JPS62289549A - Production of n-(alpha-alkoxyethyl)-carboxylic acid amide - Google Patents

Abstract

PURPOSE:To obtain a compound useful as a synthetic intermediate for N- vinylcarboxylic acid amide as a synthetic raw material for chemicals, by reacting a primary carboxylic acid amide with acetaldehyde and an alkanol in the presence of a strongly acidic cation exchange resin catalyst. CONSTITUTION:A primary carboxylic acid amide (e.g. formamide) shown by formula R1CONH2 (R1 is H, methyl or ethyl) is reacted with acetaldehyde and a straight-chain or branched alkanol (e.g. methanol) shown by formula R2OH (R2 is 1-4C alkyl) in the presence of a strongly acidic cation exchange resin (e.g. Amberlite 15) simultaneously or by successively adding the raw materials to give the aimed substance. The reaction is preferably carried out in a molar ratio of the primary carboxylic acid amide, acetaldehyde and the alcohol of 1:5-20:5-20. EFFECT:The aimed substance is obtained from readily obtainable inexpensive raw materials by one stage reaction in high yield.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention is an intermediate of N-vinylcarboxylic acid amide that can be used as a raw material for the synthesis of polyvinylamine, which is a water-soluble polymer, and chemicals such as taurine and cysteamine. 122 method of N-(α-alkoxyethyl)-carboxylic acid amide. More specifically, N-(α-alkoxyethyl
- Method for producing carboxylic acid amide 1II-y.

[Prior Art and its Problems] Conventionally, various methods have been proposed as methods for synthesizing N-(α-alkoxylethyl)-carboxylic acid amides.

(A) JP-A-50-76014 describes N-acyl-
A method for decarboxylating and alkoxylating α-alanine by electrolytic oxidation in an alcohol solvent is disclosed in (a) JP-A-55-1
Publication No. 54589 describes a method of alkoxylation by electrolytic oxidation in N-ethylcarboxylic solvent (
(1) U.S. Pat.
No. 54,377 discloses a method of reacting dimethyl acecool with a carboxylic acid amide in the presence of an acid catalyst.

Furthermore, (e) West German Patent No. 1.273.533 discloses a method of reacting a carboxylic acid amide with an aldehyde and an alcohol, or a carboxylic acid amide and a 7-setal, in Japanese Unexamined Patent Publication No. 149551/1983. The publication describes N-(α) obtained from formamide and acetaldehyde.
-hydroxyethyl)-formamide is disclosed.

However, both of these methods have significant drawbacks. That is, in the methods (a) and (b) above, the raw materials N-acyl-α-alanine and N-ethylcarboxylic acid amide are expensive, and mass production is difficult due to the use of electrochemical methods. Electrolytic cell and electrode maintenance tube 1! !
! etc. have problems.

In addition, method (1) requires the same molar amount of hydrogen halide relative to the aldehyde as a raw material to synthesize the α-halogenoalkyl ether as a raw material, and is not necessarily an economically advantageous production method.

Furthermore, method (1) has the disadvantage that it is necessary to separately synthesize dimethyl acecool and isolate it for use.

In general, as a method for producing acetals of lower alcohols, a method using acetaldehyde and alcohol as raw materials in the presence of an acid catalyst has been known for a long time, but this reaction is accompanied by a by-product of water in an amount equal to the amount of the acetal produced. This is an equilibrium reaction, and it is necessary to use a large amount of dehydrating agent in order for the reaction to proceed sufficiently. Furthermore, the operation of reaction distillation, which is generally employed to increase the conversion rate in equilibrium reactions, is extremely difficult to implement due to the low boiling point of acetaldehyde.

It is also possible to use a large excess of alcohol to carry out the reaction favorably in equilibrium, but in order to form an azeotrope between acetal/alcohol and acetal/water, pure acetal can be obtained by a simple distillation operation. difficult to obtain. Therefore, it includes the acetal synthesis step (1
) is not an industrially advantageous method.

Furthermore, in the method (e), the reaction is carried out using hydrochloric acid, para-toluenesulfonic acid, para-toluenesulfonic acid chloride, thionyl chloride, etc. as a catalyst, but the raw material carboxylic acid amide is limited to secondary niamide. Moreover, in the case of linear carboxylic acid 7amide, the yield is extremely low. For example, N
The yield of N-(α-ethoxyethyl)-N-methylacetamide from -methylacetamide and acetaldehyde dimethyl 7-cetal is only 26%.

In Zarani's method, N-(α-alkoxyethyl)
-As an intermediate for obtaining formamide, it has only been suggested that N-(α-hydroxylethyl)-carboxylic acid amide may be obtained from formaldehyde and acetaldehyde using potassium carbonate as a catalyst, and even if this method is adopted, However, a two-step reaction operation is required, and the raw material is limited to formaldehyde, which provides a relatively stable N-(α-hydroxyegul) form. For example, the intermediate N-(α-hydroxyethyl>-acetamide, which is made from aledamide as a raw material) is an unstable compound that cannot be isolated, and the same ``IJ manufacturing process'' as with formaldehyde cannot be carried out. As described above, the conventional method for synthesizing N-(α-alkoxyethyl)-carboxylic acid amide cannot be said to be convenient or widely applicable.

E. Purpose of the present invention: The present invention aims to solve the problems of the prior art by using readily available and inexpensive acetaldehyde, primary carboxylic acid amide, and alcohol as raw materials to achieve the desired purpose through a one-step reaction. The purpose of the present invention is to provide a method for synthesizing N-(α-alkoxy nibbles) in high yield.

[Means for Solving the Problems] The objects of the present invention are achieved by carrying out a one-step reaction of primary carboxylic acid amide, acetaldehyde and alcohol in the presence of a strongly acidic cation exchange resin according to the method of the present invention. .

In the reaction to synthesize acetal from acetaldehyde and alcohol, hydrochloric acid and sulfur F! ! It has long been known that 'V8&acids are effective catalysts.

Further, as described in the above-mentioned US Pat. No. 4,554,377, N
When synthesizing -(α-methoxyethyl)-7cetamide, a homogeneous catalyst such as methanesulfonic acid or concentrated sulfuric acid can be used to obtain the desired product in high yield. It has been widely known that the use of such heterogeneous catalysts results in lower yields.

Therefore, it is conceivable to use these homogeneous catalysts when synthesizing N-(α-alkoxyethyl)-carboxylic acid amide from primary carboxylic acid amide, acetaldehyde, and alcohol due to the similarity of the reactions. , according to the study results of the present inventors, contrary to expectations, the target N
It was found that the yield of -(α-alkoxyethyl)-carboxylic acid amide was extremely low. On the other hand, surprisingly, when a strongly acidic cation exchange resin is used as a catalyst for the above reaction, N-(α-alkoxyethyl
- It was discovered that a carboxylic acid amide can be obtained, and the present invention was completed.

The strongly acidic cation exchange resin used in the present invention may be either a gel type or a porous type; examples of the former include "Diaion 5K-IB", "Amberlite IR-120BJ", "Dowex 50WJ (
Both are product names). Examples of the latter include "Diaion PK-2164, r Amberlite 200C", "Amberlyst 15J", and "Dowex MSC-IJ" (all product names).

As the primary carboxylic acid amide of the present invention, an aliphatic primary carboxylic acid amide can generally be used. These include formamide, acetamide, propionamide, etc., among which formamide and acetamide are particularly preferred.

In addition, as the alcohol used as a starting material, aliphatic or aromatic aliphatic alcohols can generally be used, and these include methanol, ethanol, n-propanol, isopropanol, n-butanol, 5ec-butanol, etc. will be combined.

Among these, methanol, ethanol and isopropanol are preferred.

The ratio of primary carboxylic acid amide, acetaldehyde, and alcohol used is usually 1:2.0-50:2゜0-50.
(molar ratio) is selected from the range of 1:5 to 1:5.
A range of 20:5 to 20 (molar ratio) is particularly preferred. If the amount is less than this, the conversion rate of the primary carboxylic acid amide will decrease significantly, and even if it is used more than this, no improvement in the conversion rate can be expected.

Further, the ratio of acetaldehyde to alcohol used is usually selected from the range of 1:0.5 to 20 (molar ratio), and particularly preferably 1:2 to 5 (molar ratio). If it is less than this, by-products such as valaldehyde and ethylidene bisamide will be produced and the selectivity of the target product will be reduced, and if it is more than this, the reaction rate will be significantly reduced, so both are not preferred. The proportion of the strongly acidic cation exchange resin used as a catalyst is normally selected from the range of 1 to 30% by weight, preferably 2 to 15% by weight, based on the primary carboxylic acid amide.

If the temperature is too low, the reaction rate will decrease, and if the temperature is too high, undesirable side reactions may occur.

The compounds obtained by the method of the invention 7 are primarily intermediates for eg N-vinylcarboxylic acid amides "12'El", which, as mentioned at the outset, are homo- and copolymers and useful Can be induced by chemicals.

Conversion to the corresponding N-vinylcarboxylic acid amide is carried out in known manner, preferably by pyrolysis at temperatures of about 60 DEG to 350 DEG C.

Examples of the present invention will be described in detail below in comparison with comparative examples, but the invention is not limited to these examples as long as the gist of the present invention is not departed from. Further, throughout this specification, all temperatures are in degrees Centigrade, and parts and percentages are on a diameter basis unless otherwise specified. Next to the Examples and Comparative Examples of the present invention, a reference example for obtaining a corresponding N-vinyl compound by using bt[I of methanol from a product obtained according to the method of the present invention is shown.

[Examples and Comparative Examples] Example 1 Three-necked flask (100 ml) equipped with a thermometer and a dry ice-ethanol trap on the Dimroth condenser
) to acetamide (1180 mg, 20 mmo + )
, methanol<25.6g, 80Qmmol) was added and stirred to dissolve. Next was the strongly acidic cation exchange resin “Amberlyst 15” (trade name: Rohm & Co., Ltd.).
Hearth formal dress) (150 mo) was added, cooled in a water bath,
Acetaldehyde (17,6 g, 400 mmol)
was added dropwise over 10 minutes.

After the completion of the dropwise addition, the reaction was carried out at 50°C for 5 hours, and then the catalyst was filtered and determined by gas chromatography. The conversion rate of acetamide was 85%, indicating that N-(α-methoxyethyl)-acetamide was selected! It was $95%.

After distilling off acetaldehyde, methanol and dimethyl acecool under normal pressure and then under reduced pressure, chloroform (10 ml) and saturated aqueous sodium hydrogen carbonate solution (5 ml) were added to the residue and the mixture was thoroughly shaken. When the chloroform layer was separated and chloroform was distilled off under reduced pressure using an evaporator, extremely pure N-(α-methoxyethyl)-
Acetamide (1850 mq) was obtained as a viscous liquid. The yield was 79% based on the charged acetamide.

1) 1-NMR spectrum 6 (ppm, measured in CDCLS): 1.32 <38SCp30H-1 doublet) 2.03
(3H, C-tan 3CO-1-child I!ri 3.30 (31C
C=, 0-1-Hayabusa line) 5.00-5.50 (1H, C
H30 tool - 1 multiplet) Jomai' - as a catalyst instead of [Amberlyst 15] desert sulfur M (0
The operation was carried out in exactly the same manner as in Example 1, except that 1ml) was used. The conversion rate of acetamide was 88%, and the selectivity of N-(α-methoxyethyl)-7cetamide was 36%.

Comparative Example 2 The operation was carried out in exactly the same manner as in Example 1, except that methanesulfone M (0.1 g) was used as a catalyst instead of "Amberlyst 15". Acetamide conversion rate 90%, N
-(α-methoxyethyl)-acetamide selectivity 65
%Met.

Example 2 A three-lobe flask (2000
methanol <768 g, 24 mol) in
Strong acidic cation exchange resin [Diaion PK-21
6J (Product name: Mitsubishi Kasei Corporation, H+ type) (Wet body 10m1
) was added. Cool in a water bath, and when the internal temperature reaches 5 to 10°C, add acetaldehyde (352Q, 3mol I > 2
It dripped over time. Reaction for 3rI at 60°C,
When the mixture was cooled and determined by gas chromatography, the conversion rate of acetaldehyde was 88% and the selectivity of acetaldehyde dimethyl acetal was 92%.

Add acetamide (29,5(), 0°5mol) to this reaction solution.
! ) was added and reacted at 60°C for 6 hours.

After cooling, quantitative determination by gas chromatography showed that the conversion of acetamide was 83% and the selectivity of N-(α-methoxyethyl)-acetamide was 80%.

Example 3 Operation J3 and post-treatment were carried out in exactly the same manner as in Example 1, except that ethanol was used instead of methanol, and N-(α
-ethoxyethyl)-acetamide (1929 mg) was obtained as a viscous liquid. The yield was 73% based on the charged acetamide.

1H-NMR spectrum δ(op m, CDC
Measured in L 3): 1.16 (3H1C tool, CH20-1 Mikawa Line) 1.32
(3H, CFi3CH-1 doublet) 2.00 (3H
, (43GO-1-pu13.30~3.73 (2H,
CH2O shell, 0-1 multiplex a) 5.10 to 5.57 (11-1, CH2O dan-1 multiplex a
) Example 4 The same operation as in Example 1 was performed except that isopropanol was used instead of methanol.

After the reaction was completed, the catalyst was removed by filtration, and saturated aqueous sodium carbonate solution (20 ml) was added. After shaking well, am was extracted. The aqueous layer was extracted three times with chloroform (10 ml) and combined with Ti. When the low boiling point seafood was distilled off under reduced pressure, N-(α-isopropoxyethyl)-acetamide (2200 rrl) was obtained as a colorless viscous liquid as a residue. The yield was 76% based on the charged acetamide.

'HNMR spectrum δ (ppm, measured in CDCl2): 1.07-1.30 [6H.

(C Otori.) 2CH-1 multi-width line] 1.29 (3HSCj43CH-1 double line) 1,
99 (3 to 1, C and 4 3 co-, --
Jli line) 3.54 to 4.00 [1H1 (C13)2C20-1 multiplet] 5.19 to 5.64 (IH, CH3C O-1 multiplet) Example 5 Instead of isopropanol The operation was carried out in exactly the same manner as in Example 4 except that n-butanol was used, and N-(α-n-
Butoxynibble)-acetamide (2280 ffl) was obtained as a colorless viscous liquid.

1H-NMR spectrum δ (Dpm, measured in CDCl2); 0.73-1.70 (IOH,C and 3CH2Cti
2 CH20-, 130 on C, 10-, multiplet) 2.00 (3H, (43GO-1-multiplet) 3.22~
3. ' 67 (2H, n-C5H7-cFi2-o-
1 multiplet) 5, 03-5. 57 (1H, C 13
Cl10-, multiplet) Example 6 The procedure was carried out in exactly the same manner as in Example 4, except that 5ec-butanol was used instead of isopropanol, and N-(α-
5ec-butoxyethyl)-7cetamide (2350m
Q> was obtained as a colorless viscous liquid. The yield was 74% based on the charged acetamide.

1H-NMR spectrum δ (ppm, measured in CDCLS); 0.68-1.67 (111-1, Cl3C feet);

Cto + (Cto1) O-, CLl 3 Cto
−, many η! =3 line) 2.00 (3H, C tool, co-1- double line) 3, 4
0 to 3.80 (1H, C 13 CH2CH (CH3)
O-1 multi-φ line) 5.17 to 5.67 (1H, CH3CFiO-1 multiple line) Example 7 Formamide (910 mg, 20 mm) was substituted for acetamide <1180 mg, 20 mmol.

The procedure was carried out in exactly the same manner as in Example 1, except that 1) was used. Implementation V! Post-treatment was carried out in the same manner as in 41 to obtain N-(α-methoxyethyl)-formamide (1340m9). The yield was 65% based on formamide.

Example 8 Propionamide (1460 mg, 20 mmol) was used instead of acetamide (1180 mcx, 2 C mmol).
The procedure was carried out in exactly the same manner as in Example 1, except that 1) was used.

Pure N-(α-methoxyethyl)-propionamide (2070 mg) was obtained as white crystals by chloroform extraction. The yield was 79% based on the charged propionamide.

1) -1-N MR spectrum δ (ppm, measured in CDC 3); 1.16 (3N, CFi3CH2C〇-1 triple a) 1.32 (3)1. Cjj3CH20-1 triple line) 2
．． 28<2H, CH3G 1 soil 2 co-, quartet) 3.29 (3H, C tan, 0-1- doublet) 5.03~5
．． 52 (11-1, CH3C ■ 0-1 multiweight> Reference example Synthesis of N-vinylacetamide by thermal decomposition of N-(α-methoxyethyl)-acetamide A three-necked flask (50 ml) equipped with a nitrogen introduction tube and a dropping funnel ) to length 4
It was connected to a quartz tube with a diameter of 0 cm and a width of 2.10 m. The inside of the quartz tube was filled with a quartz ring, and the other side of the quartz tube was cooled to -78°C. The pressure was reduced to 22 mmHa using a vacuum pump. The quartz tube was heated to 550°C in an electric furnace, and the three-necked flask was heated to 150°C in an oil bath. N-(α-methoxyethyl)-acetamide (23° Oa) synthesized by the method of Example 1 was added dropwise from the dropping funnel over 25 minutes. The pyrolyzate was condensed into a cooled receiver. When the components in the receiver were analyzed by gas chromatography, it was found that N
-(α-methoxyethyl)-acetamide (2,Oq)
In addition, the target product N-vinylacetamide (14,3
g). This corresponded to a conversion rate of 91.3% for N-(α-methoxyethyl)-acetamide and a selectivity for N-vinylacetamide of 93.7%.

Sender: Showa Denko Co., Ltd. Knee;

Claims (1)

[Claims] (1) A method for producing N-(α-alkoxyethyl)-carboxylic acid amide, which is represented by the following general formula R_1CONH [wherein R_1 represents either a hydrogen atom, a methyl group, or an ethyl group] primary carboxylic acid amide (a), acetaldehyde (b) and a linear or branched alkanol (c) represented by the general formula R_2OH [wherein R2 represents an alkyl group having 1 to 4 carbon atoms]
3 as a raw material and a strongly acidic cation exchange resin as a catalyst.
A method characterized by reacting seed materials simultaneously or sequentially.