JP3586309B2 - A method for producing an alkyl isothiocyanate. - Google Patents
A method for producing an alkyl isothiocyanate. Download PDFInfo
- Publication number
- JP3586309B2 JP3586309B2 JP07997295A JP7997295A JP3586309B2 JP 3586309 B2 JP3586309 B2 JP 3586309B2 JP 07997295 A JP07997295 A JP 07997295A JP 7997295 A JP7997295 A JP 7997295A JP 3586309 B2 JP3586309 B2 JP 3586309B2
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- Prior art keywords
- alkyl
- producing
- isothiocyanate
- riboflavin
- reaction
- Prior art date
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【０００１】
【産業上の利用分野】
アルキルイソチオシアネ−トはチオウレア合成の中間体、農薬或は抗生物質の修飾剤として有用な５位にメルカプト基を有するテトラゾ−ルの合成原料など有機合成上有用である。
【０００２】
【従来の技術】
アルキルイソチオシアネ−トはＵ．Ｓ．Ｐ：３，９２３，８５２ 、Ｕ．Ｓ．Ｐ：４，７１３，４６７ に記載されているごとく、一般にアルキルジチオカルバメ−トを触媒の存在下に酸素酸化して得る方法の外、クロル炭酸メチル、クロル炭酸エチルと反応させて得られた中間体を熱分解する方法〔Ｏｒｇ．Ｓｙｎｔｈｅｓｉｓ Ｃｏｌ．Ｖｏｌ．ＩＩＩ，５９９（１９５５）、 ＢＰ．８９２，７９０（１９５９）、ＧＰ．１，１７８，４２３（１９６４）、該化合物のチオウレアを中間体として合成し、これに２分の１当量の硫酸を加え、熱分解する方法（Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．７９，３６８３−６（１９５７） 〕、過酸化水素で分解する方法〔Ｇｅｒ．Ｏｆｆｅｎ．２，１０５，４７３（１９７２） 〕、その外チオフォスゲンを使用する方法がある。〔Ｆｒ．１，５２８，２４９（１９６８）〕などがあるが、製造コストの問題、使用原料が猛毒であったり、排ガス処理に問題があるなど必ずしも満足のいくものでない上、生体化合物のような反応環境に敏感な化合物にとっては何れの反応も過激であり、耐えられないことが多い。
【０００３】
【発明が解決しようとする課題】
本発明は反応環境に敏感な生体化合物を使用するアルキルイソチオシアネ−トの合成に当たって、温和な反応条件での反応を実現することにあり、かつイソチオシアネ−ト生成系で重要なことはジチオカルバミン酸からの硫化水素の脱離である。即ち硫化水素の脱離を促す化合物を添加するか、硫化水素の酸化による場合が多い。本発明は生化学反応に近い反応雰囲気で酸素含有ガスによる酸化、特に空気酸化により、イソチオシアネ−トを得ることを目的とするものである。
【０００４】
【課題を解決するための手段】
本発明は以下の通りである。
（１）リボフラビン及び／又はリボフラビン誘導体の存在下、アルキルジチオカルバミン酸を酸素含有ガスで処理することを特徴とする、アルキルイソチオシアネ−トの製造法。
（２）前記酸素含有ガスが空気である、（１）記載のアルキルイソチオシアネ−トの製造法。
（３）前記アルキルジチオカルバミン酸のアルキル基の炭素数が１〜１０である、（１）又は（２）記載のアルキルイソチオシアネ−トの製造法。
（４）前記アルキルジチオカルバミン酸のアルキル基がフェニル基で置換され、また炭素鎖の２位以降に二重結合が含まれていてもよい、（１）又は（２）記載のアルキルイソチオシアネ−トの製造法。
【０００５】
本発明は生体内で酸化還元反応に関与しているリボフラビン（ビタミンＢ２）及び／又はそれらの誘導体を有機酸化触媒として使用し、生体内での酸化に近い条件での酸化反応を実現したのである。
【０００６】
本発明におけるリボフラビン及び／又はそれらの誘導体の添加量は０．０１モル％〜５０モル％の範囲が良く、好ましくは０．１ モル％〜１０モル％であり、更に好ましくは０．１ モル％〜５モル％の範囲である。
【０００７】
本発明に使用される反応溶媒としては、例えば二硫化炭素の外、塩化メチレン、クロロホルム、四塩化炭素、１，２−ジクロロエタン等ハロゲン系炭化水素、ベンゼンやトルエン等の芳香族系炭化水素及びエチルエ−テルや１，２−ジメトキシエタン等のエ−テル系溶媒が挙げられる。
【０００８】
本発明における反応温度は通常０〜５０℃、好ましくは２０〜３０℃である。
【０００９】
反応は回転数がモニタ−できる撹拌機、温度計、滴下ロ−トと冷却トラップがセットされた４つ口フラスコにメチルアミン水溶液、塩化メチレン及び生成物の同定及び定量を容易にするための内部標準薬として既知量のペンタデカンを仕込み、氷冷、撹拌下室温で二硫化炭素を滴下、ジチオカルバミン酸を形成させた後、リボフラビン及び／又はリボフラビン誘導体などの適量を添加し、一定量の空気を吹き込みながら室温で７時間撹拌を続けた。生成物はガスクロマトグラフィ−で分析し、イソチオシアネ−ト生成を確認した。
【００１０】
次に実施例によって本発明を説明する。
【実施例１】
（メチルイソチオシアネ−トの調製）
回転数がモニタ−できる撹拌装置を準備し、５００ｍｌの４つ口フラスコにテフロン羽根を付けた撹拌棒、温度計、滴下ロ−トと冷却トラップをセットした。４０％のメチルアミン水溶液６５ｍｌ（０．７５ｍｏｌ） と塩化メチレン３００ｍｌ及び生成物の同定及び定量を容易にするための内部標準試薬として既知量のペンタデカンをフラスコに仕込み３００ｒｐｍ で撹拌した。氷浴中２０〜２５℃で二硫化炭素４１ｍｌ（０．６９ｍｏｌ） を約３０分で滴下し、系内の温度を２０〜２５℃に保ちながら、１時間熟成した後、リボフラビン１．２ ｇ（０．００３ｍｏｌ）を添加し、続いてフラスコにガス導入管をセットし、空気１００ｍｌ／ｍｉｎ の流量で吹き込みながらその温度で７時間撹拌を続けた。反応はガスクロマトグラフィ−でチェックし、内部標準から収率を求めた。収率１３％と収率は低いもののメチルイソチオシアネ−ト生成が確認された。
【００１１】
【実施例２】
実施例１に従ってリボフラビンの代わりにリボフラビンリン酸エステル１．５ ｇ（０．００３２ｍｏｌ） を添加し、同様の反応を行った。実施例１と同様メチルイソチオシアネ−トの生成が確認された。
【００１２】
【実施例３】
実施例１に従ってリボフラビンの代わりにリボフラビンリン酸エステル０．７５ｇ（０．００１６ｍｏｌ） とリボフラビン酪酸エステル１．０５ｇ（０．００１６ｍｏｌ） を添加し、同様の反応を行った。実施例１と同様メチルイソチオシアネ−トの生成が確認された。
【００１３】
【実施例４】
実施例１の方法にに従って次の生成物の生成が確認された。
【発明の効果】
従来の生体化合物ようの合成方法は毒性の強いチオフォスゲンや酸素などの使用が必須であり、必要とするものが容易に得られなかった。リボフラビン及び／又はそれらの誘導体を触媒としてに使用することで、アルキルジチオカルバミン酸よりアルキルイソチオシアネ−トの製造において温和な条件での酸化・硫黄脱離反応が可能になった。[0001]
[Industrial applications]
Alkyl isothiocyanate is useful in organic synthesis, such as an intermediate in the synthesis of thiourea, a raw material for the synthesis of a tetrazole having a mercapto group at the 5-position, which is useful as a modifier for pesticides or antibiotics.
[0002]
[Prior art]
Alkyl isothiocyanates are described in US Pat. S. P: 3,923,852; S. P: As described in 4,713,467, in addition to the method of generally obtaining an alkyldithiocarbamate by oxygen oxidation in the presence of a catalyst, it is obtained by reacting with methyl chlorocarbonate and ethyl chlorocarbonate. A method for thermally decomposing an intermediate [Org. Synthesis Col. Vol. III, 599 (1955), BP. 892,790 (1959), GP. 1, 178, 423 (1964), a method in which thiourea of the compound is synthesized as an intermediate, a half equivalent of sulfuric acid is added thereto, and thermal decomposition is performed (J. Am. Chem. Soc. 79, 3683-6). (1957)], a method of decomposing with hydrogen peroxide [Ger. Offen. 2, 105, 473 (1972)], a method of using thiophosgene, and [Fr. 1, 528, 249 (1968)]. However, it is not always satisfactory because of the production cost problem, the raw material used is very poisonous, and there is a problem with exhaust gas treatment. In addition, any reaction is extreme for compounds that are sensitive to the reaction environment such as biological compounds. And is often unbearable.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to realize a reaction under mild reaction conditions in the synthesis of an alkyl isothiocyanate using a biological compound which is sensitive to a reaction environment, and an important thing in an isothiocyanate producing system is dithiocarbamic acid. Desorption of hydrogen sulfide from methane. That is, in many cases, a compound that promotes desorption of hydrogen sulfide is added or oxidation of hydrogen sulfide is performed. An object of the present invention is to obtain isothiocyanate by oxidation with an oxygen-containing gas, particularly air oxidation, in a reaction atmosphere close to a biochemical reaction.
[0004]
[Means for Solving the Problems]
The present invention is as follows.
(1) A method for producing alkyl isothiocyanate, comprising treating an alkyl dithiocarbamic acid with an oxygen-containing gas in the presence of riboflavin and / or a riboflavin derivative.
(2) The method for producing alkyl isothiocyanate according to (1), wherein the oxygen-containing gas is air.
(3) The method for producing alkyl isothiocyanate according to (1) or (2), wherein the alkyl group of the alkyldithiocarbamic acid has 1 to 10 carbon atoms.
(4) The alkylisothiocyanate according to (1) or (2), wherein the alkyl group of the alkyldithiocarbamic acid is substituted with a phenyl group, and a double bond may be contained in the carbon chain from the second position. Manufacturing method.
[0005]
According to the present invention, riboflavin (vitamin B2) and / or a derivative thereof involved in a redox reaction in a living body is used as an organic oxidation catalyst to realize an oxidation reaction under conditions close to oxidation in a living body. .
[0006]
The amount of riboflavin and / or a derivative thereof in the present invention is preferably in the range of 0.01 mol% to 50 mol%, preferably 0.1 mol% to 10 mol%, and more preferably 0.1 mol%. ５5 mol%.
[0007]
Examples of the reaction solvent used in the present invention include, in addition to carbon disulfide, methylene chloride, chloroform, carbon tetrachloride, halogenated hydrocarbons such as 1,2-dichloroethane, aromatic hydrocarbons such as benzene and toluene, and ethyl ether. Ether solvents such as ter and 1,2-dimethoxyethane.
[0008]
The reaction temperature in the present invention is usually 0 to 50 ° C, preferably 20 to 30 ° C.
[0009]
The reaction is carried out in a four-necked flask equipped with a stirrer capable of monitoring the number of revolutions, a thermometer, a dropping funnel and a cooling trap, to facilitate the identification and quantification of methylamine aqueous solution, methylene chloride and products. A known amount of pentadecane is charged as a standard drug, carbon disulfide is added dropwise at room temperature under ice-cooling and stirring, and dithiocarbamic acid is formed. The stirring was continued at room temperature for 7 hours. The product was analyzed by gas chromatography to confirm the formation of isothiocyanate.
[0010]
Next, the present invention will be described with reference to examples.
Embodiment 1
(Preparation of methyl isothiocyanate)
A stirrer capable of monitoring the number of rotations was prepared, and a stirring bar equipped with Teflon blades, a thermometer, a dropping funnel and a cooling trap were set in a 500 ml four-necked flask. A flask was charged with 65 ml (0.75 mol) of a 40% aqueous solution of methylamine, 300 ml of methylene chloride, and a known amount of pentadecane as an internal standard reagent for facilitating identification and quantification of the product, and stirred at 300 rpm. 41 ml (0.69 mol) of carbon disulfide was added dropwise in about 30 minutes at 20 to 25 ° C. in an ice bath, and the system was aged for 1 hour while maintaining the temperature in the system at 20 to 25 ° C., and then 1.2 g of riboflavin ( (0.003 mol), followed by setting a gas inlet tube in the flask and continuing stirring at that temperature for 7 hours while blowing air at a flow rate of 100 ml / min. The reaction was checked by gas chromatography, and the yield was determined from the internal standard. Although the yield was as low as 13%, formation of methyl isothiocyanate was confirmed.
[0011]
Embodiment 2
According to Example 1, 1.5 g (0.0032 mol) of riboflavin phosphate was added instead of riboflavin, and the same reaction was carried out. Formation of methyl isothiocyanate was confirmed as in Example 1.
[0012]
Embodiment 3
According to Example 1, instead of riboflavin, 0.75 g (0.0016 mol) of riboflavin phosphate and 1.05 g (0.0016 mol) of riboflavin butyrate were added, and the same reaction was carried out. Formation of methyl isothiocyanate was confirmed as in Example 1.
[0013]
Embodiment 4
According to the method of Example 1, the formation of the following product was confirmed.
【The invention's effect】
Conventional methods for synthesizing biological compounds require the use of highly toxic thiophosgene, oxygen, and the like, and the required compounds cannot be easily obtained. By using riboflavin and / or a derivative thereof as a catalyst, oxidation / sulfur elimination reaction under mild conditions in the production of alkyl isothiocyanate from alkyl dithiocarbamic acid has become possible.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP07997295A JP3586309B2 (en) | 1995-03-09 | 1995-03-09 | A method for producing an alkyl isothiocyanate. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP07997295A JP3586309B2 (en) | 1995-03-09 | 1995-03-09 | A method for producing an alkyl isothiocyanate. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08245564A JPH08245564A (en) | 1996-09-24 |
| JP3586309B2 true JP3586309B2 (en) | 2004-11-10 |
Family
ID=13705248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP07997295A Expired - Fee Related JP3586309B2 (en) | 1995-03-09 | 1995-03-09 | A method for producing an alkyl isothiocyanate. |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3586309B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100447131C (en) * | 2005-08-09 | 2008-12-31 | 沈阳化工研究院 | Method for preparing 1-tert butyl-3-(2,6-diisopropyl-4-phenyl cxypheny) thiourea |
-
1995
- 1995-03-09 JP JP07997295A patent/JP3586309B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100447131C (en) * | 2005-08-09 | 2008-12-31 | 沈阳化工研究院 | Method for preparing 1-tert butyl-3-(2,6-diisopropyl-4-phenyl cxypheny) thiourea |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH08245564A (en) | 1996-09-24 |
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