Practice Problems in Pericyclic Reactions.

Copyright (c) 1994 - 1997 H. S. Rzepa

The following are a set of practice problems in Pericyclic Mechanisms, prepared by Henry Rzepa for the for a second year course at the Department of Chemistry, Imperial College. Each of these problems is intended to take between 1-3 hours to solve. They are NOT typical of examination questions! Please note also that the compound numbers are not consecutive between questions.


Qu. 1 When compound 1 is heated, a transient intermediate 2 is formed, rapidly rearranging to two new compounds 3 and 4. An aqueous workup of this mixture, in which traces of acid were present, showed that 4 had been converted to 5. Suggest structures for compound 2-4, and mechanisms for all the steps in this sequence.

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Qu. 2 When compound A is heated, carbon dioxide and benzonitrile (PhCN) are eliminated and the final observed product is the indole G. It is thought that the mechanism of the reactions proceeds via a series of intermediates B - F, the structures of two of which (D and E) are shown below. Suggest probable structures for the other species B, E and F and mechanisms for all the reactions. Pay attention to why both C and D give the same intermediate E, any selection rules that may relate to individual steps and the nomenclature of each step.


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Qu. 3. a) When molecules 1 and 2 (E = CO2Me) are heated together, the transient intermediates 3 and 4 are formed, with the eventual isolation of 5 and 6 as the two final products. Propose structures for 3 and 4 and a mechanism for the formation of 5 and 6.

b) Propose structures for A and B and mechanisms for the following transformations.


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Qu. 4 Photolysis of compound 7 in benzene as solvent produces the triene 8, which then decomposes thermally to give butadiene and tetralin (12), via it is thought the intermediates 9, 10 and 11. Propose and classify the mechanisms for these transformations, and suggest a structure for 11.

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Qu. 5. a). Suggest a mechanism for the following reaction which explains the observed stereochemistry;

b). Propose a structure for 1 consistent with the spectral evidence and classify the type of pericyclic reaction occuring, paying particular attention to the expected stereochemistry of the product. 1H nmr includes the following; d 1.43 (3H, s), 1.52 (3H, triplet, J 1.5Hz), 3.76 (1H, multiplet), 5.71 (1H, multiplet), 5.73 (1H, double doublet, J 10, 1.5Hz), 5.79 (1H, doublet, J 10Hz), 6.74 (1H) + phenyl protons. No carbonyl peak is evident from the infra-red spectrum and no cyclopropyl group is present in 1.


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Qu. 6. Tropylium tetraborate can be reduced with Zn/Hg to ditropyl [A].

Ditropyl is in equilibrium with an isomer, which when refluxed with an excess of the dimethyl ester of acetylene dicarboxylic acid (DMAD= MeO2C-CC-CO2Me) reacts to give a single adduct [B] with the following nmr properties; d 6.0 (4H, t, 4Hz), 4.05 (4H, broad singlet), 3.75 (12H, s), 1.2 (4H, double doublet, 3Hz, 2Hz), 0.9 (2H, triplet, 3Hz). When [B] is subjected to flash vacuum pyrolysis at 600 (FVP) two compounds [C] and [D] are formed. Compound [D] is stable and has the following nmr spectrum; d 7.62 (8H, symmetrical multiplet), 3.90 (12H, s). The 1H nmr spectrum for compound [C] includes the presence of vinylic protons (4H), but on standing these slowly disappear and a signal at d 7.37 (6H) due to benzene takes their place. Suggest possible structures for [B] - [D], paying particular attention to possible isomeric forms, the mechanisms of their formation and their nmr spectral properties. There is no need to propose a mechanism for the conversion of [C] to benzene.

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Qu 7. a) Propose a mechanism for the following transformation, identifying any intermediates that might be involved;

b) The following transformation can take place via two alternative pathways, one involving intermediates 2 and 3, the other involving a single intermediate 4. When 13C label is introduced into the reactant, the product can be shown to have the label distributed as shown. Suggest possible structures for the intermediates 2-4, and on the basis of the labelling information, indicate which mechanistic pathway is actually followed.


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Qu 8. When compound 5 is photolysed in heptane, a solution of "x" is formed. This solution shows the following nmr properties. At -76 complex multiplets in the 1H nmr spectrum are seen at δ 6.3-4.8 and at 3.3- 1.4 ppm. As the temperature is raised, both multiplets are broadened and portions of each multiplet move together and coalesce to a single multiplet at d 3.82 at a temperature of 78. The integral of this coalesced multiplet is 1/6 of the total proton integral. On recooling to -76, the spectrum returns to its previous appearance. If the solution is subjected to catalytic hydrogenation, compound 7 is one of the products. If the solution is heated to 98, "x" then reacts to form a new compound 6 in which the two vinyl groups are specifically trans.

Suggest possible structure(s) for the unknown "x", paying particular attention to stereochemistry and the nmr behaviour. Suggest a conformational explanation for why 6 has trans stereochemistry (Hint: what must the most stable conformation of the precursor to 6 be and how would you estimate this quantitatively?)

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Qu. 9. Classify the type of thermal reaction occuring in the sequences below, indicating clearly any stereochemical implications.

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Qu. 10. Classify the type of (thermal) pericyclic reaction occuring for each of the eight steps shown below, showing clearly how many electrons are involved in each step, and discuss any obvious (or indeed less obvious!) stereochemical implications and nomenclature.

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Qu 11. a) Propose a mechanism for the following transformation, including an explanation for the formation of two products and indicating the number of electrons involved in each step. Extrapolating from this explanation, suggest a related third product that might have formed, but as it happens was not detected with these particular substituents.

b) In the following sequence, the technique of flash vacuum pyrolysis results in the trapping of HNCO, HCN and a novel third product Z on a cold finger. The species Z shows at least one ir band in the region 2280 cm-1. When trapped with two quivalents of methanol, Z gives the product shown. Suggest possible identities for the two intermediates X and Y as well as Z, and mechanisms for all the reactions, including details of nomenclature for each step.


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Qu 12. In the following sequence, suggest possible structures for the intermediates L, M and N, together with mechanisms and nomenclature for their formation. Discuss whether each step is formally allowed by the pericyclic selection rules for thermal reactions, or whether it requires the presence of traces of acid or base.

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Qu 13. Suggest a nomenclature for the following three substrates;

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Qu 14. When a mixture of hexa-2,4-dienol, CS2, KOH and prop-2-ynyl bromide is stirred for 12 hours at room temperature, the expected compound 1 is not isolated. Instead an oil "A" with the following spectroscopic properties is obtained; [[nu]]max 1646 cm-1, dH 1.70 (3H, d, J 6Hz), 2.23 (1H, t, J 3Hz), 3.73 (2H, d, J 3Hz), 4.84 (1H, dd, J 7, 8 Hz), 5.16 (1H, d, J 10 Hz), 5.27 (1H, d, J 17 Hz), 5.51 (1H, dd, J 8, 16.5 Hz), 5.72 (1H, dq, J 6, 16.5 Hz), 5.88 (1H, ddd, J 7, 10, 17 Hz). On heating to 180*C, compound 2 was isolated in 62% yield, via the presumed intermediate shown. Identify compound "A", suggest mechanisms for the subsequent reactions of 1, and assign the spectroscopic data, including a discussion of the coupling constants. In compound 2, suggest a probable stereochemical assignment for the methyl group marked with a



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Qu 15. The 1,3 elimination of HCl from the imidoyl chloride isomers shown proceeds rapidly at 0*C to give the two compounds 3 and 4. On standing at room temperature, these rearrange to "X" or "Y", for which the following spectral data are obtained. X: dH 0.56 (3H, d, J 6.2 Hz), 2.40 (1H, dq, J 9.8, 6.2 Hz), 2.85 (1H, d, J 9.8 Hz), 8.51 (1H, s), 7.18-7.55 (9H, m); dC 5 (q), 15 (d), 33 (d), 54 (s), 155 (s) + aromatics. Y: dH 1.08 (3H, d, J 6.2 Hz), 0.49 (1H, dq, J 5.5, 6.2 Hz), 2.66 (1H, d, J 5.5 Hz), 8.16 (1H, s), 7.25-7.55 (9H, m); dC 28 (q), 14 (d), 32 (d), 58 (s), 153 (s) + aromatics. On refluxing in benzene, either "X" or "Y" interconvert via the presumed intermediacy of compound 5, which in turn slowly isomerises to 6, the final isolated product. Suggest structures for "X" and "Y" based on spectral and mechanistic evidence and propose likely mechanisms for their formation and subsequent reactions, paying particular attention to the stereochemistry of the species involved. (Hints: Try drawing alternative resonance forms of 3 and 4, and pay particular regard to the differences in the chemical shifts of X and Y. The multiplicities of the carbon nmr signals are those obtained with off-resonance decoupling).



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Qu 16. The synthesis of the naturally occuring coumarin ester Gravelliferone is accomplished by heating the compound [1] in the presence of weak base. Two intermediates [2] and [3] are thought to be implicated in the mechanism. Suggest a possible structure for [2] and mechanisms for the overall transformation, indicating any steps that might involve the base.



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Qu 17. 1-Nitropropene when added slowly to a solution of phenyl isocyanate and triethylamine (which together act as a dehydrating reagent) in the presence of norbornadiene forms a mixture of two isomeric compounds A and B. These both show three similar vinylic nmr peaks, but are distinguished by different couplings in the non-vinylic region. A: δ3.45 (J 8, 1.5 Hz), and 4.82 (J 8, 1.3 Hz) and B: δ3.87 (J 9.5, 4.2 Hz), and 5.29 (J 9.5, 4.3 Hz). Flash vacuum pyrolysis of A+B yields cyclopentadiene and a new compound C, the latter having the following 1H nmr spectrum: δ 5.61 (J 10.9, 0.9Hz), 5.90 (J 17.8, 0.9 Hz), 6.47 (J 1.7Hz), 6.8 (J 17.8, 10.9 Hz), 8.32 (J 1.7 Hz), which includes three vinylic and two aromatic resonances, and one surprisingly low ortho aromatic coupling. Suggest structures for A, B and C, mechanisms for their formation and an interpretation of the different couplings manifested for A and B (Hint: try using the MacroModel modelling program).



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Qu 18. Random dot autostereograms are a way of representing three dimensional images. Does this compound contain any chiral centres?



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Qu. 19. The transformation of [A] to [B] by heating has been extensively studied kinetically. The evidence seems to suggest that direct conversion does not occur. Synthesis of the triene [Z] suggests it is converted to [B] very rapidly. Mechanisms have been proposed which indicate that whilst direct conversion of [A] to [Z] is possible, it cannot be the exclusive pathway, since an intermediate [E] is detected during reaction. [E] cannot convert thermally to [Z] at the temperatures used, but would have to go via [Y]. It is also possible that [Y] too is formed directly from [A], but this is thought less likely on steric grounds.

Suggest possible structures for [E], [Y], [Z], mechanisms for all the possible conversion routes shown with arrows below, and explain the cause of the steric grounds referred to above.


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Qu. 20. Reaction of two equivalents of the [1,3] dipolar species [S] with pyridine gives a 43% yield of the adduct [P]. The 1H NMR of [P] is δ 3.15 (dd, J 17, 6.8Hz), 4.00 (dd, J 17, 11.5), 6.20 (dd, J 11.5, 8.5), 6.42 (dd, J 11.5, 1.2), 6.45 (multiplet, J 11.5, 8.5, 6.8, 1.2), 6.8-8.4 (20H, aromatics). Three intermediates [M], [N and [O] are thought to be involved. Suggest possible structures for [N] and [P], together with mechanisms for their formation, assignment of the NMR data for [P] and any stereochemical conclusions derived from this data.

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Qu 21.

When compound 1 is treated with base and heated, it rearranges to give the products shown. The 13C isotope is distributed unequally between two products. Explain this result in mechanistic terms, and clearly indicate the type of reactions occurring and their nomenclature.


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Qu. 22. Propose a mechanism for the following transformation.


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Qu. 23. Shown below are stages in the total syntheses of two interesting molecules. Describe the type of reaction occuring at each stage, including details of nomenclature and the number of electrons involved. Suggest structures for the intermediates A, B and C, and propose mechanisms for each stage.

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Qu. 24. PThe molecule below when heated gives rise to varying amounts of the products D-H. Propose mechanisms to account for the formation of each product. Some of these reactions will be pericyclic reactions, some (such as the aromatising loss of hydrogen) will include steps that are not. Indicate clearly which are the pericyclic steps.


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