Piperidine from the hydrolysis of piperine

This thread is a report of work still in progress but was driven by my need for a small amount of piperidine and I have no recovered 34.9g of slightly moist piperidine hydrochloride from the hydrolysis of piperine.

There are about 10 threads on the SM site on the extraction of piperine from pepper corn but only 2 on the hydrolysis and they are both useless. For this reason I have started a new thread.

These experiment were developed from a YouTube video produced by Chem Player (https://www.youtube.com/watch?v=KDGIYEaGCZw&t=1s). He used 7g of piperine he had previously extracted from pepper corns but because the yield of piperidine could only be about 2g at best and I was more interested in obtaining piperidine in workable quantities I chose to buy 100g of commercial 95% piperine extract and scale up Chem Player’s method by a factor of 5, e.g. using 35g of crude piperine, for my first attempt.

The Hydrolysis
25.160g of 85% potassium hydroxide flakes were placed in a 500 ml conical flask containing a fairly large (about 45mm) stir bar. 200ml of 95% ethanol (rectified spirit) were then added and the mixture stirred until the alkali had dissolved. 35.060g of commercial piperine extract (note 1) was then added to the reaction mixture.

Photo 1 Flask with KOH in rectified spirit
Photo 2 The yellow slurry after adding the piperine

A brilliant yellow suspension formed immediately but gradually, on heating, the piperine dissolves giving a deep honey brown–orange solution. A reflux condenser was added to the flask and it was gently heat to boiling then refluxed for 4½ hours. After about 20 minutes refluxing a crystalline precipitate starts to form. As refluxing continued the amount of solid makes the slurry rather thick and but not difficult to stir though a large stir bar is needed.

Photo 3 The dark honey brown but clear solution after 10 minutes
Photo 4 The crystalline precipitate after about 2 hours reflux

After the reflux period, the suspension was allowed to cool a little and then the condenser re-arranged for simple distillation; no temperature monitoring was required. The liquid was distil off until the residue becomes too thick to stir, this resulted in about 170ml of distillate. When the flask was cool enough to be handled with bare hands 70ml of water were added and the solid stirred up into a dark brown slurry then it was left to cool to room temperature. The slurry was filtered at the pump with a 70mm Buchner funnel and the cake washed with about 30ml of the distillate and then with about 40ml of rectified spirit to give an almost white cake. The cake was drained as dry as possible and finally dried on a watch glass. The yield of crude potassium piperinate was 27.714g which is about a 92.8% yield though it is still rather impure (note 2).

Photo 5 The set-up for the removal of the solvent
Photo 6 The filtrate after collecting the first crop of K piperinate

The filtrate was returned to the flask and distilled again until the residue was again difficult to stir and then cooled (note 3). All of the distillates were combined and rendered weakly acid with 30% hydrochloric acid, about 13ml were required. The acidified distillate was then distilled again with temperature monitoring; the first 230ml or so distilled below 95°C and was kept for recovery of the alcohol. Another 70-80ml of increasingly cloudy distillate passed over and was discarded; it smells distinctly of pepper and probably consists of some un-hydrolysable essential oil in water. The small amount of slightly discoloured liquid left in the flask was transferred to a shallow bowl and evaporated to dryness with constant stirring on a hotplate. The yield of very pale yellow piperidine hydrochloride was 12.66g (It took several attempt to get the weight this low, the product is very soluble and deliquescent).

Photo 7 The crude dried potassium piperinate
Photo 8 The dried piperidine hydrochloride

Recovery of Piperinic acid
The crude potassium piperinate (27.714g) was dissolved in 200ml of hot water, cooled to a little above room temperature and filtered. The filter cake consists of a very little off-white residual piperine and weighed 1.517g.

Photo 9 Dissolving the potassium salt in water - the insoluble is partly piperine
Photo 10 The filtered K piperinate solution

The clarified solution was acidified with 30% hydrochloric acid until it was strongly acid and left to stand for several hours, the result was an almost solid butter-like pale yellow mass. The mass was slurried with a stirring rod and filtered at the pump using a 90mm Buchner (note 4) funnel and washed with cold water. The cake was dried in a warm location for several days to obtain a constant weight; the product is a fine pale yellow powder resembling sulphur and is quite odourless. The yield was 24.698g (theory 25.43g for a 95% starting material).

Photo 11 Filtering off the precipitated free piperinic acid
Photo 12 The dried filter cake of crude piperinic acid

A little potassium chloride efflorescence was observed on the final dry solid so the dried crude product was ground to a powder (it’s hard and brittle), dispersed into 200ml of water and heated to about 70°C and cool. It was filtered and sucked dry at the pump and then air dried at 35°C to constant weight yielding 20.301g of pale yellow powder. Attempts to recrystallize small portions of the piperinic acid with various solvents indicate that the best solvent is pure isopropanol, about 40ml being required per gram of acid being recrystallized.

Notes
Note 1: The piperine extract was bought from an online supplier and claims to be 95%. It is a very pale yellow free flowing powder.
Note 2: An attempt was made to recrystallize the potassium salt from water and while this is easily done and the very steep solubility gradient means recovery is high the crystals were very fine and fluffy and difficult to wash on the Buchner funnel. Some residual piperine is also present and necessitates the filtration of the solution.
Note 3: The residue in the flask was leached with a little recovered clear methylated spirit and transferred to a filter funnel. The dark brown filtrate was discarded as it contained much resin but also some residual piperine and with larger quantities may be worth leaching with hydrochloric acid. The light brown cake when dried weighed 2.79g. This was stirred into about 15ml of boiling water and filtered, the small amount of light brown residue is probably mostly unaltered piperine but was discarded (<1g), the filtrate was left to crystallise, it set almost solid but when stirred up became a slurry that was drained with suction in a small Buchner funnel, washed with a little rectified spirit and dried. The pale straw coloured material is crude potassium piperinate, yield was 0.870.
Note 4: with a smaller diameter funnel the volumous precipitate forms a cake too thick to wash easily.

Discussion
The next process will be the liberation of free piperidine. At the moment I plan to do this with either solid sodium hydroxide pellet or calcium hydroxide powder. I plan to arrange a flask for distillation and then place an excess of the alkali in it with a large stir bar and then run in slowly from a sealed dropping funnel the piperidine hydrochloride solution. The latter compound is extremely soluble in water and so the amount of additional water to be absorbed by the alkali is actually small. Piperidine boils at 106°C without vacuum assistance but vacuum equipment may help the disengagement of the base from the solid alkali.

I am still working up some of the residues so I am not going to discuss recoveries just yet but you can work them out yourself (I'll cover this in the final write-up for pre-pub) but taking the 95% piperine claim into account and the fact that the final crude piperidine hydrochloride may still be a little damp the recovery of piperidine as hydrochloride is probably about 80%, which is pretty good. Working with larger quantities than Chem Player probably greatly reduces mechanical losses and the addition of water at the end of the distillation helps drive off the remaining piperidine too.

Further Experiments
I am current carrying out a second hydrolysis using a slightly different protocol. I this case I refluxed for 7 hours then simply cooled the slurry of crystals to room temperature and filtered of the crystals. They were washed with about 50ml of rectified spirit on the filter and then dispersed into 200ml of fresh rectified spirit and filtered. The cake was drained as dry as possible and the dried on a large watch glass at 35°C. This gave 49.511g of pale yellow crude potassium piperinate from 65.1g of piperine.

The filtrates were returned to the original flask and distilled until about 450-500ml had distilled off. The residue was cooled and filtered, the cake was washed with 30ml of distillate and 30ml of fresh rectified spirit. When dried this gave a further 3.696g of crude potassium piperinate. The filtrate smelled strongly fishy so was returned to the flask, 50ml of water added and the distillation continued until a thick tarry residue was all that remained.

All of the filtrates were combined, acidified with 30% hydrochloric acid, about 24ml were required, and distilled in stages in progressively smaller flasks until only a little pale yellow liquid remained. This was poured into a shallow bowl and evaporated with constant manual stirring until it became a dry crumbly yellowish solid. Heating and stirring were continued until when a cold watch glass was place over the bowl not mist of condensation form on the it. This gave another 22.231g of pretty dry piperidine hydrochloride, slightly darker than in the first experiment.

The potassium piperinate from this experiment can't be pure since this would represent almost 100% recovery and I recovered another 1.87g of rather brownish K salt from the gunk left at the end of distillation by leaching it with alcohol until all of the brown tar had dissolved. I am currently trying to purify this material.

Many thanks for the comments guys.

@AvBaeyer, do you think I could dry mix in a flask the piperidine hydrochloride with say NaOH or KOH pellet by shaking them together and using the heat of the reaction to drive off the anhydrous piperidine or do you think this might get out of hand? Might it be better to add the saturated hydrochloride solution to a large excess of KOH pellets?

My original idea was to use excess calcium hydroxide with perhaps a few coarse lumps of calcium oxide, load the flask quickly and then gently shake, I am pretty sure the reaction would then self perpetuate. The idea here is than the calcium chloride forms lower hydrates that require near red heat to remove the water of hydration so the calcium salt would effectively remove the water and only dry piperidine would distil off. Again I can see that there is no way to control the reaction once started.

@ChemPlayer My lab at this time of year is rather cold and damp, about 3-5 C at the moment. My analytical balance I keep in a small heated office and the piperidine salt from the first batch has been in there for about 5 days and doesn't appear to have gained more than about 0.05g so it may not be as hydroscopic as I had first imagined but it is insanely soluble in water and hangs on to the last bit of water tenaciously.

Any ideas what to try with the piperinic acid apart from making piperinal? Interestingly I noticed it is structurally related to sorbic acid too:



I was wondering if it will function as a diene and condense with a suitable dienophile like maleic anhydride to form a 4-phenyl-dihydrobenzene-1,2,3-tricarboxylic acid; I read somewhere that sorbic acid will take part in such reactions. I also read somewhere that 2,3-dimethylbutadiene condenses with maleic anhydride to form 4,5-dimethyldihydrophthalic acid but I can't remember the conditions or the reference. Or is this just wishful thinking .

Quote: Originally posted by Boffis

@AvBaeyer, do you think I could dry mix in a flask the piperidine hydrochloride with say NaOH or KOH pellet by shaking them together and using the heat of the reaction to drive off the anhydrous piperidine or do you think this might get out of hand? Might it be better to add the saturated hydrochloride solution to a large excess of KOH pellets?

Quote: Originally posted by AvBaeyer

I hydrolyzed N-formylpiperidine with excess 6M HCl, then distilled the reaction solution to a syrupy consistency. The last 50% or so of the distillation was done under aspirator vacuum (ca. 30mm). I did not try to take it to complete dryness. Sodium hydroxide (50% aqueous) was added until pH>14 by pH paper. The resultimg mixture was carefully distilled collecting distillate in the range 90-106. Piperidine forms an azeotrope with water (bp 92.8°C, 65% of piperidine by mass). Solid KOH was added to the distillate (procedure repeated twice) then the liquid portion was distilled again collectiing at 104 - 107 C. My overall yield from N-formylpiperidine was ca 80%. AvB