Transcription
Benzyl chloride is a really useful building block in organic chemistry, and this is why I'm interested in it. I'm personally going to use it to make something called denatonium benzoate, which is supposed to be the most bitter compound known. What's interesting is that denatonium benzoate is made by reacting benzyl chloride with lidocaine. Very conveniently, I extracted lidocaine in a previous video, so this is what I'm going to use.
Benzyl chloride has also been used historically as a chemical weapon because it's a pretty potent lacrimator. A lacrimator, in general, causes severe eye, respiratory, and skin irritation, as well as pain, vomiting, and sometimes even blindness. The reason for benzyl chloride doing this is when it touches a wet surface, it hydrolyzes and produces hydrochloric acid. A lacrimator, in general, will also stimulate the nerves of the lacrimal gland to produce tears. Anyway, that's a little bit off-topic, but the point in mentioning this is to be very careful because it's a strong irritant. When I worked with it, I didn't wear any sealed goggles, so my eyes were attacked pretty easily. Working with it can be pretty bothersome, but the worst is when you clean out the glassware; it can leave your eyes watery and burning for a few hours even if you wash them out. So it's important to be careful.
There are several ways to make benzyl chloride, but the easiest one is to start with something called benzyl alcohol. We then use hydrochloric acid to do a basic substitution reaction and swap the OH of the alcohol for the Cl in the hydrochloric acid. The benzyl alcohol is soluble, but the benzyl chloride isn't, so our product separates, and then we isolate it. So that's the basic overview, and now we can get started.
I started off by adding 600 milliliters of 31.45% hydrochloric acid to a one-liter round-bottom flask. I then turned on some super strong stirring—very, very strong stirring. I poured in 78 milliliters of benzyl alcohol. Just for safety purposes, the addition should be done relatively slowly. The next thing that we need to do is set up a reflux. This reaction is kind of slow, so we need to heat it to speed it up. In this reflux, we're going to be boiling the solution below, and our cold water condenser above is going to recondense anything that boiled off.
One important thing to note is that I've set up a trap using a beaker and an inverted funnel. When the hydrochloric acid solution is boiled, the condenser will recondense both the benzyl alcohol and the water, but hydrochloric acid vapor will pass through because I don't want to fill my garage with hydrochloric acid vapors for obvious reasons. I set up a trap to neutralize them. As the hydrochloric acid escapes from the funnel, it will be pushed into a sodium hydroxide solution, which will neutralize it. It might be a little bit hard to see, but there is a tube leading from the top of the condenser to the funnel. Here's a closer shot of the trap, and this is how I set it up. I just pour in a random amount of sodium hydroxide; then, on top of this, I pour in some water, just enough to cover the mouth of the funnel.
With the trap set up and our condenser running, we're ready to start the reflux. As the solution heated up, it became cloudy. If we look back at our trap, you can see a little bit of bubbling coming out. Eventually, we'll know we've achieved a reflux when there's liquid dripping back into the flask. We don't have to carry out the reflux very long, and we only have to keep it at boiling for around 10 minutes. Once we've heated it for 10 minutes, we can take it off heat and let it cool.
The purpose of the inverted funnel is illustrated here. Our apparatus is a closed system, and as it cools down, the air will contract and pull a slight vacuum. This will pull water from our trap into our apparatus. With the inverted funnel, you can see that it does suck back up, but the water never makes it to the tubing. If we use just a tube and no inverted funnel, water would be sucked very easily back into our apparatus and into our reaction flask.
As the reflux cools, you can see a layer forming on the top, and this is the product, benzyl chloride. I'll also take the time as it cools to talk about what happened in this reaction. So what we were doing was reacting benzyl alcohol with hydrochloric acid to produce benzyl chloride and water. In the introduction, I mentioned that benzyl chloride reacts with water and can form hydrochloric acid, so you might wonder how we're supposed to get a decent yield from this reaction when we use so much water. The answer to this is that it's actually an equilibrium reaction. So you are right to think that water is going to be hydrolyzing some of the benzyl chloride; however, the rate of hydrolysis is actually relatively pretty slow, and by including a large excess of hydrochloric acid, we're strongly favoring the forward reaction. In general, the hydrolysis of benzyl chloride in hydrochloric acid is extremely slow to non-existent.
Anyway, I'll quickly go over what's happening in this reaction and how the chlorine and the OH switch positions. So what's going on here is known as a substitution reaction. Logically, this makes sense because we're simply substituting an OH for a chlorine. Hydrochloric acid is a strong acid, and in water solutions, it's completely dissociated into H+ and Cl-. Under these strongly acidic conditions, the OH of the benzyl alcohol is going to be protonated. When the OH is protonated, it forms H2O, which is water, and it's very stable on its own and kind of wants to detach from the molecule.
Now, this is a part where things get a little bit tricky. In substitution reactions, there are two main types: SN1 and SN2. If this were an SN1 reaction, the water would leave, and there would be left behind a positive charge on the carbon. This positive charge would then be attacked by the negative chlorine, and this would form our final product. If this were an SN2 reaction, no positive charge would form, and instead, the chlorine would attack at the exact same time that the water is popping off.
So now the big question is which mechanism is it going to follow, and how would we know this? The main factor that will determine the mechanism is the substitution count of the carbon that's attached to the water. This basically means we need to know how many other carbons this carbon is attached to. As I showed before, an SN1 mechanism requires the formation of a positive charge, which isn't very favorable, so it's only really going to happen if the charge can be stabilized somehow. The carbon with the positive charge is most stable when it has three other carbons attached to it. I won't really get into much detail why, but the other carbon groups can donate a little bit of electron density and reduce the severity of the positive charge. When there's only one carbon attached, there isn't as much electron density that can be donated, so the carbon with the positive charge isn't as happy. Because of this, the trend for SN1 is its most favorable when the carbon has three other carbon substituents; least favorable when it only has one. The trend for SN2 is the exact opposite, and this is also mostly due to substitution count because we need this chlorine to come around and attack. If there's lots of stuff in the way, namely other carbon groups, it's going to have a hard time doing this. It, therefore, has the easiest time when there's only one other carbon attached because there's nothing in its way to block it from attacking.
When the carbon only has one substituent, the mechanism is pretty clear-cut because SN1 is really not favored, but SN2 is highly favored. The same thing goes for the tertiary, or when there are three carbons attached; the SN2 is highly unfavored, and the SN1 is highly favored. The hardest part is when we're working with a secondary carbon because this is going to be a mix of both mechanisms, and it's kind of hard to predict which one will predominate. Anyway, that's a huge tangent and a topic for another video, and I think we should get back to the reaction at hand.
So, knowing everything that I just explained, when we look at our benzyl alcohol, we see that the carbon attached to the OH is a primary carbon. Things get a little bit complicated here because, although it's a primary carbon, its only substituent is an aromatic ring. Without going into too much detail, the aromatic ring is capable of stabilizing this positive charge through something called resonance. So, instead of the positive charge lying just on the primary carbon, it's actually spread out across the ring. This stabilizes it and actually allows us to have a charged primary carbon and undergo SN1 reactions. So what happens is we actually get a mixed combination of SN1 and SN2, like we would if we were working with a secondary carbon. We get SN2 because it's a primary carbon, and generally primary carbons favor an SN2, but we also get SN1 due to the stability given by this aromatic ring. Anyway, that was a lot longer than I thought it was going to be, but I hope you enjoyed the little tidbit of more in-depth chemistry.
Once it had cooled, the entire apparatus was dismantled, and I placed the stopper in the top. I then set up a one-liter separatory funnel and poured in all of the contents of my flask. The one-liter flask was washed with a little bit of hydrochloric acid to get out any benzyl chloride that might remain. It's going to be hard to remove everything, though, and there will be some leftover in the flask. The top of the separatory funnel is then capped, and I let it sit here until the layers separate. The stopper at the top is then removed, and the aqueous layer below is drained away. Remember that the layer below is pretty much just acid and it must be handled with care. It will also have very small amounts of benzyl chloride dissolved into it, so this also must be taken into account. Anyway, the bottom aqueous layer is removed, and we're left with a nice, crystal-clear layer of benzyl chloride above.
We now have to clean up the benzyl chloride, and to do this we start by adding 50 milliliters of saturated sodium bicarbonate solution. This will react and remove any hydrochloric acid that remains dissolved in the benzyl chloride. After the bicarbonate solution is added, we cap, shake it, and vent frequently. When neutralizing acid with sodium bicarbonate, we produce a lot of CO2 gas, so it's very important to vent frequently. Then, just like before, we put it back on the stand, and we let the layer separate. Our bottom layer this time is actually the benzyl chloride, and we drain this off. The upper layer is our sodium bicarbonate solution, and we drain this off and discard it. The benzyl chloride is then poured back into the separatory funnel, and we wash it again with 50 milliliters of sodium bicarbonate solution. For the sake of time, I don't show the second washing here, though. It's washed one last time with 100 milliliters of saturated sodium chloride solution. The sodium chloride solution serves to pull water out of the benzyl chloride and dry it up a little bit. This was our final washing step, but the benzyl chloride was still white due to the presence of water. I then poured some sodium hydroxide solution into the separatory funnel to neutralize the benzyl chloride that remained in it. We see here our still crude benzyl chloride product that's white. To clear it up, we'll have to remove the water, and to do this we'll use a drying agent. In my case, I decided to use calcium chloride, and I dumped a whole bunch in. I really didn't measure how much I used, and I almost definitely used way too much. After mixing it and then letting it sit for a while, we can see we have a nice clear solution.
Although the solution is nice and clear, it's still crude, and we have to distill it. So the benzyl chloride is simply decanted into a round-bottom flask. We then carry out a fractional distillation of the benzyl chloride. There's a significant amount of contaminants mixed in with the benzyl chloride that we have, and using a fractional distillation lets us have the best separation. I use a heating mantle for this distillation, and I didn't have one small enough for the round-bottom flask, so I had to adapt to it using some aluminum foil. So with stirring, we start to heat our crude benzyl chloride. One important thing to do is to insulate both the flask and the column. If this isn't done, the benzyl chloride will probably recondense inside the column before it even makes it over. So after a short period of time, you can see we have a pretty violent boil going on in the flask. You can actually see where the benzyl chloride is recondensing on the colder part of the glass. It's going to take a little while because the benzyl chloride is going to have to warm up the entire flask and the entire column before anything passes over. We have to look closely at the temperature of the thermometer, and we only start collecting at around 177 degrees Celsius. Everything that comes over below this temperature is discarded. So when we hit 177 degrees Celsius, I quickly removed the round-bottom flask and placed on a new one. We've fixed this round-bottom flask in place, and we keep collecting. We collect everything between 177 degrees Celsius and about 180. The moment the temperature goes up higher than 180 degrees Celsius, we stop the distillation, and we remove our flask. Benzyl chloride has a boiling point of around 179, so the bracket of 177 to 180 is good. Collecting anything above or below this bracket would be contamination.
When the distillation is done, we're left with a high-boiling yellow liquid in the flask. At this point, you must be careful because all of the glassware is going to be coated with benzyl chloride. To clean the glassware, we're going to first have to wash it with sodium hydroxide solution. I pour some into the round-bottom flask to neutralize the remains, and then I place it on the side. I then pour sodium hydroxide solution through the column to neutralize any benzyl chloride that's stuck in there. The rest of the apparatus is also cleaned with sodium hydroxide solution, and then it can be cleaned with water as usual.
To the benzyl chloride we've collected, it's still a little bit cloudy due to the presence of water. To dry it up, I pour in a bunch of molecular sieves. These will selectively pull water out of the benzyl chloride and dry it. After leaving it for about an hour, we're left with a very nice clear solution of benzyl chloride. I then prepared a small bottle by filling it a little bit with molecular sieves and sealing the top with Teflon tape. Into the bottle, I decant my benzyl chloride but leave the molecular sieves behind. This way, when the benzyl chloride is put away to storage, it sits with fresh molecular sieves. I put Teflon tape on the top to really make sure that the cap is sealed well and that no benzyl chloride leaked out. I then capped it nice and tightly and labeled the bottle.
So, in the end, the final yield was 69 grams of benzyl chloride. This corresponds to a yield of about 73%, which is pretty much expected. As I said before, I'll be using the benzyl chloride to make denatonium benzoate, and I'll post this in a future video. I already filmed it, but I filmed it with my new camera, and I'm trying to get all of the footage that I filmed with my old camera out first. Again, here's a list of the videos that I'm currently editing and future videos I plan to film. In the videos being edited category, you can vote for the one that you want me to publish next, and in the future video category, you can vote for the one that you want me to film next. Also, if you're feeling generous, please donate to my Patreon account because with a bigger budget per video, I can do more things. Also, instead of stockpiling videos, I've decided I'm going to publish them as soon as I edit them, so in the next month or so, there's going to be a lot of videos coming out on my Patreon. I also added a milestone, and if we get to 250 per video, I'll commit to doing videos for at least six months.