Download ENGLISH VERSION Exam Organic Chemistry 2

ENGLISH VERSION Exam Organic Chemistry 2 (KD1100)
Wednesday May 21, 2008, 08.00-13.00
Allowed answering aid: molecular models
Periodic system and tables of bond energies, pKa-values and NMR-shifts are attached after the
questions
Total of 10 questions, each worth 10p (total 100p).
Requirements: A 90-100p
B 80-89p
C 70-79p
D 60-69p
E 50-59p
Fx 45-49p
F
0-44p
A supplementary exam will be arranged for students with results of 45-49p. This exam will take
place on Wednesday June 4, 2007, at 10.00-12.00 in the Erdtman-room, Organic Chemistry,
Teknikringen 30, Level 7. No special registration necessary. Please note that the minimum
requirement for the course have to be demonstrated in this case also.
The make-up exam will take place on Thursday August 28, 08.00-13.00.
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Answer every question on separate sheets to facilitate grading
write name, programme and year on each sheet
Motivate your answers, normally both text and figures are necessary
Please observe that the questions are not necessarily organized in order of difficulty
(question 10 is not essentially the most difficult!)
Good luck!
Olof Ramström
1
a) Name the following substances with the used common names or according to IUPAC
(4p):
O
MgBr
O
O
N
b) Draw detailed structures of the substances below. (4p)
o
o
o
o
lithium aluminum hydride
an aromatic cation with 6 π-electrons
the most stable enol of pentane-2,3-dione
the hydrate of benzaldehyde
c) How is Hückel’s rule formulated and what is meant by the n? (2p)
1 (9)
ENGLISH VERSION 2
a) Draw the π-orbital levels for the enolate ion. Indicate the approximate form of each
orbital, how many electrons they contain, and what orbital constitute the HOMO. (7p)
b) Which of the orbitals of the enolate ion reacts with the electrophile in a typical aldol
addition? (1p)
c) Explain briefly why the enolate ion preferentially reacts from the C-atom and not from
the O-atom. (2p)
3
Complete the following reaction sequence. No mechanisms required. (2p per correct
structure)
O
Br
HO
H
OH
A
Mg
C 6H 11 O2 Br
H+
ether
B
C 6H 11 MgO 2Br
1)
O
H
2) H+, H 2O
E
C7 H 14 O2
4
CH 3 OH
C
D
H+
C6 H 12 O2
C6 H 12 O2
Acetylcholine acts as a transmitter substance at the transfer of nervous impulses
(neurotransmitter) between nerve cells. After the transfer, the substance is quickly
degraded to inactive components, a reaction that can take place at neutral pH.
Acetylcholine may otherwise be degraded in as well acidic as basic solution. Describe
with detailed mechanisms how the hydrolysis of acetylcholine occurs in acid and base,
respectively (3p each), and design a possible mechanism for how the enzyme
acetylcholinesterase can catalyze the hydrolysis at neutral pH (4p).
O
a)
O
N
Cl
N
Cl
O
b)
O
O
c)
O
N
H +, H 2O
HO -, H 2O
?
?
acetylcholinesterase, H2 O
Cl
2 (9)
?
ENGLISH VERSION 5 Imines are nitrogen analogs of carbonyl compounds and behave similarly in many
reactions.
a) Describe with mechanism how the imine below can be prepared from a suitable
carbonyl compound. (4p)
N
H
F3C
b) How does the following reaction proceed? Indicate reagents and mechanism. (4p)
O
O
N
+
H
N
H
c) Propose reagents for the synthesis of Meclizine outlined below. Meclizine is an
antiemetic that can be used for motion sickness. (2p)
N
O
N
?
Cl
Cl
Meclizine
6
a) Sketch out the 1H-NMR spectrum for the substance below (diisobutylcarbonate). (4p)
O
O
O
b) Analysis of the compound X resulted in the following data:
Molecular formula = C11H14O2
Index of hydrogen deficiency (IHD) = 5 (= number of double bond equivalents, DBE)
The IR spectrum indicated no absorption in the area 3200-3600 cm-1 (no OH-groups)
and strong absorption at 1720 cm-1 (C=O group).
3 (9)
ENGLISH VERSION The 1H-NMR spectrum showed five signals:
•
•
•
•
•
7,2-7,3 ppm, 5H, multiplet
3,9 ppm, 1H, quartet
3,7 ppm, 2H, singlet
3,3 ppm, 3H, singlet
1,3 ppm, 3H, doublet
What structure has the substance X? Draw the 1H-NMR spectrum and indicate what
proton signal corresponds to what proton. (6p)
7
a) Polystyrene can be produced from styrene using free radical polymerization, describe
briefly the mechanism. AIBN is a radical initiator that in presence of light or heat
generates radicals. You may use A. to describe these. The parenthesis and the letter n
means that the structure is repeated n times. (4p)
n
AIBN
light or
heat
polystyrene
styrene
b) Describe with mechanism what happens in the reaction below. What is this reaction
type? (6p)
Cl
n
AlCl3
?
+
Cl
8
A benzophenone structure was used as starting material in the synthesis of Meclizine
mentioned above. Design a synthetic route to this substance starting from benzene and
suitable reagents. The synthesis may proceed in many steps, but indicate possible
weaknesses and byproducts in each step. (10p)
O
Cl
4 (9)
ENGLISH VERSION 9 a) Nitromethane (CH3NO2) has a relatively low pKa-value. Draw the reaction between
nitromethane and suitable base (B) and explain briefly why the pKa is low. (2p)
b) Nitromethane can be used as a reagent to produce noradrenaline (norepinephrine), a
transmitter substance in the sympathetic nervous system. Complete the synthetic
sequence below and indicate the reagents/reactants 1, 2, 3 and the byproduct 4.
Describe the mechanism in the last step in detail. No consideration of
stereochemistry required. (6p)
OH
1
H3 C NO2
OH
NO 2
NH 2
2
O
O
O
nitr omethane
O
3
OH
NH2
+4
HO
OH
nor adrenaline
c) What can be formed if the intermediate product after the first step is treated with the
reagents in the last step? No mechanisms required. (2p)
OH
NO2
3
?
O
O
10 The Biginelli reaction is a so called multicomponent reaction named after the Italian
chemist Pietro Biginelli who developed it already in 1891 (Chem. Ber. 1891, 24, 1317).
The reaction gives rise to dihydropyrimidones, which often are of pharmaceutical value.
Propose with detailed mechanisms and suitable reagents how the Biginelli reaction to the
dihydropyrimidone BP below occurs. Use the three starting materials S1, S2 and S3. (10p)
O
O
NH 2
O
O
NH
N
H
O
O
S1
BP
5 (9)
H
O
S2
H2 N
O
S3
ENGLISH VERSION 6 (9)
ENGLISH VERSION Average ”Bond Strengths”
Bond Dissociation Energies (BDE)
Average Bond Dissociation Energies (kcal/mol)
a
b
c
d
e
f
H
C
N
O
F
Si
S
Cl
Br
I
H
104
99
93
111a
135
76
83
103
87
71
C
99
83b
73c
86d
116e
72f
65
81
68
52
N
93
73c
39
53h
65
92
58
46
O
111a
86d
53h
47
45
108
52
48
56
F
135
116e
65
45
37
135
Si
76
72f
92
108
135
53
91
74
56
S
83
65
58
60
61
52
Cl
103
81
46
58
Br
87
I
71
52
91
61
68
48
74
52
52
56
56
Average value. Approximately 103 kcal/mol for alchols
and 119 kcal/mol for water
C=C 146 kcal/mol C≡C 200 kcal/mol
C=N 147 kcal/mol C≡N 213 kcal/mol
C=O 176 kcal/mol for aldehydes and 179 kcal/mol for ketones
C=Si 111 kcal/mol
N=N 111 kcal/mol N≡N 226 kcal/mol
Release of strain energy upon ring opening
Cyclopropane
27 kcal/mol
Cyclobutane
26 kcal/mol
Epoxide
25 kcal/mol
Aromatization energy
Benzene
36 kcal/mol
Pyridine
28 kcal/mol
Delocalization of lone pair
Carboxylic ester ~7 kcal/mol
Carboxylic amide 17 kcal/mol
Hydrogen bonds
4-10 kcal/mol (usually)
7 (9)
46
36
ENGLISH VERSION SOME APPROXIMATE pKa VALUES
HC NH
-10
Strong Mineral Acids
<0
(CN)3CH
-5
CH3OH2
-2
H O
F 3C
R CO2H
4-6
H
14
NH2
15
O
0
0
12
H
O
Cl
NH2
CF3CO2H
O
H2O
15-16
R OH
16-18
18
OH
5
N
H
H2S
7
H2NNH3
8
HCN
9
O
H
H
17
O
H
19-20
O
10
R2NH2
H
OH
OR
24-25
H
10
CN
25
R
R CH2NO2
10
R C C H
O
11
RSH
H
O
O
9
H
RSH
O
11
O
OR
H
H2O2
O
11
12
O
RO
OR
25
13
H
8 (9)
NR2
~30
(C6H5)3PCH3
35
NH3
33
(I-Pr)2NH
37
R CH3
>50
ENGLISH VERSION CHARACTERISTIC PROTON CHEMICAL SHIFTS*
Type of Proton
Structure
Chemical Shift, ppm
Tetramethylsilane (TMS)
(CH3)4Si
0
Cyclopropane
C3H6
0.2
Primary
R-CH3
0.5-1
Secondary
R2-CH2
1-1.5
Tertiary
R3-CH
1-2
Amino
RNH2
1-5
Hydroxylic
R-C-OH
1-6
Allylic
C=C-CH3
1.5-2
Esters
H-C-COOR
2-2.5
Acids
H-C-COOH
2-3
Carbonyl Compounds
H-C-C=O
2-3
Acetylenic
C≡C-H
2-3
Benzylic
Ar-C-H
2-3
Iodides
H-C-I
2-4
Bromides
H-C-Br
2.5-4
Alcohols
H-C-OH
3-4
Ethers
H-C-OR
3-4
Chlorides
H-C-Cl
3-4
Esters
RCOO-C-H
3.5-4.5
Vinylic
C=C-H
4-6
Fluorides
H-C-F
4-4.5
Phenolic
Ar-OH
4-12
Aromatic
Ar-H
6-9
Aldehydic
R-(H-)C=O
9-10
Enolic
C=C-OH
15-17
Carboxylic
RCOOH
10-12
* Fritt modiferad från: http://wwwchem.csustan.edu/tutorials/nmrtable.htm
9 (9)