Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
 Pages:  1  
Author: Subject: Optimizing Henry reaction conditions (substituted benzaldehydes + nitromethane)
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 10-9-2017 at 11:14
Optimizing Henry reaction conditions (substituted benzaldehydes + nitromethane)


So, initially I was confused by how every single write-up of a Henry reaction seemed to use a totally different solvent, totally different catalyst, different reaction time, different workup, different reduction method if the nitrostyrene wasn't the desired product, etc. And there never seemed to be an explanation for the choices that were made. So I figured I'd put some effort into understanding and optimizing this reaction. Since the precursors are easy to come by, I figured I'd limit the scope to reacting substituted benzaldehydes with nitromethane, to yield a nitrostyrene.

1) Dehydrating the initial nitroalcohol
Fortunately, dehydrating the nitroalcohol doesn't require much effort at all for benzaldehydes; it's actually harder to not dehydrate it. Simply heating to 40C or more will dehydrate it, if it's not dehydrated already.

2) Use glacial acetic acid as a solvent?
I noticed this being done quite often, and had no idea why. Seeing as this reaction is base-catalyzed, an acidic solvent didn't seem like a good idea. Some research led me to realize that if water isn't present, then GAA doesn't really behave as an acid for the purposes of the Henry reaction, but that still didn't tell me anything about why anyone would choose to use it. It smells quite strongly, and other solvents are much cheaper, after all.

3) How should water be removed to drive the reaction forward?
This too, seemed to be glossed over in any examples I looked at. Acids would stop the reaction by reacting with the base catalyst, so silica gel and polyphosphoric acid were out. Basic desiccants tended to be heterogeneous, and only proceeded very slowly. They also tended to have a lot of the product stick to them. A common solutions was to use a nonpolar solvent, especially an aromatic one like toluene, but this could make workup difficult. Another solution mentioned was to use nitromethane as the solvent, although this seemed slow and rather wasteful.

4) What catalyst to use, and how much of it?
Primary amines seemed to be a popular choice for the reaction of benzaldehydes and nitromethane. They'd be used in anywhere from stoichiometric amounts to very small catalytic amounts. Quantity of the base seems to affect both reaction rate and purity. Catalysts were usually not OTC though, and some examples included methylamine, cyclohexylamine, and octylamine.

5) Temperature?
Lower temperatures seemed to result in slower reactions but better quality yields. About the lowest temperature possible seemed to be roughly 40C, that is, the nitrostyrene dehydration temperature.

For the base catalyst, I had phenylethylamine HCl from Purebulk.com, which came out to about $20 for 500 grams. Neutralizing the HCl with NaOH just resulted in a mess, but melting the salt and adding KOH flakes produced a sticky KCl paste on the bottom and sides of the container, that did not mix with the PEA base at all. The PEA base could then just be poured off into a separate container. It also worked great as a Henry reaction catalyst. PEA can also be obtained by phenylalanine decarboxylation.

When the reaction is complete, it's necessary to add water and acid to neutralize the base. Once the reaction is over, it's then important to keep the nitrostyrene acidic, or else the various base-catalyzed reactions will resume. This seemed to explain why GAA was a common solvent then; you'd only need to add water, at which point the GAA would commence behaving as an acid. That didn't seem like the best explanation though.

I realized why GAA was such a common solvent, when adding the base too fast without stirring immediately. Certain areas of the vessel with high concentrations of solvent began generating reddish-brown side products. Since the dehydration of the nitroalcohol produces water, and water can cause this reaction to generate side-products, it's important to remove the water fast enough that it doesn't interfere with the reaction. For this reason, it's common to use a small enough amount of base that it can't generate water faster than it can be removed. However, another solution is to use GAA as the solvent. In this case, if water begins to accumulate, then the GAA will start to act as an acid, putting the brakes on the reaction. When sufficient water is removed, the GAA stops acting as an acid, and the reaction resumes. Clever.

However, for best yields, the ideal solvent would dissolve the reactants fairly well, but would not dissolve the nitrostyrene well at all. Since methanol, ethanol, and isopropanol all have this property, this is certainly within the realm of possibility. Another property of an ideal solvent would be if it formed an azeotrope with water. That way, water could be removed via its azeotrope with the solvent. Isopropanol has an azeotrope that's 15% water, although a lot of isopropanol is needed to remove water this way. A better solvent for this purpose is n-butanol, with approximately a 50% azeotrope with water. However, it has the disadvantage of dissolving nitrostyrenes well.

Methanol is the only common solvent I'm aware of that forms an azeotrope with nitromethane, and in fact, repeated crystallizations from methanol are required to remove excess nitromethane if it exists at the end of the reaction. However, for this reason, methanol should not be used as a solvent for the Henry reaction with nitromethane. Since ethanol is prohibitively expensive, the logical choice is isopropanol.

Of course, it's possible to have the advantages of all these solvents by mixing them. I've found that using at least 50% isopropanol, then equal parts n-butanol, and glacial acetic acid is pretty close to an ideal solvent system, provided the nitromethane is only in 20% excess or less. (Nitromethane is an excellent solvent of nitrostyrenes.) This allows all the advantages of the constituent solvents, plus nitrostyrene crystals will precipitate out as they form. The reaction can be run slow, since the GAA prevents side-reactions from the presence of water, and the n-butanol removes water via azeotropic evaporation. I ran this reaction for a few days in a TLC jar, and the solution was a yellow-orange color without a hint of the red color that tends to accompany side-reactions. The bottom of the jar was covered with enormous yellow crystals, which I had to remove, because they were insulating the reaction vessel from the heat source underneath. Heat source was a $3 coffee cup warmer I bought on eBay from China. I've included pictures of the crystals I've collected so far, and already more are growing. Of course, with crystals like this, recrystallization seems pointless. Not that I mind.


IMG_20170910_102904.jpg - 346kB

1505076468647825220168.jpg - 326kB

[Edited on 9/10/17 by Melgar]




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
alking
National Hazard
****




Posts: 250
Registered: 11-3-2016
Member Is Offline

Mood: No Mood

[*] posted on 11-9-2017 at 05:11


Awesome write up! Well done. I've wondered about a lot of these things myself, some I figured out, and I think just about the rest you did. I do have one important question that remains however and that is what variables go into choosing a catalyst? I noticed that methylamine works well on unsubstituted catalysts for instance, I can get an ~80% yield, yet the more substituted the nitrostyrene the more side products are formed. On a tri substituted compound for instance there is a considerable amount of polymerization unless GAA is used as a buffer and even then there's quite a lot. I've read from one reference that isopropylamine works better for substituted nitrostyrenes, but no reason or source for the claim was given. I do happen to have a big bag of PEA I purchased years ago as a supplement.
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 11-9-2017 at 11:49


Quote: Originally posted by alking  
Awesome write up! Well done. I've wondered about a lot of these things myself, some I figured out, and I think just about the rest you did. I do have one important question that remains however and that is what variables go into choosing a catalyst? I noticed that methylamine works well on unsubstituted catalysts for instance, I can get an ~80% yield, yet the more substituted the nitrostyrene the more side products are formed. On a tri substituted compound for instance there is a considerable amount of polymerization unless GAA is used as a buffer and even then there's quite a lot. I've read from one reference that isopropylamine works better for substituted nitrostyrenes, but no reason or source for the claim was given. I do happen to have a big bag of PEA I purchased years ago as a supplement.

For the catalyst, you want a strong enough base that the reaction will proceed at a fairly rapid pace. Primary amines work well because with them, the reaction proceeds a bit differently, because water is eliminated at the start when the imine forms. As a result there's less of a chance of it interfering later. In this case, the nitroalkane reacts with an imine, not an aldehyde, but to the same end result. Just, instead of water being eliminated, the original imine is.

I chose PEA because it was aromatic, stable, and a rather strong base for a primary amine. It's also very OTC, and has a high enough boiling point that evaporative losses would be negligible. Like most amines, its solubility in water is significant, and thus it'd wash away almost entirely in a water rinse. It's also a very harmless, and totally legal member of the phenethylamine family, and so having a small amount in your end product will almost certainly not have noticeable negative effects.

I really don't know what the benefits of other catalysts are, other than the ones that you use when the nitroalcohol is what you actually want.




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
Cryolite.
National Hazard
****




Posts: 269
Registered: 28-6-2016
Location: CA
Member Is Offline

Mood: No Mood

[*] posted on 11-9-2017 at 12:42


What was the benzaldehyde here? Just unsubstituted stuff, or something phenolic or otherwise electron rich?
View user's profile View All Posts By User
Crowfjord
National Hazard
****




Posts: 390
Registered: 20-1-2013
Location: Pacific Northwest
Member Is Offline

Mood: Ever so slowly crystallizing...

[*] posted on 11-9-2017 at 13:34


I've also recently started investigating 2-phenylethylamine as a catalyst for nitrostyrene formation. In addition to the reasons Melgar gives above, my reasoning for its use also include stearic bulk, which should help it to eliminate more easily from the addition product. I used it as the acetate, formed in situ from the HCl by adding the stoichiometric amount of sodium acetate and a little acetic acid as solvent. I found it to work well with the one benzaldehyde I tested, 5-bromoveratraldehyde.
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 12-9-2017 at 09:53


Quote: Originally posted by Crowfjord  
I've also recently started investigating 2-phenylethylamine as a catalyst for nitrostyrene formation. In addition to the reasons Melgar gives above, my reasoning for its use also include stearic bulk, which should help it to eliminate more easily from the addition product. I used it as the acetate, formed in situ from the HCl by adding the stoichiometric amount of sodium acetate and a little acetic acid as solvent. I found it to work well with the one benzaldehyde I tested, 5-bromoveratraldehyde.

I know I spent a ridiculous amount of time trying to figure out how to isolate the base from the salt without distillation, including doing things like adding reactive metals to the molten salt. All to no avail; salts would precipitate out as soon as the liquid was added to a nonpolar solvent. The magic bullet was potassium hydroxide though. (Potassium carbonate would probably also work) Turns out that potassium salts barely dissolve at all in anything that isn't water, and potassium hydroxide would form a nice clean phase separation, where sodium hydroxide didn't at all. Since I noticed this phenomenon, I've been trying KOH for a lot more things lately.

What you did would probably work, (and if you got it to work, then obviously it did) but it's nice being able to remove as many variables as possible. It's also nice to have a 100 mL reagent bottle with a transparent, viscous yellowish liquid in it that's labeled "phenylethylamine, free base" on it, that I can pipette a few mL out whenever I want. :)

Quote:
What was the benzaldehyde here? Just unsubstituted stuff, or something phenolic or otherwise electron rich?

There were a few oxygens attached to the ring. No acidic phenol hydrogens though.

[Edited on 9/12/17 by Melgar]




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
alking
National Hazard
****




Posts: 250
Registered: 11-3-2016
Member Is Offline

Mood: No Mood

[*] posted on 12-9-2017 at 16:24


Quote: Originally posted by Melgar  
Quote: Originally posted by Crowfjord  
I've also recently started investigating 2-phenylethylamine as a catalyst for nitrostyrene formation. In addition to the reasons Melgar gives above, my reasoning for its use also include stearic bulk, which should help it to eliminate more easily from the addition product. I used it as the acetate, formed in situ from the HCl by adding the stoichiometric amount of sodium acetate and a little acetic acid as solvent. I found it to work well with the one benzaldehyde I tested, 5-bromoveratraldehyde.

I know I spent a ridiculous amount of time trying to figure out how to isolate the base from the salt without distillation, including doing things like adding reactive metals to the molten salt. All to no avail; salts would precipitate out as soon as the liquid was added to a nonpolar solvent. The magic bullet was potassium hydroxide though. (Potassium carbonate would probably also work) Turns out that potassium salts barely dissolve at all in anything that isn't water, and potassium hydroxide would form a nice clean phase separation, where sodium hydroxide didn't at all. Since I noticed this phenomenon, I've been trying KOH for a lot more things lately.
[Edited on 9/12/17 by Melgar]


Why not do an a/b to isolate it? Dissolve HCl in water, basify with NaOH/KOH, extract with some low bp NP, DCM, Ether, Chloroform, etc. Strip the NP then you should have rather pure PEA.
View user's profile View All Posts By User
zed
International Hazard
*****




Posts: 2273
Registered: 6-9-2008
Location: Great State of Jefferson, City of Portland
Member Is Offline

Mood: Semi-repentant Sith Lord

[*] posted on 12-9-2017 at 18:24


Phenethylamine as catalyst! Now, that is a good idea!

I have run such reactions with butylamine as catalyst, a small volume of absolute ethanol as solvent, and a week of gentle heat to promote the reaction. It worked very,very well.

Still, not as well as your procedure seems to work. A bonus, is the large crystals you produced.

Smaller crystals are more pure, but in this reaction......somewhat counter-intuitively, bigger is better.


Rinsing reaction crud off of tiny crystals, inevitably leads to a significant losses of product . Bigger crystals, equals less total surface area, equals higher yield.

Nice! Thank you.


[Edited on 13-9-2017 by zed]

[Edited on 13-9-2017 by zed]
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 13-9-2017 at 01:33


Quote: Originally posted by alking  
Why not do an a/b to isolate it? Dissolve HCl in water, basify with NaOH/KOH, extract with some low bp NP, DCM, Ether, Chloroform, etc. Strip the NP then you should have rather pure PEA.

The problem here is the high affinity that PEA has for water. Any nonpolar solvent with significant amounts of PEA dissolved in it, would then dissolve water as well, on account of the PEA pulling it into that layer. And it gets worse. The water that's pulled into that layer will pull some alkali hydroxide along with it, meaning you can't really count on the alkali hydroxide's desiccating properties, since it's present in both layers. Or to simplify, PEA base is too polar to go into the nonpolar phase preferentially.

However, what I did actually is a variant of the standard A/B extraction, just solventless. Although I don't add water, water does form on account of the HCl neutralization (edit: also, because commercial KOH always contains a percentage of water), and that small amount of water is actually enough to dissolve both KOH and the amine HCl salt, thus allowing the reaction to continue. What I've figured out though, is that whether you use KOH or NaOH is actually quite important, since the main difference between sodium and potassium salts is their solubilities in different solvents. And whether an A/B extraction works or not hinges on those differences.

Oh, also, the way I did it, there is essentially no workup, which I see as a major advantage. I did notice that when rinsing out the potassium salts, the PEA base DID form a separate layer, unlike with the corresponding sodium salts, and even when there was a lot of water present.

Quote:
Phenethylamine as catalyst! Now, that is a good idea!

I have run such reactions with butylamine as catalyst, a small volume of absolute ethanol as solvent, and a week of gentle heat to promote the reaction. It worked very,very well.

Still, not as well as your procedure seems to work. A bonus, is the large crystals you produced.

Smaller crystals are more pure, but in this reaction......somewhat counter-intuitively, bigger is better.


Rinsing reaction crud off of tiny crystals, inevitably leads to a significant losses of product . Bigger crystals, equals less total surface area, equals higher yield.

Nice! Thank you.

You're welcome!

I initially tried to use phenylethylamine when attempting to run the reaction in toluene. I figured I should use a base that was structurally similar to toluene to increase its solubility, and benzylamine has way too many weird exceptions regarding the way it reacts. Phenethylamine could be purchased at health supplement stores, so it just seemed like a really obvious choice, even though I couldn't find any literature examples that used it. I guess if you have access to commercial chemical suppliers, PEA wouldn't be a first choice, but it does work great as an OTC catalyst.

I'm curious how your water was removed in the reaction you described though? Just ordinary evaporation? I'd expect the ethanol to evaporate very quickly, resulting in a solventless reaction, or a reaction where nitromethane was the solvent. Did you use an excess of nitromethane then?

One aspect of this reaction that seemed almost counterintuitive, is that crystals won't form unless the isopropanol concentration is high enough. Initially when I was adding isopropanol, I only added it because it was cheap, and because my reactions that worked best all seemed to include it. But then I noticed how much better the reactants dissolved in it than the product did, and realized that this was a solubility difference that could be exploited. I'm wondering now if it'd be possible to greatly improve yields using this procedure, seeing as the product is removed from the reaction almost as soon as it forms.

I'm debating whether or not to get into nitrostyrene reduction to amines, in this thread. Lately I've been surprised at how well Zn/HCl works for reducing nitro groups and all the associated reduction intermediates, considering nobody seems to take it very seriously. However, zinc has a very high hydrogen overvoltage, meaning that if there's anything around to reduce, it'll reduce that rather than generate hydrogen. Seeing hydrogen bubbles is actually a good indication of reaction completion.

The downside of this is removing zinc salts, but I've been experimenting with using phosphoric acid (combined with HCl to expose new metal) to react with the zinc. Zinc phosphate is very insoluble in just about everything, so it could be removed by filtering.

I would have tried zinc/HCl sooner, except that my results with Zn/GAA were terrible, and I incorrectly assumed that a stronger acid would cause more problems.

[Edited on 9/13/17 by Melgar]




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
alking
National Hazard
****




Posts: 250
Registered: 11-3-2016
Member Is Offline

Mood: No Mood

[*] posted on 13-9-2017 at 08:29


Zinc/HCl is strong enough to reduce a nitro group to an amine? I thought it would stop at the imine/oxime stage?
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 2421
Registered: 3-11-2013
Member Is Offline

Mood: Big

[*] posted on 13-9-2017 at 09:42


Zn/HCl reduces terminal nitrostyrenes efficiently. It fails to efficiently reduce secondary nitroalkenes, instead producing a ketone.

Secondary nitroalkenes can be reduced by activated aluminum or via the oxime (many methods) which is reduced by metallic Na/EtOH.
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 13-9-2017 at 13:40


Quote: Originally posted by alking  
Zinc/HCl is strong enough to reduce a nitro group to an amine? I thought it would stop at the imine/oxime stage?

As far as I can tell, that combination will reduce virtually any nitroalkane to an amine, and even nitrostyrenes (but not nitropropenes) to amines. Reduction of nitrostyrenes isn't very clean unless temperatures are controlled, although an ice/salt bath is reported to work well.




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
Corrosive Joeseph
International Hazard
*****




Posts: 914
Registered: 17-5-2015
Location: The Other Place
Member Is Offline

Mood: Cyclic

[*] posted on 13-9-2017 at 14:24


Zinc-HCl reduces aromatic nitro and aliphatic terminal nitro groups to amines very well.

Secondary nitroalkenes give a mix of products which hydrolyze in excess acid to the ketone.

Don't forget this - http://orgsyn.org/demo.aspx?prep=cv1p0413

Attached here is by far the best review available on the net for nitrostyrene/nitroalkane reduction.

Apologies for slight topic drift. I will whip myself later.


/CJ

Attachment: An_Experimental_Evaluation_of_the_Zinc_Hydrochloric_Acid_Reduction_of_Nitrostyrenes_Final.pdf (265kB)
This file has been downloaded 1239 times

View user's profile View All Posts By User
AvBaeyer
International Hazard
*****




Posts: 628
Registered: 25-2-2014
Location: CA
Member Is Offline

Mood: No Mood

[*] posted on 14-9-2017 at 05:29


CJ:

What is the source of the review? It is well done and extremely interesting.

AvB
View user's profile View All Posts By User
kmno4
International Hazard
*****




Posts: 1455
Registered: 1-6-2005
Location: Silly, stupid country
Member Is Offline

Mood: No Mood

[*] posted on 14-9-2017 at 07:09


Quote: Originally posted by Melgar  
Optimizing Henry reaction conditions (substituted benzaldehydes + nitromethane)

Hm.....
I read this and I cannot see any "optimizing". First thing, Henry reaction gives nitroalcohols, their dehydration has nothing to do with same condensation and its conditions.
How many substituted benzaldehydes have you tested, 10, 20... ?
How many amines have you tested ? Yields ?
It is known, that experimental results strongly depend on kind of benzaldehyde/amine or base/temperature/solvent(s) system and its acidity.
Some conditions are more universal, others are not.
There are many cheap amine catalysts (ammonium acetate, urotropine... etc).
What you have written here, has nothing to do with the tile above. Literature about various variants of Henry reaction is very extensive.




Слава Україні !
Героям слава !
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 14-9-2017 at 11:50


Quote: Originally posted by kmno4  

Hm.....
I read this and I cannot see any "optimizing". First thing, Henry reaction gives nitroalcohols, their dehydration has nothing to do with same condensation and its conditions.
How many substituted benzaldehydes have you tested, 10, 20... ?
How many amines have you tested ? Yields ?
It is known, that experimental results strongly depend on kind of benzaldehyde/amine or base/temperature/solvent(s) system and its acidity.
Some conditions are more universal, others are not.
There are many cheap amine catalysts (ammonium acetate, urotropine... etc).
What you have written here, has nothing to do with the tile above. Literature about various variants of Henry reaction is very extensive.

The idea was to come up with a set of considerations that are important when deciding your reaction conditions, and then describe in a general sense, how they interact with each other. I tried to include as much information as I could that was particularly hard for me to find, and tried to keep it open-ended enough to use as guidelines for optimizing this reaction generally. And I obviously don't know everything about this reaction, but I thought it would be useful to start a conversation. That's why the title was "Optimizing Henry reaction conditions" and not "Optimized Henry reaction conditions".

Also, if you're saying that the reaction name is wrong, then please enlighten me as to what the dehydrating version of the nitroaldol reaction is called? When a primary amine is used as a catalyst, it wouldn't be accurate to call it a Henry reaction with subsequent dehydration, which is what I usually see it called. I know it wouldn't be technically correct to refer to it as a nitroaldol reaction, since there's no nitroaldol product, so I'd think it'd be most accurate to refer to it as a variant of the Henry reaction, no?

I'd like to work more on figuring out how functional groups affect optimal reaction conditions, since I have yet to find any good information that explains this. Hell, the nitroaldol reaction page on wikipedia says that solvent and catalyst selection doesn't affect yields at all! And I've never even seen a description of the nitroaldol/Henry/Knoevenagel reaction where it's indicated that water is being removed via azeotropic evaporation, even though there are writeups of reactions where this is obviously the case.

[Edited on 9/15/17 by Melgar]




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
Crowfjord
National Hazard
****




Posts: 390
Registered: 20-1-2013
Location: Pacific Northwest
Member Is Offline

Mood: Ever so slowly crystallizing...

[*] posted on 14-9-2017 at 12:52


I think it's a Knoevanagel condensation when an amine catalyst is used. This might affect the information found when gathering data.
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 14-9-2017 at 22:54


Quote: Originally posted by Crowfjord  
I think it's a Knoevanagel condensation when an amine catalyst is used. This might affect the information found when gathering data.

Knoevanagel condensations can apparently refer to any aldol-type reaction catalyzed by any type of amine, unless I'm mistaken. And if that is what they should be called, well, there are plenty of books and published papers out there that don't call them that.

There seems to be a debate on what to call this reaction in this Vespiary post too, which as a bonus, gives reaction conditions for a lot of benzaldehyde + nitromethane reactions. Those conditions aren't all optimal, of course, but it's certainly good to have conditions that have been published and proven to work at least moderately well:

https://www.thevespiary.org/talk/index.php?topic=8824.0

edit: A convenient modification to this reaction, especially for those nitroalkenes that oxidize in air, is to rinse them with an ascorbic acid solution before putting them aside for later. The acidity and antioxidant properties of the ascorbic acid are very helpful for preventing degradation.

[Edited on 9/15/17 by Melgar]




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
Crowfjord
National Hazard
****




Posts: 390
Registered: 20-1-2013
Location: Pacific Northwest
Member Is Offline

Mood: Ever so slowly crystallizing...

[*] posted on 15-9-2017 at 07:13


Quote: Originally posted by Melgar  

Knoevanagel condensations can apparently refer to any aldol-type reaction catalyzed by any type of amine, unless I'm mistaken. And if that is what they should be called, well, there are plenty of books and published papers out there that don't call them that.
[Edited on 9/15/17 by Melgar]


Yeah, you're right. Knoevanagel condensations can use aromatic or tertiary amines, so that doesn't really capture this specific reaction; the mechanisms can differ depending on catalyst chosen. For example, if a nitroalkane is reacted with an aldehyde using a tertiary amine as base, the nitroalcohol is formed, at least as an intermediate. Nicodem has asserted in the past that the primary amine-catalyzed condensation is a Knoevanagle, for example in this thread. This reaction is probably still a subset of Knoevanagel condensations, but the literature is loose on the naming conventions in this particular case. It certainly complicates the research.
View user's profile View All Posts By User
Corrosive Joeseph
International Hazard
*****




Posts: 914
Registered: 17-5-2015
Location: The Other Place
Member Is Offline

Mood: Cyclic

[*] posted on 16-9-2017 at 12:03


Quote: Originally posted by AvBaeyer  
CJ:

What is the source of the review? It is well done and extremely interesting.

AvB



@ AvB - I pulled it from another forum but I believe the document was originally authored and posted on the HyperLab forum by a user known as 'persona'.

" an experimental evaluation of the Zinc Hydrochloric Acid reduction of nitrostyrenes - 23.11.2007 - www.hyperlab.info - Post #514742"

Unfortunately the forum is in Russian but the quality of work and write-ups there is second to none.




/CJ
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*****




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 16-9-2017 at 18:17


Saying this reaction is actually a Knoevanagel condensation is like saying that a platypus is actually a vertebrate. While it's technically true, it's not a very useful way to categorize it.

Although I had anticipated this being the case, it has become more obvious that the crystals you collect will be smaller in subsequent crops, and the last one will require extracting a rather small amount of nitrostyrene from a rather large amount of solvent. Nitrostyrenes only have a medium-to-low solubility in this solvent mixture, but that's a lot more than zero. However, if you have plenty of time, I see no reason that it wouldn't be possible to start on a small scale with only a fraction of your reactants, then top off all your solvents and add more reactants every time you collect crystals from it. I left for about a week, and when I came back, it had changed from the color of about apple juice, to the color of tea. However, I didn't smell any butanol, so my suspicion is that it ran out, and wasn't able to get rid of water as efficiently. Or something like that. N-butanol seems to play an important beneficial role that I don't quite understand yet, probably via the formation of an azeotrope that I don't know about.




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
zed
International Hazard
*****




Posts: 2273
Registered: 6-9-2008
Location: Great State of Jefferson, City of Portland
Member Is Offline

Mood: Semi-repentant Sith Lord

[*] posted on 18-9-2017 at 18:04


Actually, I primarily used absolute ethanol and butylamine, in the condensation of nitroethane with benzaldehydes. Very good yields were obtained without physical removal of water from the reaction medium.

When it comes to H2O; ethanol has a powerful grip. It simply rips off the water, and refuses to give it back. Produces a big solid block of crystals and a small amount of residual liquid ethanol/butylamine/H2O/with a little dark crud......in it. With large nitroalkene crystals created, a little ice-cold ethanol rinses the residual liquid/gunk right off, without very much loss of product.

Not as interesting as what you are doing. You have evolved a very thoughtful approach.

New to me. Different solvent, different catalyst, different way of driving the reaction.



[Edited on 19-9-2017 by zed]

[Edited on 19-9-2017 by zed]
View user's profile View All Posts By User
Gl3n
Harmless
*




Posts: 8
Registered: 2-5-2017
Member Is Offline

Mood: No Mood

[*] posted on 30-6-2018 at 13:19


I just came across this while utfse, sorry if I’m bringing a dead post up but I just read this and did have what might be additional useful information.

It was mentioned that this reaction might not run below 40C, I have had it run at no more then ambient temperatures 32-50F? in an uninsulated garage in the middle of winter in the north-east US. I followed the methods as listed on Rhodiums Chemistry page under Ultrasound Promoted Nitrostyrene Synthesis. While the true temperatures at the site of the reaction may be much greater then the ambient temperature I had the reaction run to 90% of the theoretical yield after about 24 -48hrs with the US bath not exceeding 25C. This method utilizes ammonium acetate as a catalyst, GAA/nitromethane as solvents and in my experience, compared to refluxing using published amounts of the same reactants results in a much cleaner reaction without the nasty side products. I am extremely interested in combining this methodology with US as in a closed system it would eliminate solvent loss and if the results are anything like what have been shown it would make for a simple, odor free, low cost system.
It does however leave the question of whether Ultrasound results in a nitroalcohol or nitrostyrene? My MP determination was based on flame sealed capillary tubes and a remote sensing digital barbecue thermometer. The MP was sort of all over the place so I don’t know that I did not actually produce a beta hydroxy nitrostyrene instead of a nitrostyrene. Now that I think about it I have been interested in making some beta hydroxy compounds but I guess it’s possible that’s what I had all the time. To be honest I never did anything with the results of those experiments so maybe I should test them and try to figure out what I actually produced.
View user's profile View All Posts By User
Gl3n
Harmless
*




Posts: 8
Registered: 2-5-2017
Member Is Offline

Mood: No Mood

[*] posted on 4-7-2018 at 17:39


Melgar,
What molar ratio of PEA did you utilize? Or volume per molar reaction size etc? I have also run a Leminger reaction to at least 80%, higher yields resulting from a slower, temp controlled, reaction. No non-polar utilized only dry IprOH washes after basification, The salts prevent the water/alcohol layers from mixing and the dry IprOH prevent ZnOH salts and hydrates from forming. No clogged up filters or emulsions etc.
Also how bad did the liquefaction of PEA HCl smell? If this were attempted should it be carried out in a fume hood?

[Edited on 5-7-2018 by Gl3n]
View user's profile View All Posts By User
alking
National Hazard
****




Posts: 250
Registered: 11-3-2016
Member Is Offline

Mood: No Mood

[*] posted on 5-7-2018 at 11:22


PEA should not smell much due to the high bp.
View user's profile View All Posts By User
 Pages:  1  

  Go To Top