Computational Chemistry in Organic Chemistry Lecture Using Webmo Brian J

Home , Conformational isomerism

Computational Chemistry in Organic Chemistry Lecture using WebMO Brian J. Esselman,* Aubrey J. Ellison,* and Jia Zhou

Department of Chemistry, 1101 University Avenue, Madison, WI 53706

5 ABSTRACT

Advances in computational software and hardware have allowed computational chemistry to

become a more integrated component of undergraduate organic chemistry curriculum. With a few

exceptions, most of this attention has been given to small lecture activities or individual laboratory

exercises. To allow students to fully utilize the insights of computational chemistry, it must become

10 fully integrated into all aspects of instruction. Here we present out on-going efforts in integrating

computational chemistry into the entire lecture curriculum via carefully chosen examples on lecture

slides, problem sets, and assessments. Rather than having students perform these calculations

themselves, as they do in our laboratory course, we have taken advantage of the HTML-export feature

of WebMO to provide students with direct links to computational data. As students work through our

15 curriculum, their learning is supported by the ability to view relevant molecular geometries, charge

distributions, orbitals, vibrational modes, etc. We are confident that use of these tools leads to better

learning outcomes.

INTRODUCTION

Coinciding with the availability of student-friendly software, computational chemistry has been

20 introduced in many graduate and undergraduate courses over the past few decades.1-7 Many excellent

examples of lecture and laboratory exercises have been presented in the literature across college-level

instruction. Given the obvious ability of computational chemistry to help students understand and

visualize the three-dimensional nature of molecules and highlight the connection between structure

and reactivity, it is unsurprising that instructors of general, organic, and inorganic chemistry have

25 seized upon this capability. Importantly, computational results can provide chemical insights to

students without the need to understand the details of how the calculations were performed. Hence,

many published exercises designed for early undergraduate chemistry students are able to avoid

delving deeply into the details of quantum mechanics and computational chemistry. This

demonstrates the ability of computational results to provide chemical insights to students without the

30 need to understand the details of how the results were obtained. While there is definitely substantial

value in a proper understanding of quantum mechanics, levels of theory, basis sets, optimization

routines, etc., these topics can be reserved for upper-level physical chemistry and computational

chemistry courses without sacrificing substantial student understanding of structure and bonding in

the introductory courses.

35 Stand-alone computational chemistry exercises have the inherent drawback of time, cognitive load,

and effort required to learn how to perform the calculations. This burden, in cases of infrequent

implementation, can easily overshadow the insights derived from the exercise that would be useful to

the early college student. A few university courses8-10 and department-wide chemistry programs11-13

have embedded computational chemistry throughout the curriculum. These implementations reduce

40 the cognitive load on students in any particular computational exercise as students become

increasingly familiar with the software due to repeated exposure. Additionally, students and

instructors inherently see the benefit of mastering the new software necessary to complete their

calculations, knowing that this skill will serve them well in their future coursework. Undoubtedly,

such repeated utilizations can provide a more meaningful and longer-lasting impact on students’

45 understanding of three-dimensional structures and chemical bonding.

In organic chemistry, there are two very natural avenues for computational chemistry to support

the curriculum: supporting analysis of experimental data and elucidating how the electronic or

molecular structure drives the chemical outcome. In the organic laboratory, many authors have

demonstrated that computational chemistry can help students assign IR or NMR spectra.4, 14-22 This

50 support can allow students to make assignments and perform analyses that may be beyond their

abilities without computational predictions. Further, a number of authors have demonstrated the

utility of calculations to help students predict or rationalize the outcome of an organic reaction in

lecture and laboratory settings,23-26 helping students obtain a deeper understanding of many

important concepts. Student exercises have been used to investigate conformational isomerism,9-10, 27-

55 31 structure and relative energy of reactive intermediates,19, 21, 25-26, 32-37 the selectivity of an organic

reaction,19, 25-26, 38-42 assessing relative acidity,43-44 evaluation of a reaction mechanism,45 etc. All of

these examples provide other educators a template for how they can enhance their curricula and lead

to better student learning.

We wish to take this process one step further and integrate computational outputs throughout the

60 entire organic lecture curriculum. Focusing on interpreting computational results will provide the

benefits of a deeper conversation about structure, bonding, and reactivity, without substantially

adding to the cognitive load and time necessary for students to perform the calculations. Based upon

previous work,30, 46-47 we have embedded WebMO7-HTML exports into our course materials: student

handouts, problem sets, lecture slides, discussion activities, and exams. In a manner similar to

65 Springer,46 we present computationally generated images of molecules alongside more common two-

dimensional images in lecture. We have extended this use of three-dimensional images from WebMO

to include all course content, allowing students to view structures and orbitals in a virtual model kit.

Alongside these computer-generated structures, we encourage students to use wedge-dash notation

for molecules drawn on paper and traditional model kits to help build their representational

70 translation. While we have just begun this modernization of our curricular materials, we intend to

make virtually all images of molecules presented in course content accessible via student engagement

with HTML links. Even during this early adaptation and implementation, we have observed several

important anecdotal outcomes. Our students seem to have a deeper grasp of three-dimensional

structures, an improved understanding of how atomic and molecular orbitals influence chemical

75 reactivity, and a greater mechanistic focus on why and how reactions occur. As an intended

consequence, students are able to move away from pattern recognition and memorization and toward

utilizing key concepts to rationalize reactivity. We have changed our own teaching frame of mind to be

more focused on how the molecular and electronic structure leads to the function of the molecule.

This article presents some of our initial work and reflections.

80 CURRICULAR IMPLEMENTATION

The representative examples shown here are from 1st and 2nd semester organic chemistry lectures

(CHEM 343 and CHEM 345) at the University of Wisconsin–Madison. This is the main sequence of

organic chemistry and has between 200 and 300 students per lecture in a wide range of majors.

Together, these courses cover the topics presented in the 6th edition of Organic Chemistry by Loudon

85 and Parise.48 The course does not have a laboratory component, and students may take the

laboratory course (CHEM 344) concurrently with or subsequent to CHEM 345. Students may have

some exposure to computational chemistry through use of computational outputs in general chemistry

or later in CHEM 344 where they run calculations to support their understanding of molecular

structure and properties.9-10 Regardless of their level of exposure to output files prior to CHEM 343,

90 virtually none of these students have used any computational chemistry software to perform

calculations themselves. These representative examples demonstrate the usage of WebMO-HTML

exports in lecture notes, problem sets, and on course assessments. Each figure, in the following

section, is an authentic image of computational results used in our courses and instruction to support

student learning. These figures include examples of geometry optimizations, vibrational frequencies,

95 NMR chemical shift predictions, and Natural Bond Orbital (NBO) calculations. The NBO calculation

generates and visualizes the molecular orbitals and natural bond orbitals; we use whichever is most

impactful for illustrating a concept to students. In general, MOs are useful for depicting conjugated

systems as MOs inherently show the delocalization of electrons throughout a molecule. NBOs are

useful for depicting lone pairs and bonds using the hybridizations and localized notions of bonding

100 common in organic and general chemistry.

1st semester examples

Starting with the very first lecture, students are introduced to computational depictions of

chemical structures. The early introduction is done in such a way that computational models are

intentionally presented in parallel with Lewis structure drawings. This pairing serves to build student

105 confidence and understanding in translating two-dimensional representations into accurate chemical

geometries, as well as to demonstrate the utility of computational models. Figure 1 shows the WebMO

output of methane embedded directly into the lecture slide. Incorporation of the live output allows its

manipulation by the instructor, demonstrating geometric shape at the same time as providing initial

familiarity with the WebMO interface. Adjacent to the active WebMO window are traditional,

110 instructor-drawn depictions of methane. The juxtaposition of the three-dimensional visualization and

two-dimensional drawing can then be used to demonstrate how wedge-dash notation better aligns with

geometric reality than a simple two-dimensional Lewis structure. As the semester progresses,

students will continue to have static images or live outputs of WebMO molecules presented in lecture

in conjunction with two-dimensional hand drawings.

115

Figure 1. The first usage of WebMO to support a review lecture on Lewis structures. The methane WebMO output is embedded directly

into the lecture slide to allow the instructor to manipulate the WebMO image live without the need to switch between applications. The slide

also contains a clickable link to the methane WebMO output for student use after lecture through the pdf export.

While model kits have been used for conveying three-dimensionality of molecular structures for

120 quite some time, computational molecular depictions add to the depth and breadth of topics that can

be presented by including optimized geometries, molecular orbitals, and more accurate charge

distributions. As an example, Figure 2 shows the reactive carbocation intermediate from HBr addition

to 1-methylcyclohexene. Use of WebMO images can quickly highlight the loss of a p bond and

subsequent change of the C-atom hybridizations throughout the reaction, supporting the electron-

125 pushing mechanism. In the first step, WebMO can be used to display the NBO-depiction of an empty

p orbital on the carbocation intermediate, focusing student attention on this (formally) empty orbital.

With the depiction of the empty p orbital of the carbocation, students can more easily visualize the

structural and electronic factors that contribute to regio- and stereochemical outcomes. For molecules

like 1-methylcyclohexene, the regiochemistry of cation formation is largely controlled by the relative

130 stability of the carbocation. For aliphatic carbocations, hyperconjugation is dominant stabilization

factor, application of which requires students to visualize the overlap of filled orbitals with the

carbocation p orbital. The computational depiction reinforces this concept because of the plainly

visible alignment of the C–H and C–C bonds with the empty p orbital in the optimized carbocation

structure. Additionally, visualization of the geometry changes, otherwise difficult to convey with hand-

135 drawn structures, as well as depiction of the NBO of the empty p orbital on C7H13+ showing the orbital

shape, helps students to rationalize the possibility of a nucleophilic addition to either face of the

intermediate. Such visualization of computational results promote a better connection between

reactivity and stereochemistry than an electron-pushing mechanism can do alone.

- + 140 Figure 2. Lecture slide NBO depiction of the formally empty (occupancy = 0.43 e ) p orbital on C7H13 formed in the electrophilic addition

of HBr to 1-methylcyclohexene.

As shown in Figure 3, student understanding of the regiochemistry and stereochemistry of

halohydrin formation can be enhanced by providing computational geometries for each mechanistic

step together with the relevant orbitals. The acceptor orbitals on each electrophile (s*Br–Br on bromine

145 and s*C–Br on the bromonium ion) are displayed, corresponding to each of the s bonds that break

during the course of the reaction. The initial addition of bromine to isobutene is more complex than

depicted here, as the orbitals shown are for only one donor-acceptor interaction. More correctly, this

step involves two simultaneous donor-acceptor interactions in a concerted three-membered ring

formation. Students can rationalize that as the p orbital electrons are transferred to the s*Br–Br orbital,

150 the bond order of Br2 is lowered to zero and the corresponding s bond is broken. Students can see

that the p bond on isobutene has a symmetric orbital density above and below the plane of the

molecule, either lobe of which can react with bromine. Two parallel reactions are displayed to show

how the two enantiomeric bromonium intermediates are formed as a result of the orbital symmetry of

isobutene. The two enantiomeric intermediates react via an SN2 reaction with a water nucleophile.

155 When bromonium ions are depicted in most textbooks, they are shown as having two equivalent sC–Br

bonds. In contrast, the WebMO image showcases the lengthening of the sC–Br bond connected to the

more substituted carbon atom. This difference in bond length coincides with an increase in positive

charge at the more substituted carbon atom and allows students to rationalize the regioselectivity of

the SN2 reaction. Additionally, it is apparent from the location and shape of the s*C–Br orbital that the

160 nucleophilic water must approach the electrophilic carbon from the back side of the sC–Br bond.

Finally, there is a subtle feature of this SN2 reaction that becomes more apparent with the

computationally predicted structure: the geometry around the C-atoms of the three-membered ring are

flattened (the C-atoms are more sp2-like) allowing the nucleophile to effectively approach the s*C–Br

orbital by reducing the impact of the steric repulsion of alkyl substituents on the more substituted C-

165 atom. Once again, the teaching of halohydrin formation by simultaneously using the electron-pushing

mechanism and computational outputs helps students rationalize the Markovnikov regiochemistry

and anti stereochemistry far more effectively than a combination of electron-pushing formalism and

model kit usage.

170 Figure 3. Lecture slide depicting electrophilic addition of bromine to isobutene. Occupied orbital on isobutene depicted in red/blue and

unoccupied orbitals on bromine and the bromonium ion depicted in yellow/green.

Later in the semester, the course delves into the SN2-ring opening of epoxides, which is closely tied

conceptually to halohydrin formation. With the familiarity of bromonium ions already presented in

lecture and student handouts, we ask students to analyze the structure and derive reactivity from

175 WebMO images of the protonated and non-protonated epoxide of 2,2-dimethyloxirane (Figure 4).

Structurally, there are subtle differences between the protonated and non-protonated epoxide that are

not always well-captured in two-dimensional drawings. To assist in student interpretation, calculated

bond lengths and partial charges are provided for each structure. In 2,2-dimethyloxirane, the C–O

bond lengths are nearly identical. The protonated 2,2-dimethyloxirane, however, bears a strong

180 similarity to a bromonium cation in the depletion of electron density on the tertiary carbon, resulting

in a longer, weaker bond on the more substituted side. This tertiary carbon also shows a flatter

geometry, as it is more sp2-like, reducing steric repulsion for nucleophilic substitution. Using these

structures, students are able to predict that the unprotonated epoxide reacts via a normal SN2

reaction at the least substituted carbon atom, while the protonated epoxide displays a reversal of

185 regiochemistry. This exercise helps students rationalize the difference in regioselectivity for epoxides

reacting under acidic versus basic conditions, drawing from their previous conceptual understanding.

Figure 4. Annotated problem set answer key discussing of the geometry changes of 2,2-dimethyloxirane and protonated 2,2-

dimethyloxirane

190 2nd semester examples

Our 2nd semester course begins with spectroscopy and spectrometry (1H-NMR, 13C-NMR, 13C-NMR

APT, HSQC, IR, and EI-MS). As has been previously reported, there are numerous ways of supporting

student analysis and interpretation of the experimental spectra with computational chemistry.4, 14-22

Figure 5A shows a typically-assigned IR spectrum of vinyl propionate.49 Using WebMO’s HTML-export

195 feature and editing of line of code, it is possible to directly link the assigned stretches (C(sp2)–H,

C(sp2)=O, C(sp2)=C(sp2), and C(sp2)–O), giving students a quick visual connection between vibrational

mode and the absorption observed in the IR spectrum. Figure 5B shows the 13C-NMR spectrum of

ethyl acetate with the isotropic NMR chemical shifts provided. While most of our students can assign

C1 and C2 with ease, the computational NMR prediction allows students to confidently assign each of

200 the methyl group 13C-NMR signals (C3 and C4). For IR and NMR analysis, students are made aware

that the predicted relative position of signals is more reliable than the absolute absorption frequency

or chemical shift. For example, students do not seem confused by the vinyl propionate

computationally-predicted IR stretches of the C=O (1840 cm-1) and C=C (1736 cm-1) being too high

compared to experimental values (1762 and 1649 cm-1, respectively). Nor has anyone raised concern

205 about the over-prediction of the ethyl acetate carbonyl 13C-atom NMR chemical shift by 10 ppm. Our

hope is that students are learning to use these tools as guides or to confirm their assignments.

Furthermore, we expect that students are increasing their awareness of the difference between a

predicted or estimated value and its empirical or experimental counterpart. It is critical to emphasize

to students that the experimental value is the real one and should be trusted.

210

Figure 5. Annotated problem set answer keys with linked computational predictions of associated spectra. A) The optimization and

vibrational frequency calculation allows students to view each of the vinyl propionate key functional group stretches identified in the

experimental IR spectrum on the answer key. B) An NMR calculation provides estimated chemical shift data for each 1H- (not shown) and

13C- atom nucleus referenced to TMS for support in assigning the experimental 13C NMR spectrum.

215 Electrophilic aromatic substitution (EAS) reactions are a standard part of second semester organic

chemistry, where aromatic p systems react as nucleophiles. While some instructors have explored

EAS activation and directing effects via computational investigations of the aryl substrate, we employ

computational chemistry to help students rationalize the regioselectivity of these reactions using the

arenium cation intermediates. The charge distribution in the aryl substrate or the electron density

220 distribution of its highest-energy occupied molecular orbital (HOMO) can indicate the more

nucleophilic carbon atoms of the ring. While this is correlated to their relative reactivity, it is a missed

opportunity to explore the potential energy surface (PES) of this reaction and connect the relative rates

of product formation to the transition states of their rate-determining steps. Using a more rigorous

approach, our students use Hammond’s Postulate and the energies of the high energy cationic

225 intermediates (A and B, Figure 6) to rationalize the outcome of these kinetically controlled EAS

reactions. An example exam question is provided in Figure 6, where students were asked to

rationalize the experimental spectra provided from the reaction of bleach with 4'-

methoxyacetophenone in acidic conditions.50 As part of that analysis, students were instructed to

rationalize the energy difference between the two regioisomeric arenium cations (A and B) using

230 resonance arguments. Computational data were provided to highlight the combined impact of the p

conjugation represented by the associated resonance structures, steric interactions, and dipole-dipole

interactions on the potential energy surface rather than simply asking students to depict the p

conjugation. For exams, where students do not have access directly to a computer, the data is

provided and organized/pre-analyzed for them to allow the students to use the data to make useful

235 conclusions. (For a graduate course, where academic misconduct was less of a concern, students

were given computational data to use directly via HTML exports during the exam.)

Figure 6. Annotated exam answer key with the two regioisomeric chlorination arenium cations of 4'-methoxyacetophenone (A and B).

Resonance structures are provided for the lower-energy arenium cation A.

240 Arguably the most important reaction of 2nd semester organic chemistry lecture courses is the

attachment of a nucleophile to a carbonyl. We have adapted a recently published lab exercise10 into a

problem set question for the lecture course where students use computational outputs depicting the

relevant HOMO and LUMO orbitals to rationalize the attachment of cyanide to acetone. Figure 7

shows a small portion of this question in which the trajectory of attachment (Bürgi-Dunitz Angle51)

245 corresponds to a favorable overlap of the large lobes of the nucleophile’s HOMO and electrophile’s

LUMO. This also highlights the nucleophilicity and electrophilicity of the bond-forming carbon atoms

in this reaction. Students can view the motion of the atoms at the transition state and visualize how

the acetone geometry changes as the cyanide approaches. Throughout the course of the question,

students view the optimized structures of cyanide, acetone, the two molecules coming together in the

250 transition state, and the resulting tetrahedral intermediate. As the question progresses, students view

the relevant orbitals (HOMO of cyanide and LUMO of acetone) of this reaction and compare the LUMO

on isobutylene to acetone to rationalize the differences in reactivity of pC–O and pC–C bonds. It is hard

to imagine students making these comparisons in the absence of computational data to support and

assist in their analysis.

255

Figure 7. Annotated problem set answer key displaying the reaction of acetone with a cyanide nucleophile.

With the understanding of the fundamentals of organic reactivity, molecular comparisons become

central to rationalizing reactivity as the course progresses. Computational chemistry can be used to

showcase the differing electrophilicity of the carbonyl and b C-atoms of a,b-unsaturated carbonyl-

260 containing compounds. Figure 8 presents a lecture slide with NBO charge data and depictions of the

LUMO for chalcone and protonated ethyl 2-butenoate. While resonance structures are traditionally

drawn to show the electron-withdrawing effect of the O-atom on the carbonyl and b C-atoms in both

molecules, the inclusion of the charge data and LUMO provides additional depth. These data allow

students to clearly see that the carbonyl C-atom will be more electrophilic in a neutral or protonated

265 system than the b C-atom, which is difficult to ascertain from resonance structures alone. This allows

students to rationalize the preference for nucleophiles to attach to the carbonyl C-atom for a,b-

unsaturated carbonyl-containing compounds, which further allows them to rationalize 1,2- versus 1,4-

conjugate additions for these systems without relying almost entirely upon memorization of reaction

rates.

270

Figure 8. LUMO acceptor orbitals and NBO charge data of two a,b-unsaturated carbonyl compounds: chalcone (top) and protonated

ethyl 2-butenoate (bottom)

COMPUTATIONAL METHODS Calculations

275 All of the calculations here were obtained using Gaussian 0952 or Gaussian 1653 using WebMO

installed on the University of Wisconsin–Madison Chemistry Department educational computer cluster

(Sunbird). Nearly all geometry optimization and vibrational frequency calculations were carried out

using B3LYP/6-31G(d). Subsequent NMR or NBO calculations were carried out to obtain NMR

chemical shift data or depictions of relevant orbitals. For most of the molecules presented in

280 undergraduate organic chemistry textbooks, the optimization will take a few minutes to a few hours,

and NMR or NBO calculations add only a small fraction of the optimization time to the total time to

generate the desired computational output. A significant advantage of the WebMO-based approach

presented here is that it can be implemented for little to no cost. At institutions with a computer

cluster running any modern computational software, WebMO can be added for a relatively low cost.

285 For an institution without the necessary infrastructure to maintain a computational cluster, the free

version of WebMO can be linked to GAMESS2-3 (also free) to generate computational data from an

individual PC.

The B3LYP/6-31G(d) level of theory and basis set is adequate for calculation of most geometries

and properties of organic molecules for the undergraduate level. B3LYP/6-31G(d) calculations do not

290 handle all molecules with experimental accuracy and instructors should use all computational data

with caution. As needed, both the level of theory and the basis set can be improved for better

modeling of experimental data in a one-time calculation. Additionally, instructors must use care when

translating two-dimensional structures into three dimensions. Many of the images drawn in textbooks

and on websites of organic molecules are not the low-energy conformation or even a stable structure.

295 HTML export and embedding

As shown in Scheme 1, once the desired computational output is obtained, selecting the HTML-

export feature of WebMO creates a .tar file containing the necessary files to open that output in a

modified local HTML WebMO version, similar to what the user sees in WebMO itself. These files can

be given directly to students via a learning management system or via the construction of a simple web

300 site with links to the hosted HTML files. Alternately, we have found it convenient to place links to the

relevant computational outputs directly into the documents we use for lecture presentations,

discussion notes, problem sets, exams, etc. By editing one line of the Javascript code, it is possible to

generate clickable items that direct students to specific content (orbitals, dipoles, vibrational modes,

charge distribution, etc). in the output file, further minimizing student barriers for usage of WebMO.

305 Students can click on these links at the moment that they are most relevant and be taken directly to

the three-dimensional structure, important orbital, or property.

Scheme 1. Work flow for generating and posting computational outputs for students.

RESULTS AND DISCUSSION

310 Initial Reflections on Implementation

The representative examples shown here provide students with an easily accessible resource that will

enhance their understanding of organic chemistry. Having the WebMO images embedded in all aspects

of the course materials provides a framework that allows instructors to focus on how reactivity is driven

by physical organic principles. Instruction carried out in this manner forces students to move further

315 away from memorizing reactions, patterns of reactivity, or oversimplified criteria for predicting reaction

outcomes. We have found that exposure to computational chemistry results, even without students

performing the calculations, improves student ability to focus on key concepts: p conjugation,

hyperconjugation, electrophilicity, nucleophilicity, bond strength, etc. Finally, student intuition about

molecular and electronic structure is enhanced by repeated exposure to more realistic depictions of

320 molecules and orbital geometries

CONCLUSION AND FUTURE DIRECTIONS

We believe that the benefits of including computational chemistry in the early undergraduate

curriculum have not been fully explored or understood. Given the relatively recent wide-spread

availability of these tools, instructors have not fully grasped their utility in teaching students to think

325 about the reactions of organic chemistry and the properties of molecules using computational results.

Certainly, organic chemistry instructors have been focusing on the relationship between electronic

structure and the reactivity of molecules since before use of computational chemistry in the classroom.

Computational chemistry just makes that focus easier for instructors to engender in their students.

Students can see depictions of s bonds, p bonds, lone pairs, acceptor orbitals, etc. This ability to

330 visualize the electronic structure directly can reduce the cognitive load of trying to predict the reactivity

of a molecule, in a manner more similar to an expert who can fluidly move between two- and three-

dimensional representations. To understand the behavior of an organic molecule, students must view a

two-dimensional image, assign the hybridization of the atoms using a valid method, determine the three-

dimensional geometry of each atom, and then use the hybridization and three-dimensional structure to

335 understand how the orbitals might lead to a particular reactivity. The value of the computational

outputs is to provide the scaffolding necessary for students to translate organic molecules in such a way

that they can predict reactivity. With exposure to these images and their repeated use, students should

become more able to predict the reactivity of analogous molecules without the computational outputs.

It is easy to imagine a future in which computational chemistry is an embedded component of all

340 chemistry textbooks from the high school level onward. As the migration of textbooks to an online

platform continues to accelerate, it would be easy for all depicted molecules to become clickable links

highlighting their structure, properties, or relevant orbitals. This external support for courses would

allow educators to routinely enhance instruction with readily-available data and to easily develop

curricula where computational chemistry is a natural and authentic component.

345 While we will continue to grow the organic chemistry curriculum described to include more direct

application of computational chemistry outputs, it is clear that students would benefit from these types

of implementations at the general chemistry and high school levels. Currently, two related projects are

underway, providing computational outputs to high school teachers and their students via WebMO-

HTML exports.

350 ASSOCIATED CONTENT Supporting Information

Examples of lecture notes, problem sets, and assessments associated with the chapters of Organic

Chemistry48 are available upon request.

AUTHOR INFORMATION 355 Corresponding Authors

*E-mail: Brian J. Esselman ([email protected]), Aubrey J. Ellison ([email protected])

ACKNOWLEDGMENTS The authors gratefully acknowledge the input of the many teaching assistants and students that

have helped refine the curricular approach. We also thank the participation of Nicholas Hill, Maria

360 Zdanovskaia, Asif Habib, Cara Schwarz, and Amy Van Aartsen on this project and related projects that

have improved our approach to implementing calculations within the organic curriculum. We thank

Paul McGuire, Alan Silver, and J. R. Schmidt for their assistance with WebMO and computational

resources. Computer resources are partially supported by National Science Foundation Grant CHE-

0840494.

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