![]() | |
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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 |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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: | |
![]() ![]() | |
Danger | |
H302, H314 [1] | |
NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
Tropinone is an alkaloid, famously synthesised in 1917 by 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]
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]
The 1917 synthesis by Robinson is considered a classic in total synthesis [8] due to its simplicity and biomimetic approach. Tropinone is a bicyclic molecule, but the reactants used in its preparation are fairly simple: succinaldehyde, methylamine and acetonedicarboxylic 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%. [5]
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 " 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 " physiological pH".
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 corresponding ecgonidine alkyl ester has only a pair of enantiomers.
IBX dehydrogenation (oxidation) of cycloheptanone (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 double Michael reaction (i.e. conjugate addition).
![]() | This section is empty. You can help by
adding to it. (April 2022) |
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]
![]() | |
![]() | |
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 |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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: | |
![]() ![]() | |
Danger | |
H302, H314 [1] | |
NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
Tropinone is an alkaloid, famously synthesised in 1917 by 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]
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]
The 1917 synthesis by Robinson is considered a classic in total synthesis [8] due to its simplicity and biomimetic approach. Tropinone is a bicyclic molecule, but the reactants used in its preparation are fairly simple: succinaldehyde, methylamine and acetonedicarboxylic 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%. [5]
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 " 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 " physiological pH".
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 corresponding ecgonidine alkyl ester has only a pair of enantiomers.
IBX dehydrogenation (oxidation) of cycloheptanone (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 double Michael reaction (i.e. conjugate addition).
![]() | This section is empty. You can help by
adding to it. (April 2022) |
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]