 | |
 | |
| Names | |
|---|---|
| IUPAC name 8-Methyl-8-azabicyclo[3.2.1]octan-3-one | |
| Other names 3-Tropinone | |
| Identifiers | |
| |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
|
| DrugBank |
|
| ECHA InfoCard | 100.007.756 |
| UNII | |
| |
| |
| Properties | |
| C8H13NO | |
| Molar mass | 139.195 g/mol |
| Appearance | Brown solid |
| Melting point | 42.5 °C (108.5 °F; 315.6 K) |
| Boiling point | (decomposes) |
| Hazards | |
| GHS labelling: | |
  [1] | |
| Danger | |
| H302,H314[1] | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Tropinone is analkaloid, famously synthesised in 1917 byRobert Robinson as asynthetic precursor toatropine, a scarce commodity duringWorld War I.[2][3] Tropinone and the alkaloidscocaine and atropine all share the sametropane core structure. Its corresponding conjugate acid at pH 7.3 major species is known as tropiniumone.[4]
The first synthesis of tropinone was byRichard Willstätter in 1901. It started from the seemingly relatedcycloheptanone, but required many steps to introduce the nitrogen bridge; the overallyield for the synthesis path is only 0.75%.[5] Willstätter had previously synthesized cocaine from tropinone, in what was the first synthesis and elucidation of the structure of cocaine.[6]
The 1917 synthesis by Robinson is considered a classic intotal synthesis[8] due to its simplicity and biomimetic approach. Tropinone is abicyclic molecule, but thereactants used in its preparation are fairly simple:succinaldehyde,methylamine andacetonedicarboxylic acid (or evenacetone). The synthesis is a good example of abiomimetic reaction orbiogenetic-type synthesis becausebiosynthesis makes use of the same building blocks. It also demonstrates atandem reaction in aone-pot synthesis. Furthermore, the yield of the synthesis was 17% and with subsequent improvements exceeded 90%.[5]
This reaction is described as an intramolecular "doubleMannich reaction" for obvious reasons. It is not unique in this regard, as others have also attempted it in piperidine synthesis.[9][10]
In place of acetone, acetonedicarboxylic acid is known as the "synthetic equivalent" the 1,3-dicarboxylic acid groups are so-called "activating groups" to facilitate the ring forming reactions. The calcium salt is there as a "buffer" as it is claimed that higher yields are possible if the reaction is conducted at "physiologicalpH".
The main features apparent from the reaction sequence below are:
Some authors have actually tried to retain one of the CO2H groups.[11]
CO2R-tropinone has 4 stereoisomers, although the correspondingecgonidine alkyl ester has only a pair of enantiomers.
IBX dehydrogenation (oxidation) ofcycloheptanone (suberone) to 2,6-cycloheptadienone [1192-93-4] followed by reaction with an amine is versatile a way of forming tropinones.[12][13] The mechanism evoked is clearly delineated to be a doubleMichael reaction (i.e. conjugate addition).
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The reduction of tropinone is mediated byNADPH-dependent reductase enzymes, which have been characterized in multiple plant species.[15] These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine.[16]
