DEMONSTRATION pubs.acs.org/jchemeduc
Demonstration of a Runaway Exothermic Reaction: Diels Alder Reaction of (2E,4E)-2,4-Hexadien-1-ol and Maleic Anhydride Brendon A. Parsons† and Veljko Dragojlovic* Wilkes Honors College, Florida Atlantic University, Jupiter, Florida 33458, United States
bS Supporting Information ABSTRACT: In a demonstration that involves a solvent-free Diels Alder reaction of (2E,4E)-2,4-hexadien-1-ol and maleic anhydride, one can use relatively small quantities of reactants to illustrate the process of scaling up a solvent-free reaction, including consideration of reactivity of the starting substances, scale of the reaction, and size and shape of the reaction vessel. Upon being mixed, the two solid compounds form a melt and react in the liquid phase to form a solid product. In a 50 mL beaker on a 5.00 mmol scale, the reaction was relatively uneventful. However, an increase to a 10.00 mmol scale in the same size beaker resulted in a vigorous exothermic reaction, which produced dark insoluble syrupy material. When water was added to the reaction mixture, the reaction was faster, with only a modest increase in the reaction temperature and 1,3,3a,4,5,7a-hexahydro-5-methyl3-oxo-4-isobenzofurancarboxylic acid was obtained as a pure white solid. The demonstration may help students understand the role of solvents in organic reactions, why most reactions are carried out in solvents, as well as potential problems that may be encountered when developing solvent-free reactions. KEYWORDS: First-Year Undergraduate/General, Second-Year Undergraduate, Demonstrations, Organic Chemistry, Physical Chemistry, Safety/Hazards, Addition Reactions, Green Chemistry, Heat Capacity, Phases/Phase Transitions/Diagrams FEATURE: Tested Demonstration
T
he Diels Alder reaction is a common industrial process as well as a frequent undergraduate organic chemistry laboratory exercise. Cyclopentadiene, one of the commonly used reactive dienes, is obtained by cracking dicyclopentadiene and has to be either used immediately or stored at a low temperature ( 20 °C). Under ordinary conditions, it undergoes a spontaneous and highly exothermic dimerization into dicyclopentadiene1 and has been implicated in a fatal accident.2 As an alternative to the use of cyclopentadiene in undergraduate organic chemistry laboratory, a Diels Alder reaction of (2E,4E)-2,4hexadien-1-ol1 and maleic anhydride (2) in toluene was described in this Journal.3 Paddon-Row, Sherburn, and co-workers established that the reaction proceeds by an initial endo-selective Diels Alder reaction followed by intramolecular esterification (Scheme 1).4 Recently, the same reaction has been reported as a solvent-free green chemistry laboratory exercise.5 7 Upon being mixed, (2E,4E)-2,4-hexadien-1-ol (1) (mp 28 33 or 30.5 31.5 °C8) and maleic anhydride (2) (mp 51 56 or 52.8 °C9) form a melt and react in the liquid phase to form a solid 1,3,3a,4,5,7a-hexahydro-5-methyl-3-oxo-4-isobenzofurancarboxylic acid (4) (mp 161 °C).10 Phase diagrams that illustrate the melting behavior of mixtures are available in physical chemistry textbooks.11 Detailed discussions of solid solid reactions have been published.12 14 Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc.
The experiment was introduced to the undergraduate organic chemistry students shortly after its initial report.6 The demonstration described herein was performed along with the laboratory exercise described in this Journal.5 Students encounter the Diels Alder reaction in the second half of the first-semester organic chemistry course and this demonstration is performed after the material has been covered in class. This demonstration is not only an alternative to common Diels Alder experiments, but is also a good case study of a possible runaway exothermic reaction.
’ JUSTIFICATION With increased emphasis on green chemistry and solvent-free reactions in undergraduate organic chemistry curricula, considerations of laboratory safety and design of safe laboratory procedures and industrial processes are gaining in importance. After a recent fatal accident in Florida caused by a runaway exothermic reaction,15 the Chemical Safety and Hazard Investigation Board recommended increased education of undergraduate chemical engineering students on reactive chemical hazards.16 Published: August 18, 2011 1553
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Journal of Chemical Education
DEMONSTRATION
This demonstration was originally developed as a laboratory exercise to be performed in 10 mL beakers and involved the mixing of equimolar amounts of the reagents on a 0.45 mmol scale.a When the experiment was carried out as described,5 7 it was reproducible and safe. In fact, if carried out in a 50 mL beaker, the reaction can be scaled up at least 10 times (up to a 5 mmol scale) and still be performed safely. However, when the reaction was carried out on a larger scale (∼10 mmol or larger) or in a vessel, such as a test tube, that did not allow efficient heat dissipation, a vigorous reaction accompanied by the evolution of noxious fumes ensued. Thus, the larger-scale, solvent-free reaction was performed as a demonstration rather than as a student experiment. A goal of this exercise was for students to observe a reaction under different conditions and to identify optimal reaction conditions.
’ EXPERIMENTAL DETAILS Experiments were carried out in 50 mL beakers. Reaction scale of 5.00 mmol refers to reaction of 5 mmol maleic anhydride with 5 mmol (2E,4E)-2,4-hexadien-1-ol and reaction scale of 10 mmol refers to a reaction of 10 mmol of each reagent. Maleic anhydride and either solid or liquidb (2E,4E)-2,4-hexadien-1-ol were mixed in a 50 mL beaker. Temperature measurements were taken by means of a Vernier LabPro data docking station equipped with a TI-83 Plus graphing calculator and a temperature probe. Detailed procedure is provided in the Supporting Information.
’ RESULTS AND DISCUSSION Reaction Scale and Phases (Solid versus Liquid) of the Reactants
When maleic anhydride and either solid or liquid (2E,4E)-2,4hexadien-1-ol were mixed in a 50 mL beaker on a 5.00 mmol scale, the reaction was relatively uneventful. After approximately 3 min, a melt formed (endothermically), which slowly solidified into a new compound (exothermically). The reaction was expected to be exothermic as a Diels Alder reaction involves conversion of two π bonds into two σ bonds. As the temperature change is not accompanied by any other visual change, except a slow formation of a solid, the students may miss it (Table 1, entries 1 and 2). An increase to a 10.00 mmol scale resulted in a vigorous exothermic reaction accompanied by a color change, bubbling, and fuming (Table 1, entries 3 and 4). Because a bottle of (2E,4E)-2,4-hexadien-1-ol usually contains a mixture of a solid and a liquid, one may be tempted to take out the required amount of liquid rather than deal with the solid. However, in reactions on a 10 mmol scale, the two phases show remarkably different reactivity. Reaction of solid (2E,4E)-2,4-hexadien-1-ol proceeded to first form a melt, which crystallized into a white solid. On the other hand, after an induction time of about 2 min, the mixture of liquid (2E,4E)-2,4-hexadien-1-ol and solid maleic anhydride suddenly became dark. The color change was followed by a violent reaction. The resulting product was a dark brown viscous liquid, which did not crystallize upon standing.c Temperature graphs are shown in Figure 1.
’ HAZARDS Maleic anhydride is corrosive, is a skin irritant, and is irritating to the mucous membranes. Toxicological properties of (2E,4E)2,4-hexadien-1-ol have not been fully investigated. It may cause irritation of skin, eyes, and respiratory tract. One should wear eye protection and gloves. Scheme 1. A Diels Alder Reaction of (2E,4E)-2,4-Hexadien-1-ol (1) and Maleic Anhydride (2) To Produce 1,3,3a,4,5,7a-Hexahydro-5-methyl-3-oxo-4-isobenzofurancarboxylic Acid (4)
Figure 1. Temperature curves for reactions of solid (s) and liquid (l) (2E,4E)-2,4-hexadien-1-ol with solid maleic anhydride on 5 and 10 mmol scales.
Table 1. Temperature Change in the Course of Reaction of (2E,4E)-2,4-Hexadien-1-ol with Maleic Anhydride Ti/°C
Tminc/°C
Tmax/°C
ΔTd/°C
-
24.0
23.9
37.1
13.2
-
24.1 25.7
23.4 23.8
35.7 89.4
12.3 65.6
solid
-
24.7
23.9
77.4
53.5
liquid
-
24.7
24.7
152.5
127.8
10
liquid
0.70
23.0
21.8
54.1
32.3
10
solid
0.70
23.5
20.8
55.2
34.4
Entrya
Reaction Scaleb/mmol
Phase of (2E,4E)-2,4-hexadien-1-ol
1
5
liquid
2 3
5 10
solid liquid
4
10
5e
10
6 7
Water/mL
a
Reactions were carried out in 50 mL beakers unless noted otherwise. b A 5 mmol reaction scale refers to a reaction of 5 mmol (2E,4E)-2,4-hexadien-1-ol with 5 mmol maleic anhydride and 10 mmol reaction scale refers to a reaction of 10 mmol (2E,4E)-2,4-hexadien-1-ol with 10 mmol maleic anhydride. c There was an initial endothermic formation of a melt. d ΔT = Tmax Tmin. e Reaction in a test tube. 1554
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Journal of Chemical Education
DEMONSTRATION
Figure 3. Two layers formed in a reaction in a test tube. Figure 2. Temperature curve for a test tube reaction in which two layers did not form (solid line), starting with solid (2E,4E)-2,4-hexadien-1-ol, and for the reactions in which two liquid layers did form starting with liquid (2E,4E)-2,4-hexadien-1-ol (short dashed line) or starting with solid (2E,4E)-2,4-hexadien-1-ol (long dashed line).
An instructor can offer the following rationale to the students. Most reactions, including Diels Alder reactions, require a liquid (or a vapor) reaction medium for reactant molecules to collide with the correct orientation. In a reaction involving solid (2E,4E)-2,4-hexadien-1-ol, the two solids first form a liquid phase (a melt), after which the reactants undergo an intermolecular Diels Alder reaction followed by an intramolecular esterification.5 Both the Diels Alder reaction and the esterification are exothermic processes. Formation of the melt takes several minutes and, as the overall process is relatively slow, the heat released in the course of the reaction dissipates into the atmosphere, and the temperature increase is 53 57 °C. Furthermore, breaking of the crystal lattice (melting) of (2E,4E)-2,4hexadien-1-ol is an endothermic process and some of the heat is absorbed in that process. However, when liquid (2E,4E)-2,4hexadien-1-ol is mixed with maleic anhydride, the same quantity of heat is released over much shorter period of time; temperature increase is much higher (65 66 °C) due to the lack of endothermic melting process and because heat dissipation to the atmosphere is less efficient on such a short time scale. It is important to point out to the students that the rate of dissipation of heat by conduction increases linearly with temperature. However, reaction rate constants increase exponentially with temperature.d Thus, if the reaction temperature is not controlled, a runaway exothermic reaction may result. Shape and Size of the Reaction Vessel
In this demonstration, only reactions on a 10 mmol scale were performed. The efficiency of heat dissipation depends in part on the surface area of the reaction mixture other things being equal, which in turn depends on the shape and size of the reaction vessel. In a reaction vessel of a smaller diameter, the surface area of the reaction mixture in contact with either the vessel walls or the air is smaller and the heat dissipation is less efficient. Thus, use of a vial,e which has only a slightly smaller diameter (27 mm) than a 50 mL beaker (40 mm), resulted in a considerably more vigorous reaction. Use of a test tube (10 130 mm) was particularly hazardous as the result was an extremely vigorous reaction (Figure 2 and Table 1 entry 5), which was sometimes accompanied by formation of two liquid layers (Figure 3). This experiment could be particularly dangerous if performed by students as they may not notice formation of the two layers.
Figure 4. Comparison of temperature change when starting with either solid (s) or liquid (l) (2E,4E)-2,4-hexadien-1-ol in dry or wet beakers on a 10 mmol scale.
GC MS analyses have shown that the top layer contained a considerable amount of unreacted (2E,4E)-2,4-hexadien-1-ol (1) along with several byproducts and that the bottom layer was a mixture of unreacted maleic anhydride (2) and the reaction product 4. Handling of the test tube containing these two partially reacted layers may result in the mixing of the two, now warm, liquids causing a very vigorous reaction with temperatures reaching ∼150 °C. Addition of Water to the Reaction
There was an interesting effect of moisture on the reaction rate.17 f The possibility that wet glassware may be used is always present in a teaching laboratory. When a wet 50 mL beaker (0.70 mL, 39 mmol, of water for a 10 mmol scale reaction) was used, the solid solid reaction was considerably faster (elapsed time to Tmax of 250 vs 350 s), but ΔT was actually lower (34.4 vs 53.5 °C, Figure 4 and Table 1, entries 4 and 7). The reaction on liquid (2E,4E)-2,4-hexadien-1-ol in the absence of water gave a brown syrupy product, which was not able to be dissolved and analyzed.g The reaction in the presence of a small amount of water produced a pure product (Table 1 entry 7), according to GC MS analysis, 1H NMR (Supporting Information), and melting point (163 165 °C). Even though the reaction was carried out in the presence of water, no hydrolysis of the initially formed anhydride was observed. As a general rule, an intramolecular reaction (in this case formation of a lactone) is considerably faster compared to an intermolecular one (in this case hydrolysis of the anhydride). Experiments combining maleic anhydride with three different diene substrates in the presence of 1555
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Journal of Chemical Education Scheme 2. Diels Alder Reactions Involving Maleic Anhydride in the Presence of Water
DEMONSTRATION
solvent-free reaction, released heat is transferred mainly to the other reactant and product molecules and, if there are no efficient ways to dissipate the energy, the result may be a runaway reaction. Thus, in low-boiling solvents such as toluene or benzene, this Diels Alder reaction was carried out under reflux.3,4 On a smaller scale (up to ∼5 mmol), the reaction could be performed solvent-free either under microwave irradiation or at room temperature,5 but on a larger (gram) scale, water had to be used as a heat sink. Moreover, as conduction of heat is dependent on the surface area of the reaction mixture, small differences in shape and size of the reaction vessels resulted in relatively large differences in the efficiency of heat dissipation and played a crucial role in the outcome of reactions on a borderline scale. Such problems are avoided when a reaction is carried out in a dilute solution.
’ ASSOCIATED CONTENT
bS water showed little or no hydrolysis of the resulting anhydride under identical experimental conditions (Scheme 2).17 Even though the difference between the experiments with and without water was obvious, most students mistook the fast reaction rate in a wet beaker for a reaction running out of control. However, one student correctly speculated that the large heat capacity of water was responsible for the moderate temperature increase and another student suggested that in an industrial-scale reaction, a water mist sprayer should be used. If students have difficulty understanding this concept, or are not able to come up with an adequate observation, the instructor can ask them: “What would happen if instead of water one used the same amount of acetone?” An instructor can also carry out this demonstration for the students (caution: reaction is highly exothermic and acetone will boil). Additional details of our study of Diels Alder reactions in the presence of a small volumeh of water are provided in a previous publication.17 Interestingly, while the reaction worked quite well with wet reactants,17 “on water” reaction18 21 failed. Apparently the use of a larger volume of water separated the reactants, which are poorly soluble in water, and even vigorous stirring yielded no discernible reaction. A rate acceleration of a Diels Alder reaction by the presence of water is generally explained by the “hydrophobic effect”,22 26 in which nonpolar solutes become concentrated within water cavities. However, in this case, the presence of water increased the rate of solid solid reaction, but it did not increase the rate of liquid solid reaction (Figure 4). The hydrophobic effect would lead to the opposite prediction; hence, hydrophobicity may not be the correct explanation for the effect. Instead, the polar functional groups on both the alcohol and anhydride reactants may allow them to hydrogen bond to water. Thus, brought together, the two organic reactants may then form a melt faster, this yielding the observed increase in the reaction rate. Role of a Solvent in a Chemical Reaction
One can use this opportunity to explain the role of solvent as a heat sink in conventional reactions. The solvent not only provides a reaction medium, but also allows for an efficient dissipation of heat. Any heat released in the course of the reaction is easily transferred, first to the solvation shell of the product molecules, and then into the bulk solvent. On the other hand, in a
Supporting Information Detailed procedure; list of chemicals and equipment; additional temperature graphs; 1H NMR spectrum of the reaction product; student handout; answers to the student handout; and MPEG movies of the demonstrations. This material is available via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. Present Addresses †
Department of Chemistry, University of Washington, Seattle, Washington 98195-1700, United States.
Notes
Eugene Losey (Department of Chemistry, Elmhurst College, Elmhurst, Illinios) and John Olson (Department of Chemistry, University of Alberta, Augustana Campus, Camrose, Alberta, Canada) tested this demonstration.
’ ACKNOWLEDGMENT We thank Thomas Goodwin from Hendrix College for providing additional information about the laboratory experiment he developed, Marc Hill from the Wilkes Honors College for help in acquiring the temperature data and CHM 2204 L students for testing this exercise. ’ ADDITIONAL NOTE a This demonstration was originally developed as a laboratory exercise by Thomas Goodwin at Hendrix College. b
2,4-Hexadien-1-ol has a low melting point,8 and at a room temperature, a stock bottle usually contains a soft solid accompanied by some liquid (a photograph is provided in Supporting Information).
c
Some crystallization was observed after 24 h.
d
According to the Arrhenius equation, the rate constant varies with exp( Ea/RT). However, for Ea values greater than 15 kJ/ mol and temperatures below 400 K, the increase in rate constant
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Journal of Chemical Education with temperature is approximately exponential. We thank anonymous reviewer who suggested adding this note. e
Disposable scintillation 20 mL vials (#FS 74515-20, Kimble Glass, Inc., Vineland, NJ 08360) were used.
DEMONSTRATION
ACS Symposium Series 721, American Chemical Society: Washington, DC, 1999; pp 79 80. (25) Tiwari, S.; Kumar, A. Angew. Chem., Int. Ed. 2006, 45, 4824– 4825. (26) Jung, Y.; Marcus, R. A. J. Am. Chem. Soc. 2007, 129, 5492–5502.
f
We would like to thank Salvatore Lepore from the Department of Chemistry, Florida Atlantic University for suggesting this demonstration.
g
One of the reviewers was able to obtain a sample for GC MS analysis by swirling the solid residue with dichloromethane and filtering the resulting suspension through cotton.
“Small volume” is a relative term. In this case, it indicates that, compared to traditional “on water” reactions, which are carried out in ∼3 5 M suspensions,18 the reactions here were carried out in a comparatively small volume of water. h
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