Note: Descriptions are shown in the official language in which they were submitted.
Background of the Invention
Field of the Invention
_.
The instant invention generally relates to an
improved process for producing bis-(N,N-disubstituted amir.o)
compounds such as bis-(N,N-dimethylamino)ethane or bis-
(morpholino ethyl)ether directly from a diol and a
secondary amine compound; and more particularly, to an
improved selective liquid phase process for directly
producing certain bis-(N,N-disubstituted amino) compound in
the presence of certain specific catalytically effective
substances.
Prior Art
Bis-(N,N-disubstituted amino) compounds such as the
alkanes, ethers and the like are generally well-known compounds
having established utility as polyurethane catalysts. For
1~7838Z
example, bis-(morpholino-N-alkyl)ethers generally have
established utility as polyurethane catalysts. The entire
class of these ether compounds is useful in catalyzing urethane
systems, including the C-alkyl substituted bis-(morpholino-
N-alkyl)ether compounds ~herein one or both of the morpholine .
moieties contain C-(substituted) alkyl radicals on one or
more of the carbon atoms and/or ~herein the N-alkyl moiety
is either a branched or straight chain divalent radical.
The N,N'-dimorpholino alkanes are also generally useful in
catalyzing urethane systems including the corresponding
C-alkyl substituted compounds.
Bis-(N,N-disubstituted amino) compounds such as
the bis-(N,N-disubstituted amino) alkanes have generally
been prepared by methods involving halogenated reactants or
intermediates. For example, in one method, N-(2-chloroethyl)
morpholine is reacted ~ith morpholine. Such methods of prepara-
tion are unsatisfactory in that the halogenated reactants are
not readily available, and the methods involve caustic
neutralization of the product and the concomitar.t disposal
of polluting by-products, such as the alkali halide salts.
Additionally, the bis-(N,N-disubstituted) ethers
such as bis-(morpholino-N-alkyl)ethers have been prepared by
many methods. Examples of some of the more ~ell-known methods
are disclosed in U. S. Patent No. 3,787,354. In one method
.. ~ . . . . .. .
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for bis-(morpholinoethyl)ether synthesis, N-(2-chloro-
ethyl)morpholine is reacted with N-(2-hydroxyethyl)- ~
morpholine (HEM) and sodium. See, for example, J. Amer. Chem. -
Soc., 62, 1448 (1940) and Acta Chem. Scand., 8, 350 (1954).
Another method involves the reaction of triethanolamine in
the presence of hydrochloric acid. See, for example, J. Pharm.
Soc. Japan, 75, 1367 (1955). Still another method involves the
reaction of morpholine with bis-(2-chloroethyl)ether. See, for
example, Bull. Soc. Chim. France, 3537 (1965). As mentioned
above, many of these processe s involve caustic neutralization
with atter.dant problems~ Ir. addition, these methods involve the ;
use of chemical intermediates which are difficult to obtain and/or
produce the desired product in low yield wherein the reaction
product mixture contains by-products which are difficult to
separate by known methods.
In addition, there are procedures described in the
literature for preparing bis-(N,N-disubstituted amino)
compounds in the presence of various catalysts. For example, ~;
it is disclosed in U. S. Patent No. 3,843,648 that N-amino-
alkylated morpholines are produced by the cGndensation of
N,N-dimethylaminoethanol and morpholine in vapor phase in
the presence of AlP04 catalyst or a silica-alumina cracking
oatalyst at temperatures of 200C to 400C.
Additionally, it has been disclosed that certain
phosphoric acid compounds are effective as catalysts in
promoting condensation reactions between some types of amines,
and tertiary aminoalkanols. These reactions are carried out under
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:, .,
relatively mild liquid phase processing conditions. For
example, U. S. Patent No. 3,121,115 to Meuly teaches a ~-~
process for aminoalkylating certain amines having a
replaceable amino hydrogen, particularly aromatic primary -~
and secondary amines, which includes heating the amine
compourd with an N-tertiary aminoalkanol at from 150 C to -~
250 C in liquid phase with continuous water removal in the
presence of a phosphoric acid compound such as aqueous or
anhydrous orthophosphoric acid, phosphorus pentoxide or
an alkyl phosphoric acid. However, the disc~osed process
requires long reaction times.
Further, the corresponding bis-ethers are known to
be produced in a vapor phase reaction with, for example,
N-(2-hydroxyethyl)morpholine (HEM) in the presence of an
lS activated alumina catalyst. See, for example, J. Amer. Chem.
Soc., 36, 298 (1941). This method suffers the attendant
problems of vapor phase synthesis with low yields and
extensive by-product formation.
Unexpectedly it has now been found that bis-
(N,N-disubstituted amino) compounds can be selectively
produced directly from the readily available corresponding
N,N-disubstituted amine and a diol compound in liquid
phase without the attendant deficiencies of previously
knowr. processes. Under rigorous reaction conditions, i.e.
temperatures in the 250 C to 350 C range, the inventive
process is surprisingly selective to the desired product.
The expected extensive decomposition and concomitant pro-
- duction of unwanted side products is minimized. Additionally,
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the compounds effective in catalyzing the synthesis of th~
instant invention are readily available. The instant process
does not require an expensive neutralization step nor is it
attended by vapor phase reaction deficiencies such as vaporizing
the reactants, low con~ersion rates, low selectivities, catalyst
deactivation and the like. Additionally a diamine such as
piperazine may be utilized as the amine compound to produce
oligomeric products.
Summary of the Invention
According to the broad aspect of the instant invention,
a compound having at least one secondary amino group is reacted
with a diol compound,and preferably an alkylene diol, in the
presence of a catalytically effective amount of certain
phosphorus-containing compounds at temperatures of from about
250C to about 350C at pressures sufficient to maintain the
reactants and products in liquid phase.
The products selectively formed in practicing the
instant invention can be depicted by the general formula:
~N-R-N ~
R2 R2
wherein R is the divalent hydrocarbon-containing nucleus of
a diol, and each Rl and R2, independently, is an alkyl radical
having from 1 to about 18 carbon atoms, or each pair, Rl and R2,
ta~en together with the nitrogen atom to which each is attached,
form a morpholino group, a p~perazino group, an N'-(s~bst~tu~ed)
piperazino group, a C-alkyl substituted morpholino group, a
(C-alkyl substituted) piperazino group, or an tN-substituted)
(C-alkyl substituted) piperazino group.
.. .. ... . . . . .
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In accordance with one aspect of the invention,
bis-(morpholino-N-alkyl)ether compounds are selectively
produced directly from morpholine and an oxydialkanol compound
in a catalyzed reaction process which includes initially con-
tacting the reactants in the presence of a catalyticallyeffective amount of certain phosphorus-containing substances
at temperatures of from about 250C to 350C while reaction
pressures sufficient to retain the mixture substantially in
liquid phase are maintained.
In a preferred embodiment, a bis-(morpholino-d,~-
alkane compound is selectively produced by use of morpholine
and the corresponding alkylene diol in accordance with the
inventive process.
Description of the Preferred Embodiments
In accordance with the inventive process, the
bis-(N,N-disubstituted amino) compounds produced are the result
of a trimolecular di-dehydration of an N,N-disubstituted amine,
such as morpholine, and a diol, such as an alkylene diol, a;
dialkanolamine, an N-(alkyl~dialkanolamine, an oxydialkanol
and the like. Thus, by varying the nucleus of the diol, one
can achieve9 for example, the corresponding bis-(N,N-
disubstituted amino)alkane compound, the bis-(N,N-disubstituted~
N-alkyl)ether, or the bis-(N,N-disubstituted-N-alkyl)amine.
Additionally, the amine compound can contain two
secondary amines in the same molecule, thus providing sites
for- oligomeric addition. For example, piperazine and ethylene
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1C~783~3Z
diol can form a corresponding polyethylene polyamine compound
under appropriate reaction conditions in accordance with the
invention.
The N,N-(disubstituted)amines which are useful in
the practice of this invention can be generally characterized
as secondary amines. These comp~unds can be depicted by the
formula:
~R
HN
wherein each Rl and R2, independently, is an alkyl radical having
from 1 to about 18 carbon atoms, or Rl and R2, taken together
with the nitrogen atom to which each is attached form a
morpholine group, a piperazine group, an N-substituted
piperazine group, a C-alkyl substituted morpholine group, a
piperazine group or an N-substituted C-alkyl substituted
piperazine group. Illustrative amines include dimethylamine,
diethylamine, dihexylamine, ethylpropylamine, morpholine,
piperazine, 2-methylmorpholine, 2-ethylpiperazine, 2,6-
dimethylmorpholine and the like.
Preferred NjN-(disubstituted~amines in the practice
of this invention are those of the above formula wherein each R
and R2, independently, is an alkyl radical having from ab~ut
2 to about 4 carbon atoms?a morpholine group,or ~he C-alkyl
substituted morpholines wherein the C-alkyl substituents are
lower alkyl radicals such as methyl, ethyl and.the like.
.
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-~he diol compounds that can be used in accordance
with the invention need only contain more than one primary or
secondary hydroxy moiety wherein the remainder o~ the molecule
is non-deleterious to the reaction. Generally, the diol
compounds are of the formula
OH - R- OH
wherein R is a hydrocarbon containing,divalent moiety which
can consist of, for example, an alkylene radical, a dialkylene
ether radical, or a dialkylene amine radical. Preferably, R is
an alkylene radical of from 2 to about 5 carbon atoms and more
preferably an n-ethylene radical.
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 acids 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 aqueous
or anhydrous phosphoric acids such as orthophosphoric acid,
pyrophosphoric acid, metaphosphoric acid, and condensed
. ~. . . . . -
.. . . . . .. . . .
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phosphoric aclds such as polyphosphoric acids. Accordingly,
an example of a 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 aïkyï or aryl substituLted phosphoric
acids or phosphorous acids which may be em?loyed 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 ha~e from 1 to about 8
carbon atoms in each alkyl group and about 6 to about 20 carbon
atoms in each aryl group.
Specific examples of alkyl and aryl substituted phos-
phorous and phosphoric acids that may be used in accordance
with the invention are phenylphosphinic, ethylphosphonic,
phenylphosphonic, naphthaphosphonic, and methylphosphinic
acids. Examples of the alkyl and aryl substituted phosphorous
and phosphoric acid esters are methylphenyl phosphonate,
dimethylphenyl phosphonate, methylphenyl phosphinate, ethyl
naph~haphosphinate, and propylmethyl phosphonate.
.. - .. -... . .. . . .
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The above-mentioned phosphorus compounds are not
intended to be exhaustive of those which may be employed as
a catalyst material in the process of the present invention.
Those materials are set forth to specify types of phosphorus
compounds that we have found to be particularly effective as
catalysts. Yet, of the compounds and types of compounds
mentioned, we especially prefer to~employ those that have
been found to be most reactive under the processing conditions
of the invention. These especially preferred compounds include
boron phosphate, aqueous and anhydrous orthophosphoric acid,
pol~phosphoric acid, aluminum phosphate, ferric phosphate,
aqueous and anhydrous orthophosphorous acid, triethylphosphite,
triethylphosphate, and diethylphosphite, to name a few. Only
a catalytically effective amount of the pho~phbrus substance
is required to effect the condensation reaction between the
reactants resulting in the formation of essentially salt-free
product in good yield.
The quantity of phosphorus compound employed as the
catalyst ln the inventive process may vary widely, depending
upon its reactiv~ty, the reactants present and particular
processing conditions employed. Usually this catalytic amount
is within the range of from about 0.01 to about 10.0 wt. %,
based upon the amount of diol compound material present; and-
preferably the catalyst is employed in an amount of from about
0.5 to about 5.0 wt. % based upon the amount of diol compound.
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Any of the above-mentioned phosphorus compounds may
be employed as the catalyst of the process either alone, in
combination with one of the other mentioned phosphorus
compounds, or in combination with acidic compounds such as
boric acid and the like. These latter acid compounds are
generally ineffective as catalysts by themselves in the
inventive process.
According to a greatly preferred embodiment, an
alkylene diol and morpholine are intimately contacted by
admixing. The admixture is heated in the presence of the
phosphorus-containing substance at a temperature of from about
250C to about 350C and preferably at a temperature of about
275C to about 325C, under a pressure sufficient to maintain
the reactlon mass ~n liquid phase which normally ranges from
about 200 to about 2,000 psig. The react~on is allowed to
proceed at the temperature employed until the desired amount
- of conversion is obtained. Preferably the reaction is carried
out under such conditions for a time period sufficient to
provide a total reactants con~ersion of from about 10% to
about 75% which is usually within the range of about 0,5 to
about 5.0 hours.
The alkylene diol and the morpholine are contacted
for reaction at molar ratios of from about 1:1 to about 1:5.
Preferably, the morpholine compound i5 employed in excess,
such a~ about 0.5 to about 0.33 moles of alkylene diol per
mole of morpholine.
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Generally 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 0.1
to about 4.0, preferably from about 0.5 to 1.5, grams total
reactants per milliliter of total reactor volume per hour.
In such continuous reaction processes, the above-
described phosphorus-containing catalyst materials may be
employed as a feed stream alone or admixed with a reactant
feed stream, or they may be employed as a fixed bed catalyst
in the continuous reactor system. Generally speaking, these
fixed bed catalysts comprise the phosphorus-containing
catalyst material supported on a material such as silica,
silica-alumina, alumina, dia~omaceous earth, etc., con-
ventionally employed as inert reactor packing materials.
Such fixed bed supported catalysts and procedures for their
; preparation are well-known in the art and many are readily
available commercially.
It is not critical to control the amount of water
of reaction present during the heating of reactants and
catalyst, such as by removal thereof as it is formed.
Usually, we prefer to retain the water in the reaction zone
and remove it from the reaction mass during recovery of the
product.
\` ~0'7~38Z ,
The desired N,N-disubstituted amine compound may ~-
be readily recovered from the reaction product mass by conven-
tional procedures, such as distillation, without difficulty.
For example, the reaction product mass may be directly distilled,
or initially filtered to remove a small amount of formed solids - ;
which usually are amine salt complexes of the phosphorus
compound eatalyst, and then distilled.
It should be realized that when the diol compound is,
for example, a diethanolamine, that cyclization to the corres-
ponding bis-N,N'disubstitutedpiperazine compound is possible
as a side reaction, resulting in a sacrifice in yield of the
desired product. Accordingly, when these diol compounds or
their eorresponding C-alkyl substituted homologs are utilized, a `
large excess of the secondary amine compound is preferred.
Additionally, as mentioned hereinbefore, when
piperazine is utilized as the amine reagent, two secondary
amine reaction sites are present on a single molecule. Thus
polymerization to various polyamine compounds is possible. -~
While the concept of polyamine formation is within the scope
of the invention, many times it is desired to form the bis- ;
(piperazino)alkane. In order to aecomplish this selectivity,
the proeess of the instant invention is carried out wherein
an exeess of piperazine is utilized at temperatures o~ 275C
to about 325C.
13 r
` ` 107838Z
, .
The invention will be further illustrated by the
following specific examples, which are given by way of
illustration and not as limitations on the scope of this
invention.
Example I
To a l-liter stirred stainless steel autoclave was
charged 261 g (3.0 moles) morpholine, 95 g (1.25 mole) 1,2-
monopropylene diol, and 8 g (0.029 mole) aqueous 30% ortho-
phosphorous acid. After the autoclave was purged with
nitrogen and sealed the mixture was heated to 300 C and held
for 2.0 hours under a pressure of 450-650 psig with continuous
stirring. After cooling, the crude reaction mass was analyzed
by gas-liquid chromatography which showed it contained on a
lights-water free basis, area %, 48.7 morpholine, 10.3
monopropylene diol, and 24.3 area % of an unknown component.
The reaction product mixture was distilled employing a 1 x 12
inch Vigreux column and 82 g of a colorless liquid, b.p.
113-114C/1.8 mm was collected. Nuclear magnetic resonance
(NMR) spectroscopy established the identity of the liquid
collected as 1,2-di-(4-morpholino)propane.
Example II
Employing the general procedure and equipment of
Example 1, 174 g (2 moles) of morpholine, 44 g (0.5 moles)
of 2-butenediol-1,4 and 6 g (0.022 mole; 4.4 mole %) of 30%
phosphorous acid were charged into the autoclave and heated
under a nitrogen atmosphere at 280 C and 500 psig for about
14
. ~
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~07838Z
1 hour. After cooling, the reaction mass was recovered and
distilled. Upon distillation, unreacted morpholine and 50 g
of a colorless liquid boiling at 148-150C/3 mm Hg were
recovered. The colorless distillate was shown by 2~
5 analysis to be 1,4-bis (N-morpholino)-2-butene. The NMR
analysis was further verified by titration.
Example III
According to the general procedure and equipment
of Example I, 261 g (3 moles) morpholine, 96 g (1.06 moles)
of 1,3-butylene diol and 8 g (0.029 moles; 2.8 mole %)
of 30% phosphorous acid were charged into the autoclave
and heated under a nitrogen atmosphere for 2 hours at
300C and 425-615 psig. After cooling,the reaction nass
was recovered and distilled into 5 fractions as listed in
15 Table I below.
TABLE I
Pressure,
Fraction Grams mm B.p., C
. . _
22 0.6 79-85
2 36 1.3 85
3 23 1.0 85-92
4 20 1.8 92-128
48 1.8 128-137
Fractions 1-4 were shown by analysis to consist essentially
of morpholinobutanol and predominantly 4-(N-morpholino)-
2-butanol and 3-(N-morpholino) -l-butanol. The fifth
fraction, i.e. that fraction having a boiling point of
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~L~783~2
128-137C/1.8 mm Hg was shown by analysis to consist
essentially of pure 1,3-bis (N-morpholino)butane.
Example IV
Employing the general procedllre and reaction equipment
described in Example I, 262.0 g (3.0 moles) morpholine,
106.0 g (1.0 mole) oxydie~hanol and 11.4 g (0.1 mole~
85% orthophosphoric acid were heated, with stirring, at
300C for 3.0 hours under a pressure of 375-540 psig.
Analysis of the reaction product mass by gas-liquid chroma-
tography (lights-water free basis, area ~/O) showed it contained
20.6 morpholine, 4.5 oxydiethanol, 9.6 hydroxyethoxyethyl-
morpholine, 21.1 1,2-bis-(morpholino)ethane, 31.0 2,2'-
dimorpholinodiethyl ether and 2.() heavies.
Example V
Employing the procedure described in Example I, a
ser~es of runs were conducted to obtain 1,2-ethylenedipipera-
zine employing varying amounts of piperazine and ethylene
diol and various types and amounts of acidic phosphorus-
containing compounds as catalyst, as set forth in the follow-
ing Table II. In all runs the reactant-catalyst mixture was
heated at a temperature of 290C under autogenous pres~ure for
2.0 hours. Conversion of ethylene diol was essentially complete
in all cases. Gas-liquid chromatography analytical results of
each reaction product are also set forth in the following Table II.
The results of Table II demonstrate the varied types of acidic
phosphorus-containing compound~ that may be employed as a
catalyst in the inventive process.
16
. ~ , ~ .. ., . . . .. . ~ . , .
AL-2677-1
1~7838Z
o
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17
AL-2677-1
1078382
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.
18
.
