Introduction: Chemiluminescence demonstrations that use peroxyoxalate “glowstick” systems are very popular in a variety of lecture demonstrations and classroom activities1-3 . These reactions are very eye catching and easy to do; however, until recently, the range of oxalate diesters available has been limited. The most frequently encountered oxalate diesters (Figure 1 below) are bis(2,4,6-trichlorophenyl) oxalate (TCPO),1,4,9 bis(2,4-nitrophenyl) oxalate (DNPO)4 and latterly, bis(2,4,5-trichloro-6-carbopentoxyphenyl) oxalate (CPPO).5 All of these materials function very well, however the phenol products formed from the reaction are a concern due to their toxicity, the halogenated phenols also require careful disposal. In addition to toxicity concerns, these compounds can be quite expensive, when sourced commercially.
Figure 1
In recent years excellent progress has been made to replace the more traditional oxalate diesters with analogues that use and release more environmentally benign phenols, the starting materials are also cheap and readily available. These new bisoxalate esters are derived from vanillin (DVO)6 and methyl salicylate (DMO),7 more recently it has been reported that an oxamide derived from benzotriazole (ODBT)8 is also easily prepared and can be used safely.
Overview: For several years we have found DVO and DMO to be particularly useful for making simplified “glowsticks” where the chemiluminescence reaction is conducted in a screw-cap centrifuge tube.3 This activity is part of an outreach program and necessitates ready and frequent access to multigram batches of each compound. We have not experienced problems making the desired oxalate diesters, however the original procedures use different solvents and bases, so we have made minor modifications to allow a common procedure to access both compounds efficiently. A concise overview of the known reaction conditions is shown in Scheme 1 below.
In addition to disclosing a modified procedure for making both DVO and DMO, we report that 2′-hydroxyacetophenone can also be employed in the same procedure to make a new oxalate diester, bis(2-acetylphenyl) oxalate (DAO, structure below). We have found that DAO also serves as a useful alternative to TCPO in chemiluminescence demonstrations, it shares many of the advantages (non-halogenated, cheap and readily available) currently provided by the vanillin and methyl salicylate derived oxalate diesters.
Procedure: In the majority of cases, phenol-derived oxalate diesters are prepared by adding neat oxalyl chloride to an ice-cold mixture of the required phenol and base in an appropriate solvent. Care is required during the addition of oxalyl chloride since the reaction releases a significant quantity of fumes and there is a risk of thermal runaway if cooling is inadequate and/or the oxalyl chloride is added too quickly. We have found that a more convenient alternative is simply to add a dilute solution of oxalyl chloride in toluene (ca. 0.7M), to a mixture of phenol and base in ice-cold toluene. This approach allows more control over the oxalyl chloride addition rate, toluene is also relatively easy to dry and we have found that the solutions of oxalyl chloride in dry toluene can be stored for several weeks if required.9 The ability to prepare stock solutions of oxalyl chloride in advance has proved to be advantageous when several batches of material are produced in parallel. This procedure has been found to work well with vanillin, methyl salicylate and 2′-hydroxyacetophenone without any modifications when changing the phenol, a general and relatively simple procedure is provided below, yields are typically in the 70-80% range.
IMPORTANT: The following synthetic procedure should be carried out in a fumehood.
A 500mL 3-neck flask was equipped with a large magnetic stirring bar, condenser,NOTE 1 stopper, dropping funnel (figure 2). The desired phenol (36mmol)NOTE 2 was dissolved in toluene (45mL), before triethylamine was added (4.5mL) and the stirred solution was cooled in an ice bath. Pre-prepared oxalyl chloride solution (45mL of 0.71M solution in toluene) was added dropwise over 15 minutes to a vigorously stirred mixture of the ice-cold reagent mixture.NOTE 3 On completion of the oxalyl chloride addition, the ice bath was removed and the reaction mixture was allowed to stir overnight (ca. 16 hours) at room temperature. The reaction was quenched by adding water (75mL) dropwise to the reaction mixture over a period of 5 minutes to the rapidly stirred reaction mixture.NOTE 4 The resulting crude product was isolated by suction filtration using a Büchner funnel, washed with ice-cold toluene (2 × 10mL) and allowed to dry. If desired, all three products can be recrystallised from propan-2-ol; however, we have found the dried material is satisfactory for use in chemiluminescence demonstrations (1H NMR spectra are provided in supporting information).
NOTE 1: The condenser is in place for precautionary reasons; significant exotherm release has not been noted and the reactions are not externally heated. However, there is potential for an exothermic reaction if oxalyl chloride were accidentally added very rapidly.
NOTE 2: 36mmol vanillin = 5.5g, 36mmol methyl salicylate = 5.5g, 36mmol 2′-hydroxyacetophenone = 4.9g.
NOTE 3: White fumes will be observed in the flask as soon as the oxalyl chloride makes contact with the triethylamine, these subside as the reaction proceeds. The reaction must be efficiently stirred since the resulting triethylamine hydrochloride usually leads to the formation of a thick suspension.
NOTE 4: This step is essential since water will destroy any residual oxalyl chloride and it dissolves the triethylamine hydrochloride by-product to leave a suspension of crude product.
Figure 2
Hazards:
Oxalyl chloride (CAS number: 79-37-8) is a lachrymator, corrosive on skin or eye contact and releases HCl on contact with water.
Toluene (CAS number: 108-88-3) is flammable and should be considered as harmful by inhalation, ingestion or skin absorption.
Triethylamine (CAS number: 121-44-8) is flammable, corrosive on skin or eye contact and is foul smelling.
Vanillin (CAS number: 121-33-5) does not pose a significant toxicity hazard but should be considered a potential irritant.
Methyl salicylate (CAS number: 119-36-8) does not pose a significant toxicity hazard but should be considered a potential irritant.
2′-Hydroxyacetophenone (CAS number: 118-93-4) does not pose a significant toxicity hazard but should be considered a potential irritant.
Example Chemiluminescence Procedure (adapted from ref 3): To a 15mL screw cap centrifuge tube, add sodium percarbonate* (ca. 100mg) and 2-3 mg of fluorescer.** Prepare a stock solution of the oxalate by dissolving 50-60 mg10 of the desired oxalate diester in 50mL of ethyl acetate and transfer 8-9 mL of the resulting solution to the tube. Add 1mL of water to the mixture, tighten the cap and vigorously shake the tube. (CAUTION! Vent pressure regularly).
* Laundry bleach powder containing sodium percarbonate can also be used.
**Perylene, rubrene, anthracene, 9,10-diphenylanthracene and 9,10-bis(phenylethynyl)anthracene) all work very well as fluorescers in these reactions.
Figure 3– Activated 0.003M solutions of oxalates in ethyl acetate, using
sodium percarbonate as oxidant and perylene as the fluorescer
Left to Right above: oxalate diesters derived from methyl salicylate (DMO),
2′-hydroxyacetophenone (DAO) and vanillin (DVO)
Conclusion: We have presented a modification of the published procedures for the preparation of multigram quantities of oxalate diesters derived from vanillin and methyl salicylate. The modified protocol allows a common procedure to be followed to access both compounds efficiently. In addition, the use of 2′-hydroxyacetophenone to form the corresponding oxalate diester has been reported, this material has also been employed successfully in chemiluminescence demonstrations. It is hoped that these protocols will prove to be useful to educators who frequently use chemiluminescence demonstrations for teaching or outreach purposes. It is also hoped that ready access to non-halogenated oxalate diesters will facilitate their wider use in place of halogenated analogues.
References:
1. https://eic.rsc.org/exhibition-chemistry/the-glow-stick-reaction/3010386... (accessed 5/29/2019)
2. Kuntzleman, T. S; Rohrer, K; Schultz, E. The Chemistry of Lightsticks: Demonstrations to Illustrate Chemical Processes. J. Chem. Educ. 2012, 89, 910-916.
3. Smellie, I. A; Aldred (née Prentis), J. K. D; Bower, B; Cochrane, A; Macfarlane, L; McCarron, H. B; O’Hara, R; Patterson, I. L. J; Thomson, M. I; Walker, J. M. Alternative Hydrogen Peroxide Sources for Peroxyoxalate “Glowstick” Chemiluminescence Demonstrations. J. Chem. Educ., 2017, 94, 112-114.
4. Mohan, A. G; Turro, N. J. A. Soluble, A Facile and Effective Chemiluminescence Demonstration Experiment. J. Chem. Educ. 1974, 51, 528-529.
5. Eghlimi, A.; Jubaer, H.; Surmiak, A.; Bach, U. Developing a Safe and Versatile Chemiluminescence Demonstration for Studying Reaction Kinetics. J. Chem. Educ. 2019, 96, 522-527.
6. Jilani, O.; Donahue, T. M; Mitchell, M. O. A Greener Chemiluminescence Demonstration. J. Chem. Educ. 2011, 88, 786-787.
7. Cambrea, L. R; Davis, M. C; Groshens, T. J.; Meylemans, H. A. A Soluble, Halogen-Free Oxalate from Methyl Salicylate for Chemiluminescence Demonstrations. J. Chem. Educ. 2013, 90, 1253-1254.
8. Roncaglia, F. Designing and Using a Safer, Greener Azole Oxamide for Chemiluminescence Demonstrations. J. Chem. Educ. 2017, 94, 1288-1290.
9. Use of oxalyl chloride in toluene has been reported for the synthesis of bis(2,4,6-trichlorophenyl) oxalate (TCPO), in this case a 2M solution was prepared and added to 3.5mmol of 2,4,6-trichlorophenol in the presence of triethylamine. See Pay, A. L.; Kovash, C.; Logue, B. A. General Chemistry Laboratory Experiment To Demonstrate Organic Synthesis, Fluorescence, and Chemiluminescence through Production of a Biphasic Glow Stick J. Chem. Educ. 2017, 94, 1580-1583.
10. We have found that 0.003-0.005M solutions of the oxalate diesters work best, this is in line with this study: Rauhut, M. M; Bollyky, L. J; Roberts, B. G; Loy, M; Whitman, R. H; Iannotta, A. V; Semsel, A. M; Clarke, R. A. Chemiluminescence from Reactions of Electronegatively Substituted Aryl Oxalates with Hydrogen Peroxide and Fluorescent Compounds. J. Am. Chem. Soc. 1967, 89, 6515-6522.
Acknowledgements: Many people from the University of St. Andrews have been made significant contributions to this work, they are as follows: All of the synthesis development work was conducted by Daniel Armstrong, Georgina Brown, Chloe Fletcher, Kirill Mamonov, Timothy McDonald, Elliot Stuart-Morrison, and Callum White as part of our CH3441 and CH5441 modules from April 2018 to April 2019. Iain Patterson has provided many helpful suggestions, assisted in testing, and provided invaluable technical help preparing this document. Finally, Dominic Stewart, Kevin Jones, and Adrian Allan (Dornoch Academy) are also sincerely thanked for their help in testing and for their helpful suggestions.
Supporting Information: 1H NMR spectra