Introduction to Rearrangement Reactionsby JAMES

in ORGANIC CHEMISTRY 1 ,  ORGANIC REACTIONS

The previous four posts on acid-base, substitution, addition, and elimination covered the 4 main reactions in organic chemistry I. Now it’s time to go beyond those mainstays to introduce a few of the less common (but still important) reactions you learn in organic chemistry 1. They will be rearrangements, radical substitution, and cleavage (oxidative cleavage).Let’s look at rearrangements in this post. As with everything in this series, the point is not to understand why just yet, but to be able to see from the diagrams what bonds are broken and formed. You need to understand how to read line diagrams. But other than that no further skills are required. The point here is to be able to follow the plot – to see what is happening. A later series of posts will go into more detail as to why things happen, but it takes time to build up that knowledge.Rearrangement reactions are really interesting. They can accompany many of the reactions we’ve previously covered such as substitution, addition, and elimination reactions. In fact, if you don’t look closely, sometimes you can miss the fact that a rearrangement reaction has occurred. Let’s look at a substitution reaction first.

On the top is a “typical” substitution reaction: we’re taking an alkyl halide and adding water. The C-Br bond is broken and a C-OH bond is formed. If you look at the table on the right you’ll see this follows the typical pattern of substitution reactions.

However if we change one thing about this alkyl halide – move the bromine to C-3 instead of C-2 – now when we run this reaction we see a different product emerge. It is also a substitution reaction (we’re replacing Br with OH) but it’s on a different carbon. That’s because if you look closely, you can see there are actually 3 bonds broken and 3 bonds formed. The C2-H bond broke and the C3-H bond formed.Very strange!

This represents a rearrangement reaction – when you see a group “move” from one carbon to another. Let’s look at another example.

Here we have an addition reaction. On top, nothing special – as with all additions, we break a C-C double bond (π bond )and form two new single bonds to the adjoining carbons (H and Cl). But look at the bottom example. If we use that alkene instead, we find that the Cl ends up on C3, notC-2. Again, examining the bonds broken/formed, we see that there’s an extra pair of events: the C3-H bond was broken and the C-2H bond was formed. In other words, the hydrogen “migrated” from one carbon to another. Weird!

Finally, let’s look at an elimination reaction. If you take an alcohol like the one below and add an acid (like H2SO4, pictured) and help the reaction along with some heat, you break the C1-OH and C2-H bonds, and form a

new double bond between C1-C2. This is, in other words, a typical elimination reaction.

But if you take a slightly modified alcohol like the bottom example (with an extra methyl group on C1) and try the same reaction, something strange happens again. Analyzing the bonds broken and formed,  there’s an “extra” bond being broken and an “extra” bond being formed here. If you look closely you can see that one of the methyl groups on C1 (we’ll call it C8) moved over to C2.

So what can we conclude about rearrangement reactions?

1. they can accompany many of the reactions we’re already familiar with, such as substitution, addition, and elimination reactions.

2. They involve the “movement” of an atom (H in the top two examples, C in the third) from one carbon to another.

What other insight might we glean from these examples? Here’s two questions.

1. look up, if you don’t know already, what “primary, secondary and tertiary alcohols and alkyl halides are.

2. In the substitution reactions and the elimination reactions, classify every alcohol (or alkyl halide) according to whether it is primary, secondary or tertiary. Notice any difference between the “normal” cases and the “rearrangement” cases?

For more detail on rearrangement reactions, start here: Rearrangement Reactions (1) – Hydride ShiftsNext Post: Introduction To Free-Radical Substitution Reactions

Rearrangement Reactions (1) – Hydride Shiftsby JAMES

in ALCOHOLS ,  ALKYL HALIDES ,  ORGANIC CHEMISTRY 1 ,  ORGANIC REACTIONS

For nucleophilic substitution, the pattern of bonds that form and break is pretty straightforward. You break C-(leaving group) and you form C-(nucleophile). A straight swap. But every once in awhile you might see a “weird” substitution reaction. If you look closely at the pattern of bonds formed and bonds broken in the second reaction below, there’s an extra set!

In other words it’s a substitution reaction where the hydrogen has moved. We call these movements “rearrangements”, for reasons that will become clear shortly.

The big question is, what’s going on? How did this happen? 

As it turns out, reactions that go through carbocations can sometimes undergo rearrangements. And looking back at substitution reactions, recall that theSN1 reaction goes through a carbocation intermediate. In this post we’ll go through when you’ll expect to see a rearrangement reaction.Let’s think back to carbocations. They’re carbon atoms with six electrons bearing a positive charge. In other words, they’re electron deficient – 2 electrons short of a full octet. So it would make sense that carbocations become more stable as you increase the number of electron donating groups attached to them. Alkyl groups are a perfect example. That’s why carbocation stability increases as you go from primary to secondary to tertiary.

(It’s also worth pointing out that carbocations are also stabilized by resonance, which allows the positive charge to be delocalized or “spread out” over a greater area on the molecule.)

So what does this have to do with rearrangements? As it turns out,  if  a situation exists where an unstable carbocation can be transformed into  a more stable carbocation, a rearrangement is possible. One rearrangement pathway where an unstable carbocation can be transformed into a more stable carbocation is called a hydride shift. Look at the diagram below.

In this reaction we have a secondary carbocation on the left hand side. In this rearrangement reaction, the pair of electrons in the C-H bond is transferred to the empty p orbital on the carbocation. In the transition state of this reaction, there’s a partial C-H bond on C3 and a partial C-H bond on C2. The transition state here is kind of like that split second in a relay race where one sprinter is passing the baton to another sprinter and they both have their hands on it. Then, as the C2-H bond shortens and the C3-H bond weakens, we end up with a carbocation on C3 (a tertiary carbocation) in the product which is more stable.Note that we only need one arrow to show this occurring!Here are some examples of “allowed” rearrangement reactions. Notice how we’re always going from a less substituted carbocation to a more substituted carbocation. One exception is at the very bottom; the rearrangement is favorable because the new carbocation is resonance stabilized.

Now we’re ready to show how the rearrangement reaction occurs with the SN1. Recall that the first step in the SN1 is that the leaving group leaves to give a carbocation. In the case below, the carbocation that is formed is secondary, and there’s a tertiary carbon next door. Therefore, a rearrangement can occur to give the more stable tertiary carbocation, which is then attacked by the nucleophile (water in this case). Finally, the water is deprotonated to give the neutral alcohol. So this is an example of an SN1 reaction with rearrangement.

I’ve given some more examples of SN1 reactions with rearrangements below. See if you can draw the mechanisms! In the next post we’ll talk about a slightly different rearrangement pathway with substitution reactions.

Next Post: Rearrangement Reactions (2) – Alkyl ShiftsRearrangement Reactions (2) – Alkyl Shiftsby JAMES

in ORGANIC CHEMISTRY 1

In the last post we saw how certain carbocations can sometimes rearrange (through hydride shifts)to give more stable carbocations.

However, sometimes there are situations where a hydride shift would not lead to a more stable carbocation, such as in this case. If a hydride shift occurred, we’d be going to a less stable (primary) carbocation.

You might note something with this example, however: it is possible for a more stable tertiary carbocation to be formed if an alkyl   group migrates instead!

The most common situation where alkyl shifts can occur is when a quaternary carbon (that’s a carbon attached to 4 carbons) is adjacent to a secondary carbocation. How does this work? Well, the pair of electrons from the C-C bond can donate into the empty p orbital on the carbocation (side note: this means they have to be aligned in the same plane). In the transition state, there are partial bonds between the carbon being transferred and each of the two adjacent carbon atoms. Then, as one bond shortens and the other lengthens, we end up with a (more stable) tertiary carbocation.

Rearrangements can potentially occur any time a carbocation is formed. That includes SN1 reactions (and as we’ll later see, elimination and addition reactions).

 Here’s an example of an SN1 with an alkyl shift (note that the CH3 groups here are just shown as lines).

It doesn’t always have to be a methyl group that moves. One interesting example is when a carbocation is formed adjacent to a strained ring, such as a cyclobutane. Even though the CH3 could potentially migrate in this case, it’s favorable to shift one of the alkyl

groups in the ring, which leads to ring expansion and the formation of a less strained, five-membered ring.Here’s an example of an SN1 where an alkyl shift leads to ring expansion.

Having gone through two types of rearrangements in substitution reactions, the next series of posts will cover a different class of reactions: elimination reactions.

Molecular Rearrangementhttps://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/Questions/Rearang/rngprb1.htm

Six reactions in which molecular rearrangement takes place are shown below. Formulas and some other information about the products are provided. Draw a structural formula for each of the designated products. To draw a formula use the Drawing Window on the right below. Do not draw hydrogen atoms, and do not attempt to indicate stereochemical configurations. When you are finished, check your answer by pressing the appropriate Check Product button.

        

        

A response to your answer will appear in the evaluation window below.