Sciencemadness Discussion Board - Benzoin and related acyloins via thiamine

Benzoin and related acyloins via thiamine

Boffis - 29-6-2016 at 19:52

There are several threads on this forum concerning the preparation of benzoin, such as that of Magpie, and from time to time there has been discussion of the dimerization of benzaldehyde via thiamine instead of cyanide. There are several procedure for the preparation of benzoin from benzaldehyde using thiamine as the catalyst in place of sodium or potassium cyanide and I have found mention of the use of thiamine in the preparation furoin on Wikipedia but without references.

Having attempted Vogel’s preparation of furoin (1) using sodium cyanide and finding the resulting material very difficult to purify and the yield very poor I decided to try the action of thiamine on furfuraldehyde. Before trying this procedure on my precious furfural however, I decided to try it on benzaldehyde as I have plenty of this compound. Most of the procedures I have found on the web are for micro or semi micro scale preparations so I scaled up one of these procedures, an anonymous college lab procedure, that I found on the internet.

Benzoin from benzaldehyde via Thiamine nitrate:
To a 500ml round-bottom flask containing a 35mm stir-bar were added 7.034g of thiamine mono-nitrate and 20ml of water, the compound did not dissolve completely. To the milky suspension was added 75ml of rectified spirit and 4ml of 40% sodium hydroxide solution. The stirrer was turned on and when the initial bright yellow colour had faded 39ml of benzaldehyde was added all at once. The flask was placed in a water bath at 50°C and the temperature slowly raised to 60°C over about 15-20 minutes. The flask was then maintained at 60°C for a period of 2 hours and allowed to cool a little before being poured into a 250ml beaker. Crystals formed rapidly and when the mixture had cooled to room temperature it was chilled in the fridge to 5°C (about 2 hours). The crystals were filtered at the pump and washed with 50ml of 1:1 rectified spirit and water mixture, this removed most of the yellow colour from the cake. The filter cake was then slurried into a further 50ml of the alcohol water mixture and again filtered at the pump, sucked as dry as possible and then turned out onto a watch glass and dried. The cake was dried at 35°C for 24 hours and weighed 16.87g representing a yield of 41.6% of creamy white Benzoin. The Mp was 133-134.5°C a little below the published figure of 135-137°C.

Furoin from furfural via Thiamine nitrate:
This is basically the same as the previous procedure but with furfural in place of benzaldehyde. To a 500ml RB flask containing a 35mm stir-bar were added 7.065g of thiamine mono-nitrate and 20ml of water. The stirrer was started and 75ml of rectified spirit and 3.3ml of 50% sodium hydroxide solution were added. Once the transient yellow colour had faded 40ml (46.4g) of freshly prepared furfural were added all at once, the reaction mixture became dark brown. The flask was placed in a water bath at 50°C and maintained at this temperature for 1.5 hours (Note 1). After about 1 hour a pale crystalline precipitate began to form and the reaction mixture became paler, eventually an amber colour. When the heat was turned off the mixture was stirred for a further 10-15 minutes and then poured into a 250ml beaker and allowed to cool to room temperature, the flask was rinsed with a little (perhaps 5-8ml) of rectified spirit. The mixture was finally chilled in the fridge overnight at 5°C. The mixture solidified but when stirred liquefied, the slurry was filtered at the pump and the yellow cake washed with 1:1 rectified spirit and water until the runnings were colourless, about 70ml were required.

The filter cake was dried at about 35°C on a large watch glass for 24 hours. The crude, yet almost pure white crystalline product weighed 33.57g (72.3% of theory) and melted at 135-136.5°C which is close to the ideal melting point of 135-137°C.

Note 1 Furfuraldehyde is more succeptable to the effects of alkali then benzaldehyde and so a lower temperature was use in this initial attempt. The reaction time was shortened slightly because after 1.5 hours the reaction mixture was already the thick slurry of crystals.

References:
(1) A. I. Vogel Textbook of Practical Organic Chemistry 3rd ed 1956

The improved yield of furoin using thiamine as the catalyst is astonishing, 72% as against 13% for the cyanide process (in my hands) and the utterly amazing improvement in quality; beautiful, almost pure white crystals without recrystallization as apposed to light brown crystals after two recrystallization and charcoal treatment, leaves me in no doubt that the thiamine catalyzed dimerisations of furfural is the way to go.

Thiamine hydrochloride probably works equally well.

Before I post this to the Prepublication section I will try recrystallizing the products and also include some photographs.

CuReUS - 30-6-2016 at 04:35

Quote: Originally posted by Boffis

3.3ml of 50% sodium hydroxide solution were added....Thiamine hydrochloride probably works equally well.

thiamine hydrochloride works just as well.Also using NaOEt instead of NaOH will increase the yield to 83%
http://www.sciencedirect.com/science/article/pii/S0040403900...

Boffis - 30-6-2016 at 09:47

@CuReUS. Thats interesting information I hadn't spotted this paper because of its obscure title. Presumably I would need to to work in anhydrous ethanol. Although given the extra work involved in working with dry solvents I am not sure the extra 10% yield is worth it for me in spite of the troubles with furfural distillations.

The reason that food supplement compounders prefer the thiamne nitrate salt appears to be because it is less hydroscopic than the hydrochloride and is therefore easier to get.

Does anyone know if pyridine-2-carboxaldehyde will undergo this type of condensations to give pyridoin?

AvBaeyer - 30-6-2016 at 18:18

Boffis,

Nice work and nice write up. Thanks.

AvB

Dr.Bob - 1-7-2016 at 17:53

Great work, furans are tough to work with in my experience, so that is steller.

2-pyridinealdehyde does work in many reactions as does benzaldehyde. I don't know for sure if it works in the benzoin type condensation, but it seems reasonable.

PHILOU Zrealone - 2-7-2016 at 11:17

Just realized that furoin once oxydized is a very strange molecule, if rings opening is possible...

OC4H3-CHOH-CO-C4H3O -oxydation-> OC4H3-CO-CO-C4H3O
OC4H3-CO-CO-C4H3O + 2 H2O -rings opening-> O=CH-CH2-CH2-CO-CO-CO-CO-CH2-CH2-CH=O

Thus decan-1,10-dial-4,5,6,7-tetrone...probably too reductive to exist as open molecule... pentan-2,3,4-trione is already a challenge...

If NH2OH in excès is used during the opening...one could maybe get an octa-oxime of it.

HO-N=CH-CH2-CH2-C(=NOH)-C(=NOH)-C(=NOH)-C(=NOH)-CH2-CH2-CH=NOH or fuzed furazane rings by dehydration.

If one is able to rehydrate and reduce furoin...then maybe one could get decan-1,2,3,4,5,6,7,8,9,10-decol (1,2,3,4,5,6,7,8,9,10-decahydroxydecane)

I'm more than eager to see if this can make a decanitrate ester...for sure more dense than hexanitromanite and in the same range of impact sensitivity (probably a little less sensitive)...and with 4 O atom (positive OB) disponible to burn some stabiliser plasticizer... :cool:

Boffis - 6-7-2016 at 16:55

Hi Philou,

Do you have any references to the ring opening of furans? I have a paper that describes the preparation of maleodialdehyde dioxime via ring opening of pyrrole with hydroxylamine so it looks plausible. It could certainly lead to some weird compounds. One of my target compounds is furildioxime using only 2 equivalences of hydroxylamine.

PHILOU Zrealone - 7-7-2016 at 13:46

Quote: Originally posted by Boffis

Hi Philou,

Do you have any references to the ring opening of furans? I have a paper that describes the preparation of maleodialdehyde dioxime via ring opening of pyrrole with hydroxylamine so it looks plausible. It could certainly lead to some weird compounds. One of my target compounds is furildioxime using only 2 equivalences of hydroxylamine.

Opening is said to happen in dilute acid upon warming (doesn't work in the cold!)...but care must be taken because too concentrated acids (or Lewis acids) lead to rapid polymersation condensation.

Pyrrole with hydroxylamine leads to ring opening and succinaldehyde dioxime (butandial dioxime)...
cyclo-(-NH-CH=CH-CH=CH-) + 2 NH2OH -->HO-N=CH-CH2-CH2-CH=N-OH + NH3(g)
HO-N=CH-CH2-CH2-CH=N-OH <==--> O=N-CH2-CH2-CH2-CH2-N=O

The "easy" interconversion of furane into pyrrole and into thiophene is interesting.

Nice target compound by the way your furildioxime...
OC4H3-CHOH-CO-C4H3O -oxydation-> OC4H3-CO-CO-C4H3O
OC4H3-CO-CO-C4H3O + 2 NH2OH --> OC4H3-C(=N-OH)-C(=N-OH)-C4H3O + 2 H2O
Maybe this will turn nearly spontaneously into difuranyl-furazan by dehydration and cyclization of the two oxime hydroxy groups.

[Edited on 8-7-2016 by PHILOU Zrealone]

Boffis - 14-7-2016 at 10:21

A Note of Caution!!

I repeated the preparation of furoin described above a couple of days ago almost exactly as I described but it failed totally and I got zero yield!!! I dilute the reaction mixture with water and recovered some of the furfural, now somewhat brown and syrupy. Not knowing what to do with the material I mixed up a new batch of catalyst and repeated the reaction. This time it worked!! The resulting furoin (11.39g) was rather darker than before and the yield rather less but it worked. Further small scale experiements have now revealed what I believe to be the problem.

It appears that after the addition of the alkali to the slurry of thiamine nitrate it is necessary to stirr and warm slightly, not only until it has dissolved but until the yellow colour is decolourised, this can take 10 minutes or more. If you add the aldehyde too soon the reaction fails completely!! I tried this out with a 3rd batch of furoin and then I tried it with 2-pyridinecarboxaldehyde, making sure that the yellow colour had fades before the addition of the aldehyde. Both reactions appear to have been successful.

Boffis - 16-7-2016 at 12:47

Well the third batch of Furoin gave me a 60.0% yield of pure white crystalline product after just washing on the filter. The pyridoin preparation was even more amazing. The bright orange product is beautifully crystalline, washed easily on the filter and gave a 86% yield!

PHILOU Zrealone - 17-7-2016 at 05:01

Quote: Originally posted by Boffis

Well the third batch of Furoin gave me a 60.0% yield of pure white crystalline product after just washing on the filter. The pyridoin preparation was even more amazing. The bright orange product is beautifully crystalline, washed easily on the filter and gave a 86% yield!

Tumbs up!
Good work!