JPS5919102B2 - Method for producing N-alkyl derivatives of cyclic alkylene imine - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for converting cyclic alkyleneimines into N-
It relates to a method of alkylation.

Various methods for N-alkylating aliphatic heterocyclic nitrogen compounds have been previously described. According to Hoben, Weyl, 4th edition, Vol. 11/1, page 112 and below, a distinction is made between methods using catalysts that perform hydrogenation-dehydrogenation actions and methods using catalysts that perform dehydration action. The amine is reacted with the alcohol or carbonyl compound under pressure and heat, often in the presence of a hydrogenation catalyst and hydrogen.

Perky Patent No. 694,068 describes the reaction of morpholin and alcohol at 150 to 300° C. and at a pressure of 35 to 350 atmospheres using a catalyst consisting of nickel or cobalt, copper and titanium dioxide. It describes what to do.

According to German patent application B 13494, when a mixture of aliphatic ketones and piperidine or pyrrolidone is treated with hydrogen in the presence of nickel, cobalt and a catalyst at relatively high temperatures and pressures, N -alkyl-piperidine and -pyrrolidone are formed.

Journal of,Organic,Chemistry,No.2
1 (1956), pages 86 and 87, describes the alkylation of piperazine with an alcohol at 200° C. using Raney Nickel.

Methylation is 50 to 9 with formaldehyde and hydrogen.
It is carried out in one stage at 0° C. and a pressure of 30 to 50 atmospheres using a cobalt catalyst. The disadvantage of hydrogenation methods is that high pressure, often expensive catalysts and hydrogen are required to carry out the reaction.

Reactions using dehydrating catalysts are widely available according to Hoben and Weyl, but this document concerns reactive agents which are generally of little pharmaceutical importance.
Catalysts that react with acidity must also be avoided. Although little is known about alkylating cyclic imines at the nitrogen atom, Garik and co-workers [COll.
OfCzechOslOvalcChemicalCO
33 (1968), No. 2, pp. 609-613], the reaction of piperidine and alcohol in the presence of aluminum oxide to form N-alkyl-piperidine was investigated and The rate was only 19-56% of theory. Aluminum oxide, phosphoric acid, alumosilicate and other dehydrating catalysts are described, for example, in German Pat. No. 617,990 or Ind. En8. Chem. PrOd. Re8.
DevelOpm. 7, p. 159 (1968), it is mainly used for the alkylation of aromatic amines. It is an object of the present invention to provide a process by which the N-alkylation of cyclic alkyleneimines can be carried out with aliphatic hydroxyl compounds at atmospheric pressure. However, when the reaction is carried out in the presence of a catalyst consisting of silicon dioxide containing phosphoric acid, and when the reaction is carried out in the gas phase, the above object is achieved in particular in the presence of a catalyst consisting of silicon dioxide containing phosphoric acid. It has been found that this can be achieved with the advantage of high yields and very good reactivity when using silicon dioxide with a specific surface area of 50 i/t.

The cyclic alkylene imine in the present invention which is alkylated at the secondary amine hydrogen generally has the following formula [wherein R1 is
saturated C2-C,2-polymethylene groups having up to 2 methyl and/or ethyl substituents,
or a difunctional group selected from a C3-ClO polymethylene heterochain group having 1 to 2 nitrogen, oxygen and/or sulfur atoms inserted into the chain.

Therefore, suitable imino compounds in the present invention include, for example, ethyleneimine, propyleneimine-(1,3) (=azacyclobutane); 5-membered cyclic compounds such as butyleneimine (=pyrrolidine), imidazolidine, 1- Methylimidazolidine, oxazolidine, thiazolidine, 6-membered cyclic compounds such as piperidine, 3-propylpiperidine, piperazine, N-alkylpiperazine, perthrow(1,3)-oxazine, perhydropyrimidine, perthrow(1,3)-thiazine , 7-membered cyclic compounds such as hexamethyleneimine (=perhydroazepine), perhydrothiazepine and cyclic compounds with higher imino groups such as decamethyleneimine and its derivatives. Preferred imines are morpholine, piperazine, pyrrolidine, piperidine and hexamethyleneimine. Suitable alcohols include saturated lower aliphatic alcohols such as methanol, in particular methanol, and also ethanol and isopropanol.

The reaction is carried out in the gas phase, the catalyst being used in a fixed bed or in a fluidized bed.

Therefore, it becomes clear that a suitable imine is required that satisfies the structural condition that it must be able to evaporate without being decomposed at the reaction temperature. If the vapor pressure of the compound at the reaction temperature is not sufficient for complete evaporation, the compound is converted into the gas phase, for example with the aid of a carrier gas stream or under reduced pressure. The reaction temperature is 15%
The temperature is preferably 0 to 350°C, particularly 180 to 300°C.

Normally it operates at normal pressure, but slightly elevated or lower pressures, for example from 0.1 to 5 atmospheres, may be used. The catalyst preferably has a molecular weight of 50 to 500, especially 300 to 450 i/F.
It consists of SiO2 with a specific surface area of 7 and preferably 0.1 to 20, in particular 2 to 10% by weight of phosphoric acid, based on the total weight of the catalyst.

Thus, using such catalysts, N-alkylations are carried out in particular in high yields. 60 in fluidized bed catalyst equipment
Particle sizes of between 1000 microns and 1000 microns are suitable. When using a fixed bed catalyst device, the catalyst is a sphere,
Used in the form of cords or in irregular forms. Suitable catalysts are prepared by known methods.

It is particularly advantageous to prepare suitable catalysts in the following manner. By adding sulfuric acid, commercially available soda water glass is converted into water-rich silicic acid hydrogel through an intermediate stage of silicic acid sol, and this is desalted (eluted) with aqueous ammonia.

Peptization (liquefaction) occurs when the desalted hydrogel is treated with an appropriate amount of phosphoric acid with the addition of oxalic acid in a mill or other device that generates shear forces. When the aqueous phase obtained is blown into, for example, a flue gas stream, a granular powder is produced which is suitable as a fluidized bed catalyst. Silicate gel cords may also be produced by other suitable drying methods. The internal surface area of the obtained catalyst is measured, for example, by the known BET method.

An overview of the field of production of such catalysts can be found in Ullmann/SEN's 10 pages.
c11nischenChemie 3rd edition Volume 9 No. 27
5 and below and Volume 15, page 712 and below.

It is advantageous to carry out the reaction in this way.

Evaporate the amine and alcohol at a suitable temperature,
For example, by mixing in a molar ratio of 4:1 to 1:1 (alcohol to amine), or by completely evaporating the corresponding mixture at a correspondingly high temperature, the vapor mixture is passed over the catalyst and condensed after the reaction. urge In this case, inert gaseous diluents such as nitrogen can also be present. The reaction of the amine is generally 90 to 98% when the catalyst is limited as described above, and the yield of the reacted amine is theoretical in the space/time/yield of 200 to 600 y per hour per reaction chamber 11. reaching 90 to 96%. A particular advantage of this process is that high yields and high space-time yields are achieved in less restrictive equipment under conditions that are easy to adjust and maintain.

N-alkyl derivatives of cyclic imines can be used, for example, as auxiliaries.
Used as an intermediate, drug or catalyst.

Thus, for example, N-methylmorpholine is used as a rubber auxiliary, and N-methylpiperazine is known as a psychoactive drug. Example 1 As a test device that can be easily converted to an industrial scale,
0m7! An electrically heated quartz tube with a length of 40 CrfL and a quartz evaporator are used.

The quartz tube is installed vertically and consists of up to 90% by weight of silicon dioxide and up to 10% by weight of phosphoric acid, and has a length of 400 d.
/y specific surface area (measured by BET method) and 15 to 1
It contains a catalyst particle size of 60 to 200 microns with a pore radius of 00A. A mixture consisting of 40% by weight of morpholine and 60% by weight of methanol was evaporated every hour at 160° C. for 106 y, and at 200° C. for 20 y of fluidized bed catalyst.
0111 and condensed in a subsequent cooler.

A condensate 105y consisting of up to 40.5% by weight of N-methylmorpholine is obtained every hour. This corresponds to a reaction of 95% and a yield of 91% with respect to the reacted morpholin. 50? By fractional distillation on a packed column of length N-methylmorpholine is obtained with a purity of 99%.

Example 2 The test is repeated as described in Example 1.

Instead of an amount of 1067 per hour, 2407 per hour is conducted over the catalyst at 280°C. The reaction was 95%,
The yield of N-methylmorpholin is 88%, based on the reacted morpholin. It is easy to see from this change in test conditions that the reaction is relatively insensitive to changes in the conditions. Example 3 In the apparatus described in Example 1, 40% by weight of pyrrolidine and 6% methanol were evaporated every hour at 165°C.
A mixture 50y consisting of 0% by weight is reacted at 190°C.

The reaction is 93% and the yield of N-methylpyrrolidine based on the reacted pyrrolidone amounts to 89%. EXAMPLE 4 120 ml of a mixture of 57% by weight piperazine and 43% by weight methanol are evaporated every hour at 160 DEG C. and introduced at 220 DEG C. onto the fluidized bed as described in Example 1.

The reaction of piperazine is 49.3%.

The weight ratio of N-methylpiperazine and N-N-dimethylpiperazine is 85:15. The overall yield of both derivatives is 93%. Example 5 The procedure is as described in Example 4, but instead of 120 ml, 60 ml per hour are now passed over the catalyst at 180 DEG C.

In the 34% reaction, the proportion of singly alkylated piperazine is 92% and the proportion of doubly alkylated piperazine is 8%.

Claims (1)

[Claims] 1. A method for N-alkylating a cyclic alkylene imine with an aliphatic hydroxyl compound or its ether at normal pressure in the presence of a dehydrating catalyst, using silicon dioxide containing phosphoric acid as a catalyst, and A method for N-alkylating a cyclic alkylene imine at normal pressure, characterized in that the reaction is carried out in a gas phase.