Lista 4

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Problems 141 
Substitution at C(sp 3 ) usually occurs by an S N 1 mechanism under acidic con-
ditions; the S N 2 mechanism is operative at C(sp 3 ) only when the C(sp 3 ) is I o , 
the nucleophile is very good, and the conditions are very strongly acidic. 
(However, substitution at heteroatoms such as S and P usually occurs by an S N 2 
mechanism under acidic conditions.) 
Substitution at C(sp 2 ) normally occurs by an addit ion-el imination mechanism 
under acidic conditions. Electrophiles add to nucleophilic C = C ir bonds, i n -
cluding most arenes, and nucleophiles add to C = N , C = 0 , and electrophilic C = C 
TT bonds. Arylamines can undergo substitution of the NH2 group by a diazonium 
ion mechanism. 
Under both acidic and basic conditions, a carbonyl compound is elec-
trophi l i c at the carbonyl carbon and nucleophilic at the a-carbon. S imi lar ly , 
under both acidic and basic conditions, an a,/3-unsaturated carbonyl compound 
is electrophilic at the carbonyl and /3-carbons and nucleophil ic at the a-
carbon after a nucleophile has already added to the /3-carbon. Carbonyl mech-
anisms di f fer under acidic and basic conditions only in the protonation and 
deprotonation steps: under acidic conditions, nucleophilic addit ion is always 
preceded by protonation of the electrophile and fo l l owed by deprotonation o f 
the nucleophile. 
1. Rank each set of compounds by the ease w i t h which they ionize under acidic 
conditions. 
PROBLEMS 
(a) Me Me Me 
Me Me 
(b) ci ci C l 
(c) 
OTs 
OTs 
OTf H 3 C OTf 
H 3 C H 3 C H 3 C 
142 3. Polar Reactions under Acidic Conditions 
(f) A c H N N ^ ^ / \ r AcHN 
(g) 
AcO 
Br 
4 1 Ph 
Ph- OH 
Ph 
2. Indicate the major product of each of the fo l lowing reactions, and draw a rea-
sonable mechanism for its formation. 
(a) 
B r 80% aq. EtOH 
(b) 
Ph 
- 0 H CH3CO7H 
(C) 
Ph 
- O H cat. TsOH 
benzene 
(d) 
H 
B r ^ \ " C H 3 
Ph 
H C O . H 
(e) - O H HC1 
H^O 
-O 
(f) Q ^ O H 
CH3OH 
cat. TsOH 
(g) 
- O H 
cone. HBr 
(h) „-Bu d U - H B r > 
3. When /3-caryophyllene (1) is treated with sulfuric acid in ether, a large assort-
ment of produets is formed. Init ia l ly , after 1 is consumed, compounds 2 through 
4 are the major hydrocarbon produets. As time goes on, compounds 2 through 
Problems 143 
4 disappear, and compounds 5 through 9 appear in the reaction mixture. A t 
longer times, compounds 5 through 9 disappear, and compounds 10 through 12 
become the final hydrocarbon produets. A large number of alcohols were also 
formed. Draw mechanisms explaining the formation of each o f these produets. 
Your mechanism should also accountfor the sequence of their formation. 
H 3 C H 
H 3 C - \ 
C H 3 
H 3 C H 
H 3 C 
H 3 C 
H 3 C H 
H , c U 
C H 3 H 3 C H 
H 3 C ~ A 
H 3 C 
C H 3 H 3 C H 
H 3 C U 
H 3 C 
H 3 C H 
H 3 C ^ \ — , H C H 3 
H 3 C ,CH3 
1 0 \ 11 
4. Draw mechanisms for the fo l lowing reactions. 
(a) OSiMe 3 0 > 
o 
5 M L i C 1 0 4 in ether H 0 
( L i + is Lewis acidic) 
C H 3 1 2 
O OSiMe 3 
(b) 
(c) 
(d) 
0 H l ) n - B u N 3 . T f O H f^^Y' 
C H 3 2) N a B H 4 " L ^ N ^ 
O 
Ph 
EtO 
F 3 C F 2 C H 
2 AlMe 3 
C H 3 
n-Bu 
C H 3 C H 3 
k . Q / Ph (no Ai/) L ^ Q / Ph 
Br 
H 3 C O H 
F 3 C F 2 C 
EtO 
Ph 
144 3. Polar Reactions under Acidic Conditions 
but 
EtO 
F 3 C F 2 C H 
EtO C F 2 C F 3 
OH 
(e) 
PC 
(f) 
H , C Et 
(g) q 
(h) 
(i ) 
HiO, A 
Br HO 
O HO 
£ • t 
. C 0 2 H 
CH3 m 
- N . .Ph 2 ) N a O C H 3 
[ ) N B S 
C H O 
ascorbic acid 
(j) The product, one example of an azo dye, was used for a long time as the 
coloring agent i n margarine until it was discovered that i t was carcinogenic. 
\
„ NaNO. Me 2 NPh , , .% 
PhNH-> \ * , N . . . . 
H->S04 N ' N — \2 
(k) When p-nitroaniline and salicylic acid are used as starting materiais in the 
reaction in ( j ) , A l i zar in Yel low R, an azo compound used to dye wool , is 
obtained. What is the structure o f A l i zar in Yel low R? 
(1) The fo l lowing reaction helps explain why piperidine is a federally con-
trolled substance. 
Problems 145 
O 
H + 
- C H 3 
" O 
^ N a N 0 2 
(o) | > — C H 2 N H 2 H 2 S O 4 
(p) The fol lowing reaction is the key step in the biosynthesis of cholesterol. 
Compounds that inhibit the enzyme that catalyzes the reaction have been 
studied intensively recently because of their potential as anticholesterol drugs. 
(q) The Wallach rearrangement. 
The f o l l owing pieces of information should help you: (1) When 1 8 0 - l a -
beled water is used as solvent, the product is labeled. (2) When one N in 
the starting material is selectively labeled w i t h 1 5 N , the label is found to 
be randomly distributed in the product. (3) The key intermediate is dica-
tionic. 
(r) Think o f the M e 3 S i + group as a big proton. 
146 3. Polar Reactions under Acidic Conditions 
O ^ O M e 
M e 3 S i S ° * " ^ r 
Me 3 S i H N L , Õ Y 
O 
H 
OSiMe 3 ° ^ N \ ^ ° 
I O H I | 
N M e 3 S i O T f > ^ / S N ^ N ^ ^ E t 
' O S i M e , H 2N ) ' 
o 
Et 
OSiMe 3 
.X. ' . 0 . ^ O M e Me 3 SiHN f 
+ * f M e 3 S i O T f HQ, M e Q J 
H 
Y 
SSiMe 3 
OSiMe 3 
Et 
Et 
(s) First draw a mechanism for formation o f the five-membered r ing. Then 
draw a mechanism by which the five-membered r ing is converted into the 
six-membered r ing simply by heating (no acid present). 
C H , 
H Br 
H 
C H 3 
\H 
Br 
H 
(t) The fo l l owing two pieces of information should help you draw the mech-
anism. (1) The rate-determining step involves cleavage o f the C - C l bond. 
(2) The rate decreases dramatically as the number of C atoms between N 
and C l increases. 
° y P h 
P h ^ ^NL „ Y ~ ~a 
o 
~J 
(u) M e ^ Me 
,OH 
O 
H ? 0 , A H 
P h ^ Y 
o 
O Ph 
O 
H 2 S 0 4 
0 ° C ^ 0 
Me j 
Ph 
( V ) H 3 C 
H 3 0 + 
O C H ^ 
Problems 147 
(w) o o 
vtr o H + N 2 C H C 0 2 E t 
S11CI4 
, C 0 2 E t 
-78 °C 
Me Me 
(x) SnCh is a Lewis acid. 
O 
M e ' 
Me O H 
Ph 
+ N 2 C H C 0 2 E t 
S n C l , 
H 
CO^Et 
(y) Note the stereochemistry of the product! What does this tell you about 
the mechanism? 
O 
Ph 
(z) 
N H 2 
O 
O 
NaNQ 2 11 
O H HC1 ' P Í T ^ ^ O H 
Cl 
r \ ^ í L . R J S Í O - ^ V 1 ^ 
I )—R 2 
R 3 S i O ^ % ( * R 2 
TsOH 
(bb) r ~ \ 
M e 3 S i \ -N 
N—N O r H , // \ l r t 3 l ^ 
M e 3 S i -
H 3 0 + 
(cc) Me 
Ph / 
M e O — * 
< D D ) H 3 C _ / ° \ ^ C H 3 H 2 Q > 
\\ H 2 S 0 4 
HO NH^ 
V 
O c 5 = s / % v ^ C H 3 
Ph v — O M e 
Problem 3.11. Draw mechanisms explaining the formation of both electrophilic aromatic 
substitution produets. 
N 0 2 
Problem 3.12. Draw reasonable mechanisms for the following reactions: 
M e ( X . N H , M e ( X ^ A 
NaNO> K l (a) 
H C I 
MeO MeO 
(b) / \ - N H , N a N 0 2 PhOH 
HC1 \ = / N \ - O H 
Problem 3.13. In the Stiles reaction, the highly reactive compound benzyne is obtained by 
treatment of anthranilic acid (2-aminobenzoic acid) with NaN02 and HCI. Draw a mechanism 
forthis reaction. 
N H 2 
N a N Q 2 
H C I * 
Problem 3.14. Draw a mechanism for the following electrophilic substitution reaction. 
SiMe 3 
C H 3 C O C l 
A1C1 3 H 3 C 
H 3 C 
, C H i 
O