Talk:Piperidine

Heterocyclic
There is no mention that piperidine is a heterocyclic compound. I fix it.--84.163.86.13 00:03, 10 October 2006 (UTC)

Piperidine compounds
No, piperidine is not the same as piperidine compounds. Some editors are obsessed with the following idea:

Piperidine is a structural component of fireant venom.

Piperidine is a structural component of neuroleptics.

ergo: Neuroleptics cause symptoms like fireant venom

etc. See also article on phenothiazine:

Phenothiazine is an insecticide

Phenothiazine compounds are neuroleptics

ergo: Neuroleptics are bugspray and cause anticholinesterase toxicity.

etc. etc.

I have added a few more examples of piperidine toxic compounds to add to this kind of logic. You can check it out.

And: Please don't revert edits without a comment. This is not a looney bin. 70.137.181.232 (talk) 09:24, 21 July 2008 (UTC)

Added Piperidine alkaloid, which is an insecticide. So, for the records, piperidine compounds fight insects, everywhere. 70.137.181.232 (talk) 00:46, 25 July 2008 (UTC)

I am in favor of the information you added to the piperdine article staying in. The article is quite small compared to many other articles on Wikipedia and i am in favor of the article being expanded to be exhaustive in all compounds containing piperidine. 65.28.227.116 (talk) 04:09, 29 July 2008 (UTC)

Disgressions
I have just reinstated my recent edits that had been reverted (diff. Here are my detailed reasons:

Cacycle (talk) 02:50, 25 July 2008 (UTC)
 * Quinine is a bad example, it contains quinuclidine, not piperidine
 * The whole section about ditran has nothing to do with this article
 * The rest of that section was written in a very unencyclopedic tone and/or had not much to do with piperidine itself
 * The neuroleptics are not synthesized from piperidine and were clearly in the wrong section
 * The piperidine structure is so common that it does not make sense to randomly list compounds that have it in their structure

The mentioned neuroleptics are not "synthesized from" piperidine, but are piperidine compounds. Checked. 70.137.181.232 (talk) 03:31, 25 July 2008 (UTC)

I didn't fall over the quinine (didn't add it either). Ditran etc are piperidine compounds, some neuroleptics too. They are not synthesized from piperidine. I agree that the piperidine structure is common. The bulbocapnine was indeed far fetched. So, *sigh*, I agree with your edit. The whole conspiracy theory now down the drain. *sigh*. Can't we at least mention, that anabasine is an insecticide? 70.137.181.232 (talk) 03:02, 25 July 2008 (UTC)

70.137.181.232 (talk) 03:43, 25 July 2008 (UTC)
 * Sigh* the whole educational effort now ruined *sigh*. Censored! *THEY* don't want us to know the *TRUTH*.

I am in favor of the information you added to the piperdine article staying in. The article is quite small compared to many other articles on Wikipedia and i am in favor of the article being expanded to be exhaustive in all compounds containing piperidine. 65.28.227.116 (talk) 04:07, 29 July 2008 (UTC)


 * The only compound which contains piperidine is 1 - piperidine. If you misspoke, and meant "compounds containing the piperidine substructure", a search of PubChem shows 1249853 hits. So, either way doesn't work. --Rifleman 82 (talk) 04:24, 29 July 2008 (UTC)


 * That does'nt however mean that there is 1249853 piperidine compounds however. 65.28.227.116 (talk) 04:33, 30 July 2008 (UTC)


 * Pray tell, what does this 1249853 number represent then, in your opinion? --Rifleman 82 (talk) 05:39, 30 July 2008 (UTC)

Dispute on piperidine
If piperidine is used as a precursor to commerically significant compounds, then this application merits mention, IMHO. The mere presence of the piperidine-skeleton is more questionable. Otherwise the benzene article would or could indicate it is "in" thousands of compounds, which would be silly. It is very possible that piperidine is a common pharmacophore, a concept that could be explained. In WE-chem, we are constantly dealing with all sorts of editors, often from advocates for some political cause or conspiracy, who cannot suppress an urge to fill these pages with tangential information (e.g. that Socrates drank a tea containing a molecule related to piperidine!), the main virtue of such information being that it is merely true, vs pertinent and notable.--Smokefoot (talk) 17:23, 28 July 2008 (UTC)


 * I think there is always some room in the articles about functional groups, heterocycles, and common ring systems, to discuss the properties that are general to the compounds having a given substructure, as well as some specific examples. However, the discussion needs to be focused and avoid too many random-looking examples, or even worse, a selection of not-so-random examples that gives wrong ideas to the reader. One of the statements that was removed during the edit war was that "Many pharmaceutical drugs contain a piperidine ring because the group tends to impart favorable pharmacokinetic properties such as water solubility and bioavailability. Most piperidines induce the liver enzyme CYP2D6, resulting in faster metabolism, such as in many beta-blockers and antiarrhythmics". This kind of information, if true, seems highly relevant, but can we have a reference, please? I did a quick search to see if I could find an article about piperidine as a building block in drug molecules, but I couldn't find it. --Itub (talk) 17:46, 28 July 2008 (UTC)
 * That cited part on pharmacokinetics is utter nonsense. That might actually be true for that unnamed class of compounds, but it is clearly not a general feature of the piperidine moiety. You could equally well attribute this to methylene groups. Cacycle (talk) 00:52, 29 July 2008 (UTC)

The article simply states that piperdine is a structrual component of these drugs which is true: risperidone, raloxifene, minoxidil, thioridazine, haloperidol, droperidol, and mesoridazine. Nowhere is it stateed that the drugs are synthesised from piperidine. Dr CareBear (talk) 14:18, 28 July 2008 (UTC)
 * The sentence, as it is there now, suggests that the compound 'contains' piperidine ("Piperidine is found in the following drugs"), which is untrue (and that was true quite a couple of times in the edits). It would be better to say that it is a structural component of the drug.  --Dirk Beetstra T  C 14:51, 28 July 2008 (UTC)


 * Perfect.--Stone (talk) 15:54, 30 July 2008 (UTC)
 * Not really: see Beetstra's and Cacycle's comments. Piperidine is NOT found in ANY drug. The presence of the piperidine skeleton is of no specific pharmacological significance: six membered hydrocarbons are routine as are amines, so inevitably the piperidine skeleton is pervasive.--Smokefoot (talk) 17:36, 30 July 2008 (UTC)

In reply: Piperidine, pharmacological significance
Yes, the presence of the piperidine skeleton is of some pharmacological significance, however not in the way how some editors imagine (giving pharmaceuticals the properties of ant venom). The significance is that frequently a functional amino group is embedded into the semi-rigid conformation of the piperidine skeleton, to arrive at derivatives with altered pharmacological profile (keeping the distances to other functional groups constant): The alteration may stem from the semi-rigid conformation, or from the increased lipid solubility due to the 5-C chain, or from details in receptor binding affinity by the bulky ring addition, or from steric hindrance of metabolic attacks, to give examples. Or from a combination of the above and other factors.

Substance examples:

Phencyclidine vs. open chain analogs

Phenmetrazine vs. Methamphetamine similar for Phendimetrazine oooh, made a mistake there these have a morpholine ring. The corresponding piperidine analog is not commercialized, because it has an extremely long duration of action.

Thioridazine vs open chain neuroleptic analogs (increased central activity)

N-ethyl-Piperidil-3-benzilate vs. Benactyzine (increased central activity and duration of action)

Pethidine and derivatives vs. open chain analogs

You are however right, that no common simple property of the piperidine compounds is inherited from the parent compound, as naive editors assume. So there is a common theme of alterations which may be achieved by this embedding; but it has no single, simple and consistent explanation, more like a mix of the above mentioned possible mechanisms plus others, like change of metabolic pathways due to the steric hindrance of certain metabolic attacks in the open chain analog etc. and things become more complex if we take the possibility of active or toxic metabolites into account. Embedding the active amino group is simply one of the building blocks in drug design and individually leads itself to new SARs to play with. I would not call this "no significance".


 * I've read a bit of medicinal chemistry myself as well, but the texts I saw generally talked in more general "rules of thumb". For example, if to increase hydrophobicity, add more carbons, as you say. To reduce flexibility, add a ring. If you need a hydrogen bond donor, add an amine or alcohol. If you need to protect something from oxidation, block it with something (maybe fluorine) or see if you can remove it. To increase solubility... and so on. But I've never seen a rule that says "add piperidine", although to some extent it may stem from the more general rules because it is a ring, it is an amine, and it has five methylenes. Of course, the books include specific case studies and some may include piperidine. But the ones I've seen don't focus the discussion on the piperidine itself. Is there really enough we can generalize? What references can you cite about it? Cacycle made a good point in comparing it with methylene: a vague statement such as "piperidine can improve pharmacokinetics" can be true of nearly any functional group found in a drug. Most groups are added either to improve pharmacokinetics or pharmacodynamics, but is this specific group notable enough to mention here? To give an example, I would say that trifluoromethyl is more notable because I've seen reviews focusing specifically on the use of trifluoromethyl in medicinal chemistry. I haven't seen anything like that for piperidine. If there is something, it would be a great source for this article. --Itub (talk) 05:58, 1 August 2008 (UTC)

We are confusing several contributions here. "It improves pharmacokinetics, leads to induction of 2d6... etc" is a kind of unfounded overgeneralization by somebody else, which I have removed. However remarking (See list of examples) that embedding an amino-alkyl chain of an existing substance into the ring to add e.g. conformational rigidity, make it more lipophilic, change receptor (or subtype) affinity or prevent metabolic attacks by steric hindrance is a safe bet. (The latter is even more pronounced in some quinuclidine analogs, which have no dangling ends) I said it is common repertory, leading to new SARs individually. So no generalization possible. The examples show that it is common, just out of my hat, to build conformationally rigid analogs of open chain substances. Even historically such progress is frequently observed. But even claiming that it improves any aspect of the substance is an overgeneralization. It simply adds new degrees of freedom to the design, and may add the above mentioned properties, which may be of benefit or not, depending on the objective of the design. There is no philosophers stone. But the common use of this trick gives it some notability. As I said the same true for some other typical structure components. Trifluormethyl is easier to describe, as it has a more localized function, than the transfer from an open chain to some ring embedding. Thank you for responding at all. 70.137.164.136 (talk) 07:08, 1 August 2008 (UTC)

Example, assuming we have to replace a functional alkylaminoalkyl: Embedding in the piperidine ring vs. metabolic attack: Dealkylation hindered by "no dangling end". Deamination hindered by steric hindrance. (Out of my hat) Memories alread a bit dusty after the long years. 70.137.164.136 (talk) 07:45, 1 August 2008 (UTC)

Article, remarks
So, kinnings, I am running out of patience. Here my take: The inclusion of natural "piperidine alkaloids", like solenopsin, anabasin, coniine, conhydrine is fully justified, as in the usual alkaloid classification in literature historically such distinction is being made, and such classification is being used. The addition of "unencyclopedic tangential" information, like that Socrates was executed by coniine, or anabasine is a nicotine like alkaloid, used as an insecticide, doesn't harm and adds a little to historical and everyday life context for the lay reader. We really don't need to encrypt this article to be readable or at least partially understandable only for chemists. I will be glad to point to scientific teaching materials (The chemistry of the plant alkaloids), which gladly include such slightly tangential information, historical information and case reports. We don't need to be more catholic than the pope here. Regarding examples of the occurence of the piperidine structural motif in pharmaceuticals: Yes, give a few examples. Why not also include the JB-329 piperidilbenzilates, even if somebody, somewhere may wonder how everything is apparently connected to everything in the universe. No need to censor that. Of course these really include the "structural motif", not piperidine. And the structural motif is present in 1 Mio (!) other chemicals, so we have to focus on a few more commonly used pharmaceuticals there. My focus on toxic examples was "all true". but biased by selection, in an attempt of a "reductio ad absurdum".

Now kinnings: A serious word to Dr Carebear and another anon editor:

Chemistry doesn't work like cooking chicken soup. In chicken soup you cook a soup on chicken, then it is a chicken soup and tastes like chicken. If you add salt it becomes more salty, if you add pepper it becomes more peppery. It is a mixture of the components. (Chicken, salt, pepper)

In chemistry this is not true for chemical compounds and chemical components. Ordinary salt is Sodium chloride, a compound of the flammable metal Sodium and the toxic Chlorine gas. But it retains none of these properties.

Anon: you said "containing piperidine" and "including the piperidine structure" would be the same, and I am mincing words. No I am not mincing words, but you need a chemistry class, as seen by the example of ordinary salt, which is not chlorine poison gas any more. I told you to discuss, others have told you the same. You are a candidate for blocking for vandalism, see your talk page.

Carebear: I have explained (for Phenothiazine) that in friendly words on your talk page, and you are still reversing edits without comment and discussion. This is mental. Stop it. Your neuroleptic bugspray theory is crap, for the same reason, why table salt is not poison gas, in the same logic. Discuss further edits. This has been explained to you since a year, by reasonable people, on your talk page. If you don't listen then it is either vandalism, or lack of intellectual capacity, or hooliganism. I would propose you abstain from editing chemical articles. 70.137.164.136 (talk) 07:36, 31 July 2008 (UTC)

Piperidine, natural occurence
Piperidine (itself, not piperine) has been obtained from pepper (Spaeth and Englaender, Ber.1935,68, 2218; cf. Pictet and Pictet, Helv. Chim. Acta, 1927, 10, 593),from Psilocaulon absimile N.E.Br (Aizoaceae) in which it occurs to the extent of 4.5% (Rimington, S. Afr. J. Sci, 1934, 31, 184), and in Petrosimonia monandra (Juraschewski and Stepanov, J. Gen. Chem., U.R.S.S., 1939, 9, 1687) (from ref below)


 * I think this is worth including in the article. --Itub (talk) 16:38, 31 July 2008 (UTC)

Piperidine alkaloids
The Lobeline group belongs also to the Piperidine alkaloids. (ref Book: The Plant Alkaloids, Thomas Anderson Henry (Formerly Director Wellcome Chemical Research Laboratories and Superintendent of Laboratories, the Imperial Institute London), 4th ed. 1949, The Blakiston Company)

This book is also a rich source of "unencyclopedic information" about the effects on frogs, extraction, plant synthesis pathways, commercial and historical importance. And it is written in "unencyclopedic tone". It is instead cacyclopedic.

Download from this site (very interesting website for WP freaks)

http://www.sciencemadness.org/library/index.html

70.137.164.136 (talk) 08:40, 31 July 2008 (UTC) 70.137.164.136 (talk) 08:48, 31 July 2008 (UTC)

unencyclopedic?
And cacycle may please explain, what he means by "unencyclopedic tone". More catholic than the pope? I still believe that many things in scientific articles can be explained in plain english, for plain people. I know that we have to deprogram fresh academics from their academic babble until they finally notice that they are not writing on their damn thesis any more. Keep it educational for plain people too. e.g. "Scientific American" is also readable for normal educated people, WP should learn from that. (or if that is too prole for you, think you write for your CEO) 70.137.164.136 (talk) 09:03, 31 July 2008 (UTC) 70.137.164.136 (talk) 13:19, 31 July 2008 (UTC)

Consensus version
It is of nobody's interest that the article is protected indefinitely. Can we come up with a consensus version which most, if not all of us can agree with?

I will start with

Piperidine and its derivatives are widely used building blocks in the synthesis of pharmaceuticals.

(Adapted from article text.) I left the second sentence out because it is IMHO patently false.

--Rifleman 82 (talk) 07:03, 1 August 2008 (UTC)
 * Which sentence are you talking about? Hundreds of drugs do include a piperidine moiety, although as 70.(and basically everyone else) said above, "piperidine is not the same as piperidine compounds". I wouldn't like to see this article without any mention of "piperidine-containing" drugs; I'd like to see it free of fallacious arguments that have been pushed before on other articles (such as phenothiazine). Fvasconcellos (t·c) 14:40, 1 August 2008 (UTC)

Rifleman, the patently false sentence you deleted is patently false because you locked it on a version by somebody who doesn't understand the difference between "contains" and "contains the structure". Maybe patch that back to the right version and then unlock. I see nobody is discussing here any more. We can do the edits ourself. I will however be much obliged, if Carebear discusses before inserting anything. Given the 1 year period reasonable people have been trying to discuss with him without success, this is now enough. But we can't lock all neuroleptics for that reason. Just removed the last instance of his "anticholinesterase blocking" insecticide-neuroleptic theory from an article, as well as faulty hidden redirections and hidden links from "anticholinergic" to "cholinesterase inhibitor" by him. If this is not vandalism or hooliganism, then it is lack of intellectual capacity, disqualifying for edits. This is also a matter of civility. 70.137.164.136 (talk) 23:49, 2 August 2008 (UTC)

Sorry, didn't notice Fvas' comment. I think this statement ("Piperidine is found in the following drugs: risperidone, raloxifene, minoxidil, thioridazine, haloperidol, droperidol, and mesoridazine.") is patently false in that while it contains the piperidyl moiety, it doesn't contain the compound piperidine per se.

Since 65.* and carebear have declined comment here, I'll unprotect the page. If edit-warring starts again, I'm afraid we'll have to come back here. --Rifleman 82 (talk) 06:59, 3 August 2008 (UTC)


 * Calling patently false a statement that can be corrected by adding two words is a bit too strong IMO. It's just an imprecision. The names of heterocycles are also commonly used as if they were functional groups. For example, the article on pyridine in Encyclopaedia Britannica begins with the words: "any of a class of organic compounds of the aromatic heterocyclic series characterized by a six-membered ring structure composed of five carbon atoms and one nitrogen atom. The simplest member of the pyridine family is pyridine itself, a compound with molecular formula C5H5N."  Sometimes it is obvious from the context whether one is talking about the specific compound or the family, and sometimes it is a good idea to be explicit. --Itub (talk) 10:03, 4 August 2008 (UTC)

Why mentioning Socrates can be a good idea
The mention of Socrates in this article has been the subject of much ridicule, and now it has been deleted. Yet I think such a mention was useful. The article still mentions coniine and poison hemlock, but now many readers will wonder what the hell those things are. A good principle for making technical writing comprehensible is to try to connect the things that readers may not know yet with those that they are likely to know. I think readers are more likely to know about Socrates and his death than to remember the name of the plant that was used to kill him. Therefore adding a short phrase about Socrates makes the article more likely to grab the reader's attention. I agree that we may be trying to be more Catholic than the Pope here in avoiding interesting "trivia". I've seen countless perfectly serious chemistry textbooks, review articles, and research papers that include this type of "trivia" to help put things into perspective, or just to make the writing more interesting. --Itub (talk) 11:44, 4 August 2008 (UTC)


 * To show how many book authors have thought it was worth mentioning Socrates in the context of piperidine and piperidine alkaloids in particular, see . --Itub (talk) 11:49, 4 August 2008 (UTC)
 * Agree - I was one of the ridiculers, but I concede the point. I did not think that any C-substituted piperidines should be developed much less mentioned as "see also"'s (the piperidinyl tetrasulfide is made from piperidine, so it is actually a derivative operationally).  But given that many cmpds containing the piperidine skeleton are mentioned, it may be useful to mention that one such species was in Socrates tea. This derivtive vs skeleton angle has recently been developed for ethanolamine and ethylenediamine by another editor.  It's not my preference (cup of tea, shall we say) for all the reasons we wrangled with, but the info is there and perhaps welcome.--Smokefoot (talk) 12:24, 4 August 2008 (UTC)

odor
on this page it says that Piperidine smells like pepper but my own experience and everyone i have discussed it with has described the smell as that of semen. when i tried to include this interesting factoid into the article my edit has been reverted and called vandalism. wtf? —Preceding unsigned comment added by 203.217.76.219 (talk) 11:39, 18 October 2010 (UTC) YES, it does, and everyone I've discussed it with says so as well. It does NOT smell like pepper, AT ALL! — Preceding unsigned comment added by Chilledmonkeybrainz (talk • contribs) 18:09, 21 September 2011 (UTC)

http://www.slcc-science.org/chem/giddings/chem1120/ch15/15_index.htm Under II-H-2e: "Piperidine is an organic compound with the molecular formula C5H11N. It is a heterocyclic amine with a six-membered ring containing five carbon atoms and one nitrogen atom. It is a clear liquid with a semen-like odor." I added semen-like to the description of the odor. It is without a doubt the only accurate description of the odor. It smells nothing like pepper or ammonia but I left those descriptions there for now. Cytokinetics (talk) 04:05, 27 July 2014 (UTC)
 * Correct! Some open chained polyamines have a similar odor (triethylenetetramine (TETA) e.g.). I guess the aliphatic amine forms a H-bridged ring so it fits the same odor receptor as piperidine or pyrrolidine (smells similar to piperidine). --FK1954 (talk) 10:40, 13 July 2016 (UTC)
 * I have to add that piperidine does NOT smell like pepper. Not a bit. And to find a similarity to the odor of ammonia you need a lot of fantasy... --FK1954 (talk) 10:44, 13 July 2016 (UTC)

As one who did a fair bit of Maxam-Gilbert sequencing at Cold Spring Harbor Lab in the early 1980s, I concur on the semen smell. I was in my 20s and alone in the lab doing a piperidine cleavage when our middle-aged female dishwasher/media person walked into the lab. You should have seen the confused disgusted look I got. I'm not suggesting we link to the Marcy Playground song page ( sex and candy ) But it is a fair description of the chemicals odor Docpelletier (talk) 22:18, 14 December 2016 (UTC)

I can atest to the odor. Also a stronger reference: https://link.springer.com/article/10.1007/BF00988831#citeas My edit was also reverted by User:Smokefoot, but I found that ref. Seba~enwiki (talk) 13:10, 27 December 2019 (UTC)

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