Sciencemadness Discussion Board

What conditions favor dehydration of aldol condensation products?

FireLion3 - 8-3-2014 at 12:46

Most literature, formal and informal, imply after the Ph-Nitroalcohol is formed during a Nitroaldol condensation of a benzaldehyde and nitroalkane, a subsequent dehydration takes place to form the Ph-Nitroalkene. Other write ups on this reaction appear use Sodium Bisulfite to preserve the Hydroxyl group, although I do not know very much about that particular variation. In some discussions I have encountered, they discuss having to go out of their way following the condensation to acetylate the hydroxyl group so that it can be removed, when condensations of the same molecules imply an automatic dehydration.

Curiously I stumbled upon this particular reaction using a phase transfer catalyst.

Comprehensive Organic Reactions in Aq Media - 436 Pages
Quote:

"The Henry (nitroaldol) reaction was reported under very mild reaction conditions in aqueous media using a stiochiometric amount of nitroalkane, and an aldehyde, in NaOH 0.025 M and in the presence of cetyltrimethylammonium chloride (CTACl) as cationic surfactant. Good to excellent yields of β-nitroalkanol are obtained. Under these conditions several functionalities are preserved, and side reactions such as retro-aldol reaction or dehydration of 2-nitroalcohols are avoided.

The relevant study:
http://www.organic-chemistry.org/abstracts/literature/527.sh...

What is it that favors the dehydration of nitroalcohols to nitroalkenes? I have noticed that dehydrations seem to be self implied for molecules where the secondary hydroxyl group is connected to a carbon that is connected to the benzene ring. Is this because the double bonds on benzene ring are electron withdrawing and favor dehydration? Acids are rarely used in these reactions. In the descriptions of these reactions I always see "formation of the nitroalcohol followed by subsequent dehydration", amongst the reaction procedure.


Can anyone offer some knowledge? I haven't really learned much about base-catalyzed dehydration reactions... almost all of the ones I have encountered in literature have been acid-catalyzed and run at high temperatures, but many dehydrations of some of these molecules happen at relatively low temperatures.

I have read in some places such as
http://home.hiram.edu/chemistry/organic/Student%20Notes-aldo...

That the dehydration can be favored, something to do with the product having extended conjugation, resulting in the expulsion of the water to form the alkene?


http://www.chemgapedia.de/vsengine/vlu/vsc/en/ch/12/oc/vlu_o...
Quote:

Dehydration can occur relatively easily, since the new double bond is in conjugation with the carbonyl group's double bond. Therefore, if no spontaneous dehydration takes place, it can be easily enforced under normal circumstances. When dehydration takes place, the entire reaction is called aldol condensation. Dehydration proceeds effectively under acidic conditions, as water is a good leaving group. In contrast, under basic conditions, dehydration rarely takes place during the reaction, as the hydroxide anion is not an adequate leaving group.




[Edited on 8-3-2014 by FireLion3]

Nicodem - 11-3-2014 at 10:43

Quote: Originally posted by FireLion3  
What is it that favors the dehydration of nitroalcohols to nitroalkenes?
...
Can anyone offer some knowledge? I haven't really learned much about base-catalyzed dehydration reactions... almost all of the ones I have encountered in literature have been acid-catalyzed and run at high temperatures, but many dehydrations of some of these molecules happen at relatively low temperatures.

E1cB eliminations require a base for the deprotonation step. See the mechanism to understand why. An acid cannot catalyze an E1cB, but can catalyze an E1 or E2 elimination provided the leaving group can be activated by protonation (hydroxy, alkoxy, etc.). These things are well explained in most organic chemistry textbooks, so you would better consult a book where the explanation is better suited for fast learning, rather than asking them on a forum where people don't really have the time for a detailed explanation.

Electra - 11-3-2014 at 16:36

FireLion, some nitroalcohols more easily undergo dehydration without extreme conditions because of an existing conjugation between aromatic system and the nitro-group.

http://en.wikipedia.org/wiki/Conjugated_system

The electrons are delocalized and the alkene is more stable than the nitroalcohol, allowing for dehydration to easily occur. This is why in some cases additional reagents are required to prevent the dehyrdation so the compound can be reduced to the amine whilst maintaining the hydroxyl group.

[Edited on 12-3-2014 by Electra]

kmno4 - 12-3-2014 at 01:26

The problem is interesting for me too.
I used to do a little literature research, but it seems that products of
Henry reaction very strongly depend on experimental conditions.
In general, most of nitroalcohols seems to be stable comounds, dehydration does not occur without catalyst.

Few articles attached (JOC article is mentioned in the first post):

Facile Synthesis of 2-Nitroalkanols Mediated with LiAlH4 as Catalyst.[Synlett]

A Convenient Synthesis of 1-(2-Furyl)-2-nitroalk-1-enes on Alumina Surface without Solvent. [Synthesis]

Nitroaldol Reaction in Aqueous Media: An Important Improvementof the Henry Reaction [JOC]

Attachment: nit.7z (199kB)
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Edit:
THE NITROPARAFFINS[Chem.Rev]
Also attached.

[Edited on 12-3-2014 by kmno4]

Attachment: cr60103a003.7z (669kB)
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