DE2454355A1 - 2,5-DI-LOW-ALKOXYBENZYLAMINE, 2,5-DIHYDROXY-BENZYLAMINE AND METHOD FOR PRODUCING THEREOF - Google Patents

Description

PATENT ANWXLTE

DR. E. WIFGAND DIPL-ING. W. MIEMANN DR. M. KÖHLER DIPL-ING. C GERHARDT

MÖNCHEN HAMBURG

TELEPHONE = 5554 7 «8000 MDNCH E N -2,

TELEGRAMMEiKARPATENT MATHILDENSTRASSE 12

TELEX: 529048 KARP D

V. 4-220V74 - Ko / Ne. November 15, 1974

• Fuji Photo Film Co., Ltd. Minami Ashigara-Shi Kanagawa (Japan)

2,5-di-lower alkoxybenzylamines, 2,5-dihydroxybenzylis amines and processes for their preparation

The invention relates to a process for the preparation of 2,5-di-iedrig-alkoxybenzylamines and their derivatives with additional substituents on the benzene ring in one Step and also relates to a process for the preparation of 2,5-Dih.ydroxybenzylaminen and their derivatives with additional Substituents on the benzene nucleus and the compounds produced thereby.

. According to the invention are 2,5-di-lower alkoxybenzylamines with additional substituents on the benzene nucleus, 2,5-dihydroxybenzylamines with additional substituents on the Benzolkern, a one-step process for the production of 2,5-di-lower-alkoxybenzylamines or their derivatives

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with additional substituents on the benzene nucleus, in which a 2,5-di-lower-alkoxybenzaldehyde or a derivative thereof has additional substituents on the benzene nucleus in the 3-, 4- and / or 6-positions, in which the substituents are one or may be several alkyl groups with 5 or fewer carbon atoms or a halogen atom ^ in the presence of ammonia is catalytically reduced> and a process for the preparation of 2,5-dihydroxybenzylamines or their derivatives with too- " additional substituents on the benzene nucleus in which the 2,5-di-lower alkoxybenzylamine prepared above or its Derivative with additional substituents on the benzene nucleus is dealkylated, indicated.

The 2,5-dihydroxybenzylamines and their derivatives with additional substituents on the benzene nucleus are suitable as developing agents for a photographic light-sensitive Silver halide material or an intermediate therefor (for example, for a color developing agent) as a raw material for the preparation of a polymer with antioxidant properties by reacting with a polymers containing a maleic anhydride unit, as a general antioxidant or an intermediate therefor and as intermediates for dyes and medicines.

The 2,5-di-lower-alkoxybenzylamine and its derivatives with additional substituents on the benzene nucleus are used as an intermediate for the preparation of the above 2,5-dihydroxybenzylamine and its derivatives with additional substituents on the benzene nucleus are suitable.

The production of benzylamine by adding benzaldehyde together with ammonia using a hydrogenation a nickel catalyst is subjected or the synthesis of o-methylbenzylamine by adding o-methylbenzaldehyde together

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is subjected to hydrogenation with ammonia using a nickel catalyst is known (J. Am. Chem. Socl, 61, 3566 (1939)).

However, these methods have a tendency to generate a large amount of secondary amine, d. H. Bis (2,5-dimethoxybenzyl.) Amine as a by-product, if ammonia in an amount less than the stoichiometric amount, based on the aldehyde as the starting material. The above tendency also occurs when there is a substituent in the o-Stelluhg in relation to the aldehyde group. In general, the presence of substituents on the benzene nucleus of benzaldehyde often hinders the smooth The course of the reaction and reduces the yield of benzylamine derivatives, which have additional substituents on the benzene nucleus.

In addition, it is also known to produce p-methoxybenzylamine by treating p-methoxyphenylchloromethane with ammonia and an alcohol (Liebigs Ann. Chem., 117 , 240). However, it is by no means known to produce a large amount of 2,5-dimethoxybenzylamine or a derivative thereof having additional substituents on the benzene nucleus in an efficient manner and in high yield as the main product. There is only one known method of producing 2,5-dimethoxybenzylamine in low yield by a cumbersome process for forming an aldoxime from 2,5-dimethoxybenzaldehyde and then treating it with alcohol and alkali. .

One such method of making the final product by treating the aldoxime with alcohol and alkali does not allow the production of a large amount of 2,5-Eimethoxybenzylamin or a derivative with additional substituents on the benzene nucleus in an effective manner and high yield.

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Therefore, it is an object of the invention to provide a method for efficiently producing a 2,5-di-lower alkoxybenzylamine and its derivatives with additional substituents on the benzene nucleus in large quantities and in high yield.

Another object of the invention is a process for the preparation of useful 2,5-dihydroxybenzylamine and its derivatives with additional substituents on the benzene nucleus.

A further object of the invention consists in new derivatives of 2,5-di-lower-alkoxybenzylamine, those on the benzene nucleus are additionally substituted and new derivatives of 2,5-dihydroxybenzylamine, which are additionally substituted on the benzene nucleus are.

In order to achieve the above tasks, an experiment as described in Liebigs Ann. Chem., 117-240 , made to make 2,5-dimethoxybenzylamine by making 2,5-dimethoxyphenylchloromethane and then treating the same with ammonia and alcohol. However, the process resulted in a very low yield in the first stage of the synthesis of 2,5-dimethoxyphenylchloromethane and the production of a large amount of impurities, and could not be used effectively at all for the production of 2,5-dimethoxybenzylamine.

It has been found that when a 2,5-di-lower-alkoxy- (methoxy, ethoxy and the like. ^ benzaldehyde or a derivative thereof with additional substituents on the benzene nucleus in the 5> -t 4- and / or 6-position (the derivatives thereof with additional substituents on the benzene nucleus in the 3- »4- and / or 6-positions are new) is catalytically hydrogenated together with ammonia, a 2,5-di-lower-alkoxybenzylamine or a derivative thereof with additional substituents on

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Benzene nucleus in one step quite unexpectedly in high yield and can be obtained with much fewer by-products, the reaction being easy to carry out.

This fact is very surprising given the usual methods lead to a low yield of the end product and require a relatively complicated process for implementation.

It was also found that when the thus obtained 2,5-dialkoxybenzylamine or a derivative thereof with additional substituents on the benzene nucleus further with or without prior Isolation is dealkylated, 2,5-dihydroxybenzylamine or a derivative thereof having additional substituents on the benzene nucleus can be easily obtained in high yield.

The invention thus also provides 2,5'-di-lower alkoxybenzylamine and 2, 5-dihydroxybenzylamine compounds the general formula

(D

wherein R is an alkoxy group with A to 5 carbon atoms, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy and pentoxy groups, X is an unsubstituted or substituted lower alkyl group with 5 or fewer carbon atoms or a halogen atom, such as bromine or chlorine and η denote an integer from 1 to 3 or the general formula

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(ID

where X and η have the meaning given above.

The objects of the invention can thus be effectively achieved by the above method.

The following is the. Invention described in detail.

The term "additional substituents on the benzene nucleus" as used herein means one or more alkyl groups with 5 or fewer carbon atoms, such as one Methyl, ethyl, isopropyl, butyl or tert-pentyl group (Including substituted alkyl groups in which the substituent is a halogen atom, preferably a chlorine or Bromine atom or an alkoxy group with up to 5 carbon atoms, preferably a methoxy, ethoxy or propoxy group can be) and a halogen atom, such as bromine or chlorine atom on the benzene nucleus. The term used here "Lower alkoxy" refers to an alkoxy group with up to 5 carbon atoms, such as a methoxy, Ethoxy, propoxy, isopropoxy, butoxy, pentyloxy group and the like

The lower alkoxy units R in the 2,5-dialkoxybenzaldehyde or its derivative and in the 2,5-dialkoxybenzylamine or its derivative can be identical or different. Furthermore, if two or more additional substituents X are present on the benzene nucleus in the 3-, 4- and 6-positions, these can be identical or different .

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The molar ratio of 2,5-di-lower alkoxybenzaldehyde or its derivative with additional substituents on the benzene nucleus to form ammonia is preferably in the range of about 1: 1 to 1:12, more preferably 1: 3 to 1:10, however, the appropriate amount is ammonia as long as it is used becomes, at least an approximately equimolar amount or more »and it can be increased outside of the range specified above, as long as this takes into account the size of the plant and the quantities the solvent used, the work-up method and the like. Is practical.

The catalysts that can be used in this process include Raney nickel, Raney cobalt, palladium carbon, Platinum black or the like, as in Lecture on Experimental Chemistry 17, Volume 2, pages 245 to 4-30, Maruzen, (1956) and L.F. Fieser and M. Fieser Reagents for Organic Synthesis, Volume 1 (1967), Volume 2 (1969) and Volume 3 (1972), John Wiley and Sons. Raney Nickel is under consideration of reactivity, availability and cost. A preferred amount of the catalyst is in the range of about 3 to 10 wt.%, Based on the 2,5-di-lower alkoxybenzaldehyde or its derivative.

Although the catalytic reduction without a solvent expires, it becomes in terms of the solubility of ammonia and the solubility of 2,5-dimethoxybenzaldehyde and its derivative with additional substituents on the benzene nucleus, a solvent such as, for example, preferred Alcohol, e.g. B. methanol, ethanol or propanol; a carboxylic acid ester such as butyl acetate; an ether for example diethyl ether or tetrahydrofuran; an aromatic hydrocarbon, for example benzene, To use toluene or xylene or a ketone, for example methyl ethyl ketone or acetone. A suitable amount

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of the solvent is in the range of about 0.6 to 6 times, preferably 2 to 4 times, based on the weight of the weight of the 2,5-di-lower alkoxybenzaldehyde or its derivative.

The catalytic reduction proceeds at a considerably high rate when a 2,5-di-lower alkoxybenzaldehyde or a derivative thereof with additional substituents on the benzene nucleus is dissolved in a solvent. Hence will it in the reductive amination of a derivative of a 2,5-di-lower alkoxybenzaldehyde with additional substituents on the benzene nucleus preferred, the above solvent depending to correctly select from the chemical properties of the derivative used.

Further, when the purification of the generated amine is required after the catalytic reduction, the solvent becomes also depending on the type of purification either by distillation or precipitation of the amine salt selected by adding an acid. That is, in the case of the amine salt being precipitated by adding an acid the ethers, esters and aromatic hydrocarbons described above are preferably used, the non-polar Are solvents in which the amine salt has poor solubility. On the other hand, in the case of cleaning of the amine produced by distillation, a wider choice of solvent can be made and any of the solvents described above can be used.

The synthesis can be efficiently carried out at an elevated temperature. The temperature range can be appropriate Depending on the type of source material, you can choose however, is generally in the range of about 30 to 180 ° C., preferably 50 to 130 ° C. The reaction time can also appropriately chosen depending on the starting material

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but is preferably in the range of about 30 minutes up to -5 hours, in particular 40 minutes to 2 hours. When the temperature used is increased, it is a short one The reaction time is sufficient, and vice versa, when the temperature is decreased, the required reaction time is longer. The hydrogen gas pressure used is preferably in Range from about 20 to 120 atm, especially 50 to 80 atm. The above-described ranges for the temperature, the reaction time and the hydrogen gas pressure are in view on the reaction rate and the course of the reaction are preferred.

The 2,5-di-lower-alkoxybenzylamines and their derivatives with additional substituents on the benzene nucleus, through the reductive amination can be formed. easily by dealkylation into the corresponding 2,5-dihydroxybenzylamine or its derivatives are converted with additional substituents on the benzene nucleus.

On dealkylating agents for 2,5-di-lower alkoxybenzylamine or its derivatives with additional substituents on the benzene nucleus include, for example, hydrogen halide acids, e.g. B. hydrochloric acid, hydrobromic acid or hydriodic acid and salts containing nitrogen heterocyclic compounds, for example their hydrogen halide acid salts such as picoline hydrochloride or pyridine hydrochloride. Hydrobromic acid becomes preferably used from the standpoint of easiness of reaction, easiness of treatment after reaction, recovery and recovery of the excess dealkylating agent and the life of the dealkylating agent. A suitable amount of hydrobromic acid or hydriodic acid is about 6 to 18 times, especially 8 to 12 times the weight, based on the

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Weight of the di-lower alkoxybenzylamine compound used.

The dealkylation proceeds effectively at a temperature of about 100 ° C or higher. In particular if the dealkylation is preferred, it is carried out at a temperature of about 140 to about 180 ° C. for 2 to 4 hours. If the dealkylation is carried out at lower temperatures below about 100 ° C, the reaction time is prolonged, the reaction product is noticeably colored and the post-treatment becomes difficult. Furthermore, the dealkylation preferably carried out in a stream of an inert gas, such as nitrogen gas, to carry out the oxidation to prevent the end product.

Specific examples of 2,5-di-lower alkoxybenzylamines and their derivatives with additional substituents on the benzene nucleus and 2,5-dihydroxybenzylamines and their derivatives with additional substituents on the benzene nucleus, which can be obtained according to the invention, are as follows indicated without limiting the invention.

(1) 2,5-dimethoxybenzylamine

(2) 2, ^ - Dimethoxy-J-methylbenzylamine

(3) 2,5-dimethoxy-3-ethylbenzylamine

(4-) 2,5-Dimethoxy-3-tert-butylbenzylamine

(5) 2, Jj-Dimethoxy ^ -bromobenzylamine

(6) 2,5-dimethoxy-6-bromobenzylamine

(7) 2,5-dimethoxy-3-chlorobenzylamine

(8) 2,5-diethoxybenzylamine

(9) 2,5-diethoxy-3-methylbenzylamine

(10) 2,5-diethoxy-3-ethylbenzylamine

(11) 2 _> 5-diethoxy-3-tert.-butylbenzylamine-

(12) 2,5-diethoxy-3-bromobenzylamine

(13) 2,5-diethoxy-6-bromobenzylamine

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(14 x) 2 _T 5-diethoxy-3-chlorobenzylamine

(i) '2 _tf 5-dihydroxybenzylamine

(2) ¹ 2 _$ 5-dihydroxy-3-methylbenzylamine

(3) '2 "5-dihydroxy-3-ethylbenzylamine

(4) '2 _r 5-di-hydroxy-3-tert-butylbeiicylamine

(5) ¹ 2,) 5-dihydroxy-3.-bromobenzylamine

(6) '2 _t) 5-dihydroxy-6-bromobenzylamine 2,, 5-dihydroxy-3-chlorobenzylamine

The invention is described below with reference to FIG the examples explained in more detail. Unless otherwise stated, all parts, percentages and ratios relate to and the like on weight.

Example 1 , Production of 2,5-diniethoxybenzylamine

166 g of 2,5-dimethoxybenzaldehyde _→ 500 ml of methanol containing 100 g of liquid ammonia dissolved therein and 10 g of Raney nickel catalyst were reacted in an autoclave under a hydrogen pressure of 80 atm and with heating at 120 ° C. for 3 hours. After the reaction, distillation under reduced pressure gave 153 g of the desired product having a boiling point of 96 to 98 ° C./1 mm Hg (yield 91.5%).

Example 2

■ '.- ■ Production of 2,5-dihydroxybenzylamine hydrobromide

150 g of 2,5-dimethoxybenzylamine were heated in %, 1600 ml of 48% hydrobromic acid in an oil bath temperature

: '509825/1063

a, -

temperature from 160 to 170 ° C and in a stream of nitrogen refluxed for 3 hours. After the reaction, the reaction mixture was cooled and those precipitated Crystals were filtered off, dried and then recrystallized from ethanol to give 127 g of the desired Product obtained with a melting point of 233 to 234 ° C (yield 64.2%).

The invention has been described above on the basis of preferred embodiments, without being limited thereto be.

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Claims (18)

Claims 1 * Process for the preparation of 2,5-di-lower alkoxybenzylamines or their derivatives with additional substituents on the benzene nucleus in one stage, characterized in that that a 2,5-di-lower-alkoxybenzaldehyde or its derivative with additional substituents on the benzene nucleus in the 3-j 4- and / or 6-positions, in which the substituents one or more alkyl groups having 5 or fewer carbon atoms or a halogen atom, is catalytically reduced with hydrogen in the presence of ammonia. 2. The method according to claim 1, characterized in that that the alkyl group is a methyl group, an ethyl group, an isopropyl group, a butyl group or a tert-pentyl group and the halogen atom is a bromine atom or a chlorine atom. 3. The method according to claim 1 or .2, characterized in that that the 2,5-di-lower-alkoxybenzylamine or its derivative with additional substituents on the benzene nucleus Contains 1 to 5 carbon atoms in the lower alkoxy moiety. 4 ·. Method according to claim 1 to 3 »characterized in that that the molar ratio of 2,5-di-lower alkoxybenzaldehyde or its derivative with additional substituents on the benzene nucleus to ammonia in the range from about 1: 1 to 1:12 and the hydrogen at a pressure of about 20 to 120 atmospheres is used. 5. The method according to claim 1 to 4-, characterized in that that the process is carried out in a solvent. 6. The method according to claim 5 »characterized in that that as a solvent an alcohol, a carboxylic acid ester, an ether, an aromatic hydrocarbon or a 509825/1063 245A355 Ketone is used. 7. The method according to claim 1 to 6, characterized in that that the catalytic reduction with a Raney nickel catalyst, a Raney cobalt catalyst, a palladium-carbon catalyst, or platinum black will. 8. · The method according to claim 7 »characterized in that that the catalytic reduction takes place with Raney nickel. 9. The method according to claim 1 to 8, characterized in that that the reduction takes place at a temperature in the range from about 30 to 180 ° C. 10. Process for the preparation of 2,5-dihydroxybenzylamine or its derivatives with additional substituents on the benzene nucleus, characterized in that a 2,5-di-lower alkoxybenzaldehyde or its derivatives with additional Substituents on the benzene nucleus in the 3-> 4- and / or 6-positions, in which the substituents are one or more Mean alkyl groups having 5 or less carbon atoms or a halogen atom, with hydrogen in the presence of Ammonia to form a 2,5-di-lower alkoxybenzylamine or a derivative thereof with additional substituents on the benzene nucleus is catalytically reduced and then that 2,5-Di-lower alkoxybenzylamine or its derivative dealkylated will. 11. The method according to claim 10, characterized in that the dealkylation with a hydrohalic acid or a salt of a nitrogen-containing heterocyclic compound. 12. The method according to claim 11, characterized in that that the hydrohalic acid is hydrochloric acid, hydrobromic acid or hydriodic acid and the salt of the nitrogen-containing heterocyclic compound picolin 509825/1063 hydrochloride or pyridine hydrochloride. 13. The method according to claim 10 to 12, characterized in that that dealkylation at a temperature of about 100 ° C or higher. 14 ·. Method according to claim 13 »characterized in that that the dealkylation takes place in the presence of an inert gas. 15 · The method according to claim 10 to 14 ·, 'characterized in, that the dealkylation is carried out with hydrobromic acid or hydroiodic acid. 16. The method according to claim 15? characterized, that the. Hydrobromic acid or hydroiodic acid in an amount about 6 to 18 times by weight based on the weight of the di-lower alkoxybenzylamine compound or whose derivative is present with additional substituents on the benzene nucleus. 17 · 2,5-di-lower alkoxybenzylamine compound of general formula. . ". (D wherein R is an alkoxy group having 1 to 5 carbon atoms, X is an unsubstituted or substituted lower alkyl group having 5 or less carbon atoms or a halogen atom and η is an integer of 1 to 3. 18. 2,5-dib.ydroxybenzylamine compound of the general Formula: 509825/1063 OH (H) wherein X is a lower alkyl group having 5 or fewer carbon atoms or a halogen atom and η an integer from 1 to 3. 509825/1063