CA1074317A - Production of an n-(substituted) piperazine compound - Google Patents
Production of an n-(substituted) piperazine compoundInfo
- Publication number
- CA1074317A CA1074317A CA253,358A CA253358A CA1074317A CA 1074317 A CA1074317 A CA 1074317A CA 253358 A CA253358 A CA 253358A CA 1074317 A CA1074317 A CA 1074317A
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- aryl
- accordance
- dialkanolamine
- phosphorus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- 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
- C07D295/02—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
- C07D295/023—Preparation; Separation; Stabilisation; Use of additives
-
- 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
- C07D295/084—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
PRODUCTION OF AN N-(SUBSTITUTED) PIPERAZINE COMPOUND
(D#75,Oll-3-F) Abstract of the Disclosure An improved process for producing an N-(substituted) piperazine compound is disclosed wherein an N-(substituted) dialkanolamine is contacted with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance at a temperature of from about 250°C to about 350°C
under a pressure sufficient to maintain the mixture essentially in liquid phase, said N-(substituted) dialkanolamine compound having the formula:
(D#75,Oll-3-F) Abstract of the Disclosure An improved process for producing an N-(substituted) piperazine compound is disclosed wherein an N-(substituted) dialkanolamine is contacted with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance at a temperature of from about 250°C to about 350°C
under a pressure sufficient to maintain the mixture essentially in liquid phase, said N-(substituted) dialkanolamine compound having the formula:
Description
Background of the Invention Field of the Invention This invention relates to a process for the preparatlon of ~-(substituted) piperazine compounds such as N-methylpiperazine, and more particularly, pertains to an improved liquid phase catalyzed process for preparing N-(substituted) piperazine compounds.
Prior Art N-(substituted) piperazine compounds are well-known having eRtablished utility in a myriad of applications in the chemical as well as the food related arts, ~.
, . . . . , . . ~
, ~ ", ~
~ ~ , ,, . ~.. . . . . . . '. ~ , ~07~317 Many methods of producing piperazine are well-known.
In one method for piperazine synthesis, diethanolamine and ammonia are reacted at relatively high temperatures and high pressures, e.g. 1,700 to 1,850 psig, see for example U. S.
Prior Art N-(substituted) piperazine compounds are well-known having eRtablished utility in a myriad of applications in the chemical as well as the food related arts, ~.
, . . . . , . . ~
, ~ ", ~
~ ~ , ,, . ~.. . . . . . . '. ~ , ~07~317 Many methods of producing piperazine are well-known.
In one method for piperazine synthesis, diethanolamine and ammonia are reacted at relatively high temperatures and high pressures, e.g. 1,700 to 1,850 psig, see for example U. S.
2,910,477. It has also been disclosed that N,N'-bis-(2-hydroxyethyl)piperazine can be produced by heating diethanol-amine in the presence of a molar excess of a carboxylic acid containing 8 or more carbon atoms. See for example German Patent 1,002,359.
Additionally, it has been disclosed that N,N'-bis-(2-hydroxyethyl)piperazine can be produced by the bimolecular dehydration of diethanolamine with certain inorgar,ic acid catalysts and particularly phosphoric acid and acid salts. See for example U. S. 2,636,033.
Unexpectedly it ha~ been found that N-(substituted) piperazine compounds, including the N-(substi~uted) C-(alkyl substituted) piperazines, can be produced direc~ly from the readily available and easily obtainable corresponding N-(substituted) dialkanolamine and ammonia. One outstanding feature of the instant invention resides in the simplicity and availability of the reactants.
Summary of the Invention In accordance with the broad aspects of the instant invention, N-(substituted) piperazine compounds of the formula:
R H
/ R R~
R'-N R ~ -H
~, R H
7herein eaeh R is independently hydrogen, a lower alkyl radical or a substituted lower alkyl radical and R' is an alkyl radical, a sub-stituted alkyl radical, an aryl radical, or a substituted aryl radical are produced by a process which includes contacting an N-(substituted) dialkanolamine compound with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance at a temperature of from about 250C to about 350C under pressure sufficient to maintain the mixture essentially in liquid phase; and, recovering from the resultant reaction mixture said N-(substituted) piperazine compound. Said phosphorus-containing substance is selected from the group consisting of acidic metal phosphates, phosphoric acids and their anhydrides, or phosphorus acids and their anhydrides, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous acids and phosphoric acids, alkali metal monosalts of phosphoric acid, the thioanalogs of the fore-going, and mixtures thereof. By varying the N-(substituted) di-alkanolamine utilized, one can achieve, for example, C-(alkyl sub-stituted) N-(substituted) piperazine.
eseri.ption of the Preferred Embodiments In accordanee with this invention, a process for producing an N-(substituted) piperazine compound is provided. In brief, the preferred process comprises the steps of reacting an N-(substituted) dialkanolamine compound and, more particularly an N-(substituted) diethanolamine with ammonia in the presence of a eatalytieally effective amount of a phosphorus-containing substance at a tempera-ture of from about 275C to about 325C under pressure sufficient to maintain the mixture essentially in liquid phase.
The N-(substituted) piperazine compounds that can be produced in accordance with the instant invention can be depicted by the formula:
R'-N /N-H
Additionally, it has been disclosed that N,N'-bis-(2-hydroxyethyl)piperazine can be produced by the bimolecular dehydration of diethanolamine with certain inorgar,ic acid catalysts and particularly phosphoric acid and acid salts. See for example U. S. 2,636,033.
Unexpectedly it ha~ been found that N-(substituted) piperazine compounds, including the N-(substi~uted) C-(alkyl substituted) piperazines, can be produced direc~ly from the readily available and easily obtainable corresponding N-(substituted) dialkanolamine and ammonia. One outstanding feature of the instant invention resides in the simplicity and availability of the reactants.
Summary of the Invention In accordance with the broad aspects of the instant invention, N-(substituted) piperazine compounds of the formula:
R H
/ R R~
R'-N R ~ -H
~, R H
7herein eaeh R is independently hydrogen, a lower alkyl radical or a substituted lower alkyl radical and R' is an alkyl radical, a sub-stituted alkyl radical, an aryl radical, or a substituted aryl radical are produced by a process which includes contacting an N-(substituted) dialkanolamine compound with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance at a temperature of from about 250C to about 350C under pressure sufficient to maintain the mixture essentially in liquid phase; and, recovering from the resultant reaction mixture said N-(substituted) piperazine compound. Said phosphorus-containing substance is selected from the group consisting of acidic metal phosphates, phosphoric acids and their anhydrides, or phosphorus acids and their anhydrides, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous acids and phosphoric acids, alkali metal monosalts of phosphoric acid, the thioanalogs of the fore-going, and mixtures thereof. By varying the N-(substituted) di-alkanolamine utilized, one can achieve, for example, C-(alkyl sub-stituted) N-(substituted) piperazine.
eseri.ption of the Preferred Embodiments In accordanee with this invention, a process for producing an N-(substituted) piperazine compound is provided. In brief, the preferred process comprises the steps of reacting an N-(substituted) dialkanolamine compound and, more particularly an N-(substituted) diethanolamine with ammonia in the presence of a eatalytieally effective amount of a phosphorus-containing substance at a tempera-ture of from about 275C to about 325C under pressure sufficient to maintain the mixture essentially in liquid phase.
The N-(substituted) piperazine compounds that can be produced in accordance with the instant invention can be depicted by the formula:
R'-N /N-H
-3-wherein each R is independently hydrogen or a lower alkyl radical and R' is an alkyl radical which can itself be substituted, an aryl radical or a substituted aryl radical.
Examples of these compounds are N-methylpiperazine, N-phenyl piperazine, N-(aminoethyl)piperazine, N-(2-N'N'-dimethylamino-ethyl)piperazine, N-methyl-3,5-di-ethyl piperazine and the like.
The above list is given only as an example of the class of compounds that can be formed and not as an exhaustive list of the N-(substituted) piperazines that can be prepared in accordance with the invention.
It will be realized by those skilled in the art that both R and R' may contain substituted moieties which are nondeleterious to the reaction, such as for example oxy, thio,or tertiary amino moieties.
The N-(~ubsti~uted) alkanolamine compound that can be used has the general formula:
H R R' R H
OH - C - C - N - C - C - OH
R R R R
wherein each R is independently hydrogen or a lower alkyl radical. The preferred N-(substituted) dialkanolamine compound is of the above formula wherein each R is independently hydrogen. R' in the above formula is an alkyl radical, a substituted alkyl radical, an aryl radical, or a substituted aryl radical. In addition, the alkyl radical may be cyclic or heterocyclic.
~07~3i7 Suitable phosphorus-containing substances which can be employed include, for example, acidic metal phosphates, phosphoric acid compounds and their anhydrides, phosphorous acid compounds and anhydrides, alkyl or aryl phosphate esters, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous and phosphoric acids, alkali metal monosalts of phosphoric acid, the thioanalogs of the foregoing, and mixtures of any of the above.
More particularly, suitable acidic metal phosphates include boron phosphate, ferric phosphate, aluminum phosphate, etc.
Suitable phosphoric acid compounds include aqueaus or anhydrous phosphoric acids such as orthophosphoric acid, pyrophosphoric acid, metaphosphoric acid, and condensed phos-phoric acids such as polyphosphoric acids. Accordingly, anexample of ~ suitable phosphorous acid is orthophosphorous acid.
In addition, any commercially available mono-, di-, or tri-alkyl or aryl phosphate or phosphite ester can be employed as the catalyst in the inventive process. Additionally, bis(phosphates) and secondary phosphate esters such as those disclosed in U. S. 3,869,526 and U. S. 3,869,527, respectively, can be used. Preferably, the lower alkyl esters are employed such as those having from 1 to about 8 carbon atoms per alkyl group. Preferred aryl esters contain from about 6 to about 20 carbon atoms and may include a phenyl group or alkyl-substituted phenyl group.
Further, suitable alkyl or aryl substituted phos-phorous and phosphoric acids which may be employed as a catalyst include alkyl phosphonic acids, aryl phosphonic acids, alkyl phosphinic acids and aryl phosphinic acids.
Preferably, such acids include alkyl or aryl groups and have from 1 to about 20 carbon atoms in each aryl or alkyl group.
Specific examples of alkyl and aryl substituted phos-phorous and phosphoric acids that may be used in accordance with the invention are phenylphosphinic acid, ethylphosphonic acid, phenylphosphonic acid, naphthaphosphonic acid, and methyl-phosphinic acid. Examples of the alkyl and aryl substituted phosphorous and phosphoric acid esters are methylphenyl phosphonate, dimethylphenyl phosphonate, methylphenyl phos-phinate, ethyl naphthaphosphinate, and propylmethyl phos-phonate, The above-mentioned phosphorus-containing substances are not intended to be exhaustive of those that can be employed as a catalyst in the inventive process. Those materials set forth are merely intended to be representative of the types of substances that we have found to be particularly effective.
Yet, of the substances and the types of compounds mentioned, we particularly prefer to employ those that are known to be mos~ reactive such as orthophosphoric acids, polyphosphoric acids, boron phosphate, aluminum phosphate, ferric phosphate, and orthophosphorous acid, Of these, most preferred is ortho-phosphorous acid.
The phosphorus-containing substance is employed in only a catalytically effecti~e amount, normally from about 0.1 to about 10.0 mole percent, most often 1.0 to 5.0 mole percent based on the N-(substituted) dialkanolamine material employed as a reactant. Most often the amount of catalyst used is 1.0 to 3.0 mole percent. Preferably, the phosphorus-containing substance is not employed in an amount higher than about 5.0 mole percent, based upon the N-(substituted) dialkanol-amine reactant present, inasmuch as phosphorylation reactantscan occur if higher amounts are used which adversely affect the yield of desirable products. The particular amount employed for a given reaction can vary widely, however, depending upon the reactivity of the catalyst material, reactivity of reactants, types of reactants employed and particular processing con-ditions employed.
The specific phosphorus-containing substance employed as a catalyst can be employed alone, in combination with other phosphoru~-containing substances or can be used in combination with other acid materials. For example, it has been found that phosphoric acid-i~pregnated silicas or admixtures of orthophosphorous acid and silica-alumina can be utilized.
~ther materials that may be used with the phosphorus-containing substance include alpha- and gamma-aluminas, silica, carborundum, etc. When an additional catalyst is used it i8 present in an amount of 0.1 to 10.0 weight percentage additional catalyst based upon dialkanolamine employed.
The reactants and the catalyst~ all described hereinabove, are admixed in any desired manner so as to provide intimate admixture of reactants and intimate contact thereof with the catalyst. The admixture is then heated to a temperature of from above about 250C to about 350C, preferably about 275C to about 325C, under a pressure sufficient to maintain the reaction mass in liquid phase which normally ranges from about 500 to about 4,000 psig, depending upon reactants employed. More often the pressure range is l,500 to 3,500 psig. The reaction is allowed to proceed at the temperature employed until the desired amount of conversion is obtained.
Time of reaction has not been found to be critical and complete conversion can usually be determined by the c~s-sation of formation of water of reaction. It is also not critical to control the amount of water of reaction present during the reaction, such as by removal thereof as it is formed.
Usually, we prefer to carry out the reaction at the above-described temperatures for about 1/2 to about 5 hours.
Normally, the N-(substituted) dialkanolamine compound and the ammonia are reacted at molar ratios of from about 1:1 to about 20:1 preferably about 2:1 to about 10:1 moles ammonia per mole N-(substituted) dialkanolamine compound.
The process of the invention can be carried out batchwise or continuously employing well-known batch and continuous processing techniques and conventional processing apparatus. Where the process is carried out continuously, we prefer to employ space velocities of reactants of from about O.l to about 4.0, and preferably from about 0.5 to 2.0, grams total reactants per milliliter of total reactor volume per hour.
The desired N-(substituted) piperazine compound can be readily recovered from the reaction product mass in substantially pure form by conventional procedures, such as ~07431~7 distillation, without difficulty. For example, the reaction product mass may be directly distilled, or initially filtered to remove formed solids which usually are amine salt complexes of the phosphorus-containing substance, and then distilled.
The desired N-(substituted) piperazine compound can then be separately collected overhead in salt-free form. ~uch distillation recovery procedures are well-known in the art and, therefore, will not be more particularly discussed herein.
10The following example illustrates the nature of the inventive process but is not intended to be limitative thereof.
Example To a dry nitrogen purged l-liter stainless steel autoclave equipped with a stirring means was charged an 15aqueous solution consisting of 248.0 g (2.0 moles) N-(methyl) diethanolamine, and 0.036 ~oles H3PO3. The autoclave contents were padded with nitrogen and 85.5 g (5.0 moles) anhydrous ammonia was metered into the autoclave while the contents were heated to a temperature of about 300C for 2 hours under a constant pressure of about 2,300 psig. Upon cooling, the crude reaction product was recovered and analyzed by GLC A %
methods. The recovered crude product analyzed as follows:
% N-(methyl)diethanolamine conversion, greater than 79.1, % selectivity to N-(methyl)morpholine, about 1.1; % selectivity to N-(methyl)piperazine5 about 13Ø Selectivity to higher condensates of N-(methyl)diethanolamine or N-(methyl)piperazine/
N-(methyl)diethanolamine accounted for the remainder of the product.
While the invention has been explained in relation to its preferred embodiment, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification and is intended to cover such modifications as fall within the scope .of the appended claims.
Examples of these compounds are N-methylpiperazine, N-phenyl piperazine, N-(aminoethyl)piperazine, N-(2-N'N'-dimethylamino-ethyl)piperazine, N-methyl-3,5-di-ethyl piperazine and the like.
The above list is given only as an example of the class of compounds that can be formed and not as an exhaustive list of the N-(substituted) piperazines that can be prepared in accordance with the invention.
It will be realized by those skilled in the art that both R and R' may contain substituted moieties which are nondeleterious to the reaction, such as for example oxy, thio,or tertiary amino moieties.
The N-(~ubsti~uted) alkanolamine compound that can be used has the general formula:
H R R' R H
OH - C - C - N - C - C - OH
R R R R
wherein each R is independently hydrogen or a lower alkyl radical. The preferred N-(substituted) dialkanolamine compound is of the above formula wherein each R is independently hydrogen. R' in the above formula is an alkyl radical, a substituted alkyl radical, an aryl radical, or a substituted aryl radical. In addition, the alkyl radical may be cyclic or heterocyclic.
~07~3i7 Suitable phosphorus-containing substances which can be employed include, for example, acidic metal phosphates, phosphoric acid compounds and their anhydrides, phosphorous acid compounds and anhydrides, alkyl or aryl phosphate esters, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous and phosphoric acids, alkali metal monosalts of phosphoric acid, the thioanalogs of the foregoing, and mixtures of any of the above.
More particularly, suitable acidic metal phosphates include boron phosphate, ferric phosphate, aluminum phosphate, etc.
Suitable phosphoric acid compounds include aqueaus or anhydrous phosphoric acids such as orthophosphoric acid, pyrophosphoric acid, metaphosphoric acid, and condensed phos-phoric acids such as polyphosphoric acids. Accordingly, anexample of ~ suitable phosphorous acid is orthophosphorous acid.
In addition, any commercially available mono-, di-, or tri-alkyl or aryl phosphate or phosphite ester can be employed as the catalyst in the inventive process. Additionally, bis(phosphates) and secondary phosphate esters such as those disclosed in U. S. 3,869,526 and U. S. 3,869,527, respectively, can be used. Preferably, the lower alkyl esters are employed such as those having from 1 to about 8 carbon atoms per alkyl group. Preferred aryl esters contain from about 6 to about 20 carbon atoms and may include a phenyl group or alkyl-substituted phenyl group.
Further, suitable alkyl or aryl substituted phos-phorous and phosphoric acids which may be employed as a catalyst include alkyl phosphonic acids, aryl phosphonic acids, alkyl phosphinic acids and aryl phosphinic acids.
Preferably, such acids include alkyl or aryl groups and have from 1 to about 20 carbon atoms in each aryl or alkyl group.
Specific examples of alkyl and aryl substituted phos-phorous and phosphoric acids that may be used in accordance with the invention are phenylphosphinic acid, ethylphosphonic acid, phenylphosphonic acid, naphthaphosphonic acid, and methyl-phosphinic acid. Examples of the alkyl and aryl substituted phosphorous and phosphoric acid esters are methylphenyl phosphonate, dimethylphenyl phosphonate, methylphenyl phos-phinate, ethyl naphthaphosphinate, and propylmethyl phos-phonate, The above-mentioned phosphorus-containing substances are not intended to be exhaustive of those that can be employed as a catalyst in the inventive process. Those materials set forth are merely intended to be representative of the types of substances that we have found to be particularly effective.
Yet, of the substances and the types of compounds mentioned, we particularly prefer to employ those that are known to be mos~ reactive such as orthophosphoric acids, polyphosphoric acids, boron phosphate, aluminum phosphate, ferric phosphate, and orthophosphorous acid, Of these, most preferred is ortho-phosphorous acid.
The phosphorus-containing substance is employed in only a catalytically effecti~e amount, normally from about 0.1 to about 10.0 mole percent, most often 1.0 to 5.0 mole percent based on the N-(substituted) dialkanolamine material employed as a reactant. Most often the amount of catalyst used is 1.0 to 3.0 mole percent. Preferably, the phosphorus-containing substance is not employed in an amount higher than about 5.0 mole percent, based upon the N-(substituted) dialkanol-amine reactant present, inasmuch as phosphorylation reactantscan occur if higher amounts are used which adversely affect the yield of desirable products. The particular amount employed for a given reaction can vary widely, however, depending upon the reactivity of the catalyst material, reactivity of reactants, types of reactants employed and particular processing con-ditions employed.
The specific phosphorus-containing substance employed as a catalyst can be employed alone, in combination with other phosphoru~-containing substances or can be used in combination with other acid materials. For example, it has been found that phosphoric acid-i~pregnated silicas or admixtures of orthophosphorous acid and silica-alumina can be utilized.
~ther materials that may be used with the phosphorus-containing substance include alpha- and gamma-aluminas, silica, carborundum, etc. When an additional catalyst is used it i8 present in an amount of 0.1 to 10.0 weight percentage additional catalyst based upon dialkanolamine employed.
The reactants and the catalyst~ all described hereinabove, are admixed in any desired manner so as to provide intimate admixture of reactants and intimate contact thereof with the catalyst. The admixture is then heated to a temperature of from above about 250C to about 350C, preferably about 275C to about 325C, under a pressure sufficient to maintain the reaction mass in liquid phase which normally ranges from about 500 to about 4,000 psig, depending upon reactants employed. More often the pressure range is l,500 to 3,500 psig. The reaction is allowed to proceed at the temperature employed until the desired amount of conversion is obtained.
Time of reaction has not been found to be critical and complete conversion can usually be determined by the c~s-sation of formation of water of reaction. It is also not critical to control the amount of water of reaction present during the reaction, such as by removal thereof as it is formed.
Usually, we prefer to carry out the reaction at the above-described temperatures for about 1/2 to about 5 hours.
Normally, the N-(substituted) dialkanolamine compound and the ammonia are reacted at molar ratios of from about 1:1 to about 20:1 preferably about 2:1 to about 10:1 moles ammonia per mole N-(substituted) dialkanolamine compound.
The process of the invention can be carried out batchwise or continuously employing well-known batch and continuous processing techniques and conventional processing apparatus. Where the process is carried out continuously, we prefer to employ space velocities of reactants of from about O.l to about 4.0, and preferably from about 0.5 to 2.0, grams total reactants per milliliter of total reactor volume per hour.
The desired N-(substituted) piperazine compound can be readily recovered from the reaction product mass in substantially pure form by conventional procedures, such as ~07431~7 distillation, without difficulty. For example, the reaction product mass may be directly distilled, or initially filtered to remove formed solids which usually are amine salt complexes of the phosphorus-containing substance, and then distilled.
The desired N-(substituted) piperazine compound can then be separately collected overhead in salt-free form. ~uch distillation recovery procedures are well-known in the art and, therefore, will not be more particularly discussed herein.
10The following example illustrates the nature of the inventive process but is not intended to be limitative thereof.
Example To a dry nitrogen purged l-liter stainless steel autoclave equipped with a stirring means was charged an 15aqueous solution consisting of 248.0 g (2.0 moles) N-(methyl) diethanolamine, and 0.036 ~oles H3PO3. The autoclave contents were padded with nitrogen and 85.5 g (5.0 moles) anhydrous ammonia was metered into the autoclave while the contents were heated to a temperature of about 300C for 2 hours under a constant pressure of about 2,300 psig. Upon cooling, the crude reaction product was recovered and analyzed by GLC A %
methods. The recovered crude product analyzed as follows:
% N-(methyl)diethanolamine conversion, greater than 79.1, % selectivity to N-(methyl)morpholine, about 1.1; % selectivity to N-(methyl)piperazine5 about 13Ø Selectivity to higher condensates of N-(methyl)diethanolamine or N-(methyl)piperazine/
N-(methyl)diethanolamine accounted for the remainder of the product.
While the invention has been explained in relation to its preferred embodiment, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification and is intended to cover such modifications as fall within the scope .of the appended claims.
Claims (9)
1. A process for producing an N-(substituted) pipera-zine compound of the formula:
wherein each R is independently hydrogen, a lower alkyl radical or a substituted lower alkyl radical and R' is an alkyl radical, a substituted alkyl radical, an aryl radical, or a substituted aryl radical comprising the steps of contact-ing an N-(substituted) dialkanolamine with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance selected from the group consisting of acidic metal phosphates, phosphoric acids and their anhydrides, or phosphorus acids and their anhydrides, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous acids and alkali metal monosalts or phosphoric acid, the thioanalogs of the foregoing and mixtures thereof at a temperature of from about 250°C to about 350°C under a pressure sufficient to maintain the mixture essentially in liquid phase, said N-(substituted) dialkanolamine having the formula:
wherein each R is independently selected from the group consisting of hydrogen and lower alkyl radicals, and R' is ??
selected from the group consisting of alkyl radicals, substituted alkyl radicals, aryl radicals and substituted aryl radicals; and, recovering from the resulting reaction mixture said N-(substituted) piperazine compound.
wherein each R is independently hydrogen, a lower alkyl radical or a substituted lower alkyl radical and R' is an alkyl radical, a substituted alkyl radical, an aryl radical, or a substituted aryl radical comprising the steps of contact-ing an N-(substituted) dialkanolamine with ammonia in the presence of a catalytically effective amount of a phosphorus-containing substance selected from the group consisting of acidic metal phosphates, phosphoric acids and their anhydrides, or phosphorus acids and their anhydrides, alkyl or aryl phosphite esters, alkyl or aryl substituted phosphorous acids and alkali metal monosalts or phosphoric acid, the thioanalogs of the foregoing and mixtures thereof at a temperature of from about 250°C to about 350°C under a pressure sufficient to maintain the mixture essentially in liquid phase, said N-(substituted) dialkanolamine having the formula:
wherein each R is independently selected from the group consisting of hydrogen and lower alkyl radicals, and R' is ??
selected from the group consisting of alkyl radicals, substituted alkyl radicals, aryl radicals and substituted aryl radicals; and, recovering from the resulting reaction mixture said N-(substituted) piperazine compound.
2. The process in accordance with Claim 1 wherein said contacting is accomplished at a temperature of from about 275°C to about 325°C.
3. The process in accordance with Claim 1 wherein said contacting is accomplished at a pressure ranging from about 500 psig to about 4,000 psig.
4. The process of Claim 3 wherein said pressure range is from about 500 psig to about 4,000 psig.
5. The process in accordance with Claim 1 wherein the mole ratio of said ammonia reactant to said N-(substituted) dialkanolamine reactant ranges from about 1:1 to about 20:1.
6. The process in accordance with Claim 5 wherein mole ratio is 2:1 to 10:1.
7. The process in accordance with Claim 1 wherein said phosphorus-containing substance is phosphorous acid.
8. The process in accordance with Claim 1 wherein said phosphorus containing substance is present in an amount of from about 0.1 to about 10.0 mole percent based upon the amount of said dialkanolamine present.
-??-
-??-
9. The process in accordance with Claim 1 wherein said N-(substituted) dialkanolamine is N-methyl diethanolamine.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58300575A | 1975-06-02 | 1975-06-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1074317A true CA1074317A (en) | 1980-03-25 |
Family
ID=24331295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA253,358A Expired CA1074317A (en) | 1975-06-02 | 1976-05-26 | Production of an n-(substituted) piperazine compound |
Country Status (2)
| Country | Link |
|---|---|
| BE (1) | BE842462A (en) |
| CA (1) | CA1074317A (en) |
-
1976
- 1976-05-26 CA CA253,358A patent/CA1074317A/en not_active Expired
- 1976-06-01 BE BE167538A patent/BE842462A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BE842462A (en) | 1976-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4044053A (en) | Preparation of polyalkylene polyamines | |
| US4036881A (en) | Preparation of polyalkylene polyamines | |
| US4552961A (en) | Preparation of polyalkylene polyamines using phosphorus amide catalyst | |
| EP0073520B1 (en) | Preparation of polyalkylene polyamines from ammonia, alkyleneamine and alkanolamine | |
| JPH0445505B2 (en) | ||
| US4103087A (en) | Production of di-(N,N-disubstituted amino) alkanes | |
| US4617418A (en) | Polyalkylene polyamines via vapor phase reaction | |
| CA1078381A (en) | Production of bis-(morpholino-n-alkyl) ethers | |
| US4049657A (en) | Preparation of N-(aminoalkyl)piperazine | |
| JPS61236752A (en) | Production of acyclic ethylene amine | |
| CA1074317A (en) | Production of an n-(substituted) piperazine compound | |
| EP0093434B1 (en) | Preparation of polyalkylene polyamines | |
| EP0078000B1 (en) | A process for preparing allylamines from allyl alcohol | |
| US4888425A (en) | Preparation of polyalkylene polyamines | |
| US4092316A (en) | Synthesis of C-alkyl-triethylenediamines | |
| CA1074314A (en) | Method of producing morpholine compound | |
| CA1070305A (en) | Method of producing morpholine compound | |
| CA1074312A (en) | Method of producing an n,n'-(disubstituted) piperazine compound | |
| CA1224896A (en) | Preparation of polyalkyline polyamines using phosphorus amide catalyst | |
| US4066649A (en) | Method of producing n,n'-(dimethyl) piperazine compounds | |
| CA1092114A (en) | Method of producing an n-(substituted) morpholine compound | |
| US5639916A (en) | Amination of allylic alcohols | |
| CA1078382A (en) | Production of bis-(n,n-disubstituted amino) compounds | |
| NO761856L (en) | ||
| US4299956A (en) | Method of making N-(2-methoxyethyl)morpholine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |