DE2731259A1 - PROCESS FOR THE MANUFACTURING OF SUBSTITUTED BENZALDEHYDE - Google Patents

Description

Process for the preparation of substituted benzaldehydes

It is known that in the o-position an electron-attracting Benzaldehydes containing substituents are extremely difficult to access.

Although o-nitrobenzaldehyde, for example, has been around for a long time belongs to the known substances and was technically produced, an advantageous synthesis for Establishing this connection. In general, for example, o-nitrobenzaldehyde is referred to as difficult to access, and numerous existing patents such as German Patent No. 48722 (1889) or Japanese Patent No. 307097 (1959) and publications such as H. Cassebaum, J. Prakt. Chemie, 4th series, Vol. 29, 1965, with however The production of this aldehyde is the subject of very imperfect information. Also those in Org. Synth., Coil. Vol. III, 641, described method gives the aldehyde in a modest overall yield of 18% starting from o-nitrotoluene.

The invention relates to a process for the preparation of benzaldehydes which have an electron-attracting position in the o-position The radical R contains using appropriately substituted o-toluene compounds as starting material. A electron-attracting substituent R is in particular the nitro group, also the cyano group or a halogen atom, such as

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e.g. chlorine, bromine, iodine or fluorine.

The inventive method consists in that one an o-substituted compound of the formula I,

(D

in which R means an electron-withdrawing substituent, under irradiation with visible light (range: 3800-8000 A), such as the light of a tungsten lamp (light bulb), in an inert solvent, especially in the presence of a halogenated one Hydrocarbons, such as carbon tetrachloride or hexachloroethane, in high yield to a mixture of Mono- and dibromides of the formulas II and III

(II) or I Il * (III)

The mixture of II and III obtained brominates with treatment with an alkali metal formate, especially sodium formate, in an inert solvent, preferably in dimethyl sulfoxide, into a mixture of one in the o-position by an electron-attracting one Group substituted benzaldehyde and the formic acid ester of the benzyl alcohol correspondingly substituted in the o-position of formulas IV and V

st ^ s CH ₀ OCHO (IV) or Γ IJ ^l (V)

Transferred, and the mixture of IV and V in high yield Hydrolysis and subsequent oxidation of component V with hydrous nitric acid uniformly to the substituted one converts o-benzaldehyde of the formula IV.

The invention relates to a sequence of process steps that consist of a uniform starting product, one by one electron-withdrawing group in the o-position substituted toluene compound, via mixtures of intermediates to one

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leads to a uniform end product. The by John R. Sampey et al., J. Am. Chem. Soc, j> 2, 1839 (1940) o-nitrotoluene with bromine under irradiation with visible light leads to an extremely low yield of bromination of the side chain. A. Cassebaum, Zschr.f. Chemistry, Ji, 340 (1969), uses catalytic UV irradiation for the side chain bromination, with a relatively modest yield, for example o-Nitrobenzyl bromide and a relatively large amount of unreacted o-nitrotoluene can be obtained. Surprisingly the side chain bromination according to the present invention leads to a high conversion and excellent yield Mixture of a benzyl bromide appropriately substituted in the o-position and benzal bromide. The resulting mixture of the two bromides can be converted into a mixture of one in the o-position convert substituted benzaldehyde and the formic acid ester of the correspondingly substituted benzyl alcohol, with under the reaction conditions, the benzaldehyde substituted in the o-position is formed directly from the dibromide. Used instead of of the alkali metal formate, e.g. sodium acetate, the result is not the correspondingly substituted benzaldehyde, but the diacetate of the corresponding benzaldehyde. Without separation, the o-substituted benzyl formate present in the mixture obtained becomes hydrolyzed and oxidized, so that the one in the o-position as a single end product is created by an electron-attracting radical substituted benzaldehyde is formed.

The small amount of the substituted toluene not reacted in the process steps described can after Separation can in turn be re-used. On the other hand, complete bromination to the benzyl-benzal bromide mixture can be achieved if the bromination is extended for an extended period of time, up to about 14 hours.

Side-chain bromination is allowed among the process steps described des o-nitrotoluene are particularly emphasized, since these according to John R. Sampey et al., J. Am. Chem. Soc,

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62 , 1839 (1940), has been described as difficult to execute in the visible light range. The method described by H. Cassebaum, Zschr. F. Chemie, 340 (1969), leads to the formation of a dibromide of the side chain with low conversion and partial nuclear bromination when exposed to light in the UV range. It has now been found that mono- or dibromides of o-nitrotoluene obtained, for example, decompose in the UV range, ie are photolabile, which prevents a high yield.

The bromination described according to the invention takes place with elemental bromine under irradiation with visible light in an inert solvent, especially in the presence of a halogenated one Hydrocarbons, such as carbon tetrachloride or hexachloroethane, and at elevated temperatures, e.g. Reflux temperature of the reaction mixture.

The reaction of the resulting mixture of the mono- and dibromo compounds of the formulas II or III with an alkali metal formate, in particular sodium formate, is also carried out in an inert solvent, in particular dimethyl sulfoxide Dimethylformamide or hexamethylphosphoric triamide, at one

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Temperature between 20 ° to 1OO ° C, but especially at a temperature of 80 ° to 90 ⁰ C.

The hydrolysis and subsequent oxidation of the resulting mixture of benzaldehyde substituted in the o-position and the formate of the correspondingly substituted benzyl alcohol is carried out using water-containing nitric acid at a temperature between 20 ° and 60 ° C, but preferably at a slightly elevated temperature of 35 ° to 40 ^° C. A nitric acid of higher concentration is used, for example about 50% to about 75%, preferably one with a density of about 1.5 (65%).

However, there is also the possibility of direct hydrolysis of the o-position by an electron-attracting radical substituted benzal chloride. According to the present process, it is definitely possible to control the bromination in such a way that that predominantly benzal bromide is formed.

Kliegel, Ber., Vol. 40, p.4939 (1907) provides, for example, o-nitrobenzaldehyde from the corresponding o-nitrobenzal chloride by acid hydrolysis with concentrated sulfuric acid, wherein however, it also only receives a yield of about 40% of contaminated o-nitrobenzaldehyde.

One stage of the invention thus relates to a particularly advantageous hydrolysis of benzal bromide substituted in the o-position, by making a compound of the formula

-CHBr,
ΙΪ

hydrolyzed with aqueous nitric acid. The hydrolysis is usually carried out in higher concentration aqueous nitric acid carried out, using about 50 to about 807oiger nitric acid, preferably nitric acid with a density of about 1.5 (about 65%) is used. The aqueous nitric acid serves at the same time as a solvent or diluent, i.e. the reaction takes place in the absence of an additional solvent or diluent

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carried out. The hydrolysis is carried out at a temperature of about 10 ⁰ C to about 100 ⁰ C, preferably at a temperature of about 60 ° C to about 90 ⁰ C.

Running parallel to the above hydrolysis, the invention includes a further hydrolysis possibility in that the hydrolysis is carried out in aqueous medium in the presence of a phase transfer catalyst or a crown ether, an inorganic base and / or a carboxylate.

The phase transfer catalyst used here is predominantly quaternary ammonium salts, for example tetra-lower alkylammonium salts, in particular corresponding halides, such as tetra-n-butylammonium chloride or bromide, or aryl-lower alkyltrin-lower alkylammonium salts, in particular corresponding halides, e.g. benzyltriethylammonium chloride.

Crown ethers that can be used instead of the phase transfer catalysts are cyclic polyalkylene, in particular Polyethylene ethers, which can contain further substituents, including fused-on aromatic rings and which have complexing properties, especially for cations, such as for metallic cations, e.g. potassium ions. In this context, reference is made to the publication by Gokel and Durst, Principles and Synthetic Applications in Crown Ether Chemistry in the journal Synthesis, Vol. 1976, p. 168. Cyclic polyethylene ethers are particularly preferred with 12 to 21 ring members, of which 5 to 7 are oxygen atoms, like the crown [15.5] ether and primarily the crown [18.6] ether.

Inorganic bases are understood to mean, in particular, metallic bases, such as alkali metal or alkaline earth metal bases, in particular the corresponding hydroxides, hydrogen carbonates and carbonates. So you can start the reaction in the presence of sodium or Potassium hydroxide j Sodium or potassium hydrogen carbonate or Perform sodium or potassium carbonate. In an analogous manner, the corresponding hydroxides, hydrogen carbonates and

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Carbonates of calcium and magnesium can be used.

With a carboxylate is in the presence of a phase transfer catalyst or a crown ether obtained primarily an acylal of the benzaldehyde substituted in the o-position, which solvolyzed to the free o-substituted benzaldehyde.

Carboxylate is understood to mean the salt of an organic carboxylic acid, the salts primarily being metal, such as Alkali metal or alkaline earth metal salts, also ammonium salts of such acids, in particular of corresponding aliphatic, also aromatic carboxylic acids, such as lower alkanecarboxylic acids, E.g. formic or propionic acid, primarily acetic acid, as well as benzoic acid come into question. Alkali metal, such as sodium or potassium, and also calcium lower alkanoates with 2 to 4 carbon atoms are preferably used, in particular the corresponding acetates and primarily sodium or potassium acetate, including salts the formic acid or these themselves act reductively and the resulting aldehyde partly to the corresponding benzyl alcohol can reduce.

The reaction in the presence of a phase transfer catalyst is usually carried out in a two-phase system, which consists of an aqueous and an organic phase, the latter also consisting of the low-melting reaction substrates, e.g. o-nitrobenzal bromide (m.p. 46 ° C) alone or together with an additional organic solvent such as a suitable one Hydrocarbon such as toluene can be formed.

The amounts of the carboxylate and phase transfer catalyst compounds to be used according to the invention can be considerable vary. If a base is added to the reaction mixture to neutralize the acid formed and this thereby is converted back into the carboxylate compound, could theoretical catalytic amounts, i.e. less than equimolar amounts, e.g., from about 1 mole percent to about 50 mole percent (based on the starting material) both the carboxylate, as

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also use the phase transfer connection. The latter are usually given in catalytic amounts, e.g. of about 1 Mol percent to about 30 mol percent (based on the starting material), with equimolar amounts or an excess of the phase transfer catalyst can be used. The carboxylate compound will usually be about equimolar Amounts, if appropriate in a deficit, and preferably in an excess.

To neutralize the acid corresponding to the carboxylate reagent, which, if in the preferred aqueous medium is worked, is formed in the hydrolysis of the acylal intermediate, and to accelerate this hydrolysis can be a Base are added. Inorganic bases are usually used, such as corresponding metallic bases, e.g. alkali metal or Alkaline earth metal bases, in particular the corresponding hydroxides, hydrogen carbonates or preferably carbonates, such as Sodium or potassium hydroxide or hydrogen carbonate, and preferably Potassium or primarily sodium carbonate. The corresponding hydroxides and hydrogen carbonates can be used in an analogous manner or carbonates of calcium and magnesium are used, calcium carbonate as the sparingly soluble base may optionally be preferred. Preferably a readily soluble base, such as an alkali metal carbonate, e.g. sodium carbonate, in the course of the reaction, usually added in portions. If necessary, this is the reaction mixture temporarily cooled before adding the base, e.g. by at Use of a carbonate or hydrogen carbonate foaming to prevent. A sparingly soluble base, e.g. calcium carbonate, can, however, also be present in the reaction mixture from the start are present.

If the reaction substrate forms the organic phase of the two-phase transfer system in the molten state, the reaction in the presence of the phase transfer catalyst is preferably carried out at a temperature above 40 ° C, e.g.

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a temperature of about 45 ° C to about 16O ° C, preferably from about 8O ⁰ C to about 130 ° C, usually under normal pressure, if necessary under increased pressure, for example in a bomb tube or autoclave and / or under an inert gas atmosphere, for example nitrogen or argon.

If the hydrolysis is carried out by means of crown ethers, then these are usually used in catalytic amounts, e.g. in amounts from about 1 mol percent to about 30 mol percent (based on the starting material) at about equimolar, optionally below or excess amounts of the carboxylate, preferably one Potassium carboxylate, such as potassium acetate, in an anhydrous or aqueous medium. Inert ones are used, preferably non-polar organic solvents or a mixture of such solvents as benzene or primarily acetonitrile if necessary with water. Usually one works at elevated temperatures, e.g. at temperatures of about 50 ° C up to about 130 ° C, e.g. at the boiling point of the reaction mixture, if necessary in a closed vessel and / or in an inert gas atmosphere.

If the hydrolysis is carried out solely by means of an inorganic base, then when using easily soluble inorganic Bases, for example an alkali metal base, preferably in a pH range from about 7.5 to about 11, and in the presence of a sparingly soluble base, for example an alkaline earth carbonate, such as calcium carbonate, worked in a pH range below 7.5; the pH value decreases depending on the solubility of the alkaline earth carbonates used during the reaction down to about 4.

If desired, in the phase transfer catalytic reaction in the presence or absence of additional reagents, such as an emulsifier, for example a nonionic, surface-active polyoxyalkylene sorbitan ester, e.g. polyoxy-

(r)

Ethylene sorbitan monolaureate (TWEEN ^ 20) and / or one ionic reagent such as an alkali metal salt, in particular

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-halides, e.g. sodium bromide, are used.

In the process modifications described above The use of carboxylate produces a diacylal of o-substituted benzaldehyde as an intermediate, in particular that o-substituted benzaldiacetate formed when using a preferred acetate, whereby under anhydrous, i.e. not hydrolytic reaction conditions, larger amounts of the diacylal compound arise. This can be done in a simple manner and converted into the o-substituted benzaldehyde in good yields by solvolysis, in particular by hydrolysis will; under the appropriate conditions, the formation of the free aldehyde takes place in the reaction medium. The hydrolysis of a according to the invention obtainable diacylal compound des O-substituted benzaldehyde to the free o-substituted benzaldehyde can be acidic, neutral or preferably weakly alkaline conditions, e.g. in the presence of one of the above-mentioned inorganic bases, such as sodium carbonate or Calcium carbonate.

A preferred form of the present invention relates to the reaction of o-nitrobenzal bromide with an alkali metal, e.g. sodium acetate, in the presence of a catalytic amount of a tetra-lower alkyl ammonium halide, e.g. tetra-n-butylammonium bromide, and in an aqueous medium at a temperature of about 80 ° to about 120 ° C, wherein by adding a Base, in particular an alkali metal or alkaline earth metal carbonate, e.g. sodium or calcium carbonate, the reaction mixture is kept in a pH range from about 6 to about 11 will.

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Compared to the closest prior art, i.e. compared to that of K. Liegl, Ber., Vol. 40, 4939 (1907), described process, you get the o-substituted benzaldehyde by the new process in high yield and without substantial impurities.

For example, o-nitrobenzaldehyde can be

for the indigo synthesis according to A. v. Use Baeyer. It finds also used as a diagnostic aid in medicine, for example in diabetes. The correspondingly producible o-cyanobenzaldehyde can be used as an intermediate product for the production of coronary and peripheral dilatation effective, antihypertensive pharmaceuticals (cf. DOS 19 63 188) and as starting material for the production of pharmaceutical syntheses important o-cyaninnamic acids are used. Furthermore, for example, o-cyanobenzaldehyde is used as a stabilizing agent Additive to methyl chloroform (cf. US Pat. No. 3,364,270) and as an additive to fibers containing polyvinyl alcohol for Improvement of the elasticity and dyeability (cf. US patent 3,071,429) used.

In the following examples, the parts are parts by weight and the temperatures are given in degrees Celsius.

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- Vf-

example 1

a) bromination

41.1 g of OTNitrotoluene dissolved in 500 ml of carbon tetrachloride are heated to reflux in the sulphonation flask, the daylight lamp (200 W) switched on, and the solution of 57.6 g of bromine (18.3 ml, D = 3.14) in 50 ml of carbon tetrachloride was added > ff added dropwise in portions of approx. 5 ml. As the portions are added, each waited until the reaction solution has been decolorized again. (The first serving takes about 30 minutes.) While the reaction gives off gaseous hydrobromic acid through the condenser and a very small amount of bromine. After 10 hours, the reaction has ended and the solution is allowed to cool, with it becomes slightly cloudy and is therefore filtered through a sintered funnel. (Insoluble material weighs 0.35 g and consists of a Mixture of unknown acids.) The solvent is stripped off in a rotary evaporator, whereby after renewed concentration from a little carbon tetrachloride a light yellow oil remains, which solidifies in the refrigerator; 68.7 g. Results from the KMR ^ spectrum of a sample The product has the following molar composition: 54% o-nitrobenzyl bromide, 33% o-nitrobenzal bromide and 12.5% o-nitrotoluene (Starting material). The mixture is referred to as A in the further description.

b) formate reaction

38.0 g of mixture A, dissolved in 200 ml of dimethyl sulfoxide, are mixed with 13.7 g of sodium formate (202 mM) and the suspension in a nitrogen atmosphere to 85-90 ° C (internal temperature) warmed up. After 4 hours it is cooled and poured into 1000 ml of ice water poured. The pH is adjusted to 2 by adding 30 ml of 2N hydrochloric acid and the mixture is extracted twice with 300 ml of ethyl acetate each time. the combined extracts are washed thoroughly with water, with 30 ml shaken saturated sodium bicarbonate solution and finally

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washed again. After drying over magnesium sulfate and distilling off the solvent in vacuo, 27.5 g of yellow oil, a mixture of o-nitrobenzaldehyde and o-nitrobenzyl alcohol formate, are obtained, which will be referred to as B in further processing.
c) hydrolysis

To 50 ml of nitric acid (65%, D = I.40, 27.3 g of mixture B are added dropwise with stirring in a nitrogen atmosphere. Two to three minutes after the addition (which takes 10 minutes) the clear solution warms up gradually with the formation of nitrous gases. The reaction flask is cooled with an ice bath so that the internal temperature is between 35 ° C and 40 ° C. An oil soon begins to separate and the temperature gradually drops to room temperature (after removing the cold bath) Minutes' reaction time, 300 ml of ice water are poured into the flask, after which the crude product separates out in crystalline form. This is taken up in 200 ml of ethyl acetate (after adding a further 200 ml of water) and the aqueous-acidic phase is extracted again with 200 ml of ethyl acetate The layers are washed twice with 200 ml of water each time and extracted with 50 ml of saturated sodium bicarbonate solution Ren with hydrochloric acid 1.50 g of o-nitrobenzoic acid (corresponding to 5.4% of theory). The organic phase is washed again with water, dried over magnesium sulfate and concentrated in vacuo. This gives 22.7 g of light yellow oil which crystallizes on cooling and seeding, but still contains o-nitrotoluene. To determine the yield, the crude product is chromatographed on 200 g of silica gel with benzene. The yellow zone containing the product is eluted with benzene and the eluate is concentrated in vacuo. This gives 18.91 g of o-nitrobenzaldehyde. Melting point 41-43 ° C, corresponding to 76.1% d.'fh. based on o-nitrotoluene used. (Yield based on converted o-nitrotoluene: 87.0 % of theory)

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Examples of acid hydrolysis of o-substituted benzal bromides

Example 2

A mixture of 0.35 g of o-nitrobenzal bromide (1.18 mM) and 3.0 ml concentrated nitric acid (65%) is stirred for 3 hours in a nitrogen atmosphere at 78-80 °. After cooling it will Ice was added and the product which precipitated was taken up in ethyl acetate. The remaining aqueous phase is again extracted with ethyl acetate, and the combined organic solutions with aqueous sodium hydrogen carbonate solution and washed water. The solution, dried over magnesium sulfate, is concentrated under reduced pressure, yielding 0.149 g o-Nitrobenzaldehyde can be obtained in the crude state as a crystalline residue. The solution of the crude product in benzene is through a silica gel column prepared with 5 g of silica gel, filtered and the eluate evaporated under reduced pressure. This gives 0.133 g of pure o-nitrobenzaldehyde, mp 41 ° -43 °; Yield: 74% of theory

Example 3

A mixture of 0.5 g of o-nitrobenzal bromide (1.68 mM) and 0.5 ml 60% (weight / vol) nitric acid is used for 3-1 / 2 hours at 90 ° (Internal temperature) stirred. The cooled solution (the o-nitrobenzal bromide goes into solution in the course of 2-1 / 2 hours) is poured onto ice and the product which precipitates out in crystalline form is dissolved in ethyl acetate taken up, and the aqueous phase washed with ethyl acetate. The combined organic solutions are washed neutral and dried over magnesium sulfate. The crystalline, brown-colored crude product that after evaporation of the solvent is obtained under reduced pressure (0.177 g), yields after chromatographic purification

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o-nitrobenzaldehyde in a benzene solution using a silica gel column, F 41-43 °; Yield: 0.161 g = 63% of theory

Hydrolysis of the o-substituted benzal bromides by the phase transfer catalysis process.

Example 4

26.4 g of anhydrous sodium carbonate and 3.0 g of tetra-n-butylammonium chloride are slurried in 60 ml of water and heated to 100 ° in an argon atmosphere. Add 48.5 g o-nitrobenzal bromide and stirred for 7 hours at 100 °. After cooling off is diluted with water and extracted with 50 ml of ethyl acetate, then again with this solvent. the combined organic solutions are washed three times with water, dried over magnesium sulfate and reduced under reduced pressure Evaporated pressure. The oily residue is chromatographed on silica gel in benzene. 24.4 g of o-nitrobenzaldehyde are isolated as a raw product; Yield: 75% of theory

Example 5

A mixture of 20 ml of water, 1.0 g of tetra-n-butylammonium chloride, 1.0 g of the emulsifier "TVJEEN ® 20 SD", 4.4 g of sodium hydrogen carbonate and 5.9 g of o-nitrobenzal bromide are added in an argon atmosphere Heated to 140 ° in a bomb tube for 15 hours. After the usual work-up as in Example 4, 2.3 g of o-nitrobenzaldehyde are obtained (77% of theory)

Example 6

A mixture of 10 ml water, 2.95 g o-nitrobenzal bromide, 1.8 g sodium hydrogen carbonate, 0.5 g emulsifier "TWEEN (r) 20 SD" and 0.5 g of tetra-n-butylammonium hydrogen sulfate is as under Example 4 described implemented. 1.1 g of o-nitrobenzaldehyde (73% of theory) with a melting point of 43-45 ° are obtained.

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Example 7

The mixture of 0.3 g of o-nitrobenzal bromide (1.01 mM), 0.3 g Benzyltriethylammonium chloride (phase transfer catalyst), 5.0 g of sodium acetate and 5.0 ml of water is added in a nitrogen atmosphere for 4 hours in a flask fitted with a reflux condenser, a stirrer and a thermometer is provided, heated at 118 °. After that, after cooling, it is diluted with water and extracted with 50 ml of ethyl acetate, then washed with the same solvent. The united organic Solutions are washed with water three times, dried over magnesium sulfate and evaporated under reduced pressure. The oily residue is chromatographed on 2 g of silica gel (benzene). 0.128 g of crude product is obtained in the form of yellowish crystals. Obtained after chromatographic purification 0.123 g of o-nitrobenzaldehyde, melting point 41-42 ° (yield: 80% of theory).

Example 8

The mixture of 0.3 g of o-nitrobenzal bromide (1.01 mM), 0.15 g of benzyltriethylammonium chloride, 5.0 g of sodium acetate, 5.0 ml of water, 0.5 ml of toluene and 0.1 g of calcium carbonate are stirred for 6 hours at 115 ° in a nitrogen atmosphere. It is processed as in Example 7 given. 0.134 g of crude product is obtained in the form of yellow-brown crystals. Obtained after chromatographic purification 0.124 g of pure o-nitrobenzaldehyde, F. 41-42 ° (yield: 81% of theory).

Example 9

A mixture consisting of 1.00 g of o-nitrobenzal bromide (3.37 mM), 5.0 g of sodium acetate (62.5 mM), 5.0 ml of water and 0.20 g of tetran-butylammonium bromide (0.62 mM) is stirred for 4 hours in a bath at 130 ° in a nitrogen atmosphere, the Internal temperature does not exceed 117 °. The work-up takes place as described under Example 1 and provides 0.516 mg of crystalline material. The chromatographic

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Purification of the crude product obtained (silica gel 18 g, benzene) gives the following yields: 0.01 g of o-nitrobenzal bromide (1% of theory) 0.462 g of o-nitrobenzaldehyde (90.5% of theory), and 0.024 g of o-nitrobenzaldiacetate (2.8% of theory).

Example 10

A mixture of 5.00 g of o-nitrobenzal bromide, 5.0 g of Natriuj - acetate, 0.20 g of tetra-n-butylairinonium bromide and 5.0 ml of water is heated to reflux. After 15 minutes, 0.40 g of sodium carbonate are added, and the same again an hour later Amount: additional portions of 0.40 g each are added after a total of 7 and 10 hours. Four hours after the last addition of sodium carbonate (during this period so much water is added that the internal temperature does not rises above 117 °) as described in Example 1, worked up. The chromatographic analysis of the crude product (2.375 g) gives the following yields: 0.008 g of starting material, · 2.106 g of o-nitrobenzaldehyde (79% of theory); and 0.159 g of o-nitrobenzaldiacetate (3.7% of theory).

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Example 11

A mixture of 2 g of o-nitrobenzal bromide (6.75 m> l), 1.39 g anhydrous potassium acetate (14.15 niM) and 0.072 g of crowns {IS. 6] ether (0.27 mM) in 5 ml of acetonitrile is heated to boiling under reflux for 7 hours. The solvent is under removed under reduced pressure and the residue partitioned between water and ethyl acetate. The aqueous layer becomes extracted again with ethyl acetate; the combined organic phases are washed twice with water and Dried over magnesium sulfate. After concentrating under reduced The crude product (1.637 g of brown oil) is obtained under pressure, and the following after chromatographic purification Yields give: 0.606 g of starting material (30.3% of theory); 0.142 g of o-nitrobenzaldehyde (13.9% of theory), and 0.868 mg of o-nitrobenzaldiacetate (51.0% of theory)

To a solution of 1.0 g (4.25 mil) of o-nitrobenzaldiacetate in 15 ml of methanol is added 10 ml of water and 1 drop of phenolphthalein solution. Now 4.25 ml of a 2-n. aqueous sodium carbonate solution added; after 30 minutes the addition is complete and the solution is slightly red in color. Stirring is continued for 15 minutes, and A ₁ O mL of 2-n hydrochloric acid. Most of the methanol is drawn off under reduced pressure at about 40 °, the o-nitrobenzaldehyde initially separating out as an oily but later in crystalline form. The o-nitrobenzaldehyde is separated off by extracting twice with 50 ml of diethyl ether each time and obtained from the organic phase after washing with water and drying over magnesium sulfate by evaporating the solvent in the form of pale yellow crystals; Yield: 0.590 g (91% of theory)

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Claims (36)

Claims ί 1. J Process for the preparation of benzaldehydes which are substituted in the o-position by an electron-withdrawing group R, characterized in that a correspondingly substituted toluene compound of the formula I, (D in which R is a nitro group, a cyano group or a halogen atom means under irradiation with visible light to form a mixture of the mono- and dibromide of the formulas II and III (II) or I II * (III) brominated, the resulting mixture of II and III under treatment with an alkali metal formate in a. Mixture of one in o-position correspondingly substituted benzaldehyde and the formic acid ester of the corresponding benzyl alcohol Formulas IV and V ^> v ^ CH ₉ OCHO (IV) or LlT (V) Transferred, and the mixture of IV and V by hydrolysis and Subsequent oxidation of component V by treatment with hydrous nitric acid uniformly to the corresponding in converts o-substituted benzaldehyde of the formula IV. 2. The method according to claim 1, characterized in that the bromination of the toluene compound of the formula I in one inert solvent is run. 3. The method according to claims 1 and 2, characterized in that that the bromination of the toluene compound of the formula I is carried out in a halogenated hydrocarbon. 70988A / 0790 ORIGtNAL INSPECTED 4. The method according to claims 1 to 3, characterized in that that the bromination of the toluene compound of the formula I is carried out in carbon tetrachloride or hexachloroethane. 5. The method according to claim 1, characterized in that the bromination using a tungsten lamp as Light source of visible light is carried out. 6. A method according to claims 1 to 5, characterized in that the bromination is carried out at a temperature between 0 ° and 120 ⁰ C. 7. A method according to claims 1 to 6, characterized in that the bromination is carried out at a temperature between ⁰ and 90 C. 8. The method according to claim 1, characterized in that the resulting mixture of substituted benzyl bromide and benzal bromide by adding sodium formate all in one inert solvent into a mixture of the appropriately substituted benzaldehyde of the formula IV and the formic acid ester of the correspondingly substituted benzyl alcohol of the formula V converted. 9. The method according to claims 1 to 8, characterized in that that the resulting mixture of substituted benzyl bromide and benzal bromide by adding sodium formate in Dimethyl sulfoxide as a solvent in a mixture of substituted Benzaldehyde of the formula IV and the formic acid ester of the correspondingly substituted benzyl alcohol of the formula V transferred. 709884/0790 - -2T - 3 2 7 3 1 2 b 9 10. The method according to claim 1, characterized in that the hydrolysis and oxidation of the contained in the mixture Formates of the substituted benzyl alcohol of the formula V at a temperature between 20 ° and 60 ° C with higher nitric acid Concentration, such as about 50% to about 75% carries out. 11. The method according to claims 1 and IC, characterized in that that the hydrolysis and subsequent oxidation of the formate contained in the mixture of the substituted benzyl alcohol of formula V at a temperature of 35 ° to 40 ° C with nitric acid with a density of about 1.4 (65%). 12. A process for the preparation of o-nitrobenzaldehyde, thereby characterized in that o-nitrobenzal bromide is hydrolyzed in an aqueous medium in the presence of nitric acid to give o-nitrobenzaldehyde. 13. Process for the preparation of o-nitrobenzaldehyde, characterized in that o-nitrobenzal bromide is used in an aqueous medium hydrolyzed in the presence of a phase transfer catalyst and an inorganic base. 14. The method according to claim 13, characterized in that the hydrolysis is carried out in the presence of a quaternary ammonium salt and a metallic base. 15. The method according to claim 13 or 14, characterized in that that the hydrolysis is carried out in the presence of a tetra-lower alkyl ammonium salt and an alkali metal or alkaline earth metal base. 16. The method according to any one of claims 13 to 15, characterized characterized in that the hydrolysis is carried out in the presence of tetran-butylammonium chloride or bromide and an alkali metal or alkaline earth metal carbonate. 709884/079 0 Y 273125a 17. The method according to claim 13 or IA, characterized in that that the hydrolysis in the presence of Benzyltriethylammoniumchlorid or bromide and an alkali metal or Alkaline earth metal carbonates. 18. The method according to any one of claims 13 to 17, characterized characterized in that one works in the absence of an organic solvent at a temperature above 40 ° C. 19. Process for the preparation of o-nitrobenzaldehyde or a diacylal thereof, characterized in that one treated o-nitrobenzal bromide with a carboxylate in the presence of a phase transfer catalyst or a crown ether, and, if desired or necessary, a process obtainable acylal of o-nitrobenzaldehyde to the free o-nitrobenzaldehyde hydrolyzed. 20. The method according to claim 19, characterized in that men with an alkali, alkaline earth or ammonium salt organic acid in the presence of a quaternary ammonium salt as a phase transfer catalyst. 21. The method according to claim 19 or 20, characterized in that one with an alkali, alkaline earth metal or ammonium salt an aliphatic carboxylic acid such as a lower alkanecarboxylic acid or an aromatic carboxylic acid in the presence of a Tetra-lower alkylammonium salt or an aryl-lower-alkyltrin-lower-alkyl-ammonium salt as a phase transfer catalyst. 22. The method according to any one of claims 19 to 21, characterized characterized in that one with an alkali metal or alkaline earth metal acetate in the presence of tetra-n-butylammonium chloride or bromide as a phaoene transfer catalyst. 709884/0790 S "2731269 23. The method according to any one of claims 20 to 22, characterized characterized in that one works in the presence of an inorganic base. 24. The method according to claim 23, characterized in that in the presence of an alkali metal or alkaline earth metal hydroxide, bicarbonate or carbonate works. 25. The method according to any one of claims 20 to 24, characterized characterized in that one works in an aqueous medium. 26. The method according to any one of claims 20 to 25, characterized characterized in that one works at a temperature of about 45 ° C to about 160 ° C. 27. The method according to any one of claims 20 to 26, characterized characterized in that one works at a temperature of about 80 ° C to about 130 ° C. 28. The method according to claim 19, characterized in that one with an alkali, alkaline earth or ammonium salt of an organic Reacts carboxylic acid in the presence of a crown ether. 29. The method according to claim 19 or 28, characterized in that one with an alkali, alkaline earth or ammonium salt aliphatic carboxylic acid, such as a lower alkanecarboxylic acid, or an aromatic carboxylic acid as opposed to a crown ether implements. 30. The method according to any one of claims 19, 28 or 29, characterized characterized in that one reacts with an alkali or alkaline earth metal acetate in the presence of the crown [18.6] ether. 31. The method according to any one of claims 28 to 30, characterized in that that one works in an anhydrous or aqueous medium. 709884/0790 32. The method according to any one of claims 23 to 31, characterized in that at a temperature of about 50 ° C works up to about 130 ° C. 33. The method according to any one of claims 19 to 32, characterized characterized in that a diacylal of o-nitrobenzaldehyde obtainable according to the process is used under weakly alkaline Conditions hydrolyzed. 34. The procedure described in Examples 1-14. 35. Those obtainable by the process of claims 1 to 33 Links. 36. The compounds obtainable by the process of Examples 1-14. 3 7. The method according to any one of claims 1 to 33, characterized characterized in that o-nitrotoluene is used as the Avisgangsniaterial of the formula I. 709884/0790