Organic Chemistry

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JWCL338-16 JWCL338-Solomons-v1 May 5, 2010 14:10
16 ALDEHYDES AND KETONES I.

NUCLEOPHILIC ADDITION TO THE
CARBONYL GROUP
SOLUTIONS TO PROBLEMS
O O O
16.1 (a) H H H
Pentanal 2-Methylbutanal 3-Methylbutanal

O O O
2,2-Dimethylpropanal 2-Pentanone 3-Pentanone

O
3-Methyl-2-butanone
O H
O
CH3
O
(b)
H
Acetophenone Phenylethanal 2-Methylbenzaldehyde
(methyl phenyl ketone) (phenylacetaldehyde) (o-tolualdehyde)
O H O H
CH3
CH3
3-Methylbenzaldehyde 4-Methylbenzaldehyde
(m-tolualdehyde) (p-tolualdehyde)
370
FIRST PAGES
ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 371
16.2 (a) 1-Pentanol, because its molecules form hydrogen bonds to each other.
(b) 2-Pentanol, because its molecules form hydrogen bonds to each other.
(c) Pentanal, because its molecules are more polar.
(d) 2-Phenylethanol, because its molecules form hydrogen bonds to each other.
(e) Benzyl alcohol because its molecules form hydrogen bonds to each other.
O
PCC
16.3 (a) OH H
CH2Cl2
O
SOCl2
O
(1) LiAlH ( O (
3
O
(b) OH Cl H
Et2O, −78° C
(2) H2O
O
Br2 Mg (1) H H
16.4 (a) Br
Et2O
MgBr +
Fe (2) H3O
OH O
PCC
CH2Cl2
H
(1) KMnO4, OH −, heat O SOCl2

(b) CH3
(2) H3O +
OH
O (1) LiAlH ( O (
3
O
Et2O, −78° C
Cl H
(2) H2O
OH H2CrO4 O
(c) acetone
O
O
Cl
(d)
AlCl3
FIRST PAGES
372 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP
Br CN MgBr
CN −
(e) diethyl ether
O NMgBr
H3O+
O O
(f ) (1) i-Bu2AlH, hexane, −78° C
OCH3 H
(2) H3O+
16.5 (a) The nucleophile is the negatively charged carbon of the Grignard reagent acting as a
carbanion.
(b) The magnesium portion of the Grignard reagent acts as a Lewis acid and accepts an
electron pair of the carbonyl oxygen. This acid-base interaction makes the carbonyl carbon
even more positive and, therefore, even more susceptible to nucleophilic attack.
δ+ δ− MgX
C O C O
δ+ R
Mg X
R
δ−
(c) The product that forms initially (above) is a magnesium alkoxide salt.
(d) On addition of water, the organic product that forms is an alcohol.
16.6 The nucleophile is a hydride ion.
H −
H H O H OH
16.7 O + O +
H H O H H OH
H
H
16.8 Acid-Catalyzed Reaction

+
O OH +H218O OH
HA A− OH HA
−
A −H218O HA A−
H2 18
O+ 18
OH
+OH +
18
A−
18
2 −H2O OH O
+H2O HA
18
OH
FIRST PAGES
Base-Catalyzed Reaction
OH − + H218O H2O + 18
OH −
O O− OH
H2O OH −
+ 18
OH −
18
OH − 18
H2O
OH OH
OH 18
O
− OH −
18 + OH −
O
−
16.9 OH Acetal group OH

Acetal group
O OH O OH
HO HO
O O
HO HO HO HO
OH O OH O
OH OH
OH OH
Sucrose Sucrose
H
+
H H +HO CH3 O CH3
HA
16.10
A− +
−HO CH3 H OH
O OH
O CH3 O CH3
A− HA −H2O
− +
+H2O
HA H OH A H OH2
(hemiacetal) +
O CH3
H
+ +
O CH3 +HO CH3 O CH3 A−
−HO CH3 O CH3 HA

H H
O CH3
H O CH3
(acetal)
FIRST PAGES
16.11 OH +
O H
H A + OH
O OH OH
A− +O
OH −
OH
H
H
+
A− O H HA O H −H2O
HA OH A− OH +H2O
O O
H +
O A− O
O
+ OH O HA O
16.12 HO
OH
O OH O
O
O OH
OEt OEt
16.13 (a) HA O
A
OH
O OMgI
2 CH3MgI NH4+ O
H2O
O
C
(b) Addition would take place at the ketone group as well as at the ester group. The product
(after hydrolysis) would be
OH
HO
H A
16.14 (a)
+
O O O O R O O R
HOR
+
H A−
FIRST PAGES
(b) Tetrahydropyranyl ethers are acetals; thus, they are stable in aqueous base and hydrolyze
readily in aqueous acid.
HA −ROH H2O
+
O O R O O R O
+
H
O
−
A
HO H
+
O O H O OH 5-Hydroxypentanal
Mg
Cl O Cl
(c) HO O O Et2O
HA
MgCl OMgCl
O O O O
OH
+
O
NH 4
HO +
H2O HO H
BF3 S
16.15 (a) O + HS SH
S
Raney Ni
+ CH3CH3 + NiS
H2
O BF3 S
(b) + HS SH
H S
Raney Ni
CH3 + CH3CH3 + NiS
H2
O OH OH
16.16 (a) HCN HCl, H2O
OH
H CN reflux
O
Lactic acid
(b) A racemic form
FIRST PAGES
(1) (C6H5)3P − +
16.17 (a) CH3I H2C P(C6H5)3
(2) RLi
(1) (C6H5)3P +
(b) Br P(C6H5)3
(2) RLi −
O
− +
(c) H2C P(C6H5)3
[from part (a)]
O
− +
(d) H2C P(C6H5)3
[from part (a)]
O
(1) (C6H5)3P +
(e) Br P(C6H5)3
(2) RLi
−
H
−
(1) (C6H5)3P +
(f) Br P(C6H5)3
(2) RLi
− H
+
Br (1) (C6H5)3P P(C6H5)3
(g)
(2) RLi
FIRST PAGES
O
C6H5 O−
16.18 + P(C6H5)3 H H
(C6H5)3P+
C6H5 C6H5
H H H H
(C6H5)3P O (C6H5)3P + O −
+ (C6H5)3PO
Problems
Reactions and Nomenclature
O O
16.19 (a) (b)
H H
O
O
(c) (d)
O
(e) (f)
(g) (h)
O
FIRST PAGES
O
O
(i) (j)
O
(k) (l)
O
O
(m) (n)
O
O
(o)
16.20 (a) (b)
HO H OH
(c) (d)
HO H N
NH2
(e) (f)
N O
H
NH
O O
NH2
FIRST PAGES
(g) (h)
O O S S
(i) (j) No reaction
HO H
(k) (l)
N
NH
H Ph
NO2
NO2
(m) No reaction (n)
N
OH
H PPh3Br
16.21 + base
FIRST PAGES
NNHC6H5
16.22 (a) (b)
NO2
OH
(c) (d)
OH
(e)
H3CO OCH3
16.23 (a)
H
MeO
(b)
O O
(c)
(d)
S S
FIRST PAGES
H3CO OCH3
(e)
O O
(f)
OH O
(g) + O
OH H
O
Ph H
(h) O O
N3
H H
CH3NH2, cat. HA
16.24 (a)
O
N CH3
O N
N H
cat. HA
(b)
O N
NH2
cat. HA
(c)
FIRST PAGES
O O
PPh3
(d)
(1) HS
SH
(e)
O (2) Raney Ni, H2
O OH
− + OH
CH2 PPh3 (excess)
(f )
O O HO H OH
O
H2O, HA
(g)
16.25 (a)
HO
(b)
H
(c) OH
H2N CN
NH2
FIRST PAGES
CH3
(d)
O
H
PCC
16.26 (a)
HO O H
O OH
(1) CH3MgBr
H (2) H3O+
(b)
(3) PCC
(4) CH3CH2MgBr
(5) H3O+
(1) OsO4
O
(2) HA (cat.)
H
O
(c)
O
O
(1) O3
(2) CH3SCH3 O
(d)
(3) HA (cat.)
OH
HO
OH
HA (cat.)
(e) O
O
OH
FIRST PAGES
S
O SH
SH , HA (cat.)
(f ) S
H
16.27 (a) OH OH
H+
O O
H
OH
H
H
OH
O
O O
-H+
FIRST PAGES
H H
(b) O O O
N
H+ H
OH OH2
N N N
-H+ -H2O
H
+H+
tautomerize
FIRST PAGES
H
O O
(c) HO
H+ HO
OH
HO
H
OH O O
OH OH
HO -H+
FIRST PAGES
H
O O OH
(d) H+
H H H
H H
N
OH HO N Ph
H H
H N
H
H 2N Ph -H+
+H+
H H
N H N
H2O N Ph N Ph
H
- H2O -H+
H H
H
N
Ph N
HO OH OH
16.28
(1) PCC (1) PCC
(2) MgBr (2) MgBr
(3) H3O+ (3) H3O+
FIRST PAGES
Synthesis
CH3 CH3
CH3Cl HNO3
16.29 AlCl3 H2SO4
+
NO2
CH3
O2N
remove any ortho-isomer
CH3
OH
KMnO4 SOCl2
heat
O2N O2N
O O
AlCl3
Cl
O2N O2N
H NaBH 4 OH
16.30 (a)
O O
H Ag(NH3)2+ H3O+ OH
(b)
NH3/H2O
O O
OH SOCl2 Cl
(c)
[from (b)]
FIRST PAGES
O OMgBr
MgBr
H diethyl ether
(d) + H
OH O
H3O+ H2CrO4
H
acetone
or
O O
Cl (1) AlCl3
+
(2) H3O+
[from (c)]
O OH
H (1) CH3MgI
(e) H + enantiomer
(2) H3O+
O OH
(1) MgBr
H
(f ) H + enantiomer
(2) H3O+
OH PBr3 Br
(g)
[from (a)]
CH3
Br Zn
(h)
HOAc
[from (g)]
or O S
HS S
H SH Raney Ni
BF3 (H2)
CH3
or Clemmensen reduction of benzaldehyde
FIRST PAGES
O OCH3
H CH3OH OCH3
(i)
HA
18
O O
H H218O H (See Problem 16.8

(j)
18 + for the mechanism)
H3 O
O D
H (1) NaBD4 OH
(k) +
H + enantiomer
(2) H3O
O OH
H HCN CN
(l) H + enantiomer
(a cyanohydrin)
O
OH
H NH2OH N
(m) + stereoisomer
HA
(an oxime)
H
O
N
H H H3O+ N C6H5
H
(n) + N N O + stereoisomer
H C6H5
OH (a phenylhydrazone)
H +
(o) + (C6H5)3P
−
(a Wittig reagent)
FIRST PAGES
NaNH2 I
16.31 H3C H H3C Na +
H2 OsO4
H 3C Pd/C H3C
OH
OH
OH PCC H
16.32 (a)
CH2Cl2
O O O
OH SOCl2 Cl LiAlH ( O (
3 H
(b)
Et2O, −78° C
O O
(1) KMnO4, OH − OH [as in (b)] H

(c)
(2) H3O+
O O
(1) KMnO4, OH − OH [as in (b)] H

(d)
(2) H3O+
O O
OCH3 (1)
( ( 2
AlH
, −78°C H
(e)
(2) H2O
N O H
(1)
( ( 2
AlH
, −78°C
(f)
(2) H2O
FIRST PAGES
O HO CH3 CH3
16.33
1.) CH3MgI H2SO4 1.) BH3 THF
2.) H3O + Δ 2.) NaOH, H2O2
A C7H14O B C7H12
CH3 CH3
HO O
H2CrO4
acetone
C C7H14O D C7H12O
O H O H
H3O+ O
16.34
+
heat
H H
O OH
O OH
The compound C7 H6 O3 is 3,4-dihydroxybenzaldehyde. The reaction involves hydrolysis
of the acetal of formaldehyde.
O
Br Mg MgBr (1) H
16.35 (a) racemic
Et2O (2) H3O+ OH
O
MgBr (1) OH PCC
(b) +
(2) H3O CH2Cl2
O
[from (a)]
H
− O
+
Br (1) (C6H5)3P P(C6H5)3 H
(c) C6H5
(2) C6H5Li
(a Wittig reagent)
FIRST PAGES
O
MgBr (2) H3O+ H2CrO4
(d) +
H HO acetone
[from (a)] racemic
O Ο
OH Mg
16.36 Br HO , HA Br
H Ο Et2O
A
O
O (1) H OH O
BrMg O (2) H3O+, H2O
H
B C
(1) CH3OH
O O
(2) HA
OH OCH3
(a hemiacetal) D (an acetal)
O O
16.37
(7S) (3S) (7R) (3S)
3,7-Diethyl-9-phenylnonan-2-one (dianeackerone) stereoisomers
O OCH3
16.38 PCC CH3OH
OH CH2Cl2 H HA OCH3
A
B
OCH3 O
KMnO4, OH − H3O+
cold, dilute HO OCH3 H2O HO H
OH OH
C Glyceraldehyde
The product would be racemic since no chiral reagents were used.
FIRST PAGES
O H OH HO H
16.39 NaBH4
H H + H
(R)-3-Phenyl-2-pentanone (S) (R) (R) (R)
Diastereomers
− −
(1) 2 (C6H5)3P + +
16.40 Br ( ) Br (C6H5)3P ( ) P(C6H5)3
7 (2) 2 RLi 7
A
O
2
( ) ( ) H2
11 ( ) ( ) ( ) ( ) ( )
11 7 11 Pt 11 9 11
B pressure C
16.41 (a) Retrosynthetic Analysis
N O OH
H
HO O O
OH O O
+
NH
Br MgBr
+ O
HO O
OH O
FIRST PAGES
Synthesis
Br H O Br (1) Mg
O
HA(cat.), H (2)
HO O (3) H3O+
OH O
OH
(1) H2O, HA (cat.) N
(2) PCC
O
(3) HA (cat.)
O HO
NH OH
(b) Retrosynthetic Analysis
O
OH
OH
+
MgBr
OH O
O +
MgBr
FIRST PAGES
Synthesis
−
OH (1) H2C PPh3 (excess) O
(2) PCC
H
O
(1) CH3CH2MgBr
(2) H3O+
OH OH
(1) PCC
(2) CH2CHMgBr
(3) NH4Cl/H2O
H 3C CH3 H 3C CH3 H3C CH3
OH OH2
16.42 H OH2 - H2O
OH - H2O OH OH
1,2-alkyl shift
H3C CH3 H3C CH3 H3C CH3

H
O OH
OH
H3C CH3 H3C CH3

H
OH2
O O
- H OH2
16.43 The two nitrogen atoms of semicarbazide that are adjacent to the C O group bear partial
positive charges because of resonance contributions made by the second and third structures
below.
FIRST PAGES
O O− O−
H2N H2N + H2N +
N NH2 N NH2 N NH2
H H H
This nitrogen is the most nucleophilic.
16.44 Hydrolysis of the acetal linkage of multistriatin produces the ketodiol below.
O HO
OH
O O
16.45 O O
O
NaH
O + (CH3O)2P
H O
AcO H AcO H O
16.46 Compound W is singlet δ 3.4

CH2
multiplet δ 7.3 C O IR peak near 1715 cm−1 O
CH2
(1) KMnO4, OH −, heat COH
O (2) H3O+ COH
Compound X is
C
O
multiplet δ 7.5 CH2
Phthalic acid
CH2 triplet δ 2.5
triplet δ 3.1
16.47 Each 1 H NMR spectrum (Figs. 16.4 and 16.5) has a five-hydrogen peak near δ 7.2, suggesting
the Y and Z each has a C6 H5 group. The IR spectrum of each compound shows a strong
peak near 1710 cm−1 . This absorption indicates that each compound has a C O group
not adjacent to the phenyl group. We have, therefore, the following pieces,
O
and
If we subtract the atoms of these pieces from the molecular formula,

C10H12O
C7H5O (C6H5 + C O)
we are left with C3H7
FIRST PAGES
In the 1 H NMR spectrum of Y, we see an ethyl group [triplet, δ 1.0 (3H) and quartet,
δ 2.45 (2H)] and an unsplit CH2 group signal [singlet, δ 3.7 (2H)]. This means that Y
must be
O
1-Phenyl-2-butanone
In the 1 H NMR spectrum of Z, we see an unsplit CH3 group signal [singlet, δ 2.1 (3H)]
and two triplets at δ 2.7 and 2.9. This means Z must be
O
4-Phenyl-2-butanone
16.48 That compound A forms a phenylhydrazone, gives a negative Tollens’ test, and gives an IR
band near 1710 cm−1 indicates that A is a ketone. The 13 C spectrum of A contains only four
signals indicating that A has a high degree of symmetry. The information from the DEPT
13
C NMR spectra enables us to conclude that A is diisobutyl ketone:
O
(a) (b) (c) (d )
Assignments:
(a) δ 22.6
(b) δ 24.4
(c) δ 52.3
(d) δ 210.0
16.49
O
Compound B
FIRST PAGES
Challenge Problems
16.50 (a) O H stretch at about 3300 cm−1 ; C O stretch at about 1710 cm−1
O OH
(b) (Intramolecular hemiacetal
from C)
16.51 H3CO OH
H3CO
E
QUIZ
16.1 Which Wittig reagent could be used to synthesize ? (Assume any other
needed reagents are available.)
−
P(C6H5)3
(a) + (d) More than one of these
−
P(C6H5)3
(b) + (e) None of these
−
(c) P(C6H5)3
+
16.2 Which compound is an acetal?
OH
OCH3
(a) (d) More than one of these
(b) (e) None of these

O OCH3
O
(c)
O
FIRST PAGES
O
H
16.3 Which reaction sequence could be used to convert ( ) to ( ) ?
4 4
(a) O3 , then Me2 S, then AlCl3 , then OH
(b) (1) H2 , P-2 cat.; (2) Hg O

( ) O
2
/THF-H2 O; (3) NaBH4 , HO− ; (4) PCC
O
(c) HCl, then OH

(d) O3 , then Me2 S, then H2 SO4 , HgSO4 , H2 O, heat
O
(e) OH , then H2 O2 , OH− /H2 O
16.4 Complete the following syntheses. If more than one step is required for a transformation,
list them as (1), (2), (3), and so on.
A B
NBS
(a) CH3
hv THF
N O
C
A
OH O
(b) Cl Cl
H
B C
O
Cl
O
FIRST PAGES
B
A C6H5Li
(c) Br
−
C
P(C6H5)3
+
O A O B
(d)
H
OH C OH
NH2
N
(racemic) (racemic)
16.5 An industrial synthesis of benzaldehyde makes use of toluene and molecular chlorine
Cl
as starting materials to produce Cl . This compound is then converted to
benzaldehyde. Suggest what steps are involved in the process.
16.6 In the case of aldehydes and unsymmetrical ketones, two isomeric oximes are possible.
What is the origin of this isomerism?
FIRST PAGES

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P1: QZI/SRB P2: xxx Printer: Bind Rite

JWCL338-16 JWCL338-Solomons-v1 May 5, 2010 14:10

16 ALDEHYDES AND KETONES I.

Pentanal 2-Methylbutanal 3-Methylbutanal

2,2-Dimethylpropanal 2-Pentanone 3-Pentanone

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 371

(1) KMnO4, OH −, heat O SOCl2

372 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

16.6 The nucleophile is a hydride ion.

16.8 Acid-Catalyzed Reaction

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 373

16.9 OH Acetal group OH

−HO CH3 O CH3 HA

374 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 375

376 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 377

378 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

16.20 (a) (b)

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 379

(i) (j) No reaction

(m) No reaction (n)

380 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 381

382 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 383

384 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 385

386 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 387

388 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

remove any ortho-isomer

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 389

or Clemmensen reduction of benzaldehyde

390 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

H H218O H (See Problem 16.8

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 391

(1) KMnO4, OH − OH [as in (b)] H

(1) KMnO4, OH − OH [as in (b)] H

392 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 393

[from (a)] racemic

3,7-Diethyl-9-phenylnonan-2-one (dianeackerone) stereoisomers

The product would be racemic since no chiral reagents were used.

394 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

(R)-3-Phenyl-2-pentanone (S) (R) (R) (R)

16.41 (a) Retrosynthetic Analysis

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 395

(b) Retrosynthetic Analysis

396 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

H 3C CH3 H 3C CH3 H3C CH3

H3C CH3 H3C CH3 H3C CH3

H3C CH3 H3C CH3

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 397

16.46 Compound W is singlet δ 3.4

If we subtract the atoms of these pieces from the molecular formula,

398 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

(a) (b) (c) (d )

ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 399

16.2 Which compound is an acetal?

(b) (e) None of these

400 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP

(a) O3 , then Me2 S, then AlCl3 , then OH

(b) (1) H2 , P-2 cat.; (2) Hg O