U.S. patent application number 09/793420 was filed with the patent office on 2001-09-13 for process for preparing cyanoacetamide.
This patent application is currently assigned to DEGUSSA-HUELS AKTIENGESELLSCHAFT. Invention is credited to Imig, Manuela, Kalz, Thomas, Kaufhold, Manfred.
Application Number | 20010021787 09/793420 |
Document ID | / |
Family ID | 7633908 |
Filed Date | 2001-09-13 |
United States Patent
Application |
20010021787 |
Kind Code |
A1 |
Imig, Manuela ; et
al. |
September 13, 2001 |
Process for preparing cyanoacetamide
Abstract
Cyanoacetamide is prepared without additional catalyst by
esterification of crude cyanoacetic acid with a monohydric alcohol
which forms an azeotrope with water and has 4 to 10 carbon atoms,
reacting the resulting ester with ammonia in the presence of a
basic catalyst to give cyanoacetamide, and work-up by a mechanical
separating operation and a thermal treatment.
Inventors: |
Imig, Manuela; (Marl,
DE) ; Kaufhold, Manfred; (Marl, DE) ; Kalz,
Thomas; (Herne, DE) |
Correspondence
Address: |
OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC
FOURTH FLOOR
1755 JEFFERSON DAVIS HIGHWAY
ARLINGTON
VA
22202
US
|
Assignee: |
DEGUSSA-HUELS
AKTIENGESELLSCHAFT
Weissfrauenstrasse 9
Frankfurt
DE
60287
|
Family ID: |
7633908 |
Appl. No.: |
09/793420 |
Filed: |
February 27, 2001 |
Current U.S.
Class: |
558/445 |
Current CPC
Class: |
C07C 253/30 20130101;
C07C 255/19 20130101; C07C 253/30 20130101 |
Class at
Publication: |
558/445 |
International
Class: |
C07C 255/24 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 8, 2000 |
DE |
100 11 191.2 |
Claims
What is claimed is:
1. A process for preparing cyanoacetamide from cyanoacetic acid and
ammonia, comprising: (1) optionally, azeotropically distilling out
water from cyanoacetic acid with a first monohydric alcohol having
4 to 10 carbon atoms; (2) esterifying said cyanoacetic acid with a
second monohydric alcohol without additional catalyst; distilling
out the water/alcohol mixture, thereby providing a crude ester; (3)
optionally purifying said crude ester by distillation out from high
boilers, thereby providing a purified ester; (4) reacting said
crude ester or said purified ester with ammonia in the presence of
a basic catalyst, thereby providing crude cyanoacetamide; and (5)
working up the crude cyanaoacetamide by a mechanical separating
operation and thermal treatment.
2. The process according to claim 1, wherein said first alcohol is
n-butanol or i-butanol.
3. The process according to claim 1, wherein said second monohydric
alcohol n-butanol or i-butanol.
4. The process according to claim 1, wherein the molar ratio of
said second monohydric alcohol to cyanoacetic acid in the
esterification is from 1:1 to 4:1.
5. The process according to claim 1, wherein the molar ratio of
said second monohydric alcohol to said cyanoacetic acid is from
1.5:1 to 2.5:1.
6. The process according to claim 1, wherein said purifying of said
crude ester proceeds in a short-path distillation apparatus.
7. The process according to claim 6, wherein said short-path
distillation apparatus is a short-path evaporator.
8. The process according to claim 1, wherein said basic catalyst is
an alkaline metal alcoholate or alkaline earth metal
alcoholate.
9. The process according to claim 8, wherein said alkali metal
alcoholate is sodium methoxide, potassium methoxide, sodium
ethoxide, potassium ethoxide or mixtures thereof.
10. The process according to claim 8, wherein said alkaline earth
metal alcoholate is magnesium methoxide, magnesium ethoxide or
mixtures thereof.
11. The process according to claim 1, wherein said mechanical
separating operation is a filtration or a deposition using a
hydrocyclone.
12. The process according to claim 1, wherein said esterifying
proceeds at a temperature of from 100 to 140.degree. C.
13. The process according to claim 1, wherein an amount of said
basic catalyst is of from 0.5 to 10 mol % based on an amount of
said cyanoacetic acid.
14. The process according to claim 1, wherein an amount of said
basic catalyst is from 1 to 5 mol % based on an amount of said
cyanoacetic acid.
15. The process according to claim 1, wherein said reacting of said
crude ester or said purified ester with said ammonia proceeds at a
temperature of from 10 to 100.degree. C.
16. The process according to claim 1, wherein said ammonia is used
in a stoichiometric amount.
17. The process according to claim 1, wherein said ammonia is in
the gaseous state.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention relates to a process for preparing
cyanoacetamide by esterification without additional catalyst.
During this esterification crude cyanoacetic acid is reacted with a
monohydric alcohol which forms an azeotrope with water. The
resulting ester is reacted with ammonia in the presence of a basic
catalyst to give cyanoacetamide, followed by work-up using a
mechanical separating operation and thermal treatment.
[0003] 2. Discussion of the Background
[0004] Cyanoacetamide is an important intermediate for preparing
drugs and pharmaceutical products. It is used inter alia for
preparing malononitrile.
[0005] Syntheses of cyanoacetamide from cyanoacetic esters are
known from the literature. For example, Organic Synthesis Collect.,
Volume 1, pg. 179 describes a process in which ethyl cyanoacetate
is reacted with concentrated aqueous ammonia. This results in
wastewater which is polluted with organic products and which must
be disposed of. Moreover, it is necessary to work up the mother
liquor to achieve a good yield. Processes of this type are
complicated and not economic.
[0006] European Patent Application EP-A-0 583 694 describes the use
of butanol in a large excess of 5 to 30 times the molar amount of
cyanoacetic acid and a strongly acidic catalyst for the
esterification. The esterification times are very long despite the
catalyst. (For example, a reaction time of 13 hours is disclosed in
the Examples of EP-A-0 583 694.
SUMMARY OF THE INVENTION
[0007] It is an object of the present invention to develop a
process for preparing cyanoacetamide which is technically simple to
implement, for example, in an industrial process, with short
reaction times and with little complexity. It is another object of
the present invention to develop a process for preparing
cyanoacetamide, that does not yield waste which is complicated and
costly to dispose of.
[0008] These and other objects have been achieved according to the
invention, the first embodiment of which includes a process for
preparing cyanoacetamide from cyanoacetic acid and ammonia,
comprising:
[0009] (1) optionally, azeotropically distilling out water from
cyanoacetic acid with a first monohydric alcohol having 4 to 10
carbon atoms;
[0010] (2) esterifying said cyanoacetic acid with a second
monohydric alcohol without additional catalyst;
[0011] distilling out the water/alcohol mixture, thereby providing
a crude ester;
[0012] (3) optionally purifying said crude ester by distillation
out from high boilers, thereby providing a purified ester;
[0013] (4) reacting said crude ester or said purified ester with
ammonia in the presence of a basic catalyst, thereby providing
crude cyanoacetamide; and
[0014] (5) working up the crude cyanaoacetamide by a mechanical
separating operation and thermal treatment.
DETAILED DESCRIPTION OF THE INVENTION
[0015] The object of the present invention is achieved by
esterifying a low-cost crude cyanoacetic acid with an unbranched or
branched monohydric alcohol having 4 to 10, preferably 4 to 6,
carbon atoms without additional catalysts. The resulting ester is
further reacted in crude or after only the higher boiling fractions
have been removed by distillation. This resulting ester is
preferably reacted with gaseous ammonia in the presence of a basic
catalyst to give cyanoacetamide.
[0016] The work-up takes place by a mechanical separating operation
such as filtration or separation in a hydrocyclone, and a thermal
treatment such as vacuum-drying.
[0017] Surprisingly, it has been found that the synthetic route via
the esters, preferably via the butyl esters, provides the following
considerable advantages:
[0018] the esters can be prepared without an additional
catalyst,
[0019] the work-up of the ester is omitted,
[0020] direct conversion to the amide is possible,
[0021] with the exception of monohydric alcohol, the mother liquor
produced in the amide preparation is free of valuable product,
or
[0022] additional concentration of the mother liquor can be omitted
during repeated crystallization. Thus, the process according to the
invention for preparing cyanoacetamide is particularly simple and
economic.
[0023] The invention therefore relates to a process for preparing
cyanoacetamide from crude cyanoacetic acid, which optionally
contains water. The process includes the following steps:
[0024] (1) Azeotropic distillation with unbranched or branched
monohydric alcohols with 4 to 10 carbon atoms to remove the water
dissolved in the starting material, where appropriate.
[0025] (2) Azeotropic water/alcohol distillation in the
esterification of the crude cyanoacetic acid with monohydric
alcohols, wherein the esterification is free of additional
catalyst.
[0026] (3) Optionally, initial purification of the ester by
distilling the ester off from high boilers.
[0027] (4) Reaction of the ester with ammonia in the presence of a
basic catalyst, where appropriate in a monohydric alcohol having 4
to 10 carbon atoms.
[0028] (5) Work-up by a mechanical separating operation and a
thermal treatment.
[0029] The process according to the invention requires no
additional solvents either in the first two or in the third stage.
It has the advantage that only very small amounts of auxiliaries
are required and the monohydric alcohol which is employed in excess
can be recovered by simple distillation of high boiling fractions
and can be recycled. The preferred monohydric alcohol is
butanol.
[0030] The molar ratio of alcohol to cyanoacetic acid is 1:1 to
4:1, preferably 1.5:1 to 2.5:1. The molar ratio includes all values
and subvalues therebetween, especially including 1.6:1; 1.7:1;
1.8:1; 1.9:1; 2.0:1; 2.1:1; 2.2:1; 2.3:1 and 2.4:1. This ratio
determines the bottom temperature under atmospheric pressure, which
is preferably not above 140.degree. C. because of the low stability
of the acid. For this reason, it is preferable to operate under
vacuum conditions. The temperature for the esterification is
preferably 100 to 140.degree. C. The temperature includes all
values and subvalues therebetween, especially including 105, 110,
115, 120, 125, 130 and 135.degree. C.
[0031] Preferred suitable monohydric alcohols are unbranched or
branched alcohols which form an azeotrope with water and have 4 to
10, and more preferably 4 to 6 carbon atoms. Butanols are
particularly preferred, especially n-butanol and i-butanol.
[0032] The catalysts used for reacting the ester with ammonia are
compounds which are basic or have a basic action. Preferred
catalysts are alkali metal alcoholates or alkaline earth metal
alcoholates such as sodium methoxide, potassium methoxide, sodium
ethoxide, potassium ethoxide, magnesium methoxide and magnesium
ethoxide. These catalysts can be used singly or as mixtures. The
catalysts are used in very small amounts of from 0.5 to 10 mol %,
preferably 1 to 5 mol % and more preferably 1 to 2.5 mol % of
catalyst, based on the amount of acid originally employed.
[0033] The ammonia is preferably used in a stoichiometric amount
and preferably in the gaseous state. The temperature for reacting
the ester with ammonia is 10 to 100.degree. C., preferably 20 to
80.degree. C. The temperature includes all values and subvalues
therebetween, especially including 20, 30, 40, 50, 60, 70, 80 and
90.degree. C.
[0034] The cyanoacetamide can be purified by recrystallization (see
Org. Synthesis Coll. Volume 1, page 179 et seq.). Depending on the
required quality, particularly with regard to the color of the
cyanoacetamide, it is preferred to prepurify the crude ester before
the amide preparation.
[0035] The distillation apparatus is preferably a short-path
apparatus, and more preferably a short-path evaporator.
[0036] Having generally described this invention, a further
understanding can be obtained by references to certain specific
examples which are provided herein for purposes of illustration
only, and are not intended to be limiting unless otherwise
specified.
EXAMPLES
Example 1
[0037] 1.1 Preparation of Butyl Cyanoacetate
[0038] A reaction apparatus made of glass with a four-neck flask,
stirrer, thermometer, 0.5 m-long distillation column, and
distillation apparatus with reflux divider was used.
[0039] 471.6 g (5.43 mol) of cyanoacetic acid (98% pure) and 886.0
g (11.95 mol) n-butanol were introduced into the flask and heated
to 110.degree. C. The butanol/water azeotrope started to distill
out at this temperature. After 8.75 hours, 256.7 g of distillate
were produced, and the acid number of the bottom product was 11 mg
KOH/g, which corresponds to an acid content of only 1.7% by
weight.
[0040] The reaction product was then worked up by direct
distillation, and 695.9 g of butyl ester with a purity of 99.7%
were obtained. The yield calculated from this was 90.5% based on
the cyanoacetic acid input.
[0041] 1.2 Preparation of Cyanoacetamide
[0042] A glass apparatus consisting of a three-neck flask, stirrer,
thermometer and introduction tube was used. 141.6 g (1 mol) of
n-butyl cyanoacetate (99.7% pure), 240 g of n-butanol and 3.6 g of
sodium methoxide in methanol (30% strength) were mixed and gaseous
ammonia was passed in. The exothermic reaction was kept at
30.degree. C. by cooling with water. After 7 hours, GC analysis
showed complete conversion of the butyl ester.
[0043] The reaction mixture was then filtered, and the filter cake
was washed with butanol and dried in vacuum at 40 to 60.degree. C.
76.6 g of cyanoacetamide with a melting point of
120.5-121.5.degree. C. were obtained. The yield was 91% based on
the butyl cyanoacetate input. The mother liquor contained no
valuable products apart from butanol.
Example 2
[0044] The apparatuses described in Example 1 were used. 608 g of
70% pure crude cyanoacetic acid (5.0 mol) which contained 30%
water, and 968 g (13.1 mol) of n-butanol were mixed and water was
removed. After 8.75 hours, the acid number was 3.0 mg KOH/g, which
means that the conversion of acid was more than 99%. 623.3 g of
distillate and 953 g of bottom product were obtained. 373.6 g (1.96
mol) of this were diluted with 100 g of n-butanol, and 7.2 g of
sodium methoxide solution (30% strength) were added. Then gaseous
ammonia was passed in, and the temperature was kept at 30.degree.
C. by cooling. The reaction was complete after 7 hours. The work-up
as in Example 1 afforded 140.5 g of cyanoacetamide with a melting
point of 119.5-121.5.degree. C. The yield over two reaction stages
was 85.3% based on crude acid.
[0045] The priority document of the present application, German
Patent Application No. 100 11 191.2, filed Mar. 8, 2000, is
incorporated herein by reference.
[0046] Obviously, numerous modifications and variations on the
present invention are possible in light of the above teachings. It
is therefore to be understood that within the scope of the appended
claims, the invention may be practiced otherwise than as
specifically described herein.
* * * * *