JP2553049B2 - Process for producing pyrrolidines - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention is directed to catalytic hydrogenation of 2-pyrrolidinone and / or N-alkyl-2-pyrrolidinone to produce pyrrolidine and / or
Or, it relates to a method for producing N-alkylpyrrolidine.

According to the method of the present invention, pyrrolidines can be efficiently produced with a high reaction rate and a high yield.

The pyrrolidines obtained in the present invention are aliphatic amines having a 5-membered ring structure, and are useful as intermediates for various organic syntheses, for example, as raw materials for medicines, agricultural chemicals, etc., or as additives such as catalysts / decatalysts. It is a compound. Therefore,
It is considered that the technology for industrially inexpensively producing pyrrolidines is very valuable.

[Conventional technology]

Pyrrolidines can be synthesized by the catalytic reduction of pyrrole or N-alkylprols [eg, ND Zelinsky et al.
al., Berichte (Ber.,) 62 , 2589 (1929)], the reaction of 1,4-dibromobutane with an alkylamine [eg JVBr
aun, Berichte (Ber.), 49 , 966 (1916)] or N
-Reaction of halogenoalkylbutylamine with sulfuric acid [GH
Coleman et al, Organic Synthesis (Org.Syn.),
25 , 19 (1945)]. Furthermore, there is also a method of reacting tetrahydrofuran and ammonia or an alkylamine on an alumina catalyst, but each method has advantages and disadvantages in the raw material price, the yield of the target product, the complexity of the reaction operation, etc., and is sufficient as an industrial production method. It is hard to say that it is a technically completed method.

The present inventors have conducted extensive studies to solve the above-mentioned problems, and found that 2-pyrrolidinone and / or N-alkyl-2-pyrrolidinone that can be easily synthesized from γ-butyrolactones and ammonia or alkylamines. We have reached the idea that the synthetic route used as a raw material can be an industrially inexpensive manufacturing method.

As a prior art for the catalytic hydrogenation of pyrrolidinones to synthesize pyrrolidines, a synthetic example of N-amylpyrrolidine by hydrogenation of N-amyl-2-pyrrolidinone is described in JHpa
has been by connexion reported to the den, et al. [journal of the American Chemical Soviet Saie Tay (J.Amer.Chem.Soc.), 58, 2
487 (1936)]. According to this report, N-amyl-2-
Pyrrolidinone 0.04 mol (6.2 g), using about 30 ml of dioxane as a solvent, using 3 g of copper chromium oxide catalyst as a catalyst, in a temperature range of 250 to 260 ° C., a reaction under a high pressure of hydrogen pressure of 200 to 400 atm, N-amylpyrrolidine is obtained with a yield of 87%.

[Problems to be solved by the invention]

However, in the method of Paden et al., The amount of catalyst relative to the raw material is extremely high at about 50% by weight, the reaction pressure is very high, and since a large amount of solvent is used, the energy for separating and recovering the solvent is increased. There are many problems that need to be solved as an industrial method, such as requiring a lot of.

[Means for solving problems]

In order to solve these problems, the present inventors have made diligent studies on the reaction behavior of 2-pyridinone and / or N-alkyl-2-pyrrolidinone, analysis of various reaction products, etc. The present invention has been achieved by establishing a technique for efficiently producing pyrrolidines under mild conditions.

That is, the present invention relates to a method for producing pyrrolidine and / or N-alkylpyrrolidine by catalytic hydrogenation of 2-pyrrolidinone and / or N-alkyl-2-pyrrolidinone, in which the reaction zone liquid is kept at a substantially constant temperature. It is characterized in that a copper-based catalyst is suspended in a phase, 2-pyrrolidinone and / or N-alkyl-2-pyrrolidinone is supplied to the suspension, and a reaction product is taken out from a reaction zone in a vapor phase together with hydrogen gas excess. The present invention provides a method for producing pyrrolidine and / or N-alkylpyrrolidine.

Detailed Description of the Invention When the hydrogenation reaction of N-alkyl-2-pyrrolidinone is carried out at a low pressure (for example, 60 atm) using a batch autoclave and the catalyst amount is 10% by weight or less based on the raw material, N-alkyl- The conversion rate of 2-pyrrolidinone decreases significantly in the latter stage of the reaction, and if the reaction time is increased or the reaction temperature is increased to increase the conversion rate, the target product N
-The selectivity of alkylpyrrolidine is still reduced. Analysis of these reaction behaviors revealed that N-alkyl-2-
As the cause of the decrease in the conversion rate of pyrrolidine, the water produced along with the progress of the hydrogenation reaction inhibits the reaction, and the produced water partially hydrolyzes N-alkyl-2-pyrrolidinone as a raw material. It was supposed to be done. Furthermore, the produced N-alkalipyrrolidine is highly reactive,
In order to cause the successive reactions relatively quickly under hydrogenation conditions,
It is also possible to cause a decrease in selectivity. That is,
In order to accelerate the hydrogenation reaction of N-alkyl-2-pyrrolidinone and maintain the selectivity of highly reactive N-alkylpyrrolidine, water and N-alkylpyrrolidine produced by the hydrogenation reaction are retained. It is desirable to take out the product promptly out of the reaction system.

The present inventors have conducted various studies from such a viewpoint, suspending a copper-based catalyst in a reaction zone liquid phase maintained at a substantially constant temperature, and supplying N-alkyl-2-pyrrolidinone thereto, It has been found that it is possible to produce N-alkylpyrrolidines with high reaction rates and yields by withdrawing the reaction product with hydrogen gas excess from the reaction zone in the vapor phase and reached the present invention.

Next, one embodiment of the method of the present invention will be specifically described with reference to FIG. FIG. 1 shows a hydrogenation reactor 1, a reflux pipe 2, a condenser 3, a gas-liquid separator 4, an unreacted raw material / reaction product separator 5, a raw material storage 6 and preheaters 7, 8. It will be. In the reactor 1 containing the liquid phase of the reaction zone containing the suspension of the catalyst, the raw material is recycled from the pipe 19 and the unreacted raw material is recycled from the pipe 17 after being heated in the preheater 8 and then supplied via the pipe 10. Hydrogen gas is fed through the pipe 18 and preheated by the preheater 7, and then supplied to the reactor 1 through the pipe 9. The reactor 1 may be equipped with a suitable stirring device. . The vapor phase flowing out from the reactor 1 is supplied to the condenser 3 via the pipe 11 to condense the oil component, and further sent to the gas-liquid separator 4 via the pipe 12 to separate the vapor phase and the condensed phase. The reflux pipe 2 controls the ratio of the amounts of the raw material pyrrolidinone contained in the outflowing vapor phase, the target product N-alkylprolysine and the target product N-alkylpyrrolidine, and the raw material is refluxed to the reactor 1. This is aimed at the effect (the boiling point of N-alkylpyrrolidine is generally much lower than that of the corresponding N-alkyl-2-pyrrolidinone).

The gas phase part from the gas-liquid separator 4 is mainly composed of hydrogen, part of which is discharged from the pipe 20 to the outside of the system, and the rest is piped.
It is recirculated to the reactor 1 via line 9 with hydrogen from line 18 via line 13. On the other hand, the liquid phase is sent to the separator 5 via the pipe 14 to separate the raw material and the reaction product, and the reaction product distillate is sent to the purification system via the pipe 15. The separated fraction mainly containing unreacted raw materials is sent to the storage device 6 via the pipe 16 as a pipe. This is pipe 17
It can be sent again to the reactor 1 via.

The flow chart in FIG. 1 can be variously modified without departing from the basic idea of the present invention, and the related devices can be freely enhanced or omitted, and the flow chart is not limited to that in FIG.

According to such an operation mode, the target pyrrolidines can be efficiently obtained, but by adopting this operation mode, the reaction heat can be easily controlled as a secondary effect. There is no need for a separate catalyst separation step.

The raw material pyrrolidinones that can be used in the present invention are 2-pyrrolidinones and / or N-alkylpyrrolidinones. Examples of these raw materials include 2-pyrrolidinones such as 2-pyrrolidinone, 5-methyl-2-pyrrolidinone, 3-methyl-2-pyrrolidinone and 5-ethyl-2-pyrrolidinone, and N-methyl-2.
-Pyrrolidinone, N-ethyl-2-pyrrolidinone, N-
n-propyl-2-pyrrolidinone, N-iso-propyl-2-pyrrolidinone, N-n-butyl-2-pyrrolidinone, N-iso-butyl-2-pyrrolidinone, N-sec-butyl-2-pyrrolidinone, N- n-hexyl-2-pyrrolidinone, N-cyclohexyl-2-pyrrolidinone, N
-Phenyl-2-pyrrolidinone, N-benzyl-2-pyrrolidinone, Nn-dodecane-2-pyrrolidinone, 1,
Examples thereof include N-alkyl-2-pyrrolidinones such as 5-dimethyl-2-pyrrolidinone and 5-ethyl-N-methyl-2-pyrrolidinone.

As the catalyst used in the present invention, a copper-based catalyst supported on a carrier or without a carrier is effective. For example, hydrogenation in general,
A copper oxide-chromium oxide catalyst used as a dehydrogenation catalyst,
Examples thereof include copper oxide-zinc oxide catalysts, copper oxide or metal-supported catalysts, and Raney-copper catalysts. further,
A catalyst modified by adding an additive for controlling the activity / selectivity of these catalysts can be used. An example is a copper oxide-chromium oxide catalyst to which barium or manganese is added. A specific example of a preferable copper-based catalyst is a copper oxide-chromium oxide-based catalyst.

The catalyst used in the present invention is used by suspending it in a solvent which becomes liquid under the reaction conditions. At this time, the concentration of the catalyst suspended in the solvent is 0.001 to 30% by weight, preferably 0.01 to 20% by weight. Generally, the activity of the catalyst is high in the early stage of the reaction, so a method is adopted in which the catalyst is added at a low concentration in the early stage of the reaction, and the catalyst is added at any time when the catalyst activity has decreased to a certain extent to carry out the reaction at a higher concentration. It

The solvent used in the present invention must be liquid under the reaction conditions, but the reaction product (pyrrolidine, N-
It is extremely close to the boiling point of (alkylpyrrolidine), is hydrolyzed under this reaction condition, significantly reduces the catalytic performance, or has high reactivity with the raw material and / or reaction product, and promotes a side reaction. Unless otherwise specified, a widely used high-boiling solvent can be used.

Examples of these solvents include hydrocarbon compounds, oxygen-containing compounds and nitrogen-containing compounds. More specifically, the hydrocarbon compound is n-dodecane, n-
Hexadecane, liquid paraffin, tetralin, octahydroanthracene, heavy alkylbenzene and the like can be mentioned. Further, as the oxygen-containing compound, ortho-
Examples thereof include dimethoxycatechol, diphenyl ether, and dialkyl ether of polyethylene glycol (eg, tetraethylene glycol dimethoxy ether, doryethylene glycol diethoxy ether). As the nitrogen-containing compound, tertiary amines (particularly saturated amine) are preferable. For example, tributylamine, trihexylamine, N-dodecylpyrrolidine, etc. can be mentioned. It is also possible to use a high boiling point amine, which is produced in a trace amount in the production process of pyrrolidines, as a solvent. Since the pyrrolidinone used as a raw material generally has a large boiling point difference from the pyrrolidines produced, a method of using this as a reaction solvent can be considered, but it is partially hydrolyzed by the water produced by hydrogenation. It is not a preferable method because it is decomposed or partially converted into a polymer.

The hydrogenation reaction conditions can be set to any conditions as long as there is no problem in the embodiment of this process. The reaction temperature is about 100 to 400 ° C, preferably about 150 to 300 ° C. The reaction pressure is from atmospheric pressure to 200 atm, preferably 2 to 150 atm. The hydrogen flow rate is sufficient if the reaction product is taken out from the reaction zone, and a hydrogen flow rate of 2 to 10,000, preferably 3 to 5,000, is usually used in terms of the molar ratio of hydrogen to the raw material.

〔Example〕

Example 1 In the apparatus shown in the flow chart of FIG. 1, 150 ml of fluid paraffin was introduced into the reactor 1 (internal volume 300 ml),
Commercially available copper oxide-chromium oxide catalyst (N-20 manufactured by JGC Corporation)
3) 5 g was suspended. While supplying a small amount of hydrogen gas from the pipe 18 to the reactor 1 through the pipe 9, while controlling the heating to a reaction temperature of 240 ° C. and a reflux pipe temperature of 140 ° C., the reaction pressure was set to 5
Set 0Kg / cm ^2, 200 is a hydrogen gas flow rate in the gas outlet pipe 20
It was controlled to be Nl / hour. Then, the raw material N-methylpyrrolidinone was supplied from the pipe 19 through the pipe 10 at a rate of 100 mmol / hour (note that in this example, the gas and the raw material were not circulated using the pipes 13 and 17). The liquid product obtained from the tube 14 was collected, and the liquid product was analyzed by gas chromatography. The reaction reached a stable state within a few hours, and the analysis results of the liquid product for 4 hours after entering the stable state showed that the single-stream conversion of N-methylpyrrolidinone was 9%.
5.9 mol% of converted N-methylpyrrolidinone to N
The selectivity to methylpyrrolidine was 99 mol%.

Examples-2 to 6 Using the various raw materials in the same manner as in Example-1, the reaction conditions were changed to the conditions shown in the table, and 2-pyrrolidinone (Example-
2), N-methylpyrrolidinone (Example-3), N-ethylpyrrolidinone (Example-4), N-sec-butylpyrrolidinone (Example-5) and N-cyclohexylpyrrolidinone (Example-6) as raw materials The experiment was done. The reaction results are shown in Table 1.

Comparative Example-1 N- in an autoclave with induction rotary stirring having an internal volume of 50 ml
Methylpyrrolidinone 14.1 g, the same catalyst as in Example-1 1.0 g
And gas replacement, then the reaction pressure is 60 Kg / cm
The reaction was carried out at ² G and 250 ° C. for 4 hours. After cooling, the reaction product was analyzed by gas chromatography (internal standard method). As a result, an N-methylpyrrolidinone conversion rate of 45.2 mol% and an N-methylpyrrolidine selectivity of 84 mol% were obtained. Although the reaction time was extended to 6 hours under the same conditions, the gas absorption rate was greatly reduced compared to the initial stage of the reaction, and the conversion rate did not exceed 50 mol%.

Comparative Example-2 When the reaction was carried out under the same conditions as in Comparative Example-1 except that the reaction temperature was 280 ° C and the reaction time was 6 hours, the conversion rate of N-methylpyrrolidinone was 41 mol%, and N-methylpyrrolidinone was obtained. The selectivity to pyrrolidine was 34 mol%.

[Brief description of drawings]

FIG. 1 is a flow chart for explaining the present invention. 1 ... Reactor, 2 ... Reflux tube, 4 ... Separator 5 ... Separator, 6 ... Reservoir

Claims (1)

(57) [Claims] 1. A catalytic hydrogenation of 2-pyrrolidinone and / or N-alkyl-2-pyrrolidinone to produce pyrrolidine and / or
Or in the method for producing N-alkylpyrrolidine,
A copper-based catalyst is suspended in a liquid phase of a reaction zone maintained at a substantially constant temperature, and 2-pyrrolidinone and / or N 2 are suspended therein.
-Alkyl-2-pyrrolidinone is supplied and the reaction product is taken out of the reaction zone in vapor phase together with hydrogen gas excess, a process for producing pyrrolidines.