WO2001079147A1

WO2001079147A1 - Method for the production of aromatic or heteroaromatic aldehydes or ketones by oxidative decarboxylation

Info

Publication number: WO2001079147A1
Application number: PCT/EP2001/003222
Authority: WO
Inventors: Berthold Winkler; Wolfram Hendel; Ferdinand Heu; Peter Pöchlauer
Original assignee: Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg
Priority date: 2000-04-17
Filing date: 2001-03-21
Publication date: 2001-10-25
Also published as: CA2404180A1; EP1274670A1; AU2001254716A1; JP2004501074A

Abstract

A method for the production of substituted aromatic aldehydes or ketones and optionally substituted heteroaromatic aldehydes or ketones of formula (I) by reacting a compound of formula (II) in a suitable solvent in the presence of a carbonyl compound of formula (III), optionally in the presence of oxygen at a normal pressure or high temperature and at temperatures of 5-200 DEG C.

Description

METHOD FOR PRODUCING AROMATIC OR HETEROAROMATIC ALDEHYDES OR KETONES BY OXIDATIVE DECARBOXYLATION

Aromatic aldehydes and ketones are important intermediates in the chemical, pharmaceutical and cosmetic industries, so that a number of processes for producing the same are already known in the literature, but are unsatisfactory for industrial use

In addition to the variants of the Reimer-Tiemann reaction (Chem Rev 60 (1960), 169), for example under pressure, with transition catalysts or with cyclodextines, the hydroxymethylation of phenol with subsequent oxidation, and the reaction of phenol with glyoxylic acid and subsequent oxidative decarboxylation of the almond acid derivatives obtained as an intermediate in the presence of metal salts (eg US 2,640,083)

The oxidation of hydroxyphenylglycine to hydroxybenzaldehyde using metal catalysts is known from Chem Abstr (1982) 597981. However, as comparative experiments have shown, the reaction is very difficult due to the high proportion of by-products

Tetrahedron Letters No 24, pp 2139-2140 (1971) describes a process for the oxidative decarboxylation of aliphatic α-amino acids, in particular leucine and valine, using isatogens, such as isatin or ninhydrm, to give the corresponding aldehydes and isatogen reduction products When using other amino acids, such as phenylalanine, it is stated, however, that tar-like or oily by-products are obtained

It has now been unexpectedly found that aromatic amino acids which are substituted on the aromatic and optionally substituted heteroaromatic amino acids can be converted to the corresponding aldehydes and ketones in high yield and purity using special carbonyl compounds as a catalyst in combination with oxygen or in molar amounts The invention accordingly relates to a process for the preparation of substituted, aromatic aldehydes or ketones and optionally substituted, heteroaromatic aldehydes and ketones of the formula

in Ar are a mono- or polysubstituted aromatic or an optionally mono- or polysubstituted heteroaromatic radical and the substituents OH, Ci-C _δ- alkyl, Ci-Cε-alkoxy, Cι-C ₆ carboxylic acids or esters with 1 -6 carbon atoms in the ester part, methylenedioxy phenyl, halogen, SO3H, NO2, N ₃ , NR1R2 or SR1, where R 1 and R _{2 can} be independently of one another H, phenyl or Ci-Cε-alkyl and R is H or an unsubstituted one or poly-substituted alkyl group with 1 -12 C atoms, unsubstituted or substituted benzyl, diphenylmethyl and the substituents are heteroaromatics, halogens, NO2, N ₃ , SO3H, NR ₁ R ₂ or SR ₁ , where R ₁ and R ₂ are independently H , Phenyl or Cι-C6-alkyl may be, which is characterized in that a compound of the formula

in which Ar and R have the above meaning, in a suitable solvent in the presence of a carbonyl compound of the formula

R ₃ C (O) (CH = CH) _n C (O) (X) _y R ₃ ^' III

in which n is 0 or an integer from 1 to 3, y is 0 or 1, X can be NR ^ O or S0 ₂ and R ^ H, -CC ₆ alkyl or CH ₂ COOH, R ₃ and R ₃ ^' from each other independently represent H, OH, Ci-Ce-alkyl, -C-C ₆ alkoxy or phenyl or together a (-C = C-) _m bond with m equal to 1 or 2, or optionally by OH, Ci-Ce-alkyl , -C-C ₆ alkoxy, -C-C ₆ carboxylic acids or esters with 1-6 C atoms in the ester part, phenyl, halogen, S0 ₃ H, N0 ₂ , N ₃ , NR1R2 or SRi, wherein R 1 and R ₂ independently of one another can be H or Ci-Ce-alkyl, substituted condensed ring system which may contain a hetero atom optionally substituted by Ci-Ce-alkyl or CH ₂ COOH, optionally in the presence of oxygen at atmospheric pressure or elevated pressure and at temperatures from 5 to 200 ° C to the corresponding aldehyde or ketone of formula I is implemented

In the process according to the invention, compounds of the formula II are converted into the corresponding aldehydes or ketones of the formula I. Suitable compounds of the formula II are α-amino acids which have a substituted aromatic or an optionally substituted heteroaromatic radical Ar

Aromatic and heteroaromatic radicals Ar are radicals which are derived from aromatics or heteroaromatics having one or more heteroatoms or from condensed ring systems which may have one or more heteroatoms, such as benzene, pyrrole, furan, thiophene, pyndine, Pyran, thiopyran, pyπmidin, indene, imidazole, pyrazole, thiazole, oxazole, naphthalene, anthracene, chino n, isoquinone, benzo (g) ιsochιnolιn, indole, coumarone, thionaphthene, acπdin, etc. The aromatic residues are one or more Substituents from the group OH, methylenedioxy, linear, branched or cyc cal Ci-Cε-alkyl or -CC ₆ alkoxy radical, -C ₆ -carboxylic acids or esters with 1 -6 C atoms in the ester part, phenyl , Halogen, SO ₃ H, N0 ₂ , N ₃ , NR1 R2 or SRi, where Ri and R _{2 can} independently be H, phenyl or a linear, branched or cychscher Ci-Cε-alkyl radical, substituted. The heteroaromatic radicals can be unsubsti - tuiert or through one or more of the above substituents may be substituted Ar is preferably an aromatic radical or a fused ring system with at most one heteroatom, such as phenyl, pyrrolyl, pyridinyl, thiophenyl, naphthyl, etc. Particularly preferred are aromatic radicals with only one ring and at most one heteroatom, phenyl, pyrrolyl, pyridyl, thiophenyl, etc. Preferred substituents are OH, C 1 -C ₄ alkoxy, such as methoxy, ethoxy, propoxy and butoxy, and NR ₁ R ₂ with R 1 and R ₂ being H or C 1 -C ₄ alkyl, OH and C ₁ -C ₂ alkoxy are particularly preferred

P-Hydroxyphenylglycm or p-alkoxyphenylglycme, such as p-methoxyphenylglycine, α-substituted amino acids such as methylphenylglycine or methylenedioxyphenylglycine and dihydroxy- or polyhydroxyphenylglycine are very particularly preferably used for the process according to the invention

The starting compounds can be used as a racemate or in enantiomerically pure form as the R or S enantiomer

The reaction of the starting compounds of formula II to the corresponding aldehydes or ketones of formula I is carried out in a suitable solvent. Suitable solvents are water or water mixtures with organic and / or inorganic acids, such as acetic acid, sulfuric acid, hydrochloric acid, etc. or with glycerol, dioxane or Pyπdin, which have a pH between 1-12

Water mixtures with organic and / or inorganic acids are preferably used. Water or a water / acetic acid, water / hydrochloric acid or water / sulfuric acid or water / sulfuric acid / acetic acid mixture is particularly preferably used

According to the invention, the starting compounds are oxidized in the presence of a carbonyl compound of the formula III either in catalytic amounts with oxygen or in molar amounts to the corresponding aldehydes or ketones In formula III, n is 0 or an integer from 1 to 3. Preferably n is 0 or 1, y is 0 or 1, X is NR, O or SO ₂ and Ri H, a linear, branched or cyc's Ci-Cε-alkyl radical or CH ₂ COOH

R ₃ and R ₃ ^' can independently of one another be H, OH, a linear, branched or cych C ₁ -C ₆ -alkyl or C ₁ -C ₆ alkoxy radical or phenyl, or together a (-C = C-) _m bond with m equal to 1 or 2, or an optionally by OH, Ci-Cε-alkyl, -C-C ₆ alkoxy, -C-C ₆ carboxylic acids or esters with 1-6 C atoms in the ester part, phenyl, halogen, SO ₃ H, NO ₂ , N ₃ , NR1R2 or SRi, where R 1 and R ₂ can be, independently of one another, H, phenyl or Ci-Ce-alkyl, substituted condensed ring system which is optionally substituted by Ci-Ce-alkyl or CH ₂ COOH may contain substituted heteroatom form

Suitable catalysts are accordingly α-keto acids, α-ketolactones, α-ketolactams α-ketoaldehydes, 1, 2-diketones, aldehyde carboxylic acids, dialdehydes, dicarboxylic acids or their esters, quinones and the like

Examples of these are glyoxal, phenylglyoxal, methylglyoxal, diacetal, oxalic acid, maleic acid, glyoxylic acid, glyoxylic acid ester, phenylglyoxylic acid, pyruvic acid, pyruvic acid ester, phenyl pyruvic acid, benzil, p-benzoquinone, o-benzoquinate, iso, iso acidate, indigo, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, isin acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, iso acid, isin acid, iso acid, iso acid, isin acid, iso acid, isin acid, iso acid, isin acid, iso acid, iso acid, isin, acid, iso etc. Isatm and substituted isatins, such as N-methylsatin, isatinsulfonic acid, diacetyl, glyoxylic acid or its esters, phenylglyoxylic acid, pyruvic acid or its esters, phenylglyoxal or p-benzochmon, are preferably used. Isatm, N-methylhsatin, isatinsetylsulfonic acid, diacetylsulfonic acid, Pyruvic acid or p-benzoquinone

The carbonyl compounds can optionally also be used in the form of a salt

Depending on the type of carbonyl compound, it is used either in combination with oxygen in catalytic amounts of 1 to 30 mol%, preferably 1-20 mol%, as is the case, for example, for isatm or isatin sulfonic acid, or in equimolar amount. ge or in an amount of 1, 1 to 5, preferably from 1, 4 to 3.5 mol of carbonyl compound per mol of starting compound

The carbonyl compound can be used either in homogeneous form or in heterogeneous form on a suitable support

The reaction according to the invention is preferably carried out when the carbonyl compound is used in catalytic amounts, in the presence of oxygen, for example in the form of pure oxygen, in the form of air or in the form of an N2 / θ2 mixture. In this case, air or oxygen or the like is used during the reaction Blown N2 / O2 mixture into the reaction mixture

This is particularly advantageous when using Isatm or substituted isatins. For example, the Isatm acting as an oxidizing agent is regenerated by the oxygen present

The reaction can be carried out at normal pressure or at elevated pressure. A pressure of between 1 and 7 bar, particularly preferably between 1 and 5 bar, is accordingly set

The reaction temperatures in the process according to the invention, depending on the pressure selected, are between 5 and 200 ° C., preferably between 15 and 150 ° C. and particularly preferably between 50 and 100 ° C.

The isolation of the desired aldehyde or ketone of the formula I is carried out depending on the state of matter by conventional isolation methods, such as extraction, distillation, crystallization and the like

The process is preferably suitable for the preparation of aldehydes or ketones of the formula I in which Ar is an aromatic five- or six-membered ring with a maximum of one heteroatom or a condensed ring system with a maximum of one heteroatom, which is represented by OH, methylenedioxy, C 1 -C ₄ - Alkoxy, such as methoxy, ethoxy, Propoxy and butoxy, and NR ₁ R ₂ with R ₁ and R ₂ is H or -CC ₄ alkyl, particularly preferably substituted by OH and -C-C ₂ alkoxy and R is H or an unsubstituted or poly-substituted alkyl group 1-12 C atoms, unsubstituted or substituted benzyl, diphenylmethyl and the substituents heteroaromatics, halogens, NO ₂ , N ₃ , SO ₃ H, NR ₁ R ₂ or SRi, where R 1 and R ₂ are independently H, phenyl or Ci-Cε-alkyl mean

Hydroxy or polyhydroxybenzaldehydes, such as 4-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde or alkoxybenzaldehydes, such as p-methoxybenzaldehyde, or ketones such as acetophenone are very particularly preferably produced by the process according to the invention

The aldehydes and ketones of the formula I are obtained in high yields and with high purity

Example 1: Reaction of 4-hydroxyphenylglycine with isatin and oxygen

4.9 g of 4-hydroxyphenylglycine (29.3 mmol) and 0.77 g of isatin (5.2 mmol) were dissolved in 50 ml of 50% acetic acid at 90 ° C. Then air was bubbled in with vigorous stirring for 15.5 hours. After the reaction had ended, the mixture was diluted with three times the amount of water and extracted with MTBE (3 × 100 ml). The combined organic phases were washed with NaHCO ₃ and water. 2.4 g of 4-hydroxybenzaldehyde were obtained as a reddish brown product (yield: 68%; purity: 77% by weight).

Example 2: Reaction of 4-hydroxyphenylglycine with isatin-5-sulfonic acid

16.67 g of 4-hydroxyphenylglycine (100 mmol) and 2.85 g of isatin-5-sulfonic acid Na salt dihydrate (10 mmol) in a mixture of 84 ml of acetic acid and 150 ml were placed in a 250 ml Schmizo double-walled vessel with a stirrer and intensive cooler Water was stirred at 90 ° C. and air (18 hours, 150-200 ml / min) was blown into the red-colored clear reaction solution through an inlet tube. The end product was extracted with MTBE (3x100 ml), washing the combined org. Phases isolated with NaHCO ₃ solution and spun in on a Rotavapor. 9.7 g of 4-hydroxybenzaldehyde were obtained as a beige, powdery solid (79.4% yield) with a purity of 97.3% by weight.

Example 3: Sulfonation of isatin and use of the product as a catalyst for the oxidation of 4-hydroxyphenylglycine

In a 50 ml 2-neck round-bottom flask with a magnetic stirrer, 3.0 g of isatin (20.4 mmol) were added in portions to 6.0 ml of conc. Sulfuric acid (107 mmol) was added at room temperature and the resulting dark red viscous solution was stirred at 80 ° C. After complete conversion (3.5 hours), 4.17 g of this solution (corresponding to approximately 6 mmol of isatin sulfonic acid) in 50 ml of water were slowly stirred into a 100 ml Schmizo double-walled vessel with an intensive cooler. For this solution, the 50 ml of concentrated acetic acid and 10.3 g of 4-hydroxyphenylglycιn (60 ml) were added, heated to 90 ° C. and oxygen (30-40 ml / min) was introduced. After about 20 hours the extraction was carried out with MTBE (3 × 100 ml) Combined org phases were washed with NaHCO ₃ solution and concentrated on a Rotavapor

4-Hydroxybenzaldehyde was obtained as a beige product with a purity of 97.0% by weight (51% isolated)

Example 4 Reaction with pyruvic acid

2.6 g pyruvic acid (29.5 mmol) was added to a solution of 3.3 g 4-hydroxyphenylglycine (19.8 mmol) in 50 ml water and stirred at 80 ° C. for six hours. The product was treated with MTBE (3x 50 ml) extracted, the org phase washed with NaHCO ₃ solution and water and evaporated

1.5 g of 4-hydroxybenzaldehyde were obtained as a beige-colored product (62% yield) with a purity of 92.6% by weight

Example 5 Reaction with Glyoxylic Acid

4.5 g of 50% solution of glyoxylic acid solution (30.6 mmol) were added to a solution of 3.4 g of 4-hydroxyphenylglycine (20.5 mmol) in 50 ml of water at 90 ° C. and the mixture was stirred for 3 hours MTBE (3x 50 ml) extracted, the organic phase washed with NaHCO ₃ solution and water and evaporated in. 0.93 g of 4-hydroxybenzaldehyde was obtained as a beige-colored product (37.2% yield) with a purity of 98.5% by weight

Example 6 Reaction with diacetyl

In a 250 ml three-necked flask, 19.9 g of 4-hydroxyphenlyglycine (119 mmol) were stirred in 100 ml of water, adjusted to pH 1 with concentrated hydrochloric acid (6.5 ml) and heated to 80 ° C. The clear solution was 26.3 g of diacetyl (239 mmol) added. After 2.5 hours the hydroxyphenlyglycine was completely reacted. de diluted with water (50 g), extracted 3 times with MTBE (100-150 ml) and the combined org. Phases rotated. The viscous residue was taken up in water (20 ml) and heated and the black oil which separated out was separated off (at 60-70 ° C.). Colorless crystals separated from the aqueous solution: 3.2 g with a purity of 96.6% by weight. Two further fractions were obtained from the mother liquor (0.78 g; 94.2% by weight and 1.32 g; 84.2% by weight). Overall yield: 5.3 g (36%).

Example 7: Reaction of S-methylphenylglycine with isatin sulfonic acid and oxygen

A mixture of 16.5 g (100 mmol) of S-α-methylphenylglycine and 2.5 g (10 mmol) of isatin sulfonic acid Na salt in 170 ml of dilute acetic acid (50%) was stirred at 90 ° C. Oxygen was bubbled into the mixture for 31 hours. After cooling to room temperature, the mixture was extracted with 2 × 100 mL MTBE, the MTBE phases were combined and washed neutral with 200 mL dilute KOH. After removing the LM in vacuo, a slightly colored residue (5.6 g) containing 80% acetophenone was obtained (yield 36%).

Example 8: Reaction of S-methylphenylglycine with isatin

A mixture of 49.6 g (300 mmol) of S-α-methylphenylglycine and 4.4 g (30 mmol) of isatin in 500 g of dilute sulfuric acid (3%) was stirred at 85 ° C. Oxygen was bubbled into the mixture for 17 hours. After cooling to RT, the mixture was extracted with 2 x 200 mL MTBE and the resulting acetophenone was purified by distillation. (34% yield, purity: 98 HPLC-FI%) Example 9 Reaction of 3,4-dihydroxyphenylglycine with isatin sulfonic acid

A mixture of 18.3 g (100 mmol) of 3,4-dihydroxyphenylglycine and 2.5 g (10 mmol) of isatin sulfonic acid Na salt in 150 mL water and 6.2 g conc. Sulfuric acid was stirred at 95 ° C. Oxygen was stirred for 14 hours introduced into the mixture after cooling to RT, the mixture was extracted with 2 x 100 mL MTBE, the MTBE phases were combined and washed neutral with 200 mL dil KOH. After removing the LM in vacuo, 3,4-dihydroxybenzaldehyde was obtained (66% Yield)

Comparative Experiment 1 Reaction of 4-Hydroxyphenylglycιn with CuCI ₂ and O2 (Comparison to Chem Abstr (1982) 597981)

10.0 g of 4-hydroxyphenylglycine (60 mmol) and 0.8 g of copper (II) chlorine (6 mmol) were dissolved in 200 ml of water in a 250 ml double-jacketed vessel and adjusted to pH = 10 with 10% sodium hydroxide solution (46 g) Oxygen (30 ml / min) was introduced at 94 ° C. for 15 hours. After 15 hours, HPLC analysis showed 41% by weight of 4-hydroxybenzaldehyde with 100% conversion. Working up by extraction with MTBE (4x100 ml) gave 1.83 g ( 25%) of 4-hydroxybenzaldehyde with a purity of 87% by weight

Comparative Example 2 Reaction of 4-Hydroxyphenylglycιn with CuC and O ₂ (Comparison to Chem Abstr (1982) 597981)

5.0 g of 4-hydroxyphenylglycine (30 mmol) and 4.0 g of copper (II) chloride (30 mmol) were dissolved in 75 ml of water in a 100 ml double-jacketed vessel. At 90 ° C., oxygen (25 ml / min) was introduced and the reaction was monitored by means of HPLC. After 10 hours and with a conversion of 80%, only 6% by weight of product was formed, in addition 17.2% by weight of 4-hydroxybenzamide and a number of uncharacterized aromatic by-products were found

Claims

claims

1 Process for the preparation of substituted, aromatic aldehydes or ketones and optionally substituted, heteroaromatic aldehydes or ketones of the formula

in the Ar is a mono- or polysubstituted aromatic or an optionally mono- or polysubstituted heteroaromatic radical and the substituents OH, methylenedioxy, Ci-Ce-alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ carboxylic acids or esters with 1 -6 carbon atoms in the ester part, phenyl, halogen, S0 ₃ H, NO ₂ , N ₃ , NR ₁ R ₂ or SRi, where R 1 and R ₂ independently of one another are H, phenyl or C ₁ -C ₆ - Can be alkyl and R is H or an unsubstituted or multiply substituted alkyl group with 1 -12 C atoms, unsubstituted or substituted benzyl, diphenylmethyl and the substituents are heteroaromatics, halogens, NO ₂ , N ₃ , SO ₃ H, NR1R ₂ or SRi, where Ri and R ₂ independently of one another are H, phenyl or Ci-Cβ-alkyl, characterized in that a compound of the formula

R ₃ C (O) (CH = CH) _n C (O) (X) _y R ₃ ^' III in which n is 0 or an integer from 1 to 3, y is 0 or 1, X NR ^ O or can be SO ₂ and Ri H, Ci-Ce alkyl or CH ₂ COOH, R ₃ and R ₃ ^' of one independently of one another are H, OH, Ci-Cε-alkyl, Ci-C _δ -alkoxy or phenyl or together a (-C = C-) _m bond with m equal to 1 or 2, or one optionally by OH, Ci-Ce- Alkyl, Ci-Cβ-alkoxy, Ci-Cε-carboxylic acids or esters with 1-6 C atoms in the ester part, phenyl, halogen, SO ₃ H NO ₂ , N ₃ , NR1R2 or SRi, where Ri and R ₂ from each other can independently be H, phenyl or Ci-Ce-alkyl, substituted condensed ring system, which may contain a hetero atom optionally substituted by Ci-Cβ-alkyl or CH ₂ COOH, optionally in the presence of oxygen at normal pressure or elevated pressure and at temperatures from 5 to 200 ° C to the corresponding aldehyde or ketone of formula I is implemented

A method according to claim 1, characterized in that in the compound of formula I and II Ar a mono- or polysubstituted aromatic, an optionally mono- or polysubstituted heteroaromatic with one or more heteroatoms or an optionally mono- or polysubstituted condensed ring system , which optionally has one or more heteroatoms, from the group consisting of benzene, pyrrole, furan, thiophene, pyπdin, pyran, thiopyran, pyπmidin, indene, imidazole, pyrazole, thiazole, oxazole, naphthalene, anthracene, chinohn, isoquinone, benzo ( g) ιsochιnolιn, indole, coumarone, thionaphthene, acπdin, where the substituents from the group OH, methylenedioxy, Ci-Cε-alkyl, Ci-Cδ-alkoxy, phenyl, halogen, NR1R2 or SRi, wherein R 1 and R ₂ from one another can independently be H, phenyl or Ci-Cβ-alkyl and R is H or an unsubstituted or multiply substituted alkyl group with 1-12 C atoms, unsubstituted or substituted benzyl, D can be iphenylmethyl and the substituents can be heteroaromatics, halogens, NO ₂ , N ₃ , SO3H, NR1R ₂ or SRi, where R and R ₂ independently of one another are H, phenyl or Ci-Ce-alkyl

A method according to claim 1, characterized in that as a compound of formula II hydroxyphenylglycine or -CC ₄ alkoxyphenylglycine, 3,4- Dihydroxyphenylglycine, 2,4-dihydroxyphenylglycine, 3,4,5-trihydroxyphenylglycine, 3-hydroxy-4-methoxyphenylglycine, 4-hydroxy-3-methoxy-phenylglycine or 3,4-methylenedioxyphenylglycine, α-methylphenylglycine, α-methyl-4- hydroxyphenylglycine, α-methyl-3,4-dihydroxyphenylglycine, α-methyl-3,4-methylenedioxyphenylglycine or α-methyl-4-methoxyphenylglycine can be used.

A method according to claim 1, characterized in that water or aqueous mixtures with organic and / or inorganic acids or with glycerol, dioxane or pyridine, which have a pH between 1 and 12, are used as the solvent.

A method according to claim 1, characterized in that α-keto acids, α-ketolactones, α-ketolactams, α-ketoaldehydes, 1, 2-diketones, aldehyde carboxylic acids, dialdehydes, dicarboxylic acids or their esters or quinones are used as the carbonyl compound of the formula III.

A method according to claim 1, characterized in that as the carbonyl compound glyoxal, phenylglyoxal, methylglyoxal, diacetal, oxalic acid, maleic acid, glyoxylic acid, glyoxylic acid ester, phenylglyoxylic acid, pyruvic acid, pyruvic acid ester, phenylpyruvic acid, benzil, p-benzoquinone, indigo, isoquinoline, o-benzoquinone , N-methylisatin, isatin sulfonic acid, isatin acetic acid can be used.

A method according to claim 1, characterized in that, depending on the type of carbonyl compound, this is used either in combination with oxygen in catalytic amounts of 1 to 30 mol% or in an equimolar amount or in an amount of 1.1 to 5 mol of carbonyl compound per mol of starting compound becomes. A method according to claim 7, characterized in that isatin and substituted isatins are used in a catalytic amount of 1-20 mol%.

A method according to claim 1, characterized in that in the reaction of the compound of formula II to the corresponding aldehyde or ketone of formula I, when using isatin or substituted isatins, oxygen in the form of pure oxygen, air or N ₂ / θ ₂ - Mixture is passed through the reaction mixture. , A method according to claim 1, characterized in that the reaction takes place at a pressure between 1 and 7 bar and a reaction temperature between 15 and 150 ° C.