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...

Diastereomeric Alkenes

Yes, it's a new post. I know. I hardly posted at all this year with school, then finished that in June, made two posts, and disappeared. No posts in July or August. It was not my intention to put this project on hiatus. I am sorry I failed you. I don't even know what kept me away for most of this time, but recently, there has been one thing: I am planning a trip. It's a pretty big one, actually. I'll be going to Germany. Since this is going to happen fairly soon and since my German is not so good, working on becoming as fluent in the language as I can be takes priority over writing new posts here. I guess this means I have to go on an actual, planned hiatus. Or, if you prefer, this means I'll have to extend the current hiatus, albeit interrupted by this solitary post. Whatever.

My primary reason for choosing German as a language to learn in the first place was its connection to chemistry. I haven't written about that here, so I'll explain. Germany as a region has long been a powerful contributor to the body of scientific knowledge. This was especially true in the nineteenth century, a formative period for many branches of chemistry. Because of this, in the twentieth century, in American colleges that required students to study a foreign language, chemistry majors traditionally chose German and were often encouraged to do so because it would allow them to access chemical literature that had only ever been published in German. The utility behind this is probably all but vanished these days, as any text that's of practical use to a chemist is probably available in English. But I enjoy history and the prospect of some day being able to read old chemistry texts in German has some sort of allure for me.

The German classes I took this year in school didn't do much in the way of making me comfortable with the language (the instructor mostly just played videocassettes from the 1990's), but they did make me really want to visit Germany. And so, here we are, with me abandoning you yet again. I'm really quite sorry about that.

Rest assured, this blog will be back with a vengeance. After the chapter I've been covering, there's material that I really like and I am excited about presenting it to you. Just seeing this material in the book makes me brainstorm different ways to cover it. There's some really cool chemistry to come once I finish this chapter, which I wish I'd already done over the summer instead of putting it off. So yeah, I should be back home and caught up on everything else by, let's say, October 29th or so. Mark your calendars for late October. Back with a vengeance. Really. More frequent updates. Better updates. Awesome chemistry. But not yet. You'll have to wait for my return. It will totally be worth the wait, though.

In honor of my trip, I'm going to skip ahead a bit to something with an obvious connection to organic chemistry's German roots. We'll return the to the material we were on shortly after I get back. And really, now might be as good a time as any to talk about this. By now, I'm sure you have a decent grasp of one type of stereoisomerism. But as you might have guessed, having a chiral center isn't the only way for stereoisomerism to occur. There are other ways that have nothing to do with a carbon atom bonded to four different groups. In fact, I initially wanted to write a post introducing all of the different ways for this to happen that I knew of, but I couldn't find a way to make it work. I did, once upon a time, say this, though...

Constitutional isomers often have dramatically different chemical properties. Their physical properties differ too. They might have different functional groups. In contrast, stereoisomers don't exhibit such bold differences. Two compounds that are stereoisomers of each other not only have the same atoms, but the atoms are connected in the same way. Their properties are almost identical. But the spatial positions of the atoms are different.

And a chiral center isn't the only way for that to happen. So, here's one of the other types of stereoisomerism, and it's a lot easier to demonstrate graphically in two dimensions than the type you already know about. There's just one thing I've probably never mentioned here that you need to keep in mind: unlike single bonds, there is no rotation along a double bond. Behold...
Can you spot the difference? Don't get too excited about it: everyone else notices it too. Same atoms. The atoms are connected in the same way, with an A and a B connected to a carbon that is double-bonded to another carbon also connected to an A and a B. But the spatial arrangement is different, no matter how we oriented these in three dimensions (try it if you want). We have a notation system (cis/trans) that makes this pretty easy, as seen in the drawing I just made. The "cis" version of this molecule has both A's on one side of the double bond and both B's on the other side of it. The "trans" version has an A and B on each side. They're diastereomers, which you recall from my last post means that they are stereoisomers, but not mirror images of each other. Easy, right?

But what if instead of just having two different kinds of groups, we have three or four? This notation system doesn't have a way to deal with those situations! For that, we need the E,Z system as my textbook calls it or Z-E Isomerie as the German Wikipedia calls it. And it's at this point that I realize I've gotten ahead of myself. In order to explain this, I need to use information that would come from a post I haven't written yet, probably the post I was supposed to have written if I didn't skip ahead to this section because I remembered it having something German in it. So despite my failure here, this still seems like a good post to end on before my trip.

If I had class, I'd rewrite this post and just make the whole thing be about cis/trans notation and save E/Z for later. Since I don't, I'll find some way to squeeze the German connection into this post. E and Z are really just more comprehensive versions of cis and trans, which themselves come from Latin instead of German: "cis" means "on the same side" or something like that and "trans" means "across" probably. In the E/Z system, each group is assigned a priority, but I haven't yet written about the rules for determining priority. They're the same ones that are used in the notation system for chiral centers, which is yet another Latin-based system. But since this simpler system already has the Latin words, for the comprehensive system, we use the German words. Crazy, I know. Eventually, I hope to show some examples of names of molecules with "E" or "Z" in them. "Z" stands for zusammen (together) and "E" stands for the word entgegen (against). I leave it to you to figure out which one corresponds to "cis" and which one corresponds to "trans."

Meso Compouds

Remember way back when I said this?

A molecule that contains more than one stereogenic center might be chiral, but it might not. More on this later.

Well, it's later now. This post is on meso compounds. Please, no jokes about the name. Mostly because I am lazy, I will just start with the exact same example as this textbook: 2,3-dibromobutane.
And of course you spotted the tetrahedral stereogenic centers, right? We have a carbon attached to a methyl group, a hydrogen, a bromine, and another, identical carbon. So that's two chiral centers.

I don't think that I've mentioned it so far, but a molecule with two chiral centers can have, at most, four stereoisomers. I suppose that at this point I should introduce wedges and dashes to make three-dimensional interpretations of these stereoisomers, but I won't, so there. Actually, I should have done that a while ago. Fine, I'll get around to it at some point. Moving on...

Anyway, I'll probably just make a video to explain this, because it's even worse than trying to explain what a tetrahedral stereogenic center is using just words. But the short version is that we can arrange the bonds around both centers to have one version of the molecule, take its mirror image and have a pair of enantiomers, then take one of those forms and switch two bonds to have a third stereoisomer that is neither superimposable on either of the previous two molecules nor a mirror image of either of them. But this molecule is superimposable on its mirror image, so it has no enantiomers. It is achiral, even though it has two stereoisomers that are chiral. And that makes it a meso compound.

Also, the term for the relationship between stereoisomers that are not enantiomers is diastereomers.

Tetrahedral Stereogenic Centers in Cyclic Compounds

A carbon atom that is part of a ring can potentially be a tetrahedral stereogenic center. It should be so obvious that I don't need to tell you this, but I'd better do it anyway: since two of the bonds on the potential center must attach in the ring, the two remaining bonds must be to two different substituents. Just to be safe, I shall illustrate this graphically.

So here is an example of a ring carbon that is not a tetrahedral stereogenic center...
And here is one that is...
That's pretty straightforward. Now, don't cry or anything, but that is not quite all there is to it. There is one more detail about this that sort of warrants a separate post. I think even you will find it rather easy, in principle. There is one further requirement in order for this hypothetical carbon atom to serve as a tetrahedral stereogenic center: there must be some difference between the two bonds in the structural sequence of the ring as we trace the path around it. No really, I worded it that way on purpose to dishearten you. It's actually not difficult.

We start with the central carbon atom and move along both ring bonds. Are the atoms that those two bonds attach to the same? And are the atoms that those atoms attach to the same? And so on. Eventually, both paths will converge (halfway across the ring). If both of those paths are identical, then the carbon in question is not a tetrahedral stereogenic center. However, if the paths are different, then the carbon is a tetrahedral stereogenic center.

And that's it! But just to be sure you don't forget about this, which you will anyway, let's demonstrate with an example. My textbook uses this example. Here's a compound that is achiral...
You've been practicing your nomenclature, right? So you already know that this is a skeletal structure for methylcyclohexane with one of the hydrogens drawn in for some reason. The reason is that the carbon we're focusing on is attached to that hydrogen, a methyl group (Me), and twice to the ring. But tracing both paths along the ring, we find that they are identical, arriving at a ring carbon attached to two hydrogens, a ring carbon attached to two hydrogens, and then meeting halfway along the bond between two ring carbons. So what we have is not a tetrahedral stereogenic center and this molecule is achiral.
If you only learned how to name compounds from this blog, you would not yet know that this is 3-methylcyclohexene. Don't worry about that. The important thing here is that, as before, we have a carbon attached to a methyl group, a hydrogen, and twice to a ring. However, this time, as we trace the paths of both ring bonds, going one way takes us to a ring carbon attached to two hydrogens and going the other way takes us to a ring carbon attached to one hydrogen and double-bonded to another ring carbon. The paths are not identical, so we have a tetrahedral stereogenic center, and this molecule is chiral.

Video!

Since you still don't get how tetrahedral stereogenic centers work, I made a video to help explain it. If that doesn't work, I don't know what to tell you.

Introduction to Determining Chirality

Stereoisomerism can be a lot trickier to identify than constitutional isomerism. With this in mind, and to some extent because I am too busy to make really good posts right now but also want to keep this project moving, there will be a series of short posts on the subject, starting with this one.

In order for any of this to make sense, you need to understand what it means for a particular atom to be a tetrahedral stereogenic center. Don't panic. Just peruse the previous entry and make sure you grasp the concept I am describing. The pictures are probably best for this, but what we're basically dealing with are atoms attached four different groups. This is because when an atom (usually carbon) is attached to four different groups, it is not superimposable on its mirror image. And, if it helps any, this concept can be extended to macroscopic things in our everyday lives. The textbook contrasts gloves and socks. In a pair of socks, the two individuals are identical (usually). But in a pair of gloves, the right glove and the left glove are not interchangeable.

Chiral molecules are like gloves (or shoes, for that matter). Even though the properties of the isomers are virtually identical, they are, in principle different from each other and these differences can manifest in ways that are relevant to us. An obvious demonstration of this is in pharmaceuticals, where often only one of the isomers has the desired effect, but the drug is sold and administered as a mixture of both versions. I should do a post on the thalidomide incident. Not right now, though. But maybe later.

Anyway, this isomerism can show up in other types of situations and hopefully I'll soon get to some of them, but for now, we shall focus on chirality that arises from tetrahedral stereogenic centers. Here are some points to keep in mind about these types of chiral molecules.

1. A molecule for which the mirror image is superimposable is achiral. A molecule for which the mirror image is not superimposable is chiral.

2. A carbon that is bonded to four groups, none of which are identical to each other, is a stereogenic center (aka chiral center). This does not necessarily mean that the molecule itself is chiral as we shall see.

3. A molecule that contains exactly one stereogenic center is chiral. Always. No exceptions.

4. A molecule that contains more than one stereogenic center might be chiral, but it might not. More on this later.

Stereogenic Centers

The fifth chapter in this textbook is all about stereochemistry. I considered skipping it, but decided against it. However, for now I am skipping a lot of the fourth chapter. It's not that I'm tired of alkanes, it's just that the remaining sections dealt with conformations and I'd rather get back to that stuff later.

While constitutional isomerism is interesting, most of the time we'll be discussing constitutional isomers in terms that they are completely different compounds. It's just important to keep in mind that they are made up of the same atoms in the same proportions. In case you've forgotten, the thing that makes compounds constitutional isomers is that the atoms are connected to each other in different ways for each molecule.

Constitutional isomers often have dramatically different chemical properties. Their physical properties differ too. They might have different functional groups. In contrast, stereoisomers don't exhibit such bold differences. Two compounds that are stereoisomers of each other not only have the same atoms, but the atoms are connected in the same way. Their properties are almost identical. But the spatial positions of the atoms are different.

There are multiple ways for molecules to exhibit stereoisomerism. But we won't go over all of them at once. Instead, we'll take this slowly. It seems only natural to start with the case of stereogenic centers, specifically tetrahedral chiral centers, but don't worry about those terms right now. The important thing to grasp is the concept.

I am a big fan of the written word. I strive to be as good as I can at communicating concepts verbally. However, this concept is just so much easier to convey using a picture. So here you go.
I made this in ChemSketch and it's supposed to be CHBrClF (a carbon attached to a hydrogen, a bromine, a chlorine, and a fluorine). It doesn't really matter what the things attached to the central carbon are, though, so long as they are all different things. They could be other atoms or even organic groups like methyl, ethyl, and so on. A carbon (or another atom) attached to four groups, none of them identical, is a stereogenic center. It is chiral because it is non-superimposable on its mirror image. Here's the mirror image.
I had to mess around with the program a bit to get this to work, but other than that, does it look exactly the same as the previous molecule? Yes? Look again. With the white ball (representing hydrogen, but whatever) on top, we can look down and starting from brown and going clockwise, we will necessarily have a different order for each of these. It's unavoidable. They're almost the same, but they're different in this one respect. A classic example is the difference between a right hand and a left hand. But for this type of stereoisomerism, all that we need is one central atom with four different groups attached to it. Usually, the central atom is carbon and one or more of the groups are part of an organic molecule (rather than just the single atoms used in my example).

Examples of Naming Cyclic Alkanes

Once again, I steal some problems from my textbook and do them here.
It's a ring made of six carbons, so it's a cyclohexane. Only one of the positions in the ring has any groups attached to it, and both groups are methyl groups, so it's 1,1-dimethylcyclohexane.
Another cyclohexane, obviously. This one has two groups at two different ring positions. The positions are across from each other in a 1,4 relationship. But which group gets numbered "1" and which one gets numbered "4"? Well, one is a methyl group and the other is a butyl group (four carbons in a straight chain). Alphabetical order determines which one comes first, so this is 1-butyl-4-methylcyclohexane.
The chain is bigger than the ring this time. So this compound is, as far as naming goes, defined as a five-carbon chain with a group attached at the first carbon, and the group that is attached is a cyclopropane ring. Therefore, we have 1-cyclopropylpentane.
The ring is a cyclopentane. Three groups this time, and all of them methyl groups, which makes naming this easy. Almost so easy that you could do it by yourself. But how do we number these groups? It doesn't matter which way we count, the smallest number we can start with is 1. This compound is 1,2,3-trimethylpentane.
This one is trickier. We definitely have a cyclohexane ring, but what are those groups attached to it. Well, let's start with the smaller one. It's an isopropyl group. See that? Probably not. Well, I told you, so now you know. Isopropyl group. The other one has four carbons. You might remember that there are four such groups possible. And if you have really been paying attention, it's clear that this is a sec-butyl group. Alphabetical order again, but the only prefix that matters for that is "iso-." That means the sec-butyl group is first. So this compound is 1-sec-butyl-2-isopropylcyclohexane.

Well, that's way that I learned to name this. And it's even the name that my solutions manual gives. But ChemSketch generated a different name that I am guessing is the true systematic name using proper IUPAC rules. The only difference is that the groups can't be written as isomeric forms of their straight-chain versions. This makes the nomenclature a bit messier (but it also scales up nicely, while the shortcut I'm using doesn't.

And that, children, is how to name cycloalkanes. I don't actually know what topic I'll cover next. You'll just have to wait to find out.

Nomenclature of Cycloalkanes

This will not cover all cycloalkanes. In fact, for now we're only dealing with compounds that have a single ring. But then I didn't really cover all acyclic alkanes either. But what you should have with this post is a basic idea of cycloalkane nomenclature.

Rings themselves are named by how many carbons they consist of. So, for example, this molecule...
...is cyclohexane. But you already know that, of course. I mean, you do, right? You'd better, seeing as I already told you that this is cyclohexane. Yes, it was back in October, but so what? I mean, you are supposed to read and remember everything I write here. You know, I'm getting the feeling that you're not being much of a team player here. Yeah, it sure seems like I'm the one doing all the work. Look, it's just cyclohexane. It's not complicated. It's a simple molecule with a simple name. Four syllables. That's not too many. Cyclohexane. Cyclohexane. Cyclohexane. And don't you forget it.

Speaking of earlier posts, in this one I showed cyclopropane. Unless you're as awful at geometry as you are at chemistry, you should be able to make the connection that if the triangle is cyclopropane and the hexagon is cyclohexane, a square is cyclobutane and a pentagon is cyclopentane. Yes, and a heptagon is cycloheptane and so on. All we're doing is using those chemical numeric prefixes I showed earlier and counting the numbers of carbon atoms making up the ring. You can count, right? You can at least do that much.

But watch out. Not everything in the molecule is necessarily part of the ring...
That is methylcyclohexane (in glorious 3-D). Seven carbons, but only six of them form a ring. The pesky seventh one is attached to the ring. And if you've already forgotten how skeletal structures work, the hydrogens attached to the carbons are not drawn in. All but one of the ring carbons has two hydrogens. One of them has only one hydrogen and is also bonded to that carbon outside the ring, which itself has three hydrogens. So it's a methyl group. Hence the name: methylcyclohexane.

Of course multiple groups could be attached to the ring. In that case, we use numbers. This compound...
...goes by the name 1-ethyl,3-methylcyclohexane. And if you think in terms of the rules you learned for acyclic alkanes, this makes sense. We have to number the positions on the ring somehow. So we're starting at first substituent alphabetically. Here, I'll even put the numbers in...
This system of numbering positions on rings will be used a lot in the future, so you should be comfortable with it. But it seems straightforward enough to me, so I'm not going to reiterate it further.

We might also end up with two groups attached at the same position on a ring. Not to worry...
That's 1,1-dimethylcyclopentane. The same general principles from naming acyclic alkanes still apply. This does run into limitations of course. I won't be covering those now. But I do think that I should to a follow-up post in which I name some examples from homework problems in the textbook. And just so that you can follow along, there is one more tiny little thing that you need to know about cycloalkanes. If a ring is attached to a hydrocarbon chain that is longer than the number of positions in the ring (like if a cyclopentane ring had an octane chain attached to it), the compound is named based on the chain (so that example I just made up would be 1-cyclopentyloctane).