19F Benchtop NMR Spectroscopy for Rapid Hydroxyl Value Determination in Polymers

When analyzing polymers using nuclear magnetic resonance (NMR) spectroscopy, well-defined end-groups (e.g., methoxy, acrylate, vinyl) are typically desired, as these allow for a direct comparison between these end-groups and the repeating monomeric units. This provides a path for rapid and facile determination of the number of repeating units in a polymer, as well as its number-average molecular weight (M_n).¹ However, many polymers and raw materials used for polymer production are terminated with hydroxyl functionalities, which cannot be used for these purposes, due to their high lability and tendency to exchange with protons in solution, leading to inaccurate integration values.

The hydroxyl value of a polymer, often referred to as HOV, provides key insight into the stability and reactivity of polymers. To determine this parameter, typically, acetic anhydride is used to acetylate the hydroxyl groups, and water is then added to neutralize the remaining acetic anhydride. Reported in mg KOH/g of polymer, the HOV is a measure of how many milligrams of potassium hydroxide are required to neutralize the residual acetic acid.

In industry, HOV assays are often performed according to ASTM E222.² This method is expensive and wasteful, requiring the use of a pressure bottle, an acetylation mixture prepared fresh daily (127 mL of acetic anhydride in 1 L of pyridine), hydrochloric acid, potassium hydroxide, phenolphthalein, and heating to 98 ± 2 °C for 2 to 4 hours. Conversely, we have proposed two methods which make use of quantitative NMR (qNMR),³ require very little solvent, and only small amounts of reagents.

One of these methods is closely based on work previously reported by Foli et al.⁴ Here, trifluoroacetic anhydride in chloroform is used to transform the hydroxyl groups in the polymer into trifluoroacetyl functionalities (Figure 1), providing a useful fluorine handle for ¹⁹F NMR analysis. By adding an appropriate internal calibrant for qNMR, the hydroxyl value can easily be quantified.

Figure 1. General reaction scheme for the transformation of hydroxyl groups into trifluoroacetyl fragments using trifluoroacetic anhydride in chloroform.

The results of analyses on polyoxyl 10 oleyl ether samples using this approach are summarized in Table 1. As evidenced by the data, this method performs well under reproducibility conditions, with relative standard deviation (RSD) values ranging between 0.4–1.6%.

Table 1. Summary of the HOV obtained for polyoxyl 10 oleyl ether polymers using ¹⁹F benchtop NMR spectroscopy. The averages of triplicate analyses are shown, and the RSD values are included in parentheses. The certificate of analysis (CoA) values, as provided by the suppliers, are included for comparison.

*In accordance with the method outlined in ASTM E222, the HOV are reported to the nearest 0.1 unit if the value is below 100, and to the nearest 1 unit if the value is above 100.

The summary presented herein demonstrates that benchtop NMR spectroscopy can be used for the accurate and reproducible determination of HOV in polymers. The use of ¹⁹F NMR allows for the use of non-deuterated solvents and makes use of the larger chemical shift range of fluorine signals, especially when compared to the relatively narrow range of signals observed via ¹H NMR. This method is significantly less wasteful and more direct than the typical ASTM approach used in industry. For many additional experimental details on both methods mentioned here, including ¹⁹F NMR spectra, as well as results using additional polymers, such as poly(ethylene glycol), polyoxyl 20 cetostearyl ether, poly(ethylene glycol) monomethyl ether, and poloxamers, please check out our application note on the subject.

References
(1) Izunobi, J. U.; Higginbotham, C. L. J. Chem. Educ. 2011, 88, 1098–1104.
(2) ASTM Standard E222, 2017, Standard Test Methods for Hydroxyl Groups Using Acetic Anhydride Acetylation, ASTM International, West Conshohocken, PA.
(3) Pauli, G. F. Phytochem. Anal. 2001, 12, 28–42.
(4) Foli, G.; Degli Esposti, M.; Toselli, M.; Morselli, D.; Fabbri, P. Analyst 2019, 144, 2087–2096.