U.S. patent application number 09/833210 was filed with the patent office on 2002-01-17 for process for producing trifluoromethylbenzylamines.
Invention is credited to Kume, Takashi, Narizuka, Satoru.
Application Number | 20020007086 09/833210 |
Document ID | / |
Family ID | 18624755 |
Filed Date | 2002-01-17 |
United States Patent
Application |
20020007086 |
Kind Code |
A1 |
Narizuka, Satoru ; et
al. |
January 17, 2002 |
Process for producing trifluoromethylbenzylamines
Abstract
The invention relates to a process for producing a
trifluotomethylbenzylam- ine represented by the following general
formula (1), 1 where each R independently represents a halogen
selected from the group consisting of fluorine, chlorine, bromine
and iodine, an alkyl group having a carbon atom number of 1-4, an
alkoxy group having a carbon atom number of 1-4, an amino group, a
hydroxyl group or a trifluoromethyl group, and n represents an
integer from 0 to 4. The process includes hydrogenating a
trifluoromethylbenzonitrile by hydrogen in an organic solvent in
the presence of ammonia and a catalyst containing a platinum group
element. This trifluoromethylbenzonitrile is represented by the
following general formula (2), 2 where R and n are defined as
above. With this process, it is possible to obtain the
trifluoromethylbenzylamine at an extremely high yield.
Inventors: |
Narizuka, Satoru; (Saitama,
JP) ; Kume, Takashi; (Saitama, JP) |
Correspondence
Address: |
CROWELL & MORING LLP
Intellectual Property Group
P.O. Box 14300
Washington
DC
20044-4300
US
|
Family ID: |
18624755 |
Appl. No.: |
09/833210 |
Filed: |
April 12, 2001 |
Current U.S.
Class: |
564/375 |
Current CPC
Class: |
C07C 209/48 20130101;
C07C 211/29 20130101; C07C 209/48 20130101 |
Class at
Publication: |
564/375 |
International
Class: |
C07C 29/48 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 13, 2000 |
JP |
2000-112628 |
Claims
What is claimed is:
1. A process for producing a trifluoromethylbenzylamine represented
by the following general formula (1), said process comprising
hydrogenating a trifluoromethylbenzonitrile S represented by the
following general formula (2) by hydrogen in an organic solvent in
the presence of ammonia and a catalyst comprising a platinum group
element, 5where each R independently represents a halogen selected
from the group consisting of fluorine, chlorine, bromine and
iodine, an alkyl group having a carbon atom number of 1-4, an
alkoxy group having a carbon atom number of 1-4, an amino group, a
hydroxyl group or a trifluoromethyl group, and n represents an
integer from o to 4, 6where R and n are defined as above.
2. A process according to claim 1, wherein said
trifluoromethylbenzonitril- e is selected from the group consisting
of 3,5-bis(trifluoromethyl)benzoni- trile,
3-trifluoromethylbenzonitrile, and
4-trifluoromethylbenzonitrile.
3. A process according to claim 1, wherein said platinum group
element is selected from the group consisting of ruthenium,
rhodium, palladium, osmium, iridium, and platinum.
4. A process according to claim 1, wherein said catalyst further
comprises a carrier carrying thereon said platinum group
element.
5. A process according to claim 1, wherein said catalyst comprises
an activated carbon carrying thereon palladium.
6. A process according to claim 1, wherein said catalyst is in an
amount of 0.0001 to 10 moles per 100 moles of said
trifluoromethylbenzonitrile.
7. A process according to claim 1, wherein said hydrogenating is
conducted under a pressurized condition caused by an addition of
said hydrogen.
8. A process according to claim 1, wherein said ammonia is in an
amount of from 1 to 30 parts by weight per 100 parts by weight of
said trifluoromethylbenzonitrile.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a process for producing
trifluoromethylbenzylamines useful in the pharmaceutical and
agricultural chemical fields.
[0002] Numerous processes for obtaining primary amines by
hydrogenation of nitrile compounds have been reported. In addition,
numerous processes for obtaining primary amines of
fluorine-containing aromatics from fluorine-containing aromatic
nitrite compounds have also been reported.
[0003] J. Pharm. Sci., 54, 1204 (1965) discloses that a benzylamine
(yield: 56-68.5%) is obtained by a catalytic hydrogenation of the
corresponding trifluoromethylbenzonitrile in the presence of
hydrogen chloride using a catalyst (palladium/carbon). In such a
hydrogenation, selectivity is lowered, in case that a primary amine
is obtained by a hydrogenation of a trifluoromethyl-containing
nitrile compound. Therefore, a subsequent purification (e.g.,
distillation) becomes very complicated.
[0004] U.S. Pat. No. 6,175,041 B1 discloses a process for producing
3,5-bis(trifluoromethyl)benzylamine by a hydrogenation of
3,5-bis(trifluoromethyl)benzonitrile in the presence of ammonia in
an organic solvent under a hydrogen pressurized condition (40
kg/cm.sup.2) using a Raney catalyst. This process requires such a
high pressure.
[0005] Processes for obtaining trifluoromethylbenzylamines from
aromatic nitrile compounds having a trifluoromethyl group have
problems that remain to be solved, and an industrially useful
process for producing trifluoromethylbenzylamines has yet to be
established.
SUMMARY OF THE INVENTION
[0006] It is therefore an object of the present invention to
provide a process for producing a trifluoromethylbenzylamine easily
and inexpensively.
[0007] According to the present invention, there is provided a
process for producing a trifluoromethylbenzylamine represented by
the following general formula (1), 3
[0008] where each R independently represents a halogen selected
from the group consisting of fluorine, chlorine, bromine and
iodine, an alkyl group having a carbon atom number of 1-4, an
alkoxy group having a carbon atom number of 1-4, an amino group, a
hydroxyl group or a trifluoromethyl group, and n represents an
integer from 0 to 4. The process comprises hydrogenating a
trifluoromethylbenzonitrile by hydrogen in an organic solvent in
the presence of ammonia and a catalyst comprising a platinum group
element. The trifluoromethylbenzonitrile is represented by the
following general formula (2), 4
[0009] where R and n are defined as above. With this process, it is
possible to obtain the trifluoromethylbenzylamine at an extremely
high yield.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0010] The trifluoromethylbenzonitrile represented by the general
formula (2) used in the present invention is a benzonitrile having
at least one trifluoromethyl group. This benzonitrile may also have
a substituent group that is inactive under the conditions of the
hydrogenation of the present invention. Examples of such
substituent group include halogens (i.e., fluorine, chlorine,
bromine and iodine), alkyl groups each having a carbon atom number
of 1-4, alkoxy groups each having a carbon atom number of 1-4,
amino groups, hydroxyl groups and trifluoromethyl groups. Specific
examples of the trifluoromethylbenzonitrile include
[0011] 2-trifluoromethylbenzonitrile,
8-trifluoromethylbenzonitrile,
[0012] 4-trifluoromethylbenzonitrile,
[0013] 2-bromo-5-trifluoromethylbenzonitrile,
[0014] 2-chloro 5-trifluoromethylbenzonitrile,
[0015] 2-fluoro-5-trifluoromethylbenzonitrile,
[0016] 4-iodo-2-trifluoromethylbenzonitrile,
[0017] 4-iodo 3-trifluoromethylbenzonitrile,
[0018] 2-methoxy-5-trifluoromethylbenzonitrile,
[0019] 3-methoxy-4-trifluoromethylbenzonitrile,
[0020] 4-hydroxy-2-trifluoromethylbenzonitrile,
[0021] 4-methoxy-3-trifluoromethylbenzonitrile,
[0022] 2-amino-3-trifluoromethylbenzonitrile,
[0023] 2-amino-5-trifluoromethylbenzonitrile,
[0024] 2-amino-6-trifluoromethylbenzonitrile,
[0025] 3-amino-5-trifluoromethylbenzonitrile,
[0026] 4-amino-2-trifluoromethylbenzonitrile,
[0027] 4-amino-3-trifluoromethylbenzonitrile,
[0028] 2,3-bis(trifluoromethyl)benzonitrile,
[0029] 2,4-bis(trifluoromethyl)benzonitrile,
[0030] 2,5-bis(trifluoromethyl)benzonitrile,
[0031] 2,6-bis(trifluoromethyl)benzonitrile,
[0032] 3,4-bis(trifluoromethyl)benzonitrile,
[0033] 3,5-bis(trifluoromethyl)benzonitrile,
[0034] 2,8,6-tis(trifluoromethyl)benzonitrile,
[0035] 2,4,6-tris(trifluoromethyl)benzonitrile,
[0036] 2,3,4,6-tetraquis(trifluoromethyl)benzonitrile,
[0037] 2-amino-4,6-bis(trifluoromethyl)benzonitrile,
[0038] 4-amino-3,5-bis(trifluoromethyl)benzonitrile and 4-chloro
3,5-bis(trifluoromethyl)benzonitrile. Of these,
3,5-bis(trifluoromethyl)b- enzonitrile,
3-trifluoromethylbenzonitrile, and 4-trifluoromethylbenzonitr- ile
are particularly preferable. These trifluoromethylbenzonitriles
having trifluoromethyl groups can be produced by various processes.
For example, 2-trifluoromethylbenzonitrile can be obtained by
fluorinating 2-trichloromethylbenzonitrile with antimony
trifluoride, while 4-trifluoromethylbenzonitrile can be obtained by
heating 4-trifluoromethylaniline diazoate with
K.sub.3[Cu(CN).sub.4].
[0039] The reduction of the benzonitrile compound is conducted by
catalytic hydrogenation. Although both heterogeneous and
homogeneous catalysts can be used as the catalyst of the catalytic
hydrogenation, heterogeneous catalysts are preferable in
consideration of their ease of removal. The catalyst used in the
process of the invention contains a metal (active species) that is
a platinum group element selected from ruthenium, rhodium,
palladium, osmium, iridium, and platinum. Thus, metals or metal
oxides such as palladium or platinum oxide, or these supported on a
carrier such as activated carbon, alumina or diatomaceous earth,
can be used. Examples of the catalyst include palladium-loaded
activated carbon, palladium hydroxide-loaded activated carbon,
palladium-loaded barium sulfate, palladium-loaded calcium
carbonate, palladium-loaded strontium carbonate, palladium black,
palladium-loaded silica gel, platinum dioxide, platinum-loaded
activated carbon, platinum black, ruthenium-loaded activated carbon
and rhodium-loaded activated carbon. Although the amount of the
catalyst may vary according to its type, it is preferably 0.0001-10
moles, more preferably 0.001-1 mole, per 100 moles of the
benzonitrile compound represented by the general formula (2).
[0040] Examples of the reaction solvent include alcohols,
hydrocarbons, ethers, carboxylic acids, esters, amides, and water.
Typical examples of these solvents include methanol, ethanol,
benzene, toluene, xylene, ethyl benzene, isopropyl benzene,
tetralin, mesitylene, tetrahydrofuran, diethyl ether, acetic acid,
ethyl acetate and dimethylformamide, and two or more types of these
solvents can be used in combination.
[0041] The process of the present invention can be carried out
under pressurization by hydrogen. Upon this, a pressure of 0.5-25
MPa is preferable, while that of 1-10 MPa is more preferable. If
the reaction pressure is less than 0.5 MPa, a longer time is
required for reaction. If the reaction pressure exceeds 25 MPa,
although there are no problems in terms of the reaction, this is
not preferable with respect to the strength of the apparatus,
reaction procedure and pressurization procedure.
[0042] The process of the present invention can be carried out at
-20 to 100.degree. C., preferably -20 to 50.degree. C., more
preferably in the vicinity of room temperature. Here, room
temperature refers to the temperature in the absence of heating or
cooling. If the reaction temperature is below -20.degree. C., the
reaction requires a longer period of time. If the reaction
temperature is above 100.degree. C., the amount of reaction
by-products increases and the yield of the target product decreases
correspondingly, thus making this undesirable.
[0043] In the process of the present invention, the amount of
ammonia added is preferably 1-30 parts by weight to 100 parts by
weight of the trifluoromethylbenzonitrile as the starting material.
Although liquid ammonia is normally used, it may also be introduced
as a gas. In addition, basic substance(s) can also be added to the
reaction system. Examples of basic substances that can be used
include hydroxides, oxides, carbonates and so forth of alkaline
metals or alkaline earth metals. Specific examples of such basic
substances include sodium hydroxide, potassium hydroxide, lithium
hydroxide, calcium hydroxide, magnesium hydroxide, barium
hydroxide, sodium carbonate and potassium carbonate. Basic
substance(s) can also be added to the reaction system in the form
of an aqueous solution prepared to an arbitrary concentration.
[0044] The process of the present invention can be carried out
either a batch operation or a continuous operation. In the case of
using a batch operation, the reaction can be carried out, as
follows. At first, predetermined amounts of the
trifluoromethylbenzonitrile represented by the general formula (2),
the catalyst containing a platinum group element, and an organic
solvent are charged into a corrosion-resistant, pressure-proof
reaction vessel made of stainless steel, glass or having a glass
lining. Then, the atmosphere of the reaction vessel is replaced
with an inert gas. Then, a predetermined amount of ammonia is
added. After that, hydrogen is introduced by adding pressure to a
predetermined pressure. Then, the reaction vessel is heated and
held at a predetermined temperature with stirring, to carry out the
reaction. As the reaction progresses, absorption of hydrogen occurs
and the pressure inside the reaction vessel decreases. However, the
pressure inside the reaction vessel can be maintained constant by
continuously or intermittently introducing hydrogen. After
confirming that absorption of hydrogen is no longer occurring, the
reaction vessel is cooled, then the contents are removed, and then
filtered to separate into an organic matter and the catalyst. The
reaction product obtained in this manner is subjected to processing
including rinsing with water, drying and distillation in accordance
with routine methods, allowing the obtaining of the
trifluorobenzylamine of high purity.
[0045] In general, polar solvents such as methanol have been used
for the nitrile hydrogenation solvent. In that case, ammonia is
frequently added for the purpose of inhibiting secondary amines
formed as a by-product in nitrile hydrogenations. Since the
solubility of ammonia is high in these polar solvents, they are
also used for reasons of easier workability during charging.
However, in the case of the trifluoromethylbenzonitriles of the
present invention, polar solvents such as alcohol cause an addition
reaction to the trifluoromethylbenzonitriles, and since, for
example, methoxyimine is generated in the case of methanol, the use
of such polar solvents may result in a significant decrease in
yield. Moreover, the reaction products (e.g., methoxyimine) of this
addition reaction may turn into dimers and trimers, due to heating
and so forth during distillation in following isolation procedures.
However, at the reaction temperature suitable for conducting the
process of the invention, there is no occurrence of addition of
solvent to the starting material, thereby making it possible to
obtain the target product (i.e., the trifluoromethylbenzylamine) at
high yield. The following nonlimitative examples are illustrative
of the present invention.
EXAMPLE 1
[0046] At first, a 1-liter autoclave equipped with a mechanical
stirrer was charged with 50 g (0.21 mol) of
3,5-bis(trifluoromethyl)benzonitrile, 200 ml of 2M-ammoniacal
methanol solution (containing 400 mmol of ammonia), and 3 g of a
catalyst (i.e., a carbon powder (50% wet) carrying thereon 5%
palladium), followed by introduction of hydrogen to have a pressure
of 1 MPa. Then, the reaction mixture was stirred, while the
reaction temperature was maintained at 20.degree. C. and while
hydrogen was gradually introduced into the autoclave in a manner to
maintain the total pressure at 1 MPa. After conducting the reaction
for 5.3 hr, the reaction was stopped, followed by removing the
catalyst by filtration. As a result of analyzing the obtained
reaction liquid by gas chromatography,
3,5-bis(trifluoromethylbenzylamine was formed at a yield of
87.0%.
EXAMPLE 2
[0047] At first, a 1-liter autoclave equipped with a mechanical
stirrer was charged with 200 g (0.84 mol) of
3,5-bis(trifluoromethyl)benzonitnle, 200 ml of methanol, and 6 g of
a catalyst (i.e., a carbon powder (50% wet) carrying thereon 5%
palladium), followed by introduction of 14 g of liquid ammonia and
then introduction of hydrogen to have a pressure of 1 MPa. Then,
the reaction mixture was stirred, while the reaction temperature
was maintained at 20.degree. C. and while hydrogen was gradually
introduced into the autoclave in a manner to maintain the total
pressure at 1 MPa. After conducting the reaction for 3 hr, the
reaction was stopped, followed by removing the catalyst by
filtration. As a result of analyzing the obtained reaction liquid
by gas chromatography, 3,5-bis(trifluoromethyl)benzylamine was
formed at a yield of 85.1%.
[0048] The entire disclosure of Japanese Patent Application No.
2000-112628 filed on Apr. 13, 2000, including specification, claims
and summary, is incorporated herein by reference in its
entirety.
* * * * *