Logic Puzzle #12: Torsion Angle and Coupling … Solution

Couplings can be affected by the torsion angle. The couplings can be expressed mathematically with a cos θ relationship. At certain values of θ, the couplings are expected to be relatively weaker to non-existent.

Based on the torsion angle, fragment B is expected to exhibit a prominent coupling between the red and gold nuclei. Fragment A, exhibiting a torsion angle of 90º, will generally lead to a weak or non-evident coupling on an NMR spectrum.

At the initial stages of an elucidaton of an unknown structure, the torsion angle(s) is usually not known. As such, an elucidator must be prepared to expect the unexpected coupling(s). 

Logic Puzzle #12: Torsion Angle and Coupling

For a simple case, the torsion angle (or dihedral angle) is described as the angle between 4 contiguous atoms or 3 successive bonds. In NMR, the magnitude of the coupling is directly related to the torsion angle between the vicinal nuclei (see the Karplus equation for more details).

Below are two animations, A and B, for identical fragments differing only in the torsion angle. Assuming the following fragments exhibit a rigid geometry, which torsion angle would generally contribute to a prominent coupling between the red and gold nuclei?

A (torsion angle at 90º)                 B (torsion angle at 35º)

                     

Logic Puzzle #8: Strong Coupling or Peak Overlap? … Solution

There are two approaches to deciding which scenario best fits the NMR data in the puzzle. A structure elucidator can provide evidence that one scenario is more probable than an other and/or eliminate one scenario on the grounds of insufficient/contradictory data to support it.

For the following 1H NMR spectrum, if the integral of the doublet at 7.42 ppm equates to 1 H atom from a single structure, then the 1H signals at 7.58-7.59 ppm integrating to 2.57 (and assuming all signals are accounted for) relate to overlapping signals (probably a doublet overlapping with a singlet) from a mixture of compounds at varying concentrations.

Another approach, as Adolfo has nicely provided, the magnitude of the strong coupling demonstrated by the signals at 7.58-7.59 ppm indicates a nearby partner on the left side circa 7.70 ppm. Since this appears not to be the case, then by process of elimination, the signals at 7.58-7.59 ppm relate to two overlapping multiplets.

 

Logic Puzzle #8: Strong Coupling or Peak Overlap?

The goal of this puzzle is to distinguish between strong coupling and peak overlap.

For the following 1H NMR spectrum, are the 1H signals at 7.58-7.59 ppm exhibiting strong coupling or are they two overlapping multiplets or both?

 

Logic Puzzle #7: Almost Missed It … Solution 2

With intense solvent signals present on a spectrum, a smaller signal(s) can easily be missed. If 2D NMR data is available, then this extra information can assist in clarifying whether a small signal(s) is obscured by larger signals.

On the 1H-13C HMBC below, the correlations for CDCl3/CHCl3 (due to 1J coupling responses and more) are more intense in comparison to the weak correlation at approximately 6.9 and 77.3 ppm. In this case, the weak correlation is attributed to a quaternary carbon obscured by a set of intense solvent signals.

 

Logic Puzzle #7: Almost Missed It … Solution

‘How many signals are present?’ is such a simple question, and yet, it is a fundamental question to an elucidator. Mistaken a signal or overlook one and the elucidator can run the risk of wasting time and effort.

The 13C [1H] NMR spectrum below shows 3 discernible signals that are attributed to the solvent CDCl3. In addition, one can begin to speculate on weaker signals; there might a fourth signal at ~77.2 ppm (most likely due to residual CHCl3), possibly a fifth at ~77.5 ppm, perhaps a sixth one at ~77.3 ppm and maybe more.

The next step is to examine additional data and verify whether the ‘weak’ signals are real or not. This can include:

1. comparing the weak signals to other structural signals,

2. applying deconvolution/peak fitting to this region,

3. checking 2D NMR data,

4. acquiring data in a different solvent,

5. modifying the acquisition parameters to exclude the solvent or increase S/N, etc.

Logic Puzzle #7: Almost Missed It

When dealing with small sample concentrations of an unknown compound, the NMR region where a large solvent signal appears rarely gets a second look. However, a large NMR signal can easily obscure a small signal. From one elucidator to another, check the solvent signal for any structural signals.

In the 13C [1H] NMR spectrum below, how many signals are present?

If the spectrum is zoomed in, how many signals can be seen now?

Logic Puzzle #6: Dealing with an Extra 13C Peak … Solution

Socrates is known for saying ‘Know thyself’, along the same line, chemists should ‘Know thy instrument’. The example below is one such case.

The 13C NMR [1H] spectrum below exhibits 6 signals. If an unknown compound comprises of 7 carbon atoms, then the following scenarios, or combinations thereof, are possible to account for missing or extra carbon peaks on the spectrum:

1. the 13C peaks are too weak to be clearly evident,

2. the 13C peaks are overlapping (equivalent or coincidental), and/or

3. the 13C peaks may pertain to instrument artefacts, mixtures or impurities.   

The carbon signals are 111 and 118 ppm may account for 2 carbons atoms each. This is based on the relative intensities of the peaks and this is a characteristic prevalent for aromatic carbons. The total count is now at 8 atoms. The higher atom count indicates the presence of an artefact or impurity. The signal at the exact centre of the spectrum, 100 ppm, can be attributed to a quadrature spike – an artefact produced from the instrument. If so, the total count matches the known carbon count.

Although this analysis is not conclusive, it is worth noting that there are several other possible interpretations and only additional data will help substantiate one possibility over the other.

Thank you Adolfo, Maxa and Serge for your comments.

Logic Puzzle #6: Dealing with an Extra 13C Peak

Structure elucidation by NMR involves a deep understanding of various technical aspects behind data acquisition. Being aware of how the instrument works can facilitate the process and reduce the aggravation.

For today’s puzzle, an unknown compound is known to comprise of 7 carbon atoms and exhibit the following 13C NMR spectrum with 1H decoupling. How can the 7 atoms be accounted for in the spectrum below?

Logic Puzzle #5: Coupling + Tilting + Integration = Benzene … Solution

The goal of this puzzle is to determine the respective benzene ring systems that would exhibit the following 1H NMR spectrum.

The number of substituted benzene ring systems that would exhibit the following 1H NMR spectrum is 3 (assuming no repeating units). The keys to solving this puzzle lie with the determination of which multiplets are coupled in combination with the integral information.

 

Starting with the easy set of multiplets, M08 and M07 are coupled to each other. The second order effects (evident by tilting towards each other) and the similar coupling constants (roughly +/- 0.2 Hz) support this claim. Along side the integral ratio of 2:2, this pattern is intrinsic for a para-substituted benzene ring. Next, the multiplets M01, M03 and M05 are coupled. The 1:2:2 integral ratio and identical coupling constants support a mono-substituted benzene ring. Finally, M02, M04 and M06 are coupled. The 1:1:1 integral ratio and meta-coupling pattern (post#2 link) indicate the presence of a 1,2,4-trisubstituted benzene ring system.

Logic Puzzle #5: Coupling + Tilting + Integration = Benzene

The goal of this puzzle is to determine the respective benzene ring systems that would exhibit the following 1H NMR spectrum.

For the following aromatic region of the 1H NMR spectrum, how many benzene ring systems are present?

Logic Puzzle #5: Coupling + Tilting + Integration = Benzene

The goal of this puzzle is to determine the respective benzene ring systems that would exhibit the following 1H NMR spectrum.

For the following aromatic region of the 1H NMR spectrum, how many benzene ring systems are present?

Logic Puzzle #4: Correlating to the Correct 13C Signal … Solution

The goal of this puzzle is to resolve the ambiguity exhibited within a 2D NMR spectrum and thus provide the correct signal correlation. Although this exercise may seem a trivial one, it is important to go over the rationale when correlating one signal to another.

For the following 1H-13C HSQC-DEPT NMR spectrum it is important to note that the 2 correlations are phased positively (red) and thus represent either a CH or CH3 group and not a CH2. Next, one must ensure that the carbons at 61.5 and 62.2 ppm are 1 carbon each. Although this detail is not certain, we will assume this to be the case. Finally, it is best to start with the easy part first. The 1H signal at 3.50 ppm is correlated to the 13C signal at 62.2 ppm. By process of elimination, one can conclude that the 1H signal at 2.73 ppm is correlated to the 13C signal at 61.5 ppm (see this post for more details).

Ambiguity in correlating 1D and 2D NMR data can routinely occur. Some extra steps that can help avoid this issue are re-aligning the data and/or re-processing the ‘raw’ data with different parameters.

 

Logic Puzzle #4: Correlating to the Correct 13C Signal … Solution

The goal of this puzzle is to resolve the ambiguity exhibited within a 2D NMR spectrum and thus provide the correct signal correlation. Although this exercise may seem a trivial one, it is important to go over the rationale when correlating one signal to another.

For the following 1H-13C HSQC-DEPT NMR spectrum it is important to note that the 2 correlations are phased positively (red) and thus represent either a CH or CH3 group and not a CH2. Next, one must ensure that the carbons at 61.5 and 62.2 ppm are 1 carbon each. Although this detail is not certain, we will assume this to be the case. Finally, it is best to start with the easy part first. The 1H signal at 3.50 ppm is correlated to the 13C signal at 62.2 ppm. By process of elimination, one can conclude that the 1H signal at 2.73 ppm is correlated to the 13C signal at 61.5 ppm (see this post for more details).

Ambiguity in correlating 1D and 2D NMR data can routinely occur. Some extra steps that can help avoid this issue are re-aligning the data and/or re-processing the ‘raw’ data with different parameters.

 

Logic Puzzle #4: Correlating to the Correct 13C Signal

The goal of this puzzle is to resolve the ambiguity exhibited within a 2D NMR spectrum and thus provide the correct signal correlation.

The following 1H-13C HSQC-DEPT NMR spectrum shows two one-bond correlations linked to the 1H signals 2.75 and 3.50 ppm and two closely spaced 13C signals at 61.5 and 62.2 ppm. Does the 1H signal at 2.75 ppm correlate to the 13C signal at 61.5 ppm or the one at 62.2 ppm?

Note: the blue line was added to help align the correlation to the F1 domain.

Logic Puzzle #4: Correlating to the Correct 13C Signal

The goal of this puzzle is to resolve the ambiguity exhibited within a 2D NMR spectrum and thus provide the correct signal correlation.

The following 1H-13C HSQC-DEPT NMR spectrum shows two one-bond correlations linked to the 1H signals 2.75 and 3.50 ppm and two closely spaced 13C signals at 61.5 and 62.2 ppm. Does the 1H signal at 2.75 ppm correlate to the 13C signal at 61.5 ppm or the one at 62.2 ppm?

Note: the blue line was added to help align the correlation to the F1 domain.

Logic Puzzle #2: How to link 3 Fragments

The goal of this puzzle is to logically combine a set of fragments using valence and NMR information.

In this puzzle, three fragments are correlated through 2-3J coupling responses (represented by a green arrow) that were extracted from a 1H-13C HMBC data (spectrum not shown). The carbon atoms with the 13C chemical shifts displayed in blue indicate the presence of an adjacent heteroatom. Based on these criteria, what 'complete' fragment(s) supports the data and is there anything missing?

In order to accommodate these restrictions, a logical fit is to consider a trivalent atom, e.g. nitrogen.

Logic Puzzle #2: How to link 3 Fragments

The goal of this puzzle is to logically combine a set of fragments using valence and NMR information.

In this puzzle, three fragments are correlated through 2-3J coupling responses (represented by a green arrow) that were extracted from a 1H-13C HMBC data (spectrum not shown). The carbon atoms with the 13C chemical shifts displayed in blue indicate the presence of an adjacent heteroatom. Based on these criteria, what 'complete' fragment(s) supports the data and is there anything missing?

In order to accommodate these restrictions, a logical fit is to consider a trivalent atom, e.g. nitrogen.

Signals can simply disappear on a DEPT-135 experiment

There are many advantages in working with a 1H-13C HSQC-DEPT spectrum over a 13C DEPT-135 and a 1H-13C HSQC (see Post 1 & Post 2). In most cases, a 1H-13C HSQC-DEPT is more valuable than either one of those experiments.

The aliphatic region of a 1H-13C HSQC-DEPT is spectrum below. Two coincidental carbon signals are overlapping at 38.51 ppm, one pertaining to a CH while the other a CH2 group. The DEPT-135, attached to the F1 domain, exhibits a weak 13C signal that can easily be misconstrued, for example as an impurity, if not for the extra information from the 2D NMR experiment.

Signals can simply disappear on a DEPT-135 experiment

There are many advantages in working with a 1H-13C HSQC-DEPT spectrum over a 13C DEPT-135 and a 1H-13C HSQC (see Post 1 & Post 2). In most cases, a 1H-13C HSQC-DEPT is more valuable than either one of those experiments.

The aliphatic region of a 1H-13C HSQC-DEPT is spectrum below. Two coincidental carbon signals are overlapping at 38.51 ppm, one pertaining to a CH while the other a CH2 group. The DEPT-135, attached to the F1 domain, exhibits a weak 13C signal that can easily be misconstrued, for example as an impurity, if not for the extra information from the 2D NMR experiment.