How to Interpret an HSQC-COSY Experiment

Where a COSY or TOCSY spectrum can be a challenge for a structure with severe spectral overlap, collecting an HSQC-TOCSY spectrum can be a better choice. An HSQC-TOCSY experiment stands for Heteronuclear Single Quantum Coherence-Total Correlation Spectroscopy and other variants include HMQC-TOCSY, HSQC-COSY, etc. Depending on the mixing time, the hybrid experiment generally offers information on both short-range and long-range coupled nuclei.

For the diol fragment below, 1H-13C HSQC correlations are expected for C-H atoms labeled 4, 5 and 9.

On the 1H-13C IDR-HSQC-COSY spectrum below, the three HSQC signals are phased negative (blue). (Note: the acronym IDR stands for Inverted Direct Response.) If a rectangle is draw connecting two HSQC signals, the COSY signals (phased positive) are located at the opposite corners of the rectangle. The spectrum shows a COSY correlation between protons 4 and 5, and between protons 4 and 9.

 

How to Interpret an HSQC-COSY Experiment

Where a COSY or TOCSY spectrum can be a challenge for a structure with severe spectral overlap, collecting an HSQC-TOCSY spectrum can be a better choice. An HSQC-TOCSY experiment stands for Heteronuclear Single Quantum Coherence-Total Correlation Spectroscopy and other variants include HMQC-TOCSY, HSQC-COSY, etc. Depending on the mixing time, the hybrid experiment generally offers information on both short-range and long-range coupled nuclei.

For the diol fragment below, 1H-13C HSQC correlations are expected for C-H atoms labeled 4, 5 and 9.

On the 1H-13C IDR-HSQC-COSY spectrum below, the three HSQC signals are phased negative (blue). (Note: the acronym IDR stands for Inverted Direct Response.) If a rectangle is draw connecting two HSQC signals, the COSY signals (phased positive) are located at the opposite corners of the rectangle. The spectrum shows a COSY correlation between protons 4 and 5, and between protons 4 and 9.

 

Teaching and Learning by Spectral Data … Part 2

Part 1 of the series Teaching and Learning by Spectral Data explored the difference between presenting an NMR problem set to a student in the form of an alphanumerical text or as an actual NMR spectrum. Continuing on the same problem set, another issue arises. Is the information on the elements and the 1H NMR spectrum adequate for deducing the unknown?

From the following 1H NMR spectrum, the following fragments can be deduced:

1. the multiplet at 7.24-7.57 ppm (m, 5H) indicates a mono-substituted benzene ring system,

2. the pairing of the J values and the integral information indicates a CH3-CH2 and a CH=CH (trans) fragments (tilting is also evident),

3. the chemical shift for the CH2 at 4.45 ppm indicates an adjacent oxygen atom,

4. the chemical shifts for the CH=CH fragment, 6.49 and 7.83 ppm, indicate an adjacent oxygen atom and/or benzene ring.

The elucidation cannot be completed without additional analytical or spectral data such as elemental analysis, MS, IR, 13C NMR, 2D NMR, etc.

Teaching and Learning by Spectral Data … Part 2

Part 1 of the series Teaching and Learning by Spectral Data explored the difference between presenting an NMR problem set to a student in the form of an alphanumerical text or as an actual NMR spectrum. Continuing on the same problem set, another issue arises. Is the information on the elements and the 1H NMR spectrum adequate for deducing the unknown?

From the following 1H NMR spectrum, the following fragments can be deduced:

1. the multiplet at 7.24-7.57 ppm (m, 5H) indicates a mono-substituted benzene ring system,

2. the pairing of the J values and the integral information indicates a CH3-CH2 and a CH=CH (trans) fragments (tilting is also evident),

3. the chemical shift for the CH2 at 4.45 ppm indicates an adjacent oxygen atom,

4. the chemical shifts for the CH=CH fragment, 6.49 and 7.83 ppm, indicate an adjacent oxygen atom and/or benzene ring.

The elucidation cannot be completed without additional analytical or spectral data such as elemental analysis, MS, IR, 13C NMR, 2D NMR, etc.

Teaching and Learning by Spectral Example ... Part 1

There are many ways to teach the process of elucidating unknown structures. Offering a student a visual guide, such as seeing firsthand a spectral dataset, can enhance the learning process and better equip the student on future work.

Presented below is a typical elucidation question from a university test. The numerical values have been extracted from a 1H NMR spectrum and the student is basically left to focus on elucidating the unknown.

If a 1H NMR spectrum is presented with the question, as shown below, the student is faced with the tasks of interpreting the spectrum and elucidating the unknown.

Although both approaches can serve a purpose, the latter approach enhances the experience of learning how to elucidate an unknown.

Teaching and Learning by Spectral Example ... Part 1

There are many ways to teach the process of elucidating unknown structures. Offering a student a visual guide, such as seeing firsthand a spectral dataset, can enhance the learning process and better equip the student on future work.

Presented below is a typical elucidation question from a university test. The numerical values have been extracted from a 1H NMR spectrum and the student is basically left to focus on elucidating the unknown.

If a 1H NMR spectrum is presented with the question, as shown below, the student is faced with the tasks of interpreting the spectrum and elucidating the unknown.

Although both approaches can serve a purpose, the latter approach enhances the experience of learning how to elucidate an unknown.

Verifying, Confirming, Making Sure … Part 2

In the constant pursuit of new pharmaceutical drugs, process chemists (sometimes referred to as medicinal or synthetic chemists) must investigate all impurities detected in a new drug manufacturing process. The chemist’s procedure is simple: identify, elucidate and synthesize each and every single impurity.

The chromatogram (UV detector set at 254 nm) below shows three peaks. The large peak at 5.51 min. is the active pharmaceutical ingredient (API). The two small peaks on either side of the API are impurities from the manufacturing process. Depending on the dose and potency of the drug substance, typical regulatory requirements for impurities mandate that any peak with a threshold greater than 0.1% be identified, elucidated and synthesized.