Claims
- 1. A chlorinated .beta.-ketoester of the formula: ##STR19## wherein R1 represents alkyl of 1 through 4 carbon atoms.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 81 23684 |
Dec 1981 |
FRX |
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Parent Case Info
This application is a continuation of application Ser. No. 450,267, filed Dec. 16, 1982 now abandoned.
The present invention relates to new chlorinated .beta.-ketoesters of the general formula: ##STR3## wherein R represents an alkyl radical containing 1 to 6 carbon atoms or an alkenyl radical containing 2 to 6 carbon atoms, and R.sub.1 represents an alkyl radical containing 1 to 4 carbon atoms, and to their preparation and their use.
The ketoesters of general formula (Ia) or (Ib) are of real industrial and economic value insofar as they are used as intermediates for the synthesis of vitamins or perfumes. More particularly, the ketoesters of general formula (Ia) or (Ib) wherein R represents the 4-methylpent-3 enyl radical is an intermediate for the synthesis of pseudo-ionone, which is useful for preparing vitamin A.
It is known, in particular from E. W. WARNHOFF et al., Organic Syntheses, Coll. Vol. IV, 162 (1963), to prepare .alpha.-chloroketones by reaction of sulphuryl chloride with the corresponding ketone, but, when the ketone is unsaturated, addition of chlorine on to the double bond takes place. According to E. M. KOSOWER et al., J. Org. Chem., 28, 630 and 633 (1963), the halogenation of saturated or unsaturated ketones can be carried out by means of a cupric halide, preferably cupric chloride, in the presence of lithium chloride, the reaction being carried out in dimethylformamide at a temperature between 80.degree. and 90.degree. C. However, the use of a process of this type generally leads to polyhalogenated products and the yields are not quantitative.
According to the present invention, the chlorinated .beta.-ketoesters of general formula (Ia) or (Ib) are obtained by reaction of cupric chloride with a compound of the general formula: ##STR4## (wherein R and R.sub.1 are as hereinbefore defined) in the presence of lithium chloride, the reaction being carried out at a temperature between 15.degree. and 50.degree. C. in a basic polar aprotic solvent such as N-methylpyrrolidone, dimethylformamide, dimethylacetamide, tetramethylurea or hexamethylphosphotriamide. It is particularly advantageous to carry out the reaction in N-methylpyrrolidone.
In general, the halogenation is carried out by means of an excess of cupric chloride in the presence of a virtually stoichiometric amount of lithium chloride. In this way, the products of general formula (Ia) or (Ib) are obtained with virtually quantitative yields and without the formation of polyhalogenated products.
The compounds of general formula (IIa) or (IIb) can be obtained by selective addition of a ketoester of the general formula: ##STR5## (wherein R.sub.1 is as hereinbefore defined) on to a butadiene of the general formula: ##STR6## wherein R is as hereinbefore defined.
In general, the reaction is carried out in water, or in an aqueous-alcoholic medium containing at most 50% of an aliphatic alcohol containing 1 to 3 carbon atoms, in the presence of a catalyst consisting on the one hand of at least one water-soluble phosphine, and on the other hand of at least one transition metal compound, the catalyst being in solution in water and the transition metal compound being a rhodium compound.
Suitable water-soluble phosphines are those described in French Patent 76 22824 and more particularly those which correspond to the general formula: ##STR7## wherein Ar.sub.1, Ar.sub.2 and Ar.sub.3, which are identical or different, each represent a radical selected from amongst the group comprising optionally substituted phenylene radicals and naphthylene radical, M represents a cationic radical of inorganic or organic origin, so selected that the phosphine of general formula (V) is water-soluble, and n.sub.1, n.sub.2 and n.sub.3, which are identical or different, represent zero or an integer 1, 2 or 3, at least one of n.sub.1, n.sub.2 and n.sub.3 being greater than or equal to 1.
The rhodium compound used must be water-soluble or capable of dissolving in water under the reaction conditions by means of a coordination reaction with the water-soluble phosphines. RhCl.sub.3 and [RhCl(-cycloocta-1,5-diene)].sub.2 are of very particular value.
The amount of rhodium compound used is such that the number of gram atoms of elementary rhodium per liter of reaction solution is between 10.sup.-4 and 1.
The amount of phosphine is selected so that the number of gram atoms of trivalent phosphine relative to one gram atom of rhodium is between 0.1 and 200.
The minimum amount of water is that which is sufficient to dissolve all the catalyst and at least part of the reactants.
The reaction temperature is generally below 200.degree. C. and is preferably between 50.degree. C. and 125.degree. C.
It is particularly advantageous to carry out the reaction in the presence of an excess of the ketoester of general formula (III), relative to the butadiene of general formula (IV).
To improve the reactivity, it is possible to add an inorganic base (alkali metal or alkaline earth metal hydroxides, carbonates or bicarbonates) or an organic base (aliphatic or aromatic tertiary amines) to the reaction medium at a concentration of between 0.005 and 5 mols of base per liter of aqueous solution.
The chlorinated .beta.-ketoester products of general formula (Ia) or (Ib) are particularly useful for preparing the ethylenic ketones of the general formula: ##STR8## (wherein R is as hereinbefore defined) in the form of a mixture of the E,E or E,Z isomers.
The process for the preparation of the ethylenic ketones of general formula (VI) consists in decarboxylating a chlorinated .beta.-ketoester of general formula (Ia) or (Ib) to give an a-chloroketone of the general formula: ##STR9## (wherein R is as hereinbefore defined) which is dehydrohalogenated to give an ethylenic ketone product of general formula (VI).
According to the present invention, the decarboxylation and dehydrohalogenation reactions can be carried out without isolating the .alpha.-chloroketone of general formula (VIIa) or (VIIb).
It is known, in particular from A. P. KRAPCHO et al., J. Org. Chem. 43 (1), 138 (1978), to decarboxylate gem-diesters, .beta.-ketoesters or .alpha.-cyanoesters in the presence of an excess of an inorganic salt such as lithium chloride, the reaction being carried out in aqueous dimethyl sulphoxide at the reflux temperature of the reaction mixture.
Furthermore, it is known, in particular from E. W. WARNHOFF et al., Organic Syntheses, Coll. Vol. IV, 162 (1963), to dehydrohalogenate an .alpha.-halogenoketone in the presence of lithium chloride, in dimethylformamide at a temperature of about 100.degree. C.
It has now been found that the .alpha.-chloro-.beta.-ketoesters of general formula (Ia) or (Ib) lead to the .alpha.-chloroketones of general formula (VIIa) or (VIIb), with virtually quantitative yields, by treatment with lithium chloride, in a basic polar aprotic solvent such as N-methylpyrrolidone, dimethylformamide, dimethylacetamide, tetramethylurea or hexamethylphosphotriamide (preferably N-methylpyrrolidone), at a temperature of about 130.degree. C., in the presence of water or a strong inorganic acid such as hydrochloric acid or sulphuric acid. It is particularly advantageous to carry out the reaction in the presence of a strong inorganic acid in order to avoid the secondary deacylation reaction.
In general, the reaction is carried out in the presence of a molar amount of lithium chloride, representing about 1 to 5 times the molar amount of the ketoester of general formula (Ia) or (Ib). Preferably, the amount of lithium chloride used is approximately the stoichiometric amount.
The amount of water or inorganic acid is approximately the stoichiometric amount.
Depending on the composition of the reaction mixture, the decarboxylation is complete after a heating time between 10 minutes and 5 hours at a temperature of about 100.degree. C.
The .alpha.-chloroketones of general formula (VIIa) or (VIIb) are preferably converted to the ethylenic ketones of general formula (VI) by heating in the presence of lithium chloride, in a basic polar aprotic solvent such as N-methylpyrrolidone, dimethylformamide, dimethylacetamide or hexanethylphosphotriamide (preferably N-methylpyrrolidone), optionally in the presence of a very basic tertiary amine such as 2,4,6-trimethylpyridine (collidine) or ethyldicyclohexylamine. The molar amount of the tertiary amine represents about 1 to 5 times the molar amount of the ketoester of general formula (Ia) or (Ib). Preferably, the amount of tertiary amine used is approximately twice the stoichiometric amount. The dehydrohalogenation reaction is generally complete after a heating time of 1 to 20 hours at a temperature between 80.degree. and 160.degree. C.
To carry out the process according to the invention more conveniently, it is particularly advantageous to carry out the decarboxylation and dehydrohalogenation reactions without intermediate isolation of the .alpha.-chloroketone of general formula (VIIa) or (VIIb), using the system lithium chloride/inorganic acid/tertiary amine in solution in N-methylpyrrolidone, at a temperature between 80.degree. and 160.degree. C. for 1 to 20 hours.
The ketones of general formula (VI) which are obtained by the process of the present invention can optionally be purified by -physico-chemical methods such as distillation or chromatography.
The following non-limitative Examples illustrate the present invention.
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
| 3277147 |
Machleidt et al. |
Oct 1966 |
|
Non-Patent Literature Citations (3)
| Entry |
| Karrer, P. et al, Chem. Abstracts, 46:2550e, 1952. |
| Kosower et al, J. Organic Chemistry, 28, 630-33, 1963. |
| Tetrahedron Letters No. 40 (Oct. 1972), P. L. Slotter, pp. 4067-4070. |
Continuations (1)
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Number |
Date |
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| Parent |
450267 |
Dec 1982 |
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Patent Grant
4906414
