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1. Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed ________
commercially. Its indications are the treatment of pleural mesothelioma and non-small cell lung
cancer. Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs
called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine
synthesis.
Answer the following questions about the compound: (8 p = 7×1 p [a-d, g-i] + 0.5 p [e, f])

a) Give the hybridisation state for atoms a, b, c, e.

b) Give the oxidation number for atoms c, d, f.
c) Draw a line through all bonds which can be hydrolysed under acidic conditions (with heat).
d) What is/are the name(s) of the functional group(s) atom f is part of?
e) Which configuration has carbon atom e according to the R/S-system (Cahn-Ingold-Prelog)?
f) Is the encircled moiety aromatic? (Yes/No)
g) What is the charge of the molecule in water at pH 7?
h) Should the compound show absorption in the UV range (Yes/No)? If yes, encircle the cyclic
moiety/ies (only) responsible for the UV-absorption.
i) Cleavage of the amide bond produces an amino acid. Draw this amino acid in Zwitter ionic form.
[Extra point alert: j) Name the amino acid in i). (0.5p)
k) Which part of the molecule would mainly be involved in the recognition by the enzymes it
inhibits? Draw a box around this moiety to distinguish it from above used circles (1 p)]
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2. Answer the following questions with regards to the compound shown below. ________
a) What is the name of the compound according to IUPAC rules? The stereochemistry should
become evident from the name. (1 p)
b) Give the product of the catalytic hydrogenation of the compound shown below incl. the
stereochemistry. (1.5 p)
c) Give a detailed, curved-arrow mechanism for the reaction of the compound shown below with
HBr, incl. all protonation and deprotonation steps and resonance structures (clearly indicate the
stereochemistry). (3 p)
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3. The structures of aniline (A) and pyridine (B) are shown below. Both are aromatic compounds ________
containing a nitrogen atom, however, they have very different reactivities.
a) How does the basicity of aniline compare to that of ammonia (NH3)? Explain. (1.5 p)
b) Compare the ability to react in an electrophilic aromatic substitution reaction of these
compounds with that of benzene. Explain. (2 p)
[Extra point alert: c) What are the products when A and B are subjected to bromination? (1 p)
d) Why is pyridine a weaker base than ammonia? (1 p)]

A B
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4. Propose a sequence of reactions that will accomplish the following transformation. What are a, b,
d and the intermediate C? (2 p)
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5. Draw all possible hydrogen bonds between hydroxyethylethylether (IUPAC name=2‐
ethoxyethan‐1‐ol). (1 p)
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6. A biomedical researcher obtains compound X as a side product in a synthesis and decided to ________
characterise it further. The following analyses were done:

a) Several mg of the compound were send for elemental analysis and gave the molecular formula
C4H8O2.

b) The following 1H-NMR and IR spectrum were obtained for compound X:

Chemical Net Multiplet

shift intensity information
1.21 ppm 3 triplet

1.99 ppm 3 singlet

4.11 ppm 2 quadruplet
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c) Reflux of compound X under acidic conditions produced compounds Y and Z. These two
compounds were separated and analysed spectroscopically. Compound Y gave the following 1H-
NMR and IR spectrum.

Chemical Net Multiplet

shift intensity information
1.96 ppm 3 singlet
11.42 ppm 1 singlet
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d) Compound Z gave the following mass spectrum:

What are compounds X, Y and Z (names and structural formula)? Motivate your answer by
explaining all spectra and reactions (e.g. splitting in mass spectrum, downfield signal in NMR,
functional groups, reaction names, etc.)! (5 p)
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7. Give structural formulas for the main products in the following reactions (clearly indicate the
stereochemistry in d). (5 × 1p)

a)

b)

c)

d)

e)
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8. In organic chemistry functional groups are important. Therefore it is required to be able to identify
them and know them.
a) Encircle and name the functional groups in the following compound. Clearly indicate which
group is which. (2 p)

Give the general structural formula for the following compound classes (3 × 1 p)

b) acid chloride

c) ether

d) primary thiol
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9. Assume a fictitious reaction: 𝐴 + 𝐵 →
←
𝐶 which proceeds via one transition state.
a) Calculate G given that H for this reaction is -252.0 J/mol and S is 1.0 J/K/mol at 25°C (0°C
≈ 273K). (Note: If you cannot give exact final numbers, describe how you can calculate it.) (1 p)
b) Draw the energy diagram for the reaction (clearly indicate substrate, product, activation energy,
transition state(s) and intermediate(s), if any). (2 p)
c) What influence does a catalyst have on the reaction? (1 p)
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10. Give a detailed, curved-arrow mechanism for the following reaction, incl. all protonation and
deprotonation steps and resonance structures. (4 p)
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11. In proteins carbohydrates can be linked to amino acids via glycosidic bonds. One of these bonds ________
is the (-)O-glycosidic link of N-acetylgalactosamine to serine. Hint: recall that hemiacetals can
react with alcohols to acetals.
a) Draw the Fischer projection of D-N-acetylgalactosamine. (1 p)
b) Draw serine β-linked to N-acetylgalactosamine (i.e. on carbon 1). (1 p)
c) Carbohydrates can undergo mutarotation. Define the concept of mutarotation. (1 p)
You want to study the glycosylation of proteins and have synthesised 11C labelled N-
acetylgalactosamine with an activity of 16000Bq.
d) How much of the labelled carbohydrate is left after 1 hr? (1 p)
[Extra point alert: e) Which radiation is emitted from the sample and how can it be detected (1
p)]
Extra info: 11
C: + decay, half-life: 20 min

N-acetylgalactosamine serine
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12. You have synthesised amphetamine from phenylpropan-2-one in 2 steps (see below). ________
a) The reaction was incomplete and you want to separate the product from the substrate (note:
both are liquids at room temperature with similar boiling points). How can this be easily done?
Explain how and why. (2 p)
b) Draw the intermediate A and give the reagent(s) b required for the reaction? (1 p)
[Extra point alert: c) Using very alkaline conditions (e.g. using ethoxide EtO-) and heat which
reaction would phenylpropan-2-one rather follow? Give the name of the reaction and the product.
(2 p)]