Monday, June 29, 2009

The 100th blog: a Milestone in Structure Elucidation

Structure elucidation is a skill learnt through years of practice. One of the best ways to learn is to learn by example. I feel that there is no better way to do this than mentoring through specific scenarios step-by-step. My intentions behind this blog are to offer a unique source for chemists who use a variety of tools such as NMR, MS, IR, etc. to determine the structural composition for an unknown.


Here are my top 10 picks for P2C2E that I feel have the most potential to impact a chemist who is learning to do elucidations of unknown compounds.


10. Molecular ion or adduct? - Identification of Adduct Ions


9. Missing a peak? - Hampering Data Interpretation


8. Exercise, exercise - The Coupling Exercise


7. NMR, MS, oh my! - Using complementary elucidation tools to solve for an unknown structure


6. Strong coupling? What’s that? - Interpreting strong coupling information from a 1H NMR spectrum


5. Problem Solver - Gearing up the Right Thought Process for Solving Problems


4. I can’t solve this - Stuck on a Structure Elucidation problem? You need Out of the Box thinking, right?


3.  1 + 1 = 1 - Assembling a set of Fragments to Complete a Candidate Structure


2. I need more data? - Why collect NMR or MS^n data? 


1. A 1H NMR is not enough? - Is it possible to elucidate an unknown with just a 1H NMR spectrum?









The 100th blog: a Milestone in Structure Elucidation

Structure elucidation is a skill learnt through years of practice. One of the best ways to learn is to learn by example. I feel that there is no better way to do this than mentoring through specific scenarios step-by-step. My intentions behind this blog are to offer a unique source for chemists who use a variety of tools such as NMR, MS, IR, etc. to determine the structural composition for an unknown.


Here are my top 10 picks for P2C2E that I feel have the most potential to impact a chemist who is learning to do elucidations of unknown compounds.


10. Molecular ion or adduct? - Identification of Adduct Ions


9. Missing a peak? - Hampering Data Interpretation


8. Exercise, exercise - The Coupling Exercise


7. NMR, MS, oh my! - Using complementary elucidation tools to solve for an unknown structure


6. Strong coupling? What’s that? - Interpreting strong coupling information from a 1H NMR spectrum


5. Problem Solver - Gearing up the Right Thought Process for Solving Problems


4. I can’t solve this - Stuck on a Structure Elucidation problem? You need Out of the Box thinking, right?


3.  1 + 1 = 1 - Assembling a set of Fragments to Complete a Candidate Structure


2. I need more data? - Why collect NMR or MS^n data? 


1. A 1H NMR is not enough? - Is it possible to elucidate an unknown with just a 1H NMR spectrum?









Tuesday, June 23, 2009

Distinguishing Impurities … Part 2


A previous blog described how integrals and coupling information can assist in discerning an unknown structure signal from an impurity(ies).  Before proceeding to acquire 2D NMR data to confirm the information, there is the option to purify/rewash the sample (assuming there is enough sample to do this) followed by a spectral comparison of the before and after the wash; any differences in the integrals may assist in identifying signals from an impurity.


Illustrated below are 2 1H NMR spectra differing in sample preparation. The top spectrum, washed once before acquisition, shows 2 impurity signals at 1.68 and 2.14 ppm. The bottom spectrum is for the same sample but washed a second time. When comparing the 2 spectra, only the 2 singlets have changed significantly in area, thus, indicating a separate entity in relation to the remaining signals.  


ImpuritiesOn1H_2_June222009


One advantage of knowing which signals belong to an unknown structure  is that these signals, and only these signals, are used in searching across a library or database. This will help in reducing false positives and allow more flexibility to narrow down the number of hits.






Distinguishing Impurities … Part 2


A previous blog described how integrals and coupling information can assist in discerning an unknown structure signal from an impurity(ies).  Before proceeding to acquire 2D NMR data to confirm the information, there is the option to purify/rewash the sample (assuming there is enough sample to do this) followed by a spectral comparison of the before and after the wash; any differences in the integrals may assist in identifying signals from an impurity.


Illustrated below are 2 1H NMR spectra differing in sample preparation. The top spectrum, washed once before acquisition, shows 2 impurity signals at 1.68 and 2.14 ppm. The bottom spectrum is for the same sample but washed a second time. When comparing the 2 spectra, only the 2 singlets have changed significantly in area, thus, indicating a separate entity in relation to the remaining signals.  


ImpuritiesOn1H_2_June222009


One advantage of knowing which signals belong to an unknown structure  is that these signals, and only these signals, are used in searching across a library or database. This will help in reducing false positives and allow more flexibility to narrow down the number of hits.






Monday, June 15, 2009

Distinguishing Impurities … Part 1

One of the trickiest parts of interpreting NMR data is identifying what signal belongs to the unknown compound and what can be classified as an impurity. In this case, impurities are described as extra signals coming from a solvent(s), a side product(s), extraction/purification process, etc. 


The 1H NMR spectrum below is for an unknown compound. The spectrum shows a highly coupled system with the exception of two singlets at 2.14 and 1.68 ppm. In addition, the integrals of the 2 singlets show a relative integral of 1 proton. This indicates the possibility of 2 CH groups adjacent to 3 quaternary carbons. Although is not necessarily incorrect, it does raise 2 yellow flags that either singlet (or both) does not belong to the unknown. The next step would be to check this possibility against 2D NMR data.


ImpuritiesOn1H_June142009



Distinguishing Impurities … Part 1

One of the trickiest parts of interpreting NMR data is identifying what signal belongs to the unknown compound and what can be classified as an impurity. In this case, impurities are described as extra signals coming from a solvent(s), a side product(s), extraction/purification process, etc. 


The 1H NMR spectrum below is for an unknown compound. The spectrum shows a highly coupled system with the exception of two singlets at 2.14 and 1.68 ppm. In addition, the integrals of the 2 singlets show a relative integral of 1 proton. This indicates the possibility of 2 CH groups adjacent to 3 quaternary carbons. Although is not necessarily incorrect, it does raise 2 yellow flags that either singlet (or both) does not belong to the unknown. The next step would be to check this possibility against 2D NMR data.


ImpuritiesOn1H_June142009



Thursday, June 4, 2009

Exchangeables Protons acquired in different Deuterated Solvents

A deuterated solvent can impact whether exchangeable protons, such as OH or NH, are visible on a 1H NMR spectrum. The advantage of eliminating any contribution from an exchangeable proton(s) is to simplify spectral interpretation. One disadvantage of not seeing exchangeable protons is the deficiency to the total proton count in establishing the molecular formula.


The diagram below compares two 1H NMR spectra for the same functional group in two different deuterated solvents. The 1H NMR spectrum in deuterated-DMSO shows two doublets whereas the spectrum acquired in deuterated-methanol shows only the singlet for the CH group.


ExchangeableProtonsAndSolvents_Jun42009



Exchangeables Protons acquired in different Deuterated Solvents

A deuterated solvent can impact whether exchangeable protons, such as OH or NH, are visible on a 1H NMR spectrum. The advantage of eliminating any contribution from an exchangeable proton(s) is to simplify spectral interpretation. One disadvantage of not seeing exchangeable protons is the deficiency to the total proton count in establishing the molecular formula.


The diagram below compares two 1H NMR spectra for the same functional group in two different deuterated solvents. The 1H NMR spectrum in deuterated-DMSO shows two doublets whereas the spectrum acquired in deuterated-methanol shows only the singlet for the CH group.


ExchangeableProtonsAndSolvents_Jun42009