Sciencemadness Discussion Board

knoevenagel condensation NaOH catalyst?

Klaus - 4-8-2018 at 11:49

I have found a synth that describes the condensation of benzaldehyde and nitromethane using NaOH water solution as a catalyst - I'm posting it below.
Can someone explain the mechanism of the reaction and what is this white precipitate?
Will this reaction work with nitroethane aswell?

I had 6ml of benzaldehyde I was going to throw away anyway, so I cooled it in ice water, added 3.5ml of nitroethane and 10ml 100% EtOH and added some NaOH water solution. Some white precipitate fell out but really was a tiny amount. I ended up adding something like a 100ml NaOH solution. Also, there still is an organic layer. I know this was a long shot but wanted to see what will happen anyway.

Anyway, here is the reaction:

1. Procedure
In a 6-l. wide-mouthed bottle, packed in a pail with a freezing mixture of ice and salt and fitted with
a mechanical stirrer, a thermometer, and a separatory funnel, are placed 305 g. (5 moles) of
nitromethane (p. 401), 530 g. (5 moles) of benzaldehyde (Note 1), and 1000 cc. of methyl alcohol. A
solution of sodium hydroxide is prepared by dissolving 210 g. (5.25 moles) of sodium hydroxide in
approximately an equal volume of water and cooling. It is then diluted to 500 cc. with ice and water,
poured into the funnel, and added with stirring to the nitromethane mixture at such a rate that the
temperature is kept at 10–15° (Note 2) and (Note 3).
A bulky white precipitate forms rapidly during the addition of the alkali. The mixture gets so thick
that stirring becomes difficult and it may be advisable to add 100 cc. more of methyl alcohol. After
fifteen minutes' standing, the pasty mass is converted to a clear solution by the addition of 3–3.5 l. of ice
water containing crushed ice (Note 4). Hydrochloric acid (made by diluting 1000 cc. of concentrated
hydrochloric acid with 1500 cc. of water) is placed in a 15-l. mixing jar and the reaction mixture run
into this from the separatory funnel at such a rate that the stream just fails to break into drops (Note 5).
A pale yellow crystalline mass separates almost immediately as the alkaline solution comes in contact
with the acid. After the stirring is stopped, the solid settles to the bottom of the jar. The major part of the
cloudy liquid layer is removed by decantation, and the residue filtered by suction and washed with water
until free from chlorides. This product is freed from all but a negligible amount of water by melting in a
beaker immersed in hot water. Two layers are formed, and on cooling again the lower layer of
nitrostyrene freezes; the water may then be poured off. The crude nitrostyrene is purified by dissolving
in 420 cc. of hot ethyl alcohol (Note 6), filtering the solution into a warm suction flask to remove solid
impurities, and then cooling until crystallization is complete. The yield of crude product melting at 56–
58° is 650–670 g. The yield of recrystallized nitrostyrene melting sharply at 57–58° is 600–620 g. (80–
83 per cent of the theoretical amount). The whole procedure, including purification, can be done in a
day.
2. Notes
1. Technical benzaldehyde which had been washed with sodium carbonate solution, dried, and distilled
under reduced pressure, was used in this preparation.
2. The first few cubic centimeters of sodium hydroxide solution should be added cautiously to the
nitromethane mixture since, after a short induction period, there is a considerable evolution of heat and
the temperature may rise from − 10° to 30° or even higher in spite of good stirring. If necessary, this rise
in temperature is easily checked by adding a handful of crushed ice directly to the mixture. After this
initial reaction the rest of the alkali may be added more rapidly.
3. The condensation induced by sodium hydroxide is almost instantaneous above 10°. The procedure
may be interrupted with safety after the addition of alkali, and the product will not change on standing
overnight in an ice chest.
4. After the product has been dissolved in water the resulting alkaline solution is much more sensitive
and should be used up as rapidly as possible and the temperature kept below 5°.
5. The alkaline solution must be added slowly to the acid, for the reverse procedure always forms an oil
containing a saturated nitro alcohol. A large excess of acid at room temperature is used, conditions
which facilitate the formation of the desired unsaturated nitro compound.
6. The vapors of hot solutions of nitrostyrene are very irritating to the eyes and nose, and the skin of the
face is sensitive to the solid substance.
3. Discussion
Nitrostyrene can be prepared by the condensation of benzaldehyde and nitromethane. This may be
accomplished by the use of small amounts of a primary aliphatic amine,1 a method which requires a
number of days for the reaction to go to completion, or preferably by the use of alkali as first discovered
by Thiele.2 Alternatively, nitrostyrene can be prepared from benzil, nitromethane, and sodium ethoxide,
3
or from styrene and nitrosyl chloride.

Metacelsus - 4-8-2018 at 12:25

The base-catalyzed mechanism proceeds through the nitronate salt of nitromethane. It's quite similar to an aldol condensation. You can find more information by searching the "Henry reaction."

zed - 4-8-2018 at 12:34

http://www.orgsyn.org/demo.aspx?prep=CV1P0413

From Organic Synthesis.

In the distant past, I attempted this reaction, substituting Nitroethane for Nitromethane.

I followed procedure exactly. It produced a 0% yield.

There are lots of nifty ways to produce B-Nitropropenyl-Benzenes, but this isn't one of them.

Klaus - 4-8-2018 at 12:42

Quote: Originally posted by zed  
http://www.orgsyn.org/demo.aspx?prep=CV1P0413

From Organic Synthesis.

In the distant past, I attempted this reaction, substituting Nitroethane for Nitromethane.

I followed procedure exactly. It produced a 0% yield.

There are lots of nifty ways to produce B-Nitropropenyl-Benzenes, but this isn't one of them.


The reaction described is with nitromethane which I'm trying to substitute for nitroethane, to clarify. And this is sad to hear. Is there a chance you screw up?
I don't know if the alcohol used has something to do with the reaction or is merely a solvent though.

[Edited on 4-8-2018 by Klaus]

clearly_not_atara - 4-8-2018 at 15:21

zed's pretty good, I'd believe he did it right. Primary amines are good bases for the reaction; phenethylamine is OTC I'm pretty sure.

happyfooddance - 4-8-2018 at 17:07

I tried the same procedure as zed once on a maybe 10mmol scale, following it to the T (using nitroethane). While my yield was close to his, it was not 0%, I was left with a filter paper with a fine yellow dust that smelled like cinnamon. However, it was practically zero yield so I abandoned this method.

Doing a little more research led me to believe that this method does indeed work with nitroMETHANE, to produce the beta-nitrostyrene. Orgsyn rarely lies, and the procedure certainly needs to be followed precisely (to avoid self condensation of the aldehyde).

Metacelsus - 5-8-2018 at 05:28

I've done a condensation using nitromethane, although with ammonium acetate in refluxing glacial acetic acid, not NaOH in methanol. Yield was quite good (approx. 90%). I have no experience with using nitroethane.

lowtech - 5-8-2018 at 05:53

I once used concentrated KOH solution in MeOH as a catalyst for this type of reaction and it works, with nitromethane. Yield was not very high tho, around 40 %. There are plenty of ways doing this reaction better.
Sometimes catalyst is difficult to obtain, but methylamine isn´t impossible to make. Also you could bubble ammonia into the solution of aldehyde in GAA.

S.C. Wack - 5-8-2018 at 08:19

Nitrostyrene/propene does oil out but the nose knows what's in the perfume I suppose, but if there's not tar or aldehyde or nitrostyrene that leaves undehydrated nitro alcohol...what else? How fine is the line between dehydration and the acid doing bad things, in the nitropropene series? This is in fact the start of one of the better syntheses of racemic PPA and so on, where neutralizing the base results not in the nitropropene but the nitro alcohol.

Vogel/etc. lab manuals might mention the white precipitate is a nitro alcohol salt.

For TS2 Rhodium gave a method using nitroethane and piperonal, so maybe there's a relevant thread at the arcHive. IIRC NaOH has been preferred for benzaldehydes with free phenols, like vanillin.

kmno4 - 5-8-2018 at 23:00

One remark -
Very often and erroneously, the nitro-Mannich reaction is called the Henry reaction, equally by amateurs and professionalists.
The Henry reaction gives beta-nitroalcohols as products and is catalysed by strong bases, the nitro-Mannich reaction gives beta-nitroamines and requires NO strong base catalyst.

Under some experimental conditions, both products turn to unsaturated nitrocompounds, by elimination of water (Henry) or amine (nitro-Mannich) molecules.

BTW.
The OS procedure works (also with few modifications), but I was not able to obtain more product than 60-70% of theory.