HU204764B - Process for n-alkylation of aliphatic amines or aminoalcohols - Google Patents

Abstract

N-alkylated aliphatic amines or aminoalcohols of formula X-A-N(R)-B-X (1) are prepd. by reductive N-alkylation of corresponding amines or amino-alcohols contg. at least one -N-H-bond with aliphatic aldehydes of formula PCHO (III) in the presence of hydrogen and a supported Pt metal catalyst. - In formula (I): R: 1-4C alkyl gp.; X: hydrogen atom, hydroxyl gp. or N(R)2 gp. where R is as above and both R gps. in formula (I) may be identical or dissimilar. A: -Y- or (-Y-O)p-Y- gps. and B: -Y- or (-Y-O)q-Y- gps. where the values of p. and q. are independently 1,2 or 3 and Y represents a linear to branched 1-6C alkylene gp.; Y gps. may be identical or dissimilar, but simultaneously either only A or only B may contain an ether-linkage; conversely X-A- and/or X-B- may present cyclo-hexyl, cyclo-pentyl, methyl- or methyl-cyclopentyl gps. X-A- and X-B- may also form piperazine, morpholino gps. when linked with N(R) gps., provided the other X gp. in (1) may not be else than an N(R)2 gp. The formula (III): P:hydrogen atom or 1-3C alkyl gp.

Description

The present invention relates to an improved process for the reductive N-alkylation of aliphatic amines or amino alcohols with short chain alcohols. The process of the present invention provides compounds of formula (I)

X-A-N (R) -B-X ff) 5

in the formula

R is C 1-4 alkyl,

X is hydrogen, hydroxy or -N (R) ₂ , wherein R is as defined above, and the groups R in the compound of formula (I) may be the same or different, and the two X groups may be the same or different,

A is -Y- or (-Y-O) p -Y-, and B is -Y- or (-Y-O) q -Y-, wherein p and q are independently 1.2 or 15 3, and

Y represents a straight or branched C 1 -C 6 alkylene group and the Y groups may be the same or different, but at most one of A and B may contain an ether bond, or XA and / or XB may be cyclohexyl, cyclopentyl, or a group XA or XB together with the linked -N (R) - 25 group may form a piperazino or morpholino group, provided that the compound of formula (I) the other group X can only be -N (R) ₂ - by preparing the compounds of formula (Π)

W-A-N (R ') - Z (Π)

in the formula

Z is hydrogen or -B-W '; A and B are as defined above, p

W and W 'independently represent hydrogen, hydroxy, amino, or -NHR or -N (R) ₂ , wherein R ₁ is C 4 -C 4 alkyl, and in R 40 -N (R) ₂ , the R groups may be the same or different, and

R 'is hydrogen or (C 1 -C 4) -alkyl, provided that the compounds of formula (H) always contain at least one -N-H 45 substituent on each of the nitrogen atoms attached to the C 1 -C 4 substituent.

The compounds of formula I are widely used in the plastics industry. 50

A known process for the preparation of compounds of formula I is the reductive N-alkylation of compounds of formula H with aldehydes in the presence of hydrogen and a hydrogenation catalyst. Most of the known methods relate to the N-methylation of amines with 35-37% aqueous formaldehyde in 55 solutions. The use of relatively higher numbers of aldehydes with higher carbon numbers is associated with the use of relatively fewer and most precious metal catalysts. A very widely used catalyst is cobalt oxide, which is used in admixture with 60 other oxides and or or phosphoric acid. Thus, the German patents describe the use of phosphoric acid-doped cobalt oxide catalysts in the N-methylation of amines. N-methylation is also provided by the process disclosed in German Patent No. 2,618,580, wherein the cobalt oxide catalyst is used in admixture with copper, manganese, molybdenum and sodium oxide and added with phosphoric acid. The process is suitable for N-methylation of both amines and amino alcohols. According to the cited publications, a temperature of 80 to 105 ° C and a pressure of 200 bar are required to obtain a satisfactory yield. No. 634 of 2017 French Patent Specification No. 4,684,198 discloses a cobalt chromium oxide catalyst doped with phosphorus pentoxide and loaded on silica support for amine methylation. To achieve a yield of nearly 90%, a temperature of 140 ° C and a pressure of 300 bar are required.

No. 59199655. Japanese Patent No. 4,198,125 discloses reductive N-methylation of amines in batch mode in the presence of Raney nickel catalyst in 37% aqueous formaldehyde solution. The disadvantage of the process, apart from batch operation, is that the color stability of the product is inadequate and alkaline is added to the reaction mixture to ensure color stability.

Several processes are known for reductive alkylation, wherein palladium or platinum is used as the catalyst. The metal is applied on a carbon support in an amount of 1 to 10% by weight. N-methylation of amines in the presence of a supported noble metal catalyst is described in U.S. Pat. German Patent Nos. 60130, 551, 61236, 751, and 62281846; Reductive N-alkylation of amines with higher aldehydes is described in U.S. Pat. No. 142,868. European Patent Nos. 3,707,503 and 4,163,026. United States of America and U.S. Pat. German Patent Publication. A common feature of all known noble metal catalyst processes is that the reaction is carried out in a batch mode, usually using a high noble metal catalyst, and is usually only suitable for the alkylation of amines, but not for the N-alkylation of amino alcohols.

It is an object of the present invention to provide a process for the preparation of amines and amino alcohols of general formula (I) on a reductive alkylation bed of low-precious metal catalysts in a continuous operation at a lower pressure than previously used. If the process is carried out batchwise, a very good yield can be obtained even if the pressure is considerably lower than usual.

In our experiments we found that when the compounds of formula (Π) with aldehydes of formula (ΙΠ)

P-CHO (III)

- Reductive N-alkylation of P in the presence of a supported noble metal catalyst and hydrogen in the presence of a hydrogen atom or a C 1 -C 3 alkyl group

During the reaction, 1-10 moles of alcohol can be removed from the aldehyde (ΠΙ) by the addition of one mole of hydrogen to 1 mole of aldehyde, or such an alcohol is produced directly in the reaction mixture at a substantially lower pressure than used hitherto, may be carried out in the presence of a low noble metal supported catalyst, optionally in continuous mode, to give the desired compounds of formula (I) in greater than 90% yield for both amines and amino alcohols

The present invention relates to a process for the preparation of N-alkylated amines or amino alcohols of the formula I by reductive N-alkylation of the amines or amino alcohols of the formula H with aliphatic aldehydes of the formula III in the presence of hydrogen and a supported platinum metal catalyst. by. According to the invention, the reductive alkylation can be derived from the alkylating aldehyde by the addition of 1 mole of hydrogen to 1 to 10 moles of alcohol, optionally generated in the reaction mixture itself, per mole of aldehyde.

a) on a supported catalyst containing 0.1 to 2% by weight of a platinum group metal, at a temperature of 50 to 200 ° C, at a pressure of 10 to 100 bar, with a liquid load of 0.2 to 4 dm ³ / dmxh, 100-1000 dm ³ / dm ³ gas / liquid the ratio being maintained in a continuous mode using hydrogen or a hydrogen-inert gas mixture containing at least 40% by volume of hydrogen, or

b) on a supported catalyst containing from 0.1 to 10% by weight of a platinum group metal, in the presence of 0.1 to 5% by weight, based on 1 mol of amine of the formula II, at 50 to 200 ° C and 2 to 100 bar; This is done for 15 hours at a batch rate.

Preferably 3-6 moles of the appropriate alcohol are used per mole of aldehyde (III). The aldehydes of formula (ΙΠ) may be introduced into the reaction either alone or in aqueous solution; however, the aqueous solutions should contain aldehyde in a concentration of at least 20% by weight.

The metal component of the catalyst can be any platinum group metal or any combination thereof. The carrier may be alumina, preferably a gamma modification thereof, aluminosilicate or activated carbon. A catalyst bed is formed which allows continuous operation

The reaction is conveniently carried out at a temperature of 80-150 ° C and a pressure of 25-60 bar.

The aldehydes of formula (III) are preferably employed in a molar ratio of 11.1 to the hydrogen atom to be replaced; from our practical experience, the transformation is now complete. When a larger excess of aldehyde is used, the excess is hydrogenated to the corresponding alcohol; Thus, the required alcohol can be developed in the reaction mixture itself.

The continuous use of the process of the present invention can provide very long production periods (2500 hours or more) during which the yield of the target product for both amines and amino alcohols is consistently greater than 90%. Our practical experience has shown that failure to use the appropriate alcohol at the required molar ratio with the aldehydes of formula (III) and to develop the required amount of alcohol in the reaction mixture results in a significant reduction in target yield and a reduction in catalyst life.

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

The process is suitable for reductive N-alkylation of a wide variety of amines and amino alcohols, and the desired compounds are formed in good yield.

- Reactants are completely transformed, so less and simpler purification operations are required to separate the target product.

- The process requires a low noble metal catalyst and the catalyst has a very long service life.

- The process can be carried out at significantly lower pressures than conventionally used, significantly reducing equipment and operating costs

- The process can also be performed in state-of-the-art, automated, high-productivity continuous mode equipment.

Because of the foregoing, the process of the present invention makes the compounds of Formula I extremely economically commercially available.

The invention is illustrated in detail by the following non-limiting Examples.

Example 1

On a 1 dm ³ catalyst containing 1 wt% palladium on activated carbon in a pressurized tubular reactor, 0.12 dm ³ (2 moles) of amino-ethanol, 0.36 dm ^{3 of} 37 wt% aqueous formaldehyde solution (4.9 moles of formaldehyde) 0.49 dm ³ (12.1 moles) of methanol and 400 dm ³ of 75% by volume hydrogen and 25% by volume nitrogen were passed through. The reaction was carried out at 100 ° C and 45 bar. Upon complete conversion of the reactants, the desired NN-dimethylaminoethanol was formed in 98% yield.

Example 2

On a catalyst in a pressurized tubular reactor with a volume of 1 dm ³ of 0.8 wt% palladium-on-carbon, 0.058 dm ³ (0.54 mole) of diethylenetriamine, 0.24 dm ^{3 of a} 37 wt% aqueous formaldehyde solution (3.3 mole of formaldehyde), 0.63 dm ³ (15.6 moles) of methanol, and 300 dm ³ of a gas mixture containing 75% by volume hydrogen and 25% by volume nitrogen. The reaction was carried out at 90 ° C and 50 bar. Upon complete conversion of the reactants, pentamethyldiethylenetriamine was formed in 91% yield.

Example 3

1 dm ³ palladium on activated carbon in a pressure-resistant tubular reactor

EN 204764 Β 0.14 dm ³ (1.1 mol) of N, N-dimethyl-1,3-propylene diamine per hour, 0.2 dm? 37% w / w aqueous formaldehyde solution (2.75 moles formaldehyde), 0.92 dm? (22.8 moles) of methanol and a gas mixture of 200 dm ³ , 75 volumes of hydrogen and 25 volumes of nitrogen were passed through. The reaction was carried out at 110 ° C and 60 bar. Upon complete conversion of the reactants, the desired NHH'H'-tetramethyl-1,3-propylenedianyanine was formed in 94% yield.

on a catalyst containing 0.11 dm per hour? (1.1 moles) of 2- (2-aminoethoxy) ethanol, 0.2 dm ^{3 of a} 37 wt% aqueous formaldehyde solution (2.75 moles of formaldehyde), 0.8 dm ³ (19.8 moles) methanol and a gas mixture containing 350 dm ³ of 75 volumes of hydrogen and 25 volumes of nitrogen were passed through. The reaction was carried out at 140 ° C and 70 bar. Upon complete conversion of the reactants, the desired 2- [2- (dimethylamino) ethoxy] -etanoT was formed in 90% yield.

Example 4

0.068 dm / h on a 1 dm ³ catalyst containing 1 wt% palladium on activated carbon in a pressurized tubular reactor? (0.68 mole) of 15 aminoethyl ethanolamine, 0.18 dm ^{3 of a} 37% aqueous solution of formaldehyde (2.5 moles of formaldehyde), 0.63 dm ³ (15.6 moles) of methanol and 150 dm ^{3 of} hydrogen was passed. The reaction was carried out at 100 ° C and 40 bar. With complete conversion of the reactants, the desired trimethylaminoethyl ethanolamine was formed in 90% yield.

Example 5

Placed pressure vial 1 25 Gatun volumetric dm ^3, 0.6 wt% of platinum catalyst comprising a gamma alumina carrier with 0.1 dm ³ per hour (1.7 mol) amino etauolt 0.2 dm ³ (3.6 mol of acetaldehyde, 1.05 dm ³ (18 moles) of ethanol, and 400 dm 2, 75% by volume hydrogen and 25 volumes of nitrogen. The reaction was carried out at 140 ° C and 50 bar.

Example 6

1 dm ³ catalyst volume, 0.5% by weight of rhodium deposited pressure vial containing a gamma-alumina support of 0.1 dm ³ per hour (1.8 mol) of aminoethanol 0.315 dm ³ (3.6 mol) of 40 butiral- carbaldehyde 0.9 dm ³ (9.8 moles) of n-butanol and 200 dm ^{3 of} hydrogen were passed through. The reaction was carried out at 145 ° C and 55 bar. With the complete conversion of the reactants, Ν, Ν-di-n-butylaminoethanol was formed in 92% yield.

Example 7 ·

1 dm ³ volume, containing 1% ruíéniumot gamma alumina support catalyst disposed pressure vial hour 0.1 dm ³ of 50 (0.875 mol) of cyclohexylamine, 0.13 dm ³ (1.8 mol) of propionaldehyde, 0.37 dm ³ (4.95 moles) of n-propanol and 200 dm ^{3 of} hydrogen were passed. The reaction

At a temperature of 135 ° C and a pressure of 55 bar, the desired N, N-di-n-55 cyclohexylamine was formed in 94% yield with full conversion of the reactants.

Example 8

I dm ³ volume, 0.6 wt% of platinum deposited pressure vial gamma alumina hormone N6

Example 9

On a 1 dm ³ catalyst containing 1.5 wt% palladium on activated carbon in a pressurized tubular reactor, a mixture of 0.07 dm ³ (0.29 mole) of polyoxypropylene diamines per hour was 0.4 dm ^{3 of a} 37 wt% aqueous formaldehyde solution (2 moles of formaldehyde) were passed through 0.8 dm ³ (19.8 moles) of methanol and 200 dm ^{3 of} hydrogen. The polyoxypropylene diamine used. H ₂ N-CH ₂ -C (CH ₃ ) - [O-CH ₂ CH (CH ₃ )] _p -NH ₂ , where p is 2.3 and the average molecular weight of the mixture is 230 It was carried out at a temperature of 160 ° C and a pressure of 75 bar. With the complete conversion of the reactants, the desired mixture of tetramethyl-polyoxypropylene diamines was formed in 9% yield.

Example 10

1 dm ³ volume mténiumot containing 0.5% gamma-alumina binder catalyst per hour, 0.083 dm ³ (0.7 mol) of N- (2-ethyl-aminp) piperazine 0.2 dm ³ pressure-resistant tube reactor positioned 37wt aqueous formaldehyde solution (2.75 moles formaldehyde), 0.85 dm ³ (21 moles) methanol and 300 dm ³ hydrogen were passed. The reaction was carried out at 95 ° C and 45 bar. Upon complete conversion of the reactants, the desired N- [2- (dimethylamino) ethyl] -N'-methylpiperazine was formed in 90.5% yield.

Example 11

0.3 dm ³ (1.5 moles) of dicyclohexylamine, 0.22 dm ^{3 of a} 37 wt% aqueous formaldehyde solution in a 1 dm ³ catalyst containing 1.5 wt% palladium on activated carbon in a pressurized tubular reactor mole of formaldehyde, half of which forms methanol) and a gas mixture of 250 dm ^{3 of} 75 volumes of hydrogen and 25 volumes of nitrogen was passed through. The reaction was carried out at 120 ° C and 45 bar. The reaction of the complete reactants with the desired N-methyldicyclohexyl- arnine was formed in 91% yield

Example 12

In a pressurized autoclave with a volume of 20 dm ³ , with stirring, 1 dm ³ (16.7 moles) of ethanolamine, 3 dm ³ (53.35 moles) of acetaldehyde, 9 dm ³ (154.2 moles) of ethanol and 45 g of 5 wt% palladium active on a carbon support. The pressure of the autoclave was maintained at 5 bar with the introduction of hydrogen gas. AL4

The reaction was carried out at 80 ° C for 6 hours with stirring at 204764 ° C. Upon complete conversion of the reactants, the desired Ν, Ν-dimethylaminoethanol was formed in a yield of 93.5%.

Example 13

In a pressurized autoclave with a volume of 20 dm ³ , with stirring, 1 dm ³ (7.54 moles) of n-hexylamine, 8.5 dm ³ (210.4 moles) of methanol, 1.7 dm ^{3 of} 37% aqueous formaldehyde (23.3 moles of formaldehyde) and 8 g of 8% palladium on carbon in catalyst were weighed. The pressure of the autoclave was maintained at 6 bar by the introduction of hydrogen gas. The reaction was carried out at 95 ° C for 8 hours with constant stirring. The NN-dimethyl-n-hexylamine was obtained in 94% yield with the complete conversion of the reactants.

Example 14

This example is provided by way of comparison to demonstrate that, if the reaction is carried out in the absence of alcohol and the mixture is not developed in situ at least 1 mol of alcohol per mole of aldehyde, the yield of the process is significantly reduced.

All were carried out as described in Example 1 except that no methanol was added to the reactor. The reaction mixture contained 4.94 moles of formaldehyde per mole of aminoethanol; considering that the addition of the two methyl groups requires 4 moles of formaldehyde, only 0.94 moles of methanol could be formed from the excess formaldehyde under the reaction conditions. With the complete conversion of the reactants, the desired Ν, Ν-dimethylaminoethanol was formed in only 70.8% yield.

Claims (2)

PATENT CLAIMS A process for the preparation of N-alkylated amines or amino alcohols of the formula I X-A-N (R) -B-X (I) in the formula R is C 1-4 alkyl, X is hydrogen, hydroxy or -N (R) ₂ , wherein R is as defined above, and the R groups in the compound of formula (I) may be the same or different, with the two X groups being the same or different, A is -Y- or (-YQ) _p -Y-, and B is -Y- or (-YO) _q -Y-, wherein p and q are independently 1, 2 or 3, and Y represents a straight or branched C 1 -C 6 alkylene group and the Y groups may be the same or different, but at most one of A and B at the same time may contain an ether bond, or XA and / or XB may be cyclohexyl, cyclopentyl, may represent methylcyclopentyl or cyclopentylmethyl, or XA or XB together with the attached -N (R) group may form a piperazino or morpholino group, provided that the other moiety in the compound of formula (I) X can only be -N (R) ₂ -, amines of formula II or amino alcohols W-A-N (R ') - Z (II) in the formula Z is hydrogen or -B-W 'A and B are as defined above, W and W 'independently of one another are hydrogen, hydroxy, amino or -NHR or -N (R) ₂ , wherein R is C 1 -C 4 alkyl, and in -N (R) ₂ , the R groups may be the same or different, and R 'is hydrogen or (C 1 -C 4) -alkyl, provided that the compounds of formula (II) always contain at least one -N-H bond with the aliphatic aldehydes of formula (III) P-CHO (in) wherein P is hydrogen or (C 1 -C 3) alkyl by reductive N-alkylation of hydrogen with a supported platinum group metal catalyst, characterized in that the reductive alkylation can be derived from the alkylating aldehyde by up to 1 mole of hydrogen per mole of aldehyde. in the presence of alcohol, optionally developed in the reaction mixture itself a) on a supported catalyst containing from 0.1 to 2% by weight of a platinum group metal, at a temperature of 50 to 200 ° C, at a pressure of 10 to 100 bar, with a liquid load of 0.2 to 4 dm ³ / dm ³ per hour, 100-1000 dm ³ / dm ³ / fluid ratio using hydrogen or a hydrogen inert gas mixture containing at least 40 volumes of hydrogen in a continuous mode, or b) on a supported catalyst containing from 0.1 to 10% by weight of a platinum group metal, in the presence of 0.1 to 5% by weight, based on 1 mol of amine (Π), at 50 to 200 ° C and 2 to 100 bar; We do it in batch mode for 15 hours. (Priority: December 12, 1990) 2. A process for the preparation of N-alkylated amines or amino alcohols of formula Ia X - (CH ₂ ) _n - N (R) - (CH ₂ ) _m - X '(la) - in the formula R is C 1-4 alkyl, X and X 'are independently hydrogen, hydroxy or -N (R) ₂ wherein R is as defined above and R groups in the compound of formula (I) may be the same or different, n is an integer from 2 to 6, m is An integer from 1 to 6, and when n and / or m is 5 or 6, X- (CH ₂ ) _n - or X '- (CH ₂ ) _m - is cyclopentyl, cyclopentylmethyl, methyl may also be cyclopentyl or cyclohexyl, amines or amino alcohols of formula Ha W- (CH 2) _n -N (R ') - Z (Ha) in the formula Z is hydrogen or - (CH2-W ') wherein m is as defined above, W and W * independently of one another are hydrogen, hydroxy, amino, or -NHR or -N (R) 2, wherein R 1 is C 4 -C 4 alkyl, and in -N (R) 2, the R groups may be the same or different; R 1 is hydrogen or C 1 -C 4 alkyl, and n is fend, with the proviso that the compounds of formula Ha always contain at least one N-H 15 bond with the aliphatic aldehydes of formula III P-CHO. (ΙΠ) wherein P represents a hydrogen atom or a C 1-3 alkyl group by reductive N-alkylation of hydrogen and its carrier in the presence of a platinum group metal catalyst, characterized in that the reductive N-alkylation can be deduced from 1 mole of hydrogen by alkylation molar amount of alcohol used in the presence of 0.1-2% by weight supported catalyst containing a platinum group metal, at a temperature of 50-200 ° C, dm folyadékteiheléssel, 100-1000 10-100 psi, 0.2-4 dm ³ / dm ^{3 three} Xora / dm ³ gas / liquid ratio using hydrogen or a hydrogen-inert gas mixture containing at least 40% hydrogen by volume in a continuous mode. (Priority: 10/10/1989)