IChO 1992 · Theory problem 9

Reactions of insect pheromones

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Pheromones are chemicals or mixtures of certain chemicals secreted by insects and some animals for communication. They bring about certain responses in another individual of the same species. In the problem below you will find a number of pheromones undergoing reactions which were used in determining their structures. In each case give the structure or structures of the products produced. Show geometric (cis/trans) isomers where appropriate (in part (9.5). You may ignore other forms of stereoisomerism.

9.1

Figure 1

isoamyl acetate,
bee alarm pheromene

9.2

i)

Figure 2

2-heptanone
ant alarm pheromone

ii)

Figure 3

iii)

Figure 4

9.3

i)

Figure 5

green peach -
aphid pheromone

ii)

Figure 6

9.4

(i)

Figure 7

(ii)

Figure 8

(iii)

Figure 9

9.5

i)

Figure 10

ii)

Figure 11

iii)

Figure 12

iv)

Figure 13

v)

Figure 14

vi)

Figure 15

Official English text of the problem.

Answers

Where stereochemical SMILES are given, one representative of each required relative configuration is shown; its mirror image need not be listed separately.

  • 9.1: Sodium ethanoate (sodium acetate), CC(=O)[O-].[Na+], and 3-methylbutan-1-ol (isoamyl alcohol), CC(C)CCO.

  • 9.2(i): Sodium hexanoate, CCCCCC(=O)[O-].[Na+], and triiodomethane (iodoform), IC(I)I.

  • 9.2(ii): Heptan-2-ol, CC(O)CCCCC.

  • 9.2(iii): As printed, ethanol quenches the Grignard reagent, producing ethane, CC, while heptan-2-one, CC(=O)CCCCC, remains available. If ordinary dry-ether Grignard conditions were intended, followed by acidic work-up, the product is 3-methyloctan-3-ol, CCC(C)(O)CCCCC.

  • 9.3(i): Per molecule of pheromone:

  • one propan-2-one (acetone), CC(=O)C;
  • one 4-oxopentanal, CC(=O)CCC=O;
  • one 2-oxopentanedial, O=CC(=O)CCC=O;

  • two methanal (formaldehyde), C=O.

  • 9.3(ii): At the usual aldehyde-to-carboxylic-acid endpoint:

  • one propan-2-one, CC(=O)C;
  • one 4-oxopentanoic acid (levulinic acid), CC(=O)CCC(=O)O;
  • one 2-oxopentanedioic acid (α-ketoglutaric acid), O=C(O)C(=O)CCC(=O)O;
  • two methanoic acid (formic acid), O=CO.

Further oxidation can convert the one-carbon products into carbon dioxide, O=C=O; additional peroxide oxidation is discussed below.

  • 9.4(i): Direct dehydration gives:
  • 3-methylhex-3-ene: \(E\) CC/C(C)=C/CC; \(Z\) CC/C(C)=C\CC;
  • 4-methylhex-2-ene: \(E\) C/C=C/C(C)CC; \(Z\) C/C=C\C(C)CC.

A favorable hydride rearrangement also permits: - 3-methylhex-2-ene: \(E\) C/C=C(C)/CCC; \(Z\) C/C=C(C)\CCC; - 2-ethylpent-1-ene, C=C(CC)CCC.

  • 9.4(ii): 4-Methylhexan-3-one, CCC(=O)C(C)CC.

  • 9.4(iii): 4-Methylhexan-3-yl ethanoate (acetate), CC(=O)OC(CC)C(C)CC.

  • 9.5(i): trans-1,2-Dibromo-1-methylcyclohexane, C[C@]1(Br)[C@H](Br)CCCC1. The bromine atoms occupy opposite ring faces.

  • 9.5(ii): cis-1-Methylcyclohexane-1,2-diol, C[C@]1(O)[C@@H](O)CCCC1. The hydroxyl groups occupy the same ring face.

  • 9.5(iii): 1-Methylcyclohexan-1-ol, CC1(O)CCCCC1.

  • 9.5(iv): Both cis-1-bromo-2-methylcyclohexane, C[C@H]1[C@@H](Br)CCCC1, and trans-1-bromo-2-methylcyclohexane, C[C@H]1[C@H](Br)CCCC1. Here cis/trans describes bromine relative to methyl.

  • 9.5(v): trans-2-Methylcyclohexan-1-ol, C[C@H]1[C@H](O)CCCC1. The hydroxyl and methyl groups occupy opposite ring faces.

  • 9.5(vi): Methylcyclohexane, CC1CCCCC1.

Solution

The equations below give balanced molecular or net ionic reactions. Common species are water, O; hydrogen ion, [H+]; hydroxide ion, [OH-]; and hydronium ion, [OH3+]. Metals and solid metal oxides are represented by their chemical formulas.

9.1

The substrate is 3-methylbutyl ethanoate, commonly called isoamyl acetate, CC(=O)OCCC(C)C. Heating with sodium hydroxide, [Na+].[OH-], causes ester saponification:

\[ \ce{CH3COOCH2CH2CH(CH3)2 + NaOH -> CH3COONa + HOCH2CH2CH(CH3)2}. \]

Hydroxide attacks the ester carbonyl carbon. Collapse of the tetrahedral intermediate and proton transfer give the alcohol and the resonance-stabilized acetate ion. The basic medium leaves the carboxylic product as its sodium salt.

9.2(i)

Heptan-2-one, CC(=O)CCCCC, contains the methyl-ketone group \(\ce{CH3CO-}\), so it undergoes the iodoform reaction:

\[ \ce{CH3CO(CH2)4CH3 + 3I2 + 4NaOH -> CH3(CH2)4COONa + CHI3 + 3NaI + 3H2O}. \]

Iodine is II, and the inorganic salt product is sodium iodide, [Na+].[I-].

The three hydrogens of the carbonyl-adjacent methyl group are successively replaced by iodine. Hydroxide then induces cleavage between that carbon and the carbonyl carbon. The methyl carbon becomes iodoform; the remaining six-carbon fragment becomes hexanoate.

9.2(ii)

Sodium borohydride, [Na+].[BH4-], reduces the ketone carbonyl to a secondary alcohol. Ethanol, CCO, supplies a proton to the initially formed alkoxide.

An idealized balanced equation in ethanol is

\[ \ce{4CH3CO(CH2)4CH3 + BH4^- + 4C2H5OH -> 4CH3CH(OH)(CH2)4CH3 + [B(OC2H5)4]^-}. \]

Here the boron residue is represented as tetraethoxyborate, [B-](OCC)(OCC)(OCC)OCC; its actual speciation depends on water content.

Hydride adds to the carbonyl carbon, and protonation of oxygen produces heptan-2-ol. Its newly formed stereocentre need not be specified.

9.2(iii)

There is a material incompatibility in the printed scheme: ethylmagnesium bromide, CC[Mg]Br, is shown in ethanol.

A Grignard reagent undergoes rapid proton transfer with ethanol:

\[ \ce{C2H5MgBr + C2H5OH -> C2H6 + C2H5OMgBr}. \]

The products are ethane and ethoxymagnesium bromide, represented by CCO[Mg]Br. This organomagnesium SMILES specifies connectivity; it does not describe solvent coordination or aggregation.

The subsequent acidic work-up hydrolyses the magnesium ethoxide:

\[ \ce{C2H5OMgBr + H3O+ -> C2H5OH + Mg^2+ + Br^- + H2O}. \]

Magnesium(II) ion is [Mg+2], and bromide ion is [Br-]. The printed hydroxide is also neutralized:

\[ \ce{OH^- + H3O+ -> 2H2O}. \]

Thus the conditions as printed do not support the usual Grignard addition.

If dry ethereal conditions were intended—for example, diethyl ether, CCOCC, without the printed hydroxide—the ethyl group adds to the ketone carbonyl. Subsequent acidic work-up gives the tertiary alcohol. The combined balance for these sequential operations is

\[ \begin{aligned} &\ce{CH3CO(CH2)4CH3 + C2H5MgBr + H3O+}\\ &\quad\ce{-> CH3C(OH)(C2H5)(CH2)4CH3 + Mg^2+ + Br^- + H2O}. \end{aligned} \]

The longest chain containing the hydroxyl-bearing carbon has eight carbons. Both hydroxyl and methyl are at carbon 3, giving 3-methyloctan-3-ol.

9.3(i)

The substrate is \((E)\)-β-farnesene, systematically \((6E)\)-7,11-dimethyl-3-methylidenedodeca-1,6,10-triene, CC(C)=CCC/C(C)=C/CCC(=C)C=C.

Its connectivity can be written as

\[ \ce{(CH3)2C=CH-CH2-CH2-C(CH3)=CH-CH2-CH2-C(=CH2)-CH=CH2}. \]

Ozone, [O-][O+]=O, cleaves all four double bonds. With reductive zinc work-up:

  • an alkene carbon bearing no hydrogen becomes a ketone carbonyl;
  • an alkene carbon bearing one hydrogen becomes an aldehyde carbonyl;
  • a terminal \(\ce{=CH2}\) carbon becomes formaldehyde.

Reading the fragments along the original skeleton gives acetone, 4-oxopentanal, 2-oxopentanedial, and two formaldehyde molecules.

A balanced equation is

\[ \begin{aligned} &\ce{C15H24 + 4O3 + 4Zn + 8H+}\\ &\quad\ce{-> CH3COCH3 + CH3COCH2CH2CHO}\\ &\qquad\ce{+ OHC-C(=O)-CH2-CH2-CHO + 2HCHO}\\ &\qquad\ce{+ 4Zn^2+ + 4H2O}. \end{aligned} \]

Zinc(II) ion is [Zn+2].

The carbon check is

\[ 3+5+5+2(1)=15. \]

There are eight carbonyl groups in total, as expected from cleavage of four double bonds.

9.3(ii)

Hydrogen peroxide, OO, gives an oxidative work-up. At the standard carboxylic-acid endpoint, each aldehyde group is oxidized according to

\[ \ce{RCHO + H2O2 -> RCOOH + H2O}. \]

The ketone carbonyl groups remain in the formal cleavage products. Consequently:

  • acetone remains acetone;
  • 4-oxopentanal becomes 4-oxopentanoic acid;
  • both aldehyde groups of 2-oxopentanedial become carboxyl groups, giving 2-oxopentanedioic acid;
  • each formaldehyde becomes formic acid.

A balanced overall equation for that endpoint is

\[ \begin{aligned} &\ce{C15H24 + 4O3 + H2O2}\\ &\quad\ce{-> CH3COCH3 + CH3COCH2CH2COOH}\\ &\qquad\ce{+ HOOC-C(=O)-CH2-CH2-COOH + 2HCOOH + H2O}. \end{aligned} \]

This is a net balance; it does not specify the laboratory excess of oxidant.

Further oxidation introduces an endpoint qualification. Formic acid can be oxidized to carbon dioxide:

\[ \ce{HCOOH + H2O2 -> CO2 + 2H2O}. \]

The α-keto acid can also undergo peroxide-mediated oxidative decarboxylation, producing butanedioic acid (succinic acid), O=C(O)CCC(=O)O:

\[ \begin{aligned} &\ce{HOOC-C(=O)-CH2-CH2-COOH + H2O2}\\ &\quad\ce{-> HOOC-CH2-CH2-COOH + CO2 + H2O}. \end{aligned} \]

The acid list in Answers is therefore the conventional functional-group cleavage answer; an exhaustive oxidation endpoint requires additional assumptions about the work-up.

9.4(i)

The starting alcohol is 4-methylhexan-3-ol, CCC(O)C(C)CC. Sulfuric acid, OS(=O)(=O)O, and heat promote dehydration. Each alkene-forming channel has the balance

\[ \ce{CH3CH2CH(OH)CH(CH3)CH2CH3 <=> C7H14 + H2O}. \]

Protonation of the hydroxyl group followed by loss of water gives the secondary 4-methylhexan-3-yl carbocation, CC[CH+]C(C)CC.

Removal of a β-hydrogen from either adjacent carbon gives the two direct elimination products:

  • removal from carbon 2 gives 4-methylhex-2-ene;
  • removal from carbon 4 gives 3-methylhex-3-ene, after renumbering.

Of these, 3-methylhex-3-ene is the more substituted, Zaitsev alkene.

A 1,2-hydride shift from the adjacent methine carbon produces the more stable tertiary 3-methylhexan-3-yl carbocation, CC[C+](C)CCC. Elimination from its three adjacent carbon groups gives:

  • 3-methylhex-3-ene again;
  • 3-methylhex-2-ene;
  • 2-ethylpent-1-ene.

All three internal alkene constitutions admit \(E/Z\) isomerism; their explicit SMILES appear in Answers. The terminal methylene product has no \(E/Z\) pair. The printed conditions do not determine product proportions or the extent of subsequent alkene equilibration.

9.4(ii)

Acidified dichromate oxidizes a secondary alcohol to a ketone. The carbon skeleton is retained:

\[ \begin{aligned} &\ce{3CH3CH2CH(OH)CH(CH3)CH2CH3 + Cr2O7^2- + 8H+}\\ &\quad\ce{-> 3CH3CH2COCH(CH3)CH2CH3 + 2Cr^3+ + 7H2O}. \end{aligned} \]

The reagent ion is dichromate, [O-][Cr](=O)(=O)O[Cr](=O)(=O)[O-]; the reduced chromium species is chromium(III), [Cr+3].

Each alcohol loses two hydrogen atoms, giving 4-methylhexan-3-one.

9.4(iii)

Ethanoic acid (acetic acid), CC(=O)O, reacts with the alcohol by acid-catalysed Fischer esterification:

\[ \begin{aligned} &\ce{CH3CH2CH(OH)CH(CH3)CH2CH3 + CH3COOH}\\ &\quad\ce{<=> CH3CH2CH(OC(=O)CH3)CH(CH3)CH2CH3 + H2O}. \end{aligned} \]

Carbonyl protonation facilitates attack by the alcohol oxygen; proton transfers and water elimination produce 4-methylhexan-3-yl acetate. The reaction is reversible.

9.5

Every substrate in this part is 1-methylcyclohex-1-ene, CC1=CCCCC1. For describing addition, call the methyl-bearing alkene carbon C1 and the adjacent alkene carbon C2.

9.5(i)

Bromine, BrBr, in carbon tetrachloride, ClC(Cl)(Cl)Cl, adds across the double bond:

\[ \ce{C7H12 + Br2 -> C7H12Br2}. \]

A bridged bromonium intermediate is opened by bromide from the opposite face, giving anti addition. The product is therefore trans-1,2-dibromo-1-methylcyclohexane.

To draw it, put one bromine on a solid wedge and the adjacent bromine on a hashed wedge.

9.5(ii)

Under the usual mild alkaline conditions, permanganate, [O-][Mn](=O)(=O)=O, gives syn dihydroxylation:

\[ \ce{3C7H12 + 2MnO4^- + 4H2O -> 3C7H14O2 + 2MnO2 + 2OH^-}. \]

The inorganic precipitate is manganese(IV) oxide, \(\ce{MnO2}\).

Both oxygen atoms are delivered to the same alkene face through a cyclic intermediate. The product is cis-1-methylcyclohexane-1,2-diol.

Draw both hydroxyl groups as solid wedges, or both as hashed wedges.

9.5(iii)

Acid-catalysed hydration has the net balance

\[ \ce{C7H12 + H2O -> C7H14O}. \]

Protonation that places the carbocation at the methyl-bearing carbon gives the more stable tertiary carbocation. Water attacks that carbon, and deprotonation gives the Markovnikov product, 1-methylcyclohexan-1-ol.

Draw the methyl and hydroxyl groups attached to the same ring carbon. There is no distinct cis/trans pair for this product.

9.5(iv)

Hydrogen bromide, [H]Br, adds by a radical chain mechanism in the presence of peroxide:

\[ \ce{C7H12 + HBr -> C7H13Br}. \]

A bromine radical, [Br], adds to C2, leaving the more substituted radical at C1. Hydrogen abstraction from another hydrogen bromide molecule then completes the anti-Markovnikov addition.

This radical sequence is not stereospecific. It produces both:

  • cis-1-bromo-2-methylcyclohexane, with methyl and bromine on the same face;
  • trans-1-bromo-2-methylcyclohexane, with methyl and bromine on opposite faces.

9.5(v)

Borane, [BH3], undergoes concerted syn addition: boron attaches to the less substituted carbon C2, while hydrogen attaches to C1. Oxidation replaces the carbon–boron bond with a carbon–oxygen bond with retention of configuration.

A balanced overall equation in basic solution is

\[ \ce{3C7H12 + BH3 + 3H2O2 + OH^- -> 3C7H14O + [B(OH)4]^-}. \]

The boron-containing product is tetrahydroxyborate, [B-](O)(O)(O)O.

The newly added hydrogen at C1 and hydroxyl group at C2 are syn. Since the original methyl group at C1 lies opposite that newly added hydrogen, methyl and hydroxyl are trans.

The product is therefore trans-2-methylcyclohexan-1-ol. Draw methyl on a solid wedge and hydroxyl on a hashed wedge, or the mirror-image arrangement.

9.5(vi)

Hydrogen, [H][H], adds over platinum:

\[ \ce{C7H12 + H2 -> C7H14}. \]

Hydrogenation removes the double bond and gives methylcyclohexane. Although surface hydrogenation delivers hydrogen syn, the product has no distinct cis/trans isomers.

The solution was checked against the official solution. Where this solution differs from the official solution, the official solution contains an error or a misprint.