METHOD FOR PREPARING 2-ALKENYL-2-OXAZOLINES

PREPARATION DE 2-ALKENYL-2-OXAZOLINES

English Abstract

ABSTRACT
2-Alkenyl-2-oxazolines are prepared by (A)
reacting an anhydrous 2-alkyl-2-oxazoline with formaldehyde
in a molar ratio of at least 1.5 moles of oxazoline per
mole of formaldehyde to form 2-(.alpha.-hydroxymethylalkyl)-2-
-oxazoline (I), (B) recovering (I) from the reaction product
and (C) reacting (I) with a hydroxide of an alkali or
alkaline earth metal.
The process of step (A) is conducted at 90°-115°C
and the process of step (C) is conducted at 95°-200°C.
The present process results in higher yields of
desired product than the prior art processes that employed
either an excess of formaldehyde or equimolar quantities of
formaldehyde and 2-alkyl-2-oxazoline in step (A).

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing a 2-alkenyl-2-oxa-
zoline comprising the steps of:
(A) reacting an anhydrous 2-alkyl-2-oxazoline
with formaldehyde in a molar ratio of at least 1.5 moles of
2-alkyl-2-oxazoline per mole of formaldehyde, thereby form-
ing the 2-(.alpha.-hydroxymethylalkyl)-2-oxazoline,
(B) recovering the 2-(.alpha.-hydroxymethylalkyl)-2-
-oxazoline from the reaction product of Step A, and
(C) reacting the 2-(.alpha.-hydroxymethylalkyl)-2-
-oxazoline from step B with an alkali or alkaline earth
metal hydroxide, thereby forming the 2-alkenyl-2-oxazoline.
2. The process of Claim 1 wherein said 2-alkyl-
-2-oxazoline corresponds to the formula:
<IMG>
wherein R is alkyl of from 1 to about 18 carbon atoms
having replaceable hydrogen on the .alpha.-carbon atom.
3. The process of Claim 2 wherein R is a linear
alkyl group.
4. The process of Claim 3 wherein R is methyl or
ethyl.
5. The process of Claim 1 wherein the molar ratio
of oxazoline to formaldehyde is from 2 to 10.
6. The process of Claim 5 wherein the molar ratio
is from 3 to 5.
12

7. The process of Claim 1 wherein the reaction
temperature in step A is from 90° to 115°C.
8. The process of Claim 7 wherein the reaction
temperature of step A is from 95° to 105°C.
9. The process of Claim 1 wherein the alkali or
alkaline earth metal hydroxide is sodium hydroxide, potassium
hydroxide, lithium hydroxide or barium hydroxide and the
reaction temperature of step C is from 95° to 200°C.
10. The process of Claim 9 wherein the alkali or
alkaline earth metal hydroxide is sodium hydroxide.
11. The process of Claim 10 wherein step C is
conducted in the absence of a solvent or in the presence of
a lower alkyl monoether of a polyalkylene glycol.
12. The process of Claim 11 wherein said lower
alkyl monoether of a polyalkylene glycol is the monomethyl
ether of triethylene glycol.
13. The process of Claim 1 comprising the steps
of:
(A) reacting anhydrous 2-ethyl-2-oxazoline with
paraformaldehyde, having a formaldehyde content of at least
about 95 weight percent, in a molar ratio of from 3 to 5
moles of 2-ethyl-2-oxazoline per mole of formaldehyde at a
reaction temperature of from 95° to 105°C, thereby forming
2-(.alpha.-hydroxymethylethyl)-2-oxazoline,
(B) recovering the 2-(.alpha.-hydroxymethylethyl)-2-
-oxazoline from the reaction product of step A by fractional
distillation, and
13

(C) reacting the 2-(.alpha.-hydroxymethylethyl)-2-
-oxazoline from step B with sodium hydroxide dissolved in
an aqueous solution of the monomethyl ether of triethylene
glycol at a reaction temperature of from 100° to 105°C
under reduced pressure, thereby forming 2-isopropenyl-2-
-oxazoline which is distilled from the reaction mixture
essentially at the rate it is formed.
14

Description

~078393
The present invention is a process for preparing
2-(-hydroxymethylalkyl)-2-oxazolines and 2-alkenyl-2-
-oxazolines.
The 2-alkenyl-2-oxazolines are particularly useful
compounds due to their difunctionality. Of these, the 2-
-vinyl- and 2-isopropenyl-2-oxazolines are perhaps two of
the more useful compounds due to their reactivity in vinyl
polymerizations. 2-Isopropenyl-2-oxazoline, for instance
has a reactivity much like an acrylate in vinyl polymeri- ~
zations.
Prior art methods of preparing 2-alkenyl-2- ~-
-oxazolines have heretofore utilized relatively expensive
reagents in multistep processes and the product yield was
normally low.
The teachings of U.S. Patent 3,535,332, issued to
Runge et al, October 20, 1970, and of French Patent 1,557,954
are of particular interest relative to the instant process.-
~oth of these references teach that 2-hydroxyalkyl-2-oxa-
zolines can be prepared by reacting a 2-alkyl-2-oxazoline
with formaldehyde and that such compounds can be subsequently
dehydrated to form the 2-alkenyl-2-oxazolines. In these
reactions, the 2-hydroxyalkyl-2-oxazolines were prepared by
~` reacting a 2-alkyl-2-oxazoline with an excess of formalde-
hyde even though the ~road teachings indicated that equi-
molar amounts of reactants could ~e used. The disclosure
in U.S. Patent 3,523,123, issued to Wehrmeister August 4,
1970, is similar in this regard. The dehydration of the 2-
-hydroxyalkyl-2-oxazolines was thermally and/or catalytically
induced. French Patent 1,557,954 is the only reference
which in fact shows the preparation of 2-isopropenyl-2-
18,036-F -1-

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. 1078393
-oxazoline; a compound which (along with 2-vinyl-2-oxazoline)
is unique among other 2-alkenyl-2-oxazolines due to its
extremely high reactivity. ~ ,
The defects of the prior art have been substantially
overcome by the present invention which is a process for pre-
paring a 2-alkenyl-2-oxazoline comprising the steps of:
(A) reacting an anhydrous 2-alkyl-2-oxazoline with
formaldehyde in a molar ratio of at least 1.5 moles of 2-
-alkyl-2-oxazoline per mole of formaldehyde, thereby forming
the 2-(a-hydroxymethylalkyl)-2-oxazoline,
(B) recovering the 2-(a-hydroxymethylalkyl)-2-
- -oxazoline from the reaction product of step A, and
(C) reacting the 2-(a-hydroxymethylalkyl)-2-
-oxazoline from step B with an alkali or alkaline earth
metal hydroxide, thereby forming the 2-alkenyl-2-oxazoline.
r . Steps A and C individually as well as the combin-
ation o steps A-C are thought to be novel processes.
Step A
Step A is conducted by reacting an anhydrous or
essentially anhydrous 2-alkyl-2-oxazoline with formaldehyde
to thus make the corresponding 2-(~-hydroxymethylalkyl)-2-
-oxazoline.
Any 2-alkyl-2-oxazoline can be used herein so long
as the 2-alkyl groups bear replaceable hydrogen on the ~-
-carbon atom (i.e. adjacent to the oxazoline ring). The
oxazoline reactants can bear inert ring substituents (e.g.
alk~l groups) in the 4-and/or 5-ring positions. Preferred
reactants correspond to the formula
H C- N
1 / C-R
H2C--
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- wherein R is an alkyl (preferably linear) group of from
1 to about 18 carbon atoms. The most preferred reactants
are 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline since these
are the reactants leading to 2-vinyl-2-oxazoline and 2-iso-
propenyl-2-oxazoline, respectively. Other examples of
suitable oxazoline reactants include: 2-propyl-, 2-butyl-,
2-hexyl-, 2-heptyl-, 2-nonyl-, 2-undecyl-, 2-heptadecyl-2-
~oxazolines and the corresponding 2-substituted 4-methyl-2-
-oxazolines, 4-ethyl-2-oxazolines, 4-butyl-2-oxazolines, 4,4-
-dimethyl-2-oxazolines and 4,5-dimethyl-2-oxazolines.
The yield of the desired 2-(a-hydroxymethyl)-2-
-oxazoline product is maximized when excess 2-alkyl-2-oxa-
zoline is used in the process. Normally, we use at least
about 1.5 moles of 2-alkyl-2-oxazoline per mole of formalde-
hyde. The preferred ratio of reactants, however, is from
about 2 to about 10 moles of oxazoline reactant to formalde-
hyde and the most preferred ratio is from about 3 to about
S moles of oxazoline reactant per mole of formaldehyde.
In addition to the utilization of excess oxazoline
reactant in the process, we have found that product yields
are maximized by conducting the reaction under anhydrous ar
substantially anhydrous conditions. For this reason, we -
prefer to predry the oxazoline reactant (normally with
molecular sieves or solid sodium hydroxide) and use a source
of formaldehyde that is low in water content. Paraformalde-
hyde having a 95 percent or greater formaldehyde content
is commercially available and is the preferred formaldehyde
source. Formaldehyde per se and other non-aqueous sources
of formaldehyde (e.g. trioxane and other polymers of for-
maldehyde) are suitable, however.
1~ 036-F -3-

~078393
The process may be conducted at any suitable
temperature ~hat promotes the reaction and is below the de-
composition temperature of the desired product. Satisfactory
reaction rates have been observed at temperatures of from
about 90 to about 115C and temperatures of from about 95
to abou~ 105C are normally preferred. At these temperatures,
reaction times of from about 2 to about 8 hours are conven-
tional. Inert organic solvents (e.g., benzene, toluene, etc.)
may be used if desired but we prefer to conduct the process
without using a solvent.
Step B
The 2-(a-hydroxymethylalkyl)-2-oxazoline may be
recovered from the reaction product of Step A by any of
several conventional techniques, for example, by solvent
extraction or fractional distillation. In those instances
where the oxazoline reactant and product are liquids and/or
low melting solids, fractional distillation under reduced
pressure at a temperature below the decomposition temper-
ature of 2-~-hydroxymethylalkyl)-2-oxazoline is normally
used. In this manner, the excess oxazoline reactant and
water normally codistill and are recovered. The reactan~
oxazoline/water distillate can then be dried and the 2-
-alkyl-2-oxazoline recycled back into Step A. The 2_l-
-hydroxymethylalkyl)-2-oxazolines are higher boiling and
thus recovered from the distillation as the "pot residues"
which can be used per se in Step C but are preferably
further purified (generally by distillation using a falling
film still or other conventional techniques) before use.
We have found that the overall yield of the 2-
-alkenyl-2-oxazoline is maximized when Step B is conducted
as soon as practical after Step A.
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.
Step C
In this step, the 2-(a-hydroxymethylalkyl)-2-
-oxazoline is dehydrated by contacting same with an alkali
or alkaline earth metal hydroxide, thereby forming the 2~
-alkenyl-2-oxazoline. This~ reaction may be conducted at any
- temperature sufficient to promote the dehydration but we
have found satisfactory reaction rates normally occur at
temperat~res of from a~out gS to about 200~C under
reduced pressure (e.g., from about 10 to about 150 mm.Hg).
Essentially any alkali or alkaline earth metal
hydroxide can be used in Step C but the efficiency of the
alkali or alkaline earth metal hydroxides to promote the
dehydration tends to correlate with the degree of solubllity
of the alkali or alkaline earth metal hydroxide in hot water.
That is, the more water soluble the alkali or alkaline earth
metal hydroxide is in hot water the more efficient it
- appears to be in dehydrating the 2~ hydroxymethylalkyl)-
-2-oxazoline. Lithium hydroxide, sodium hydroxide, potassium
hydroxide and barium hydroxide are the preferred catalysts
and sodium hydroxide is most preferred, ~ased upon its
efficiency and relative costs.
Step C may be conducted in a batchwise or contin-
uous manner and we prefer to conduct it in a continuous
manner. In the continuous process, the 2-(a-hydroxymethyl-
alkyl)-2-oxazoline is added to the alkali or alkaline earth
metal hydroxide catalyst at reaction temperature. The 2-
-alkenyl-2-oxazoline can-normally be volatilized at the
reaction temperatures under reduced pressure and is codis-
tilled with water from the reaction vessel. Thus, the 2-
~ hydroxymethylalkyl)-2-oxazoline is metered into the
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1078393
reaction vessels at substantially the same rate at which
the 2-alkenyl-2-oxazoline/water mixture is removed as over-
heads. The 2-alkenyl-2-oxazoline can be conveniently
recovered from the 2-alkenyl-2-oxazoline/water solution
using conventional solvent extraction techniques.
Inert organic solvents which remain liquid at the
reaction temperature may be included in Step C if desired.
However, we find that Step C is preferably conducted either
neat or in the presence of a lower alkyl monoether of a
polyalkylene glycol. The latter compounds are known to be
solvents for the alkali and alkaline earth metal hydroxides
and are, therefore, preferred organic solvents for use in
this step. This known class of compounds include, for
example, the methyl, ethyl, propyl and butyl ethers of
diethylene glycol, triethylene glycol, etc. The monomethyl
ether of triethylene glycol appears to be the most efficient
when sodium hydroxide is used as the catalyst.
EXAMPLE 1 - Preparation of 2-Isopropenyl-2-oxazoline
~-Ethyl-2-oxazoline ~594 g; 6.0 moles) and 9S
; 20 percent paraformaldehyde (63.2 g; 2.0 moles~ were charged
to a reaction vessel equipped with a mechanical stirrer and
condenser. The reaction mixture was heated to 100C with
stirring and maintained under these conditions for 4 hours.
A sample of the reaction mixture was then analyzed by ~apor
phase chromatography with the following results: 60.7 -
- weight percent 2-ethyl-2-oxazoline; 37.9 weight percent 2-
-(à-hydroxymethylethyl)-2-oxazoline; and the remaining 1.4
weight percent was not identified. On these data, the
- conversion of 2-ethyl-2-oxazoline was 98.5 percent and the
the percent yield of 2-(a-hydroxymethylethyl)-2-oxazoline
:
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1078393
was 96.5 percent. The excess 2-ethyl-2-oxazoline was
removed from the reaction mixture by distillation under
reduced pressure leaving the desired 2-(a-hydroxymethylethyl)-
-2-oxazoline as the still bottoms.
Sodium hydroxide beads (60.0 g; 1.5 mole) were
- - added to a reaction vessel equipped with a mechanical stirrer,
a dropping funnel and a distillation column packed with 1/4
inch (0.64 cm.) glass beads. This materiaI was heated to a
pot temperature of approximately 175C at a pressure of 150
mm.Hg. ~o this heated system was added the 2-(a-hydroxy-
methylethyl)-2-oxazoline from the above (containing 100 ppm
of a polymerization inhibitor) at a rate of approximately
1 g. per minute. A11 volatiles passing through the distil-
lation column were collected in a cold trap and analyzed by
vapor phase chromatography using 1,2,4-trichlorobenzene as
an internal standard. The mixture contained 2.5 weight
percent unreacted 2-ethyl-2-oxazoline; 11.7 weight percent
water; and 85.8 weight percent 2-isopropenyl-2-oxazoline.
This amounts to a 97.8 percent yield of 2-isopropenyl-2-
-oxazoline.
Similar high yields were obtained when the dehy-
dration was conducted using sodium hydroxide dissolved in
the monomethyl ether of triethylene glycol and a-minor
; amount of water. Data obtained on a series of such dehy-
drations indicate that the effective life of the sodium
hydroxide catalyst was extended by using this material as a
reaction medium.
EXAMPLE 2 - Preparation of 2-(~-dodecenyl)-2-oxazoline
Using the same ratio of reactants and substantially
the same process conditions, 2-lauryl-2-oxazoline was
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~78393
reacted with paraformaldehyde at 100C for 5 hours. The
2-~-hydroxymethylalkyl)-2-oxazoline product crystallized
out of the liquid reaction mixture. The solid product was
separated by filtration and recrystallized in n-hexane. The
recrystallized product was obtained as a white crystalline
solid melting at 64-67C. The yield of recrystallized
product was 70 percent, based on formaldehyde. A portion of
this recrystallized material (15 g; 0.06 mole) was warmed
to a melt and added dropwise to sodium hydroxide beads
-10 (20 g.) preheated to a temperature of 175C at 0.5 mm.Hg.
~he 2-(a-dodecenyl)-2-oxazoline was immediately volatilized
and was collected in a cold trap cooled with ice water. The
product was thus obtained as a liquid boiling at 127~C at
0.03 mm.Hg in 71 percent yield, based on the starting 2-
-~-hydroxymethyllauryl)-2-oxazoline.
EXAMPLE 3 - Preparation of 2-Vinyl-2-oxazoline
Using the same reaction conditions set forth in
Example 1, 2-methyl-2-oxazoline was reacted with formalde-
hyde, thereby forming 2-hydroxyethyl-2-oxazoli~e in approxi-
mately 83 percent distilled yield~ The proauct had a ~oil-
ing point of 55-58C at 0.5 mm~HgL Dehydration of the
product was likewise performed under conditions similar to
Example l. Sodium hydroxide beads (20 g.) were heated to
150C at 150 mm~Hg. To this was added dropwise the 2-
-hydroxyethyl-2-oxazoline (56 g; 0.49 mole) and the volatiles
thus formed collected in a receiver cooled with ice water.
The condensed volatiles were identified as an aqueous
solution of 2-vinyl-2-oxazoline which boiled at 83-85C at
150 mm. Hg. No impurities appeared to be present in the
aqueous solution of the 2-vinyl-2-oxazoline and the recovered
product amounted to a material balance of over 95 percent~
18,036-F -8-

- ~o78393 . .
;
EXAMPLE 4 - Preparation of 2-Isopropenyl-2-oxazoline
A stainless steel reaction vessel was loaded with
paraformaldehyde (96.7 percent) and 2-ethyl-2-oxazoline in
a molar ratio of approximately 4 moles of oxazoline per
mole of fonmaldehyde. The ~xazoline reactant was predried
over 3 A molecular sieves and contained only 490 ppm water.
The reaction mixture was blanketed with dry nitrogen and
the system closed. The reaction mixture was heated to
100C and maintained at this temperature for a period of
4.5 hours. The excess 2-ethyl-2-oxazoline was subsequently
distilled from the reaction mixture at 20 mm~Hg pressure.
The distillation took two hours and was terminated when the
overhead temperature reached 97Co This gave 30 parts by
weight of pot residue containing 92 weight percent 2~
; 15 -hydroxymethylethyl)-2-oxazoline and 74.5 parts by weight
t of distillate containing 98 weight percent 2-ethyl-2-oxazo-
line, 1.5 weight percent 2-(a-hydroxymethylethyl)-2-oxazo- t
li~e, 0.52 weight percent water, and a trace of 2-isopro-
, penyl-2-oxazoline. About 1.2 parts by weight of the reaction
mixture was removed during the course of reaction as samples~
The yield of 2-(-hydroxymethylethyl)-2-oxazoline was thus
94 percent, based on formaldehyde charged and 92 percent
based on 2-ethyl-2-oxazoline consumed.
The crude 2 (~-hydroxymethylethyl~ oxazoline
was flash distilled in a continuous distillation in which an
aliquot of the crude material was heated to distillation
tem~erature and thereafter the crude material was added at
essentially the same rate at which the distillate was taken
overhead. The overhead temperature was 87-97C/2.6-5 mm.Hg.
18,036-F _g_

~0783g3
Sodium hydroxide beads (43.9 parts by weight) and
water (28.9 parts by weight) were charged to a reaction
vessel containing a mechanical stirrer, heating means, and
distillation apparatus. The mixture was stirred unt~l the
sodium hydroxide dissolvèd after which the monomethyl ether
of triethylene glycol (150.6 parts by weight) was added.
Pressure over the system was reduced to 40 mm.Hg and the
mixture heated to 97C, ca~sing some of the water to distill
- overhead at approximately 36C and leaving a ~olution of
the sodium hydroxide in the pot.~ The distilled 2-(a-hydroxy-
methylethyl)-2-oxazoline was then added to the reaction -
flask at a controlled rate by means of a metering pump.
During this addition, 2-isopropenyl-2-oxazoline and water
were formed which were simultaneously removed overhead
during the reaction at a head temperature of 56-59C and
a pot temperature of from 102-108C/39-40 mm.Hg. After
the addition of the 2-(a-hydroxymethylethyl)-2-oxazoline
was complete, the pot temperature was raised to 150C o~er
a twenty minute period to drive out the last of the avail-
able 2-isopropenyl-2-oxazoline. The water-white clear
distillate was analyzed by vapor phase chromatography usin~
1,~,4-trichlorobenzene as an internal standard. This analy- -
sis showed the distillate to be 83.9 weight percent 2-iso-
propenyl-2-oxazoline, 15.6 weight percent water (by Karl
Fischer analysis) and 0.28 weight percent 2-ethyl-2-oxazoline.
This represents a 97.1 percent yield of 2-isopropenyl-2-oxa-
zoline based on the 2-(a-hydroxymethylethyl)-2-oxazoline
charged.
The products in the above reactions were also
identified by infrared and nuclear magnetic resonance
spectroscopy.
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Other 2-alkenyl-2-oxazolines could be similarly
prepared using the appropriate 2-alkyl-2-oxazoline and
formaldehyce reactants as et forth above.
~ .~
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