55th International Mendeleev Olympiad, 2021

1st theoretical tour Solutions

Problem 1 (author Nikitina V.N.)

1. a) Silver sulfide is formed on the surface of a silver coin as a result of oxidation with
atmospheric oxygen in the presence of H2S (0.5 points):
4Ag + 2H2S + O2 = 2Ag2S+ 2H2O
b) During boiling, hydrocarbonate decomposes to give carbonate and carbon dioxide
(0.5 points):
2NaHCO3 = Na2CO3 + CO2 + H2O
c) Aluminum reduces silver from sulfide in alkaline media (1.5 points):
3Ag2S +2Al + 5Na2CO3 + 8H2O = 6Ag + 2Na[Al(OH)4] + 3NaHS + 5NaHCO3
2. The pH of solution is determined by sodium carbonate, since the amounts of
hydrosulfide and hydrocarbonate formed in the reaction can be neglected (0.5 points).
C(Na2CO3) = ½ ∙ 20 g / 84 g/mol / 0.4 L = 0.2976 » 0.3M
To calculate the pH of a carbonate solution, one should consider its hydrolysis:
CO32– + H2O = HCO3– + OH–
The equilibrium constant of this reaction (0.5 points)
Keq = [HCO3–][OH–]/[CO32–] = [HCO3–]Kw / [CO32–][H+] = Kw / Ka2,
where Ka2 = [H+][CO32–]/[HCO3–]. In our case [OH–] = [HCO3–], since these two particles are
formed mainly by the reaction above, then Keq = [OH–]2 / [CO32–] » [OH–]2 / сCO32–= Kw / Ka2.
Therefore [OH–] = (сCO32– ∙ Kw / Ka2)½ = = 7.74·10–3, рОН = 2.1, рН = 11.9 (1.5 points)
3. Let us calculate the minimum mass of aluminum foil for reaction 1c. To do this, it is
necessary to calculate the volume of sulfide covering the coin (product of the coin area by
the thickness of the coating). The surface area of the coin S is the sum of the areas of two
circles of radius r = 1 cm and the side surface of thickness d and length 2pr (0.5 points):
S = 2pr2 + 2prd = 7.54 cm2
Let us calculate the mass of sulfide in the surface layer with a thickness of l = 42 nm
(0.5 points):
m(Ag2S) = ρSl = 7.32 g/cm³ ∙ 7.54 cm2 ∙ 42∙10–7 cm = 0.232 mg
Foil mass corresponding to this amount of silver sulfide (0.5 points):
m(Al) = 0.232 mg / 247.8 g/mol ∙ 2/3 ∙ 27 g/mol = 0.0168 mg
4. From the expression for the complex stability constant it follows that
[Al(OH)4–] / [Al3+] = b(Al(OH)4–)·[OH–]4 = 3·1025. Thus, almost all aluminum is bound in
the hydroxocomplex: α[Al(OH)4–] = 100% (1.5 points)
5. Aluminum and silver form a galvanic pair when in contact. In this case, the reduction
reaction proceeds at the cathode, and oxidation at the anode. Therefore, the cathode is the
silver coin, and the aluminum foil is the anode:
Cathode (silver coin): Ag2S + 2e = 2Ag + S2–
or Ag2S + H2O + 2e = 2Ag + HS– + OH– (1 point)
– –
Anode (aluminum foil): Al + 4OH – 3e = Al(OH)4 (1 point)

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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions

Problem 2 (authors Ilievski F., Karpushkin E.A.)

1. (1 point per reaction, 10 points in total)
O O Sn(C H COO)
O 1. NaOH 7 15 2
O
n O n
2. HCl HO H
n O O 2n
O
O
NH2
N
n
2 S + n n
+ n/4 S8 S n
n
n NH2 N
O
UV-initiated thia-Michael addition polymerization. Note that the acrylate Michael
acceptor is much stronger than the allyl acceptor, thus leaving the allyl as a pendant group.
H H
N O S N O
HS UV S
a + a O O room O O
S S a
SH temperature

O O
n HO OH O
OH + n HO O
n
O O
Suzuki polycondensation:

B(OH)2 O OC8H17 O
C8H17O
Pd(0)
n + n Br Br
OC8H17 n
B(OH)2 O C8H17O O

Ring-opening metathesis polymerization:

Cl PCy3 H+
O O O O n
N Ru N
n Cl n
PCy3

As in cellulose, chitin contains β(1-4) glycosidic linkages:

O

OH NH OH
n O
O O O N O O
HO O HO
HO O P O P O chitin synthase
NH NH
O- O- n
HO OH O
O

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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions

Problem 3 (author Mezentsev-Cherkes I.V.)

1. По описанию и приведенной цветовой схеме можно предположить, что
зашифрованы соединения марганца. Подтвердим это предположение расчетом. Для
металлов широко известны кислородсодержащие минералы, поэтому запишем
состав как ХnOm. The formula must satisfy the equation ω(X) = M×n / (M×n + 16×m).
Taking n = 1 and m = 2 we find that M (X) = 55 g/mol and the mineral is pyrolusite,
MnO2 (1 point for calculation, 0.25 points for the formula and the historical name).
2. Taking into account the color and the fact that the mass fractions of oxygen are equal,
it can be assumed that the charge of an anion and the oxidation state of a central atom are
changed, which leads to MnO43–, MnO42–, MnO4– and Mn2+ for X1 – X4 respectively
(0.25 point for each compound, cation may vary, 1 point in total).
3. (0.5 points for each reaction, 3 points in total)
KOHp- p, t ° C
1) 2K3MnO4 + Br2 ¾¾¾¾ ® 2K2MnO4 + 2KBr
t° C
2) 3K2MnO4 ¾¾® 2K3MnO4 + MnO2 + O2
3) 3K2MnO4 + 2H2O = 2KMnO4 + MnO2 + 4KOH
t° C
4) 2KMnO4 + 4KOH ¾¾® 2K2MnO4 + O2 + 2H2O
5) 5K2C2O4 + 2KMnO4 + 3H2SO4 = 2MnSO4 + K2SO4 + 10CO2 + 8H2O
Ag +
6) 2MnSO4 + 5(NH4)2S2O8 + 8H2O ¾¾® 2HMnO4 +5(NH4)2SO4 + 7H2SO4
4. MnSO4 + (NH4)2HPO4 + NH3∙H2O = NH4MnPO4∙H2O¯ + (NH4)2SO4 (0.5 points for
the reaction and 0.5 points for NH4MnPO4∙H2O)
If we assume that there is only one Mn atom in the X6 compound, the molar mass will be
142, which after considering every possible combination with P and O will lead to a dead
end. The presence of nitrogen is excluded due to the fact that on heating ammonium will
volatilize as ammonia. Therefore, we can assume to be two manganese atoms in X6. Then
the molar mass is 284, which corresponds to manganese pyrophosphate (0.75 points, 0.5
points for the reaction, 0.75 points for structure, 3 points in total).
t° C
2NH4MnPO4∙H2O ¾¾® Mn2P2O7 + 2NH3 + 3H2O
O O 4-

P P
O O O
O O
5. Taking into account the Sidgwick's rule, we can come to the conclusion that in the
compound Mn(CO)5 there is one electron missing for the 18 electronic environment.
Therefore, only in the case of the formation of dimers the Sidgwick rule is fulfilled;
compound C corresponds to Mn2(CO)10 (0.5 points). In the reaction with chlorine one
electron is provided to the coordination environment of manganese. Thus, the composition
of the compound D corresponds to Mn(CO)5Cl (0.5 points, 0.5 points for the reaction,
1.5 points in total):
Mn2(CO)10 + Cl2 = 2Mn(CO)5Cl
Problem 4 (author Gulevich D.G.)
1. In order to determine the temperature of a person by thermometer in figure, you need
to find the change in the volume of mercury. Knowing the value of division and
determining the height h from the volume of the cylinder (πr2h), we find the final
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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions
temperature. During measurements the amount of heat Q = cmΔT was transferred to the
mercury, where m = ρV0 – mercury mass. Change in the volume of mercury under heating
ΔV = V – V0 = V0αΔT, from where
a × Q × Ar (Hg)
DV = .
r (Hg) × c(Hg,l)
a × Q × Ar (Hg) 1.8 ×10-4 K -1 ×115 J × 200.6 g/mol
h= = = 1.4 cm .
r (Hg) × c(Hg,l) × p × r 2 13.55 g/cm3 × 27.88 J/mol × K × 3.14 × (0.5 ×10-1 ) 2 cm 2
Since the scale of the thermometer is 1 mm, the mercury has risen by 14 divisions and the
human temperature is 36.4°С, i.e. the person is healthy (2 points).
2. During the phase transition, the change in entropy is ΔtrН/Тtr, the freezing point of
mercury (1 point)
m(Hg) D melt Н 0.7 g 2.29 kJ/mol
T= = = 235 K = -38°C
Ar (Hg) D melt S 200.6 g/mol 0.034 J/K
3. The change in entropy ΔS of mercury with an increase in temperature from -60 to
+40°С consists of ΔS1 when heating liquid mercury from -60°С to the melting point,
ΔmeltS and ΔS2 when heating liquid mercury from -38°С to 40°C (1 point for each
calculation stage, 3 points in total).
Tmelt 235
DS1 = n × cs ln = 3.5 ×10 -3 × 28.28 × ln = 9.72 ×10 -3 J/K ,
Ti 213
T 313
DS3 = n × cl ln f = 3.5 ×10 -3 × 27.88 × ln = 2.80 ×10 -2 J/K .
Tmelt 235
ΔS = ΔS1 + ΔmeltS + ΔS2 = 9.72∙10-3 = 3.40∙10-2 + 2.80∙10-2 = 7.17∙10-2 J/K.
4. a) During electrolysis the following processes occur:
C: Tl+ + e- + nHg = Tl×nHg
A: 2HCOO- - 2e- = 2CO2↑ + H2↑
2HCOOTl + 2nHg ¾¾¾¾ electrolysis
® 2Tl×nHg + 2CO2↑ + H2↑
b) According to Faraday's law, we determine the mass of thallium released at the cathode:
Ar (Tl) × I × t 204.4 × 0.73 × 5 × 60
m (Tl) = = = 0.464 g , therefore
ne × F 96485
m(Tl) 0.464
w(Tl) = = × 100% = 8.5%.
m(Hg) + m(Tl) 5 + 0.464
c) A mixture of hydrogen and carbon dioxide will be released on the anode. By the
reaction stoichiometry ν(CO2) = ν(Tl) = 2ν(H2) = 2.26∙10-3 mol. Then the molar fractions
of carbon dioxide and hydrogen in the gas mixture will be equal to 0.67 and 0.33
respectively. Average molar mass of the gas mixture Mср = 0.67∙44 + 0.33∙2 = 30.1 g/mol.
Then by the Mendeleev - Clapeyron equation
M × p 30.14 × 10 -3 × 101325 3
r= = = 1.23 kg/m .
RT 8.314 × 298
(0.5 points for the processes on the electrodes, 1 point for calculation of the mass of Tl,
0.25 points for determination of the amalgam composition, 0.5 points for calculation of the
average molar mass of the gas mixture, 0.25 points for determination of density, 3 points
in total).
5. (0.5 points for each, 1 point in total)
3Hg + 2KMnO4 + 8HCl = 3HgCl2 + 2MnO2 + 2KCl + 4H2O
Hg + 2FeCl3 = 2FeCl2 + HgCl2
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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions
Problem 5 (author Khvalyuk V.N.)
1. Unlike most other acids, the density of aqueous solutions of CH3COOH changes non-
monotonically with an increase in the mass fraction of the acid: it increases to
1.0700 g/cm3 (78–80% acid), and then decreases. As a result, at 20°С 70 % and 86%
aqueous solutions have the same density equal to 1.0685 g/cm3. Therefore, by measuring
the density of a solution with a hydrometer, it is impossible to determine where which
solution is. To solve the problem, small volumes of water should be added to each of the
solutions, mixed and the density of the resulting solutions should be measured again. In
the case of a 70% solution, dilution will lead to a decrease in the density of the solution,
and in the case of an 86% solution, to an increase. The correct answer is e (1 point).
2. Electrolytic dissociation of acetic acid (0.25 points):
CH3COOH ⇄ CH3COO– + H+
The constant of equilibrium (Ka acetic acid) (0.25 points):
c(H+)×c(CH3COO–)
Ka = c(CH COOH) = 1.75∙10–5
3
Let's designate the analytical concentration (all forms) of acetic acid in the marinade as со.
The concentration of H+ ions in the marinade is 10–рН = 10–3.50 mol/dm3. According to the
equation, the concentration of CH3COO– ions is also 10–3.50 mol/dm3, i.e. 10–3.50 mol/dm3
CH3COOH underwent dissociation. Then the equilibrium concentration of the molecular
form of the acid is equal to с(CH3COOH) = (со – 10–3.50). Substitute these values into the
expression for the equilibrium constant (0.5 points):
10–3.50×10–3.50 –5
со – 10–3.50 = 1.75×10
Solving this equation we get со = 6.03∙10–3 mol/dm3. M(CH3COOH) = 60 g/mol (0.5 points)
To prepare 12.0 dm3 marinade one should take 6.03∙10–3 ∙ 12.0 = 72.36∙10–3 mol or
4.34
72.36∙10–3 ∙ 60 = 4.34 g CH3COOH. Required volume of 9% vinegar is equal to
0.09×1.070
3
= 45.1 см (0.5 points, 2 points in total)
3. Before adding of baking soda c(H+) = 10–pH = 10–2.50 mol/dm3 (0.25 points):
10–2.50×10–2.50 –5
со – 10–2.50 = 1.75∙10
Solving this equation we get со = 0.5746 mol/dm3. In the initial marinade (before the
addition of baking soda), the analytical acid concentration is 0.5746 mol/dm3. When
baking soda is added, the reaction proceeds (0.25 points):
CH3COOH + NaHCO3 = CH3COONa + CO2↑ + H2O
Suppose that to achieve the final result (pH = 4.0), x mol of solid NaHCO3 should be
added for each 1 dm3 of the marinade. After adding soda, the concentration of CH3COOH
in the marinade will be (0.5746 – x) mol/dm3. Since the pH in the final marinade should be
equal to 3.5, then c(H+) in it: 10–3.5 mol/dm3. Consequently, 10–3.5 mol/dm3 CH3COOH
should dissociate to form of 10–3.5 mol/dm3 of each of the H+ and CH3COO– ions. Then the
equilibrium concentration of the molecular form CH3COOH will be
(0.5746 – x – 10–3.5) mol/dm3. The CH3COONa formed in the reaction completely
dissociates with the formation of x mol/dm3 of CH3COO– ions. Then the equilibrium
concentration of CH3COO– ions will be equal to (10–3.5 + x) mol/dm3. Substitute the

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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions
equilibrium concentrations of all particles in the expression for the dissociation constant
10–3.5×(x + 10–3.5)
(0.5 points): 0.5746 – x – 10–3.5 = 1.75×10–5
Solving this equation we get х = 0.0298 (1 point).
M(NaHCO3) = 84 g/mol. Therefore, one should add 0.0298 ∙ 12 = 0.3576 mol or
0.3576 ∙ 84 = 30.0 g NaHCO3 to 12.0 dm3 of marinade (1 point, 3 points in total)
4. If in the process of "quenching" you mix soda and acetic acid in a molar ratio of 1 : 1,
then they will completely react and, due to the small volume of the reaction mixture, this
will lead to a very rapid release of all carbon dioxide into the atmosphere. There will be
practically no effect of "raising" the dough from adding such a mixture to the dough.
Therefore, this reaction can NOT be the interaction of components in the process of
"quenching":
NaHCO3 + CH3COOH = CH3COONa + H2O + CO2↑
For the effect of "swelling" to be observed, it is necessary that the reaction of the
formation of CO2 occurs in the volume of the dough during the heating of the product in
the oven at the initial stage of baking, but until the moment when a crust forms on the
surface of the product, which will not allow the dough to increase in volume due to gas
evolution. This cannot be a thermal decomposition reaction of baking soda (although this
will lead to an increase in the volume of the dough due to the released CO2), but in this
case the reaction product is sodium carbonate, which impairs the taste of the final product,
which is unacceptable. In addition, in this case, the role of acetic acid and the need for the
stage of "quenching" the soda are not at all clear. The process that will allow the formation
of a "lush" dough is the hydrolysis of sodium acetate, which is formed at the stage of
"quenching" of soda (2.0 points in total).
CH3COONa + H2O ⇄ CH3COOH + NaOH
As the temperature rises, the hydrolysis of CH3COONa intensifies, and the resulting acetic
acid reacts with the "unquenched" baking soda to form CO2, which raises the dough. The
resulting sodium acetate undergoes hydrolysis again and is involved in the gas formation
process many times, theoretically until it is completely consumed of NaHCO3.
5.00
5. In 5.00 g it consists 84 = 0.0595 mol = 59.5 mmol NaHCO3 (0.5 points).
0.09×5.00×1.07
In 5.0 cm3 of 9% vinegar it consists 60 = 8.03∙10–3 mol = 8.03 mmol
CH3COOH (0.5 points).
The baking powder contains (59.5 – 8.03) = 51.47 mmol of unquenched NaHCO3 (0.5
points).
As mentioned in paragraph 4, the sodium acetate formed at the quenching stage repeatedly
participates in the process of gas formation, theoretically (if we exclude the volatilization
of the acid outside the dough) until all the soda has reacted with the formation of CO2.
Therefore, the maximum amount of CO2 produced will be equal to 51.47∙10–3 ∙ 22.4 =
= 1.15 dm3 (0.5 points, 2 points in total)

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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions

Problem 6 (authros Volochnyuk D.M., Avramenko N.N.)

1,2. The solution to this problem would be best to start with a drawing of all the possible
isomers of formula С3H6O. There are only 8 (0.25 points for each, 2 points in total).
O OH O O
O HO O
O

1 2 3 4 5 6 7 8
There are a large number of solutions of this O O
I II III
problem, but their idea is common. O
1.NaH
First of all, it is necessary to find the H2
2.(CH3O)2SO2
1. CaCO3
Pd cat. 2. T
transformation that unambiguously leads to
some isomer. For example, heating C O CH2O O O2 O

(which can be acid because it reacts with A SiO2 H cat OH

B C
thionyl chloride) with calcium carbonate is NaBH4
Cl
the classic method to obtain acetone. Due 1. SOCl2 1. Me3SiCl O
HO
this, he got his name acetone from lat. 2. B2H6 2. NaOH
V
acetum – vinegar. Therefore, C is acetic 3. H2O2
F VI
OH
acid, and III is acetone. HOCl
After that the part of the chain is deciphered 1. MeSO2Cl,
O O
based on basic knowledge of organic OH KOH Et3N
EtOH OH 2. NaBHEt3
chemistry. Cl OH VII
H
G
Decryption of the last part of the chain can cause some difficulties. However, this can be
done using the elimination method. Of the isomeric compounds, cyclopropanol remained,
respectively, this is IV. Further, in CF3CO3H, it is necessary to recognize the reagent for
the Bayer-Villiger reaction. So, E is cyclopropyl methyl ketone. On the other hand, D is a
cyclic enolate acylation product. Mechanically, its conversion to cyclopropyl methyl
ketone is represented as ring opening – decarboxylation – ring closure (4 structures, 0.25
points, 2 points in total and 0.5 points for each structure and plus 0.1 point for each
compliance, 4.8 in total).
O O O O O
O OH
O 1. SOCl2 -
+I CF3CO3H OH-
O O-
Baeyer O
OH 2. D Villiger
C OK E IV
O I
3. Alcohols, due to hydrogen bonds, have the highest Tbp – category c. Non-cyclic
ethers have the smallest Tbp – category a. the rest are b (see table).
4. The number of signals in the 1H NMR spectrum corresponds to the number of
nonequivalent proton groups.
Hc Hd O Ha
Hb Hb Hd Ha Ha O
O Hc Ha O Hd
Ha Ha Hb
Hc Hb Ha Ha
Ha Hc Hc Hc
Hd Hd
I II III IV
Ha O
Hc O
Ha O Ha H Ha
O Hd Hc d
Ha Hb Ha H Hc Hb H Ha
Hb Hb H Hd Hb H a a
a
e Hb Ha
V VI VII VIII
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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions
1 1
N Тbp H NMR N Тbp H NMR
I b (49°С) 3 V c (97°С) 5
II a (6°С) 4 VI b (50°С) 2
III b (56°С) 1 VII b (35°С) 4
IV c (101°С) 4 VII b (35°С) 4
(i. 3 – 0.2 points for each cell in the table, 1.6 points in total; i. 4 – 0.2 points for each cell
in the table, 1.6 points in total)

Problem 7 (author Karpushkin E.A.)

1. Monomer M is consumed in the reactions 2, 3, and 4. The monodisperse product is
obtained under conditions of fast (instant) initiation followed by slow propagation of the
chains. Termination does not compete with propagation (kt is much less than other rate
d[M]
constants), hence reaction 4 can be neglected. Therefore, dt = –ki,2[I–][M] – kp[Pn–][M].
At each moment, total concentration of the anionic species (I– and Pn–) equals the starting
concentration of the initiator, whereas rate constants of reactions 2 and 3 are equal. Thus,
d[M]
dt = –kp[I]0[M]. This is the first-order kinetic equation with the solution as [M] =
= [M]0e–kp[I]0t (the answer with ki,2 instead of kp also accepted) (2 points)
2. Since the growth of the macromolecules is uniform, the average degree of
polymerization is proportional to the amount of the consumed monomer, which is
proportional to the conversion. Hence, average degree of polymerization is a linear
increasing function of the conversion starting from the origin. Since the polymerization
rate is decreased with the monomer consumption (i. 1), the rate of the conversion growth
[M]
is steadily decreased. The conversion equals 1 – [M] = 1 – e–kp[I]0t, and the required plot is
0
an increasing curve achieving its maximum value.

Any plot in agreement with the equation given as the answer in i. 2, if any, is considered
correct (2 points, 1 point for each plot).
3. a) The interaction of MontONa with A is a reversible exchange:
MontO
Br + NaBr
MontONa +
A O(CH2)12N(CH3)3 MontOI O(CH2)12N(CH3)3

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 55th International Mendeleev Olympiad, 2021
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[MontOI][NaBr]
with the equilibrium constant of K = . The initial amount of MontONa is
[MontONa][A]
1.00 g ∙ 0.92 meq/g = 0.92 meq (an equivalent in this reaction corresponds to a mol of the
acidic exchange sites in the sodium form), and the initial amount of A is
0.52 g / 500.56 g/mol = 1.04 mmol. With an account for the molar masses of the cation of
A (420.66 g/mol) and sodium (22.99 g/mol), the exchange reaction involving 1 mmol of
the acidic sites of montmorillonite leads to an increase in its mass by 0.40 g. Since the
montmorillonite mass increased by 0.20 g, the reaction involved 0.50 mmol of each of A
and acidic sites of MontONa, giving 0.50 mmol of MontOI and NaBr. Then K =
0.50 ∙ 0.50
= (0.92 – 0.50)(1.04 – 0.5) = 1.1.
b) (3 points: 1 point for each reaction, 1 point for the constant calculation)

MontO-
Li Li MontO-
+
MontOI O(CH2)12N(CH3)3
O(CH2)12N(CH3)3
MontOI*
4. 25 g ∙ 0.85 / 104.15 g/mol = 204 mmol of styrene involved in the polymerization
corresponds to 0.50 mmol of the initiator MontOI*, hence the degree of polymerization
equals 408, and the polymer structure (do not forget quenching with methanol) is:
(H3C)3N(H2C)12O

H
MontO- 408
s-Bu Ph Ph
1 eq. of montmorillonite corresponded to 420.66 g (cation of A) + 57.12 g (sec-butyl
group) + 408 ∙ 104.15 g (styrene units) + 1.008 g (terminal hydrogen atom) = 42972 g of
the polymer. Total exchange capacity of MontONa equals 0.92 meq/g but only
0.50 mmol/g of the acidic sites are modified with the initiator and thus active in
polymerization (i. 3a), hence equivalent mass of MontO in polymerization (sodium ion
excluded) = 1000 / 0.50 – 22.99 = 1977 g. Thus, mass fraction of MontO in the composite
is 1977/(1977 + 42972) = 4.4% (3 points).

Problem 8 (author Ilievski F.)

1. The scheme is rather straightforward and can be approached from many directions. If
we compare the structure of MK-4482 and the starting molecule of ribose, we can see that
the anomeric site at the MK-4482 has the β-configuration. Based on the scheme, one can
conclude that this stereoselective linkage occurs in the convergent step between A and B.
Based on reaction conditions, the structure of A and B can be easily deduced as
pentaacetylated ribose as well as bi-protected tautomer of the uracil. The reaction between
A and B is the so called improved variation of the silyl-Hilbert-Johnson reaction, where
the nucleoside structure is formed and the TMSO group is removed. Then the alkaline
hydrolysis removed the acetyl protecting group from OH-functions leading to uridine D.
Transformation of D to F results in installation of acetonide protection group (compound
E) with subsequent esterification of the primary group with isobytiric anhydride.
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 55th International Mendeleev Olympiad, 2021
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Afterwards introducing an triazole moiety at the enol tautomer of the uracil segment leads
to compound G. Finally, a nucleophilic substitution with hydroxylamine gives compound
H, which after acetonide deprotection in weakly acidic environment affords MK-4482 (8
structures, 0.75 point each, 6 points in total).
O OH Ac2O O OAc
HO pyridine AcO 1. TMSOTf H
O
SnCl4 N
HO OH AcO O
A OAc MeCN O N
AcO
H TMSCl 2. NaHCO3,
O N O pyridine TMSO N OTMS H2O AcO OAc C

HN 135°C N B KOH/K2CO3
THF
O H
N O H
O Acetone N
O O
N H2SO4 O N
(iPrCO)2O HO Et3N HO
DMAP E D
Et3N O O HO OH
O H
N O O N
O O POCl3 N
N O N N
1,2,4-triazole O N
O
Et3N O
G
O O
F O O
NH2OH
iPrOH
O H H
N O
N N
O O N
O N OH HCO2H O OH
N
O O
HO OH O O
MK-4482 H

The proposed reaction scheme is quite clear and can be inferred from the phosphorylation
and the enzyme presence. Namely, the carboxypeptidase cleaves the isobytiryl fragment,
giving EIDD-1931 which makes this nucleoside a substrate for a phosphokinase, yielding
the monophosphate. Monophosphates per se do not penetrate the cell due to their high
negative charge. Moreover, the transformed nucleoside into nucleotide is rapidly
diphosphorylated giving the active nucleotide triphosphate, which is a substrate to RNA-
dependent RNA polymerase (4 structures, 0.5 points, 2 points in total).
O H O H
N N N N
O O OH Carboxyesterase O OH
N N
O O HO
EID-1931
HO OH H2O HO OH
OH ATP
Z
O H H
N N ADP O N
O O OH Nucleotide kinase O N
O N O OH
O P O N
P O - P O
P O O -
O O-
-
O O- O- OH
Y HO ATP AMP HO OH X

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 55th International Mendeleev Olympiad, 2021
1st theoretical tour Solutions
2. The structure of the tautomers shows the hydrogen donor and acceptor moieties for
formation of Watson-Crick pairs. Analoguosly to uridine, the tautomeritism occurs at the
hydroxamate segment which in the case of pairing with adenosine, the –OH group must be
oriented trans. (0.5 points for each tautomer, 0.5 point for each base pairing, 2 points in
total).
H H
N OH O
N HN H O
N N H H
N N N N
N N
O N N H N
O O N N
OH
HO O O H O
HO
OH HO HO OH
Adenosine HO OH HO OH HO
Guanosine
References
1. Benkovics, T., McIntosh, J., Silverman, S., Kong, J., Maligres, P., Itoh, T., Yang, H.,
Huffman, M., Verma, D., Pan, W., Ho, H., Vroom, J., Knight, A., Hurtak, J., Morris, W.,
Strotman, N., Murphy, G., Maloney, K. and Fier, P., 2020. Evolving to an Ideal Synthesis
of Molnupiravir, an Investigational Treatment for COVID-19. ChemRxiv, 2020.
DOI:10.26434/chemrxiv.13472373.v1
2. Ueda, T., Nishino, H., On the Hilbert-Johnson procedure for pyrimidine nucleoside
synthesis. J. Am. Chem. Soc., 1968. – 90(6). – 1678. DOI: 10.1021/ja01008a067
3. Vasudevan, N., Ahlqvist, G., McGeough, C., Paymode, D., Cardoso, F., Lucas, T.,
Dietz, J., Opatz, T., Jamison, T., Gupton, F., Snead, D. A concise route to MK-4482
(EIDD-2801) from cytidine. Chem. Commun., 2020. – 56. – 13363.
DOI:10.1039/D0CC05944G
Verwoerd, D., Kohlhage, H., Zillig, W. Specific Partial Hydrolysis of Nucleic Acids in
Nucleotide Sequence Studies. Nature, 1961. – 192. – 1038. DOI:10.1038/1921038a0

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