17 -46 continued

-- OH OH
CI OH o
(I) 0 FeCi;
6 6 AICI3
I
CI2 KOH �CI Zn(
HCI H g )
¢
�
--

17-47 (a
-- .

J)
IJ,.

( bl (el

;;; N 0 1 (d) noacylreaacttioniodoesn: Frnotiedeloccur-Crafonts

yN02 US03 H ri
gr nogs
ups wi lt
i h
kest
N0r o ng
2 deact i v at i n g
(e) CH30q0C
'CHl
C(CH3h
¢H
( l Br *
or
OCH3 Br (gl CI (h)¢CH3
�
S03H (koCH] (I) COOH
basic workup

(i) Ph-C-� -o-� oCCH2CH3 U) �

I � I
YN02 NH2
to Isolate
free amine

CH3 CH 2Br CH 2Br

�

H� _

�I
N02
aCOOH �I

(m) HN-C-CH 0 3
.. .
CH2CH3
� stronger o,p-director than CH3
I II

�
CH3 Co �I CH3
17-48 Major products are shown. Other isomers are possible.
II

388
as (same
H
E)
17-50
< } CH2CH2COOH product
stmolarteinculg matar weierigahtl 150 mollosseofcular weilgohtss of132H20
IR spectrum: The dominant peak is the carbonyl at 1710 cm-I. No COOH stretch.
=

NMR ospectsignalricum:regis eachTheon wifromsplthitinint7.eggrat3is-7.compl

i8onhasvaliciunateteeofgratd but2H;ionththofeesein4H,temustgratso itobehne tirihsnehelgtwmust
pofuadjacent
l. In themethyl
regioneofnes, 2.CH6-3.2CH2, 2th.ere
18 =

areThetwaromat be di s ubst i t u t e d.
Carbon NMR:alsoFshowi our ofngthae diaromat itcusitegdnalbenzene.
s talAl, insodiicnatdiincatg eC-H; two are ishort , with noandattatched
8

hydrogens,
meth� ylenes. s ubst i d are carbons n a carbonyl wo
8
are

I�S\ o
(F-� CH2CH2 - C -8 or cO
___

c:=:::>

. , , �
lose 1 H retain molecular weight 132
The product must be the cyclized ketone, formed in an intramolecular Friedel-Crafts acylation.
17-51
(a)

"w.��
H
H

A
..
+

(jl .H
� Br H
389
17(b)-51Assume
continuedthe free-radical initiator is a peroxide.
R�rdR r'J RO- initiation
RO H - Br --- ROH Br- }
r C'
--- 2

�� I H )-Br· ro � lC. BrH .. -.- (9, � �C BrH

- + +

0
H propagatstep 1 i o n H H
---

..

propagat
step 2
i o n Br- +

17-5� 2 H CI
HO:.. m �, �
Attack A a subst i t u t e d benzyne
+

..HO:..- 2CO HOmC�nH Ho m H

�, � - 0 l! �I
product A
I
�

Attack B
____ /'"
+ '7

OH H�
product B
lJlJ
----

390
17-53 The electron-w ithdrawing carbonyl group stabilizes the adjacent negative charge. resonance
plus
:0:
H-OEt dJ forms
�
OO
°

��\ ��::o: - ... C U

Na+ plus other resonance forms

r

Na'
•
•

\ �
' H . h-
H

0
+

HcO .
° H

:�
�A)
U plresonance
us
H .

forms
H
+ Na·f.

(a)17-5�
4 (b) � (d) � H3h

� � �

(e) (f) � H

17-55
�

< }-Q
()
� 0H
-y
o- H2S04 C + HS04- H30+
6 H 2 0 6
+ 2 --- + 2 +

colorless conjugat
yellow ed­
andConcent
prot ratnatedessulthfeuriwatc acier dto"dehydrat
o prevent t ees"reverse
h the alcohol
react, iproduci
o n. ng addi
Upon
many water molecules for the acid to protonate, and triphenylmethanol is regenerated.
a hignhlg ymoreconjugat
wat eer,d,however,
colored carbocati
there areotn,oo

391
17-56 C:O H
l; �
o Cl is this Cl is this YCl
(why
tishomer?)
e major (why
tishomer?)
e major
17-(a) 57
bromination at C-2 Br
�<H�
�'b
H (
""'C�
o
�-i -zfH
- HH� i�
�
H three resonance forms
:Br: +
,- 0 y Br
• • _

�H
bromination at C-3
H
��C Br
/ (,.0yH
� Br
H Honly two resonance forms
_

�:�!: j
O(H
Br
(b) Attackforms
resonance at stgiabiveslizaninginattetarmedi
C-2 bilizednatbyiotnhreeat C-2resonance
ck ataC-3.te staBromi wil occurforms,moreas readil
opposedy. to only two
392
17-58
abbreviate h phenylalanine as
NH2 NH2
I I
P CH2 - CHCOOH R

F ·0 · F •

II
• :0:.
.

I
+
02 N - ..;N,.. - ../N
:0 C :0
... • ...

N02 N, _
0/
/+ a o-:/�'o-

1(j
1
�
R �
� .
1. . C
NH2R �
.
+ +
H2 R H2 R
+N -/H +
-0/ - / - "'-
I I I
0 0
..
I
.. .. ..

I
C_

� 'O- - ../N,.. ; / N,
-

:0 /+ O·
• •

O-/ :0 + O. .

CH2Ph
I
HN-CHCOOH
° N ° N
2 2
N H2 R
...

N02 N02

393
 i + H

>b�: } � 1
�
)l )l
17-59

H-C�
/
·. 0·. � ·. 0

H3C CH3 H3C CH3 � H H OH

OH +OH OH

:Cl : CH3 Ho i CH3 Ho i CH3 Ho i CH3

CH3 CH3 CH3 CH3

OH OH OH
plhuers
OH
r
otresonance
I I I I

l � ��[J ["1 I :CH

"
forms
H 't
-�
.. .. ..

HO XCH, '!?� CH, C-CH3 C-CH3

I
CH3 H CH3 L (�H3 CH3

OH

OH

CH3
Ho -O-FQ- OH .. .. HO � C-CH3
H20: �
�:� CI H3
bisphenol A
CH3
plus other resonance forms
394
 17-a) 6Thi0 s is an example of kinetic versus thermodynamic control of a reaction. At low temperature, the
(kinet
be formedic product predomimatneatlyes:equalin trathisecase,
at approxi s at alC.mostAta10001 : 1 C,mihowever,
00 xture of ortenough
ho andenergy
para. These
i s twdoedisfomers
provi or t h e must
to occur rapidly; the large excess of the para isomer indicates the para is more stable, even
rat(b)ioTheof product
products from
as thethreact
e 00iConreact
whiciohnwaswil runequiinliitbiratal ye asat i1000t is warmed,
C. and at 1000 C wil produce the same
desulfonation
though it is formed initially at the same rate as the ortho.

17-6 1
0
Br2 Mg CH3CCH2CH3 H+
6 Q Q FeBr3 ether
II

Br MgBr CH3 -C -CH2CH3

--- -- • --

(possible alternative syntheses include acylation followed by Grignard) OH I

17-62

from
benzene chi oro­
+

reactive sites NaOH at 350°C

As wetiosawn, leaviin Chapt
addi ng twoeris16,olattheed carbons
benzene ofrinthgse oncenttheer ends.
ring ofBenzyne
anthraceneis suchare suscept
a react iivbeleditoenophi
electrlophie thatlicthe
+

reluctant anthracene is forced into a Diels-Alder reaction.

J -<r
17-(a 63 Cl
CI NaOH -<r 0- Na+
CI CICH2COO- Na+ ;Y��H
CI � Cl � CI �
CI Cl 2,4Cl,5-T
w.
• •

11

cl a, 0 :CC � Cl
2 Cl- CI � 0 � CI
(This is the

TCDD
compound used to
+ pois on Ukrainian

Two
shownnuclhere,eophithilsicreactaromationiwoul
c substd folitutloiownsthform a newaddisix-membered
tion-eliminriatniog.n mechani
(Thoughsnotm.)
political leader,

e standard
Boris Yushchenko.)

395
17(c)-63Tocontmininimuedize fOnTIation of TCDD during synthesis: 1) keep the solutions dilute; 2) avoid high
taddemperat ure; 3)ofrepltheahalce ochlacetoroacet
an excess ate. ate with a more reactive molecule like bromoacetate or iodoacetate; 4)
ToT. The
separat2,4e,5TCDD
- T wi l from
di s 2,v4e,5in-Tanataqueous
sol the end ofsoltuhteiosyntn ofhaesiweak
s, takebaseadvant
l i k e aNaHC03.
ge of the aciThedicTCDD propertwiiels ofremai2,4,n5-
caninsolbeublpreci
e andpitcanatedbefromfilteaqueous
red or extsolractuteiodninbytoaddian organi
ng acicdsol. vent like ether or dichloromethane. The 2,4,S-T
17-64
a( ) �:O:�H+ �:OH
�O �O
+

0
.. =-'\

plfOnTISus 3 wiresonance
- ----. �

charge onththposie tive

o

OH benzene ring
OH OH
plfOnTISus resonance
wie charge
th
posi t i v
onon tthhee oxygen
ring and
: OH
o

OH
�O:
('i�
¢
onplthuebotsoxygen
resonance fOnTIS
---.J...-J

h benzene
of th eriphenol
ngs, , OH
o o

HO OH and the oxygen in the ring

onplutshresonance
e ring and fOnTIS
on thewioxygen
th positive charge
o

396
 ..

red dianion
(c)
°

17-65
6 Hfumi2SO4ng q CH3
Br2 Br I� Br H2O Br I� Br
CH
O
3
S03H
..

¢ AICl3
..

para posiS03Htion blocked

A
..

17-66 A benzyne must have been generated from the Grignard reagent.
((I Br � �S MgBr
0 1
1 + 0
+

� F �
.

\--�----- �----�)
V

°
t

397
17-67 The intermediate anio� n forcesHtheOHloss of hydroxide. ax
For simplicity, abbreviate I NHCH3 >1 R
H OH
CH3
I

Li +
.0

H
.0

R
\
OH-

�c c2R ___ s:,

+

c .
H
ffR a .. ..-;
H OH /OH H I I

L/ H 'C:Y HO
plus
I

plresonance
us other
I
.. �R
r :·

H �
resonance
• ---.-

H"S: .0 .o
�
forms forms tI Li·
� ,C CH3
DJ'-R
H H .
H
I

'"cH3CH,o - H- u�
y
�
plus
NHCH3

resonance
H

forms
17-68 OH lcqui v . ¢1
OH equiv.
NaOH CH3I_ � Cl-C(CH3h � C(CH3h
BHA, butyl.ted hydroxy.niso\c
¢
OH

I
YOCH3
hydroquinone plus other isomer
• •

AlCl3 .0

OH OCH3

OH 2equiv.
CH3I A Cl- C(CH3: (H3C)3C : c(CH3h
BIrr, butyl.ted hydroxytoluenc
6 AICI; Y AlCl3 V
OH OH

CH3 CH3

398
i17-69 ve the probl
denticalSolmechani sm.) em by writing the mechanism. (See the solution to problem 17-2S(a) for an
J):I Br �
�
attack C- ;
"
l.5(OH Br Br

HC-
-
�B •

r
•

I� I I
HO:
2
• •

..
02N N02

Hydroxi d e at t a ck on C-l put s t h e

02 N N02

negat ive charge

notaniohave t h e ongroups,
carbonssoththatesedo
ns are not stabilized.
N02

Hydroxi
negat i ve dcharge
e attackononcarbons
C-2 putwis tthhe
also stabilized by resonance onto

niatrbiolgroups, ion bythereby

delThiocalsiniincreasi
g tnhge athtee
the nitro group

Br stnegat iizvate charge. ztienrmedi

OH is formed preferential y.
a J3t:Cr -�H
Br

only product formed

..

02 N N02 02N ...... N02

also stabilized by resonance onto
the nitro group

399
18-1(a) 5-hydroxyhexan-3-one; ethylj3-hydroxypropyl ketone
((bc)) t3-rapns-2-met
henyl buthaoxycyclnal;j3-pohenyl butyraldehyde
CHAPTERl�KETONESANDALDEHYDES

(d) 6,6-dimethylcyclohexa-2,4-dienone;dehyde hexanecarbal no common (or nameif you named this enantiomer); no common name
18-2 O 5 el e ment s of unsat u rat i o n
(R,R)

(a) C9Hl IH5H doublO e t (very smal l coupl i n g const a nt ) at 9. 7 al d ehyde hydrogen, next t o CH
mUl t i p l e peaks at 7. 2
IH multiplet at 3.6 and 3H doublet at 1.4 CHCH3 -7. 4 monosubst i t u t e d benzene
=:}

0 =:}

0 =:}

-CH- -CH
0 0 =:}

<� CH3 �
o
II
+ +

Thelookssplliikteinagquart of theet duehydrogen onsplcarbon-2, nextthe tadjacent

o the aldCH3. ehyde,Aisclwortoserhexami
examininatniog.n ofIn tihtse overal lsho\NS that
I

each t o t h e i t i n g from peaks

alconstdehydepeak of the quartandet tishesplmetit hinyltohydrogens
hydrogen two peaks:arethnotis isequiduevtaloetnt,he splso iitt iins gtofrombe expect
the aleddehyde
t h at t hydrogen.
h e coupl i n gThe
sh:lpe, it

coupl ainntgsconst
wil notantsbe, thequaley . Ifbea hydrogen
must consi d ered is separat
coupledeltyo, justdifferentas you neiwoul
ghboring
d by hydrogens
drawi n g a byitdiinfferent
spl g tree for
each type of adjacent hydrogen.
(b) clCgHgO 5 el e ment
upeaksteatr of 1974 peaks atcarbonyl s of un sat u rat
128-145carbon (tmono-ori o n para- s ubst i t u t e d benzene ring
peak at 26 methyl next to carbonyl or benzene h e smal l peak hei g ht suggests a ket o ne rat h er t h an an al d ehyde)
=:}

0 =:}

0 =:}

< }- C -CH3 or CH3 -o- C- H

0 =:}

more likely also possible

o

M18-cLaffert
3 A compound y rearrangement has to haveto occur. a hydrogen Butan-2-onoaney carbon hasy posino (y-hydrogen.
or other atom) in order for the
tion-no carbon
a
CH3-C -CH2 -CH3 t
o
II

a J3

401
18-4
�H2CH2CH2CH2CH2CH3
CH3 It 1j :+R:C-CH3 :I�C-CH3
; Lr ]
[
t

85 rnIz 43
rnIz
--- ---

�+CH2CH2CH2CH2CH2CH3
43

rnIz 85
128

McLafferty rearrangement

The first value is the to the second value is the n to The values are approximate.
(a) 200 nm; 280 nm; this simple ketone should have values similar to acetone
18-5
n*; n*.

si(b)mi230lar tonm;Fig310ure nm;18-7:conjugat

ketonee(280d systnmembase(210)valpluue)s 2plalusk30yl groups
nm for (20)the conj230;ugattehdedoubl
valueeofbond310 nm310 nm
n

<

(280;c) 280simnm;ilar reasoni

360 nm;ngconjugat
for the otedhersysttreansim (210)
tion, stplaurtsin1gextwirtah doubl e bondbase(30)valpluuse 4ofal290kyl groups (40)
is

an average
=

(d) 270 nm; 350 nm; same as in (c) except only 3 alkyl groups instead of 4
=

REMINDERS ABOUT SYNTHESIS PROBLEMS:

getsBegilonger.n your analysis by comparing thateetaapproach
There may be more t h an one l e gi t i m to a synthesis, especial y as the list of reactions
rgetoneto tofhe tstheartsmaling lmatnumber
erial. ofIf react
the product hasformmorecarbon­
carbons t h an t h e react a nt , you wi l l need to use
carbonWherebonds.possible, work backwards from the target back to the starting material. i o ns t h at
1.

4. KNOW THE REACTIONS. problems. There is no better test of whether you know the reactions than
2.

3.
attempting synthesis

402
18-6 Alclarbon-bond-
carbon- three target fmolormieculng ereact
s in ithions.s problSo far,em thave
h ere more
are t h thantysipesx carbons,
ree of react isoonsaltlhanswers
at form wil include
carbon-carbon
(albonds:kylatitohne andGrigacylnardatreact SN2 substitution by an acetylide ion, and the Friedel-Crafts reactions
ion) ionon,benzene.
f 0 OH 0
0 Bf � 0 MgB l) H �
ether 2) H30+ � H2C�; �
(a)

(b) Bf 0
..

identical sequence as in part (a)

UI �
OR 0
..

~
Cl �... � ithis more s metheffiodcusiientngasFriit eidels onl-Craft
y one s acylstepation
o AlCl3 U
o

(c) a synthesi s as in part (a) could also be used here

OR
� Br Mg � MgBr
0
� �
2) H30+ L-.l 6H �C
�4
1)

OR
L-.l � L-.l
..

(:j' Br Na+ -C=CH (:j' C=CH Hg2+, H20

H2SO4 og
18-7
.. ..

(a) (J BuLi (J BrCH2CH2Ph (J H30+... PhCH2CH2 -CH0

SXS S C'" S S X S HgCI2
H H H PhCH2CH2 H
II

::- I
... ..

• •

(b) (J CH3I (J BuLi (J Ph H30+ 0 Ph

S ::-C" S SXS Ph � HgCI2 �
H CH3 H Br �
from
• •
.. ... ... �

(a)

403
18-7 continued
(c) rl PhCH2Br SrlS BuLi PhCH2Br SrlS HgCl H30+ Ph � Ph o

S' " S
CH 2
PhCH2 H PhCH2 CH2Ph
• • • •

• .

X X

rl Q- CH2B' rl BuLi PhCH2CH2Br

I

from (a)

(d)
o-:x ('j()
H (a) H
S:-C"S S S
-

� Ph
� •

Ph H30+ , HgCl2
I

('j
� � �
18-8 0
from

( a) (b) �0 (c) CH3(CH2h -C0 -CH2CH3

if
II

Ih

18-9 0
(a) CH3(CH2h -C-CH2CH3 (b) (siPhCH2CN
II

mple SN2) (c) PhCH2C\l-(J

(a) I � Br � MgB' CH3CH2C= � H30+ CCH2CH3
o

O ether O
18-10
II

O
(b) CH3CH2C::N BrMgCH2CH2CH2CH3 --- H30+ �
--

H30+
+ --

(c) CH3(CH2hCOOH 2 CH3CH2Li -----

+
�
o

CH2Br CN MgBr 6 CH2C -o

6 H,o '
o

NBS. 6 NaCN.
(

6 I�
d

6 ::::'--1�---

404
IS-II OH (d)
(a) CH, H (b)
o CH
o
II

(C) � �
o

V V
IS-12dirRevi
more ect routew tehwie remithPhBrfewer
ndersstonepsp.i s402.usualThere
ly betareter. often more than one correct way to do syntheses, but
( a ) � . Mg OH 0
a

-..;: :: PhMgBr H30 + � Cr03,H20 �

o

H •
Ih
V V H2S04 V V
PhBrMg
• •

� PhMgBr . H30+
VV
• •

(c) 0
� Li A I H 4 H,o'. �
OH
OR NaBH4
CH30H
VV
HC::CCH2CH3
VV ( s ol v ent )
.. •

(d) 0 t NaNH2 OH
�Ih
H Na_
+ C::CCH2CH3 H30+ � C�CCH2CHJ
replIS-13acedThethreetriahydri
cetoxyborohydride
des. ion is similar to borohydride, BH4-, where three0acetoxy groups have
V
• •

(a ) C (b) .... C... .... C...0 :0:

" '- 0 0 ' 0
o o

0 0 0 '
� O - B + R--1' H
Na+ H- 0� -O -1/\ \. - Na-+ +. )!.::
)
R H
II II II

O O H
1
• •

�O-B-=-H
�
-I

0
/ /
--

y �
• .
I I

y y
H3CCOO-H
o o

1O-H
405
R+ H H
ylides. TrimCH3ethylphosphine has a-hydrogensCH3that could be removedCH3by butyl ithium, generating undesired
BuLi CH3-P-CHR CH2-P-CH
18-14

CH3-P-CH 2 R 1+ -
2R
CH3 CH3
1+

CH3
1+

desired ylide wrong ylide

1 1 1
� +

: �h PPh3
rotation '" I" I I
�+

HMe MeH
• •

.. \\
\

H I I I C - C """ H Ph3PO :O---! PPh) /

"""" ' 1.:1:1 I I I
Me cis-2-butene Me +

H',
Me �Me/ H
r
_

Thefashistoen,reochemi
yet the tsrtirpyhenyl
is inpverthosphied. nThee oxinuclde emustophielleimitripnathenyle wipthosphi ne mustry.attack the epoxide anti
.
....
..
f- . -
- " ,

h syn geomet
(b) :0: rotate and
'H
in an

el i m i n at e ..
O PPh3
. .

o . fl 1 7
trans
"

o ..

�
:
,

(a) CH2=CHCH2Br 1)2) Ph3P PhCHO

CIS

BuLi .. CH2=CHCH-PPh3 +
PhCH=CH-CH=CH2
18-16

1) Ph3P... PhCH-PPh3 O=CH-CH=CH2.. PhCH=CH-CH CH2

�

OR 2) BuLi
+

PhCH=CH -CH2Br 1)2) Ph3P

-

BuLi... PhCH=CH-CH-PPh3
=

(b)

CH2-PPh3 PhCH=CH-CH=O PhCH CH-CH CH2

+

+
� = =

406
The18-17onesManyshownalkhere
enes form
can bethesyntphosphoni
hesized ubym tsalwot difromfferentthe Wilesst ihignreact
deredionsalk(asyl halin itdhe.e previous problem).
(a) PhCHzBr 1) Ph3P BuLi.. PhCH-PPh3 )l
+

+
o
PhCH=C(CH3)z
(b) BuLi CHz-PPh3
-
2) H3C CH3

(c) PhCHzBr Ph3P.. PhCH-PPh3 PhCH CH-CH 0.. PhCH CH-CH CHPh
2)

2) BuLi
O �CHz
1) + = =

CHz-PPh3 �
= =

+ _

U U
+

18-18
(a)
OH
Cl3C-C-H I

OH I

"
:O: � H-OH OH
CH3 -C-CH3 CH3 -C-CH3 HO- I
. .

OH OH
I

I I
+

18-19

lofeasthydratamounte great est amount

of hydrat e
407
 :0 : H-CN 3 OH
CH3CH2-C-H CH CH2 -C-H
�
18-20

'"""
. .

I I

I
CN CN
..

(c) t-Bu-C-t
err -Bu t - B
:o:� '"""
u-C-t I
- B u H-CN OH
� :C N CN - t - B u-C-t I
- B u
CN
::::..;:::
:: � ::=

0
I I

OH
(a)�
18-21

V HCN vi'
(b) OHI pcc 0 OH
� . .
H H - �
· II
H HCN �H CN
(c) OH
CHCOOH
I

u
Nposioteti:veMechaniand smsivofe charnuclgees.ophiThese
negat ack atescararebonylverycashorrbont-lifvredequentas eachly incharcludegespeciis quiecsklwiythneutbotrhalized
lic attspeci
tbbyheenisaSolrapiadmoni
udtioprnsoshedtManual
on tr ansfwierl; ishow
n factt,htesehese stepsstearpseasthoccur
e fasterstingofatththeewholsamee mechanit i m e, evensm.thoughIn mostyoucahases,ve
transfers in one stetop show is legitimstateepsasofloangmechani sm separstoodatetlhy.atThethesepraracteice offashowi st steps.ng these proton
two
all
as it is under two

408
(a)
18-22

(J<-:NH;
0:

H H
)' H
H

(J h : JW �20: O �

d,+NHPh HO+3 . C} NHPh HO+

:0:\ :o-�
(
HI
3

H20:
_

two fast prot'---./

on transfers
• •
• •

Ph-C-H
:o:�
1 ��
Ph-C-H
:O�
��
H- O-H
- Ph-C-H( 1+

NHCH3
1

NHCH,
(twro fast�
1 1 1
----
• •

proton transfers
+ - H20
Ph-C-H .. H20: i Ph-C-H Ph-�-H }
II
�U�CH3 II
�

H- NCH3
I

plposiusttihvreee charge
resonance
on theforms
benzenewith
: NCH
3

ring

409
 Z E isomers.a double bond is formed, stereochemistry must be considered. The two compounds are
t18-he 23andWhenever
Z

18-25 This mechanism is the reverse of the one shown in 18-22(c) on the previous page.
H20: H-O-H
Ph - C - H H30+ Ph-C-H Ph-C-H
+ � .. Ph-C-H
.�

1+
.NCH3
.1 1
j
1 plus th+ree resonance forms with ') t
NCH3
II H-NCH3
I NHCH3
I
• �

H -
( Positive charge on the benzene ring
�
• •

: II0 : H-O: -CH3NH2 H-O:

..
H-O:
Ph-C-H .. Ph-C-H .. Ph-C-H .. H 3 0+ Ph-C-H
. . ..

1 I 1
H-NHCH3 I CH3
+
t (I �
....f----

NH

Ph-C-H
H-O+ +

VII
18-26 02N
NH2-NH -O- N02 A
o

abbreviY. ate "Z"

..

:o � + H-O-H
\ )

CH3-C-CH3
Q: CH3-C-CH3
:o:�
H30+
--- CH 3 -C-CH 3 H 30 CH3 -C-CH
'-- :NH2Z H2 :
I I ( 1 +
+ � 0 I
NHZ
I
NHZ
(k�
-­ •
3

two fast proton transfers

CH3 -�-CH t
H-NZ
•
3
I
..
 N-
(b) oJ 2NH N ",NHPh
Ph )l Ph
(d)

o
I�
.b

(a) PhCHO + H2NNH -C -NH2 ho + H2NOH

18-28

(b)
II

(c) 0 0 02N
H2 N-NHPh
(d)
0 + NH2-NH � }-N02
oJ
(e) C(f NH2 CH3
+

I o
0

·0· + � :O-H
+
:O-H O-H
Ph-CH H Ph-CH
plus resonance forms

. . �

Ph-CH•• }-H�CH3 .-----l Ph- 1 +

18-29

. �
with (+) on benzene ring

II
II +1
"---.:.
. I

: OCH 3
--- ---- CH
'" J

H.qCH3 �
�k
)

: � � : } H 2 0 H-O-H
Ph-CH ---H+ Ph-CH
,----- :O-H
j Ph CH ,...-W ---j
�� ili � I
plus resonance forms

� +1)

1 + �CH3 (�H3 OCH3 OCH3al

(+ ne ring

hemiacet
I
...
....
_

H..2:0CH3 OCH3
Ph-CH Ph-CH acetal
I

OCH3 OCH3
VI

I I

41 1
18-30CH3 CH3 CH31 CH31
:000: ""\H 0+
1 1
:0, :�
.�H20: ! V
t +

�
• • • .

. .

CH3 H CH3 H
0+ 0
H�
:0
f
0
1
: o
:O
1
O-H 1 + 1"

H20:
. . • . . . . .

t -CH30H
.. ..f---
....

oo:0 / H : O�H :0:

H2O:
+

6 .. •

6 •

6
18-31
(b) 0
CH3 -CH + 2 (CH3hCHOH
(c) 0 0 (d)
II

+ 2 HO OH r\
O HO) O + HO
�
(e)0 HOD
H+
(f)

HO )(l OH II
o

412
�';led lX�U uo p�nu!luo:>
WSlUnlj:>�W S!SAI0.1pAlj

t
:9
zH

o o- -Q�Q+0
:0 '0 '0: 0: 0 0 �:o
H
H-O�
H J� J, J,

'---(q)
. ..... +
H-O H-O:
• • • •

'----1 '----1 '---1 -1

+
+
��
HO

0- Q
H - 0 '0: H 0: 0:
J,

'----1
+
-
• •
J,

'----1
+
• •

FHQ
Q-Q � :0: (n)

H
+6 :0·o/�
H

:0 -------
+
(b)18-33hydrol
contiynsiueds mechanism continued
r
OH
+ r
OH
I\
6-6 �6
.. H + H

((·O �
:0, .... OH
C,
____
H-O� .... OH
C
� rOH ·0· +

� H30+
(c) The mechanisms of fonnation of an acetal and hydrolysis of an acetal are identical, just the reverse
order. Thipaths,hasthentothbee reverse
true because thave
his process iws antheequiidentlibiricalum:minifimthume forward stpatepsh. folThiloswis tmihenimum
HO

energy st e ps t
Principle Microscopic Reversibility, text section 8-4A.o fol l o energy a
famous

(d)
of

CO-;
o ;;o:CO
9 RJ 0 � + o �
00-00
··� • • • O +0 • •
:0
I

�
H H

H20:

CJ:::'t �+ CCl �CCl �

/h·· + O� OH OH '--- R
'--- RH OH \ � +O
H
1
OH

;-0- W � CO
��
0 OH .: OH

18-34 tAlAlhidtseehydes arecolreduced fastcreaseer thselaneketctivonesity). (keeping

.. .
1 equivalent reaction d wil l i n
be usedrnatiforvely,thissodireductum itorin;acetseeoxyborohydri
problem 18-13.de could
a
0

( ) A NaBH4

equivalent
V CHO CH30H

1\
1

HO OH ..

414
18-34 continued equivalent
0
(c) CH2B' HO OH o 0
1
(\
Mg o 0 (\ 0 (\

6 H+ a ether a + H� CH2 R' CH

..
2 MgB' ..

\.. )
V

Theoxygen,last stdehydrat
ep protoesnattheesalthceohol, 0 t

and hydrolyzes the acetal. ..

[MgBr]+

t
HC::C -CH2 -CH2 C
+
H30

18-35
- - CH3
a

(a) oCOO O
II

(b) DCOOH (c) COO:

HOafter adding H+ : Ag o y
0
after adding H+
A gO

(d) HO COOH
HO V
415
 j
18-36 :
hydrazone formation -000
0, ..
+ H0 �

cJ'-
:OH
• •

..
• •

"
2
NHNH2_
(I " NJfNH 2

two ofastn transfers

",-- :NH2NH2 :OH
H--./ ..
prot

reduction of the hydrazone

C ....... N
H-N

..
O
II
•
•

-·..N
� ('i2:�IIN
�H
H
C� H --
O
"H"OH H
V V

416
18-37
(a) (b) (c) 1\
(d)
� �
H H H
H

CO V H ' 'H
18-38 Please refer to solution 1-20, page 12 of this Solutions Manual.
18-39 nIgUPplacement
regardi namesoffiposirst; ttihoenn numbers.
common names. Please see the note on p. 136 of this Solutions Manual
(a)(b) hept hept aan-n-24--oone;ne; metdi-nh-propyl
yl n-pentketyloneketone (gh)) 4-3-phenyl
( bromo-p2rop--met2h-eylnalhexanal; ci n ; no common
namal d ehyde name
AC

(d)((ec)) buthept anal; no simdiplpehenyl

benzophenone; commonketoname
ne (i) hexa-2,
(j) 3- o xopent 4-dainalenal; ;nonocommon
commonname name
a
(18-f) 4propanone; nal ; but y
acetralodneehyde accept s "acet o ne") (
(Ik)) 3-
ci o
s -xocycl
2 , 4 -di o
m pent
et h a
yl necarbal
c ycl o pent daehyde;
none; no
no common
common name
name
0 I0n order of increasing equil0 ibrium constant for hydrat0ion:
(lUPAC

lofeasthydratamountion l o
2
o

ofgreathydrat
est amount
ion
II II I I

CH3-C-CH3 < C CH C-H < H-C-H

18-4 1
-

II
o
-
CH3
I
b2
H-C-CH -C-CH3 -
I
}c �
9H

f!
CH 3

18-42
A By1t--t1t
comparison with similarly substituted molecules shown in the text:
o

* value (210) plus 3 alkyl groups (30) 240 nm

U CH3 n--t1t* base
300-320 nm =

417
18-43
C6HJ002 indicates two elements of unsaturation.
Thetwo elIRement
absorpts ofiounn atsat1708
u rat i em·
o n. 1 suggests asiketngloene,ts inorthpossi
The e rat biolyoftw2o: ket3 inodinescatsienacehitghhlerey symmet
are two rioxygens
c mol e ande.
cul
liThekelysintoglbeet atCH22.15on thise probabl other siydemetof hthyle next to carbonyl
carbonyl . , and the singlet at 2.67 integrating to two
NMR
(5 (5 is

> H3C -C -CH2 -CH2 -C -CH3

Since the molecular formula is double this fragment, the molecule must be twice the fragment.
o o
II II

Two questofionshydrogens.
numbers, arise. WhyWhyis tdon' he inttethgrate twioonmet: hylandenesnotshow4 : 6?splIint tiengratg? iAdjacent
on provi,des a hydrogens, not absoluwite th
identical chemical shifts, do not split each other; the signals for ethane or cyclohexane appear as singlets.
2 3 ratio,

ant18-heal4unknown
4dehyde ormusta ketabeCone,JOa HIketbut2Oone.ainegat
The formul ndicatievse 5Tolelelement
ns tesstofpreclunsatudesurattihoen.possiA solbiliidty2,of4-DanNPaldderiehyde;vativtheerefore,
suggests
identical

ThemonosubstNMR ishows
t u t e d the typicatal et7.hyl3 pat5H,temulrn attip8le1.t)0. The tsirinpglleet)t andat 3.7.5i s a CHquartet
benzene (3H,
2 , but ), andte fara downfield,
qui
apparently deshielded by two groups. Assemble the pieces:
(5 2 (2H,
8 ( (5

0- CH2 C [
o
II
+ +

18-45
(a) 0 H " CH,CH3 . H
CHCH3
H /C ,�CH
CH2 2
) (

r
+

H J:CH2 CH2
..

rn/z44 mass 42
II I

rn/z 86
+ II

)H>-. �CH3 .
(b) � CH 0....... H . CH/CH3
CH3/C,�,CH2 CH/3 C',CH
+

CH
+

CH2
..
o

rn/z 114CH3 CH3 mass 42

II I I
II
I

z72
+

rn/

418
18-45 continued .
(c) O} (
[ r
+
H . CH3 ....... H
•

CH 0

mJz 58 mass 56
II I I CHCH3

mJz 114
..
C .Jr-.... CH ....... C" + II
H3C"""" 'c"""" 'CH3 H3C -""':CH2 CHCH3

18-46
H2

�O HO XO
0

OH
+ X
ATol18-mol4le7nsecultestariniodincofatemJa zket70one.meansThe°a carbonyl
0
0

fairly smal(CO)l molhaseculmasse. A28,solsoid semi 70 - derivativmass

c28arbazone42, enough e andfora negat
only ive
canmoreincarbons.
fer the presence The molofecula doubl
ar formul
e bonda isorprobabl
a ring yin addition(mtoassthe70);carbonyl with t.wo elements of unsaturation, we 3

Thecm-IIRregishows a st r ong peak at 1790 cm- I, indicative of a ketone in a small ring. No peak in the 1600-1650
=

C4H60

carbons are these: o n shows the absence of an alkene. The onl y possi b i l i t i e s for a smal l ri n g ket o ne contain ing f our

4<)' �
0 0

A B

The HNdoes show can dias4Htinguitripslhetthatese.3.1;Nothmetis sihylgnaldoublcomeset appears ienttwheo NMR spect r(C-um,2rulandingC-out4) adjaThecent to
3

from t h met h yl e nes

CH3

the carbonyl
roughl y a qui, nspltetitbecause
by the twoof splhydrogens
it ing by onfourC-3.neigThehborisinggnalprotforons.the methylene at C-3 appears at 2.0,
MR B.
NMR &

unknownion ofis cycl

TheIR absorpt obutanone,at 1790Thecm-symmet I ry inediricsatticedofbysmalthelcarbon NMR rulrinegsstoutraistn rstuctrengturehensThe
8

t h e carbonyl i s charact
carbon-oxygen double bond, increasing its frequency of vibration. (See Section 12-9 in the text.)
A.
ri n g ket o nes; B.

18-48The conjugated diene has a maximum at 235 nm (see ved Problem 15-3) and the ketone has a
the

(a) mum at about 237 nm, so the to transition cannotSolbe used to differentiate the compounds.
maxi
(b) The ketone has an n to transition around 315 nm that the diene cannot have.
n*
n n*

41 9
18-49 (X
(a) (�l���etal) (e) acetal
H
0H H
=(
o
II
+

6
O

(hemi
old: ahemi
cetalketal) (f) diether, inert to hydrolysis
CH3CHCH2
2 -C -CH3 + 2 CH0
3 H
OH
o

(b) + CHC
3 Ho
, H

(c) acetal imine(s) (

0"
H2 0
........CH
(g) + I

",CH

(d) (olacetd:alketal) (h) imine 0=0

NH2

1\ -Q
18-50
+ HN
2

(a)
HO OH

..
G.o: II
: NH2NHPh
:0: �
I
:o�
I 1+
+NHNHPh 2 • NHNHPh
H-O-H
(
,--
H30+ H30+

I O. I
3
HC-C-H .. H 3C-C-H .. H3C-?-H .. HC-C-H
3
H

(� J
two fast proton transfers
NHNHPh

: NNHPh 2 i � NNHPh NNHPh

� -H }
+
II I
H3C-C-H .. HC-C-H
0:
3 H3C-

l l -
---

"----/' U
II H
H- • •

1+ ·
I I
O-H :O-H

hemiacetal
I

:kV
CH3-CH CH3-CH
O
•

H CH3
OCH3

OCH3

I
I

acetal
CH3-CH

OCH3

420
18-(c) 50 continued. � ,P h ) crP h 3 P O C H2 ..

U"---- CH2 tPh, �V C�2 V rCH2

� ' ; Ph'
+

: C0

o
� �

(d) o
-

/\ /\
: O � O-H
/\
0 o
° � °0�-H 'O-H
:�H30+
�
:
+ +

9
�
. ---- ..

OH Hi)
OH <---JOHH : �
H-+/0 �O r'0"� H
"c/ OH
· ' H
O
/ �/+

H 30+ H2 0.
o

o ,. 0 :
.

...

l 0' H H
OH :
-6 r�:. 6
• • �
+

HO� o
I
+

(e) � H1 +
H H,O+ � m o : 02 ' O -H
��
N
+H
H �
..
c 1 1
N/
+
•
..
�
H

H
O.. C,H 4) <;:,H
' + H 0 ' O - H r:J2-�';- H H ..H3. EJD2 :�.;-H
HH H
� �b +
/ .'

N
H

H
--

H H
.. +

H
/N, /N, /N �

.
, I

� O· C,; 0.
� 'H H30+ 0 N H 3
'
C ,H0 '/ •

•
� .'

H 'H �
• •

/N
421
18-51 o OH OH
(a) CH3-CH KCN .. H30+ ..
HCN CH3-CH-C::N 0=CH3-CH-COOH ,Ph
HC
PhCH2Br Ph3P BuLi .. PhCH -PPh3 ..
II I I

o
0 0 1 equivalent 0 0 6
+

(c) NaBH4
(b)

Al ternat iv ely, usin g sodi u m triacetoxyborohydri de

..

CH30H .. sele cti vel y reduces t h e al d ehyde; see Problem

CHO CH20H
o 1I10equi/\val0ent1! �o NaBH4 H OH 30+.
18-13.

(d) 0 � ,H CHPH" 11
C C
0'" '0 Q 0'"C'0 Q�1I0
'

LJ '--1

CH3CH2CH2Br PPh3
tBuLi CHCH2CH3 5112:113
+

1 equi v al e nt
t

(e) 0 HO/\OH.. o CII3CH2CH -PPh�

o o
1130+.
C C H o o,..C,0 Co
+

0'" '0
,II

o 1 equiH2valent.. roo
LJ LJ
II

(
ro Pt OH
(g)
f) ro RaneyH2 .. co- H
o
OH
Ni

(h) roo NaBH4

CII,oIl· roll
422
18-52 All of these reactions would be acid-catalyzed.
(a) q + H2NOH (b ) 0
+
H2N 'O
�CHO
(c) (d) ro +
o

� O � 1\
� NH 2+ LJ I
0 HO OH
�

,
C H3 (f)
o

ONH2 O=CCH3 +
\
6 + CH30H 2

18-53
(c )

a( ) °2N (b) 0
C NH2
N/ N H � } N O ,
cf N - r - II

V
(c) NOH (d) 1\ (e) CH3-CHOCH3
L � OCH}
I

(g) ( h )
I

( f) OH CH2C H3
H -OCH3
CH < }- CCH2CH3 rl
...

I N
SX S
I

CH3CH2 H

423
18-54
(a) (] BuLi CH31
SX S S, .. ..... S
(]
_C S(]S
H H H CH3XH
..
..

C '/ HeH, /' CH, H2O:

C:··S ' H t "c
:··S ' HH
• •

+
.. .. ..

HS �S-H

H ..... C ..'CH3
..
0:
II

(stcr)engtMercuri c i o n, Hg 2+, assists the hydrolysis in two ways. First, mercuric ion is a Lewis acid of moderate
h, performing the same function as a proton from a protic acid.
Theits charge:
effectiveven of Hge2xed+ aswia Lewi
enesscompl th a s acifur,d tihs epartmercury
sul ly dueatom
stil has a positive charge, attracting the sulfur's electrons.
to

Athisecond expl a nat i on for mercuri c i o n' s effect i v eness i n hydrol y si s of S ...... Hg2+
sulfromofuracetthateaoequi
lms.s liesThiin sthestacompl
l i b ri u m, bl
shiefcompl
t i n
ex formed
g t heexequi
betivweleeny removes
effect
l i b ri u m t o
the ion andHSCHthe2CHtwo2SH
product . ( A n exampl e
of whose principle? His initials are "Le Chatelier".) S
t

Thiols are often referred to as "mercaptans" because of their ability to CAPTure MERcury.
424
18-55 icTheallykeyaffectto thitheis rproblchemistem irsy.understanding that the relative proximity of the two oxygens can
dramat
0
()
Thedescribed: 1 , 2 -
"second"twoisomer d i oxane 1,
Thetwo oxygens 3 - d i
"third" isbondedo xane
omer descrito thbeed: l, 4 -di o xane
Thean excel"firstle"nti ssolomerventdescri bed:gh
oxygens (al t hou
o

connect e d by a si gma bondbondarei s same sp 3 carbon constitute an toxic), thapart ese oxygens are far
aeasiperoxi
l y cl d
e e.
avedThe to 0-0
gi v e radi c al s . acetal whiacichd.isSeehydroltheyzed in
aqueous enough t o
dently. It is a simple ether. act i n depen­
In the presenceradiofcalorgani
compounds, react cions mechanism below.
can be explosive.
Mechanism of acetal hydrolysis
0 2 "C ' H H2O:
C:0 (:'0
. .
H
CH
+
/
.. .. ..-
•

" ' " '

H H

HO �O - H ---

:0 / H
H/C, H
I

}
• •

....
..
f--. ..
-i�
+

425
(a)18-56 (b) 6 (c) NOH (d) 1\

6 6 0
] CH ] CH]

(e) N-N-Ph PoH (g) no reaction (h)

H

er
(t)
/

.;; C

6H
H

(i) 0) c5 (k) Na+ -(j ON (I)

0 0
HO COOH

18-57 Thecomesnewfrombondthteoprotcarbonic solcomes

oxygen vent. from the or shown in bold below. The new bond
(a) NaBD4
NaBH4 NaBD4, to

0 OH
H2O

(b) OD
II I

NaBD4
CH3 - C - CH2CH3 .. .. CH3 - C - CH2CH3
I

D
0

(c) OD
" D 20 I

NaB
CH3 - C - CH2CH3 .. .. CH3 - C - CH2CH3
I

D
0
" H4 D 20 I

iThi18-t prefers
58 Whito lapproach
e hydridefromis a smal legroup, the actsiduealofchemi cal especi e, sthsuppl ythinegsiitd,eAlopposi
H4-, itsefaitherlymetlarge,hyl . so
CH3 - C - CH2CH3 .. .. CH3 - C - CH2CH3

t h e l ss hi n dered t h e mol cul e at i s ,

I

s forces the oxygen to go to the same side as the methyl, producing the isomer as the major product. cis

� O
�fd
H

Q
H
H

lessndered AI·
" /
C H3C 0

hiface
/ H+

majproductor
_-,

� H
H � ---.

"- I -
..

H H H
H·
CIS CH3
H
H

426
18-(a) 59
BuLi CHz -PPh3O•O O CH2 lAndoubl essexocycl
steablbond.e tihcandoublan endocycl
e bond i sic
methylenecyclohexane
- +

(b)reactTheion direstffisciulnttyheinstsyntabilhitesiy ofzinthgemetdoublhyleenecycl

bond ionhexane
si d e th e from
rin g cycl
( e ohexanone
ndocycl i c ) withoutoutsusiidentghethrienWig t ig
versus
(exocyclic). HOoCH] :
H20. +.
6
Amechani
dehydratsmiopassi
+ CH] MgBr

n folnlgowithrough
ng the a
�

t cold maj o r
+

mi n or
carbocat i o n i n t e rmedi a t e will gi v e t he
El

more assubsttheitmajuted,orendocycl
bond product . icThedoublonley Br CH3
he exocyclis toicdodoublan e o K+ -O-I-Bu
HB r

chance
bondeliasmofitnhatmaking
eimajon usior ntproduct
give Hofmann orientgaatibulon k(Cyhaptbaseerto7).
E2 E2
•

c5 6 minor major
+

18-60 CI -CCHzCH2CH3 zn(Hg� �

(a) • � HCI V
°
°

0
II

(b) V C'N CH3CHzMg ether

Br H3O+ 1 .0 C-CH2CHl
°

¢l
II

Cl OH V OCH3
CI2 • 6 ,!;l 6 HCl •
• �

NaOH I) Na0
0 AICI3 3500 C 6 CH31 .0 AlCuCICI3
co

2)
1

CHO
(e)

0::5
.0

(d) H Cr 0 0
Z 2 7 I: conc. H2SO:
c6
°

0:>
I � •

AlwittehrnatSOCIivelz,yt,htenhe cyclacidizchledobyridFericouledeld-Cberaftmades
acylation with AICI3.
�

427
 ()N-N-C-NH
18-61 H 0 I II
(a) OHCP , 0C(b) (c) 2
I II II

(y h H
()
.0- C-H
V + AgO
('I ()CH1
(e)
(d) OCH2CH3
I
c: � (f)

()OCH2CH3 d
CI, H
+ c
� H ether
18-62
CH3Mg1 H30 ..
r03, H20
�
OH H2S04 �
(a) ..
�
I
o o

(b)�C=CH HgS040
H2H2S04 � ..

(c) ('I ('I

1) BuLi
.. ..
+ /"'.-..
I I
SXHS CH31 Sx S CH3 CH2hBr S� HgCI..2 �
--��

2)
( 1) BuLi
2)
H 3 0 0
H CH3 Hc CH3
(d) � H2S04 r03, H20
�
..

(e) � OH excess +CH�Li 1)

o
H30 � 2)
o

M +
(f) �
CH3 g1 H30
�
.. �
_

C=N ether
o

,CH3
(g) 03 1)
Me2S � + CH3
2)
..
O=C o
\

428
18-63 o

(a) � H O PCC
---.-
�H
o

(b) �CH2 �H
(c) �C=CH

1) BuLi o

�H
..

HgCl2

Cl o

(e) � Cl KOH
---.-

H20 �H
(This reaction needs a solvent like THF to keep all reactants in solution.)
o o
(f) � II 1) LiAIH4 PCC II
� �H
..

2)
OH H30+ OH � --

ft
(
OR �
ft SOCl,
" � Cl
Ot-BuhH
OH
18-64

(a) � (b) � + � (c) �

o o 0 o

(e)
+

18-65
(a) ketone: no reaction
(b) aldehyde: positive
(c) enol of an aldehyde-tautomerizes to aldehyde in base: pOSitive
(d) hemiacetal of an aldehyde in equilibrium with the aldehyde in base: positive
(e) acetal-stable in base: no reaction
(f) hemiacetal of an aldehyde in equilibrium with the aldehyde in base: positive

429
18-66 A
stirouctns uisrethofe heptcanan-2-01
be deduced from itsioreact J K.
ion wibethGrigandnard reactWhationsiswicommon tn-2-one,
o both product s
ofmustthesebeThereact
heptan-2-one. part; t h e react ns must t h hept a A
so
S(lX
S �C=CH
~
H H3 BuLi '
C

�H�
1)
) 4B
D
H2S04
HgS04F
G

S S H 20
�CH3 E

1 MgBr Hg 2 ++
� H30
1) CH3CHO +B

2)
� a2Cr207 �
H30 OH N 0
c
H2S04 • A

N�
MgBr
� 1)
J
PhMgBr+ 1)
6 0�
! H3:'
K
2) H30
�OOH
�Ph
OH
I

430
18-67 The very st r11:
ong t o 11:*
a bsorption at nm in tbhe spectrum suggest
225 IUV s a conj u gat e d ketone or
alThedehyde. IR
ba senceTheof peaksconfiatrms this: strong,m I conj u gate d car onyl at em- and smal l 1690
al k ene at 16 10 em-I.
2700-2800 e -
shows that the unknown is not an aldehyde.
96
The molecular ion at leads to the molecular formula:
o
II
96
-64 b
,
C=C-C-C
'(
I
32 =>
mass units add car ons and hydrogens 2 8
64
mass
molecular formula C6H80 elements of unsaturation
= = 3

Two elements of unsaturation are accounted for ibn the enone. The other one is likely a ring.
NMR
neiTheghboringshows carbonstwo(twovinyldoupeaks
hydrogens.
one =
neigh
1
b orin g t
H )
at 86.0
blet: neighboring H . says that the two hydrogens are on
The dou l e
..-I--.

I
H H 0
I II + 1 + 6 + 1
C-C=C-C-C C H ring
NComo metbinhiylngstarehe piapparent NMR, 6H
eces: in the so the group of peaks at is most likely CH2 groups. 82.0-2.4 3

b b
The mass spectral fragmentation can e explained y a "retro" or reverse Diels-Alder fragmentation:
+ +

� H xC
. .
0 0 II
H TH 2 CHz
�CHz -- + II
H CHz H CHz C Hz
loss of 28

rnIz 96 rnIz 68

HNMR ,
Ibnecause
the of the resonance
one of the form
vinylthydrogens appears at I3
Thi s is t y pi c al of an a,j3-unsaturated carbonyl
87.0.
hat shows deshielding of the -hydrogen.
87.0 --.....
H H 0 I I II
H H :0: +1 I I
C-C=C-C-C ....
..
f--. -t
..
�

13 a
C-C-C=C-C 13 a

431
(a) Building a model wil help visualize this problem.
18-68

• •

y
:O-"":CH O CH20HI
H
w
--
I
y H H I
:O+-"":CH O CH20H :O +CCH:O CH20H
- -
I
• •
y H " ··H
I

HO OH
open-chaiOHn fonn
OH HO y .y CH20H �
HO OH same as HO � OH
OH
cyclic fonn-hemiacetal
(b) Yes, the cyclic fonn of glucose wil give a positive Tollens test. In the basic solution of the Tollens test,
tconcent
he hemiratacetion.al iHowever, s in equilibitriiusmthewiopen-chai
th the open-chai
n al d n aldtehyde
ehyde h at wisthwiththe cycl
react si l v icifonn
er o n, inevenmuchthough
so largerthere is
as
oxionlof tydhieazedcyclsmalbyiclsiamount
lfonnver iwion,lofmore
open-chai
cycl inc fonn
fonn present
wi l open at tanyo replgiavceentthime consumed
e, more open-chaiof the open-chai
n fonn. n fonn
Event isually all
the
carboxylate. Chatelbeier'dragged
Le s Principkilecstkirinkgesandagaiscreami
n! ng through the+open-chain fonn to be oxidized to
cyclic fonn """"" open-chain fonn NOTAg carboxyl •
oxidized attoe
libriumration smal
latargerequiconcent at equilerliconcent
brium ration reversible

432
18-69

Any
belongscarbonto thwie acetth twalofamioxygens
ly. Ifbonded
one of tthoeitoxygen
with singroups
gle bondsan
is OR,
then the functional group is a hemiacetal. Thus, the functional
C-2
groupketatal as iits came is
a hemifromacetaal.ket(Tohene.ol) d name for this g;rollp
hemi
OH H
(b) Models wil help. Ignore stereochemistry for the mechanism.
OH
1 oo f' H+
0
H
HO o *' HO O�
o

HO OH HO OH

\ H
OH I OH
00 \. (00 H
,... 00,...
H
o HO ---" C-O
+

OH HO OH

H2�
1 OH
HOH2C OH
HO OH
same as
HO OH OH H

433
18-70
Recall that "dilute acid" means an aqueous solution, and aqueous acid wil remove acetals.
&H
XMgJ
1__)) _ _ _+�
2 H30 -=�. _ �
V U
+ I

Ht II

H3C()' OH �aBH4 � H
OH H 3 C OH 0
H G � )) CH3MgI
(2removes
H30)
+
acetal
cY OH excess �
(P�
OH 0 0 equi1v .
(\
+
PCC
--
H HO + OH .. --
Ag no reaction
H D A

j H2Cr04
B A
is identical to
H20
�H
PhNHN NNHPh o 0
cr OH
c

j HCIZn
E

(Hg)

(i'oH
o

434
18-7 1

C, H HSfI fI
0

fi
II

()
0+ 0
II
H3 .. '
I fu Ph/"C, CH2 Ph HgCI2 Ph/"C CH2Ph
SH S/" /S
' BuLi S 1)
/S
-
..
-----. , ,
H
W 2)
� Ph C H PhCH 2
18-72
)(a H H
Cl:
�
d --- (1-:
H w
OH �
H
l...... _� H
•

C+'
o 0"""" � H
� R

�H /..
__

RH

0=:OR
(b) This is not an ether, but rather an acetal, stable to base but reactive with aqueous acid.
(C)Q- .. 9-: - ROH. { QtC:o H}
H O:R W

U
H2� !
O-O-HH -Ct- .. H H2.. Q
O
O
w
('O +
· -H
H

/
o

t
.. 0
'--- .. / · \

/ '-... . H
• •

H : -

�� +-H .. . 0
l...... _ : H �- � \L)
" U -H
J
O
H O-
o I
- H H2 o IIY"\ o II
I I :0- I :0:
• •

• •
H + H
435
18-73
(a) First, deduce what functional groups are present in A and B. The IR of A shows no alkene and no
carbonyl: the strongest peak is at 1060 cm-1, possible a C-O bond. After acid hydrolysis of A, the IR of B
shows a carbonyl at 17 15 cm-1: a ketone. (If it were an aldehyde, it would have aldehyde C-H around
2700-2800 cm-1, absent in the spectrum of B.) What functional group has C-O bonds and is hydrolyzed to
a ketone? An acetal (ketal)!
°
R'O OR '
'\.. / II
C R-C-R
/ ,
R R B
A
mol. wt. 1 16 =>

C6H 1 ZOZ
There is only one ketone of formula C4HgO: butan-2-one.
°
II
H3C - C - CHzCH3 t---
...
..

A must have the same alkyl groups as B. A has one element of unsaturation and is missing only CZH4 from
the partial structure above. The most likely structure is the ethylene ketal. Is this consistent with the NMR?
03.9 (singlet, 4H)
�
HzC-CH2
I \
0 O A

o 1.3 (singlet, 3 H) i H3C

X� - CH3 } 00.9 (triplet, 3H)

0 1.6
(quartet, 2H)
What about the peaks in the MS at rnJz 87 and WI? The 87 peak is the loss of 29 from the molecular
ion at 1 16.
+
.

'W
plus two resonance
forms with positive
charge on the oxygen
H3C CHz-CH3 atoms

rnJz116

plus two resonance

_---I..�
..... forms with positive
charge on the oxygen
The peak at rnJz 10 1 atoms
comes from loss of CH3
from the molecular ion at rnJz 101
1 16.
436
 }
18-73 continued

. : or:"
"c O H

/ "-
Me Et

3VH p
1 1
: -H : . :0:
II H20 II
C+
• •
....
..1--__
• _ C � C
/ "- / "- / "-
Me Et Me Et Me Et
B

18-74 The strong UV absorption at 220 nm indicates a conjugated aldehyde or ketone. The IR shows a
strong carbonyl at 1690 em-I, alkene at 1625 em-I, and two peaks at 2720 em-I and 28 10 em-I -aldehyde!
o
II
C==C- C-H
The NMR shows the aldehyde proton at 89.5 split into
a doublet, so it has one neighboring H. There are
only two vinyl protons, so there must be an alkyl group coming off the B carbon:
H H 0 ,..-----,.
I I II
I
H H 0
R-C==C-C- H I II
CH3-C==C-C- H
The only other NMR signal is a 3H doublet: R must be methyl.
"crotonaldehyde"
18-75 .r-" ·0·
� EtO· I ...
" �: ;
EtO l.O
"
D
(a) 0 0 •

II H II � :O.
I) R
EtO -P � O.
.

. -
•
EtO-P 0
R + " II I� I
. .

P,- ·B P,- ..... 1'\'-- 1

EtO""'" I EtO""'" I C -
• �

+ -- --
C ...... -- ...... C R- C-C - R ' R-C ..!.. C -R'
OEt 1 OEt I R './ "' R '
I I I I
R'
I R'
R R R
R

R R'
, /
(EtOhP02- C==C

�
+
437 '
R'
18-75
(b) conti(X
R
nued OEt�
: -OEt +
� /1
� OEt
(c)
(i)(EtOhP + Br � .... COOMe .. (Et0}z0P, � .... COOMe

� COOMe (CH3}zCHCHO MeO­

_

� � -EtBr � �

I
t
(-------
...
..
°

-- �)
(ii)
(EtOhP BrCH2COOMe .. (EtOhOP COOMe
+ +
-EtBr "- � -' ------
�
COO M y -----

eO-
18-76
(a)�
U e2 ..
NM H+0

H
('::�( )�.- H
1
\!!.)C+

(b) Aminoacetallinkage�� in the dashed bOXCS' 2 � ((c) The first step in the mechanism in part

-olD
painucla) ri.seosiprTheodtes,oninatthowever,
roiogensn of ofthearethamie partDnNe'Asofelaromat
ectron
.----1 N�lo
: /.: : rithnegs,aromat and tihcietyelofecttrhone ripaing.rs (areSeerequi r ed ifcor
:
HO N : N HO the ion
W W
16-42
solof tuhteioarn otomatproblicityemof these fornuclaedescript
'0 : '0 : osidwie l not
)
I 1 I
I

�-----
-' .�---- --
bases. ) Prot o nat i o n of t h e ni t r o gen
OH
deoxyadenosine deoxycytidinOHe 438
dioccur
ute unlacidethsssewitnucl
ltherefore hlel notacidprotis extonatremele they Nstrandong;
eoside wil be stable.
 CHAPTER 19-AMlNES

19-1 These compounds satisfy the criteria for aromaticity (planar, cyclic 1t system, and the Huckel number
of 4n + 2 1t electrons): pyrrole, imidazole, indole, pyridine, 2-methylpyridine, pyrimidine, and purine. The
systems with 6 1t electrons are: pyrrole, imidazole, pyridine, 2-methylpyridine, and pyrimidine. Th�
systems with 1 0 1t electrons are: indole and purine. The other nitrogen heterocycles shown are not aromatic
because they do not have cyclic 1t systems.

19-2

Q
(a) CH3 (b) NH2 (c)
H3C- �-NH2
I I
CH3-CHCHO
CH3
N
H3C/ ...... CH3
(d) (e) (f)

19-3
(a) pentan-2-amine (b) N-methylbutan-2-amine
(c) 3-aminophenol (or meta-) (d) 3-methylpyrrole
(e) trans-cyclopentane-l,2-diamine (f) cis-3-aminocyclohexanecarbaldehyde
19-4
(a) resolvable: there are two asymmetric carbons; carbon does not invert
(b) not resolvable: the nitrogen is free to invert
(c) not resolvable: it is symmetric
(d) not resolvable: even though the nitrogen is quaternary, one of the groups is a proton which can
exchange rapidly, allowing for inversion
(e) resolvable: the nitrogen is quaternary and cannot invert when bonded to carbons
19-5 In order of increasing boiling point (increasing intermolecular hydrogen bonding):
(a) triethylamine and n-propyl ether have the same b.p. < di-n-propylamine
(b) dimethyl ether < dimethylamine < ethanol
(c) trimethylamine < diethylamine < diisopropylamine

19-6 Listed in order of increasing basicity. (See Appendix 2 for a discussion of acidity and basicity.)
(a) PhNH2 < NH3 < CH3NH2 < NaOH
(b) p-nitroaniline < aniline < p-methylaniline (p-toluidine)
(c) pyrrole < anil ine < pyridine
(d) 3-nitropyrro\e < pyrrole < imidazole

19-7
(a) secondary amine: one peak in the 3200-3400 cm-i region, indicating NH
(b) primary amine: two peaks in the 3200-3400 cm-i region, indicating NH2
(c) alcohol: strong, broad peak around 3400 cm-i

439
 NMR 8l.15,
19-8
lypes of
A compound with formula
H, with the NH2 C4H"N has no elements of unsaturation. The proton
appearing as a broad peak at
NMR
meaning that there are four different groups
shows five

of hydrogens on the four carbons. The carbon also shows four carbons, so there is no symmetry in
this structure; that is, it does not contain a t-butyl group or an isopropyl group.

The multiplet farthest downfield is a

There is a 2H multiplet at 8l.05, 3H H.
8l.35, CHNH2 81.15, 3HCH CH2
the broad
deshielded by the nitrogen; integration shows it to be one
peak at
80.90. The latter two signals must represent methyl groups next to a
a doublet at
and a
and a triplet at
respectively. So far:
NH2I
-C­
H HC-C-
3 H
The pieces shown above have one carbon too many, so there must be one carbon that is duplicated: the
CH,
80.90 H, / 8 .
only possible one is the and the structure reveals itself.

2 8 (multiplet)

H3C-C� -CH-CH 8 l.05

(triplet)

3 (doublet)

8l.35 / NH� I

(multiplet)
8l.15
"'---r""'"

(singlet)

(b) 4l.0 CH3

-- 44.7 25.8 (c) (d)

0
CH3CH2-N -CH2CH3 CH3C+ H2-CH
I
+
�12.51.41/
II
CH3 C H2CH2OH
7.t9 20l.t 9 10.t 0 63.t 6
(An older printing of the text
used values of 13.8,47.5, and
58.2. The values shown here
are taken from a spectrum.)

19-10
(a)

[H)C+;�2-r��1-CH2CHf iCH-) CH2-t-�H2 - CH)-CH2-�=CH2} �

j
mlz 87
CH3CH229 58 +
. mlz

mass

CH3
15
+ •

mass

(c) The fragmentation in (a) occurs more often than the one in (b) because of stability of the radicals
produced along with the iminium ions. Ethyl radical is much more stable than methyl radical, so pathway
(a) tS preferred.
.
440
19- 1 1 Nitration at the 4-position of pyridine is not observed for the same reason that nitration at the 2-
position is not observed: the intermediate puts some positive character on an electron-deficient nitrogen, and
electronegative nitrogen hates that. (It is important to distinguish this type of positive nitrogen without a
complete octet of electrons, from the quaternary nitrogen, also positively charged but with a full octet. It is
the number of electrons around atoms that is most important; the charge itself is less important.)

1+ +
-N
• •

GOOD: - N- VERYBAD:
1 I
mechanism
�
a�� 0 :�l)
N02
H NO H NO H

�II
o

f
� _J
N 0
D
+-

N
·

+N
VERYBAD­
'.
-- ---

N
� 6 N

not produced
N does not have
an octet of electrons because of
unfavorable
in termediate

19- 12 Any e lectrophilic attack, including sulfonation, is preferred at the 3-position of pyridine because the
intermediate is more stable than the intermediate from attack at either the 2-position or the 4-position.
(Resonance forms of the sulfonate group are not shown, but remember that they are important!)

The N of pyridine is basic, and in the strong acid mixture, it will be protonated as shown here. That is part
of the reason that pyridine is so sluggish to react: the ring already has a positive charge, so attack of an
electrophile is slowed.

441
 �-o:OoCH3 j;�- o�H �5Hl
19- 13
Cl

19- 14
I c �

GOOD
_
_

�'
0 0

__
..

N _N N
-Cl �
N

(a)

� : NH�
� _ jlC
/
-0 0

N Br

GOOD

stabilized by induction

� NH2
from nitrogen

(jib:,
N - �
NH :
This is a benzyne-type mechanism. (For simplicity above, two steps of benzyne generation are shown as one
step: first, a proton is abstracted by amide anion, fol lowed by loss of bromide.) Amide ion is a strong
enough base to remove a proton from 3-bromopyridine as it does from a halobenzene. Once a benzyne is
generated (two possibilities), the amide ion reacts quickly, forming a mixture of products.

Why does the 3-bromo follow this extreme mechanism while the 2-bromo reacts smoothly by the addition­
e limination mechanism? Stability of the intermediate! Negative charge on the electronegative nitrogen
makes for a more stable intermediate in the 2-bromo substitution. No such stabilization is possible in the 3-
bromo case.
442
 H�
19-15
I),
H
n n
+
..--.... ..--....
CH3 - I HC03- CH3 - I

H
Pr- N-H .. Pr- N-H � Pr- N - ..
I

19- 16

(b) excess NH3 + Br

�
--- H2N
�

(c) excess NH3 + PhCH2Br

19- 17
°
II
(a) CH3C -NHCH2CH3

19- 18 If the amino group were not protected, it would do a nucleophilic substitution on chlorosulfonic acid.
Later in the sequence, this group could not be removed without cleaving the other sulfonamide group.

NH-�
6�
NH-S03H

====::> A
I � both
c.

Y
/ / I
sulfonamide,

� J
2NH2

19-19

sulfathiazole
continued on next page

443
 ¢
19-19 continued
OCHl +

9'-'::
NHCOCH3 NH2

9
NH2

6
�
HCI •

h- H20
!1
S02CI S02 S02
I I

NH NH

6 6
sulfapyridine
19-20 CH3

t?
lll
o
H3C, ,..CH3 I

(a)� (b) N (c) N

a
CH3
+ + H2C=CH2

H1C-N�
�N-CH]
CH3
(d) (e) ,

H3C, ,CH3 ,CH3

CXJ V \H1 (I)

19-2 1 Orientation of the Cope elimination is similar to Hofmann elimination: the less substituted alkene is
the major product.
HO' �
�
(a)� (b) H2C=CH2
+
N
+
+(CH3hNOH
major � minor
+ (CH3CH2)2NOH

(c) 0 + (CH,hNOH (d) H2C=CH2

+0
N
+ r0
N�
OH
OH
nunor

19-22 The key to this problem is to understand that Hofmann elimination occurs via an E2 mechanism
requiring anti coplanar stereochemistry, whereas Cope elimination requires syn coplanar stereochemistry.
(a)
H
F
H(CH3h
CH3
, .:- ...;
/ � C Hofmann orientation loses a hydrogen from the CH3 and the N(CH3h
H 2C
� \ group to make the less substituted double bond
H

444
19-22continued
(b) Hofmann elimination
(CH3) 3N+ \�
f�CH3
5=H(CH3h
,) H ",CH(CH3h
'I,
"
,,\

IIC::::: C"
"I
"C C .. �
"--\
---
"'
H�
H HO: H3C CH3
H3C E
(Saytzeff product-more highly substituted)
Cope elimination

.. H"

H3C
IIC-C
� - "'
" "
'1
/
,CH3

CH(CH3h
,\\

Z
(Saytzeff product-more highly substituted)
19-23

+
o
Aliphatic diazonium ions are very unstable, rapidly decomposing to carbocations.

(b) /' " NO (c) NO (d) +

N2 Cl-
N I

Aryl diazomum IOns are

�
19-24
o
The diazonium ion can do aromatic substitution like any other electrophile.
6 relatively stable If kept cold.

�
i
-
03S -o- � N=N

HO
�(CH3h �
� N=NV-
--- -03S -o- �
H
I+

}
j
- _ N(CH3h _

most slgmflcant resonance contnbutor ..

..
. .. . plus two other resonance forms
with positive charge on the ring
_

:Cl: (or some other base)

-
03S -< >- N N -< >- N(CH3h
=

methyl orange 445

 N2+ CI-
19-25
(a) F

(b)
8 N2+ CI-
HCI a
NaN02
CI
HBF4
• -
t::..
6
a
from (a)
CuCI ..

6
° °
II II
(c) � HN-CCH3
(SCCHl 2 NH

8 3
*
CH3C-;I : I CH31- CH3'¢rI CH3 H30+ CH3 � I CH3 9'
..

� t::..

CH3 NaN%2 HCI CH". +

H q N 2 CI-
CH3 CH3 H3P02 CH3 CH3
'¢r
9'
�I �I •

CH3 CH3
+ +
(d) N2 CI- B N2 CI-
r (e) I

a
from (a)
CuBr ..

6 a KI
..
6
+ +
(f) N2 CI- CN (g) N2 CI- OH
a CuCN ..
6 a H2SO4
H2O
t::..
..
6
+
(h) N2 CI-
a HO� }-OH + .. < }-N'Ni }-OH
HO
446
oxiAltmernate iGeneral
19-26
siviselolya, tcateguid.alUse
delinNa(CH3COOhBH
es for choice of reagent
i n solforutioreduct
ytic hydrogenation works in most cases. n ivethamie imniatnieoorn: iuseminLiiumAliHon4 when
when is not tihseoliamteid.ne or
(a)
(i' H 0
(b)
PhCH2 -C -CH3 II
0 H2NOH..
NOH II Li A
1)
PhCH2 - C -CH3 H2O PhCH2 -CH -CH3l H 4 ..
NH2
I

if 2) I

(c) H I
0 Na(CH3COOhBH CH2Ph I

0 Ph)l H + ..

0
(d) 0 N,Ph NHPh
(e) 0
6 +
2) -.
H+
NOH
6 1)
2) H2O 6
LiAlH4 ..

6 6 H2NOH
W
..
1)
2)
LiAlH4
H2O ..

c5 OR
H
c�H
19-27
0-r
LiAlH4 r"
(a) H I
0
Cl �
0 00 H20 0
1)
+ --- ..
2)

(b)

CI 'l)
a HN� HNJ)
6 I)UAIH20H� 6
6 + ---

:::::... :::::...
A

447
2)
A
 Use a large excessBrof ammonia to avoid multip�
19-28 le alkylations of each NHnitr2ogen.
� excess NH3 + ____

19-29
(a) �N: o
BrCH2Ph C<N- CII2Ph NH2NH2 H2NCH2Ph
..
o

!l
..

Br(CH2hCH3 c<N - (CH2)sCH3 NH2NH2 H2N(CH2)sCH3

o o

(b)� o o

v--t -
:::-...
I !l
•

(c)� Br(CH2hCOO- �
o o
o o

N: must use anion :::-... I N -(CH2hCOO- NH2NH2 1) ' !l

� tthoeavoiphthdalprotimideonataniingon 0
-4_ .. ... H2N(CHlhCOOH
----

H+ 2)
o

19-30 Assume that LiAIH4 or Hz/catalyst can be usedH interchangeably.

(a) PhCH2Br NaN3 PhCH2N3 Pt2 PhCH2NH2
+ -- ..

(b)� Br � � C = N LiAlH4 � NH2 1)

V V H20 • V 2)

(c) 0 LiAIH4 1) � TsCl

� OH H20
2)
•

pyridine � OH Ts ..
O

Li A I H 4 + NaN3
1)
�NH2 H20 �N3 •

2)

OR 0 C2 SO l NH3 �o o

� OH � Cl
..
NH2 -

LiAIH4 + H20 1) 2)

�NH2
�
� OTs��C=N LiH20AIH4 �NH2 -
1)
..
from (c) 2)

448
19-30 continued
(e) Br\�H NaN3 H N3 LiAIH4 � NH2
� �
1)
..
� SN2-
•

R inversion S

(D Br\�H NaCN Li
1) A IH 4 �H2NH2
� SN2-
.. ..
R
inversion S

(g) 0 KCN HO� CN Li A I H 4 H �

� HCN
1)
.. ..

19-3 1
used viTortualreduce
l y i n t enirchangea
troaromatblyic. s,Assume
the reducia workup
ng reagentin base al pl.us HCI)can be
s (H2toplgiusvea tmethe freeal catamialynste, fiornala metproduct
(a)
o nHCl
S •

(b) Br Br Br
o 6 ¢ ¢
N0orth2o
FeHCI •

f;
U Br
nHCI ))
S

U Br
(d) 2)
from (a) COOH COOH
6 U NO Jr FeHCI ..

. �.. :0: }
2

19-32 CH30 y-:�H :0: B, �' 0

hCH T-C � H
P 2-
, II
- ,"-, R-C- � : R-C=N,: R-C N) Br
II .. -
----
, U II
�
..
'
CH3 H H H H
, (
� ,
449 mechan;,m cont;nued on next page : � !
- H
19-32 continued

i :0:- -.. � U· i �U - Br-

(:0:- "" .. t II ..-
:0:

R-N=C-OH .. .. � ---
:OH R-N=C=O
I
R-C=N-Br --- R-C-N-Br '-,1 ..

t
• •

t
?� :OH2 R-N:I - CO2 ----l.. R-NI.-
:0: :0:
II � �H OH
R-N-C-OH H""OH.. R-..7� C-
-.. II ..
+ - �
.
H

� H HJ H H

'"
Stinteereochemi
rmedi a t es, t
e.g.,
ry at a
ei tchi
h er
carbontcane thebeleiavinvertngegroup.
r al
a carbon
carbocat
d durinHowever,
i
i s
o l
n
g substitutwhen
o st
or i
a f t h
freee carbon
radic algoes
. Confit hrough
g
ion bythaenuclcarboneophiretleaifrom urat i a
o npl a
atnar
a chi
thfoure sidpaie rs ofr al � NH2
opposi
electrons, as in this Hofmann rearrangement, it retains its configuration. n s al l R
H CH3
1(a)9-34The acyl azide of the Curtius rearrangement is similar to the N-bromoamide of the Hofmann
rearrangement
gratiosnms.to theinistocyanat
mimechani hat bothehave an amiydsiesnithtrrough
and hydrol ogen withethcarbami
a good cleaciavidngtogroup the amiatntaeched.
are idSubsequent
entical in botalhkyl
(manb) Theor beast
leavi"n, gasgroup
we in thtoe say.Curtius rearrangement is N2 gas, one of the best leaving groups known "to
used
(c) ,----------------,,

.-----------------,
abbreviate as "R"
 19-35 Please refer to solution 1-20, page 12 of this Solutions Manual.
((b)19-a)3prisecondary
6 mary amine; 2,2-dimethylpropan-l-amine, or neopentylamine
amierocyclne; iN-met heylandpropan-2- agroup;
mine, or3-niisopropyl minetehylamine
(c) te rtiary het
(d)(e) tquatertiaeryrnaryaromatheteicrocyclc ami n
iec oxiammoni a ni t r o t ropyri d
umhylio-n;N-N,mNet-dihylmaetnihliylnepioxiperiddeinium iodide
(f)(g)tteertrtiiaaryryaromat ami n
ic amiic nammoni d e; N-et
e; N-ethuylm-N-ion;metpyrihyldaininiluimnechloride
het e rocycl
(h) secondary amine; N,4-diethylhexan-3-amine
19-37 ShownH in order of increasing basicity. In sets a-c, the aliphatic amine is the strongest base.
(a) Ph-N-Ph < PhNH2 < o NH2 aliphatic amine is the strongest base
I

(b) N < N < I

H H
aliphatiicciamity woul ne isdtbehe lstorstongest base; pyrrol e's
pyrrole 0
0 aromat i f prot o nat e d
(c) CNH < HN "N < �
aliphatiicciamity woulne isdtbehe lstorstongest base; pyrrol e's
\ I aromat if prot o nat e d
pyrrole
(d) O NH2 < < I
O N H 2 Basi c i t y is a measure of t h e abi l ity to
I �
donat e t h e pai
amine. lElikeectN0ron-wi r of el ect r ons on
thdrawibasingcity,th e
02N h H3C h groups
whileinelcrease 2
ectron-donat decrease
basicityin. g groups like

(e) �
° CH3
NH 2 <
O NH2 cr CH2NH2 aliphatic amine is the strongest base
I I h
< I h (amides are not basic)
h

Congrat
ructureuNputlaHti2soinstsheleifleeyouctastron-donat
stbecause elgotectthronisinonedensiritgyhton! CH3
N. th e is onlThey second
slightlystelructectruon-donat
re i s more ingbasibycin(byductabout
ion so1 tpKhe first
unit)

diortfferent reason: st e ri c i n hi b i t i o g ofbyresonance.

n resonance. (See The ltahste stlarstucttoupireciisnthAppendi
e strongestx Twobaseofforthisa Manual
complet.e)lyThe
nhg,osometthanhatylalthiinepthateelrferes
ribecomes onwipaithrthonThee itshopropyl
ecticramine. substconjituuentgatsedonwiNthandtheiaromat
epKbN iofs not2-met t forcesicthpie NRsyst2em.out ofEssentplanariial tyy, twihitsh the
hyly -alN,ipNhat-diiectamihylannielbecause
ine is 6.9th, eabout 2.5icpKrinunig istssomewhat N
more basic
telheanctranionlwiine.thdrawi
It is notng asbystinrongductiaobase as a t e rt i ar aromat
make the N significantly more basin,cyet. the ortho methyl reduces the pi overlap of the nitrogen's electrons to
451
19-38
(a) not resolvable:
(c) not resolvable:
planar ric
symmet (b) resol
resol
(d)
vvablablee:: asymmet
nitrogen rnicversicarbonon is very slow
i
(e) not resolvable: symmetric where the
(g) not resolvable in conditions
proton on N can exchange
(h)resol
resolvvablablee:: asymmet
(f)
asymmetrriiccninittrrogen,
ogen, unabl
unablee to iinnvertvert
to

side of the aciditywiandpKbth tbasi

19-39 The values of
reaction
discussion of
he weaker
of amines or pKa
acid and base will
city. ) be favored at equilibrium. (See Appendix forThea
of the conjugate acids can be obtained from Table 19-3.
2

(a )
�JII + CH3COO-
�
N+
products are favored

I
H
pKa
I[J + CH3COO­
8.75

(b) I[) ..--

reactants are favored
N
H H
.N,
H
pKa "'- 1

(c )

o
H
o N
+ products are favored

+
pKa 1 1. 12

d) NH2 n
O Q OI pKaH N+,H
NH3
(
�
I +
H �
+
....
products are favored

pKa 4.60 1 1.27

19-40
(a) PhCH2CH2NH2 ( )
e
cr(\� NH,

retentgiuraton ofion
confi
eN, CHJ
19-4 1
(a) PhCH2CH2CH2NH2 (b) �NH2
(
e)
d��- (d
) o OH

(e) (D (h) NH2after workup

CH3 �N
I OI with base
�

452
19-4 1
(i) og continued
NHCH1 U) 0 CH2CH2NHCHl (k) NHCH3
I

qH
CH3(CH2)3CHCH2CH3

(I) (m) /"'N� (0)

Q
CH2NH2 (n)
I
PhCH2CHCH3 �
�
LiAIH4 H20 OCH2CH3 N02
- �
(p) ..
HO CN HO CH 2NH2

0
19-42

(a) CH3 � NH2 NaN0 CH3 � N2 Cl-

+
CH3 CN
2 Cuctt
I
o 0
/
-
�

0
HCl

(b) CH1 CN 1)LiAIH4 CH3 � CH2NH2

o
..
2) H20

'O 0
from (a)
+
(c) CH1 N2 Cl- CH1 I
Kl
---

'O
from (a)
CH3 � OH
+
N2 Cl-
o
(d) CH1
H2S04
..
H20

'O '0I 0I
from (a)
°
II
(e) CH3 NH2 CH3 NHCOCH3 HN03 CH3 NHCOCH3
CH3C-Cl
�
I •

�
-
�
(+ isomer)

0
H2S04 °2N

JJH3O
CH3 NH2 +
after workup ?' I !1
with base �
°2N

(f) CH3 '0I NH2

+
°
=<J Na(CH3COOhBH- CH1 � � --o
� o
453
19-43 This fragmentation is favorable because the iminium ion produced is stabilized by resonance. Also,
there are three possible cleavages that give the same ion. Both factors combine to make the cleavage facile,
at the expense of the molecular ion.
+

t? +
.
CH3 CH3
I I
CH3 -NH2 ---
oCH3 + ....
..f--
. -l..
� C = NH2
mass 15 I
CH3 CH3
58
mlz 58
mlz 73
19-44

�-o
Cl-C

0
(a)
�I
..

O
(b) NH2
�I +

1) LiAlH4
..
(e) /N�o
CN-CH3 C CH3
H202
..

/o
C (
(I)
C CH3
H202 t:.
N-CH3 .. N� ----
N.
oH
"'CH3

(g) CH3 Y'1( COOH SOCl2

..
o

454
19-45 The problem restricts the starting materials to six carbons or fewer. Always choose starting materials
with as many of the necessary functional groups as possible.

HO-Q-NH2
(a)

phenacetin

Mg

-< ) O
(c) HO HO
methamphetamine
NBS
HO .. HO CH2B'

O
HO
H2, Pt
HO CH2CH2NH2 ..
dopamine
19-46

455
 �
continued
19-46
(b)
N� 00=7 Pt CO
H 2 H 2
�n C
--­

o
H2 R: 1
) NH, � H+
H H

r'Y:l -­
��: !) H :.I NH2
H NH2
TI

l bas :
• •

W-
HO:..�
1 }
co
H+O: H 1
- H20 ..

..... N.
co +
I
H 1 H
t
Pt (X)�
H2
co
HH 1
---

�
..N base: �
� N)
�
+
1
H)
19-47

(a)a0C "
C ...Cl NH3 o C , o
I I

CH2NH2 o
I I

'OH SOCl2 Li A I H 4
aI r?'Y NH 2 r?'Y 1)
•

2)H20 0
:::::-...
.. ..

(b) c' o
I I
a CH2NH2
aI NH3
H
:::::-...
Na (C H3COOhBH +
I �

::::
:::: : :-...

(c) C o

NH CI-C-CH3 CN-C-CH3
II
LiAIH4 N - CH2CH3
2)H20 " C
1)
•

456
19-47continued r-, Na(CH3COOhBH 0- r-,
0 o HN0
(d)
+ .. N0
(e) HO� OH SOCI2... CI �CI � NH H2N � NH2
o 0 o 0 / 0 0 _

LiAl y 2)H20 1)

H2N�NH2
19-48 0

�C
(a) �Br +
-N --
NH2NH2 �NH2 ..

L1

0
(b) CH2CH3 H3 CH]
6
�
I
HNO] ..
H2SO4 Q QNH2
�

N02
I
Sn '"
HCI
NH3 � NH2
____

(c) � OH SOCI2 � CI
Nao�
...

Ph 0 Ph 0 0 Ph

� H2 N Ph
�
-�
(d) �Br NH2NH2 NH2
+ --
...
L1
Ph Ph
o

(e)�Br KCN � CN 2 iAOH4"' � NH2 ...

I
1) L l

)H2
Ph Ph Ph

457
19-49
(a) When guanidine is protonated, the cation is greatly stabilized by resonance, distributing the positive

1
charge over all atoms (except H):

..
NH
II
H, N-C- NH,
�
.. w
�
..
NH2
II .. +
H,N-C- NH, �H,N- - NH, �H'N=
..
NH2
�
I ..
�
NH2
I
NH,
• •

NH, }
• • I +
H2N-C=NH2
.
(b) The unprotonated molecule has a resonance form shown below that the protonated molecule cannot
have. Therefore, the unprotonated form is stabilized relative to the protonated form. This greater
stabilization of the unprotonated fonn is reflected in weaker basicity.

H2N
..-o� N
\
o·
+ //
.
..

-
:0:

(c) Anilines are weaker bases than aliphatic amines because the electron pair on the nitrogen is shared with
the ring, stabilizing the system. There is a steric requirement, however: the p orbital on the N must be
parallel with the p orbitals on the benzene ring in order for the electrons on N to be distributed into the TC
system of the ring.

If the orbital on the nitrogen is forced out of this orientation (by substitution on C-2 and C-6, for example),
3
the electrons are no longer shared with the ring. The nitrogen is hybridized sp (no longer any reason to be
2
sp ), and the electron pair is readily available for bonding � increased basicity.

H H

\/ C ___
As surprising as it sounds, this aniline is about as
basic as a tertiary a liphatic amine, except that the
H aromatic ring substituent is electron-withdrawing
by induction, decreasing the basicity slightly. This
phenomenon is called "steric inhibition of
resonance". We will see more examples in future
chapters. A lso, it is the last topic in Appendix 2.
(See another example in the solution to 19-37(f).)

458
19-50 In this problem, sodium triacetoxyborohydride will be represented as Na(AcOhBH.

/'.... /'.... . /'... /'.... /'....

........, -O /'....... ...., -. OTs --- ...., -. CN
. /'...
/'....... ..
KCN 1) LiAIH4 NH2
/ ........, ........,
(a) TsCI _

/ --- / /
H pyridine 2) H20
( b) H C H2
3 �
--- � ..
PCC HN
�
OH O NHCH3
Na(AcOhBH

-
(c) �OH 3 �NH2
TsCI �OTs
NH
•

pyridine
cr03 Na(AcOhBH /"'--.../
�H 2 0.. H2 ./"--./
II + �N •
I

� HN�
H S 4
O o
H20 0 /"'--.../
(ACOhBH

I
I I

tpcc
CH3-CH �N�

CH3CH20H
(r � a Na0't
o
"
(d)
CH3 �CH20H �CH2Br
-H C

V PctV
aCH2NHCH2CH2CH] •
Na(AcOhBH

�NH2 from (c)

o
(e)
(rCH3 � (rCOCI ac-" NH2COOH

I I I
o ---?"

j
·
•
� KMn04 � NH3 �
Br2
NaOH

N02 � NH2
..
0
Na
�HNO] �
HCI

(I) 0
I
�
.&
�
AICI3
0
CI
• I
.&
0
H2SO4
•

.&
0
zna[g
HCI
J y .&

�
Clemmensen
°
H2Cr04 SOCI2
N02 reduces both NH2
�OH .. --- CI 459
 o� y� � � IuY
19-50 continued °
(g)

U
' / AICl3
l

I
Zn(Hg
HCI h
HN03 Fe, HCI
�
H 2SO4
•
f)I
I h

,? 5 Y
H2N
° after workup with base
H2C

Y
'
OH Cl

�oI
19-5 1
°
(a) II
CI- CCH2CH2CH3 Zn(Hg)
� •
HCI

b( ) '--C
O N-CH1

Hofmann elimination

-Q- -Q-
(c)

Ph � N02 � Ph NH2
HCI

�
t)
19-52 S H
H I

� '''''

coniine
460
19-53
unknown X
(a)
-fishy odor � amine
-molecular weight 10 1 � odd number of nitrogens
� if one nitrogen and no oxygen, the remainder is C6H)S
Mass spectrum:
�

� a-cleavage
-fragment at 86 = M - 15 = loss of methyl the compound is likely to
have this structural piece: CH3 N -

IR spectrum:
-no OH, no NH � must be a 3° amine
-no C=O or C=C or C=N or N02

NMR spectrum:
--only a triplet and quartet, integration about 3 : 2 � ethyl group(s) only

assemble the evidence: C6H)SN, 3° amine, only ethyl in the NMR:

(b) React the triethylamine with HCI. The pure salt is solid and odorless.
+
(CH3CH2hN + HCI -. (CH3CH2hNH CI -
salt
(c) Washing her clothing in dilute acid like vinegar (dilute acetic acid) or dilute HCI would form a water­
soluble salt as shown in (b). Normal washing will remove the water-soluble salt.

---

yQ o H
H

(b) Both answers can be found in the resonance forms of the intermediate, in particular, the resonance
form that shows the positive charge on the N. This is the major resonance contributor; what is special
about it is that every atom has a full octet, the best of all possible conditions. That does not arise in the
benzene intermediate, so it must be easier to form the intermediate from pyrrole than from benzene.
Also, acylation at the 3-position puts positive charge at the 2-position and on the N, but never on the
other side of the ring, so this substitution has only two resonance forms. The intermediate from acylation
at the 3-position is therefore not as stable as the intermediate from acylation at the 2-position.
461
19-55
(a)
'Q F
000
o o F
li
+
NH2R
0
0
0o-;
1 � 1j
F
+
N HzR
0II F
+
NH2R

Y
N+
_
� 0 N+
I
OZN

I I
-

I
-0'"
0
oo : 0'"
'c.

... ..
0 0

I
...
:0'"
N:"
N H zR ..
0
�.. �
..
� � � 00
C-
+ 1
N02 ... N.... _
+
N.... _ N+ 0 0-

0'" 0 0 '" 0 :0'" 0:

y
(b) Why is fluoride ion a good leaving group from A but not from B (either by SNI or SN2)?

F Nu

� ��
_ A
N02 :NU
HC
I C
A B
NOz
Formation of the anionic sigma complex A is the rate-determining (slow) step in nucleophilic aromatic
substitution. The loss of fluoride ion occurs in a subsequent fast step where the nature of the Jeaving group
does not affect the overall reaction rate. In the SN 1 or SN2 mechanisms, however, the carbon-fluorine hond
is breaking in the rate-determining step, so the poor leaving group ability of fluoride does indeed affect the
rate.

t>-.
t
lrl� ________________

nucleophilic aromatic
substitution
delocalized ,
(c) Amines can act as nucleophiles as long as the electron pair on the N is
available for bonding. The initial reactant, methylamine, CH3NHZ' is a very
reactive nucleophile. However, once the N is bonded to the benzene ring, the
electron pair is delocalized onto the ring, especially with such strong electron­
withdrawing groups like N02 in the ortho and para positions. The electrons
on N are no longer available for bonding so there is no danger of it acting as a
nucleophile in another reaction.
N02
462
19-56 Compound A
Mass spectrum:
-molecular ion at 73 = odd mass = odd number of nitrogens;
if one nitrogen and no oxygen present � molecular formula C4H11N
�

- -
-base peak at 44 is M - 29 this fragment must be present:

�
-, t
N
CH3-
I
CH2CH3
EITHER OR H-C-CH2CH3
I
44 �
a-cleavage
H
2

IR spectrum:
-two peaks around 3300 cm-I indicate a 1 ° amine; no indication of oxygen
NMR spectrum:
-two exchangeable protons suggest NH2 present
-I H multiplet at 8 2.8 means a CH-NH2 A

The structure of A must be the same as 1 above:

Compound B
an isomer of A, so its molecular formula must also be C4H11N

IR spectrum:
-only one peak at 3300 cm-I � 2° amine
NMR spectrum:
-one exchangeable proton � NH
B
-two ethyls present
The structure of B must be:

+
- CH2 = NCH2CH3
I
H resonance-stabilized
rnJz 58

19-57
(a) The acid-catalyzed condensation of P2P (a controlled substance) with methylamine hydrochloride gives
an imine which can be reduced to methamphetamine. The suspect was probably planning to use zinc in

-
muriatic acid (dilute HCl) for the reduction.

0Jl + Cl

methamphetamine
phenyl-2-propanone, P2P
(phenylacetone)
(b) The jury acquitted the defendant on the charge of attempted manufacture of methamphetamine. There
were legal problems with possible entrapment, plus the fact that he had never opened the bottle of the
starting material. The defendant was convicted on several possession charges, however, and was awarded
four years of institutional time to study organic chemistry.

463
1 9- 58
Mass spectrum:
H H

t I
-molecular ion at 87 = odd mass = odd number of nitrogens present
\
� molecular formula CS H13N R CH2NH2 -.. C = N+
\
-if one nitrogen and no oxygens
/
� 30
-base peak at mJz 30 structure must include this fragment H H
mJz 3 0
IR spectrum:
�
1 1 ° amine
-two peaks in the 3300-3400 cm- region
NMR spectrum:
-singlet at 80.9 for 9H must be a t-butyl group
-2H signal at 8 1 .0 exchanges with D20 � must be protons on N or °

{
8 1.0

� l
H3

80.9 CIl3_ CH2- ,

� t H3
82.4
Note that the base peak in the MS arises from cleavage to give these two, relatively stable fragments:
CH3 H H
I \ /
CH3 -C· + C=N+
1 / \
CH3 H H
19-59 (a tough problem) mJz 30

molecular formula CII Hl6N2 has 5 elements of unsaturation, enough for a benzene ring; no oxygt:ns
:: is present, there are not enough elements of unsaturation left for a
precludes N02 and amide; if C:::N
benzene ring, so benzene and C=N are mutually exclusive

IR spectrum:
--one spike around 3300 cm-1 suggests a 2° amine
-no C=N
-CH and C=C regions suggest an aromatic ring

Proton NMR spectrum:

- 5H multiplet at 8 7.3 indicates a monosubstituted benzene ring (the fact that all the peaks are huddled
around 7.3 precludes N being bonded to the ring)
-1 H singlet at 8 2.0 is exchangeable � NH of secondary amine
-2H singlet at 83.5 is CH2; the fact that it is so strongly deshielded and unsplit suggests that it is between
a nitrogen and the benzene ring

< >-
fragments so far:

CH, -N + NH + 4C + 8H + I clement of unsaturation

continued on next page 464

19-59 continued
Carbon NMR spectrum:
-four signals around 5 125-138 are the aromatic carbons
-the signal at 5 65 is the CH2 bonded to the benzene
-the other 4 carbons come as two signals at () 46 and () 55; each is a triplet, so there are two sets of two
equivalent CH2 groups, each bonded to N to shift it downfield
fragments so far:
<} CH2-N + NH + CH2 CH2 + CH2 + 1 element of unsaturation
CH2

There is no evidence for an alkene in any of the spectra, so the remaining element of unsaturation must be
a ring. The simplicity of the NMR spectra indicates a fairly symmetric compound.
Assemble the pieces:

19-60

Jl
(a) (b)
H
� N�
�H CH3
0
Ph
�a(AcO h BH
11

(
�
N�
V

(
HN�

465
1 9-6 1 Not only is substitution at C-2 and C-4 the major products, but substitution occurs under surprisingly
mild conditions.
Begin by drawing the resonance forms of pyridine N-oxide:
..-
:0: :0: :0: :0:
1+ 11+ 11+ 11+

.. .. . .. .. .. ..
OR (�) RO
N - - N

0 �
C-
H
Resonance forms show that the electron density from the oxygen is distributed at C-2 and C-4;
these positions would be the likely places for an electrophile to attack.

-
Resonance forms from electrophilic attack at C-2
..
.
a a .. (:f c�
:0: :0: ·. ·0··. ­ ·. ·0·....
1++ II + 1+ 1+
N E N E E E
N N
H " _ H " H " - H
.0 0 HC
+ 0 � +CH
N does not have an GOOD! All atoms
octet; not a significant have octets.
resonance contributor
Resonance forms from electrophilic attack at C-3

( \ .. a
..-
·. ·0··. ­ ·. ·0··.­ :0:
1+ 1+ 1+

Q
H� CH
N N N'
,,=
+
H - H " - H
� �
C
H E These two Eresonance forms place twoE
positive charges on adjacent atoms-not good.
Resonance forms from electrophilic attack at C-4
..-
:0:
..
:0:
- :0:
.-
.
:0:
1+ 1++ 11+ 1+

.. .. .. ..
OR
H E
-
0
H E
N does not have an
0 -Q
H E
GOOD! All atoms
HC
+
H E
octet; not a significant have octets.
resonance contributor
continued on next page 466
19-61 continued
The resonance forms from electrophilic attack at C-3 are bad; only one of the three is a significant
contributor, which means that there is not much resonance stabilization. When the electrophile attacks at
C-2 or C-4, however, there are two forms that are good plus one great one that has all atoms with full
octets. Clearly, attack at C-2 and C-4 give the most stable intermediates and will be the preferred sites of

�
(f0: �C-!l
attack.

<>?: 0/9.:
CH3
19-62 H H + I�

O
I

O
I H-N-H
(aJ
....
..f--l
. .
H� NC I!3 - Q.H
�

B- is the conjugate base B:

of the acid HB 1�
,...... d 9..
�
CH3 CH3
I I

d··
H-N: H - N:
C-OH C H
'-""1+
-

H
� �

called an aminal

continued on next page

467
19-62
.�
cr
continued
0
(b) O:'�
H -B +C - C-OH
q • •
..

B- is the conjugate base

of the acid HB 11 B:

. -H20 .
o 0
/ �H�_ O�:·· +
aD -' �� � o�:.
C /'
C - OH H�B - C - OH

0::0 � (X/O I enamme

H
To this point, everything is the same in the two mechanisms.
But now, there is no H on the N to remove to form the imine.
The only H that can be removed to form a neutral intermediate
is the H onC next to the carbocation.
(c) A secondary amine has only one H to give which it loses in the first half of the mechanism to form the
neutral intermediate called an aminal, equivalent to a hemiacetal. In the second half of the mechanism, the H
on an adjacent carbon is removed to form the neutral product, the enamine. The type of product depends
entirely on whether the amine begins with one or two hydrogen atoms.

468
 CHAPTER 20-CARBOXYLIC ACIDS

20-1 CH3
I

cf:�:�
(a) CH3CH2 CHCOOH

(f)
tH
(d) OH (c)

'>
H H

) N H2
(
(g) COOH (h) COOH
N
.
(1)
I COOH
� COOH
Cl
HOOC �
-

� CI CH3

0(y 0 H
o
(j) HOOC � COOH (k)
� COOH (I)

Cl V a
20-2 IUPAC name first; then common name.
(a) 2-iodo-3-methylpentanoic acid; a-iodo-p-methylvaleric acid
(b) (Z)-3,4-dimethylhex-3-enoic acid
(c) 2,3-dinitrobenzoic acid; no common name
(d) trans-cyclohexane-1,2-dicarboxylic acid; (trans-hexahydrophthalic acid)
(e) 2-chlorobenzene-\ ,4-dicarbox ylic acid; 2-chloroterephthalic acid
(f) 3-mcthylhexanedioic acid; p-methyladipic acid
20-3 Listed in order of increasing acid strength (weakest acid first). (See Appendix 2 for a review of acidity.)
Br
(a) CH3CH2COOH < CH3 - CHCOOH <
I

I
CH3 - CCOOH
I

Br Br
The greater the number of electron-withdrawing substituents, the greater the stabilization of the carboxylate
ion.
(b) CH3CHCH2CH 2COOH < CH3CH2CCH2 COOH < CH3CH2 CH2 CHCOOH
I I I
Br Br Br
The closer the electron-withdrawing group, the greater the stabilization of the carboxylate ion.
(c) CH3CH2 COOH < CH3-CHCOOH < CH3 - CHCOOH < CH3-CHCOOH
o C�N
I I I
N02
The stronger the electron-withdrawing effect of the substituent, the greater the stabilization of the
carboxylate ion.

469
 �COOH �CHO
20-4
�
"- CH20H H2S04
Y
shake with ether and water
ether water
�COOH
isoln etublhere �CH20H
�CHO
shake with NaOH (aq)
ether NaOH (aq) ionized form
�
byunchanged
NaOH � CH2OH COON a t ca� b oxyl i c
{ ........",- -CHO acidify with HCl (aq) and ether in e sol u bl
of
aCId is
water
/"'-.. /"'-.. /"'-..

HCl (aq)
./ ........",-

ether
�COOH NaCl
evaporate ether t
�COOH

470
20-5 The principle used to separate a carboxylic acid (a stronger acid) from a phenol (a weaker acid) is to
neutralize with a weak base (NaHC03), a base strong enough to ionize the stronger acid but not strong
enough to ionize the weaker acid.

�-o- OH 0° < }- co,

y
shake with ether and NaHC03 (aq)

ether NaHC03 (aq)

,-------- -------�\
A
< }- cooNa
CH3
\..
-Q-
� OH +
-
00
)
! 1. add HCl
2. filter or extract
y
shake with NaOH (aq) � COOH
�
- pure

ether NaOH (aq)

00 CH3-Q- oNa
! evaporate ! 2.1. filter
add HCl
or extract

CH3 -Q- 0H
Q� pure

471
20-6 The reaction mixture includes the initial reactant, reagent, desired product, and the overoxidation
product-not unusual for an organic reaction mixture.

(a) < :N � COOH eHO�

� e H er03
,, 2
� H _0- -----------)
y
____________

( )
shake with ether and water

ether water
some compoundS
�eOOH "N have appreciable
solubility in both
C ether and water

�
b.p. 137°
eHe 20H �eHO
b.p. 102° e
(b) Pentan-l-ol cannot be removed from pentanal by acid-base extraction. These two remaining products
can be separated by distillation, the alcohol having the higher boiling point because of hydrogen bonding.

20-7 The eOOH has a characteristic IR absorption: a broad peak from 3400-2400 cm-I, with "shoulder"
a

around 2700 cm-I. The carbonyl stretch at 1695 cm-I is a little lower than the standard 1710 cm-I,
suggesting conjugation. The strong alkene absorption at 1650 cm-I also suggests it is conjugated.

472
(a) The ethyl pattern is obvious: a 3H triplet at b 1.15 and a 2H quartet at b 2.4. The only other peak is the
20-8
COOH at b 11. 9 (a 2.1 b uni t offset added t o 9. 8).
o
II
CH3CH2-C-OH

(b)
o
£

II Q
3H
H-C-CH2CH3
.i! £

Q
2H
TMS
.i!
IH

1 :1 II II I
8 7 6 b (p5pm 4 3 2 1 0
10 9
)
I I I I I I I I I I I

Theand tmulhe CH2tipletgroup.

betweenThese2 andcoupli3ngis const
<5 <5 drawnantass area pentprobabl
et as ythough it wer, in ewhisplciht equal
unequal case lhyebyactthuealalspldehyde
t i t i n g protteornn
pat
wi(c)l Thebe achemi
complcealx shimulfttiofpletht.e aldehyde proton is between b 9-10, not as far downfield as the carboxylic acid
proton. Also, the aldehyde proton is split into a triplet by the CH2, unlike the COOH proton which always
splappearit insg,asinastsieadnglofet.thFie nquartally,etthshown
CH2e iins spltheitacibydan. extra proton, so it wil give a multiplet with complex
20-9 :OH
• •
.
:OH
.

+ C1 ........ C ........
I
/ OH + h
:I"
H2C==C H2C-C\ OH
\
.. ..

H H

t ..
+OH
II
..
:OH
I
C .
/ ....... OH /C�
""'
+
OH
H2C==C H2C==C
\ \
.. ..

H H

473
 [ CH3CH2tCH' H0-OH ]
20-10
ig
t
:OH
CH3masCs H,· H2C==C/C,9,..H
+ I

87 CH3 CH3
+

plasushown
s resonance
im/z n8720-9forms
29 \
-

m/z1l6
McLafferty rearrangement
H3C I1�H� : H3C,CH H,0..:
�ft'C 'OH
t t

CH2 HC/',/.C,OH
II I

mass 42 CH3
-- +

CH3
m/z1l6
I

mlz74
(a) �C C� orconc.1 ) 03,KMn04
20-11
2) H20 �COOH
C-:::) conc. KMnO� C:COOH
•

(h)
H 0+ COOH
CH2CH20HH2Cr04 6CH2COOH
< }- Br etMgher < }- MgBr D H30+ 6
t, , 3

(c ) o

I �
I

Br Mg CO2 H30+ COOH

-­ � --- •

(d) � PB r3 �
ether �
COOH
� -- --- �

(e) conc. KMn04

Q
CH3
t"H30+
COOH
Mgether CO2 H30+ �COOH
•

¢
(f) �I
-- --- •

OR �I KCN �CN H30+ �COOH

•
t, •

474
20-12 (a) +
:O-H ..
:O-H ..
:O-H }
first intennediate RC-�H RC+- OH RC==�H II

·i 1 1 +

}
:O-H :O-H iY-H
• • • •

� �

:OR.. :OR..
second intennediat RC(
i �
/
\\
RC
+OR
� RC \

(b) Theomechani
successi n of st e ps smthofataciared-catalreaadylyzedvernucly famieophiliarlitco acylyou.substitution may seem daunting, but it is simpl)'
atwork.tack,TypiTheandcaalsixlleyavi,sttehpsneseg argroup
mechanileavismsng,havewithsiaxlistt eleps:resfouronanceprotstoanbitlriansfzatioersn t(htrwoownon,intwthoatoff)makes, a nuclthe eophilic
a

e labeled in the mechanism below: whole thing

StepB nuclprotprotooennophioffonl(ereatsonance
tacks stabilization)
lprotpreaviotoonnngoffongroup leaves (resonance stabilization)
StepA

Step C

i :O-H
Step D

+
CH)C-OH.. CH)C-OH. CH3C=OH.. fL
Step F

:O-H :O-H+
Step E

1 +
1
• • • •

II 1
� .
• • • •

/
H ........CH2CH3
_ _

.. �
StepA

Step B
o

O-H
CH3C-OH
1

H /R� .... H2CH3 H '" ..... CH2CH

StepC

3
AI
l ""0 .....

1 }
StepD

- H20 CH3C:O-H /
+ CH3C /
:O-H
CH3C
+
//'0
O-H .
\
:RCH2CH3 +RCH2CH3 :�CH2CH3 \\ \
---I�� � �

Step E

475
Applyin(cg) thAle lstsetpsepsasaroute reversi
20-12
lined onble,thwhie previch isousthepage:reason(atbbrhe ePrviinacitinpgleOCH2CH3
of MicroscopiOEtc Rever
) sibility applies.
nucIprotprotooenophin offonl(eresonance
attacks stabilization) -B B is the acid catalyst
as

protleavionngongroup leaves (resonance stabilization) :hydr- oilsysithserconjeactiuogatns,ewatbase,er usual althoughly removes

in
H
Step B
StepA

proton off
StepC
StepD H+

Step F

:O-H
StepE

1+
'OEt
O
/

:O-H \ :O-H
a a �O:t (f
: O-H c1� C H
C+ C 'OEt
:O- H

cr �
+1C I I

+
� CH HC �
+

:O-H
1 + I)' O· ·H2
aA)Et \
aAEt H
C-O: C-O:
:O - H H �
•
.
I • •

Step B St.pC

� H-Ok
�11 Step D +�

:OHQO� EtOH :O-H

same seri e s cr
ms as above-- - � I ( H �
C-O:
Oil H1
I

offorresonance � +· OEt
1). \H
• •
-

..
___
_-
StepE

II :OH, OH StepF

(JC=O I

476
20-13 For the sake of space in this problem, resonance forms will not be drawn, but remember that they
are critical!

X='
'0' '0'
XJ '!J
�· + ....H+H + H�
Ph Ph
+
).? 5
0 plus resonance forms ).? plus 6 resonance forms
·0 .... H
Ph �H Ph � OH
+
H�CH 3 +
H� CH 3
H H
O .... O ....
Ph10 H �+
�
Ph1 OH
....0+
;» H .... "CH 3 ;» H ·'CH 3
H� CH 3 + H� CH 3 +
• •

t 0h-t-OH ·0 .... H
H

c: +
• • • •

h H
'CH 3 'CH 3
H+ H+ �

+ ,-
H ...0. ..... H H ... 0. ..... H

Ph +Ho
Ph +OH
+

o
,-

+ -H20 t -H20
'CH 3 'CH 3

+
Ph / c '" H plus resonance forms
O'CH 3
4 yO� plus 5 resonance forms
p
Ph
.\ CAN LOSE H+
(+
, HERE'S THE DIFFEREN CE! o TO
HR CH 3+ CANNOT LOSE H+ TO 'C � MAKECARBONYL
H "'" CH 3
�O
• •
MAKE CARBON YL
+H� CH 3
o
Ph H II
O'CH
+
CH
Ph O"'" 3
H� CH 3
3 �

..... CH 3
�H
o

Ph o
'CH 3
477
20-14
(a)
°
R-C-OH H+
II
�
{R-C-OH
:0 :
� R-C-OH
II
} ..
+I
:0:-
I
++I
.

'- H H •

• •

BAD-two adjacent
positive charges
OH C=O
(b) Protonation on the gives only two resonance forms, one of which is bad because of adjacent positive
charges. Protonation on the is good because of three resonance forms distributing the positive charge

i+
over three atoms, with no additional charge separation.

: 0: � H+ : O-H : O-H
t
: O-H+
RC-OH
II II + � RC=9 H
RC-RH �RC-RH I I
.
• •

..
•

�
•
• •

(c) The carbonyl oxygen is more "basic" because, by definition, it reacts with a proton more readily. It does
so because the intermediate it produces is more stable than the intermediate from protonation of the OH.
20-15
(a) OH OH
Jv COOH Jv COOCH3
�
+ CH30H �
H20 +

use CH30H �
remove water with
as solvent molecular sieves
(b) ° °
HC -OH useCH30H
II
+
CH30H .. HC-OCH3
II

remove by
as solvent distillation
b.p.32°C
(c) � COOCH2CH3
.. + H20
�
�
remove water with
molecular sieves or
by distillation

478
20-16 The asterisk (" * ") denotes the 18 0 isotope.
(a) and (b)
i + • • • •

1
:O-H : O-H
I +
: O-H

.. .. .. f
" 1+
�
j
• • • •

CH3C-OII � CH3C-OH � CH3C=OH

.. �
/ 0*

,.:.---- O-H
H ' " CH3

O-H
1 1
CH3C-OH .. CH3C-OH

� �
1
/0*' 1+
0 * CH3 H " CH O*
/ '
H " CH3

(c) The 18 0 has two more neutrons, and therefore two more mass units, than 160. The instrument ideally
..
suited to analyze compounds of different mass is the mass spectrometer.
20-17 + O-Et
I I II
: O-Et : o -Et
(a)
first intermediate: H -C+ ---- H-C H-C ----

\ \\ + \
: O-Et O-E t : O-Et

.. ..
H + O-H
II
I I
• •

: O- : O-H
second intermediate: H-C+ ---- H-C ---- H-C
\ \\ + \
: O-Et O-Et : O-Et

The more resonance forms that can be drawn to represent an intermediate, the more stable the intermediate.
The more stable the intermediate, the more easily it can be formed, that is, under milder conditions. These
intermediates are highly stabilized due to delocalization of the positive charge over the carbon and both
oxygens. A trace of acid is all that is required to initiate this process.

479
20-17
continued + }
i �
(b) :O :� :O - H
. .
:O-H
. .
:O - H
-O t
1+ +
HC-OEt H+
II II I

r
HC=OEt
• •

.. HC-OEt

� . .
H/R'H t
:O - Et
I
IF

HC-OH
I

i P-
OH

H-)5-Et :O-H
r:-' : O-H
o
. .
:O- H +O-H
HC-OH
I) - EtOH / / //� H "
.. HC+ ---- HC \ ---- HC H-C
\ \
OH
\
I \
OH : RH +OH :OH
. .

20-18
(a) H 3C 'O I
0 I I
C ....
OH
�

20-19 o
(a)

(b) ar
?'
I
2
o
II
CH -C - Cl LiAl(O-t-BuhH ar
?'
�I
2
CH -C - H
o
II

�
..

B214 selectively reduces a carboxylic

acid in the presence of a ketone.
Alternatively, protecting the ketone as
an acetal, reducing the COOH, and
removing the protecting group would
also be possible but longer.
480
20-20 �
:0 : Li+ '\ HO HO
.

\ \ I
R -C- R' + H+ R - C - R' R - C - R'
:6:
. / \
HR:---./
H+ +1) H
H-�-

1-
Li+
a hydrate
H20

Y
o : O-H l
..
·· + O-H
R- � - R' f
\I ..
H20: I IV
R - C - R' R - C - R'
+
20-21

CH3CH2 - C - OH -{ � _ H_2-10..
(a) 0
+ 2 Li _
�

(b) RC - OH
O
20-22
..
o: Jt? �Cl + CPh;'0iYCI
:0 :0 :
�-
Y + Cl If
HO HO,

-{
• • • •

I Cl
Ph 0 0

tt :0.:
� + � �. '0'
. ..-' H+Oy O � CI
.......f---
r-
_
.

...."
plus three other
•

H (-O � Cl resonance forms (

• • • •

-
Cl 1
�

with positive charge Cl

• •

Ph 0 on the benzene ring Ph 0

plus resonance forms

:o�oj(
'0'
� R �� �Cl
'0'
�Cl -:O o
I'"
P�
.. I( '
Cl',/\0
ph
IrJ
° .. Ph )l Cl + O=C=O +

+ Cl

481
20-23
(a) Co
: :0 :
II
Ph -C� .. CH3
II
Cl + H-O-CH2 Ph C
",1+
-
-

H-OCH2CH3

�� R t
.. Ph C-�CH2CH3

CIIO: ?j
-

3
(b) H :0 :
I

+1 U
CH3 -C-C1

�
CH -C-C1 + H-N-CH3

H-N-CH3
I
• •

d'
20-24
(a) 0

oH

(b) o
� OH � Cl
0

20-25 Please refer to solution 1-20, page 12 of this Solution Manual.

20-26
(a) 3-phenylpropanoic acid (b) 2-methylbutanoic acid
(c) 2-bromo-3-methylbutanoic acid (d) 2-methylbutanedioic acid
(e) sodium 2-methylbutanoate (f) 3-methylbut-2-enoic acid
(g) trans-2-methylcyclopentanecarboxylic acid (h) 2,4,6-trinitrobenzoic acid
(i) 7,7-dimethyl-4-oxooctanoic acid
20-27
(a) f3-phenylpropionic acid (b) a-methylbutyric acid
(c) a-bromo-f3-methylbutyric acid, (d) a-methylsuccinic acid
or a-bromoisovaleric acid
(e) sodium f3-methylbutyrate (f) /3-aminobutyric acid
(g) o-bromobenzoic acid (h) magnesium oxalate
(i) 4-methoxyphthalic acid
482
 -8 (X )
20 2

( H-t O-
(a) 0 (b) COOH (c)
Mg2+
II
CH3 - C - OH
� 2
COOH
(e) 0 (f) 0
II II
ClCH2 -C - OH CH3-C - Ci

)2 < }- C - O- Na+
0- (h) 0 (i) 0 II
FCH2-C-0- Na+
o

20-29 Weaker base listed first. (Weaker bases come from stronger conjugate acids.)
(a) ClCH2COO- < CH3COO- < PhO­
(c) PhCOO- Na+
20-30
(a)
(b) (X
7"1
COOH
+ 2 NaOH
(X I
COO- Na+
� COOH � COO- Na+
(c)
CH3 -Q- COOH no reaction

(d) CH3 - CHCOOH + CH3CH2COO- Na+

I
CH3- CHCOO- Na+
.-
I
Br Br
(e)
< }- COOH + Na+ -0 -1 � .. < }-
COO- Na+ + HO -1 �
2-031 0 o
OH
� O�
II II
CH3C-OCH2CH3 < < CH3CH2CH2 -C - OH
lowest b.p. (n°C) (b.p. 143°C) highest b.p. (l62°C)
.
The ester cannot form hydrogen bonds and will be the lowest boiling. The alcohol can form hydrogen
bonds. The carboxylic acid forms two hydrogen bonds and boils as the dimer, the highest boiling among
these three compounds
20-32
} 2.
Listed in order of increasing acidity (weakest acid first):
(a) ethanol < phenol < acetic acid EWG electron-withdrawing group
(b) acetic acid < chloroacetic acid < p-toluenesulfonic acid =

(c) benzoic acid < m-nitrobenzoic acid < o-nitrobenzoic acid Acidity increa�es. with:

(e)
Br
COOH <
0=
(d) butyric acid < (3-bromobutyric acid < a-bromobutyric acid
n- Cl
COOH <
[yF
1. closer proxImIty of EWG
great number of EWG
3.
increasing strength
COOH (electronegativity) of EWG
483
20-33 lAceti
are fairSubstiy easitcuents
lyacisynthesi
d derivatives
z ed (or areareoftcommerci
en used aasl ya avai test lofablelee),ctroni
and c effects
pK a val u es ofarea series
easil ofmeasured
y substituentbys:titthey
riats ion.
possibTwo le because the on carbon-2
CH2 is sp of aceti c aci d can express
3 hybridized and no pi overlap is possible. onl y an inductive effect ; no resonance effect
hdrawintconclusi
wieletctron-wi becausenognsaleflcanfectfourbeinsubsti
ghdrawi drawntutedfromacitheds aregivenstronger
creases in t h e order :
pKa valthuanes.acetiFirst,c acialldfour
OH Cl CN N02 . . (It i
substituents
Second,
s al w the
ays a
are teludeectron­
magni
safe assumpti of thoen
that nitro is the strongest electron-withdrawing group of all the common substituents.) < < <

20-34
(a)of a Ascorbi c aci
structurel y acidi
iSees unusual
d i s not
callecdbecause a carboxyl
an ene-diofothel where i c aci d . It i
one carbonyl
adjacent
s an exampl
of the OHgroup. e
groups HOCH2
H� " OH 0 0
part (c). HO
_
-ene
OH
(b)of acetiAscorbic aci d , pKa 4.71, is alm ost identical to the aci d i ty
(c)givesThethcemore
acid, acipKadi4.74. '(ol
{ }
c H wi l l be t h e one th at, when removed, di
, I

}
more stable conjugate base.
R -<;l(0 _R -}:(O �� -}:(O� R -}:(O_R 1�O
start here

:0 OH :0: OH HO OH HO :0: HO 0:
{ t t
. . _ . .

e
. . _ . .

»(
R 0 !. : 0 -
THREE
r esonance fOnTIS more
aci d i c onl y two resonance fOnTIS
�� (d)present
is In the assligthhtle conjugate
y basic pHbase, of physi ologiec,alwhose
ascorbat fluid,structure
ascorbic canacid
:R OH '\..J. beof part
represented
(c). by any of the three resonance fOnTIS on the left
• •

20-35
Q) (b) 0- (C) � (d) 2�COOH
o
(a) � CH2COOH
r; �
- CH20H �
(e) o- COOH Ph (g) (h) COOH
�o C
(f)
\ CH3CH2 -CHCH20H
I
H �
� V-- COOH
(i) COOH (k)
COOH
� CHO
484
20-36 Mg .. CO2 H30+ KCN Hp+
(a)�
� COOH
Br
--- .. OR ... .�
ether

(b)�
conc. KMn04
.. 2 ,./"-COOH
�, H30+

OR H2Cr04 ..
0 0
Ag+ ..
�H � OH
(c)

NH3 (aq)

.. � H
(d) 0 SOCI2 0
LiAI(Ot-BuhH 0
� OH �C I
11) LiAlH4 .. �
OH
PCC J
2) H30+
... �COOCH3
(e) � CH30H CH2N2
COOH OR ...
H+
OR SOCI2 C H3 0 H
�COOH .. �COCI .. �COOCH3

(f) O'COOH LiAlH4

..
H30+
...
O' CH2OH OR B2H6
...

(g) CH2COOH SOCI CH3 NH2 QgHN'

U � ... I CH3
1 h h 0

(h) CI
I
( (X --I
CI H2
--
(X CI

( COOH
+

� COOH PI COOH
Diels-Alder

485
20-37 � }- COOH < }- OH o- CH,oH 0-,
----V
_

shake with ether and HCl (aq)

('hCOOH, PhOH, PhCH20H) +

PhNH3 Cl-
V
shake with NaOH (aq)
shake with NaHC03 (aq) and ether
NaOH (aq) ether
NaCI PhNH2
!
PhCOONa
evaporate
shake with
shake with
NaOH (aq)
ether and
HCl (aq) < }-pureNH2
evaporate �
ether
NaCI PhCOOH �
•
COOH
_ pure

ether NaOH (aq)

PhONa
!
PhCH20H
evaporate

< }-pureCH20H evaporate.. pure

NaCI PhOH

486
20-38
H "OH OH
(a)

CH3 1;(t N
S
"",

0
OH +

racemic
(R + S)

(b) Isomers which are R,S and S,S are diastereomers.

20-39 TsCI KCN PhCH2CH2CN H30+.. PhCH2CH2COOH

!
(a) PhCH2CH2OH pyridine �
.. ..

P B r3
Mg CO2 H30+
PhCH2CH2Br .. PhCH2CH2COOH
cr (f
.. ..

ether
(b) CH2 HB
r
CH3 Mg ('-r( CH3
V
Br ether..
---t
..
� COOH

(d)
c;cr� � COOH

o o
O�
Br 1\

,
HO
h
yV
o
W�

() 6 (l
(e)
:
Li
COO 2

dD
_ _
H_30_ +... HO OH ..

W, �

487
20-40
(a) Mass spectrum:
-
-mlz 152 ==> molecular ion ==> molecular weight 15 2
-m1z 107 => M 45 => loss of COOH
-m1z77 => monosubstituted benzene ring,
H
-Q
K +

IRspectrum: H H
-3400-2400 cm-i , broad ==> O-H stretch of COOH
-1700 cm-i ==> C=O
-1240 cm-i ==> C - O
-1600 cm-i ==> aromatic C=C
NMR spectrum:
� 6.8-7.3, two signals in the ratio of 2H to 3H ==> monosubstituted benzene ring
� 4.6, 2H singlet ==> CH2 , deshielded

Carbon NMR spectrum:

� 170, small peak ==> carbonyl
� 115-157 , four peaks ==> monosubstituted benzene ring; deshielded peak indicates oxygen
substitution on the ring
(b) Fragments indicated in the spectra:
<> COOH
mlz77
mlz 14 mlz 45 and from IR
This appears deceptively simple. The problem is that the mass of these fragments adds to 136, not
152-we are missing 16 mass units oxygen! Where can the oxygen be? There are only two
�

possibilities:
<} O - CH2COOH <} CH2-O - COOH
How can we differentiate? Mass spectrometry! 8157
( } CHj O - COOH ( Yat CH2COOH This structure is consistent
93 J
91
carbonNMR.
8
with the peak at 157 in the
phenoxyacetic acid
The mlz 93 peak in the MS confirms the structure is phenoxyacetic acid. The CH2 is so far downfield
in the NMR because it is between two electron-withdrawing groups, the 0 and the COOH.
(c) The COOH proton is missing from the proton NMR. Either it is beyond 10 and the NMR was not
scanned (unlikely), or the peak was broadened beyond detection because of hydrogen bonding with DMSO.

488
20-41
6
(a) 0
a-valemlactone

(b) : O�\
o
r �OH �

V
. .
O· o·
tt='�:
t+ ....
H-O : H-O :
. .

O
0: ---
0+ ---
0:

o AD:
6
20-42
CoII:� CH3 :0 :.. :0:
. .

/
�
I + I +

/' C ....... O=C Ph-C - O=C-CH3 Ph - C - O - C - CH3

• .

.
Ph Cl \ I I
• •

I I
• •

O-H Cl :O - H Cl :O - H .

o
II
:0:
(s:
.. Ph - CII - O - C - CH3
II I
Ph-C-O - C-CH3 Ph-C-O. - C - CH3
-?:
---

II · · :� H �
:cl II
Ccl
• • •

:0: :O+ -H
plus two other resonance forms
20-(a) 43 CH3 ester (an ester in a ring
� is called a lactone)
--q CH3
acetal H30+
CH3
CH2CO 'l OH alcohol
carboxylic
Compound 1 acid
489
Compound 2
20-(b) 4Compound
3 continued has 8 carbons, and Compound 2 has 6 carbons. Two carbons have been lost: the two
1
carbons of the acetal have been cleaved. (This is the best way to figure out reactions and mechanisms:
find out which atoms of the reactant have become which atoms of the product, then determine what
bonds have been broken and formed.)
(c) Acetals are stable to base, so the acetal must have been cleaved when acid was added.
CH3
oAo
5 � CH3
H30+

4 CH2COOH
2 1

(d) The carbons have been numbered above to help you visualize which atoms in the reactant become
which atoms in the product. The overall process requires cleavage of the acetal to expose two alcohols.
3°
The alcohol at carbon-3 can be found in the product, so it is the primary alcohol at carbon-5 that reacts
with the carboxylic acid to form the lactone.

+ 0-H resonance stabilized;

H3C --'( leaves the reaction

H
+

..
� :.O C\
H-.a �- H
H,+

Q
: OH OH O-H
�'----{ .
O� +- H +0 :0
CH3
_
•.
CH3 two fast
- •

c5-
:O - H OR H+ transfers

:·0 0 !
OR

.
H20
..
.Q·O
-
�
0:
.
o",-,,-H
H - O:

0 .Q
:O-H :O-H
.. C' +
•
H
,
+0 ...

CH3 CH3
•

....
..
11--
. -
.. •
CR3" CH 1

OH OR 490 OH OR
20-words44 about
(A more complete discussion of acidity and electronic effects can be found is Appendix 2.) A few
the two types of electronic effects: induction and resonance. Inductive effects are a result of
polarized bonds, usually because of electronegative atom substituents. Resonance effects work through
(J 11:

systems, requiring overlap of p orbitals to delocalize electrons.

All substituents have an inductive effect compared to hydrogen (the reference). Many groups also have a
resonance effect; all that is required to have a resonance effect is that the atom or group have at least one p
orbital for overlap.
The most interesting groups have both inductive and resonance effects. In such groups, how can we tell the
direction of electron movement, that is, whether a group is electron-donating or electron-withdrawing?
And do the resonance and inductive effects reinforce or conflict with each other? We can never "tum off'
an inductive effect from a resonance effect; that is, any time a substituent is expressing its resonance effect,
it is also expressing its inductive effect. We can minimize a group's inductive effect by moving it farther
away; inductive effects decrease with distance. The other side of the coin is more accessible to the
experimenter: we can "tum off' a resonance effect in order to isolate an inductive effect. We can do this
by interrupting a conjugated system by inserting an sp3 -hybridized atom, or by making resonance overlap
11:

impossible for steric reasons (steric inhibition of resonance).

These three problems are examples of separating inductive effects from resonance effects.

(a) and (b) In electrophilic aromatic substitution, the phenyl substituent is an ortho,para-director because it
can stabilize the intermediate from electrophilic attack at the ortho and para positions. The phenyl
substituent is electron-donating by resonance.

+ plus other
.. .. resonance forms

H H H
+

E E E

BUT:
o o
< }-CH2-C-O-H is a stronger acid than H -CH2 -C -0 II

- H
The greater acidity of phenylacetic acid shows that the phenyl substituent is electron-withdrawing, thereby
stabilizing the product carboxylate's negative charge. Does this contradict what was said above? Yes and
group because of the CH2
no. What is different is that, since there is no p-orbital overlap between the phenyl group and the carboxyl
group in between, the increased acidity must be from a pure inductive effect. This
structure isolates the inductive effect (which can't be "turned off') from the resonance effect of the phenyl
group.
(2)
We can conclude three things: (1) phenyl is electron-withdrawing by induction; phenyl is (in this case)
electron-donating by resonance; (3) for phenyl, the resonance effect is stronger than the inductive effect
(since it is an ortho,para-director).

491
 o o
20-44 continued
(c) The simpler case first-induction only:
II II

CH30-CH2 -C-O-H is a stronger acid than H-CH2 -C-O-H

There is no resonance overlap between the methoxy group and the carboxyl group, so this is a pure inductive

o
effect. The methoxy substituent increases the acidity, so methoxy must be electron-withdrawing by
induction. This should come as no surprise as oxygen is the second most electronegative element.
The anomaly comes in the decreased acidity of 4-methoxybenzoic acid:
-< >- -< >- C
0
CH30 C -0 - H is a weaker acid than H - 0-H

Through resonance, a pair of electrons from the methoxy oxygen can be donated through the benzene ring to
the carboxyl group-a stabilizing effect. However, this electron donation destabilizes the carboxylate anion
as there is already a negative charge on the carboxyl group; the resonance donation intensifies the negative
charge. Since the product of the equilibrium would be destabilized relative to the starting material, the
proton donation would be less favorable, which we define as a weaker acid.

VC O
. .

:0:
CH3O - -H• •
+ -

o o
Methoxy is another example of a group which is electron-withdrawing by induction but electron-donating
by resonance.
(d) This problem gives three pieces of data to interpret:
II II
(1) CH3-CH2-C-O-H is a weaker acid than H-CH2-C-O-H

�
Interpretation: the methyl group is electron-donating by induction.
(2) CH3

< 0 - H is a weaker aeid than < >- 0 -H

CH3
Interpretation: the methyl group is electron-donating by induction. This interpretation is
consistent with (1), as expected, since methyl cannot have any resonance effect.
(3) CH3

� ct is a stronger
o-� it
\4- O-H
acid than
-
O-H
CH3
(1 )
Interpretation: this is the anomaly. Contradictory to the data in and (2), by putting on two methyl
groups, the substituent seems to have become electron-withdrawing instead of electron-donating. How?
Quick! Turn the page!

492
20-44 continued
Steric inhibition of resonance! In benzoic acid, the phenyl ring and the carboxyl group are all in the same
plane, and benzene is able to donate electrons by resonance overlap through parallel p orbitals. This
stabilizes the starting acid (and destabilizes the carboxylate anion) and makes the acid weaker than it would
be without resonance.
..
< � C - � -H
:0:
..
..
�
0:9:
C-O-H plus other resonance forms
+

Putting substituents at the 2- and 6-positions prevents the carboxyl or carboxylate from coplanarity with the
ring. Resonance is interrupted, and now the carboxyl group sees a phenyl substituent which cannot stahdizc
the acid through resonance; the stabilization of the acid is lost. At the same time, the electron-withdrawing
inductive effect of the benzene ring stabilizes the carboxylate anion. These two effects work together to
make this acid unusually strong. (Apparently, the slight electron-donating inductive effect of the methyls is
overpowered by the stronger electron-withdrawing inductive effect of the benzene ring.)
•

�---�!�o-H
•
" CH3
•
H" "

H
"" 0
\'
\ \\
\\

• - t··- ���.-----..---­
. "
o
CH3
COOH group is perpendicular this three-dimensional view down the C-C bond
to the plane of the benzene ring­ between the COOH and the benzene ring shows
no resonance interaction.

o
that COOH is twisted out of the benzene plane
�H � OH
o
20-45
(a)
stock bottle students' samples
(b) The spectrum of the students' samples shows the carboxylic acid present. Contact with oxygen from the
air oxidized the sensitive aldehyde group to the acid.

CH2I2 A
(c) Storing the aldehyde in an inert atmosphere like nitrogen or argon prevents oxidation. Freshly prepared
unknowns will avoid the problem.

h �COOH
A
20-46 H
Ph' I'
SOCl2
Zn, cuci H"" IIIIICOOH ..
' H" ",COCI
H Ph H Ph H
(Simmons-Smith
reaction, Sec. 8-9A)

(Hofmann
rearrangement)

�AH �A
Br 2 ' HO-
H ,,,,, IIIIINH2" H20 H"',' II'''CONH2
H
493
20-47 Products are boxed.

-
(a) All steps are reversible in an acid-catalyzed ester hydrolysis. (abbreviating O CH2CH3 as OEt)
Step A p oton on (resonance stabilization)
Step B nucleophile attacks
r H B is the acid catalyst
Step C proton off :B- is the conjugate base, although in
Step 0 proton on hydrolysis reactions, water usually removes H+
Step E leaving group leaves (resonance stabilization)

F
Step proton off
..
:O-H
1+
vC'OEt

\
(f
:O-H :O-H :O-H
1 1
C HC + C1 'OEt
ac�a �O�t
� CH HC+ 0
+
!
O/��Et
:O-H :O-HH� :O-H
1 :OH2 1 + .OH2 1 /
..-----....
C-O:�
I H C-O·
� I "
" �:REt
\

\
• •
•

Step B StepC
V:REt
V A

� A-a)
StepD
�11 +k�

cr� ( :OH
t;)
+ H
1- EtOH 1
\
I
same series
Step E
"/

of resonance .......E---.�
-; ,

forms as above ....""-...

Step
F
I :OA,

494
20-47 continued
(b) .. -

:0:
+ HI C)h]

·�..0 / .·0//H.�.H :0/H.. :0��/,...-:H.OH

(c) •

~
\\ OH
HI'B. � + • •

\ OH
• •

\
+

s.�
--- .. •

OH : OH : OH

I"
: O-H
OC :0:

I
:..IO-H +O-HII .....,
0:
II
A cyclic ester is called
: B-
a

lactone. Lactones form when

00: 00:
c c c OH
O�:
the nucleophile is just a
few carbons away from the
•

�
·
carbonyl electrophile.

495