Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
  • C07C33/05—Alcohols containing rings other than six-membered aromatic rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
  • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
  • C07C1/325—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom
  • C07C1/326—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom the hetero-atom being a magnesium atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
  • C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
  • C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
  • C07C13/54—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings
  • C07C13/547—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings at least one ring not being six-membered, the other rings being at the most six-membered
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
  • C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
  • C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
  • C07C13/54—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings
  • C07C13/605—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings with a bridged ring system
  • C07C13/615—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings with a bridged ring system with an adamantane ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
  • C07C35/22—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C2603/00—Systems containing at least three condensed rings
  • C07C2603/02—Ortho- or ortho- and peri-condensed systems
  • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
  • C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
  • C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes

Definitions

• This invention relates to a process for making intermediates for the synthesis of SH-dibenzo-[a,d]-cycloheptenes which are substituted at the S-carbon atom with Ian aminopropy-l radical.
• the invention also includes the synthesis of certain novel compounds produced by said process.
• aminopropyl compounds which are formed from the intermediates of the present invention are useful in the treatment of mental health conditions as they are antidepressants and serve as mood elevators or psychic energizers. These compounds are preferably administered in the form of their acid salts and these salts are included in the scope of this invention.
• the process of the present invention may be repre sented by the following flow sheet.
• the starting compound namely, the S-halo-SH-dibenzo-[a,d]-cycloheptene, which may be substituted by X, X and Y as defined above, may be made using the process described by G. Berti in the Gazz. Chim. Ital. 87, 293-309 (1957); F. J. Villani, C. A. Ellis, C. Teichman and C. Bigos, J. Med. Pharm. Chem, 5, 373 (1962); and M. Protiva et al., ibid, 4, 411 (1961), and the references cited therein.
• the first step in the method of the present invention involves the condensation of a 5-halo-5H-dibenzo-[a,d]-cycloheptene with an allyl or a 1, 2' and 3'-alkyl substituted allyl magnesium halide to form the corresponding S-allyl-SH-dibenzo- [a,d]-cycloheptene.
• S-chloro-SH-dibenzo-[a,d]-cycloheptene is reacted with allyl magnesium bromide in dry diethyl ether under reflux to form S-aHyl-SH-dibenzo-[a,d]-cycloheptene.
• the next step in the method involves the addition of a molecule of water to the S-allyl intermediate to form the corresponding S-(y-hydroxypropyl) -5H-dibenzo-[a,d]- cycloheptene.
• the desired addition is accomplished by a process of hydroboration, which term denotes herein reaction with a suitable boron compound, subsequent oxidation and hydrolysis to form the desired hydroxy compound.
• Suitable boranes contain preferably at least one B-H bond in the molecule as, for example, amine boranes, alkyl boranes, aryl boranes, alkylaryl boranes, borane-aluminum oxides, and the like.
• a basic solution of hydrogen peroxide is a preferred hydrolysis medium, although others may be used as well.
• the 'y-hydroxy compounds are obtained, they are converted to the useful aminopropyl compounds by a process of halogenation with a hydrogen halide to produce the corresponding halide derivative, and amination with an amine to form the desired end product or S-aminopropyl derivative. These steps are described in the copending application, Serial Number 188,873, filed April 19, 1962.
• the 5-allyl intermediate is converted to the 5-' -bromopropyl intermediate by a peroxidecatalyzed addition of hydrogen bromine.
• the bromo intermediate then is converted to the aminopropyl end compound by direct amination according to the aforementioned copending application.
• a stirrer, addition funnel, and ether-type condenser are charged 4.8 g. of clean magnesium turnings and 15 ml. of dry ethyl ether.
• 17 g. of allyl bromide in 10 ml. of dry ethyl ether is added dropwise with stirring at a rate sufficient to maintain a gentle reflux. Stirring and refluxing is continued until all the metal is gone.
• reaction mixture is then cooled below the point of reflux, but not so low as to cause the Grignard reagent to precipitate, and 10 g. of S-chloro-SH-dibenzo-[a,d]-cycloheptene in 20 ml. of dry ether is added with stirring in 15 minutes.
• the reaction mixture is stirred and allowed to react at room temperature for /2 hour.
• the reaction mixture then is chilled in an ice bath and treated with 45 ml. of saturated ammonium chloride solution.
• the layers are separated and just enough water is added to dissolve the solid salts in the aqueous layer.
• the latter is extracted with 2x25 ml. of ether.
• the combined organic layers are washed with 25 ml. of saturated salt solution, dried over magnesium sulfate and the solvent removed in vacuo to yield the desired product as an oil. This oil is further purified by chromatography on alumina.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Priority Applications (10)

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Publications (1)

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Cited By (5)

Citations (10)

• 1962
  • 1962-07-12 US US209311A patent/US3270067A/en not_active Expired - Lifetime
• 1963
  • 1963-06-05 GB GB22384/63A patent/GB1042472A/en not_active Expired
  • 1963-06-17 AT AT485063A patent/AT260202B/de active

Patent Citations (10)

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