DE1445423A1 - Process for the preparation of tertiary amines - Google Patents

Description

concerning
Process for the preparation of tertiary amines

The invention "relates to the preparation of tertiary amines. In particular" it relates to the preparation of H-cyclohexylpiperidines, which may be substituted in the piperidine ring by a lower alkyl group p

Various processes for the production of U-cyelohexylpiperidine have previously been reported, but all these older processes are so impractical and inefficient that they are only laboratory features. Terfahreh, published in Japan 64, 253-5 (1944), introduces a general procedure. Production of 1-alkylpiperidines. It describes a process for the hydrogenation of a & emisehes of! »Yridine and phenol in & the present of Hahey-III.

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which it requires high hydrogen pressures is just about
reported a yield of 1.2 '$ H -cyclohexylpiperidine.
Such a production of W-Oyclohexy! Piperidine is obviously impractical and uneconomical.

lin aim of the invention is therefore a new process for the preparation of N-Oyclohexylpiperidin, in which
the ^ iperidine nucleus can be substituted by a lower alkyl group. Another object of the invention is a
Low pressure process for the preparation of N-cyclohexylpiperidines of the type indicated above. Another object of the invention is to achieve high yields of N-gyelohexylpiperidines by a catalytic hydrogenation process
generally used, inexpensive raw materials. Another object of the invention is an economical process for the production of F-cyclohexylpiperidine which can have an alkyl substituent in the heterocyclic ring.

These and other objects are achieved by a process for the preparation of tertiary imines of the formula

achieved ϊ wöb§i in the Öer formula H gin WägsiistöffäiJöm öler an aäärige aikyi group means »iläbh äiesem

be phenol, hydrogen and pyridine, alkyl pyridine, piperidine or O-alkylpiperidine in the presence of a catalytic Amount of palladium at a hydrogen pressure of less reacted than 7 atmospheres (100 psig.).

In a simple embodiment, pyridine is in a hydrogenation vessel, e.g. B. a Parr shaker, a Flask or other low pressure device, along with an equimolar amount of phenol. After adding The hydrogenation device is used for 0.05 to 1 part of metallic palladium on a support per 100 parts of pyridine and phenol flushed in the usual way with nitrogen and then with hydrogen to remove all oxygen from the flask to remove. The hydrogenation is then carried out by external heating and shaking of the hydrogenation flask is initiated and continued until the hydrogen uptake has ceased. laughed quit The catalyst is filtered off after uptake of hydrogen and the filtrate is separated into its constituents by distillation.

The following examples show the hydrogenation times required and the yields obtained

example 1

A mixture of 21.2 g (0.25 mol) piperidine, 23.5 g (0.25 mol) phenol, 2., 0 g catalyst, consisting of 5 $> PaI-

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Charcoal on carbon (catalyst ratio: 0.224 ^ metal, based on the total weight of the participants) and 1.0 g of a filter aid were placed in a Parr hydraulic flask. The mixture was heated up to a maximum temperature of 96 ° C and bej_. Hydrogenated to a maximum hydrogen pressure of 4.15 atmospheres (59.0 psig.). Over 6 hours were about "" 75 f ^a of the theoretical amount of hydrogen "absorbed and in less than 15 hours, the theoretical amount of hydrogen. Pas mixture was filtered and the filtrate was distilled, whereby a major fraction i with an analytically determined content of 98.8» JJ-cyelohexylpiperidine was obtained. The infrared spectrum of this fraction was identical to that of an analytical sample of H-cyelohexylpiperidine... "

In the above experiment, the catalyst was based on aluminum oxide precipitated, it was under otherwise identical reaction conditions largely achieved the same result.

Example 2;

A mixture of 19.8 g pyridine, 23.5 g phenol, 2 g Catalyst made of 5 $ palladium (0.23 ^, based on the total, weight of the reaction participants) on activated carbon and One gram of filter aid was placed in a Parr shaker with a maximum temperature of 97 ° 0 and a ma-

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ximal hydrogen pressure of 4.15 atmospheres (59 »1 psig.) hydrogenated. Uach 6 hours were recorded over $ 60> of the theoretical amount of hydrogen and after 22 hours the hydrogenation "was completed, filtration was laughing gas chromatographic analysis of the crude mixture of the reaction products have a content of 92.5 $> N-Gyclohexylpiperidin and 7.3 f <> piperidine.

Example 3:

Mn mixture of 18.6 g (0.2 mol) of OC-picoline, 18.8 g (0.2 mol) of phenol, 2 g of catalyst made from 5 1 ° palladium (0.27 #, based on the total weight of the Ee action participants) on activated charcoal and 1.0 g of a filter aid was hydrogenated at a maximum hydrogen pressure of 4.13 atmospheres (58.7 psig.) and a maximum temperature of 100 ° C. After 22 hours the catalyst was filtered off, a clear, colorless solution being obtained. The gas chromatographic analysis of this solution showed a content of 66.5 $ N-cyclohexyl-2-methylpiperidine, 9.5 $> 2-methylpiperidine, 0.7 ° / ° unreacted oC-picoline, 10.8 $ cyclohexanol and 12.6 f> other saturated cyclic compounds.

Example 4s

A mixture of 18.6 g of ß-picoline, 18 ^ 8 g of phenol * 2.0 g of catalyst from 5 ° palladium on activated carbon and 1.0 g of a

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121

Filter aid was hydrogenated under a maximum pressure of 4.18 atmospheres (59.5 lpsig.) And at a maximum temperature of 105.5 ° C. After 18 hours, almost the theoretical amount of hydrogen had been absorbed. Uach DEM filtration was in clear, colorless solution by gas chromatographic analysis of a content of 95.2 fi JT-Oyclohexyl-3-methylpiperidine, 3 ° f not in Eeaktion getretenem .beta.-picoline, 0.2 fo cyclohexanol and 0.3 ί ° 3-methylpiperidine detected. The solution of the reaction products was fractionally distilled under reduced pressure, a main fraction being obtained with an analytically determined content of 99 ^σ β> pure F-cyclohexyl-3-diethylpiperidine.

In the above experiment, the catalyst was based on aluminum oxide precipitated, so largely the same result was obtained under otherwise identical reaction conditions.

Example 5? ■

A mixture of 24.2 g (0.2 mol) of 2-n-propylpyridine, 18.8 g of phenol, 1.74 g of catalyst from 5 ^ palladium (0.20 fo \ based on the Gesamtgewicnt of the reactants) on activated carbon and 1.0 g of a filter aid was hydrogenated in a Parr schiittel device at a maximum temperature of 94 Ό and a maximum hydrogen pressure of 4 * 11 atmospheres (58> 4 psigo) ο in less than 23 hours the theoretical amount of hydrogen was added from the reaction mixture . the

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Filtration led to a clear, colorless liltrat in which by gas chromatographic analysis, a content τοη 51.8 io N-cyclohexyl-2-n-propylpip.eridin, 27.6 fi 2-n-propylpiperidine, 11.8 fo cyclohexanone and 8 , 7 f ° cyclohexanol was found.

Example 6; ~ "

A mixture of 24.2 g of 4-n-propylpyridine, 18.8 g of phenol, 2.3 g of palladium catalyst made of 5 ° metallic palladium (0.27 °, based on the total weight of the reaction participants) on activated carbon and 1.0 g of a filter aid was hydrogenated under a maximum pressure of 4.11 atmospheres (5 &, 5 psig) and at a maximum temperature of 96 ° 0. After the uptake of hydrogen (24 h), the mixture was filtered and the filtrate Analyzed by gas chromatography, a content of 97.8 fo N-cyclohexyl-4-n-propylpiperidine was found.

The above examples show that the process according to the invention a practical and economical pressure synthesis made possible by N-cyclohexylpiperidine, the latter in the piperidine ring may be substituted by a lower alkyl group · The obtained by this new process Results are very surprising and unexpected, since an identical procedure, but using alkyl-substituted ones Phenols, together with substituted or unsubstituted

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tuted pyridines. or piperidines as starting material, failed completely, do η. that no measurable hydrogen uptake could be observed when a mixture is equimolar Amounts of cresol and pyridine or piperidine after. method according to the invention was treated.

The advantages of the invention are that from cheap, commercially available starting materials high yields of bicyclic saturated compounds in a simple, one-step process Processes that do not require high pressures, and small amounts of catalyst are excellent Deliver results »

For practical reasons, 0.05 to 1 fo metallic palladium, based on the total amount of phenol- and (alkyl-substituted) pyridine or piperidine in the starting material, is used. If smaller amounts of catalyst used, the hydrogen consumption for economic Liehe carrying out the process may be too slow and catalyst ratios, fi over 1 lead to any results improvers, as a catalyst ratio within the range specified above.

It is extremely surprising that the invention Process using a palladium catalyst and pyridine or an alkyl-substituted pyridine as starting material

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can be carried out, since pyridine usually "at Yerwen-. Since this catalyst cannot be saturated, there is no reaction for the hydrogenation of a pyridine ring among the mild conditions of the process according to the invention known. A further advantage of the method according to the invention "consists that the catalyst can be reused, i.e. H., after the catalyst has been filtered off from the hydrogenation mixture, it can be used for subsequent reductive condensation reactions can be used without cleaning or regeneration. The catalyst can be based on activated carbon, zirconium oxide, bentonite, aluminum oxide, Silicon dioxide, kieselguhr and the like usually used catalyst supports are deposited.

The hydrogenations according to the invention are preferably carried out in a temperature range from 60 to 120 ° 0 and at water, fabric prints performed at less than 7 atmospheres (100 psig.) whereby so-called low pressure hydrogenation devices are used can be.

In most embodiments of the invention the use of a solvent is undesirable, although the presence of an inert solvent is necessary for the process is not disadvantageous and only requires a more complicated isolation procedure for the desired tertiary amine * Is However, the alkylpyridine or alkylpiperidine used as the starting material is a solid, then the use of a inert solvent boiling above 60 ° C. is desirable be. The term "inert" is intended to mean that the solvent

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tel does not act on any of the reactants in the reaction mixture, under the circumstances described above, suitable solvents are, for. B. alcohols such as ethanol, propanol, isopropanol, butanol and ethyl acetate. In order to achieve the best results, an inert solvent with a boiling point ■ above 80 ° 0 is chosen to enable higher reaction temperatures without the use of excessive pressure. »

Claims

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Claims (5)

1A-25,949 Claims 1. Process for the preparation of tertiary amines of the formula wherein R is a hydrogen atom or a lower alkyl group "means, characterized in that one a mixture of phenol with one of the heterocyclic compounds * Pyridine, pyridine substituted by a lower alkyl group, piperidine or on a G atom by a never Third alkyl group-substituted piperidine with gaseous hydrogen at a pressure of from atmospheric pressure to about .7 atü and a temperature of about 60 ° G to 120 ° G in the presence hydrogenated catalytic amounts of palladium. 2. The method according to claim 1, characterized in that 0.05 to 1.0! Parts of palladium each 100 parts total weight of phenol plus heterocyclic! Respondents applies. 3. The method according to claim 1, characterized in that equimolar amounts of phenol and heterocyclic Hydrogenated reactant. - 12 - 8 0 9 8 0 9/1121 4. The method according to claim 5> characterized in that there is used as the heterocyclic reactant pyridine. 5.. Process according to Claim 3, characterized in that the heterocyclic reaction participants Picoline Uses .-- 8098G9 / 1121