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					               Preparatory Problems IChO 2012

  Preparatory Problems

44th International Chemistry Olympiad

       Co-Editors: Michael P. Doyle
         and Andrei Vedernikov

 Department of Chemistry and Biochemistry
  University of Maryland at College Park

Tel: 001 301 405 1788; Fax: 001 301 314 2779


               November 2011

      Published 2011 American Chemical Society
                  All rights reserved
             Commercial sale is prohibited
             Preparatory Problems IChO 2012

         Contributing Authors

  Seth N. Brown, University of Notre Dame
  Michael P. Doyle, University of Maryland
  Daniel E. Falvey, University of Maryland
   George R. Helz, University of Maryland
   Kaveh Jorabchi, Georgetown University
  Douglas A. Julin, University of Maryland
     J.L. Kiappes, University of Oxford
  John Kotz, State University of New York
Evguenii Kozliak, University of North Dakota
   Amy S. Mullin, University of Maryland
 Garegin A. Papoian, University of Maryland
   Elena Rybak-Akimova, Tufts University
Andrei N. Vedernikov, University of Maryland

                                Preparatory Problems IChO 2012

We are happy to provide Preparatory Problems for the 44th International Chemistry
Olympiad. These problems were prepared with reliance on fundamental topics that
are traditionally covered in high school chemistry courses supplemented with six
topics of advanced difficulty for the Theoretical part and one topic of advanced
difficulty for the Practical part. These topics are listed under “Topics of Advanced
Difficulty”, and their applications are given in the problems. In our experience
each of these topics can be introduced in two to three hours. Whenever possible the
relevance of the problem in the chemical sciences, and to the complex world in
which we live, is given. Solutions will be sent to the head mentor of each country
by email by February 1st of 2012. We welcome any comments, corrections, or
questions about the problems to

We hope that these problems will be useful in your efforts to prepare students for
the 44th IChO, and we look forward to seeing you in Washington, DC, and at the
University of Maryland.

The authors who have contributed to the Preparatory Problems bring a wide
diversity of experiences with unique expertise and, in several instances, prior
experiences as Olympians, and they are the key elements in designing the
problems. The American Chemical Society, with Cecilia Hernandez and Mary
Kirchhoff for implementation, facilitated meetings for members of the Scientific
Committee and arranged the publication of the Preparatory Problems.

                               University of Maryland, November 30, 2011


Michael P. Doyle and Andrei Vedernikov

                                    Preparatory Problems IChO 2012

Physical constants, symbols and conversion factors                               6
Topics of Advanced Difficulty                                                    7

Theoretical Problems
Problem 1    Structure of Boron Hydrides and NMR Spectroscopy                     8
Problem 2    Structure of Aluminum Halides                                        9
Problem 3    Polyoxoanions of Boron                                              10
Problem 4    Boron Nitride and Its Solid State Structure                         11
Problem 5    The Tin Pest: Solid State Structure and Phase Equilibrium           12
Problem 6    Silanes: Thermochemistry and Bond Dissociation Enthalpy             13
Problem 7    Lewis Acid-Base Chemistry                                           14
Problem 8    Nitrogen Oxides: Chemistry, Reaction Equilibrium and Thermodynamics 15
Problem 9    Isomerism of Coordination Compounds of Metals                       16
Problem 10 Absorption Spectroscopy                                               17
Problem 11 Solution Equilibria                                                   18
Problem 12 First Order Rate Processes and Radioactivity                          19
Problem 13 Kinetics and Mechanisms of Isomerization of an Octahedral
              Metal Complex                                                      20
Problem 14 Metal Phthalocyanines: Mechanism of Reduction                         21
Problem 15 Isotope Effects in Azo Coupling Reactions                             22
Problem 16 Fluorescent Lamps: Heating Inert Gas Atoms by Electrons               24
Problem 17 Molecular Motors                                                      25
Problem 18 Particles in a Box Problem and Conjugated Polyenes                    27
Problem 19 Toluene in a Superacid Solution                                       29
Problem 20 Mechanism of Catalysis by Lactate Dehydrogenase                       31
Problem 21 Substrate Specificity of Subtilisin                                   34
Problem 22 Electro-spray Ionization Mass-spectrometry of Peptides                36
Problem 23 Persistent Carbenes                                                   39
Problem 24 The Diels–Alder Reaction                                              40
Problem 25 Pericyclic Reactions and the Woodward–Hoffmann Rules                  41
Problem 26 Synthesis of Tetracycline                                             44
Problem 27 Synthesis of Antiviral Drugs                                          45

Practical Problems, Safety                                                      48
Problem 28 Analysis of Sodium Sesquicarbonate (Trona)                           49
Problem 29 Analysis of Copper in a Nickel Coin                                  53
Problem 30 Synthesis and Analysis of Iron Oxalate Complex                       55
Problem 31 Synthesis and Reduction of an Imine: Green Synthesis of a
             New Compound                                                       59
Problem 32 Kinetics of Ferricyanide Oxidation of Ascorbic Acid                  67
Problem 33 Synthesis of a Mannich Base: a Mannich Mystery                       70

                                       Preparatory Problems IChO 2012

Physical Constants, Symbols and Conversion Factors
Avogadro's constant, NA = 6.0221∙1023 mol–1
Boltzmann constant, kB = 1.3807∙10–23 J∙K–1
Universal gas constant, R = 8.3145 J∙K–1∙mol–1 = 0.08205 atm∙L∙K–1∙mol–1
Speed of light, c = 2.9979∙108 m∙s–1
Planck's constant, h = 6.6261∙10–34 J∙s
Mass of electron, me = 9.10938215∙10–31 kg
Standard pressure, P = 1 bar = 105 Pa
Atmospheric pressure, Patm = 1.01325∙105 Pa = 760 mmHg = 760 Torr
Zero of the Celsius scale, 273.15 K
1 nanometer (nm) = 10–9 m
1 picometer (pm) = 10–12 m

                               Preparatory Problems IChO 2012

Topics of Advanced Difficulty


Kinetics. Steady-state approximation. Analysis of reaction mechanisms using
steady state approximation and hydrogen/deuterium kinetic isotope effects.

Spectroscopy. NMR spectroscopy. Analysis of 1st order 1H NMR spectra and
simplest X-nucleus NMR spectra (e.g., X = 11B). Signal multiplicity, intensity and
coupling constant. Variation of NMR spectra with temperature. Mass
spectrometry: principles.

Structure of inorganic compounds. Stereochemistry and isomerism of coordination
compounds. Crystalline solids: basic unit cells and cell parameters, Bragg’s law.

Thermodynamics. Equilibrium constant, reaction Gibbs energy and enthalpy.

Pericyclic reactions.

Quantum mechanics. Particle in a circular box problem. Electronic transitions.


Thin layer chromatography.

                                         Preparatory Problems IChO 2012

                                 Theoretical Problems

Problem 1. Structures of Boron Hydrides and NMR Spectroscopy

The study of boranes (boron hydrides) has played an especially important role in understanding
broad structural principles. Work in this area began in 1912 with the classic research of Alfred
Stock (1876–1946), and chemists soon learned that the boranes had unusual stoichiometries
and structures and an extensive and versatile reaction chemistry. William Lipscomb
(1919–2011) received the Nobel Prize in 1976 “for his studies of boranes which … illuminated
problems in chemical bonding.”

a) Predict the most likely structure for the BH 4 ion.
b) The 1H NMR spectrum of the BH4 ion is illustrated below. It consists of a 1:1:1:1 multiplet
  along with a smaller 7-line multiplet. (The nuclear spin for 1H is ½, for 11B it is 3/2 and for
       B it is 3.) Interpret this spectrum.

c) Explain why the 11B NMR spectrum of the BH4 ion is a 1:4:6:4:1 quintet with JB-H = 85 Hz.
d) The molecular structure of Al(BH4)3 is symmetrical, with all B atoms and the Al atom being
  in one plane and 120o angles between the three Al–B lines. Each BH4 ion is bonded to
  aluminum through Al–H–B bridge bonds, and the line through the bridging H atoms is
  perpendicular to the AlB3 plane. The reaction of Al(BH4)3 with additional BH4 ion produces
  [Al(BH4)4] . The 11B NMR spectrum of the ionic compound [Ph3MeP][Al(BH4)4] in solution
  has a well-resolved 1:4:6:4:1 quintet (with J = 85 Hz). At 298 K, the 1H NMR spectrum has a
                                      Preparatory Problems IChO 2012
  multiplet at 7.5–8.0 ppm, a doublet at 2.8 ppm (J = 13 Hz), and a broad signal at 0.5 ppm. The
  broad signal remains broad on cooling to 203 K. Interpret this spectrum. (Note that the
  nuclear spin for 11B is 3/2 and for 31P is ½.)

Problem 2. Structure of Aluminum Halides

Aluminum is important in industrial economies as the metal and as a component of alloys. Its
compounds are widely used as catalysts in the production of organic compounds and polymers.
For example, aluminum chloride (AlCl 3) is a catalyst in Friedel-Crafts alkylations.
Organoaluminum compounds, such as Al 2(CH3)6 and [(C2H5)2AlCl]2, are used in organic
synthesis and as components of Ziegler-Natta polymerization catalysts.
  A. Aluminum Halides.
a) In the solid state, aluminum chloride, AlCl 3, has a layer lattice with six-coordinate
   aluminum (m.p. = 192 °C; sublimes at 180 °C), but aluminum chloride in the vapor state is
   a dimer, Al2Cl6. Draw the Lewis structure for the dimer and describe the bonding in this
   compound using Lewis and VSEPR (valence shell electron pair repulsion) theories.
b) Aluminum bromide, AlBr3, is a low melting solid (m.p. = 98 °C, sublimes at 255 °C),
   whereas aluminum fluoride, AlF3, has a very high melting point (m.p. = 1291 °C). Is the
   structure and bonding in aluminum fluoride and aluminum bromide likely to be similar to
   aluminum chloride?
  B. An Organoaluminum Halide
If [(C2H5)2AlCl]2 is treated with NaF, the air-sensitive fluorine analog, [(C2H5)2AlF]x, is
isolated. As noted in question A above, aluminum halides are at least dimeric under many
conditions, as is (C2H5)2AlCl. Is [(C2H5)2AlF]x also dimeric or could it be monomeric,
trimeric, tetrameric, and so on?
c) The molar mass of [(C2H5)2AlF]x was determined by measuring the freezing point
   depression of a solution in benzene. A 1.097 g sample of the compound dissolved in 65.26 g
   of benzene had a freezing point of 5.276 °C. (In this experiment, the freezing point of
   benzene was 5.500 °C, and the calibrated freezing point depression constant was
   –5.57 °C /molal.) What is the value of x in [(C2H5)2AlF]x?
d) Sketch a possible Lewis structure for [(C 2H5)2AlF]x.

                                     Preparatory Problems IChO 2012
Problem 3. Polyoxoanions of Boron

Like silicon, boron is found in nature in the form of oxo compounds, and never as the element.
Like silicon, boron-oxygen compounds are characterized by great diversity and complexity. In
these compounds boron can be bonded to three O atoms in a triangle (as in B(OH) 3, BO33– or
B3O63–) or to four atoms at the corners of a tetrahedron (as in [BO 4]5–).
  One of the most important boron-oxygen compounds is the ionic compound borax, whose
formula is normally written as Na 2B4O7∙10H2O. The compound is used widely in the
manufacture of borosilicate glass, glass fiber, and insulation.
  Hydrolysis of the borohydride ion (BH 4 ) produces hydrogen gas and a borate. Because of
the possible use of borohydride salts as possible hydrogen storage devices, the aqueous
chemistry of borates has again been studied thoroughly.
a) The species in a solution of 0.5 M boric acid, B(OH) 3, were recently studied, and a plot of
  the fraction of total boron species in solution at equilibrium as a function of pH was
  published. The main species are boric acid as well as B(OH) 4–, B4O5(OH)42– (the anion
  found in the mineral borax), and B3O3(OH)4–.
      i. Indicate which curve in the plot below corresponds to a particular boron-oxygen
      ii. Sketch the structure of each of the four boron-oxygen species above.

b) Borax is a good primary analytical standard for the titrimetric determination of acids.
   Others analytical standards of the same kind are anhydrous sodium carbonate and TRIS,

                                     Preparatory Problems IChO 2012
   (HOCH2)3CNH2. Borax and TRIS react with acids according to the following balanced
Borate ion:
  B4O72–(aq) + 2 H3O+(aq) + 3 H2O(l)  4 H3BO3(aq)
  (HOCH2)3CNH2(aq) + H3O+(aq)  H2O(l) + (HOCH2)3CNH3+(aq)
Which primary standard–Na2CO3, borax, or TRIS–will lead to the smallest relative error?
Assume there is a weighing error of 0.1 mg in weighing the standard and that you will titrate
40.0 mL of 0.020 M HCl.

Problem 4. Boron Nitride and Its Solid State Structure

Boron-nitrogen chemistry has attracted significant attention in part because a B–N unit is
isoelectronic with C–C. Furthermore, the radius of carbon and its electronegativity are roughly
the average of those properties for B and N.
  One of the simplest boron-nitrogen compounds is H3N–BH3, the ammonia-borane adduct.
Pyrolysis of this compound leads to the generation of H 2 gas and polyborazylene.
                      H3N–BH3(s)  2.5 H2(g) + (polyborazylene, BNH)
(If an efficient and low-cost method can be found to regenerate H 3N–BH3 from BNH, the
substance could be used to generate hydrogen in fuel-cell powered applications.) Further
heating polyborazylene results in boron nitride, BN.
  Boron nitride exists in several forms, the most common polymorph being one that is similar
to graphite. Another, formed by heating the graphite-like form under pressure, has the same
structure as zinc blende, ZnS. Boron nitride is thermally and chemically stable and is used in
high temperature ceramics. Most recently, layers of the graphite-like form, hexagonal BN,
have been combined with sheets of graphene to produce new materials.
a) A model of a portion of hexagonal boron nitride is illustrated below. How is it similar to, or
  different from, the structure of graphite?

                                     Preparatory Problems IChO 2012

b) The ZnS-like structure of BN, illustrated below, is a face-centered cube of nitrogen atoms
  with boron atoms in one half of the tetrahedral holes of the lattice. If the density of this form
  of BN is 3.45 g/cm3, what is the B–N bond length?

Problem 5. The Tin Pest: Solid State Structure and Phase Equilibrium

The ductility and malleability typical of metals has made metals essential structural elements
in modern construction. The thermodynamically stable form of elemental tin at 298 K and
ambient pressure is white tin, which has mechanical properties typical of metals and therefore
can be used as a building material. At lower temperatures, however, a second allotrope of tin,
gray tin, becomes thermodynamically stable. Because gray tin is much more brittle than white
tin, structural elements made of tin that are kept at low temperatures for prolonged periods may
crumble and fail. Because this failure resembles a disease, it has been termed the "tin pest".

                                     Preparatory Problems IChO 2012
a) Given the thermodynamic data below, calculate the temperature at which gray Sn is in
  equilibrium with white Sn (at 1 bar = 10 5 Pa pressure).
                 Substance              ∆fHº (kJ mol–1)              Sº (J mol–1 K–1)
                Sn (s, gray)               –2.016                          44.14
               Sn (s, white)                0.000                          51.18
b) Crystalline white tin has a somewhat complex unit cell. It is tetragonal, with a = b = 583.2
  pm and c = 318.1 pm, with 4 atoms of Sn per unit cell. Calculate the density of white tin in
  g cm–3.
c) Gray tin adopts a face-centered cubic structure called the diamond lattice, illustrated below.
  When a crystalline sample of gray tin is examined by X-ray diffraction (using Cu K
  radiation,  = 154.18 pm), the lowest-angle reflection, due to diffraction from the (111)
  family of planes, is observed at 2 = 23.74º. Calculate the density of gray tin in g/cm 3.



d) The pressure at the bottom of the Mariana Trench in the Pacific Ocean is 1090 bar. Will the
  temperature at which the two allotropes of tin are in equilibrium increase or decrease at that
  pressure, and by how much? In your quantitative calculations, you may assume that the
  energy (E), entropy (S), and molar volume of the two phases of tin are independent of
  temperature and pressure.

Problem 6. Silanes: Thermochemistry and Bond Dissociation Enthalpy

Bond dissociation enthalpies (or bond dissociation energies) are a measure of bond strength in
chemical compounds. As such they can be useful in estimating whether a reaction is exo- or
endothermic, that is, in estimating the enthalpy change occurring on reaction.
  One use of dissociation enthalpies is to determine element–element bond strength, a
parameter that can often not be measured directly. Here we wish to determine the Si–Si bond
                                     Preparatory Problems IChO 2012
  Silicon hydrides SinH2n+2 are called silanes. Most of them contain Si–Si bonds, but they
become increasingly unstable as the number of silicon atoms increases.
a) Calculate the Si–Si bond dissociation enthalpy of Si 2H6 from the following information:
  Bond dissociation enthalpy for H–H = 436 kJ/mol
  Bond dissociation enthalpy for Si–H = 304 kJ/mol
  ∆fH [Si(g)] = 450 kJ/mol
  ∆fH [Si2H6(g)] = 80.3 kJ/mol
b) Compare the calculated Si–Si bond energy with that for the carbon-carbon single bond
  (bond dissociation enthalpy = 347 kJ/mol). What implications does this have for the
  thermodynamic stability of silanes with n = 2 or greater as compared to analogous alkanes?

Problem 7. Lewis Acid-Base Chemistry

A unifying idea in chemistry is the theory of acid-base behavior put forward by G. N. Lewis
(1875–1946) early in the 20 th century. That is, acids are electron-pair acceptors, whereas bases
are electron-pair donors. There are thousands of molecules that can be classified as Lewis
acids or bases, and hundreds of studies of the quantitative aspects of Lewis acid-base
chemistry were carried out in the 20 th century. One person deeply involved in such work was
H. C. Brown (1912–2004), who received the Nobel Prize (1979) for his work using Lewis base
complexes of the Lewis acid borane (such as C 4H8O–BH3) in synthetic organic chemistry.
  Trisilylamine, N(SiH3)3, like all amines, is potentially a Lewis base. This question explores
this function with this interesting compound.
a) The NSi3 framework of the compound is essentially planar. Account for this observation.
b) Consider the following reaction enthalpies, ∆rHo, for acid-base reactions of trimethylborane
  [B(CH3)3] with given Lewis bases.
  Lewis Base                         ∆rHo (dissociation) (kJ/mol)
  NH3                                57.5
  N(CH3)3                            73.7
  N(C2H5)3                           about 42
  C7H13N (quinuclidine)              83.4

                                     Preparatory Problems IChO 2012


     i. Using N(CH3)3 as the reference base, explain why the other Lewis bases have smaller
       or larger values of the reaction enthalpy.
     ii. Explain why trisilylamine does not form a stable complex with trimethylborane.
c) Gaseous (CH3)3NB(CH3)3 is introduced into an evacuated vessel at 100.0 °C to give the
  initial pressure of 0.050 bar. What is the equilibrium pressure of B(CH3)3 at this
  temperature? (For the dissociation of (CH 3)3NB(CH3)3: ∆dissocHo = 73.7 kJ·mol–1 and
  ∆dissocSo = 191 J·K–1·mol–1.)

Problem 8. Nitrogen Oxides: Chemistry, Reaction Equilibrium and Thermodynamics

Nitrogen oxides play a critical role in atmospheric chemistry. They are produced in internal
combustion engines from the high-temperature combination of O2 and N2 in air, and contribute
to photochemical smog in many large cities. In the stratosphere, nitrogen oxides contribute to
the photochemical degradation of ozone that maintains a steady state of this ultraviolet-
absorbing gas. Some of the chemistry of nitrogen oxides is described below.
  A. Interconversion of Nitrogen Oxides.
A colorless, gaseous, paramagnetic nitrogen oxide A is allowed to react with excess O2, and
the mixture passed through a trap at –120 ºC, in which condenses a colorless solid B. A sample
of B (2.00 g) is introduced into a 1.00 L evacuated container and its red-brown vapor
equilibrated at various temperatures, giving rise to the pressures recorded below.
      T, ºC                                   p, atm
      25.0                                    0.653
      50.0                                    0.838
a) Identify compounds A and B.
b) What chemical reaction takes place when B is introduced into the evacuated container? Give
  ∆Hº and ∆Sº values for this reaction.
  B. Reactivity of Nitrogen Oxides
Compound B (from Part A above) reacts with F2 to form a colorless gas C. Compound C reacts

                                        Preparatory Problems IChO 2012
with gaseous boron trifluoride to form a colorless solid D. A 1.000 g sample of compound D is
dissolved in water and titrated with 0.5000 M NaOH to a phenolphthalein endpoint, which
requires 30.12 mL of the titrant.
c) Give structural formulas for compounds C and D, and explain the results of the titration of
d) Compound D reacts with excess nitrobenzene to give a major organic product E. Give the
  structural formula of E.

Problem 9. Isomerism of Coordination Compounds of Metals

Transition elements such as iron, copper, platinum, silver, and gold have played a central role in
the development of human society. At the end of the 19th century Alfred Werner developed the
field of coordination chemistry, and ideas from that field were important in the overall
development of modern chemistry. These elements and their compounds are now used in
countless ways, and their importance in biology is widely recognized.
        A. Isomerism

Coordination compounds exhibit several forms of isomerism.
        •         Stereoisomers are isomers that possess identical constitution, but which differ in
                  the arrangement of their atoms in space. Stereoisomers include optical isomers
                  (enantiomers) and geometric isomers (diastereoisomers).
        •         Structural or constitutional isomers have the same empirical formula but differ in
                  their atom-to-atom connections.
a) How many stereoisomers are expected for each of the following four-coordinate, square
  planar platinum(II) compounds? Draw the structure of each.
       i. (PPh3)2PtCl2 (Ph = phenyl);
       ii. [Pt(NH3)(pyridine)(NO2)(NH2OH)]+ (The Russian chemist Chernyaev first synthesized
            the diastereoisomers of this compound in 1926.) (Here both NO2– and NH2OH are N-
            bonded to the platinum(II) ion);
       iii. Pt(en)Cl2 (where en = ethylenediamine, H2NCH2CH2NH2).
b) Draw each stereoisomer of the following octahedral, six-coordinate cobalt(III) and
  chromium(III) complexes.
       i. Co(py)3Cl3 (where py = pyridine);
       ii. [Cr(ox)2(H2O)2]– (where ox = oxalate ion, [O2C–CO2]2–);
                                     Preparatory Problems IChO 2012
       iii. [Co(en)(NH3)2Cl2]+.
       B. Chemotherapy Agents
There has been a concerted effort to find transition metal complexes that can act as drugs in the
treatment of cancers. A particularly important recent example is a Ru(III) complex, the anion of
which has the formula [Ru(DMSO)(imidazole)Cl4]–. Complexes of DMSO,                       H
dimethylsulfoxide [(CH3)2SO], are interesting in part because the DMSO ligand
can bind to the metal ion either through the O atom or the S atom.
c) What is the total number of stereoisomers and structural isomers possible for          N
   [Ru(DMSO)(imidazole)Cl4]–?                                                        Imidazole
      C. OLEDs and an Aluminum Coordination Compound
In an organic light-emitting diode (OLED), a film of an organic compound emits light in
response to a current. OLEDs are now used in computer monitors and in the screens on mobile
phones and personal digital assistants (PDAs). One molecule used successfully in OLEDs is
the aluminum(III) complex of 8-hydroxyquinoline. By incorporating different substituents,
different wavelengths of light are emitted.




                        8-hydroxyquinoline (C9H6NO) complex of Al3+

This water-insoluble compound is also used in the gravimetric analysis for aluminum in a
d) Assuming octahedral coordination around the Al 3+ ion, how many stereoisomers are
   possible for the complex (C 9H6NO)3Al? Sketch the structure of at least one of the

Problem 10. Absorption Spectroscopy

Although pH is almost always determined by glass electrode in modern laboratories, situations
exist in which optical measurements employing indicators can be used advantageously. One

                                      Preparatory Problems IChO 2012
instance is the determination of pH in seawater. Because of the high concentration of dissolved
salts, electrode-based pH determinations in seawater suffer from systematic errors that are too
large for some applications. An example is determination of PCO2-driven pH changes in the
ocean. Anthropogenic CO2 releases cause an annual pH shift in North Pacific surface waters of
only about –0.0017.
   Thymol blue (molar mass 466.59 g·mol–1) is a dye that is a diprotic acid. The concentration of
the non-ionized form, H2In0, is negligible near seawater pH and can be neglected. At 298K, the
second ionization constant of thymol blue, corrected for the salinity of seawater, is Ka2 = 10–8.090.
Molar absorption coefficients (ελ) of HIn– and In2– at two wavelengths (λ) are as follows:

                         Species     ε436 nm (L·mol–1·cm–1)     ε596 nm (L·mol–1·cm–1)
                           HIn–              13900                       44.2
                           In2–               1930                      33800

Measurements were made on a sample of seawater contained in a 10.00 cm optical cell:
                                                      Absorbance 436 nm         Absorbance 596 nm
      Sample alone                                            0.052                   0.023
      Sample plus thymol blue indicator solution              0.651                   0.882

Calculate the pH and the molar concentration of thymol blue in the sample. Because the value of
Ka2 has been salinity corrected, activity coefficients should be neglected (i.e., considered to equal

Problem 11. Solution Equilibria

Lead chromate has been widely used as a paint pigment, although this usage has been curtailed
by environmental concerns in recent decades. Both components of this compound are hazardous
to human health. Chromate is of particular concern because it is extremely mobile in
groundwater. Therefore, humans can be exposed when they drink water from wells that are
located at great distances from industrial sources of chromium.
a) Suppose that PbCrO4(s) in a landfill dissolves to equilibrium in a groundwater that has
   pH = 6.000. Using the following equilibrium constants, calculate the equilibrium
   concentrations of Pb2+, CrO42–, HCrO4– and Cr2O72–.

                                           Preparatory Problems IChO 2012

             Quantities in parentheses () below are concentrations in mol·L–1. Assume that activity
             coefficients of all dissolved species equal 1.00 and therefore can be ignored.

b) A toxicologist wishes to know at what total dissolved chromium concentration (CrT) the
     equilibrium concentration of HCrO4– equals that of Cr2O72– in the human stomach. Supposing
     that stomach fluid can be represented as a dilute solution with pH = 3.00, calculate CrT.

Problem 12. First Order Rate Processes and Radioactivity

In nature, the long-lived radioactive elements, Th and U, give rise to sequences of shorter-lived
radioactive isotopes. If nuclear decay occurs in closed systems, activities of daughter nuclides
become equal to parent activities on a time scale related to the daughter’s half-life. Departures
from this rule indicate that other processes in addition to radioactive decay are affecting the
daughter’s abundance. Opportunities to identify and study the rates of these processes arise.
     In water from a lake, the rate of radioactive decay of dissolved 222Rn (half-life, t½, 3.8 d) is
found to be 4.2 atoms·min–1·(100 L)–1. All of this 222Rn is produced by decay of dissolved 226Ra
(t½ 1600 y), which has an activity of 6.7 atoms min–1 (100 L)–1. These activities do not change
measurably with time. Because every atom of 226Ra that decays produces an atom of 222Rn, the
deficit in 222Rn activity implies that 222Rn is being lost from the lake by an unknown process in
addition to radioactive decay.
a) Calculate the concentration of 222Rn in the lake in units of both atoms (100L)–1 and moles L–1.
b) Supposing that the unknown process obeys a first order rate law, calculate the rate constant
     for this process in units of min–1.
c) Based on periodic properties of elements, is the unknown process most likely a biological,
     chemical or physical process?
d)         Rn decays exclusively by alpha emission. Identify its radioactive decay product (including
     the mass).

                                                Preparatory Problems IChO 2012
Problem 13. Kinetics and Mechanisms of Isomerization of an Octahedral Metal Complex

Coordination complexes of the transition metals can undergo a variety of reactions. Among these
are electron transfer, substitution, rearrangement, and reaction at a coordinated ligand. Some of
these reactions have been thoroughly studied and their mechanisms are generally well
understood. This question examines the kinetics of the isomerization of a six-coordinate complex
and uses the steady state approximation to develop rate laws for two possible pathways of
       The cis isomer of the cation [Co(en)2Cl2]+ (where en = ethylenediamine) can be
converted to the trans isomer in the presence of Cl– ion by two possible mechanisms: a)
Associative and b) Dissociative.

            Associative Mechanism
                      Cl          +                                                       Cl         +
              NH2            Cl                 k1                         k2   NH2            NH2
                     Co               + Cl–              [Co(en)2Cl3]                    Co          + Cl–
              NH2          NH2                  k-1                             NH2
                    H2N                                 Assoc. Intermed.                  Cl

                cis isomer                                                            trans isomer

        Dissociative Mechanism
                      Cl          +                                                       Cl         +
              NH2            Cl           k1                               k2   NH2            NH2
                     Co                          [Co(en)2Cl]2+ + Cl–                    Co
             NH2           NH2            k-1                                   NH2
                                                Dissoc. Intermed.                              NH2
                    H2 N                                                                  Cl

                cis isomer                                                            trans isomer

        H2N         NH 2 = ethylenediamine, NH 2–CH2CH2–NH2

a) For each of the mechanisms above derive the rate law using the steady state approximation.
b) Show what happens to each of the rate laws when (i) the first step is rate-limiting and (ii)
   when the second step is rate-limiting.
c) Derive an equation for the observed rate constant, kobs, in each of the four cases.
d) Is it possible to tell which is the rate-determining step in the associative mechanism based on
   the observed rate law?

                                        Preparatory Problems IChO 2012
Problem 14. Metal Phthalocyanines: Mechanism of Reduction

Phthalocyanines and their metal complexes were discovered in 1920 by accident, when 1,2-
dicyanobenzene (phthalonitrile) was heated in a copper jar. An amazingly thermally stable blue
powder was collected. Besides thermal stability, metal phthalocyanines also have a property of
being excellent catalysts of a number of oxidation reactions. This feature of phthalocyanines is
due to the ability of the dianionic phthalocyanine (Pc) ligand to stabilize metals in various
oxidation states; this is illustrated by the following problem.
a) Given the atom connectivity in a metal-free phthalocyanine molecule provided below, draw
   the structure of iron(III) phthalocyanine chloride, with a correct pattern of double bonds.

b) Dithionite anion occurs in aqueous solution at equilibrium with its monomer, SO2–, a free
   radical species. Draw the Lewis structure of dithionite anion and write a reaction of its
   dissociation into SO2–.
c) Another reduced sulfur species, sodium hydrosulfoxylate, NaHSO2, is also known. Show
   which common sulfur species can be used to synthesize sequentially both a metal dithionite
   anion and a hydrosulfoxylate anion using suitable reducing agents.
d) This question concerns the dithionite reduction of phthalocyanine complexes.
      i. The following kinetic equation was obtained for the iron(III) phthalocyanine (PcFeIII)
         reduction to iron(II) phthalocyanine by dithionite:
       S2O42– + PcFeIII  PcFeII + sulfur containing products; the reaction is relatively fast.
       rate1 = k [PcFeIII][S2O42–]
      ii. By contrast, for the iron(II) phthalocyanine reduction to iron(I) phthalocyanine the
       following kinetic equation was obtained:
       S2O42– + PcFeII  PcFeI + sulfur containing products; the reaction is very slow.
       rate2 = k [PcFeII][S2O42–]0.5.

                                     Preparatory Problems IChO 2012
      iii. For cobalt(II) phthalocyanine reduction with dithionite to Co(I) phthalocyanine, yet
       another kinetic equation could be obtained:
       S2O42– + PcCoII  PcCoI + sulfur containing products; the reaction is slow.
       rate3 = k3 [S2O42–]
   Propose mechanisms for the reactions above that would allow you to account for the
   difference in the observed kinetic orders.

Problem 15. Isotope Effects in Azo Coupling Reactions

Because chemical reactions depend principally on electrostatics, different isotopes of the same
element generally have almost indistinguishable chemical properties. However, when the
fractional difference in mass is large, the slight dependence of chemical properties on nuclear
mass can result in perceptibly different reactivities. This is most commonly observed with
isotopes of hydrogen, with compounds of protium ( 1H) often displaying quantitatively distinct
reaction rates compared with those of deuterium ( 2H, abbreviated D) or tritium (3H,
abbreviated T). In particular, the reduced masses of bonds to hydrogen, and thus the quantum
mechanical zero-point energies of vibrations involving these bonds, E0 =       h, where
=        with k being the force constant of the bond to H and  = reduced mass =
                                                                                       m1  m2
with m1 and m2 the masses of the two bonded atoms, depend significantly on the mass of the
hydrogen isotope. Heavier isotopes have larger reduced masses and lower zero-point energies.
If a bond to hydrogen is broken during an elementary reaction, the vibrational frequency of the
bond in the transition state, and hence its zero-point energy, is very low. Since compounds of
all hydrogen isotopes therefore have similar or identical energies in the transition state, but
heavier isotopes have lower energies in the reactants, compounds of protium will have a
smaller activation energy and, therefore, react faster than those of deuterium or tritium. The
ratio (kH/kD), called a primary kinetic isotope effect when a bond to hydrogen is broken, is
often in the range of 5–8 at ambient temperatures. Secondary kinetic isotope effects, where a
bond remote to the site of isotopic substitution is broken, are typically much smaller, usually
with kH/kD < 1.4.
   Kinetic isotope effects have proven invaluable in the study of reaction mechanisms because
of their ability to shed light on the details of processes that make or break bonds to hydrogen.
A classic example is the study of the reaction between 2-naphthol-6,8-disulfonate and
                                    Preparatory Problems IChO 2012
4-chlorobenzenediazonium ion to form a highly colored azo dye:
                                   O3S            H/D                        N2

                                                                 +                      3

                                             1                               Cl

a) Propose a synthesis of 4-chlorobenzenediazonium ion 2 from benzene.
b) Propose a structure for compound 3 (with H in 1), and explain the selectivity of the reaction.
c) The kinetics of the reaction between compound 1H (compound 1 with hydrogen
  substitution) and compound 2 was studied in buffered aqueous solution (pH = 6.6) in the
  presence of variable amounts of pyridine. The reaction was found to be first order in both
  1H and in 2 under all conditions. Describe in detail the experiments by which one could
  measure the second-order rate constants and determine the order of the reaction in each
d) In the absence of pyridine, the reaction between 1H with 2 is faster than the reaction of 1D
  with 2 (k1H/k1D = 6.55). In contrast, the analogous reaction between 4 and 5 shows no
  discernible isotope effect (k4H/k4D = 0.97). Explain these results.
                                                        +                         6

                                         4                              5

e) The second-order rate constants of reaction of 1H and 1D with 2 are tabulated as a function
  of pyridine concentration in the table below. Account for the variation of rate and isotope
  effect with [py], both qualitatively and quantitatively. (The pyridine concentrations listed
  are those of the free-base form of pyridine, they have been corrected for the protonation of
  pyridine at pH 6.6).
             [py], mol L–1    k1H, L mol–1 s–1                       k1D, L mol–1 s–1          kH/kD
              0.0232            6.01                                  1.00                  6.01
              0.0467            11.0
              0.0931            22.4
              0.140             29.5
              0.232             46.8
              0.463             80.1
              0.576             86.1
              0.687             102.
              0.800             106.
              0.905             110.                                  30.4                  3.62

                                       Preparatory Problems IChO 2012
f) Predict the variation of the rate constant for the reaction of 4H with 5 as pyridine
  concentration is increased.
g) Explain the observed variation of the isotope effect of reactions of 1 with the structure of the
  diazonium salt used (all reactions in the absence of pyridine):

Diazonium ion:        N2         N2          N2


                      Cl                     NO2

k1H/k1D:            6.55        5.48        4.78

Problem 16. Fluorescent Lamps: Heating Inert Gas Atoms by Electrons

Fluorescent lamps provide around 80% of the world’s needs in artificial lighting. They
consume several times less energy per light output than incandescent light bulbs, and hence are
important in the fight to reduce world’s energy consumption. Fluorescent lamps are filled with
low pressure noble gas, such as argon, and also mercury vapor at even lower pressure.
Electrical discharge in fluorescent lamps causes partial ionization of Hg, resulting in
emergence of electrons and equal number of ionized Hg atoms. Collisions of electrons with
neutral Hg atoms lead to the electronic excitation of the latter atoms, which emit UV light
when decaying back to the ground state. The UV light strikes the glass surface of the tube
covered with a phosphor, which produces a glow of visible light that we can see.
  The electric field between the tube cathode and the anode continuously transfers energy to
the electrons. The electrons redistribute the energy among themselves, quickly reaching the
temperature on the order of 11,000 K. Similarly, neutral Ar atoms also quickly equilibrate
thermally among themselves. However, because of a very large mass mismatch between
electrons and argon, collisions between electrons and Ar atoms are extremely inefficient in
transferring the electrons’ energy to Ar atoms. Hence, the argon temperature in a tube is much
lower than the electrons’ temperature.
  Using the steady state approximation, find the steady state temperature of neutral Ar gas in
middle column of the fluorescent lamp, given that electrons’ temperature, Te, is 11,000 K and
the temperature of the outer tube wall, Twall, is 313 K.

In all calculations use the following specific parameters describing a typical fluorescent lamp
having dimensions of 120 cm in length and 3.6 cm in diameter, and Ar pressure of 3 Torr
                                      Preparatory Problems IChO 2012
(1 Torr = 1 mm Hg; 1/760th of 1 atm pressure).
a) What is the total frequency, , of electron-Ar collisions in the tube having volume of
   4.9·10–3 m3 and concentration of free electrons ne = 5.0·1017 m–3, if the mean collision time
   of an electron with Ar atoms is = 7.9·10–10 s?
b) What is total rate of energy transfer from electrons to Ar in the tube, Je-Ar, in Joule·s–1?
   Assume that only a small fraction of electron’s energy, fe->Ar = 2.5·10–5, is transferred to an
   Ar atom per single collision, and the average energy of electrons and Ar atoms is              ,

   where kB is the Boltzmann constant and T is the corresponding temperature. Note that in a
   collision between an electron and Ar atom, the energy is transferred in both directions.
Assuming a linear drop of temperature from the tube center of the wall, the total thermal
energy transfer rate from heated Ar gas in the middle to the tube wall is

                                    , where Ar is the thermal conductivity of argon,

Ar = 1.772·10–4 J·s–1·m–1·K–1, Rtube is the tube radius, Rtube = 3.6 cm, and St indicates the total
area of the tube whose length is 120 cm.
c) At the steady state, derive an expression for the temperature of the neutral Ar gas in the
   fluorescent lamp tube, TAr.
d) Compare the energy loss through the heat transfer by Ar atoms to the tube walls with the
   total energy input of a 40 W fluorescent lamp (1W = J·s–1 ).
e) Recalculate TAr for the Ar pressures of 1 and 10 atmospheres, respectively. The only change
   in the parameters above will be in , which is inversely proportional to the pressure,  ~ P–1.
   The thermal conductivity of Ar, Ar, is independent of pressure in this regime of pressures.

Problem 17. Molecular Motors

Molecular motors are ubiquitously used by cells for many purposes, including transporting
various cargos from one part of the cell to another. One important motor protein is kinesin,
which walks on filamentous tubes called microtubules made of another protein tubulin. In fact,
kinesin is an enzyme, an ATPase, powered by hydrolysis of adenosinetriphosphate, ATP.

                                      Preparatory Problems IChO 2012

Consider placing a macroscopically long microtubule into a solution of free kinesin, Pfree, with
the concentration [Pfree] and assume that there is equilibrium between tubule-bound kinesin
(Pbound), free kinesin and binding sites (Site) available on the surface of the microtubule:
                                      Pbound         Pfree + Site
The occupancy of single binding sites by kinesin molecules is governed by the law of mass

where [Site] is the total concentration of binding sites on the microtubule, [Pbound] is the
concentration of the kinesin molecules bound to the microtubule, and Kd is the equilibrium
   When the kinesin molecule is bound to a microtubule, it moves unidirectionally along its
surface with a speed, v = 640 nm/s.
   Imagine a geometric plane, which is oriented perpendicular to the microtubule and
intersects the microtubule at some specific position along the tube. This plane is called a cross
section. Estimate the rate of passage of kinesin molecules through an arbitrary cross section of
the microtubule in units of kinesin molecules per second. This rate of passage of kinesin
molecules is related to the rate at which the microtubule–derived nanomotor moves in one or
another direction. Use the following information:
       There are n = 16 kinesin binding sites per each l = 5 nm length of the microtubule.
       Kinesin molecules move independently of each other.
       Assume that kinesin molecules bound on the microtubule sites and free kinesin
          molecules in solution are in a dynamic equilibrium.
       Use the following parameters: Kd = 0.5∙10–6, [PFree] = 100 nM, and [Site] = 10 μM.

                                      Preparatory Problems IChO 2012
Problem 18. Particles in a Box Problem and Conjugated Polyenes

The energy levels of -electrons in molecules with conjugated bonds can be calculated with
varying degrees of accuracy, depending on the complexity of the model. The most sophisticated
and accurate approaches involve complex theoretical methods for solving the multi-particle
Schrödinger equation. A simplified yet still powerful approach is to treat the -electrons as
independent “particles in a box.” This model is useful for determining the energies of -electrons
and the electronic spectra of such molecules as ethylene or molecules with conjugated double
bonds. In this problem, use the “particle in a box” model to describe the -electron states of
ethylene as well as linear and cyclic conjugated molecules.
       The particle in a box model yields the energy levels for -electrons by treating them as
moving freely along the length of the conjugated -bonds. An example of a hydrocarbon with a
non-branched chain of conjugated -bonds is trans-1,3,5-hexatriene shown below.

       The allowed quantum states occur for electronic wavefunctions that have wavelengths of
 = nL/2, where n is an integer starting with n = 1 and L is the length of the molecule. The
effective molecule lengths are L = 289 pm for ethylene and L = 867 pm for trans-1,3,5-
hexatriene. The allowed energy states for the -electrons are given by Eq. 1.

                                       En                                          (Eq. 1)
                                              8me L2
       In Eq. 1, n is the quantum number for the energy state and is an integer between 1 and ∞,
h is the Planck’s constant in J∙s, me is the mass of the electron in kilograms and L is the length of
the box in meters. Use two significant figures for your calculations.
a) Use the particle in a box model to determine the following:
       i. the first two energy levels for the -electrons in ethylene;
       ii. the first four energy levels for the -electrons in 1,3,5-hexadiene.
b) For each species, fill the energy levels with the -electrons, keeping in mind the Pauli
   principle for electron pairing. Identify the quantum number n of the highest occupied energy
   level of each species.

                                      Preparatory Problems IChO 2012
c) Use the highest occupied and lowest unoccupied energy levels to predict the wavelength of
   light that can be used to excite a -electron from the highest energy occupied state to the
   lowest energy unoccupied state for each species.
d) The molecule in carrots that makes them appear orange is -carotene. Use the particle in a
   box model to predict the energy gap between the highest occupied state and the lowest
   unoccupied state. Use this energy to determine the maximum wavelength for absorption of
   light by -carotene. Use a length for -carotene of L = 1850 pm.

       Some molecules have cyclic conjugated -systems. Benzene and coronene are examples
of such molecules.

       For molecules with “circular” -electron distributions, the quantized energy levels are
given by Eq. 2.
                                       En                                         (Eq. 2)
                                              8 2me R 2
       In this case, the quantum number n has integer values between 0 and  and R is the
radius of the ring in meters. Unlike the linear particle in a box problem, the circular problem
allows for both positive and negative integer values for n for clockwise and counterclockwise
motion. Also, for the circular problem, n = 0 is an eligible quantum state. For this problem,
assume that the ring radii are 139 pm for benzene and 368 pm for coronene.
e) Describe the benzene’s -electron system using the particle-in-the-ring equation for energy
   levels. Draw a diagram depicting all occupied energy levels as well as the lowest-unoccupied
   energy level. When building the energy levels, keep in mind the Pauli principle for electron
   pairing and that there may be several states with the same energy referred to as degenerate

                                        Preparatory Problems IChO 2012
   states. Make sure that you use the right number of  electrons. Use two significant figures in
   your answers.
f) Now, draw a similar energy level diagram for coronene and calculate the quantized energy
   values for the occupied energy levels and the lowest unoccupied energy level. Use two
   significant figures in your answers.
g) Calculate the energy gaps between the highest occupied and lowest unoccupied energy levels
   for benzene and coronene.
h) Predict whether benzene or coronene is colored. The recommended way is to determine the
   longest wavelength of light absorption in nanometers (with two significant figures) for each
   molecule assuming that the electronic transition responsible for it is one between highest
   occupied and lowest unoccupied energy levels of each particular molecule.

Problem 19. Toluene in a Superacid Solution

Dissolving toluene in a mixture of HF–SbF5 generates species B which has a temperature
dependent 1H NMR spectrum (60 MHz) shown below. The upper figure shows the entire
spectrum at –97 oC with the following parameters (chemical shifts are given in the ppm scale,
: 9.38 (d, 2H), 8.40 (d, 2H), 5.05 (m, 2H), 3.30 (t, 3H). The lower figure shows the signals from
the upper figure in the range of 5–10 ppm as the temperature is raised.


a) Provide a structure for B consistent with the –97 °C spectrum.
b) Assign each of the peaks in the –97 °C spectrum to the corresponding proton(s) in your
   structure for B.
c) Provide structures and/or chemical equations that explain why the spectrum changes with
   increasing temperature. Label your structures.
d) On the basis of the data provided and theoretical considerations, predict qualitatively the
   relative stabilities of your structures.
e) The peak at 3.30 ppm in the –97 °C spectrum corresponds to a methyl group. Why is it a
   triplet (J = 4.4Hz)?

Preparatory Problems IChO 2012

                                                      Preparatory Problems IChO 2012
Problem 20. Mechanism of Catalysis by Lactate Dehydrogenase

The structures of the 20 amino acids found in proteins are shown in the Figure at the end of this
The enzyme lactate dehydrogenase (LDH) catalyzes the reversible reduction of pyruvate anion to
lactate anion, with NADH as the reducing agent. The reaction is formally the transfer of hydride
ion (H ¯) from NADH to pyruvate:
                                                        NH2                                                                     NH2
                                                O                                                                           O
               H3C       CO2-
                                                  H                                          H3C              CO2-
                                   + H+ +                        N       R                                              +              N   R
                     O                            H
                 pyruvate                               NADH                                        lactate                     NAD+

       The enzyme also catalyzes a reaction of sulfite (SO32-) and NAD+:
                                                        NH2                                                       NH2
                                                O                                                        O

                                SO32-       +                    N       R
                                                                                                                        N   R

       The structure of the substrates pyruvate and NADH bound in the active site of LDH is
shown schematically in Scheme 1. Several key amino acid residues in the active site are
indicated. The dotted lines between fragments of LDH indicate weak intermolecular interactions
among groups in the active site.
                                                                     Scheme 1
                                                                             Gln-102                Thr-246
                                                                     O             NH2       H3C            OH
                                                  H2N        NH
                                                             H               CH3
                                    His-195                      O           C                          N     R
                                                        N    H                           H
                                                N                    O            O              Dihydronicotinamide
                                            H                                          O
                                                                     H            H          NH2
                                   O        O                    HN               NH
                                                                                           H3C          C2H5

                                        Asp-168                              NH
                                                            Arg-171                                Ile-250

       The pH dependence of the rate of the reactions catalyzed by LDH was determined with
pyruvate and NADH as the substrates for the forward reaction, and with lactate and NAD+ as the
substrates for the reverse reaction. The data indicate the participation in catalysis of a group with
pKa = 7, which corresponds to His-195 of LDH.
       The pH vs. reaction rate [log(kcat/Km)] curves were different depending on whether the
rate of the forward (pyruvate + NADH) or reverse (lactate + NAD+) reaction was measured, as
shown in Figure below.
                                                    Preparatory Problems IChO 2012

log (k cat /Km)   A                                                               B

                                                           log (k cat /Km)
                        5     6     7     8     9    10                               5   6   7    8   9   10
                                    pH                                                        pH
a) Which curve in the Figure above corresponds to the reaction with pyruvate and NADH?
            Which curve corresponds to the reaction with lactate and NAD+?

                  As shown in Scheme 1, the side chains of Arg-109 and His-195 are very close to the
carbonyl group of pyruvate.
b) What type of weak intermolecular interactions exists between Arg-109 and the carbonyl group
            of pyruvate, and between His-195 and the carbonyl group of pyruvate? What is the electronic
            basis of this interaction?

                  The side chain of Ile-250 lies directly below the plane of the dihydronicotinamide ring of
NADH (Scheme 1).
c) What type of intermolecular interaction would the side chain of Ile-250 make with NADH?

                  The function of Arg-109 in catalysis by LDH was investigated by site-directed
mutagenesis. Arg-109 was changed to glutamine, and the catalytic activity of the mutant enzyme
was studied. The results were:
                       The rate of the (pyruvate + NADH) reaction catalyzed by the mutant enzyme was 1400-
                        fold less than the reaction catalyzed by the wild-type enzyme.
                       The ability of the mutant enzyme to bind pyruvate in the active site was also reduced,
                        but by only about 15-fold compared to the wild-type enzyme.
                       The rate of the reaction of sulfite with NAD+ was unaffected by the mutation.
d) Given the observations above, what is the function of Arg-109 in catalysis by LDH?

                      The side chain of Asp-168 is thought to interact non-covalently with the side chain of
His-195 (see Scheme 1). Two hypotheses were proposed for the function of Asp-168 in catalysis
by LDH:

                                       Preparatory Problems IChO 2012
  1) The interaction between Asp-168 and His-195 might serve to hold the His-195 in the
  correct position to interact with pyruvate.
  2) The interaction between Asp-168 and His-195 might serve to polarize His-195, which
  would make His-195 a stronger base.
  To test these possibilities Asp-168 was changed to Ala (Mutant 2), and to Asn (Mutant 1), and
the catalytic properties of the mutant enzymes were compared to those of the wild-type enzyme.
  The results are summarized in the following table:

  Constant       Wild-type     Mutant 1      Ratio:           Mutant 2         Ratio:
                                          Wild-type /                         Wild-type /
                 (Asp-168)     (Asn-168 )                     (Ala-168 )
                                           Mutant 1                           Mutant 2
                                   Forward reaction:
Km (pyruvate),      0.06           10           0.006             3.3            0.018
   kcat, s–1        250            20            12.5             5.5              45
   kcat/Km,        4.2·106       2·103          2080            1.7·103           2500

                                    Reverse reaction:
 Km (lactate),       40           120            0.33             80               0.5
   kcat, s–1          9           0.12            75             0.09             100
   kcat/Km,        2.2·102         1             225             1.13             200

e) Given the facts above, which of the proposed functions, (1) or (2), of Asp-168 is better
supported by the data?

                                         Preparatory Problems IChO 2012
The 20 amino acids found in proteins (side chains are shaded in gray).

Problem 21. Substrate Specificity of Subtilisin

See the Figure in Problem 20 for the structures and 3-letter abbreviations of amino acids.
Subtilisin is a serine protease produced by the bacterium Bacillus amyloliquefasciens that
catalyzes hydrolysis of peptide bonds in proteins:
                         O       R                         O                    R

                                         + H2O                       +
                             N                                 O-         +
                     R                                 R

       More generally, serine proteases catalyze transfer of an acyl group from a donor molecule
such as an amide or ester RCO-L, to an acceptor nucleophile such as water, Nuc:
                             O                                 O

                                         + Nuc                            + L
                         R           L                     R        Nuc

                                       Preparatory Problems IChO 2012

The Figure below shows a schematic of a peptide substrate bound in the active site of subtilisin
(the gray surface represents the enzyme itself). Ser221 and His64 are two amino acid residues in
the active site that are essential for catalysis of peptide bond hydrolysis.

        Subtilisin has an extensive substrate binding site in which are bound four amino acid
residues on the N-terminal side of the peptide bond that is hydrolyzed. The side chains of these
four residues are bound in four “subsites” in the enzyme, called S1–S4. Amino acid residues of
subtilisin whose side chains project into the sub-sites are indicated in the Figure above: Gly166 in
subsite S1, Asn62 in subsite S2, and Tyr104 in subsite S4. The chemical and structural properties of
these residues from the enzyme determine which peptide substrates are bound and hydrolyzed by
the subtilisin.
        The peptide-p-nitroanilide substrate with the sequence: Ala-Ala-Pro-Phe-p-nitroanilide
is hydrolyzed rapidly by subtilisin because the four amino acid residues in the substrate fit well
into the binding sub-sites (the Ala-Ala-Pro-Phe residues are bound in subsites S4–S1,
   Site-directed mutagenesis can be used to change residues in the binding subsites of subtilisin
to alter the substrate specificity of the enzyme. In one experiment, Gly166 was changed to Ile
(Gly166Ile mutant) and the catalytic activity of the mutant enzyme was tested with the following
peptide substrates:
                                       Preparatory Problems IChO 2012
               I       Ala-Ala-Pro-Phe-p-nitroanilide
               II      Ala-Ala-Pro-Ala-p-nitroanilide
               III     Ala-Ala-Pro-Glu-p-nitroanilide
               IV      Ala-Ala-Pro-Tyr-p-nitroanilide
a) Which peptide would be hydrolyzed most rapidly (highest kcat/Km) by the Gly166Ile mutant

      In a second experiment, residues in subsites S1, S2, and S4, were changed to aspartate,
either individually or in combinations. The mutants that were made are:
       Mutant 1:       Gly166 to Asp
       Mutant 2:       Gly166 to Asp and Asn62 to Asp
       Mutant 3:       Gly166 to Asp, Asn62 to Asp, and Tyr104 to Asp
       The catalytic activity of the mutant enzymes was tested with the following peptide-p-
nitroanilide substrates:
               I       Ala-Ala-Pro-Phe-p-nitroanilide
               V       Ala-Ala-Lys-Phe-p-nitroanilide
               VI      Arg-Ala-Lys-Arg-p-nitroanilide
               VII     Arg-Gly-Lys-Glu-p-nitroanilide
               VIII    Ala-Ala-Pro-Arg-p-nitroanilide
               IX      Ala-Gly-Glu-Arg-p-nitroanilide
               X       Phe-Gly-Lys-Arg-p-nitroanilide
               XI      Leu-Gly-Phe-Arg-p-nitroanilide
               XII     Ala-Ala-Lys-Arg-p-nitroanilide
               XIII    Arg-Gly-Ala-Arg-p-nitroanilide
               XIV     Arg-Gly-Lys-Phe-p-nitroanilide
b) Which substrate would be hydrolyzed most rapidly by each mutant enzyme?

Problem 22. Electro-spray Ionization Mass-spectrometry of Peptides

The pioneering work of John Fenn (2002 Nobel Prize) on the use of electrospray ionization (ESI)
for mass spectrometry opened new possibilities for analyzing biologically important non-volatile
molecules. ESI has since been used in numerous biological applications, resulting in emergence
of proteomics that aims at large-scale characterization of proteins in organisms.

                                             Preparatory Problems IChO 2012
       A bio-analytical chemist considered the use of ESI mass spectrometry to measure the
relative abundance of myoglobin in two protein mixtures. Realizing the challenges of whole
protein analysis, this chemist decided to reduce the problem to the peptide level. The relative
concentrations of a peptide in two samples can be measured by isotope tagging. Consider the
analysis scheme described below.
      First, the proteins in two samples were digested using trypsin, and the digested samples
were lyophilized (the solvent was evaporated, leaving behind the peptides). For isotope tagging
of the peptides two methanolic solutions were prepared by dropwise addition of 160 µL of acetyl
chloride to methanol cooled in an ice bath using 1 cm3 of CH3OH in one case and 1 cm3 CD3OH
in the second case.
a) Write equation(s) for the chemical reaction(s) involved in the preparation of methanolic
  solutions of acetyl chloride.
       The CH3OH solution was added to the digested lyophilized peptide sample 1. The
CD3OH solution was combined with digested lyophilized peptide sample 2. After 2 hours both
methanolic solutions were evaporated to dryness. 10 µL of 0.1% acetic acid in water was used to
dissolve each of the residues and the resulting solutions were mixed. The mixture was then
injected into a high-performance liquid chromatography-ESI mass spectrometer where the
tagged peptides were separated and detected by a mass spectrometer.
       The summary of the workflow is shown below:

                                  Sample 1                             Sample 2

                                                1) Tryptic digestion
                                                2) Lyophilization

                                  Digest 1                             Digest 2

                      CH3OH solution                  2 hours                CD3OH solution

                                   Tag 1                                Tag 2

                                               1) Lyophilization
                                               2) 0.1% AcOH in water

                                   Mix 1                                 Mix 2

                                              HPLC-ESI-MS analysis

                                      Preparatory Problems IChO 2012
b) What chemical modification of peptides occurs in isotopic tagging reactions, resulting in Tag
  1 and Tag 2? What is the role of acetyl chloride?
       Peptides undergo multiple protonation during ionization to form cations with the overall
charge of +1, +2, +3 etc. As a result, a peptide with monoisotopic mass M (molecular mass
based on most abundant isotopes of elements) can produce in its ESI mass spectrum signals of
[M+H]+, [M+2H]2+, and [M+3H]3+ ions. The ion charge (“charge state”) corresponding to a
given peak in a mass spectrum can be determined from the mass-to-charge (m/z) spacing
between the isotopic peaks.
       A series of peaks corresponding to a tagged peptide in the mass spectrum of the mixture
of two samples (Mix 1 and Mix 2) was found at m/z values of 703.9 (100), 704.4 (81), 704.9
(36), 705.4 (61), 705.9 (44), and 706.4 (19). The numbers in parentheses show the relative areas
under the peaks.
c) What is the charge state of the tagged peptide in this series of peaks?
d) Identify the monoisotopic peak corresponding to the light isotope tagged peptide and calculate
  the monoisotopic mass of the tagged peptide based on this peak.
e) Which m/z values have contributions from the heavy isotope tagged peptide?
f) Calculate the monoisotopic mass of the untagged peptide.
       Analysis of the peptide mass and fragmentation patterns led the chemist to the conclusion
that this series of peaks belongs to a tagged peptide originating from myoglobin.
g) Assuming that ionization efficiency is not affected by isotopes, calculate the relative
  abundance of myoglobin in the two protein samples using the relative areas of peaks in the
h) What would the relative peak intensities be if our chemist used 13CH3OH rather than CD3OH?
  The isotopic distribution patterns can be assumed to be the same for 12CH3OH and 13CH3OH
  tagged peptides within the experimental errors of mass spectrometric measurements.
i) Which of the reagents is a better choice for relative quantification of samples: 13CH3OH or

                                        Preparatory Problems IChO 2012
Problem 23. Persistent Carbenes

Compounds of the formally divalent carbon atom having two unshared electrons, either paired or
unpaired, are known as carbenes. Free or metal–coordinated carbenes are often considered as
unstable and short-lived intermediates in a number of organic reactions.
           In the 1950s Ronald Breslow proposed that stable carbenes exist as intermediates in
reactions involving vitamin B1, which occur in human body. The first persistent (stable) carbenes
were isolated in 1990s, and some representatives are shown below. Some stable carbenes now
find applications in chemistry, as organocatalysts and ligands, as well as in coordination
chemistry of metals, and they are available commercially.

a) Draw Lewis structures for the simplest carbene, CH2, the one in which all the electrons are
   paired (singlet carbene), and the one where there are two electrons of the same spin (triplet
b) Draw resonance structures for I–IV that would help you to account for their persistence.
c) Which other factors may be responsible for the persistence of these species?
d) The triplet carbene CH2 is noticeably more stable than the singlet carbene. In contrast, all the
   compounds I–IV above are formally derived from the singlet carbene CH2; their triplet
   analogs are much less stable and have not been isolated. Why?
e) Fill in the structures of the missing compounds A–D in the scheme leading to a persistent
   carbene D:
                 CH3                                               PhNH3Cl
                           BrC2H4OH             I2/PPh3            HC(OEt)3            KOC(CH3)3
    H 3C            NH2                  A                   B                   C                    D
                                                  H                 HCOOH

f) A reaction very typical in carbene chemistry is carbene dimerization which may be reversible.
   Write a reaction scheme for dimerization of I.

                                      Preparatory Problems IChO 2012
Problem 24. The Diels–Alder Reaction

In 1928, Otto Diels and Kurt Alder first reported the reaction that would eventually carry their
names. The reaction between a conjugated diene and a dienophile provides a cyclohexene, as
shown in the simplest example below:

When the reaction partners are substituted, the possibilities increase as asymmetric centers are
formed in the reaction. The Diels–Alder reaction is one of the most useful tools available to a
synthetic organic chemist.
a) E. J. Corey, a professor at Harvard University and recipient of the 1990 Nobel Prize in
   Chemistry, employed the Diels–Alder reaction in his landmark synthesis of the
   prostaglandins. Draw the product of the following reaction and place a star (*) next to the
   chiral centres.

   Due to its popularity, many chemists have sought to produce and employ even more useful
variants of the reaction. Two of the most straightforward are hetero- and retro-Diels–Alder
reactions. In a hetero reaction, one of the carbons in either the diene or dienophile is replaced
with a heteroatom (N, O, S, etc.) such that the 6-membered ring of the product is a heterocycle.
In the retro-Diels–Alder reaction, a cyclohexene transforms to a diene and olefin.
b) Both of these reactions appear in the following reaction sequence towards pseudotabersonine:

      i. Draw the reactive intermediate D, as well as the final product of the reaction E.
      ii. Suggest an “electron-pushing” mechanism for both parts of the transformation.
c) Triazenes are able to provide aromatic rings via a Diels–Alder process. Suggest an electron
   pushing mechanism for the following reaction. Draw the other two products of the reaction:
                                     Preparatory Problems IChO 2012

d) Danishefsky’s diene, named for Samuel Danishefsky of Columbia University, contains acid
   labile functional groups, which can be selectively removed after the Diels–Alder reaction.
   Draw the missing structures in the scheme of Danishefsky’s synthesis of disodium

Problem 25. Pericyclic Reactions and the Woodward–Hoffmann Rules

A pericyclic reaction is a concerted reaction where formation of new bonds and cleavage of
reacting covalent bonds occur simultaneously, without formation of intermediates, via a cyclic
transition state. You have already encountered one of the important groups of pericyclic
reactions in the previous problem: the Diels–Alder reaction. Inspired by aspects of his work on
the synthesis of vitamin B12 in collaboration with Albert Eschenmoser, R. B. Woodward (Nobel
Laureate in Chemistry, 1965) began studies with Roald Hoffmann to understand the principals
which restrict and determine the outcomes of pericyclic reactions.
        Based on deductions from frontier molecular orbital theory, Woodward and Hoffmann
devised a set of rules, for which Hoffmann won the Nobel Prize in Chemistry in 1981, along
with Kenichi Fukui who independently reached similar rules via an alternative methods. These
chemists realized that for thermally–driven chemical reactions, the highest occupied molecular
orbital (HOMO) was the relevant orbital; in photochemically–driven reactions, in contrast, an
electron is excited from the HOMO by light to the lowest unoccupied molecular orbital
(LUMO), making this the relevant orbital.
        Two types of reactions governed by the rules are the Diels–Alder reaction (an example of
cycloaddition) and electrocyclic reactions. For electrocyclic reactions, the Woodward–Hoffmann
rules are:

                                       Preparatory Problems IChO 2012

Number of -Electrons            Thermal                        Photochemical
Involved in the reaction
4n                               Conrotatory                    Disrotatory
4n+2                             Disrotatory                    Conrotatory

These rules predict the stereochemical course of reactions as shown:

a)    Based on these rules, predict the stereochemical outcome of the following electrocyclic


b) These reactions are employed by nature in the synthesis of a class of natural products called
     the endiandric acids. All of the reactions shown below are either electrocyclic or
     cycloadditions (Diels–Alder).
        i. Draw the missing structures (Y, Z, endiandric acids F and G) in the scheme below.

                                            Preparatory Problems IChO 2012
         ii. Fill in the table for reactions (i)–(v):
Reaction               Diels–Alder?         electrocyclic?   Number of        con- or dis-
                                                             electrons         rotatory

      Another interesting result of pericyclic reactions can be found in the bullvalene family of
compounds. The relevant type of rearrangement is the Cope rearrangement, the archetype of
which is shown below:

Although the compounds on both sides of the equilibrium are 1,5-hexadiene, the 13C atoms
(shown as bold dots) show the movement of the electrons, and subsequently relocation of the
          In this synthesis of polyketide natural products, one employs a Claisen rearrangement
(similar to the Cope reaction but with one carbon in the starting material replaced with an
oxygen) and electrocyclizations.

c) This synthesis of the polyketide natural product, SNF4435 C, features a Claisen rearrangement
      oxygen) and electrocyclizations.
         i. Draw the structures of the missing products in the scheme below:

                                      Preparatory Problems IChO 2012

      ii. How many electrocyclizations occur during the step labeled V, which is carried out
       under thermal conditions? Identify each cyclization by the number of -electrons
       involved and as con- or dis-rotatory.

Problem 26. Synthesis of Tetracycline

Tetracycline is a broad spectrum antibiotic that is active against penicillin-resistant Gram-
positive bacterial organisms. The first synthesis of a tetracycline was reported by R. B.
Woodward (Harvard University) and the Pfizer Pharmaceutical Company in 1962. Three of the
four rings were synthesized by the following steps.
   Complete the reactions and identify the structures of compounds A–I.
                                             Preparatory Problems IChO 2012
Hints: (1) the conversion of E to F involves only one methanol reactant; (2) compounds A, B, C,
      D, and E have proton NMR spectra with two hydrogen signals above 7.8 ; these
      absorptions are not present in compounds G, H, and I.
Note: psi = pound per square inch; 1 psi equals 6,894.76 Pascals.

                                   + CH3COOCH3                            A + CH3OH


                  base                       BrCH2COOCH3
       A                            B                                 C
                - (base)H+

                                            base             H3O+
      C         + CH2=CHCOOCH3                         D                  E    + CO2 + 3CH3OH

                   CH3OH                           H2, 200 psi                 Cl2
       E                                F                             G                       H
                 H+(selective                      Pd (catalyst)              -HCl

                   HF                   CH3OOCCOOCH3
       H                       I
                  -H2O                        base
                                                                      OCH3 O             OH

           Cl                                                                                          N(CH3)2
                                                                              H3C        OH
                               COOCH3                                                                       OH

                               OH                                                                                NH2

           OCH3 O        OH                   several steps
                                                                                     O        OH       O    O

Problem 27. Synthesis of Antiviral Drugs

An important class of molecules comprised of both natural and designed products is the
iminosugars. While not true carbohydrates, they are able to mimic sugars, acting as inhibitors of
many enzymes. Due to this ability, they have been shown to have significant activity as
antivirals, as well as in treatments of some genetic disorders such as Gaucher’s disease. Inspired

                                     Preparatory Problems IChO 2012
by the significant activity, a number of synthetic organic chemists have pursued these targets.
Consider two syntheses of the glucose mimic, DNJ.

a) Draw structures of the missing intermediates along their route, A–D:

b) i. Draw the missing intermediates in the synthesis, J–P.

                                     Preparatory Problems IChO 2012
     ii. The triflate group (Tf) transforms a hydroxyl group into a better leaving group. Rank the
       following groups in terms of leaving group ability from best (1) to worst (5).

     iii. Although it occurs in a single flask, the transformation of Q to DNJ can be considered
       to occur in 3 distinct steps. Suggest structures for the two intermediates Q' and Q" that
       arise as the reaction proceeds:

c) Rather than the organic solvents required for the two syntheses of DNJ, the synthesis of this
  furanose-mimicking iminosugar employs only water as the solvent–a fact which makes the
  synthesis cheaper and greener. Draw the missing structures for the intermediates, X and Y,
  that can be isolated as individual compounds and for the transitive intermediate, Z.
  Hint: In this case, the tungsten catalyst selectively provides the (S, S) epoxide of the
  remaining olefin.

                                     Preparatory Problems IChO 2012

                                Practical Problems

The participants of the Olympiad must be prepared to work in a chemical laboratory and be
aware of the necessary rules and safety procedures. The organizers will enforce the safety rules
given in Appendix A of the IChO Regulations during the Olympiad. The Preparatory Problems
are designed to be carried out only in a properly equipped chemistry laboratory under competent
supervision. Since each country has own regulations for safety and disposables, detailed
instructions are not included herein. Mentors must carefully adapt the problems accordingly.
  The safety (S) and risk (R) phrases associated with the materials used are indicated in the
problems. See the Appendix A and B of the Regulations for the meaning of the phrases. The
Regulations are available on the website . Safety cautions for the
practical questions must be provided by the Mentors. Major cautions are:
       • Use fume hoods if indicated.
       • Safety goggles, a laboratory coat and rubber gloves should be worn at all times in the
       • Never pipette solutions using mouth suction.
       • Dispose of reagents into the appropriate labeled waste containers in the laboratory.

                                     Preparatory Problems IChO 2012
Problem 28. Analysis of Sodium Sesquicarbonate (Trona)

                                        An image of trona

The common mineral trona, sodium sesquicarbonate, is used in detergents and in glass making.
The mineral is composed of sodium carbonate, sodium bicarbonate, and water
[xNa2CO3∙yNaHCO3∙zH2O]. The objective of this experiment is to determine the formula of the
  To determine the formula, three experiments can be done. The first is the titration of a sample
of the compound to determine the relative amounts of carbonate and bicarbonate ions.
  x CO32–(aq) + x H+(aq)  x HCO3–(aq)
  (x + y) HCO3–(aq) + (x + y) H+(aq)  (x + y) H2CO3(aq)
A second experiment can be done in which the sample is thermally decomposed to sodium
carbonate, carbon dioxide, and water.
xNa2CO3∙yNaHCO3∙zH2O(s)  [x + (y/2)] Na2CO3(s) + (y/2) CO2(g) + [(y/2) + z] H2O(g)
Finally, a third experiment can be done in which the sample is reacted with aqueous HCl.
  xNa2CO3∙yNaHCO3∙zH2O(s) + (2x + y) HCl(aq) 
                              (2x + y) NaCl(aq) + (x + y) CO2(g) +6y (x + y + z) H2O(liq)
Combining the results of these three experiments will give the values of x, y, and z.

Note: This experiment was adapted from N. Koga, T. Kimura, and K. Shigedomi, J. Chem.
Educ., 2011, 88, 1309.

Chemicals and Reagents
• Sodium sesquicarbonate
• HCl (aq), hydrochloric acid
• Indicators for titration (phenolphthalein and methyl orange)

                                     Preparatory Problems IChO 2012

Table of Chemicals:
Compound           State                   S-Phrase                 R-Phrase
Sodium             Solid, 5 g              2 22 26                  36 37 38
HCl(aq) for        Solution in water, 50   26 36 37 39 45           23 25 34 38
titration          mL; ~0.10 M
HCl for            Solution in water, ~1   26 36 37 39 45           23 25 34 38
decomposition      M, 100 mL

Equipment and Glassware:
      Analytical balance (± 0.0001 g)
      Volumetric flask, 100 mL
      Volumetric pipette, 10 mL
      Pipette bulb or pump
      Erlenmeyer flask, 100 mL (3)
      Burette, 50 mL
      Burette stand
      Hot plate
      Ice water bath
      Bunsen burner
      Crucible
      Crucible tongs
      Beaker, 100 mL (3)


A. Titration of Sodium Sesquicarbonate (SSC) with Hydrochloric Acid
All mass measurements should be done to the maximum allowed number of significant figures.

In this portion of the experiment you will determine the relative amounts of carbonate ion and
bicarbonate ion in a sample of SSC. You will titrate a sample with standardized HCl to a

                                     Preparatory Problems IChO 2012
phenolphthalein endpoint, which indicates when the carbonate ion has been converted to
bicarbonate ion.


Then the resulting solution is further titrated with standardized HCl to a methyl orange endpoint
where bicarbonate ion, from the SSC sample and from the first titration step, has been titrated.


1. Dissolve a weighed amount of SSC (about 2.5 g) in distilled water in a 100.0 mL volumetric
  flask. Mix thoroughly and fill with water up to the mark.
2. Transfer 10.0 mL of the SSC solution to a small Erlenmeyer flask using a 10 mL transfer
3. Add several drops of phenolphthalein solution to the titration sample.
4. Titrate the sample using standardized HCl (~0.1 M, known exactly) until the solution turns
  colorless. Record the volume of the standard solution of HCl required for the titration as V1
5. Add several drops of methyl orange indicator to the solution from step 4. (The solution will
  become light yellow.)
6. Titrate the sample solution with standardized HCl until the solution turns red or red-orange.
  (Note: Students often have problems seeing the methyl orange end point. You should consider
  doing a test sample before trying to carry out an exact titration.)
7. Add boiling chips to the sample solution and heat the solution to boiling for 1 or 2 min. Cool
  to room temperature (using a water bath). If the sample solution turned back to yellow, repeat
  the procedures (6) and (7). If the red coloration did not change, record the volume of the
  standard solution of HCl required for the second titration as V2 mL.
8. Repeat the procedures (2)–(7).

                                       Preparatory Problems IChO 2012
B. Thermal Decomposition of Sodium Sesquicarbonate

In this portion of the experiment you will determine the percent mass loss on heating a sample of
sodium sesquicarbonate. You can combine the results of the thermal decomposition with the
titration results in Part A to determine x, y, and z.

1. Record the mass of a crucible or small evaporating dish.
2. Add approximately 1 g to the crucible or evaporating dish and then weigh the sample and dish
   or crucible precisely.
3. Gently heat the crucible or evaporating dish with a burner flame for 3 min. Then heat with a
   hotter flame until decomposition is complete. (Be careful that solid pieces do not escape the
4. After cooling the crucible or dish to room temperature, determine the total mass precisely.
5. Repeat the steps (1)–(4).

C. Reaction of Sodium Sesquicarbonate with Acid

In the third portion of the experiment you will confirm a value for z in xNa2CO3∙yNaHCO3∙zH2O
by decomposing the sample with acid and calculating the percent mass loss in that reaction.

1. Weigh about 0.5 g of SSC (s) and record the mass precisely.
2. Transfer about 20 mL of 1 M HCl into a beaker and record the total mass of beaker and HCl
3. Add SSC to the dilute HCl little by little, avoiding splashing of the solution.
4. After adding all the SSC, allow the solution to stand for 5 min or so.
5. Record the total mass of the beaker and the resultant solution precisely.
6. Repeat the procedures (1)–(5).

Treatment of Data
Use the results of the three experiments to calculate x, y, and z in xNa2CO3∙yNaHCO3∙zH2O.

                                     Preparatory Problems IChO 2012
Problem 29. Analysis of Copper in a Nickel Coin

United States nickels ($ 0.05 coins) consist of an alloy of nickel and copper (called
“cupronickel”). Cupronickel alloys of similar composition are used for production of coins is
some other countries. In this experiment you will determine the exact mass percentage of
copper in a coin made of a copper-nickel alloy by dissolving the coin in nitric acid and
determining the dissolved Cu(II) by iodometric titration.
• US nickel ($0.05 coin) or other material made of a cupronickel alloy.
• Nitric acid solution, HNO 3 (aq), 8 mol∙L–1
• Sodium thiosulfate pentahydrate, Na 2S2O3∙5H2O
• Potassium iodide solution, KI, 10% w/v
• Starch solution, 2% w/v

Compound          State                     S-Phrase                 R-Phrase
HNO3(aq), 8 M     Aqueous solution          1/2 23 26 36 45          8 35
Na2S2O3·5H2O      Solid                     24 25                    36 37 38
KI                10 %                      26 36 37 39 45           36 38 42 43 61

Apparatus and Glassware
• Analytical balance (± 0.0001 g)
• Hotplate
• Erlenmeyer flasks, 250 mL and 125 mL
• Volumetric flask, 100 mL
• Volumetric pipet, 1.00 mL
1. Weigh the coin and then dissolve it by placing it in a 250 mL Erlenmeyer flask and then
  carefully adding 40 mL nitric acid solution. Heat the flask on a hotplate while the
                                     Preparatory Problems IChO 2012
  dissolution takes place, over ~20 min (the flask should be in a fume hood, as NO 2 gas is
  evolved). After dissolution of the coin is complete, continue to boil the solution for 20 min,
  then allow the flask to cool to room temperature. Dilute the solution to 100.00 mL with
  distilled water.
2. While the nickel is dissolving, make up 50 mL of ~0.04 mol∙L–1 sodium thiosulfate solution.
  You will need to know the exact concentration of this solution; commercial crystalline
  Na2S2O5∙5H2O is sufficiently pure that the concentration can be determined accurately from
  its mass. The thiosulfate solution should be made up fresh on the day of the titration, as it
  degrades over time.
3. Into a 125 mL Erlenmeyer flask add 15 mL 10% (w/v) KI solution, then 1.00 mL of the
  diluted copper-containing solution.
4. Titrate the yellow-orange slurry with the sodium thiosulfate solution until the color has
  faded to pale yellow. Then add 1 mL of the starch solution and titrate to the starch
  endpoint. At the endpoint, the mixture should be milky and white or very pale pink. The
  titration can be repeated on a fresh aliquot of the copper-containing solution, and the results
  averaged, for improved precision.

Questions and Data Analysis
1. Give balanced chemical equations for the reactions that take place when:
     i. The coin dissolves in nitric acid.
     ii. The copper/nickel/nitric acid solution is added to the potassium iodide solution.
     iii. The sodium thiosulfate solution is titrated into the mixture.
2. Calculate the mass percentage of copper in the coin.
3. If the coin is dissolved at room temperature, and the boiling step is omitted, then the amount
  of copper is overestimated, and the endpoint is not stable (the mixture turns white, but then
  spontaneously turns purple again within a few seconds). Explain why.
4. The Canadian nickel coin is mostly steel, with nickel plating and a small amount of copper.
   Could this procedure be used to analyze the copper content of a Canadian nickel coin?
   Explain why or why not.

                                       Preparatory Problems IChO 2012
Problem 30. Synthesis and Analysis of Iron Oxalate Complex

Iron is one of the most important transition metals used in industry. The ability of iron to readily
change its oxidation state accounts for numerous applications of this metal in chemical and
biochemical redox processes. The most common oxidation states of iron are +2 and +3; in both
of these oxidation states, the metal can bind to several (usually up to six) donor atoms, such as
the nitrogen atoms in various amines or organic heterocycles, the oxygen atoms in water or
hydroxide ion, and carboxylates and other similar molecules or anions. In this experiment, an
iron(III) oxalate complex will be prepared in two steps from an iron(II) precursor. Iron(III)
oxalate complex is an interesting compound, in particular, because it is photosensitive. This
compound is used in chemical actinometry for determining the number of photons that passes
through the system. Upon exposure to visible or UV light, green crystals of iron(III) oxalate
complex gradually decompose into a yellow-orange product.
   Upon reacting an iron(II) salt with an oxalate, followed by oxidation in the presence of excess
oxalate, one of three possible iron(III) oxalate complexes could be produced:
                 O                              O                                  O

           O           O                 O                O                 H2O          O
                Fe                              Fe                                 Fe
           O           O                 O                OH2               H2O          OH2

                 O                              OH2                                OH2

        K3[Fe(C2O4)3].3H2O           K[Fe(C2O4)2(H2O)2].3H2O              [Fe(C2O4)(H2O)4](HSO4).3H2O

                                 O          O   O
                                        =                     = oxalate (ox2-)
                                 O          O   O

   The number of oxalate ligands in the iron(III) oxalate complex synthesized in the present
experiment will be determined by titration with potassium permanganate solution.

Chemicals and Reagents
      Ferrous ammonium sulfate hexahydrate, (NH4)2[Fe(H2O)2(SO4)2]∙6H2O
      6 M H2SO4(aq)
      Oxalic acid (H2C2O4), 1M solution (or solid, H2C2O4∙2H2O)
      Potassium oxalate , K2C2O4, 2 M solution (or sodium oxalate, Na2C2O4, 2 M solution)
      Aqueous hydrogen peroxide, H2O2, 6% solution
      Ethanol, C2H5OH

                                       Preparatory Problems IChO 2012
      KMnO4 solution (~0.02 M)

Compound                          State                 S-Phrase             R-Phrase
(NH4)2[Fe(H2O)2(SO4)2]·6H2O       Solid                 24/25                36/37/38
H2SO4(aq) , 6 M                   Solution in water     26 30 45             35
H2C2O4·2H2O                       Solid                 24/25                21/22
K2C2O4, 2 M                       Solution in water     24/25                21/22
H2O2                              6 % solution in       1/2 17 26 28         5 8 20 22 35
                                  water                 36/37/39 45
C2H5OH                            Liquid                7 16 24 25 36 37     11 20 21 22 36 37 38
                                                        39 45                40
KMnO4, 0.02 M                     Solution in water     60 61                8 22 50 53

Equipment and Glassware
      Erlenmeyer flasks, 125 mL (2), 50 mL (1), 25 mL (3)
      Pasteur pipettes and rubber pipette bulbs
      Hot plate
      Graduated cylinder, 25 mL
      Hot water bath
      Ice water bath
      Conical funnel, paper filters
      Fritted funnel for vacuum filtration
      Setup for vacuum filtration (stand, clamps to secure flasks, aspirator, filtering flask,
       conical rubber adaptor).
      Burette, 10 mL, with burette stand
      Small funnel to fill the burette

A. Preparation of iron(III) oxalate complex.
Part A, Step 1
a) In a 25 mL Erlenmeyer flask, dissolve 1.0 g of ferrous ammonium sulfate hexahydrate,
  (NH4)2Fe(SO4)2∙6H2O, in 3 mL of H2O to which has been added 3 drops of 6 M H2SO4.
2. While continuously swirling the flask, add 5.0 mL of 1 M oxalic acid (H2C2O4), and carefully
  heat the mixture to boiling (it is important to continuously swirl the flask while heating).
  Remove the flask from the hot plate and let the solid settle to the bottom of the flask.

                                       Preparatory Problems IChO 2012
3. Separate the solid product from the liquid by decantation: Do not disturb the solid product on
  the bottom of the flask. (Transfer the liquid to an Erlenmeyer flask and label as Liquid Waste).
  To wash the solid product, add ~3 mL of hot water to the flask (heat water in the Erlenmeyer
  flask up to about 80 oC on a hot plate), swirl the mixture, allow the mixture to settle and
  pipette off the liquid layer without disturbing the solid product (transfer liquid to the Liquid
  Waste container). Repeat the washing step one more time.

Part A, Step 2
1. To the wet solid, add 2 mL of 2 M potassium oxalate (K2C2O4).
2. With the flask in a 40 oC water bath, carefully add 2 mL of 6% H2O2 (continuously swirl the
3. Transfer the flask to a hot plate, add 1.5 mL of 1 M oxalic acid (H2C2O4), and bring the
  mixture to a boil. Let the mixture boil for 1 min.
4. Remove the flask from the heat and cool to room temperature.
5. Separate the solid from the liquid using gravity filtration (collect the filtrate in a clean, 50-mL
  Erlenmeyer flask).
6. Cool the filtrate in an ice-water bath. To precipitate the product from the solution, add 8 mL
  of ethanol to the filtrate and swirl the flask.
7. Collect the solid product by vacuum filtration.
8. Air-dry the crystals (alternatively, dry the crystals between two sheets of filter paper).
9. Transfer the dry crystals to a clean, dry pre-weighed vial. Determine the mass of crystalline
  iron(III) oxalate complex produced.

Part B. Analysis of Iron (III) Oxalate Complex
Part B, Step 1 Standardize the ~0.02 M KMnO4 solution.
1. Place ~0.02 M KMnO4 solution into a 10 mL burette. Into a 125-mL Erlenmeyer flask, add
  about 0.020 g of precisely weighed sodium oxalate. To this Erlenmeyer flask, add 20 mL of
  water and 5 mL of 6 M sulfuric acid (H2SO4). Warm up the content of the flask in a hot water
  bath (maintained at ~80 °C).
2. Titrate the sodium oxalate solution using the ~0.02 M KMnO4 solution; stop the titration
  when addition of the last drop of KMnO4 changes the color of the titrated solution to light-
  pink, and the color persists for ca. 1 minute. Record the volume of KMnO4 used for this
  titration, and determine the molarity of KMnO4 solution.

                                      Preparatory Problems IChO 2012
Part B, Step 2
1. Into a 125 mL Erlenmeyer flask, add ~0.020 g of the precisely weighed iron(III) oxalate
  product obtained in Part A. To this Erlenmeyer flask add 20 mL of water and 5 mL of 6 M
  sulfuric acid (H2SO4). Warm the content of the flask in a hot water bath (maintained at
  ~80 °C).
2. Titrate the hot solution in the flask with potassium permanganate of known concentration until
  a slight pink color that persists for ~30 sec. (use the solution standardized in Part B, Step 1).
  Record the volume of permanganate used for titration.

Data Treatment
1. Write down the equation of the chemical reaction that occurs in Part A, Step 1. Explain the
  role of sulfuric acid in this preparative procedure.
2. Calculate the percentage of oxalate in the iron(III) oxalate complex. Determine the
  composition of the synthesized iron(III) oxalate complex (select one of three possible
  structures provided in the Introduction).
3. Calculate the yield of iron(III) oxalate complex you obtained in Part A.
4. Write balanced equations of chemical reactions that were used in Part B, Step 2.

                                     Preparatory Problems IChO 2012
Problem 31. Synthesis and Reduction of an Imine: Green Synthesis of a New Compound

This reaction is an example of a green synthesis of an organic compound. The new functional
group you will generate is important in many physiological processes as well as a crucial
synthetic intermediate for a variety of drugs (e.g., Zetia® for lowering cholesterol, and
Gleevec® and Taxol® for treating cancer). These three drugs alone grossed over $6 billion in
2006, the most recent year for which data were accessible.
   The compounds you are making are traditionally synthesized in solvents such as
dichloromethane or toluene over the course of many hours, often while boiling the reaction
solution the entire time. In contrast, you are performing these same reactions using a benign
solvent with reaction times of less than 15 min at room temperature. Our solvent, ethyl lactate
(EL), is derived from renewable resources and is biodegradable. These reactions have been
optimized previously by adjusting the polarity of the EL with water to attain the best
combination of product quality and reaction speed. A few drops of lactic acid (LA), an acid
found naturally in dairy products and in fatigued muscles, is used as a catalyst in some of the

Chemicals and Reagents
      Ethyl lactate
      Lactic acid
      Sodium chloride
      Substituted aniline (see below)
      Substituted aldehyde (see below)
      Ethanol
      Sodium tetrahydridoborate
      Methanol
      Hydrochloric acid (6 M)
      Dichloromethane
      TLC solvent: 50:50 ethyl acetate/hexanes
                                Preparatory Problems IChO 2012
Table of Chemicals:
Compound                        State         S-Phrase            R-Phrase
Ethyl lactate                   Liquid        2 24 26 39          10 37 41
Ethanol                         Liquid        7 16 24 25 36 37  11 20 21 22 36 37 38
                                              39 45             40
Methanol                        Liquid        1/2 7 16 36/37 45 11 23/24/25
Sodium tetrahydridoborate       Solid         22 26 36 37 39 43 25 34 43
HCl                             6 M aqueous   26 36 37 39 45    23 25 34 38
Dichloromethane                 Liquid        23-24/25-36/37      40
p-Anisidine                     Solid         45 53               45 23/24/25 68
p-Bromoaniline                  Solid         26 36/37/39         20/21/22 36/37/38
p-Chloroaniline                 Solid         53 45 60 61         23/24/25 43 45
p-Ethoxyaniline                 Liquid        28 36/37 45         23/24/25 33
p-Fluoroaniline                 Liquid        26 36/37/39 45      22 34
p-Iodoaniline                   Solid         36/37               20/21/22 37/38
p-Toluidine                     Solid         53 45 61            45 23/25 36 50
p-Nitrobenzaldehyde             Solid         26 28               36 37 38 41
Salicylaldehyde                 Liquid        24/25               21/22
o-Vanillin                      Solid         26 36 37 39         20 21 22 36 37 38
p-(Dimethylamino)benzaldehyde   Solid         22 24/25 26         22 36/37/38
p-Fluorobenzaldehyde            Solid         16 26 36            10 36/37/38
Hexanes                         Liquid        53 45               45 22
Ethyl acetate                   Liquid        16 26 33            11 36 66 67

                                      Preparatory Problems IChO 2012
Table of Suggested Aniline/Aldehyde Combinations and Composition of Solvent (Ethyl L-
Lactate : Water) Used for Reaction
Aniline                         Aldehyde                        Amount of Solvent in mL,
                                                                Fraction of Ethyl L-lactate
                                                                by Volume / Comment
p-Anisidine                     p-Nitrobenzaldehyde             26 mL, 80% / use 23 mL to
(p-methoxyaniline)                                              dissolve the
p-Bromoaniline                  Salicylaldehyde                 5 mL, 80%
p-Bromoaniline                  o-Vanillin                      5 mL, 80%
p-Chloroaniline                 p-Nitrobenzaldehyde             26 mL, 90% / use 23 mL to
                                                                dissolve the
p-Ethoxyaniline                 p-Nitrobenzaldehyde             26 mL, 90% / use 23 mL to
(p-phenetidine)                                                 dissolve the
p-Fluoroaniline                 Salicylaldehyde                 5 mL, 90%
p-Fluoroaniline                 p-Nitrobenzaldehyde             26 mL, 80% with 2 drops
                                                                lactic acid / use 23 mL to
                                                                dissolve the
p-Iodoaniline                   p-Fluorobenzaldehyde            5 mL, 80%
p-Iodoaniline                   o-Vanillin                      5 mL, 80%
                                                                with 2 drops lactic acid
p-Toluidine                     Salicylaldehyde                 5 mL, 80%
p-Toluidine                     p-(Dimethylamino)benzaldehyde   8 mL, 80%
                                                                with 2 drops lactic acid
p-Toluidine                     p-Nitrobenzaldehyde             26 mL, 80% / use 23 mL to
                                                                dissolve the

Equipment and Glassware:
• Graduated cylinders, 10 mL (2)
• Beral pipets (6)
• Beakers, 50 mL (2)
• Hot plate
• Spatulas
• Buchner filter funnel with filter flask and filter paper
• Small flasks for recrystallization (2)
• Melting point apparatus and capillaries
• Small vials with caps (2)
• Vials with caps (preferably without liner), 20 mL (2)
                                      Preparatory Problems IChO 2012
• UV lamps (optional)
• TLC spotters
• TLC plates (silica with fluorescent indicator A254)
• Chamber for TLC development
• Magnetic stirrer
• Ice water bath

Experimental Directions for Imine Preparation:

1. The reactants. Select a pair of reactants.
      i. Calculate the mass corresponding to 0.010 mol for each of your compounds.
      ii. Draw the structure of each compound and of the imine expected from this pair of
2. Begin chilling 50 mL of brine (saturated aqueous NaCl) and 50 mL of distilled water in an ice
3. Reaction solvent. Find the proper solvent ratio for your reaction in the table of reactants
  above. Solvent ratios are expressed as % ethyl (L)-lactate in distilled water. The total volume
  of the solvent is 5.0 mL unless otherwise specified. Measure the volumes of ethyl lactate and
  water in a graduated cylinder. If you need lactic acid (LA), add the indicated number of drops.
  Mix thoroughly.
4. Prepare your reactants. Label two 50-mL beakers. Then, follow the set directions
  corresponding to the phases of your reactants. For the steps marked with an asterisk* check
  volumes in the table of reactants above.

  If two solids:
       Weigh the mass corresponding to 0.010 mol of the aniline directly into a labeled beaker;
  do the same for the aldehyde using a second labeled beaker.
       *Add 2.0–2.5 mL of your solvent to both beakers. Be certain to leave about 0.5–1.0 mL
  solvent on reserve to use as a rinse.
       Warm the beakers gently in the hood to dissolve both solids. This part should only take a
  few seconds. Mix thoroughly, and allow both solutions to cool to room temperature.

                                      Preparatory Problems IChO 2012
  If one solid, one liquid:
       Weigh the mass corresponding to 0.010 mmol of the aniline in a labeled beaker; do the
  same for the aldehyde using a second labeled beaker.
       *Add 3.5 mL of your solvent to the beaker containing the solid. Add 1.0 mL solvent to
  the beaker containing the liquid. Leave the remaining 0.5 mL solvent on reserve to use as a
  rinse. Mix thoroughly. Heat gently to dissolve the solid then allow the solution to cool to
  room temperature. Do not heat the liquid.
  If two liquids:
  do the same for the aldehyde using a second labeled beaker.
       Add 2.0–2.2 mL of your solvent to both beakers. Be certain to leave about 0.6–1.0 mL
  solvent on reserve to use as a rinse. Mix thoroughly. No heat is necessary.
5. Reaction. Do this next step as quickly as possible! Combine the solutions from two beakers
  and swirl a few times to mix. Some of the reactions are complete within seconds. Immediately
  use 0.5 mL solvent to rinse the beakers and add the rinse to the reaction beaker. Quickly, swirl
  the solution in the beaker a few times to make sure it is completely homogeneous. All of step
  5 should be completed in less than 5 s. Record the “combine” time.
6. Observe. Let the reaction mixture sit undisturbed for up to 15 min. Watch carefully, and
  record all observations. Note the exact time you see first crystals, and label this time as “begin
  Once crystal formation appears to be complete, note the time again and label it as “end
  crystallization”. Record the color of the solid at this point.
       Let the reaction sit undisturbed another 5 min. Note whether or not there is a color change
  (some reactions may become a lighter color, and you should indicate this). Then, put the
  reaction beaker in an ice bath for 5 min. Note the times.
7. Wash: Add 10 mL of ice-cold brine to your solid. Use a clean spatula to transfer the solid
  gently in the brine until there are no solid chunks remaining. Some products are very compact,
  and you might need to scrape the surface of the solid gently to avoid chunks. You should end
  up with a suspension.
8. Vacuum filter this mixture.
9. Rinse and vacuum filter again: Rinse the beaker with 10 mL of ice-cold distilled water and
  then pour this liquid evenly over the crystals in your Buchner funnel. This step will ensure
  that the surface of the crystals is rinsed of any compounds adhering to the surface of the
  crystals. Scrape any residue with a spatula and transfer it to the crystals in the Buchner funnel.
                                      Preparatory Problems IChO 2012
  Reconnect the vacuum hose to draw the liquid through the filter. Discard the filtrate into the
  waste container.
10.Recrystallize. Dry your crystals as well as possible on the filter, then recrystallize your crude
  product from ethanol or methanol to obtain a pure sample.
11.Weight and Determine the Melting Point: Allow the recrystallized product to dry as well as
  possible on the Buchner funnel and then obtain the melting point. Weigh your dried product.
12.Fluorescence (optional): Many of the imines have a beautiful fluorescence. To observe this,
  follow the procedure below:
   a)   Transfer pea-sized portions of your crude product into two small vials (with caps). Label
        one vial as “W” and the other as “HCl”.
   b) Add two drops of distilled water to the small vial labeled “W”. Add two drops 6 M HCl
        to the vial labeled “HCl”. Cap both vials tightly and allow the samples to sit undisturbed
        for at least 5 min. (The solids will not dissolve.) Note any color changes. Take the vials
        to a dark room. Turn your vials upside down and evaluate the fluorescence of both
        samples while the room is completely dark. The water-containing vial will serve as the
        control for the acid-containing vial. Record your observations.
   Long wave UV: use the UV lamp set to 365 nm.
  Short wave UV: use the UV lamp set to 254 nm. Do not look into the UV lamp when it is
  on-it can damage your eyes.
Warning: Do not look into the UV lamp when it is on-it can damage your eyes.

                                        Preparatory Problems IChO 2012
Experimental Directions—Imine Reduction:

The toxicities of the imines and amines are unknown. In addition to goggles and a lab coat wear
gloves throughout the experiment.

                                    Y                                                   Y
                                             NaBH4                       H
                      N                                                  N
         X                                                    X

1. Yield and Stoichiometry: Based on the amount of imine to be used, calculate the theoretical
  yield of reduced product.
2. Prepare at least six TLC spotters. Store the spotters in a clean, dry beaker until you are
  ready to use them.
3. Prepare your imine TLC standard: Place about 0.05 g of your imine in a small vial.
  Dissolve in about 2 mL of dichloromethane. Cap tightly to keep the solvent from evaporating.
4. Reduction and Workup:

  a)    Place approximately 0.8–1.0 g of your imine in a 20 mL vial. Record the exact amount
        that you use.
  b)    Leave a small amount of imine in the original vial so that you can do color and melting
        point comparisons later.
  c)    Into a small vial weigh 0.2–0.3 g NaBH4. Cap tightly.
  d)    Add 5 mL methanol to the 20 mL vial with your imine. Add a small magnetic stir bar to
        the vial, cap loosely and begin stirring. The sample will not dissolve but will form a
  e)    With a spatula, add about 1/5 of the NaBH4 to the methanol suspension of the imine.
        Cap the vial LOOSELY. The reaction is exothermic; it is accompanied by evolution of
        hydrogen gas. Capping tightly could result in your vial exploding. Not capping at all can
        result in evaporation of methanol.
  f)    While waiting for the bubbling to end, perform TLC analysis of your imine standard.
        Spot a tiny amount at your start point, let the solvent evaporate, and then use the UV
        lamp at 254 nm to verify you have enough sample. Develop the plate in 50:50 ethyl
        acetate/hexanes. Afterward, visualize with the UV lamp. Calculate the Rf value.

                                        Preparatory Problems IChO 2012
  g)    After the bubbling subsides, add another 1/5 of the NaBH4. Repeat this process until all
        of the NaBH4 has been used. The whole process should take 10–15 minutes.
  h)    At some point during the addition steps, your imine will briefly dissolve and then a pale
        or white precipitate will immediately form. Record all of your observations.
  i)    Once the bubbling has completely stopped, do another TLC. This time, you will spot
        two lanes. One lane will contain a fresh aliquot of the imine standard used for the first
        TLC. The other lane will contain the product mixture, which you will prepare for TLC
        analysis as follows:
              Use a Pasteur pipet to transfer 1–2 drops of the final suspension to a small vial.
              Dissolve this mixture in 1–2 mL of dichloromethane. Use this solution to spot the
              plate. Again, use the UV lamp to verify you have enough sample spotted. Develop
              and visualize the plate as before. Once you have finished the TLC analysis, draw
              sketches of both plates in your report. Staple the plates on top of the corresponding
              pages that you hand in at the end of lab.
  j)    Add 10 mL 5% sodium bicarbonate to your reaction mixture. Mix thoroughly and filter
        the resulting solid.
  k)    Once all solid has been transferred to the filter paper, rinse the solid with 10 mL of cold
        distilled water. Allow the sample to air dry. You might want to recrystallize the product
        from methanol.
5. Analysis of the Reduction Product:
  a)   Obtain the melting point. Some of the melting points may be rather high.
  b)   If possible, obtain 1H and 13C NMR spectra.

Treatment of Data
a) Give the structures for the substituted aniline, the aldehyde, the imine, and the reduction
b) Report the melting points of the imine and the reduction product.
c) Optional: Report the 1H NMR and 13C spectrum of the imine and the reduction product.
   Report your observations of the fluorescence on the imine.

                                      Preparatory Problems IChO 2012
Problem 32. Kinetics of Ferricyanide Oxidation of Ascorbic Acid
                                                           L-Ascorbic acid

                                         HO        OH
   L-Ascorbic acid, also known as vitamin C, is an essential human nutrient. It is believed to
play a biochemical role as an antioxidant, protecting against damage from reactive oxidants by
virtue of its ability to be easily oxidized itself. In this experiment, you will investigate the
kinetics of oxidation of ascorbic acid by hexacyanoferrate(III) ion, Fe(CN)63–, also known as
ferricyanide, running the reaction in the presence of more than 10-fold excess of the reducing
agent. The bright yellow color of ferricyanide ion (max = 416 nm) is lost on its reduction to
colorless ferrocyanide ion [hexacyanoferrate(II), Fe(CN) 64–], allowing one to monitor the
progress of the reduction of ferricyanide spectrophotometrically.

• L-Ascorbic acid (abbreviated HAsc)
• Potassium hexacyanoferrate(III) (potassium ferricyanide), K 3[Fe(CN)6]
• Aqueous hydrochloric acid solution, 0.120 mol·L–1
• Deionized water

Compound             State                    S-Phrase                  R-Phrase
K3[Fe(CN)6]          Solid                    50(B) 61                  32, 52, 53
HCl(aq), 0.12 M      Solution in water        26 36 37 39 45            23 25 34 38

Apparatus and Glassware
• Analytical balance (± 0.0001 g)
• Volumetric flasks (2), 10 mL or 25 mL
• UV-visible spectrophotometer capable of measuring absorbance at 416 nm
• Spectrophotometric cuvette, 1 cm path length
• Plastic Beral pipettes, 1 mL (4), graduated in increments of 0.25 mL

                                      Preparatory Problems IChO 2012

1. Prepare stock solutions of ascorbic acid (~0.060 mol∙L–1) and of potassium ferricyanide
   (~6.0  10–3 mol∙L–1) (10 or 25 mL each). The concentrations need not be exactly as stated,
   but you should record the exact concentrations of the stock solutions.
2. Using the Beral pipettes to dispense the solutions, mix 0.75 mL deionized H 2O, 1.50 mL
   aqueous HCl, and 0.50 mL of the ascorbic acid stock solution and place the solution in a
   cuvette. If you have a single-beam spectrophotometer, blank the spectrophotometer using
   this solution. If you have a double-beam spectrophotometer, make up a second identical
   solution and use this as the reference sample.
3. Initiate the reaction by adding 0.25 mL of the ferricyanide stock solution to the above
   mixture and mixing thoroughly. If your cuvette has a lid that seals tightly, you can mix the
   solution in the cuvette itself. If the cuvette does not have a tight-fitting lid (or has a
   volume less than 3 mL), you will need to mix the solution in a small vial, then transfer a
   portion of the mixed solution into the cuvette. As quickly as possible, replace the cuvette
   in the spectrophotometer and begin measuring the absorbance at 416 nm as a function of
4. Record absorption at 416 nm, A416, as a function of time over the course of 10 minutes. In
   the early part of the reaction (when the absorbance is changing rapidly), you should record
   the absorbance frequently (every 10 seconds or so), but as the reaction slows, you can
   make less frequent readings if you wish (every 30 seconds or so).
5. Repeat steps 2–4 as needed to explore the effect on the rate of varying the ascorbic acid
   concentration in the range [HAsc] = 0.005–0.015 mol∙L–1 and of the acidity in the range
   [H+] = 0.01–0.10 mol∙L–1. If the reaction is slower than the initial experiment, you may
   need to extend the monitoring period to 15 or 20 minutes in order to allow the reaction to
   go nearly to completion (the absorbance, A416, should fall below 0.02).

Questions and Data Analysis
a) Give a balanced chemical equation for the oxidation of ascorbic acid by
   hexacyanoferrate(III) ion. Include a structural formula for the oxidation product of ascorbic
b) Determine the reaction order in Fe(CN)63–, and justify your determination.

                                    Preparatory Problems IChO 2012
c) Determine the reaction order in HAsc, and justify your determination.
d) Ascorbic acid readily ionizes to form the ascorbate anion, Asc –, with a pKa = 4.10
   (Ka = 7.9·10–5). Indicate which proton in ascorbic acid is readily ionized and explain why it
   is so acidic.
e) The dependence of the reaction rate on [H +] is somewhat complex (it does not exhibit a
   simple, integer order). A plausible explanation for this is that both ascorbic acid (HAsc)
   and ascorbate anion (Asc –) can be oxidized by hexacyanoferrate(III) ion, but that they have
   different reactivities. Use this model to analyze your data quantitatively to determine the
   relative reactivity of ascorbate anion and ascorbic acid toward Fe(CN)63–.

                                      Preparatory Problems IChO 2012
Problem 33. Synthesis of a Mannich Base: a Mannich Mystery

  The Mannich condensation is a widely used reaction to form highly substituted amines. In
the key step in this reaction, an enolate or its equivalent adds to an iminium ion that is often
formed in situ from an amine and an aldehyde. In this way, three molecules are condensed to
form the final product. In particular, reactions of phenols and formaldehyde in the presence of
primary or secondary amines gives rise to benzylic amines, with reaction taking place
exclusively in the activated positions ortho or para to the phenol group:
               OH                                                 OH
       R1                             H                    R1
                     + CH2O +         N                                     NRR'
                                                                                    + H2O
                                  R       R'

               R2                                                 R2

  In this experiment, you will explore the Mannich reaction between 2,2-dimethyl-1,3-
diaminopropane with excess 2,4-di-tert-butylphenol and formaldehyde. Because the starting
amine has two primary amino groups, one could envision many different possible Mannich
products that could be formed in this reaction. In fact, one product is formed selectively and
can be isolated in moderate yield. You will be asked to suggest a structural formula of this
product based on its 1H NMR spectra provided below.

• 2,2-Dimethyl-1,3-diaminopropane, NH2CH2C(CH3)2CH2NH2
• 2,4-di-tert-butylphenol, C6H3(C[CH3]3)2OH
• Aqueous formaldehyde, 37% (w/v)
• Ethanol
• Methanol
• Hexane/ethyl acetate mixture for TLC (3:1 v/v)

                                     Preparatory Problems IChO 2012

Compound             State                   S-Phrase                 R-Phrase
2,2-Dimethyl-1,3- Liquid                     26 36/37/39 45           10 22 24 35
2,4-di-tert-      Solid                      22 36                    22 36 37 38
Formaldehyde(aq) 37 % solution in            1/2 26 36/37/39 45 51    23/24/25 34 40 43
C2H5OH            Liquid                     7 16 24 25 36 37 39      11 20 21 22 36 37 38 40
CH3OH                Liquid                  1/2 7 16 36/37 45        11, 23/24/25 39/23/24/25
Hexanes              Liquid                  53 45                    45 22
Ethyl acetate        Liquid                  16 26 33                 11 36 66 67

Apparatus and Glassware
• Balance (± 0.01 g precision or better)
• Erlenmeyer flask, 125 mL
• Teflon-coated stirbar
• Hotplate/stirrer
• Graduated cylinder, 10 mL
• Büchner funnel
• Filter flask and source of vacuum (e.g., water aspirator)
• Silica gel-coated TLC plates and development chamber
• Melting point apparatus
• Ice water bath
• Spatulas

1. To the 125 mL Erlenmeyer flask add 0.35 g 2,2-dimethyl-1,3-diaminopropane, 2.2 g
   2,4-di-tert-butylphenol, 10 mL ethanol, and a stirbar. Stir the mixture until it becomes
   homogeneous, then add 1.0 mL 37% aqueous formaldehyde solution.
2. Heat the mixture to a gentle boil, with stirring, on the hotplate/stirrer. Maintain at a gentle
   boil for 1.5 hr. Alternatively, the heating can be carried out in a round-bottom flask under a

                                      Preparatory Problems IChO 2012
   reflux condenser, using a heating mantle or oil bath to heat the flask, with the solution
   maintained at reflux for 1.5 hr.
3. Take the flask off of the hotplate, remove the stirbar from the solution, and allow the
   reaction mixture to cool to room temperature. If no solid has formed, scratch the inner sides
   of the flask with a spatula to initiate crystallization. After the solution has reached room
   temperature, chill the flask in an ice bath for at least 10 minutes.
4. Suction-filter the precipitate on the Büchner funnel. Wash the solid thoroughly with 10 mL
   methanol to remove any unreacted 2,4-di-tert-butylphenol. After the wash, leave the
   precipitate on the Büchner funnel with the vacuum on (to suck air through the precipitate)
   for at least 15 min. This serves to dry the solid by evaporating any residual methanol.
5. Scrape the solid into a tared container and measure the yield of product.
6. Characterize the product by its melting point (it is between 200–250 °C) and by thin layer
   chromatography (silica gel, eluting with 3:1 hexane:ethyl acetate (v/v)).

Questions and Data Analysis
a) The 1H NMR spectra of the product, recorded in CDCl 3 solution at 500 MHz at –40 °C
   and at 55 °C, are shown below. For each temperature, the full spectrum from 0–12 ppm is
   shown, then an expansion of the region from 1.5–4.5 ppm. Peak positions, where listed, are
   given in ppm. Some small impurities in the solvent are observable; they are marked with
   asterisks (*) and should be ignored. Based on these spectra, suggest a structural formula for
   the observed product.

                                    Preparatory Problems IChO 2012

b) Suggest an explanation for the change in appearance of the 1H NMR spectra with
c) Calculate a percent yield of product.
d) Report the melting point and Rf value of the compound.

                                                           Preparatory Problems IChO 2012

                                                           Periodic Table of the Elements
     MAIN-GROUP                                                                                                                                  MAIN-GROUP ELEMENTS
      1A                                                                                                                                                                                   8A
      (1)                                                                                                                                                                                 (18)
       1                                                                                                                                                                                    2
1     H                                                                                                                                                                                    He
    1.008           2A                                                                                                            3A        4A        5A         6A         7A            4.003
      3              4                                                                                                             5         6         7          8          9             10
2     Li           Be                                                                                                             B         C         N          O          F              Ne
    6.941         9.012                                            TRANSITION ELEMENTS                                           10.81     12.01     14.01     16.00       19.00          20.18

      11            12                                                                                                            13        14        15         16         17             18
3    Na            Mg                                                                       8B                                    Al        Si        P          S          Cl             Ar
    22.99         24.31       3B       4B         5B         6B         7B                                      1B       2B      26.98     28.09     30.98     32.07       35.45          39.95
    39.10         40.08      44.96    47.87     50.94      52.00       54.94      55.85    58.93      58.69    63.55    65.41    69.72     72.61     74.92     78.96       79.90          83.80

    85.47         87.62      88.91    91.22     92.91      95.94      (97.9)      101.1    102.9      106.4    107.9    112.4    114.8     118.7     121.8     127.6       126.9          131.3

    132.9         137.3     138.9     178.5     180.9      183.8       186.2      190.2    192.2      195.1    197.0    200.6    204.4     207.2     209.0     (209.0)    (210.0)        (222.0)

      87            88        89       104       105        106        107        108      109        110      111      112      113       114       115        116       117            118
7     Fr           Ra        Ac         Rf       Db         Sg          Bh         Hs       Mt         Ds       Rg       Cn      Uut       Uuq       Uup        Uuh        Uus            Uuo
    (223.0)       (226.0)   (227.0)   (261.1)   (262.1)    (263.1)    (262.1)     (265)    (266)      (271)    (272)    (285)    (284)     (289)     (288)     (292)       (294)          (294)

                                                                                              INNER TRANSITION ELEMENTS

                                        140.1     140.9      144.2      (144.9)    150.4    152.0      157.3    158.9    162.5    164.9     167.3     168.9      173.0      174.0
                                Preparatory Problems IChO 2012
7   Actinides    Th      Pa       U       Np        Pu        Am        Cm        Bk         Cf       Es        Fm        Md        No         Lr
                232.0   231.0    238.0   (237.1)   (244.1)   (243.1)   (247.1)   (247.1)   (251.1)   (252.1)   (257.1)   (258.1)   (259.1)   (260.1)

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