Tropinone

Source: Wikipedia, the free encyclopedia.
Tropinone
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 Edit this at Wikidata
UNII
  • InChI=1S/C8H13NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-7H,2-5H2,1H3/t6-,7+ checkY
    Key: QQXLDOJGLXJCSE-KNVOCYPGSA-N checkY
  • InChI=1S/C8H13NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-7H,2-5H2,1H3/t6-,7+
    Key: QQXLDOJGLXJCSE-KNVOCYPGBG
  • Key: QQXLDOJGLXJCSE-KNVOCYPGSA-N
  • CN1[C@@H]2CC[C@H]1CC(=O)C2
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:
GHS05: CorrosiveGHS07: Exclamation mark[1]
Danger
H302, H314[1]
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Tropinone is an

Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I.[2][3] Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure. Its corresponding conjugate acid at pH 7.3 major species is known as tropiniumone.[4]

Synthesis

The first synthesis of tropinone was by Richard Willstätter in 1901. It started from the seemingly related cycloheptanone, but required many steps to introduce the nitrogen bridge; the overall yield 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]

Willstatter tropinone synthesis [7]

Robinson's "double Mannich" reaction

The 1917 synthesis by Robinson is considered a classic in

tandem reaction in a one-pot synthesis. Furthermore, the yield of the synthesis was 17% and with subsequent improvements exceeded 90%.[5]

Robinson tropinone synthesis

This reaction is described as an intramolecular "double Mannich 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 "

physiological pH
".

Reaction mechanism

The main features apparent from the reaction sequence below are:

  1. Nucleophilic addition of methylamine to succinaldehyde, followed by loss of water to create an imine
  2. Intramolecular addition of the imine to the second aldehyde unit and first ring closure
  3. Intermolecular Mannich reaction of the enolate
    of acetone dicarboxylate
  4. New enolate formation and new imine formation with loss of water for
  5. Second intramolecular Mannich reaction and second ring closure
  6. Loss of 2 carboxylic groups to tropinone
Tropinone synthesis

Some authors have actually tried to retain one of the CO2H groups.[11]

CO2R-tropinone has 4 stereoisomers, although the corresponding ecgonidine alkyl ester has only a pair of enantiomers.

From cycloheptanone

Michael reaction
(i.e. conjugate addition).

Biochemistry method

[14]

Reduction of tropinone

The reduction of tropinone is mediated by

NADPH-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]

Reduction of tropinone

See also

References

  1. ^ a b "Tropinone". Substance Information. ECHA.
  2. doi:10.1039/CT9171100762
    .
  3. PMID 10649349
    .
  4. ^ Chemical Entities of Biological Interest Identification code: ChEBI:57851 "tropiniumone"
  5. ^
    ISBN 978-0-85404-544-0
    .
  6. PMID 11699882
    .
  7. ISBN 978-0-12-372532-5
    .
  8. S2CID 143267467
    .
  9. PMID 10669562
    .
  10. PMID 11425577
    .
  11. doi:10.1021/jo01362a022
    .
  12. ^ U.S. patent 8,609,690
  13. PMID 11878978
    .
  14. PMID 30538251
    .
  15. doi:10.1016/0031-9422(92)80247-C
    .
  16. PMID 10626376
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Tropinone&oldid=1211213148"