JP2001002666A - Production of pyrrolidine compounds - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently obtain a pyrrolidine compound useful as an intermediate or raw material for medicines or agrochemicals under the control of a side reaction by adding water to the reaction system on the reaction of a 1,4- alkanediol with ammonia or an alkylamine. SOLUTION: This method for producing a pyrrolidine compound comprises reacting (A) a 1,4-alkanediol (for example, 1,4-butanediol) with (B) ammonia or an alkylamine (for example, methylamine) in the presence of a catalyst (for example, alumina). Therein, water is added to the reaction system. The molar ratio of the component B/the component A is preferably 1 to 50, and the molar ratio of the water/the component A is preferably 0.3 to 25. The reaction is preferably a gas phase distribution system reaction using a solid acidic catalyst at a temperature of 200 to 500 deg.C at a pressure of 0.5 to 50 kg/cm2G. When water contained in the pyrrolidine compound is distilled off, tetrahydrofuran is preferably added to obtain the highly pure product.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing pyrrolidines, and more particularly to a method for producing pyrrolidines by reacting a 1,4-alkanediol with ammonia or an alkylamine in the presence of a catalyst and a method for purifying the same. About.

[0002]

BACKGROUND OF THE INVENTION Pyrrolidines are useful compounds as intermediates for pharmaceuticals and agrochemicals. In particular, pyrrolidines are used as polypyrroles obtained by polymerizing pyrroles obtained by dehydrogenation in condensers and as inhibitors for preventing pipeline blockage. Are useful as raw materials for polyacryloylpyrrolidine. As a general method for producing pyrrolidine, many methods for reacting a cyclic ether such as tetrahydrofuran (THF) with ammonia in the gas phase have been disclosed (JP-A-1-268681, JP-A-3-26881).
No. 14570). However, cyclic ethers are generally more expensive than the corresponding 1,4-alkanediols, and there is a need for a method for producing pyrrolidines using less expensive 1,4-alkanediols as raw materials.

As a method for reacting 1,4-alkanediol with ammonia in the gas phase to obtain pyrrolidines,
There is a method in which the reaction is carried out in the presence of a solid acid catalyst such as alumina. However, when the reaction temperature is high, side reactions tend to occur.
In particular, when 1,4-butanediol is used as 1,4-alkanediol, 1,4-butanediol is decomposed into butadiene and water, or pyrrolidine once formed reacts with tetrahydrofuran to form pyrrolidinobutene. Kind easily formed. In addition, pyrrolidinobutenes react with pyrrolidine to produce 1,4-di- (1-pyridinyl) -butane or thermally decompose to produce butadiene and 2,5-dihydropyrrole. The boiling point difference between 2,5-dihydropyrrole and pyrrolidine is only about 4 ° C., and a high number of stages is required for distillation separation. It is desirable that the amount is small, and at the same time, butadiene which is a by-product is easily coked to shorten the catalyst life, and it is important to suppress the by-product reaction.

[0004] Further, 1,4-butanediol is dehydrated to tetrahydrofuran, and water is always produced as a by-product in a pyrrolidine-forming reaction obtained by reacting tetrahydrofuran with ammonia. The resulting pyrrolidine is
The purity of pyrrolidine by precision distillation is 99.
Although about 8% can be obtained, pyrrolidine azeotropes with 1 to 2% of water, so there is a problem that water cannot be sufficiently removed.

[0005]

SUMMARY OF THE INVENTION The object of the present invention is to
In a method for obtaining pyrrolidines by reacting 4-alkanediol with ammonia or an alkylamine, a by-product reaction, in particular, pyrrolidinobutenes from the obtained pyrrolidines and tetrahydrofurans and 1,4-di- (1-pyridinyl) -By suppressing the by-product reaction of butanes,
It is an object of the present invention to provide a method for improving the yield of pyrrolidines, reducing by-products, and improving catalyst life, and a method for producing high-purity pyrrolidine for removing water from hydrous pyrrolidine.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that water is added to a reaction system for reacting a 1,4-alkanediol with ammonia or an alkylamine. From pyrrolidines to pyrrolidinobutenes and 1,4-di- (1-pyridinyl)
The present invention has found that it is possible to suppress the side reaction that generates -butanes, and furthermore, it is possible to greatly reduce the water content by adding tetrahydrofuran to water-containing pyrrolidine and performing azeotropic distillation. Was completed.

That is, the present invention provides a method for producing pyrrolidines, which comprises reacting a 1,4-alkanediol with ammonia or an alkylamine in the presence of a catalyst by adding water to the reaction system. Is the way.

In the present invention, the amount of water to be added is 1,4.
-The method for producing a pyrrolidine as described above, wherein the molar ratio to the alkanediol is 0.3 to 25.

In the present invention, when water contained in pyrrolidine is separated by distillation using a distillation column, tetrahydrofuran is added to draw out an azeotropic mixture of tetrahydrofuran-water from the top of the column and to remove the azeotropic mixture from the bottom of the column. A method for producing pyrrolidine, characterized in that pyrrolidine having a purity is obtained.

[0010] The present invention also provides a method for producing a pyrrolidine obtained by reacting the above-mentioned 1,4-alkanediol with ammonia or an alkylamine in the presence of a catalyst. This is a pyrrolidine production method characterized by extracting an azeotropic mixture of tetrahydrofuran-water from the top of the column and obtaining high-purity pyrrolidine from the bottom of the column.

The present invention also relates to a method for producing pyrrolidines, wherein the azeotropic mixture of tetrahydrofuran-water obtained by the above-mentioned azeotropic distillation method is again used as a raw material for pyrrolidine synthesis.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Production of Pyrrolidine As the 1,4-alkanediol used as a raw material in the present invention, hydrogen atoms on four carbon atoms of 1,4-butanediol (may be abbreviated as BDO) are each independently hydrogen, alkyl And those having a substituent selected from a group, an alkylene group and an aryl group. Specifically, 1,4-butanediol, 1,4-pentanediol, 1,4-hexanediol, 2,5-
Hexanediol, 4,4-dimethyl-2,5-hexanediol and the like can be mentioned. Among these, 1,4-butanediol is preferably used.

As the other raw material used in the present invention, ammonia or an alkylamine is used. As the alkylamine, a primary lower alkylamine having 1 to 4 carbon atoms such as methylamine, ethylamine, propylamine and butylamine is used.

The catalyst used in the present invention is not particularly limited as long as it has an activity in the present reaction. A crystalline or non-crystalline metal oxide and a complex thereof are used. For example, zeolite, alumina,
Silica-alumina, silicoaluminophosphate, titanium oxide, silica-magnesium oxide, silica-zirconium oxide, silica-titanium oxide, alumina-titanium oxide,
Alumina-zirconium oxide, tin oxide, niobium oxide,
Examples include copper oxide, zinc oxide, chromium oxide, vanadium oxide, iron oxide, and thorium oxide. Of these, crystalline or non-crystalline metal oxides exhibiting solid acidity are preferred, and alumina, silica alumina, silicoaluminophosphate and zeolite are particularly preferred. The shape, surface area, pore distribution, composition and the like of these metal oxide catalysts are not limited, and catalysts ion-exchanged with metal ions for improving the activity of the catalyst can be used.

In the reaction of the present invention, the 1,4-alkanediol is reacted with ammonia or an alkylamine by adding water to the reaction system in the presence of the above-mentioned catalyst. The reaction mode is not particularly limited, and may be a batch reaction or a flow reaction, and may be a liquid phase reaction or a gas phase reaction. Among these, a gas-phase flow system reaction using a catalyst exhibiting solid acidity is preferred.
When the reaction is carried out in a gas phase flow system, any of a fixed bed system and a fluidized bed system may be used.

In the reaction of the present invention, the reaction temperature is 20
The temperature is preferably from 0 to 500 ° C, particularly preferably from 280 to 400 ° C. When the reaction temperature is lower than 200 ° C., the progress of the reaction is slow. When the reaction temperature is higher than 500 ° C., the selectivity of pyrrolidines decreases and the deactivation of the catalyst is remarkable.

In the reaction of the present invention, the reaction pressure is not particularly limited, and may be under reduced pressure or under increased pressure.
When the reaction of the present invention is carried out under the pressure of a gas phase flow system, the total of the partial pressure of the reaction raw material and the partial pressure of the product is 0.5 to 50 kg /
It is preferred to carry out the reaction at cm ² G, in particular 1-30
The reaction is preferably performed at kg / cm ² G. If the sum of the partial pressures exceeds 50 kg / cm ² G, the raw material 1,4-alkanediol reaches the dew point, which is not preferable.

In the reaction of the present invention, the molar ratio of ammonia or alkylamine / 1,4-alkanediol is
1-50 are preferable, and 2-20 are especially preferable. When the molar ratio is less than 1, the selectivity of pyrrolidines decreases,
If it exceeds 50, the productivity will decrease and the amount of ammonia or alkylamine to be recovered will increase, which is not desirable industrially.

In the reaction of the present invention, the amount of water to be added to the reaction system is preferably such that the molar ratio of water to 1,4-alkanediol of the raw material is 0.3 to 25, particularly 0.5 to 15%.
Is preferred. When the molar ratio of water is less than 0.3 with respect to 1,4-alkanediol, the selectivity for pyrrolidines decreases, and when it exceeds 25, the space-time yield decreases, which is not preferable. In addition, if the amount of water is equivalent to the amount of water,
It can be added to the reaction system in the state of steam. Also,
It may be supplied as an aqueous solution such as aqueous ammonia.

When the reaction of the present invention is carried out in a gas phase flow system,
The space velocity corresponding to the reaction time (total amount of supplied gas (liter) / catalyst amount (liter) / hour under standard conditions) is:
100-7000 hr ^-1 is preferable, and especially 200-4
500 hr- ¹ is preferred. Space velocity is 100 hr ^-1
If it is less than 7, the productivity is low, and if it exceeds 7,000 hr ^-1 , the BDO conversion rate is undesirably small.

With the above raw material composition and reaction conditions, 1,
When a 4-alkanediol is reacted with ammonia or an alkylamine, the conversion of the 1,4-alkanediol is high, and THF which coexists with the obtained pyrrolidines is used.
By-products of pyrrolidinobutenes by the reaction with pyrrolizinobutenes, and by-products of heavy fractions such as 1,4-di- (1-pyrrolidinyl) -butane due to the reaction between pyrrolidinobutenes and pyrrolidines, and further dehydrogenation of pyrrolidines Can suppress side reactions such as by-products of 2,5-dihydropyrrole and by-products of butadiene due to decomposition, and can produce pyrrolidines at a high production rate. In the present invention, as a by-product, T
Although HFs are produced, THFs can be separated and recovered at the reactor outlet and recycled as a reaction raw material.

2. Purification of pyrrolidine The pyrrolidine-containing reaction product obtained in the above reaction is purified by distillation. However, since pyrrolidine azeotropes with 1 to 2% of water, it is difficult to remove water sufficiently by ordinary distillation. Can not. The purification method of the present invention comprises a third component having a boiling point of 6 or less as an azeotrope with water at a boiling point (88 ° C.) or lower of pyrrolidine.
In this method, tetrahydrofuran (THF) at 6 ° C. is added to hydrous pyrrolidine, water and THF are extracted as an azeotropic mixture from the top of the tower, and high-purity pyrrolidine is obtained from the bottom of the tower.

Specifically, the hydrous pyrrolidine obtained in the above reaction is distilled and purified in the first distillation step to a degree close to an azeotrope containing about 2% of water, and the pyrrolidine is About 10 to 200 times (weight) with respect to the moisture in,
Preferably 10 to 100 times (weight), particularly preferably 2 times
THF equivalent to 0 to 90 times (weight) is added, the second stage distillation operation is performed, and the THF-water azeotropic composition and THF are extracted from the top of the column to remove water, and to remove water from the bottom of the column. High-purity pyrrolidine having a content of 0.5% or less can be obtained.

Since THF is an intermediate in the reaction between alkanediol and ammonia or alkylamine as described above, the azeotropic mixture containing a small amount of water extracted from the top of the column is again azeotropically distilled. Although it can be used as a dehydrating agent for use, it can be recycled to a pyrrolidine synthesis reaction raw material, and a very economical pyrrolidine production method can be obtained by combining the above production method and the azeotropic dehydration method.

[0025]

EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not particularly limited to the examples. In addition, the supply rate, yield, and selectivity in the examples were determined as follows. (1) Butanediol (BDO) supply rate: 25 ° C., liquid supply amount at normal pressure (liter) / catalyst (liter)
/ Hour. (2) Space velocity: Determined by the total amount of supplied gas (liter) / catalyst (liter) / hour at 25 ° C. and normal pressure. (3) BDO conversion: (1-moles of unreacted BDO at reaction tube outlet per unit time / moles of BDO in reaction tube inlet feed per unit time) × 100 (%) (4) Tetrahydrofuran (THF) Yield: (moles of THF in reaction tube exit product per unit time / moles of BDO in reaction tube entrance feed per unit time) × 10
0 (%) (5) Yield of pyrrolidine (PD): moles of PD in reaction tube outlet product per unit time / number of moles of BDO in reaction tube inlet feed per unit time) × 100 (%)

(6) 2,5-dihydropyrrole (DH
P) Yield: DH in reaction tube outlet product per unit time
P moles / B in reactor tube feed per unit time
DO mole number) × 100 (%) (7) Pyrrolidinobene (PDB) yield: mole number of PDB in reaction tube outlet product per unit time × 2 / BDO mole in reaction tube inlet feed per unit time Number) × 1
00 (%) (8) Light product yield: number of moles of butadiene, propylene, etc. in the reaction tube outlet product per unit time / number of moles of BDO in the reaction tube inlet feed per unit time) × 10
0 (%) (9) Yield of heavy product: reaction tube outlet per unit time Number of moles of 1,4-di- (1-pyrrolidinyl) -butane etc. in product / reaction tube inlet per unit time B in feedstock
DO mole number) × 100 (%) (10) Pyrrolidine (PD) selectivity: PD mole number in reaction tube outlet product per unit time / (1—reactor tube outlet unreacted BDO mole per unit time− Number of moles of THF in reaction tube outlet product per unit time) × 100 (%) (11) Selectivity of pyrrolidinobutene (PDB): Number of moles of PDB in reaction tube outlet product per unit time × 2 / (1)
-Number of moles of unreacted BDO at the reaction tube outlet per unit time-Number of moles of THF in the product at the reaction tube outlet per unit time) x
100 (%)

Example 1 Alumina catalyst (X-CY (1.6) extruded product manufactured by Criterion) was crushed into a SUS-316 reaction tube having an inner diameter of 10 mm, and sieved to a range of 0.71 to 1.41 mm. 2 ml were filled. In the upper part of the catalyst layer, 15 to 2
It was filled with 0-mesh silica sand to obtain an evaporative pre-tropical zone. The reaction tube was heated using an annular electric furnace installed outside, and the catalyst layer and the pre-evaporation zone were adjusted to maintain a predetermined temperature. Ammonia gas flows from the upper part of the reaction tube,
Hold for hours. Thereafter, at 350 ° C., ammonia, BD
O and water were supplied from the upper part of the reaction tube. Ammonia, BD
O: water molar ratio 5: 1: 1, space velocity 3150hr
The supply rates of ammonia, BDO, and water were controlled to be ^-1 . Table 1 shows the reaction results 4 to 5 hours after the start of the reaction.

Examples 2 to 6 The reaction was carried out in the same manner as in Example 1 except that the reaction temperature, the molar ratio of ammonia, BDO, and water and the space velocity were changed. Table 1 shows the results.

Example 7 A reaction was carried out in the same reactor as in Example 1 using silica alumina (Neobead SA manufactured by Mizusawa Chemical Co., Ltd.) as a catalyst. Table 1 shows the results.

Example 8 A reaction was carried out in the same reactor as in Example 1 using silicoaluminophosphate (SAPO-11 manufactured by JGC Universal Co., Ltd.) as a catalyst. Table 1 shows the results.

Example 9 A reaction was carried out in the same reactor as in Example 1, using zeolite (Zeolite β manufactured by NE Chemcat) as a catalyst. Table 1 shows the results.

Example 10 Under the same conditions as in Example 6, the reaction was continuously carried out for 120 hours. After 120 hours, the BDO conversion is 100%, P
The D yield was 87.1% and the THF yield was 3.4%, and hardly changed compared to the initial stage after the start of the reaction.

[0033]

[Table 1]

Comparative Example 1 A reaction was carried out in the same manner as in Example 1 except that nitrogen was supplied in an equimolar ratio to BDO instead of water. Table 2 shows the results.

Comparative Examples 2 to 9 The reaction was carried out in the same manner as in Example 1 except that no water was supplied and the catalysts and reaction conditions shown in Table 1 were employed. Table 2 shows the results.

[0036]

[Table 2]

As is clear from Tables 1 and 2, Example 1 and Comparative Example 1 compare the effects of nitrogen dilution and water addition at the same contact time and the same BDO supply rate. Although the addition of water increases the THF yield, the PD yield increases, and the PD selectivity is greatly improved. Comparing Comparative Examples 1 and 2, the contact time was shortened by the nitrogen dilution, and
Although the yield is slightly increased, the PD selectivity hardly changes. Example 1 and Comparative Example 2 compare the effect of water addition at the same BDO supply rate. Although the contact time is shortened by the addition of water, the PD selectivity and the PD yield increase, indicating that the water addition is effective for improving PD productivity. Examples 2 to 6 and Comparative Examples 3 to 6 compare the effects of water addition under low THF yield conditions. Even under low THF yield conditions, the production of light / heavy by-products is mainly suppressed, and a high PD yield is obtained. Examples 7 to 9 and Comparative Examples 7 to 9 compare the effect of adding water on catalysts other than alumina, and it can be seen that adding these catalysts is effective for adding water.

Example 11 To a hydrous pyrrolidine solution comprising 100 parts by weight of pyrrolidine and 2 parts by weight of water, 80 parts by weight of tetrahydrofuran was added.
Distillation was performed using a distillation apparatus equipped with a 7-stage Sneader fractionator. At 65 ° C., the THF-water azeotrope is about 7
5 parts by weight, whose composition is pyrrolidine / water / THF
= 0 / 1.7 / 73 (parts by weight). Next, 66 ° C
Yields about 31 parts by weight of a THF-water mixture, the composition of which is pyrrolidine / water / THF = 23.5 / 0.2
/ 7 (parts by weight). Finally, about 77 parts by weight of pyrrolidine was obtained as a bottom, and the composition was pyrrolidine / water / THF = 76.5 / 0.1 / 0.0. As a result of analyzing the water content of the residue by the Karl Fischer method, it was found that the water content of the residue was 0.
It was found to be 39%, a very low water content pyrrolidine.

Comparative Example 10 The same distillation operation as in Example 11 was carried out except that THF was not added in the distillation of Example 11. First, 88 ° C
In the vicinity, 51 parts by weight of a pyrrolidine-water azeotrope are obtained, the composition of which is pyrrolidine / water = 50/1 (parts by weight)
Met. 51 parts by weight of the bottom was obtained, and the composition of the bottom was pyrrolidine / water = 50/1. Each fraction contained about 2% water and could not be dewatered by distillation.

[0040]

The process for producing pyrrolidines by reacting a 1,4-alkanediol with ammonia or an alkylamine in the presence of a catalyst according to the present invention in the presence of water can be carried out by a by-product reaction. And pyrrolidinobutenes derived from pyrrolidines and tetrahydrofurans
By suppressing the by-product reaction of (1-pyridinyl) -butane and 2,5-dihydropyrrole, it is possible to improve the yield of pyrrolidines, reduce by-products, and improve the catalyst life. Further, by adding azeotropic distillation to tetrahydrofuran, which is an intermediate of the above reaction, to hydrous pyrrolidine, high-purity pyrrolidine can be obtained.

Claims (5)

[Claims] 1. A reaction between a 1,4-alkanediol and ammonia or an alkylamine in the presence of a catalyst,
A method for producing pyrrolidines, wherein water is added to a reaction system. 2. The process for producing pyrrolidines according to claim 1, wherein the amount of water to be added is 0.3 to 25 in a molar ratio to 1,4-alkanediol. 3. When distilling off water contained in pyrrolidine by distillation using a distillation column, an azeotropic mixture of tetrahydrofuran-water is extracted from the top of the column by adding tetrahydrofuran to obtain high-purity pyrrolidine from the bottom of the column. A method for producing pyrrolidine. 4. The method for producing pyrrolidine according to claim 3, wherein high-purity pyrrolidine is produced from pyrrolidine obtained by the method according to claim 1 or 2. 5. A method for producing pyrrolidine, wherein the azeotropic mixture of tetrahydrofuran-water obtained by the dehydration operation according to claim 3 is used again as a raw material for pyrrolidine synthesis.