DE3809260A1 - Selective etherification of phenyl ketone cpds. in 4-position - Google Patents

Abstract

In the prodn. of 4-etherified phenyl ketones (I) by reacting aromatic ethers (II) with acylating agents (III) of the formulae: cycloalkyl; R2 and R3 = H, F, Cl, Br, 1-4 C alkyl or 3-7 C cycloalkyl; R4 = 1-16 C alkyl, 2-16 C alkenyl, 3-7 C cycloalkyl, 7-12 C aralkyl, 8-12 C aralkenyl or 6-12 C aryl; X = Cl, Br, -OCOR4, 1-4 C alkoxy, OH, NH2, NH-1-4 C-alkyl or N(1-4 C alkyl)2; the is that the reaction is carried out in the presence of zeolite catalysts (IV), having a pore size of min. 5 A, of the formula: Mm/z(mMe1O2.nMe2O2).qH2O (IV); M = an exchangeable, z-valent cation; Me1 and Me2 = the of the anionic skeleton; n/m = the ratio of the elements and = 1-3000, pref. 1-2000; q = the amt. of adsorbed water.

Description

The invention relates to a method for producing phenyl ketones etherified in the 4-position by reaction of aromatic ethers which have a free 4-position, with conventional acyclizing agents on medium or wide pore zeolites that have a pore size of at least Have 5 Å.

Aromatic ketones containing ether groups, for example 4-methoxy-acetophenone or 4-methoxy-propionphenone strong interest in the fragrance industry or as an intermediate for other syntheses. The usual Method for the production of aromatic ketones is the homogeneous Friedel-Crafts acylation of aromatic Hydrocarbons with carboxylic acid derivatives; in In this form, acylation is also practiced industrially. As is well known, at least stoichiometric, usually however excessive amounts of the catalyst required, such as Lewis acids (AlCl₃, FeCl₃, BF₃, ZnCl₂, TiCl₄) or protonic acids (polyphosphoric acid, HF). For example, reference is made to the monograph  by G.A. Olah, "Friedel-Crafts and related reactions, Wiley-Interscience, New York, Vol. I-IV (1963-1964) or on DE-OS 35 19 009. The problem of technical performed Friedel-Crafts catalytically, namely high costs due to increased corrosion as well considerable effort in handling, separation and Disposal of the ultimately used catalyst, is well known.

In the special case of using ether groups Aromatics is also with an ether cleavage or a rearrangement of the ether oxygen bound hydrocarbon residues in the core count.

A method for the production of in 4- Position etherified phenyl ketones of the formula

by reacting aromatic ethers of the formula

with acylating agents of the formula

X-CO-R⁴ (III),

being in the formula

R¹ is C₁-C₁₂-alkyl, C₂-C₁₂-alkenyl, C₃-C₇-cycloalkyl or C₆-C₁₀-aryl,
R² and R³ independently of one another are hydrogen, fluorine, chlorine, bromine, C₁-C₄-alkyl or C₃-C₇-cycloalkyl,
R⁴ is C₁-C₁₆ alkyl, C₂-C₁₆ alkenyl, C₃-C₇ cycloalkyl, C₇-C₁₂ aralkyl or C₆-C₁₂ aryl and
X represents chlorine, bromine, -OCOR⁴, C₁-C₂-alkoxy, hydroxyl, amino, N-C₁-C₄-alkyl or N (C₁- C₄-alkyl) ₂,

found, which is characterized in that the implementation in the presence of zeolite catalysts formula

M _{m / z} [ m Me¹O₂ · n Me²O₂] · q H₂O (IV),

wherein

M is an exchangeable cation,
z means the valence of the cation,
Me¹ and Me² represent the elements of the anionic framework,
n / m means the ratio of the elements and assumes values of 2-3000, preferably 2-2000, and
q means the amount of water sorbed,

the zeolites have pore sizes of at least 5 Å,
is carried out.

R¹ can be C₁-C₁₂-alkyl, preferably C₁-C₄-alkyl, particularly preferably C₁-C₂-alkyl, very particularly preferred Methyl; Examples are besides methyl, ethyl, propyl, Isopropyl, butyl, isobutyl, the isomeric amyls, hexyls, Octyle, decyle, dodecyle. R¹ can also be C₂-C₁₂- Alkenyl, preferably C₂-C₄ alkenyl, such as vinyl, Propenyl, butenyl, the isomeric amylenes, hexenes, octenes, Decene, Dodecene. R¹ can also be C₆-C₁₀ aryl, such as phenyl or naphthyl, preferably phenyl. R1 can furthermore mean C₃-C₇-cycloalkyl, such as cyclopropyl, Cyclobutyl, cyclopentyl, methyl-cyclopentyl, cyclohexyl, Methyl-cyclohexyl or cycloheptyl. R² and R³ can be independent from each other C₁-C₄-alkyl, preferably C₁-C₂-alkyl, is particularly preferably methyl. R¹ and R² can continue independently of each other C₃-C₇-cycloalkyl of  mean above, preferably cyclopropyl, cyclopentyl and cyclohexyl. R⁴ can be C₁-C₁₆ alkyl, preferred C₁-C₁₂ alkyl, particularly preferably C₁-C₄ alkyl, for example of the type mentioned above. R⁴ can furthermore C₂-C₁₆ alkenyl, preferably C₂-C₄ alkenyl, for example of the type mentioned above. R⁴ can further C₃-C₇-cycloalkyl, for example the above Kind, mean. R⁴ can also be C₇-C₁₂ aralkyl, preferably C₇-C₉-aralkyl, mean, for example benzyl, 1-phenyl-ethyl, 2-phenyl-ethyl, naphthyl-methyl, Naphthyl-ethyl; benzyl is particularly preferred. R⁴ can continue to mean C₆-C₁₂ aryl, such as phenyl, naphthyl or biphenyl, preferably phenyl.

The residues mentioned can in turn be caused by fluorine, Chlorine, bromine, C₁-C₄-alkyl, C₁-C₄-alkoxy or C₁-C₄- Alkylthio may be substituted. R⁴ can continue through a second carboxyl group or its functional Be substituted.

Suitable acylating agents are those derived from formula (III) Acids, their halides, their esters, their anhydrides, their substituted or unsubstituted Amides in question; the anhydrides and the Chlorides in question.

A representative example of the invention Implementation is the reaction of anisole with acetic anhydride, which are illustrated by the following formula scheme leaves:  

The disadvantages of the known methods mentioned avoided by the inventive method. It is although already known, lower alkyl-substituted benzenes without hydroxyl groups in the presence of zeolites with carboxylic acids or carboxylic acid derivatives, preferably in the Gas phase to convert to aromatic ketones. Here are with acetic acid on pentasils (EP 2 39 383) or to Zeolite SE-Y (DE-OS 26 16 583) sales only in on the order of 5%. Higher sales according to FR 25 92 039 or J. Org. Chem. 51 (1986), 2128-2130 only achieved with longer-chain carboxylic acids. On the other hand, in US 46 52 683, US 46 68 826 and EP 2 27 331 reports phenol with carboxylic acids in the gas phase on silicalite or H-ZSM 5 to preferably 2-hydroxyphenyl-lower alkyl ketones to acylate; partially kick however, by-products such as phenylacetate or Derived products, for example heterocycles such as 2- Methyl chromon and 4-methyl-coumarin. Mixtures of these These are also esters, ketones and heterocycles Result of the reaction of phenols with acetic anhydride in the gas phase, for example on mordenite (Kin. Catal. 23: 417-420 (1982/2); cited from C.A. 97, 72 012 f).

In view of the prior art mentioned, it was not to be expected in the process according to the invention  also with short-chain carboxylic acid derivatives, such as acetic anhydride, excellent sales of 75% or more can be achieved that continue with high selectivity of 98-100% 4-alkoxyphenyl ketones instead of 2-alkoxy isomers are obtained and that finally the alkoxy aromatics under the reaction conditions Zeolites when used in their acidic form no ether cleavage and / or rearrangement reactions go into phenols or cresols.

Aromatic ethers for the process according to the invention Examples are the following: anisole, o- and m- Methyl anisole, o- and m-chloro or bromoanisole, o-ethyl anisole, Phenetol, o- and m-methylphenetol, m-chlorophenetol, Propoxy, butoxy, isobutoxy, amyloxy, Octyloxy, decyloxy, lauryloxy, cyclohexyloxy, Benzyloxy-, hexenyloxy-benzene, -3-chlorobenzene, -3- methybenzene, -2-ethylbenzene, diphenyl ether, 2-chlorodiphenyl ether, -3-methyl-diphenyl ether.

Acylating agent for the process according to the invention are for example the following: acetic acid, acetic acid chloride, Acetic acid bromide, acetic anhydride, Methyl acetate, acetic acid amide, propionic acid, Propionic acid chloride, propionic anhydride, butyric acid, Butyric acid chloride, butyric anhydride, isobutyric acid, Isobutyric acid chloride, isobutyric anhydride, pivalic acid chloride, Pivalic anhydride, valeric acid, Valeric acid chloride, valeric anhydride, caproic acid chloride, Isooctanoic acid chloride, lauric acid chloride,  Chloroacetic acid chloride, dichloroacetic acid chloride, dichlorofluoroacetic acid chloride, Chlorobutyric acid chloride, Methoxyacetic anhydride, butylmercaptoacetic acid, Butylmercaptoacetic acid chloride, acrylic acid, methacrylic acid chloride, Cyclopropyl carboxylic acid chloride, cyclohexane carboxylic acid chloride, Phenylacetic acid chloride, phenylacetic anhydride, Dihydrocinnamic acid chloride, cinnamic acid chloride, Benzoic acid chloride, benzoic anhydride, Methyl benzoate, o-, m-, p-fluorine, chlorine, -Bromine and iodo-benzoic acid chloride, o-, m-, p-methyl-, Isopropyl, methoxybenzoic acid chloride, dichloro, dimethyl, Methoxy-methylbenzoic acid chloride, chloromethylbenzoic acid chloride, Malonic anhydride, dimethylmalonic acid dichloride, succinic anhydride, glutanic anhydride, Phthalic anhydride, phthalic dichloride, tetrahydrophthalic anhydride.

The amount of acylating agent can be used in the invention Process varies widely will. The acylating agent is generally used in a stoichiometric ratio to aromatic ether a. But it can also be an advantage to have a component to use in excess, for example Ether with 0.5-5 mol, preferably 0.5-2 mol, based on the acylating agent.

The process according to the invention is carried out in the presence of zeolite catalysts of the formula (IV). The basic structure of zeolites is crystalline aluminosilicates, which are made up of a network of SiO₄ or AlO₄ tetrahedra. The individual tetrahedra are linked with each other by oxygen bridges across the corners and form a spatial network that is evenly interspersed with channels and cavities. The individual zeolite structures differ in the arrangement and size of the channels and cavities and in their composition. Interchangeable cations are stored to compensate for the negative charge of the lattice. Zeolites which can be used according to the invention fall under the formula (IV). In this, q H₂O forms a sorbed water phase that can be removed reversibly without the structure losing its structure. In (IV) Me¹ is generally aluminum, but this can be partially replaced by other elements such as B, Ga, In, Fe, Cr, V, As, Sb or Be. When replacing it with the divalent Be two countercations are required so that the value for m must be doubled. Furthermore, in (IV) Me² is mainly silicon, but it can be replaced by other tetravalent elements, such as Ge, Ti, Zr or Hf.

A detailed representation of zeolites is for example in the monograph by D.W. Breck "Zeolite Molecular Sieves, Structure, Chemistry, and Use ", J. Wiley and Sons, New York, 1974.

Zeolites of the following structure types are preferred for the process according to the invention: faujasite, L, mordenite, mazzite, offretite, gmelinite, cancrinite, ZSM 12, ZSM 25, zeolite β , ferrierite, ZSM 5, ZSM 11, heulandite, ZSM 22 , ZSM 23, ZSM 48, ZSM 43, ZSM 35, PSH-3, zeolite ρ , ZSM 38, CSZ-1, ZSM 3, ZSM 20, charbarite, particularly preferably zeolite L, mordenite, ZSM 5, ZSM 11, ZSM 12 , ZSM 23 and Offretit. The zeolite types mordenite, L, ZSM 5 and ZSM 11 are very particularly preferred.

As exchangeable cations, the zeolites can be those of Li, Na, K, Mg, Cu, Ca, Zn, rare earth metals, Ti, Zr, Sin (IV), Cr (III), Fe (II), Mn (II), Co , Ni and others included. According to the invention, preference is given to those zeolites in which at least some of the metal ions have been replaced by hydrogen ions, preferably 50 to 100%, particularly preferably 80 to 100% of all metal cations originally present. The acidic H⁺ forms of the zeolites are preferably prepared by exchanging metal for ammonium ions and then calcining. Another possibility is to carry out the proton exchange with mineral acids in the case of zeolites which have an n / m value of 10 or greater. The H-forms of the zeolites of the structure type mordenite, ZSM 5, ZSM 11, zeolite L, ZSM 12, ZSM 23 and offretite are therefore further preferred for the process according to the invention.

The zeolite catalyst can be in an amount of 1-100 % By weight, preferably 5-50% by weight, particularly preferably 10 up to 30 wt .-%, based on the total weight of the to be converted organic reactants used will.  

The zeolite catalyst is multiple for the invention Process reusable. Should after multiple Reuse loss of activity, it can be regenerated in a manner familiar to the person skilled in the art be, for example by washing, acid treatment and calcining.

The acylation reaction can generally be carried out in the Melt are carried out, provided that the melting or allow boiling point ratios of the reactants. Of course, solvents can also be used can also be used. Come as a solvent those in question under the reaction conditions compared to the zeolites and acylating agents used are inert, for example hydrocarbons or halogenated hydrocarbon such as petroleum ether, cyclohexane or dichlorobenzene, ether, such as tetrahydrofuran or dioxane. This list is by no means exhaustive.

The process according to the invention can be continuous or discontinuously, with normal, decreased or increased Pressure. Furthermore, the invention Acylation in the gas phase or in the Liquid phase can be carried out. For the implementation in the gas phase, the zeolite catalyst is in lumpy shape attached in a reaction tube. For the liquid phase becomes the zeolite catalyst in general used in powdered form. The preferred Embodiment is in the liquid phase; she can  carried out in the bottom, trickle or suspension procedure will. The above, in itself uncritical Application of pressure is carried out for the preferred used in the liquid phase only for low-boiling Reactants in this preferred keep liquid phase.

The process according to the invention is carried out at one temperature from 25-400 ° C. For the gas phase, the higher temperature range, for example 140-400 ° C applied, for the liquid phase the lower temperature range, for example 25-250 ° C, preferably 120 applied up to 200 ° C.

Isolation and purification of the acylated end products takes place after completion of the implementation by known customary Techniques, for example according to the previous one Separation of the catalyst by distillation and / or Recrystallization and / or chromatographic methods.

Unused raw materials can, as well the recovered catalyst, again in the invention Procedure can be traced.

The pressure for the liquid phase can be adjusted Autogenous pressure in an autoclave; he can but also by an additive inert gas pressure of for example additional 0.01-50 bar amplified will. Inert gases are, for example, N₂, He, Ar, or CO₂.

Examples

The following zeolites were used in the examples:

Example 1

216.3 g (2 moles) anisole, 102.1 g (1 mole) acetic anhydride and 40 g of zeolite powder were placed in a 1 liter autoclave, who was lined with a teflon shirt  with stirring and 20 bar nitrogen pressure to 160 ° C heated and kept at this temperature for 3 h. To The composition was cooled by gas chromatography certain. The result is shown in Table 1.

Examples 2 to 8

A mixture of 54 g (0.5 mol) anisole, 25.5 g (0.25 mol) acetic anhydride and 8 g activated Zeolite powder was heated to reflux (140 °) and in At certain intervals, samples were taken for gas chromatography Determination taken. The results go from Table 1.

Comparative example

Example 2 was repeated without a catalyst; the Results are also shown in Table 1.

Example 9

Using the same procedure as in Example 2 37.9 g (0.35 mol) anisole with 35.7 g (0.35 mol) acetic anhydride implemented in the presence of 8 g of zeolite powder. Results in Tab. 1.

Example 10

Analogously to Example 2, 32.5 g (0.3 mol) of anisole were added 45.9 g (0.45 mol) of acetic anhydride in the presence of 8 g of zeolite powder implemented. Results in Tab. 1.  

Example 11

To a suspension of 20 g zeolite powder in 108 g (1 mol) anisole were at a reflux temperature of 140 ° C 39.3 g (0.5 mol) of acetyl chloride were added dropwise in the course of 2 h, the temperature dropped temporarily to 80 ° C. The mixture was stirred for a further 8 hours at the reflux temperature and determined the composition by gas chromatography. Table 2 contains the results.

Example 12

A mixture of 54.0 g (0.5 mol) anisole, 19.8 g (0.25 mol) acetyl chloride and 15 g zeolite powder heated to reflux with stirring, the temperature rose to 90 ° C in the course of 10 h. The result of gas chromatographic analysis is shown in Table 2 forth.

Example 13

Analogously to Example 11, 54 g (0.5 mol) of anisole, 39.5 g (0.5 mol) acetyl chloride and 15 g zeolite powder together implemented. The result of gas chromatography Determination is shown in Table 2.

Example 14

Analogously to the procedure of Example 2, 27 g (0.25 mol) anisole, 16.25 g (0.125 mol) propionic anhydride  and 2.95 g of zeolite powder at the reflux temperature of 150 ° C implemented with each other. The gas chromatographic Findings are shown in Table 3.

Example 15

Using the same procedure as in Example 12 27 g (0.25 mol) anisole, 11.6 g (0.125 mol) propionic acid chloride and 3 g of zeolite powder reacted with one another, the reflux temperature of 105 over 5 hours rose to 157 ° C. The result of gas chromatography Analysis is shown in Table 3.  

Table 1 Acylation of anisole with acetic anhydride (Ac₂O) in the molar ratio anisole: Ac₂O = 2: 1; Product composition in area% of the gas chromatographic Analysis (deviation from 100% are method-specific errors). 2-MAP = 2-methoxy-acetophenone; 4-MAP = 4- Methoxyacetophenone; U = turnover; S = selectivity to 4-MAP.

Table 2

Acylation of anisole with acetyl chloride in the molar ratio anisole: acetyl chloride = 2: 1 (Examples 11 and 23) or 1: 1 (Example 13). Further information as in Table 1

Table 3

Acylation of anisole with C₂H₅CO-X in a molar ratio of 2: 1 (X = OCO-C₂H₅ in Example 14; X = Cl in Example 15). 2-MPP or 4-MPP = 2- or 4-methoxypropiophenone. Further information as in Table 1 or 2.

Claims (9)

1. Process for the preparation of phenylketones of the formula etherified in the 4-position by reacting aromatic ethers of the formula with acylating agents of the formula X-CO-R⁴, where in the formula R¹ is C₁-C₁₂-alkyl, C₂-C₁₂-alkenyl, C₃-C₇-cycloalkyl or C₆-C₁₀-aryl,
R² and R³ independently of one another are hydrogen, fluorine, chlorine, bromine, C₁-C₄-alkyl or C₃-C₇-cycloalkyl,
R⁴ is C₁-C₁₆ alkyl, C₂-C₁₆ alkenyl, C₃-C₇ cycloalkyl, C₇-C₁₂ aralkyl or C₆-C₁₂ aryl and
X represents chlorine, bromine, -OCOR⁴, C₁-C₄-alkoxy, hydroxyl, amino, N-C₁-C₄-alkyl or N (C₁-C₄-alkyl) ₂, characterized in that the reaction in the presence of zeolite catalysts of the formula M _{m / z} [ m Me¹O₂ · n Me²O₂] · q H₂Oworin M is an exchangeable cation,
z means the valence of the cation,
Me¹ and Me² represent the elements of the anionic framework,
n / m means the ratio of the elements and assumes values of 2-3000, preferably 2 to 2000, and
q means the amount of water sorbed,
wherein the zeolites have pore sizes of at least 5 Å. 2. The method according to claim 1, characterized in that that 0.5-5 moles of ether, preferably 0.5-2 moles of ether per Mol acylating agent can be used. 3. The method according to claim 1, characterized in that as the acylating agent, the anhydrides or Acid chlorides are used. 4. The method according to claim 1, characterized in that in the presence of 1-100 wt .-%, preferably 5-50 % By weight, particularly preferably 10-30% by weight of zeolite Catalysts based on the total weight of the organic reaction partner to be implemented becomes. 5. The method according to claim 1, characterized in that the organic reactants to be reacted are in the liquid phase. 6. The method according to claim 1, characterized in that that Me¹ is a trivalent element, preferably aluminum alone, is. 7. The method according to claim 1, characterized in that zeolites of the structures faujasite, L, mordenite, mazzite, offretite, gmelinite, cancrinite, ZSM 12, ZSM 25, zeolite β , ferrierite, ZSM 5, ZSM 11, Heulandit, ZSM 22, ZSM 23, ZSM 48, ZSM 43, ZSM 35, PSH-3, zeolite ρ , ZSM 38, CSZ-1, ZSM 3, ZSM 20, chabarite, preferably structure types L, mordenite, ZSM 5, ZSM 11, ZSM 12, ZSM 23 or offretite, particularly preferably structure types of mordenite, ZSM 5 L or ZSM 11, are used. 8. The method according to claim 7, characterized ,, that 50 to 100%, preferably 80 to 100% of the exchangeable Cations are H⁺ ions. 9. The method according to claim 8, characterized in that the H⁺ forms of mordenite, ZSM 5, ZSM 11, L, ZSM 12, ZSM 23 and Offretit can be used.