Disclaimer for P2C2E

The following weblog represents my experiences in and out of the lab. As such, the presented material serves as a personal resource and should in no way be considered as a comprehensive approach to lab work or otherwise. I do not warrant or assume any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed.

 

Reader discretion is advised.

 

Readers cannot assume that the external sites will abide by the same Policy to which P2C2E adheres. It is the responsibility of the reader to examine the copyright and licensing restrictions of the linked pages and to secure all necessary permissions.

 

The material listed from this weblog site may not be freely distributed and copied without the written permission from the author. For contact details, please visit the About Me section. 

 

To cite the weblog P2C2E, please follow the sample guideline below:

 

Moser, A. "How to reference 1D and 2D NMR data? … Part 1" Philosophy to Chemistry to Elucidation. 2008. http://acdlabs.typepad.com/elucidation/2008/08/how-to-referenc.html.

 

Revised: Oct 30, 2008

Disclaimer for P2C2E

The following weblog represents my experiences in and out of the lab. As such, the presented material serves as a personal resource and should in no way be considered as a comprehensive approach to lab work or otherwise. I do not warrant or assume any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed.

 

Reader discretion is advised.

 

Readers cannot assume that the external sites will abide by the same Policy to which P2C2E adheres. It is the responsibility of the reader to examine the copyright and licensing restrictions of the linked pages and to secure all necessary permissions.

 

The material listed from this weblog site may not be freely distributed and copied without the written permission from the author. For contact details, please visit the About Me section. 

 

To cite the weblog P2C2E, please follow the sample guideline below:

 

Moser, A. "How to reference 1D and 2D NMR data? … Part 1" Philosophy to Chemistry to Elucidation. 2008. http://acdlabs.typepad.com/elucidation/2008/08/how-to-referenc.html.

 

Revised: Oct 30, 2008

Identifying Peak Overlap on an HMBC Spectrum

Carbon peaks that overlap on an 1H -13C HMBC experiment can be tricky to deal with especially when additional experiments do not help to clarify the situation. A good approach is to keep note of any high correlation counts for a carbon resonance, and subsequently, treat the carbon resonance as possibly multiple carbons with coincidental chemical shifts.

The 1H -13C HMBC spectrum and attached 1D 1H NMR spectrum below illustrate a carbon resonance at 76 ppm with 7 proton correlations. Treating this as a single carbon will result in a structural dead end to the elucidation process. The next step is to treat the carbon as 2 carbons resonances.

    

The corresponding structure is shown below to illustrate the point.

Identifying Peak Overlap on an HMBC Spectrum

Carbon peaks that overlap on an 1H -13C HMBC experiment can be tricky to deal with especially when additional experiments do not help to clarify the situation. A good approach is to keep note of any high correlation counts for a carbon resonance, and subsequently, treat the carbon resonance as possibly multiple carbons with coincidental chemical shifts.

The 1H -13C HMBC spectrum and attached 1D 1H NMR spectrum below illustrate a carbon resonance at 76 ppm with 7 proton correlations. Treating this as a single carbon will result in a structural dead end to the elucidation process. The next step is to treat the carbon as 2 carbons resonances.

    

The corresponding structure is shown below to illustrate the point.

Unassigned Protons can serve as Warning Flag

When the incorrect number of directly-bonded protons are assigned to carbons, the elucidator is left with extra protons. (This can happen in situations with a highly-crowded region on a 1H NMR spectrum.) Where possible, tallying the expected number of exchangeable protons can serve as a warning flag that something is amiss.

The following carbons, shown below, were assigned as C, CH, CH2 or CH3. As such, three protons remain unassigned. Assuming the compound contains no ammonia, the carbon assignments were incorrectly done and thus should be reinvestigated.

 

The structure methamphetamine, shown below, illustrates that a methyl was incorrectly set to a methine.

Unassigned Protons can serve as Warning Flag

When the incorrect number of directly-bonded protons are assigned to carbons, the elucidator is left with extra protons. (This can happen in situations with a highly-crowded region on a 1H NMR spectrum.) Where possible, tallying the expected number of exchangeable protons can serve as a warning flag that something is amiss.

The following carbons, shown below, were assigned as C, CH, CH2 or CH3. As such, three protons remain unassigned. Assuming the compound contains no ammonia, the carbon assignments were incorrectly done and thus should be reinvestigated.

 

The structure methamphetamine, shown below, illustrates that a methyl was incorrectly set to a methine.

Interpreting an HSQC or HMQC or HETCOR experiment

The 1H-13C HMQC, HSQC, DEPT-HSQC, HSQC-TOCSY and HETCOR experiments offer the elucidator information on the proton-carbon connectivity. The interpretation process comes down to 3 basic assignments: the correlation belongs to a methyl, methylene or methine carbon. A methyl or methine carbon exhibits at most a single correlation between the 1H and 13C axes. A methylene group can exhibit 1 or 2 correlations depending on whether the protons are anisochronous.

Three regions of a 1H -13C HSQC spectrum for quinine are shown below.

A single 1H-13C correlation is observed for a CH and CH3.

For anisochronous methylene protons, 2 correlations are observed.

Interpreting an HSQC or HMQC or HETCOR experiment

The 1H-13C HMQC, HSQC, DEPT-HSQC, HSQC-TOCSY and HETCOR experiments offer the elucidator information on the proton-carbon connectivity. The interpretation process comes down to 3 basic assignments: the correlation belongs to a methyl, methylene or methine carbon. A methyl or methine carbon exhibits at most a single correlation between the 1H and 13C axes. A methylene group can exhibit 1 or 2 correlations depending on whether the protons are anisochronous.

Three regions of a 1H -13C HSQC spectrum for quinine are shown below.

A single 1H-13C correlation is observed for a CH and CH3.

For anisochronous methylene protons, 2 correlations are observed.

Anisochronous Protons on a 1H NMR Spectrum

In NMR, nuclei can be classified as isochronous or anisochronous. “Where diastereotopic protons show the same chemical shift, they are said to be accidentally equivalent or isochronous, and where they have different chemical shifts the protons are described as anisochronous.” Stereochemistry by David G. Morris, Royal Society of Chemistry (Great Britain) Published by Royal Society of Chemistry, 2001.

The 1H NMR spectrum is shown for geminal protons, coloured in red, within a ring system. The spectrum illustrates protons from a methylene group (CH2) with different chemical shifts that are coupled to each other. The protons are termed as diastereotopic and anisochronous.

Other examples of this property are seen at the following links: DEPT-HSQC, HSQC/HMBC and 1H/DEPT-HSQC.

Anisochronous Protons on a 1H NMR Spectrum

In NMR, nuclei can be classified as isochronous or anisochronous. “Where diastereotopic protons show the same chemical shift, they are said to be accidentally equivalent or isochronous, and where they have different chemical shifts the protons are described as anisochronous.” Stereochemistry by David G. Morris, Royal Society of Chemistry (Great Britain) Published by Royal Society of Chemistry, 2001.

The 1H NMR spectrum is shown for geminal protons, coloured in red, within a ring system. The spectrum illustrates protons from a methylene group (CH2) with different chemical shifts that are coupled to each other. The protons are termed as diastereotopic and anisochronous.

Other examples of this property are seen at the following links: DEPT-HSQC, HSQC/HMBC and 1H/DEPT-HSQC.

Assembling a set of Fragments to Complete a Candidate Structure

The progression of a structure elucidation process is to examine the experimental data, compare the results to literature if possible, build a set of fragments based on the available data and finally assemble the fragments until a candidate structure(s) is reached. The assembly part is very much like working on a jigsaw puzzle. When all the pieces are present, it is as easy as matching up the right pieces by examining the overlap and/or trying out different combinations.

The following fragments #1-5 represent all the available information extracted from a set of experimental data. The letter A represents an open point of attachment.

The goal of the elucidator is to sort out what pieces belong together and which do not. Although more than one answer is possible, a candidate structure, 6-{[5-(trifluoromethyl)cyclopenta-1,4-dien-1-yl]methyl}-2,3-dihydropyridin-4(1H)-one, is colour-coded to illustrate how the fragments fit together to complete the structure.

Assembling a set of Fragments to Complete a Candidate Structure

The progression of a structure elucidation process is to examine the experimental data, compare the results to literature if possible, build a set of fragments based on the available data and finally assemble the fragments until a candidate structure(s) is reached. The assembly part is very much like working on a jigsaw puzzle. When all the pieces are present, it is as easy as matching up the right pieces by examining the overlap and/or trying out different combinations.

The following fragments #1-5 represent all the available information extracted from a set of experimental data. The letter A represents an open point of attachment.

The goal of the elucidator is to sort out what pieces belong together and which do not. Although more than one answer is possible, a candidate structure, 6-{[5-(trifluoromethyl)cyclopenta-1,4-dien-1-yl]methyl}-2,3-dihydropyridin-4(1H)-one, is colour-coded to illustrate how the fragments fit together to complete the structure.