Question 1 - start each question on a new page.

(a)            Heterocycle 1, which is synthesised from meta-chloronitrobenzene 2, is a key

intermediate in the synthesis of a drug which is undergoing clinical trials for use against COVID- 19.

(i)          Give a retrosynthetic analysis to show how 1 could be synthesised from 2, 3           (9)

and any other suitable reagents.  Using your retrosynthetic analysis, outline a forward synthesis of 1 giving suitable reagents for each step.

(ii)         Give a curly arrow mechanism for the reaction in your synthesis which forms         (6)

the quinoline ring and explain the regiochemistry of the ring formation step.

(b)            Give a curly arrow mechanism for the reaction below, clearly indicating the role of              (5)

ZnI2, and draw the structure of intermediate A.

Question 2 - start each question on a new page.

The greenhouse warming potential, GWP, of a gas A, relative to CO2, can be estimated as

aATA (1 − e−tf⁄TA)     

GWPA  =

where aA is the radiative forcing resulting from a 1 kg increase of the compound A, termed radiative      efficiency, TA is the atmospheric lifetime ofA, aCO2 and TCO2 are the comparable quantities for CO2 and tf is the time horizon.

Explain why the radiative efficiency of CO2, quoted in units of W m一2 ppm一 1, changed from 0.0147 in 2001 to 0.0141 in 2007.

Convert the radiative efficiencies of CO2, SF6 and CHCl2F, given in Table 1,   into units of W m一2 kg一 1 . Assume that the mean dry mass of the atmosphere is 5.135 × 1018 kg and the mean molecular weight of dry air is 28.97 g mol一 1 .

Table 1 

Gas         Radiative efficiency 

CO2              0.0141 W m一2 ppm一1

SF6                 0.681 W m一2 ppb一1

CHCl2F         0.18 W m一2 ppb一1

(iii)        Based on your answers to part (a)(ii), calculate the GWPs for SF6 and CHCl2F

for a tf of 100 years. Assume TSF6 = 1278 years, TCHCl2F = 1.7 years, and TCO2 = 150 years.

Comment on how the ratio GWPSF6 /GWPCHCl2F would change if the time horizon was 20 years rather than 100 years

Question 2 continued

(b)          Glyoxal, OCHCHO, is produced in the atmosphere by oxidation of numerous volatile organic

compounds, mainly isoprene, and has been proposed as an important source of organic aerosol.

(i)          In a tropical forest, glyoxal is calculated to have the following atmospheric lifetimes at midday:

1 hour against photolysis;

6 hours against oxidation by OH

8 hours against uptake by aqueous particles to form aerosol.

Calculate the total atmospheric lifetime of glyoxal and the fraction of                       (3)

atmospheric glyoxal that will form aerosol.

(ii)         Isoprene emission in the forest is estimated to be 7 × 1011 molecules cm一2 s一 1 .

The glyoxal molar yield from isoprene oxidation is 5%.

.   Assuming an atmospheric boundary layer height (mixing depth) of 1 km       (3)

and that the only losses of glyoxal are those described in part (b)(i), write out an expression for the steady state concentration of glyoxal, and thus  estimate its concentration.  Give your answer in units of molecules cm一3 .

.   Assuming that aerosol in the forest is in steady state and has a lifetime of     (5)

4 days, calculate the mean concentration of organic aerosol from the       glyoxal formation pathway in µg C m一3 .  Comment on the importance of this formation pathway, given the observed concentration of organic       aerosol in the forest of ~ 3 µg C m一3 .

Question 3 - start each question on a new page.

Ionomer-coated electrode surfaces can achieve high current density electroreduction of CO2 to ethene in 7 M potassium hydroxide aqueous electrolyte.

(a)         Write out a balanced chemical reaction for the reductive conversion of CO2 into                   (2)

ethene.  Assign the oxidation states of each element in each reactant and product.        Hence, justify why the reaction requires 12 electrons per molecule of ethene produced.

(b)         (i)          Show why a 7 M aqueous solution of potassium hydroxide would be expected        (2)

to have a pH of approximately 15.

(ii)         Derive an equation to quantify how the reduction potential for the conversion         (4)

of CO2 to ethene will change as a function of pOH.

(c)         Calculate, in μmol s一1, the rate of ethene production when a total current density of              (4)

1.3 A cm一2  is applied to an electrode of area 5 cm2 and the Faradaic efficiency of ethene production is 38%.

Question 3 continued

(d)         To assess the effect of the electrode surface composition on gas availability, reduction of oxygen to water was studied using cyclic voltammetry and electrodes coated with   different volumes of ionomer.  Results of the study, with voltage reported versus the   reversible hydrogen electrode (RHE), are shown in Figure 1 below.

Figure 1

Giving justification, use the data in Figure 1 to identify the ionomer coating that:

    is most effective in terms of maximum current per volume of ionomer.        (3)

Under the conditions used in the cyclic voltammetry experiments,

ERHE = 一0.866 V vs SHE.  Estimate the equivalent voltage scan range for the same    experiments conducted using a saturated calomel electrode (SCE) reference using the relationship ESCE = 0.244 V vs SHE.

Question 4 - start each question on a new page.

(a)         Reactions of three organometallic complexes are shown below.  For each reaction,

describe the fundamental organometallic processes occurring, draw reaction schemes        showing the structures of any intermediates or transition states, and in each case comment on the selectivity shown for the final product.

(b)         A three-step reaction sequence starting from a dimanganese carbonyl precursor is given below.

Analytical data for the intermediates (A and B) and the final products (C and D) is provided.  Identify the compounds A to D, draw their structures, and comment on how the data provided allow for identification of the compounds.

All the reactions proceed with the stoichiometries shown.

Note: you are not required to perform an analysis of the stretching bands using group theory.

Selected Analytical Data

A         White solid, with an IR spectrum that shows three stretching bands between 2139 and

1998 cm– 1 .  The 13C NMR spectrum shows 2 environments in the ratio 1:4.

B         White solid, that has an IR spectrum similar to A, that shows three stretching bands

between 2109 and 1988 cm– 1 .  The 1H NMR spectrum shows four different signals, with relative integrals 1:1:1:2.  EI-MS gives a molecular ion at m/z = 236.

C         White solid, that shows four stretching bands in the IR spectrum, between 2074 and 1961

cm– 1 .  The 1H NMR spectrum shows 3 signals with relative integrals 2:2:1.

D         Toxic gas that shows a single IR stretch at 2143 cm– 1 .  RMM = 28.

Question 5 - start each question on a new page.

Cyclic peptides containing an arginine-glycine-aspartate (RGD) sequence are being investigated as potential tumour imaging agents.  Cyclic RGD peptide analogue 3 can be synthesised by solid phase peptide synthesis from Wang resin-bound dipeptide 1 as outlined below.

(i)          Showing your working, assign the R/S configuration at the positions labelled a       (2) and b in 2.

(ii)         Outline a strategy for the multistep conversion of 1 to 2 including in your               (4)

answer:

    the structures of the required amino acids with protection as

appropriate;

Note: the structure of the Pbf protecting group does not need to be shown.

    additional reagents that are required;

    the correct sequence of steps.

Question 5 continued

(iii)        Draw a curly arrow mechanism for the conversion of 2 to 3 in the presence of        (3)

the coupling reagent HBTU and a base.

Note: you may use abbreviated structures of the peptide as shown below.

(iv)        During the conversion of 2 to 3, a diastereomeric by-product is formed that

results from oxazolone formation.

●    With the aid of a diagram, explain how oxazolone formation can lead to racemisation of amino acids.

Note: abbreviated structures may be used.

●    Give the structure of the diastereomeric by-product that forms during the conversion of 2 to 3.

(b)         Shown below is the synthesis of disaccharide A starting from N-acetylglucosamine

derivative 4.

(i)          Precursor 4 can be converted to partially protected intermediate 5 in four                (5) steps.

    Identify suitable protecting groups R1 and R2 that can be installed

selectively at the indicated positions.

    Identify reagents required to convert 4 to 5 in four steps and give a

reaction scheme that shows the structures of all intermediates.

(ii)         Give the structure of A, commenting on the stereochemical outcome of the             (3)

reaction.

 Question 6 - start each question on a new page.

(a)    Explain briefly how substituent inductive and mesomeric effects contribute to the terms

Q g对q Q+ in the context ofthe Hammett equation.

(b)    Substituted benzenes undergo nitrosation when treated with NaNO2 in acid. Two

mechanisms have been suggested for this reaction.

(i)     De2c写!pe po从 车pe b ^gIne Lo写 车pe 对!车写o2g车!o对 写egc车!o对 cg对 pe op车g!对eq> 8!^!对8     (3) details ofthe experiments and calculations used.

(ii)    lpe exbe写!me对车gII入 qe车e写m!对eq b ^gIne Lo写 车p!2 写egc车!o对 !2 一6.1. Identify which  (3)

oLmecpg对!2m2 J g对q 了 !2 co对2!2车e对车 从!车p 车pe b ^gIne> 8!^!对8 LnII?n2车!L!cg车!o对.

Question 6 continued

(iii)        Identify the Q barameter that is most appropriate for measuring the rate of

nitrosation of compound 1 to give compound 2, shown below.  Explain your choice using appropriate resonance-stabilised structures.

(iv)        Giving your reasons, suggest a monosubstituted benzene that would have a

higher rate of nitrosation than 1.

Note: Q barameter values are given in the databook.

(v)         Predict which ring system in the diphenyl derivative 3 would undergo a selective nitrosation reaction, giving your reasons.

The aromatic substituents in compounds 4 and 5 influence their conformational          preference.  Draw the preferred most stable conformer for each compound and briefly explain your reasoning.