n-amyl alcohol

I recently finished a protracted synthesis of n-amyl alcohol. This utilized a Grignard reaction with n-butylMgBr acting as Grignard reagent and gaseous formaldehyde acting as substrate.

n-butylMgBr + CH2O --> Grignard adduct

Grignard adduct + H2O --> n-amyl alcohol + MgBrOH


1. Reaction of the Grignard Reagent with CH2O
My basis was 0.5 mole of the Grignard reagent, the preparation of which is documented here: link1 The reactor vessel was a 3-neck 500ml RBF. Gaseous CH2O was produced by depolymerizing 24g (0.27 mole) of trioxane camp fuel using a supported H3PO4 catalyst in a tube furnace kept at 220°C. The solid trioxane was boiled in a 3-neck RBF heated in a 140°C oil bath and carried into the furnace as a gas using 1SCFH argon. This technology is documented here: link2. The dry CH2O was sparged into the 500ml reactor over a period of 3 hours.


Trioxane feed system picture


Tube furnace with 1” quartz tube containing the H3PO4 catalyst


Reactor system

Paraformaldehyde formed in the 10mm ID sparge tube (slightly submerged) and had to be unplugged with a wooden dowel, once. Paraformaldehyde also formed in the outlet tubing of the reactor, which included a reflux condenser topped with a CaCl2 guard tube w/cotton plugs and a rubber hose leading to an inverted funnel over water. The only place total pluggage was noted was at the end of the sparge tube.

About half way through the run I noted that the liquid level of boiling trioxane was not dropping as fast as I expected. Although this was not visible I suspect the 4-5mm outlet of a ground glass fitting w/tublature was partially plugged with recrystalized trioxane. The argon supply fitting on the 100ml RBF neck was popping now and then after the boil-off rate was increased.

The 500ml reactor with the reaction product was sealed and set aside for 3 days while I dealt with an electrical problem with my hood/hood light.

2. Workup (hydrolysis)
The day before yesterday the product was dumped onto about 200ml of crushed ice in a 600mL beaker. This was followed by the addition of 6M HCl. I added the acid until the opaque white mix turned clear. This required ~100ml (0.6 mole). There was only a small layer of oily yellow liquid floating on top of the aqueous layer. Although I realized that most all of the 200ml of ether had been evaporated, the thinness of this layer was not a good sign.

I split the 350mL batch in two and extracted each portion with 25ml of ether. The aqueous layer was discarded. The combined ether layers was placed over anhydrous Na2SO4 overnight to dry.

Yesterday the ether was removed by simple distillation.

Today, the paltry product, a golden liquid, was transferred to a 25ml RBF and distilled. A few drops came over early but most came over at 133°-140°C. The Wiki bp value for n-amyl alcohol is 137°-139°C.


Boiling point of the product


Picture of n-amyl alcohol product

3. Yield
The yield was 3.4g, for a %yield of 7.7%.

4. Discussion & Conclusions

This is the completion of a long-held fantasy, ie, making a normal alcohol via Grignard synthesis.

This was an extremely complex system due to the fact that there were 3 reactions occurring simultaneously. There were nine separate requirements for electrical power. Also, ether and gaseous formaldehyde were being handled.

Proof that CH2O entering the reactor is truly anhydrous would be good to have.

Prevention or amelioration of the trioxane and paraformaldehyde plugging occurring throughout the gas train would facilitate an increase in yield.

Because I was wary of the exothermic heat that would be generated during the formation of the adduct I did not heat the reactor until the last hour of the gassing. Thereafter I kept it at a gentle boil. Heating throughout the run would likely increase yield.

5. References
1. Organic Syntheses, 1983, 61, 65, “2-HYDROXYMETHYL-2-CYCLOPENTENONE”
2. A Textbook of Practical Organic Chemistry, by A.I. Vogel, 3rd Edition, p.253, “n-Hexyl Alcohol”

Questions, comments, and suggestions are welcomed.




[Edited on 27-2-2016 by Magpie]

Quote: Originally posted by UC235

I find it rather interesting that every intro organic textbook uses formaldehyde in the grignard discussion when such a transformation is extremely impractical.

Quote: Originally posted by Delta

Can you dissolve formaldehyde in anhydrous ethers to make a solution that could be used at a later date?

Quote: Originally posted by Dr.Bob

Just a thought, however, as a quartz tube furnace is not a common household item. (I don't even have one, so that is pretty rare.)

Quote: Originally posted by UC235

I find it rather interesting that every intro organic textbook uses formaldehyde in the grignard discussion when such a transformation is extremely impractical.

Quote: Originally posted by Magpie

Quote: Originally posted by Delta   Can you dissolve formaldehyde in anhydrous ethers to make a solution that could be used at a later date? I would be surprised if it was not soluble. But to an extent to be practical would be another question.