Process for preparing 3-isochromanone

Details Process for preparing 3-isochromanone Process for preparing 3-isochromanone

2000-01-24

2001-03-27

Lambkin, Deborah C. (Department: 1626)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06207840

ABSTRACT:

This invention relates to a chemical process and more particularly to a process for preparing 3-isochromanone which is useful in the manufacture of certain agricultural products.
3-Isochromanone is a well known compound and a number of methods for its preparation are described in the chemical literature. In particular, a process is described in WO097/00850 which comprises reacting an o-xylene-&agr;,&agr;′-dihalide derivative with carbon monoxide and water in an organic solvent in the presence of a catalyst and a hydrogen halide capturing agent followed by treatment with an acid. In this process the hydrogen halide capturing agent is preferably an inorganic base. The use of amines in palladium-catalyzed carbonylation reactions are discussed in
J. Org. Chem. [
1993] 58, 1538-45 and in U.S. Pat. No. 4,713,484. These references relate, however, to the alkoxycarbonylation of allylphosphates and acetates and to the preparation of carboxylic acid salts.
Thus, according to the present invention, there is provided an improved process for the preparation of 3-isochromanone which comprises contacting an o-xylene-&agr;,&agr;′-dihalide with carbon monoxide in a two-phase liquid medium, in which one phase is aqueous and the other phase is water-immiscible, in the presence of a catalyst and a hindered amine base.
The o-xylene-&agr;,&agr;′-dihalide starting material has the general formula:
where X is a halogen atom such as chlorine, bromine or iodine, especially chlorine or bromine. o-Xylen-&agr;,&agr;′-dichloride is a particularly convenient starting material.
The process of the invention is carried out in a two-phase liquid medium, one phase comprising water and the other phase conveniently comprising a water-immiscible organic solvent. Any suitable water-immiscible organic solvent may be used. Examples are saturated or aromatic hydrocarbons or halogenated derivatives thereof, such as chlorinated or fluorinated derivatives, for example methylene chloride, toluene or chloro- or fluorobenzene. Xylene is particularly convenient from a manufacturing standpoint. Where the hindered base is a liquid and water-immiscible, it may itself act as the solvent without the need to employ an additional solvent. An example of a base which may be used in this way is N,N-diisopropylethylamine.
It may, however, be convenient to include in the two-phase liquid medium one or more other water-immiscible solvents or a water miscible solvent, provided that at least two-phases are maintained, one of which is aqueous.
Suitably the molar ratio of water:water-immiscible solvent is in the range of 1:50 to 50:1, preferably 1:1 to 10:1 and typically 1:1 to 3:1, for example about 5:2.
There will usually be a molar excess of water used in relation to the quantity of o-xylene-&agr;,&agr;′-dihalide starting material. Preferably the molar ratio of water:o-xylene-&agr;-&agr;′-dihalide will be in the range of 100:1 to 1:1 typically 20:1 to 5:1, for example about 10:1.
The carbon monoxide will normally be dispersed into the two-phase medium either at atmospheric pressure or at pressures up to 100 atmospheres, for example at from 1 to 10 atmospheres. The pressure chosen will depend on the equipment in which the reaction is carried out and the required reaction rates and yield.
Any suitable carbonylation catalyst may be used in the process of the invention, particularly Group VIII (first, second and third triads) metal catalysts, for example palladium, cobalt or iron catalysts. Especially suitable are palladium catalysts, for example palladium (0) and palladium (II) catalysts, which may be water-soluble or water-insoluble, supported on a carrier, such as carbon, silica or calcium carbonate, a polymer or other inert solid, or unsupported. Supported catalysts have the advantage of facilitating catalyst recovery and recycling. Ligands such as triphenylphosphine may be used in conjunction with certain palladium catalysts or it may be beneficial to pre-reduce the catalyst with hydrogen, or another suitable reducing agent.
Suitable water-soluble palladium catalysts in the form of phoshine complexes are described, for example, by J. Kiji et al in
Chem. Lett.,
957-960 (1988). Suitable water-insoluble palladium catalysts include bis(triphenylphosphine)palladium dichloride and tetrakis(triphenylphosphine)palladium (0) which are described by L. Cassar et al in
J. Organometallic Chem.,
121 (1976), C55-56, in DE-A-2526046 and by X. Huang et al in
Chem.
&
Ind.,
Sep. 3, 1990, 548. Palladium (II) catalysed carbonylation reactions are also discussed by V. Grushin et al in
Organometallics,
12 (5), 1890-1901 (1993). The use of a supported carbonylation catalyst in the form of palladium-black is described by T. Ito et al in
Bull. Chem. Soc. Japan,
48 (7), 2091-2094 (1975). The use of soluble triphenylphosphine ligands to activate palladium catalysts is described by D. Bergbreiter et al in
J. Mol. Catalysis,
74 (1992), 409-419. Typical examples of suitable catalysts are palladium chloride, dihydrotetrachloropalladium, tetrakis(triphenylphosphine)palladium (0), dichlorobis(triphenylphosphine)palladium (II), palladium/carbon, palladium on calcium carbonate and palladium on Montmnorillonitel™. Other suitable catalysts and ligands, including water soluble ones, are described in WO 97/00850. The ligands may be used in amounts up to 1000 mole equivalents of palladium, and suitably in the range of from 1 to 200 mole equivalents of palladium. The amount of palladium catalyst used may be in the range of 0.000001 to 0.5 mole equivalents of the o-xylene-&agr;,&agr;′-dihalide.
The hindered amine base will usually be one which has at least two aliphatic, preferably branched aliphatic, or cycloaliphatic groups or one in which the N atom is in a cycloaliphatic or aromatic ring, substituted in a manner that induces steric crowding around the N atom. Typically it will be of low water solubility and have a pK
a
of the conjugate acid of about 10. Thus, it may be a heteroaromatic base such as pyridine or a substituted pyridine, for example 2,6-dimethylpyridine. Or it may be a secondary amine, providing it is sufficiently sterically hindered. An example of a suitable secondary amine is 2,2,6,6-tetramethylpiperidine. Preferably, however, it is a tertiary amine of formula R
1
R
2
R
3
N wherein R
1
, R
2
and R
3
are independently C
1-10
alkyl (especially C
1-6
alkyl) C
3-6
cycloalkyl, aryl (especially phenyl, but also pyridyl) or aryl(C
1-4
)alkyl (especially benzyl), or wherein two or three of R
1
, R
2
and R
3
join together with the nitrogen atom to which they are attached to form one, two or three, 5-, 6- or 7-membered alicyclic rings optionally fused and optionally containing a second ring nitrogen atom.
Alkyl groups are straight or branched chain and, unless stated otherwise, contain from 1 to 10, especially from 1 to 6, particularly from 1 to 4, carbon atoms. Examples are methyl, ethyl, iso-propyl, n-propyl, n-butyl, sec-butyl and tert-butyl. Cycloalkyl groups comprise 3 to 6 carbon atoms and are optionally substituted by C
1≢
alkyl. Examples are cyclohexyl, 2-methylcyclohexyl and 2-ethylcyclohexyl.
Suitable tertiary amines of formula R
1
R
2
R
3
N are, for example, N,N-diisopropylethylamine, N,N-dimethylaniline, triethylamine, t-butyldimethylamine, N,N-diisopropylmethylamine, N,N-diisopropylisobutylamine, N,N-diisopropyl-2-ethylbutylamine, tri-n-butylamine, N,N-dicyclohexylmethylamine, N,N-dicyclohexylethylamine, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]-octane or 2- or 4-dimethylaminopyridine.
There will usually be a molar excess of hindered amine base used in relation to the quantity of o-xylene-&agr;,&agr;′-dihalide starting material. Preferably the molar ratio of amine: o-xylene-&agr;-&agr;′-dihalide will be in the range of 10:1 to 1:1, typically 5:1 to 2:1, for example 4:1 to 2.5:1.
As the process is carried out in a two-phase system, it may be advantageous to include a phase transfer catalyst. By the term “phase transfer catalyst” i

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