Beruflich Dokumente
Kultur Dokumente
Stefan Svensson
2007-04-23
Compendium
On
Problems in Physical-Organic Chemistry
Page
1
4
6
8
13
16
18
20
26
(Nr of problems)
Part 1:
Part 2:
Part 3:
Part 4:
Part 5:
Part 6:
Part 7:
Part 8:
Table:
General problems
Acids- Bases
Hammett Relationships
Orbital Symmetry reactions
Problems related to Nucleophilic Substitutions
Problems related to Elimination reactions
Problems related to Addition reactions
Miscellaneous problems
Hammett realationships
(14)
(11)
(10)
(17)
(20)
(12)
(11)
(25)
Most of the problems can be considered as self-studying problems, but some of them may
need further explanation.
Problems marked with * are considered to be more advanced.
A solution guide supports the compendium.
IFM/ Kemi
Stefan Svensson
20020423
General problems
Predict the most stable conformation for each of the following molecules and explain
the basis of your prediction.
C(CH3)3
CO2CH3
OH
(a)
Cl
JACS 91(7020)1976
C(CH3)3
(b)
JACS 92(51510)1970
a ) From examination of its structural formula, why would you expect azulene to be
aromatic?
b ) Azulene has a dipole moment of 1.08 D. Draw resonance structures as a basis for
assigning a direction to the dipole.
1.4 * Consider following equillibrium data for 2-halocyklohexanones i two different solvents.
O
Halogen
Br
Cl
F
% Axial (Heptane)
85
76
48
% Axial (1,4-dioxane)
62
37
15
1.5
1.6
COOMe
+
COOMe
COOMe
COOMe
b)
i
ii
c)
ii
CH3I
OC2H5
CH3OC2H5
+I
(CH3) 3CCH2OC2H5 + I
CH3I
NH3
CH3NH3
+I
ii
CH3I
NH2
CH3NH2
+I
1.7 Indicate whether the relationship in each of the following pairs of compounds is identical,
enantiomeric, or diastereomeric:
a)
b)
CHO
H
NH2
HO
H
CH2 OH
H
CH2 OH
H
OH
H
NH2
CHO
H3 C
CH3
d)
CH3
CH3
e)
H
Cl
Cl
H
O
c)
f)
H
Cl
1.8
Ph
CH3
H
H
Cl
CH3
Ph
The structure orginally proposed for cordyceic acid, []D= +40.3o, has been shown to
be incorrect. Suggest a reason to be skeptical about the original structure, which is
given below:
COOH
HO
OH
HO
OH
1.9
Indicate which of the following molecules are chiral and which are achiral.
For each molecule that is achiral, indicate the element of symmetry that is present in
the molecule
(a)
CH3
H3 C
(b)
H3 C
(c)
CH3
H 3C
(f)
(e)
(d)
CH3
CH3
H3C
1.10
a ) The dipole moment of the hydrocarbon calicene (see structure below) has been
estimated to be as large as 5.6 D.
b ) The measured dipole moment of p-nitroaniline (6.2 D) is larger than the value
calculated using empirical group moments (5.2 D).
c ) The dipole moment of furan is smaller than and in the opposite direction from that of
pyrrole.
(JACS, 94 (8851)1972)
a)
_
c)
Calicene
0.71 D
O
N
H
1.80 D
_
1.11. In the reaction profile below, which of the labels A, B, C, and D correspond to the
kinetic product, the thermodynamic product, an intermediate, and a transition state?
1.12 When some salts are dissolved in water, the water cools as a result. Why might this be?
Why, in that case, does the salt dissolve at all?
1.13 Which of the following sets of curly arrows show the imaginary movement of electrons
in resonance structures, and which show real movement of electrons in reactions? Draw
the alternative resonance structures/reaction products to which they lead.
1.14 Mevalonic acid readily forms a lactone, but this is not the only lactone it could form.
What is the alternative lactone, and why does it not form?
HO
OH
Mevalonic acid
HO
Part 2:
2.1
CH3 O
Acids- Bases
>
OH
O2N
OH
>
O2N
H3C
OH
H3C
2.2
The pKa value for m-nitrophenol is 9.3, and that for the para isomer is 7.2.
Provide an explanation for the difference in effect of the para and meta nitrogroups.
2.3
2.4
Pyrrole
Predict which member of each of the following pairs is the stronger acid.
a) m- and p-cyanophenol
b)
OH
c) NCCH2 CN
d)
and
and
CO2CO2H
and
e)
OH
f)
NCCH2 CH2 CN
CO2-
and
O
g)
OH
and
N
H
CO2H
OH
N
H
2.5*
Predict the energetically preferred site of protonation for each of the following
molecules and explain the basis of your prediction.
a) PhCH
O
b) CH3C NHCH3
N Ph
c)
d)
N
H
JACS 85(724)1963
NH2
2.6*a) In H2O, phenol (pKa 10) is about 6 pKa units less acidic than aliphatic carboxylic
acids such as acetic acid (pKa 4). In the gas phase, phenol and acetic acid have
comparable acidities. Why?
b ) In H2O, acetic acid (Ka = 1.8x10-5) is about three times more acidic than the
pyridinium ion (Ka = 6.2x10-56. In MeOH ( = 34), the relative acidities are reversed.
The pyridinium ion dissociates about the same amount in both solvents (Ka = 2.8 x 106 in MeOH), but acetic acid dissociates almost 105 times less in MeOH (Ka =
2.2x10-10). Thus in MeOH, the pyridinium ion is some 104 more acidic than acetic
acid. Explain the reversal.
2.7
CH3
( c ) COOH
(d)
(iv)
COOH
(g) COOH
COOH
2.8
and
CH2
COOH
NO2
(i) CH3COOH
COCH3
( h ) COO
and
CH2
and
(v)
COOH
and
and
(ii)
(f)
(j) HOCH2COOH
Discuss the pKa valus of the carboxylic acids given. (A lower pKa indicates a stronger
acid.)
a)
CH3 COOH
c)
d)
e)
COOH
COOH
COOH
FCH2 COOH
2.57
4.14
COOH
OMe
OMe
4.17
COOH
g)
4.76
b)
f)
3.27
4.47
4.09
2.9. What is the function of TiCl4, when it acts as a catalyst in alkylations of silyl enol ethers
with alkyl halides?
2.10. Which is more basic of the hydroxide (OH -) and hydroperoxide (HOO -) anions, and
which is more nucleophilic? Why?
2.11. Which would you expect to give the greater proportion of O-alkylation on reaction with
the sodium salt of ethyl acetoacetate, propyl iodide, or propyl bromide? Why?
Part 3:
Hammett Relationships
Hammett constants for different substituent are given in the Table on the last page.
3.1
Relate the substituent constant values of table:Hammett constants, to the electrondonating or -withdrawing character of each substituent. How does this compare with
qualitative predictions of substituent effects on acidity? Why might you expect m and
p values for the same substituent to be different
3.2
Match the values with the appropriate reactions. Explain your reasoning.
Reaction constants: +2.45, +0.75, -2.39, -7.29.
Reactions:
a)
nitration of substituted benzenes
b)
ionization of substituted benzenthiols
c)
ionization of substituted benzenephosphonic acids
d)
reaction of substituted N,N-dimethylanilines with methyl iodide.
3.3. Determine the value of for the reaction shown from the data given:
Y
O
SO2
CH2 SO3 -
+ OH -
k (M-1s-1)
Y
H
CH3 O
CH3
Br
NO2
OH
37,4
21,3
24,0
95,1
1430
JACS 92,860(1970)
3.4
The basicity of a series of substituted benzyldimethylamines has been measured.
Determine whether these basicity data are correlated by the Hammet equation.
What is the value of ? What interpretation do you put on its sign?
X
CH2 N (CH3 )2
X
pKa
p-CH3O p-CH3
9,32
9,22
CH2 N (CH3 )2
p-F
8,94
9,03
m-NO2
8,19
+ H+
p-NO2
8,14
p-Cl
m-Cl
8,83
8,67
JACS 89,1158(1967)
3.5
PhCH2 CMe2 Cl
PhCH=CMe2 +
HCl
From the following results for the effect of substituents in the phenyl ring on the rate
of the reaction, determine the Hammett value for this reaction.
Substituent
Relative rate (k/k0)
m-Cl
2.23
m-F
2.21
m-Me
1.77
m-t-Bu H
1.38 1.00
m-Me
0.77
p-MeO
0.60
3.6
The following partial rate factors(kf) were obtained for the bromination of monosubstituated benzenes hy hypobromous acid in 50 % aqueous dioxan containing
perchloric acid.
Substituent
kf
p-Me
58.9
p-t-Bu m-Me
38.9
2.51
m-t-Bu H
2.57
1.00
p-Cl
0.22
p- Br
0.15
Show that the values of kf fit a Hammet equation using + values and determine the
value of . Predict the kf value for p-fluorobenzene.
Do these results allow you to distinguish between H2+OBr and Br + as the brominated
spieces?
3.7*
OH
PhCH NHNHCONH2
k1
k -1
k2
The second step ( k2) is acid-catalysed. The effect of substituents in the benzene ring
of benzaldehyde upon the rate of reaction depends upon the pH, as shown by the
following figures.
Substituent
Relative rate
pH
p-OMe p-Me
H
p-Cl m- NO2 p- NO2
1.75
0.52
0.54
1.00
1.14
3.36
4.93
7.00
0.81
0.90
1.00
1.15
1.21
1.53
Continued next page
Calculate the Hammett value at both pH's and explain the difference in terms of a
change in the rate determining step.
3.8* The reaction between ethyl chloroformate and aniline is a two-step process, involving
addition followed by elimation.
O
EtO C Cl +
NH2
OH
NH C OEt
Cl
k1
k-1
k2
NH C OEt
The following kinetic data were obtained for the effect of substituents in the aniline on
the rate of reaction:
Substituent
p-OMe
p-Me m-Me
286
66.5
H p-Br
42.
5.57
4
1.53
1.92
0.13
What may be deduced about the rate determining step in this reaction from the plot
of log kobs against -.
Suggest an experimental check on the proposed mechanism.
7
3.9*
"
CH2
CH2 OSO2
CH
+ HOSO2
CH2
A kinetic study of the effect of substituents in ring B, with same substituent in ring
A, on the rate of reaction gives a good Hammett plot with slope of . Values of
have been determined as a function of the substituent in ring A, with following
results.
Substituent in ring A
Hammet value
p-MeO
1.24
p-Me
1.24
H
1.08
m-MeO
1.06
p-Cl
1.01
m-Cl
0.94
O
OMe
OMe
OMe
O2 N
Me
a
OMe
NO2
O
MeO
4.1
O
OMe
Part 4:
MeO
b)
d)
c)
e)
f)
CH3
g)
h)
H2C
CH3
CH2
4.2
Carry out an orbital symmetry analysis to determine if the each of the following
thermal transformations is allowed or forbidden.
b)
+ CH2 =CH2
a)
C6H5
N3
C6H5
+ HC CCO2CH3
N
N
CO2CH3
4.3
!
HO
4.4
Which of the following reactions are allowed according to the orbital symmetry
conservation rules? Explain.
H
(a)
H CO2 CH3
CO2 CH3
(b)
CO2 CH3
CH3 CO2
=
JACS 74, 4867(1952)
(c)
- N2
N2
(d)
(e)
S
+
(CN)2 C
C(CN)2
4.5 a)
S CN
CN
CN
CN
Tetrahedron Lett.
2011 (1976)
A:
H
J.Org.Chem 33(4258)1968
4.5
OCH3
OCH3
B:
OCH3
OCH3
4.6
CH3CO2 CH CH CH
CH2
JACS 100(637)1978
O
O
4.7
Suggest a mechanism by which each transformation could occur. More than one step is
involved in each case.
(a)
OCH3
CCH2 Br
H2 C
Ag O2 CCF3
Na2 CO3
H
H2 O
O
JACS 95, 1338(1973)
(b)
150o C
JACS 93, 1292(1971)
OH
(c)
100o C
CH3 CH
370o C
(d)
Give the structure, including stereochemistry, of the products expected for the following
reactions.
a)
b)
CH3
CH3
4.8
CCH
Ph2 C
JACS 96,2270(1974)
KH, THF
20 h, 25 oC
OH
JACS 97,4765(1975)
CH CH2
c)
PhCH2 CHSCH
CH2
H2 O
DME, reflux, 12 h
CH CH2
10
JACS 95,2693(1973)
d)
CH3 CO2 C
e)
4.9
JACS 96,4673(1974)
CCO2 CH3
JACS 95,2381(1973)
HO
Tetrahedron 5,70(1959)
H OH
b)
AcOH
H3C
H 3C
H3C
CH3
Tetrahedron 24,6029(1968)
CH3
AcO
c)
CO2CH3
CO2CH3
CH3CO2
Tetrahedron Lett.3719(1969)
CO2CH3
a)
CH3
H O
H
O
SPh
b)
OCH3
c)
H H
O
OCH3
CH2OH
H
H H
SPh
H
HOCH2
< 25 oC
H
H
d)
CH3
CH2OH
CH2OH
JACS 104,5555 (1982)
CH3
CH2
CH2
CH2
11
4.11 When 14C-labelled allyl 2,6-dimethyl ether undergoes para Claisen rearrangement, the
carbon atom originally attached to oxygen becomes attached to the aromatic ring.
Suggest a mechanism to account for that result.
OH
O
H3C
H3C
CH3
CH3
CH3
H
CH3
H
4.13 The conservation of orbital symmetry suggest that [1,3] superficial shifts are symmetry
forbidden while [1,5] shifts are allowed. Show how a consideration of the products of
the thermal rearrangement of 7,8-dideuteriocycloocta-1,3,5-triene might prove this
prediction.
H
D
H
D
CH3
CH2
(1)
4.15* At 170 1-mesityl-3-methylallene (1) isomerizes to a mixture of 2,5,7-trimethyl-1,2dihydronaphthalene (2) and cis-1-mesitylbuta-1,3-diene (3) in a two-step process.
H
CH3
CH3
CH3
(2)
CH3
CH3
CH C CH CH3
CH3
CH3
CH3
CH
(1)
CH
CH3
CH2
CH
(3)
Suggest a mechanism for these reactions and describe the processes in terms of the
conservation of orbital symmetry.
12
4.16 Arrange the following pairs of reagents in order of their rate of reaction with each other.
What will be the products of these reactions?
O
+
+
a
MeO
+
c
CO2 Me
+
O
CO2 Me
4.17 Draw a molecular orbital diagram for hexatriene (draw -orbitals only, and do not
worry about the relative sizes of the coefficients of the orbitals). Which is the HOMO
and which is the LUMO?
4.18. What is the product of the reaction between the olefin shown below and phenyl azide?
Part 5:
5.1
Explain the observation that the rate of the SN1 reaction of many RX derivatives is
retarded by the addition of X-.
5.2
The rate of formation of tert-butyl ethyl ether from the reaction of 2-bromo-2methylpropane (tert-butyl bromide) with ethanol does not increase if the better
nuleophile sodium ethoxide is added. Explain this observation.
-
(CH3 )3 CO C2 H5
H2 O
no reaction
H2 O / HCl
(CH3 )3 CCl
5.4
Account for the observation that 1-bromo-1-phenylethane reacts with methanol to give
product with 27 percent inversion, while reaction with sodium methoxide produces 100
percent inverted product.
5.5
The rate of reaction is the same when tert-butyl alcohol reacts with either HCl or HBr.
However, if an equimolar mixture of HCl and HBr is used, tert-butyl bromide is the
major product and tert-butyl chloride is the minor product . Explain these results.
13
5.6.
Br
1-Bromo[2,2,2]bicyclooctane
Cyclohexen oxide
5.7
5.8
Solvolysis of A in aqueous ethanol proceeds about 600 times faster than the
comparable reaction of tert-butyl bromide. Consider steric factors to explain this rate
of enhancement.
CH3
[(CH3 )3 CCH2 ] C Cl
Compound A
2
5.9
Account for the observation that the slow rate of hydrolysis of a primary chloroalkane
can be markedly increased by adding a small amount of potassium iodide.
but
CH3 CH2 CH2 Cl + H2 O
5.10
KI
slow
fast
Account for the observation that 1,1-dimethyl rather than the 1,2-dimethyl product is
favoured when hydrazine is alkylated with iodomethane.
Na2 CO3
H2 NNH2
+
2 CH3 I
H2 NN(CH3 )2
Hydrazine
1,1-Dimethylhydrazine
Iodomethane
14
5.11
CH2OH
NaOH
H2O
5.12
5.13
What is the effect on the rate of the following reactions from an increase in a solvent
dielectric constant ().
CH3
a)
b)
CH3
N CH
CH2
3
CH3
+
+
CH3O2C - C
S CH2
H3C
C - CO2CH3
N
CH3
CO2CH3
CO2CH3
5.14 In most instances hydrolysis of an alkyl halide is catalysed by hydroxide ion. However,
the rate of hydrolysis of t-butyl chloride in aqueous ethanol is almost unaffected by
addition of potassium hydroxide. Suggest a reason for this and explain why this effect is
observed with a t-butyl compound.
5.15 Hydrolysis of dimethylene chlorohydrin is a simple SN2 reaction.
ClCH2 CH2 OH + H2 O
5.17 What would you expect would be the product of the reaction between the ,unsaturated carbonyl compound below and a thiol?
O
15
5.18 Enolates are often made by treatment of the carbonyl compound with LDA, itself
prepared from diisopropylamine and butyllithium. Why is butyllithium not used directly
to form the enolate?
5.19 Ethyl bromide and ethanol can be interconverted by hydrolysis of ethyl bromide and
reaction of ethanol with bromide ion. For each direction, should the reaction be run in
acid or base, and why?
5.20 In aliphatic nucleophilic substitution reactions, fluoride is the most difficult of the
halides to displace. However, in aromatic nucleophilic substitutions, it is the easiest to
displace. Why?
Part 6:
6.1
Provide an explanation for the different product mixtures obtained when 3-methyl-2bromobutane is treated with chloride or acetate in acetone.
Cl
Cl- / acetone
Br
(CH3)2CH CH CH3
50 %
(CH3)2C CH CH3
50 %
(CH3)2CH CH CH3
(CH3)2CH CH CH2
OAc
AcO -/ acetone
89 %
6.2.
11 %
(CH3)2CH CH CH3
Account for the change in ratio of 1-alkene to 2-alkene product as the base changed in
the dehydrobromination of 2-bromo-2,3-dimethylbutane.
Base =
1-ene / 2-ene =
C2H5O-
0.25
(CH3) 2CO-
CH3CH2C(CH3) 2O-
(CH3CH2) 3CO-
4.3
2.7
11.4
6.3
6.4
Elimination of HCl from A gives kinetic data consistent with an E1cB mechanism.
Explain why the unusual E1cB process might be expected in this example.
Compound A
O
Cl
p-ClC6H4C CH CHC6H4Cl-p
Cl
16
6.5
Account for the following change in the ratio of the 1-pentene to 2-pentene products as
the leaving groups changes
X
CH3 CH2 CH2
NaOEt
EtOH
CH CH3
X=
1-ene / 2-ene =
- Br
0.45
- OTs
0.97
- S+(CH3) 2
6.7
CH
CH3
- N+(CH3) 3
! 50
- SO2CH3
7.7
6.6
6.7
6.8
Account for the observation that elimination of HCl is more rapid from A than B.
Cl
H
6.9
Cl
H
Cl
Cl
H
H
Hydrogen chloride is eliminated from DDT (1,1,1-trichloror-2,2-di-pchlorpohenylethane) by the action of ethoxide ion in alcoholic solution.
Cl
2
CH CCl3
Cl
C
2
CCl2
HCl
Br
Et
6.11. Which of these bromoalkenes will give an alkyne and which will give an allene on
elimination with base?
Br
Br
17
6.12 Which of the following compounds would you expect to give a greater ratio of
elimination to substitution on treatment with sodium ethoxide? What would the effect
on these ratios be of using potassium t-butoxide instead of sodium ethoxide?
O
Br
Br
Part 7:
7.1
7.2
Heats of formation of isomeric aldehydes and ketones indicate that ketones are
typically 5-10 kcal/mol (20-40 kJ/mol) more stable than aldehydes. Refer to the
resonance structures for 2-propanone (acetone) and propanal as a basis for
rationalizing this general observation.
7.3
7.4
CH CH
(1)
H+
C CH3
+ H2 O
HC CH
OH
C CH3
+ MeOH
H3 C
H3 C
C
O + NH2 OH
H3 C
k obs
OH
C NHOH
H3 C
H3 C
C
H3 C
NOH
+ H2 O
1,5
1,0
0,5
pH
2
4
6
Figure 4. Variation of rate of reaction with pH for
the reaction of acetone and hydroxylamine
7.6
7.7
7.8
Optically active threo- and erythro- 3-phenyl-2-butyl tosylate were each allowed to
solvolyze in acetic acid until about 60 percent had been converted to product.
Chemically unchanged starting material was then recovered, and it was found that the
threo-tosylate was 94 % racemized but the erythro-tosylate was still optically pure.
Show how these support the phenonium ion intermediate.
H
H3C
H
CH3
H
CH3
OTs
H
H3C
HOAc
C
H
CH3
H
H3C
H
H3C
C
OAc
+
C
OAc
H
CH3
threo-3-Phenyl-2-butyl acetate
7.9
Show how water labelled with oxygen 18 can be used to verify alkyl oxygen cleavage
in acid-catalysed hydrolysis of tert-butyl acetate.
Tert-butyl acetate
O
CH3C O C(CH3) 3
7.10 Arrange the following carbonyl compounds in order of their reactivity towards
nucleophiles.
7.11 When propene is treated with bromide in the presence of chloride ions, a mixed halide is
formed. What is its structure, and why does this particular compound form?
19
Part 8:
Miscellaneous problems
8.1
8.2
8.3
H2 SO4
! 80 o C
SO3 H
! 160 o C
Hydrolysis of phthalamic acid (1) to phthalic acid (2) was thought to involve
elimination of ammonia and intermediate formation of phthalic anhyride.
O
C
CONH2
COOH
H2 O
C
O
COOH
COOH
(2)
(1)
This possibility was investigated by an analysis of the products of reaction between
13
phthalamic acid labelled with C in the amide group and water enriched with 18O.
Show how this could demonstrate the intermediacy of phthalic anhydride and suggest
how the products might be analysed.
8.4
For the following pairs of reactions, ondicate which you would expect to be more
favorable and explain the basis of your prediction.
a)
N(CH3 )2
or
(CH3 )3 C
b)
c)
N(CH3 )2
(CH3 )3 C
JACS 104(4706)1982
or
NO2
NO2
HO
or
HO
20
8.5
The reaction between water and -butyrolactone is pH independent and must involve
attack by an undissociated water molecule on the lactone. Hydrolysis by water
18
18
containing O results in an acid containing O in the -hydroxy group.
CH3
1 8OH
CH CH
O
+ H2 1 8O
200 o C
CH2 CO2 H
CH3
CO2 H
8.7
CH
CH2
H2 O
H+
O COCH3
O2N
C
CH2
O2N
+ H2 O
In the presence of acetate ion, nitromethane reacts readily with bromine to give,
initially, monobromonitromethane.
21
8.10* Substituted methyl benzoates hydrolyse rapidly in 95 % sulphuric acid. A study of the
effect of substituents in the phenyl ring on the rate of reactions gave the following
results.
Substituent
p-Me
m-Me
m-Cl
m-Br
104 k sec-1
2,41
1,51
0,65
0,035
0,032
Determine the value of p for this reaction and predict the rate constant for the hydrolysis
of methyl p-fluorobenzoate.
For the hydrolysis of methyl o-methylbenzoate and methyl p-methoxybenzoate the rate
-4
-1
-4
-1
constants are 182 x 10 scc and 10.2 x 10 scc , respectively.
Comment on these results.
Substituents have very little effect upon the rate of hydrolysis of methyl benzoates in
dilute sulphuric acid. Compare hits observations with the results given above and
suggest an explanation. (Values of can be found in the Table on the last page))
8.11* Comparisation of the gas phase acidity of benzonic acids with pKa values of the same
compounds in aqueous solution provides some interesting relationships.
a ) The trend in acidity as a function of substituents is the same but the magnitude of the
substituent effect is much larger in the gas phase. (The G for any given
substituent is about ten times larger in the gas phase.)
b ) Whereas acetic acid and benzonic acid are of comparable acidity in water, benzonic
acid is much more acidic in gas phase.
c ) While the substituent effect in the gas phase is assumed to be nearly entirely an
enthalpy effect, it can be shown that in solution the substituent effects is largely the
results of changes in S.
Discuss how the change from gas phase to water solution can cause each of these
effects.
JACS 94, 2222(1977)
8.12* The rates of hydrolysis of the three related esters have been studied as a function of pH,
with results shown in Figure 7.
The entropy of activation for the hydrolysis of 1 is -41.0 e.u.
(1)
O
O C OEt
O
O C OEt
OH
OCH3
(2)
O
O C OEt
HO
(3)
22
Lg kobs
-30
- 40
(3)
(1)
(2)
pH
11
10
12
Figure 7. Plot of the rate of hydrolysis of the three esters versus pH.
(a)
EtOH
H2 O
(b) Ph2 C C O +
PhCH CH2 *
PhC
H C
PhC
CH2 *
H C
CH3 CH2 C
OC2 H5
H+
H OC2 H5
fast
+ H2 O
fast
slow
CH2 *
CH3 CH2 C
OC2 H5
H*
O + HOC2 H5
CH3 CH2 C
H*
Ph
Ph
H*
8.14* Keto acids are fairly readily iodinated by molecular iodine and the mechanism appears
to be the same as that for acetone
The rate of reaction in the absence of a catalyst has been studied as a function of n, with
the following results.
a ) Iodination of the anion:
n
108 k sec-1
1
29,8
23
2
179
3
72
4
3,4
5
3,2
1
0,20
2
0,32
8.16 Treatment of benzene with sodium in liquid ammonia in the presence of an alcohol
produces 1,4-cyclohexadiene; this is known as Birch reduction. Treatment of anisole
gives 1-methoxy-1 ,4-cyclohexadiene, not 3-methoxy1,4-cyclohexadiene. Why?
8.17 A reaction between methylene and cis-2-butene gave trans-1,2-dimethylcyclopropane.
What does this tell us about the electronic configuration of the carbene in this reaction?
8.18 The first mixture of two carbonyl compounds shown below gives a mixture of four
compounds when treated with base, but the second mixture gives a single product under
the same conditions. Explain.
O
O
+
H
O
H +
Base
Four products
Base
One product
O 2N
8.19 Reaction of the ketone shown below with hydroxylamine gives an oxime, A, that
rearranges on treatment with acid to give a further product, B, hydrolysis of which gives
the carboxylic acid and the amine shown. What are the intermediates, A and B, and
what is the geometry of the oxime?
O
NH2OH
H+
H+/H2O
NH2
O
+
HO
8.20 Sulphides are readily oxidized to sulphoxides on treatment with hydrogen peroxide.
Write a mechanism for this transformation under acidic conditions. Sulphoxides can, in
turn, be oxidized to sulphones. The mechanism of this reaction is the same as the
oxidation of sulphides in neutral or acidic conditions, but in base a different mechanism
operates. Suggest a likely mechanism.
24
Br
Base
Intermediate
8.22*When the amino acid threonine is treated with nitrous acid in the presence of chloride
ions, two isomeric products are formed in addition to the expected product. What is the
mechanism of their formation, and what would you expect their stereochemistry to be?
OH
OH
OH
HONO
Cl -
OH
NH2
+ 2 other products
Cl
8.23 a)We know that it is generally the acyl-oxygen bond that is cleaved in ester hydrolysis
rather than the alkyl-oxygen bond. One of the main pieces of experimental evidence for
this came from an experiment that used 180. How might such an experiment be carried
out? What result would you expect, and how would this be different if the alkyl-oxygen
bond were cleaved?
b) When the alkyl group of an ester is tertiary, hydrolysis under acidic conditions takes
place with alkyl-oxygen cleavage. Could this be distinguished from the above
mechanism kinetically? Apart from 180 labelling, what other evidence might be used to
verify this mechanism?
8.24. Treatment of methyl -bromopropionate with hydrazine gives a mixture of products as
shown below. A possible mechanism for the reduction is that the hydrazine function is
somehow oxidized to an azo function, which then undergoes an elimination reaction to
give the enolate, and hence the reduced product. Suggest a way of discovering whether
this mechanism is possible.
O
NH2 NH2
OMe
NHNH2
Br
NHNH2
NHNH2
O
O
NHNH2
[O]
O
NHNH2
NHNH2
NHNH2
N
N
Base
8.25 When acetone is brominated, the rate of reaction is independent of the concentration of
bromine. Deuteriated acetone is brominated mote slowly than normal acetone. What do
these facts tell us about the mechanism of there action?
25
TABLE
Hammett Relationship
Required values for exercises of the constants are given in the following table. The most
complete collection is that of D.H. McDaniel and H.C. Brown
(J.Org.Chem, 23, 420 (1958).
Table
Substituent
p-MeO
m-MeO
p-Me
m-Me
p-But
m-But
p-F
m-F
p-Br
m-Br
p-Cl
m-Cl
p-CO2Et
p-NO2
m-NO2
- 0,27
0,12
- 0,17
- 0,07
- 0,20
- 0,10
0,06
0,34
0,23
0,39
0,23
0,37
0,45
0,78
0,71
26
Hammett constants
+
- 0,78
0,05
- 0,31
- 0,07
- 0,26
- 0,06
0,07
0,35
0,15
0,41
0,11
0,40
0,48
0,79
0,67
- 0,27
- 0,17
- 0,07
0,22
0,38
0,68
1,27
0,70