JPH0544473B2 - - Google Patents
Info
- Publication number
- JPH0544473B2 JPH0544473B2 JP9336885A JP9336885A JPH0544473B2 JP H0544473 B2 JPH0544473 B2 JP H0544473B2 JP 9336885 A JP9336885 A JP 9336885A JP 9336885 A JP9336885 A JP 9336885A JP H0544473 B2 JPH0544473 B2 JP H0544473B2
- Authority
- JP
- Japan
- Prior art keywords
- parts
- reaction
- phosphoric acid
- butyl ether
- daap
- 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 - Lifetime
Links
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 52
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 36
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 31
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 27
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 238000006640 acetylation reaction Methods 0.000 claims description 9
- IZASLLIUFQPKOG-UHFFFAOYSA-N diazanium;acetyl phosphate Chemical compound [NH4+].[NH4+].CC(=O)OP([O-])([O-])=O IZASLLIUFQPKOG-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000021736 acetylation Effects 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 37
- RRAWMVYBOLJSQT-ABZYKWASSA-N (2r,3s)-5-[6-amino-8-(pyren-2-ylamino)purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound C=1C(C2=C34)=CC=C3C=CC=C4C=CC2=CC=1NC1=NC=2C(N)=NC=NC=2N1C1C[C@H](O)[C@@H](CO)O1 RRAWMVYBOLJSQT-ABZYKWASSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- 235000011007 phosphoric acid Nutrition 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000006386 neutralization reaction Methods 0.000 description 15
- LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- 239000000203 mixture Substances 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- XLTYXMRRKLJRNE-UHFFFAOYSA-N acetyl acetate;ethyl acetate Chemical compound CCOC(C)=O.CC(=O)OC(C)=O XLTYXMRRKLJRNE-UHFFFAOYSA-N 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
- -1 ethyl acetate Chemical compound 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
Description
【発明の詳細な説明】
＜産業上の利用分野＞
本発明は、アセチルリン酸ジアンモニウムの製
造方法、更に詳しくは、生体エネルギー伝導物と
して多くの生化学反応に重要な働きをするアデノ
シントリリン酸の製造原料として有用なアセチル
リン酸ジアンモニウム（以下「DAAP」と略記
する）を、工業的に効率良く製造することのでき
る新規かつ改良された製造方法に関するものであ
る。[Detailed Description of the Invention] <Industrial Application Field> The present invention relates to a method for producing diammonium acetyl phosphate, and more specifically, to adenosine triphosphate, which plays an important role in many biochemical reactions as a bioenergy conductor. The present invention relates to a new and improved production method that can industrially and efficiently produce diammonium acetyl phosphate (hereinafter abbreviated as "DAAP"), which is useful as a raw material for the production of.
＜従来の技術＞
DAAPを工業的に製造する方法としては、
リン酸を酢酸エチル溶媒中で無水酢酸と反応さ
せ、この反応溶液をアンモニアで飽和したメタノ
ール溶液中に加えることによつてDAAPを析
出・分離させる方法（J.Org.Chem44、864）、
リン酸を各種溶媒中でケテンと反応させ、その反
応生成物にメタノールを加え、アンモニアを吹込
むことによつてDAAPを析出させる方法（J.Org.
Chem40、2516、米国特許明細書第4088675号）
が知られている。<Conventional technology> As a method for industrially manufacturing DAAP,
A method of precipitating and separating DAAP by reacting phosphoric acid with acetic anhydride in an ethyl acetate solvent and adding the reaction solution to a methanol solution saturated with ammonia (J.Org.Chem 44 , 864);
A method of precipitating DAAP by reacting phosphoric acid with ketene in various solvents, adding methanol to the reaction product, and blowing in ammonia (J.Org.
Chem 40 , 2516, U.S. Pat. No. 4,088,675)
It has been known.
＜発明が解決しようとする問題点＞
しかし、これらの方法では、リン酸をアセチル
化する際に使用する溶媒と反応物の析出分離に使
用するアルコールとが混合するため、これらを分
離回収して反復使用するには、蒸留塔等の特別の
回収装置を必要とする；しかも、この種の溶媒回
収装置は大量の製品を扱う際には適しているが、
本発明の如く特別の用途に使用する物の製造原料
として限られた量を安価に効率良く製造しようと
する場合には必ずしも好適なものとは言えない；
更に反応物の析出分離に際し、従来広く用いられ
ている酢酸エチルを溶媒とするときには、その析
出物の粒径が小さく、ために過に多くの時間を
要する；という問題があつた。<Problems to be Solved by the Invention> However, in these methods, the solvent used to acetylate phosphoric acid and the alcohol used to precipitate and separate the reactants mix, so it is necessary to separate and recover them. Repeated use requires special recovery equipment, such as a distillation column; and although this type of solvent recovery equipment is suitable for handling large quantities of product,
It is not necessarily suitable when trying to manufacture a limited amount of a product at a low cost and efficiently as a raw material for a product used for a special purpose as in the present invention;
Furthermore, when ethyl acetate, which has been widely used in the past, is used as a solvent for precipitation and separation of reactants, there is a problem in that the particle size of the precipitates is small and therefore an excessively long time is required.
＜問題点を解決するための手段＞
本発明者は、上記の問題点を解決するため、リ
ン酸のアセチル化剤として取扱いの容易な無水酢
酸を選択し、このアセチル化反応に使用する溶媒
および反応物の析出分離に用いる溶媒の種類と組
合せについて種々検討した結果、上記溶媒として
ｎ−ブチルエーテルを選択すれば、驚くべきこと
に、アセチル化反応における反応性及び収率が他
の如何なる溶媒に比べても高いこと、DAAP生
成後の反応液よりのDAAPの分離析出が容易に
行なえること、並びに反応液よりの溶媒の回収、
再使用が容易になり反応系全体の簡略化が計れる
ことを見出し、本発明に到達したもので、本発明
は、ｎ−ブチルエーテル中でリン酸を無水酢酸に
よりアセチル化し、得られた反応混合物をアンモ
ニア水で中和し、反応液を静置して分相し、上相
のｎ−ブチルエーテルを回収後、下相のDAAP
水溶液にアルコールを加えてDAAPを析出させ、
DAAPをアルコール水溶液より分離回収するこ
とを特徴とするDAAPの製造方法に係わるもの
である。<Means for Solving the Problems> In order to solve the above problems, the present inventor selected acetic anhydride, which is easy to handle, as an acetylation agent for phosphoric acid, and the solvent and As a result of various studies on the types and combinations of solvents used for precipitation and separation of reactants, it was surprisingly found that if n-butyl ether was selected as the solvent, the reactivity and yield in the acetylation reaction would be lower than that of any other solvent. DAAP can be easily separated and precipitated from the reaction solution after DAAP is produced, and the solvent can be recovered from the reaction solution.
The present invention was developed based on the discovery that reuse is easy and the entire reaction system can be simplified.The present invention involves acetylating phosphoric acid with acetic anhydride in n-butyl ether, and converting the resulting reaction mixture into Neutralize with aqueous ammonia, leave the reaction solution to separate the phases, recover the upper phase of n-butyl ether, and then collect the lower phase of DAAP.
Add alcohol to the aqueous solution to precipitate DAAP,
The present invention relates to a method for producing DAAP, which is characterized by separating and recovering DAAP from an aqueous alcohol solution.
次に、本発明を更に詳細に説明する。 Next, the present invention will be explained in more detail.
アセチル化反応で使用されるリン酸は、
H3PO4濃度85〜105％、好ましくは出来るだけ
100％に近いものを使用する。リン酸濃度は低く
てもアセチルリン酸は生成するが、混在する水に
よつて消費される無水酢酸が増すため経済的に不
利である。一方、リン酸濃度が105％以上になる
と混在する縮合リン酸が製品のアセチルリン酸塩
に混入してくるため、アセチルリン酸塩の品質が
低下する
反応に使用する溶媒としては、ｎ−ブチルエー
テルを使用する。これは、後述する実施例１およ
び添付図面に示したように、酢酸エチル等のエス
テル系溶媒や他のエーテル系溶媒、あるいはケト
ンを用いると、反応の終了に３時間以上を要す
る。 Phosphoric acid used in the acetylation reaction is
H3PO4 concentration 85-105 %, preferably as much as possible
Use something close to 100%. Although acetyl phosphoric acid is produced even if the phosphoric acid concentration is low, it is economically disadvantageous because the amount of acetic anhydride consumed by the mixed water increases. On the other hand, if the phosphoric acid concentration exceeds 105%, condensed phosphoric acid will be mixed into the acetyl phosphate product, resulting in a decrease in the quality of the acetyl phosphate product.The solvent used for the reaction is n-butyl ether. use. As shown in Example 1 and the accompanying drawings, when an ester solvent such as ethyl acetate, another ether solvent, or a ketone is used, it takes 3 hours or more to complete the reaction.
また、ｎ−ブチルエーテルと類似し、ｎ−ブチ
ルエーテルと同様に工業的にも広く利用されてい
るイソプロピルエーテルを用いても、反応は長時
間を要し、その上、リン酸との混合液は冷却によ
つて固化しやすくなるため取扱いが煩雑となる。
しかし、ｎ−ブチルエーテルについてはかような
欠点もなく、以後の工程における操作が容易に行
なえる特徴をもつている。 Furthermore, even when using isopropyl ether, which is similar to n-butyl ether and is widely used industrially like n-butyl ether, the reaction takes a long time, and in addition, the mixture with phosphoric acid is cooled. It becomes difficult to handle because it solidifies easily.
However, n-butyl ether does not have such drawbacks and has the characteristic that it can be easily operated in subsequent steps.
この使用量はリン酸１部に対して0.5〜10部
（部は重量部、以下同じ）好ましくは１〜５部使
用する。溶媒は少なすぎると反応液の粘性が高く
なり操作および反応温度のコントロールが難しく
なる。しかし、必要以上に増しても反応装置が大
型化するだけで経済的に不利となる。リン酸とｎ
−ブチルエーテルは混合時発熱するので冷却して
から無水酢酸を添加し、アセチル化反応を行なわ
せる。このときの無水酢酸はリン酸〔H3PO4の
モル数＋水のモル数〕の1.0〜1.5倍のモル数とす
る。さらに反応温度は−20℃〜８℃、好ましくは
−５℃〜５℃とする。特に反応温度が８℃以上に
なると縮合リン酸が副生して製品のアセチルリン
酸塩の品質が低下する。又、この反応は発熱反応
であるため、冷却して反応温度をコントロールす
る。反応時間は無水酢酸を５〜30分で添加しその
後30〜60分撹拌を続けるだけで充分である。 The amount used is preferably 0.5 to 10 parts (parts by weight, the same applies hereinafter) per 1 part of phosphoric acid, and preferably 1 to 5 parts. If the amount of solvent is too small, the viscosity of the reaction solution will increase, making it difficult to control the operation and reaction temperature. However, increasing the amount more than necessary only increases the size of the reactor, which is economically disadvantageous. phosphoric acid and n
-Butyl ether generates heat when mixed, so acetic anhydride is added after cooling to carry out an acetylation reaction. The number of moles of acetic anhydride at this time is 1.0 to 1.5 times that of phosphoric acid [number of moles of H 3 PO 4 + number of moles of water]. Furthermore, the reaction temperature is -20°C to 8°C, preferably -5°C to 5°C. In particular, when the reaction temperature is 8° C. or higher, condensed phosphoric acid is produced as a by-product and the quality of the acetyl phosphate product deteriorates. Furthermore, since this reaction is exothermic, the reaction temperature is controlled by cooling. As for the reaction time, it is sufficient to add acetic anhydride over 5 to 30 minutes and then continue stirring for 30 to 60 minutes.
このアセチル化反応によつて、ほぼ全量のリン
酸はアセチルリン酸となり、同時に酢酸が副生す
る。この反応液は、アンモニア水で中和してアセ
チルリン酸を安定なアセチルリン酸アンモニウム
にする。この中和反応は従来法ではアセチルリン
酸アンモニウムに対して不溶で酢酸アンモニウム
に対して可溶なアルコールを混在させて生成した
DAAPを析出させ分離回収していたが、本発明
ではアンモニアは水溶液で添加して、反応液をｎ
−ブチルエーテルを含む上相と、アセチルリン酸
を含む下相に分相して、各々を分離後、DAAP
を含む下相にはアルコールを加えて、DAAPを
析出させ、別する。即ち、本発明は、DAAP
が水中で安定に存在することに着目して達成され
たもので、これによつて、ｎ−ブチルエーテルと
アルコールの各々は単離、精製による再使用が容
易となる。つまり中和工程でのｎ−ブチルエーテ
ルを含む上相は、水洗して酢酸を除くだけで再使
用が可能となり、その上、ｎ−ブチルエーテルの
水に対する溶解度は0.03％（重量）と非常に小さ
く、又、エステル系溶媒のような加水分解も起ら
ないため殆んど全量を回収できる。 Through this acetylation reaction, almost all of the phosphoric acid becomes acetyl phosphoric acid, and at the same time acetic acid is produced as a by-product. This reaction solution is neutralized with aqueous ammonia to convert acetyl phosphoric acid into stable ammonium acetyl phosphate. In the conventional method, this neutralization reaction was performed by mixing an alcohol that is insoluble in ammonium acetyl phosphate but soluble in ammonium acetate.
Previously, DAAP was precipitated and separated and recovered, but in the present invention, ammonia is added in the form of an aqueous solution, and the reaction solution is
- After separating the upper phase containing butyl ether and the lower phase containing acetyl phosphate, DAAP
Alcohol is added to the lower phase containing DAAP to precipitate it and separate it. That is, the present invention provides DAAP
This was achieved by focusing on the fact that n-butyl ether and alcohol exist stably in water, and as a result, each of n-butyl ether and alcohol can be easily reused by isolation and purification. In other words, the upper phase containing n-butyl ether in the neutralization process can be reused simply by washing with water to remove acetic acid. Moreover, n-butyl ether has a very low solubility in water of 0.03% (weight). Furthermore, unlike ester solvents, hydrolysis does not occur, so almost the entire amount can be recovered.
この中和工程は中和熱の発生が大きいため、充
分冷却して、５℃以下、好ましくは０℃以下で行
なう。５℃以上となると反応液中のアセチルリン
酸が一部加水分解を受け、リン酸と酢酸となる傾
向が認められ好ましくない。アンモニアの量は、
生成するアセチルリン酸を完全に中和する量以上
で、同時に副生する酢酸まで中和できる量以下と
する。具体的には、原料リン酸のH3PO4の２倍
モルから４倍モル、好ましくは３〜3.8倍モル数
とする。アンモニア量が多すぎると次工程で析出
するDAAPの過性が著しく低下する。一方、
アンモニアの量が少なすぎると、次工程でアルコ
ールによる析出が不充分となり生成率が低下する
傾向がある。 Since this neutralization step generates a large amount of heat of neutralization, it is carried out with sufficient cooling at a temperature of 5° C. or lower, preferably 0° C. or lower. When the temperature exceeds 5°C, acetyl phosphoric acid in the reaction solution tends to be partially hydrolyzed to form phosphoric acid and acetic acid, which is not preferable. The amount of ammonia is
The amount should be at least enough to completely neutralize the acetyl phosphoric acid that is produced, but not more than the amount that can also neutralize the by-product acetic acid. Specifically, the molar amount is 2 to 4 times, preferably 3 to 3.8 times, the amount of H 3 PO 4 in the raw material phosphoric acid. If the amount of ammonia is too large, the transient nature of DAAP precipitated in the next step will be significantly reduced. on the other hand,
If the amount of ammonia is too small, precipitation by alcohol will be insufficient in the next step, and the production rate will tend to decrease.
又、アンモニアはアンモニア水で添加するが、
アンモニア水の濃度は大きすぎるとアルカリ添加
時に添加した周辺における反応が激しく、一時的
な温度上昇やアンモニアの一部がガス化して揮散
するため好ましくない。一方、濃度を下げすぎる
と、次工程でのアルコール添加によるDAAPの
析出に要するアルコール量が増大するので好まし
くないため、一般的にはアンモニア濃度５〜15％
が適当である。ただし、中和初期においては発熱
が激しいため、低濃度のアンモニア水を用いると
操作が容易である。さらに、反応液の分相は中和
初期つまり少量のアンモニア水添加によつて起る
ため、中和反応を途中で停止してｎ−ブチルエー
テルを含む上相を除いてから、中和反応を再開す
ることもできる。この場合、アンモニアをアルコ
ール溶液で添加したり、アルコールを反応液に添
加してアンモニアガスで中和することもできる。 Also, ammonia is added with aqueous ammonia,
If the concentration of ammonia water is too high, the reaction around the alkali added during addition will be intense, resulting in a temporary temperature rise and part of the ammonia being gasified and volatilized, which is not preferable. On the other hand, if the concentration is lowered too much, the amount of alcohol required to precipitate DAAP due to the addition of alcohol in the next step will increase, which is undesirable, so the ammonia concentration is generally 5 to 15%.
is appropriate. However, since heat generation is intense in the early stages of neutralization, the operation is easier if aqueous ammonia with a low concentration is used. Furthermore, since phase separation of the reaction solution occurs at the initial stage of neutralization, that is, by adding a small amount of ammonia water, the neutralization reaction is stopped midway and the upper phase containing n-butyl ether is removed before restarting the neutralization reaction. You can also. In this case, ammonia can be added as an alcohol solution, or alcohol can be added to the reaction solution and neutralized with ammonia gas.
中和分相後、下相の反応液には中和反応でアン
モニア水として用いた水の1.0〜10倍のアルコー
ルを混入してDAAPを析出させて酢酸塩と分離
する。このとき、アルコール添加量が少なすぎる
とDAAPは溶液に残る量が増して収率が低下す
るので注意を要する。このDAAPは過性のよ
い粒径の揃つた顆粒状となるため遠心分離機等で
速やかに別できる。別により回収した
DAAPは付着している水、酢酸塩等をアルコー
ル洗浄で除いて乾燥する。 After the neutralization separation phase, 1.0 to 10 times more alcohol than the water used as aqueous ammonia in the neutralization reaction is mixed into the lower phase reaction solution to precipitate DAAP and separate it from acetate. At this time, care must be taken because if the amount of alcohol added is too small, the amount of DAAP remaining in the solution will increase and the yield will decrease. Since this DAAP is in the form of granules with good permeability and uniform particle size, it can be quickly separated using a centrifuge or the like. Collected separately
DAAP is washed with alcohol to remove adhering water, acetate, etc., and then dried.
以上の方法によつて純度のよいDAAPを速や
かに高純度で製造できる。一方、中和工程で分離
したｎ−ブチルエーテルを含む上相は、水洗して
酢酸を除くことにより容易に回収できる。さらに
液に混在しているアルコールは既存の蒸留法に
よつて水と分離回収できる。また、アルコール
は、価格および回収の容易さを考慮するとメタノ
ールが有利である。 By the above method, DAAP with good purity can be rapidly produced with high purity. On the other hand, the upper phase containing n-butyl ether separated in the neutralization step can be easily recovered by washing with water to remove acetic acid. Furthermore, alcohol mixed in the liquid can be separated and recovered from water using existing distillation methods. Furthermore, methanol is advantageous as the alcohol in view of price and ease of recovery.
＜実施例＞
つぎに、この発明の実施の態様を実施例及び比
較例に基づいて説明するが、各例中の部および％
はそれぞれ重量部および重量％を示す。<Example> Next, embodiments of the present invention will be explained based on Examples and Comparative Examples.
indicate weight parts and weight %, respectively.
実施例 １
アセチル化溶媒の種類を変えたアセチルリン酸
塩の合成
95％リン酸50部（H3PO447.5部、水2.5部）と
酢酸エチル100部の混合液を窒素雰囲気で満たし
て２℃から−２℃に冷却して無水酢酸90部を15分
で添加する。以後、上記温度を保つたまま反応を
続ける。一定時間反応を行なつたあと、反応液は
−40℃に冷し、5.5％アンモニアを含むメタノー
ル溶液500部で反応液温度０℃以下にて中和する。
これによつて生成した沈澱物はブツフエナー過
器で別して、さらにメタノール300部、次にジ
エチルエーテル100部で洗浄して一日減圧乾燥し
た。この生成物について、DAAPの濃度をヒド
ロキサム酸法および酵素法（以下各例とも同じ）
でリン酸基準の収率を求めた。Example 1 Synthesis of acetyl phosphate using different types of acetylation solvent A mixed solution of 50 parts of 95% phosphoric acid (47.5 parts of H 3 PO 4 , 2.5 parts of water) and 100 parts of ethyl acetate was filled with nitrogen atmosphere. Cool to -2°C and add 90 parts of acetic anhydride over 15 minutes. Thereafter, the reaction is continued while maintaining the above temperature. After carrying out the reaction for a certain period of time, the reaction solution is cooled to -40°C and neutralized with 500 parts of a methanol solution containing 5.5% ammonia at a reaction solution temperature of 0°C or less.
The precipitate thus produced was separated using a Butuchen filter, washed with 300 parts of methanol, then 100 parts of diethyl ether, and dried under reduced pressure for one day. For this product, the concentration of DAAP was determined by the hydroxamic acid method and the enzyme method (the same applies to each example below).
The yield was determined based on phosphoric acid.
次に、反応溶媒の酢酸エチルに代えて、ｎ−ブ
チルエーテル、酢酸ｎ−ブチル、イソプロピルエ
ーテル、またはメチルイソブチルケトンを使用し
た他は前記と同様にしたときの反応時間と収率の
関係についても調べた。以上の結果を添付図面に
示す。これによつて、ｎ−ブチルエーテルを用い
るとアセチル化反応は迅速に行なわれることが確
認できた。 Next, we investigated the relationship between reaction time and yield in the same manner as above except that n-butyl ether, n-butyl acetate, isopropyl ether, or methyl isobutyl ketone was used instead of ethyl acetate as the reaction solvent. Ta. The above results are shown in the attached drawings. This confirmed that the acetylation reaction was carried out quickly when n-butyl ether was used.
実施例 ２
96％リン酸205部（H3PO4197部）とｎ−ブチ
ルエーテル480部の混合液を２℃に冷却して無水
酢酸316部を30分で添加し、さらに１時間反応を
続ける。この間の反応温度は３〜−５℃を保つ。
次に反応液を−20℃に冷却し12.6％アンモニア水
870部（NH3110部）を反応温度０℃以下に保ち
ながら１時間で添加する。この反応液は５分間静
置し、上相と下相に分相したところで上相を除
く。下相は撹拌しながらメタノール1200部を加え
ると析出物が生成する。10分間静置後、デカンテ
ーシヨンによつて上澄を除いたあと遠心分離機で
別する。過物は400部のメタノールで洗浄し
て再過し、一日減圧乾燥して340部を得た。Example 2 A mixture of 205 parts of 96% phosphoric acid (197 parts of H 3 PO 4 ) and 480 parts of n-butyl ether was cooled to 2°C, 316 parts of acetic anhydride was added over 30 minutes, and the reaction was continued for an additional hour. . During this time, the reaction temperature is maintained at 3 to -5°C.
Next, the reaction solution was cooled to -20℃ and diluted with 12.6% ammonia water.
870 parts (110 parts of NH 3 ) are added over 1 hour while maintaining the reaction temperature below 0°C. This reaction solution is allowed to stand for 5 minutes, and when the phase is separated into an upper phase and a lower phase, the upper phase is removed. When 1200 parts of methanol is added to the lower phase while stirring, a precipitate is formed. After standing still for 10 minutes, remove the supernatant by decantation and separate using a centrifuge. The filtered residue was washed with 400 parts of methanol, filtered again, and dried under reduced pressure for one day to obtain 340 parts.
生成物はDAAPで91％、酢酸アンモニウム６
％、リン酸アンモニウム３％であつた。 Product is 91% DAAP, ammonium acetate 6
%, ammonium phosphate 3%.
なお、DAAPの収率はリン酸基準では90％と
なる。 Note that the yield of DAAP is 90% based on phosphoric acid.
更に、分離した上相は100部の水で２回洗浄し
て混在する酢酸等を除き、461部のｎ−ブチルエ
ーテルを回収した。ｎ−ブチルエーテルの回収率
は96％となる。 Further, the separated upper phase was washed twice with 100 parts of water to remove mixed acetic acid and the like, and 461 parts of n-butyl ether was recovered. The recovery rate of n-butyl ether is 96%.
実施例 ３
97％リン酸50部（H3PO448.5部）とｎ−ブチル
エーテル280部の混合液に５〜０℃で無水酢酸72
部を15分で添加し、さらに50分反応を続けた。こ
れに10％アンモニア水60部を滴下して静置して反
応液を分相する。上相を除いたあと、6.8％アン
モニアを含むメタノール溶液300部をさらに滴下
した。この間の反応温度は０〜−30℃であつた。
中和後、30分静置して、上澄液をデカンテーシヨ
ンで除いてから、析出物を遠心分離機で別し、
さらにメタノール120部で洗浄、再過を行なつ
て、一夜減圧乾燥した。生成物は79部であつた。
これはDAAPで90％を含む。収率は82％となる。
又、上相については100部の水で１回洗浄してｎ
−ブチルエーテル263部を回収した。回収率は94
％である。Example 3 Add 72 parts of acetic anhydride to a mixture of 50 parts of 97% phosphoric acid (48.5 parts of H 3 PO 4 ) and 280 parts of n-butyl ether at 5 to 0°C.
part was added over 15 minutes and the reaction continued for an additional 50 minutes. 60 parts of 10% ammonia water is added dropwise to this and left to stand to phase-separate the reaction solution. After removing the upper phase, 300 parts of a methanol solution containing 6.8% ammonia was further added dropwise. The reaction temperature during this period was 0 to -30°C.
After neutralization, let it stand for 30 minutes, remove the supernatant by decantation, and separate the precipitate with a centrifuge.
Further, the mixture was washed with 120 parts of methanol, filtered again, and dried under reduced pressure overnight. The product was 79 parts.
This includes 90% in DAAP. The yield will be 82%.
For the upper phase, wash once with 100 parts of water.
-263 parts of butyl ether were recovered. Recovery rate is 94
%.
実施例 ４
実施例１に従つて反応を行ない、メタノールの
代りにエタノールを使つた。析出したアセチルリ
ン酸アンモニウムは、メタノール洗浄したあと、
別し一夜減圧乾燥し365部を回収した。これの
DAAPの含有量は92％、収率94％となる。Example 4 The reaction was carried out according to Example 1, using ethanol instead of methanol. After washing the precipitated ammonium acetyl phosphate with methanol,
It was separated and dried under reduced pressure overnight, and 365 parts were recovered. of this
The content of DAAP is 92% and the yield is 94%.
また、ｎ−ブチルエーテルは96％で回収でき
た。 In addition, 96% of n-butyl ether could be recovered.
実施例 ５
実施例１に従つて反応を行なつた。ただし、中
和反応は、６％アンモニアメタノール溶液1830部
で行なつた。中和後10分間静置してデカンテーシ
ヨンし、ブツフエナー過器でアセチルリン酸を
別する。過物は、メタノール600部で十分洗
浄し、一夜減圧乾燥する。生成物は372部で、エ
ーテル臭を有する。これのDAAPの含有量は85
％で、収率91％となる。液には水3000部を加え
てｎ−ブチルエーテルをメタノールから回収し
た。回収量394部、回収率82％となつた。Example 5 The reaction was carried out according to Example 1. However, the neutralization reaction was carried out using 1830 parts of a 6% ammonia methanol solution. After neutralization, leave to stand for 10 minutes, decant, and separate acetyl phosphate using a Butufener filter. The residue was thoroughly washed with 600 parts of methanol and dried under reduced pressure overnight. The product is 372 parts and has an ethereal odor. The content of DAAP in this is 85
%, yield is 91%. 3000 parts of water was added to the liquid to recover n-butyl ether from methanol. The amount collected was 394 copies, resulting in a recovery rate of 82%.
比較例
アセチル化反応の溶媒に酢酸エチルを用いた。
96％リン酸102部（H3PO498部）酢酸エチル550
部の混合液を１〜−２℃に保ちながら無水酢酸
180部を30分で滴下し、さらに４時間反応を続け
る。この反応液を−30℃まで冷し、５％アンモニ
アメタノール溶液580部を０℃以下に保ちながら
滴下して中和する。Comparative Example Ethyl acetate was used as a solvent for the acetylation reaction.
102 parts of 96% phosphoric acid (98 parts of H3PO4 ) 550 parts of ethyl acetate
acetic anhydride while keeping the mixture at 1~-2℃.
Add 180 parts dropwise over 30 minutes and continue the reaction for an additional 4 hours. The reaction solution is cooled to -30°C, and 580 parts of a 5% ammonia methanol solution is added dropwise to the solution while maintaining the temperature below 0°C to neutralize it.
中和後、ブツフエナー過器で析出物を別
し、さらに320部のメタノールで洗浄したあと一
夜減圧乾燥する。生成物は178部であつた。これ
のDAAPの含有量は84％、収率86％となる。 After neutralization, the precipitate was separated using a Butuchen filter, washed with 320 parts of methanol, and then dried under reduced pressure overnight. The product was 178 parts. This has a DAAP content of 84% and a yield of 86%.
＜発明の効果＞
以上の説明からわかるように、本発明の方法に
よれば純度の高いアセチルリン酸アンモニウムが
迅速に製造できる。しかも溶媒は循環再使用が容
易であるため、製造原価を著しく下げることがで
きアセチルリン酸塩の工業的な利用範囲を大幅に
広げることが可能となつた。<Effects of the Invention> As can be seen from the above explanation, according to the method of the present invention, ammonium acetyl phosphate with high purity can be rapidly produced. Moreover, since the solvent can be easily recycled and reused, manufacturing costs can be significantly reduced, and the range of industrial applications of acetyl phosphate can be greatly expanded.
添付図面は、反応溶媒の種類による反応時間と
アセチルリン酸塩収率との関係を示すグラフであ
る。
The accompanying drawing is a graph showing the relationship between reaction time and acetyl phosphate yield depending on the type of reaction solvent.
Claims (1)
よりアセチル化し、得られた反応混合物にアンモ
ニア水を加えて中和し、反応液を静置して分相
し、上相のｎ−ブチルエーテルを回収後下相の水
溶液にアルコールを加えてアセチルリン酸ジアン
モニウムを析出させ、これを水溶液より分離回収
することを特徴とするアセチルリン酸ジアンモニ
ウムの製造方法。 ２ 上相のｎ−ブチルエーテルを回収後、水洗し
てリン酸と無水酢酸とのアセチル化溶媒として再
使用することを特徴とする特許請求の範囲第１項
に記載の製造方法。[Claims] 1. Phosphoric acid is acetylated with acetic anhydride in n-butyl ether, aqueous ammonia is added to the resulting reaction mixture to neutralize it, the reaction mixture is allowed to stand, the phases are separated, and the upper phase is separated. 1. A method for producing diammonium acetyl phosphate, which comprises adding alcohol to the lower phase aqueous solution after recovering n-butyl ether to precipitate diammonium acetyl phosphate, and separating and recovering this from the aqueous solution. 2. The manufacturing method according to claim 1, wherein after recovering the upper phase n-butyl ether, it is washed with water and reused as a solvent for acetylation of phosphoric acid and acetic anhydride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9336885A JPS61251691A (en) | 1985-04-30 | 1985-04-30 | Production of diammonium acetylphosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9336885A JPS61251691A (en) | 1985-04-30 | 1985-04-30 | Production of diammonium acetylphosphate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61251691A JPS61251691A (en) | 1986-11-08 |
| JPH0544473B2 true JPH0544473B2 (en) | 1993-07-06 |
Family
ID=14080349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9336885A Granted JPS61251691A (en) | 1985-04-30 | 1985-04-30 | Production of diammonium acetylphosphate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61251691A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104860984A (en) * | 2014-02-24 | 2015-08-26 | 浙江海正药业股份有限公司 | Preparation method of acetyl diammonium phosphate |
-
1985
- 1985-04-30 JP JP9336885A patent/JPS61251691A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61251691A (en) | 1986-11-08 |
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