Why Camphor Reduction is the Perfect Experiment for Teaching Green Chemistry

The awareness and application of Green Chemistry practices have grown significantly within the chemistry community in recent decades, contributing to the global sustainability movement.¹ Institutions and organizations are increasingly integrating Green Chemistry principles into their everyday practices, aiming to eliminate intrinsic hazards rather than focusing on reducing risk through exposure minimization.

The principles of Green Chemistry are composed of a set of practices and emerging research.²

They include:

1. Preventing waste;
2. Maximizing atom economy;
3. Designing less hazardous chemical syntheses;
4. Designing safer chemicals and products;
5. Using safer solvents and reaction conditions;
6. Enhancing energy efficiency;
7. Using renewable feedstocks;
8. Avoiding chemical derivatives;
9. Using catalysts instead of stoichiometric reagents;
10. Designing chemicals and products that degrade after use;
11. Implementing real-time analysis to reduce pollution;
12. Minimizing the risk of accidents.³

This article will explore how the use of the Spinsolve benchtop NMR spectrometer can incorporate Green Chemistry principles into undergraduate organic chemistry laboratories.

The transformation of camphor to isoborneol/borneol is a commonly conducted experiment in undergraduate organic chemistry laboratories. This process typically involves the reduction of camphor to an isoborneol/borneol mixture using a reducing agent (e.g. NaBH₄), or the oxidation of isoborneol/borneol using more environmentally friendly reagents such as bleach or oxone.4

After isolating and purifying the products, students often analyze the isolated products using analytical techniques such as melting point determination, IR spectroscopy, GC or GC-MS, and NMR.

Scheme 1. Reduction reaction of camphor to form isoborneol and borneol. Image Credit: Magritek

The procedure for reducing camphor frequently includes adding NaBH₄ to a solution of camphor in methanol. The reaction mixture is stirred for 30 minutes, after which water is added, resulting in the precipitation of the products.

This reaction generates a mixture of isoborneol and borneol products from the two different approaches in which NaBH₄ can interact with camphor (Scheme 1).

The product mixture can be isolated by filtration and may be further purified to remove residual water. It is then analyzed using various analytical methods, typically including melting point determination and IR spectroscopy.

NMR Data & Discussion

Although data acquired from melting point analysis and IR can confirm the presence of isoborneol and borneol, it cannot determine the diastereomeric ratio between isoborneol and borneol in the product mixture without physically separating and purifying each isomer.

Gas chromatography (GC) can be employed to separate the two isomers and analyze the diastereomeric ratio. However, GC requires the use of carrier gases with longer measurement times, leading to increased laboratory waste production.

NMR analysis of the product mixture using benchtop NMR spectrometers enables the structural verification of isoborneol and borneol, in addition to their diastereomeric ratio, with a short measurement time. Benchtop NMR spectrometers do not require liquid cryogens or carrier gases, thereby reducing the waste generated from analytical instrumentations in the laboratory (Principle 1 of Green Chemistry).

Figure 1. 1D ¹H spectrum of isoborneol-borneol mixture in CDCl₃ (concentration: 30 mg/mL; measurement time: 1 minute). Image Credit: Magritek

Figure 1 displays the 1D ¹H spectrum of the isolated product mixture from the camphor reduction reaction in CDCl₃, collected on Spinsolve 80 Carbon ULTRA. The structure of both isomers can be verified via analysis of the NMR signals. The diagnostic signal for isoborneol can be observed as a multiplet at 3.6 ppm, while the signal for borneol can be observed as another multiplet at 4.0 ppm.

Since each signal corresponds to a single proton, normalizing the total integral to 100 allows each signal's integral to represent the percentage of its respective product in the mixture. Based on this approach, the diastereomeric ratio of isoborneol to borneol in the mixture is determined to be 75:25.

The Spinsolve Benchtop NMR spectrometer, featuring the exceptional lineshape of the ULTRA model, enables sample analysis in protonated solvents through the effective application of the WET solvent suppression technique.

For the camphor reduction experiment, students can simply transfer an aliquot (0.5 mL) of the reaction mixture in methanol to an NMR tube at the end of the 30-minute reaction period. This can eliminate the work-up procedure, thereby reducing waste production (Principle 1 of Green Chemistry), allowing the use of safer solvents (Principle 5 of Green Chemistry), and enabling real-time analysis to prevent pollution (Principle 11 of Green Chemistry).

The reaction aliquot can then be evaluated directly using NMR with WET solvent suppression.

Figure 2 presents the 1D ¹H spectra of the reaction mixture acquired with and without solvent suppression. In the ¹H spectrum collected without solvent suppression (red trace), the diagnostic signal for isoborneol is shown to be significantly overlapped with the methanol signal.

Although well-separated from the methanol signal, the diagnostic signal for borneol also experiences an elevated baseline due to the tail of the methanol peak. This affects the calculation of diastereomeric ratio of the products.

The 1D ¹H spectrum (with ¹³C decoupling) obtained with WET solvent suppression exhibits a clear resolution of the isoborneol signal at 3.25 ppm from the residual methanol signal at 3.09 ppm. 

Although the chemical shift separation between these two signals is 0.16 ppm (or 12.8 Hz at 80 MHz field strength), the calculated diastereomeric ratio of the two products remains consistent at 75:25 (isoborneol:borneol).

This efficient application of WET solvent suppression with high selectivity on the Spinsolve ULTRA spectrometers enables precise and quantitative analysis of mixtures in protonated solvents.

Figure 2. 1D ¹H spectrum (with ¹³C decoupling) of isoborneol-borneol mixture in protonated methanol collected without solvent suppression (red trace) and with solvent suppression (cyan trace). (concentration: 30 mg/mL; measurement time: 1 minute). Image Credit: Magritek

Conclusions

As outlined in this article, the Spinsolve spectrometer can be seamlessly integrated into undergraduate organic laboratory exercises.

As Green Chemistry awareness and adoption grow, Spinsolve facilitates the application of many of its principles in existing laboratories by enabling the use of protonated solvents to cut down on waste and allow for real-time data analysis of reaction processes.

This approach enhances students’ understanding of Green Chemistry implementation while also providing practical experience that prepares them for professional careers after graduation.

References and Further Reading:

1. Ganesh, K.N., et al. (2021). Green Chemistry: A Framework for a Sustainable Future. Organic Process Research & Development, 25(7), pp.1455–1459. https://doi.org/10.1021/acs.oprd.1c00216.
2. Warner, J.C., Cannon, A.S. and Dye, K.M. (2004). Green chemistry. Environmental Impact Assessment Review, (online) 24(7), pp.775–799. https://doi.org/10.1016/j.eiar.2004.06.006.
3. Anastas, P.T. and Warner, J.C. (2000). Green Chemistry: Theory and Practice. (online) Oxford University Press. Oxford, New York: Oxford University Press. Available at: https://global.oup.com/academic/product/green-chemistry-9780198506980.
4. Lang, P.T., Harned, A.M. and Wissinger, J.E. (2011). Oxidation of Borneol to Camphor Using Oxone and Catalytic Sodium Chloride: A Green Experiment for the Undergraduate Organic Chemistry Laboratory. Journal of Chemical Education, 88(5), pp.652–656. https://doi.org/10.1021/ed100853f.

This information has been sourced, reviewed and adapted from materials provided by Magritek.

For more information on this source, please visit Magritek.