Note: Descriptions are shown in the official language in which they were submitted.
~ ~ 7~66 ~
LIQUID PHASE PREPARATION
OF 2-SUBSTITUTED-2-OXAZOLINES
WITH ORGANIC ZINC SALT CATALYSTS
2-Substituted-2-oxazolines form a known class of
compounds having many members and many utilities. The chem-
istry of such oxazolines has been summarized, for example,
by Wiley et al., Chemical Reviews, Vol. 44, 447 (1949), by
Seeliger et al., Angew. Chem. International Edition, Vol. 5,
No. 10, 875 (1966), and by Frump, Chemical Reviews, Vol. 71,
No. 5, 483 (1971).
One of the prior art processes for preparing
2-substituted-2-oxazolines is the cyclodehydration of
N-(b-hydroxyalkyl)carboxamides. This cyclodehydration
occurs in vapor phase over alumina (U.S. Patent 3,562,263
and Frump, as mentioned above, page 485) and in liquid phase
over certain salts of manganese, cobalt, rare earth metals,
molybdenum and tungsten (U.S. Patents 3,681,329 and
3,681,333). The latter two patents indicate that the
cyclodehydration reaction is brought about by heating the
hydroxyamide and catalyst together in a distillation
apparatus from which the oxazoline product distills from
the reaction mixture as it is formed along with the
by-product water.
,~
18,266E-F 1~
In another process, 2-substituted-2-oxazolines
are prepared by heating N-(2-hydroxyalkyl)carboxamides in
the presence of certain inorganic iron salts (European
Patent Publication 0033752, published August 19, 1981,
The Dow Chemical Company). However, this process does
not result in as high yields as does the invention described
in this application.
The present invention is a cyclodehydration
process for making a 2-substituted-2-oxazoline characterized
by reacting in the liquid phase an N-(2-hydroxyalkyl)-
carboxamide having the formula
R-C-~I-CH2CH20H
where R is alkyl of l to 17 carbon atoms or phenyl, or
a carboxylic acid/amine salt precursor of said carboxamide
with a catalytic amount of an organic zinc salt.
The temperature/pressure relationship is normally
adjusted such that the oxazoline and water codistill from
the reaction mixture essentially as fast as they are formed.
The N-(b-hydroxyalkyl)carboxamides used in the
instant process have the formula
o
I. R-C-NH-CH2-CH2-OH
wherein R is alkyl of 1 to 7 carbon atoms, or phenyl,
or a carboxylic acid/amine salt precursor of said
carboxamide. Such carboxamides are typically prepared
18,266E-F -2-
--3--
by reacting a carboxylic acid or a lower alkyl ester
of the carboxylic acid with an ethanolamine of the
formula
2 2 2
The carboxylic acid/amine salt which is formed initially in
these reactions can be used in the instant process in place
of the carboxamide. When such carboxylic acid/amine salts
are used, the carboxamide is generated ln situ. R in formula
I is preferably methyl, ethyl or phenyl and more preferably
methyl or ethyl. Examples of suitable N-(b-hydroxyalkyl)-
carboxamides include compounds of formula I having the
following values for R: CH3, C2H5, C3H7, C7H15, CgH19,
CllH23~ C17H35~ C6H5~ C6H4CH3~ C6HsCH2, CH3(CH2~7CH=CH(CH2)7
and cyclohexyl.
The catalysts in the instant cyclodehydration
reaction are organic zinc salts which are soluble in the
carboxamide reactant or liquid reaction medium. The term
"soluble" is not meant to imply that the zinc salt is solu-
ble or miscible in all proportions with the carboxamide or
liquid reaction medium, but instead has at least a minimum
solubility (e.g., at least about 100 parts per million or
more) at reaction temperature. Such zinc salts are used in
the process in catalytic amounts. Normally, the zinc
salts are charged in amounts of from 0.005 to 0.4 mole of
zinc salt per mole of carboxamide reactant, but more or
less of the zinc salts can be used, if desired. Car-
boxylic acid salts of zinc having the formula (RC00 )2Zn
wherein R is a Cl-C20 aliphatic or alicyclic radical or an
inertly-substituted C1-C20 aliphatic or alicyclic carboxylic
acid radical may be used as catalysts in the invention.
18,266E-F -3-
fi
--4--
Suitable carboxylic acid zinc salts include, for example,
zinc acetate, zinc formate, zinc propionate, zinc stearate
and zinc neodecanoate. Zinc acetate is the current pre-
ferred catalyst.
The instant cyclodehydration reaction may be con-
ducted neat or in solution with a suitable inert solvent.
By "inert" is meant inert in the process. Suitable such
inert solvents include, for examPle, chlorinated hydro-
carbon solvents, aromatic hydrocarbons, cycloaliphatic hydro~
carbons and aliphatic hydrocarbons. It is preferred however,
to conduct the reaction neat.
The reaction temperature must, obviously, be suf-
ficient to promote the cyclodehydration reaction and is nor~
mally selected in the range of from about 140C to about
280C. Preferred reaction rates have beèn observed at tem-
peratures of from about 160C to about 250C. The instant
cyclodehydration reaction is also preferably conducted under
reduced pressure. This facilitates product recovery in that
frequently a reaction temperature may be chosen which is
above the boiling point of the 2-substituted-2-oxazoline
product and below the boiling point of the N-(b-hydroxy-
alkyl)carboxamide. In this manner, the 2-substituted-2-
-oxazoline can be removed from the reaction mixture as a
volatile gas essentially as fast as it is formed. This is
very desirable since the instant cyclodehydration reaction
is a reversible process and by removing the products, the
reaction is forced to completion by substantially reducing
the reverse reaction. Water normally codistills with the
2-substituted-2-oxazoline product.
The instant process may be conducted in a batch
process or by a continuous process. In the preferred con-
tinuous process the N-(b-hydroxyalkyl~carboxamide reactant
18,266E-F -4-
--5--
is metered into the reaction vessel at essentially the
same rate as the 2-substituted-2-oxazoline and water are
removed.
The following examples further illustrate the
invention.
Example 1 - Preparation of 2-Ethyl-2-Oxazoline Over Zinc
Acetate Dihydrate
Zinc acetate dihydrate (10.0 g; 0.045 mole) and
95.4 percent pure N-(b-hydroxyethyl)propionamide (20.0 g;
0.162 mole) were charged to a reaction vessel e~uipped with
a stirring means, a metering pump, and a 5-plate distillation
column with a take-off head. The pressure over the
reaction mixture was adjusted to 50 mm Hg and the reaction
mixture heated to 200C. The reaction mixture was held at
200C and 95.4 percent pure N-(b-hydroxyethyl)propionamide
(290 g; 2.35 mole) was pumped in at approximately 0.9 g/min
to the system. As the propionamide was added to the reac-
tion mixture, a water-white distillate was collected over-
head through the distillation apparatus at a head temperature
of 40C 45C. After the addition of the propionamide was
complete, the pot was heated to 220C to drive off the last
amounts of 2-ethyl-2-oxazoline. The overhead distillate
temperatuxe reached a maximum of 41C during this post-
-heating step. A total of 294.8 g of water-white distillate
was thus obtained overhead leaving 21.7 g of a tan, wet
paste remaining in the pot. Analysis of the distillate
overheads by gas chromatography using an internal standard
and a Karl Fischer water titration showed the material
to be 2-ethyl-2-oxazoline, water and very minor amounts of
18,266E-F -5-
--6--
unreacted propionamide and 2-methyl-2-oxazoline. The impur-
ities in the propionamide reactant were: water (approxi-
mately 1 percent); monoethanolamine (approximately 2-3 per-
cent); and the amidoester of propionic acid and monoethanol-
amine (approximately 1 percent).
The oxazoline was produced in 96.2 percent yield,
based on the pure N-(b-hydroxyethyl)propionamide charged to
the system. The amount of water produced according to analy-
sis was 93.0 percent of theory. The 2-ethyl-2-oxazoline can
be easily separated from the mixture by selective extraction
using diethylbenzene followed by distillation.
ExamPle 2
In another experiment, 2-ethyl-2-oxazoline was
prepared in 82 percent yield by warming a propionic acid/-
ethanolamine salt in the presence of approximately 2 molepercent zinc acetate dihydrate at a temperature of 200C/50
mm Hg. This was a batch experiment in which the acid/amine
salt and catalyst were initially charged and warmed to the
indicated reaction temperature. There was a pause in the
rise in temperature during which the acid/amine salt was
converted to the amide. Otherwise, this reaction proceeded
the same as Example 1 above. The product was similarly
recovered as an overhead distillate with water.
Other catalysts and carboxamide reactants as set
forth above could be similarly used to produce the 2-substi-
tuted-2-oxazolines.
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