JPS648619B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing aralkylamines by reacting an aralkenal or an aralkanal with a secondary amine. As is well known, tertiary amines can be obtained by reacting secondary amines with carbonyl compounds in the presence of hydrogen and a hydrogenation catalyst (Houben-Weyl, “Methoden der organischen
Chemie”, Volume 4/2, pp. 328 onwards, Volume 11/
Volume 1, pp. 602 et seq., p. 643 et seq.). German Patent No. 1179947 describes the synthesis of N-alkylated aromatic amines by reductive alkylation of aromatic amines using palladium-silver catalysts under protection of the aromatic system. . According to the description in German Patent Application No. 2118283, an aliphatic or alicyclic carbonyl compound and a secondary amine are similarly reacted in the presence of hydrogen using a palladium-silver catalyst. Aliphatic or cycloaliphatic tertiary amines can be produced by The advantage of this catalyst is that it allows the ring alkylation of secondary amines with saturated carbonyl compounds in high yields and with almost no by-products. Suitable carbonyl compounds include, in particular, saturated ketones such as acetone, methyl ethyl ketone, cyclopentanone, cyclohexanone and also aldehydes which in principle cannot be used or are difficult to use in aldol condensations, such as formaldehyde, isobutyraldehyde, 2 -Ethyl hexanal is mentioned. German Patent Application No. P2830999 discloses that stereoisomeric N-
The preparation of -aralkyl-2,6-dimethylmorpholine is described. By the way, the formula: [In the formula, R ¹ represents a hydrogen atom, an aliphatic group having 1 to 10 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms. , R ² , R ³ and R ⁴ each represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X ¹ , X ² , X ³ and X ⁴ each represent a hydrogen atom. or represents an alkyl group having 1 to 4 carbon atoms, and A is

[Formula] or

[Formula] (where X ⁵ , X ⁶ , and X ⁷ each represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents a number of 2, 3, or 4) The tertiary amine represented by the formula: A secondary amine represented by [wherein X ¹ , X ² , X ³ , X ⁴ and A each represent the above];
formula: Reacting with a carbonyl compound represented by [wherein R ¹ , R ² , R ³ and R ⁴ each represent the above, and the dotted bond may be a double bond or a single bond], carrying out the reaction in the presence of hydrogen and a hydrogenation catalyst containing palladium on an inert support in admixture with an oxide of zinc, cadmium, manganese and/or one of the rare earth metals, in particular praseodymium or neodymium; It turns out that it can be obtained in a simple way. Inert supports can consist, for example, of aluminum oxide, silicic acid or activated carbon. The reaction is carried out for example between 10°C and 200°C, advantageously
It is carried out at temperatures between 20°C and 160°C. Furthermore, the reaction is
Can work at normal pressure or at pressures up to 300 bar. An advantage of the process according to the invention is that, in particular, unstable carbonyl compounds, such as amines, can be added to the double bond, with β
- It is possible to use unsaturated aldehydes or ketones or aldehydes or ketones which can be used in aldol condensation and still obtain a single final product. Another advantage of the process according to the invention is that the desired end products of the formula are produced in extremely pure form due to the high selectivity of the catalysts used. That is, for this type of reaction, the expected by-products, e.g., due to hydrogenation of the carbonyl compound, the formula: Alcohol or formula: The unsaturated amine represented by is hardly produced. Slightly selective catalysts, such as the known palladium-
When silver catalysts (DE 1179947, DE 2118283) are used, significant amounts of the above-mentioned by-products are produced (the results of these methods cannot be used in the implementation of the present invention). (This will be described later as Comparative Example 13 and Comparative Example 18 in comparison with the above example.) Furthermore, when operating based on the method of the present invention, if a sterically homogeneous product is used as a raw material, a sterically homogeneous product can be obtained. It has the advantage of being In this case, the isomerization that often occurs with hydrogenation catalysts (Houben-Weyl, “Methoden der Organischen
Chemie, Vol. 4/2, pp. 276-283) are not observed. According to the method of the invention, the amine component is present in a stoichiometric amount or up to 10 times the molar amount relative to the carbonyl compound. It can be used in excess. Suitable raw materials for the formula include, for example, the following carbonyl compounds: 3-phenyl-2-methyl-prop-2-enal, 3-phenyl-2-methyl-propanal, 3-phenyl-3-methyl-prop-2-enal, 3-phenyl-3-methyl-propanal, 4-phenyl-but-3-en-2-one,
4-phenyl-butan-2-one, 3-(4'-methylphenyl)-2-methyl-prop-2-enal, 3-(4'-methylphenyl)-2-methylpropanal, 3-(4'- isopropylphenyl)-2-methyl-prop-2-enal, 3-
(4′-isopropylphenyl)-2-methyl-propanal, 3-(4′-tertiary butylphenyl)
-2-methyl-prop-2-enal, 3-
(4'-Tertiary butylphenyl)-2-methyl-propanal, 3-phenyl-2-ethyl-prop-2-enal, 3-phenyl-2-ethylpropanal, 3-phenyl-2-isopropyl-propanal -2-enal, 3-phenyl-2-isopropyl-propanal, 3-(4'-isopropylphenyl)-3-methyl-prop-2-enal, 3-(4'-isopropylphenyl)-3- Methylpropanal, 3-(4'-tert-butylphenyl)-3-methyl-prop-2-enal, 3
-(4'-tertiary butylphenyl)-3-methyl-
Propanal, 4-(4'-tert-butylphenyl)-but-3-en-2-one, 4-(4'-tert-butylphenyl)-buten-2-one, 3-
(4'-methoxyphenyl)-2-methyl-prop-2-enal, 3-(4'-methoxyphenyl)
-2-methyl-propanol, 3-(4'-isopropoxyphenyl)-2-methyl-prop-2-
enal, 3-(4'-isopropoxyphenyl)
-2-methyl-propanal, 3-(4'-cyclohexylphenyl)-2-methyl-propanal-2-
enal, 3-(4'-cyclohexyl phenyl)
-2-methyl-propanal, 3-(4'-cyclopentylphenyl)-2-methyl-propanal-2-
enal, 3-(4'-cyclopentylphenyl)
-2-Methyl-propanal. This known starting material can be prepared by aldol condensation of a suitable substituted benzaldehyde with an aliphatic aldehyde or an aliphatic kent. These hydrogenated compounds are obtained from unsaturated products by partial hydrogenation of carbon-carbon double bonds (US Pat. No. 2,976,321). Tertiary amines of the formula which can be reacted by the process of the invention include, for example, the following compounds: pyrrolidine, piperidine, 2-methylpiperidine, 3-methylpiperidine, 4-methylpiperidine, 2,6-dimethyl Piperidine, 3,5-dimethylpiperidine, 4-ethylpiperidine, morpholine, 2-methylmorpholine, 2-ethylmorpholine, 3-methylmorpholine, 2,6-dimethylmorpholine, 3,5-dimethylmorpholine, 2,
5-dimethylmorpholine, 2,6-diethylmorpholine, piperazine, 1-methylpiperazine, hexamethyleneimine, 2,3-dimethylhexamethyleneimine, 3,5,5-trimethylenehexamethyleneimine and 3,3,5- Trimethylhexamethyleneimine. The reaction can be carried out without a solvent or in the presence of a solvent that is inert under the reaction conditions. Examples of the solvent include: methanol, ethanol, propanol, tetrahydrofuran, dioxane, anisole, ethylene glycol methyl ether, 1,2-
Dimethoxyethane, methyl-t-butyl ether, cyclohexyl methyl ether, di-n-butyl ether, toluol, cyclohexane. The reaction can be carried out continuously or batchwise, preferably in the liquid phase. The catalyst system used according to the process of the invention contains on the one hand palladium as the hydrogenation metal and on the other hand the additive components zinc, cadmium, manganese or a rare earth metal oxide or a mixture of rare earth metal oxides. , the additive components can be alone or in mixtures with one another other than palladium. These catalyst additives provide improved selectivity of the hydrogenation catalyst. According to the present invention, rare earth metal oxides include lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), thulium (Tm),
Examples include oxides of ytterbium (Yb) and lutetium (Lu). _{Preference is} given to the following rare earth metal oxides: _{La2O3 , Pr2O3} and _Nd2O3 . In the catalyst system used according to the invention, the rare earth metal oxides can be present in pure form or as a mixture of a number of rare earth metal oxides, such as those produced industrially. Examples of inert carriers include those already mentioned above.
In addition to Al ₂ O ₃ , SiO ₂ and activated carbon, aluminum silicate and magnesium silicate may also be mentioned. The palladium content of the catalyst in the support material is
It is not significant and may vary widely. Preferably the content is 0.05-15% by weight. Catalyst (zinc, cadmium, manganese, rare earth metal oxides)
Advantageously, the content of the additive components is from 0.01 to 10% by weight, based on the carrier. The weight ratio of the additive component of the catalyst to the palladium metal is, for example, 400:1.
~1:150, advantageously 50:1 to 1:10. For example, the catalyst is used as a strand or powder with a diameter of 5 mm and a length of 10 mm. The catalyst is produced, for example, by impregnating the support material with a solution of metal carbonate and subsequently heating it. The compounds prepared by the process of the invention are known and can be used as intermediate products in plant protection agents or as active substances in known plant protection agents (Federal Republic of Germany). Patent Application Publication Nos. 2752096, 2752135, and 2656747). "Parts" described in the following examples and comparative examples represent "parts by weight", and in this case, parts by volume and parts by weight are:
There is a relationship between “” and “Kg”. Example 1 In a cylindrical reaction tube with a volume of 500 parts by volume, 0.5 parts by weight of Pd on Al ₂ O ₃ as support, Pr ₂ O ₃ (95%
A catalyst having a composition of 5% by weight (Pr ₂ O ₃ , the remainder consisting of other rare earth metal oxides) is charged and heated to 130°C. On top of this catalyst bed, 3-phenyl-2-methyl-prop-2-enal (α
- Methyl cinnamaldehyde) 146 parts and cis-2,6
- 115 parts of dimethylmorpholine are fed at 60 parts per hour. At the same time, 100,000 parts by volume of hydrogen
Pass through the reaction tube in countercurrent at a pressure of 50 bar. The reaction product exiting the reaction tube is cooled under pressure and then depressurized. At that time, the crude product is
60 parts are produced, which is purified by distillation. crude product
Distilling 100 parts gives 77.5 parts of N-(3'-phenyl-2'-methylpropyl)-cis-2,6-dimethylmorpholine (boiling point = 95° C./0.01 mbar). This corresponds to a yield of 83% of theory. Example 2 In the same apparatus as described in Example 1, a catalyst with a composition of 0.50% by weight of Pd, 0.11% by weight of Zn and 0.10% by weight of Cd on Al ₂ O ₃ as support was charged. and heat to 100℃. On top of this catalyst bed, 3-phenyl-2-methylprop-2-enal (α-
Methyl cinnamaldehyde) 146 parts and cis-2,6-
60 parts/hour of a mixture consisting of 115 parts of dimethylmorpholine are fed. At the same time, add 10,000 parts by volume of hydrogen to 50
Pass through the reaction tube in countercurrent at a pressure of bar. The product exiting the reaction tube is cooled under pressure and then depressurized. In the process, 60 parts per hour of crude product are produced, which is purified by distillation. 100 parts of the crude product was distilled to give 75.5 parts of N-(3'-phenyl-2'-methylpropyl)-cis-2,6-dimethylmorpholine.
(equivalent to 81% of the theoretical value). Example 3 Using the same catalyst in the same equipment as described in Example 1, 261 parts of methanol, 3-phenyl-2
2,6- with 146 parts of methyl-prop-2-enal (α-methyl cinnamaldehyde) and 75% by weight of cis compounds and 25% by weight of trans compounds
a mixture of 115 parts of dimethylmorpholine per hour.
Supply 120 parts and react at 120°C. Simultaneously with the mixture, 100,000 parts by volume of hydrogen are passed in cocurrent through the reaction tube at a pressure of 50 bar. The reaction product exiting the reaction tube is cooled under pressure and then depressurized.
In the process, 120 parts per hour of crude product are produced, which is purified by distillation. Distill 200 parts of this crude product,
75% by weight of cis compounds and 25% by weight of trans compounds
N-(3'-phenyl-2'-methyl-propyl)-2,6-dimethylmorpholine with (boiling point =
155-157°C/12 mbar) 80.5 parts are obtained.
This corresponds to a yield of 86% of theory. Example 4 Using the same catalyst in the same equipment as described in Example 1, 317 parts of methanol, 202 parts of 3-p-tert-butylphenyl-2-methyl-prop-2-enal and cis-2, 6-dimethylmorpholine
A mixture consisting of 115 parts was fed at 120 parts per hour at 130°C.
React with. At the same time with the above mixture, hydrogen 100000
The volume is passed through the reaction tube in countercurrent at a pressure of 50 bar. The reaction product exiting the reaction tube is cooled under pressure and then depressurized. 120 parts of crude product are produced per hour, which is purified by distillation. 200 parts of the crude product was distilled to give N-(3'-(p-tert-butylphenyl)-2'-methyl-propyl)-cis-2,6-dimethylmorpholine (boiling point = 206
℃/18 mbar) 88.5 parts are obtained. this is,
This corresponds to a yield of 92.5% of theory. Example 5 In a stirred autoclave with a volume of 1000 parts by volume, 3
-p-tertiary butylphenyl-2-methyl-propanal 153 parts, piperidine 70 parts, methanol 230 parts
A mixture of 20 parts of a catalyst consisting of 0.5% by weight of Pd on Al ₂ O ₃ and 5% by weight of Nd ₂ O ₃ was heated at 70 °C under hydrogen pressure.
Hydrogenation is carried out until the pressure remains constant at 50 bar. Subsequently, the autoclave is cooled, the catalyst is removed and the liquid is purified by distillation. N-(3'-
195 parts of (p-tert-butylphenyl)-2'-methyl-propyl)-piperidine (boiling point = 117 DEG C./0.2 mbar) are obtained. This yield is higher than the theoretical value of 94
%. Example 6 In the apparatus detailed in Example 5, 153 parts of 4-(p-tert-butylphenyl)-butan-2-one,
2,6-dimethylmorpholine (cis compound 75%/
A mixture of 115 parts of trans compound (25%), 270 parts of methanol and 20 parts of the catalyst detailed in Example 5 is hydrogenated at 140° C. and a hydrogen pressure of 50 bar until the pressure remains constant. Subsequently, the autoclave is cooled, the catalyst is removed and the liquid is purified by distillation. N-(4'-(p-tert-butylphenyl)
195.5 parts of -but-2'-yl)-2,6-dimethylmorpholine (75% cis/25% trans) (boiling point = 143° C./0.3 mbar) are obtained.
This yield is 86% of theory. Example 7 It is carried out analogously to Example 5, but using 2,2,4-trimethylazetidine as the amine component. In this case, the final product is N-
(3'-p-tert-butylphenyl)-2'-methyl-propyl)-2,2,4-trimethyl-azetidine (boiling point = 134°C/0.3 mbar) is obtained. This yield is 93% of theory. Example 8 The procedure is as in Example 5, but the starting materials are 3-p-tert-butylphenyl-2-methyl-prop-2-enal as carbonyl component and 2,3-dimethylhexamethyleneimine. Used as an amine component. In this case, the final product is N-(3'-(p-tert-butylphenyl)-2'-methyl-propyl)-2,3-dimethylhexamethyleneimine, (boiling point = 144°C/0.01 mbar) is obtained. This yield is 95% of the theoretical value.
%. Example 9 Performed as in Example 5, but using pyrrolidine as the amine component. The final product is N-(3'-(p-tert-butylphenyl)-2'-
Methyl-propyl)-pyrrolidine (boiling point = 115
°C/0.3 mbar) is obtained. This yield is
This is 96% of the theoretical value. Example 10 In a stirred autoclave with a volume of 1000 parts, 3
-190 parts of p-isopropylphenyl-3-methyl-propanal, 111 parts of 2-methylmorpholine, 300 parts of methanol and 0.5% by weight of _Pd on _Al2O3 ,
A mixture of 20 parts of a catalyst consisting of 0.11% by weight of Zn and 0.1% by weight of Cd is hydrogenated at 120° C. and a hydrogen pressure of 50 bar until the pressure remains constant. Continuing,
The autoclave is cooled, the catalyst is separated and the liquid is purified by distillation. N-(3'-(p-isopropylphenyl)-3'-methylpropyl)-2-methylmorpholine (boiling point = 122°C/0.05 mbar)
You will get 266 copies. This yield is 82% of theory. Example 11 The procedure is as in Example 10, but the starting materials are 3-p-methoxyphenyl-2-methyl-propanal as carbonyl component and cis-
2,6-dimethylmorpholine is used as the amine component. As a result, the final product is N-
(3'-p-methoxyphenyl)-2'-methyl-propyl)-cis-2,6-dimethylmorpholine (boiling point = 129°C/0.1 mbar) is obtained. This yield is 82% of theory. Example 12 3-p-tert-butylphenyl-2-methyl-prop-2-enal 101 dissolved in 900 parts of methanol in a stirrer having a volume of 2000 parts by volume.
A mixture of 61 parts of cis-2,6-dimethylmorpholine and 61 parts of cis _- 2,6-dimethylmorpholine was used as a hydrogenation catalyst 5 having a composition of 10% by weight of Pd, 0.11% by weight of Zn, and 0.1% by weight of Cd on _{Al 2 O 3}
hydrogenation at 30°C and normal pressure until hydrogen adsorption is complete. The catalyst is separated off and the liquor is worked up by distillation. At that time, N-(3′-(p-tert-butylphenyl)-2′-methyl-propyl)
-cis-1,6-dimethylmorpholine (boiling point =
206°C/18 mbar) 141 parts are obtained. This corresponds to a yield of 93%. Comparative Example 13 0.36 wt% _Pd , 4.8 wt% Ag and
Using a catalyst with a composition of 1.05% by weight of Mn, it is operated exactly as in Example 1, with the same starting materials and under the same reaction conditions. The reaction product obtained in this case has the following composition according to gas chromatographic analysis: N-(3'-phenyl-2'-methyl-propyl)
-cis-2,6-dimethylmorpholine 22% by weight,
N-(3'-phenyl-2'-methyl-prop-2'-
enyl)-cis-2,6-dimethylmorpholine 14
36.2% by weight of 3-phenyl-2-methyl-propanol and 27.8% by weight of cis-2,6-dimethylmorpholine. Example 14 In a stirred autoclave with a volume of 5000 parts by volume, 2500 parts by volume of methanol, 366 parts of cis-2,6-dimethylmorpholine, 606 parts of 3-p-tert-butylphenyl-2-methyl-prop-2-enal and A mixture consisting of 35 parts of a catalyst consisting of 0.5% by weight of Pd, 5% by weight of Pr ₂ O ₃ , 1% by weight of Mn and the balance Al ₂ O ₃ was heated stepwise first at 50° C. under a hydrogen pressure of 50 bar and then at 90° C. and finally at 120°C and 50 bar of hydrogen pressure until the pressure remains constant. Subsequently, the autoclave is cooled, the catalyst is removed and the liquid is purified by distillation. N-(3'-
856 parts of p-tert-butylphenyl-2'-methyl-propyl)-cis-2,6-dimethylmorpholine (boiling point = 206° C./24 mbar) are obtained. This corresponds to a yield of 94% of the theoretical value (3-p-tert-butylphenyl-2-methyl-prop-2-
against Enard). Example 15 In a stirred autoclave with a volume of 1000 parts, 3-
153 parts of p-tert-butylphenyl-2-methyl-propanal, 75 parts of hexamethyleneimine, 230 parts of methanol and 0.5% _Pd on _Al2O3 , ₅ % _Pr2O3 ,
A mixture consisting of 20 parts of a catalyst consisting of 1% Mn is charged. Next, hydrogenation is carried out at 90° C. and a hydrogen pressure of 50 bar until the pressure remains constant. Afterwards, the autoclave is allowed to cool, the catalyst is removed and the liquid is purified by evaporation. At that time, N-[3-(p-tert-butylphenyl)-2'-methyl-propyl]
-207 parts of hexamethyleneimine (boiling point = 130°C/0.26 mbar) are obtained. The yield is 96% of theory (based on 3-p-tert-butylphenyl-2-methyl-propanal). Example 16 Carry out in the same manner as Example 14, but using 3-phenyl-2-methyl-propylene as the carbonyl component.
2-Use Enal. N-(3'-phenyl-2'-methylpropyl)-cis-2,6-dimethylmorpholine (boiling point = 95° C./0.05 mbar) is obtained as the final product. This yield is 93% of theory. Example 17 It is carried out analogously to Example 15, but using 3,5-dimethylpiperidine as the amine component.
At that time, the final product is N-[3'-(p-tert-butylphenyl)-2'-methylpropyl]-
3,5-dimethylpiperidine (boiling point = 135℃/0.4
millibar) is obtained. Comparative Example 18 0.36 wt% _Pd , 4.8 wt% Ag and
Using a catalyst with a composition of 1.05% by weight of Mn, it is operated exactly as in Example 14, with the same starting materials and under the same reaction conditions. The reaction product obtained in this case has the following composition according to gas chromatographic analysis: N-(3'-p-tert-butylphenyl-2'-methyl-propyl)-cis-2,6- 46% by weight of dimethylmorpholine, 25% by weight of N-(3'-p-tert-butylphenyl-2'-methyl-prop-2-enyl)-cis-2,6-dimethylmorpholine, 3-
18% by weight p-tert-butylphenyl-2-methyl-propanol and 11% by weight cis-2,6-dimethylmorpholine.

Claims (1)

[Claims] 1 Formula: [In the formula, R ¹ represents a hydrogen atom, an aliphatic group having 1 to 10 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms. , R ² , R ³ and R ⁴ each represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X ¹ , X ² , X ³ and X ⁴ each represent a hydrogen atom or represents an alkyl group having 1 to 4 carbon atoms, A is [Formula] or [Formula] (where X ⁵ , X ⁶ , and X ⁷ each represent a hydrogen atom or have 1 to 4 carbon atoms represents an alkyl group, n represents a number of 2, 3 or 4], represented by the formula: [In the formula, X ¹ , X ² , X ³ , X ⁴ and A each represent the above] and a secondary amine of the formula, [In the formula, R ¹ , R ² , R ³ and R ⁴ each represent the above, and the dotted bond may be a double bond or a single bond]. in the presence of hydrogen and a hydrogenation catalyst containing palladium mixed with oxides of zinc, cadmium, manganese and/or praseodymium or neodymium on an inert support. A method for producing aralkylamine, characterized by: