DE10358922A1 - Enzymatic acrylation of aryl ketones - Google Patents

Abstract

Process for the enzyme-catalyzed preparation of (alk) acrylates of the general formula (I) DOLLAR F1 by esterification or transesterification of aryl ketones of the general formula (II) DOLLAR F2 with (alk) acrylic acid, an (alk) acrylic acid ester of the general formula (III) or a (Alk) acrylic acid anhydride of the general formula (IIIa) DOLLAR F3 in the presence of an enzyme catalyzing the esterification or transesterification.

Description

The The invention relates to a method for enzyme-catalyzed preparation of (alk) acrylates, in particular of (meth) acrylates.

ester of (meth) acrylic acid become common by acid catalyzed Esterification of (meth) acrylic acid with the corresponding alcohol at temperatures> 100 ° C prepared, wherein the resulting reaction water with an entraining agent is removed by azeotropic distillation.

durch Umsetzung von 2-Hydroxy-4-(2-hydroxyethoxy)benzophenon mit Acrylsäure in Benzol in Gegenwart katalytischer Mengen para-Toluolsulfonsäure. Dabei wird in Gegenwart von Hydrochinon als Stabilisator gearbeitet und das gebildete Reaktionswasser azeotrop abdestilliert. Nach Beendigung der Reaktion wird Benzol abdestilliert und das Produkt mit Cyclohexan ausgefällt. Durch Umsetzung mit Methacrylsäure wird das entsprechende Methacrylat erhalten. US 3,365,421 describes the preparation of the following compound (Ia)

by reacting 2-hydroxy-4- (2-hydroxyethoxy) benzophenone with acrylic acid in benzene in the presence of catalytic amounts of para-toluenesulfonic acid. In this case, working in the presence of hydroquinone as a stabilizer and distilling off the water of reaction formed azeotropically. After completion of the reaction, benzene is distilled off and the product is precipitated with cyclohexane. By reaction with methacrylic acid, the corresponding methacrylate is obtained.

links of the type of compound (Ia) are in particular as UV stabilizers significant.

adversely on the acid catalyzed, Chemical esterification of (meth) acrylic acid are the high temperatures of generally> 100 ° C, which lead to the formation of by-products, which for the discoloration the obtained (meth) acrylates are causal. Also is generally required the presence of stabilizers. Further to lead the acidic conditions of esterification to form by-products by rearrangements and transesterifications. Another disadvantage of the acid-catalyzed Chemical esterification is the low selectivity of the reaction in the presence of several, chemically different OH groups.

It is known, (meth) acrylic acid ester by enzyme-catalyzed esterification or Um esterification of alcohols with acrylic acid or alkyl acrylates.

Warwel et al., Biotechnol. Lett. 196, 10, pp. 283-286 describe the enzymatic Transesterification of saturated and unsaturated Fatty alcohols with methyl or ethyl acrylate.

Just OK et al., J. Mol. Cat. B enzyme. 1999, 7, pp. 273-282 describe the lipase-catalyzed Transesterification of 1-ethylhexanol with methyl acrylate.

Hajjar et al., Biotechnol., Lett. 1990, 12, p. 825-830 describe the enzymatic Transesterification of cyclic and open-chain alkanediols with ethyl acrylate.

gate et al., Enzyme. Microb. Technol. 1990, 12, p 299-304 describe the transesterification of ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, 1,4-butanediol and glycerol with methyl or ethyl (meth) acrylate. The transesterification is catalyzed by the pig liver ester (PLE), which has been treated with glutaraldehyde and polyacrylamide hydrazide. The special one Pretreatment of the enzyme is necessary to it over the aqueous substrate solution to stabilize.

EP-A 0 999 229 discloses the lipase-catalyzed esterification or transesterification of (meth) acrylic acid or Alkyl (meth) acrylates with polyoxyalkylenes such as polyethylene glycol.

Goede et al., Biocatalysis 1994, 9, pp. 145-155 describe the enzymatic Transesterification of alkyl glucosides to (6-O-acryloyl) alkyl glucosides.

Athawale et al., Tetrahedron Lett. 2002, 43, p. 4797-4800 describe the lipase-catalyzed Transesterification of the terpene alcohols geraniol and nerol with methyl methacrylate.

worin bedeuten:

wobei R in R_n gleich oder verschieden sein können,
R¹ einen unsubstituierten oder mit linearem oder verzweigtem C₁-C₁₂-Alkyl, C₁-C₁₂-Alkoxy, C₁-C₁₂-Alkylthio, OH, Di(C₁-C₄-alkyl)amino, Phenyl, Benzyl und/oder Morpholin-4-yl ein oder mehrfach substituierten Phenylrest, -CR⁵R⁶R⁷
worin R⁵, R⁶ und R⁷ gleich oder verschieden sind und Wasserstoff, lineares oder verzweigtes C₁-C₁₂-Alkyl, C₁-C₁₂-Alkoxy, C₅-C₈-Cycloalkyl, OH, Di(C₁-C₄-alkyl)amino, Phenyl oder Benzyl bedeuten, wobei auch zwei der Reste R⁵, R⁶ und R⁷ zu C₅-C₈-Cycloalkyl verbunden sein können,
R² H, OH, lineares oder verzweigtes C₁-C₁₂-Alkyl, Phenyl, Benzyl,

R³ H oder lineares oder verzweigtes C₁-C₁₂-Alkyl,
Z -CO-, -O-CO- oder -NH-CO-,
n 0 bis 30,
x 0 oder 1
bereitzustellen, welches selektiv ist und die Nachteile des Standes der Technik nicht aufweist.The object of the invention is a process for the preparation of (alk) acrylates of the general formula (I)

in which mean:

where R in R _{n may be the} same or different,
R ^{1 is} an unsubstituted or linear or branched C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylthio, OH, di (C ₁ -C ₄ alkyl) amino, phenyl, benzyl and / or morpholin-4-yl mono- or polysubstituted phenyl, -CR ⁵ R ⁶ R ⁷
in which R ⁵ , R ⁶ and R ^{7 are} identical or different and are hydrogen, linear or branched C ₁ -C ₁₂ -alkyl, C ₁ -C ₁₂ -alkoxy, C ₅ -C ₈ -cycloalkyl, OH, di (C ₁ -) C ₄ alkyl) amino, phenyl or benzyl, it also being possible for two of the radicals R ⁵ , R ⁶ and R ⁷ to be linked to C ₅ -C ₈ -cycloalkyl,
R ^{2 is} H, OH, linear or branched C ₁ -C ₁₂ -alkyl, phenyl, benzyl,

R ³ H or linear or branched C ₁ -C ₁₂ -alkyl,
Z is -CO-, -O-CO- or -NH-CO-,
n 0 to 30,
x 0 or 1
which is selective and does not have the disadvantages of the prior art.

worin R_n, R¹, R², Z, X und n die oben angegebene Bedeutung haben, mit (Alk)acrylsäure oder einem (Alk)acrylsäureester der allgemeinen Formel (III) oder (Alk)acrylsäureanhydrid der allgemeinen Formel (IIIa)

worin
R⁴ H oder einen C₁-C₃₀-Alkylrest bedeutet und
R³ die oben angegebene Bedeutung hat,
in Gegenwart eines die Veresterung bzw. Umesterung katalysierenden Enzyms.The object is achieved by a process for the enzyme-catalyzed preparation of (alk) acrylates of the general formula (I) by esterification or transesterification of aryl ketones of the general formula (II)

in which R _n , R ¹ , R ² , Z, X and n have the abovementioned meaning, with (alk) acrylic acid or an (alk) acrylic ester of the general formula (III) or (alk) acrylic anhydride of the general formula (IIIa)

wherein
R ^{4 is} H or a C ₁ -C ₃₀ -alkyl radical and
R ^{3 has} the meaning given above,
in the presence of an esterification or transesterification catalyzing enzyme.

If R ¹ as substituent is C ₁ -C ₁₂ -alkyl, C ₁ -C ₁₂ -alkoxy or C ₁ -C ₁₂ -alkylthio, the alkyl radical used is linear or branched C ₁ -C ₄ -alkyl (methyl, ethyl, n-butyl). Propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl), particularly preferred is methyl. The same applies to the case where R ² or R ^{3 is} C ₁ -C ₁₂ -alkyl. Preferred di (C ₁ -C ₄ alkyl) amino is dimethylamino. Preferred R ² is H or OH, preferred R ³ is H or methyl. If R ^{1 is} substituted phenyl, it is preferably substituted 1-3 times. n in R _n is preferably 1 to 10, particularly preferably 1 to 3.

Preferably, R ^{1 is} selected from the following radicals

mit n = 1, 2 oder 3.Examples of aryl ketones (II) are the following compounds (IIa) to (IIg).

with n = 1, 2 or 3.

Suitable (alk) acrylic acid derivatives which can be used for the esterification or transesterification of the compounds (II) are the (alk) acrylic acids themselves, their anhydrides and (alk) acrylic esters of C ₁ -C ₃₀ -alkanols. Preference is given to C ₁ -C ₆ (meth) acrylates, with particular preference being given to methyl, ethyl, propyl, butyl and 2-ethylhexyl (meth) acrylate, and to anhydrides of (meth) acrylic acid.

in the In general, the (alk) acrylic acid or the (alk) acrylate in the molar excess used. Preferably the molar ratio (Alk) acrylic acid compound (III) to compound (II) of 50: 1 to 1: 1, in particular of 20: 1 to 3: 1.

The used according to the invention Enzyme is a hydrolase (E.C.3.-.-.-), preferably an esterase (E.C. 3.1.-.-), glycosylase (E.C. 3.2.-.-) or protease (E.C. 3.4. in particular a lipase (E.C.3.1.1.3) in free or immobilized Shape. Particularly preferred are Novozyme 435 (lipase from Candida antarctica B) or lipase from Achromobacter sp., Alcaligenes spl., Aspergillus sp., Burkholderia sp., Candida sp., Mucor sp., Penicillium sp., Pseudomonas sp., Rhizopus sp., Thermomyces sp., wheat germ or porcine pancreas. The enzyme is generally used in amounts of 0.1 to 10 wt .-%, based on the compound (II) used.

The reaction may be carried out in an additional organic solvent or in the absence of an additional organic solvent. Suitable organic solvents are at For example, methyl tert-butyl ether, THF, toluene, 1,3-dioxolane, acetone, 1,4-dioxane, dimethoxyethane, cyclohexane, methylcyclohexane, toluene, hexane and mixtures thereof. The reaction can also be carried out in the (alk) acrylic acid derivative (III) as the sole solvent, preferably it is carried out in the (alk) acrylic acid derivative (III) as a solvent. In this case, the water content of the reaction mixture is preferably ≦ 5 vol .-%.

The Reaction is generally carried out at a temperature of 0 to 100 ° C, preferably from 20 to 80 ° C carried out.

Preferably, the reaction water liberated during the reaction or the liberated alcohol R ⁴ OH is suitably removed from the reaction equilibrium, preferably continuously. The separation can be carried out by means of molecular sieves, distillation in vacuo or by means of suitable semipermeable membranes.

The Implementation period is usually in the range of about 3 to 72 h.

The Implementation is characterized by a very high selectivity. So the esterified to the (poly) etherol chain OH groups are esterified, while phenolic or tertiary OH groups can not be esterified.

The Thus prepared (alk) acrylates (I) can be used as photoinitiators become. Because they are no discoloration they are particularly suitable for use in paint formulations suitable.

The The invention is further illustrated by the following examples.

Example 1a

In To a round-bottom flask, 0.4 mol of 2-hydroxy-4- (2'-hydroxyethoxy) benzophenone 1 (103.3 g), 8.0 mol of methyl acrylate (688.7 g) and 4.0 g of Novozym 435 (immobilized Lipase from Candida antarctica type B, Novozymes, Denmark) mixed and while 24 h at 40 ° C touched. The immobilized enzyme was filtered off and the excess Methyl acrylate removed on a rotary evaporator in vacuo.

you received 115.9 g (93% yield) of an orange oil, the slowly crystallized. The NMR analysis confirmed the Structure 2. GC analysis showed a content of 99% of the acrylated Benzophenone 2 and a residual content of the starting material 1 of 1%. This Product was used without further workup.

Example 1b

The batch 1a was doubled and stirred at 40 ° C for 24 h. The enzyme was filtered off and the filtrate (1 dissolved in methyl acrylate) used without further workup. The GC analysis showed a turnover of na 100% of the acrylated benzophenone 2 and a residual content of the starting material 1 of <0.1%.

Example 1c

A Mixture of 2 mmol 2-hydroxy-4- (2'-hydroxyethoxy) benzophenone 1 (517 mg), different amounts of methacrylate and 20 mg Novozym 435 were 24, 36 or 72 h at 20, 40 or 60 ° C shaken. The conversion was filtered by gas chromatography after filtering off the enzyme certainly. The results are shown in Tables 1 to 3.

Table 1 Sales at 20 ° C

Table 2 Sales at 40 ° C

Table 3 Sales at 60 ° C

Example 2

In To a round-bottom flask, 30 mmol of 2-hydroxy-4'-hydroxyethoxymethylpropiophenone 3 (6,73 g), 300 mmol of methyl acrylate (25.83 g), 6.0 g of molecular sieve powder 5 Å and 300 mg Novozym 435 (immobilized lipase from Candida antarctica type B) mixed and during 24 h at 20 ° C touched. After filtration, the excess became Methyl acrylate removed on a rotary evaporator in vacuo.

you received 7.24 g (87% yield) of a colorless, crystalline powder. NMR analysis confirmed the Structure 4. GC analysis showed a content of 99.3% of the acrylated Benzophenone 4 and a residual content of the reactant 3 of 0.7%. This Product was used without further workup.

Claims (10)

Process for the enzyme-catalyzed preparation of (alk) acrylates of the general formula (I)

in which mean:

wherein R in R _{n may be} identical or different, R ^{1 is} an unsubstituted or linear or branched C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylthio, OH, di (C ₁ C ₄ alkyl) amino, phenyl, benzyl and / or morpholin-4-yl mono- or polysubstituted phenyl radical, -CR ⁵ R ⁶ R ⁷ in which R ⁵ , R ⁶ and R ^{7 are} identical or different and are hydrogen, linear or branched C ₁ -C ₁₂ -alkyl, C ₁ -C ₁₂ -alkoxy, C ₅ -C ₈ -cycloalkyl, OH, di (C ₁ -) C ₄ alkyl) amino, phenyl or benzyl, wherein also two of the radicals R ⁵ , R ⁶ and R ⁷ may be connected to C ₅ -C ₈ cycloalkyl, R ^{2 is} H, OH, linear or branched C ₁ -C _12- alkyl, phenyl, benzyl,

R ^{3 is} H or linear or branched C ₁ -C ₁₂ -alkyl, Z is -CO-, -O-CO- or -NH-CO-, n is 1 to 30, x is 0 or 1 by esterification or transesterification of aryl ketones of the general formula (II)

wherein R _n , R ¹ , R ² , Z, X and n have the abovementioned meaning, with (alk) acrylic acid, an (alk) acrylic ester of the general formula (III) or an (alk) acrylic anhydride of the general formula (IIIa)

wherein R ^{4 is} H or a C ₁ -C ₃₀ -alkyl radical and R ^{3 has} the meaning indicated above, in the presence of an esterification or transesterification catalyzing enzyme. A method according to claim 1, characterized in that R ^{1 is} selected from the following radicals

Method according to claim 1 or 2, characterized the (alk) acrylate (III) is selected from methyl, ethyl, Propyl, butyl, 2-ethylhexyl (meth) acrylate and (meth) acrylic anhydride. Method according to one of claims 1 to 3, characterized that the esterification or transesterification in a separate solvent carried out becomes. Method according to one of claims 1 to 3, characterized in that the esterification or transesterification in the (alk) acrylic acid derivative (III) as a solvent carried out becomes. Method according to one of claims 1 to 5, characterized that the esterification or transesterification catalyzing enzyme is selected from lipases, esterases or proteases. Method according to one of claims 1 to 6, characterized in that the aryl ketones (II) are selected from the following compounds (IIa) - (IIg)

with n = 1, 2 or 3. (Alk) acrylates of the general formula (I), can be produced according to the method according to one of claims 1 to 7. Use of (alk) acrylates according to claim 8 as photoinitiators. Use of (alk) acrylates according to claim 8 in paint formulations.