Dibenzosuberone is an organic chemical with use in drug synthesis. Chemically speaking, it is

benzophenone Benzophenone is a naturally occurring organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. Benzophenone has been found in some fungi, fruits and plants, including grapes. It is a white solid with a low melting point and ros ...

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.

Applications

It is the precursor needed to make many tricyclic antidepressants: #

Amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headac ...

Amineptine Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family. It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a le ...

# Butaclamol (& Taclamine & Dexclamol) # Butriptyline # Cotriptyline # Cyheptamide # Deptramine 521-79-1# Deptropine # Hepzidine # Piroheptine #

Nortriptyline Nortriptyline, sold under the brand name Aventyl, among others, is a tricyclic antidepressant. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. Its use f ...

# Noxiptiline # Oxitriptyline # Trecadrine # Ciheptolane
WAS-4206

AY-8794
9660-95-8# Desoxypipradrol analog:
PC10895908
(Amitriptyline-

Pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Ot ...

hybrid)

Synthesis

Although in Lednicer’s notes

hydroiodic acid Hydroiodic acid (or hydriodic acid) is a colorless liquid. It is an aqueous solution of hydrogen iodide with the chemical formula . It is a strong acid, in which hydrogen iodide is ionized completely in an aqueous solution. Concentrated aqueous ...

(HI) reduction gave the

stilbene Stilbene may refer to one of the two stereoisomers of 1,2-diphenylethene: * (''E'')-Stilbene (''trans'' isomer) * (''Z'')-Stilbene (''cis'' isomer) See also * Stilbenoid Stilbenoids are hydroxylated derivatives of stilbene. They have a C6–C ...

, according to background literature it appeared as if it the reduction went straight through to (3). Synthesis: Dibenzosuberone synthesis

The

aldol reaction The aldol reaction (aldol addition) is a Chemical reaction, reaction in organic chemistry that combines two Carbonyl group, carbonyl compounds (e.g. aldehydes or ketones) to form a new β-hydroxy carbonyl compound. Its simplest form might invol ...

between phthalide 7-41-2(1) and

benzaldehyde Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is among the simplest aromatic aldehydes and one of the most industrially useful. It is a colorless liquid with a characteristic almond-li ...

gave benzalphthalide 75-61-1(2). This was then reduced with

and

red phosphorus Red phosphorus is an Allotropes of phosphorus, allotrope of phosphorus. It is an amorphous polymeric red solid that is stable in air. It can be easily converted from white phosphorus under light or heating. It finds applications as matches and fir ...

to give 2-bibenzylcarboxylic acid 890-85-1(3). Alternatively, a

catalytic hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...

can be performed using

dipentene Limonene () is a colorless liquid aliphatic hydrocarbon classified as a cyclic monoterpene, and is the major component in the essential oil of citrus fruit peels. The (+)-isomer, occurring more commonly in nature as the fragrance of oranges, ...

as the source of hydrogen. Although this is a slightly lower yielding method, it does not have the limitations of using

, which is a safety hazard on a large scale. The ring closure with

polyphosphoric acid In chemistry, a phosphoric acid, in the general sense, is a phosphorus acid, phosphorus oxoacid in which each phosphorus (P) atom is in the oxidation state +5, and is chemical bond, bonded to four oxygen (O) atoms, one of them through a double b ...

gave dibenzosuberone (4) in good yield, although

Friedel–Crafts reaction The Friedel–Crafts reactions are a set of organic reaction, reactions developed by Charles Friedel and James Crafts in 1877 to attach substituents to an Aromatic hydrocarbon, aromatic ring. Friedel–Crafts reactions are of two main types: alky ...

is an alternative method. An alternative procedure is described: Dibenzosuberone synthesis2

Phthalic anhydride Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commer ...

(1) and

phenylacetic acid Phenylacetic acid (conjugate base phenylacetate), also known by various synonyms, is an organic compound containing a phenyl functional group and a carboxylic acid functional group. It is a white solid with a strong honey-like odor. Endogenously ...

(2) in the presence of sodium acetate also gives benzalphthalide 75-61-1 (3). Apparently an aldol type addition, followed by a dehydration and decarboxylation explains the mechanism. Base catalyzed hydrolysis to 2-(Phenylacetyl)benzoic acid 3148-55-9(4), and

also gives 2-bibenzylcarboxylic acid 890-85-1(5). Alternatively, benzalphthalide 75-61-1can be catalytically hydrogenated over

Raney Nickel Raney nickel , also called spongy nickel, is a fine-grained solid composed mostly of nickel derived from a nickel–aluminium alloy. Several grades are known, of which most are gray solids. Some are pyrophoric, but most are used as air-stable s ...

in IPA solvent to 2-(2-phenylethyl)benzoic acid in 96% yield (importantly methanol and ethanol gave no reduction. The intramolecular cyclization step was optimized with

Nafion Nafion is a brand name for a sulfonated tetrafluoroethylene based fluoropolymer-copolymer synthesized in 1962 by Dr. Donald J. Connolly at the DuPont Experimental Station in Wilmington Delaware (U.S. Patent 3,282,875). Additional work on the polym ...

-H. A milder and greener approach was recently devised:

References

{{Chemical classes of psychoactive drugs Dibenzocycloheptenes Cyclic ketones