JP2004099506A - Method for producing amino acid amide - Google Patents
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Abstract
Description
【０００１】
【発明の属する技術分野】
本発明は高品質のアミノ酸アミドの水溶液を高収率で製造する方法に関する。アミノ酸アミドは親水性の高い化合物で、医楽や農薬の中間原料として有用である。
【０００２】
【従来の技術】
アミノ酸アミドの製造方法として、アミノニトリルをケトンの存在下で水和反応する方法が種々知られている。特開昭５２−２５７０１号公報には、α−アミノニトリルとケトンを水性媒体中ｐＨ１１〜１４で反応させ、α−アミノ酸アミドを得る方法、特開昭５７−１５８７４３号公報には、反応液のｐＨを１４以上に保ちつつ、ケトンの存在下、水性媒体中でα−アミノニトリルを水和反応する方法が知られている。また、本発明者らは特開２００１−１６３８４５号公報において、アミノニトリルを塩基及びケトンの存在下、含水アルコール溶媒中で水和反応する方法を提案した。得られたアミノ酸アミドを単離する方法として、特開昭５２−２５７０１号公報には、ケトンを蒸留等で回収する方法、特開昭５７−１５８７４３号公報には、反応液の濃縮のみで高品質のアミノ酸アミドを単離できる事が開示されており、本発明者らは特開２００１−１６３８４５号公報ので、冷却のみでアミノ酸アミドを単離できる方法を提案した。
【特許文献１】特開昭５２−２５７０１号公報
【特許文献２】特開昭５７−１５８７４３号公報
【特許文献３】特開２００１−１６３８４５号公報
【０００３】
【発明が解決しようとする課題】
しかしながら、アミノ酸アミドの水溶液を得ようとする際、特開昭５２−２５７０１号公報及び、特開昭５７−１５８７４３号公報の方法はいずれもケトンを多く使用するため、α−アミノ酸アミドの単離を行う、または水溶液として用いるために蒸留、濃縮等の操作を行うと、生成したα−アミノ酸アミドとケトンが環化物を生成し、目的物の収率を大幅に低下させ、また製品純度も低下させるという問題を有している。特開２００１−１６３８４５号公報の方法では使用するケトンは少量で済み、冷却のみでアミノ酸アミドを単離できるため、環化物生成は殆ど無いが、単離操作による収率の低下は避けられない。単離操作を行わず、反応終了後に溶媒を水に置換して用いると、触媒として使用したアルカリ金属の水酸化物や、アミノ酸アミド反応液に残存しているシアンのアルカリ金属塩も残留して製品純度を低下させる問題があった。
【０００４】
本発明は、このような従来からの問題点を解決し、アミノ酸アミドの収率低下が無く、アルカリ金属の無機塩及びシアンのアルカリ金属塩を十分に低減したアミノ酸アミドの水溶液を製造する方法を提供することを目的とする。
【０００５】
【課題を解決するための手段】
本発明者らは上記課題を解決すべく鋭意検討した結果、ケトンの存在下でアミノニトリルを水和反応させて得られた、アミノ酸アミド反応液から触媒であるアルカリ金属及び夾雑不純物であるシアンのアルカリ金属塩を効率的に除去するには、特定のアルカリ金属塩の水溶液による洗浄によりアルカリ金属及びシアンのアルカリ金属塩を選択的に水相に除去でき、親水性の高いアミノ酸アミドの水相への損失が非常に少なくなる事を見出した。更に、アミノ酸アミドを含有する反応液に低級アルコールを追加してから洗浄操作を行うとアルカリ金属及び夾雑不純物であるシアンのアルカリ金属塩の除去率は向上し、アミノ酸アミドの水相への損失は低減できる事を見出した。本発明は、これらの知見に基づき完成されたものである。
【０００６】
すなわち本発明は、ケトンの存在下でアミノニトリルを水和反応させて得られた、下記一般式（１）
【化２】
【０００７】
【発明の実施の形態】
本発明はケトンの存在下でアミノニトリルを水和反応させて得られた、前記一般式（１）で表されるアミノ酸アミドを含有する反応液を用いる。ケトンの存在下でのアミノニトリルの水和反応は特開２００１−１６３８４５号公報に記載された方法等を用いることができる。例えば、ケトンとして、脂肪族ケトンをアミノニトリル１モルに対して、０．０１〜１モル存在させ、水をアミノニトリル１モルに対して、１モル以上使用し、アルコールとして炭素数１〜４の直鎖状または分岐状のアルコールを水に対して１〜５倍容量使用し、塩基としてアルカリ金属の水酸化物をアミノニトリル１モルに対して０．０１〜０．５モル使用し、室温〜６０℃で１〜２０時間反応させる。
【０００８】
本発明で用いられるアミノ酸アミドの具体例としては、アミノアセトアミド、２−アミノ−２−メチルアセトアミド、２−アミノ−２−エチルアセトアミド、２−アミノ−２−ｎ−プロピルアセトアミド、２−アミノ−２−イソプロピルアセトアミド、２−アミノ−２−ｎ−ブチルアセトアミド、２−アミノ−２−イソブチルアセトアミド、２−アミノ−２−ｓｅｃ−ブチルアセトアミド、２−アミノ−２−ｔ−ブチルアセトアミド、２−アミノ−２，２−ジメチルアセトアミド、２−アミノ−２−メチル−２−エチルアセトアミド、２−アミノ−２−メチル−２−イソブチルアセトアミドなどが挙げられる。
【０００９】
本発明の洗浄工程に使用する炭酸カリウム、酒石酸ナトリウム、酒石酸カリウム、及び／または酒石酸ナトリウムカリウムの水溶液の濃度は、１０〜５０％、好ましくは２０〜４０％である。使用する塩水溶液の量はアミノ酸アミドの種類、反応液量、追加有機溶媒の種類及び量等により異なり一概には言えないが、通常は反応液または有機溶媒等を追加したアミノ酸アミド含有溶液に対して０．５〜２倍量（質量）の範囲が好ましい。洗浄方法は回分洗浄、連続洗浄のいかなる方法を採用してもかまわない。回分洗浄の場合は、洗浄回数は１〜３回の範囲が特に好ましい。洗浄時の温度、圧力、及び攪拌接触時間は、特に限定されるものでなく、通常は常温、常圧、１時間程度である。塩の水溶液は攪拌接触させた後、静置し分離除去される。
【００１０】
本発明の方法では洗浄工程に先だって、反応液に少なくとも１種の炭素数１〜４の直鎖状または分岐状のアルコールを添加することにより洗浄効率をより向上させることができる。アルコールの使用量は特に制限されないが、アミノ酸アミド反応液に対して１〜５倍量（質量）が好ましい。更に、アミノ酸アミド反応液に残存しているケトンや水分を除去しておくと、アミノ酸アミドの損失を０．５％以下に抑える事ができるので、予め減圧濃縮等の方法を用いて濃縮しておいてもよい。これらのアルコールはアミノニトリルの水和反応時から用いても良いが、反応中に必要以上の量を添加すると反応速度が低下するため、反応終了後に添加するのがより望ましい。
【００１１】
洗浄工程で水相を分離除去して得られるアミノ酸アミドの溶液は、減圧濃縮等の操作により水分を０．５％以下とし、この時析出したアルカリ金属及びシアンのアルカリ金属塩はろ過で除去される。
【００１２】
ろ過後、アミノ酸アミドの溶液に含有される有機溶媒は通常水に置換される。有機溶媒を水に置換する方法は、特に限定されないが通常、蒸留、共沸等により有機溶媒を除去して水に置換する。必要に応じて減圧してもよい。
【００１３】
本発明の方法で得られたアミノ酸アミド水溶液は、そのまま、あるいは適当な濃度に調製して、生化学的加水分解反応に共することができ、アミノ酸アミドを単離する事による収率低下が無く、アルカリ金属の無機塩及びシアンのアルカリ金属塩の混入が無い光学活性アミノ酸を得る事ができる。
【００１４】
【実施例】
以下に実施例を挙げて本発明を説明するが、本発明はこれら実施例により何ら限定されるものではない。
【００１５】
実施例１
攪拌機及び温度計を付した５００ｍｌ三つ口フラスコに水５４ｇ及び水酸化ナトリウム８ｇを加えて溶解し、２−アミノ−２−ｔ−ブチルアセトニトリル１１２ｇ、メタノール９６ｇ 及びアセトン１７．４ｇを加え、３０℃で１０時間攪拌した。反応終了後、反応混合物には触媒の水酸化ナトリウム７．５ｇ、夾雑不純物としてシアン化ナトリウム１．５ｇが残存しており、液体クロマトグラフィーで分析したところ、２−アミノ−２−ｔ−ブチルアセトアミド反応収率９７％であった。反応混合物にｎ−ブタノール５７４．８ｇを加え、温度５０℃、圧力８ｋＰａで水分０．５％になるまで減圧濃縮した。得られたアミノ酸アミドのｎ−ブタノール溶液５１９．７ｇに２０％炭酸カリウム水溶液２２９．２ｇを加え、常温で１時間攪拌、３０分静置後、水相を除去し、温度５０℃、圧力８ｋＰａで減圧濃縮を行い水分０．５％以下とし、加圧ろ過にて析出した無機塩類等を除去して、洗浄されたアミノ酸アミドのｎ−ブタノール溶液４０５．４ｇを得た。得られた溶液を温度５０℃、圧力８ｋＰａで液量２４３．２ｇになるまで減圧濃縮を行った。この溶液に水２３２．８ｇを添加し、温度５０℃、圧力８ｋＰａで液量２４３．２ｇになるまで減圧濃縮を行い、この操作をもう一度繰り返して、溶媒を水に置換した。得られた水溶液の水酸化ナトリウムは０．６ｇ（含量０．２５％）、シアン化ナトリウムは０．０１ｇ（含量０．００４％）まで低減されており、液体クロマトグラフィーで分析したところ２−アミノ−２−ｔ−ブチルアセトアミドの濃度５１．８％、収量１２６．０ｇで収率はアミノニトリルに対して、９６．８％であった。
【００１６】
実施例２
実施例１と同様にして合成した、２−アミノ−２−ｔ−ブチルアセトアミドを合む、反応混合物にｎ−プロパノール５４７．８ｇを加え、３０％酒石酸ナトリウムカリウム水溶液１８０．０ｇを加え、常温で１時間攪拌、３０分静置後、水相を除去し、温度５０℃、圧力８ｋＰａで減圧濃縮を行い水分０．５％以下とし、加圧ろ過にて析出した無機塩類等を除去して、アミノ酸アミドのｎ−プロパノール溶液４２０．３ｇを得た。得られた溶液を温度５０℃、圧力８ｋＰａで液量２４０．５ｇになるまで減圧濃縮を行った。この溶液に水３２０．８ｇを添加し、温度５０℃、圧力８ｋＰａで液量２４０．５ｇになるまで減圧濃縮を行い、この操作をもう一度繰り返して、溶媒を水に置換した。得られた水溶液の水酸化ナトリウムは０．７ｇ（含量０．３０％）、シアン化ナトリウムは０．０２ｇ（含量０．００８％）まで低減されており、液体クロマトグラフィーで分析したところ２−アミノ−２−ｔ−ブチルアセトアミドの濃度５１．８％、収量１２４．６ｇで収率はアミノニトリルに対して、９５．７％であった。
【００１７】
実施例３
攪拌機及び温度計を付した５００ｍｌ三つ口フラスコに水５４ｇ及び水酸化ナトリウム８ｇを加えて溶解し、２−アミノ−２−ｓｅｃ−ブチルアセトニトリル１１２ｇ、メタノール９６ｇ 及びアセトン１７．４ｇを加え、３０℃で１０時間攪拌した。反応終了後、反応混合物を液体クロマトグラフィーで分析したところ、２−アミノ−２−ｓｅｃ−ブチルアセトアミド反応収率９７％、触媒の水酸化ナトリウム７．５ｇ、夾雑不純物としてシアン化ナトリウム１．５ｇが残存していた。反応混合物にメタノール５７４．８ｇを加え、３０％酒石酸ナトリウムカリウム水溶液１８０．０ｇを加え、常温で１時間攪拌、３０分静置後、水相を除去し、温度５０℃、圧力８ｋＰａで減圧濃縮を行い水分０．５％以下とし、加圧ろ過にて析出した無機塩類等を除去して、アミノ酸アミドのメタノール溶液４１０．７ｇを得た。得られたアミノ酸アミドのメタノール溶液に水３００．０ｇを添加し、温度５０℃、圧力８ｋＰａで液量２４３．２ｇになるまで減圧濃縮して溶媒を水に置換した。得られた水溶液の水酸化ナトリウムは０．８ｇ（含量０．３２％）、シアン化ナトリウムは０．０２ｇ（含量０．００８％）まで低減されており、液体クロマトグラフィーで分析したところ２−アミノ−２−ｓｅｃ−ブチルアセトアミドの濃度５０．９％、収量１２３．７ｇで、収率はアミノニトリルに対して、９５．０％であった。
【００１８】
比較例１
実施例１と同様の方法で合成した２−アミノ−２−ｔ−ブチルアセトアミド反応混合物に水２３２．８ｇを添加し、温度５０℃、圧力８ｋＰａで液量２４３．２ｇになるまで減圧濃縮を行い、この操作をもう一度繰り返して、溶媒を水に置換した。得られた水溶液の水酸化ナトリウムは７．５ｇ（含量３．１％）、シアン化ナトリウムは１．５ｇ（含量０．６２％）含まれており、液体クロマトグラフィーで分析したところ２−アミノ−２−ｔ−ブチルアセトアミドの濃度５１．９％、収量１２６．１ｇで収率はアミノニトリルに対して、９７．０％であった。
【００１９】
比較例２
実施例１と同様の方法で合成した２−アミノ−２−ｔ−ブチルアセトアミド反応混合物を、０℃まで冷却して析出した結晶をろ過した。得られた結晶を減圧乾燥した後、水１０８ｇに溶解した。得られた水溶液には、水酸化ナトリウムは０．６ｇ（含量０．２８％）、シアン化ナトリウムは０．０１ｇ（含量０．００５％）を含み、液体クロマトグラフィーで分析したところ２−アミノ−２−ｔ−ブチルアセトアミド濃度５０．０％、収量１０８ｇで、収率はアミノニトリルに対して、８２．９％であった。
【００２０】
比較例３
実施例３と同様の方法で合成した２−アミノ−２−ｓｅｃ−ブチルアセトアミド反応混合物２８７．４ｇを４０℃、８ｋｐａの条件で２２０ｇまで濃縮した混合物を０℃まで冷却して析出した結晶をろ過した。得られた結晶を減圧乾燥し、水１１４ｇに溶解した。得られた水溶液には、水酸化ナトリウムは０．７ｇ（含量０．３１％）、シアン化ナトリウムは０．０１ｇ（含量０．００４％）を含み、液体クロマトグラフィーで分析したところ２−アミノ−２−ｓｅｃ−ブチルアセトアミド濃度５０．０％、収量１１４ｇで、収率はアミノニトリルに対して、８７．５％であった。
【００２１】
【発明の効果】
本発明の製造法を用いることにより、アミノ酸アミドの精製による収率低下が無く、アルカリ金属の無機塩及びシアンのアルカリ金属塩を十分に低減したアミノ酸アミドの水溶液を得ることができる。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing a high quality aqueous solution of an amino acid amide in a high yield. Amino acid amides are highly hydrophilic compounds and are useful as intermediate materials for medicinal and agricultural chemicals.
[0002]
[Prior art]
As a method for producing an amino acid amide, various methods are known in which aminonitrile is hydrated in the presence of a ketone. JP-A-52-25701 discloses a method of reacting an α-aminonitrile with a ketone at pH 11 to 14 in an aqueous medium to obtain an α-amino acid amide. JP-A-57-158743 discloses a method for preparing a reaction solution. A method is known in which α-aminonitrile is hydrated in an aqueous medium in the presence of a ketone while maintaining the pH at 14 or more. In addition, the present inventors have proposed in Japanese Patent Application Laid-Open No. 2001-163845 a method of hydrating aminonitrile in a hydroalcoholic solvent in the presence of a base and a ketone. As a method for isolating the obtained amino acid amide, JP-A-52-25701 discloses a method of recovering a ketone by distillation or the like, and JP-A-57-158743 discloses a method in which only the reaction solution is concentrated. It is disclosed that amino acid amide of high quality can be isolated. The present inventors proposed a method capable of isolating amino acid amide only by cooling, as disclosed in JP-A-2001-163845.
[Patent Document 1] JP-A-52-25701 [Patent Document 2] JP-A-57-158743 [Patent Document 3] JP-A-2001-163845 [0003]
[Problems to be solved by the invention]
However, when attempting to obtain an aqueous solution of an amino acid amide, the methods disclosed in JP-A-52-25701 and JP-A-57-158743 both use a large amount of ketone, and therefore, the isolation of α-amino acid amide is difficult. Or an operation such as distillation and concentration for use as an aqueous solution, the generated α-amino acid amide and ketone form a cyclized product, which greatly reduces the yield of the target product and also lowers the product purity. Have the problem of causing In the method disclosed in JP-A-2001-163845, only a small amount of ketone is used, and the amino acid amide can be isolated only by cooling. Therefore, almost no cyclized product is produced, but a decrease in the yield due to the isolation operation is inevitable. When the solvent is replaced with water after the completion of the reaction without performing the isolation operation, the hydroxide of the alkali metal used as the catalyst and the alkali metal salt of cyan remaining in the amino acid amide reaction solution also remain. There was a problem of lowering product purity.
[0004]
The present invention solves such a conventional problem and provides a method for producing an aqueous solution of amino acid amide in which the yield of amino acid amide is not reduced and the inorganic salts of alkali metals and the alkali metal salts of cyanide are sufficiently reduced. The purpose is to provide.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to solve the above problems, and as a result, obtained from the amino acid amide reaction solution obtained by hydrating aminonitrile in the presence of ketone, alkali metal as a catalyst and cyanogen as a contaminant impurity from an amino acid amide reaction solution. To remove the alkali metal salt efficiently, the alkali metal salt of alkali metal and cyanide can be selectively removed to the aqueous phase by washing with an aqueous solution of a specific alkali metal salt, and the aqueous phase of amino acid amide with high hydrophilicity can be removed. Was found to have very little loss. Furthermore, when a lower alcohol is added to the reaction solution containing the amino acid amide and the washing operation is performed, the removal rate of the alkali metal and the alkali metal salt of cyanide which is a contaminant impurity is improved, and the loss of the amino acid amide to the aqueous phase is reduced. We found that it could be reduced. The present invention has been completed based on these findings.
[0006]
That is, the present invention provides a compound represented by the following general formula (1) obtained by hydrating an aminonitrile in the presence of a ketone.
Embedded image
[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention uses a reaction solution containing the amino acid amide represented by the general formula (1), which is obtained by hydrating an aminonitrile in the presence of a ketone. For the hydration reaction of aminonitrile in the presence of a ketone, the method described in JP-A-2001-163845 can be used. For example, as a ketone, an aliphatic ketone is present in an amount of 0.01 to 1 mol per 1 mol of aminonitrile, water is used in an amount of 1 mol or more per 1 mol of aminonitrile, and an alcohol having 1 to 4 carbon atoms is used as an alcohol. A linear or branched alcohol is used in an amount of 1 to 5 times the volume of water, and an alkali metal hydroxide is used as a base in an amount of 0.01 to 0.5 mol per 1 mol of aminonitrile. React at 60 ° C for 1-20 hours.
[0008]
Specific examples of the amino acid amide used in the present invention include aminoacetamide, 2-amino-2-methylacetamide, 2-amino-2-ethylacetamide, 2-amino-2-n-propylacetamide, and 2-amino-2. -Isopropylacetamide, 2-amino-2-n-butylacetamide, 2-amino-2-isobutylacetamide, 2-amino-2-sec-butylacetamide, 2-amino-2-t-butylacetamide, 2-amino- Examples include 2,2-dimethylacetamide, 2-amino-2-methyl-2-ethylacetamide, 2-amino-2-methyl-2-isobutylacetamide.
[0009]
The concentration of the aqueous solution of potassium carbonate, sodium tartrate, potassium tartrate and / or sodium potassium tartrate used in the washing step of the present invention is 10 to 50%, preferably 20 to 40%. The amount of the salt aqueous solution to be used varies depending on the type of amino acid amide, the amount of the reaction solution, the type and amount of the additional organic solvent, etc., and cannot be determined unconditionally. It is preferably in the range of 0.5 to 2 times (mass). The washing method may be any of batch washing and continuous washing. In the case of batch washing, the number of washings is particularly preferably in the range of 1 to 3 times. The temperature, pressure and stirring contact time during washing are not particularly limited, and are usually about room temperature, normal pressure and about 1 hour. After the salt aqueous solution is brought into contact with stirring, it is allowed to stand and separated and removed.
[0010]
In the method of the present invention, the washing efficiency can be further improved by adding at least one linear or branched alcohol having 1 to 4 carbon atoms to the reaction solution prior to the washing step. The amount of alcohol used is not particularly limited, but is preferably 1 to 5 times (mass) the amino acid amide reaction solution. Further, if ketone and water remaining in the amino acid amide reaction solution are removed, the loss of the amino acid amide can be suppressed to 0.5% or less. You may leave. These alcohols may be used during the hydration reaction of aminonitrile, but if an excessive amount is added during the reaction, the reaction rate will decrease. Therefore, it is more preferable to add the alcohol after the completion of the reaction.
[0011]
The aqueous solution of the amino acid amide obtained by separating and removing the aqueous phase in the washing step is reduced to a water content of 0.5% or less by an operation such as concentration under reduced pressure. At this time, the precipitated alkali metal and cyanide alkali metal salt are removed by filtration. You.
[0012]
After filtration, the organic solvent contained in the amino acid amide solution is usually replaced with water. The method for replacing the organic solvent with water is not particularly limited, but usually, the organic solvent is removed by distillation, azeotropic distillation, or the like, and replaced with water. The pressure may be reduced as necessary.
[0013]
The aqueous solution of the amino acid amide obtained by the method of the present invention can be used as it is or prepared at an appropriate concentration, and can be used in a biochemical hydrolysis reaction. In addition, an optically active amino acid free of contamination of an alkali metal inorganic salt and a cyan alkali metal salt can be obtained.
[0014]
【Example】
Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to these examples.
[0015]
Example 1
In a 500 ml three-necked flask equipped with a stirrer and a thermometer, 54 g of water and 8 g of sodium hydroxide were added and dissolved, 112 g of 2-amino-2-t-butylacetonitrile, 96 g of methanol and 17.4 g of acetone were added, and 30 ° C. For 10 hours. After completion of the reaction, 7.5 g of sodium hydroxide as a catalyst and 1.5 g of sodium cyanide as contaminant impurities remained in the reaction mixture. Analysis by liquid chromatography revealed that 2-amino-2-t-butylacetamide was obtained. The reaction yield was 97%. 574.8 g of n-butanol was added to the reaction mixture, and the mixture was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the water content became 0.5%. 229.2 g of a 20% aqueous potassium carbonate solution was added to 519.7 g of an n-butanol solution of the obtained amino acid amide, and the mixture was stirred at room temperature for 1 hour, allowed to stand for 30 minutes, then the aqueous phase was removed, and at a temperature of 50 ° C. and a pressure of 8 kPa. The solution was concentrated under reduced pressure to a water content of 0.5% or less, and inorganic salts and the like precipitated by pressure filtration were removed to obtain 405.4 g of a washed amino acid amide n-butanol solution. The obtained solution was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the liquid amount became 243.2 g. 232.8 g of water was added to this solution, and the solution was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until a liquid volume of 243.2 g was obtained. This operation was repeated once again, and the solvent was replaced with water. The amount of sodium hydroxide in the obtained aqueous solution was reduced to 0.6 g (content 0.25%), and the amount of sodium cyanide was reduced to 0.01 g (content 0.004%). The concentration of -2-t-butylacetamide was 51.8%, the yield was 126.0 g, and the yield was 96.8% based on aminonitrile.
[0016]
Example 2
To a reaction mixture obtained by combining 2-amino-2-t-butylacetamide synthesized in the same manner as in Example 1, 547.8 g of n-propanol was added, and 180.0 g of a 30% aqueous solution of sodium potassium tartrate was added. After stirring for 1 hour and allowing to stand for 30 minutes, the aqueous phase was removed, the solution was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa to make the water content 0.5% or less, and inorganic salts and the like precipitated by pressure filtration were removed. 420.3 g of a solution of amino acid amide in n-propanol was obtained. The obtained solution was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the liquid amount became 240.5 g. 320.8 g of water was added to this solution, and the solution was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the liquid volume reached 240.5 g. This operation was repeated once again, and the solvent was replaced with water. The amount of sodium hydroxide in the obtained aqueous solution was reduced to 0.7 g (content 0.30%) and the amount of sodium cyanide was reduced to 0.02 g (content 0.008%). The concentration of -2-t-butylacetamide was 51.8%, and the yield was 124.6 g, which was 95.7% based on aminonitrile.
[0017]
Example 3
In a 500 ml three-necked flask equipped with a stirrer and a thermometer, 54 g of water and 8 g of sodium hydroxide were added and dissolved, 112 g of 2-amino-2-sec-butylacetonitrile, 96 g of methanol and 17.4 g of acetone were added, and 30 ° C. For 10 hours. After completion of the reaction, the reaction mixture was analyzed by liquid chromatography. As a result, it was found that the 2-amino-2-sec-butylacetamide reaction yield was 97%, the catalyst was sodium hydroxide 7.5 g, and sodium cyanide 1.5 g as a contaminant impurity. It remained. 574.8 g of methanol was added to the reaction mixture, 180.0 g of a 30% aqueous solution of sodium potassium tartrate was added, and the mixture was stirred at room temperature for 1 hour, allowed to stand for 30 minutes, then the aqueous phase was removed, and concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa. The water content was adjusted to 0.5% or less, and inorganic salts and the like precipitated by pressure filtration were removed to obtain 410.7 g of a methanol solution of amino acid amide. 300.0 g of water was added to the obtained methanol solution of amino acid amide, and the mixture was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the liquid amount became 243.2 g, and the solvent was replaced with water. The amount of sodium hydroxide in the obtained aqueous solution was reduced to 0.8 g (content 0.32%), and the content of sodium cyanide was reduced to 0.02 g (content 0.008%). The concentration of -2-sec-butylacetamide was 50.9%, the yield was 123.7 g, and the yield was 95.0% based on aminonitrile.
[0018]
Comparative Example 1
232.8 g of water was added to the 2-amino-2-t-butylacetamide reaction mixture synthesized in the same manner as in Example 1, and the mixture was concentrated under reduced pressure at a temperature of 50 ° C. and a pressure of 8 kPa until the liquid volume became 243.2 g. This operation was repeated once again, and the solvent was replaced with water. The aqueous solution thus obtained contained 7.5 g of sodium hydroxide (content: 3.1%) and 1.5 g of sodium cyanide (content: 0.62%). The concentration of 2-t-butylacetamide was 51.9%, and the yield was 126.1 g, which was 97.0% based on aminonitrile.
[0019]
Comparative Example 2
The 2-amino-2-t-butylacetamide reaction mixture synthesized in the same manner as in Example 1 was cooled to 0 ° C., and the precipitated crystals were filtered. After the obtained crystals were dried under reduced pressure, they were dissolved in 108 g of water. The obtained aqueous solution contained 0.6 g of sodium hydroxide (content 0.28%) and 0.01 g of sodium cyanide (content 0.005%), and was analyzed by liquid chromatography. The concentration of 2-t-butylacetamide was 50.0%, the yield was 108 g, and the yield was 82.9% based on aminonitrile.
[0020]
Comparative Example 3
A mixture obtained by concentrating 287.4 g of the 2-amino-2-sec-butylacetamide reaction mixture synthesized in the same manner as in Example 3 to 220 g at 40 ° C. and 8 kpa was cooled to 0 ° C., and the precipitated crystals were filtered. did. The obtained crystals were dried under reduced pressure and dissolved in 114 g of water. The obtained aqueous solution contained 0.7 g of sodium hydroxide (content: 0.31%) and 0.01 g of sodium cyanide (content: 0.004%), and was analyzed by liquid chromatography. The 2-sec-butylacetamide concentration was 50.0%, the yield was 114 g, and the yield was 87.5% based on aminonitrile.
[0021]
【The invention's effect】
By using the production method of the present invention, it is possible to obtain an aqueous solution of an amino acid amide in which the yield of the amino acid amide is not reduced due to the purification of the amino acid amide and the inorganic salt of an alkali metal and the alkali metal salt of cyanide are sufficiently reduced.
Claims (4)
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| JP2002262653A JP2004099506A (en) | 2002-09-09 | 2002-09-09 | Method for producing amino acid amide |
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| JP2002262653A JP2004099506A (en) | 2002-09-09 | 2002-09-09 | Method for producing amino acid amide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011010677A1 (en) * | 2009-07-22 | 2011-01-27 | 株式会社日本ファインケム | Process for producing inorganic acid salt of 2-aminobutylamide |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5225701A (en) * | 1975-08-20 | 1977-02-25 | Stamicarbon | Process for preparing alphaaamino acid amide |
| JPS57158743A (en) * | 1981-03-26 | 1982-09-30 | Mitsubishi Gas Chem Co Inc | Preparation of alpha-amino acid amide |
| JPS6288962A (en) * | 1985-10-16 | 1987-04-23 | Asahi Medical Co Ltd | Quick separation of albumin by chromatography |
| JPS62178556A (en) * | 1986-01-22 | 1987-08-05 | デーエスエム ナムローゼ フェンノートシャップ | Manufacture of alpha-amino-alpha-hydrogen-carboxylic acid amide |
| JPH10502074A (en) * | 1994-06-23 | 1998-02-24 | フアーマシア・アンド・アツプジヨン・アー・ベー | Filtration |
| JP2001163845A (en) * | 1999-12-13 | 2001-06-19 | Mitsubishi Rayon Co Ltd | Method of producing amino acid amide |
| JP2001328971A (en) * | 2000-05-22 | 2001-11-27 | Mitsubishi Rayon Co Ltd | Method for purifying amino acid amide |
| WO2002008439A1 (en) * | 2000-07-21 | 2002-01-31 | Nippon Soda Co., Ltd. | Process for the preparation of 2-amino acids |
-
2002
- 2002-09-09 JP JP2002262653A patent/JP2004099506A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5225701A (en) * | 1975-08-20 | 1977-02-25 | Stamicarbon | Process for preparing alphaaamino acid amide |
| JPS57158743A (en) * | 1981-03-26 | 1982-09-30 | Mitsubishi Gas Chem Co Inc | Preparation of alpha-amino acid amide |
| JPS6288962A (en) * | 1985-10-16 | 1987-04-23 | Asahi Medical Co Ltd | Quick separation of albumin by chromatography |
| JPS62178556A (en) * | 1986-01-22 | 1987-08-05 | デーエスエム ナムローゼ フェンノートシャップ | Manufacture of alpha-amino-alpha-hydrogen-carboxylic acid amide |
| JPH10502074A (en) * | 1994-06-23 | 1998-02-24 | フアーマシア・アンド・アツプジヨン・アー・ベー | Filtration |
| JP2001163845A (en) * | 1999-12-13 | 2001-06-19 | Mitsubishi Rayon Co Ltd | Method of producing amino acid amide |
| JP2001328971A (en) * | 2000-05-22 | 2001-11-27 | Mitsubishi Rayon Co Ltd | Method for purifying amino acid amide |
| WO2002008439A1 (en) * | 2000-07-21 | 2002-01-31 | Nippon Soda Co., Ltd. | Process for the preparation of 2-amino acids |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011010677A1 (en) * | 2009-07-22 | 2011-01-27 | 株式会社日本ファインケム | Process for producing inorganic acid salt of 2-aminobutylamide |
| JP5613162B2 (en) * | 2009-07-22 | 2014-10-22 | 株式会社日本ファインケム | Method for producing 2-aminobutyramide inorganic acid salt |
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