Tropinone

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ImageFileL1 = tropinone.png ImageSizeL1 = 150px
ImageFileR1 = Tropinone-3D-sticks.png ImageSizeR1 = 150px
IUPACName = 8-Methyl-8-azabicyclo [3.2.1] octan-3-one
OtherNames = 3-Tropinone
Section1 = Chembox Identifiers
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CASNo = 532-24-1
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PubChem = 446337
SMILES = O=C1CC2N(C)C(CC2)C1
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Section2 = Chembox Properties
Formula = C₈H₁₃NO
MolarMass = 139.195 g/mol
Appearance = Brown solid
Density =
MeltingPtC = 42.5
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BoilingPt = (decomposes)
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Section7 = Chembox Hazards
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NFPA-H = 2
NFPA-F = 1
NFPA-R = 0
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Tropinone is an alkaloid, famously synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I. [cite journal
author = R. Robinson
title = A synthesis of tropinone
journal = Journal of the Chemical Society, Transaction
year = 1917
volume = 111
pages = 762–768
doi = 10.1039/CT9171100762] [The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century K. C. Nicolaou, Dionisios Vourloumis, Nicolas Winssinger, and Phil S. Baran Angew. Chem. Int. Ed. 2000, 39, 44 ± 122] Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure.

ynthesis

The first synthesis of tropinone was by Richard Willstätter in 1901. It started from the seemingly related cycloheptanone, but required many steps and had an overall yield of only 0.75%.Smit, W. et al. (1998) "Organic Synthesis, The Science behind the Art." Cambridge: The Royal Society of Chemistry.] Willstätter had previously synthesized cocaine from tropinone, in what was the first synthesis and elucidation of the structure of cocaine. [Andrew J. Humphrey and David O'Hagan. Tropane alkaloid biosynthesis. A century old problem unresolved. "Natural Products Reports" 2001, "18", 494-502.doi|10.1039/b001713m]

The 1917 synthesis by Robinson is considered a legend in total synthesis [Arthur J. Birch. Investigating a Scientific
1993, "47", 277-296.] due to its simplicity and biomimetic approach. Tropinone is a bicyclic molecule, but the reactants used in its preparation are fairly simple: succinaldehyde, methyl amine and acetone dicarboxylic acid (or even acetone). The synthesis is a good example of a biomimetic reaction or biogenetic-type synthesis because biosynthesis makes use of the same building blocks. It also demonstrates a tandem reaction in a one-pot synthesis. Furthermore the yield of the synthesis was 17% and with subsequent improvements exceeded 90%.

Reaction mechanism

The main features apparent from the reaction sequence below are:

#Nucleophilic addition of secondary amine to aldehyde followed by loss of water to create an imine
#Nucleophilic addition of the imine to the second aldehyde unit and first ring closure
#Intermolecular Mannich reaction of the enolate of actone dicarboxylate
#New enolate formation and new imine formation with loss of water for
#Second intramolecular mannich reaction and second ring closure
#Loss of 2 carboxylic groups to tropinone

References

External links

* [http://www.sciencelab.com/xMSDS-Tropinone-9925353 MSDS for tropinone]