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).

A Note on Complexity and Isomerism

My textbook has a table with information that I did not include in my last post, but that may improve understanding of isomerism. In case it is not obvious, the number of isomers grows with the size of a molecule. In my last post, I showed the two isomers of butane. Larger alkanes have even more, because with more atoms, there are more ways to rearrange them. Small alkanes are easy to understand in this regard. A hydrocarbon with one carbon has no isomerism. The same is true for two or three carbons. When we get to four, as already demonstrated, there are two possibilities: a straight chain and one with a branch. Five carbons means three isomers. With seven carbons, we get nine isomers, which is still manageable, but then add a single carbon and there are eighteen isomers. The table ends with icosane (C₂₀H₄₂), which has 366,319 constitutional isomers.

And that is just acyclic alkanes. There are so many other things to consider, that the complexity is staggering. And that is why we have a systematic method of naming molecules. Anything else would get pretty impractical.

Constitutional Isomers Redux

I suppose that my textbook introduces constitutional isomers in the alkanes chapter because alkanes are pretty straightforward and can ease one into the concept. Constitutional isomers can and do occur in other molecules. Isomerism is when two or more different compounds have the same molecular formulae. In other words, they have the same kinds of atoms and the same numbers of those atoms, but something makes them chemically distinct. Later on, we will explore stereoisomers, and it will be very exciting. But for now, we're looking at constitutional isomers, which differ in the way the atoms are connected to each other. Let's take a look at two molecules that are constitutional isomers of each other...

Name: n-butane (or just butane)
Molecular formula: C₄H₁₀
Condensed structure: CH₃CH₂CH₂CH₃
In stunning 3-D:
Yes, I just figured out that I could render butane three-dimensionally with my nifty software. Anyway...

Name: isobutane (or 2-methylpropane)
Molecular formula: C₄H₁₀
Condensed structure: CH(CH₃)₃
In glorious 3-D:
Both molecules have the same quantities of the same atoms. But the bonds are not identical here. A carbon bonded to two other carbons and two hydrogens is electromagnetically different from one bonded to three other carbons and one hydrogen. Also, the three-dimensional forms are quite different, and when the molecules interact with other bodies (including other molecules just like themselves) the results will be at least slightly different. Although very similar, these two compounds have different chemical and physical properties. They are more like each other than other compounds that have different atoms and other, more striking differences. Because of these facts, we use the term "constitutional isomers" to denote the relationship between these similar molecules.

But when it comes to properties, constitutional isomers are not always so similar to each other as those two. Some constitutional isomers contain different functional groups from each other and, if you remember the importance of functional groups like you should, this means they can have dramatically different chemical and physical properties...

Name: ethanol

Molecular formula: C₂H₆O

Condensed structure: CH₃CH₂OH

In brilliant 3-D:

It's an old friend: ethanol. I don't know how many times I've shown ethanol before, but you had better know that this is what it looks like. And if you managed to actually have some brain capacity, maybe you even remember that this compound is an alcohol, as it has a hydroxyl functional group. Easy, but here's a constitutional isomer of ethanol.

Name: dimethyl ether (or methoxymethane)

Molecular formula: C₂H₆O

Condensed structure: CH₃OCH₃

In spectacular 3-D:
Since the name has "ether" in it, you have deduced, unless you are a total idiot, that this is an ether (the name of the functional group is methoxy in this case). But the molecular formula is the same. The functional groups here are so unlike each other that reactions possible for one would be impossible for the other. Oh, and remember hydrogen bonding? Ethanol has it. Dimethyl ether cannot have hydrogen bonding because there is no hydrogen attached to the oxygen, so these two even have different intermolecular forces. In this way, two constitutional isomers can be quite dissimilar. What kind of atoms a molecule has and how many are very important, but the configuration of the bonds holding the atoms together in a molecule matters a lot too.

Edit: After posting this, I started going back to tag my posts. I noticed that way back in February, I wrote a post about constitutional isomers. I think this new post is better, but here is the old one. If you do not get the concept after reading this post, read the old one. If you still don't get it, tell me, I guess. It seems fairly simple to me and I think I did an adequate job of explaining it both times, but maybe I am wrong...

Constitutional Isomers

Earlier today I said that I was going to do a post on isomers tomorrow. Well, I'm so anxious to talk about isomers that I am starting it early. Only half an hour left until tomorrow anyway as I'm typing this sentence, so maybe I won't finish it until it's tomorrow. We'll see.

Constitutional isomers are compounds that have the same atoms, but arranged in a different structure. This is completely different from resonance structures, because both isomers are real molecules and can have very different properties. So don't get the two mixed up. Remember, resonance structures have double-headed arrows between them. Isomers don't. Because I'm lazy, I'll just use the first example I find in my book...
Both molecules have the same atoms. They each have three carbons, one oxygen, and six hydrogens. But in molecule A, the double bond is between two of the carbons and the oxygen is bonded to a hydrogen. In molecule B, the double bond is between the oxygen and the carbon it's attached to, while the other carbons each have three hydrogens.

Remember how it's bonding that really makes molecules what they are? These compounds have different bonding structures, so I would expect them to have very different chemical and physical properties.

Addendum: People should know what common or important molecules look like. I just realized, as I was about to close my textbook, that "molecule B" is, in fact, acetone, a chemical you might be familiar with. Acetone is an important solvent. I used it in the laboratory all the time in my chemistry classes. It's also in paints and stuff. And it's used to make acrylic glass. As for the other molecule (A), its name is 2-propenol and I'm pretty sure it's just an enol form of acetone, so basically it is highly unstable and will typically turn into acetone by itself. But that's a topic for another day.