demonstration of a runaway exothermic reaction: diels–alder reaction of (2 e ,4 e...

Published: August 18, 2011

Copyright r 2011 American Chemical Society andDivision of Chemical Education, Inc. 1553 dx.doi.org/10.1021/ed100129z | J. Chem. Educ. 2011, 88, 1553–1557

DEMONSTRATION

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Demonstration of a Runaway Exothermic Reaction: Diels�AlderReaction of (2E,4E)-2,4-Hexadien-1-ol and Maleic AnhydrideBrendon A. Parsons† and Veljko Dragojlovic*

Wilkes Honors College, Florida Atlantic University, Jupiter, Florida 33458, United States

bS Supporting Information

The Diels�Alder reaction is a common industrial process aswell as a frequent undergraduate organic chemistry labora-

tory exercise. Cyclopentadiene, one of the commonly usedreactive dienes, is obtained by cracking dicyclopentadiene andhas to be either used immediately or stored at a low temperature(�20 �C). Under ordinary conditions, it undergoes a sponta-neous and highly exothermic dimerization into dicyclopen-tadiene1 and has been implicated in a fatal accident.2 As analternative to the use of cyclopentadiene in undergraduate organicchemistry laboratory, a Diels�Alder reaction of (2E,4E)-2,4-hexadien-1-ol1 and maleic anhydride (2) in toluene was describedin this Journal.3 Paddon-Row, Sherburn, and co-workers estab-lished that the reaction proceeds by an initial endo-selectiveDiels�Alder reaction followed by intramolecular esterification(Scheme 1).4 Recently, the same reaction has been reported as asolvent-free green chemistry laboratory exercise.5�7 Upon beingmixed, (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 solid1,3,3a,4,5,7a-hexahydro-5-methyl-3-oxo-4-isobenzofurancar-boxylic acid (4) (mp 161 �C).10 Phase diagrams that illustratethe melting behavior of mixtures are available in physicalchemistry textbooks.11 Detailed discussions of solid�solid reac-tions have been published.12�14

The experiment was introduced to the undergraduate organicchemistry students shortly after its initial report.6 The demon-stration described herein was performed along with the labora-tory exercise described in this Journal.5 Students encounter theDiels�Alder reaction in the second half of the first-semesterorganic chemistry course and this demonstration is performedafter thematerial has been covered in class. This demonstration isnot only an alternative to commonDiels�Alder experiments, butis also a good case study of a possible runaway exothermicreaction.

’ JUSTIFICATION

With increased emphasis on green chemistry and solvent-freereactions in undergraduate organic chemistry curricula, consid-erations of laboratory safety and design of safe laboratoryprocedures and industrial processes are gaining in importance.After a recent fatal accident in Florida caused by a runawayexothermic reaction,15 the Chemical Safety and Hazard Investi-gation Board recommended increased education of undergrad-uate chemical engineering students on reactive chemicalhazards.16

ABSTRACT: In a demonstration that involves a solvent-free Diels�Alder reactionof (2E,4E)-2,4-hexadien-1-ol and maleic anhydride, one can use relatively smallquantities 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 solidcompounds form a melt and react in the liquid phase to form a solid product. In a50 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 avigorous exothermic reaction, which produced dark insoluble syrupy material.When water was added to the reaction mixture, the reaction was faster, with only amodest increase in the reaction temperature and 1,3,3a,4,5,7a-hexahydro-5-methyl-3-oxo-4-isobenzofurancarboxylic acid was obtained as a pure white solid. Thedemonstration may help students understand the role of solvents in organicreactions, why most reactions are carried out in solvents, as well as potential problems that may be encountered when developingsolvent-free reactions.

KEYWORDS: First-Year Undergraduate/General, Second-Year Undergraduate, Demonstrations, Organic Chemistry, PhysicalChemistry, Safety/Hazards, Addition Reactions, Green Chemistry, Heat Capacity, Phases/Phase Transitions/Diagrams

FEATURE: Tested Demonstration

1554 dx.doi.org/10.1021/ed100129z |J. Chem. Educ. 2011, 88, 1553–1557

Journal of Chemical Education DEMONSTRATION

This demonstration was originally developed as a laboratoryexercise to be performed in 10 mL beakers and involved themixing of equimolar amounts of the reagents on a 0.45 mmolscale.a When the experiment was carried out as described,5�7 itwas reproducible and safe. In fact, if carried out in a 50mL beaker,the reaction can be scaled up at least 10 times (up to a 5 mmolscale) and still be performed safely. However, when the reactionwas carried out on a larger scale (∼10 mmol or larger) or in avessel, such as a test tube, that did not allow efficient heatdissipation, a vigorous reaction accompanied by the evolution ofnoxious fumes ensued. Thus, the larger-scale, solvent-free reac-tion was performed as a demonstration rather than as a studentexperiment. A goal of this exercise was for students to observe areaction under different conditions and to identify optimalreaction conditions.

’EXPERIMENTAL DETAILS

Experiments were carried out in 50mL beakers. Reaction scaleof 5.00 mmol refers to reaction of 5 mmol maleic anhydride with5mmol (2E,4E)-2,4-hexadien-1-ol and reaction scale of 10mmolrefers to a reaction of 10 mmol of each reagent. Maleic anhydrideand either solid or liquidb (2E,4E)-2,4-hexadien-1-ol were mixedin a 50 mL beaker. Temperature measurements were taken bymeans of a Vernier LabPro data docking station equipped with aTI-83 Plus graphing calculator and a temperature probe. Detailedprocedure is provided in the Supporting Information.

’HAZARDS

Maleic anhydride is corrosive, is a skin irritant, and is irritatingto the mucous membranes. Toxicological properties of (2E,4E)-2,4-hexadien-1-ol have not been fully investigated. It may causeirritation of skin, eyes, and respiratory tract. One should wear eyeprotection and gloves.

’RESULTS AND DISCUSSION

Reaction Scale and Phases (Solid versus Liquid) of theReactants

Whenmaleic anhydride and either solid or liquid (2E,4E)-2,4-hexadien-1-ol were mixed in a 50 mL beaker on a 5.00 mmolscale, the reaction was relatively uneventful. After approximately3 min, a melt formed (endothermically), which slowly solidifiedinto a new compound (exothermically). The reaction wasexpected to be exothermic as a Diels�Alder reaction involvesconversion of two π bonds into two σ bonds. As the temperaturechange is not accompanied by any other visual change, except aslow 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 avigorous exothermic reaction accompanied by a color change,bubbling, and fuming (Table 1, entries 3 and 4). Because a bottleof (2E,4E)-2,4-hexadien-1-ol usually contains a mixture of a solidand a liquid, onemay be tempted to take out the required amountof liquid rather than deal with the solid. However, in reactions ona 10 mmol scale, the two phases show remarkably differentreactivity. Reaction of solid (2E,4E)-2,4-hexadien-1-ol pro-ceeded to first form a melt, which crystallized into a white solid.On the other hand, after an induction time of about 2 min, themixture of liquid (2E,4E)-2,4-hexadien-1-ol and solid maleicanhydride suddenly became dark. The color change was followedby a violent reaction. The resulting product was a dark brownviscous liquid, which did not crystallize upon standing.c Tem-perature graphs are shown in Figure 1.

Scheme 1. A Diels�Alder Reaction of (2E,4E)-2,4-Hexa-dien-1-ol (1) and Maleic Anhydride (2) To Produce1,3,3a,4,5,7a-Hexahydro-5-methyl-3-oxo-4-isobenzofuran-carboxylic Acid (4)

Table 1. Temperature Change in the Course of Reaction of (2E,4E)-2,4-Hexadien-1-ol with Maleic Anhydride

Entrya Reaction Scaleb/mmol Phase of (2E,4E)-2,4-hexadien-1-ol Water/mL Ti/�C Tminc/�C Tmax/�C ΔTd/�C

1 5 liquid - 24.0 23.9 37.1 13.2

2 5 solid - 24.1 23.4 35.7 12.3

3 10 liquid - 25.7 23.8 89.4 65.6

4 10 solid - 24.7 23.9 77.4 53.5

5e 10 liquid - 24.7 24.7 152.5 127.8

6 10 liquid 0.70 23.0 21.8 54.1 32.3

7 10 solid 0.70 23.5 20.8 55.2 34.4aReactions were carried out in 50mL beakers unless noted otherwise. bA 5mmol reaction scale refers to a reaction of 5 mmol (2E,4E)-2,4-hexadien-1-olwith 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.cThere was an initial endothermic formation of a melt. dΔT = Tmax � Tmin.

eReaction in a test tube.

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 10mmol scales.



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 collidewith the correct orientation. In a reaction involving solid(2E,4E)-2,4-hexadien-1-ol, the two solids first form a liquidphase (a melt), after which the reactants undergo an intermole-cular Diels�Alder reaction followed by an intramolecularesterification.5 Both the Diels�Alder reaction and the esterifica-tion are exothermic processes. Formation of the melt takesseveral minutes and, as the overall process is relatively slow,the heat released in the course of the reaction dissipates into theatmosphere, and the temperature increase is 53�57 �C. Further-more, breaking of the crystal lattice (melting) of (2E,4E)-2,4-hexadien-1-ol is an endothermic process and some of the heat isabsorbed in that process. However, when liquid (2E,4E)-2,4-hexadien-1-ol is mixed with maleic anhydride, the same quantityof heat is released over much shorter period of time; temperatureincrease is much higher (65�66 �C) due to the lack ofendothermic melting process and because heat dissipation tothe atmosphere is less efficient on such a short time scale. It isimportant to point out to the students that the rate of dissipationof heat by conduction increases linearly with temperature.However, reaction rate constants increase exponentially withtemperature.dThus, if the reaction temperature is not controlled,a runaway exothermic reaction may result.

Shape and Size of the Reaction VesselIn this demonstration, only reactions on a 10 mmol scale were

performed. The efficiency of heat dissipation depends in part onthe surface area of the reaction mixture other things being equal,which in turn depends on the shape and size of the reactionvessel. In a reaction vessel of a smaller diameter, the surface areaof the reaction mixture in contact with either the vessel walls orthe 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 morevigorous reaction. Use of a test tube (10 � 130 mm) wasparticularly hazardous as the result was an extremely vigorousreaction (Figure 2 and Table 1 entry 5), which was sometimesaccompanied by formation of two liquid layers (Figure 3). Thisexperiment could be particularly dangerous if performed bystudents as they may not notice formation of the two layers.

GC�MS analyses have shown that the top layer contained aconsiderable amount of unreacted (2E,4E)-2,4-hexadien-1-ol (1)along with several byproducts and that the bottom layer was amixture of unreacted maleic anhydride (2) and the reactionproduct 4. Handling of the test tube containing these twopartially reacted layers may result in the mixing of the two,now warm, liquids causing a very vigorous reaction with tem-peratures reaching ∼150 �C.

Addition of Water to the ReactionThere was an interesting effect of moisture on the reaction

rate.17 f The possibility that wet glassware may be used is alwayspresent in a teaching laboratory. When a wet 50 mL beaker(0.70 mL, 39 mmol, of water for a 10 mmol scale reaction) wasused, the solid�solid reaction was considerably faster (elapsedtime to Tmax of 250 vs 350 s), butΔT was actually lower (34.4 vs53.5 �C, Figure 4 and Table 1, entries 4 and 7). The reaction onliquid (2E,4E)-2,4-hexadien-1-ol in the absence of water gave abrown syrupy product, which was not able to be dissolved andanalyzed.g The reaction in the presence of a small amount ofwater produced a pure product (Table 1 entry 7), according toGC�MS analysis, 1H NMR (Supporting Information), andmelting point (163�165 �C). Even though the reaction wascarried out in the presence of water, no hydrolysis of the initiallyformed anhydride was observed. As a general rule, an intramo-lecular reaction (in this case formation of a lactone) is consider-ably faster compared to an intermolecular one (in this casehydrolysis of the anhydride). Experiments combining maleicanhydride with three different diene substrates in the presence of

Figure 2. Temperature curve for a test tube reaction in which two layersdid 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 withliquid (2E,4E)-2,4-hexadien-1-ol (short dashed line) or starting withsolid (2E,4E)-2,4-hexadien-1-ol (long dashed line).

Figure 4. Comparison of temperature change when starting with eithersolid (s) or liquid (l) (2E,4E)-2,4-hexadien-1-ol in dry or wet beakers ona 10 mmol scale.

Figure 3. Two layers formed in a reaction in a test tube.



water showed little or no hydrolysis of the resulting anhydrideunder identical experimental conditions (Scheme 2).17

Even though the difference between the experiments with andwithout water was obvious, most students mistook the fastreaction rate in a wet beaker for a reaction running out ofcontrol. However, one student correctly speculated that the largeheat capacity of water was responsible for the moderate tem-perature increase and another student suggested that in anindustrial-scale reaction, a water mist sprayer should be used. Ifstudents have difficulty understanding this concept, or are notable to come up with an adequate observation, the instructor canask them: “What would happen if instead of water one used thesame amount of acetone?” An instructor can also carry out thisdemonstration for the students (caution: reaction is highlyexothermic and acetone will boil). Additional details of our studyof Diels�Alder reactions in the presence of a small volumeh ofwater are provided in a previous publication.17 Interestingly,while the reaction worked quite well with wet reactants,17 “onwater” reaction18�21 failed. Apparently the use of a larger volumeof water separated the reactants, which are poorly soluble inwater, and even vigorous stirring yielded no discernible reaction.

A rate acceleration of a Diels�Alder reaction by the presenceof water is generally explained by the “hydrophobic effect”,22�26

in which nonpolar solutes become concentrated within watercavities. However, in this case, the presence of water increasedthe rate of solid�solid reaction, but it did not increase the rateof liquid�solid reaction (Figure 4). The hydrophobic effectwould lead to the opposite prediction; hence, hydrophobicitymay not be the correct explanation for the effect. Instead, thepolar functional groups on both the alcohol and anhydridereactants may allow them to hydrogen bond to water.Thus, brought together, the two organic reactants may thenform a melt faster, this yielding the observed increase in thereaction rate.

Role of a Solvent in a Chemical ReactionOne can use this opportunity to explain the role of solvent as a

heat sink in conventional reactions. The solvent not onlyprovides a reaction medium, but also allows for an efficientdissipation of heat. Any heat released in the course of the reactionis easily transferred, first to the solvation shell of the productmolecules, and then into the bulk solvent. On the other hand, in a

solvent-free reaction, released heat is transferred mainly to theother reactant and product molecules and, if there are noefficient ways to dissipate the energy, the result may be arunaway reaction. Thus, in low-boiling solvents such as tolueneor benzene, this Diels�Alder reaction was carried out underreflux.3,4 On a smaller scale (up to ∼5 mmol), the reactioncould be performed solvent-free either under microwave irra-diation or at room temperature,5 but on a larger (gram) scale,water had to be used as a heat sink. Moreover, as conduction ofheat is dependent on the surface area of the reaction mixture,small differences in shape and size of the reaction vesselsresulted in relatively large differences in the efficiency of heatdissipation and played a crucial role in the outcome of reactionson a borderline scale. Such problems are avoided when areaction is carried out in a dilute solution.

’ASSOCIATED CONTENT

bS Supporting InformationDetailed procedure; list of chemicals and equipment; addi-

tional temperature graphs; 1H NMR spectrum of the reactionproduct; student handout; answers to the student handout; andMPEG movies of the demonstrations. This material is availablevia 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.

NotesEugene 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 forproviding additional information about the laboratory experi-ment he developed, Marc Hill from the Wilkes Honors Collegefor help in acquiring the temperature data and CHM 2204 Lstudents for testing this exercise.

’ADDITIONAL NOTEaThis demonstration was originally developed as a laboratoryexercise by Thomas Goodwin at Hendrix College.

b 2,4-Hexadien-1-ol has a low melting point,8 and at a roomtemperature, a stock bottle usually contains a soft solid accom-panied by some liquid (a photograph is provided in SupportingInformation).

c Some crystallization was observed after 24 h.

dAccording to the Arrhenius equation, the rate constant varieswith exp(�Ea/RT). However, for Ea values greater than 15 kJ/mol and temperatures below 400 K, the increase in rate constant

Scheme 2. Diels�Alder Reactions Involving MaleicAnhydride in the Presence of Water



with temperature is approximately exponential. We thank anon-ymous reviewer who suggested adding this note.

eDisposable scintillation 20 mL vials (#FS 74515-20, KimbleGlass, Inc., Vineland, NJ 08360) were used.

fWe would like to thank Salvatore Lepore from the Departmentof Chemistry, Florida Atlantic University for suggesting thisdemonstration.

gOne of the reviewers was able to obtain a sample for GC�MSanalysis by swirling the solid residue with dichloromethane andfiltering the resulting suspension through cotton.

h “Small volume” is a relative term. In this case, it indicates that,compared to traditional “on water” reactions, which are carriedout in ∼3�5 M suspensions,18 the reactions here were carriedout in a comparatively small volume of water.

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demonstration of a runaway exothermic reaction: diels–alder reaction of (2 e ,4 e...

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