A New Approach To Teaching Organic Chemical Mechanisms Stephen H. Wentland Houston Baptist University, Houston, TX 77074
The difficulty that many students experience with organic chemistry is well-known. There is much to learn: many reactions concerning several functional groups, and many concepts t h a t students cannot readily visualize. Learning the vast number of reactions could be facilitated if there was some simple way of integrating the material. I have developed such a way based on electron flow. The electron flow converting reactants to products, that is, the mechanism of the reaction, can be described using five simple steps or operations. Then, just a s amino acids are sequenced to form proteins, the five operations can be sequenced to describe most of the heterolytic mechanisms encountered in the first year of organic chemistry. The continual repetition of these five operations provides a continuity undergirding the study of organic reactions, enabling students to perceive similarities and differences among them. Basing this study upon the five operations, we make the fundamental character of each reaction more apparent, thus helping students to understand its driving force. Furthermore, this approach has been adapted to a n interactive computer format (described below) that helps students master the fundamentals of this approach. The Five Operations-General
Considerations
The five operations are defined in terms of the electronic configuration of the involved atoms. The terms used are
'nbepnonbonding electron pair 'sep--shared electron pair, a covalent bond va-vacant atomic orbital, a two-electron vacancy in the valence level These terms link structure and mechanism. Once students learn to see the structure of the reactants in these terms, they can choose the appropriate operations, then sequence the operations to describe the mechanism. Thus, they determine the outcome of the reaction.
Ionization and Neutralization The first two operations, ionization and neutralization, describe electron flow over two atoms and are shown in Figure 1. Ionization
A-CB sep
I
A.
vao
+ :B~
nbep
2 atoms, 1 electron pair involved arrow: from between A and B to on B 1 bond is broken. F rsl atom becomes 1 Ln t more posmve (sep
-
vao) Second alom oecomes 1 Jnll more negalwe (sep- noep,.
I
Neutralization
A. T : B
-
AB nbep sep 2 atoms, 1 electron pair involved arrow: from on B to between A and B 1 bond is formed. First atom becomes 1 unit less positive (vao + sep). Second atom becomes 1 unit less negative (nbep -sep).
vao
Figure 1. The ionization and neutralization operations. The neutralization operation describes bond formation (heavy line) according to the Lewis theory of acids and bases, whereas the ionization operation describes the opposite process: bond breaking (broken line). Representative examples of these operations are shown in eqs 1 3 .
reactant structure + operation + product sequence Correct use of this is facilitated by previous knowledge of the functional groups involved in the reaction. Thus, each operation is introduced into the course when these key functional groups are studied. How this may be done is described in "Integration with Functional Group Approach" below. Each operation precisely depicts the bonds broken and farmed the locations of the arrows representing the electron flow the resulting charge alterations Each operation shows the charge on the initial and terminal atoms changing by one unit. Defining charge alterations a s a +1 change greatly expands the scope of the operations. As shown below, atoms bearing charge (either + or -) a t the start of the electron flow are treated just as easily as neutral atoms.
Use of the ionization and neutralization operations are indicated by I and N over the reaction arrow, and the atoms in the electron flow by the letters a and b. I n this way, students more readily correlate the atoms in the operations with the corresponding atoms in the reactions. This practice will be extended,to all the remaining operaVolume 71
Number 1 January 1994
3
tions. Note that the charge on each atom in the electron flow changes by +lunit. Discussion of acidity, basicity, and conjugate acids and bases follows easily from this treatment. S Ndisplacements ~ are easily described using the ionization and neutralization operations (eq 4). SNI Displacements
1,3-Electron Pair Displacement A:?
8
.Tc
-
A-8
+ :C-
nbep sep sep 3 atoms, 2 electron pairs involved firstarrow: from on A to between A and B second arrow: from between 8 and C to on C 1 bond is formed, 1 bond broken.
nbep
-
First atom becomes 1 unit less ne ative (nbep sep) Central atom undergoes no charge Jteration (sep -sep Third atom becomes 1 unit more negative (sep -nbep). Stereochemical features, such as the sp2hybridization of the inkrmed~atecarbwation and the ensuing formation of a raccmic mixturc, are casily incorporated into this trcatment. The 1,3-Electron Pair Displacement
The third operation, the 1.3-electnm pair displacement, is shown in Figure 2. This operation descrihes electron flow encompassing three atoms, the initiating atom (A), central atom (Bj, and eledron-accepting atom (0.The initiating atom has a nbep, and thus is electron-rich (a base or a nucleophile). The electron-accepting atom has the tendency to accept a nbep. In this operation the electron richness is "pushed" (or displaced) from the first to the third atom. As result, one bond is formed (heavy line) while another is broken (broken line). The initiating atom bemmes less negative while the electron-accepting atom becomes more negative. There is no charge alteration on the central atom because S N Displacements ~
a
Addition-Elimination to Carbonyl Groups
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Journal of Chemical Education
Figure 2. The 1,8electronpair displacement operation electrons are entering and leaving this atom simultaneously The 1.3-electron pair displacement operation (1.3-e~d) . . readily descnbcs s~:! nucleobhilic displacements (eqs 5-7,. In all these rrdctions the initiatina atom is a nucleophile that becomes less negative, and the electron-accepting atom is a leaving group that becomes more negative. In eq 5, the iodide anion, a potential nucleophile, does not redisplace the isopropoxide anion because isopropoxide is a much poorer leaving group under the reaction conditions. Similar considerations hold true in eq 6. In eq 7 an acid-catalyzed S Ndisplacement, ~ the neutralization operation, shows how the acidic medium makes the electronaccepting atom electron-deficient, and thus also makes the leaving group more effective. For the sake of simplification, protonations and deprotonations are shown without the involvement of solvent throughout this paper. The 1,3-electron pair displacement can be used to describe additions and eliminations to carbonyl groups (eqs 8-9). Both examples describe displacement a t acyl carbons; eq 8 occurs under basic conditions, and eq 9 under acid conditions. In each example, the first displacement is a n addition (pi bond broken) initiated by a nucleophile, and the second displacement is a n elimination (pi bond formed) initiated by an electron-rich oxygen atom. In eq 9 the neutralization operation again shows how the acid medium increases t h e effectiveness of the leaving group. The addition and elimination reactions follow the same format a s the Sp42 substitutions described previously, all being examples of the 1,3-electron pair displacement. Thus, learning the simpler substitution aids in the learning of the more complex additions and eliminations. The l,3-electron pair displacement can be used to describe the hybrid structures in electron-rich resonance systems, such as the carboxylate and phenoxide anions (eqs 10 and 11). Here the 1,3-electron pair displacement does not describe the conversion of reactant to product; rather, it shows the relationship between resonance contributors. (The double-headed arrow between contributors makes this important distinction.) The contributors differ in the location of a nbep and pi bond, and this relationship is shown by the electron flow in the 1,3-electron pair dis-
H-OEt
Highly
ResonanceStabilized Carbanion
Figure 3. The Ciaisen Condensation.
be done analogously. All the elaborations of the l,3-electron pair displacement shown above can be brought together to describe complex reactions such as the Claisen Condensation, as shown in Figure 3. The electron flow in the formation of the two carbanions is identical to that in an S N ~ displacement, and the electron flow in the addition and elimination steps forming the Pketoester is identical to the addition and elimination reactions described earlier. Finally, the resonance stabilization in the two carbanions is treated as previously described for electron-rich hybrid structures. This scheme again illustrates how complex systems can be learned as elaborations of simple systems using the 1,3-electron pair displacement operation. Related topics easily follow from this treatment, for example, the equilibrium between reactants and products and the driving of the reaction to completion by the formation of a highly stabilized carbanion. Similar reactions, can be also described similarly, for example, the aldol and Knoevenagel condensations, malonic and acetoacetic ester syntheses, and the Michael and Wittig reactions.
Resonance: Electron-Rich Systems Caitoxylate anion:
1,3-ElectronPair Abstraction
Hybrid Phenoxide anion:
While the 1,3-electron pair displacement describes electron-rich systems, the fourth operation, the l,3-electron pair abstraction, describes electron flow in electron-deficient systems. The 1,s-electron pair abstraction (Fig. 4) also encompasses three atoms. These are the initiating atom (A), central atom (B), and electron-donating atom (C).The initiating atom has a vao (and is thus an electrophile), wheras the electron-donating atom can accommodate a vao. In this operation, the electron deficiency "pulls" (or abstracts) electrons from the third to the first atom. As this occurs. one bond breaks while another forms, and the initiating atom becomes less ~ositivewhile the electron-donatine atom becomes more positive. Again there is no charge alteration on the central atom because electrons enter and leave this atom simultaneously While the initiating atom must have a vao, it need not have a positive charge.
4 \. 0
s-
-
Contributors
1$-Electron Pair Abstraction
Hybrid +A
0 C
+
A-B
vao sep sep 3 atoms, 1 electron pair involved arrow: from between B and C to between A and B 1 bond is formed, 1 bond broken.
placement. Thus, from the structure of one contributor, the structures of the other contributors can be readilv determined. These contributors are then mentally "averaged" to form the hyhrid structure. Description of the amide bond
+ C' vao
--
First atom becomes 1 unit less positive jvao sep). Central atom undergoes no charge alterallon (sep sep) Third atom becomes 1 unit more positive (sep -vao).
Figure 4. The 1,3-electronpair abstraction operation Volume 71 Number 1 January 1994
5
Electrophilic Additions
(13)
The 1,3-electron pair abstraction (1,3-epa) can be used to describe the 1,2-shifts that occur in electmphilic systems (eq 12). The initiating atom is a carbocation, and a new, more-stable (i.e., more-substituted) carbocation is formed on the electron-donating atom. The central atom is the shifting (or migrating) hydride atom, and the driving force for these reactions is the formation of a more stable carbocation. Shiftsin which the mieratine atom is carbon are described analogously. Electro~hilicaddition to alkenes can be readilv described G t h the 1,3-electron pair abstraction operation (eqs 13-14). Equation 13 is a hydration, eq 14, an oxymercuration. In both, the initiating atom is a cation, while the central and the electron-donating atoms are the less substituted and more substituted alkene carbons. Neutralization of the intermediate carbocations by water, followed by the loss of a proton, complete these reactions. Discussion of Markovnikov's Rule and, in the case of the second reaction, the hybrid intermediate and anti-addition, follows easily from this treatment. This operation is also useful in describing E l eliminations (eq 15). The initiating atom is a carbocation formed by the ionization of a carbon-bromine bond. The central atom is an adjacent carbon, and the electron-donating atom is a hydrogen that is bonded to the central atom. In this case there are two different central atoms, leading to the formation of two alkenes as explained by Saytzeff's Rule.
-
(14)
L
anti
pradud
hwd
addition E l Elimination E l Elimination
J
-
Resonance: Electron-Deficient System C~
Resonance: Electron-Deficient Systems
The 1,3-electronpair abstraction can be used to describe hybrid structures in electron-deficient systems (eqs 16-17). In eq 16 two contributors "average" to form the hybrid structure of an allylic cation. In eq 17 four contributors "average" to form the hybrid structure of a benzyl cation. In each case, the contributors differ in the location of a pi bond and a vao. Thus, their structural relationship is aptly described by the electron flow of the 1,3-electmn pair abstraction. Thus, given one contributor, all the others may be easily determined using this operation. Again, the double-headed arrow indicates that the structures are contributors to a hybrid rather than participants in a reaction. AU the above elaborations of the l,3-electron pair abstraction can be combined to describe electrophilic aromatic substitution reactions such as the FriedelCratts alkylation (Fig. 5). Formation of the carbocation is shown using the neutralization and ionization o~erations. The electron flows in the addition of the electrophile to the benzene rinr! and in the elimination of a omton from the ring are iientical to those in the electrkphilic additions and E l elimination described earlier. The description of the hybrid intermediate is analogous to that of the benzyl carbocation also described previously. Again, seeing the 1,3-electron pair abstraction operation pervade the entire scheme assists students in learning the individual steps. This treatment is easily elaborated to include 1,2-shifts in the initially formed carbocation, in ortho, meta, and para orientation effects, and in other electrophilic aromatic substitution reactions. 1.5-Electron Pair Displacement
The fifth (and last) operation, the l,5-electron pair displacement (Fig. 6 ) encompasses five atoms. These 6
Journal of Chemical Education
cific aspects upin khich studeits need to improve. Electron Flow Elaborated
Figure 5. The FriedeCCrafts alkylation. are the initiating atom (A), three interior atoms (B-Dl, and finally an electron-accepting atom (El. The initiating atom has a nbep (is typically a base), whereas the electron-accepting atom has the tendency to accept a nbep. In this operation, the electron richness is "pushed" (or displaced) from the first to the fifth atom. This results in a regular alternation between bond forming and breaking such that two bonds are formed while two are broken. The initiating atom becomes less negative while the electron-accepting atom becomes more negative. The electronic configuration on each of the interior atoms remains constant, so these atoms undergo no charge alteration. Equations 18-20 show reactions readily described by the 1,5-electron pair displacement (1,5-epdj. Equations 18 and 19 describe E2 eliminations, in which the initiating atom is an ethoxide oxygen, and the electron-accepting atom is bromine. The interior atoms form a hydrogen-earbon-carbon chain to the bromine leaving group. Two such chains are possible, so two alkenes are formed, with the major isomer predicted hv Savtzeff's Rule. Eouation 20 describes the acidycataiyzed brominatibn of the enol form of a ketone.
Mechanisms more complex than those discussed above may be approached using the five operations. Two examples follow in which the nucleophile or electrophile is characterized by a polarized sep instead of a nbep or vao. These reactions take place by a concerted mechanism in which the polarized sep breaks while the nucleophilic or electrophilic atom adds to a pi bond. The nature of these reactions may be made more vivid by describing them as occurring sequentially instead of concertedly, with the first step being the (hypothetical) separation of the polarized sep into a vao and n b e ~The . reaction of a Grignard reage& with a carbonyl compound is shown nsine both the concerted mechanism (eq 21) and sequential (eq22) approach. In the sequential approach the "ionization" vividly reveals the nucleo~hiliccharacter of the Grimard reaeent. and the followiAg addition shows the siiilarity or the Grirmard reaction to other nucleo~hilicadditions. (The "I" over the first reaction arrow iniicates the exaggerated character of the "ionization", and signals that this step is simply a way of viewing the Grignard reagent.) Metal hydride additions mav be treated similarlv. The addition ofbromine to an alkene (eqs 23-24) is treated analoeouslv. - . The intermediate is thoueht - to be the bromonium ion. The sequential approach clearly shows why the bromine atom in this intermediate becomes electron-deficient and why nucleophilic attack on this intermediate takes place on the more substituted carbon. The final step can also be shown as the reaction of the open contributor with the bromide anion using the neutralization operation. 1,5-Electronpair Displacement: Applications
Interactive Computerized Instruction For any teaching approach to he effective, students must develop a working command of the basics, so I have adapted this approach to a computerized format. For each step in the reaction mechanism the computer presents the structure of the reactants and prompts the user to successively choose 'the appropriate operation the particular atoms involved in the electron flow the startinn and end~aintsof the arrows the resulting charge 'alterations When all the correct responses have been entered, the structure of the ~ r o d u c tis eiven. and the reactants fur the next step arc prcsentcd Ths sequence I S r ~ ~ e a t eu n d t ~ thc l end of the rcnctlon IS reached. The coktinual repetition of these four choices helps students develop a a e a t e r command of the five operations until they can use them almost automati'cally. Furthermore, the instant feedback provided for each
-
Volume 71 Number 1 January 1994
7
Grignard Reaction
Through this treatment students become more aware of the electrophilic nature of the bromine atom and of the similarity of this reaction to the electrophilic additions thev have previouslv studied. he concerted mechaniim wodd then bidescribed and related to the sequential approach.
Concerted Mechansim
Integration with Functional Group Approach
Sequential broach
Most organic texts (and courses) are organized around the functional moup: Each chapter presents predominantly the properties, principies, &d reactions of one kind of compound. The approach presented in this paper ran be easily incoiporated into tlus organization. Onc such way of domg so follows. (1) During the presentation of structure and bonding, the ionization and neutralization operations are introduced to provide the foundation for the later operations. (2) During the presentation of alkyl halides, the 1,3electron pair displacement is intmdueed. This permits discussion of Snl and Sn2 substitution and the interconversion of alkyl halides, alcohols, and related compounds. (3) During the presentation of alkenes, the 1,3-el-tran oair abstraction is introduced. This allows dlrcus.iran of electrophrlrc addnon, E l elimmatwn, and 1.2-shins. The prcscnlnrion of nlkyl hnhdrs and alkenes, alung with their corresponding mechanistic operations, may be inverted if desired. (4) The 1.5-electron pair displacement is also introduced during the presentation of alkenes. Although desirable, it is not essential that this oneratian be introduced before the 1.3-electron par dwplawment. When all operatiuns haw been introduecd, drsmiptmn of all the remainma functional groups can be done in any order desired.
Alkene Bromination Concerted Mechanism
Sequential Approach
Summary Using the five mechanistic operations to describe mechanisms provides a common element woven throughout the reactions of organic chemistry. From this perspective students see complex mechanisms a s straightforward elaborations of more simple ones. Thus, they learn to see similarities among the various reactions and to appreciate differences a s well. Because the mechanistic operations are defined in terms of structure. students learn to link reactants with appropriate operations and mechanisms. From mechanisms thev can predict the outcome of reactions. Furthermore. these simple ~ d i e dhere to . operations. . . a .. relatively simple mechanisms, can serve a s a "bridge" to the studv of more com~lexones. Finallv. this approach has been adapted to a computerized form& to as& students in obtaining a working knowledge of the fundamentals. This approach leads to a greater understanding and appreciation of organic chemistry a s attested by the many stud e n t s from several universities who have t a k e n my courses. Acknowledgments I wish to thank Houston Baptist University for a sabbatical during which this approach was developed.
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Journal of Chemical Education
s+ B
cydic mntributor
-
A: + nbep
II
1,bElectron Pair Displacement n r B-C-D'.E-A-B + C=D sep sep sep sep
+
-:E nbep
5 atoms, 3 electron pairs involved First arrow: from on A to between A and B Second arrow: from between Band C to between C and D Third arrow: from between D and E to on E
I
2 bonds formed, 2 bonds broken.
--
First atom becomes 1 unit less negative (nbep sep). Second atom undergoes no charge alteration (sep sep). Third atom undergoes no charge alteration (sep -+ sep). Fourth atom undergoes no charge alteration (sep sep). nbep). Fifth atom becomes 1 unit more negative (sep
Figure 6. The 1.5-electron pair displacement operation.
