CAS号 [108-56-5] 生产工艺。   草乙酸二乙酯（丁酮二酸二乙酯）

CAS名：Butanedioic acid, 2-oxo-, 1,4-diethyl ester.   历史参考文献：Beil. 3. E4, 1809.

CAS名：Butanedioic acid, 2-oxo-, 1,4-diethyl ester, ion(1-), sodium. CAS号 [40876-98-0]。

用途：有机合成，医药中间体。LookChem网登录生产与经营单位：酯体44家，其钠盐89家。反应类别：缩合，成盐。

BIOS 986, 305-307.（=胶卷PB 77764）。 Oxal acetic ester sodium salt dry. (Hoechst).  英国人译自德文，无资料来源。

反应式：本人有加注（资料原件无反应式），暂未找到德文原件。

Process:  操作步骤： 

The water circulating through the coils of the still (Frederking) is adjusted to 75 – 80℃.  250 litres of sodium ethylate solution from the ester plant（100 – 120 gm. per litre M. W. 40）is charged and stirred for 5 minutes.  A 10 cc. sample is then titrated with N.HCl. against Delta paper.  For example, if 28.9 cc. of N.HCl is required, then 250 litres of sodium ethylate is equivalent to 28.9 kg. sodium ethylate M. W. 40.  Mulyiplication of the weight of sodium ethylate （in this case 28.9）by (a) 3.5 gives the amount of diethyl oxalate required, and (b) 2.5 gives the amount of ethyl acetate required.

109.2 kg. diethyl oxalate and 60.0 kg. ethyl acetate are then run in one after the other.  The internal temperature is raised quickly to 70℃. and held at this temperature for 0.5 hour.  When nothing further distils over condensation is complete.

To dry the product, the batch is heated carefully, to avoid frothing, to 73 – 74℃, when 40 – 50 litres distils over to receiver (3).  Next heat to 80℃. obtaining 180 – 200 litres of distillate.

To complete drying, distil twice with 400 mm. mercury vacuum and once with 600 mm. mercury vacuum.  The vacuum is broken with nitrogen between the distillations, the purpose being to break up the mass inside the still.  In this process a total of 60 litres of distillate is obtained.  When the distillate becomes turbid due to dry product being sucked over, drying is finished.

The finished product most remain somewhat moist with alcohol for subsequent size reduction in the pre-crusher and impact mill, and the ground product is discharged to iron containers.

The total distillate containing approximately 70 parts per weight of alcohol, 24 parts per weight benzene and 6 parts per weight of ethyl acetate and diethyl oxalate is pumped to acetic ester plant.

Yield: 149.3 kg. oxal acetic ester salt 88% M. W. 210 = 131.4 kg. 100% = 86.5% of theory. （收率86.9%。）（Based on 109.2 kg. diethyloxalate）。

Strength Determination:  含量测定：

94 gm. of phenyl hydrazine sulphonic acid 100% M. W. 188（抄注：[98-71-5]）is heated to 70 – 80℃. with 1000 cc. water and 8 cc. of glacial acetic acid.  The sodium oxal acetic ester is then added and the hydrazine sulphonic acid slowly disappears.  The end point is reached when a small sample made alkaline with caustic soda no longer reduces Fehling’s solution. Strength is given by  100 X 105 / a  where (a) is the amount of oxal acetic ester required the prescribed end point.

It will be noticed that the quantities of diethyl oxalate and of ethyl oxalate do not agree with the formula given, i. e. 3.5 and 2.5 X “Titre”; this discrepancy was not noticed at the time of abstracting the original German process.  The yield of 86.5% theory is certainly based on 109.2 kg. diethyl oxalates.

Plant: 设备：

(1) Frederking still 1050 mm. diameter X 800 mm. high with cast-in heating coil.  Cast steel agitator 11 r. p. m. and 2 baffles, one baffle carrying thermometer pocket.  The cover is heated by separated heating coil, also the flange and bottom.  The still is heated by warm water circulation.  The cover carries feed inlets for sodium ethylate solution, diethyl oxalate and ethyl acetate.  There is opening in the bottom of the dryer for emptying.

(2) Steel coil condenser 9 sq. m. capacity.

(3) Copper vacuum receiver 0.4 cu. m. containing cooling coil with feed from condenser via sight glass, vacuum and nitrogen connections, blow-leg and run-off to receiver (4).

(4) Steel receiver 2.6 cu. m. as distillate receiver.   (5) Pre-crusher with draughting arrangement.   (6) Alpine Simplex hammer mill with draughting.

(7) Steel measure vessel 0.58 cu. m. for diethyl oxalate.   (8) Steel measure vessel 0.58 cu. m. for ethyl acetate.

Annual production: 1939  98,OOO kg.  1943  82,000 kg.  这是1939年和1943年的产量。此资料未见国内有人翻译，本人也不再反应！

（日）《有机化合物辞典》。1985年。P. 175.  オキサ酢酸エチル。 Ethyl oxalacetate; Diethyl oxalacetate. 化审2-1344，

BP 132℃ (24 mmHg).  D20/4 1.131.  N17/d 1.4561. 油状の液体，水に不溶，エタノ-ル，ベンゼン，エ-テルと任意の刻合で混合する。190℃でマロン酸ジエチルに分解する。

【制法】ジュウ酸ジエチル，酢酸エチルの混合物にナトリウムを作用させる。（抄注：未见引用BIOS的译文）。

侯乐山 主编《中国精细化工产品集 – 原料及中间体10396种》。2006年。P. 226-227.  丁酮二酸二乙酯（草乙酸二乙酯）。

中国化工信息中心  全国精细化工原料及中间体行业协作组 出版。《版权所有  未经允许  不得翻印》。

【产品性状】无色透明液体。沸点131-132℃（3.2 kPa），相对密度1.131（20/4℃），折射率1.456（17℃）。溶于丙酮，苯，乙醚，乙醇。

【生产方法】由草酸二乙酯与乙酸乙酯在乙醇钠存在下缩合而得。

【用途】有机合成中间体。在医药上用于合成阿卡明（抄注：[2574-78-9]）和白内停等药物。

张大国 编著《精细有机单元反应合成技术手册》。化学工业出版社 出版。2014年。P. 586. #143102. 丁酮二酸二乙酯。

定 价：180.00元   全书687页。《版权所有  违者必究》

前言：其中提到，本书在编写过程中参阅了大量的书籍和其它科技文献，等。

【分子式】C8H12O5   【分子量】188.18

【性质】与侯乐山的资料相同，不再抄录。 【用途】有机合成中间体。用于生产治疗肝炎药阿卡明等。

【制法】配料比：草酸二乙酯 ：乙酸乙酯 ：甲醇钠 ：三氯乙烯 = 1 : 0.44 : 0.85 : 3.9。

将甲醇钠和少量乙酸乙酯加热至80 – 86℃回流10 min，蒸馏回收甲醇近干，冷却至15℃加草酸二乙酯，搅拌，滴加乙酸乙酯，控制温度为40 – 50℃。丁酮酸二乙酯钠析出，放置2 – 3 h，加水及三氯乙烯溶解稀释，滴加盐酸至pH = 1。静置分层，分取三氯乙烯提取液，母液用三氯乙烯提取4次，合并提取液。水洗后用无水硫酸钠干燥。过滤，滤液回收三氯乙烯后。减压蒸馏，收集131 – 132℃（3.09 kPa）馏份，得丁酮二酸二乙酯。收率53%。

【抄注】这是最新的资料，书中无草乙酸二乙酯钠盐的合成工艺。国内出版物为什么没有引用BIOS的资料，过时了？

陈忠源 2020年6月22日星期一。