IR, NMR and MS of a Sulfonyl Chloride compound

The best use of a set of tools for a structure elucidation are those that have a general target or goal in mind. Random experiments for the sake of collecting data are a sure sign of inexperience. With that said, Infrared (IR) spectroscopy is a great tool for identifying or confirming a functional group(s). It is an under utilized tool that can complement information from NMR and MS.

The IR, NMR and MS spectra for butane-1-sulfonyl chloride are shown below.

Sulfonyl chloride exhibits strong characteristic bands in the IR region of 1410-1370 and 1204-1166 cm-1. The alkane CH stretching bands appear around 3000-2800 cm-1.

The MS illustrates two ions at m/z 57 and 99. The ion peak at m/z 57 is characteristic of a hydrocarbon chain. The ion peak at m/z 99, although weak, is characteristic for a sulfonyl chloride group and exhibits an A+2 peak at m/z 101 due to the 37Cl isotope.

The 1H NMR spectrum exhibits 4 distinct multiplets attributed to the hydrocarbon chain. The deshielded multiplet at 3.68 ppm indicates the presence of a strong-electron withdrawing atom or group.

Using any 2 of the 3 techniques can facilitate the elucidation process and assist in confirming the structure.

IR, NMR and MS of a Sulfonyl Chloride compound

The best use of a set of tools for a structure elucidation are those that have a general target or goal in mind. Random experiments for the sake of collecting data are a sure sign of inexperience. With that said, Infrared (IR) spectroscopy is a great tool for identifying or confirming a functional group(s). It is an under utilized tool that can complement information from NMR and MS.

The IR, NMR and MS spectra for butane-1-sulfonyl chloride are shown below.

Sulfonyl chloride exhibits strong characteristic bands in the IR region of 1410-1370 and 1204-1166 cm-1. The alkane CH stretching bands appear around 3000-2800 cm-1.

The MS illustrates two ions at m/z 57 and 99. The ion peak at m/z 57 is characteristic of a hydrocarbon chain. The ion peak at m/z 99, although weak, is characteristic for a sulfonyl chloride group and exhibits an A+2 peak at m/z 101 due to the 37Cl isotope.

The 1H NMR spectrum exhibits 4 distinct multiplets attributed to the hydrocarbon chain. The deshielded multiplet at 3.68 ppm indicates the presence of a strong-electron withdrawing atom or group.

Using any 2 of the 3 techniques can facilitate the elucidation process and assist in confirming the structure.

Interpreting a 1H-13C HMBC spectrum

Like a COSY experiment, an HMBC dataset offers many combinations of atom connectivity. The goal for the elucidator is to assess each correlation and narrow down a set of fragments that support the data.

For every correlation in a 1H-13C HMBC spectrum, an elucidator must decide whether a correlation corresponds to a 2J, 3J or 4J coupling (NOTE: this is dependent on what the coupling constant is set to in the HMBC sequence). Below is a structural list for all H to C connections—heteroatoms are not shown in the list for the sake of simplicity. The 2J coupling, outlined with a blue box, the 3J coupling, outlined in a green box, and the 4J coupling, outlined with a purple box, offers 3, 6 and 14 possible combinations, respectively.

Interpreting a 1H-13C HMBC spectrum

Like a COSY experiment, an HMBC dataset offers many combinations of atom connectivity. The goal for the elucidator is to assess each correlation and narrow down a set of fragments that support the data.

For every correlation in a 1H-13C HMBC spectrum, an elucidator must decide whether a correlation corresponds to a 2J, 3J or 4J coupling (NOTE: this is dependent on what the coupling constant is set to in the HMBC sequence). Below is a structural list for all H to C connections—heteroatoms are not shown in the list for the sake of simplicity. The 2J coupling, outlined with a blue box, the 3J coupling, outlined in a green box, and the 4J coupling, outlined with a purple box, offers 3, 6 and 14 possible combinations, respectively.

How to deal with ambiguity in an HMBC spectrum? … Part 3

Nine times out of ten, the consequence of an incorrect assignment of a 2D correlation to a 1D resonance is a structural dead end. That is, the fragments cannot be pieced together to present a clear-cut candidate(s). Dealing with ambiguity in an HMBC spectrum is a common area where the structure elucidation process can go off-track and hit that structural dead end.

The 1H-13C DEPT-HSQC spectrum below illustrates 2 terminal alkene CH2 groups with coinciding 13C resonances at 112.0 ppm.

The 1H-13C HMBC spectrum (optimized to 8 Hz) illustrates a correlation between the 13C resonance at 112.0 ppm and a 1H resonance at 5.38 ppm for a CH group.

Recognizing the overlapping 13C resonances, there are two possible fragments to consider. The fragment below illustrates such a scenario where a misassignment can inhibit an elucidation.

Note: three fragments are possible if you consider both carbons correlated to the same 1H resonance.

How to deal with ambiguity in an HMBC spectrum? … Part 3

Nine times out of ten, the consequence of an incorrect assignment of a 2D correlation to a 1D resonance is a structural dead end. That is, the fragments cannot be pieced together to present a clear-cut candidate(s). Dealing with ambiguity in an HMBC spectrum is a common area where the structure elucidation process can go off-track and hit that structural dead end.

The 1H-13C DEPT-HSQC spectrum below illustrates 2 terminal alkene CH2 groups with coinciding 13C resonances at 112.0 ppm.

The 1H-13C HMBC spectrum (optimized to 8 Hz) illustrates a correlation between the 13C resonance at 112.0 ppm and a 1H resonance at 5.38 ppm for a CH group.

Recognizing the overlapping 13C resonances, there are two possible fragments to consider. The fragment below illustrates such a scenario where a misassignment can inhibit an elucidation.

Note: three fragments are possible if you consider both carbons correlated to the same 1H resonance.

How to deal with ambiguity in an HMBC spectrum? … Part 2

The best approach when dealing with severe ambiguity in assigning a correlation(s) to a 1D resonance(s) in a 1H-13C HMBC spectrum is to take into account all possible assignments. The drawback to this approach is it adds to the complexity of the structure elucidation process rather than simplifying it.

The HMBC spectrum below illustrates a severe case of ambiguity in assigning a correlation to a single 13C resonance. The spectrum exhibits a correlation that can be assigned to a 13C resonance at 129.10 and/or 129.13 ppm.

The elucidator will take the first possible assignment (3.52, 129.10 ppm) and attempt to construct a set of structures (or fragments). Subsequently, the elucidator will take the alternate assignment (3.52, 129.13 ppm) and build a second set of structures. This approach of using multiple assignments will ensure no possibility is overlooked.

TIP: The curved arrows, used to track what nuclei are coupled to each other, are drawn as dotted lines to indicate an ambiguous assignment. Visually, the elucidator can differentiate this ambiguous assignment from curved arrows with solid lines used for definite assignments.

How to deal with ambiguity in an HMBC spectrum? … Part 2

The best approach when dealing with severe ambiguity in assigning a correlation(s) to a 1D resonance(s) in a 1H-13C HMBC spectrum is to take into account all possible assignments. The drawback to this approach is it adds to the complexity of the structure elucidation process rather than simplifying it.

The HMBC spectrum below illustrates a severe case of ambiguity in assigning a correlation to a single 13C resonance. The spectrum exhibits a correlation that can be assigned to a 13C resonance at 129.10 and/or 129.13 ppm.

The elucidator will take the first possible assignment (3.52, 129.10 ppm) and attempt to construct a set of structures (or fragments). Subsequently, the elucidator will take the alternate assignment (3.52, 129.13 ppm) and build a second set of structures. This approach of using multiple assignments will ensure no possibility is overlooked.

TIP: The curved arrows, used to track what nuclei are coupled to each other, are drawn as dotted lines to indicate an ambiguous assignment. Visually, the elucidator can differentiate this ambiguous assignment from curved arrows with solid lines used for definite assignments.

How to deal with ambiguity in an HMBC spectrum? … Part 1

Generally, a 1H-13C HMBC experiment offers a wealth of connectivity information about an unknown structure(s). However, an elucidator may be faced with the issue of ambiguity in assigning a correlation(s) to a 1D resonance(s).

A correlation with an ambiguous assignment may be assessed in one of 5 ways:

-reprocess the HMBC data using a different weighing function to try and narrow down an assignment,

-look for additional information among the other experiments to confirm one assignment over an other,

-ignore the ambiguous correlation and see if there is adequate HMBC data to continue the elucidation,

-make an assumption and assign the correlation to a 1D resonance at the risk of being incorrect, or

-consider multiple assignments at the risk of complicating the elucidation process.

The case below illustrates a mild form of ambiguity in an HMBC spectrum. (A subsequent blog will demonstrate how to deal with a severe case of ambiguity.) The HMBC spectrum exhibits 2 adjacent CH2 resonances, at 41 and 42 ppm, whereby one or both carbons are correlated to the 1H resonance at 2.37 ppm. From afar, the correlation appears to be linked to both carbons. However, upon closer examination of the correlation, the carbon at 42 ppm seems to be the better choice.

TIP: Zooming-in on a correlation can sometimes help resolve the uncertainty associated with the assignment.

How to deal with ambiguity in an HMBC spectrum? … Part 1

Generally, a 1H-13C HMBC experiment offers a wealth of connectivity information about an unknown structure(s). However, an elucidator may be faced with the issue of ambiguity in assigning a correlation(s) to a 1D resonance(s).

A correlation with an ambiguous assignment may be assessed in one of 5 ways:

-reprocess the HMBC data using a different weighing function to try and narrow down an assignment,

-look for additional information among the other experiments to confirm one assignment over an other,

-ignore the ambiguous correlation and see if there is adequate HMBC data to continue the elucidation,

-make an assumption and assign the correlation to a 1D resonance at the risk of being incorrect, or

-consider multiple assignments at the risk of complicating the elucidation process.

The case below illustrates a mild form of ambiguity in an HMBC spectrum. (A subsequent blog will demonstrate how to deal with a severe case of ambiguity.) The HMBC spectrum exhibits 2 adjacent CH2 resonances, at 41 and 42 ppm, whereby one or both carbons are correlated to the 1H resonance at 2.37 ppm. From afar, the correlation appears to be linked to both carbons. However, upon closer examination of the correlation, the carbon at 42 ppm seems to be the better choice.

TIP: Zooming-in on a correlation can sometimes help resolve the uncertainty associated with the assignment.

Fulvene versus Benzene

Failures, as are successes, are an integral part of a structure elucidator’s role. What differentiates a good elucidator from a bad one is the capability of an elucidator to learn from his/her failures. The most common obstacle that can hold a structure elucidation process from becoming a success is structural bias. (This is based on my experiences with elucidators worldwide.)

A good stance to best avoid structural bias is to be aware of different alternative structures especially those not commonly encountered during a routine structure elucidation. Below is a case in point. The unknown is comprised of two fragments such that the hybridization states of all the carbons are sp2 and the ring size is restricted to 5 or 6. For clarity reasons, the carbon atoms in red are the ones to be arranged.

Two candidate structures are shown below. A common structural bias is to take the 6 sp2 carbons and complete a benzene ring (right structure). The alternative structure is work out a fulvene group (left structure). References are included for both structures.

Fulvene versus Benzene

Failures, as are successes, are an integral part of a structure elucidator’s role. What differentiates a good elucidator from a bad one is the capability of an elucidator to learn from his/her failures. The most common obstacle that can hold a structure elucidation process from becoming a success is structural bias. (This is based on my experiences with elucidators worldwide.)

A good stance to best avoid structural bias is to be aware of different alternative structures especially those not commonly encountered during a routine structure elucidation. Below is a case in point. The unknown is comprised of two fragments such that the hybridization states of all the carbons are sp2 and the ring size is restricted to 5 or 6. For clarity reasons, the carbon atoms in red are the ones to be arranged.

Two candidate structures are shown below. A common structural bias is to take the 6 sp2 carbons and complete a benzene ring (right structure). The alternative structure is work out a fulvene group (left structure). References are included for both structures.

Stuck on a Structure Elucidation problem? You need Out of the Box thinking, right?

Attempting a challenging structure elucidation of an unknown and being unable to solve the problem can put a damper on a hectic workload and possibly on your skills as an elucidator. Emotionally, the excitement of working on a challenging elucidation problem leads into frustration -- results are what count. Subsequently, the elucidator faces the following choices:

-collect more data,

-question the data or the instrument or the instrument operator,

-discard everything and start from scratch,

-leave it alone for a few days and then come back to it with a clear mind,

-hand it off for someone else to do,

-forget about it and pretend it never existed, or

-file it in the cabinet under the X-file for another day.

The diagram below presents the situation whereby an elucidator is fixated on a core fragment and thus unable to budge from the enclosed Structural Bias box. A classic example is the elucidation of a synthetic product whereby the chemist synthesized an unknown compound far from what he/she intended. The elucidator then falls for the bias of a specific fragment upon seeing the synthetic route.

How to avoid the Structural Bias box? There is no easy answer (or answers) other than to simply broaden your scope of knowledge. Definitely, the willingness and enthusiasm to never give up is a plus while ensuring every idea is panned out to its fullest. Also, be sure to be open to more than one solution as you venture outside of your comfort zone. Explore the literature and databases in search of that elusive tidbit that could unlock the missing piece. Finally, focus on piecing the data together in new and creative ways.

Stuck on a Structure Elucidation problem? You need Out of the Box thinking, right?

Attempting a challenging structure elucidation of an unknown and being unable to solve the problem can put a damper on a hectic workload and possibly on your skills as an elucidator. Emotionally, the excitement of working on a challenging elucidation problem leads into frustration -- results are what count. Subsequently, the elucidator faces the following choices:

-collect more data,

-question the data or the instrument or the instrument operator,

-discard everything and start from scratch,

-leave it alone for a few days and then come back to it with a clear mind,

-hand it off for someone else to do,

-forget about it and pretend it never existed, or

-file it in the cabinet under the X-file for another day.

The diagram below presents the situation whereby an elucidator is fixated on a core fragment and thus unable to budge from the enclosed Structural Bias box. A classic example is the elucidation of a synthetic product whereby the chemist synthesized an unknown compound far from what he/she intended. The elucidator then falls for the bias of a specific fragment upon seeing the synthetic route.

How to avoid the Structural Bias box? There is no easy answer (or answers) other than to simply broaden your scope of knowledge. Definitely, the willingness and enthusiasm to never give up is a plus while ensuring every idea is panned out to its fullest. Also, be sure to be open to more than one solution as you venture outside of your comfort zone. Explore the literature and databases in search of that elusive tidbit that could unlock the missing piece. Finally, focus on piecing the data together in new and creative ways.

t-Butyl group towers over other 1H resonances

Like a methoxy group, a t-Butyl group stands out over other 1H resonances. For organic compounds, the 1H resonance for a t-Butyl group generally towers over other 1H resonances because it integrates to ~9 protons (assuming the presence of 1 t-Butyl group and no overlap with other resonances). The basic 1H NMR pattern of the CH3 groups is a typical singlet, although not always the case, and ranging in chemical shift between 0.5 and 2.0 ppm. The 13C NMR spectrum shows the CH3 resonances between 20 and 42 ppm.

The 1H NMR spectra below illustrates the 3 patterns for a t-Butyl group to be on the lookout for.

t-Butyl group towers over other 1H resonances

Like a methoxy group, a t-Butyl group stands out over other 1H resonances. For organic compounds, the 1H resonance for a t-Butyl group generally towers over other 1H resonances because it integrates to ~9 protons (assuming the presence of 1 t-Butyl group and no overlap with other resonances). The basic 1H NMR pattern of the CH3 groups is a typical singlet, although not always the case, and ranging in chemical shift between 0.5 and 2.0 ppm. The 13C NMR spectrum shows the CH3 resonances between 20 and 42 ppm.

The 1H NMR spectra below illustrates the 3 patterns for a t-Butyl group to be on the lookout for.

The advantages of overlaying an HSQC spectrum with an HMBC spectrum

When trying to elucidate an unknown structure using 2D NMR information, an elucidator gains an advantage by analyzing all of the NMR data as a whole rather than as individual pieces. Although complicated at first, this different perspective at viewing the NMR data can facilitate the elucidation process.

The following list are a few advantages for overlaying (also referred to as collect or dual mode) an HSQC with an HMBC:

HMBC correlations can be used to differentiate overlapping HSQC correlations (and vice versa),

by lining-up the correlations for both experiments, fragments can be quickly pieced together,

the number of HMBC correlations per HSQC correlation can be determined easily,

quaternary carbons can be directly differentiated and viewed alongside the protonated carbons.

Shown below are the spectral data of a 1H NMR, an 1H-13C HSQC (green) and an 1H-13C HMBC (red) for an indole group (assigned chemical shifts are shown in blue). The different correlation colours enable the elucidator to simply distinguish the 2D NMR experiments. Carbons 111, 119.4, 119.8, 121 and 125 ppm, shown in green, are the protonated carbons from the HSQC data, thus differentiating the quaternary carbons at 116 and 128.5 ppm. The 13C resonance at 111 ppm shows 2 1H correlations: 7.17 and 7.34 ppm (illustrated with black arrows). The 1H resonance at 7.34 ppm (13C at 111 ppm) shows 3 13C correlations: 119.4, 121 and 128 ppm.

The advantages of overlaying an HSQC spectrum with an HMBC spectrum

When trying to elucidate an unknown structure using 2D NMR information, an elucidator gains an advantage by analyzing all of the NMR data as a whole rather than as individual pieces. Although complicated at first, this different perspective at viewing the NMR data can facilitate the elucidation process.

The following list are a few advantages for overlaying (also referred to as collect or dual mode) an HSQC with an HMBC:

HMBC correlations can be used to differentiate overlapping HSQC correlations (and vice versa),

by lining-up the correlations for both experiments, fragments can be quickly pieced together,

the number of HMBC correlations per HSQC correlation can be determined easily,

quaternary carbons can be directly differentiated and viewed alongside the protonated carbons.

Shown below are the spectral data of a 1H NMR, an 1H-13C HSQC (green) and an 1H-13C HMBC (red) for an indole group (assigned chemical shifts are shown in blue). The different correlation colours enable the elucidator to simply distinguish the 2D NMR experiments. Carbons 111, 119.4, 119.8, 121 and 125 ppm, shown in green, are the protonated carbons from the HSQC data, thus differentiating the quaternary carbons at 116 and 128.5 ppm. The 13C resonance at 111 ppm shows 2 1H correlations: 7.17 and 7.34 ppm (illustrated with black arrows). The 1H resonance at 7.34 ppm (13C at 111 ppm) shows 3 13C correlations: 119.4, 121 and 128 ppm.