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Organic Chemistry

Jonathan Clayden, Nick Greeves, Stuart Warren, Peter Wothers

Chapter 32

Determination of stereochemistry by spectroscopic methods - all with Video Answers

Educators


Chapter Questions

Problem 1

A revision problem to start you off easily. A Pacific sponge contains $2.8 \%$ dry weight of a sweet-smelling oil with the following spectroscopic details. What is its structure and stereochemistry?
Mass spectrum gives formula: $\mathrm{C}_9 \mathrm{H}_{15} \mathrm{O}$ IR $1680,1635 \mathrm{~cm}^{-1}$
$\delta_{\mathrm{H}} 0.90(6 \mathrm{H}, \mathrm{d}, J 7), 1.00(3 \mathrm{H}, \mathrm{t}, J 7), 1.77(1 \mathrm{H}, \mathrm{m}), 2.09(2 \mathrm{H}, \mathrm{t}, J$ 7), $2.49(2 \mathrm{H}, \mathrm{q}, J 7), 5.99(1 \mathrm{H}, \mathrm{d}, J 16)$, and $6.71(1 \mathrm{H}, \mathrm{dt}, J 16,7) \delta_{\mathrm{C}} 8.15(\mathrm{q}), 22.5(\mathrm{two} \mathrm{qs}), 28.3(\mathrm{~d}), 33.1(\mathrm{t}), 42.0(\mathrm{t}), 131.8(\mathrm{~d})$, $144.9(\mathrm{~d})$, and $191.6(\mathrm{~s})$

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06:11

Problem 2

Reaction between this aldehyde and ketone in base gives a compound A with the ${ }^1 \mathrm{H}$ NMR spectrum: $\delta 1.10(9 \mathrm{H}, \mathrm{s}), 1.17(9 \mathrm{H}$, s), $6.4(1 \mathrm{H}, \mathrm{d}, J 15)$ and $7.0(1 \mathrm{H}, \mathrm{d}, J 15)$. What is its structure? (Don't forget stereochemistry!) When this compound reacts with HBr it gives compound B with this NMR spectrum: $\delta 1.08(9 \mathrm{H}, \mathrm{s})$, $1.13(9 \mathrm{H}, \mathrm{s}), 2.71(1 \mathrm{H}, \mathrm{dd}, J 1.9,17.7), 3.25(\mathrm{dd}, J 10.0,17.7)$, and $4.38(1 \mathrm{H}, \mathrm{dd}, J 1.9,10.0)$. Suggest a structure, assign the spectrum, and give a mechanism for the formation of $B$.

Nima Gharibi
Nima Gharibi
Numerade Educator
03:13

Problem 3

In Chapter 20 we set a problem asking you what the stereochemistry of a product was. Now we can give you the NMR spectrum of the product and ask: how do we know the stereochemistry of the product? You need only the partial NMR spectrum: $\delta_{\mathrm{H}} 3.9(1 \mathrm{H}, \mathrm{ddq}, J 12,4,7)$ and $4.3(1 \mathrm{H}, \mathrm{dd}, J 11,3)$.

Zubair Abdulla
Zubair Abdulla
Numerade Educator
08:07

Problem 4

Two diastereoisomers of this cyclic ketolactam have been prepared. The NMR spectra have many overlapping signals but the proton marked in green can clearly be seen. In isomer A it is $\delta_{\mathrm{H}} 4.12(1 \mathrm{H}, \mathrm{q}, J 3.5)$, and isomer B has $\delta_{\mathrm{H}} 3.30(1 \mathrm{H}, \mathrm{dt}, J 4,11,11)$. Which isomer has which stereochemistry?

Dr.  Satish  Ingale
Dr. Satish Ingale
Numerade Educator
04:09

Problem 5

How would you determine the stereochemistry of these two
compounds?

Chloe Schroeder
Chloe Schroeder
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Problem 6

The structure and stereochemistry of the antifungal
antibiotic ambruticin was in
part deduced from the NMR
spectrum of this simple
cyclopropane. Interpret the NMR spectrum and show how it gives
definite evidence on the stereochemistry.
δH 1.13 (3H, d, J 8), 1.32 (3H, t, J 7), 1.47 (9H, s), 1.71 (1H, t, J
5), 2.2 (1H, ddq, J 5, 12, 7), 4.3 (2H, q, J 8), 6.05 (1H, d, J 17), and
6.75 (1H, dd, J 17, 12)

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06:54

Problem 7

One of the sugar components in the antibiotic kijanimycin has the gross structure and NMR spectrum shown below. What is its stereochemistry? All couplings in Hz; signals marked * exchange with $\mathrm{D}_2 \mathrm{O}$.

Allison Krajewski
Allison Krajewski
Numerade Educator
03:16

Problem 8

The structure of a Wittig product intended as a prostaglandin model was established by the usual methods-except for the geometry of the double bond. Irradiation of a signal at $3.54(2 \mathrm{H}, \mathrm{t}$, $J 7.5)$ led to an enhancement of another signal at $\delta_{\mathrm{H}} 5.72(1 \mathrm{H}, \mathrm{t}, J$ 7.1) but not to a signal at $\delta_{\mathrm{H}} 3.93(2 \mathrm{H}, \mathrm{d}, J 7.1)$. What is the stereochemistry of the alkene? How is the product formed?

Ian Kaigh
Ian Kaigh
Numerade Educator

Problem 9

How would you determine the stereochemistry of this cyclopropane? The NMR spectra of the three protons on the ring are given: $\delta_{\mathrm{H}} 1.64(1 \mathrm{H}, \mathrm{dd}, J 6,8), 2.07(1 \mathrm{H}$,

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05:28

Problem 10

A chemical reaction produces two diastereoisomers of the product. Isomer A has $\delta_{\mathrm{H}} 3.08(1 \mathrm{H}, \mathrm{dt}, J 4,9,9)$ and 4.32 ( $1 \mathrm{H}, \mathrm{d}, J 9,4$ ) while isomer B

Ian Kaigh
Ian Kaigh
Numerade Educator

Problem 11

Muscarine, the poisonous principle of the death cap mushroom, has the following structure and proton NMR spectrum. Assign the spectrum. Can you see definite evidence for the stereochemistry? All couplings in Hz ; signals marked * exchange with $\mathrm{D}_2 \mathrm{O}$.
$\delta_{\mathrm{H}} 1.16(3 \mathrm{H}, \mathrm{d}, J 6.5), 1.86(1 \mathrm{H}, \mathrm{ddd}, J 12.5,9.5,5.5), 2.02(1 \mathrm{H}$, ddd, $J 12.5,2.0,6.0), 3.36(9 \mathrm{H}, \mathrm{s}), 3.54(1 \mathrm{H}, \mathrm{dd}, J 13,9.0), 3.74 (1 \mathrm{H}, \mathrm{dd}, J 13,1.0), 3.92(1 \mathrm{H}, \mathrm{dq}, J 2.5,6.5), 4.03(1 \mathrm{H}, \mathrm{m}), 4.30^* (1 \mathrm{H}, \mathrm{d}, J 3.5)$, and $4.68(1 \mathrm{H}, \mathrm{m})$.

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04:50

Problem 12

An antifeedant compound that deters insects from eating food crops has the gross structure shown below. Some of the NMR signals that can clearly be made out are also given. Since NMR coupling constants are clearly useless in assigning the stereo-chemistry, how would you set about it?

$$
\begin{aligned}
& \delta_{\mathrm{H}} 2.22(1 \mathrm{H}, \mathrm{~d}, J 4), 2.99(1 \mathrm{H}, \mathrm{dd}, J 4,2.4), 4.36(1 \mathrm{H}, \mathrm{~d}, J 12.3), \\
& 4.70(1 \mathrm{H}, \mathrm{dd}, J 4.7,11.7), 4.88(1 \mathrm{H}, \mathrm{~d}, J 12.3)
\end{aligned}
$$

Zubair Abdulla
Zubair Abdulla
Numerade Educator
06:39

Problem 13

The seeds of the Costa Rican plant Ateleia herbert smithii are avoided by all seed eaters (except a weevil that adapts them for its defence) because they contain two toxic amino acids (IR spectra like other amino acids). Neither compound is chiral. What is the structure of these compounds? They can easily be separated because one $(\mathrm{A})$ is soluble in aqueous base but the other $(\mathrm{B})$ is not.
A is $\mathrm{C}_6 \mathrm{H}_9 \mathrm{NO}_4$ (mass spectrum) and has $\delta_{\mathrm{C}} 34.0(\mathrm{~d}), 40.0(\mathrm{t}), 56.2 (\mathrm{s}), 184.8(\mathrm{~s})$, and $186.0(\mathrm{~s})$. Its proton NMR has three exchanging protons on nitrogen and one on oxygen and two complex signals at $\delta_{\mathrm{H}} 2.68\left(4 \mathrm{H}, \mathrm{A}_2 \mathrm{~B}_2\right.$ part of $\mathrm{A}_2 \mathrm{~B}_2 \mathrm{X}$ system ) and $3.37(\mathrm{X}$ part of $\mathrm{A}_2 \mathrm{~B}_2 \mathrm{X}$ system) with $J_{\mathrm{AB}} 9.5, J_{\mathrm{AX}} 9.1$, and $J_{\mathrm{BX}}$ small.
B is $\mathrm{C}_6 \mathrm{H}_9 \mathrm{NO}_2$ (mass spectrum) and has $\delta_{\mathrm{C}} 38.0(\mathrm{~d}), 41.3(\mathrm{t}), 50.4 (\mathrm{t}), 75.2(\mathrm{~s})$, and $173.0(\mathrm{~s})$. Its proton NMR spectrum contains two exchanging protons on nitrogen and $\delta_{\mathrm{H}} 1.17(2 \mathrm{H}, \mathrm{ddd}, J 2.3$, $6.2,9.5), 2.31(2 \mathrm{H}$, broad m), $2.90(1 \mathrm{H}$, broad t, $J 3.2)$, and 3.40 ( 2 H , broad s).
Because the coupling pattern did not show up clearly as many of the coupling constants are small, decoupling experiments were used. Irradiation at $\delta_{\mathrm{H}} 3.4$ simplifies the $\delta_{\mathrm{H}} 2.3$ signal to $(2 \mathrm{H}$, $\mathrm{ddd}, J 5.8,3.2,2.3)$, sharpens each line of the ddd at 1.17 , and sharpens the triplet at 2.9 .
Irradiation at 2.9 sharpens the signals at 1.17 and 2.9 and makes the signal at 2.31 into a broad doublet, $J$ about 6 . Irradiation at 2.31 sharpens the signal at 3.4 slightly and reduces the signals at 2.9 and 1.17 to broad singlets. Irradiation at 1.17 sharpens the signal at 3.4 slightly so that it is a broad doublet, $J$ about 1.0 , sharpens the signal at 2.9 to a triplet, and sharpens up the signal at 2.31 but irradiation here had the least effect.

This is quite a difficult problem but the compounds are so small ( $\mathrm{C}_6$ only), have no methyl groups, and have some symmetry so you should try drawing structures at an early stage.13 The seeds of the Costa Rican plant Ateleia herbert smithii are avoided by all seed eaters (except a weevil that adapts them for its defence) because they contain two toxic amino acids (IR spectra like other amino acids). Neither compound is chiral. What is the structure of these compounds? They can easily be separated because one $(\mathrm{A})$ is soluble in aqueous base but the other $(\mathrm{B})$ is not.
A is $\mathrm{C}_6 \mathrm{H}_9 \mathrm{NO}_4$ (mass spectrum) and has $\delta_{\mathrm{C}} 34.0(\mathrm{~d}), 40.0(\mathrm{t}), 56.2 (\mathrm{s}), 184.8(\mathrm{~s})$, and $186.0(\mathrm{~s})$. Its proton NMR has three exchanging protons on nitrogen and one on oxygen and two complex signals at $\delta_{\mathrm{H}} 2.68\left(4 \mathrm{H}, \mathrm{A}_2 \mathrm{~B}_2\right.$ part of $\mathrm{A}_2 \mathrm{~B}_2 \mathrm{X}$ system ) and $3.37(\mathrm{X}$ part of $\mathrm{A}_2 \mathrm{~B}_2 \mathrm{X}$ system) with $J_{\mathrm{AB}} 9.5, J_{\mathrm{AX}} 9.1$, and $J_{\mathrm{BX}}$ small.
B is $\mathrm{C}_6 \mathrm{H}_9 \mathrm{NO}_2$ (mass spectrum) and has $\delta_{\mathrm{C}} 38.0(\mathrm{~d}), 41.3(\mathrm{t}), 50.4 (\mathrm{t}), 75.2(\mathrm{~s})$, and $173.0(\mathrm{~s})$. Its proton NMR spectrum contains two exchanging protons on nitrogen and $\delta_{\mathrm{H}} 1.17(2 \mathrm{H}, \mathrm{ddd}, J 2.3$, $6.2,9.5), 2.31(2 \mathrm{H}$, broad m), $2.90(1 \mathrm{H}$, broad t, $J 3.2)$, and 3.40 ( 2 H , broad s).
Because the coupling pattern did not show up clearly as many of the coupling constants are small, decoupling experiments were used. Irradiation at $\delta_{\mathrm{H}} 3.4$ simplifies the $\delta_{\mathrm{H}} 2.3$ signal to $(2 \mathrm{H}$, $\mathrm{ddd}, J 5.8,3.2,2.3)$, sharpens each line of the ddd at 1.17 , and sharpens the triplet at 2.9 .
Irradiation at 2.9 sharpens the signals at 1.17 and 2.9 and makes the signal at 2.31 into a broad doublet, $J$ about 6 . Irradiation at 2.31 sharpens the signal at 3.4 slightly and reduces the signals at 2.9 and 1.17 to broad singlets. Irradiation at 1.17 sharpens the signal at 3.4 slightly so that it is a broad doublet, $J$ about 1.0 , sharpens the signal at 2.9 to a triplet, and sharpens up the signal at 2.31 but irradiation here had the least effect.

This is quite a difficult problem but the compounds are so small ( $\mathrm{C}_6$ only), have no methyl groups, and have some symmetry so you should try drawing structures at an early stage.

Zubair Abdulla
Zubair Abdulla
Numerade Educator