English Description:

Technical field
The invention belongs to the application technical field of catalytic hydrogenation,
specific in order to prepare the para-aminomethyl benzoic acid catalytic
hydrogenation as relieving the acidic method of hemal ring under the amiable
condition.
Background Art
Tranexamic acid whether anti-form, to aminomethyl hexahydrobenzoate, it can
through to bind to the reversibility of 2,6-diaminocaproic acid is blocked on
plasminogen member, thus produced and resisted fibrinogenolytic effects, the
effective extensive situation used for hemorrhage, usually used in air passage,
hemorrhage of digestive tract, capillary hemorrhage, surgical operative
hemorrhage,etc..
Relieving the acidic synthetic method of hemal ring mainly has amphi, a is a methyl
acrylate method, produce tranexamic acid through a series of reactions by methyl
acrylate and chloro-butadiene; Another kind is a para-aminomethyl benzoic acid
method, passed the catalytic hydrogenation, transformed and produces tranexamic
acid by para-aminomethyl benzoic acid.Because should use hypertoxic cyanide in
the methyl acrylate method, mainly use the para-aminomethyl benzoic acid method
to produce tranexamic acid industrially.
The para-aminomethyl benzoic acid method is produced in the tranexamic acid
process, the catalytic hydrogenation is the most important step, to aminomethyl
hexahydrobenzoic acid to the ammonia Toluol first one that got sym-form and antiform through the catalytic hydrogenation, transform the sym-form to aminomethyl
hexahydrobenzoic acid and turn into the anti-form to aminomethyl
hexahydrobenzoic acid, i.e. tranexamic acid.Catalyst that catalyzed is usually
precious metal such as Pt, Rh, Ru.
US 3932497 uses Ru catalyst, supports Ru on inert supports such as alumina,
diatomaceous earth, activated carbon, barium sulfate precipitated, calcium
carbonate, Ru content in catalyst is 1-10 wt%.At 150 of temperature, hydrogen
pressure 100 kg/cm2Leave and react, the transformation efficiency of paraaminomethyl benzoic acid is 100%, it is 97% to the formic yield of cyclohexyl group
of aminomethyl.Last catalyst for 49062444 times JP,will 45 g para-aminomethyl
benzoic acid, 16.7 g KOH, 100 ml H25% Ru-C O and 25 g adds into high pressure
autoclave, at 90 of temperature, hydrogen pressure 90 kg/cm2Leave and react,
the product gets 43.5 g to aminomethyl hexahydrobenzoic acid after processing.

GB 2084145 uses Pd, Pt, Rh mixed catalyst, separately Pd, Pt, Rh supports on the
activated carbon to make 5% Pd-C, 5% Pt-C, 5% Rh-C catalyst, add these three
kinds of catalyst mixing into high pressure autoclave, add para-aminomethyl
benzoic acid, water, hydrochloric acid, reaction temperature is 10-60 , hydrogen
pressure 1-10 kg/cm2,Reaction 6 h, about 80% to the formic yield of cyclohexyl
group of aminomethyl.
JP 58032848 uses Rh catalyst, supports Rh on the activated carbon to get final
product 5% Rh-C catalyst, reaction temperature is 40 s, hydrogen pressure 30
kg/cm2,Reaction 3 h, reaches 90% to the formic yield of aminomethyl cyclohexen.
Mainly use PtO industrially at present2Make catalysts, the ratio of components is
para-aminomethyl benzoic acid: Platinum dioxide: Sulfuric acid: Water =1:0.
05:0.56:33,it add para-aminomethyl benzoic acid and water into at reaction tank, it
is if you can't down, add by sulfuric acid not to stir, heating make dissolve, add
platinum dioxide, eliminate pot inject the hydrogen and begin to react behind the
air.About 40 , hydrogen pressure 0.5-1.5 kg/cm2The reaction relieves to no longer
hydrogen uptake of the amount of theory reached of hydrogen uptake.Eliminate my
hydrogen, filter reaction solution, take out platinum black.Heat filtrate to 90 ,
neutralize with barium hydroxide, come pH=7-7.5.After lefting standstill, filter off
the barium sulfate precipitated.Wash the filter residue with water, mix filtering,
wash liquids, get the sym-form liquid to aminomethyl cyclohexanecarboxylic acid
(concentration concentrates to carboxylic benzylamine reaction solution to 5 liters
for every 10 grammole) after concentrating.The ratio of components of the
conversion process is to the aminomethyl cyclohexanecarboxylic acid sym-form
liquid (v): Barium hydroxide (w): Water (v): Ethanol (v) =1:2.1:1.6:6.61.Sym-form
liquid and barium hydroxide will be added into the reaction tank to aminomethyl
cyclohexanecarboxylic acid, airtight, heat it up to 200 , the pressure is 18-20
kg/cm2,React for 14 hours.The reaction is finished, it is cold to 60-70 , water and
heat up to 90 , neutralize to pH with sulfuric acid (30%) =5.52-5.56.Stand for
more than 2 hours, filter, the filter cake is washed with water.Mix and filter the wash
liquid, add appropriate amount of activated carbon, boiling decoloring.Filter,
concentrate it until every 10 grammole are 6 liters to carboxylic benzylamine, add
ethanol and devitrify.Cool, filter, crystallization is washed with ethanol, the filter, dry
to get tranexamic acid.
Catalyze hydrogenation process use Ru catalyst, have more harsh reaction
conditions, HTHP expect much the apparatus, not suitable for the industrial
production; Use Rh catalyst, because Rh is costly, makes the production cost
increase; Use Pt catalyst, the mild condition of reaction, but the reaction time is
longer.
Invention content

An object of the present invention is to provide a kind of reaction time short, the
para-aminomethyl benzoic acid of high productive rate method for preparing
tranexamic acid of catalytic hydrogenation, use high active hydrofining catalyst at
the same time, make para-aminomethyl benzoic acid prepare the catalytic
hydrogenation in the tranexamic acid process and go on under the reaction
condition that more Gentle.
To achieve the above-mentioned object, the technology solution of the invention is,
use Pt-M/C catalyst (M =Ru, La, Ce, Co, Ni), it can be used for the para-aminomethyl
benzoic acid catalytic hydrogenation, its method is specific: a), add 0.3 Pt-M/C
catalyst (M into sequentially in high pressure autoclave =Ru, La, Ce, Co, Ni), a time
of para-aminomethyl benzoic acid, 30 times of deionized water and 0.6 times of
H2SO4The cosolvent, vacuumize airtightly to-0.08 ~ -0.06Mpa;
b), replace for 2 times of air in high pressure autoclave with the nitrogen, spend the
nitrogen of hydrogen exchange twice, and it is 0.3-0.5 MPa to concoct the hydrogen
pressure, heats it up to 30-60 , reaction 2-4 h produces aminomethyl
cyclohexanecarboxylic acid correctly;
c), aminomethyl cyclohexanecarboxylic acid is through catalyzing correctly in the
alkaline-earth metal, 220 , 2.0-2.5the inversion of configuration gets tranexamic
acid under MPa condition.
The main reaction equation that the invention relates to is:

In the invention, the preparation method of Pt-M/C catalyst is: Impregnate a

activated carbon in H of amount of 0.01-1 times2PtCl6And include M ion of 0.01-1
times (M =Ru, La, Ce, among Co or mixed solution of Ni), soak fully and after
dipping, use reduction of reducing agent, reduce and finish postcooling, filter,
Aqueous, make Pt-M/C catalyst, wherein the loading of Pt in Pt-M/C catalyst is 1-5%,
the loading of M is 0.1-5%.
The preferred embodiments used as the invention: The reducing agent that said PtM/C catalyst uses in the course of preparing is hydrazine hydrate, KBH4CH3A or
their mixture in COONa.
The beneficial results of the invention are:
1. Catalyst preparation method is simple, through the dipping, reduce and support
the active constituent on the activated carbon, have reduced the expensive metallic
consumption, has raised the expensive metallic utilization rate.

2. Because the catalyst activity is high, only need to react for 2-4 hours, the
transformation efficiency of para-aminomethyl benzoic acid can be more than 98%,
and can be more than 95% to the aminomethyl cyclohexanecarboxylic acid yield
and shorten the reaction time, improve the unit productive rate.
3. It is milder that para-aminomethyl benzoic acid catalyzes the reaction condition
adopted in the hydrogenation process, reaction temperature is 30-60 , hydrogen
pressure 0.3-0.6 MPa, is suitable for the commercial process.
Specific embodiment
Now binding embodiments will make further detailed description to the invention.
Embodiment 1
Take accelerant preparation of a gram as examples: 0.135g H2PtCl6And
0.05g La (NO3)3Dissolve into 30ml water, impregnate 1g activated carbon
in this solution, impregnate 12 h, heat it to 100 , drip reduction of
hydrazine hydrate, reduce and finish postcooling, filter, Aqueous, make PtLa/C catalyst.
Catalytic hydrogenation: Add 0.3 gPt-La/C catalyst, 1 g para-aminomethyl
benzoic acid, 30 ml deionized water into high pressure autoclave, 0.6 g
H2SO4,Airtight, vacuumize until-0.08 Mpa, replace air twice with nitrogen,
hydrogen exchange nitrogen twice, the reaction temperature of heating is
to 60 , hydrogen pressure 0.5 MPa, reaction time 4 h, the paraaminomethyl benzoic acid transformation efficiency is 99.3%; Make to
aminomethyl cyclohexanecarboxylate until alkaline-earth metal catalyze,
220 , the inversion of configuration gets tranexamic acid under 2.0MPa
condition.
Embodiment 2
Accelerant preparation: 0.135g H2PtCl6And 0.4g Ni (NO3)2Dissolve into
30ml water, impregnate 1g activated carbon in this solution, impregnate
12 h, heat it to 100 , drip KBH4Reduction of solution, reduce and finish
postcooling, filter, Aqueous, make Pt-Ni/C catalyst.
Catalytic hydrogenation: Add the 0.3 above-mentioned catalyst, 1 g paraaminomethyl benzoic acid, 30 ml deionized water into high pressure
autoclave, 0.6 g H2SO4,Airtight, vacuumize until-0.06 Mpa, replace air
twice with nitrogen, hydrogen exchange nitrogen twice, the reaction
temperature of heating is to 50 , hydrogen pressure 0.6 MPa, reaction

time 3 h, the para-aminomethyl benzoic acid transformation efficiency is

98.6%; Make to aminomethyl cyclohexanecarboxylate until alkaline-earth
metal catalyze, 220 , the inversion of configuration gets tranexamic acid
under 2.5MPa condition.
Embodiment 3
Accelerant preparation: 0.135g H2PtCl6And 0.4g Co (NO3)2Dissolve into
30ml water, impregnate 1g activated carbon in this solution, impregnate
12 h, heat it to 100 , drip CH3COONa solution, reduces and finishes
postcooling, filter, Aqueous, make Pt-Co/C catalyst.
Catalytic hydrogenation: Add the 0.3 above-mentioned catalyst, 1 g paraaminomethyl benzoic acid, 30 ml deionized water into high pressure
autoclave, 0.6 g H2SO4,Airtight, vacuumize until-0.07 Mpa, replace air
twice with nitrogen, hydrogen exchange nitrogen twice, the reaction
temperature of heating is to 40 , hydrogen pressure 0.5 MPa, reaction
time 4 h, the para-aminomethyl benzoic acid transformation efficiency is
97.6%; Make to aminomethyl cyclohexanecarboxylate until alkaline-earth
metal catalyze, 220 , the inversion of configuration gets tranexamic acid
under 2.2MPa condition.
Embodiments 4
Accelerant preparation: 0.135g H2PtCl6And 0.03g RuCl3Dissolve into 30ml
water, impregnate 1g activated carbon in this solution, impregnate 13 h,
heat it to 95 , drip NaOH solution and glacial acetic acid, reduces and
finishes postcooling, filter, Aqueous, make Pt-Ru/C catalyst.
Catalytic hydrogenation: Add 0.3 g catalyst, 1 g para-aminomethyl benzoic
acid, 30 ml deionized water into high pressure autoclave, 0.6 g
H2SO4,Airtight, vacuumize, replace the air, reaction temperature is 30 ,
hydrogen pressure 0.4 MPa, reaction time 4 h, the para-aminomethyl
benzoic acid transformation efficiency is 99.5%.
Embodiment 5
Accelerant preparation: 0.135g H2PtCl6And 0.4g Ce (NO3)3Dissolve into
30ml water, impregnate 1g activated carbon in this solution, impregnate
11 h, heat it to 105 , drip hydrazine hydrate, KBH4Mixed solution,last
postcooling, filter, Aqueous, make by Pt-Ce/C catalyst.
Catalytic hydrogenation: Add 0.3 g catalyst, 1 g para-aminomethyl benzoic
acid, 30 ml deionized water into high pressure autoclave, 0.6 g

H2SO4,Airtight ,,Vacuumize, replace the air, reaction temperature is 60 ,

hydrogen pressure 0.5 MPa, reaction time 2 h, the para-aminomethyl
benzoic acid transformation efficiency is 99.6%.