 CH2 Cl] 0.1 mol L 1?
(c) If [I ] 0.1 mol L 1 and [CH3 CH2 Cl] 0.2 mol L 1? Br
A B
(d) If [I ] 0.2 mol L 1 and [CH3 CH2 Cl]K 0.1 molSOClL2 ,1? HBr
(e) If [I ] 0.2 mol L 1 and [CH3 CH2 Cl] 0.2 mol pyr L 1? NaH
O