Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
2 ~ a ~
Wo 90/13546 1 PCT/EP90/00631
A process for the production of 2-oxazolines
This invention relates to a process for the production
of 2-oxazolines corresponding to g~neral formula I
N ~ I
~ ~ 0 J (~)
in which Rl is
an aryl or aralkyl radical optionally substituted in the
aromatic nucleus,
an alkyl group containing 5 to 6 carbon atoms,
a hydroxy-substituted alkyl group containing 1 to 6 carbon
atoms,
an alkoxy-substituted alkyl group containing 1 to 6 carbon
atoms in the alkyl group and 1 to 18 carbon atoms in the
alkoxy group or
a group corresponding to general formula II
R -(OCzHs)p-o-cH2- (II)
in which
R2 is an alkyl or alkenyl group containing 1 to 18 carbon
atoms, more especially a methyl group and
p is a number in the range from 1 to 10, more particu-
larly 1 to 2,
by condensation of carboxylic acid ethanolamides or precur-
sors ~hereof in the liquid phase in the presence of cata-
lysts, precursors being understood to be carboxylic acids
and carboxylic acid esters with lower alkanols or glycerol
as the first components and 2-aminoethanol as the second
component.
2-Oxazolines substituted in the 2-position are
valuable intermediate products which are used inter alia as
.
~0~ '8
wo 90/13546 2 PCT/EP90/00631
solvents or plasticizers and, in particular, as polymeriza-
tion components.
Numerous processes have been described for the prepar-
ation of compounds of this class.
The most simple method is based on the cyclodehydra-
tion of N-2-hydroxyethyl carboxylic acid amides (Chem. Rev.
44, 447 et seq (1949), Chem. Rev. 71, 4~5 et ~ (1971)).
However, cyclization of the unsubstituted N-2-hydroxyethyl
carboxylic acid amides requires very drastic conditions or
the presence of special catalysts. Whereas gas-phase reac-
tions in the presence of dehydrating metal oxides, such as
Al2O3, SiO~Al2O3, Al2O3/TiO~, Tio2 or MgO, have proved to be
suitable for the preparation of readily volatile, short-
chain 2-alkyl-2-oxazolines, the more volatile, relatively
long-chain 2-alkyl-2-oxazolines are better prepared in the
liquid phase. Compounds of manganese, cobalt, molybdenum,
tungsten, iron, cadm~um, zinc and tin and also compounds of
the rare earth metals have been described as catalysts for
the liquid-phase reaction (cf. US-PS 3,562,263, BE-PS 666
829, C.A. 87, 135353, C.A. 87, 135352, US-PS 3,681,329, US-
PS 3,681,333, EP-OS O 033 752, US-PS 4,543,414, US-PS
4,354,029, US-PS 4,443,611, EP-OS 0 105 944 and EP-OS 0 164
219). However, the catalysts described in the publications
cited above do not lead to good yields in the production of
relatively long-chain 2-fatty alkyl-2-oxazolines.
It has now been found that special titanium and
zirconium compounds are eminently suitable as catalysts in
a process of the type mentioned at the beginning, enabling
yields of up to about 90% of the theoretical, based on the
starting compound, to be obtained.
Accordingly, the present invention relates to a
process of the type mentioned at the beginning in which
a) carboxylic acids corresponding to general ~ormula
(III)
2~7~8
WO 90/13546 3 PCT/EP90/00631
R1-COOH (III)
in which Rl is as defined above,
esters of these carboxylic acids with monoalkanols contain-
ing l to 4 carbon atoms or glycerides of these carboxylic
acids are condensed with 2-aminoethanol or
b~ ethanolamides of these carboxylic acids
in the presence of titanium or zirconium compounds corre-
sponding to general formula IV
M(oR3)4 (IV)
in which
M represents tetravalent titanium or zirconium and
R3 is an alkyl group containing at least 2 and more par-
ticularly 2 to 4 carbon atoms, an acyl group containing at
least 2 and more particularly 2 to 10 carbon atoms or a 2-
aminoethyleneoxy group or a residue of a B-diketone corre-
sponding to general formula V
R4-C=CH-Co-R (V)
in which
R4 and R5 may be the same or different and represent
radicals from the group consisting of alkyl groups contain-
ing l to 4 carbon atoms and phenyl optionally substituted
in the p-position, two of the groups R3 together being
formed by the two-bond radical of a dihydric alcohol
containing 2 to 4 carbon atoms,
in the presence of titanyl acetyl acetonate
or in the presence of condensation p~oducts of titanium(IV)
or zirconium(lV) tetraalkoxylates corresponding to general
2 ~
lW0 90/13546 4 PCT/EP90/00631
formula IV, in which M and R3 are as defin~d above, with
polyfunctional alkanols, more particularly containing 3 to
12 carbon atoms and 2 to 6 hydroxyl groups, and the 2-
oxazolines ~hus obtained are isolated with removal of the
water and alcohol or glycerol formed.
The starting materials used in the process according
to the invention are, in particular, the following car-
boxylic acids and esters thereof with lower alkanols or
glycerol and ethanolamides thereof
benzoic acid which may contain 1 to 3 substituents; typical
substituents are C14 alkyl groups, more particularly methyl,
C14 alkoxy groups more particularly methoxy, and halogen
atoms, such as chlorine and bromine;
phenyl acetic acid or phenyl propionic acid which may be
substituted in the aromatic nucleus by 1 to 3 of the
substituents mentioned above;
caproic and oenanthic acid;
hydroxycarboxylic acids containing 2 to 7 carbon atoms,
more particularly hydroxyacetic acid, (glycolic acid),
hydroxypropionic acid, hydroxybutyric acid, hydroxyvaleric
acid, hydroxycaproi~ acid, more particularly the ~-hydroxy-
substituted isomers thereof, and optionally lactones there-
of;
alkoxy-substituted carboxylic acids which, formally, are
alkoxylation products of the above-mentioned hydroxycar-
boxylic acids and contain 1 to 18 carbon atoms in the
alkoxy group: methoxy-substituted carboxylic acids are
preferred;
ether carboxylic acids corresponding to the following
formula
R2- (OC2H5) p-O-CH2-COOH
in which R2 and p are as defined above; typical examples are
the ether carboxylic acids obtained by catalytic oxidation
,
2 3~ 8
WO 90/13546 5 PCT/~P90/00631
of adducts of ethylene oxide with primary, saturated or,
optionally, even unsaturated alcohols containing 1 to 18
carbon atoms, such as methanol, ethanol, propanol, butanol,
pentanol and hexanol, and also saturated or unsaturated
fatty alcohols, including technical mixtures thereof, such
as caproic, oenanthic, caprylic, capric, undecenyl, lauryl,
myristyl, cetyl, stearyl, oleyl, elaidyl, linoleyl and
linoleyl alcohol, as described for example in DE-A 26 36
123, EP-B 0 039 111, EP-B 0 018 681 and DE-A 31 35 946.
Particularly preerred ether carboxylic acids are
methoxyethoxy acetic acid and methoxyethoxy ethoxy acetic
acid.
The carboxylic acid ethanolamides suitable ~or use in
the process according to the invention may be obtained by
standard methods, ~or example by reaction of the acid
chlorides or the C14 alkyl esters of the carboxylic acids
with ethanolamine.
The titanium or zirconium compounds suitable for use
as catalysts in the process according to the invention are
known and, for the most part, are commercially available.
Condensation products of titanium(IV) or zirconium(IV)
tetraalkoxylates with polyfunctional alkanols containing 3
to 12 carbon atoms and 2 to 6 hydroxyl groups, such as
glycerol, trimethylol propane and pentaerythritol, are
esterification and/or transesterification catalysts, which
are described for example in US-C 4,705,764, to which
reference is hereby made. Another suitable polyalkanol is
polyvinyl alcohol. The titanium or zirconium tetra-(2-
aminoethoxylates) also suitable as catalysts may be pre-
pared from titanium or zirconium tetraal~oxylates and 2-
amino-ethanol.
In one pre~erred embodiment of the invention, esters
of titanic acid (H4TiO4) or zirconic acid (H4ZrO4) or mixed
anhydrides of titanic or zirconic acid with organic acids
corresponding to general formula IV, in which M = Ti or Zr
.
.
2~7(~
Wo 90/135~6 6 PC~/EP99/006~1
and R3 is an alkyl group containing at least 2 or more than
2 carbon atoms and more particularly 2 to 4 carbon atoms or
an acyl group containing 2 or more than 2 carbon atoms,
more particularly 2 to 10 carbon atoms, derived from a
monocarboxylic acid, are used as catalysts.
In another advantageous embodiment of the invention,
catalysts from the group consisting of titanium or zir-
conium tetraethylate, tetrapropylate, tetraisopropylate,
tetrabutylate and tetraacetate are used.
In another advantageous embodiment of the invention,
titanium or zirconium acetyl acetonates corresponding to
general formula (VI)
(R60) mM (ACA) n (VI )
in which R6 is an alkyl group containing 1 to 4 carbon
atoms, ACA is an acetyl acetonate group and m is the number
0 and n is the number 4 or m is the number 2 and n is the
number 2,
are used as catalysts.
In another advantageous embodiment of the invention,
polycondensation products of esters of titanic acid with
monoalkanols containing 2 to 10 carbon atoms with penta-
erythritol are used as catalysts.
In another advantageous embodiment o~ the inventisn,
the catalysts to be used in accordance with the invention
are used in a quantity of 0.1 to 10 mol-%, preferably in a
quantity of 0.5 to 5 mol-% and more preferably in a quan-
tity of 005 to 3 mol-%, based on the carboxylic acid
ethanolamide or precursors thereof.
In another advantageous embodiment of the invention,
the condensation reaction is carried out at 150 to 270DC,
the reaction preferably being carried out in vacuo in an
inert gas atmosphere. The water o~ reaction formed may be
distilled off together with the 2-oxazolines and separated
2 0 ~ ~ 7 ~ 8
WO 90/13546 7 PCT/EP9OJ00631
therefrom during the distillation, entrained residual water
being removed with typical drying agents, such a~ anhydrous
sodium sulfate or molecular sieve (4A). However, the
water of reaction may also be removed from the reaction
mixture before th~ actual distillation of the 2-oxazolines
by azeotropic distillation with high-boiling entraining
agents, such as for example tetralin or cumene.
In another preferred embodiment of the invention, the
2-oxazolines may be directly prepared from carboxylic acids
or carboxylic acid esters corresponding to general formula
VII
Rl-CooR7 (VII)
in which R1 is as defined above and R7 is hydrogen or an
alkyl group containing 1 to 4 carbon atoms,
or from glycerides of caxboxylic acids corresponding to the
formula Rl-COOH, more particularly triglycerides, by
reaction thereof in the presence of ethanolamine to form
the carboxylic acid ethanolamides and leaving the reaction
mixture to react in a second step in which the reaction
temperature is further increased. Preferred starting
materials are the readily obtainable carboxylic acid methyl
esters and glycerides. They are reacted in the presence of
ethanolamine and the claimed catalysts in a first step at
elevated temperature, preferably at atmospheric pressure,
with removal of water and alcohol or glycerol to form
carboxylic acid ethanolamides and in a second step, the
reaction mixture is left to react, preferably in vacuo,
with a further increase in the reaction temperature. The
ethanolamine is preferably used in a 50 to 400 mol-%
excess, based on the starting material, unreacted or excess
ethanolamine being removed ~rom the reaction mixture before
the second step. A reaction temperature of 100 to 170~C is
preferably applied in the first step, a reaction tempera-
2~7~
WO 90/135~6 8 PCT/EP90/00631
ture of 175 to 250C preferably being applied in the second
step. The catalysts are preferably used in a quantity o~
0.1 to 10 mol-%, preferably 0.5 to 5 mol-% and moxe prefer-
ably 0.5 to 3 mol-~, based on the the starking material
used. Titanium tetraalcoholates, more particularly select-
ed from the group consisting of titanium tetraethylate,
tetrapropylate, tetraisopropylate and tetrabutylate, are
again preferably used. Alternatively, mixed anhydrides of
titanic acid with monocarboxylic acids, particularly those
containing 1 to 4 carbon atoms, preferably titanium tetra-
acetate, are used. Other preferred catalysts are titanium
or zirconium acetyl acetonates corresponding to general
formula VI, the above-mentioned polycondensation products
of esters of titanic acid with monoal~anols containing 2 to
10 carbon atoms with pentaerythritol and also titanium(IV)
or Zr(IV) tetraaminoethanolates.
In this variant of the process, the reaction is
preferably carried out in vacuo and the water of reaction
formed is distilled off together with the 2-oxazolines with
further separation during distillation or the water of
reaction is removed by azeotropic distillation before
distillation of the 2-oxazolines.
It is of particular advantage in this regard to carry
out the first and the second stages of the reaction as a
one pot reaction in one and the same reactor.
The invention is illustrated by the following Ex-
amples.
Example 1.
2-Phenyl-2-oxazoline.
A mixture of
1042 g (7.5 mol) benæoic acid methyl ester (98%),
921 g (15 mol) ethanolamine (99.5%) and
25.5 g (0.075 mol, 1 mol-~) titanium tetrabutylate
was introduced into a stirred reactor equipped with a
2(~708
WO 90/13546 9 PCT/EP~0/00~31
fractionating column, descending condenser with distilla-
tion receivers, a vacuum source with a cold trap for the
water of reaction, a thermometer and an inlet pipe for
inert gas.
The reaction mixture was heated under nitrogen; the
methanol formed at 128 to 160C was distilled off under
normal pressure.
The excess ethanolamine was then distilled off in
vacuo at 87C/20 hPa.
The benzoic acid ethanolamide thus obtained was heated
in vacuo to 178-226C, the 2-phenyl-2-oxazoline formed and
water distilling over simultaneously at 122C/20 hPa. Most
of the water was condensed in the cold trap. To free the
oxazoline distilled over from any water entrained, a
molecular sieve (4A) was introduced as drying agent into
the distillation receivers.
2-Phenyl-2-oxazoline, which still contained small
quantities of benzoic acid ethanolamide, was obtained in a
yield of 836.7 g (75% of the theoretical, based on the
benzoic acid methyl ester used).
Pure 2-phenyl-2-oxazoline having the following charac-
teristic data was obtained in a yield of 775.3 g (70% of
the theoretical) by redistillation using a thin-layer
evaporator (Bp. = 120 to 125~C at 19 hPa):
nD20= 1.5672
IR: 1650 (C=N); 1260, 1065 (C-0-C=); 975, 945, 900cm~
(oxazoline).
Example 2.
2-Hydroxymethyl-2-oxazoline. [104]
Glycolic acid methyl ester was reacted with ethanol-
amine by the method described in Example 1. The following
quantities were used:
135.1 g (1.5 mol) glycolic acid methyl ester
WO 90/13546 10 PC~/EP90/00631
184.2 g (300 mol) ethanolamine (99.5%)
5.1 g (0.015 mol, 1 mol-%) titanium tetrabutylate. [340]
Yield = 31.6 g (0.3 mol) - 20% of the theoret.
Sublimation point = 98C ~21 hPa~.
20.7 g pure 2-hydroxymethyl-2-oxazoline were obtained
after recrystallization.
Analysis:
C4H7N02 (101.107)
calculated: C 47.52 H 6.98 M 13.85
found: C 47.5 H 7.00 N 13.6
IR: 1680 (C=N); 1209, 1099 (C-0-C=3; 981, 956, 922cm
(oxazoline);
lH-NNR: delta (in ppm)= 4.76 (lH,s), 4,24 (2H,t,J = 7 Hz),
3.86 (2Ht,J= 7 HZ)o
Example 3.
2-(5-Hydroxypentyl)-2-oxazoline. [187~
Caprolactone was reacted with ethanolamine by the
method described in Example 1. The following quantities
were used:
230.6 g (2.0 mol) caprolactone
245.5 g (4~0 mol) ethanolamine ~99.5~)
6.8 g (0.02 mol, 1 mol-%) titanium tetrabutylate
Yield: 249.8 g (approx. 80% purity). (1.06 mol ; 53%)
Bp. = 140C (0.03 hPa).
77.2 g of the title compound with a purity of 95% were
obtained by redistillation in vacuo (Bp. = 114C at 1.2
hPa).
Example 4.
Methoxymethyl-2-oxazoline. [118]
Methoxyacetic acid was reacted with ethanolamine by
the method described in Example 1. The following quanti-
ties were used:
180.2 g (2.0 mol) methoxyacetic acid (purity > 95%)
.
2~3~08
NO 90/13546 11 PCT/EP90/00631
245.5 g (4.0 mol) ethanolamine
6.8 g (0.02 mol, 1 mol-%) ~itanium tetrabutylate.
Yield: 188.6 g (82% of the theoretical).
Bp. = 130C to 163C (167 hPa).
124.4 g (5~% of the theoretical) of pure 2-methoxy-
methyl-2-oxazoline, Bp. 69C/20 hPa, are obtained after
redistillation ln vacuo.
Analysis-
C5H8N02 (115.134)
calculated: C 52.16 H 7.88 N 12.17
found: C 52.0 H 7.94 N 12.3
IR: 1668 (C=N); 1191, 1122 (C-0-C=); 982, 948, 918cm
(oxazoline):
lH-NMR: delta (in ppm)= 4.31 (2H,t,J = 7 Hz), 4.12 (2H,s),
3.90 (2H,t,J = 7 Hz), 3.46 (3H,s).
Example 5.
2-(2,5-Dioxahexyl)-2-oxazoline. ~156]
3,6-Dioxaheptanoic acid (methoxyethoxy acetic acid)
was reacted with ethanolamine by the method described in
Example 1. The following quantities were used:
235 g (1.50 mol) 3,6-dioxaheptanoic acid (purity approx~
80-85%)
215 g (3 mol) ethanolamine (99.5%)
6.0 g (0.0175 mol, 1 mol-%) titanium tetrabutylate.
Yield = 209.1 g (88% of the theoretical).
Bp. = 140 to 180C (0.5 hPa).
129.1 g (61% of the theoretical) of the title compound
were obtained after redistillation in vacuo (Bp. = 57 to
66C at 0.01 hPa).
Analysis:
C7Hl3N03 (159.187)
calculated: C 52.82 H 8.23 N 8.80
found: C 52.8 H 8.51 N 8.77
n 20= 1.4571
2~7~8
NO 90/13546 12 PCT/EP90/00631
IR: 1669 (C=N); 1199, 1116 (C o-C=); 982, 950, 907cm
(oxazoline);
H-NMR: delta (in ppm)= 4.30 (2H,t,J = 7 Hz), 4.24 (2H,s),
3.89 (2H,t,J = 7 Hz), 3.7446 (2H,dd,J = 3.4 Hz), 3.58
(2H,dd,J = 3.4 Hz), 3,38 (3H,s).
Example 6.
2-(2,5,8-Trioxanonyl)-2-oxazoline. [206]
3,6,9-Trioxadecanoic acid (methoxyethoxy ethoxy acetic
acid) were reacted with ethanolamine by the method de-
scribed in Example 1. The following quantities were used:
231.6 g (1.24 mol) 3,6,9-trioxadecanoic acid (puriky
approx. 95~)
159.6 g (2.6 mol) ethanolamine (99.5~)
4.4 g (0.013 mol, 1 mol-%) titanium tetrabutylate.
Yield = 187.0 g (75% of the theoretical).
Bp. = 167 - 182C (0.4 - 2.6 hPa).
149.1 g (59%) of the pure title compound were obtained
after redistillation in vacuo (Bp. = 101 - 106C at O.lS
hPa).
Analysis:
CgH17N04 (203.24)
calculated: C 53.19 H 8.43 N 6.89
found: C 53.8 H 8.49 N 6.92
25 nD20= 1.4602
IR: 1669 (C=N); 1198, 1109 (C-0-C=); 982, 950, 907cm
(oxazoline);
lH-N~R: delta (in ppm)= 4.30 (2H,t,J = 7 Hz), 4.23 (2H,s),
3.88 (2H,t,J = 7 Hz), 3.75 (2H,m), 3.70 (2H,m), 3.65
(2H,m), 3.55 (2H,m), 3.38 (3H,s).
Example 7.
Preparation of a 2-substituted 2-oxazoline from m-tolylic
acid
. .
:. :
2~7~g
~0 gO/13546 13 PC~/EP9OJ00631
m-Tolylic acid was reacted with ethanolamine by the
method described in Example 1 to form 2-(3-methylphenyl)-
2-oxazoline. The following quantities were used:
347.3 g (2.5 mol) m-tolylic acid (98%)
307.0 g (5.0 mol) ethanolamine (99.5%)
25.5 g ~0.075 mol, 3 mol-%) titanium tetrabutylate
Yield = 241 g (60% of the theoretical) 2-(3-methylphenyl)-
2-oxazoline
Bp. = 128 - 142C (16 hPa).
IR: 1650 (C=N); 1268, 1067 (C-O-C=); 979, 951, 910cm~
(oxazoline).
H-NMR: delta (in ppm) 7.78 (lH,s); 7.72 (lH,m); 7.29
(2H,m); 4.42 (2H,t,J = 7 Hz); 4.04 (2H,t,J = 7 Hz); 2.37
(3H,s).
Example 8.
Preparation of a 2-substituted 2-oxazoline from m-methoxy-
benzoic acid
m-Methoxybenzoic acid was reacted with ethanolamine by
the method described in Example 1 to form 2-(3-methoxyphen-
yl)-2-oxazoline. The following quantities were used:
232.9 g (1.5 mol) m-methoxybenzoic acid (98%)
184.2 g (3.0 mol3 ethanolamine (99.5%)
15.3 g (0.045 mol, 3 mol-%) titanium tetrabutylate
Yield = 116 g (44% of the theoretical) 2-(3-methoxyphenyl)-
2-oxazoline.
Bp. = 122 - 157C (17-19 hPa)
IR: 1650 (C=N); 1270, 1043 (C-O-C=); 930, 951, 910cm
(oxazoline).
lH-NMR: delta (in ppm) 7.54 (lH,dt,J = 6; 1 Hz); 7.50
(lH,t,J = 1 Hz); 7.32 (lH,t,J = 6 Hz); 7.03 (lH,dt,J = 6;
1 Hz); 4.43 (2H,t,J = 7 Hz); 4.06 (2H,tJ = 7 Hz); 3.86
(3H,s).
~ ' .
2 ~
WO 90/13546 14 PCT/~P90/00631
Example 9.
Preparation of 2-phenyl-oxazoline from benzoic acid
methyl ester in the presence of titaniumtIV) diisopropoxy-
bis-acetyl acetonate
Benzoic acid methyl ester was reacted with ethanol-
amine by the method described in Example 1 to form 2-
phenyl-2-oxazoline. The followiny quantities were used:
272.3 g (2.0 mol) benzoic acid methyl ester, 98%
244.3 g (4.0 mol) ethanolamine (99.5%)
7.3 g (0.02 mol, 1 mol-%) titanium(IV) diisopropoxybis-
acetyl acetonate.
Yield = 236 g (82% of the theoretical) 2-phenyl-2-oxazo-
line.
Bp. = 107 - 120C (20 hPa)
Example 10.
Preparation of 2-phenyl-2-oxazoline from benzoic acid
ethanolamide in the presence of titanium tetrabutylate.
Benzoic acid ethanolamide was reacted as in Example 1
(second step) to form 2-phenyl-2-oxazoline. The following
quantities were used:
330.4 g (1.9 mol) benzoic acid ethanolamide (95%)
7.3 g (0.02 mol, 3 mol-%) titanium tetrabutylate
Yield = 216 g (77% of the theoretical) 2-phenyl-2-oxazo-
line.
Bp. = 112 - 114UC (19 hPa).
