Sciencemadness Discussion Board

CCl4 Alternative ?

Plan_B - 8-8-2015 at 22:45

Hello.

I'm trying to brominate a cyclopentyl-ketone.
The literature dictates I use Bromine in Carbon tetrachloride.
What is a good alternative for CCl4 I can use ?


Thanks in advanced!

ParadoxChem126 - 8-8-2015 at 23:17

Chloroform or even dichloromethane will likely work. As long as the solvent is inert to the reactants (including bromine), it can be used.

Plan_B - 9-8-2015 at 01:29

Thank you for your answer!

kecskesajt - 9-8-2015 at 03:11

Chloroform isn't a great idea.It can be brominated.

Pumukli - 9-8-2015 at 05:40

CCl4 has a bit higher boiling point than methylene chloride does. It may cause problems if the reaction temperature is expected to be above say 40 Celsius.

But your question is still valid, it is not always straightforward to find a good alternative to "old-school" chemicals like CCl4. Actually, sometimes I find an interesting synthesis which requires this compound as a solvent and I immediately try to substitute it (mentally) with chloroform or methylene-chloride but sometimes I feel that it might just won't work.

Edit:
I see you found the alternative path: started to search for another brominating agent (NBS) and/or another recipe that does not require CCl4. ;)


[Edited on 9-8-2015 by Pumukli]

ParadoxChem126 - 9-8-2015 at 12:03

Chloroform is unlikely to be brominated under these conditions. A free radical halogenation with bromine requires very strong ultraviolet irradiation and the reaction still is quite slow.

The boiling point of chloroform is likely not a major issue because its boiling point is higher than that of bromine. The temperature during the addition of the bromine solution must be maintained low enough to prevent evaporative losses and boiling of the bromine. An ice bath is often employed for this purpose. Dichloromethane may or may not be suitable depending on the temperatures expected to be reached during the reaction.

On a side note, the boiling point of carbon tetrachloride is only 15 degrees C higher than that of chloroform.

[Edited on 8-9-2015 by ParadoxChem126]

Praxichys - 9-8-2015 at 12:10

I have used tetrachloroethylene for such reactions with good success. It is relatively inert and is sold cheaply around here as automotive brake cleaner in an aerosol can with carbon dioxide. It has a BP of 121C which makes it superior to chloroform and dichloromethane for these types of reactions.

Oscilllator - 9-8-2015 at 17:26

Quote: Originally posted by kecskesajt  
Chloroform isn't a great idea.It can be brominated.

I believe this really only happens under the influence of UV light, so this shouldn't be to much of a problem for OP. Chloroform/dichloromethane is commonly used as a dilutant for bromine so there isn't to much of a risk here.

kecskesajt - 9-8-2015 at 21:33

Quote: Originally posted by Oscilllator  
Quote: Originally posted by kecskesajt  
Chloroform isn't a great idea.It can be brominated.

I believe this really only happens under the influence of UV light, so this shouldn't be to much of a problem for OP. Chloroform/dichloromethane is commonly used as a dilutant for bromine so there isn't to much of a risk here.

UV light isn't avoidable.It will always make radicals.
But at this temperature,It is very slow.

CuReUS - 10-8-2015 at 05:21

can't you just use acetic acid ?
https://en.wikipedia.org/wiki/Ketone_halogenation

PHILOU Zrealone - 10-8-2015 at 08:39

Tetrachloroethylene as mentionned above by Praxichys.
Also used as alternative to CCl4 in dry cleaning laundries!

But also:
Trichlorethylene.
Tetrachloroethane (1,1,2,2).
Tetrabromoethane (1,1,2,2).

CCl4 is toxic and hepatotoxic but so does on a lower extand CH2Cl2, CHCl3 and other halogenated hydrocarbons.
As long as you do it under a good hood using comon sense...you may work with CCl4.

byko3y - 10-8-2015 at 17:22

Man, I was breathing with dichloromethane and chloroform fumes and I'm completely okay. Moreover, some time ago chloroform was used for analgesia. But tetrachlorocarbon is dangerous, because is metabolized into phosgen. Unstabilized chloroform is also dangerous after long or improper storage.
Also, I don't get it how you are going to halogenate anything in unsaturated hydrocarbon - your solvent will be halogenated first. Correct me if I'm wrong.

PHILOU Zrealone - 11-8-2015 at 10:44

Quote: Originally posted by byko3y  
Man, I was breathing with dichloromethane and chloroform fumes and I'm completely okay. Moreover, some time ago chloroform was used for analgesia. But tetrachlorocarbon is dangerous, because is metabolized into phosgen. Unstabilized chloroform is also dangerous after long or improper storage.
Also, I don't get it how you are going to halogenate anything in unsaturated hydrocarbon - your solvent will be halogenated first. Correct me if I'm wrong.

Did you got a blood analysis to say you are completely OK?

In blood analysis you may get liver indicator of toxicity (hepato enzymes).

When I was working in an organic synthesis lab during summer for 1 month with lab T° around 35°C we were performing silica gel chromatography with CH2Cl2 and even if working in a hood to fill the solvent, you had to open it somehow...you could see and feel the vapors of CH2Cl2 flowing outside the hood.
Ambiant T° was very close to boiling point and so vapour pressure was high.

I had a blood analysis prior to the job and a second one afterwards and all hepatotoxicity indicators had increased by a lot. After a while away from lab (jobless) a third blood analysis revealed all indicators back to normal.

So yes you can live without troubles for a while when working with HVOS (halogenated volatile organic solvents), but you may get troubles on the long term...like professional painters that display after a few years nerve decay illness.

CHCl3 was used as aenestetic long ago, but was replaced because of its hepatotoxicity... so does chloral hydrate.

FriedBrain - 11-8-2015 at 11:37

Something may be added: A friend of mine, a very good organic chemist told me once, that it can't be always that easy to change the solvent (e.g. in a bromination), because the intermediates could change and you'll may the yields of the isomers change. But I can just mistaken him, but it sounds possible.
But what you should take care of, is the reaction time/temperature, because Chloroform has some lower boiling point, I would at least reflux longer (if necessary). If it's not necessary, I think Dichloromethane should work just fine.

Sniffity - 11-8-2015 at 14:43

Another issue which hasn't been raised yet is the environmental concerns related to the use of carbon tetrachloride. While you can certainly work safely with CCl4 if you follow proper procedures; the environmental damage caused by CCl4 is still hard to avoid.

If I'm not mistaken, chloroform has much less environmental concerns than CCl4.

FriedBrain - 11-8-2015 at 15:03

Quote: Originally posted by Sniffity  
Another issue which hasn't been raised yet is the environmental concerns related to the use of carbon tetrachloride. While you can certainly work safely with CCl4 if you follow proper procedures; the environmental damage caused by CCl4 is still hard to avoid.

If I'm not mistaken, chloroform has much less environmental concerns than CCl4.


I'm sure he won't do this synthesis in a 100L scale, so the environmental damage is likely none, if he will work with proper precautions and don't just let it all evaporate. Because it's pretty hard to get and so valuable everyone would work economical, so after the bromation the CCl4 can be distilled to have some pure one again. No reasonable waste containing chlorinated hydrocarbons should be poured in the sink or environment of course.

Amos - 11-8-2015 at 16:49

Quote: Originally posted by kecskesajt  
Chloroform isn't a great idea.It can be brominated.


Can you stop making comments like this without sources or details? You might have derailed a completely valid synthesis.

Amos - 11-8-2015 at 16:57

Quote: Originally posted by byko3y  
Man, I was breathing with dichloromethane and chloroform fumes and I'm completely okay. Moreover, some time ago chloroform was used for analgesia. But tetrachlorocarbon is dangerous, because is metabolized into phosgen. Unstabilized chloroform is also dangerous after long or improper storage.
Also, I don't get it how you are going to halogenate anything in unsaturated hydrocarbon - your solvent will be halogenated first. Correct me if I'm wrong.


You are wrong, so I'll correct you. Halogenating aliphatic hydrocarbons, at least when the halogen is chlorine, bromine, or iodine, doesn't just happen when you combine the two on their own at STP. The procedure for making chloromethanes, for example, requires very high temperatures and pressure and perhaps a catalyst as well. Dichloromethane and chloroform are generally suitable solvents for bromination, as can be seen here: https://youtu.be/6tEs7P6UUVQ?t=15m30s

Sniffity - 11-8-2015 at 20:07

Quote: Originally posted by Amos  
Quote: Originally posted by byko3y  
Man, I was breathing with dichloromethane and chloroform fumes and I'm completely okay. Moreover, some time ago chloroform was used for analgesia. But tetrachlorocarbon is dangerous, because is metabolized into phosgen. Unstabilized chloroform is also dangerous after long or improper storage.
Also, I don't get it how you are going to halogenate anything in unsaturated hydrocarbon - your solvent will be halogenated first. Correct me if I'm wrong.


You are wrong, so I'll correct you. Halogenating aliphatic hydrocarbons, at least when the halogen is chlorine, bromine, or iodine, doesn't just happen when you combine the two on their own at STP. The procedure for making chloromethanes, for example, requires very high temperatures and pressure and perhaps a catalyst as well. Dichloromethane and chloroform are generally suitable solvents for bromination, as can be seen here: https://youtu.be/6tEs7P6UUVQ?t=15m30s


Shouldn't chains (3+ carbons) of aliphatic hydrocarbons be brominated in the presence of light?

I might be wrong here, but I remember that a way to differentiate between saturated and unsaturated hydrocarbons was adding bromine to them and putting both in a dark place: The unsaturated hydrocarbon reacts with bromine in the absence of light, whilst the saturated one only does so in the presence of light...

Or am I mistaken?

Edit: Check Organic Chemistry, Wade, Seventh Edition, Volume 1, Chapter 4. They give the example of Propane being halogenated at 25C, in the presence of light.

Also claim that:
Br2 -> 2 Br Radicals: Activation energy of 192 kJ per mole.
CH4 + Br radical -> CH3 radical + HBr: Activation energy of 75 kJ per mole.
CH3 radical + Br2 -> CH3Br + Br radical: Activation energy of 4 kJ per mole.

Edit2:
I'm NOT suggesting that chloroform will be halogenated under these conditions. I'm only saying aliphatic hydrocarbons can be halogenated at STP.

Edit3:
Also, if I'm not mistaken, the standard, commercial procedures for making chloromethane is not halogenation of methane, but a reaction involving methanol and HCl, which does require high temperatures and a catalyst.

[Edited on 12-8-2015 by Sniffity]

Amos - 12-8-2015 at 04:15

Quote: Originally posted by Sniffity  
Quote: Originally posted by Amos  
Quote: Originally posted by byko3y  
Man, I was breathing with dichloromethane and chloroform fumes and I'm completely okay. Moreover, some time ago chloroform was used for analgesia. But tetrachlorocarbon is dangerous, because is metabolized into phosgen. Unstabilized chloroform is also dangerous after long or improper storage.
Also, I don't get it how you are going to halogenate anything in unsaturated hydrocarbon - your solvent will be halogenated first. Correct me if I'm wrong.


You are wrong, so I'll correct you. Halogenation of aliphatic hydrocarbons, at least when the halogen is chlorine, bromine, or iodine, doesn't just happen when you combine the two on their own at STP. The procedure for making chloromethanes, for example, requires very high temperatures and pressure and perhaps a catalyst as well. Dichloromethane and chloroform are generally suitable solvents for bromination, as can be seen here: https://youtu.be/6tEs7P6UUVQ?t=15m30s


Shouldn't chains (3+ carbons) of aliphatic hydrocarbons be brominated in the presence of light?

I might be wrong here, but I remember that a way to differentiate between saturated and unsaturated hydrocarbons was adding bromine to them and putting both in a dark place: The unsaturated hydrocarbon reacts with bromine in the absence of light, whilst the saturated one only does so in the presence of light...

Or am I mistaken?

Edit: Check Organic Chemistry, Wade, Seventh Edition, Volume 1, Chapter 4. They give the example of Propane being halogenated at 25C, in the presence of light.

Also claim that:
Br2 -> 2 Br Radicals: Activation energy of 192 kJ per mole.
CH4 + Br radical -> CH3 radical + HBr: Activation energy of 75 kJ per mole.
CH3 radical + Br2 -> CH3Br + Br radical: Activation energy of 4 kJ per mole.

Edit2:
I'm NOT suggesting that chloroform will be halogenated under these conditions. I'm only saying aliphatic hydrocarbons can be halogenated at STP.

Edit3:
Also, if I'm not mistaken, the standard, commercial procedures for making chloromethane is not halogenation of methane, but a reaction involving methanol and HCl, which does require high temperatures and a catalyst.

[Edited on 12-8-2015 by Sniffity]


I said chloromethanes, as in all 4 chlorides of methane. And yes, chloromethane itself has a separate route, but I was just saying that to illustrate how difficult it is to directly halogenate methane.

A halogenation at 25 C of propane likely requires pressure; after all, propane is a gas at standard pressure at that temperature while bromine is not. And I imagine "light" refers to a UV source. So though to some extent some bromination of straight-chain alkanes may occur given simply light exposure, it shouldn't be a risk for DCM or chloroform, because these are commonly used as lab solvents for bromine during brominations.