CA2029428A1 - Preparation of alcohol-extended and amine-extended piperazines - Google Patents

Abstract

ABSTRACT

A process for preparing alcohol-extended and amine-extended piperazines comprising contacting a difunctional aliphatic alcohol with a reactant amine, wherein at least one of the aliphatic alcohol or the reactant amine contains a piperazine moiety, in the presence of a catalyst containing a tungsten heteropoly acid. For example, monoethanolamine reacts with piper-azine in the presence of a 12-tungstophosphoric acid catalyst to yield predominately N-(2-aminoethyl)piper-azine, which is an amine-extended piperazine.

37,087-F

Description

-- 2 ~ 8 , , .

PREPARATION OF ALCOHOL-EXTENDED
AND AMINE-EXTENDED PIPERAZINES

. .

This invention relates to a process for preparing alcohol-extended piperazines~ such as N-(2-hydroxyethyl)piperazine, and amine-extended piperazines, such as N-(2-aminoethyl)piperazine, bls(piperazinylalkanes), and oligo(piperazinylalkanes).
Hereinafter, bis(piperazinylalkanes) will be referred ~o as bispiperazines.

Alcohol-extended and amine-extended pipera-zines are useful intermediates in the preparation of melt adhesive polymers and fine industrial chemicals, including veterinary antihelmintic pharmaceuticals, insecticides, and high temperature lubricating oils.

U.S. 3,364,218 teaches the self-condensation of N-(2-hydroxyethyl)piperazine to poly-1,4-ethylene-piperazine in the presence of hydrogen and a solid acidcatalyst, such as silica-alumina, alumina, tungsten oxide, aluminum phosphate, and acid clays. It is difficult to control the degree of polymerization in .
this process. Accordingly, it is difficult to obtain 37,087-F -1-, , . ~ :

3~

high yields of N-(2-aminoethyl)piperazine, bis(piperazinylethanes), tris(pipera2inylethanes)5 or other specific oligo(piperazinylethanes). Moreover, cyclic compounds, such as 1,4-diaza-[202.2]
-bicyclooctane, are produced as undesirable by-products.
In addition, the catalysts employed in this process lose their physical integrity in the presence o~ amines and water; therefore, the process is hampered by catalyst losses and separation problems.

U.S. 4,552,961 discloses a process for the preparation of polyalkylene polypiperazines comprising reacting piperazine with alkylene glycols or alkanol-amines in the presence of a catalyst of phosphorus amide. Disadvantageously, this catalyst is homogeneous and must be separated from the product stream.

It would be advantageous to have a catalytlc ~rocess for preparing alcohol-extended and amine--extended piperazines. It would be more advantageous if the degree of polymerization of such a process could be controlled, and selective alcohol-extended and amine--extended piperazines could be prepared in high yields.
It would be even more advantageous, if the catalyst for such a process was insoluble in the reaction mixture.
With an insoluble catalyst the problems of leaching, plugging, and catalyst separation would be avoided, and the amination process would be more suitable for industrial adaptation.

This invention is a process for preparing alcohol-extended and amine-extended pipera~ines comprising contacting in the presence of a catalyst a 37,o87-F -2-, ., : -. :
., ; . . . :: :: :::~: . :

~2~

difunctional allphatic alcohol with a reactant amine, wherein at least one of the aliphatic alcohol or reactant amine contains a piperazine moiety. The catalyst is a composition containing a tungsten heteropoly acid. The contacting is conducted under reaction conditions such that a mixture of alcohol--extended and/or amine-extended piperazines is produced.

Advantageously, the process of this invention is capable of producing a wide range of alcohol-extended and amine-extended piperazines in high selectivity. Moreover, the process of this invention does not produce significant amounts of undesirable cyclic by-products. More advantageously, the catalyst of this in~/ention is insoluble in the reaction mixture;
therePore, catalyst losses are minimized and separation of the product stream from the catalyst i9 relatively easy. These combined advantages render the process of this invention suitable for industrial use.

Alcohol-extended piperazines and amine--extended piperazines are useful lntermediates in the preparation of melt adhesive polymers and fine industrial chemicals, including veterinary antihelmintic pharmaceuticals, insecticides, and high temperature lubricating oils.
The products of the process of this invention are alcohol-extended and amine-extended piperazines.
These products are described in detail hereinafter; but, are easily illustrated by the following three examples.
The first comprises N-(2-hydroxyethyl)pipera7ine, which is an alcohol-extended piperazine and which is prepared by reacting ethylene glycol with piperazine. The second 37,087-F -3-', , ~ . ! ' ~ ' :

' , , ~ ' ' ' ` ~ ' ' ' 2 ~ 2 ~ ~ 2 ~ :

comprises N-(2-aminoethyl)piperazine, which is an amine~
-extended piperazine and which is prepared by reacting monoethanolamine with piperazine. The third comprises bis(piperazinyl)ethane, which is also an amine-extended piperazine and which is prepared by reacting N-(2-hydroxyethyl)piperazine with piperazine. It is observed that in each example the products are linearly-extended materials obtained by the condensation of a difunctional alcohol with a reactant amine.

At least one of the reactants must contain a piperazine moiety in order for the process to yield an alcohol-extended or amine-extended piperazine product.
Accordingly, it is within the scope of this invention for the difunctional alcohol to contain the piperazine moiety, as in the amination of N~(2 hydroxyethyl) piperazine by ammonia or a primary aliphatic amine.
Likewise, it is within the scope of this invention for the reactant amine to contain the piperazine moiety, as in the amination of ethylene glycol by piperazine or N-(2 aminoethyl)piperazine. It is also within the scope of the invention for both the difunctional alcohol and the reactant amine to contain a piperazine moiety, as in the amination of N-(2-hydroxyethyl)piperazine by piperazine to yield bis(piperazinyl)ethane. It is to be understood, therefore, that at least one of the difunctional alcohol or the reactant amine must contain a piperazine group.

The difunctional aliphatic alcohols which are employed in the process of this invention include any aliphatic alcohol containing (a) at least one hydroxyl moiety bound to a primary carbon atom~ and (b) at least 37,087-F _4_ ' 2 ~ d ~

one additional moiety selected from the group consisting of hydroxyl, primary amine or secondary amine function-alities. Examples of suitable difunctional alcohols include diols such as ethylene glycol and propylene glycol, triols such as glycerol, and higher polyols;
polyether polyols such as diethylene glycol, poly~
propylene glycols, and higher homologues; alkanolamines such as monoethanolamine and N-(2-aminoethyl)ethanol-amine; polyether amino alcohols .such as 2-(~-aminoeth-oxy)ethanol; and hydroxyalkyl-substituted piperazines, such as N-(2-hydroxyethyl)piperazine, N,N'-bis(2 -hydroxyethyl)piperazine, and N-(2-hydroxyethyl)bis-piperazines. The difunctional alcohols are not limited to the aforementioned examples, and other equally suit-able difunctional alcohols can be employed in the prac-tice of this invention.

In those reactions wherein the difunctional alcohol does not contain a piperazine moiety, the preferred difunctional alcohols are represented by the general formula:

37,087-F _5_ , ' ,,, , ,, . . ",, ,,, ~3~

H H
A ~B-- ( ~ ) æ CH2 OH
R R

;:

wherein A is OH or NHR; each B is independently NR or O;
each R is independently hydrogen, hydroxy~ amino (NH2), a lower alkyl moiety of C1-C12 carbon atoms such as methyl, ethyl or propyl 9 a hydroxyalkyl or aminoalkyl 5 moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety, such as phenyl, or tolyl; x is an integer from 2 to 12; k is an integer from O to 150; and z is an integer from 1 to 12. Some examples of difunctional alcohols which satisfy this formula include monoethanol-amine, ethylene glycol, propylene glycol, and N-( 2 -aminoethyl)ethanolamine. Preferably, R is hydrogen.
More preferably, R is hydrogen, x is 2, and z is 1.
Most preferably, R is hydrogen, A is NH2, k is 0, z is 25 1, and the difunctional alcohol is monoethanolamine.

In those reactions wherein the difunctional alcohol contains a piperazine moiety, the preferred difunctional alcohols are represented by the general 3 formula:

37,087-F -6-:

.

`` .

Z `~ 2 ~

S
HOCH ~ C~ H2~

wherein each B is independently NR or ~; each R is independently hydrogen, hydroxy, amino (NH2), a lower alkyl moiety of Cl-C12 carbon atoms such as methy:L, ethyl or propyl, a hydroxyalkyl or aminoalkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety, such as phenyl, or tolyl; each y is independently an integer from 0 to 12; j is an integer from 1 to 6; and n is an integer from 0 to 6. Some examples of difunctional alcohols which satisfy this formula are N-(2-hydroxyethyl)piperazine, N-(2-hydroxyethyl)bis-piperazine, N,N'-di(2-hydroxyethyl)piperazine, and N,N' -di(2-hydroxyethyl)bispiperazine~ Preferably, R
is hydrogen. More preferably, R is hydrogen, each y is independently 1 or 2, j is 1 or 2, n is 0-2, and B is NR. Most preferably, R is hydrogen, y is 1, j is 1, n 3o is 0, and the compound is N-(2-hydroxyethyl)piperazine.

The reactant amines which are employed in the process of this invention include ammonia and any pri-mary or secondary aliphatic amine which is capable of aminating the difunctional alcohol. Examples of suit-37,087 F -7~-.

.
: : ~
.

:: ~

d ~

able reactant amines include primary and secondary monoamines such as ethylamine, propylamine, n-butyl-amine, hexylamine, octylamine, diethylamine, dipropyl-amine, dibutylamine, dihexylamine, dicyclohexylamine, and dioctylamine; linear and branched alkylene diamines or polyamines such as ethylenediamine, propylenediamine, diethylenetriamine, triethylenetetramines, and tetra-ethylenepentamines; alkylene ether polyamines such as 2-(~-aminoethoxy)ethylamine; piperazine and oligo- -(piperazinyl alkanes) such as bispiperazines and tris-piperazines; aminoalkyl-substituted piperazines such as N-(2-aminoethyl)piperazine and N,N'-bis(2-aminoethyl) ;
piperazine; and mixtures of the above-identified amines.
While the aforementioned reactant amines are represen-tative of those .~hich are suitable in the process of this invention, other reactant amines not recited herein may be equivalent and equally suitable.

In those reactions wherein the reactant amine does not contain a piperazine moiety and is an alkylene-polyamine or alkylene ether polyamine, the preferred species are represented by the general formula-/ H \ H

RHN ---tCI)x B ~ C)x NHR
R k R
3o wherein each B is independently NR or 0; each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms such as methyl, ethyl or propyl, a hydroxyalkyl or aminoalkyl moiety of C1-C12 37,o87-F _~_ ,::

2 ~
g carbon atoms, or a monocyclic aromatic moiety) such as phenyl, or tolyl; each x is independently an integer from 2 to 12, and k is an integer from 0 to 150. Some examples of reactant amines which satisfy this formula include ethylenediamine, diethylenetriamine, 2,2'-di(aminoethyl)ether, and triethylenetetramine.
Preferably, B is NR and the amine is an alkylene-polyamine. More preferably, B is NR and R is hydrogen.
Most preferably, B is NR, R is hydrogen, each x is 2, and the amine is an ethylenepolyamine.

In those reactions wherein the reactant amine contains a piperazine moiety, preferred piperazines or aminoalkyl-substituted piperazinas are represented by the general formula:

H ~R~ C ~ C~H

wherein each R is independerltly hydrogen, hydro~y, 3o amino, a lower alkyl moiety of C1-C12 carbon atoms such as methyl, ethyl or propyl, a hydroxyalkyl or aminoalkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety, such as phenyl, or tolyl; each y is inde-pendently an integer from 0 to 12; each l is independently an integer from 0 to 6; and j is an 37,o87-F _g_ integer from 1 to 6. Some examples of reactant amines which satisfy this formula include piperazine, N (2 -aminoethyl)piperazine, N,N'-bis(2-aminoethyl)pipera-zine~ bis(piperazinyl)ethane, and N-(2-aminoethyl)bis-piperazine. Preferably, R is hydrogen. More preferably, R is hydrogen, y is 1 or 2, j is 1 or 2, l is 0-2, and B is NR. Most preferably, each R is hydro-gen, y is 0, j is 1, and each l is 0, and the compound is piperazine.

In accordance with the process of this inven-tion, any mole ratio of reactant amine to difunctional ;~
aliphatic alcohol which enables the amination reaction to proceed to the desired alcohol-extended or amine--extended piperazine products is suitable. Typically, the difunctional aliphatic alcohol is reacted with at least about one mole equivalant o~ reactant amine;
however, an excess of reactant amine can be advanta geously employed. Preferably, the mole ratio of reac-tant amine to difunctional alcohol is in the range from0.1 to 20. More preferably, the mole ratio of reactant amine to difunctional alcohol is in the range from 1 to 15; most preferably from 2 to 10.

Although, preferably, a solvent is not used in the amination reaction, it is within the scope of the invention ~or a solvent to be used, if desired. Any solvent is acceptable provided that (1) it is not reactive with the difunctional alcohol, the reactant amine, or product piperazines, and (2) it does not decompose under the conditions of the reaction. Some examples of suitable solvents include water, saturated aliphatic hydrocarbons such as pentane, hexane, heptane, octane~ nonane, and decane, and aromatic hydrocarbons 37,o87-F -10-::
::

2 ~ 8 such as benzene, toluene, and xylene. The amount of solvent employed depends on the particular reactants and reaction conditions. Any amount of solvent is accept-able that meets the intended purpose of use. Typically, the solvent constitutes from 5 weight percent to 95 5 weight percent of the feed stream. Preferably, the `
solvent constitutes from 10 weight percent to 80 weight percent of the feed stream.

The catalyst employed in the process of this invention contains a tungsten heteropoly acidO Hetero-poly acid anions are comprised of oxygen, a framework atom, and one or two atoms of a third element known as the heteroatom. In the heteropoly acid catalysts of this invention, the framework atom is tungsten. It is within the scope of this invention for one or two atoms of the tungsten cluster to be substituted with a second framework met~l, such as Ti, Zr, V, Nb, Ta, Mo, Mn, Fe, Co, Ni, and Cu. Such substituted framework clusters are still predominately tungsten clusters. The heteroatom is an element from Groups IIIA, IVA, VA, VIA, the transition elements, or the rare earth lanthanide and actinide metals of the Periodic Table. Examples of suitable heteroatoms include P, Si, Ga, Al, As, and Ge, as well as B, Co, Ce, Pr, U, and Th. The heteropoly acid can be employed in its acid form or as a metal salt, either of which can also be hydrated. The degree of water associated with the tungsten heteropoly acid can vary depending upon whether the heteropoly acid has been dried, and if dried, at what temperature. Prefer-ably, the tungsten heteropoly acid of this invention is represented by the general formula:

Cc[DdWwMmOo]

37,087-F -11 ~2~2~

wherein C is the counter cation, typically H+, NH4+, quaternary ammonium salts such as tetra(octyl)ammonium (+1), or any metallic cation such as K+, Co~2, Cu~2, or mixtures of the above; D is the heteroatom; W is tung sten, the framework atom; M is an additional framework atom, and 0 is oxygen. The letters c, d, w, m, and o are each numbers which identify the number of atoms of the corresponding element per molecular formula of the cluster. Preferably, d is a positive integer from 1 to 3; w is a positive integer from 8 to 40; m is an integer from 0 to 2; and o is a positive integer from 20 to 100.
The letter c represents a positive number sufficient to maintain overall charge neutrality by balancing the charge of the anion. Examples of suitable tungsten heteropoly acids, which satisfy the above-identified formula, include but are not limited to: H3~PW12040], H4[SiW12040]~ Na3[PW12040]~ (NH4)3[Pwl2o4o~ 2Na[ W12 40]' C3/2[P~12040]~ Al[PW12040]; as well as heteropoly-tungstates having the polyoxoanion cluster [P2WlgO62]6~~
such as H6[P2W~gO62]; open framework structures having other than 12 or 18 framework metal ions, such as H7[PW11039]~ K7[PW1103g]~ Kg[siwl1o3g]~ and Kg[GeW11039];
as well as triheteropoly acids such as H4[VPW11~o] and H5[V2PW10040]~ Ks[MnPW1103g]~ Ks[CoPW1103g], and K5[CuPW11039]. Preferably, the heteroatom is P or Si, and the heteropoly acid is a tungstophosphoric acid or tungstosilicic acid, respectively. More preferably, the heteropoly acid is a tungstophosphoric acid. Even more preferably, the heteropoly acid is a 12-tungsto-phosphoric acid species, which means that the tungsten/phosphorus mole ratio is 12/1. Most preferably, the heteropoly acid is H3[PW12040].

37,087-~ -12-~,. , ~, .

: : - . : .

The heteropoly acids of this invention can be purchased ommercially or synthesized by procedures documented in the art. See, for example, Cornprehensiue InorganicChemistry, Vol. 3 7 A. F. Trotman-Dickenson et al., eds., Pergamon Press~ Oxford, 1973, pp. 767-768, and reference~ therein.

The tungsten heteropoly acid can be soluble in the reaction mixture, and therefore, can act as a homo-geneous catalyst. Alternatively9 the tungsten hetero~poly acid can be insoluble in the reaction mixture, and therefore, can act as a heterogeneous catalyst. The solubility of the tungsten heteropoly acid varies depending upon the specific alcohol and amine reactants, the specific cation associated with the heteropoly anion, and the size of the heteropoly anion.
Preferably, the heteropoly acid is insoluble and acts as a heterogeneous catalyst, because then it is easier to separate from the produot stream.

One preferred method of ensuring that the tungsten heteropoly acid is insoluble in the reaction mixture is by applying the heteropoly acid to a support material. Any support material is acceptable provided that it does not hinder the formation of the desired alcohol-extended or amine-extended piperazines in the process of this invention. Suitable supports include carbon and refractory oxides such as alumina9 zirconia, boria, thoria, magnesia, titania, tantala, chromia, silica. kielselguhr, niobia, zeolites, as well as mix-tures thereof. Preferably, the support material is titania. The support material typically has a surface area of at least about 0.1 m2/g. Preferably, the sup-port material has a surface area in the range from 5 37,087-F -13----`` 2 ~ 2 8 m2/g to 600 m2/g; and most preferably in the range from ~`
50 m2/g to 200 m2/g. These surface areas are measured by the Brunauer-Emmett-Teller (3ET) method, which is described by R. B. Anderson in Experimental Methods in Catal~tic Research, Academic Presst New York, 1968, pp.
48-66.

The tungsten heteropoly acid can be applied to the support material in any known ~ashion, such as the impregnation technique, or by precipitation insitu from the catalyst preparation reaction. Preferably, the resulting catalyst composition is calcined in air at a temperature below the decomposition point of the heter-opoly cluster. Typically, the calcination is conducted at a temperature not greater than about 900C. Prefer-ably, the catalyst is calcined at a temperature between 175C and 500C, more preferably, between 200C and 350C. Typically, the catalyst composition is calcined for a time in the range from 2 hours to 24 hours. It will be understood that the phosphorus and tungsten are present on the calcined support in the form of tungstophosphoric groups. The exact nature of the chemical binding of the catalyst to the support is not completely understood; however, the support and calcination generally yield a catalyst having improved physical stability.

The amount of catalyst which is employed in the process of this invention is any amount which is effective in producing the desired alcohol extended and amine-extended piperazines. The amount of catalyst varies considerably depending upon the specific reac-tants and reaction conditions employed. Typically, in a batch reactor the amount of catalyst is in the range 37,o87-F -14-:

, 2~2~

from 0.1 weight percent to 20 weight percent based on the weight of reactant amine. Preferably9 the amount of catalyst is in the range from 1 weight percent to 15 weight percent based on the weight of reactant amine.

Generally, the process of this invention can be carried out in any suitable reactor, including batch reactors, continuous fixed-bed reactors, slurry reac-tors, fluidized bed reactors, and catalytic distillation reactors. Preferably, the reactor is a continuous fixed-bed reactor.

The reactants are contacted with the catalyst at any operable temperature which promotes the amination process of this invention and yields the desired alcohol-extended and amine-extended piperazine products.
Typically, the temperature is in the range from 200~C to 350C. Preferably, the temperature is in the range from 250C to 325C. More preferably, the temperature is in the range from 260C to 315C. Below the preferred lower temperature the conversion of difunctional aliphatic alcohol may be low. Above the pre~erred upper temperature the selectivity for alcohol-extended and amine-extended piperazines may decrease.

Likewise, the reactants are contacted with the catalyst at any operable pressure which promotes the amination process of this invention and yields the desired alcohol-extended and amine-extended piperazine products. Typically, the pressure is sufficient to maintain the reactants in the liquid state at the tem-perature of the reaction. Preferably, the pressure is in the range from atmospheric to 4000 psig. More preferably, the pressure is in the range from 100 psig 37,087-F -15-.; . .', ~ : :

2 ~

to 3000 psig. Most preferably~ the pressure in the range from 400 psig to 2000 psi~. In batch reactors the pressure is autogenous, and depends on the vapor pressures of the reactants and products and the tempera ture of the reaction.

When the process is conducted in a continuous flow reactor, the flow rate of the reactants can be varied. Generally, the difunctional aliphatic alcoho:L
and the reactant amine are premixed to form a feed stream, which is fed into the reactor at any operable flow rate which yields the desired alcohol-extended or amine-extended piperazine products. The flow rate is expressed as the liquid hourly space velocity (LHSV) and is given in units of grams of total reactants per milliliter of total reactor volume per hour, g ml~1 hr~1. It is preferred to employ a liquid hourly space velocity of reactants in the range from 0.1 g ml~1 hr 1 to 10.0 g ml~1 hr~1; more preferably in the range from 0.5 g ml~1 hr 1 to 4.0 g ml~1 hr~1. It should be understood that the space velocity controls the residence time of the reactants in a continuous flow reactor.

When the process is conducted in a batch reactor, the reaction time determines the length of contact between the reactants and the catalyst. Any reaction time is acceptable which allows the amination reaction to proceed to the desired alcohol-extended and amine-extended piperazine products. The reaction time will depend on the quantity of reactants, the quantity of catalyst, the temperature of the reaction and desired degree of conversion. Preferably, the reaction time in a batch reactor is in the range from 1 hour to 20 hours.

37 ~ o87-F -16-~ 2 ~

When the difunctional aliphatic alcohol and the reactant ~mine are contacted in accordance with the process of tnis invention, the alcohol and the reactant amine react to ~orm a mixture of alcohol-extended and/or amine-extended piperazine products, and water is eliminated as a by-product. These products can be fur-ther described as linearly-extended materials. If the difunctional alcohol contains two or more hydroxyl moi-eties, the reactant amine may react at each hydroxyl.
Thus, as noted hereinbefore, ethylene glycol reacts with piperazine to yield predominately N-(2-hydroxyethyl) piperazine, an alcohol-extended piperazine, and ~ono-ethanolamine reacts with piperazine to yield pre-dominately N-(2-aminoethyl)piperazine~ an amine-extended piperazine. ~igher amine-extended piperazine oligomers can also be produced, as in the reaction of piperazine with hydroxyethylpiperazine to yield bis(piperazinyl) ethane and tris(piperazinyl)ethane. Other amine--extended piperazines which can be produced in the process of this invention include N,N'-bis(2-aminoethyl) piperazine, and N,N'-bis(2-aminoethyl)bispiperazine.
Other alcohol-extended piperazines which can be produced in the process of this invention include ~,N'-bis(2 -hydroxyethyl)-piperazine and N~(2-hydroxyeth-yl)bispiperazines. In addition to the linearly-extended products, it is possible to obtain certain undesirable cyclic by-products, including, for example, 1,4-diaza--[2,2,2]-bicyclooctane.
The preferred alcohol-extended and amine--extended piperazine products can be represented by the general formula:
wherein each B is independently O or NR; each R is independently hydrogen, hydroxy, amino, a lower alkyl 37 ~ o87-F -17-i . .

2~2~2~

N N ~ )y 11 moiety of C1-C12 carbon atoms such as methyl, ethyl or propyl, a hydroxyalkyl or aminoalkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety, such a~
phenyl, or tolyl; each y is independently an lnteger from 0 to 12; h and h' are each independently integers from 0 to 6; and j' is an integer from 0 to 6. Some examples of products which satisfy this formula include N-(2-aminoethyl)piperazine, N-(2-hydroxyethyl)-piperazine, bispiperazines and higher oligomers of piperazine. Preferably, R is hydrogen. More preferably, R is hydrogen, y is 1 or 2, j' is 1 or 2, h and h' are each independently 0-2, and B is NR. Most preferably, B is NR, R is hydrogen, y is 2, h is 1, j' and h' are each 0, and the product is N-(2 -aminoethyl)piperazine.

3 For the purposes of this invention, "con-version" is defined as the weight percentage of difunc-tional aliphatic alcohol lost from the feed stream as a result of reaction. The conversion can vary widely depending upon the reactants, the form of the catalyst, and the process conditions such as temperature, pres-' ~1 ' '' 9~

sure, and flow rate. I~ithin the preferred temperature range, as the temperature increases the conversion typically increases. Within the preferred space ~elocity range, as the space velocity increases the conversion typically decreases. Typically, the conversion of the difunctional alcohol is at least about 3 weight percent. Preferably, the conversion is at least about 10 weight percent; more preferably at least about 30 weight percent; even more preferably, 45 weight percent; and most preferably, at least about 55 weight percent.

Likewise, for the purposes of this invention "selectivity" is defined as the weight percentage o~
converted difunctional alcohol which forms a particular alcohol-extended or amine-extended piperazine product.
Typically, the selectivities also vary widely depending upon the reactants, the form of the catalyst, and the process conditions. Within the preferred temperature range, as the temperature increases t~e selectivity for alcohol-extended and amine-extended piperazines typi-cally decreases. Within the preferred space velocity range, as the space velocity increases, the selectivity for alcohol-extended and amine-extended piperazines typically increases. Typically, the process of this invention achieves high selectivities to alcohol--extended and amine-extended piperazines. Preferably, the combined selectivity to alcohol-extended and amine--extended piperazines is at least about 50 weight percent, more preferably, at least about 65 weight percent, most preferably, at least about 80 weight percent. In the specific amination of monoethanolamine by piperazine, the product N-(2-aminoethyl)piperazine is produced in a selectivity of at least about 30 weight 37,087-F -19-:

.~: , '.~ .' ': ~`

percent, more preferably, at least about 50 weight percent, most preferably, at least about 60 weight percent.

The following examples illustrate the invention, but are not intended to be limiting thereof.
All percentages are given as weight percent, unless noted otherwise. In some instances the following abbreviations are used to indicate the reactants and products:
~EA monoethanolamine EDA ethylenediamine AEEA N-(2-aminoethyl)ethanolamine DETA diethylenetriamine TETA triethylenetetramine PIP piperazine AEP N-(2-aminoethyl)piperazine DIAEP N,N'-di(2-aminoethyl)piperazine PEEDA (piperazinylethyl)ethylenediamine BISPIP bispiperazine or 1,2-bis(piperazinyl) ethane DABC0 1,4-diazabicyclo-[2.2.2]-octane Example 1 (a) Preparation of Catalyst 12-Tungstophosphoric acid, H3[PW12040]-10.8 percent H20, (2.012 g, Alfa) is dissolved in 50 ml of acetonitrile to form a solution. Titania (20.004 g;
SAKI CS-200) is added to the solution, and the mixture is rotated on a rotary evaporator while the solvent is removed. The dry solid is heated under air at 200C
.

37,087-F -20-.~1 , .

:~

2 ~

overnight to yield a titania-supported tungstophosphoric acid catalyst.

(b) Amination of Monoethanolamine The titania-supported tungstophosphoric acid catalyst (30.0 g), prepared hereinabove, is loaded into a stainless steel tubular, fixed-bed, contlnuous flow reactor (approximately 20 cm3 volume) fitted at both ends with glass wool plugs. A feed stream comprising monoethanolamine, piperazine, water, and optionally, ethylenediamine and diethylenetriamine is passed through the catalyst bed at a ~lariety of reaction temperatures, pressures, and flow rates. (See Table I.) The liquid effluent from the reactor is collected and sampled by gas phase chromatography. An SE-54 capillary column (30 m x 0.25 mm dia.) is employed to measure total amine products. Isomer distributions are measured on an SE-30 capillary column (30 m x 0.25 mm dia.). The process conditions and results are presented in Table I.

37 y o87-F -21---`` 2~9~2~

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~ ~ S ~ N ~ OJ O`~ a) -1 0 U~ Lr~ ~ ~) Ir~ ~ ~ t~l _ ~
H ~i t'\l ~I ~ ~ O ~ O S.. ~1 1~ C~
_ ~_ __ ~_ _ ~_ ~ a~ bOO
Q ~n S O~ r- ~ ~ C~ bl) ~ m ~3 ~ C~ O 'D Lf~ C~ U~
oo ~ co ~n ~ c ¢ o .......... _. . ~ _ . C) ~ Z
a~ ~ ~ s o o ~r ~ o~ a~
~ ¢ ~ ~ C~ ~ ~ ~ O CL a Q. ~ H L~ ~ ~ ~ 1~ t~.i ~ al ~ ~
O ~ c _ _ ... .... _ . .
._, ~ o o o o o ~ o ~
U~ _ _ . _ _ _ C~ s~'o O ~O 3 ~ ~ 3 ~ O ~I

4~ O =S N ~D ~) ~ IS~ .,~
¢ ~ 3 ~O ~I CJ~ ~O t- a~
~O ~O ~O ~ 3 ~o 3 ~d ~ o ~o_ _ . ~ _ __ ~ _ ~ ¢ ~
C~¢ In ,_ ~ 3 t- r- IS~ a) E~
~~ u~ Ln ~ . ~ ~r ~o c~ ~ ~
H¢ ~O ~0 ~ ~ 3 ~D 3 O ~I E3 ~_ _ ........ _ _ _ ¢ a o o N O O O O ~ Ct~D
_ ~_ _ ~'. _ _ a) 0 a) ~
¢ ~) N C,~
~ o o ~ ~ o o o ~ v? c~--- - ~ -- o -~- - -. - ~, o ~ ~

¢~ ~ ~ ~o o co o~ ~ ~ O c~
t~ O N ~ ~ N oO a ~1 ~1 .
~1 L~ 3 3 ~O (y~ ~O O ~ O ^V~
___ ... . _ ..~ _ ~ OC) c) ~ a) o ~1 x 0 n c) ~ a~ c., ~o 0 c ~ o c ~D . . .. ~ . ~ ~ .o ., ~ _ ~ O ~ Q, 37087-F ~23-.

"_~ 2~J~s38 The data show that the conversion of monoethanolamine increases as the reaction temperature increases. More-over, the products which are formed are predominately alcohol-extended and amine-extended piperazines, 3o 37,087-F -24-: . .

. : .. . ; . ; ~ -:
.; , ~ ,. : . . :

Claims (25)

1. A process for preparing alcohol-extended and amine-extended piperazines comprising contacting a difunctional aliphatic alcohol with a reactant amine, wherein at least one of the difunctional alcohol or reactant amine contains a piperazine moiety, the con-tacting occurring in the presence of a catalyst under conditions such that a mixture of alcohol-extended and/or amine-extended piperazines is formed, said catalyst containing a tungsten heteropoly acid.

2. The process of Claim 1 wherein the difunctional alcohol is represented by the formula:wherein A is OH or NHR; each B is independently NR or O; each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms, a 37,087-F -25-hydroxyalkyl or aminoalkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety; x is an integer from 2 to 12; k is an integer from 0 to 150; and z is an integer from 1 to 12.

3. The process of Claim 2 wherein R is hydrogen.

4. The process of Claim 3 wherein x is 2 and z is 1.

5. The process of Claim 4 wherein R is hydrogen, A is NH2, k is 0, z is 1, and the difunctional alcohol is monoethanolamine.

6. The process of Claim 1 wherein the difunctional alcohol is represented by the formula:

wherein each B is independently NR or O; each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms, a hydroxyalkyl or amino-alkyl moiety of C1-Cl2 carbon atoms, or a monocyclic aromatic moiety; each y is independently an integer from 37,087-F -26-0 to 12; j is an integer from 1 to 6: and n is an integer from 0 to 6.

7. The process of Claim 6 wherein R is H, y is 1, j is 1 and n is 0, and the difunctional alcohol is N-(2-hydroxyethyl)piperazine.

8. The process of Claim 1 wherein the reactant amine is represented by the formula:

wherein each B is independently NR or 0; each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms, a hydroxyalkyl or amino-alkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety; each x is independently an integer from 2 to 12; and k is an integer from 0 to 150.

9. The process of Claim 8 wherein the reactant amine is an ethylenepolyamine.

10. The process of Claim 1 wherein the reactant amine is represented by the formula:

37,087-F -27- wherein each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms, a hydroxyalkyl or aminoalkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety; each y is independently an integer from 0 to 12; each 1 is independently an integer from 0 to 6; and j is an integer from 1 to 6.

11. The process of Claim 10 wherein R is hydrogen, y is 0, j is 1, each 1 is 0, and the compound is piperazine.

12. The process of Claim 1 wherein the mole ratio of reactant amine to difunctional aliphatic alcohol is at least 1.

13. The process of Claim 1 wherein the catalyst is represented by the formula Ce[DdWwMmOo]
wherein C is the counter cation, D is the heteroatom, W
is tungsten, M is an additional framework atom, O is oxygen, and c, d, w, m, and o each represent the number 37,087-F -28-of atoms of the corresponding element per molecular formula of the cluster.

14. The process of Claim 13 wherein the heteroatom is P or Si.

15. The process of Claim 14 wherein the heteropoly acid is a 12-tungstophosphoric acid,

16. The process of Claim 15 wherein the heteropoly acid is H3[PW12040].

17. The process of Claim 1 wherein the amount of catalyst is in the range from 0.1 weight percent to 20 weight percent based on the weight of reactant amine.

18. The process of Claim 1 wherein the temperature is in the range from 200°C to 350°C.

19. The process of Claim 1 wherein the pressure is in the range from atmospheric to 4000 psig.

20. The process of Claim 1 wherein the liquid hourly space velocity is in the range from 0.1 g m1-1 hr-1 to 10.0 g ml-l hr-1.

21. The process of Claim 1 wherein the alcohol-extended and amine-extended piperazines are represented by the formula:

37,087-F -29- wherein each B is independently O or NR; each R is independently hydrogen, hydroxy, amino, a lower alkyl moiety of C1-C12 carbon atoms, a hydroxyalkyl or amino-alkyl moiety of C1-C12 carbon atoms, or a monocyclic aromatic moiety; each y is independently an integer from 0 to 12; h and h' are independently integers from 0 to 6; and j' is an integer from 0 to 6.

22. The process of Claim 21 wherein B is NR, R
is hydrogen, y is 2, h is 1, j' and h' are 0, and the product is N-(2-aminoethyl)piperazine.

23. A process for preparing N-(2-aminoethyl) piperazine comprising contacting monoethanolamine with piperazine in the presence of a catalyst containing titania-supported 12-tungstophosphoric acid under conditions sufficient to prepare N-(2-aminoethyl)piper-azine in a selectivity of at least about 30 weight percent.
37,087-F -30-

24. The process of Claim 23 wherein the N-(2 -aminoethyl)piperazine is produced in a selectivity of at least about 50 weight percent.

25. The process of Claim 24 wherein the N-(2 -aminoethyl)piperazine is produced in a selectivity of at least about 60 weight percent.

37,087-F -31-