Directing Effects in Substituted Pyrroles, Furans, and Thiophenes - Online Tutor, Practice Problems & Exam Prep

Directing effects in heterocyclic compounds mirror those in electrophilic aromatic substitution (EAS) on benzene rings, focusing on ortho, meta, and para positions. The most activating group dictates substitution preference, with ortho-para directors and meta directors identified. For example, bromine is an ortho-para director, while carboxylic acid acts as a meta director. The heteroatom's preference for C2 positions influences the final substitution site, balancing the directing effects of substituents and the heteroatom in reactions like bromination, nitration, and sulfonation.

Directing Effects in Substituted Pyrroles, Furans, and Thiophenes Concept 1

Everyone. So in this video, we're going to talk about the directing effects within our common heterocyclic compounds. Here, we're going to pay close attention to our ortho, meta, and para positions in these 5-membered heterocycles. Now ortho, meta and para terms are limited to substituted benzene rings. However, identical numerical relationships exist for 5-membered aromatic heterocycles.

Here, we're going to compare our substituted benzenes to these substituted heterocycles. For the first one, we have these 2 methyl groups, and we're going to say they're ortho to one another, which means they are C1C2 to one another. We can make this one 1 and this one 2. Now, this is important. When it comes to substituents' relative positions, they're assigned through the carbon skeleton not through the heteroatom.

Now, remember when we're naming these heterocyclic compounds, we make the Heteroatom location number 1. But we're not trying to name these heterocycles, we're just trying to talk about directing effects. So just as in Benzene, these methyl groups are ortho to each other, they're also ortho to each other on this heterocycle. We're going to make this one 1 and this one 2. In the next one, we have carboxylic acid and a nitrile group.

They are meta to each other, C1C3. Just like I'm going to say these 2 are meta to each other, C1C3. And then finally, these 2 bromines are C1C4 to each other which is para. And we're going to say these are C1C2C3C4, also para to each other. Again, this is how we're going to look at the numerical relationship between our substituents on these heterocyclic compounds because that'll help us to apply directing effects to the heteroatom as well as the substituents later on.

Alright. So again, this has nothing to do with the naming of these heterocycles. This is just helping us to apply them to directing effects.

Directing Effects in Substituted Pyrroles, Furans, and Thiophenes Concept 2

We're going to take a look at the directing effects on these common heterocyclic compounds. Now, rule 1 states that directing effects are the same as electrophilic aromatic substitution (EAS) on benzene rings, referring to ortho, meta, and para positions. Recall that for disubstituted rings, the most activating group takes precedence. When it comes to directing groups, we have our ortho para directors and then we have our meta directors.

If you remember your meta directors, everything else is an ortho para director. With your meta directors, you have your nitrile group. Here, you have your positive amine group where R could be carbons or hydrogens. We have our sulfonic acid group, our nitrile, and then our carbonyl groups.

Rule 2 notes that C₂ substitution is always preferred. In the first example, we have thiophene with a bromine attached. Remember, these heterocyclic compounds are more reactive towards EAS than benzene, allowing EAS reactions to occur under milder conditions. Here, we are performing bromination without a Lewis acid catalyst, using only acetic acid instead.

Bromine acts as an ortho para director, so it influences the incoming group to position ortho to it. In terms of numbering, this could be position 2. Sulfur, the heteroatom in our heterocycle, also prefers the C₂ positions. The consensus position where both factors agree is marked by where bromination would occur.

Next, we have a carboxylic acid attached to our pyrrole ring, and we are attempting nitration. Again, this happens under mild conditions, so acetic acid is used instead of sulfuric acid. The carboxylic acid group is a meta director, hence it directs the incoming group to position 3. The heteroatom again prefers the C₂ positions, and they agree on this spot for the placement of the NO₂ group. Thus, nitration occurs there.

Finally, we consider a furan ring with a methyl group, attempting sulfonation. Methyl acts as an ortho para director, aiming for the incoming group to attach ortho to it, which would favor the C₂ position indicated by the heteroatom. This is where the sulfonic acid group would attach.

This illustrates the balancing act between the heteroatom in our heterocyclic compound and the substituents attached to the ring. The C₂ position is always preferred, but we must also consider the substituent to determine what type of directing effect it exerts, either as an ortho para director or a meta director. Keep this in mind when dealing with different types of electrophilic substitution reactions for these heterocyclic compounds.

Directing Effects in Substituted Pyrroles, Furans, and Thiophenes Example 1

Everyone. So in this example question, it says, nitration of the following compound gives a single product. Draw the structure of that product. Well, first of all, our heteroatom is oxygen; it prefers the C2 position. So the open C2 position will be right here.

The methyl group itself is an ortho para director. It wants the incoming group to go ortho or para. The ortho position, which is adjacent to it, is already occupied by this aldehyde, but the 14 position over here is free. The aldehyde itself is a meta director. We could talk about where it wants it to go, But again, meta directors have the lowest precedence in terms of the incoming group.

It wants it to go adjacent to it, so it wants to go to the same position here. So we're going to do nitration here. And so it'll go to that position where they all have agreed. But, again, remember, the meta director really doesn't have any say in where the incoming group goes because it's the least activating group. Well, here, we're going to add our NO2, our nitrile group to this position here.

So this will represent our single product for this given example question.

Write a mechanism for the formation of the mononitrated product of the following reaction.

In this practice question, it says, write a mechanism for the formation of the mononitrated product of the following reaction. So first of all, the heteroatom wants it to go to C2 to it, so it wants it to go here. At the same time, this is an ortho/para director. It wants it to go ortho to it or para to it. Para would be in the same position here. So, we can draw what the product is, and then we'll talk about the mechanism. Here we'd have the NO2 group attaching right here. Now this is nitration, and in this reaction, we're using concentrated nitric acid. So, we'd have 1 mole of this that's going to be protonated by a second mole. So here we're going to protonate. I'm just going to grab this. Oxygen holds onto the electrons. So what we're going to get initially is this. This oxygen decides it wants to make a double bond, so it does, kicking out the water, which is a good leaving group. And this creates our Nitronium ion, which is our electrophile. And this is what our heterocyclic compound will attack in an electrophilic substitution reaction. Alright. So we have that Nitronium ion. This bond here will break, attaching here. And there's an H here. So now we're going to draw what we're going to get initially. OK. So this is going to become positive, and we have an H here and our NO2 group here. We're going to lose our H+. The water that left could come back. Deprotonate here, remove this H. The bond breaks here to reform our double bond, giving us back our aromatic ring. And then we have our nitro group right here. So that can be seen as the mechanism for the formation of this final product at the end where we have our nitro group going to the C2 position of this heterocyclic compound.

Predict the product of the following EAS reaction.

• A.
• B.
• C.
• D.

How can the following compound be synthesized using benzene as the starting material?

In this practice question, it asks how the following compound can be synthesized using benzene as the starting material. We start with benzene, and on the benzene ring, we introduce a chlorine through chlorination. Next, we notice that we have thiophen ortho to the chlorine. Typically, we avoid adding groups ortho to each other, preferring para positions. However, the presence of ortho groups indicates sulfonation took place, blocking the para position, leaving ortho as the only available position. Initially, we perform chlorination using chlorine and iron(III) chloride as the Lewis acid catalyst. Following that, we need to block the para position. Since chloro groups direct incoming groups to ortho and para positions, we use a sulfonic acid group for blocking via sulfonation performed under strong conditions H2SO4. After para position is blocked, we proceed with nitration using nitric acid and sulfuric acid, ensuring the new group attaches at the ortho position. Next, acid hydrolysis is performed using either H3O+ or water with acid to execute desulfonation, removing the sulfonic acid group. Subsequently, to incorporate the thiophen group, we transform the nitro group to an amino group using Lithium Aluminum Hydride or Tin and HCl for reduction. This amine is then converted into a diazonium salt using sodium nitrite and HCl. Finally, the diazonium salt reacts with thiophen, replacing the diazonium group to position the thiophen ortho to the chlorine. Through these steps, we synthesize the desired compound with both groups at the ortho position despite typical steric challenges. This approach required a deliberate sequence of reactions, manipulating the activation of benzene ring positions to achieve the structure with both substituents ortho to each other.

Here’s what students ask on this topic:

What are the directing effects in substituted pyrroles?

In substituted pyrroles, the directing effects are similar to those in benzene rings during electrophilic aromatic substitution (EAS). The heteroatom (nitrogen) in pyrrole prefers substitution at the C2 position. Substituents on the pyrrole ring can be ortho-para directors or meta directors. For example, a carboxylic acid group is a meta director, while a methyl group is an ortho-para director. The final substitution site is determined by balancing the heteroatom's preference for the C2 position and the directing effects of the substituents.

How do ortho, meta, and para positions apply to heterocyclic compounds like furans?

In heterocyclic compounds like furans, the terms ortho, meta, and para are used to describe the relative positions of substituents, similar to benzene rings. Ortho refers to positions 1,2; meta to positions 1,3; and para to positions 1,4. The heteroatom (oxygen in furan) prefers substitution at the C2 position. For example, if a methyl group is attached to the furan ring, it acts as an ortho-para director, influencing the incoming substituent to go to the ortho (C2) or para (C4) positions.

Why is the C2 position preferred in heterocyclic compounds during EAS reactions?

The C2 position is preferred in heterocyclic compounds during electrophilic aromatic substitution (EAS) reactions because it is adjacent to the heteroatom, which can stabilize the intermediate cation formed during the reaction. This stabilization occurs through resonance and inductive effects, making the C2 position more reactive and favorable for substitution. This preference is observed in common heterocycles like pyrroles, furans, and thiophenes.

What are some examples of meta directors in substituted heterocyclic compounds?

Meta directors in substituted heterocyclic compounds include groups that withdraw electron density from the ring, making certain positions less reactive. Examples of meta directors are the carboxylic acid group (COOH), nitrile group (CN), sulfonic acid group (SO3H), and carbonyl groups (such as aldehydes and ketones). These groups direct incoming substituents to the meta position relative to themselves during electrophilic aromatic substitution (EAS) reactions.

How do ortho-para directors influence substitution in thiophenes?

Ortho-para directors in thiophenes influence substitution by directing incoming groups to the ortho (C2) or para (C4) positions relative to themselves. Thiophene's sulfur heteroatom prefers substitution at the C2 position. For example, a bromine substituent on thiophene acts as an ortho-para director, making the C2 and C4 positions more favorable for further substitution. This directing effect is due to the electron-donating nature of the substituent, which stabilizes the intermediate cation formed during electrophilic aromatic substitution (EAS).