JP4101898B2 - Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide - Google Patents
Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide Download PDFInfo
- Publication number
- JP4101898B2 JP4101898B2 JP02073097A JP2073097A JP4101898B2 JP 4101898 B2 JP4101898 B2 JP 4101898B2 JP 02073097 A JP02073097 A JP 02073097A JP 2073097 A JP2073097 A JP 2073097A JP 4101898 B2 JP4101898 B2 JP 4101898B2
- Authority
- JP
- Japan
- Prior art keywords
- manganese dioxide
- mesh
- particle size
- fractionated
- column
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Description
【０００１】
【発明の属する技術分野】
本願発明は、化成二酸化マンガン（以下、ＣＭＤと略称する）、その製法及び該ＣＭＤを酸化剤として用いる酸化方法に関する。
【０００２】
【従来の技術】
最近、乾電池用の二酸化マンガンが酸化剤としても優れた性能を有することが注目され、その用途としても広く使用されている。それらは、電解二酸化マンガン（Ｅｌｅｃｔｒｏｌｉｃ Ｍａｎｇａｎｅｓｅ Ｄｉｏｘｉｄｅ、以下、ＥＭＤと略称する）と化成二酸化マンガン（ＣＭＤ）とに大別される。
【０００３】
ＥＭＤは天然の炭酸マンガン鉱石又は天然の二酸化マンガン鉱石を８００〜１１００℃で焙焼して得られた酸化マンガン（ＭｎＯ）微粉末を希硫酸に溶解して得た硫酸マンガン溶液を電気分解することにより得られる。現在日本で生産されたＥＭＤのほとんどが乾電池用として用いられ、３３０メッシュに分画した粒度の小さな製品が市販されている。ＥＭＤの結晶は単結晶であり、結晶構造が扁平なγ−タイプであることが特徴である。
【０００４】
ＣＭＤ（Ｃｈｅｍｉｃａｌ Ｍａｎｇａｎｅｓｅ Ｄｉｏｘｉｄｅ）は、化学的に合成された二酸化マンガンである。天然の二酸化マンガンを４００乃至８００℃で低温焙焼して得られた三二酸化マンガン（Ｍｎ2 Ｏ3 ）を４００メッシュに微粉砕後、反応容器内で希硫酸水溶液と混合攪拌すると、三二酸化マンガン中の酸化マンガンは硫酸水溶液に溶解して除かれるので二酸化マンガンが不溶解結晶として得られる。この結晶を分画することなく水洗、乾燥することによって得られる。
【０００５】
この硫酸による酸化マンガン（ＭｎＯ）の溶解＝浸出は不均化反応と呼ばれることから、ＣＭＤの製造法は不均化法という名称もつけられている。
【０００６】
現在日本で生産されたＣＭＤは殆どが４００メッシュに分画され乾電池用として市販されいる。
【０００７】
上述したように、ＥＭＤ及びＣＭＤは乾電池用のみに用途及び製造が限られているため、他の有用な用途又は製造法の開発が要望されている。
【０００８】
本願発明は、新規なＣＭＤ、その製法及び該ＣＭＤを酸化剤として用いる酸化方法の開発に関する。
【０００９】
本発明のＣＭＤは種々の工業的な酸化反応に使用され得るが、例えば、ミルベマイシン類の５位の水酸基の酸化反応が挙げられる。
【００１０】
乾電池用のＥＭＤがミルベマイシンの５位の水酸基を酸化して中間体として重要な５−オキソミルベマイシンを得る方法において、酸化剤として優れた活性を有することが特開平１−１９７４８７号公報に開示されている。
【００１１】
また、ＣＭＤが、いくつかの天然物の合成の際のアリルアルコール等の酸化反応に乾電池用ＣＭＤを使用している［テトラヘドロンレターズ 第３３巻、４１８７−４１９０頁（１９９２年）。テトラへドロン 第４８巻、Ｎｏ．３５７２５１−７２６４頁（１９９２年）］。
【００１２】
これらの乾電池用の二酸化マンガンによる酸化は、少量の粒度の小さな二酸化マンガンと基質を溶解した溶媒をコルベン等の反応容器中で撹拌することよって行われている。しかし、この方法では、少し反応容器の規模が大きくしたり、工業的な反応釜を使用したりすると、攪拌に伴う攪拌羽根の破損、反応物の取出しや濾過の際の処理の困難等の問題が生じ、別の反応方法の開発が望まれていた。そこで、乾電池用の二酸化マンガンをカラムに詰め、基質を溶解した溶媒を循環する方法が上記問題を解決する方法として考えられたが、カラムに詰める二酸化マンガンの乾電池用のように粒度が小さいと溶媒が良好に循環しないという問題があり、これらの問題を解決する方法が望まれていた。
【００１３】
【発明が解決しようとする課題】
上述の状況から、本願発明が解決しようとする課題は、カラムに詰めるための適当な粒度を持ち、強力な酸化作用を有する二酸化マンガン及びその製造法を見いだすことである。
【００１４】
【課題を解決する手段】
課題を解決するために種々に二酸化マンガンについて研究した結果、本願発明者等は新規に７０乃至３６メッシュ又は３６乃至１６メッシに分画した粒度の大きなＣＭＤがカラムに詰める二酸化マンガンとして適当であり、かつ強力な酸化作用を有することを見いだし、また、それらの製造法を確立し本発明を完成した。
【００１５】
即ち、本願発明は、新規な粒度を有し、かつ強力な酸化作用を有する新規なＣＭＤに及び乾電池用ＣＭＤ製造法を改良した該ＣＭＤの製造法に関する。
【００１６】
以下に詳細に説明する。
【００１７】
ここで、上記の４００メッシュに分画された乾電池用のＣＭＤはＣＭＤ1 と称する。
【００１８】
本願発明の７０乃至３６メッシュ又は３６乃至１６メッシュに分画された大粒の二酸化マンガンのうち、３６乃至１６メッシュのＣＭＤは天然の二酸化マンガンを上記と同温度で低温焙焼して得られた三二酸化マンガン（Ｍｎ2 Ｏ3 ）を３２乃至１０メッシュに分画してカラムに充填し、希硫酸水溶液をカラムの上部又は下部から循環すると、酸化マンガンが溶解して除かれ、二酸化マンガンのみが残存する。水洗、乾燥後３６乃至１６メッシュに分画することによって得られる。７０乃至３６メッシュに分画されたＣＭＤは６２乃至３２メッシュに分画された三二酸化マンガンを上記と同条件で処理して得られる。このようにして得られたＣＭＤをＣＭＤ2 と称する。
【００１９】
ＣＭＤ1 とＣＭＤ2 の差異は、ＣＭＤ2 にあっては最終粒度が７０乃至３６メッシュ又は３６乃至１６メッシュになるよう、焙焼工程直後に分画操作を挿入し、しかも不均化反応以降の最終段階で再び分画操作を挿入していることである。また、反応容器がＣＭＤ1 の場合は回分式機械攪拌式であり、ＣＭＤ2 はカラム方式であることである。
【００２０】
カラムに適当な粒度の二酸化マンガンを充填し、基質を溶解した溶媒を循環することによる酸化反応において、基質として一般式（Ｉ）で表されるマクロライド抗生物質ミルベマイシン類を出発物質とする５−オキソミルベマイシン誘導体を製造する酸化反応を例として用い、二酸化マンガンの好適な粒度の選択及び酸化作用の評価を行った。
【００２１】
【化１】
上記式において、ＲがメチルのときミルベマイシンＡ3 、Ｒがエチル基のときミルベマイシンＡ4 、イソプロピルのときミルベマイシンＤと称される重要なミルベマイシン類である。
【００２３】
【発明の実施の形態】
本願発明の実施方法は、７０乃至３６メッシュ、３６乃至１６メッシュに分画したＣＭＤを詰めたカラムに基質を溶解した溶媒を循環させることにより実施される。
基質として使用されるミルベマイシン類は、精製したミルベマイシン類の単一物又は混合物が用いられる。例えば、特開平１−１９７４８７号公報に開示された方法で精製して得られたミルベマイシンＡ3 ＋Ａ4 混合物又は醗酵ブロスから抽出した粗ミルベマイシンＡ3 ＋Ａ4 混合物を再結晶やシリカゲルカラムクロマトグラフィーで精製したミルベマイシンＡ3 ＋Ａ4 混合物が用いられる。
【００２４】
反応温度は、一般に−１０乃至５０℃の範囲で行われるが、好適には、０乃至１０℃であり、特に好適には０乃至５℃である。
【００２５】
溶媒は、アセトン、メチルエチルケトンのようなケトン類；ジエチルエーテル、ジオキサン、テトラヒドロフランのようなエーテル類；塩化メチレンのようなハロゲン化炭化水素；酢酸エチルのようなエステル類が用いられ、好適には、ハロゲン化炭化水素であり、更に好適には、塩化メチレンである。
【００２６】
二酸化マンガンの使用量は、基質の２乃至２０倍重量であり得、好適には、５乃至１０倍重量である。
【００２７】
二酸化マンガンの粒度は、７０乃至３６メッシュ、３６乃至１６メッシュであり、好適には、３６乃至１６メッシュである。
【００２８】
【実施例】
【００２９】
【実施例１】
３６乃至１６メッシュに分画したＣＭＤ 2 の製造
内径（φ）３０ｃｍ×高さ１６０ｃｍのカラム反応槽に３２乃至１０メッシュに分画した三二酸化マンガン（Ｍｎ2 Ｏ3 ）６５ｋｇ及び水１１０ｋｇを入れ、別途、水９０ｋｇを入れた貯水槽より水をカラム反応槽の下部より供給しながら循環させる。カラム反応槽を８０乃至９０℃に加温し３０分循環後、８０乃至９０℃加温下に硫酸を加え２規定硫酸水溶液に調整し、３時間循環後、更に硫酸を加え４規定硫酸水溶液に調整後３時間循環し、反応を終了する。生成した硫酸マンガン水溶液を除去後、水洗し、水洗液を除去する。次いでアンモニア水を循環させ、ｐＨ＝５〜６に中和後、アンモニア水を除去する。残留二酸化マンガン（ＣＭＤ2 ）をカラム反応槽より取り出し乾燥すると３１ｋｇの３６−１６メッシュに分画したＣＭＤ2 が得られる。
【００３０】
【実施例２】
７０乃至３６メッシュに分画したＣＭＤ 2 の製造
実施例１と同一反応条件下で反応を行い、６２乃至３２ッシュに分画した三二酸化マンガン（Ｍｎ2 Ｏ3 ）６５ｋｇから３１ｋｇの７０乃至３６メッシュに分画したＣＭＤ2 が得られる。
【００３１】
【実施例３】
カラムに詰める二酸化マンガン粒度の決定
カラムに詰める二酸化マンガン粒度の決定は、一定粒度の二酸化マンガンを積めたカラムに基質を溶解すべき溶媒を通過させて得られる、以下の１）及び２）を求め、それらの数値より決定した。
【００３２】
１）Ｕ；カラム内の溶媒の平均流速。１秒間当たりのカラム内の流量をカラムの断面積で除した値。
２）１時間当たりカラムを通過する溶媒の容積が二酸化マンガンの容積量の１０倍であることを目安としている。そのとき必要な二酸化マンガンの圧力損失（そのときのカラムにかかる圧力）。△ｐ（ＳＶ＝１０）
数値が小さい程好適である。
【００３３】
その結果を表１に示す。
【００３４】
粒度の小さな４００又は３３０メッシュのＣＭＤ又はＥＭＤでは△ｐ（ＳＶ＝１０）が大きな圧力（６．３及び７．９）かかっていることが判る。従って、反応に用いるには不適であると判断した。また、７０乃至３６又は３６乃至２０メッシュのＣＭＤでは△ｐ（ＳＶ＝１０）が小さな圧力（約０．６又は０．１）しかかかっていないことが判る。
【００３５】
【表１】
【実施例４】
［最適な５−オキソミルベマイシンの製造に置ける二酸化マンガンの粒度の選択］
内径２ｃｍφ、長さ２５ｃｍのカラムに５０ｇの二酸化マンガンを詰め、ミルベマイシンＡ3 及びミルベマイシンＡ4 混合物（含量比＝２：８）１０ｇを塩化メチレン１００ｍｌに溶解し分液ロートに入れる。該分液ロートをカラムに接続し、溶液を一定速度でカラムを通過させ、酸化反応を行った。収率は、反応液の経時的なサンプリングを行い高速液体クロマトグラフィーにより求めた。標品は特開昭６３−２２５４１号公報に開示されたものを使用した。収率がそれ以上に上昇しない時点を反応の終点とし、終点における収率及び途中の反応収率も求め表２に表した。 反応開始より反応の終点までの時間が短いほど酸化力（酸化活性）が強く、時間が長いほど弱いことを示す。反応開始より反応の終点までの時間の長短により酸化力を評価した。この結果より、
【００３７】
【表２】
結果：４００メッシュに分画されたＣＭＤ及びＥＭＤは溶媒が通過しにくいため、反応が進まず有意な収率が得られなかった。また、７０乃至３６マッシュ、又は３６乃至１６メッシュに分画されたＣＭＤはＥＭＤに比較して優れた酸化作用を有することが判明した。
【００３９】
【実施例５】
５−オキソミルベマイシンの製造
３６乃至２０メッシュに調製したＣＭＤ2 、３０ｋｇを内径２２ｃｍ高さ１５０ｃｍのカラム反応槽に詰め、ミルベマイシンＡ3 及びミルベマイシンＡ4 混合物（含量比＝２：８）６ｋｇを塩化メチレン６５ｋｇに溶解した溶液を、０〜１０℃に冷却下に、上部より注入し循環させた。経時的収率を液体クロマトグラフィーにより求め、９９．７％を示した時点（４．５時間後）で反応を止めると、５−オキソミルベマイシン誘導体５．６５ｋｇ（収率９４％）が得られた。
【００４０】
【発明の効果】
カラムに酸化剤として二酸化マンガンを充填し、基質を溶解した溶媒を循環することによる酸化反応において、本願発明の新規な方法で製造した７０乃至３６メッシュ又は３６乃至１６メッシュに分画したＣＭＤは優れた酸化作用を示し、カラム充填用として適当であり、工業的規模で使用可能であることを確認した。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to chemical manganese dioxide (hereinafter abbreviated as CMD), a production method thereof, and an oxidation method using the CMD as an oxidizing agent.
[0002]
[Prior art]
Recently, it has been noted that manganese dioxide for dry batteries has excellent performance as an oxidizing agent, and is widely used as its application. They electrolytic manganese dioxide (E lectrolic M anganese D ioxide, hereinafter, EMD as abbreviated) is roughly classified into a chemical manganese dioxide (CMD).
[0003]
EMD electrolyzes a manganese sulfate solution obtained by dissolving manganese oxide (MnO) fine powder obtained by roasting natural manganese carbonate ore or natural manganese dioxide ore at 800-1100 ° C. in dilute sulfuric acid. Is obtained. Currently, most of the EMDs produced in Japan are used for dry batteries, and products with a small particle size fractionated to 330 mesh are commercially available. The EMD crystal is a single crystal, and is characterized by a flat γ-type crystal structure.
[0004]
CMD (C hemical M anganese D ioxide ) is chemically synthesized manganese dioxide. Manganese sesquioxide (Mn 2 O 3 ) obtained by low-temperature roasting of natural manganese dioxide at 400 to 800 ° C. is finely pulverized to 400 mesh and mixed with a dilute sulfuric acid aqueous solution in a reaction vessel. The manganese oxide therein is dissolved and removed in an aqueous sulfuric acid solution, so that manganese dioxide is obtained as an insoluble crystal. This crystal can be obtained by washing with water and drying without fractionation.
[0005]
Since dissolution of the manganese oxide (MnO) with sulfuric acid = leaching is called a disproportionation reaction, the manufacturing method of CMD is also named as a disproportionation method.
[0006]
Currently, most CMDs produced in Japan are fractionated to 400 mesh and are commercially available for dry batteries.
[0007]
As described above, since EMD and CMD are limited in use and production only for dry batteries, development of other useful uses or production methods is desired.
[0008]
The present invention relates to the development of a novel CMD, its production method and an oxidation method using the CMD as an oxidizing agent.
[0009]
The CMD of the present invention can be used for various industrial oxidation reactions, and examples thereof include an oxidation reaction of the hydroxyl group at the 5-position of milbemycins.
[0010]
JP-A-1-197487 discloses that an EMD for a dry battery has an excellent activity as an oxidizing agent in a method for obtaining 5-oxomilbemycin which is important as an intermediate by oxidizing the hydroxyl group at the 5-position of milbemycin. Yes.
[0011]
In addition, CMD uses dry cell CMD for oxidation reaction of allyl alcohol or the like in the synthesis of some natural products [Tetrahedron Letters 33, 4187-4190 (1992). Tetrahedron Vol. 48, No. 357251-7264 (1992)].
[0012]
Oxidation with manganese dioxide for these dry batteries is carried out by stirring a small amount of small manganese dioxide and a solvent in which a substrate is dissolved in a reaction vessel such as Kolben. However, with this method, if the reaction vessel is slightly larger in scale or an industrial reaction kettle is used, problems such as breakage of the stirring blades during stirring, difficulty in processing during removal of the reactants and filtration, etc. Therefore, development of another reaction method has been desired. Therefore, a method of packing manganese dioxide for dry batteries in a column and circulating a solvent in which the substrate was dissolved was considered as a method for solving the above problem. However, if the particle size is small as in the case of dry batteries of manganese dioxide packed in a column, the solvent However, there has been a problem of not circulating well, and a method for solving these problems has been desired.
[0013]
[Problems to be solved by the invention]
From the above situation, the problem to be solved by the present invention is to find manganese dioxide having an appropriate particle size for packing in a column and having a strong oxidizing action, and a method for producing the same.
[0014]
[Means for solving the problems]
As a result of various studies on manganese dioxide in order to solve the problem, the inventors of the present application are suitable as manganese dioxide newly packed in a column with CMD having a large particle size fractionated to 70 to 36 mesh or 36 to 16 mesh, In addition, they have been found to have a strong oxidizing action, and their production method has been established to complete the present invention.
[0015]
That is, the present invention relates to a novel CMD having a novel particle size and a strong oxidizing action, and a method for producing the CMD obtained by improving the CMD production method for dry batteries.
[0016]
This will be described in detail below.
[0017]
Here, the CMD for dry batteries fractionated into 400 mesh is referred to as CMD 1 .
[0018]
Of the large-sized manganese dioxide fractionated into 70 to 36 mesh or 36 to 16 mesh of the present invention, 36 to 16 mesh CMD is obtained by low temperature roasting of natural manganese dioxide at the same temperature as above. Manganese dioxide (Mn 2 O 3 ) is fractionated to 32 to 10 mesh and packed into a column. When dilute sulfuric acid aqueous solution is circulated from the top or bottom of the column, manganese oxide is dissolved and removed, leaving only manganese dioxide. To do. After washing and drying, it is obtained by fractionation to 36 to 16 mesh. CMD fractionated to 70 to 36 mesh is obtained by treating manganese trioxide fractionated to 62 to 32 mesh under the same conditions as described above. The CMD obtained in this manner is referred to as CMD 2.
[0019]
The difference between CMD 1 and CMD 2 is that in CMD 2 a fractionation operation is inserted immediately after the roasting process so that the final particle size is 70 to 36 mesh or 36 to 16 mesh, and after the disproportionation reaction That is, the fractionation operation is inserted again at the final stage. When the reaction vessel is CMD 1 , it is a batch type mechanical stirring type, and CMD 2 is a column type.
[0020]
In the oxidation reaction by filling the column with manganese dioxide of an appropriate particle size and circulating a solvent in which the substrate is dissolved, the starting material is a macrolide antibiotic milbemycin represented by the general formula (I) as a substrate. Using an oxidation reaction for producing an oxomilbemycin derivative as an example, selection of a suitable particle size of manganese dioxide and evaluation of oxidation action were performed.
[0021]
[Chemical 1]
In the above formula, these are important milbemycins called milbemycin A 3 when R is methyl, milbemycin A 4 when R is ethyl, and milbemycin D when R is isopropyl.
[0023]
DETAILED DESCRIPTION OF THE INVENTION
The method of the present invention is carried out by circulating a solvent in which a substrate is dissolved in a column packed with CMD fractionated into 70 to 36 mesh and 36 to 16 mesh.
As the milbemycins used as the substrate, a single or a mixture of purified milbemycins is used. For example, a milbemycin A 3 + A 4 mixture obtained by purification by the method disclosed in JP-A-1-197487 or a crude milbemycin A 3 + A 4 mixture extracted from a fermentation broth is purified by recrystallization or silica gel column chromatography. A milbemycin A 3 + A 4 mixture is used.
[0024]
The reaction temperature is generally in the range of −10 to 50 ° C., preferably 0 to 10 ° C., particularly preferably 0 to 5 ° C.
[0025]
Solvents include ketones such as acetone and methyl ethyl ketone; ethers such as diethyl ether, dioxane and tetrahydrofuran; halogenated hydrocarbons such as methylene chloride; esters such as ethyl acetate; Hydrocarbon, more preferably methylene chloride.
[0026]
The amount of manganese dioxide used can be 2 to 20 times the weight of the substrate, preferably 5 to 10 times the weight.
[0027]
The particle size of manganese dioxide is 70 to 36 mesh, 36 to 16 mesh, and preferably 36 to 16 mesh.
[0028]
【Example】
[0029]
[Example 1]
CMD 2 fractionated to 36-16 mesh Production of 65 kg of manganese trioxide (Mn 2 O 3 ) and 110 kg of water fractionated into 32 to 10 mesh in a column reaction vessel having an inner diameter (φ) of 30 cm × height of 160 cm, and separately added 90 kg of water. The water is circulated while supplying water from the lower part of the column reaction tank. Heat the column reaction vessel to 80 to 90 ° C and circulate for 30 minutes, then add sulfuric acid under heating at 80 to 90 ° C to adjust to 2N sulfuric acid aqueous solution. After adjustment, the mixture is circulated for 3 hours to complete the reaction. After removing the produced manganese sulfate aqueous solution, it is washed with water to remove the water washing solution. Next, aqueous ammonia is circulated, and after neutralizing to pH = 5-6, the aqueous ammonia is removed. Residual manganese dioxide (CMD 2 ) is removed from the column reactor and dried to obtain 31 kg of CMD 2 fractionated into 36-16 mesh.
[0030]
[Example 2]
CMD 2 fractionated to 70-36 mesh Production of CMD 2 which was reacted under the same reaction conditions as in Example 1 and fractionated from 65 kg of manganese sesquioxide (Mn 2 O 3 ) into 62 to 32 ash to 31 kg of 70 to 36 mesh. Is obtained.
[0031]
[Example 3]
Determination of the manganese dioxide particle size packed in the column The determination of the manganese dioxide particle size packed in the column is obtained by passing a solvent in which the substrate is dissolved through a column loaded with manganese dioxide of a certain particle size, the following 1) and 2) was determined and determined from these values.
[0032]
1) U; Average flow rate of solvent in the column. Value obtained by dividing the flow rate in the column per second by the cross-sectional area of the column.
2) As a guide, the volume of solvent passing through the column per hour is 10 times the volume of manganese dioxide. Pressure loss of manganese dioxide required at that time (pressure applied to the column at that time). Δp (SV = 10)
The smaller the value, the better.
[0033]
The results are shown in Table 1.
[0034]
It can be seen that Δp (SV = 10) is applied with a large pressure (6.3 and 7.9) in CMD or EMD having a small particle size of 400 or 330 mesh. Therefore, it was judged to be unsuitable for use in the reaction. Further, it can be seen that in a CMD of 70 to 36 or 36 to 20 mesh, Δp (SV = 10) is only applied with a small pressure (about 0.6 or 0.1).
[0035]
[Table 1]
[Example 4]
[Selection of Manganese Dioxide Particle Size for Optimal 5-Oxomilbemycin Production]
A column having an inner diameter of 2 cmφ and a length of 25 cm is packed with 50 g of manganese dioxide, and 10 g of a mixture of milbemycin A 3 and milbemycin A 4 (content ratio = 2: 8) is dissolved in 100 ml of methylene chloride and placed in a separatory funnel. The separatory funnel was connected to the column, and the solution was passed through the column at a constant speed to carry out an oxidation reaction. The yield was determined by high performance liquid chromatography after sampling the reaction solution over time. As the sample, one disclosed in JP-A-63-22541 was used. The time point at which the yield did not increase any more was taken as the end point of the reaction, and the yield at the end point and the reaction yield in the middle were also calculated and shown in Table 2. The shorter the time from the start of the reaction to the end of the reaction, the stronger the oxidizing power (oxidation activity), and the longer the time, the weaker. The oxidizing power was evaluated by the length of time from the start of the reaction to the end point of the reaction. From this result,
[0037]
[Table 2]
Result: Since CMD and EMD fractionated into 400 meshes hardly pass through the solvent, the reaction did not proceed and a significant yield was not obtained. Further, it was found that CMD fractionated into 70 to 36 mash or 36 to 16 mesh has an excellent oxidizing action as compared with EMD.
[0039]
[Example 5]
Production of 5-oxomilbemycin 30 kg of CMD 2 prepared to 36 to 20 mesh was packed in a column reaction tank having an inner diameter of 22 cm and a height of 150 cm, and 6 kg of a mixture of milbemycin A 3 and milbemycin A 4 (content ratio = 2: 8) was added to methylene chloride. The solution dissolved in 65 kg was injected and circulated from the top while cooling to 0 to 10 ° C. The yield over time was determined by liquid chromatography, and when the reaction was stopped at 99.7% (after 4.5 hours), 5.65 kg of 5-oxomilbemycin derivative (yield 94%) was obtained. .
[0040]
【The invention's effect】
The CMD fractionated into 70 to 36 mesh or 36 to 16 mesh produced by the novel method of the present invention is excellent in the oxidation reaction by filling the column with manganese dioxide as the oxidizing agent and circulating the solvent in which the substrate is dissolved. It was confirmed that it is suitable for column packing and can be used on an industrial scale.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02073097A JP4101898B2 (en) | 1996-02-02 | 1997-02-03 | Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1731396 | 1996-02-02 | ||
| JP8-17313 | 1996-06-13 | ||
| JP02073097A JP4101898B2 (en) | 1996-02-02 | 1997-02-03 | Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09268015A JPH09268015A (en) | 1997-10-14 |
| JP4101898B2 true JP4101898B2 (en) | 2008-06-18 |
Family
ID=26353812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP02073097A Expired - Fee Related JP4101898B2 (en) | 1996-02-02 | 1997-02-03 | Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4101898B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586481B (en) * | 2018-05-14 | 2020-03-24 | 浙江海正药业股份有限公司 | Extraction and crystallization process of 5-keto-milbemycin fermentation liquor |
-
1997
- 1997-02-03 JP JP02073097A patent/JP4101898B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH09268015A (en) | 1997-10-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112390841B (en) | Purification method of progesterone | |
| CN106632288A (en) | Method for preparing empagliflozin | |
| CN113214128A (en) | Preparation method of small-particle-size benzoyl peroxide | |
| CN109232470A (en) | A kind of new process synthesizing ainothiazoly loximate | |
| JP4101898B2 (en) | Method for producing novel chemical conversion manganese dioxide useful as oxidizing agent and method for oxidizing substrate using chemical conversion manganese dioxide | |
| CN110452284B (en) | Preparation method of 28-high brassinolide | |
| US3965178A (en) | Method for preparing tetrabutylammonium bromide | |
| CN106928260A (en) | A kind of double-core caged rare earth samarium (III) organic coordination compound and its preparation method and application | |
| CN105753733A (en) | AHU377 crystal form and preparation method and uses thereof | |
| CN103819489B (en) | A kind of preparation method of benzhydryl s-oxopenicillanate | |
| CN108822047B (en) | Synthesis method of natural 2-acetylpyrazine | |
| CN107573301B (en) | Preparation method of tricyclazole intermediate | |
| CN109970834A (en) | A kind of preparation method of hydrocortisone sodium succinate | |
| CN111690824A (en) | Titanium-tungsten-containing raw material acidolysis titanium extraction and method for acidolysis titanium extraction of titanium-containing raw material | |
| CN218530890U (en) | Preparation system containing compound with double disulfide structure | |
| US3959453A (en) | Method for manufacture of single crystals β-PbO2 and slender single crystals of β-PbO2 produced thereby | |
| KR19980042700A (en) | Method for preparing ruthenium (III) acetate solution | |
| CN111848554B (en) | Synthetic method of sofosbuvir intermediate impurity | |
| CN108863839B (en) | Alkali metal salt of tetranitraminoethane, preparation method thereof and high-energy material | |
| CN113351255B (en) | Co complex catalyst for preparing isobutyric acid by oxidizing isobutyraldehyde and application thereof | |
| CN112940062B (en) | Preparation method of 16-dehydroprogesterone | |
| CN110283109B (en) | Method for industrially preparing racecadotril | |
| CN107245043A (en) | A kind of preparation method that 3 methyl mercapto propyl alcohol are prepared from 3 methylthiopropionaldehydes | |
| CN109796520A (en) | A kind of extracting method of Nosiheptide fine work | |
| JPH09301966A (en) | Production of glycidyl methacrylate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040123 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20040817 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20040818 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20040830 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20040818 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20050811 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20050811 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20061130 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070410 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070607 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20070607 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20070806 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070905 Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071003 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20071031 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20071031 |
|
| A911 | Transfer of reconsideration by examiner before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20080111 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20080201 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080204 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20080318 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080321 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110328 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110328 Year of fee payment: 3 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110328 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110328 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120328 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130328 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130328 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140328 Year of fee payment: 6 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |