Friday, November 23, 2012

A Friday SN1 Haiku

Loyal reader Dave sent this in via the comments, and I thought it deserved a wider distribution:


Some of my students challenged me to do the upcoming class in haiku. Since a fractional distillation lab is pretty dull to supervise after everyone is up and running, I put the introduction to SN1 in haiku format. (Each done on a powerpoint slide with a pretty background…)

SN1 Haiku

Leaving group breaks off
Forming carbocation
SN1, first step

very reactive
intermediate species
they need electrons

tertiary good
hyperconjugation helps
resonance does too

add more Nu? No help.
the rate is independent
that’s kinetic proof

climbing two mountains
reaction coordinate
C+ is high pass

how do you decide?
SN1 or SN2?
there are many factors


Thanks Dave. Have a good Friday everyone

Tagged as: fun, substitution

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SN1/SN2/E1/E2 Decision Mind Map

Courtesy of Dave Blackburn, an organic chemistry instructor “who is giving an exam on this today”, here is a mind map of all the different concepts covered in the discussion on SN1, SN2, E1, and E2 reactions.
What’s interesting is that this mind map really boil the “SN1/SN2/E1/E2″ decision ?down to 3 options:
SN2 reactionE2 reactionFormation of a carbocation
If the carbocation is formed, of course, it can go down several different pathways (SN1, E1, possibly preceded by rearrangement).
There are five key categories covered here: substrate, nucleophile, solvent, temperature, and leaving group.?There’s no one place necessary to “start” although beginning with the “substrate” – i.e. ” primary, secondary, or tertiary alkyl halide? ” is always my first choice.
Thanks, Dave!
Click here for larger version

Tagged as: e1, e2, elimination, sn1, SN2, substitution

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Deciding SN1/SN2/E1/E2 (1) – The Substrate

Having gone through the SN1, the SN2, the E1, and the E2 reactions we can now say the following:

Both substitution reactions?and elimination reactions occur with alkyl halides (and related species)?A wide variety of nucleophiles/bases can be used to perform substitution and elimination reactionsA wide variety of solvents can be used in substitution and elimination reactionsWe also have to gauge the importance of factors such as the leaving group and temperature.

This is a lot of different factors to think about. Let’s look at some examples of situations you might encounter:

This is often one of the most difficult parts of organic chemistry for new students: how to weigh multiple (and often contradictory) factors??How do we know which factor is most important? Do we pay attention to the base, substrate, temperature, solvent? How do we go about sorting through a problem like this??As I’ve written before, deciding SN1/SN2/E1/E2 is not completely unlike how a professional bettor might evaluate which sports team is going to win on a given night (does good defence beat good offence? how important is coaching? how important is their recent performance? ) .

In this post and the next few, we’ll walk through one way of thinking about how to evaluate whether a reaction will proceed through SN1/SN2/E1/E2. It’s not 100% foolproof*, but it’s a decent enough framework for our purposes.

It starts by asking questions. In order of importance, I think they are:

The substrateThe nucleophile/baseThe solventThe temperature

It’s also a process of, at least in the beginning,?ruling things out rather than ruling things “in”. In other words, seek to decide what options are?not possible, rather than decide which are possible. It’s a subtle distinction, but a valuable one. Once you’ve crossed certain reactions off the list, you can then start asking yourself which reactions would be most consistent with the reaction conditions.

Before getting specific with each of those 4 questions, let’s start with the most important question you can ask in any situation like the ones above.

The most important step in evaluating any reaction is first to ask yourself “what type of functional group(s) are present in this molecule? This is because the type of functional group will dictate the type of reaction(s) that can occur. Note that in the questions above, all of the starting materials are?alkyl halides or?alcohols. Substitution/elimination reactions are possible for these substrates; many other reaction types (addition, for example) are not.

Question 1: The Substrate

Given that we’re looking at alkyl halides/alcohols, it’s a reasonable expectation that we should evaluate SN1/SN2/E1/E2. The next step is to identify the?type?of alkyl halide we are dealing with.
Look at the carbon that contains the best leaving group. Typically this is Cl, Br, I or some other group that can act as a good leaving group. ?Ask yourself: is this carbon primary, secondary, or tertiary?

Given what we know about SN1, SN2, E1, and E2 reactions, we can say the following:

The “big barrier” to the SN2 reaction is steric hindrance.?The rate of SN2 reactions goes primary > secondary > tertiaryThe “big barrier” to the SN1 and E1 reactions is carbocation stability. The rate of SN1 and E1 reactions proceeds in the order tertiary > secondary > primary.The E2 reaction has no “big barrier”, per se (although later we will have to worry about the stereochemistry)

So how can we apply what we know about each of these reactions to simplify our decision?

If the substrate is?primary, we can rule out SN1 and E1, because primary carbocations are unstable. ?You cannot definitively rule out E2 yet, although I will spill the beans and say that it’s almost certainly going to be SN2 unless you are using a very sterically hindered (“bulky”) base such as tert-butoxide ion (e.g. potassium t-butoxide KOtBu).

If the substrate is?tertiary,?we can rule out SN2, because tertiary carbons are very sterically hindered.

If the substrate is?secondary, we can’t rule out anything (yet).

As you can see, based on the information we’ve evaluated so far, we can’t make a definitive decision on SN1/SN2/E1/E2. We’ll have to look at some other factors before we can make a final decision. Next, we’ll evaluate the role of the nucleophile/base.

—————— Advanced readers only ————–

* One question that comes up a lot is this: are there exceptions? Keeping in mind the two themes of “steric hindrance” and “carbocation stability”, there are edge cases where we can have a particularly sterically hindered primary alkyl halide, or a particularly stable primary carbocation.

For instance, the alkyl halide below (“neopentyl chloride”) is indeed primary, but is so crowded on the carbon adjacent to the primary alkyl halide that it is essentially inert in SN2 reactions. On the SN1/E1 side, the allyl halide below, while primary, can undergo SN1/E1 reactions because the resulting carbocation is stabilized through resonance. As long as you keep in mind the “big barriers” for each reaction, you should be fine.

Tagged as: e1, e2, elimination, sn1, SN2, substitution

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In Summary: Khan Academy Videos For Organic Chemistry

In Summary – Khan Academy for Organic Chemistry

In six previous posts I went through all 73 videos by Khan Academy for organic chemistry. In this final post I wrap up what I’ve learned from watching them, from the perspective of someone who teaches introductory college-level organic chemistry.

Six previous posts:?[1?2?3?4?5?6]


What’s great about Khan Academy?What does Khan Academy cover?What’s missing?What’s done the best?What are the biggest weaknesses?How useful is Khan Academy for a typical college student learning organic chemistry?Towards version 2.0

1. What’s Great About Khan Academy?

First of all, KA gets one really big thing right: teaching a subject as a series of 10 minute videos that gradually walk through a subject. There is a huge desire for this type of instruction and the value of discovering a popular working model for delivering educational videos cannot be understated.

His style is also very approachable and non-threatening. He doesn’t make you feel stupid. This alone is a huge part of the appeal. The tools he uses are very simple and accessible to everyone. He’s also an excellent illustrator.

Thirdly, I think it’s commendable that Sal Khan just decided to start making videos on a lot of topics without asking anyone’s permission. In some circles, his videos have been unpopular with academics. Here is a particularly lazy criticism of KA. Memo to instructors who complain about KA: you have the tools to make better videos: why aren’t you doing it?

What Does Khan Academy Cover?

I count 73 videos for organic chemistry.

These can be broken down into the following categories:

Nomenclature [27]: Alkanes, alkenes, R/S nomenclature, E/Z nomenclature, alcohols, ethers, epoxides, benzene derivatives, amines, aldehydes, ketones, carboxylic acids, anhydrides, esters, amides, acyl chlorides

Structure and bonding [5] hybrid orbitals, pi bonds, alcohol properties [hydrogen bonding], resonance, Huckel’s rule

Conformations [3] Newman projections [2 videos], chair/boat shapes for cyclohexane

Stereochemistry [4] Intro to chirality, chiral examples (2 videos), enantiomers/diastereomers/constitutional isomers

Reactivity: [8] mechanisms, Markovnikov’s rule, steric hindrance, sn2 stereochemistry, solvent effects, nucleophile strength, nucleophilicity vs. basicity, carboxylic acid derivative reactivity

Reactions: [24] HBr with alkenes, H3O(+) with alkenes, polymerization of alkenes w/ acid, SN2, SN1, E2, E1, free radical alkane chlorination, epoxide ring opening, bromination of aromatics, Friedel Crafts acylation, keto-enol tautomerism, acid-base of carboxylic acids, Fischer esterification, acid chloride formation with SOCl2, amide formation from amine and acyl chloride, aldol reaction.

Addenda [2]

What does a typical introductory organic chemistry course cover that is NOT included in Khan Academy?

If I had to name my top 10 omissions, they would be this:

no discussion of organic acids and base; i.e acidity, basicity, conjugate acid, conjugate base, pKa, how to determine if an acid base reaction is favorableevaluation of resonance forms; what makes one resonance form more stable than another? Not discussion of the stereochemistry of the E2 reactiononly 3 alkene addition reactions covered [out of >15] ; no examples with stereochemistry. Missing examples like bromination, hydroboration, epoxidation, discussion of alkynes or their reactionsno discussion of carbocation rearrangementsno discussion of oxidation/reductiononly one video devoted to the concept of aromaticity, not enough to understand it; only 2 reactions of aromatic derivativesonly 3 videos on reactions of aldehydes, ketones, and carboxylic acid derivativesno discussion of the Diels-Alder or related reactions; no discussion of molecular orbitals

Of the material covered by the KA videos, what’s done the best?

The videos on nomenclature are useful for those who have never encountered these functional groups before. They provide accurate methods for naming these molecules. There was only one major mistake and this was corrected. A few minor mistakes (see notes on individual videos).

The videos on structure and bonding, including hybrid orbitals were done well.

The drawings of Newman projections were done well and have nice descriptions of how to convert a line diagram into a Newman projection.

What are the biggest weaknesses? What could be done better?

The videos on reactions tend to be shallow. There is a lot of imprecise language (e.g. “guy” instead of, say “nucleophile”). Chemical reactivity is? largely explained in an ad hoc fashion rather than in a way that ties back to fundamental concepts of physics. ?There’s an opportunity to explain a lot of organic chemistry by understanding the key factors that stabilize negative and positive charges; that isn’t done here. Arrow pushing is not done correctly. Stereochemistry? is arguably the major theme of first-semester organic chemistry, but its involvement in reactions is almost completely ignored.

What the videos really lack is a consistent description of chemical reactivity rooted in a small number of fundamental physical principles.

How Useful is Khan Academy For A Typical College Student Learning Organic Chemistry?

As they stand right now, KA videos are in no way a standalone alternative to a college-level course in introductory organic chemistry. If you watch all 73 videos, you will in no way have “learned” organic chemistry.

They are a useful supplement for nomenclature, structure and bonding, and some aspects of conformations.

For someone who finds their university lecturer intimidating, the videos on reactions and reactivity can be a light introduction to some of the topics covered in an introductory course.

Towards Version 2.0

Two questions for the future:

1) What is the minimum number of 10-15 minute videos required to teach the core concepts of Org 1 and Org 2 in a manner that would, say, prepare students for a standardized exam like the ACS?

2) What is the optimal order of those videos? Can we test outcomes to see if there is an optimal way in which these topics can be presented?

I look forward to further improvement of the organic chemistry video content at KA.

Tagged as: khan academy, video

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Boring public service announcement

MOC is growing in traffic (yea!) but that means that the hamsters inside my current server are running at the brink of exhaustion. I’m migrating/upgrading to a new server service, so no posts for a few days until this gets settled. Hopefully by next week page load times should be snappier too.


image credit

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Elimination Reactions With Rearrangments

One last (weird) reaction to show you with respect to elimination reactions. Can you see what’s weird about it?

How did that double bond get over?there??Normally when elimination occurs, we remove a hydrogen from the carbon adjacent to the leaving group. But here, something extra has taken place.

Let’s look at all the bonds that form and the bonds that break so we can track down?exactly what happens:

Notice how it differs from a typical elimination reaction? Sure, we’re forming C-C (π), and breaking C-H and C-OH, but we have an extra C-H that forms and an extra C-H that breaks.

This is a sure sign of a rearrangement step!

So what’s going on here?

Well, we start by protonating the alcohol. This allows for water to leave in the next step, which is going to form a carbocation.?Here’s the thing:?the carbocation is?secondary, and we’re adjacent to a?tertiary carbon. So if the hydrogen (and its pair of electrons) were to migrate from C3 in our example to C-2, we’d now have a tertiary carbocation, which is?more stable. Then, a base (water in this example) could remove C-H, forming the more substituted alkene (the Zaitsev product in this case). And that’s how the alkene ends up there.

OK. So that’s one mystery solved.

You might remember that these types of rearrangements can occur in SN1 reactions too. And if you read that post, you might recall that in addition to shifts of hydrogen (“hydride”, because there’s a pair of electrons attached) we can also have alkyl shifts. Here’s a final example. Note – I’ve also made a video of this, you can watch it here.

This pretty much does it for elimination reactions.

In the next series of posts, let’s go though one of the biggest questions students struggle with. Okay, now that we’ve gone through substitution and elimination reactions, HOW DO WE DECIDE WHICH ONE IS GOING TO OCCUR IN EACH SITUATION?

Great question. That’s next.

Next Series, post 1: SN1/SN2/E1/E2 Decision (1) – The Substrate

Tagged as: alkyl shift, e1, eliminations, hydride shift, rearrangement, sn1

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Khan Academy Videos for Organic Chemistry, Part 6

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In this post (the 6th of 6) we finish up going through all the Khan Academy videos for organic chemistry [videos 65-73]. For previous posts in this series, see [1 2 3 4 5]

Video #65 – Keto-Enol Tautomerism
Length: 8:03
Summary: 3-methyl 2-butanone is drawn, and the mechanism for its conversion into its enol form is shown via protonation of the carbonyl oxygen and deprotonation.
Key concepts/Skills:?keto-enol tautomerism, constitutional isomers.
Nitpicky criticisms:?A little bit of vaugeness about where H3O(+) comes from; there shouldn’t be too much in water at pH 7. Might help to say the reaction is assisted by adding acid. Could help to mention what factors favor the keto over the enol, or to give students a typical value for the position of equilibrium [about 104 favoring keto, for instance].
Red flags:?None, this is fine [except for arrows]

Video #66 – Carboxylic Acid Introduction
Length: 8:51
Summary:?A generic carboxylic acid is drawn, and the acid-base reaction between it and water is shown. It’s demonstrated that the stability of the conjugate base is due to resonance. ?Formic acid, acetic acid, and oxalic acid are also drawn.
Key concepts/skills:?acidity, resonance stabilization, carboxylic acids
Nitpicky criticisms:?It’s said that carboxylic acids are more acidic than alcohols. By how much? It would also be good to explicitly say that “the stronger the acid, the weaker the conjugate base”. When the Arhennius definition of an acid as a proton donor is mentioned [1:05] I think he means Bronsted.
Red flags:?Nothing except for the arrow pushing

Video #67 – Carboxylic Acid Naming
Length: 5:26
Summary:?Butanoic acid, hexanoic acid, 3-methyl hexanoic acid, and (E)-3-heptenoic acid are drawn and named.
Key concepts/Skills:?Carboxylic acid nomenclature
Nitpicky criticisms:?It’s fine. One weird thing though – around 5:15 it’s said that “this is only true if you’re assuming that I drew it in the actual 3 dimensional configuration in some way”. Not sure what is meant by this.
Red flags:?None

Video #68 – Fischer Esterification
Length: 17:12
Summary:?Heptanoic acid is drawn with ethanol and H2SO4. Reaction really begins at 5:00. Protonation of carbonl oxygen, addition of ethanol, ethanol losing proton, protonation of OH, and loss of water. Formation of ethyl heptanoate.
Key concepts/Skills:?Equilibrium, carboxylic acids, addition, elimination.
Nitpicky criticisms:?“Fischer”, ahem. The video begins with “let’s think about what might happen if we do this”. Little pet peeve of mine – we can appreciate things looking backward, but it’s difficult to look forward using first principles. The discussion up to 5:00 probably could have been skipped, since it’s just discussing the acidity of H2SO4.?Would be good to mention that acid makes the carbonyl group a better electrophile; also, an opportunity is missed to explain why the nucleophile attacks the carbon instead of the (positively charged) oxygen. It’s said that we’ve seen this “many, many times” in SN2 reactions but this is actually his first time drawing the addition mechanism in carbonyls. It’s good to mention the reaction is in equilibrium, but it would be better to mention *why* equilibrium favors formation of the ester. Finally I know I’m a grouch, but I just don’t like statements like “protons are flying around everywhere” (11:25).
Red flags:?The elimination step at 14:00 is drawn as a bimolecular mechanism, which is incorrect. Deprotonation should be shown as a separate step.

Video #69 – Acid Chloride Formation
Length: 11:48
Summary:?The mechanism for formation of acetyl chloride from acetic acid using SOCl2 is shown.??
Key concepts/skills:?Conversion of carboxylic acids to acid chlorides
Nitpicky criticisms:?Would be good to mention why Cl is a good leaving group. Why do we lose oxygen and not Cl in the elimination step? It would be good to mention that the gas SO2 is formed and this will drive the reaction to completion. The last step shouldn’t have an equilibrium arrow.?Heh, nobody would perform this reaction in a beaker [9:15] ?it stinks too much!
Red flags:?Just the arrow pushing (as always)

Video #70 – Amides, Anhydrides, Esters, and Acyl Chlorides
Length: 8:48
Summary:?The structures of acetamide, N-methyl propanamide, methyl ethanoate, acetic anhydride, ethanoic anhydride, propanoic anhydride, acetyl chloride, and ethanoyl chloride are drawn.
Key concepts/Skills:?Nomenclature of amides, esters, anhydrides, and acid chlorides
Nitpicky criticisms:?None
Red flags:?None

Video #71 – Relative Stability of Amides, Esters, Anhydrides, and Acyl Chlorides
Length: 11:09
Summary:?Acetamide, methyl acetate, acetic anhydride, and acetyl chloride are drawn, along with their resonance forms. The higher reactivity of anhydrides is rationalized as being due to the lower stability of the resonance form.
Key concepts/Skills:?drawing resonance structures, understanding stability of resonance structures.
Nitpicky criticisms:?If nitrogen is electron rich – more electronegative than carbon, then why might it give up its electrons? [2:44]. ?Finally, for the ester, he mentions the real reason why oxygen is less nucleophilic than nitrogen – because it is more electronegative. This is the first time this is mentioned in the whole video series. How does one differentiate between “quite stable” and “just stable”? Would be better just to show an arrow beginning with “most stable” on the left going to “least stable” on the right. Finally, he says “we’ll explore some of the mechanisms in the next few videos”, but in fact it’s just mentioned in one video.

I think ranking leaving group ability is a more powerful way to explain the relative reactivity of carboxylic acid derivatives than the relative stability of resonance forms, but overall this is a useful video.
Red flags:?No resonance structure is drawn for acetyl chloride because it is said that it “has no resonance structure” ; instead of saying it “has no resonance structure”, which is not true, it would be better to say that the resonance form is not “significant”; also, chlorine is less electronegative than oxygen, so the answer is not electronegativity (9:20) but poor orbital overlap.

Video #72 – Amide Formation From Acyl Chloride
Length: 9:01
Summary:?The reaction between butanoyl chloride and dimethylamine is shown to give N,N-dimethylbutanamide.
Key concepts/Skills:?Reactivity of acyl chlorides, nucleophilic acyl substitution.
Nitpicky criticisms:?Another instance of “Let’s think about what might happen….”. The “stability” argument from the previous video is used to explain the reactivity of acyl chlorides relative to amides, but leaving group ability is more valuable. Compare Cl(-) as a leaving group versus Me2N(-)! This explains everything.
Red flags: Just arrow pushing.

Video #73 – Aldol Reaction
Length: 11:41
Summary:?The aldol addition reaction between two aldehydes RCH2CHO in the presence of NaOH is shown.
Key concepts/Skills:?Enolates, addition reactions, aldol reaction, acidity of alpha protons, enolates as nucleophiles.
Nitpicky criticisms:?It’s said that this is a review of previous discussions of enolate ions, but in fact this is the first description of them. It would be better to consistently show the aldehyde hydrogen.
Red flags:?The arrow pushing here makes it look like the carbonyl carbon is the nucleophile, which isn’t the case [6:32].

And that’s it: 73 videos for organic chemistry from Khan Academy. Again, lots of nomenclature videos here, plus a few on reactions. Kind of disappointing that there’s so few on the reactions of aldehydes, ketones, and carboxylic acids; nothing on reduction, oxidation, extensions of enolate chemistry… a lot of work still left to do, in other words. ?In the next post I’ll write an overall summary of these videos that answers the question, “How useful are Khan Academy videos for learning organic chemistry?”.

Tagged as: khan academy, videos

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