Sciencemadness Discussion Board - Bromination of Propionic Acid in a Sealed Tube

Bromination of Propionic Acid in a Sealed Tube

Loptr - 14-9-2018 at 08:26

What sort of pressures can be expected while heating propionic acid in a sealed tube to temperatures of 160C? This snippet seems to demonstrate that alpha-bromopropionic acid can be prepared in two hours with strong heating.

I know there are other ways starting from alanine. I was interested in this route because I thought the acid halide had to be formed first in order to break the resonance structure of the carboxylic acid.

JJay - 14-9-2018 at 09:16

Probably a couple of atmospheres or so... my concern would be the vapor pressure of the bromine, which would be at something like 30-35 atmospheres.

AJKOER - 14-9-2018 at 10:03

One can apparently avoid heating by using UV light (reference: see, for example, https://pubs.acs.org/doi/abs/10.1021/ja01604a013?journalCode... ):

Br2 + hv --> .Br + .Br

RH + .Br --> .R + HBr

.R + .Br --> RBr

.R + RH --> R-R + .H

.H + RH -->.R + H2

.H + .H --> H2

.Br + Br- = .Br2- (assumes water vapor creating bromide)

R-R --> Products
....

You will, however, I suspect get a larger mix of products and the HBr as gas could increase pressure in the tube. Note, in the historical procedure cited, HBr gas is removed so the vessel is NOT sealed.

Also, heating Br2 to high temperature can also induce radical formation, but I would not like to be holding that tube if it explodes from the pressure buildup!

Do test the safety of the photolysis approach using a small amount as, for example, H2 + Cl2 (unclear with respect to Br2, a source claims the need of a flame, not photo-sensitive, see http://uki.vdu.lt/wp-content/uploads/sinergija/EN/chemija/ch...) can be made to explode with sunlight or red light. Also, in the presence of H2, O2 and Cl2 a light activated explosion (see https://www.nature.com/articles/127853a0 ) and perhaps also with Br2, so no oxygen presence. Also, heating H2 and Br2 to a high temperature will cause an explosion (see https://pubs.acs.org/doi/abs/10.1021/ja01604a013?journalCode... ) so removing gases, not just HBr but some created H2, from the mix is likely required to avoid an explosion at elevated temperatures.

[Edited on 14-9-2018 by AJKOER]

Loptr - 14-9-2018 at 12:22

How come most preparations of alpha-halocarboxylic acids use phosphorus? I know that mechanism includes the acid halide, followed by halogen addition at the alpha-carbon.

Are there issues with this approach? Less extreme conditions I guess....

Thank you, AJKOER!

EDIT: The chance of explosion is sort of off-putting.

[Edited on 14-9-2018 by Loptr]

JJay - 14-9-2018 at 12:41

Does anyone know if lactic acid responds like a secondary alcohol to Lucas' reagent?

zed - 14-9-2018 at 13:04

Maybe, why not? Perhaps it is easier than alternate routes.

There are a number of examples of @Chloro-propionic esters, being synthesized from lactic acid esters.

Diazotization/substitution of alanine, can produce a pure enantiomer. But, if your final product doesn't have a center of asymmetry; the cheapest, easiest route to synthesis, should prevail.

https://chemistry.mdma.ch/hiveboard/chemistrydiscourse/00046...

https://the-hive.archive.erowid.org/forum/showflat.pl?static...

Lactic acid is cheap, cheap, cheap. Err... I mean, inexpensive.

https://ingredi.com/l-lactic-acid-88-55-lbs-pail/?gclid=EAIa...

[Edited on 14-9-2018 by zed]

[Edited on 14-9-2018 by zed]

[Edited on 14-9-2018 by zed]

unionised - 15-9-2018 at 05:02

Quote: Originally posted by JJay

Probably a couple of atmospheres or so... my concern would be the vapor pressure of the bromine, which would be at something like 30-35 atmospheres.

My concern would be the pressure from the hydrogen bromide produced.

How would you safely open the tube?

Loptr - 15-9-2018 at 05:22

Quote: Originally posted by unionised

Quote: Originally posted by JJay

Probably a couple of atmospheres or so... my concern would be the vapor pressure of the bromine, which would be at something like 30-35 atmospheres.

My concern would be the pressure from the hydrogen bromide produced.

How would you safely open the tube?

I am not sure yet at this point. I think it might be better to use some sort of steel pipe with caps that can be screwed on and off. Or better yet, valves with hosing that can be opened to relieve pressure several feet away.

S.C. Wack - 15-9-2018 at 07:37

Quote: Originally posted by Loptr

What sort of pressures can be expected while heating propionic acid in a sealed tube to temperatures of 160C?

Wouldn't that depend on the size of the tube? So...the vapor pressure of propionic acid is the only consideration here...

So which steel is it at the hardware store that doesn't react with the acids at 160C?

If only there were bromopropionic syntheses already posted. Funny how no one ever thought of that before the forum turned to nearly total garbage.

[Edited on 15-9-2018 by S.C. Wack]

Loptr - 15-9-2018 at 07:41

Quote: Originally posted by S.C. Wack

Quote: Originally posted by Loptr

What sort of pressures can be expected while heating propionic acid in a sealed tube to temperatures of 160C?

There are several synthesis of alpha-bromopropionic acid posted to this forum. Very presumptuous of you to assume that I was only interested in the production of alpha-bromopropionic acid. I believe that I stated the purpose for my question in my initial post.

S.C. Wack - 15-9-2018 at 07:58

How exactly is it presumptuous when that is the first time you mention anything other than the a-bromo acid, and in your first post it's clear that you are asking about a single sentence in your google snippet, the one dealing with alpha-haloacid, ignoring the main dibromo thrust...ha...I don't feel presumptuous...

Loptr - 15-9-2018 at 09:21

Quote: Originally posted by S.C. Wack

How exactly is it presumptuous when that is the first time you mention anything other than the a-bromo acid, and in your first post it's clear that you are asking about a single sentence in your google snippet, the one dealing with alpha-haloacid, ignoring the main dibromo thrust...ha...I don't feel presumptuous...

Quote:

I know there are other ways starting from alanine. I was interested in this route because I thought the acid halide had to be formed first in order to break the resonance structure of the carboxylic acid.

I stated the fact that I was aware of other routes in the first sentence. The second sentence adds that I am interested in the route because of the odd addition which usually requires the acid halide being formed first. I was hoping this could extend to other carboxylic acids than just propionic acid. The interest was in the bromination reaction itself.

[Edited on 15-9-2018 by Loptr]

JJay - 15-9-2018 at 09:37

Quote: Originally posted by unionised

Quote: Originally posted by JJay

Probably a couple of atmospheres or so... my concern would be the vapor pressure of the bromine, which would be at something like 30-35 atmospheres.

My concern would be the pressure from the hydrogen bromide produced.

How would you safely open the tube?

I haven't tried this, and the vapor pressure of the hydrogen bromide is certainly a hazard, even after the tube has cooled, but I think the vapor pressure of hydrogen bromide is considerably reduced when it is dissolved in carboxylic acids.

JJay - 15-9-2018 at 09:44

Quote: Originally posted by zed

Maybe, why not? Perhaps it is easier than alternate routes.

There are a number of examples of @Chloro-propionic esters, being synthesized from lactic acid esters.

It looks like 2-chloropropionic acid is miscible with water... I wonder if lactic reacts with Lucas reagent in the manner typical of a secondary alcohol. If it does... is the product hard to salt out....

Oh and definitely take a look at the toxicity of 2-chloropropionic acid if you're thinking about making some. I don't suggest producing gallons of it in your garage.

[Edited on 15-9-2018 by JJay]

Loptr - 15-9-2018 at 09:52

Quote: Originally posted by JJay

Quote: Originally posted by zed

Maybe, why not? Perhaps it is easier than alternate routes.

There are a number of examples of @Chloro-propionic esters, being synthesized from lactic acid esters.

It looks like 2-chloropropionic acid is miscible with water... I wonder if it reacts with Lucas reagent in the manner typical of a secondary alcohol. If it does... is it hard to salt out....

Oh and definitely take a look at the toxicity of 2-chloropropionic acid if you're thinking about making some. I don't suggest producing gallons of it in your garage.

Yeah, a while back I read some where about it being a neurotoxin. Thanks for the heads up, though.

I have some DL-alanine, and plan to buy some lactic acid. I think it does behave as a secondary alcohol because it does participate in substitution reactions with halo acids to some extent, or at least that is what I recall from past google searches.

[Edited on 15-9-2018 by Loptr]

AvBaeyer - 15-9-2018 at 10:02

If you acquaint yourself with the mechanism of the Lucas reaction, you will see why it will not work with lactic acid or esters.

I find myself in partial agreement with SC Wack regarding some of the stuff posted here. Loptr posted a reasonable question. However, some of the follow-on comment is just speculative based on a shallow knowledge of some aspects of chemistry. This sort of thing happens all across this forum. A bit of searching and deeper "book learning" would go a long way to eliminating some of the nonsensical posts that appear all too frequently. Perhaps this is not the best place to post my rant, but is something that has concerned me for a long time and SC Wack lit the fuse.

AvB

Loptr - 15-9-2018 at 10:22

Quote: Originally posted by AvBaeyer

If you acquaint yourself with the mechanism of the Lucas reaction, you will see why it will not work with lactic acid or esters.

I find myself in partial agreement with SC Wack regarding some of the stuff posted here. Loptr posted a reasonable question. However, some of the follow-on comment is just speculative based on a shallow knowledge of some aspects of chemistry. This sort of thing happens all across this forum. A bit of searching and deeper "book learning" would go a long way to eliminating some of the nonsensical posts that appear all too frequently. Perhaps this is not the best place to post my rant, but is something that has concerned me for a long time and SC Wack lit the fuse.

AvB

Ok, this is what confuses me. Is lactic acid a secondary alcohol? If so, then an SN1 substitution could be take place in a Lucas type reaction. Secondary alcohols prefer SN1 reactions, so where is the issue?

EDIT: I will read up on the mechanism some more and see if I can find the issue...

[Edited on 15-9-2018 by Loptr]

AvBaeyer - 15-9-2018 at 10:28

The issue is the Sn1 mechanism with a carbonyl group attached to the carbon bearing the incipient positive charge. Consult a good organic chem text which discusses mechanisms.

AvB

JJay - 15-9-2018 at 10:39

Quote: Originally posted by AvBaeyer

If you acquaint yourself with the mechanism of the Lucas reaction, you will see why it will not work with lactic acid or esters.

I just spent some time looking at the mechanism, and now I am completely baffled... the Lucas reaction doesn't work with lactic acid??

I really must be missing something important here... I'm going to have to study the mechanism further to make sense of this curious non-reactivity.

Loptr - 15-9-2018 at 12:38

Ahh, carboxyl is electron withdrawing. The carbocation is stabilized by donors. The carbocation intermediate isn't very stable.

So in this case we see elimination rather than substitution? If so, you should get acrylic acid. Halo acid addition leads to 3-halopropionic acid through anti-Markovnikov addition being an a,b-unsaturated acid. Right?

[Edited on 16-9-2018 by Loptr]

JJay - 15-9-2018 at 15:45

Quote: Originally posted by Loptr

Ahh, carboxyl is electron withdrawing. The carbocation is stabilized by donors. The carbocation intermediate isn't very stable.

Oh, of course! I was looking at how easy it is for lactic acid to form a carbocation, not the stability of the carbocation. It can form a carbocation easily, but the carbocation is extremely reactive, so I guess it doesn't exist long enough to react with a halogen anion.

Markovnikov addition places the halogen on the most heavily substituted carbon, so if you added anhydrous hydrogen bromide to acrylic acid (in the absence of UV, peroxides, etc. that could form radicals), you would get your desired product.

Loptr - 15-9-2018 at 16:22

Actually, there seems to be an exception with a,b-unsaturated carboxylic acids. The addition is opposite of that seen with alkenes due to the electron withdrawing group.

https://www.quora.com/What-product-is-formed-on-reaction-of-...

I am trying to find the relevant chapter in my text book.

clearly_not_atara - 15-9-2018 at 18:05

In the high-pressure method, I think that bromination of the acyl hypobromite might occur. This intermediate is enolizable.

Consider instead using a sulfonyl halide with lactic acid or its esters. In some jurisdictions, tosyl chloride may be available. If not, methanesulfonyl halides can be made by halogenation of methanesulfinate salts, which are available from the Birch reduction of methylsulfonylmethane as described here:

https://www.sciencemadness.org/whisper/viewthread.php?tid=91...

Loptr - 15-9-2018 at 18:29

Quote: Originally posted by clearly_not_atara

In the high-pressure method, I think that bromination of the acyl hypobromite might occur. This intermediate is enolizable.

Consider instead using a sulfonyl halide with lactic acid or its esters. In some jurisdictions, tosyl chloride may be available. If not, methanesulfonyl halides can be made by halogenation of methanesulfinate salts, which are available from the Birch reduction of methylsulfonylmethane as described here:

https://www.sciencemadness.org/whisper/viewthread.php?tid=91...

Yeah, that is a good idea. I had thought about the sulfur halide approach since it can be used to prepare chloroacetic acid. There is also the route that uses PPA and Br2.

EDIT: Hypobromite. That's what I was looking for!

[Edited on 16-9-2018 by Loptr]

JJay - 15-9-2018 at 20:49

Quote: Originally posted by Loptr

Actually, there seems to be an exception with a,b-unsaturated carboxylic acids. The addition is opposite of that seen with alkenes due to the electron withdrawing group.

https://www.quora.com/What-product-is-formed-on-reaction-of-...

I am trying to find the relevant chapter in my text book.

You're right... it's a stability issue. If I'm understanding this correctly, other parts of an intermediate molecule pull away the halogen cation.

The Lucas reagent won't react with lactic acid in the typical manner for a similar reason. Right?

AvBaeyer - 15-9-2018 at 23:47

Loptr and JJay:

Good job! you figured it out. It's all about the electronics. The primary isolatable product from lactic acid in the Lucas reaction will be 3-chloropropionic acid as mentioned by Loptr above.

What may seem counter-intuitive in all this is the ready nucleophilic displacement of halide from alpha-haloacids and alpha-haloketones such as phenacyl halides. Again, it's all about the electronics and effects on reaction mechanisms. It pays to become familiar with these mechanisms.

AvB

Loptr - 16-9-2018 at 16:47

Quote: Originally posted by AvBaeyer

Loptr and JJay:

Good job! you figured it out. It's all about the electronics. The primary isolatable product from lactic acid in the Lucas reaction will be 3-chloropropionic acid as mentioned by Loptr above.

What may seem counter-intuitive in all this is the ready nucleophilic displacement of halide from alpha-haloacids and alpha-haloketones such as phenacyl halides. Again, it's all about the electronics and effects on reaction mechanisms. It pays to become familiar with these mechanisms.

AvB

I really appreciate what you did to help get us on the right track, AvB.

solo - 15-4-2022 at 09:32

.....with my recent bout with acid chlorides it seems to me if you made your acid chloride with your propionic acid in cyanuric chloride, then do the Finkeltein reaction in acetone with bromine to acquire the desired product .....at least that's how i see it....solo

Texium - 15-4-2022 at 10:28

Quote: Originally posted by solo

.....with my recent bout with acid chlorides it seems to me if you made your acid chloride with your propionic acid in cyanuric chloride, then do the Finkeltein reaction in acetone with bromine to acquire the desired product .....at least that's how i see it....solo

I don't understand what you're talking about. The thread is about brominating the alkyl chain of propionic acid, not making propionyl bromide. Also the Finkelstein reaction only works for making iodides from chlorides or bromides by exploiting the relative solubility of NaI in acetone. Converting a chloride to a bromide doesn't work since NaBr is insoluble in acetone. But it doesn't matter anyway. It's not like you can use the Finkelstein reaction on acyl halides since you can't do an SN2 on a carbonyl carbon...

solo - 15-4-2022 at 19:54

.....i misunderstood the topic , still on the acid chloride mind,..solo