Dibenzosuberone
Chemical compound
From Wikipedia, the free encyclopedia
Dibenzosuberone is an organic chemical with use in drug synthesis. Chemically speaking, it is benzophenone bonded by a 2 carbon bridge into a seven membered ring. In contrast to dibenzosuberenone, the 2 carbon bridge is saturated with hydrogen and is not an olefin. In the dihydro series, the two benzene rings are not only out of plane, but also helical with respect to one another.[1]
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| Names | |
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| Other names
10,11-dihydro-5H-Dibenzo[a,d]cyclohepten-5-one, dibenzocycloheptanone | |
| Identifiers | |
3D model (JSmol) |
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.013.557 |
| EC Number |
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PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C15H12O | |
| Molar mass | 208.25 g/mol |
| Density | g/cm3 (20°C) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Applications
It is the precursor needed to make many tricyclic antidepressants:
- Amitriptyline[2]
- Amineptine[3][4]
- Butaclamol (& Taclamine & Dexclamol)
- Butriptyline
- Cotriptyline
- Cyheptamide
- Cyheptropine
- Deptramine [2521-79-1] (c.f. Diphenhydramine)
- Deptropine
- Hepzidine
- Piroheptine
- Nortriptyline
- Noxiptiline
- Oxitriptyline
- Trecadrine
- Ciheptolane
- WAS-4206[5][6]
- AY-8794 [19660-95-8][7][8][9]
- Desoxypipradrol analog[10]
- PC10895908 (Amitriptyline-Pethidine hybrid)[11][12][13][14][15][16]
Synthesis
Although in Lednicer's notes hydroiodic acid (HI) reduction gave the stilbene,[17] according to background literature it appeared as if it the reduction went straight through to (3). Synthesis:[18][19][20][21]
The aldol reaction between phthalide [87-41-2] (1) and benzaldehyde gave benzalphthalide [575-61-1] (2). This was then reduced with hydroiodic acid and red phosphorus to give 2-bibenzylcarboxylic acid [4890-85-1] (3). Alternatively, a catalytic hydrogenation can be performed using dipentene as the source of hydrogen. Although this is a slightly lower yielding method, it does not have the limitations of using hydroiodic acid, which is a safety hazard on a large scale. The ring closure with polyphosphoric acid gave dibenzosuberone (4) in good yield, although Friedel–Crafts reaction is an alternative method.
An alternative procedure is described:[22][23][24][25]
Phthalic anhydride (1) and phenylacetic acid (2) in the presence of sodium acetate also gives benzalphthalide [575-61-1] (3). Apparently an aldol type addition, followed by a dehydration and decarboxylation explains the mechanism. Base catalyzed hydrolysis to 2-(Phenylacetyl)benzoic acid [33148-55-9] (4), and catalytic hydrogenation also gives 2-bibenzylcarboxylic acid [4890-85-1] (5).
Alternatively, benzalphthalide [575-61-1] can be catalytically hydrogenated over Raney Nickel in IPA solvent to 2-(2-phenylethyl)benzoic acid in 96% yield (importantly methanol and ethanol gave no reduction.[26]
The intramolecular cyclization step was optimized with Nafion-H.[27][28]
A milder and greener approach was recently devised:[29]