HU202178B - Process for producing aldehyde by hydrogenation of nitryl - Google Patents

Abstract

Nitrile gps of organic cpds. are converted to aldehyde gps. by hydrogenation in the presence of a Raney Nickel catalyst, an acid, and a salt or oxide of lead, cadmium, iron mercury, arsenic zinc, antimony or bismuth promoters. The reaction is carried out in a polar solvent in a temp. range of 0 deg.C to bpt. of solvent (15-60 deg.C) and 0.2-40 bar (1-5 bar) pressure. Following complete redn. of the nitrile gps. the catalyst is filtered out and the prod. is isolated.

Description

The present invention relates to a process for converting a nitrile group of a compound of formula I into an aldehyde group. More particularly, the present invention relates to a process for converting a nitrile group into an aldehyde group of compounds wherein R is a C 1 -C 14 alkyl group optionally substituted with a C 1 -C 4 alkoxy group, a C 2 -C 6 alkenyl group. , phenyl optionally substituted with one or more halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy or phenoxy, phenyl (C 1-4 alkyl) or naphthyl groups.

Raney Nickel Reduction of Nitriles Can Form Primary, Secondary or Tertiary Amines, Aldehydes, Alcohols, Alkanes, and N-Heterocyclic Compounds (Houben-Weil, Methoden Der Organischen Chemie, IV / 1 Reduction I, 111; Verlag, Stuttgart, New York) , 1980). The formation of aldehyde is favored when an amine-type aldehyde reagent is added to the nitrile and the resulting aldehyde derivative is no longer or only very slowly reduced by Raney nickel. Suitable reagents include phenylhydrazine and its substituted derivatives [Compt. Rend., 252, 1339 (1961) and 255, 134 (1961)], semicarbazide (Houben-Weil, Methoden der Organischen Chemie, IV / 1, Reduction I, 113, Verlag, Stuttgart). New York, 1980; No. 957,029 German Patent Specification; Angew. Chem., 67, 156 (1957)], 1,2-dianilinoethane [Chem. Bér., 90, 617 (1957)]. The disadvantages of these methods are that the use of organic excipients complicates the process and the release of the aldehyde from its derivative causes further losses.

Raney-nickel hydrogenation of nitriles can be carried out at room temperature, atmospheric pressure, tetrahydrofuran-water in the presence of a molar amount of sulfuric acid [Angew. Chem. Sus., 152, 1968; Chem. Bér., 1961, 12-2770; Arch. Pharm., 309, 766 (1976)]. The reaction time, depending on the structure of the organic nitrile, is from 2 to 15 hours with 20 to 30% by weight of Raney nickel starting from 0.1 mol of nitrile. The disadvantage of the process is that the catalyst dissolves slowly and thus deactivates in the reaction mixture, so that the catalyst / nitrile ratio must be increased above 50% by weight.

Conversion of the nitrile group to the aldehyde group can be accomplished in a 70: 85% yield, depending on the molecular structure, of a 1: 1: 2 by volume mixture of acetic acid pyridine with 3040% by weight Raney nickel catalyst and 200% by weight sodium hypophosphite. “C-on [J. Chem. Soc., 3961 (1962)]. The disadvantage of this process is that large amounts of phosphorus-containing waste water are produced.

No. 71.17767. s. According to the published Japanese Patent Publication No. 6,198, some organic nitriles can be quantitatively converted to aldehyde at room temperature in a solvent mixture of Raney-nickel catalyst in a solution of water-acetic acid-pyridine in the presence of SnCl ₄ . In our experience, the process is not reproducible: SnCl _{4 is} hydrolyzed in the specified solvent mixture and the catalyst is deactivated.

According to the German Patent No. 43,047 (1966), cyanopyridines can be converted into nicotinaldehydes with Raney nickel in aqueous medium in the presence of CO2. The disadvantage of the process is that the reduction is quite slow: for example, 3-cyanopyridine can be converted to nicotinaldehyde in only 8 hours at a total pressure of 20 bar in a yield of 72%.

Some nitriles can be hydrogenated in good yields (65-70%) to the corresponding aldehydes using Pd (OH) 2 / BaSO _{4 as a} catalyst in 0.5 M hydrochloric acid (Liebigs Annalen der Chemie, 600, 115 and 126 (1956); Angew. Chem., 6S, 60 (1957)], but in our experience many nitriles have very low yields below 10%.

Conversion of nitriles to aldehydes can be accomplished with Raney nickel catalyst or the undissolved Raney alloy itself in a solution of formic acid without the use of hydrogen gas. [J. Chem. Soc. 5880 (1964); J. Chem. Soc., 5775 (1965); No. 159,899 The conversion to the aldehyde is generally above 40%, depending on the reaction conditions and the structure of the molecule. The disadvantage of the process is that it is very high in relation to nitrile. 100-150% by weight of Raney nickel, respectively. Raney alloy is required for full conversion.

The present invention is based on the discovery that when hydrogenating a nitrile group of an organic compound to an aldehyde group using a Raney nickel catalyst in a polar solvent, an acid and a mixture of lead, cadmium, iron, mercury, arsenic, zinc, antimony, or in the presence of a bismuth salt promoter, the aldehyde production can be significantly increased compared to the reduction with the un-promoted catalyst.

According to the present invention, a compound of formula (I) wherein R is a C 1 -C 14 alkyl group optionally substituted with a C 1 -C 4 alkoxy group, a C 2 -C 6 alkenyl group, a phenyl group optionally having one or more substituents. halogen, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or phenoxy substituents for the conversion of the nitrile group of phenyl (C 1 -C ₄ alkyl) or naphthyl groups with Raney nickel catalyst in the presence of an acid, hydrogenation in a polar solvent at a temperature between 0 ° C and the reflux temperature of the solvent such that the reaction is carried out in an amount of 0.01 to 3% by weight of the lead, cadmium, iron, mercury, arsenic, zinc, antimony, bismuth salt or oxide promoter. by adding 0.5% by weight of hydrogen to 4.10 to ⁶ Pa, addition of 0.5 to 5 equivalents of acid and 1 to 25% by weight of Raney nickel with respect to the nitrile. After completion of the reaction, the catalyst is filtered off and the reaction is worked up.

It has been found that the same good results are obtained either by adding the promoter metal salt to the reaction mixture before hydrogenation or by dissolving it separately in the catalyst in a polar solvent, and after mixing, adding the promoted catalyst suspension, with or without decantation. As promoters of lead, cadmium, iron, mercury, arsenic, zinc, antimony or bismuth salts, it is desirable to select a salt which is at least partially soluble in the polar solvent used for hydrogenation. Good results can be obtained with the promoter metal salts of both inorganic acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, perchloric acid, and organic acids such as formic acid, acetic acid, tartaric acid, but using the promoter metal oxide or the promoter itself. metal, if the corresponding metal salt is formed in the hydrogenation reaction by the presence of an acid therein. The amount of metal salt of the promoter is 0.005 to 3.0% by weight, preferably 0.02 to 0.2% by weight, relative to the nitrile.

The Raney nickel can be added directly to the reaction mixture, either wet or rinsed with hydrogenation solvent or water before use. the solvent containing a metal salt of the promoter. The amount of Raney nickel in the organic compounds containing the nitrile group is 145% by weight, preferably 5-15% by weight.

The hydrogenation reaction mixture contains an inorganic acid such as hydrochloric acid, sulfuric acid, or organic acid such as p-toluenesulfonic acid, acetic acid in an amount of 0.5-5.0 equivalents relative to nitrile, preferably 0.8-1.3 equivalents.

Polar solvents include alcohols (methanol, ethanol, propanol, i-propanol, cyclohexanol, benzyl alcohol, etc.) or alcohol and other alcohol-miscible polar solvents or solvents (e.g. water, acetic acid, propionic acid, triethylamine, quinoline, ethyl diisopropylamine, ethyl acetate, butyl acetate, amyl acetate, dioxane, dimethylformamide, formamide).

The main advantages of the process according to the invention are:

- higher production than comparable known processes can be achieved,

- the reaction may be carried out under mild conditions in a standard apparatus,

- the promoted catalyst can be formed very simply in the reaction mixture itself,

- with significantly less catalyst content than previously known, below 10% by weight of nitrile, the reaction is sufficiently rapid, the nitrile reacts within a few hours,

- insolubility or deactivation of the promoted catalyst during hydrogenation is insignificant,

- the promoted Raney nickel catalyst is no longer pyrophoric by the end of the reaction, and its filtration is safe.

The following examples illustrate the process of the invention without limiting it.

Example 2 (50 g of 3,4,5-trimethoxybenzonitrile, 0.2 g of iron sulfate, 200 cm ^{3 of} ethanol, 15 cm ^{3 of} 96% sulfuric acid and 3.0 g of Raney nickel are charged into a dm ³ autoclave. After reduction with hydrogen, rinsing with stirring at 55-60 ° C and a total pressure of ^{5 to} 10 bar, the total reaction time of the nitrile is about 3.5 hours. The hydrogen consumption is 5000 cm ³ (stoichiometric The reaction mixture is cooled, filtered, acidified with 42 cm ^{3 of} 10% hydrochloric acid and stirred for half an hour, 300 cm ^{3 of} water are added and the mixture is extracted with 200 cm ^{3 of} CCU in several portions. Yield: 0 g (94.6%) of 3,4,5-trimethoxybenzaldehyde, m.p. 74-75 ° C, purity 98.7% by gas chromatography.

40 ml of benzonitrile, 300 cm ^{3 of} methanol, 24 cm ^{3 of} 96% sulfuric acid, 39 mg of cadmium acetate and 2.0 g of wet Raney nickel catalyst were charged into a pellet dm 2 flask. The flask was purged with hydrogen and magnetic stirring was started. The reduction from 23 to 27 ° C, 10 torr to about ^5. Finishes in 4 hours. Hydrogen consumption was 9000 cm ³ . The catalyst was filtered off, and the filtrate was heated with 5 cm ^{3 of} 35% hydrochloric acid and 25 cm ^{3 of} water to 60 ° C, and after cooling to 20 ° C, extracted with dichloromethane. Gas chromatography showed 99.6% conversion of benzonitrile and 92.4% yield of benzaldehyde. The product has a boiling point of 177-178 ° C and an oxime melting point of 31-32 ° C at atmospheric pressure.

Repeating the reaction as described above but without the addition of a cadmium acetate promoter, the yield at the 99.4% conversion was only 78.8%.

EXAMPLE 3 (50 g of 3,4,5-trimethoxybenzonitrile, 12 mg of HgCl 2, 200 cm ^{3 of} methanol and 18 cm ^{3 of} 96% sulfuric acid were weighed into a da dm ³ flask. 4.5 g of Raney- nickel is suspended in 50 cm ^{3 of} i-propanol, the solvent is decanted after 5 minutes and the catalyst suspension is washed with 25 cm ^{3 of} i-propanol, and after stirring with hydrogen, the reaction time is 4.7 at 20-24 ° C. h.

After working up the reaction mixture as in Example 2, the yield of 3,4,5-trimethoxybenzaldehyde was 48.3 g (95.1%). The product has a melting point of 73-75 ° C and a purity of 98.4% by gas chromatography.

EXAMPLE 4 40 g of o-toluene nitrile, 165 cm ^{3 of} methanol, 28 cm ^{3 of} water, 60 cm ^{3 of} 99% acetic acid, 0.82 g of iron sulfate and 5 g of Raney nickel were charged into a dm ³ autoclave. After purging with hydrogen, the reduction was continued with stirring at 78-81 ° C and 4 to ⁵ bar ( ⁵ Pa) until the nitrile was consumed (about 3 hours). After cooling and filtration, the filtrate was determined by gas chromatography to yield 98.8% 2-methylbenzaldehyde and 98.9% toluene nitrile conversion. The product boils in a fractional distillation of 198-200 ° C and a density of 1.039 g / cm.

Example 5

Into a 200 cm ³ hydrogenation flask were added 4.1 g of B-ethoxypropionitrile, 25 cm ^{3 of} methanol and 2.5 cm ^{3 of} 96% sulfuric acid. 0.3 g of wet Raney nickel was suspended in 10 cm ^{3 of} methanol containing 10 mg of zinc sulphate and washed with 10 cm ^{3 of} methanol after settling and decanting. After rinsing with hydrogen, stirring is started; the temperature is 22-24 ° C and the pressure is 1.110 ⁵ Pa. After about 3 hours the nitrile reduction is complete. After filtration of the catalyst, the aliquot of the mixture was determined by precipitation with 2,4-dinitrophenylhydrazine (Voger, AI: Textbook of Practical Organic Chemistry, 3rd ed., Longmans, London, 1954) to determine β-ethoxypropionaldehyde. yield 77.2%. The reaction mixture was worked up by boiling the product (distilled under argon) at 125-128 ° C.

Example 6

All proceed as in Example 5 but solvent3

202178 Β is replaced by methanol: propionic acid = 10: 1, 33 cm ^{3 by} volume, instead of methanol. The β-ethoxypropionaldehyde yield is 75.9%. Mp = 125-128 ° C (distilled under argon).

Example 7

The experiment was carried out as in Example 5, but the reduction was carried out at 1-3 ° C instead of 22-24 ° C, yield 78.5%. Mp = 125-128 ° C (distilled under argon).

Example 8

By carrying out the experiment as in Example 5, but employing other nitriles instead of δ-ethoxypropionitrile or a different metal salt of the promoter instead of zinc sulfate, the following results were obtained:

Nitrile (g) Promoter (mg) aldehyde Production % boiling point 'C Density (g / cm) Op. 'C propionitrile (2,3) lead acetate (25) propionaldehyde 78.2 46-50 0.805 acrylonitrile (2,2) cadmium acetate (15) propionaldehyde 75.6 46-50 0.805 benzocyanide (4,9) ferrous sulphate (130) phenylacetaldehyde 87.4 195 1,027 p-methoxybenzonitrile (4,5) lead nitrate (32) p-metoxibenz- aldehyde 94.3 248 1,119 3,4-Dichlorobenzonitrile (7,1) antimony tri chloride (21) 3,4-dichloro benzaldehyde 92.0 41-42 3,4 benzonltril (6.7) mercury chloride (4) 3,4-dimethoxy- benzaldehyde 95.7 281 42-44

Example 9

Into a 200-cm hydrogenation flask were charged 8 g of 3,4,5-trimethoxybenzonitrile, 60 cm ^{3 of} methanol, 2.4 cm ^{3 of} 96% sulfuric acid, 6 mg of As 2 R 3 and 0.6 g of

Raney nickel. After purging with hydrogen, stirring was started at 22-24 'Con and atmospheric pressure. After complete reaction of the nitrile with the product of Example 2, the yield of 3,4,5-trimethoxybenzaldehyde was 93.9%. M.p. 73-75 ° C. 45

Example 10

11.5 g of acrylonitrile, 150 cm ^{3 of} propanol and 12 cm ^{3 of} 96% sulfuric acid are weighed into a 500 cm ³ hydrogenation flask. Iron sulfate (0.2 g) was dissolved in methanol (40 cm @ 2) and 2 g of wet Raney nickel catalyst was suspended in this solution and the suspension was poured into a hydrogenation flask. After purging with hydrogen, from 45 to 50 ° C and 1,1.10 ⁵ Pa pressure by stirring the nitrile total elreagá- 55 LASA. The product was worked up as in Example 5, yielding 66.9% propionaldehyde. During the fractional distillation of the reaction mixture, the product boils at 48-50 ° C.

Example 11

The experiment was carried out as in Example 10, but using 21 cm ^{3 of} 35 wt% hydrochloric acid and 0.2 g of zinc bromide instead of sulfuric acid, yielding 64.7% of propionaldehyde. Mp: 48-50 ° C.

Example 12

When carried out as in Example 10 but using 52 mg bismuth nitrate instead of copper sulfate, the propionaldehyde yield was 68.2%. Mp: 48-50 ° C.

Example 13

In the same manner as in Example 10, but using 100 cm ^{3 of} i-propanol and 50 cm ^{3 of} ethanol as the solvent instead of propanol, the yield of propionaldehyde is 74.6%. Mp .: 48-50 ° C.

Example 14

By carrying out the experiment according to Example 2, but using another nitrile instead of trimethoxybenzonitrile, the following yields were obtained:

-4HU 202178Β

Nitrile (g) Aldehydes (g) Production (%) Op. (° C) Density (g / cm) boiling point (° C) o-Methoxybenzonitrile (35.0) o-Methoxybenzaldehyde (32,7) 91.3 37-39 238 p-Chlorobenzonitrile (36,0) p-chloro-benzal- formaldehyde (34.4) 93.6 47-50 213-214 3,4-Dimethoxybenzonitrile (42,0) 3,4-Dimethoxybenzaldehyde (39,5) 92.3 42-44 281 a nitrogen-caproic acrylonitrile (25.0) kapronaldehid (21.9) 85.1 0.834 131 p-phenoxybenzonitrile (51.0) p-Phenoxybenzaldehyde (46,5) 89.7 24-25 1,132 3-hydroxy-benzo pentanenitrile (31.0) 3-Hydroxybenzaldehyde (27.5) 86.5 103-105 laurilnitril (47.0) laurü aldehyde (39.8) 83.4 0.835 2-naphtho-nitrile (40.0) 2-naphthaldehyde (36.8) 90.2 59-62

Example 15

The experiment was carried out as in Example 10, but using 100 cm ^{3 of} cyclohexanol instead of propanol; propionaldehyde yield 74.1%. MP: 4850 ° C.

carpets, 10 cm acetic acid. 0.25 g of Raney nickel catalyst and 5 mg of antimony trioxide. After rinsing with hydrogen, stirring is started; the temperature is 2830 'C and the pressure is 1.05 bar. After complete reaction of the nitrile, the reaction mixture was worked up as in Example 5. The propionaldehyde yield was 74.1%. Fp .: Example 4616 35

In the same manner as in Example 4, but using 52 cm ^{3 of} 85% formic acid instead of acetic acid, the yield of 2-methylbenzaldehyde was 89.1%. Mp .: 198-200 ° C.

Example 17

The experiment was carried out as in Example 4 but instead of acetic acid, 50 g of p-toluenesulfonic acid in a solvent of 300 cm ³ of methanol and 200 cm ³ of water applied, the production of 2-methyl-benzaldehyde 85.7%. Fp .: 198-200 45 'C.

50'C.

Example 21

In the same manner as in Example 20, but using 0.5 cm ^{3 of} ethyl diisopropylamine instead of ethyl acetate, the propionaldehyde yield was 78.1%. MP: 4650'C.

Example 18

In the same manner as in Example 5, but using 20 cm ^{3 of} ethanol and 5 cm ^{3 of} dimethylformamide instead of methanol, the yield of β-ethoxypropionaldehyde was 79.0%. Mp: 126-128 ° C (distilled under argon).

Example 19 55

The experiment was carried out as in Example 9, but using ethanol: i-propanol: triethylamine = 17: 3: 1 by volume instead of methanol and having a total volume of 70 cm ³ and 5.6 cm ^{3 of} sulfuric acid instead of 2.4 cm ³ , the yield of 3,4,5-trimethoxybenzaldehyde is 90.2%. M.p .: 60

73-75 'C.

Example 20

200 cm ³ and a hydrogenation flask was added 2.2 g of acrylonitrile, 20 cm ³ of methanol, 2 cm ³ of ethyl ACE 65

Claims (1)

Patent Claim Point A process for preparing a compound of formula (I) wherein R is C 1 -C 14 alkyl optionally substituted with C 1 -C 4 alkoxy, C 2 -C 6 alkenyl, phenyl optionally substituted with one or more halo. , hydroxy, (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy or phenoxy substituent for the conversion of the nitrile group of phenyl (C 1 -C 4 alkyl) or naphthyl groups with an Raney nickel catalyst in the presence of an acid, in a polar solvent by hydrogenation at a temperature between 0 ° C and the boiling point of the solvent, wherein the reaction is carried out in an amount of 0.01 to 3% by weight of the lead, cadmium, iron, mercury, arsenic, zinc, antimony, bismuth hydrogen pressure relative% of the amount of addition to 4.10 ⁶ Pa, the nitrile is carried out in from 0.5 to 5 equivalents of acid and 1 to 25 wt% addition of Raney nickel, the total reduction pentanenitrile ut n the catalyst is filtered off and worked up.