Sticking out like a Trimethyl Ammonio Group

When dealing with a structure elucidation problem where little or no previous fragment information exists, the number of possibilities can seem endless. Although typically one envisions a neutral compound for the unknown, ionic compounds, such as salts and zwitterions, are also just as likely and thus can add to the complex nature of an elucidation.

The trimethyl ammonio group shown below exhibits an intense ¹H signal generally between 2.8 - 3.2 ppm and a ¹³C signal generally between 39 - 62 ppm.

The 1H NMR spectrum below exhibits an obvious singlet circa 3.1 ppm belonging to an R-N(CH3)₃⁺ group. Compare the difference in chemical shifts to a t-butyl group listed here.

Sticking out like a Trimethyl Ammonio Group

When dealing with a structure elucidation problem where little or no previous fragment information exists, the number of possibilities can seem endless. Although typically one envisions a neutral compound for the unknown, ionic compounds, such as salts and zwitterions, are also just as likely and thus can add to the complex nature of an elucidation.

The trimethyl ammonio group shown below exhibits an intense ¹H signal generally between 2.8 - 3.2 ppm and a ¹³C signal generally between 39 - 62 ppm.

The 1H NMR spectrum below exhibits an obvious singlet circa 3.1 ppm belonging to an R-N(CH3)₃⁺ group. Compare the difference in chemical shifts to a t-butyl group listed here.

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I assure you that your email will not be distributed to any additional source(s) other than what is being used by FeedBurner in delivering the current blog. Should there be any problems in this regard, please feel free to contact me via the comment section below so I may rectify the situation.

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              Arvin M.

Gearing up the Right Thought Process for Solving Problems

The approach behind solving a structure elucidation problem is very similar to attempting a math problem or working on a jigsaw puzzle. This similar mental framework shares a basis, but not limited to, on understanding the basic rules that define the problem, and in some cases the creativity and flexibility to redefine the problem.

When presented with a set of data, an elucidator can recognize that the data is valid and logical, address any problematic areas and explore a strategy to fix or solve it without making too many assumptions. Although various problem solving techniques exist, ultimately, it is experience that goes a long way.

  

The following reference addresses some of the underlying issues described in this blog: J.E. Davidson and R.J. Sternberg. The Psychology of Problem Solving. Cambridge University Press, 2003.

Gearing up the Right Thought Process for Solving Problems

The approach behind solving a structure elucidation problem is very similar to attempting a math problem or working on a jigsaw puzzle. This similar mental framework shares a basis, but not limited to, on understanding the basic rules that define the problem, and in some cases the creativity and flexibility to redefine the problem.

When presented with a set of data, an elucidator can recognize that the data is valid and logical, address any problematic areas and explore a strategy to fix or solve it without making too many assumptions. Although various problem solving techniques exist, ultimately, it is experience that goes a long way.

  

The following reference addresses some of the underlying issues described in this blog: J.E. Davidson and R.J. Sternberg. The Psychology of Problem Solving. Cambridge University Press, 2003.

Considering a Pyridinone Fragment

Chemical shift information offers a clue into an atom’s hybridization state. For example, carbon atoms with a carbon chemical shift greater than 90 ppm are typically considered as sp2 carbons. If 4 sp2 carbons are present, one can infer 2 alkene pairs. Five sp2 carbons and an available oxygen and nitrogen atom suggest the possibility of a pyridinone fragment.

The example below shows a 5 sp2 carbons and 2 sp3 carbons, coloured pink and blue, respectively. The chemical shift at 167 ppm for the quaternary carbon suggests the presence of an amide group.

Using the information described above, a set of 6 possible candidate structures can be pieced together.

Considering a Pyridinone Fragment

Chemical shift information offers a clue into an atom’s hybridization state. For example, carbon atoms with a carbon chemical shift greater than 90 ppm are typically considered as sp2 carbons. If 4 sp2 carbons are present, one can infer 2 alkene pairs. Five sp2 carbons and an available oxygen and nitrogen atom suggest the possibility of a pyridinone fragment.

The example below shows a 5 sp2 carbons and 2 sp3 carbons, coloured pink and blue, respectively. The chemical shift at 167 ppm for the quaternary carbon suggests the presence of an amide group.

Using the information described above, a set of 6 possible candidate structures can be pieced together.

Hampering Data Interpretation

A common misinterpretation of 2D NMR data can occur when dealing with weak correlations. Weak correlations are commonly introduced in how the sample is prepared or how the data is collected or processed. Examining the spectrum down to level of the density matrix can ensure all correlations are picked up.

The 1H-13C HMQC below shows a protonated carbon at 3.2 and 32 ppm. Since the proton multiplet at 3.6 ppm has no carbon correlation, the proton is most likely from an exchangeable group such as NH or OH group.

When the spectrum threshold is lowered to 1 % relative to the most intense correlation, a weak correlation at 2.6 and 41.9 ppm is seen. Therefore, the proton at 3.6 ppm is actually a CH group and not an exchangeable one.

Hampering Data Interpretation

A common misinterpretation of 2D NMR data can occur when dealing with weak correlations. Weak correlations are commonly introduced in how the sample is prepared or how the data is collected or processed. Examining the spectrum down to level of the density matrix can ensure all correlations are picked up.

The 1H-13C HMQC below shows a protonated carbon at 3.2 and 32 ppm. Since the proton multiplet at 3.6 ppm has no carbon correlation, the proton is most likely from an exchangeable group such as NH or OH group.

When the spectrum threshold is lowered to 1 % relative to the most intense correlation, a weak correlation at 2.6 and 41.9 ppm is seen. Therefore, the proton at 3.6 ppm is actually a CH group and not an exchangeable one.