conhydrine

This oxygenated alkaloid was isolated by Wertheim from C. maculatum.{{ cite journal | doi = 10.1002/jlac.18561000311 | title = Ueber ein neues Alkaloïd in Conium maculatum | year = 1856 | last1 = Wertheim | first1 = Th. | journal = Annalen der Chemie und Pharmacie | volume = 100 | issue = 3 | pages = 328–339 | url = https://zenodo.org/record/1427086 }} It crystallises in colourless leaflets, has a coniine-like odour, can be sublimed, and is strongly basic. It crystallises readily from ether. The salts are crystalline; the aurichloride small rhombs or prisms, mp. 133 °C; the benzoyl derivative mp. 132 °C.

On oxidation with chromic acid, conhydrine yields L-piperidyl-2-carboxylic acid.{{ cite journal | doi = 10.1002/cber.190103402290 | authorlink = Richard Willstätter | title = Oxydation des Conydrins | year = 1901 | last1 = Willstätter | first1 = Richard | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 34 | issue = 2 | pages = 3166–3171 | url = https://zenodo.org/record/1426024 }} It is converted into L-coniine either by reduction of the iodo-derivative (iodoconiine), C₈H₁₆IN, formed by the action of hydriodic acid and phosphorus at 180 °C{{ cite journal | doi = 10.1002/cber.18850180103 | authorlink = August Wilhelm von Hofmann | title = Zur Kenntniss der Coniin-Gruppe | year = 1885 | last1 = Hofmann | first1 = A. W. | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 18 | issue = 1 | pages = 5–23 | url = https://zenodo.org/record/1425375 }}{{ cite journal | doi = 10.1002/jlac.18902590205 | title = Ueber die Coniceïne | year = 1890 | last1 = Lellmann | first1 = Eugen | journal = Justus Liebig's Annalen der Chemie | volume = 259 | issue = 2–3 | pages = 193–208 }}{{cite journal | doi = 10.1002/cber.19090420113 | title = Die Synthese des β-Coniceins (l-α-Allyl-piperidin) | year = 1909 | last1 = Löffler | first1 = Karl | last2 = Friedrich | first2 = Gotthold | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | issue = 1 | pages = 107–116 | url = https://zenodo.org/record/1426333 }} or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene.{{ cite journal | doi = 10.1007/BF01522210 | title = Zur Konstitution des Konhydrins | year = 1933 | last1 = Späth | first1 = Ernst | last2 = Adler | first2 = Erich | journal = Monatshefte für Chemie | volume = 63 | issue = 1–2 | pages = 127–140 | s2cid = 95806897 }}

File:abg-conhydrine.svg

These and other observations indicate that the oxygen atom must occur as a hydroxyl group, in the n-propyl side chain in either the α- or β-position, since the γ-position would involve the production of piperidyl-2-propionic acid on oxidation. 2-β-Hydroxypropyl-piperidine suggested by Willstätter seemed to be excluded, since neither of the two forms of this product prepared by Löffler and Tschunke{{ cite journal | doi = 10.1002/cber.190904201153 | title = Über die Konstitution des Conhydrins (optisch-aktives α-Äthyl-piperidyl-alkin) | year = 1909 | last1 = Löffler | first1 = Karl | last2 = Tschunke | first2 = Reinhold | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | issue = 1 | pages = 929–948 | url = https://zenodo.org/record/1426337 }} resembled conhydrine, and these authors suggested the α-position as probably representing the alkaloid. Support for this view was provided by Hess and coworkers{{cite journal | doi = 10.1002/cber.19170500239 | title = Über die Alkaloide des Granatapfelbaumes. IV. Ein Trennungsgang für die Reindarstellung der Pelletierin-Alkaloide. Aufklärung der Konstitution des Methyl-isopelletierins (Methyl-pelletierin, Isomethyl-pelletierin). Umwandlung des Conhydrins in Methylisopelletierin. Die Konstitution des Conhydrins | year = 1917 | last1 = Hess | first1 = Kurt | last2 = Eichel | first2 = Annaliese | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 50 | issue = 2 | pages = 1386–1407 | url = https://zenodo.org/record/1426619 }}{{ cite journal | doi = 10.1002/cber.19190520513 | title = Über die Beziehung von Methyl-isopelletierin, d,l-Methyl-conhydrinon und (N-Methyl-piperidyl)-propan-1-on. Ein Isomeriefall von Verbindungen mit einem asymmetrischen dreiwertigen Stickstoffatom. VI. Mitteilung über die Alkaloide des Granatapfelbaumes | year = 1919 | last1 = Heß | first1 = Kurt | journal = Berichte der Deutschen Chemischen Gesellschaft (A and B Series) | volume = 52 | issue = 5 | pages = 964–1004 | url = https://zenodo.org/record/1426659 }}{{ cite journal | doi = 10.1002/cber.19200530202 | title = Über die Fähigkeit der Pflanze, optische Antipoden aufzubauen | year = 1920 | last1 = Heß | first1 = Kurt | last2 = Weltzien | first2 = Wilhelm | journal = Berichte der Deutschen Chemischen Gesellschaft (A and B Series) | volume = 53 | issue = 2 | pages = 119–129 | url = https://zenodo.org/record/1426671 }}

,{{ cite journal | doi = 10.1002/jlac.19254410106 | title = Neue Umwandlungen von Conhydrin und Methylisopelletierin. (V. Mitteilung zur Frage des asymmetrischen dreiwertigen Stickstoffatoms) | year = 1925 | last1 = Hess | first1 = Kurt | last2 = Grau | first2 = Reinhold | journal = Justus Liebig's Annalen der Chemie | volume = 441 | issue = 1 | pages = 101–137 }}{{cite journal | doi = 10.1002/jlac.19284620119 | title = Über das Methyl-isopelletierin. (VIII. Mitteilung zur Stereochemie des gesättigten dreiwertigen Stickstoffatoms) | year = 1928 | last1 = Meisenheimer | first1 = Jakob | authorlink = Jakob Meisenheimer | last2 = Mahler | first2 = Emil | journal = Justus Liebig's Annalen der Chemie | volume = 462 | issue = 1 | pages = 301–316 }} who showed that DL--N-methylconhydrone is N-methyl-2-piperidyl ethyl ketone, that DL-conhydrine (mp. 69–70 °C), produced by a somewhat indirect method, is identical with the product, mp. 69.5–71.5 °C, prepared by Engler and Bauer{{ cite journal | doi = 10.1002/cber.18910240244 | title = Ueber das α-Aethylpyridylketon und dessen Ueberführung in Pseudoconhydrin | year = 1891 | last1 = Engler | first1 = C. | last2 = Bauer | first2 = F. W. | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 24 | issue = 2 | pages = 2530–2536 | url = https://zenodo.org/record/1425646 }}{{ cite journal | doi = 10.1002/cber.189402702121 | title = Die Reductionsproducte des α-Methylpyridylketons und die Nichtidentität des α-Aethyl-Piperylalkins mit dem activen Pseudoconhydrin | year = 1894 | last1 = Engler | first1 = C. | last2 = Bauer | first2 = F. W. | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 27 | issue = 2 | pages = 1775–1779 | url = https://zenodo.org/record/1425742 }} by the reduction with sodium in ethyl alcohol of 2-pyridyl ethyl ketone, and that conhydrine on dehydrogenation over platinum or palladium asbestos gives rise to a mixture of tetrahydropyridyl 2-ethyl ketone and 2-α-hydroxypropyl-pyridine. Späth and Adler have shown that conhydrine can be degraded in two stages by exhaustive methylation to trimethylamine, and a mixture of two products, an oil, C₈H₁₄O, bp. 157–159 °C@744 mmHg, and a crystalline substance, C₈H₁₆O₂, mp. 75–76 °C. The oil, when heated with water at 170 °C is converted, by addition of a molecule of water, into the crystalline substance. The latter contains two active hydrogen atoms (Zerewitinoff estimation), and on exposure to hydrogen over Pd/C absorbs enough to saturate one double bond producing a new substance, mp. 94–96 °C. On oxidation with permanganate in dilute sulfuric acid, propionaldehyde and succinic acid are produced, whilst the saturated substance, mp. 94–96 °C, is oxidised to n-valeric acid. These results indicate that the substance of mp. 75–76 °C is εζ-dihydroxy-Δ^α-n-octene, that the oil, C₈H₁₄O, is the corresponding oxide, and that the representation of conhydrine as 2-α-hydroxypropyl-pyridine accounts for their production.

{{Reflist|2}}

Category:Piperidine alkaloids

Category:Neurotoxins

Category:2-Piperidinyl compounds