JPS60228444A - Preparation of substituent group-containing alicyclic enamine - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield, by reacting an alicyclic enamine with an aldehyde while a temperature in the system is kept in a specific range by reflux condensation of a solvent under reduced pressure and formed water is removed out of the system by azeotropy with an inert solvent. CONSTITUTION:An alicyclic enamine shown by the formula I (R1 is water-soluble secondary amine residue; n is 2-9) is reacted with an aldehyde shown by the formula R2-CHO (R2 is hydrocarbon residue) in the presence of an inert solvent (e.g., toluene) while a temperature in the system is kept at 85-105 deg.C by reflux condensation of the solvent under reduced pressure preferably at <=500mm.Hg, and formed water is removed out of the system by azeotropy with the inert solvent, to give the desired compound shown by the formula II. By making reduced pressure the reaction temperature can be lowered while an amount of reflux to promote dehydration from the reaction system is kept, side reactions are reduced, and the desired compound is prepared in high yield efficiently.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing a substituent-containing alicyclic enamine, and more specifically, the present invention relates to a novel method for producing a substituent-containing alicyclic enamine, and more specifically, an alicyclic enamine represented by the general formula (I) and the alicyclic enamine represented by the general formula CB). Regarding a method for producing a substituent-containing alicyclic enamine represented by the general formula [1111] in high yield by condensing aldehydes, the substituent-containing alicyclic enamine [III] is an intermediate for the synthesis of pharmaceuticals, agricultural chemicals, fragrances, etc. It is a substance useful as a raw material for 2-substituted cycloalkanones, which are useful as cycloalkanones.

Several methods are already known for producing such substituent-containing alicyclic enamines.

For example, Hemische Perichte (Chem, Bar,
) 95.1495 (1962) and Chemical and Pharmaceutical Pretin (Chem, Ph.
arm.

Bull, ) 21, 215 (1973), N-(Δ
A method for producing N-(2-alkylidene-Δ5-cyclopentenyl)-morpholine by condensation reaction of 1-cyclopentenyl)-morpholine and the corresponding aldehyde in benzene is described, and Japanese Patent Application Laid-Open No. 1983-1989 489
No. 35 describes a method in which a similar reaction is carried out in toluene.

However, in these known methods, a considerable amount of by-products are generated, so the yield is not necessarily sufficient, and the reaction time is long, which causes problems.

The inventors of the present invention have conducted intensive studies to overcome these drawbacks of the prior art, and as a result have found that it is possible to overcome these drawbacks by selecting specific reaction conditions, and have completed the present invention.

That is, an object of the present invention is to provide a method for producing a substituent-containing alicyclic enamine represented by the general formula (IID) in a simple operation, suppressing the generation of by-products, and efficiently in a high yield. The object of the present invention is to represent the general formula [I]
When condensing the alicyclic enamine represented by the formula [11] with the aldehyde represented by the above general formula [11] in the presence of an inert solvent, the system temperature is lowered to 85 to 85% by reflux condensation of the solvent under reduced pressure.
This is achieved by carrying out the reaction while maintaining the temperature at 105° C. and removing the produced water from the system by azeotroping with an inert solvent.

The alicyclic enamine used as a raw material in the present invention is represented by the above general formula [I].

R1 in the formula is a secondary amino residue, and specific examples thereof include water-soluble secondary amine residues such as morpholino group, piperidino group, pyrrolidino group, diethylamino group, dimethylamino group, etc. /1, and residues of cyclic secondary amines having 4 to 5 carbon atoms are particularly preferred. Further, n represents an integer from 2 to 9, but 2 or 3 is particularly preferable, and 2 gives good results.

On the other hand, the aldehyde to be subjected to the reaction is represented by the above general formula [■], and R2 in the formula is usually a hydrocarbon residue having 2 to 6 carbon atoms. ,
For example, ethyl group, propyl group, butyl group, pentyl group,
Alkyl groups such as hexyl groups; alkenyl groups such as propenyl and hexenyl groups: provinyl groups;
Examples include alkynyl groups such as hexynyl.

Alicyclic enamine CI) and aldehyde [1] in the present invention
The condensation reaction 1) is usually carried out as follows.

That is, aldehyde [■] equivalent to 1 mole) alicyclic enamine [
Do, 7 to 1.5 mol is used, and aldehyde […]
100 parts by weight, 0.1 to 10 parts by weight of a catalyst for dehydration reaction, and 50 to 1000 parts by weight of an inert solvent are appropriately charged into a reactor, and the mixture is heated under reduced pressure at a temperature of 85 to 105°C, preferably 90 to 100°C. will be implemented.

The catalyst for the dehydration reaction may be any commonly used catalyst such as sulfuric acid, para-toluenesulfonic acid, etc., and the inert solvent may form a minimum azeotrope with water under the reaction conditions. Any material may be used as long as it is not substantially mutually soluble.

Specific examples of such solvents include toluene, xylene, and ethylbenzene.

In addition, the reaction may be started after charging the entire amount of aldehyde [n] and alicyclic enamine (1) in advance.
Aldehyde (II) can also be added continuously or intermittently, if necessary.

In the present invention, the reaction temperature is an important requirement; if the reaction temperature is excessively high, the reaction rate will increase, but the amount of by-products will increase rapidly; on the other hand, if the reaction temperature is excessively low, the reactivity will decrease. When the reaction time is increased to increase the conversion rate, high boiling point by-products increase.

Note that at the end of the reaction, water in the system ceases to exist, so the reaction temperature may temporarily exceed the above range; however, if most of the reaction is carried out within the above range, this invention is not included Ru.

The reaction pressure may be appropriately selected so that the reaction temperature falls within the above range, but is usually 600 mHg or less, preferably 500 mHg or less. By reducing the pressure, the reaction temperature can be lowered while maintaining the reflux amount to promote dehydration from within the reaction system, reducing side reactions and efficiently obtaining the target compound 18 in high yield. can.

The water that has evaporated with the inert solvent is then removed from the system in a conventional manner. The method for removing water may be carried out according to a conventional method, and for example, a decantation method using an oil-water separation tank, a method using a dehydrating agent such as molecular sheep, etc. can be appropriately employed. The solvent after dehydration is circulated to the reaction system, thereby controlling the temperature of the reaction system.

Thus, according to the present invention, the substituent-containing alicyclic enamine represented by the general formula [m] can be obtained more efficiently and in a higher yield than conventional methods, and the generation of by-products can be suppressed to a low level. I can do it.

The present invention will be explained in more detail with reference to Examples below. In addition, parts in the examples are based on weight, and (
) is the number of moles per mole of valeraldehyde.

Example 1 161.8 parts (1.05 mol) of N-(Δ1-cyclopentenyl)-morpholine and 0.88 parts of tuyaradolenesulfonic acid were placed in a reactor equipped with a stirrer and a reflux condenser attached to an oil-water separation tank. ?1R1 (0,005 mol) and 132.5 parts (1,44 mol) of toluene were charged, and 400 r
The mixture was heated to boiling under a pressure of 100 mL. After 86.1 parts (1 mol) of n-valeraldehyde was gradually added to this mixture over 2 hours, the reaction was continued for an additional 30 minutes.

The condensed liquid of volatile components was separated into two layers in an oil-water separation tank, and the organic layer was refluxed into the reaction system while the aqueous layer was extracted from the system.

The temperature inside the reaction system was 100°C at the beginning of aldehyde addition, but gradually decreased to a minimum value of 90°C at the end of aldehyde addition.
℃, then gradually rose to 10℃ at the end of the reaction.
The temperature reached 2℃. Distillation of produced water stopped in about 2.5 hours. Bring the inside of the system to normal pressure, add 108 parts of 35% hydrochloric acid, and heat to 80°C.
After stirring for 30 minutes, 88.3 parts of an aqueous solution of 17 um of 5% sodium bicarbonate was added and stirred. After standing still and separating the two layers, the aqueous layer was removed from the system, and the entire organic layer obtained was sampled and analyzed by chromatography to quantify the product. As a result, N-(Δ1-cyclo N-(pentenyl)-morpholine and n-valeraldehyde condensate
The main product was 2-n-enthylidenecyclobentanone, which is a hydrolyzate of 2-n-henthylidene-Δ5-cyclopentenyl)-morpholine, and the yield based on B-valeraldehyde was 91 moles. Ta. Measurement of the amount of cyclopentanone remaining in the system revealed that N-Δ1-cyclopentenyl (N-Δ1-cyclopentenyl) was lost as a by-product (mainly a high-boiling point product) during the reaction.
-The amount of morpholine was 4.6 moles of the charged amount @Example 2 The same operation as in Example 1 was carried out except that the reaction was carried out while adjusting the degree of vacuum so that the reaction temperature was constant at t. When the reaction was carried out, the reaction was completed within 2.5 hours in all cases. As a result, the product 2-
The yield of n-pentylidenecyclopentanone based on n-valeraldehyde and the amount of N-(Δ1-cyclopentenyl)-morpholine lost as a by-product during the reaction (based on the amount charged) are shown in Table 1. It was shi.

Comparative Example I In the condensation reaction of N-(Δ1-cyclopentenyl)-morpholine and n-valeraldehyde, the reaction was carried out in the same manner as in Example 1, except that benzene was used as a solvent and the entire reaction was carried out under normal pressure. Ta.

The time required to complete the reaction was 4.0 hours.

As a result, the product 2-n-pentylidenecyclo4
Yield of ntanone based on n-noraldehyde: 78.5
Obtained in %. In addition, by-products and 1 are lost during the reaction.
The amount of cN-Cl3-siftenyl)-morpholine was 18.6 moles of the charge.

Patent applicant: Zeon Corporation

Claims (1)

[Claims] 1. A cycloaliphatic enamine represented by the following general formula [1] and an aldehyde represented by the following general formula [1] are condensed in the presence of an inert solvent to form a compound represented by the following general formula [11D]. When producing substituent-containing alicyclic enamines, the system temperature 'f: 85 to 105°C is reduced by reflux condensation of the solvent under reduced pressure.
1. A method for producing a substituent-containing alicyclic enamine, characterized in that the reaction is carried out while maintaining the temperature, and the produced water is removed from the system by azeotroping with an inert solvent. m [1) [IID (wherein, R1 represents a water-soluble secondary amine residue, R2 represents a hydrocarbon residue, and n represents an integer from 2 to 9.)