Week 5: Dehydration of an alcohol into an alkene

The title for this post is a bit unwieldy. I'm sure this won't be the last time that happens. I am using this title because there are multiple dehydration reactions, and there are even multiple dehydration reactions of alcohols. This post is only about a reaction in which an alcohol is dehydrated to form a π-bond between the α-carbon and the β-carbon (Greek letters are one of the most important tools in all of science and without them all sorts of bad stuff would happen somehow). I know, I know. You're confused. Again. That means it's time for a picture...
Like the reactions from the previous two weeks, this involves elimination. But those reactions involved the elimination of a halogen from the α-carbon and a hydrogen from the β-carbon. This one is called dehydration because water is removed from the alcohol. Water is lost. It's dehydration. Get it? Because that's what dehydration means. And you were probably already aware of this.

I know you probably aren't paying attention. But if you have been, you may be wondering how this happens. Surely the hydrogen on the β-carbon doesn't magically fuse to the hydroxyl group and form water because it wants to. So what's going on? How do we make an alcohol do this thing? The simple answer is acid. I know. It's awesome. Chemistry is awesome. Sulfuric acid works pretty well for this. You could use some other acid for some reason I suppose. It should be a strong acid though, because I don't traffic with weak acids.

And now an exercise for the reader. I'm serious. The acid protonates the oxygen in this reaction, forming water as a leaving group. You already know about leaving groups because they've been involved in all reactions I've done for this project (the reaction of the week one, not the whole blog) so far. The mechanism for the rest is either E2 or E1. Actually, I'll tell you that it's E2 for primary alcohols (the α-carbon is attached to only one other carbon) and that it's E1 for secondary and tertiary alcohols (the α-carbon is attached to two or three other carbons). So, from that, you should be able to figure out the rest on your own. Consider it a challenge. Well, maybe not. No, I'm not just being lazy here. I really think I've given you enough information in this and the posts on elimination reactions to see what's going on here. And it occurs to me that it may be better to try to leave some things intentionally only hinted at so that one can think about them, rather than omitting them entirely or simply spoon-feeding them to my readers (which is no one, but shut up). Well, go ahead then, deduce the rest of these reactions.

Week 4 of 52: Unimolecular elimination

Apparently January will have been the month of reactions on alkyl halides by bases and nucleophiles. I didn't initially set out to do it that way, but in retrospect it does make sense. I have no idea what reaction I'll start February with. Oh well, it's not time for that yet. It's time for unimolecular elimination.

If you've been paying close attention (which you haven't), you'll probably have deduced that this has the "unimolecular" feature of the S_N1 reaction and the "elimination" feature of the E1 reaction. So you practically know what will happen just from the name, you clever reader, you. But just in case you aren't that bright, which let's face it, is pretty likely, I'll offer a brief explanation...

• This is a two-step reaction.
• In the first step, the bond between the α-carbon and the leaving group breaks. The leaving group leaves.
• The departure of the leaving group results in the formation of a carbocation.
• In the second step, a base removes a proton from a β-carbon.
• As in the E2 reaction, the electron pair from the broken C-H bond forms a π-bond between the α-carbon and the β-carbon.

Still confused? Let's try some pictures. One note: with the S_N2 and E2 reactions, I just assumed that we were dealing with primary alkyl halides. With the unimolecular reactions, a carbocation is formed, so these reactions will be fastest with tertiary alkyl halides. So I'll draw some more groups, just to show that. So, here's the first step...
That's the same first step for both the substitution reaction and the elimination reaction. It's the second steps that are completely different. Here's S_N1...
And you already know exactly what the E2 reaction will look like now, but I'm showing you anyway, just on the off-chance that you really are that incompetent...

Week 3 of 52: Bimolecular elimination

The bimolecular elimination reaction is typically just referred to as the "E2" reaction. It has some things in common with the S_N2 reaction featured in the first week. Both are bimolecular: the reaction is driven by a collision of two molecules. Both involve the concept of a leaving group: an atom or group of atoms that can accept electron density. A classic example is an alkyl halide. In both the E2 reaction and the S_N2, something attacks the alkyl halide, and the halogen is broken away as an anion. I was being lazy for the first two weeks of this and didn't use any illustrations, so let's throw in a picture for this...
I say that's totally a step up from my previous use of pictures in this blog. Anyway, in the S_N2 reaction, which I covered in the first week, not this week, the "something" would be a nucleophile and it would attack the carbon that the halogen is bonded to, the α-carbon. The bond between the α-carbon and the halogen would break and a new bond would be formed between the nucleophile and the α-carbon. Here's a reaction mechanism. Oh, I'm leaving out the hydrogens bonded to carbon in these pictures because I want to. But realize that the α-carbon has two hydrogens attached to it that are just sitting there, not doing anything...
This week's reaction has some important differences. Firstly, the "something" is a base. Basicity and nucleophilicity are similar concepts and the same thing can behave in both ways. A nucleophile attacks a relatively exposed area of positive charge, the nucleus of the α-carbon. A base participates in a traditional acid/base reaction, reacting with a proton. No bond is formed between the base and the alkyl halide. Instead, a bond is broken. Here, I'll show you, but this time, I need to draw some hydrogens...
All of the electron density in the C-H bond at that β-carbon (it's called a β-carbon because it's adjacent to an α-carbon) is dumped onto the carbon. This simultaneously forms a double bond between the α-carbon and the β-carbon and drives the leaving group (the halogen) away. More importantly, I think making this image has placed me officially beyond all redemption.

Emphasizing this yet again, rather than providing new information about this reaction, because I know you can only handle so many new things at once: in nucleophilic substitution, the nucleophile replaces the leaving group, hence the name. In elimination, a π-bond (double bond) is formed between two carbons while the leaving group and a proton are removed, hence the name. Easy, right?

Week 2 of 52: Unimolecular nucleophilic substitution

Because you read the previous post and totally didn't forget everything I said there, you already deduced that this nucleophilic substitution reaction (S_N1) occurs in two steps. Instead of the nucleophile attaching at the same time that the leaving group is removed, first the leaving group leaves, then the nucleophile attacks the "intermediate" and together they form the product of this reaction. In order for this to happen, the bond to the leaving group has to actually break on its own. If the intermediate would not be stable, this won't happen.

I started writing this post too late in the week for me to cover relative carbocation stability, so you'll just have to believe me when I tell you that it's—important. Yeah, that wasn't very convincing. Whatever. Shut up. Carbocations in which the carbon attached to the leaving group have more bonds to hydrogen atoms are less stable. If the carbon attached to the leaving group is attached to more carbons, the carbocation will be more stable. The greater the stability, the faster the S_N1 reaction.

Also note that unlike the backside attack of the S_N2 reaction, the leaving group in this case is already out of the way, so stereochemistry (if the carbon in question is a chiral center) is randomly split between both possible configurations. That means there will be an even mixture of both possible products, not that the each individual molecule will somehow be halfway between both possible products, obviously.

Week 1 of 52: Bimolecular nucleophilic substitution

I think this was the first reaction I learned in an organic chemistry class. Regardless of whether I'm right, it will be the first reaction in this series. Now, I know the name seems intimidating to you, because you're so pathetic. But I'll confess something: I didn't remember that name when I set out to write this post. At least I don't think so. It didn't really cross my mind. I'm used to just calling this reaction by the same name everyone else calls it. The more common name for this reaction is S_N2.

"Bimolecular" in this case refers to the fact that the reaction involves a collision of two molecules. Unlike some other reactions I'll be dazzling you with, this entire reaction happens in one step. One bond breaks at the same time as another bond is formed. Consequently, the thermodynamics of this follow the "second-order rate equation." I'll be gleefully ignoring that for now, so you can too, if you want. The important thing about it is that the rate at which this reaction occurs depends on the concentrations of both molecules involved (increase the amount of either in a system, and the rate of reaction speeds up).

"Nucleophilic" refers to the fact that one of the two reactants is, well, a nucleophile. Nucleophiles are attracted to positive charge. Remember: nucleii of atoms are positively charged. Here's the part where I could elaborate on the intricacies of nucleophilicity as a property, which molecules make good nucleophiles and which ones do not and why, but it turns out that I've been procrastinating on writing this post, so we're pretty much skipping that. Anyway, I will tell you that nucleophiles are often negatively charged particles, which should be obvious anyway.

"Substitution" means that the nucleophile replaces another group. The other group is aptly known as a leaving group. You know, because it leaves. To be a leaving group, an atom or group of atoms must be able to accept electron density. This leaves less electron density on the other side of the bond (which is to a carbon atom) and more exposed nucleus for the nucleophile to do its thing. The most popular leaving groups are halogen atoms, especially bromine and iodine (they're bigger, so the electron density is spread over a larger space). One thing that I didn't remember, but that my textbook deemed noteworthy is that "all good leaving groups are weak bases with strong conjugate acids having low pK_a values."

Another fun fact that can sometimes matter is that this reaction happens by "backside attack." As you may have noted, the nucleophile reacts with the carbon atom, not the leaving group and it wouldn't make sense for it to form a bond in the same spot where the bond to the leaving group is simultaneously breaking. This means that the stereochemistry of the carbon can be completely changed. It also allows for the pickup line: "Baby, if I were a reaction, I'd be S_N2, so I could attack your backside."

Reaction of the week

I've been hesitant to commit to this, but now I suppose that I am, so go cry about it or something. The textbook I was using earlier is in Seattle right now anyway and I (at this point in time) am not. But my vision for this blog was never "Stephen Bahl condenses a textbook for you" or whatever. To be fair, I did post about some of my old labs and such. Alright, so it wasn't much, but surely it broke the monotony somewhat. And the textbook was really only ever a tool for me to introduce concepts from organic chemistry. That was what happened here. You're still confused? Try to keep up. I should explain. Fine. I will. What is wrong with you? Okay, new paragraph: go.

I am now stating it explicitly for you: this blog will change. It will continue to exist and it will continue to be written by me. It will continue to cover topics in chemistry. Those things will remain the same. They are not what is changing. Starting in January, the theme of this blog will be "reaction of the week." And I will keep it up for the duration of the year. This means that next year, I will blog about no less than fifty-two reactions. Fifty-two. 52. LII. Zweiundfünfzig. That's a lot. But it's happening. I've said I'm going to do it, so now it's too late to back down.

Not all of these will necessarily be reactions from organic chemistry. I won't mind throwing in the occasional inorganic reaction or whatever. But I have a stack of index cards in my desk right now with what appears to be upwards of seventy reactions from my organic chemistry class back in 2008. So yeah, it's not like I'm going to run out of reactions for this. 2011 shall be the year of the reaction. Or something. Oh yeah.

Polyketides

I believe my previous post made some claim about marking calendars or some such thing that is now, in retrospect, quite ridiculous. Too bad. I thought it made more sense to extend my hiatus than to come back for another single post and vanish yet again. My vacation has been over for a while, but I've actually had a lot going on. Most importantly, I will be going to a new school in January (the University of Washington) and studying (among other things) inorganic chemistry. It's exciting. But because of this, I've considered shutting down operations here. I've been practically nonexistent on this blog recently, and if I'm too busy with school to ever post again, what's the point of trying to maintain this blog? Well, I'm recommitting myself to this endeavor. I know it seemed like I was doing that in my previous post. Fine. You've got me. I messed up. Just give me one more chance. Maybe. I have plans for this blog and I am almost sure that I know how I want to proceed, but I'll save it for the next post. If my plan works out, next year, despite me going back to school, will be this blog's busiest year so far by, well, a lot. There will be many posts. How many? At least fifty-two. No really, that's my plan.

But we'll save that for my next post, which will not be next year, but sometime soon. I'll try to have at least two more posts this year after the one you're reading now. So bear with me—until my next post, at least. I'm not quite ready for it. But it will be soon. Later this week, even. For now, I'd like to talk about a different subject entirely.

I did get to do some cool, science-related things on my vacation. You know, the one that ended in October that I was supposedly going to come back from and write a bunch of posts here right after that. Yeah, that one. The museums alone gave me a ton of material I could use here (but won't, for now anyway). There was also one, completely unexpected moment that is the inspiration for this post. After a bunch of crap we're not going to talk about right now, I arrived in the city of Bonn on, let's see, the October 3rd. The hostel I had booked was a weird one that didn't have its reception open until 5:00 PM. So I found it from the train station and walked down the street to get some lunch. I had a döner for lunch. I want a döner for lunch every day. They are so good. Almost too good. It's uncanny. Anyway, I was really thirsty, so I hunted down a store where I bought some ice cream and what I thought was orange juice but turned out to be more like orange soda. That sucked, because I hate carbonated beverages, but I was so thirsty that I drank it anyway. When I walked down to the hostel, there were some people talking. One of them was an American who mentioned doing biological research. I asked her about it. We ended up talking for a while, a lot of it about science.

It just so happened that a German biochemist who was there for some reason overheard our conversation. He talked a little about his own research on polyketides. I'd heard of them before, but that was about it. For the past two months, I've occasionally been amused at the realization that I "went all the way to Europe" to learn something. Of course, I knew I would learn things there and actively attempted to do so. But somehow, the realization that I learned some individual thing I could, hypothetically, have learned just as well here, but didn't learn it until I was there is amusing. I was recently made the comment that I had to go all the way to Austria to learn that grated horseradish is awesome. Anyway, I suppose that's how learning things always is. Even when we set out to learn things, we don't know what exactly it is we are going to learn.

From what I recall, he described work on a polyketide produced by bacteria or a series of homologous polyketides produced by bacteria, but the bacteria lived in completely different hosts: one in a beetle, one in a sponge, and one in some other thing I forget. Horizontal gene transfer for the win. Anyway, one thing he emphasized was that polyketides display tremendous variability. I'll spare you pictures because I was recently lambasting my organic chemistry textbook (the one I've been using a lot for this blog) for trying to scare students away with a picture of a big biological molecule. The important thing is that this variability, the incomprehensible number of forms molecules can potentially take is, well, the whole story of biochemistry. Structure determines properties. And those properties, if they're some of the right ones anyway, are what make life possible in the first place. Almost makes me want to switch to majoring in biochemistry...