Production of dibenzosuberenone derivatives by catalytic...

Details Production of dibenzosuberenone derivatives by catalytic... Production of dibenzosuberenone derivatives by catalytic...

2002-02-26

2003-09-09

Barts, Samuel (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C568S314000, C568S315000, C568S321000, C568S326000, C568S329000

Reexamination Certificate

active

06617473

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to a preparation process for dibenzosuberenone derivatives by catalytic dehydrogenation of dibenzosuberone derivatives.
BACKGROUND OF THE INVENTION
Dibenzosuberenone (5H-dibenzo[a,d]cyclohepten-5-one) is an important raw material for preparing pharmacologically active compounds.
In the pharmaceutical industry, dibenzosuberenone is used as starting material for various pharmacologically active compounds. These active compounds are, for example, amitriptyline and nortriptyline (E. Mutschler
Arzneimittelwirkungen
, 6th. Ed., Wiss. Ver.-Ges., Stuttgart, 1991, pp. 120-123). Accordingly, there is a permanent demand for dibenzosuberenone and its derivatives.
Dibenzosuberenone can be obtained for example by bromination of dibenzosuberone with N-bromosuccinimide and elimination of the brominated intermediate (GB-A 2132618, U.S. Pat. No. 3,448,102). The bromination can also be carried out using bromine (Chem. Ber. 1989, 122, 1595-1597). For debromination, there are also various known possibilities. Debromination can be carried out using, for example, sodium selenite (J.Chem.Soc., Chem.Commun. 1990, 730-732) or chromium dichloride (U.S. Pat. No. 3,836,585).
Other possibilities for preparing dibenzosuberenone proceed, for example, photochemically (Tetrahedron 1994, 50, 8773-8780) or involve the use of a complex molybdenum compound (J.Chem.Soc., Perkin Trans. 2, 1993, 1923-1936).
However, these known preparation methods are disadvantageous. Thus, critical starting materials, such as, for example, bromine or sodium selenite, are used, the starting materials are not commercially available in the amounts required or are expensive to prepare, the yields in the reactions are insufficient, the purity of the product is poor (for example residual content of organic halogen compounds), the reaction cannot be carried out on an industrial scale or the starting materials are dangerous to handle.
Dehydrogenation of dibenzosuberone derivatives is known per se as a possibility for preparing dibenzosuberenone derivatives (Acta Chim. Acad. Sci. Hung., 1978, 98, 393). However, no hydrogen acceptor is employed, so that this reaction is a disproportionation of the starting material. As a consequence, the loss of starting material is high and the yield is low.
With the present invention, it was possible to overcome the disadvantages mentioned and to provide a process which is favourable for use in industry.
SUMMARY OF THE INVENTION
This invention, accordingly, provides a process for preparing substituted dibenzosuberenones of the formula
in which,
R
1
to R
10
are identical or different and represent hydrogen, fluorine, chlorine, iodine, bromine, cyano, a straight-chain or branched aliphatic hydrocarbon radical having 1 to 8 carbon atoms, a straight-chain or branched acyl radical having 1 to 8 carbon atoms, a substituted aryl radical, a substituted hetaryl radical, or one of the groups
—X—R
12
—X—C(═O)—Y—R
11
or —C(═O)—Y—R
11
in which
R
11
represents a straight-chain or branched alkyl radical having 1 to 8 carbon atoms,
R
12
represents a straight-chain or branched alkyl radical or acyl radical having 1 to 8 carbon atoms and
X and Y are identical or different and represent
—O—, —N(H)—, —S—, —N(R
13
)—,
where
R
13
represents a straight-chain or branched alkyl radical having 1 to 8 carbon atoms,
characterized in that dibenzosuberones of the formula
in which
R
1
to R
10
are each as defined above are catalytically dehydrogenated.
DETAILED DESCRIPTION OF THE INVENTION
The practice of the process according to the invention, with the use of unobjectionable reagents, is without problems. Moreover, commercially available starting materials are employed. The end product does not contain any undesirable halogen-containing by-products.
Straight-chain or branched aliphatic hydrocarbon radicals (R
1
to R
13
) generally contain 1 to 8, preferably 1 to 6, particularly preferably 1 to 4, carbon atoms. The following radicals may be mentioned specifically: methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, pentyl, iso-pentyl, hexyl, iso-bexyl, heptyl, iso-heptyl, octyl and iso-octyl. Preference is given to methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl. Straight-chain or branched aliphatic acyl radicals (R
1
to R
12
) generally contain 1 to 8, preferably 1 to 6, particularly preferably 1 to 4, carbon atoms. Preference is given to: acyl, propionyl, butyryl, iso-butyryl.
Aryl radicals are, in general, aromatic, cyclic hydrocarbon radicals having 6 carbon atoms. It is possible for a plurality, for example 2 or 3, of the radicals to be fused into one radical. Preference is given to: phenyl, naphthyl.
Hetaryl radicals are, in general, aromatic, cyclic hydrocarbon radicals having 2 to 5 carbon atoms and one or more, preferably one, heteroatom. Possible heteroatoms are, for example, nitrogen, oxygen and sulphur, preferably nitrogen. It is possible for a plurality, for example 2 or 3, of the aryl and hetaryl radicals to be fused into one radical. The following radicals may be mentioned specifically: furan, thiophene, pyrrole, pyridine, pyrazine, pyrimidine, indole, quinoline, iso-quinoline. Preference is given to furan, thiophene, pyrrole, pyridine.
Possible substituents of aryl and hetaryl radicals are, for example: alkyl, acyl, OR
13
, NR
13
, halogen atoms.
The group X—C(═O)—Y—R
11
can, for example, be: methyl carbamate, methyl carbonate, ethyl carbamate, ethyl carbonate.
Dibenzosuberones for the process according to the invention are compounds of the formula
in which
R
1
to R
10
are each as defined above.
The dibenzosuberones for the process according to the invention are known per se (J. Org. Chem. 1994, 59, 7968-75).
Catalytically acting elements of the 8th transition group are, for example, platinum, palladium, ruthenium and rhodium. Preference is given to palladium.
Supports for the catalytically acting elements of the 8th transition group are, for example, activated carbon and alumina. Preference is given to activated carbon.
In general, catalysts comprising 0.5 to 15% by weight, preferably 1 to 10% by weight, of an element of the 8th transition group are used for the process according to the invention.
The &agr;,&bgr;-unsaturated carbonyl compounds used are compounds such as fumaric esters, maleic esters, mesityl oxide, benzal acetone, isophorone, verbenone, crotonic esters, and the like. Particular preference is given to using dehydrogenating agents whose solubility characteristics in the liquid phase are such that separation of excess dehydrogenating agent and its reaction products in the crystallization is complete, for example dibutyl maleate.
For the process according to the invention, the &agr;,&bgr;-unsaturated carbonyl compound is employed in a ratio of from 0.2 to 10 parts by weight, based on 1 part by weight of the starting material.
The &agr;,&bgr;-unsaturated carbonyl compounds are preferably employed in excess, thus acting simultaneously as solvent. Use of a further solvent can therefore be dispensed with.
The dehydrogenation by the process according to the invention is preferably carried out in liquid phase. The liquid phase used is the reaction mixture.
The process according to the invention is generally carried out in a temperature range from 100 to 300° C. If dibutyl maleate is used, the process is preferably carried out at 220-260° C. The process can be carried out under atmospheric pressure and under elevated or reduced pressure. By way of example, the following pressure range may be mentioned: 0.2 to 10 bar.
The amount of catalyst can be from 0.001 to 30% by weight, preferably from 0.2 to 15% by weight, based on the starting material.
The process according to the invention can be illustrated by the following formula scheme:
The process according to the invention can be carried out, for example, as follows: dibenzosuberone is reacted with 10% by weight of Pd/C (10% by weight of Pd) and 1.5 times the amount (based on the weight) of dibutyl maleate. After the reaction, the mixture is filtered off, the dehydrogenating

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