CHAPTER 10—STRUCTURE AND SYNTHESIS OF ALCOHOLS

10-1 The 1993 IUPAC recommendations put the position number before the group it describes.
(a) 2-phenylbutan-2-ol (b) (E)-5-bromohept-3-en-2-ol
(c) 4-methylcyclohex-3-en-1-ol ("1" is optional) (d) trans-2-methylcyclohexan-1-ol ("1" is optional)
(e) (E)-2-chloro-3-methylpent-2-en-1-ol or (1R,2R)-2-methylcyclohexan-1-ol
(f) (2R,3S)-2-bromohexan-3-ol
10-2 IUPAC name first, then common name.
(a) propan-2-ol; isopropyl alcohol (b) cyclobutanol; cyclobutyl alcohol
(c) 1-cyclopropylpropan-2-ol; no common name (d) 3-methylpropan-1-ol; isobutyl alcohol

10-3 Only constitutional isomers are requested, not stereoisomers, and only structures with an alcohol group.
OH
(a) C3H8O OH propan-1-ol propan-2-ol

(b) C4H10O
OH
OH OH OH
butan-1-ol butan-2-ol 2-methylpropan-1-ol 2-methylpropan-2-ol
(c) C3H6O has one element of unsaturation, either a double bond or a ring.
OH *
OH OH * HO

cyclopropanol prop-2-en-1-ol prop-1-en-2-ol prop-1-en-1-ol (E or Z)

(d) C3H4O has two elements of unsaturation, so each structure must have either a triple bond, or two
double bonds, or a three-membered ring and a double bond. All structures must contain an OH. (In the
name, the "e" is dropped from "yne" because it is followed by a vowel in "ol".)
HO C C CH3 HC C CH2 H2C C CH *
* OH OH
prop-1-yn-1-ol OH OH *
prop-2-yn-1-ol propa-1,2-dien-1-ol cycloprop-1-en-1-ol cycloprop-2-en-1-ol
*The structures with the OH bonded directly to the carbon-carbon double bond are called enols or vinyl
alcohols. The structure with OH on a carbon-carbon triple bond is called an ynol. These compounds are
unstable, although the structures are legitimate.
10-4 (a) 7,7-dimethyloctane-2,6-diol (b) heptane-1,7-diol
(c) trans-cyclohex-2-ene-1,4-diol (d) 3-cyclohexylheptane-2,4-diol
(e) cis-cyclobutane-1,3-diol
10-5 There are four structural features to consider when determining solubility in water: 1) molecules with
fewer carbons will be more soluble in water (assuming other things being equal); 2) branched or otherwise
compact structures are more soluble than linear structures; 3) more hydrogen-bonding groups will increase
solubility; 4) an ionic form of a compound will be more soluble in water than the nonionic form.
(a) Cyclohexanol is more soluble because its alkyl group is more compact than in hexan-1-ol.
(b) 4-Methylphenol is more soluble because its hydrocarbon portion is more compact than in heptan-1-ol,
and phenols form particularly strong hydrogen bonds with water.
(c) 3-Ethylhexan-3-ol is more soluble because its alkyl portion is more spherical than in octan-2-ol.
(d) Cyclooctane-1,4-diol is more soluble because it has two OH groups which can hydrogen bond with
water, whereas hexan-2-ol has only one OH group. (The ratio of carbons to OH is 4 to 1 in the former
compound and 6 to 1 in the latter; the smaller this ratio, the more soluble.)
(e) These are enantiomers and will have identical solubility.
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10-6 Dimethylamine molecules can hydrogen bond among themselves so it takes more energy (higher
temperature) to separate them from each other. Trimethylamine has no N-H and cannot hydrogen bond,
so it takes less energy to separate these molecules from each other, despite its higher molecular weight.
10-7
(a) Methanol is more acidic than tert-butyl alcohol. The greater the substitution, the lower the acidity.
(b) 2-Chloropropan-1-ol is more acidic because the electron-withdrawing chlorine atom is closer to the
OH group than in 3-chloropropan-1-ol.
(c) 2,2-Dichloroethanol is more acidic because two electron-withdrawing chlorine atoms increase acidity
more than just the one chlorine in 2-chloroethanol.
(d) 2,2-Difluoropropan-1-ol is more acidic because fluorine is more electronegative than chlorine; the
stronger the electron-withdrawing group, the more acidic the alcohol.
10-8
sulfuric acid >> acetic acid > 2-chloroethanol > water > ethanol >
H2SO4 CH3COOH ClCH2CH2OH H2O CH3CH2OH least
most acidic
acidic tert-butyl alcohol > hex-1-yne > ammonia > hexane
(CH3)3COH C4H9 C C H NH3 C6H14
Sulfuric acid is one of the strongest acids known, and acetic acid is the strongest type of organic acid. On
the other extreme, alkanes like hexane are the least acidic compounds. Alkynes are more acidic than
ammonia. The N–H bond in ammonia is less acidic than any O–H bond. Among the four compounds
with O–H bonds, the tertiary alcohols are the least acidic. Water is more acidic than most alcohols
including ethanol. However, if a strong electron-withdrawing substituent like chlorine is near the alcohol
group, the acidity increases enough so that it is more acidic than water. (Determining exactly where
water appears in this list is the most difficult part.)

10-9 Resonance forms of phenoxide anion show the negative charge delocalized onto the ring only at
carbons 2, 4, and 6:

O O O O O
1
6 2 HC CH
5 3
C
4 H
Nitro group at position 2
O O O O
N N Nitro at position 2 delocalizes negative charge.
C O O

Nitro group at position 3

O
Nitro at position 3 cannot delocalize negative charge at position 2 or 4—
CH no resonance stabilization.
O
N
O
continued on next page 256
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10-9 continued
Nitro group at position 4
O O

Nitro at position 4 delocalizes negative charge.

C
N N
O O O O

Only when the nitro group is at one of the negative carbons will the nitro have a stabilizing effect (via
resonance). Thus, 2-nitrophenol and 4-nitrophenol are substantially more acidic than phenol itself, but 3-
nitrophenol is only slightly more acidic than phenol (due to the inductive effect).
10-10 OH OH

A B

(a) Structure A is a phenol because the OH is bonded to a benzene ring. As a phenol, it will be acidic
enough to react with sodium hydroxide to generate a phenoxide ion that will be fairly soluble in water.
Structure B is a 2° benzylic alcohol, not a phenol, not acidic enough to react with NaOH.
(b) Both of these organic compounds will be soluble in an organic solvent like dichloromethane. Shaking
this organic solution with aqueous sodium hydroxide will ionize the phenol A, making it more polar and
water soluble; it will be extracted from the organic layer into the water layer, while the alcohol will remain
in the organic solvent. Separating these immiscible solvents will separate the original compounds. The
alcohol can be retrieved by evaporating the organic solvent. The phenol can be isolated by acidifying the
basic aqueous solution and filtering if the phenol is a solid, or separating the layers if the phenol is a liquid.
10-11 The Grignard reaction needs a solvent containing an ether functional group: (b), (f), (g), and (h) are
possible solvents. Dimethyl ether, (b), is a gas at room temperature, however, so it would have to be
liquefied at low temperature for it to be a useful solvent.
Li
10-12 (a) CH3CH2MgBr (b) Li + LiI (c) F MgBr (d) + LiCl

10-13 Any of three halides—chloride, bromide, iodide, but not fluoride—can be used. Ether is the typical
solvent for Grignard reactions. The new C—C bond is shown in bold.
H ether H3O+
(a) MgCl + C O CH2OH
H In this solution, the
H portion of the product
ether H3O+ that came from the
(b) MgBr + C O
OH Grignard reagent is
H shown in red.
H ether H3O+
MgI CH2OH
(c) + C O
H
1) ether ether NO! My BAD!
Note: the alternative arrow symbolism This means that water is present with
could also be used, where the two steps 2) H3O+ OK H3O+ ether during the Grignard reaction!
are numbered around one arrow:
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10-14 Any of three halides—chloride, bromide, iodide, but not fluoride—can be used. Grignard reactions
are always performed in ether solvent; ether is not shown here.

(a) two methods

H H3O+
MgCl The newly-formed C—C
+ bond is shown in bold.
O OH
H H3O+ CH3
+ CH3MgI
In this solution, the
O OH
portion of the product
(b) two methods OH that came from the
MgBr O Grignard reagent is
H3O+
+ shown in red.
H
O OH

H H3O+
+ IMg

(c) two methods O OH

MgCl H3O+
H
+

O OH
MgCl H3O+
H
+

10-15 Grignard reactions are always performed in ether. Here, the ether is not shown.
(a) Any of the three bonds shown in bold can be formed by adding a Grignard reagent across a ketone,
followed by aqueous acid workup.
(i) (ii) O (iii) (i)
CH3CH2MgBr CH3CH2CH2MgBr OH
+ + C
O O
+ PhMgBr (iii)
Ph Ph Ph
(ii)
Ph H3O+ Ph The newly-formed C—C
(b) Ph MgBr + C O Ph C OH bond is shown in bold.
Ph Ph
O HO CH2CH3
H3O+
(c) CH CH MgI
3 2 +

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10-15 continued
(d) three methods, all with H3O+ workup
(iii)
(i) MgCl (ii) O (iii) O

OH
O
MgCl
(ii) (i)
H3C MgCl

10-16 O O O
− Cl– ketone
CH3 C Cl + Ph MgBr CH3 C Cl CH3 C Ph intermediate

Ph
(This is just a nucleophilic substitution where Ph MgBr
Cl is the leaving group. The unusual feature
is that it occurs at a carbonyl carbon.)
OH O
H3O+
CH3 C Ph CH3 C Ph
work-up
Ph step Ph
10-17 Acid chlorides or esters will work as starting materials in these reactions. The typical solvent for
Grignard reactions is ether; it is not shown here.
O Ph
H3O+
(a) Ph C Cl + 2 PhMgBr Ph C OH In this solution, the
portion of the product
Ph
that came from the
H3O+ Grignard reagent is
(b) OCH3 + 2 CH3CH2MgI shown in red.
O OH
OH
O C
H3O+
(c) Ph C Cl + 2 MgCl

10-18 O O O
MgBr − EtO– aldehyde
(a) H C OEt + H C OEt H C intermediate

MgBr

OH O
H3O+
C C
H H
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10-18 continued
O In this solution, the
H3 O+ portion of the product
(b) (i) HC OEt + 2 CH3CH2MgBr that came from the
OH Grignard reagent is
O OH shown in red.
H3O+
(ii) HC OEt + 2 MgBr

O
H3O+
(iii) HC OEt + 2 MgBr
OH

10-19 Ether is the typical solvent in Grignard reactions. The new C—C bond is shown in bold.
O OH
H3O+
(a) MgBr +

O
H3O+
(b) MgCl + OH

MgI O H3O+ OH
(c) +

10-20
O H3O+
(a) HC C + HC C CH2CH2OH

O H3O+
(b) CH3CH2C C + CH3CH2C C CH2CH2OH

10-21 Often, there are several synthetic routes to each structure; the ones shown here are representative.
The new bonds formed are shown here in bold. Your answers may be different and still be correct.

Li CuI Br
(a) Br CuLi
2
I

Li CuI
(b) Br CuLi
2

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10-21 continued
I
(c) Li CuI
Br CuLi
2
O
O
Cl
(d) Li CuI
Br CuLi
2

10-22 These reactions are acid-base reactions in which an acidic proton (or deuteron) is transferred to a
basic carbon in either a Grignard reagent or an alkyllithium.
D
(a) + Mg(OD)I (b) CH3CH2CH2CH3 + LiOCH2CH3

(c) (d) O (e) D

H + BrMg C C CH2CH3 + + Mg(OD)Br
H3C O– Li+

10-23 Grignard reagents are incompatible with acidic hydrogens and with electrophilic, polarized multiple
bonds like C=O, NO2, etc.
(a) As the Grignard reagent is formed, it would instantaneously be protonated by the N—H present in other
molecules of the same substance.
(b) As the Grignard reagent is formed, it would immediately attack the ester functional group present in
other molecules of the same substance.
(c) Care must be taken in how reagents are written above and below arrows. If reagents are numbered
"1. ... 2. ... etc.", it means they are added in separate steps, the same as writing reagents over separate
arrows. If reagents written around an arrow are not numbered, it means they are added all at once in the
same mixture. In this problem, the ketone is added in the presence of aqueous acid. The acid will
immediately protonate and destroy the Grignard reagent before reaction with the ketone can occur.
(d) The ethyl Grignard reagent will be immediately protonated and consumed by the OH. This reaction
could be made to work, however, by adding two equivalents of ethyl Grignard reagent: the first to consume
the OH proton, the second to add across the ketone. Aqueous acid will then protonate both oxygens.

10-24 Sodium borohydride does not reduce carboxylic acids or esters. OH

(a) CH3(CH2)8CH2OH (b) no reaction (c) no reaction (PhCOO– before (d)
O acid work-up)
O
(e) HO OCH3 (f) ester OH
O

OH
10-25 Lithium aluminum hydride reduces carboxylic acids and esters as well as other carbonyl groups.
(a) CH3(CH2)8CH2OH (b) CH3CH2CH2OH + HOCH3 (c) PhCH2OH (d) OH

HO OH HO
(e) (f) OH
+ HOCH3 HO
OH
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10-26 NaBH4 1) LiAlH4
(a) H OH OR
CH3OH 2) H3O+
O
OR
OH 1) LiAlH4
2) H3O+
O
OR
OR 1) LiAlH4
2) H3O+
O

O OH
(b) NaBH4 1) LiAlH4
OR
CH3OH 2) H3O+
NaBH4 1) LiAlH4
(c) OR
CH3OH 2) H3O+
O OH

(d) O O NaBH4 O O LiAlH4 will NOT give the desired

CH3OH product. LiAlH4 will also reduce the
ester in addition to the ketone.
O OH
10-27 Approximate pKa values are shown below each compound. Refer to Appendix 4 at the back
of the text.
CH3SO3H > CH3COOH > CH3SH > CH3OH > CH3C CH > CH3NH2 > CH3CH3
<0 4.74 ≈ 10.5 15.5 25 40 50
most acidic least acidic

10-28
(a) 4-methylpentane-2-thiol
(b) (Z)-2,3-dimethylpent-2-ene-1-thiol
(c) cyclohex-2-ene-1-thiol ("1" is optional)

10-29
HBr NaSH
Br SH 3-methylbutane-1-thiol
ROOR
hν
NBS NaSH
hν Br SH but-2-ene-1-thiol

OR HBr, 40° C
(see Problem 8-2)
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10-30
(a) 5-ethyl-4-propylheptan-2-ol; 2° (b) 4-(1-fluoroethyl)heptan-3-ol; 2°
(c) 6-bromo-3-phenyloctan-3-ol; 3° (d) 3-fluorocyclohex-3-en-1-ol; 2° ("1" is optional)
(e) trans-4-chlorocyclohex-2-en-1-ol; 2° ("1" is (f) (E)-4,5-dimethylhex-3-en-1-ol; 1°
optional) also possible is (1R,4R) (g) (1-cyclohexenyl)methanol; 1°
10-31
(a) 3-chloro-1-phenylhexane-1,5-diol (b) cis-cyclohexane-1,2-diol
(c) 2-nitrophenol (d) 3-bromo-2-chlorophenol
10-32 (a) (b) (c) (d)

(e) (f) (g) (h) (i)

(j) (k)

10-33
(a) Pentan-1-ol will boil at a higher temperature as it is less branched than 3-methylbutan-1-ol.
(b) Pentan-2-ol will boil at a higher temperature because its molecules hydrogen bond with each other,
whereas molecules of pentan-2-one have no intermolecular hydrogen bonding.
(c) Pentane-1,5-diol will boil at a higher temperature as it has two OH groups for hydrogen bonding.
Pentan-2-ol has only one group for hydrogen bonding.
(d) Heptan-2-ol will boil at a higher temperature because it has a higher molecular weight than pentan-2-ol.
All other structural features of the two molecules are the same, so they should have the same intermolecular
forces.
10-34 Refer to Table 10-4 to compare acidities of different functional groups. The strength of an acid is
determined by the stability of its conjugate base.
(a) 3-Chlorophenol is more acidic than cyclohexanol. In general, phenols are many orders of magnitude
more acidic than alcohols because phenoxide anions are stabilized by resonance.
(b) Cyclopentanethiol is more acidic than cyclopentanol. S is beneath O on the periodic table, and acidity
increases down the periodic table. Larger anions are more stable because a negative charge on a larger atom is
distributed over a larger volume, with lower electron density and greater delocalization of the negative charge.
(c) Cyclopentanecarboxylic acid is more acidic than cyclopentanol. In general, carboxylic acids are many
orders of magnitude more acidic than alcohols because carboxylate anions are stabilized by resonance.
(d) 2,2-Dichlorobutan-1-ol is more acidic than butan-1-ol because of the two electron-withdrawing
substituents near the acidic functional group.
10-35
(a) Propan-2-ol is the most soluble in water as it has the fewest carbons and the most branching.
(b) Cycloheptane-1,2-diol is the most soluble as it has two OH groups for hydrogen bonding.
Cycloheptanol has only one OH group; chlorocycloheptane cannot hydrogen bond and is the least soluble.
(c) Phenol is the most soluble as it can hydrogen bond better than cycloheptanol. Phenol is a stronger acid
and will be ionized to a greater extent than cycloheptanol. Cycloheptanol has low solubility, and 4-
methylcycloheptanol has the added hydrophobic methyl group, decreasing its water solubility.
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10-36 Products after aqueous acid workup:
(a) (b) OH (c) Ph
OH

OH

(d) This problem confuses a lot of students. When a Grignard reagent is added to a compound that has
an OH group, the first thing that happens is that the Grignard reacts by removing the H+ to give O–.
O O
ether
1 CH3MgI + CH4
OH (only one equivalent of O MgI
Grignard reagent added) If a second equivalent (or excess) of Grignard
CH3MgI reagent is added before hydrolysis, then it will
O H3 O+ add at the ketone. Acid hydrolysis will give
If no more Grignard reagent is the diol.
added before acid hydrolysis, then
the starting material is recovered. IMg O CH3 HO CH3
H3 O+
OH
O OH
MgI
OH
Ph Ph
(e) OH (f) (g) Ph (h)
Ph OH Ph Ph OH
OH
OH OH
HO OCH3 HO OH
(i) (j) O (k) (l)

OH H
H HO OH HO
(m) (n) (o) (p)
CH3
CH3 H H OH
plus the enantiomer H
plus the enantiomer
plus the enantiomer

10-37 Bromobenzene is abbreviated PhBr. The phenyl Grignard reagent is abbreviated PhMgBr.
(a) Mg O H3O+ OH
PhBr PhMgBr +
ether H Ph OR
(b) OH H2SO4 (c) two methods PhMgBr from (a)
BH3 H2O2 +
Ph ∆ Ph Ph Ph
THF HO–
from (a) + H2O from (b) OH O
with H3O+ workup
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10-37 continued
(d) NBS H2O

Ph hν Ph Br ∆ Ph OH Either SN1 or SN2 with NaOH will work.

Trans is more stable.
from (b)
O H3O+ OH OH H2SO4
(e) PhMgBr + (f) Ph
Ph Ph ∆ major
from (a)
10-38 OH CH3
Hg(OAc)2 NaBH4 1) BH3 • THF H
(a) (b)
H2O 2) H2O2, HO–
OH OH
BH3 • THF H2O2
(c)
HO–
OH
Hg(OAc)2 NaBH4
(d)
H2O
10-39 All Grignard reactions are run in ether solvent. Two arrows are shown indicating that the Grignard
reaction is allowed to proceed, and then in a second step, dilute aqueous acid is added. The new C—C bonds
are shown in bold.
O OH
H3O+
(a) + BrMg
H
Mg CH2O H3O+
(b) Br
ether OH

O H3O+ OH
(c) + BrMg
H
In this solution, the
O portion of the product
Br Mg H3O+ that came from the
(d)
OH Grignard reagent is
ether
shown in red.
Br
Mg CH2O H3O+ OH
(e)
ether
O CH3
H3O+
(f) COCH2CH3 + 2 CH3MgI C OH
CH3
O OH
BrMg H3O+
(g) H
+
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10-39 continued O
(h) Br Mg H3O+ OH
ether
10-40
BH3 • THF H2O2
(a) H plus the enantiomer
HO–
OH
H
Many strong oxidizing agents will
SH KMnO4 or HNO3 or NaOCl SO3H transform thiols to sulfonic acids.
(b)
∆
O OH O O

NaBH4 1 eq. H2
(c) (d)
CH3OH Pt catalyst
H2/Pt reduces C=C faster than C=O
O OH
NaBH4
(e) OEt OEt
CH3OH
O O
O OH
LiAlH4 H3O+
(f) OEt OH

O
10-41
ether H3O+ OH
MgBr
(a) + CH2O

OH
BH3 • THF H2O2
(b)
HO–

Br NaOH OH
(c)

O
Br Mg H3O+ OH
(d)
ether

(e) + NaSH
Br SH

Li CuI
(f) Br CuLi + Br

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10-42 The position of the equilibrium can be determined by the strength of the acids or the bases. The
stronger acid and stronger base will always react to give the weaker acid and base, so the side of the
equation with the weaker acid and base will be favored at equilibrium.

(a) CH3CH2O + OH CH3CH2OH + O

stronger stronger weaker weaker
base acid acid base
products favored

(b) KOH + Cl OH H2O + Cl O K+

Cl Cl
stronger stronger weaker weaker
base acid acid base
products favored

OH O

(c) + CH3O + CH3OH

stronger stronger weaker weaker

acid base base acid
products favored

OH O K+
(d) + KOH H2O
weaker stronger
weaker base acid stronger
acid base
reactants favored

(e) (CH3)3CO + CH3CH2OH (CH3)3COH + CH3CH2O

stronger stronger weaker weaker
base acid acid base
products favored

(f) (CH3)3CO + H2O (CH3)3COH + HO–

stronger stronger weaker weaker
base acid acid base
products favored

(g) KOH + CH3CH2OH H2O + CH3CH2O K+

weaker weaker stronger stronger
base acid acid base
reactants favored

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10-43
NaBH4 1) LiAlH4
(a) H OH OR
CH3OH 2) H3O+
O
OR OR
1) LiAlH4 1) LiAlH4
OH OR
2) H3O+ 2) H3O+
O O
O OH
NaBH4 1) LiAlH4
(b) OR
CH3OH 2) H3O+
O OH
NaBH4 1) LiAlH4
(c) OR
CH3OH 2) H3O+

O OH
NaBH4 1) LiAlH4
(d) OR
CH3OH 2) H3O+

O OH
(e) NaBH4 1) LiAlH4
H OR
CH3OH 2) H3O+
O HO
OR
O or ester OH

OH 1) LiAlH4

O 2) H3O+ HO

O O
The milder NaBH4 reduces aldehydes and
(f) NaBH4 ketones but not carboxylic acids or esters;
OCH3 OCH3
CH3OH the stronger LiAlH4 is needed to reduce
O HO acids and esters.

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10-44 (a) The goal is to synthesize the target compound (boxed) from starting materials of six carbons or
fewer. The product has 11 carbons, so the logical "disconnection" in working backwards is one six-carbon
fragment and the cyclopentane ring that could be joined in a Grignard reaction. The tetrasubstituted C=C
will come from dehydration of a tertiary alcohol produced in two possible Grignard reactions.
Route 1:
H3O+ HO
Br MgBr
+ O
Mg
ether H2SO4
∆
Route 2:
H3O+ OH H2SO4
O
+ BrMg ∆
Mg
ether
Br target

(b) The goal is to synthesize the target compound (boxed) from starting materials of six carbons or fewer.
The product has 12 carbons, so the logical "disconnection" in working backwards is two six-carbon
fragments which could be joined in a Grignard reaction. The best way to make epoxides is from the double
bond, and double bonds are made from alcohols which are the products of Grignard reactions.

Br Mg MgBr
OH H2SO4
ether H3O+ ∆
O mCPBA
H
O

target

(c) The goal is to synthesize the target compound (boxed) from starting materials of six carbons or fewer.
The product has 14 carbons, so the logical "disconnection" in working backwards is two six-carbon
fragments and the ethyl group put on with a Williamson ether synthesis at the end.

O O MgBr OCH2CH3
MgBr C CH3 C CH3
from (b) no Br CH2CH3
water! target

10-45 All steps are reversible.

H
HO H O O
HO OH H3O+ HO OH − H2O H2O
C

269 + H3O+
Copyright © 2017 Pearson Education, Ltd.
10-46 The symbol H—A represents a generic acid, where A– is the conjugate base.

H OH H OH H O H H O
H A A
(a) H C H H
H H H H H H H H
+ H A

(b) OH OH O H O
A
H A C

H H H
H H + H A

(c) O O O O
H
O H
O H C
H H H H H
H
10-47
Br MgBr D + O H

Mg D2O
ether
A B C
O isobutylcyclohexane
1) 2) H3O+
excess
H2
OH Pt
Br
Br
Br
H2SO4 2 Br2 Br

∆
D E F

10-48 This mechanism is similar to cleavage of the epoxide in ethylene oxide by Grignard reagents. The
driving force for the reaction is relief of ring strain in the 4-membered cyclic ether, which is why it will
undergo a Grignard reaction whereas most other ethers will not.

R MgX + R O MgX
O
new bond
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10-49 When mixtures of isomers can result, only the major product is shown.
CH3 H2SO4
O 1) CH3MgI CH3 H2 CH3
2) H3O+ OH ∆ Pt
A B
KMnO4 H2SO4
∆ ∆
CH3
plus the enantiomer
G OH
D
H2SO4 1) CH3MgI
∆ 2) H3O+
OH

O
F
C
1) Mg, ether
2) cyclopentanone
PhCO3H
3) H3O+
Br HBr

E
10-50 The most important component in the deskunking mixture is hydrogen peroxide. Thiols are
oxidized to structures having one, two, or three oxygens on the sulfur; all of these functional groups are
acidic, less volatile so they don't reach the nose, and less stinky. The sodium bicarbonate is basic enough
to ionize these acids, making them water soluble where the soap can wash them away.
sulfenic acids sulfinic acids sulfonic acids
H2O2 H2O2 OH H2O2 O
SH S S S OH
3-methylbutane-1-thiol OH O O

OH O
H2O2 H2O2 H2O2
SH S S S OH
2-butene-1-thiol OH O O
(but-2-ene-1-thiol)

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10-51 O
1)
Mg H
Br ether MgBr
2) H3 O+
KOH, H2O D E OH
H2SO4, ∆
OH A
Na F
1) O3, –78 °C
2) Me2S Br2
O Na+ B
H Br
Br
O G
O C + Br
O

H See note below

1) NaNH2, 150°C 2) H2O about this reaction.

O 1) Sia2BH
H C C
H I 2) H2O2, HO–
non-1-yne

2 HBr
NaNH2
J Br

Na+ C C
Br
H
O
Note about the reaction from G to non-1-yne: This
reaction is a rearrangement of internal alkynes to
terminal alkynes similar to what is described in text
CH2CH3 Section 9-8. Problem 10-51 does not rely on your
HO C C C knowing this reaction because the product of the
reaction, non-1-yne, was given to you in the problem.
CH3 K
10-52 This problem is reminiscent of problem 8-51.
1) BH3 • THF OH
(b)
(a)
Hg(OAc)2 NaBH4
OH 2) H2O2 , HO−
H2O
catalytic
OH H2SO4
(c) OsO4
OH
H2O2 HBr
KOH, ∆
or cold, dilute KMnO4
Br
Parts (d) and (e) require moving the double bond into the
ring, to form methylcyclohexene. Adding a catalytic Alternatively, the tertiary alcohol product in
amount of strong acid would do this, and addition- part (a) could be dehydrated to give
elimination will accomplish the same thing. methylcyclohexene as the major product.
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10-52 continued—See the note at the bottom of the previous page regarding (d) and (e).

1) BH3 • THF CH3

(d) syn addition of H and OH with anti-Markovnikov orientation
2) H2O2 , HO−
OH
plus the enantiomer
OH
Cl2 CH3
(e) chlorohydrin formation with anti addition of Cl and OH
H2O
Cl
plus the enantiomer
Ph
(f) mCPBA PhMgBr H3 O+
O OH
ether

New C—C bond requires Grignard;

OH is not on same carbon where
new C—C is formed suggesting the
epoxide intermediate.
10-53 OH OH

H3C CH3 F3C CF3

I II
mol. wt. 60 g/mole mol. wt. 168 g/mole
boiling point 82 °C boiling point 58 °C
dipole moment 1.66 D dipole moment 0.32 D
pKa 16.5 pKa 9.3

(a) Boiling point is a rough indicator of the strength of intermolecular forces, of which three common ones
apply to organic compounds: van der Waal's forces (or London forces), the weakest; dipole-dipole
interactions for molecules with a permanent dipole moment; and hydrogen-bonding in compounds with OH
or NH bonds, the strongest. Both I and II have the alcohol functional group and are likely to form hydrogen
bonds with their neighbors, although an argument could be made that the slightly larger F substituents with
the greater electron clouds would make hydrogen bonding more difficult in II. Rather than stretch a
possibility, let's focus on something obvious: there is a huge difference in the dipole moments of these two
compounds. Even though the molecular weight of II is much greater, thereby increasing van der Waal's
forces, the dipole moment of II is very small. We must conclude that the significantly decreased dipole-
dipole interaction of II is more important in boiling point than the increased van der Waal's interaction, a
weaker force.
(b) I has a large dipole moment because of the bond polarizations due to the electronegative oxygen. In II,
however, the bond polarization in the alcohol is counteracted by six F atoms; recall that F is the most
electronegative element in the periodic table. The oxygen pulling in one direction is balanced against the six
F atoms pulling partially away from the oxygen. (If you have studied vectors in physics, consider each
polarized C—F bond as a vector with a "down" component and a "left" or "right" component; you will see
that some portion of the left CF3 group cancels the same portion of the right CF3, leaving only a portion of the
C—F polarization to cancel the C—O polarization. Make a model!)
(c) The strength of an acid is determined by the stability of its conjugate base. The anion of I has no
particular stabilization. The anion of II, however, has six F atoms pulling electron density by the inductive
effect; that is, the negative charge on the oxygen is partially shared by the six electronegative F atoms pulling
electron density through sigma bonds. The anion of II is much more stable than the anion of I, making II the
stronger acid.
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10-54
When synthesizing isotopically-labeled compounds, it is critical to keep track of what new atoms come
from what source. If the D is wanted on a carbon, it has to come from LiAlD4 but if the D is on an
oxygen, then it must come from D2O.
H H
O O O O
(a) 1. LiAlD4 (b) 1. LiAlD4
H3C H 2. H2O H3C H H3C OH 2. H2O H3C D
D D
or an ester
D
O O
(c) 1. LiAlD4
H3C OH 2. D2O H3C D
D
or an ester
10-55 Grignard reactions are typically performed in ether solvent. Ether is not shown here.
D H
O O O O
(a) 1. CD3MgBr (b) 1. 2 CD3MgBr
H3C H 2. D2O H3C H H3C Cl 2. H2O H3C CD3
CD3 CD3
or an ester

D
O O O
(c) 1. CD3MgBr O (d) 1. 2 CD3MgBr
D3C H
2. H2O Ph Cl 2. D2O H3C CD3
CD3
or an ester
10-56 For simplicity, hydrolysis steps after Grignards are not shown.
(a)-1 MgBr (b)-1 (b)-2
O
(c)
O MgBr
H3O+ 2
(a)-2 O
H3O+ R
OH H2O Br
O
S N1 (d)
MgBr

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10-57 For simplicity, hydrolysis steps after Grignards are not shown.
(b) MgBr (c) O (d) O (e)
O H
H OH
NaBH4 1. LiAlH4
H 1. BH3•THF
CH3OH 2. H3O+
2. H2O2/NaOH

Br OH
H KOH H MgBr O
(a) (f)
cold
H to prevent E2 H

10-58 Br O
1. O3 MgBr
KOH –78 °C H H3O+ OH
(a)
EtOH 2. Me2S O ether
∆
A B C
H OH
Br O
KOH KMnO4 OH LiAlH4 H3O+ OH
(b)
EtOH NaOH, ∆ O ether OH
∆
A E F
OH
Br OH
O
KOH mCPBA PhMgBr H3O+ Ph H SO Ph
2 4
(c)
EtOH ether ∆
∆
A H I J
10-59
Approach of a nucleophile, including a Grignard reagent, 1. MgBr
on an epoxide must be from the back side, as if it were an
SN2 attack. In this example, the epoxide must have been O
epoxycyclohexane, and allyl Grignard must have come in 2. H3O+ OH
from the side of the ring opposite the epoxide. An
epoxide from a disubstituted double bond can be sluggish
to react; in this example, the rigidity of the ring helps.
10-60 Ph
Ph OH
(a) (b) OH (c) CH3 (d)

OH
HO Ph

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Students: use this space for notes or to solve problems.

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