Sciencemadness Discussion Board - Pyridine synthesis/extraction

Pyridine synthesis/extraction

SpeechDiscussionTalk - 28-12-2007 at 16:52

Hi!

Does anyone here know a good synthesis of pyridine from extremly OTC-chemicals like B6, nicotine or similar things? In "ancient" times it was made by dry destillation of bones.
In my opinion (which isn't much influenced by very much knowledge of bones btw.) this dry destillation is a pyrolysis reaction of some proteins. Maybe there is another source for these kind of proteins...

I would be grateful for any help!

not_important - 28-12-2007 at 17:58

Use the search engine before starting a thread

http://www.sciencemadness.org/talk/viewthread.php?tid=9650

http://www.sciencemadness.org/talk/viewthread.php?tid=286

skullandfeather - 28-12-2007 at 22:01

its partially responsible for the smell of coffee i hear.....

Fleaker - 28-12-2007 at 22:47

Ew, now that you mention it, I kind of can detect that odour! Thanks for ruining coffee for me :-/

In all fairness to SpeechDiscussionTalk, we do not have a good thread on the synthesis of pyridine or the acquisition from common OTC chemicals.
Don't look to me for information though, I'm no organic chemist, but I know there are people here who know how to synthesize it or extract it (that should be easy).

I remember it being mentioned that pyridine is used as a denaturant in ethyl alcohol, but in what proportions, I do not know.

Pyridine is useful indeed, many wonderful complexes can be made from it (oxidizing agents, halogenating agents) and it also serves a catalytic function in many reactions.

So why not discuss it some? I think it would be easy to buy, but why not try making it for the sake of making it?

Sauron - 29-12-2007 at 00:04

Pyridine is produced industrially by the reaction of acetaldehyde, formaldehyde and ammonia at elevated temperature and pressure over a catalyst. The three isomeric picolines are formed simultaneously and the products fractionated.

There are other processes, but none of them OTC and all of them quite industrial.

[Edited on 29-12-2007 by Sauron]

SpeechDiscussionTalk - 29-12-2007 at 04:11

The decarboxylation of niacin seems to be a good method to make pyridine. Is the decarboxylation of a compound like niacin anything else than making the the Ca-salt and gentle heating until it slowly decomposes? Should i take some other things into account i forgot, or is it really that simple from niacin?

len1 - 29-12-2007 at 04:36

I dont believe this gives a measurable yield. Decarboxilating in the 3-position is much harder than in the benzene ring due to electron deficiency there, is my understanding. Plus I have not seen such a reaction in any standard texts, rather the much more complicated condensation of acetaldehyde, formaldehyde and ammonia. Len

[Edited on 29-12-2007 by len1]

not_important - 29-12-2007 at 04:42

Yields aren't great, you'll get some bipyridines/bipyridyls and other stuff, so you'll need to fractionate the product. The actual temperature needed can be rather high, see the benzene from benzoic acid threads, including the on in Prepublication.

leu - 29-12-2007 at 19:02

1.5 g nicotinic acid and 2.5 g CaCO3, when heated to decarboxylation with a bunsen burner give 0.3 ml pyridine

len1 - 29-12-2007 at 19:17

Well now youve got me interested, I shall ahve to try this out!

Fleaker - 29-12-2007 at 19:39

I'm more interested in having a shot at the high temperature route with the aldehydes and ammonia. Apologies in advance for being damn lazy, but what pressure does it run at? If it's a few atm. I can go for it, anymore though and out of my league it will be.

len1 - 29-12-2007 at 20:12

Quote:

Originally posted by leu
1.5 g nicotinic acid and 2.5 g CaCO3, when heated to decarboxylation with a bunsen burner give 0.3 ml pyridine

Surely you mean decarboxylation with Ca(OH)2 to give CaCO3. I cant see how CaCO3 will give you anuthing until it gets 'decarboxylated' itself at 700-900C! But there wont be much organics left at that temperature... Im afraid ive got my doubts again ...

undead_alchemist - 31-12-2007 at 12:38

Pyridine on eBay.
1L
http://cgi.ebay.ca/ws/eBayISAPI.dll?ViewItem&item=120204...

leu - 31-12-2007 at 17:48

Quote:

Decarboxylation is a well known chemical reaction, the site where that information came from isn't on the internet anymore so you can either accept it or reject it; it matters little in the grand scheme of things

The person who originally posted it is a well known member who can verify that he did if he wants to, but such spoon feeding seems unlikely

It's been discussed at another forum known to many of the members:

http://www.roguesci.org/theforum/showthread.php?t=3289&h...

http://www.roguesci.org/theforum/showthread.php?s=9684ba78f1...

There at least a dozen other little known methods such as:

Patent DE944251

Example 2

A solution of 200 parts 1,5-pentanedial in 800 parts 3% sulfuric acid is added, over the course of 2 h, to a boiling solution of 1100 parts crystallized Fe2(SO4)3 and 200 parts (NH4)2SO4 in 1500 parts water. Workup as in example 1 yields 82% pure pyridine.

workup as in example 1: rxn-mixture is made alkaline and the aromatic base is distilled off.

and

While hydrogenations of pyridine forming piperidine have been the topic of many posts; the corresponding dehydrogenation of piperidine forming pyridine seems to have escaped notice so far. This reaction can be carried out either by heating to 300° with concentrated sulphuric acid, or with nitrobenzene at 200°; or with silver acetate in acetic acid

An old preparation of piperidine is by heating pentamethylenediamine hydrochloride (cadaverine); which is the result of putrefactive enzymes on lysine. Cadaverine is quite toxic in addition to being very obnoxious, but the hydrochloride salt isn't so toxic. An alternative synthesis can be found in Ber 56 625-30 (1926):

[Edited on 2-1-2008 by leu]

Attachment: pummerer.djvu (126kB)
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not_important - 31-12-2007 at 20:39

The ZIP file appears to be broken, near the end of it in the central directory the "version made by" offset is bad, looks like the zip creator stuttered and had 0x1414 instead of 0x0014. What was used to create it?

As it is a DJVU file, zipping it saves little if any space. If the zip was needed to get the board software to take it, that's one thing and perhaps the board could be configured to accept .djvu files, otherwise it might be better not to zip single .djvu files.

Sauron - 31-12-2007 at 21:21

We are having similar hassles in References. arkansas posted a zip file to me, no good. And a zip file to Rosco_Bodine also no good.

kmno4 was eventually able to recover the pdfs from Rosco's zip but, only after a lot of effort.

As for my requested files I am awaiting arkansas to kindly repost them without compression. As they are already pdf's, the only point of zipping is to make one file out of two, but useless if it fucks them up, as something seems to be doing.

solo - 1-1-2008 at 10:23

Quote:

Originally posted by leu An alternative synthesis can be found in Ber 56 625-30 (1926)

------------------------------------------------------------------------------------------

Über eine verbesserte Methode zur Darstellung von Diaminen und Amino-alkoholen
N. Putochin:
Berichte der deutschen chemischen Gesellschaft (A and B Series Volume 59, Issue 4 (p 625-630), 1926

Attachment: Über eine verbesserte Methode zur Darstellung von Diaminen und Amino-alkoholen (p 625-630) .pdf (434kB)
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leu - 1-1-2008 at 18:29

IZArc was used to zip the deja vu file, the forum software is corrupting zip files

Pyridine is produced from the reaction of pyrrole and carbene; and Tschitschibabin published his laboratory studies of various syntheses of pyridines made by passing ammonia and aldehyde vapors over granular alumina between 200 to 350 º C in JCS Abstr 1906, i, 451; 1915, i, 638; 1923, i, 1121-3

He obtained pyridine itself from the vapors of acetaldehyde and acrolein with ammonia over alumina in these experiments

Nicodem - 2-1-2008 at 08:41

I have yet to see a reaction where pyridine can not be substituted with another mild base (unless of course pyridine is used as reaction substrate). Besides any method of its preparation is uninteresting as long as it is so cheap and so easily available (you can find it in just about any organic lab).
But if it is just for the fun of preparing it, I guess nicotinic acid could be used. Though using CaCO3 (no need for Ca(OH)2 here, since nicotinic acid is an acid, as the name implies anyway, and CaCO3 is a base) seems a bit counterintuitive since it is well known that the thermolysis of calcium carboxylates gives mainly the products of decarboxylative ketonization and nearly no products of decarboxylation. For example, heating calcium acetate gives mainly acetone and not methane as one would expect from the analogy of the reaction: NaOCOCH3 + NaOH => Na2CO3 + CH4; or the analogous: NaOCOPh + NaOH => Na2CO3 + PhH. So, I would tend to believe the thermolysis of calcium nicotinate gives more bis(3-pyridyl) ketone than it would give pyridine. Though perhaps no ketonization occurs with carboxylic acids lacking any alpha hydrogens. Still, rather give it rather a try with the more classical thermolysis of sodium carboxylates in NaOH as it so well described for benzoic acid on this forum.

len1 - 2-1-2008 at 13:19

Everything is an acid and everything is a base - its just a question of how strong.

Nicotinic acid is a weak acid, weaker than benzoic because the nitrogen withdraws electrons from the ring, and CaCO3 is a weak base, the weaker the base the lower te yield in what is already a very low yield process. Try CaCO3 with benzoic acid.

[Edited on 2-1-2008 by len1]

Nicodem - 3-1-2008 at 03:43

I just remembered that decarboxylative ketonization proceeds also with acids lacking the alpha hydrogens (at least in the case of mixed calcium formate/benzoate which gives benzaldehyde). So I would skip idea of using calcium carbonate and try with NaOH according to the method used for benzoic acid.

Quote:

Originally posted by len1
Nicotinic acid is a weak acid, weaker than benzoic because the nitrogen withdraws electrons from the ring, and CaCO3 is a weak base, the weaker the base the lower te yield in what is already a very low yield process. Try CaCO3 with benzoic acid.

Nicotinic acid is indeed somewhat less acidic than benzoic acid (pKa 4.9 vs. 4.2). But that is not because electron withdrawal since electron withdrawing groups on benzoic acids increase their acidity (as long as there is no neighboring effect in o-substituted ones – like in salicylic acid, for example). For example, you can compare: p-NO2-benzoic acid (pKa 3.44), m-NO2-benzoic acid (pKa 3.45), o-NO2-benzoic acid (pKa 2.17), benzoic acid (pKa 4.20), p-MeO-benzoic acid (pKa 4.47).
Also, you confuse the proton transfer reactions in aqueous solution with what appears as an acid-base reaction among solids in melt (as is the case here). If one of the products is a gas (CO2 in our case) then the reaction will proceed almost regardless how strong the acid and base are since the reaction equilibrium will not be dependant on proton affinity, but on the removal of the volatile component (CO2). This is how glass is made from SiO2 and alkali carbonates even though silicates are more basic than carbonates - the reaction proceeds by the removal of CO2 and not as acid/base equilibrium. Another inorganic example is the reaction of boric acid (a very weak acid) with carbonates at high temperatures.

len1 - 3-1-2008 at 18:33

1) In your previous post you stated CaCO3 is a good reagent to decarboxylate niacin because its a base, now you are stating its got nothing to do with it - it actually just CO2 formation that drives equilibrium.

2) Sorry - electron withdrawl from the ring does make the COOH group more acidic, however you are out of luck with niacin - COOH is in the meta position and nitrogen lone pair mops up the protons.

3) Acidity isnt just of relevance in aquesous solutions

4) Things are actually a lot more complicated. Both drive the reaction. If it was just gas formation then CaCO3 is not needed, but the decarboxylation will occur at way too high T to save the pyridine - thats why a base is added in the reaction, it lowers delH and the reaction proceeds at a lower temp The stronger the base - the better - (thats actually part of the the reason for your observation that Ca(OH)2 doesnt decarboxylate as well as NaOH).

5) Take a close look at what you are proposing:

niacin + CaCO3 -> Pyridine + CO2 + CaCO3

CaCO3 contributes nothing to the delH of the reaction - you are suggesting it as a catalyst. Good luck with the reaction.

[Edited on 4-1-2008 by len1]

Nicodem - 4-1-2008 at 03:19

1.) Obviously, you misunderstood my post since I was saying just the opposite. I was commenting Leu's citation about nicotinic acid decarboxylation over CaCO3, expressing my opinion that the use of CaCO3 is a bad choice if pyridine is the target product since it is well known that the main path in calcium carboxylates thermolysis is not the decaboxylation but decarboxylative ketonization instead (see the attached review if you are unfamiliar with this reaction). Hence the main product would not be pyridine but bis(pyridin-3-yl) ketone (aka dipyridin-3-ylmethanone). In such ketonizations the base can indeed be used as catalyst since it is unaffected by the reaction (see the example using ThO2 in Vogel's). When such catalytic methods are not used, the carboxylates of Ca, Ba, Pb, Fe and other multivalent metals are preprepared from the corresponding carbonates or hydroxides and then subjected to the thermolysis yielding the corresponding ketones.
But if decarboxylation is the desired path, one better stick to the original conditions using NaOH in excess (like I already said). There is a mechanistic explanation on why excess hydroxide is required (you can also use thermodynamic arguments like you did, but I prefer mechanistics). And according to this reaction mechanism, the reaction can not proceed equally with CaCO3.

2.) Pyridine is not a substituted phenyl ring. Your comparison makes no sense. The electronic characteristics of pyridinyl group are different from the phenyl group. Hence the pKa of nicotinic acids are not the same as for benzoic acid, neither are they comparable from the substitution point of view (also, substituents on the meta position of benzoic acid do influence the acidity through inductive effect; see the examples in my previous post). I was not explaining the origin of their difference, but merely correcting your erroneous statement: "Nicotinic acid is a weak acid, weaker than benzoic because the nitrogen withdraws electrons from the ring". What I also found strange in your comparison with benzoic acid is in that you seem to claim that benzoic acid would form the carboxylate with CaCO3 while nicotinic acid wouldn't, even though the benzoic acid is only 5 times more acidic than nicotinic acid.

3.) Never said it is of relevance only in aq. solutions. Proton transfers occur in all kind of solvents, just the proton affinity changes with the solvent properties. I just said that you should not only count the acid/base equilibrium where there are present also other equilibriums that drive the reaction to competition.

4 and 5.) I was proposing:

A.) 2 {pyridin–3-yl}–COOH + CaCO3 => Ca(OOC–{pyridin-3-yl})2 + CO2

B.) Ca(OOC-{pyridin-3-yl})2 => CaCO3 + {pyridin-3-yl}–CO–{pyridin-3-yl}

… and side products among which there might be pyridine as indicated from Leu's post.

Obviously the reaction A proceeds without problems at the temperature where the nicotinic acid melts (238°C; though it is probably over by that T since the partial pressure of nicotinic acid is not zero at temperatures lower than that). The reaction B also requires temperatures higher than 200°C, generally 300-400°C.

Attachment: Ketonization of Carboxylic Acids by Decarboxylation_Mechanism and Scope.pdf (154kB)
This file has been downloaded 2079 times

len1 - 4-1-2008 at 03:52

I think weve reached the point of diminishing returns - youve stated your position Ive stated mine. Fortunately this isnt abstract psychology, the reaction is simple enough to be tested, putting the misunderstandings aside, there are real differences between what you and I say.

PS I mentioned CaCO3 + benzoic acid in jest, sure I dont expect it to work. Plus the fact that niacin resists decarboxilation, is in the literature, precisely because its in the meta position.

PSS I dont expect substituted benzene and pyridine rings to be identical, where do I say that? But the principle of resonance structures applies equally to both!

Now if there is an actual testable disagreement it is this:

You expect

benzoic acid + Na2CO3 -> benzene + CO2 + Na2CO3

to yield well, just as

benzoic acid + 2NaOH -> benzene + CO2 + Na2CO3 + H2O

I expect much better results in the later, for the reasons I have outlined (but you havent understood).

we shall see..

[Edited on 4-1-2008 by len1]

Nicodem - 4-1-2008 at 05:02

Quote:

Originally posted by len1
Now if there is an actual testable disagreement it is this:

You expect

benzoic acid + Na2CO3 -> benzene + CO2 + Na2CO3

to yield well, just as

benzoic acid + 2NaOH -> benzene + CO2 + Na2CO3 + H2O

I expect much better results in the later, for the reasons I have outlined (but you havent understood).

we shall see..

Read my previous post again. I said exactly the opposite, that:
benzoic acid + Na2CO3 -> benzene + CO2 + Na2CO3"
does not go because benzophenone is the main product! <-wrong, see bellow

Edit:
Sorry, this time it was me who misread your post. I thought the above was about "benzoic acid + CaCO3". I don't know why you brought out Na2CO3 when the issue was about CaCO3, but in the case of "benzoic acid + Na2CO3" the main products should be benzene, sodium phthalate and other byproducts, depending also on the temperature, closed/open system, O2 and H2O presence, etc.. Benzophenone forms only when the calcium salt is used where ketonization is the main pathway. In the themolysis of sodium benzoate less than 3% of conversion is accounted to the ketonization, while the themolysis of the potassium salt is even cleaner, yielding only benzene and potassium phthalate in 4.75 : 1 ratio. On the contrary, calcium benzoate yields benzene and benzophenone in a 2 : 1 ratio in a closed deareated system at 400-500°C (the formation of benzene is attributed to the presence of moisture in the starting material – obviously there is no explanation for its formation unless a proton donor is present). See: Energy & Fuels, 19 (2005) 365–373 and references therein for a better understanding.

[Edited on 4/1/2008 by Nicodem]

Nicodem - 4-1-2008 at 11:20

Len1, now that I caught myself in reading your posts similarly uncarefully as you do, I reread and realized where all this misunderstanding probably comes from. I noticed that you seem unaware of the mechanism of these decarboxylations. There are numerous mechanisms by which benzoic and other aromatic acids can decarboxylate. For example just to mention a few of the more common yielding the Ar-H from Ar-COOH:
a.) p- and o-hydroxybenzoic acids can decarboxylate trough a retro-Kolbe-Schmitt mechanism (inapplicable to nicotinic acid);
b.) Cu powder in refluxing quinoline can be used to promote the radical decarboxylation mechanism (often used in the lab but irrational to use for something as simple as pyridine);
c.) the thermolysis of alkali carboxylates yielding the decaboxylated and carboxylate disproportionation products (not particularly effective since the reaction is driven by carboxylate group disproportionation - hence unable to give good yields due to part of the compound forming dicarboxylic acids);
d.) and finally the decarboxylation in the NaOH melt that I was trying to promote as a better alternative in reply to Leu's post.
Then there are also the decaboxylative ketonization mentioned in previous posts, the oxidative decarboxylations like the Hunsdiecker reaction, the Kolbe electrochemical radical decarboxylation, and many others of little relevance here… and there are also more types for non-aromatic carboxylic acid.

I was talking about d, a well known reaction mentioned several times on this forum (there is even the experimental by Axt in prepublication). Here is a scheme with the mechanism included just in case I was misunderstood again (I was proposing just to substitute benzoic acid with nicotinic, nothing more complex than that!):

PhCOOH.gif - 4kB

len1 - 4-1-2008 at 13:09

You are a tricky fellow. As soon as one condenses what you are saying to a testable prediction, you try to extricate yourself by moving the goal posts.

If there is any practical meaning to you posts regarding CaCO3 is that its as good a base as Ca(OH)2 - thats what you wrote. But you think it cant be used for decarboxylatin for another reason - calcium salts produce ketones. Well then, sodium salts you think dont, and it follows sodium carbonate is as good as the hydroxide.

Nicodem - 4-1-2008 at 13:41

Huh, finally you read what I wrote correctly!

With a minor exception:

Quote:

Originally posted by len1
Well then, sodium salts you think dont, and it follows sodium carbonate is as good as the hydroxide.

In my previous post I described exactly the opposite (again!). That is, when using Na2CO3 you get the decarboxylation of the type c described in the previous post. Hence the main products are benzene and sodium phthalate in case of benzoic acid (or whatever else depending on the exact conditions). When using NaOH you get the decarboxylation of the type d as long as there are at least 2 eq. NaOH. This gives almost exclusively benzene (provided there is no O2 present). Clearly the reaction type c gives lower yields than reaction type d. Under conditions for c the theoretical maximum conversion to benzene when using Na2CO3 is 50%, the other half being lost as phthalate or terephthalate.

PS: Am I really so lousy in explaining things in English? Even though it's not my native language and I do not use it much, I find it hard to believe I'm so incomprehensible.

Nicodem - 5-1-2008 at 09:19

According to the attached paper, nicotinic acid can be decarboxylated by hydrothermolysis if one has an autoclave. Heating the aq. solution at 250°C for 120h gives 52% conversion to pyridine. At the same conditions in the presence of one eq. of HCOOH the conversion increases to 97%.

Aqueous high-temperature chemistry of carbo- and heterocycles. 1. Introduction and reaction of 3-pyridylmethanol, pyridine-3-carboxaldehyde, and pyridine-3-carboxylic acid
Alan R. Katritzky, Andrzej R. Lapucha, Ramiah Murugan, Franz J. Luxem, Michael Siskin, and Glen Brons
Energy & Fuels, 4 (1990) 493-498.

Attachment: Aqueous high-temperature chemistry of carbo- and heterocycles 1.pdf (781kB)
This file has been downloaded 1562 times

LSD25 - 16-6-2008 at 16:03

Here is a route using copper chromite catalyst - seems rather simple:

Quote:

Decarboxylation of Nicotinic Acid
Nicotinic acid (35 mg) was retluxed with quinoline (1 ml) and copper chromite (40 mg) for 20 min in a stream of nitrogen. The liberated carbon dioxide was passed through a solution of 2 N sulfuric acid (to remove pyridine vapors), and then trapped in ethanolamine- methyl cellosolve or barium hydroxide solution. The yield of carbon dioxide in the reaction was 90% of the theoretical yield.

http://article.pubs.nrc-cnrc.gc.ca/ppv/RPViewDoc?issn=1480-3...

They report the yield of CO2 rather than pyridine which is wierd, although they wanted their radioactive carbon back

Of course, what seems rather less simple is preparing the copper chromite catalyst, would it be the one on orgsyn?

http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2...

Here is another, more detailed look at the same reaction, which gives specific details:

Quote:

Decarboxylation of nicotinic acid (I). An intimate mixture of nicotinic acid (20mg.) with copper chromite (100mg.) was suspended in silicone oil (MS 550) (1ml.) and placed in the apparatus shown in Fig. 3. The apparatus was flushed with dry C02-free N2, while the tube containing the decarboxylation mixture was heated to 235C in a bath of silicone oil. The effluent gas was passed first through a 30ml. pear-shaped, double-necked flask cooled in ice, as shown in Fig. 3, to collect the pyridine (XII), and then through a bubbler containing carbonate-free 2N-NaOH (3ml.) to collect the CO2.

Decarboxylation was complete after 1 hr. at 235°. Some of the pyridine, however, remained condensed in the delivery tube. This was washed into the receiver by adding acetic acid (the solvent for the next conversion-see below) through the small entry port in the delivery tube.

http://www.biochemj.org/bj/102/0087/1020087.pdf (this came from page 6 of the PDF which also shows the apparatus).

PS The reason for the silica oil is explained on page 2 of the second PDF

Quote:

Nicotinic acid (I) is decarboxylated efficiently by heating with coppear chromite, provided that certain precautions are taken. Sublimation and decarboxylation of nicotinic acid both commence at 235C; even with a very slow gas flow rate, it is possible to drive nicotinic acid through several inches of heated copper chromite supported on asbestos, with only slight decarboxylation. Consequently, the nicotinic acid was intimately mixed with five times its weight of copper chromite catalyst and the mixture suspended in silicone oil.
Decarboxylation was complete after heating this mixture for lhr.

[Edited, reaction temp was shown as 2350 and even silicon oil will struggle at that temp

]

[Edited on 16-6-2008 by LSD25]

Magpie - 6-7-2008 at 19:43

I have a plan for making pyridine that is relatively straightforward, except for one problem: aquisition of hypophosphorous acid. Being it is List I makes this unobtainium for me.

Anyway, here's the proposed synthesis:

1. Using the Hofmann hypobromite reaction, convert nicotinamide (OTC no-flush niacin) into 3-aminopyridine. There's even an orgsyn procedure for this.

2. Diazatize the 3-aminopyridine. Then treat it with hypophosphorous acid. This removes the -NH2 group, leaving pyridine.

Those fortunate enough to live in a non-police state can likely still buy the acid. Then again you can probably buy pyridine easily also.

Nicodem - 7-7-2008 at 08:22

Ethanol and other alcohols also reduce ArN2+ to ArH + N2, though rarely in good yields. In some cases however this method actually works almost as well as hypophosphorous acid, especially on some heterocyclic compounds which 3-aminopyridine is. According to a probable mechanism, isopropanol might work better than ethanol.

The Hoffman rearrangement of nicotinamide is supposedly described in WO2005070888 (NaOCl/NaOH 0°C->90°C; 86% yield).

[Edited on 7/7/2008 by Nicodem]

ScienceSquirrel - 7-7-2008 at 08:48

For those of you fortunate to live in place where methylated spirits is still denatured with pyridine and in possesion of a good still the following procedure works nicely :cool:

1) Add hydrochloric acid dropwise to the spirits until all the pyridine is converted into it's hydrochloride salt.

2) Distill off the pet ether and methanol.

3) Distill off an ethanol fraction for solvent use.

4) Add water and strip the remaining ethanol.

5) Crystallise out your pyridine hydrochloride.

DJF90 - 14-7-2008 at 16:35

The following information was retrieved from:
http://customs.hmrc.gov.uk/channelsPortalWebApp/channelsPort...

Methylated spirits (UK composition)
90% vol. ethanol;
9.5% vol. 'wood naphtha'; and
0.5 vol. crude pyridine.

To each 1,000 litres of which is added:
3.75 litres of mineral naphtha (petroleum oil); and
1.5 grammes of methyl violet.

I am guessing that it should be 0.5% vol (as this completes the 100%) pyridine. That means that for 1ltr of distilled "meths" you can obtain (at best!) 5ml of CRUDE pyridine. This is not an especially good way of obtaining pyridine, but I admit it is better than none.

However, upon further reading, 'wood naphtha' is defined as:

"There is no prescriptive list of ingredients, but some or all of the following are found in approved synthetic wood naphtha:

pyridine;
pyridine bases;
allyl alcohol;
crotonaldehyde;
picoline;
denatonium benzoate; and
methyl alcohol.

So there may well be more pyridine in there.

S.C. Wack - 15-7-2008 at 02:32

I see the purification procedure for pyridine in the 3rd and 5th editions of Vogel and wonder just how dilute a solution of pyridine in ethanol with a correspondingly smaller addition of ZnCl2 and HCl can be, to produce a precipitate in the freezer. I've been wondering this for quite a while but have no way to test this, since there is no product denatured so sold here.

ScienceSquirrel - 15-7-2008 at 10:46

Have a look at ;

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

and

http://www.opsi.gov.uk/si/si2005/20051524.htm#5

Most modern UK methylated spirits use a substitute for wood naptha that consists of methanol and a marker.
I would guess that they pretty much use neat technical pyridine as well.

B & Q methylated spirits pretty much follows this formulation, go to;

http://www.diy.com/diy/jsp/bq/nav/nav.jsp?isSearch=true&...

and click on health and safety infomation

Raw methylated spirits has a distinct pyridine odour. On mixing methylated spirits with hydrochloric acid the result is a slighty opalescent liquid with a strong smell of petroleum spirit.

jarynth - 30-8-2008 at 18:21

Q. How to tell whether the denatured alcohol contains pyridine? In this case, the concentration would be about 0.5-1%, according to composition info found in this thread.

Here's a proposal. Possible nitrogen-containing co-denaturants include dyes and denatonium benzoate. A first strong distillation would get rid of these high-boiling compounds, while passing most of the pyridine. The distillate is then acidified with aq HCl. A second disillation would separate low-boiling compounds including ethanol, methanol, acetone, other alcohols and ketones, short alkanes, some water, etc, which constitutes a useful solvent anyway. The contents of the flask are aqueous and can be washed with copious amounts of ether, which can then be retrieved almost quantitatively by distillation for repeated use. The aqueous layer now only contains pyridine hydrochloride, which affords the pyridine by basification and subsequent fractional distillation (or is there a quicker way?).

ordenblitz - 12-9-2008 at 14:07

I completed some initial small scale testing for the production of Pyridine by decarboxylation of nicotinic acid with copper chromite.

The copper chromite was produced following the procedure outlined in Organic Syntheses, Coll. Vol. 2, p.142 (1943); Vol. 19, p.31 (1939). I opted to use the crude material obtained after calcining of the barium copper ammonium chromate feed stock. The subsequent acid washings were omitted. Thus the catalyst material obtained is reported to be: Cr2CuO4·CuO·BaCrO4
http://img390.imageshack.us/my.php?image=dsc05444ck2.jpg

A small scale retort was assembled from a test tube fitted with a stopper and a bent pipette functioning as an air condenser.
http://img145.imageshack.us/my.php?image=dsc05443vz1.jpg

Several runs were made to evaluate the effective proportion of crude chromites to C6H5NO2. It was reported in the paper by T.A. Scott that an excess of cromite was used by weight. Since their goal was careful recovery of all carbon and not production of a reagent, it seemed obvious that a 5x excess was not necessary for economy sake.

Procedure as follows. The nicotinic acid was ground in a mortar and pestle with the chromite until homogenous. This was then placed in the test tube and stopper fitted with the condenser. The assembly was placed on a 45% angle in a clamp. The lower end was gently heated using a propane flame. The sides of the tube were warmed when well into the reaction to effect the vaporization of the volatiles and carry them into the receiver vial. The first two runs were done with silicon oil but the third was done to determine if it was even necessary and it was not. In this setup the sample size is small enough to negate heat conduction issues.

The material collected was a mix of sublimated nicotinic acid and pyridine as identified by FTIR.
http://img529.imageshack.us/my.php?image=dsc05441lh9.jpg

The crude mix was weighed and then evaporated on a watch glass the re-weighed to determine the volatile proportion. Test results from 5 runs as follows:

1) 2 gm nicotinic acid, 0.5gm mixed chromites, 4 ml. silicon oil -
solid residue: 0.66 gm. volatile residue: 0.186 gm.

2) 2 gm nicotinic acid, 1.0 gm mixed chromites, 4 ml. silicon oil -
solid residue: 0.117 gm. volatile residue: 0.806 gm.

3) 2 gm nicotinic acid, 1.0 gm mixed chromites -
solid residue: 0.056 gm. volatile residue: 0.804 gm.

4) 2 gm nicotinic acid, 1.5 gm mixed chromites-
solid residue: 0.069 gm. volatile residue: 0.863 gm.

5) 2 gm nicotinic acid, 1.75 gm mixed chromites-
solid residue: 0.044 gm. volatile residue: 0.868 gm.

Obviously working with such equipment in this manner introduced some errors but it is fairly certain that using pure copper chromite is not necessary nor in such an excess for good yields.

Wiki says: "distinctively putrid, fish-like odour" I don't know if I would characterize it as fish like, but it sure smells bad.

[Edited on 12-9-2008 by ordenblitz]

Magpie - 12-9-2008 at 16:46

Nice work ordenblitz. It's good to see you posting experimental work again.

I will be needing some pyridine, shortly I hope. I have been trying to decide whether to make it or buy it. Your successful results are encouraging and I will likely give your synthesis a try.

Will it be difficult to purify the pyridine product? Can you form a salt out of the nicotinic acid and separate that out by crystallization/filtration? Or is there a better way?

Edit: On rereading it seems that you are saying that the solid residue is nicotinic acid and that the volatile residue is pyridine. In this case it seems that distillation is the obvious route to purifying the pyridine?

[Edited on 12-9-2008 by Magpie]

ordenblitz - 13-9-2008 at 09:59

Thanks. It has been a little too quiet in my lab in the past year but I have been messing about more recently. I am not in need of any pyridine however I wanted some copper chromite for another project. Mid synthesis on that I remembered this thread and decided to try it purely for the fun.

The first thing that happens upon heating is the nicotinic acid starts to vaporize and then sublimate on the inner walls of the reaction chamber. Shortly after pyridine also condenses on the inner surfaces and does, to a certain extent, dissolve and wash back the errant nicotinic acid. The papers mentioned heat of about 230 deg starts the reaction. While things did begin to happen at about that temperature, it did take more heat then I anticipated to drive to completion. As you would imagine the reacted carbonized mass is a very poor heat transfer medium so you have to pour on the flame near the end. I’m not sure I would use your good glassware for this nor probably is an electric mantle up to the job. In my opinion using a metal reactor would be preferable to glass. One could construct something from steel pipe that would serve well for this purpose. If it were elongated and mounted vertically and on the lower end most heat be concentrated, with the upper part cooler the condensed pyridine should wash back the sublimed nicotinic acid to the solid chromite effecting a better yield. A sealed reactor might be even better however there is some gas formed so it may not be practical depending on how high the internal pressure would rise. As for cleaning the product, I think a simple distillation would be all that is necessary.

Compared to my work with benzene from benzoates in my opinion this reaction is less trouble and has a better yield. With simple equipment and little time invested one could generate quite a bit of pyridine. The only time consuming part was making the copper chromite although it’s not complicated.

Magpie - 13-9-2008 at 12:25

Thanks for the additional details and insights. I just finished ordering some (NH4)2Cr2O7 and will hopefully have my own homemade pyridine some day soon.

Rant: I think it is important that we continue to develop home lab friendly procedures so as to be able to readily synthesize most of the basic (no pun intended) reagents. With ever-increasing restrictions being placed on the market place by our governments we home chemists must become evermore self-reliant. Some may ask why make pyridine when it is so commonly available. Well, when you add in the hazmat charge it becomes fairly expensive for one thing. And even if the reagent is not restricted you often times have a nagging feeling that by ordering it your name will be placed on some government list. Besides, making your own is always so much more satisfying, not only intellectually, but for the revenge it provides against stupid legislators, bureaucrats, and LE listmakers. End rant.

That's why your success is especially pleasing to me.

ordenblitz - 15-9-2008 at 17:19

I decided since I have a lot of the required intermediary copper chromite material I would try this reaction again scaled up and in glass. Damage was possible to the boiling flask but I have a few, so was prepared to sacrifice one for the cause. I was in fact completely wrong about the temperatures required and the possible heat transfer issues of the starting mix.

In a 50 ml flask was placed 24 grams of nicotinic acid intimately mixed with 12 grams of Cr2CuO4·CuO·BaCrO4 catalyst mix.
http://img75.imageshack.us/my.php?image=dsc05446ni4.jpg
http://img222.imageshack.us/my.php?image=dsc05449ue1.jpg

One should definitely start by warming this mix slowly because it will limit or avoid all together much of the sublimation of the nicotinic acid.
http://img222.imageshack.us/my.php?image=dsc05451od1.jpg

A little heat blanket is handy here to speed things along.
http://img217.imageshack.us/my.php?image=dsc05466yf6.jpg

I got in a hurry though and turned the mantle all the way up in the beginning thinking I would not have enough heat. I had to unplug and let the moving air of the hood cool things a little. You can see the white smoke of nicotinic acid filling the flask and condenser.
http://img68.imageshack.us/my.php?image=dsc05452ky8.jpg

After things got settled down and a little cooler, it really only took a setting of about 50% on my controller to keep the reaction running smoothly. This lower temperature allowed some pyridine to reflux into the mix washing back any escaped C6H5NO2. You can see small droplets forming here but really no white fumes indicating sublimed material. I did not measure the temperature of the reactants but I guess the flask to be at less then 250 deg at this point and working well.
http://img134.imageshack.us/my.php?image=dsc05480xn6.jpg

At this point I was collecting about a drop every 6 to 8 seconds. Total time of the reaction was about 40 minutes pushing it slowly. With set up and takedown all told about an hour and a half of lab time.
http://img225.imageshack.us/my.php?image=dsc05461gm8.jpg

The result was 11.8 grams of a fairly clean first run product. I will distill the pyridine after I have made a few more runs to perfect the technique at this size.
http://img225.imageshack.us/my.php?image=dsc05487rm4.jpg

I have to say that this reaction in standard glassware is very simple and easy to do. My presumption that the mantle could not generate nor the glass stand the temperatures required was completely incorrect. Also my assertion that heat transfer through the reactants would be difficult but this was also not the case. Yields are good and the reaction runs smoothly and controllably. If you take your time during the initial heat up sublimation of the nicotinic acid will be very minimal.

Magpie - 15-9-2008 at 18:03

Sweet! You have basically given us a home lab friendly procedure for making pyridine. Thank you!

I did try to make pyridine by decarboxylation of nicotinic acid with NaOH using dry distillation. I made mostly carbon and just enough pyridine to stink up the lab.

I'm curious as to the mechanism of the copper chromite catalysis. I wonder if it is known?

ordenblitz - 15-9-2008 at 18:24

LSD25, I believe, found this procedure. I just did the easy part.. mixed stuff up!
Have to say though.. it was pretty simple to do all told.
Now... what to use the pyridine for?

Magpie - 15-9-2008 at 18:47

Quote:

Now... what to use the pyridine for?

I plan to use a little in the synthesis of cinnamic acid, where it has been shown to be a catalyst.

I would think it could be used to make pyridium chlorochromate (PCC), useful for making aldehydes from alcohols. Seems like I've seen a procedure for making PCC somewhere.

jarynth - 8-10-2008 at 21:31

Very helpful data ordenblitz! And congratulaton on the experimental feel of trying several runs. Can you tell us about the recovery of the catalyst? Did you try it at all? Making the catalyst requires quantitative amounts of dichromate, which - if wasted - would drive up horribly the cost of making pyridine by this route (not to speak of the necessary expense: the cost of nicotinic acid). Clearly the cations can be recovered by brute force, but how about cleaning the tarry residues off the chromites without degrading them?

Copper salts are famous for catalyzing decarboxylation in general. I tried heating a small mixture of nicotinic acid with 1) slightly oxidized copper powder, and 2) copper sulfate, in a test tube, on an open flame. 1) only gave a white sublimate and no fishy smell before carbonizing, whereas 2) produced small droplets and almost no sublimate, and a light fishy/tarry smell was noticeable. Unfortunately this dripped back onto the solids and was impossible to extract once cool.

[Edited on 9-10-2008 by jarynth]

Magpie - 31-10-2008 at 19:17

Today I made some pyridine following the full scale method of ordenblitz. I must say that it worked very well. At first I tried the small scale method but problems with sublimation of the nicotinic acid, etc, resulted in failure.

For the full scale method I followed the procedure of ordenblitz to the letter, right down to the paper clip holding the insulating blanket. I brought up the heat very slowly, and never set the voltage controller over 65% for my 80 watt Glas-Col heater. The pyridine would come over in spurts of about 10 drops every minute at the peak of production. This slowed as the run progressed. I didn't measure the volume of product but it looked the same as that of ordenblitz. This would place the yield at very near the theoretical 13.1 ml. I didn't see any sublimation above the powder so guess that any contamination of the product would likely be a small amount of water. A picture of the distillation set up is shown below. A 2nd picture is shown in the following post.

It's Halloween - pyridine for everyone!

Magpie - 31-10-2008 at 19:21

Here's a picture of the powder following the run. You can see the sublimated nicotinic acid as a hoarfrost on the surface. This powder broke up very easily and there was no damage to the RBF.

pyridine hoarfrost.jpg - 67kB

peach - 14-11-2008 at 04:04

If you want to make a significant quantity of it, niacin will be too expensive.

The industrial synthesis is much more applicable and, for a change, doesn't require any insane pressures, temperatures or catalysts.

However, the industrial synthesis does not produce pure pyridine as I understand it. If you do some searching, you'll find it produces a number of lines based on pyridine, as well as the pure product it's self. In some work, I saw around 50% suggested as the pure pyridine yield - that was with a catalyst.

I've yet to find one that's optimized to produce pure pyridine. If anyone does know of one, give me a shout (u2u).

smuv - 14-11-2008 at 05:20

Nice work magpie! I guess I missed your post two weeks ago. As always nice setup and nice clean lab.

@ peach you might want to check out this website; some good prices on supplements in large quantity
http://purebulk.com/niacin-usp-c-65.html?zenid=da86794355fca...

Magpie - 14-11-2008 at 18:51

Thanks smuv. It really was easy once you have the catalyst.

ordenblitz - 14-11-2008 at 21:39

Jarynth,
I did not do any more work on the catalyst recovery as I did not have the time. If I were to do any more work in this area it would be on other more common copper compounds to see what else might work better. But since pyridine is of no particular use to me, simple curiosity may not be enough for me to continue.

Magpie,
Did you get any final numbers after distillation for yield? Very interesting project making the catalyst don't you think? I was most amused by the burning of the copper barium ammonium chromate. Also, you keep such a clean lab, I feel ashamed.

[Edited on 15-11-2008 by ordenblitz]

Magpie - 15-11-2008 at 08:26

Quote:

Did you get any final numbers after distillation for yield? Very interesting project making the catalyst don't you think? I was most amused by the burning of the copper barium ammonium chromate. Also, you keep such a clean lab, I feel ashamed.

No, I just transferred the pyridine directly to its storage bottle. For my intended use the quantity is more than adequate, and IMO the purity is likely already quite good.

Yes, making the catalyst was interesting. I burned the catalyst off in my muffle furnace so really wasn't able to watch it decomposing. I did expect to see brown NO2 vapors coming out the top of the door gap, but did not. Perhaps the nitrate decomposes to N2 instead.

Re: my lab: I have limited space so have to keep everything in its place. It also makes me feel like I have things under control.

ordenblitz - 15-11-2008 at 08:34

I would not have characterized any of the runs I did as producing anything near pure. If you evaporate a few drops of the distillate on a watch glass you will more then likely find a remaining tan/white colored residue.

[Edited on 15-11-2008 by ordenblitz]

unome2 - 24-5-2009 at 15:21

Here is another on the use of copper(II) nicotinate for the production of pyridine

"The Thermal Decomposition of Copper(II) Nicotinate and Isonicotinate" Thermochemica Acta, 138 (1989), 233-9

They form the salts from CuSO4 and the sodium nicotinate in solution, the formed Cu(II) nicotinate precipitates and is washed.

Lot easier, if it works, than making the copper chromite

[Edited on 24-5-2009 by no1uwant2no]

Easy pyridine from Niacin

elsolvital - 1-5-2010 at 00:00

Thanks for the posts here, I was able to make pyridine thanks to them. I made some copper chromite and used it to make pyridine. Then I tried just mixing niacin with aluminium oxide and it worked too. And then I found an even better way...

Just put the tablets whole and uncrushed in the flask and slowly distill them and you get pyridine. Too easy and it works as well as with copper chromite. I used these:

http://www.puritan.com/niacin-b-3-362/niacin-nicotinic-acid-...

Don't bother with catalysts, just distill the tablets whole!!!

chief - 1-5-2010 at 00:53

I can get the kg of Pepper at 6 EUR (white or black) ..; with the pyridine-content at 5-9 % (wikipedia) this would give 50-100 g of pyridine for 10 bucks of production-cost ...
==> Is the pyridine any useful ? Can it be sold to any people ?

UnintentionalChaos - 1-5-2010 at 01:43

Quote: Originally posted by chief

I can get the kg of Pepper at 6 EUR (white or black) ..; with the pyridine-content at 5-9 % (wikipedia) this would give 50-100 g of pyridine for 10 bucks of production-cost ...
==> Is the pyridine any useful ? Can it be sold to any people ?

We're talking about pyridine, not piperine.

AndersHoveland - 26-5-2012 at 02:38

The trimer of acetaldehyde can be reacted with ammonium hydroxide and ammonium acetate at 230 °C to make 5-ethyl-2-methylpyridine in 50-53% yield.
Org. Synth. 1963, Coll. Vol. 4, 451-453
http://syntheticremarks.com/?p=147

Link

cal - 4-8-2012 at 18:10

Do you have a English version?

Quote: Originally posted by not_important

The ZIP file appears to be broken, near the end of it in the central directory the "version made by" offset is bad, looks like the zip creator stuttered and had 0x1414 instead of 0x0014. What was used to create it?

As it is a DJVU file, zipping it saves little if any space. If the zip was needed to get the board software to take it, that's one thing and perhaps the board could be configured to accept .djvu files, otherwise it might be better not to zip single .djvu files.

Price of Pyridine prepared from Nicotinic Acid

Tempus_Edax_Rerum - 22-1-2016 at 08:09

At an 84% yeild from Niacin and the copper chromite catalyst, I was able to produce just under 14L's from 25Kgs of Niacin. I bought 25Kgs for 400 USD from a health food store online. The cost of the catalyst which I prepared, only cost about 30 USD. So if you can buy ACS grade Pyridine cheaper than 430 USD for 14L's, please tell me who your chemical supplier is.

SunriseSunset - 31-1-2016 at 10:27

Youtube Video for Copper Chromite catalyst preparation

The same guy also shows how he made pyridine in another one of his videos. From niacin (nicotinic acid) and the copper cromite catalyst. The reason you want to see these videos is because he explains and shows a lot of useful techniques for the preparations! He works at a pretty fast pace and talks pretty quick too. I like his videos a lot

[Edited on 31-1-2016 by SunriseSunset]

Magpie - 31-1-2016 at 10:34

Quote: Originally posted by SunriseSunset

The same guy ...

This is Praxichys, a member of this forum. He is now the prolific producer of a fine line of YouTube videos.

Herr Haber - 31-1-2016 at 21:40

Quote: Originally posted by UnintentionalChaos

Quote: Originally posted by chief

We're talking about pyridine, not piperine.

I could see a lot more uses for piperine than pyridine. A few bad ideas spring to mind

Pyridine is a very seldom used solvent. I got 250ml 3-4 years ago and only used about 50ml so far (probably involved in the desctrction of some kind of EM.)

What I do know about Pyridine is that I store it in my toilet among other sensitive chemicals. I replaced the HDPE bottle with real Duran glassware and an PTFE cap. I can stil hear the gurgling noise *I'm about to vomit" from my GF that was passing by behind me even though I had an extractor on (and a gas mask!).
That's the solvent I like less because it's hard to describe the other without being "rude". I mean, it's a mix of sewers, rotting fish and lady parts that havent seen a shower for 15 days.
Even considering boiling point and vapor pressure I'm sure it stinks more even in summer.
And yeah, the toilet / cabinet for nasty chems has a window that's open all year long!

I was very interested in the synth above that went directly to hydrochloride for that reason.
There are alternatives but sometimes not and I know a couple of experiments I never did just because of the stench !

NZniceguy - 27-8-2018 at 20:15

I have been sent niacinamide instead of niacin....niacin is usually a powder when I have bought it before but this is crystals....now the billion dollar question is......will the niacinamide still decarboxylate to pyridine as niacin does?

Edit....damn I see it has an NH2 group instead of the OH group....is there a reasonable way to remove the amide to get pyridene?

[Edited on 28-8-2018 by NZniceguy]

wildfyr - 28-8-2018 at 18:17

I think the trouble of getting the amide off is much more than just buying some niacin and waiting for it to arrive.

NZniceguy - 29-8-2018 at 05:11

Quote: Originally posted by wildfyr

I think the trouble of getting the amide off is much more than just buying some niacin and waiting for it to arrive.

I think you are right....guess i'll just have to wait the two weeks.....the joys of living on the opposite side of the world to everybody else.

nimgoldman - 3-9-2018 at 21:00

I have prepared pyridine successfully by decarboxylation of niacin (vitamin B3) mixed with basic copper carbonate. It has been discussed here long time ago and the method works.

Copper chromite catalyst should give you better yields and you need much less.

It's certainly not the best, cheapest or highest yielding method but if you need little bit of pyridine (say up to 500 ml), it works great.

Purification of pyridine consists of drying it with NaOH/KOH (this also precipitates niacin as salt), filtering and distillation over more NaOH/KOH.

See Nile Red and Doug's Lab videos on YT. They show the process in detail.

My first time I made something like 60 ml of crude pyridine.

NZniceguy - 8-9-2018 at 06:41

Quote: Originally posted by nimgoldman

I have prepared pyridine successfully by decarboxylation of niacin (vitamin B3) mixed with basic copper carbonate. It has been discussed here long time ago and the method works.

Copper chromite catalyst should give you better yields and you need much less.

It's certainly not the best, cheapest or highest yielding method but if you need little bit of pyridine (say up to 500 ml), it works great.

Purification of pyridine consists of drying it with NaOH/KOH (this also precipitates niacin as salt), filtering and distillation over more NaOH/KOH.

See Nile Red and Doug's Lab videos on YT. They show the process in detail.

My first time I made something like 60 ml of crude pyridine.

That is exactly what I usually do but this time i was sent NiacinAMIDE instead of Niacin so cant just decarboxylate.......I've had to reorder and wait 3 weeks for delivery due to me living on the wrong side of the world.

S.C. Wack - 8-9-2018 at 09:01

Hydrolysis of niacinamide is not difficult with HCl or NaOH.

NZniceguy - 9-9-2018 at 19:43

Quote: Originally posted by S.C. Wack

Hydrolysis of niacinamide is not difficult with HCl or NaOH.

Any chance you could give some details on that please?

nimgoldman - 9-9-2018 at 20:56

I see. I faced the same problem as I could get only NiacinAmide locally so had to order Niacin from abroad.

However, here an interesting article on the topic:

Using Niacinamide in an acidic formulation

Quote:

The conversion from Niacinamide to Niacin is called NON ENZYMATIC HYDROLYSIS. Basically that means splitting a molecule up to release water without using a biological enzyme to cleave the molecule. This type of hydrolysis reaction is quite common in organic chemistry.

...

The above study found that a 10% Niacinamide solution heated to around 89C and then taken to a pH of below 4.5 with a STRONG acid did start to hydrolyse and form Niacin and that this conversion was a first order reaction which basically means it went from Niacinamide to Niacin without turning into anything else first. The study found that between pH 4.5-6 very little of this crazy game of shape shifting occurred. In fact at pH 4.5 – 6 the half-life of the solution was found to be 1000 days which probably means that the average cosmetic formulator has little to worry about.

You're welcome.

The reaction gives off ammonia so you could tell the reaction proceeds by smell.

Removing the water should not be much of a problem since niacin has solubility of only 18 g/L and m.p. of 237 °C so hard boiling won't hurt it.

Nicotinamide has much higher solubility in water (500-1000 g/L depending on source) which is convenient.

So the procedure would be something like this:

make solution of nicotinamide in a beaker (say 50%)
add enough acid to make it strongly acidic (say pH 1.0-2.0)
heat and stir on hotplate to almost boiling
nicotinic acid will precipitate, filter, wash with cold water (to remove nicotinamide) and return filtrate to the hotplate
continue boiling off water and filtering until no more precipitation is observed
air dry or vacuum dry the collected nicotinic acid

[Edited on 10-9-2018 by nimgoldman]

S.C. Wack - 10-9-2018 at 02:52

I presume that after niacinamide is refluxed with conc. HCl for long enough, the HCl distilled off would leave niacin hydrochloride and ammonium chloride.

S.C. Wack - 10-9-2018 at 13:49

AFAIK, at this point if water is added at the rate it's distilled, in time only niacin should remain.

NZniceguy - 11-9-2018 at 06:25

Thanks guys, I shalll give it a go whilst i wait for the next lot to arrive and will let you know how i get on.

S.C. Wack - 11-9-2018 at 14:06

Presumably niacin can be refluxed indefinitely without harm in air in ~azeotropic HCl; IDK and haven't looked in to it...obviously one wouldn't want a more conc. HCl than that. The textbooks probably indicate a large molar excess for amide hydrolyses...the more the better and faster here.

Hydrolysis chart

Loptr - 11-9-2018 at 15:02