Analyzes of alkyl phosphonate mixtures

In nuclear magnetic resonance (NMR) analyzes of phosphorus-containing compounds, ¹H and ¹³C signals near phosphorus are affected by heteronuclear spin couplings. Given the natural abundance of ³¹P at 100%, these splittings are easily visible, reducing sensitivity and increasing complexity. Additionally, some of these compounds are unstable in solvents, leading to the formation of decomposition products, which further complicates the interpretation of ¹H and ¹³C spectra. On the other hand, when analyzing phosphorus-containing samples, ³¹P NMR information can be invaluable for structural analysis. To illustrate this, we will provide some examples below. In the measurements detailed in this application note, we utilized the ROYAL Probe^TM P+ [1], capable of ¹H, ³¹P, and X triple-resonance measurements. We employed a three-channel 600 MHz NMR spectrometer, the JNM-ECZL600G, featuring one high-frequency (HF) and two low-frequency (LF) channels.

Sample information

Alkyl phosphonates known as Horner-Emmons reagents are used in the olefination reaction. These include diethyl methylphosphonate 1, ethyl dimethyl phosphonoacetate 2, and diethyl (ethoxymethyl) phosphonate 3. They were mixed and dissolved in CDCl₃ to create a sample containing 4.8 vol% of each compound.

¹³C NMR spectrum

A conventional ¹³C spectrum of the sample recorded with ¹H decoupling is depicted in Fig. 1. Upon examining the expansions of this spectrum in Fig. 2, an experienced chemist may observe that several signals appear doubled, indicating splitting caused by ¹³C-³¹P coupling. However, identifying such signal doublings may prove challenging in the case of unknown samples or very complex mixtures with numerous carbon signals. To illustrate the efficacy of triple-resonance experiments, a ¹³C spectrum recorded with simultaneous ¹H and ³¹P decoupling is presented in Fig. 2c) and Fig. 2d). A straightforward comparison between the double-resonance and triple-resonance spectra allows for the unequivocal identification of carbon signals split by one-bond M¹³C-³¹P couplings, which can exceed 100 Hz in alkyl phosphonates. The signals observed at 10.85 ppm (J_CP = 144 Hz)^*1, 33.13 ppm (J_CP = 135 Hz)^*2, and 64.35 ppm J_CP = 167 Hz)^*3 can thus be attributed to the carbon atoms directly bound to phosphorus, with the one-bond coupling constants provided in parentheses. Smaller splittings are indicative of 2-bond and 3-bond interactions. Table 1 summarizes the ¹³C chemical shifts and ¹³C-³¹P coupling constants.

Fig. 2: Expanded regions of 　
a) ¹³C{¹H} and b) ¹³C{¹H}{³¹P} spectra in the range of 50-70 ppm,
c) ¹³C{¹H} and d) ¹³C{¹H}{³¹P} spectra in the range of 10-35 ppm

Table 1: ¹³C chemical shifts and coupling constants

Difficulty in interpretation of ¹H-³¹P HMBC and use of double-INEPT H-C-P experiment

Fig. 3 shows the¹H-³¹P HMBC spectrum. ¹H-³¹P coupling via 2- and 3-bonds are observed, but it is difficult to distinguish each from this spectrum. On the other hands, by measuring the ¹H-¹³C-³¹P double-INEPT as shows Fig. 4, only the 2-bonded ¹H-³¹P can be selectively extracted ^[2]. Then we can distinguish between 2- and 3-bonds by comparing them. the ¹J_CH and ¹J_CP couplings are used to obtain correlations in double-INEPT, since ¹J_CP of alkyl phosphonates have a large coupling constant as mentioned above, it is possible to extract only the H-C-P coupling by setting the parameters according to that.

Assignment of each ³¹P-¹³C coupling partners

³¹P-¹³C correlations can also provide significant insights into the structural analysis of phosphorus-containing compounds. Correctly chosen and optimized ³¹P-¹³C correlation experiments enable the identification of ¹³C coupling partners for each ³¹P nucleus. Fig. 5 illustrates a ³¹P-¹³C LR-HSQC (Long-Range Heteronuclear Single-Quantum Coherence) spectrum. The pulse program employed was a standard HSQC, with parameters optimized for long-range ¹³C-³¹P couplings, thereby capturing correlations from weak couplings as well. In Fig.6, we compare the ¹³C NMR spectrum with three slices extracted from the ³¹P-¹³C LR-HSQC spectrum for each phosphorus atom. This facilitates the assignment of ¹³C signals to individual phosphonates. Additionally, Fig. 6 demonstrates that ³¹P-¹³C LR-HSQC enables the detection of carbon atoms up to three bonds away from each phosphorus atom.

Fig. 6: Comparison of ¹³C spectrum and slices extracted from ³¹P- ¹³C LRHSQC {¹H}{¹³C} spectrum
※ one-bond correlation

Refference

• JEOL Application note NM220010E

• Tetrahedron Letters 48 (2007) 7586-7590

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