DE2647704A1 - PROCESS FOR THE PRODUCTION OF ALPHA-SUBSTITUTED KETONS - Google Patents

Description

RHONE-POULENC INDUSTRIES, Paris / France

Process for the preparation of α-substituted ketones

The present invention relates to a process for the preparation of ketones which have at least one secondary or tertiary aliphatic Carbon atom in α-position to the carbonyl group contain.

The ketones that have at least one secondary or tertiary carbon atom contained in the α-position with respect to the carbonyl group, in particular by alkylation of ketones, the contain an active hydrogen atom in a-Stelluhg, can be obtained with the aid of an alkyl halide. Generally includes this reaction is the intermediate formation of the enolate anion by reacting a strong base with the enolizable ketone and subsequent reaction of the anion with the selected alkyl halide. In certain cases, these two stages can be carried out at the same time. As suitable bases for the The alkali metal alcoholates and in particular the tertiary alkali metal alcoholates (sodium and potassium tert-butoxide) are used to form enolate; the alkali amides (sodium and potassium amides, lithium dimethyl amides); the alkali derivatives of triphenylmethane (e.g. sodium triphenylmethane) j the alkali hydrides or the alkali bases like caustic soda or potassium hydroxide. Regardless of the base used, it has been found that the alkylation reaction of different

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secondary reactions that give rise to complex mixtures of different products. For example, in addition to the monoalkylated ketone, compounds can be present which result from a di- or polyalkylation of the ketone in the α- and / or α'-position to the carbonyl group. This polyalkylation can take place even if there is no excess of alkali base in the reaction medium due to exchange reactions of the alkali metal that take place between the Ausgarigsenolate and the alkylated ketone formed (see PA Tardella, Tetrahydron Letters, 1969 , 1117-1120). It is particularly difficult to control the progress of this polyalkylation. One means of preventing this is to slowly add the alkali enamel to an excess of the alkyl halide, although such a method is of no industrial interest. Ultimately, there is no technique that allows the secondary reactions of polyalkylation to be controlled in the course of the production of α-alkylated ketones. In addition, the processes in which an alkali enolate is reacted with an alkyl halide or an enolizable ketone with an alkyl halide in the presence of an alkali base (particularly sodium hydroxide and potassium hydroxide) often give rise to ketolyzing reactions which lead to the formation of heavy products.

The present invention therefore relates to a method for Production of α-alkylated ketones, which makes it possible to avoid the disadvantages associated with the use of Processes which use the reaction of an alkyl halide with an alkali enolate, be it that this consciously or is formed in the alkylation medium.

In the following, "secondary or tertiary aliphatic carbon" is used to denote any carbon atom that has one saturated or unsaturated aliphatic or cycloaliphatic hydrocarbon radical, optionally with a or more under the reaction conditions in view of. the reactants used are substituted for inert functional groups can be heard. "Alkylation" is used to denote the

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Fixation to a carbon atom of a saturated or unsaturated one aliphatic or cycloaliphatic radical, optionally with one or more functional groups or aromatic radicals can be substituted. The term "lower alkyl" denotes an alkyl radical having 1 to 4 carbon atoms.

More specifically, the present invention relates to a method for the production of ketones which have at least one secondary or tertiary aliphatic carbon atom in the α-position to the Containing carbonyl group, with the general formula

^R i - ^c - f

Ro

Ro is a saturated or unsaturated aliphatic or cycloaliphatic hydrocarbon radical, optionally substituted with one or more inert functional groups, with .1 to 30 carbon atoms.

Typically a hydrocarbon radical with 1 to 30 carbon atoms means.

R ₂ and R, denote hydrogen or hydrocarbon radicals with 1 to 30 carbon atoms, where one of the radicals R «and R, with R _{1 can form} a divalent hydrocarbon radical with 3 to 13 carbon atoms or R ₀ and R- together form one

2 3

divalent hydrocarbon radical with 4 to 14 carbon atoms form,

characterized in that an aliphatic halide of the general formula

Ro-X (II)

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wherein Ro has the meaning given above and X is a chlorine, bromine or iodine atom, with an enoxysilane the general formula

(R)

k-n

- Si -

- R

III

wherein

R ₁ , Rp and R are as defined above, η is an integer from 1 to J> , R is a hydrocarbon radical having 1 to 20 carbon atoms or, if η is 1 or 2, one or more of the radicals R is a radical the general formula

^s o -

Ii - A -

means in which

R ₁ * Rp »R-3 and η have the meaning given above, R ₂ , a hydrocarbon radical with 1 to 20 carbon atoms, which can be the same or different from R>, A represents a valence bond, an oxygen atom, a divalent hydrocarbon radical with 1 represents up to 10 carbon atoms, in the presence of a catalyst which consists of a metal or a metal derivative of groups 1b, 2b, 5b, 4a, 4b, 5a, 5b * 6b, Jb and 8 of the Periodic Table of the Chemical Elements (Handbook of Chemistry and Physics , Edition 45, page 2).

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- £ - Al

Under the formulas I to IV, the various symbols mean in detail:

Ro is a linear or branched alkyl radical having preferably 1 to 25 carbon atoms, optionally substituted by a cycloalkyl or cycloalkenyl radical with 5 to 6 cyclic carbon atoms, an aralkyl radical with 1 to 10 carbon atoms in the alkyl part, a cycloalkyl radical with 5 <b £ s 10 cyclic Carbon atoms, optionally substituted with 1 to 3 lower alkyl radicals, a linear or branched alkenyl radical with preferably 1 to 25 carbon atoms, one or more may contain conjugated or non-conjugated ethylenic carbon-carbon double bonds, optionally substituted with a cycloalkyl radical or cycloalkenyl radical with 5 to 6 cyclic carbon atoms, an alkynyl radical with

1 or more carbon-carbon triple bonds, the

Contains 2 to 10 carbon atoms, with an aralkenyl radical

2 to 10 carbon atoms in the alkenyl radical, a cyeloalkenyl radical with 5 to 10 cyclic carbon atoms, optionally substituted with 1 to 3 lower alkyl radicals. Ro can be with anyone with regard to the enoxysilane under the reaction conditions inert functional group may be substituted. As specific examples of these functional groups, one can use the groups Name NOp-, lower alkoxy, alkoxycarbonyl and nitrile.

R,., Rg * Rz *, which can be the same or different, can mean: linear or branched alkyl radicals, cycloalkyl or aralkyl radicals such as those defined for Ro. Aryl radicals with 1 to 3 benzene rings, which optionally form an ortho- or ortho- and pericondensed system, optionally substituted with 1 "to 3 lower alkyl radicals, linear or branched alkenyl radicals, cycloalkenyl or aralkenyl radicals such as those defined for Ro, with the restriction that the Rp and R radicals do not contain any ethylenic double bond conjugated with the enolic double bond of the enoxysilane of the formula III; R ₁ can also _{form an alkylene or alkenylene radical with R 2} or R (in this case the double bond is not conjugated with the enolic double bond) containing 3 to 4 carbon atoms and of which two consecutive carbon atoms form part of one

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aliphatic or benzene hydrocarbon ring or a system of '2 to 4 aliphatic and / or .Benzene hydrocarbon rings can form.

R ₁ , R ₂ and R can also be substituted with any functional group which is inert with regard to the aliphatic halides used under the reaction conditions, such as the nitro, lower alkoxy, alkoxycarbonyl and nitrile groups.

R can mean: linear or branched alkyl radicals with 1 to 20 carbon atoms, cycloalkyl radicals with 5 to 6 carbon atoms, phenyl radicals optionally substituted with 1 to 5 lower alkyl radicals, phenylalkyl radicals with 1 to 4 carbon atoms in their alkyl part.

If η is less than 3, the various radicals R, introduced by a silicon atom may be the same or different.

R ^ means: alkyl, cycloalkyl, phenyl or phenylalkyl radicals such as those defined for R, where R ₁ can be the same or different with respect to R.

A means: a linear or branched alkylene radical with 1 to 10 carbon atoms, an alkenylene radical with 1 to Carbon atoms, a cycloalkylene radical with 5 to 6 carbon atoms, a phenylene radical.

Specific examples of the different symbols in formulas I to IV are:

RoJ is an alkyl radical such as methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, pentyl, decyl, pentadecyl, an alkaryl radical such as Benzyl, ß-phenylethyl, a cycloalkyl radical such as cyclopentyl, Cyclohexyl, cycloheptyl, cyclooctyl, 2,6,6-trimethyl-cyclohexyl, an allyl radical such as 2-methyl-allyl, buten-2-yl, 2-methylbuten-2-yl, 4-methyl-penten-3-yl, hexen-3-yl, 3,5-hexadienyl, 2,4-dimethyl-penten-3-yl, 3,4-dimethyl-penten-3-yl, 2,4-dimethylpentadien-2,4-yl, j5 * 7-dimethyl-nonatetraen-2,4,6,8-yl,

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9- [2 ', 6 ^f , 6 * -trimethyl-cyclohexen-1'-yl] -3,7-dimethyl-nonatetraen-2,4,6,8-yl, 3,7-dimethyl-octadiene- 2,6-yl, 3,7,11-trimethyl-dodecatrien-2,6,10-yl, 2- [2 ', 6 ^l , 6 ^l -trime.thylcycloh «xen-1' -yl ethyl, a 3 -Phenylpropen-2-yl radical, a cycloalkenyl radical such as the cyclohexen-2-yl radical and the 2,6,6-trimethylcyclohexen-2-yl radical

R ₁ : alkyl, cycloalkyl or aralkyl radicals such as those mentioned by way of example for Ro, aryl radicals such as phenyl, diphenyl, anthracenyl, naphthyl, tolyl or xylyl radicals, alkenyl radicals such as vinyl, allyl, methallyl, butene 2-yl-, 2-methylbuten-2-yl-, buten-1-yl-, butadien-i ^ -yl- * 2-methylbutadien-1,3-yl-, 3-methylbutadien-1,3-yl- , ^ -Methylpenten - ^ - yl-, hexen-3-yl-, hexadien-J, 5-yl-, 5-methylhexadien-3,5-yl-, 2,4-dimethylpenten-3-yl-, ^, ^ -Dimethylpentene- ^ - yl-, 2,4-dimethylpentadien-2,4-yl-, 3,7-diraethylnonatetraen-2,4,6,8-yl-, 9- [2 *, 6 ¹ , 6 '-Trimethylcyclohexen-1'-yl] -3,7-dimethyl-nonatetraen-2,4,6,8-yl-, 3,7-dimethyl-octadien-2,6-yl-, 3 * 7 » 11-trimethyl -dodecatrien-2,6,10-yl- and 2- [2 ', 6', 6'-trimethyl cyclohexen-1 ^f -yl] -äthylres te, a 2-phenylvinyl- or 3-phenylpropen-2-yl Radical, a cycloalkenyl radical such as cyclohexen-1-yl, cyclohexen-2-yl, 2,6,6-triraethylcyclohexen-1-yl or 2,6,6-tri.sthylcyclchexen-2-yl -p _l est. R ₂ and R ^: alkyl, cycloalkyl or aralkyl radicals such as those mentioned by way of example for Ro, aryl radicals such as the phenyl, biphenyl, anthracenyl, naphthyl, tolyl or xylyl radicals, alkenyl radicals such as the allyl, methallyl, 3 -Methylbuten-2-yl-, 3-methyl-penten-2-yl-, buten-3-yl-, 3-methylbuten-3-yl-, pentadien-2,4-yl-, hexen-2-yl- , 3-methylhexen-2-yl-, 2,3-dimethylbuten-2-yl-, cyclopenten-1-yl-methyl-, 3,4-dimethyl-penten-2-yl-, 2- [cyclohexen-1 ' -yl] -ethyl-, 2,4-dimethyl-penten-3-yl-, 2,4-dimethyl-pentadien-2,4-yl-, 3,7-dimethyl-nonatetraen-2,4,6,8 -yl-, 3,7-dimethyl-octadien-2,6-yl-, 3,7,11-trimethyl-dodecatrien-2,6,10-yl- or the 2- [2 ^l , 6 *, 6 ' ^{trimethyl-l-cyclohexen-1-yl]} -äthylreste, the cycloalkenyl v ic cyclohexen-2-yl, 6,6-dimethyl-cycIohexen-2-yl or 2.6,6-trimethyl-cyclohexen-2-yl.

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Examples of alkylene radicals or alkenylene radicals that _{R can form with R 2} or R are the trimethylene, tetramethylene, buten-2-ylene-1,4- or 2-methyltetramethylene radicals or the radicals of the following formulas:

R and R ^: methyl, ethyl, propyl, η-butyl, isopropyl or tert-butyl radicals, the octyl radicals, the decyl radicals or the pentadecyl radicals; Cyclohexyl or cyclopentyl radicals; the Phenyl, tolyl or xylyl radicals; the benzyl or ß-phenylethyl radicals.

A: a methylene, ethylene, trimethylene, isopropylidene, Propenylene, cyclohexylene-1,4 or p-phenylene radical.

Designate among the various meanings given above the symbols in formulas I to IV preferably have the following meanings:

Ro denotes a linear or branched alkyl radical having 1 to 4 carbon atoms, a linear or branched one Alkenyl radical with 2 to 25 carbon atoms, one or more Contains conjugated or non-conjugated ethylenic double bonds and optionally with a cyclohexyl or cyclohexenyl radical is substituted, which can be substituted by 1 to 5 methyl radicals; a cyclohexyl or cyclohexenyl radical with optionally 1 to 5 methyl groups.

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R ₁ is an alkyl radical with 1 to 6 carbon atoms.

Rp and R ,, which can be the same or different, mean Hydrogen atoms or alkyl radicals with 1 to 4 carbon atoms.

R denotes an alkyl radical with 1 to 4 carbon atoms, a phenyl radical or a benzyl radical.

X means a chlorine or bromine atom.

Among the meanings already given, Ro is the most preferred another remainder of the general formula

Y H-

R "· R · '

C CH _CH / \ _c /

R ¹¹ "R"

(V)

dar, in which:

χ represents an integer from 1 to 5 and preferably 1 to 3; R ', R ", R" ¹ and R "", which can be identical or different, represent hydrogen atoms or methyl or ethyl groups; Y represents a hydrogen atom, a methyl or ethyl radical, a cyclohexyl or cyclohexenyl radical, optionally substituted by 1 to 3 methyl radicals.

As an example of aliphatic halides of the formula II which can be used in the process according to the invention, can be called:

Alkyl halides such as methyl chloride and methyl bromide, ethyl chloride and ethyl bromide, n-propyl chloride and n-propyl bromide, isopropyl chloride and isopropyl bromide, n-butyl chloride and n-butyl bromide, tert-butyl chloride and tert-butyl bromide, n-pentyl chloride and n-pentyl bromide, n-hexyl chloride and n-hexyl bromide. Alkenyl halides such as allyl chloride, allyl bromide, methallyl chloride,

1-chloro-3-butene, 1-chloro-2-butene, 1-chloro-3-methyl-butene-3, 1-bromo-j5-methyl-butene-2, 1-chloro-2-methyl-butene-2, 1-chloro-2,3-dimethylbutene-2, 1-chloro-3,7-dimethylocten-7, 1-bromo-3,7-dimethyl-octeh-6, 1-chloro-5,5,7,7-tetramethyloetadiene-2,

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Geranyl chloride, geranyl bromide, farnesyl chloride, 1-chloro-3 * 1 » 11 * ¹ 5-tetramethyl-hexadecatetraene-2,6,10,14. Cycloalkyl halides or cycloalkenyl halides such as cyclohexyl chloride, i-chloro-2-methyl-cyclohexane, 1-chloro-2,6,6-trimethyl-cyclohexane, i-chloro-cyclohexene-2, 1-chlorocyclohexene-3, 1-chloro-2 ^ 6,6-trimethylcyclohexene-2. Alkynyl halides such as propargyl chloride and bromide. Aralkyl halides such as benzyl chloride and bromide or 2-phenylethyl chloride and bromide.

The alkyl halides of the general formula

R ¹ · «R ¹ II

TA-A X

Ϊ -H CH C

R "" R "

wherein X, Y, R ¹ , R ", R" ¹ , R ^{! MI} and χ have the meanings given above, represent a preferred class of suitable reactants for use in the process according to the invention.

Among the enoxysilanes of the formula III, the following can be mentioned by way of example and not by way of limitation:

2-trimethylsilyloxypropene 2-Trläthylsilyloxy-buten-1 2-Methyldiäthylsilyloxy-buten-2 2-n-propyldimethylsilyloxy-3-ynethylbutene-1 2-trimethylsilyloxy-butadiene-1,3 2-phenyldimethylsilyloxy-3-methyl-butene-2 3-methyl-2-trimethylsilyloxy-butadiene-1,3 2-trimethylsilyloxy-pentene-i 2-trimethylsilyloxy-pentene-2 3-trimethylsilyloxy-pentene-2 3-trimethylsilyloxy-2-methyl-pentene-2 2-trimethylsilyloxy-4-methyl-pentene-2 2-trimethylsilyloxy-pentadiene-i, 4 3-trimethylsilyloxy-pentadiene-1,3

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Λ?

2-trimethylsilyloxy-4-raethyl-hexadiene-1,4 2-trimethylsilyloxy-3,4-dimethyl-hexadiene-1,4 2-trimethylsilyloxy-hepten-2 3-trimethylsilyloxy-hepten-2 ^ -trimethylsilyloxy-hepten- ^ 2 -Trimethylsilyloxy-hepten-i 2-Trimethylsilyloxy-4-methyl-hepten-1 2-trimethylsilyloxy-4-raethyl-hepten-2 2-trimethylsilyloxy-5-methyl-heptadiene-1,5-2-trimethylsilyloxy-5-methyl-heptadiene -2,5 2-trimethylsilyloxy-hexadiene-2,5 2-triraethylsilyloxy-hexadiene-i, 4 2-trimethylsilyloxy-hexadiene-1,5 4-trimethylsilyloxy-2,6-dimethyl-hepten-5 2-TrIraethylsilyloxy-octen- i 2-trimethylsilyloxy-octene-2 5-triraethylsilyloxy-2-methyl-octadiene-2,5 5-trimethylsilyloxy-2-methyl-octadiene-1,4 1-trimethylsilyloxy-1-cyelohexyl-ethylene 1-trimethylsilyloxy-1- [ ¹ -yl] -äthylen cyclohexen-2'-yl] -äthylen 1-trimethylsilyloxy-1- [2 ', 6', 6'-trimethyl-cyclohexene ^

1-trimethylsilyloxy-i-phenylethylene 1-trimethylsilyloxy-1-phenyl-propylene 1-trimethylsilyloxy-cyclopentene 1-trimethylsilyloxy-cyclohexene • 1-trimethylsilyloxy-2-methyl-cyclohexene Bis- [propen-2-yl-oxy] -dimethylsilane, tris- [propen-2-yl-oxy] -methylsilane.

The enoxysilanes of the formula III, which are used for use in the process according to the invention, are known, easily prepared products, for example by reacting a mono-, di- or trihalogenorganosilane of the general formula

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where R and η have the meanings already given and X means a chlorine or bromine atom with an enolizable ketone, i.e. ketones which have at least one hydrogen atom in the α- and / or α'-position with respect to the carbonyl group contain. The reaction of the organo-halosilanes with the enolizable ketones can be carried out in the presence of zinc chloride and of a hydrogen acid acceptor according to the method described in Belgian patent 670 769 will.

The enolizable ketone contains various organic radicals and at least one hydrogen atom on both sides of the carbonyl group on the α- and α'-carbon atoms of this same group, so a mixture of isomeric enoxysilanes is obtained, which is used separately or in a mixture before the reaction with the alkyl halide can be. In this case, a mixture of α-alkylated ketones and α '-alkylated ketones is obtained.

The enoxysilane that arises from the reaction of the enolizable ketone with the organo-halo silane can be used before the reaction isolated with the alkyl halide or used in crude form without prior isolation. In this latter case it is sufficient to add the appropriate amount of alkyl halide to the reaction mass resulting from the preparation of the enoxysilane and optionally adding a catalyst.

The process according to the invention ultimately proves to be a way of alkylating ketones which ^{contain at least one hydrogen atom on and / or the carbon atoms in the α- and / or α 1} -position with respect to the carbonyl group, the successive conversion of an enolizable one Ketones with a halogenorganosilane and then the reaction of the enoxysilane formed with an alkyl halide to form the α-alkylated ketone corresponding to the starting ketone and the initial halogenorganosilane, which is used again for

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the step can be used to prepare the enoxysilane. Without the invention referring to a special mechanism however limited, such a method can be schematically illustrated in the following manner.

(X) _n - Si

- Si

+ nHX

A>

> 3

- Si

η Ro - X

Such a process is of great industrial interest since it allows a practically infinite number of Making ketones. In addition, the preceding preparation of the enoxysilane avoids secondary polyalkylation reactions, the processes for direct alkylation in the presence of alkali bases, in particular alkali hydroxides, are inherent, as well Reactions of the ketones with one another or with the alkylation products that occur during the conversion of the starting ketone form with the alkyl halide in a strongly basic medium and lead to the formation of heavy products.

Metals which can be used as catalysts in the process according to the invention can be, for example, and do not name the following by way of limitation

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Zr, Ti, Mo, W, Mn, Fe, Ru, Pd, Os, Cp, Cu, Ni, Zn, Cd, Sn, Pb, Sb, Re, Au as well as the lanthanides and the actinides and especially uranium.

Although the course of the reaction requires the presence of a metal makes, the form in which this is present is not critical and it can therefore be in the form of the free metal or in the form of any derivative with a variable degree of oxidation are present. Indeed, it has been found that the reaction occurs even when the metal is in free form. If a metal derivative is used, the residue bound to the metal has no particular effect on the course of the reaction Role out. As a result, you can apply to all organic or inorganic or mineral salts or to all Use complexes of metals or their derivatives with electron pair donors. As non-limiting examples for metal derivatives of the aforementioned metals one can name: the inorganic or mineral salts, such as the halides, the oxyhalides, the sulphates, the nitrates, the carbonates, the salts of heteropoly acids, such as the phosphomolydates, the Phosphotungstates, the vanadates; the salts of carboxylic acids such as the acetates, the propionates, the formates, the butyrates, the Hexanoates, heptanoates, octoates, stearates, naphthenates, benzoatesj the salts of sulfonic acids; the Chelates derived from ß-dicarbonyl compounds such as the ß-diketones. As specific examples of metal derivatives can Tin chloride, tin acetate, ferric chloride, ferricetylacetonate, cobalt bromide, nickel chloride, palladium chloride, ruthenium chloride, Cuprichloride, cuprochloride, titanium tetrachloride, zirconium tetrachloride, uranium trichloride, uranyl acetylacetonate, rhenium chloride, Zirconyl acetylacetonate, vanadyl acetylacetonate, molybdylacetylacetonate, zinc chloride, zinc acetate and zinc bromide can be mentioned.

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If the metal is used in the free state, it can be used alone or deposited in the usual way in catalysis Carriers used are used such as carbon black, aluminum oxide, silicon dioxide, the aluminosilicates, pumice stone, or the barium Calcium carbonates.

The amount of catalyst, expressed by the number of g atoms of metal or metal ions per mole of alkyl halide, can vary within wide ranges. In general, an amount of catalyst is well suited that an amount of metal between 0.00001 and 0.4 g atom or metal ions per mole of alkyl halide is equivalent to. In practice these amounts are between 0.0001 and 0.2. One could use the limits given above exceed which, however, would not bring any particular advantage.

The temperature at which the reaction is carried out depends on the reactants used. In general, a temperature between -50 and + 200 ⁰ C and preferably from -20 to 150 ⁰ C is well suited. One can work at normal pressure or at a pressure lower or higher than atmospheric pressure, for example under autogenous pressure of the reactants at the chosen temperature conditions. A simple experiment makes it possible to choose the appropriate temperature in each case.

Die'Kondensation of the alkyl halide with the enoxysilane can no difference in an organic solvent inert to the reactants used or in the absence of any solvent. In the first case one can fall back on: aliphatic hydrocarbons (Hexane, heptane), cycloaliphatic hydrocarbons (cyclohexane), aromatic hydrocarbons (benzene), ether (ethyl ether, tetrahydrofuran, diglyme (diglycol dimethyl ether)), Halogen derivatives (chloroform, carbon tetrachloride), nitriles (acetonitrile, propionitrile, benzonitrile), tertiary carboxamides

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(Dimethylformamide, dimethylacetamide, N-methylpyrrolidone).

The amounts of enoxysilane and aliphatic halide that are used to carry out the reaction can be in correspond approximately to the stoichiometry, i.e. approx. 1 mol of alkyl halide per enoxy group present in the enoxysilane, or they can differ greatly from this, it being possible in the same way to use an excess of one or the other of the "reactants". For example, an amount of alkyl halide of 5 mol per enoxy group used in the reaction could be used, but exceeded one generally does not have 2 moles of alkyl halide per enoxy group. It is preferred to work with an excess of enoxysilane with respect to the alkyl halide, this excess having no upper critical limit, and the enoxy compound itself can serve as a solvent if it is liquid under the reaction conditions. If you don't want the enoxysilane as Use solvents, the amount used can be such that the number of moles of alkyl halide per enoxy group at least Is 0.1. Ultimately, the respective amounts of alkyl halide and enoxysilane can be such that the ratio [Number of moles of halide] / [number of enoxy groups] is between 5 and 0.1 and preferably between 2 and 0.1.

As already mentioned, the inventive method allows a produce very large numbers of ketones. It has a very special interest in the production of ethylene ketones and'in particular of ketones which have isopropene groups in their structure contain. These ketones are of very great industrial interest since they are used in the perfume field will. Others are intended intermediates in organic synthesis. Among these is 2-methyl-hepten-2 and -6, which is one of the chain links in the synthesis of vitamin A. The method according to the invention is particularly suitable good for the synthesis of mono- or polyisoprenic ketones of the

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general formula

R. - C - C -

R · R ^{ff |} CH C

Hfl (VII)

wherein R ₁ , R ₂ , R ~, R ', R ", R have definitions.

ir t R, Y and χ the given

The ketones that correspond to this formula fall in particular :

2-methyl-hepten-2-one-6 geranylacetone
Farnesyl acetone

3,6,10-trimethyl-undecadien-5,9-one-2 4 ·, 7-Dimethyl-octen-6-one-3 8-methyl-nonen-7-one-4 2,7-dimethyl-octen-6-one-5 2,8-dimethyl-nonen-7-one-4 3-isopropyl-6-methyl-hepten-5-one-2 2- [5-methyl-buten-2-yl] -cyclohexanone 2,8-dimethyl-nonadien-2,7-one-4 & -Propyl-7-methyl-octen-6-one-3 ^ -Isopropylidene-o-methyl-hepten-S-one ^ 5-n-Pentyl-6-methyl-hepten-5-one-2 2,10-dimethyl-undecadien-2,9-one-6

5- [3-methyl-buten-2-yl] -2-methyl-hepten-2-one-6

2,5 »5-trimethyl-hepten-2-one-6 6,9-dimethyl-decen-8-one-5 2,8-dimethyl-5-isopropyl-nonen-7-one-4 2-methyl-decadien-2,9-one-6 5-allyl-2-methyl-hepten-2-one-6.

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In practice, the reactants can be added in any order. At the end of the reaction, the unconverted Products and those resulting from the reaction are separated in a conventional manner, for example by extraction with the help of solvents and / or distillation. The haloorganosilane formed can either be in crude form or after a Purification used for the production of enoxysilane well will. The process can easily be carried out continuously.

The following examples illustrate how the invention is put into practice can be implemented.

example 1

A 250 cc three-necked glass flask is charged with a ascending cooler, a stirring system, a dropping funnel and an argon supply, with:

75 ecm acetonitrile

170 mg zinc chloride and

97 * 5 g 2-trimethylsilyloxy-prapen (TMSP)

The stirring is started and the contents of the flask are then brought to reflux (72 ° C.). 13.75 g of 3-methyl-1-chloro-2-butene are then added over a period of 8 minutes. It is left under these conditions for 1 hour and the light or volatile ones are then distilled
Products at atmospheric pressure · In this way, between

60.5 and 75 ⁰ C a fraction consisting of trimethylchlorosilane, acetonitrile and TMSP. The residue is then at 15 mm Hg
distilled. 14.4 g of a fraction are obtained between

65 and 80 ⁰ C boils and contains 8t, 4 % 2-methyl-hepten-2-one-6, which is determined by gas-liquid chromatography. The yield based on the methylchlorobutene used is

70.6 %.

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Example 2

The procedure is as in Example 1, except that the molar ratio of TMSP / methylehlorbutene is varied. This ratio, which was 5 * 7 in Example 1, is brought to 0.85. The yield of methylheptenone in relation to the methylchlorobutene used is 68 %.

Example 5 ~

The apparatus used in Example 1 is charged with:

15 ecm acetonitrile

y \ r mg ZnCl ₂

19 * 5 g of TMSP

The contents of the flask are brought to 45 to 48 ° C. and 2.75 g of methylchlorobutene are then added over a period of 5 minutes. The mixture is left for 6 hours. JO min. Under these conditions and then treating the reaction mass as in Example 1. This gives 2.90 g of a fraction in which 74% to methylheptenone determined.

The yield based on methylchlorobutene is 65.6%.

■ Examples 4 to 7

The procedure is as in Example 1, except that the acetonitrile is replaced by various solvents. The other conditions and the results are given in the following table.

•At
game
t
•
: U
: 5
! 6th
ί 7 : ZnCl
in ²
. mg : Temp.
: ° c : TMSP
in =
: Moles / 'Solvent !Yield!
^: MH Λη% ''
; (2); 3U . 91 0.15 \ Nature ''
I.
, i If3! 170 ⁶⁶ i 0.796 [ 1
HEPTAlI ',
I. . 65 ·; 3U 92-95: 0.15
I.
, PROPI (^ -
NITRILE 62.5! 136 92-9U: 4 hours:
30 min. 0.15 ·
• I
'Y'
• BENZONI
TRIL., ϊ 25.2: ■
duration
•
. : CDI (1)
in
Mole - ' DIMETHYL
FORMAIiIDi 15 minutes 0.0263 volume
• cm3 30 min.
■ 0.1315 • 15th
I. 30 min.
•
■ 0.0263
1
t 75 0.0263:
t 15th
» - 15
1

(1). CDI refers to 1-chloro-3-methyl-butene-2 or isoprene hydrochloride (2) MH denotes methylheptenone

Examples 8-10

By working as in Example 5, a series of tests is carried out by, the results of which are shown in the table below, varying the nature of the catalyst.

j At "
! game ! catalyst weight Temp ^.: " • *
• <
: Duration ■: ■
Yield" ■ in MH: j ⁸ \ Nature] 75 - *
: j5. Hours'
:30 min. 7th «". 9 « *
• < 55 72 •
^: .3O min.
1 · Ί 62, 5 ^: ; 10 tZinc-:
tacetate— '
: dihy- '
: drat. * . 65 ί 53 :1 H.
OO min.
■ 8 (1 ): : SnCl.
•
m

(1) This experiment was carried out in 15 ecm of methylene chloride

709817/1129

- O4--

Example 11

The experiment of Example 1 is repeated, except that 510 mg of zinc chloride are added and the reaction mass is left at 75 ° C. for 15 minutes, after which the volatile products are distilled at normal pressure. In this way, 165 g of a fraction is obtained which distills between 70.8 and 75 ° C. in which chlorotrimethylsilane is determined chemically (hydrolysis and determination of the hydrochloric acid released). It is found that this fraction contains 91 % chlorotrimethylsilane, which theoretically should have been formed from the CDI fed in. In this fraction, too, the total amount of TMSP in excess with respect to CDI is determined, corresponding to 6.25 × 10 −6 mol.

The distillation residue is then rectified under a pressure of 15 mm Hg. You get 2 fractions:

A fraction of 0.25 g, determined in the one methylheptenone 50.3% by gas-liquid chromatography, and a fraction of 13.7 Z "which distilled between 45 and 70 ⁰ C and

Contains 85.5 % methylheptenone.

The yield in relation to the CDI used is 71.5 *.

Example 12

The apparatus described in Example 1 is charged with: 25 ecm acetonitrile
.56.6 mg ZnCl ₂ and

32.6 g of TMSP

The contents of the flask are brought to reflux (72 ° C.) and 4.58 g of CDI are then added over a period of 4 minutes with stirring. It is left under these conditions for 1 hour and then the volatile products, acetonitrile, are removed; Chlorotrimethylsilane TMSP in excess, by distillation under reduced pressure; 57.6 g of a fraction F _{1 are obtained} which distilled between 68 and 83 ^° C. below 760 mm Hg and 4.75 g of a fraction which ^{distills between 90 and 100 °} C. below 120 mm Hg and in which one obtains 74 % methylheptenone determined. The yield in terms of that

709817/1129

The CDI used is 64 %.

The experiment is repeated, charging the same apparatus with:
of fraction P ₁
56.6 mg ZnCl ₂
5.43 g of TMSP

and then 4.58 g CDI under the same conditions as above. Heating is continued for 1 hour 30 minutes and then the reaction mass is treated as above. A fraction of volatile products of 60.8 g (F ₂ ) is obtained and then 5.40 g of a fraction in which 65 * 4 % of methylheptenone is determined (yield / CDI used: 64 %) .

The above experiment is repeated a second time, adding 56.6 mg of ZnCl ₂ and 5.43 g of TMSP and then 4.58 g of CDI _{to fraction F 2 of the volatile components.}

The distillation of the reaction mass gives a fraction F., of volatile constituents with a weight of 63.5 g and a fraction of 5 * 6 g, which contains 63.3 % methylheptenone (yield / CDI used: 65.4 %) .

This example shows that the crude acetonitrile and the crude TMSP can be recycled without loss of yield.

Example 13

The apparatus described in Example 1 is charged with:

56 ecm acetonitrile

56.2 mg ZnCl ₂

12.1 g of acetone and

15 * 15 g of triethylamine

709817/1129

TO

Bringing the flask contents to reflux (63 ⁰ C) and then added during 7 minutes. 16.5 g of chlorotrimethylsilane with stirring. The mixture is left for 1 hr. 30 min. At 63 ⁰ C and then cooled to 20 ⁰ C. 20.4 ZnClp are then added. The mixture is brought to reflux again and 2.75 g of CDI are added over a period of 3 minutes and the mixture is left under these conditions for 30 minutes. The reaction mass is treated as in Example 1. To obtain a fraction of volatile products of 95.7 g (b.p. = ₇ gQ. 59 - 81 C) and then a ¹ --Fraktion of 6.6 g (bp _Q _ =. 85 - 115 ° C), 27 , Contains 5% methylheptenone

'95

(Yield / CDI used: 54.6 %) .

Example 14

A 100 cc glass flask equipped as in Example 1 is charged with:

30 ecm acetonitrile

12.9 g bis (isopropenyloxy) dimethylsilane and 34 mg ZnCl ₂

The mixture is brought to reflux and then 2.75 g of CDI are added over 30 minutes with stirring. The mixture is left for 1 hr. 15 min. At 82 ⁰ C and distilling the contents of the flask under reduced pressure (200 mm Hg). 9 g of a fraction are obtained which distills between 40 and 75 ° C., in which 22.4 % of methylheptenone is determined (yield: 61 % in relation to the CDI used). In addition, 30.5 g of volatile products are recovered in the dry ice / acetone traps.

Example 15

A 50 cc glass flask is charged as in Example 1 is equipped with:

15 ecm acetonitrile

16.05 g tris (isopropenyloxy) methylsilane and 11.3 mg zinc chloride

709817/1129

The feed is brought to reflux (82 ° C) and then 2.75 g of CDI is added over 3 minutes. The mixture is left for 15 min., Under these conditions, and distilled quickly under a pressure of 30 · mm Hg. This gives 13.15 g of a fraction which distilled between 35 and ⁰ C JO determined in which one 13 * 9 $> methylheptenone (yield : 55 % in relation to the CDI used).

By working as in Example 1, the catalytic activity of the following metals or metal derivatives is also investigated qualitatively: iron powder, perrichloride, perriacetylacetonate, stannous chloride (SnCl ₂ ), stannous acetate, cobalt bromide (CoBr ₂ χ 2 H ₂ O); NiCl ₂ , PdCl ₂ , RuCl ,, CuCl ₂ , TiCl ^, ZrCl ₂ ^, UCl ,, uranyl acetylacetonate, ReCl, all of which have proven to be good catalysts for the formation of methylheptenone.

Example 16

A 50 cc glass flask equipped as in Example 1 is charged with:
17 g of 1-trimethylsilyloxy-cyclohexene
15 ecm acetonitrile
1 * 85 g 92 # isoprene hydrochloride

and then 300 mg of zinc chloride. The contents of the flask are brought to reflux (82 ° C.) with stirring and left under these conditions for 1 hour 30 minutes. After cooling, the greater part of the volatile products is distilled off. This gives 17 g of a distillate which ^{passes over between 65 and 83 °} C. below 760 mm Hg, and 20 g of residue which is subjected to distillation under reduced pressure. You get two factions:

a) 11 g of a product that distills between 70 and 95 ° C below 40 mm Hg and consists of virtually all of the starting senoxysilane

b) 3 * 2 g of a product that is between 95 and 125 ° C below 40 mm Hg distilled and in which one by nuclear magnetic resonance

67 wt -.% Ketone of the formula

. 0

709817/1129

certainly.

The degree of conversion of isoprene hydrochloride is 100 % and the yield of ketone with respect to the latter is 79.5 %.

Example 17

The apparatus used in Example 16 is charged with:

23 g of 96% by weight trimethylsilyloxypropene 15 ecm acetonitrile

3 * 18 g benzyl chloride

170 mg zinc chloride

and then bring the contents of the flask with stirring for 18 hours.

to reflux (75 ° C). The reaction mass is then treated as in Example 16. 3 * 9 g of a fraction are obtained which distilled between 50 and 110 ° C below 15 mm Hg and in which one determined by gas-liquid chromatography:

59 % unconverted benzyl chloride and 17 * 8 % 3-phenyl-butanone, corresponding to a yield of 68 % with respect to the converted benzyl chloride.

709817/1129

Claims (1)

Claims Process for the preparation of ketones which have at least one secondary or tertiary, aliphatic carbon atom at least one of the α-positions with respect to the carbonyl group own the general formula (D Ro wherein Ro is a saturated or unsaturated aliphatic or cycloaliphatic hydrocarbon radical, optionally substituted with one or more inert functional groups ^ having 1 to 30 carbon atoms, R _{1 is} a hydrocarbon radical having 1 to 30 carbon atoms, R _{2 and R 1 are} hydrogen; Hydrocarbon radicals with 1 to 30 carbon atoms or one of the radicals R ₀ and R, with R ₁ forms a divalent hydrocarbon radical with 3 to 13 carbon atoms or R ₂ and R. together form a divalent hydrocarbon radical with 4 to 14 carbon atoms, characterized in that one an aliphatic halide of the general formula Ro-X wherein Ro has the meaning given above, X is a chlorine, bromine or iodine atom, with an enoxysilane of the general formula t-n - Si O (III) ORIGINAL INSPECTED - 37-- R ₁ , R ₂ and R, which have the meanings given for formula I, η is an integer from 1 to 3, R denotes a hydrocarbon radical having 1 to 20 carbon atoms or, if η denotes 1 or 2, at most one of the R radicals are a radical of the general formula -Si-A- represents where R ₁ , R ₂ , R, and η have the meaning given above, R ₂ , a hydrocarbon radical with 1 to 20 carbon atoms, which is identical or different with respect to R, A denotes a valence bond, an oxygen atom, a divalent hydrocarbon radical with 1 to 10 carbon atoms means, in the presence of a catalyst, which consists of a metal or a metal derivative of groups Ib, 2b, 5b, '! A, 4b, 5a, 5b, 6b, 7b and 8 of the periodic table of the chemical elements. 2.) Process for the preparation of ketones according to claim 1, characterized characterized in that Ro denotes: a linear or branched alkyl radical having 1 to 25 carbon atoms, optionally substituted with a cycloalkyl or cycloalkenyl radical having 5 to 6 cyclic carbon atoms, an aralkyl radical with 1 to 10 carbon atoms in the alkyl radical, a cycloalkyl radical with 5 to 10 cyclic carbon atoms, optionally substituted with 1 to 3 lower alkyl radicals, a linear or branched one Alkenyl radical with preferably 2 to 25 carbon atoms, containing one or more conjugated or non-conjugated carbon-carbon double bonds may contain, optionally substituted with a cycloalkyl or cycloalkenyl radical with 5 to 6 carbon atoms, an alkynyl radical with 1 or more Carbon triple bonds with 2 to 10 carbon 709817/1129 Substance atoms, an aralkenyl radical with 2 to 10 carbon atoms in the alkenyl radical, a cycloalkenyl radical with 5 to 10 cyclic ones Carbon atoms, optionally substituted with 1 to 5 lower alkyl groups. 3.) Process for the preparation of ketones according to claim 2, characterized in that Ro is a linear or branched one Alkyl radical with 1 to 4 carbon atoms or a cyclohexyl or cyclohexenyl radical with optionally 1 to 5 methyl groups represents. 4.) Process for the production of ketones according to claim 2, characterized in that Ro is an alkenyl radical, corresponding to the general formula R " ¹ R ^f
II
C CH C.
R " ¹¹ in which. χ denotes an integer from 1 to 5, R ¹ , R ", R" ¹ and R ¹ " ¹ , which can be identical or different, denote hydrogen atoms or methyl or ethyl groups, Y denotes a hydrogen atom, a methyl or ethyl radical , a ■ cyclohexyl or cyclohexenyl radical, optionally substituted by 1 to 3 methyl groups. 5.) Process for the preparation of ketones according to claim 4, characterized in that Ro is a 3-methyl-buten-2-yl, Means geranyl or farnesyl radical. 6.) Process according to one of claims 1 to 5 » characterized in that the radicals R ₁ , R ₂ and R are: 709817/112 9 linear or branched alkyl radicals, cycloalkyl radicals, aralkyl radicals, aryl radicals with 1 to 3 benzene rings, which optionally form an ortho- or ortho- and pericondensed system, optionally substituted with 1 to 3 lower alkyl radicals, linear or branched alkenyl radicals, cycloalkenyl radicals or aralkenyl radicals, where R ₂ and R, do not contain a double bond which is conjugated with the enolic double bond of the enoxysilane, that R ₁ with Rp or R, forms an alkylene or alkenylene radical with 3 to 4 carbon atoms, of which two successive carbon atoms are part of an aliphatic or benzene hydrocarbon ring or can form a system of 2 to 4 aliphatic and / or benzene rings. 7.) Process for the preparation of ketones according to claim 6, characterized in that R _{1 is} a linear or branched alkyl radical having 1 to 6 carbon atoms and Rp and R ^, which can be the same or different, hydrogen atoms or alkyl radicals having 1 to 4 carbon atoms represent. 8.) The method according to any one of claims 1 to 7 * characterized in that R _{1 is} methyl, ethyl, propyl, isopropyl, butyl. Represents tsohut-yl, tert-butyl, pentyl or Ilexyl radicals and Rp and R .. represent water to ff atoms or one of the radicals mentioned _{above for R 1.} 9.) The method according to any one of claims 1 to 8, characterized in that in the formula III R is: linear or branched alkyl radicals with 1 to 20 carbon atoms, cycloalkyl radicals with 5 to 6 carbon atoms, phenyl radicals, optionally substituted with 1 to 3 lower alkyl radicals, or phenylalkyl radicals with 1 to 4 carbon atoms in the alkyl radical. 10.) Process for the preparation of ketones according to claim 9, characterized in that R is an alkyl radical having 1 to 4 carbon atoms, denotes a phenyl radical or a benzyl radical. 709817/1129 11.) The method according to any one of claims 1 to 8, characterized in that in the formula VR ₂ ^ is an alkyl radical with 1 to 4 carbon atoms, a phenyl radical or a benzyl radical and A is an alkylene radical with 1 to 10 carbon atoms, a cycloalkylene radical with 5 to 6 carbon atoms or a phenylene radical. 12.) Process according to one of claims 1 to 11, characterized in that a metal or as catalysts a metal derivative from the group formed by: Zr, Ti, Mo, W, Mn, Pe, Ru, Pd, Os, Co, Cu, Ni, Zn, Cd, Sn, Pb, Sb, Re, Au, U used. 15.) Method iieraäß one of claims 1 to 12, characterized in that the metal derivatives used are salts of inorganic or organic acids or metal complexes with electron pair donors. 14.) Method according to one of claims 1 to 13 * thereby characterized in that the metal derivative is a halide, an oxyhalide, a sulfate, a nitrate, a phosphate, a carbonate, a salt of a carboxylic acid, a salt of organosulfonic acids or a chelate derived from ß-dicarbonyl compounds, used. 15. ·) The method according to any one of claims 1 to 14, characterized in that the amount of catalyst, expressed by g-atom metal or metal ions per mole of alkyl halide, between 1 χ 10 ** and 0.4 g-atom or ion per mole Halide of formula II can vary. 16.) Process according to one of claims 1 to 15, characterized in that the reaction ^{temperature is between -50 and +200 0} C and the pressure is higher or lower or equal to atmospheric pressure. 709817/1129 17 «) Method according to one of claims 1 to 16, characterized characterized in that the respective amounts of enoxysilanes and alkyl halide are such that the number of moles of alkyl halide each enoxy radical present in the enoxysilane is at most 5 and preferably at most 2. 18.) Method according to one of claims 1 to 17 * thereby characterized in that the respective amounts of enoxysilane and alkyl halide are such that ■ that the number of moles of alkyl halide is between 2 and 0.1 per enoxy radical present in the enoxysilane. 19.) The method according to any one of claims 1 to 18, characterized characterized in that ketones of the general formula are prepared O
Il
C, R ₂ I. R ¹ "CH _R , f, I- ^V CH-R ¹¹ " (VII) R ₅ , R ¹ , ip * "-ζ, -λ * ^>R" ¹ , R "", Y and χ have the meaning given by adding a halide of the general formula R "» YV R "R" · » (VI) with an enoxysilane of the general formula 70981771129 Bl ./ V ^B * (in) converts, in which X, R and η have the meaning given, 20.) Method according to one of claims 1 to 19 * thereby characterized in that the 2-methyl-hepten-2 and -6 by Reaction of 1-chloro-3-methyl-butene-2 with 2-trimethylsilyloxy-propene, Bis (isopropenyloxy) dimethylsilane, tris (isopropenyloxy) methylsilane manufactures. 709817/1129 '