CA1122981A - Preparation of stereoisomeric n-aralkyl-2,6-dimethyl-morpholine - Google Patents
Preparation of stereoisomeric n-aralkyl-2,6-dimethyl-morpholineInfo
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- CA1122981A CA1122981A CA328,740A CA328740A CA1122981A CA 1122981 A CA1122981 A CA 1122981A CA 328740 A CA328740 A CA 328740A CA 1122981 A CA1122981 A CA 1122981A
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- palladium
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
O.Z. 0050/033,283 Abstract of the Disclosure: A process for the preparation of stereoisomeric N-aralkyl-2,6-dimethylmorpholines by reacting aralkanals with stereoisomeric 2,6-dimethyl-morpholines.
Description
~lZ2~8~
- 1 O.Z. 0050~0332 Preparation of stereoisomeric N-aralkyl-2,6-dimethylmorpholines The present invention relates to a process for the preparation of stereoisomeric N-aralkyl-2,6-dimethylmorpho-lines by reacting aralkanals with stereoisomeric 2,6-dimethyl-morpholines.
The preparation of tertiary amines ~y reacting secondary amines with carbonyl compounds in the presence of hydrogen and of a hydrogenation catalyst is kIlown (Houben-Weyl "Methoden der organischen Chemie!', 4/2, page 328).
German Laid-Open Application DOS 2,118,283 describes ~he preparation of tertiary aliphatic or cycioaliphatic am~res by reaction of aliphatic or cycloaliphatic carbonyl cc,~;pounds with secondary aliphatic or cycloaliphatic amines in ~ e presence of hydrogen and of a palladium-silver catalyst.
The advantage of this catalyst is that it enables the reduc-tive alkylation of secondary aliphatic or cyc'oaliphati~
amines to be carried out with high yield and substantia'ly without formation of by-products. The side-reaction fre-quently observed on reductive alkylation of amines, ramely hydrogenation of the carbonyl compounds, with formatiorl of the corresponding alcohols, is avoided when usin~ the above catalyst. Further, Germar Patent 1,179,947 discloses that if the synthesis of N-alkylated aromatic amines is car~ied out by reductive alk~rlation of aromatic amines over a palladium-silver catalyst, the arom2tic system remains unaffected.
We have found that stereoisomeric N-aral~yl-2,6-llZZ~
dimethylmorpholines of the formula I
1 ~ CH-CH-CH-N ~ I
where R1 is hydrogen, an aliphatic radical of 1 to 10 carbon atoms or alkoxy of 1 to 6 carbon atoms and R2, R3 and R4 are hydrogen or an aliphatic radical of 1 to 4 carbon atoms, or defined mixtures of these compounds, may be obtained in a simple manner by reacting stereoisomeric 2,6-dimethyl-morpholines of the formula II
/--< II
HN~f CH3with compounds of the formula III
Rl ~ 12 13 1 4 III
where Rl, R2, R3 and R4 have the above meanings, if the reaction is carried out in the presence of hydrogen and of a hydrogenation catalyst which contains palladium mixed wi~h silver on an inert carrier.
In particular, the present invention provides a process for the preparation of a stereoisomeric N-aralkyl
- 1 O.Z. 0050~0332 Preparation of stereoisomeric N-aralkyl-2,6-dimethylmorpholines The present invention relates to a process for the preparation of stereoisomeric N-aralkyl-2,6-dimethylmorpho-lines by reacting aralkanals with stereoisomeric 2,6-dimethyl-morpholines.
The preparation of tertiary amines ~y reacting secondary amines with carbonyl compounds in the presence of hydrogen and of a hydrogenation catalyst is kIlown (Houben-Weyl "Methoden der organischen Chemie!', 4/2, page 328).
German Laid-Open Application DOS 2,118,283 describes ~he preparation of tertiary aliphatic or cycioaliphatic am~res by reaction of aliphatic or cycloaliphatic carbonyl cc,~;pounds with secondary aliphatic or cycloaliphatic amines in ~ e presence of hydrogen and of a palladium-silver catalyst.
The advantage of this catalyst is that it enables the reduc-tive alkylation of secondary aliphatic or cyc'oaliphati~
amines to be carried out with high yield and substantia'ly without formation of by-products. The side-reaction fre-quently observed on reductive alkylation of amines, ramely hydrogenation of the carbonyl compounds, with formatiorl of the corresponding alcohols, is avoided when usin~ the above catalyst. Further, Germar Patent 1,179,947 discloses that if the synthesis of N-alkylated aromatic amines is car~ied out by reductive alk~rlation of aromatic amines over a palladium-silver catalyst, the arom2tic system remains unaffected.
We have found that stereoisomeric N-aral~yl-2,6-llZZ~
dimethylmorpholines of the formula I
1 ~ CH-CH-CH-N ~ I
where R1 is hydrogen, an aliphatic radical of 1 to 10 carbon atoms or alkoxy of 1 to 6 carbon atoms and R2, R3 and R4 are hydrogen or an aliphatic radical of 1 to 4 carbon atoms, or defined mixtures of these compounds, may be obtained in a simple manner by reacting stereoisomeric 2,6-dimethyl-morpholines of the formula II
/--< II
HN~f CH3with compounds of the formula III
Rl ~ 12 13 1 4 III
where Rl, R2, R3 and R4 have the above meanings, if the reaction is carried out in the presence of hydrogen and of a hydrogenation catalyst which contains palladium mixed wi~h silver on an inert carrier.
In particular, the present invention provides a process for the preparation of a stereoisomeric N-aralkyl
2,6-dimethylmorpholine of the formula C~3 ~f H3 Rl~CH2-C~I-CH2 N~
where Rl is hydrogen, alkyl of 1 to 6 carbon atoms or methoxy or of a defined mixture of such compounds, by reacting a stereoisomeric 2,6-dimethylmorpholine of the formula ~ 2 --,, . ~ ., 112Z9~l , ~ CH3 H~ 'o or a defined mixture of such compounds with a compound of the formula fH3 1~ C~H2-cH--f=O
H
where Rl, has the above meaning, wherein the reaction is carried out in the presence of hydrogen and of a hydrogenation catalyst which contains palladium mixed with silver on an inert carrier.
The reaction is advantageously carried out at from 100 to 190C under pressures of from 5 to 300 bar.
The advantaye of the proce~s according to the inven-tion is that no isomerization reactions occur on the above hydrogenation catalyst under the stated conditions~ so that, for example,,on reacting pure cis-2,6-dimethylm~rphol_ne.,of ,,, 9~
where Rl is hydrogen, alkyl of 1 to 6 carbon atoms or methoxy or of a defined mixture of such compounds, by reacting a stereoisomeric 2,6-dimethylmorpholine of the formula ~ 2 --,, . ~ ., 112Z9~l , ~ CH3 H~ 'o or a defined mixture of such compounds with a compound of the formula fH3 1~ C~H2-cH--f=O
H
where Rl, has the above meaning, wherein the reaction is carried out in the presence of hydrogen and of a hydrogenation catalyst which contains palladium mixed with silver on an inert carrier.
The reaction is advantageously carried out at from 100 to 190C under pressures of from 5 to 300 bar.
The advantaye of the proce~s according to the inven-tion is that no isomerization reactions occur on the above hydrogenation catalyst under the stated conditions~ so that, for example,,on reacting pure cis-2,6-dimethylm~rphol_ne.,of ,,, 9~
- 3 - O.Z. 0050/0~28 the formula II with carbonyl compounds of the formula III, the pure cis-isomers of the end products I are obtained, free from their stereoisomers.
It is known that isomeriza~ions can be carried out over hydrogenation catalysts and that on using such cata-lysts for reductive alkylations of amines or for hydrogena-tions, isomerizations must always be expected to occur as side-reactions (Houben-Weyl "Methoden der organischen Chemie",
It is known that isomeriza~ions can be carried out over hydrogenation catalysts and that on using such cata-lysts for reductive alkylations of amines or for hydrogena-tions, isomerizations must always be expected to occur as side-reactions (Houben-Weyl "Methoden der organischen Chemie",
4/2, pages 276 - 283).
In the process according to the invention, the amine component may be employed in the stoichiometric amount or in up to 10-fold molar excess.
The following carbonyl compounds are examples of suitable starting materials of the formula ITI: 3-phenyl-3-methyl-propanal, 3-phenyl-2-methyl-propanal, 4-phenyl-butan-2-one, 3-(4'-methylphenyl)-2-methylpropanal, 3-(4'-isopropyl-phenyl)-2-methyl-propanal, 3-(4'-tertiary butylphenyl)-2-methyl-propanal, 3-phenyl-2-ethyl-propanal, 3-phe~yl-2-iso-propyl-propanal, 3-(4'-isopropylph.enyl)-3-methyl-propanal, 2b 3-(4'-tertiary butylphenyl)-3-methyl-propanal, 3-(4'-tertiary butylphenyl)-butan-4-one, 3-(4'-methoxyphenyl)-2-methvl-propanal and 3-(4'-.isopropoxyphenyl)-2-methyl-propanal.
The starting materials III are prepared from the corresponding substituted benzaldehydes and aliphatic a.lde-hydes or ketones by an aldol condensation followed by partial hydrogenation of the resulting carbon-carbon double bond (U,S. Patent 2,976,321). Some of the compounds C~l also be prepared by hydroformylation of substituted styrenes.
The reaction is advantageously carried cut at fr~
1~ 2Z98~
- 4 - O.Z. 0050/033283 100 -to 190C under a hydrogen pressure of from 5 to 300 bar It may be carried out without a solvent or in the presence of solvents which are inert under the reaction conditions.
Examples of suitable solvents are cyclohexane, hexane, hept&ne, toluene, o-, m and p-xylene, ethylbenzene, di-n-butyl ether, cyclohexylmethyl ether, anisole, methanol, ethanol, isopropanol, tebrahydrofuran and dioxane. The reaction can be carried out either continuously or batchwise.
The preparation of the catalyst, comprising silver and palladium on an inert carrier, is disclosed in German Patent 1,179,947 and Germa~ Laid-Open Application DOS 2,118,283.
The catalytically active metals are advantageously employed in a ratio corresponding to from 1 to 30, especially from 3 to 15, per cent by weight of palladium, based on silver.
Sometimes, ~he activity of the catalyst can be further improved by adding up to 50 per cent by weight, in particular up to 25 per cent by weight, based on silver, of manganese or vanadium oxide. Examples of suitable carriers are silica, or alumina which has been heated at a high tempera-ture and then cooled. The weight ratio of carrier tometal is, for example, 93 : 7. The catalyst may for example be used in the form of extrudates of 5 mm diameter and 1~ mm length.
The compounds prepared by the process of the inven-tion may be used as active ingredients in crop protection agents (~erman Laid-Open Application DOS 2,556,747).
In the Examples which follow, parts are by weight and bear the same relation to parts by volume as that of the kilo~am to the liter.
- ~5 ~ o.z.0050,/03328 EXA~SPLE 1 .~ c~tal~st consisting of 0036~ ~y ~.~ight of Pd, 4.8~ by weight of ~5 and 1.5~ b~ we~ght ~ Mn in the form of man~anese oxide on SiO2 as the carrier is filled into a cylindrical reaction tube having a volume of 500 parts, and is heated to 150C. Per hour, 120 parts of a mixture consisting of 204 parts of 3-(p-tertiary butylphenyl)-2-methyl-propanal and 115 parts of cis-2,6-dimethylmorpholine are passed over this catalyst bed.
At the same time, 10,000 parts by volume of hydrogen under a pressure of 200 bar are passed, in co-current, through the reaction tube. The reaction product issuing from the reaction tube is cooled under pressure, after which the pressure is let down. This gives about 120 parts per hour of crude product, which is purified by distillation.
Distillation of 120 parts of crude product gi~res107 parts of N-[3'-(p-tertiary butylphenyl)-2'-methyl-propyl]-cis-2,6-dimethylmorpholine, boiling point = 206C/l~ mm Hg~
This corresponds to a yield of 94% of theory 3-(p-Tertiary butylphenyl)-2-methyl-propanal is r~acted with a mixture of 75~0 by weight of cis-2,6-dimethyl-morpholine and 25~o by weight of trans-2,6-dimethylmorpholine in the same apparatus, under the same conditions, and in the same ratio, as those described in Example 1. The end product obtained is a mixture of 75,~ by weight of N-[~ t _ (p_ tertiary butylphenyl)-2'-methyl-propyl]-cis-2,6-dirnethyl-morpholine and 25% by weight of N-C3'-(p-tertiary butyl-phenyl)-2'-methyl-propyl]-trans-2,6-dimethylmorpholine, boiling point = 206 - 210C/18 mm Hg The yield is 94%
~;~
~12'~9~1 - 6 ~ O.Z. 0050/0~3283 of theory.
A shaking autoclave having a volume of 250 parts is filled with 50 parts of 3-(p-isopropylphenyl)-3-methyl-propanal, 100 parts of trans-2,6-dimethylmorpholine and 10 parts of the catalyst mentioned in Example 1. The auto~
clave is then heated to 140C and hydrogen is forced in until the pressure reaches 200 bar. As soon as the hydrogen absorption has ended and a constant pressure has been reached, the autoclave is cooled.
The catalyst is then removed from the reaction pro-duct by filtration and the filtrate is purified by distilla-tion. 69 parts of N-[3'-(p-isopropylphenyl)-3'-meth~
propyl]-trans-2,6-dimethylmorpholine, boiling point = 1,2C/
O.01 mm Hg,are obtained. The yield is 91~6 of theory.
The shaking autoclave mentioned in Example 3 is filled Wit}l 50 parts by volume of 3-phenyl-3-~ethyl-propanal, 100 parts of cis-2,6-dimethylmorpholine and 10 parts of the catalyst mentioned in Example 1. The autoclave is then heated to 160C and hydrogen is forced in until the pro~sure reaches 200 bar As soon as the hydrogen absorption has ended and a constant pressure has been reached, the autoclave is cooled. The catalyst is then removed from the reac-tion product by filtration and the filtrate is purified by distillation. 77.5 parts of N-(3'-phenyl-3'-methyl-propyl)-cis-2,6-dimethylmorpholine, boiling point = lC3C/
0.1 mm Hg,are obtained. The yield is 93/0 of theory.
, . . . . . _ .. .
llZZ9~1 - 7 - O.Z. 0050~033283 The procedure followed is as described in Example 4, but the starting materials used are 3-(p-methoxyphenyl)-2-methyl-propanal and cis-2,6-dimethylmorpholine. Working up the reaction product by distillation in this case gives N-[3'-(p-methoxyphenyl)-2'-methyl-propyl]-cis-2,6-dimethyl-morpholine, boiling point = 128C/0.1 mm Hg. The yield is 93% of theory, The procedure followed is as described in Example 4, but the starting materials used are 4-(p-tertiary butyl-phenyl)-butan-2-one as the carbonyl component and a mixture of 75% by weight of cis- and 25% by weight of trans-2,6-dimethylmorpholine as the amine component. Working up by distillation gives a mixture of 75% by weight of N-[4~-(p-tertiary butylphenyl)-but-2'-yl]-cis-2,6-dimethyl-morpholine and 25% by weight of N-[4'-(p-tertiary butyl-phenyl)-but-2'-yl]-trans-2,6-dimethylmorpholine, boiling point = 143C/0.01 mm Hg, The yield is 86% of theory.
The procedure follo~ed is as described in Example 4, but the catalyst used consists of 0.3% by weight of Pd and 4.5~ by weight of Ag on SiO2, the carbonyl component is 3-(p-tertiary butylphenyl)-2-methyl-propanal and the amine component is cis-2,6-dimethylmorpholine.
Working up the reaction product by distillation gives N-[3'-(p-tertiary butylphenyl)-2'-methyl-propyl~-cis-2,6-dimethylmorpholine in a yield of 92% of theory.
.
. .
In the process according to the invention, the amine component may be employed in the stoichiometric amount or in up to 10-fold molar excess.
The following carbonyl compounds are examples of suitable starting materials of the formula ITI: 3-phenyl-3-methyl-propanal, 3-phenyl-2-methyl-propanal, 4-phenyl-butan-2-one, 3-(4'-methylphenyl)-2-methylpropanal, 3-(4'-isopropyl-phenyl)-2-methyl-propanal, 3-(4'-tertiary butylphenyl)-2-methyl-propanal, 3-phenyl-2-ethyl-propanal, 3-phe~yl-2-iso-propyl-propanal, 3-(4'-isopropylph.enyl)-3-methyl-propanal, 2b 3-(4'-tertiary butylphenyl)-3-methyl-propanal, 3-(4'-tertiary butylphenyl)-butan-4-one, 3-(4'-methoxyphenyl)-2-methvl-propanal and 3-(4'-.isopropoxyphenyl)-2-methyl-propanal.
The starting materials III are prepared from the corresponding substituted benzaldehydes and aliphatic a.lde-hydes or ketones by an aldol condensation followed by partial hydrogenation of the resulting carbon-carbon double bond (U,S. Patent 2,976,321). Some of the compounds C~l also be prepared by hydroformylation of substituted styrenes.
The reaction is advantageously carried cut at fr~
1~ 2Z98~
- 4 - O.Z. 0050/033283 100 -to 190C under a hydrogen pressure of from 5 to 300 bar It may be carried out without a solvent or in the presence of solvents which are inert under the reaction conditions.
Examples of suitable solvents are cyclohexane, hexane, hept&ne, toluene, o-, m and p-xylene, ethylbenzene, di-n-butyl ether, cyclohexylmethyl ether, anisole, methanol, ethanol, isopropanol, tebrahydrofuran and dioxane. The reaction can be carried out either continuously or batchwise.
The preparation of the catalyst, comprising silver and palladium on an inert carrier, is disclosed in German Patent 1,179,947 and Germa~ Laid-Open Application DOS 2,118,283.
The catalytically active metals are advantageously employed in a ratio corresponding to from 1 to 30, especially from 3 to 15, per cent by weight of palladium, based on silver.
Sometimes, ~he activity of the catalyst can be further improved by adding up to 50 per cent by weight, in particular up to 25 per cent by weight, based on silver, of manganese or vanadium oxide. Examples of suitable carriers are silica, or alumina which has been heated at a high tempera-ture and then cooled. The weight ratio of carrier tometal is, for example, 93 : 7. The catalyst may for example be used in the form of extrudates of 5 mm diameter and 1~ mm length.
The compounds prepared by the process of the inven-tion may be used as active ingredients in crop protection agents (~erman Laid-Open Application DOS 2,556,747).
In the Examples which follow, parts are by weight and bear the same relation to parts by volume as that of the kilo~am to the liter.
- ~5 ~ o.z.0050,/03328 EXA~SPLE 1 .~ c~tal~st consisting of 0036~ ~y ~.~ight of Pd, 4.8~ by weight of ~5 and 1.5~ b~ we~ght ~ Mn in the form of man~anese oxide on SiO2 as the carrier is filled into a cylindrical reaction tube having a volume of 500 parts, and is heated to 150C. Per hour, 120 parts of a mixture consisting of 204 parts of 3-(p-tertiary butylphenyl)-2-methyl-propanal and 115 parts of cis-2,6-dimethylmorpholine are passed over this catalyst bed.
At the same time, 10,000 parts by volume of hydrogen under a pressure of 200 bar are passed, in co-current, through the reaction tube. The reaction product issuing from the reaction tube is cooled under pressure, after which the pressure is let down. This gives about 120 parts per hour of crude product, which is purified by distillation.
Distillation of 120 parts of crude product gi~res107 parts of N-[3'-(p-tertiary butylphenyl)-2'-methyl-propyl]-cis-2,6-dimethylmorpholine, boiling point = 206C/l~ mm Hg~
This corresponds to a yield of 94% of theory 3-(p-Tertiary butylphenyl)-2-methyl-propanal is r~acted with a mixture of 75~0 by weight of cis-2,6-dimethyl-morpholine and 25~o by weight of trans-2,6-dimethylmorpholine in the same apparatus, under the same conditions, and in the same ratio, as those described in Example 1. The end product obtained is a mixture of 75,~ by weight of N-[~ t _ (p_ tertiary butylphenyl)-2'-methyl-propyl]-cis-2,6-dirnethyl-morpholine and 25% by weight of N-C3'-(p-tertiary butyl-phenyl)-2'-methyl-propyl]-trans-2,6-dimethylmorpholine, boiling point = 206 - 210C/18 mm Hg The yield is 94%
~;~
~12'~9~1 - 6 ~ O.Z. 0050/0~3283 of theory.
A shaking autoclave having a volume of 250 parts is filled with 50 parts of 3-(p-isopropylphenyl)-3-methyl-propanal, 100 parts of trans-2,6-dimethylmorpholine and 10 parts of the catalyst mentioned in Example 1. The auto~
clave is then heated to 140C and hydrogen is forced in until the pressure reaches 200 bar. As soon as the hydrogen absorption has ended and a constant pressure has been reached, the autoclave is cooled.
The catalyst is then removed from the reaction pro-duct by filtration and the filtrate is purified by distilla-tion. 69 parts of N-[3'-(p-isopropylphenyl)-3'-meth~
propyl]-trans-2,6-dimethylmorpholine, boiling point = 1,2C/
O.01 mm Hg,are obtained. The yield is 91~6 of theory.
The shaking autoclave mentioned in Example 3 is filled Wit}l 50 parts by volume of 3-phenyl-3-~ethyl-propanal, 100 parts of cis-2,6-dimethylmorpholine and 10 parts of the catalyst mentioned in Example 1. The autoclave is then heated to 160C and hydrogen is forced in until the pro~sure reaches 200 bar As soon as the hydrogen absorption has ended and a constant pressure has been reached, the autoclave is cooled. The catalyst is then removed from the reac-tion product by filtration and the filtrate is purified by distillation. 77.5 parts of N-(3'-phenyl-3'-methyl-propyl)-cis-2,6-dimethylmorpholine, boiling point = lC3C/
0.1 mm Hg,are obtained. The yield is 93/0 of theory.
, . . . . . _ .. .
llZZ9~1 - 7 - O.Z. 0050~033283 The procedure followed is as described in Example 4, but the starting materials used are 3-(p-methoxyphenyl)-2-methyl-propanal and cis-2,6-dimethylmorpholine. Working up the reaction product by distillation in this case gives N-[3'-(p-methoxyphenyl)-2'-methyl-propyl]-cis-2,6-dimethyl-morpholine, boiling point = 128C/0.1 mm Hg. The yield is 93% of theory, The procedure followed is as described in Example 4, but the starting materials used are 4-(p-tertiary butyl-phenyl)-butan-2-one as the carbonyl component and a mixture of 75% by weight of cis- and 25% by weight of trans-2,6-dimethylmorpholine as the amine component. Working up by distillation gives a mixture of 75% by weight of N-[4~-(p-tertiary butylphenyl)-but-2'-yl]-cis-2,6-dimethyl-morpholine and 25% by weight of N-[4'-(p-tertiary butyl-phenyl)-but-2'-yl]-trans-2,6-dimethylmorpholine, boiling point = 143C/0.01 mm Hg, The yield is 86% of theory.
The procedure follo~ed is as described in Example 4, but the catalyst used consists of 0.3% by weight of Pd and 4.5~ by weight of Ag on SiO2, the carbonyl component is 3-(p-tertiary butylphenyl)-2-methyl-propanal and the amine component is cis-2,6-dimethylmorpholine.
Working up the reaction product by distillation gives N-[3'-(p-tertiary butylphenyl)-2'-methyl-propyl~-cis-2,6-dimethylmorpholine in a yield of 92% of theory.
.
. .
Claims (20)
1. A process for the preparation of a stereoisomeric N-aralkyl-2,6-dimethylmorpholine of the formula where R1 is hydrogen, an aliphatic radical of 1 to 10 carbon atoms or alkoxy of 1 to 6 carbon atoms and R2, R3 and R4 are hydrogen or an aliphatic radical of 1 to 4 carbon atoms, or of a defined mixture of such compounds, by reacting a stereoisomeric 2,6-dimethylmorpholine of the formula or a defined mixture of such compounds with a compound of the formula where R1, R2, R3 and R4 have the above meanings, wherein the reaction is carried out in the presence of hydrogen and of a hydrogenation catalyst which contains palladium mixed with silver on an inert carrier.
2. A process as claimed in claim 1, characterized in that the hydrogenation catalyst contains from 1 to 30% by weight of palladium, based on the silver.
3. A process as claimed in claim 1, characterized in that the hydrogenation catalyst additionally contains up to 50% by weight, based on the silver, of manganese oxide.
4. A process as claimed in claim 1, characterized in that the inert carrier is silicon dioxide or aluminium dioxide.
5. A process as claimed in claim 1, characterized in that the hydrogenation catalyst contains 0.36% by weight of palladium, 4.8% by weight of silver and 1.05% by weight of manganese in the form of manganese oxide, the inert carrier being silicon dioxide.
6. A process as claimed in claim 1, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bars.
7. A process as claimed in claim 5, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bars.
8. A process as claimed in claim 1, characterized in that the hydrogenation catalyst contains from 1 to 30%
by weight of palladium, based on the silver and additionally contains up to 50% by weight, based on the silver, of manganese dioxide.
by weight of palladium, based on the silver and additionally contains up to 50% by weight, based on the silver, of manganese dioxide.
9. A process as claimed in claim 8, characterized in that the inert carrier is silicon dioxide or aluminium dioxide.
10. A process as claimed in claim 9, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bara.
11. A process for the preparation of a stereoiso-meric N-aralkyl-2,6-dimethylmorpholine of the formula where R1 is hydrogen, alkyl of 1 to 6 carbon atoms or methoxy or of a defined mixture of such compounds, by reacting a stereoisomeric 2,6-dimethylmorpholine of the formula or a defined mixture of such compounds with a compound of the formula where R1 has the above meaning, wherein the reaction is carried out in the presence of hydrogen and of a hydrogena-tion catalyst which contains palladium mixed silver or an inert carrier.
12. A process as claimed in claim 11, characterized in that the hydrogenation catalyst contains from 1 to 30% by weight of palladium, based on the silver.
13. A process as claimed in claim 11, characterized in that the hydrogenation catalyst additionally contains up to 50% by weight, based on the silver, of manganese oxide.
14. A process as claimed in claim 11, characterized in that the inert carrier is silicon dioxide or aluminium dioxide.
15. A process as claimed in claim 11, characterized in that the hydrogenation catalyst contains 0.36% by weight of palladium, 4.8% by weight of silver and 1.05% by weight of manganese, the inert carrier being silicon dioxide.
16. A process as claimed in claim 11, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bars.
17. A process as claimed in claim 15, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bars.
18. A process as claimed in claim 11, characterized in that the hydrogenation catalyst contains from 1 to 30% by weight of palladium, based on the silver and additionally contains up to 50% by weight on the silver,of manganese dioxide.
19. A process as claimed in claim 18, characterized in that the inert carrier is silicon dioxide or aluminium dioxide.
20. A process as claimed in claim 19, characterized in that the reaction is carried out at a temperature from 100°C to 190°C under a hydrogen pressure of from 5 to 300 bars.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782830999 DE2830999A1 (en) | 1978-07-14 | 1978-07-14 | METHOD FOR PRODUCING STEREOISOMERS N-ARALKYL-2,6-DIMETHYLMORPHOLINES |
| DEP2830999.1 | 1978-07-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1122981A true CA1122981A (en) | 1982-05-04 |
Family
ID=6044396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA328,740A Expired CA1122981A (en) | 1978-07-14 | 1979-05-30 | Preparation of stereoisomeric n-aralkyl-2,6-dimethyl-morpholine |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0007093B1 (en) |
| JP (1) | JPS5515463A (en) |
| AT (1) | ATE69T1 (en) |
| CA (1) | CA1122981A (en) |
| DE (2) | DE2830999A1 (en) |
| IL (1) | IL57336A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8017808B2 (en) | 2006-03-21 | 2011-09-13 | Basf Se | Process for preparing an amine |
| US8034978B2 (en) | 2006-05-31 | 2011-10-11 | Basf Se | Process for the preparation of an amine |
| US8163963B2 (en) | 2005-10-17 | 2012-04-24 | Basf Se | Process for continuous hydrogenation or hydrogenating amination |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZW15780A1 (en) * | 1979-08-17 | 1981-03-18 | Hoffmann La Roche | Heterocyclic compounds |
| DE3105446A1 (en) * | 1981-02-14 | 1982-09-02 | Basf Ag, 6700 Ludwigshafen | METHOD FOR PRODUCING ARALIPHATIC ALDEHYDES AND / OR AMINES |
| DE3476386D1 (en) * | 1983-11-02 | 1989-03-02 | Beecham Group Plc | MORPHOLINE DERIVATIVES |
| DE3421810A1 (en) * | 1984-06-12 | 1985-12-12 | Basf Ag, 6700 Ludwigshafen | PHENYLALKYLAMINE - BIOREGULATORS |
| GB8621790D0 (en) * | 1986-09-10 | 1986-10-15 | Ici Plc | Tertiary amine compounds |
| IL89997A0 (en) * | 1988-04-25 | 1989-12-15 | Lilly Co Eli | Propanamine derivatives |
| DE4009411A1 (en) * | 1990-03-23 | 1991-09-26 | Basf Ag | N- (3-PHENYL-2-METHYLPROPYL AND METHYLPROP-2-ENYL) -AZAHETEROCYCLEN |
| BR0208063B1 (en) * | 2001-03-16 | 2012-12-25 | process for the preparation of unsubstituted 2,6-dialkylmorpholine. | |
| JP1615876S (en) | 2017-09-28 | 2018-10-15 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE790119A (en) * | 1971-04-15 | 1973-04-13 | Basf Ag | PROCESS FOR THE PREPARATION OF SECONDARY OR TERTIARY ALIPHATIC AND CYCLOALIPHATIC AMINES. |
| AT354187B (en) * | 1976-11-22 | 1979-12-27 | Hoffmann La Roche | FUNGICIDE AGENT |
| DE2656747C2 (en) * | 1976-12-15 | 1984-07-05 | Basf Ag, 6700 Ludwigshafen | Morpholine derivatives |
| DE2700680A1 (en) * | 1977-01-08 | 1978-07-20 | Basf Ag | (N)-Substd. morpholinium salt prodn. - by acid cyclisation of bis:hydroxyalkyl-ammonium salts |
-
1978
- 1978-07-14 DE DE19782830999 patent/DE2830999A1/en not_active Withdrawn
-
1979
- 1979-05-18 IL IL57336A patent/IL57336A/en unknown
- 1979-05-30 CA CA328,740A patent/CA1122981A/en not_active Expired
- 1979-06-26 JP JP7978079A patent/JPS5515463A/en active Granted
- 1979-07-11 DE DE7979102377T patent/DE2960376D1/en not_active Expired
- 1979-07-11 EP EP79102377A patent/EP0007093B1/en not_active Expired
- 1979-07-11 AT AT79102377T patent/ATE69T1/en not_active IP Right Cessation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8163963B2 (en) | 2005-10-17 | 2012-04-24 | Basf Se | Process for continuous hydrogenation or hydrogenating amination |
| US8557985B2 (en) | 2005-10-17 | 2013-10-15 | Basf Se | Process for continuous hydrogenation or hydrogenating amination |
| US8017808B2 (en) | 2006-03-21 | 2011-09-13 | Basf Se | Process for preparing an amine |
| US8034978B2 (en) | 2006-05-31 | 2011-10-11 | Basf Se | Process for the preparation of an amine |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0007093A1 (en) | 1980-01-23 |
| IL57336A0 (en) | 1979-09-30 |
| ATE69T1 (en) | 1981-06-15 |
| EP0007093B1 (en) | 1981-05-20 |
| IL57336A (en) | 1983-05-15 |
| JPS5515463A (en) | 1980-02-02 |
| DE2960376D1 (en) | 1981-08-27 |
| DE2830999A1 (en) | 1980-01-31 |
| JPH0321547B2 (en) | 1991-03-22 |
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