Process for the preparation of aromatic carbonyl compounds...

Details Process for the preparation of aromatic carbonyl compounds... Process for the preparation of aromatic carbonyl compounds...

2000-06-09

2001-12-18

Killos, Paul J. (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C568S310000, C568S311000, C568S426000, C435S147000, C562S495000, C562S496000, C560S104000, C560S105000

Reexamination Certificate

active

06331655

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a novel process for the preparation of aromatic carbonyl compounds by oxidatively cleaving styrenes using lipases and hydrogen peroxide or hydrogen peroxide donors in the presence of carboxylic acids or carboxylic esters.
BACKGROUND OF THE INVENTION
To prepare aromatic carbonyl compounds which are intended to be used as flavorings or fragrances, it is possible to utilize the oxidative cleavage of styrenes. For the preparation of vanillin, the oxidative cleavage of eugenol or isoeugenol with K
2
Cr
2
O
7
/H
2
SO
4
has been described. In industry, vanillin is prepared predominantly by the alkaline hydrolysis of lignin (spent sulphite liquor from the paper industry) and oxidative cleavage of the resulting coniferyl alcohol (Römpp Lexikon Chemie, Version 1.5).
However, the aromatic carbonyl compounds prepared in this manner, such as, for example, vanillin, have the disadvantage that they are not permitted to be referred to as natural flavorings but only as nature-identical flavorings within the meaning of Directive 88/388/EEC on flavorings. Only compounds which have been prepared by physical processes (e.g., distillation or extraction) or biotechnological processes (enzymatically or microbially) can be referred to as natural flavorings.
To prepare natural benzaldehyde, for example, cassia oil is treated with hot steam.
EP-A 542,348 describes a process for the preparation of natural phenylaldehydes using the enzyme lipoxidase. If the substrates used are eugenol or isoeugenol, the reaction with the lipoxidase gives vanillin. Disadvantages of this process are the low conversions of from 0.3 to 15%.
DE-A 19,649,655 describes a process for the preparation of vanillin from ferulic acid in the presence of the enzyme ferulic acid deacylase. However, the enzyme can only be used for the preparation of vanillin starting from ferulic acid. Other starting materials are not suitable.
U.S. Pat. No. 5,128,253 describes the preparation of natural vanillin from ferulic acid or eugenol by biotransformation. Microorganisms used are
Aspergillus niger, Rhodotorula glutinis
and
Corynebacterium glutamicum.
The main disadvantage in this preparation is the long incubation time of, on average, from 7 to 10 days.
EP-A 405,197 describes the preparation of natural vanillin by oxidation of eugenol or isoeugenol using microorganisms of the genera Serratia, Klebsiella or Enterobacter. Within short reaction times, this method too, permits only relatively low yields.
SUMMARY OF THE INVENTION
The object of the present invention was then to provide a process for the preparation of aromatic carbonyl compounds which can be used as natural flavors or fragrances, which is easy to carry out and produces the desired products in good yields and in short reaction times.
We have now found a process for the preparation of aromatic carbonyl compounds, which is characterized in that styrenes are oxidatively cleaved in the presence of carboxylic acids or carboxylic esters by lipases and hydrogen peroxide or hydrogen peroxide donors.
DETAILED DESCRIPTION OF THE INVENTION
The advantages of the process according to the present invention arc high yields, simple implementation and simple isolation of the desired product. In addition, it is possible to react a variety of starting materials with the same lipase to give a variety of products which can be used as natural flavorings. The process according to the present invention, thus, represents a universally applicable process for the preparation of aromatic carbonyl compounds from styrenes.
Lipases are usually used for esterification or transesterification. There are numerous descriptions of these applications. The use of lipases for the enzymatic epoxidation of alkenes (WO 91/043333) and for the preparation of peroxycarboxylic acids from carboxylic acids has also been described. In addition, the reaction of sulphides to sulphoxides (Björkling et al., J. Chem. Soc., Chem. Commun., 1990, 1301-1303) and the lipase-catalyzed Baeyer-Villiger oxidation (Lemoult et al., J. Chem. Soc. Perkin Trans. 1, 1995, 89-91) have been described.
In the process according to the present invention, in the first reaction step, the corresponding peroxycarboxylic acid forms from the carboxylic acid or the carboxylic ester and hydrogen peroxide. This acid reacts with the styrene used, producing, as reaction products, aromatic carbonyl compounds and the corresponding carboxylic acid.
The styrenes are preferably compounds of the formula (I)
in which
R
1
, R
2
and R
3
independently of one another are hydrogen, straight-chain or branched C
1
-C
20
-alkyl, C
3
-C
8
-cycloalkyl, C
6
-C
14
-aryl, C
7
-C
15
-arylalkyl, C
1
-C
20
-alkoxy, C
1
-C
20
-alkylamino, wherein the above-mentioned hydrocarbon radicals may be mono- or polysubstituted by hydroxyl, formyl, oxy, C
1
-C
6
-alkoxy, carboxyl, mercapto, sulpho, amino, C
1
-C
6
-alkylamino, nitro or halogen, and
Ar is phenyl, optionally mono- or polysubstituted with straight-chain or branched C
1
-C
6
-alkyl, C
3
-C
8
-cycloalkyl, C
1
-C
6
-alkoxy, hydroxyl, oxy, carboxyl, mercapto, sulpho, amino, C
1
-C
6
-alkylamino, nitro or halogen.
In a preferred embodiment, styrenes of the formula (I) are used
in which
R
1
is a straight-chain or branched C
1
-C
20
-alkyl, C
3
-C
8
-cycloalkyl, phenyl, C
7
-C
15
-arylalkyl, C
1
-C
20
-alkoxy, oxy, formyl or carboxyl,
R
2
and R
3
are hydrogen, and
Ar is phenyl, optionally mono- or polysubstituted by a straight-chain or branched C
1
-C
6
-alkyl, C
3
-C
8
-cycloalkyl, C
1
-C
6
-alkoxy, hydroxyl, formyl, oxy, carboxyl, mercapto, amino, halogen or C
1
-C
6
-alkylamino.
In a most preferred embodiment, the styrenes are isoeugenol, ferulic acid, coniferyl alcohol, cinnamaldehyde or coniferyl aldehyde.
The process according to the present invention is carried out in the presence of carboxylic acids or carboxylic esters of the formula (II)
in which
R
4
is a straight-chain or branched C
1
-C
20
-alkyl, C
3
-C
8
-cycloalkyl, C
2
-C
20
-alkenyl, C
5
-C
8
-cycloalkenyl, C
2
-C
20
-alkinyl, C
6
-C
14
-aryl, C
7
-C
15
-arylalkyl, optionally mono- or polysubstituted by hydroxyl, oxy, formyl, mercapto, C
1
-C
6
-alkoxy, C
1
-C
6
-alkylamino or halogen, and
R
5
is hydrogen, a straight-chain or branched C
1
-C
20
-alkyl, C
3
-C
8
-cycloalkyl, C
2
-C
20
-alkenyl, C
5
-C
8
-cycloalkenyl, C
2
-C
20
-alkinyl, C
6
-C
14
-aryl, C
7
-C
15
-arylalkyl, optionally mono- or polysubstituted by hydroxyl, oxy, formyl, mercapto, C
1
-C
6
-alkoxy, C
1
-C
6
-alkylamino or halogen.
Preference is given to using carboxylic acids or carboxylic esters of the formula (II) in which
R
4
is a straight-chain or branched C
1
-C
10
-alkyl, C
2
-C
10
-alkenyl, C
2
-C
10
-alkinyl, C
3
-C
8
-cycloalkyl, C
1
-C
6
-aryl or C
7
-C
6
15
-arylalkyl, and
R
5
is hydrogen, straight-chain or branched C
1
-C
10
-alkyl, C
2
-C
10
-alkenyl, C
2
-C
10
-alkinyl, C
3
-C
8
-cycloalkyl, C
1
-C
6
-aryl or C
7
-C
15
-arylalkyl.
The carboxylic acids or carboxylic esters used are most preferably acetic acid or ethyl acetate.
Lipases from
Candida antarctica
are customarily used for the process according to the present invention. Preference is given to lipases from the
Candida antarctica
strains which were deposited at the Deutsche Sammlung von Mikroorganismen [German Depository for Microorganisms] in accordance with the Budapest treaty on the deposition of microorganisms under the following number: DSM 3855, deposited on Sep. 29, 1986, DSM 3908 and DSM 3909, deposited on Dec. 8, 1986.
The lipases are obtainable by a process described in WO 88/02775 from the respective microorganisms:
After the corresponding strain has been cultivated in a suitable nutrient medium under aerobic conditions, liquid enzyme concentrates can be obtained, following removal of insoluble material (e.g., by filtration or centrifugation), by evaporation or reverse osmosis. Solid enzyme preparations can be obtained by precipitation from the soluble concentrate by adding salts or ethanol.
It is known that lipases can also be obtained by recombinan

Affiliated with

Also associated with

Rating

Process for the preparation of aromatic carbonyl compounds... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of aromatic carbonyl compounds..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of aromatic carbonyl compounds... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2585765