Process for the preparation of m-substituted alkyltoluenes by isomerization with ionic liquids as catalysts

Pursuant to 35 U.S.C. §119(e), this application claims benefit of U.S. Provisional Patent Application Ser. No. 61/303,331, filed on Feb. 11, 2010.

The present invention relates to a process for the preparation of m-substituted alkyltoluenes by isomerization of p-substituted alkyltoluenes. Substituted alkyltoluenes are important intermediates in the synthesis of fragrances of the 2-methyl-3-phenylpropanal type, such as e.g. Lysmeral® (BASF SE).

The ionic liquids used in the present invention comprising preferably an ammonium or imidazolium salt and a metal halide are described in the literature and are used inter alia in Friedel-Crafts alkylations (overview: P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-VCH, 2003, p. 174ff.).

JP 2738093 describes the isomerization of 4-tert-butyltoluene to 3-tert-butyltoluene using AlCl 3 as catalyst. Compared with 4-tert-butyltoluene, 3-tert-butyltoluene is the thermodynamically more favorable product. Using AlCl 3 as catalyst an m/p isomer mixture is formed in the equilibrium with an m/p ratio of ca. 2/1 after a reaction time of 1 h at room temperature. Besides this equilibrium, there is a further competing equilibrium which leads to the formation of toluene and 3,5-di-tert-butyltoluene. In order to reduce the amount of 3,5-di-tert-butyltoluene, the addition of toluene (1 equivalent by weight) was described in JP 2738093.

Olah et al. has described the isomerization of 4-tert-butyltoluene to 3-tert-butyltoluene and the alkylation of toluene with tert-butyl chloride (J. Am. Chem. Soc. 1988, 110, 2560-2565). Here, the catalysts used were tris(trifluoromethanesulfonates) (triflates) of boron, aluminum and gallium [B(OTf) 3 , Ga(OTf) 3 and Al(OTf) 3 ]. Here too, an equilibrium of 3-tert-butyltoluene/4-tert-butyltoluene of ca. 2/1 was established.

In the case of the industrial conversion of these processes, it is disadvantageous that the catalyst has to be separated off by means of a complex solid/liquid separating operation, or it has to be hydrolyzed by means of aqueous work-up. This produces a significant amount of chloride-containing waste and metal salts.

Compared with this, the process according to the invention allows m-substituted alkyltoluenes to be prepared efficiently by isomerization of p-substituted alkyltoluenes in the presence of ionic liquids. Advantages of the procedure according to the invention are:

1) separation off of the catalyst takes place by a technically less complex liquid/liquid separating operation;

2) the simple recyclability of the catalyst (since no aqueous work-up is required which destroys the catalyst in the case of solid AlCl 3 );

3) the higher reaction rate of the catalysis as a result of ionic liquids compared to the catalysis with solid AlCl 3 .

The present invention relates to a process for the preparation of alkyltoluenes substituted in the m position which can be obtained by isomerization of alkyltoluenes substituted in the p position. The isomerization takes place over ionic liquids as catalysts. The invention therefore provides a process for the preparation of m-substituted alkyltoluenes of the formula (I)

in which R 1 is C 1 -C 5 -alkyl, wherein a p-substituted alkyltoluene of the formula (II)

in which R 1 has the meaning given under formula (I), is isomerized in the presence of ionic liquids to give an m-substituted alkyltoluene of the formula (I).

Surprisingly, it has been found that ionic liquids catalyze the isomerization. Particularly suitable active ionic liquids are e.g. mixtures comprising the components (a) and (b), where

(a) is a first component of the formula MX 3 or MX 2 , in which M is metal, such as e.g. Al, In, Zn, Fe, and X is halogen, such as e.g. chlorine, bromine or iodine, and (b) is a second component selected from the following group: alkylammonium halide, imidazolium halide, pyridinium halide, phosphonium halide and mixtures of these compounds.

Preference is given to ionic liquids consisting of the mixture of the components (a) and (b).

The ratio of the two components (a)/(b) is >1/1.

The term “ionic liquid” refers to mixtures of the compounds (a) and (b) as described above which, after they have been homogenized and, optionally, melted, and cooled again, are liquid at a temperature of <100° C.

Preferred components (a) are AlCl 3 , AlBr 3 , ZnCl 2 , FeBr 3 and FeCl 3 . The component (a) is particularly preferably AlCl 3 . The component (b) is preferably an imidazolium halide, such as e.g. imidazolium halide mono- or polysubstituted by C 1 -C 10 -alkyl, or an alkylammonium halide, such as e.g. alkylammonium halide di-, tri- or tetra-substituted by C 1 -C 6 -alkyl. Specific examples of particularly preferred compounds (b) are: 1-ethyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium chloride, 1-hexyl-3-methylimidazolium chloride, 1-methylimidazolium chloride, triethylammonium chloride, trimethylammonium chloride, tetramethylammonium chloride, tetraethylammonium chloride, 1-butylpyridinium chloride and 1-methylpyridinium chloride is used.

The ratio of components (a)/(b) is >1/1. Preference is given to a ratio of >1/1 and <3/1. Particular preference is given to a ratio of >1.5/1 and <2.1/1. Very particular preference is given to a ratio of 2/1.

The catalyst is typically prepared by initially introducing component (a) or component (b) in a solvent and then metering in component (b) or component (a). After a reaction time of 1-12 hours at a temperature between 20-100° C., the ionic liquid is formed. The ionic liquid can either be separated off from the solvent phase by phase separation or be used in the isomerization complete as homogeneous solution of the catalyst in the solvent. Preferred solvents are aromatic hydrocarbons or chlorinated solvents. Particular preference is given to benzene, toluene, xylenes, mesitylene, 4-tert-butyltoluene and dichloromethane. Very particular preference is given to toluene.

The ionic liquid as catalyst is used in the isomerization in an amount of 0.1-100 mol %, based on the starting material of the formula (II). The preferred catalyst amount is 0.1-10 mol %. Particular preference is given to 0.5-5 mol %.

The isomerization takes place at temperatures between 0° C. and 100° C. Particular preference is given to temperatures between 10° C. and 50° C. The reaction times are 1 minute to 10 hours. Particular preference is given to reaction times between 30 minutes and 3 hours.

The isomerization can be carried out solvent-free or in a solvent. Suitable solvents are: toluene, xylenes, dichloromethane, chlorobenzene, hexane, heptane. Particular preference is given to toluene.

In the process according to the invention, a p-substituted alkyltoluene of the formula (II) is used as starting material. The alkyl radical R 1 is a C 1 -C 5 -alkyl radical, such as e.g. a methyl, ethyl, isopropyl, isobutyl, tert-butyl or isopentyl radical.

A preferred embodiment of the process according to the invention is one where the radical R 1 in the formula (II) is preferably C 1 -C 4 -alkyl, particularly preferably ethyl, isopropyl or tert-butyl.

Preferred starting materials for the isomerization are the following substrates: 4-tert-butyltoluene, 4-isopropyltoluene, 4-ethyltoluene. These produce the following m-isomers as main products (isomer ratio m/p>1/1) of the reaction: 3-tert-butyltoluene, 3-isopropyltoluene, 3-ethyltoluene. Particular preference is given to the substrate 4-tert-butyltoluene.

The reaction is generally carried out such that a mixture consisting of toluene, p-alkyl-substituted toluene and dialkyl-substituted toluene is reacted with the ionic liquid. When the reaction is complete, the phases are separated. The catalyst phase can be reused in the next batch. The second phase comprises the product of value (m-substituted alkyltoluene), and also toluene, the p-substituted alkyltoluene and a dialkyl-substituted alkyltoluene. For further work-up, this phase is subjected to an aqueous washing followed by a distillation, or is subjected directly to a distillation. The m-substituted alkyltoluenes are generally isolated by distillation. The components toluene and dialkyltoluenes that form during the reaction are by-products which can be separated off by distillation and returned to the isomerization reaction. By returning these products to the reaction mass, the equilibrium between the m-substituted alkyltoluene and the p-substituted alkyltoluene is reestablished again and again, as a result of which an increased fraction of the desired m-substituted product is obtained.

The invention further provides the preparation of the products of value of the formula (V) accessible from the m-substituted alkyltoluenes of the formula (I) by a reaction sequence consisting of oxidation, aldol condensation and hydrogenation

in which R 1 has the meaning given under formula (I) and R 2 is hydrogen or C 1 -C 5 -alkyl, preferably hydrogen or methyl, which are relevant as fragrances and aroma chemicals.

The alkyl radical R 2 is a C 1 -C 5 -alkyl radical, such as e.g. a methyl, ethyl, isopropyl, n-propyl, isobutyl, tert-butyl, n-butyl, n-pentyl or isopentyl radical. Preferably, the radical R 2 is hydrogen or methyl.

From the m-substituted alkyltoluenes of the formula (I) obtainable according to the invention

in which R 1 is C 1 -C 5 -alkyl, preferably ethyl, isopropyl or tert-butyl, it is possible, through oxidation by processes known per se (e.g. electrochemical oxidation of substituted toluenes to substituted benzaldehydes according to DE2948455), to form the m-alkyl-substituted benzaldehyde of the formula (III)

in which R 1 has the meaning given under formula (I). A subsequent aldol condensation of substituted benzaldehydes of the formula (III) with e.g. an aldehyde of the formula (IIIa)

in which R 2 is hydrogen or C 1 -C 5 -alkyl, to give substituted cinnamaldehydes of the formula (IV) is described e.g. in DE19949672

in which R 1 has the meaning given under formula (III) and R 2 is hydrogen or C 1 -C 5 -alkyl, preferably hydrogen or methyl. The hydrogenation of substituted cinnamaldehydes of the formula (IV) to substituted phenylpropanals of the formula (V) is described e.g. in DE102005049568

in which R 1 and R 2 have the meanings given under formula (IV).

Some of the aldehydes of the formula (V) obtained according to the process are known and some are new fragrances and aroma substances.

In the compounds of the type (III), (IV) and (V), R 1 is bonded to the phenyl ring in the m position and is C 1 -C 5 -alkyl, preferably C 1 -C 4 -alkyl, particularly preferably ethyl, isopropyl and tert-butyl, and R 2 is hydrogen or C 1 -C 5 -alkyl, preferably hydrogen or methyl. R 1 is very particularly preferably tert-butyl.

The invention is illustrated in more detail by the examples below without limiting it thereto. In the examples, all of the data in % are to be understood as meaning % by weight. (Abbreviations: BMIM=1,3-butylmethylimidazolium; EMIM=1,3-ethylmethylimidazolium; HMIM=1-methylimidazolium; TEA=triethylammonium; TMA=trimethylammonium; BuPy=1-butylpyridinium; m-TBT=m-tert-butyltoluene; p-TBT=p-tert-butyltoluene; o-TBT=o-tert-butyltoluene; DTBT=di-tert-butyltoluene; PhMe=toluene).