Carboxylic Acid to Acid Chloride - Online Tutor, Practice Problems & Exam Prep

Carboxylic acids can be transformed into various derivatives, including acid chlorides, amides, and nitriles. Acid chlorides, the most reactive acyl compounds, are typically synthesized using reagents like SOCl₂, PCl₃, or PCl₅. To form amides, carboxylic acids react with ammonia, often requiring heat or the dehydration agent DCC to improve yields. Nitriles are primarily produced by dehydrating amides using P₂O₅ or SOCl₂. Nitriles can be hydrolyzed back to carboxylic acids, typically in an acid-catalyzed reaction.

Synthesis of Acid Chlorides

On this page, we're going to focus on those specific Z-type reactions that turn carboxylic acid into other types of derivatives. We're going to go a little bit more in-depth on specific reagents that can transform certain types of derivatives to each other. The first one is the synthesis of acid chloride. This should be difficult to do because if you remember, acid chloride is the most reactive acyl compound. It's all the way over here. To get carboxylic acid all the way over here, I'm going to need a strong reagent. That's exactly what we're going to use. You guys should have probably seen this reaction already at some point in organic chemistry. But the most common reagent to do this is SOCl₂. That's a very common reagent to add chlorine to all kinds of things, to alcohols and to carboxylic acids. But there are other reagents we can use. We can also use that's supposed to be an or. We can also use PCl₃ or PCl₅. These reagents are full of chlorines and they're particularly good at turning a carboxylic acid into an acid chloride. This is helpful for us synthetically because once you have an acid chloride, you can turn that into any other derivative because of how reactive it is in very high yields. Awesome. Let's move on to the synthesis of amines.

Synthesis of Amides

According to my three rules, would it be favorable to turn a carboxylic acid into an amide? Does that go in the right direction in terms of favorability? Remember that carboxylic acid was in the middle of the page and amide was all the way on the left side. Yes, it would be because carboxylic acid is more reactive than an amide. That's exactly what we see. When you react carboxylic acid with ammonia, you are going to get some amide. But there is a problem.

It turns out that the energy difference between these two acyl compounds isn't high enough to give us good yields of amides. Actually, what winds up forming predominantly is an ammonium salt. The way around that is to use a lot of heat when you're doing this reaction. If you use a lot of heat, you can dehydrate the salt back to an amide. This reaction actually does follow the three rules.

You're thinking, "Why are you teaching me this if we already learned it in the three rules?" Because it turns out that your yield is just a little bit too low to make it a great way to synthesize an amide. You have to use heat in order to force it to make the amide. It turns out in order to avoid those harsh heat conditions, chemists have found another molecule that's a dehydration agent. This dehydration agent is called DCC. Here I've shown you what the structure is. You might not need to know what the structure is, but you should know that DCC and this are the same thing. DCC, when coupled with NH3, dehydrates the amide by itself. We don't need heat. It greatly increases our yield. Instead of having to use a lot of heat to get amide, we can combine NH3 with DCC and we're going to get a huge yield of our amide.

Many times, you're going to see this agent, DCC, used to boost these reactions that are already favorable but to make them happen at higher yields. The whole point of this area is that you'll understand what the role of DCC is. Let's move on to the next one.

Dehydration of Amides

We've been talking this whole time about how nitriles are carboxylic acid derivatives. But not once have I mentioned how to actually make a nitrile. It turns out that they're not that easy to make. There's actually only one reagent that we're really going to learn in this course that helps us or one type of reaction. That's a dehydration reaction. It turns out that really the major way to make nitriles in this course is going to be to dehydrate amides. This is a mechanism that I'm not going to teach you and that you're most likely not responsible for. I've never seen it on an exam. You should just know the reagents for it. We're going to use either P2O5 which is also seen sometimes as P4O10. It should be a dimer of that compound. I'm just saying this is the same thing. Or you can use SOCl2. Both of these reagents are going to dehydrate the amide and turn it into a nitrile. Why is that important? Because this is the only way to make a nitrile up until this point. We've never learned another way to do it and this helps to bring it into the family of carboxylic acid derivatives. If I want to make a nitrile, I know I have to make the amide first, and then I dehydrate the amide. Let's move on to our last reaction.

Hydrolysis of Nitriles

Finally, we know that by definition, nitriles can be hydrolyzed to carboxylic acid. This happens both in base and in acid. But typically, it's an acid-catalyzed reaction. As you can imagine, you wind up getting water attacking the carbonyl. You wind up kicking electrons up to nitrogen. I'm not going to show you guys the whole mechanism here, and it's not a mechanism that is highly emphasized in this section. But you can imagine that what you wind up getting is something that has like an imine derivative. You end up with something that looks something like this. From there, we have an acid workup. Since we're already in an acidic environment, it's not hard to imagine how through an acid workup, this imine derivative could be turned into a carboxylic acid. That's really all I want to mention. I'm much more interested for you to just memorize these reagents and not specifically know their mechanisms since these are not very important mechanisms for this section of the course.

Let's move on to the next page.

Here’s what students ask on this topic:

What reagents are commonly used to convert carboxylic acids to acid chlorides?

The most common reagents used to convert carboxylic acids to acid chlorides are thionyl chloride (SOCl₂), phosphorus trichloride (PCl₃), and phosphorus pentachloride (PCl₅). These reagents are effective because they are rich in chlorine atoms, which facilitate the substitution of the hydroxyl group in the carboxylic acid with a chlorine atom, forming the acid chloride. The general reaction can be represented as:

$R_{-\mathrm{COOH}}+{\mathrm{SOCl}}_2\to R_{-\mathrm{COCl}}+{\mathrm{SO}}_2+{\mathrm{HCl}}_{}$

Why is SOCl₂ commonly used in the synthesis of acid chlorides?

SOCl₂ (thionyl chloride) is commonly used in the synthesis of acid chlorides because it is highly effective and efficient. It reacts with carboxylic acids to replace the hydroxyl group with a chlorine atom, forming the acid chloride. The reaction also produces sulfur dioxide (SO₂) and hydrogen chloride (HCl) as by-products, which are gases and can easily be removed from the reaction mixture. This makes the reaction clean and straightforward. The general reaction is:

$R_{-\mathrm{COOH}}+{\mathrm{SOCl}}_2\to R_{-\mathrm{COCl}}+{\mathrm{SO}}_2+{\mathrm{HCl}}_{}$

What is the role of DCC in the synthesis of amides from carboxylic acids?

DCC (dicyclohexylcarbodiimide) acts as a dehydration agent in the synthesis of amides from carboxylic acids. When carboxylic acids react with ammonia (NH₃), the reaction typically produces low yields of amides due to the formation of ammonium salts. DCC helps to dehydrate these salts, converting them into amides without the need for high temperatures. This significantly increases the yield of the desired amide product. The reaction can be summarized as:

$R_{-\mathrm{COOH}}+{\mathrm{NH}}_3+{\mathrm{DCC}}_{}\to R_{-\mathrm{CONH}}+{\mathrm{DCHU}}_{}$

How are nitriles synthesized from carboxylic acid derivatives?

Nitriles are synthesized from carboxylic acid derivatives primarily through the dehydration of amides. The reagents commonly used for this dehydration process are phosphorus pentoxide (P₂O₅) or thionyl chloride (SOCl₂). These reagents effectively remove water from the amide, converting it into a nitrile. The general reaction can be represented as:

$R_{-\mathrm{CONH}}+P_2{O}_5\to R_{-\mathrm{CN}}+H_2{O}_{}$

Can nitriles be converted back to carboxylic acids? If so, how?

Yes, nitriles can be converted back to carboxylic acids through hydrolysis. This process can occur under either acidic or basic conditions, but it is typically acid-catalyzed. During hydrolysis, water attacks the carbon in the nitrile group, leading to the formation of an imine intermediate, which is then further hydrolyzed to yield the carboxylic acid. The general reaction under acidic conditions is:

$R_{-\mathrm{CN}}+H_2{O}_{}\to R_{-\mathrm{COOH}}$