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Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
Exercises Topic 8: Reactions in Organic Chemistry
1. Which of the following compounds can exist as cis-trans isomers? For each than can, draw
both isomers and the two chair conformers formed by interconversion, showing the orientations
in space of the –OH and –CH3.
(a)
(b)
(c)
Solution: Only (a) and (b) will have cis-trans isomers
(a)
CF3
H
O
O
H
F3 C
O
H
H
F3C
H
H
CF3
H
cis
O
H
trans
(b)
F3C
O
H
H
H
CF3
O
CF3
O
H
H
O
H
H
F3 C
H
trans
cis
2. Find the molecular structure of lycopene (C40H56), a compound partially responsible for the
red colour of some fruits (tomatoes) and demonstrate that it is a terpene.
3. Standard hydrogenation enthalpies, ∆Hº, for several cis-trans alkene isomer pairs are shown
in the following Table. (a) Can be used ∆Hº values as a measure for the relative stability of the
isomers? (b) Can you explain why ∆Hº for trans-2,2,5,5-tetramethyl-3-hexene is 39 kJ/mol
higher than the corresponding cis isomer while it is only 4 kJ/mol higher for the trans-2-butene?
∆HºHydrog (kJ/mol)
cis-2-butene
-119.7
trans-2-butene
-115.5
cis-2,2,5,5,-tetramethyl-3-hexene
-151.5
trans-2,2,5,5,-tetramethyl-3-hexene -112.6
Solution:(a) We know from thermochemistry the relation between enthalpy and internal energy
H=E+pV. In a chemical process, enthalpy variation is given by ∆H=∆E+∆(pV). For constant
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
pressure processes, which are the majority of the chemical process, in which solids and/or
liquids participate, ∆(pV)∼0 so ∆H∼∆E. Therefore, we can use reaction enthalpies as a measure
of the relative stability of compounds provided that the initial or final states are the same. In the
hydrogenation of alkene isomers, the initial states are different but the final states are the same
as illustrated in the following scheme for 2-butene isomers
CH3
CH3
H
H
H
CH3
CH3
H
H2
CH2
CH3
CH3
Pt
CH2
(b) The reason why cis isomers are less stable than trans is the steric stresses induced by the
substituents of the double bond. This is illustrated in the following scheme. Hydrogen atoms in
the cis-2-butene are in the same region of space creating thus a repulsive stress. This
phenomenon is more intense in cis-2,2,5,5,-tetramethyl-3-hexene since there are methyl groups
which are more voluminous than hydrogen atoms
H
H
H
H
C
C
H
H
C
H
H
CH3 H C
3
H
C
H
H
H
H
H
4. Analyze the following electrophilic addition reactions to 3-methyl-2-pentene:
a. H2/Pt.
b. Br2/ClNa.
c. H2SO4 cc followed by addition of H2O.
Solution:
CH3
CH3
CH3
CH
CH2
CH3
CH3
C
CH3
CH2
CH2
CH3
CH3
CH
Br
C
CH2
CH3
CH2
OH
Br
5. Product B discolors aqueous solutions of KMnO4. When B is treated with O3 followed by
Zn/CH3-COOH, it is transformed into acetone and formaldehyde. Deduce the structure of B.
Solution:
H3 C
H
C
H3 C
C
H
6. Which are the reaction products when propine is treated with?:
d. Water in the presence of H2SO4 and HgSO4
e. ClH in excess
Solution:
Cl
OH
O
H3C
a)
H3C
C
CH2 H3 C
C
CH3
b)
C
Cl
CH3
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
7. Which are the alkenes you will select as starting molecules to obtain the following
compounds? :
H
OH
a. (1S,2R)-1-methylcyclohexane-1,2-diol
OH
b. 2-methylpentane-2,3-diol
OH
H3 C
OH
C H3
c. butane-1,2,3,4-tetrol
Solution:
H
OH
C H3
OH
H3C
1-methylcyclohexene
OH
C H3
OH
C H3
2-methylpent-2-ene
OH
HO
OH
buta-1,3-diene
OH
8. Which are the alkynes you will select to prepare the following ketones?
O
b. pentan-3-one
a. pentan-2-one
O
Solution:
O
OH
HgSO 4
pent-1-yne
pent-1-en-2-ol
HgSO 4
O
OH
pent-2-yne
pent-2-en-3-ol
9. Which are the expected products for the following reactions?
+
2Cl2
?
+
1HBr
?
a.
b.
Solution:
+
c.
.
Cl
Cl
a.
+
2Cl2
+
1HBr
Cl
Br
Cl
Br
+
1HBr
1HBr
?
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
10. Which are the expected products for the following reactions?
a) p-Xylene (1,4-dimethylbenzene)+ Cl2/Fe
b) Toluene + CH3-CH2Cl + AlCl3
c) p-CH3O-C6H4-CH=CH-C6H5 + HBr
d) Benzene + CH3-CH2-COCl + AlCl3
e) Benzene + succinic anhydride + AlCl3
f) 1-phenyl-1,3-butadiene + 1 mol H2 + Ni/30oC/2 atm
Solution:
Cl
b)
a)
O
H 3C
O
d)
c)
Br
O
e)
O
f)
OH
11. Which are the main products in the mononitration of
a. o-nitrotoluene
b. p-nitrotoluene
c. m-dibromobenzene
d. p-nitroaniline
e. m-dinitrobenzene
f. m-cresol
(3-CH3-C6H4OH)
Solution:
g. o-cresol
h. p-cresol
i. p-C6H4-(COOH)2
(tereftalic acid),
j. p-xylene
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
[NO2+]
b)
H3 C
NO2
H3 C
NO2
O2N
d)
[NO2+]
H2 N
H2 N
NO2
NO2
O 2N
a
)
[NO2+]
H3C
H3C
NO2
O2 N
O2 N
c
)
[NO2+]
Br
Br
NO2
Br
Br
NO2
e
)
+
[NO2 ]
O2 N
O2 N
NO2
NO2
HO
g
)
HO
[NO2+]
H3C
H3C
NO2
NO2
i
)
HOOC
[NO2+]
COOH
HOOC
COOH
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
OH
OH
f)
[NO2
OH
+
H3C
H3C
H3C
NO 2
O 2N
NO 2
h)
[NO2
H3C
+
OH
H3C
OH
NO 2
j)
[NO2+
H3C
C H3
H3C
C H3
12. Design a synthetic route to obtain the following products starting from benzene
f. p-nitrotoluene
a. m-nitrophenylmethylketone
b. m-nitrotoluene
c. p-bromonitrobenzene
Solution:a) Alkylation with CH3Cl followed by nitration; b) Acylation with CH3COCl followed
by nitration; c) Nitration followed by acylation with CH3Cl; d) Bromation followed by nitration
13. The Friedel-Crafts electrophilic substitution of benzene with 2-chloro-3-methylbutane gives
two products, being one of them the most abundant. Explain the structures of both.
Solution:
Cl
AlCl3
C
+
+
C
+
C H3
1,2-dimethylpropylbenzene
1,1-dimethylpropylbenzene
14. How can you prepare diphenylmethane starting from benzene and an adequate acyl
chloride?
Solution:
O
O
Cl
+
AlCl3
diphenylmethanone
H2 /Pd
benzylbenzene
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
15. Order the following alcohols according to their acidity: Phenol, p-methylphenol, p(trifluoromethyl)phenol. Is p-cyanophenol more acid than phenol?
Solution:
p-(trifluoromethyl)phenol > Phenol > p-methylphenol
p-cyanophenol is more acid than phenol
16. Draw the structural formulas for the alkenes formed by dehydration of the following
alcohols: (a) 3-methyl-2-butanol; (b) 2-methylcyclopentanol; (c) cyclohexylmethanol
Solution:
methylenecyclohexane
2-methylbut-2-ene
3-methylcyclopentene
3-methylbut-1-ene
1-methylcyclopentene
17. Draw the structural formulas for the intermediate and final compounds when the following
alcohols are treated with a strong oxidant: (a) isopropanol; (b) menthol; (c) 2-methylpropan-2ol; (d) 1-propanol.
Solution
acetone
2-isopropyl-5-methyl-cyclohexanone
CO 2 + H2O
propanal
propionic acid
18. What are the reaction products of 2,6-diisopropylcyclohexanol and 2,6-diisopropylphenol
with aqueous sodium hydroxide?
Solution
No reaction
2,6-diisopropylcyclohexanol
2,6-diisopropylphenol
sodium 2,6-diisopropylphenolate
19. Sodium borohydride (NaBH4) is a common reducing agent in organic chemistry, less
reactive than LiAlH4. Deduce the reaction products when the following molecules are treated
O
with NaBH4
O
O
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
Solution:
OH
O
NaBH4
O
H
OH
NaBH4
O
H
OH
NaBH4
20. Deduce the parent carbonyl compounds whose reduction originates the following alcohols
OH
OH
C H2 O H
C H C H3
H
Solution:
O
C H2 O H
H
LiAlH4
benzaldehyde
OH
O
C H C H3
C H3
LiAlH4
1-phenylethanone
OH
O
LiAlH4
H
cyclohexanone
21. 2-methyl-2-pentanol can be synthesized from two carbonyl compounds A and B using
methyl magnesium bromide as Grignard reactive. A needs two moles of CH3MgBr while B
only needs one. Deduce the structural formula of A and B.
Solution:
O
+
CH3MgBr
C H3
BrMgO
C H3
+
C H3
H+
O
O
HO
C H3
BrMgO
2CH3MgBr
HO
C H3
H+
C H3
22. Propose a synthetic route to prepare p-cresol from benzene (two steps).
Solution:
H3 C
Cl
C H3
C H3
AlCl3
NaOH
O
SO 3
?
S
H2SO4
HO
O
HO
C H3
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
23. How would you prepare the following ethers using the Williamson synthesis?
O
H3 C
C H3
O
O
Solution:
NaH
O
H3 C
+
I
HO
OH
O
C H 3 NaH
H3 C
H 3C
+
I
H 3C
C H3
NaH
O
H3 C
+
I
C H3
HO
24. Propose the reaction products when acetone is treated with:
a) Hydroxylamine (NH2OH)
H
H 2N
b) Butanediol
N
O
N
+
O
c) 2,4-dinitrophenylhidrazine
d) Methyl magnesium bromide
–
–
N+
O
O
Solution:
O
propan-2-one oxime
+
H2N
OH
OH
N
H2
C
O
+
H2
C
O
HO
OH
C H2
O
2,2-dimethyl-1,3-dioxocane
N
N
H
N
O
O
C
H2
H3 C
H
H2N
C
H2
N
H3 C
O
+
O
N
–
O
+
–
N
O
+
+
O
N
O
O
N-(isopropylideneamino)-2,4-dinitro-aniline
–
H 3C
O
+
H3 C
[Mg] Br
+
H3 C
OH
C H3
2-methylpropan-2-ol
–
C H3
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
25. Find if the following molecule is D-Gucose. Draw the two possible six membered rings
formed by hydroxy addition to the aldehyde.
Solution: D-Glucose is (2R,3S,4R,5R)-2,3,4,5,6-Pentahydroxyhexanal. We need to find the R/S
configuration of each carbon. Numbers start from the aldehyde (1). We apply Cahn rules to each
carbon as shown in the following images. In these, the original image has been rotated to allow
the lowest priority atom to point away from the image
2
1 2
2
3
3
3
1
1 4 2
3
1 5 2
3
Therefore, C2 is R, C3 is S, C4 is R and C5 is also R. Therefore, this molecule is D-glucose.
Ring closening can occur by hemiacetal formation between carbon C1 and the hydroxy group
either from C4 or C5. If ring closes by C4, a five membered ring is formed. Six membered ring
(pyranose) is formed closing by C5. With a Fischer projection it is seen more clearly
H
H
O
O
H
OH
HO
H
H
OH
HO
H
H
OH
H
OH
H
OH
H
OH
OH
H
OH
H
H
Furanose ring
H
Pyranose ring
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
Hemiacetal formation transforms carbon C1 into a chiral center since it is bonded to –H. OH, -C
and –O. Therefore, there are two ways to locate these four substituents that give rise to the two
different optical isomers. To view them more clearly a special projection called Haworth
projection is commonly used:
CH2 OH
CH2 OH
O
O OH
OH
HO
OH
HO
OH
OH
OH
26. Show reagents and experimental conditions to convert cyclohexanone to each of the
following compounds
(c)
(a)
(b)
(d)
(e)
Solution:a) Oxidation with K2Cr2O7; b) Dehydration with H2SO4; c) Addition of HBr; d)
Addition of Br2; e) Hydrogenation with a catalyst as for example Pt.
27. Product A is obtained reacting benzene with one mole of CH3Cl using AlCl3 as catalyst. A
is subjected to a strong oxidation treatment giving the product D. If instead of this route,
benzene is treated with acetyl chloride (CH3COCl) in the presence of AlCl3 and afterwards,
with I2 /NaOH followed by acid treatment, the same final product D is obtained. Deduce the
structural formulas of all the compounds.
Solution:
CH3-Cl
KMnO 4
AlCl3
A
AlCl3
C
CH3COCl / AlCl3
I2 /NaOH
B
CH3-I
C
28. Propose synthetic routes to obtain benzoic acid from the following substances:
a) Toluene
b) Benzonitrile
c) Acetophenone
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
d) Benzyl alcohol
e) Benzaldehyde
Solution:
(a)
(b)
O
O
N
OH
KMnO4
OH
H2O / H+
(c)
(d)
O
O
I2 /NaOH
CH3-I
O
OH
+
OH
OH
KMnO4
(e)
KMnO 4
29. Write the reactions of acetic acid with:
a) KOH,
b) LiAlH4,
c) SOCl2,
d) NH3,
e) PCl5
and
C6H6/AlCl3
f) P2O5
g) Ethanol/H+,
h) H2/Ni catalyst
subsequently
Solution:
O
O
P2O5
KOH
–
O K+
O
O
LiAlH4
O
OH
OH
O
O
O
Ethanol/H+
O
OH
SOCl2
Cl
H2/Ni catalyst
O
NH3
O
NH2
O
C6H6/AlCl3
PCl5
Cl
with
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
30. Propose the reaction products for the following acyl nucleophilic substitution reactions:
O
a.
H 3C
O
C H3
NaOH
H2O
O
O
b.
Na+ -OCH3
H3 C
O
C H3
CH3OH
O
c.
NH3
H3C
Cl
Solution:
O
O
H3 C
O
C H3
NaOH
H2O
O
–
O Na+
H3 C
O
O
Na+ -OCH3
H 3C
O
C H3
CH3OH
2
O
H3 C
O
C H3
O
NH3
H3 C
Cl
H3 C
NH2
31. Using an acid chloride and an amine or ammonia, propose a synthetic route to obtain:
a) CH3-CH2-CONH-CH3
b) N,N-diethylbenzamide
c) Propanamide
Solution:
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
32. Hydroxyacids are molecules that behave as acids and alcohols. When the two functionalities
are separated an appropriate distance the molecule looses spontaneously a water molecule by
intramolecular esterification forming a cyclic compound named lactone. Five member rings are
called γ-lactones and six member rings δ-lactones. Find the corresponding hydroxyacids from
which the following lactones are formed:
C H3
a.
c.
O
O
H3 C
O
O
C H3
O
b.
d.
O
H3 C
O
O
Solution:
C H3
O
O
O
HO
HO
O
H3 C
OH
O
OH
O
O
C H3
O
O
HO
HO
OH
O
OH
H3 C
O
O
33. A given compound A (C2H4O2) is divided in three portions. The first one is treated with
thionyl chloride giving B which reacts with methylamine to give C. C is reduced with LiAlH4
to give D, a secondary amine (C3H9N). The second portion is treated with P2O5 to give E
which is treated with D to give two products, F, an amide (C5H11NO), and A. The third portion
is treated with methanol in acid media to give G; G is treated with ammonia giving H, which is
reduced with LiAlH4 to give a primary amine I (C2H7N). Deduce the structural formulas of
compounds A to I.
Solution: The reactions that give B, E and G products are typical nucleophilic substitutions. A
must be an acid. There is only one acid with two carbon atoms: acetic acid.
A
acetic acid
B
acetyl chloride
A
acetic acid
A
acetic acid
A
E
acetyl acetate
D
N-methylethanamine
C
N-methylacetamide
F
N-ethyl-N-methyl-acetamide
G
methyl acetate
H
acetamide
I
ethanamine
Chemistry for Biomedical Engineering. Exercises Topic 8
Open Course Ware Universidad Carlos III de Madrid. 2012/2013
Authors: Juan Baselga & María González
34. Show how n-propylamine can be prepared starting from the following substances:
a) propanal
d) propanamide
b) 1-nitropropane
e) propanol
c) propanenitrile
Solution:
Br
+
NH2
NH3
NH
O
+
H2
NH3
NH2
Pt
H
O
H2 / Pt or
N
O
N
O
NH2
SnCl2 / H+
LiAlH4
NH2
LiAlH4
NH2
NH2
O
O
NH3
?KMnO4
OH
OH
O
–
+
O NH4
H4LiAl
?
NH2
NH2