CN1227224C - 光化学方法 - Google Patents

光化学方法 Download PDF

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CN1227224C
CN1227224C CNB991086740A CN99108674A CN1227224C CN 1227224 C CN1227224 C CN 1227224C CN B991086740 A CNB991086740 A CN B991086740A CN 99108674 A CN99108674 A CN 99108674A CN 1227224 C CN1227224 C CN 1227224C
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provitamin
excimer
exciplex
radiation
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CN1243123A (zh
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A·M·布劳恩
M·杰森
H－P·波普
G·特勒舍尔
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Abstract

在有紫外光源的反应器中由7-脱氢胆固醇制备前维生素D3，这种辐射源是一种激发物或激发状态聚集发射器，它根据“电晕放电”原理在紫外光区域发射准单色光。

Description

光化学方法
本发明涉及一个在有紫外辐射源的反应器中由7-脱氢胆固醇制备前维生素D3的光化学方法。
众所周知，前维生素D3是可以由7-脱氢胆固醇(7-DHC)光照射得到。这种前维生素可以热重排成对热更加稳定的维生素D3。
至今工业上是用中压水银灯照射7-DHC进行光化合成这种前维生素。因为起始材料，主产物和副产物在同一波长区有不同的吸收效率，水银灯所产生的多色辐射有利于形成光化学的副产物，而这些副产物并无活性并且在某些情况下是有毒的。因此，就现有的技术水平，必须在转化率较低时就中断照射。未转化的7-DHC回收利用，而主产物不得不在一个成本很高的加工过程中进行纯化。
滤光效应是基质和产物在同一波长区吸收的又一结果。因此，例如前维生素的吸收光谱完全与7-DHC相重叠，并且随着转化反应的进行，前维生素的吸收光比例连续地增加。
另一转化率较低(10～20％)时就中断反应的原因是前维生素D3紧接着反应成例如速甾醇的量子产率大于形成前维生素D3的量子产率。
然而，在目前制备前维生素D3的最重要问题是中压水银灯的发射光谱和7-DHC吸收光谱之间相关性差。结果是，只有1％中压水银灯的光在280～300nm之间的理想区中是有用的。这一估计还忽略了相当大比例的由最佳波长区之外光线所得到的副产物。
本发明的目的是提供一种由7-脱氢胆固醇制备前维生素D3的光解过程，它比现有方法的缺点更少。
这个目的根据本发明可通过使用激发物或激发状态聚集发射器(excimer or exciplex emitter)作为辐射源达到，该发射器根据“电晕”放电原理在紫外光区发射准单色光。
这些发射器的发射波长是由形成激发物(excimer)或形成激发状态聚集(exciplex)的气体的组成所决定的。激发物和激发状态聚集发射器具有非常可变的特殊性能并且发射的波长范围十分窄。因此它们相应于所需的反应条件可在可得的气体和材料中进行选择并以最佳方式进行组合。使用这些发射器可以显著地降低每千克产物所需的电能。同时，激发物或激发状态聚集发射器的单色辐射显著地提高产物的纯度。
由激发物或激发状态聚集反应中形成光子的过程从激光技术中可以得知。但是激光光子源并不适合于前维生素D3的光化学合成。因为激光光子源的技术高度复杂和它们的辐射几何学不太适合于制备性的光化学以及相应的辐射强度在大面积上是不够的。
因此，用本发明所用的发射器首次采用了发射光几乎仅在光化学合成前维生素D3最佳波长区域的辐射源，用这些辐射源可以克服上面描述的缺点。因此，它们是很适合于工业上合成前维生素D3的辐射源。
充有XeBr或Br2并且发射光子波长为285nm或292nm的激发物发射器是典型的发射器，它们的发射波长在合成前维生素D3所需的最佳波长区。图3以实施例显示了XeBr灯的发射光谱。
就本发明所用的发射器而言，有形成的激发物(Br2)或激发状态聚集(exciplex)(XeBr)，它们在分解时发出具有理想波长的光子。两种发射器都已被发现当用于光化学合成前维生素D3时是良好而有效的辐射源。
本发明的方法以类似方式适于制备羟基化或酰化的前维生素D衍生物(例如1a-羟基或25-羟基或酰氧基前维生素D3)。
下面将参考附图描述本发明的实施例。
图1显示了一适合反应器的构造。
图2显示了降膜式反应器的放大剖面。
图3显示了一适合发射器的发射光谱。
7-脱氢胆固醇在甲醇/己烷中的3.5％溶液的XeBr激发物灯在284nm在一个降膜式反应器中进行照射。反应体系中的组成以一定时间间隔用高效液相色谱进行测定。以这个波长，大于93％的所得反应混合物由所需的前维生素D3组成，转化率约50％。用已知的方法可以容易地将起始材料分离开来。
图1所示的装置包括具有输出管道2的降膜式反应器1，输出管道2与接收器3直接相连。接收器含有大部分反应混合物。用于反应混合物的输送管道4从接受器通过泵5和热交换器6接至降膜式反应器。降膜式反应器设有管道7用于不断地向内部冲入氮气。
输出管道2具有一连续取样接点。
降膜式反应器1的结构在图2的更大比例的剖面图中十分清楚。它有圆筒式的外套7。一圆筒式石英下流管8共轴地置于内部。激发物发射器9放在中间，也是共轴的。
反应混合物从底部进入反应器并且以体积流在外套和下流管之间的环形空间向上传递。从那儿混合物以在下流管内侧上的膜形成向下流动。膜受到由发射器所发射的辐射10的作用。
在装置中所用溴化氙激发物发射器的以及在图3中显示的发射光谱中横坐标是发射光的波长(nm)，纵坐标是相对强度。

Claims (1)

1.一种在有紫外光源的反应器中由7-脱氢胆固醇制备前维生素D3的光化学方法，其特征在于辐射源是一种充有XeBr的激发物或激发状态聚集发射器，它根据“电晕放电”原理在合成前维生素D3所需的最佳紫外光区域发射准单色光。
CNB991086740A 1998-06-23 1999-06-22 光化学方法 Expired - Fee Related CN1227224C (zh)

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WO2000001477A1 (fr) 1998-07-03 2000-01-13 Chugai Seiyaku Kabushiki Kaisha Dispositif a rayonnement uv pour reaction photochimique et elaboration d'un derive de vitamine d avec ce dispositif
FR2823206B1 (fr) * 2001-04-05 2004-02-20 Atofina Procede photochimique semi-continu et dispositif pour sa mise en oeuvre
WO2008128783A2 (en) * 2007-04-24 2008-10-30 Dsm Ip Assets B.V. Photochemical process for the preparation of a previtamin d
CN101663269A (zh) * 2007-04-24 2010-03-03 帝斯曼知识产权资产管理有限公司 用于制造前维生素d的光化学方法
US20140221692A1 (en) 2013-02-04 2014-08-07 Chevron Phillips Chemical Company Lp Flow Reactor Vessels and Reactor Systems
CN107075551B (zh) * 2014-01-17 2020-09-01 协和发酵生化株式会社 7-脱氢胆固醇和维生素d3的制造法
JP6633535B2 (ja) 2014-10-08 2020-01-22 協和発酵バイオ株式会社 ７デヒドロコレステロール及びビタミンｄ３の製造法

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DE3270978D1 (en) * 1981-07-17 1986-06-12 Duphar Int Res Method of preparing 1-alpha-hydroxyvitamin d and 1-alpha-hydroxy-previtamin d compounds, and adduct of a previtamin d or tachysterol compound with a suitable dienophile
US4388242A (en) * 1982-03-15 1983-06-14 Canadian Patents & Development Limited Method of production of vitamin-D
DE3308592C2 (de) * 1983-03-10 1986-08-07 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen Photochemisches Verfahren zur Herstellung von Prävitamin D↓2↓ und D↓3↓ aus Ergosterin bzw.7-Dehydrocholesterin
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CA2275558A1 (en) 1999-12-23
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BR9903271A (pt) 2000-05-16
DK0967202T3 (da) 2003-08-25
ES2197547T3 (es) 2004-01-01
JP2000026405A (ja) 2000-01-25
EP0967202A1 (de) 1999-12-29
KR20000006343A (ko) 2000-01-25
US6180805B1 (en) 2001-01-30
DE59905410D1 (de) 2003-06-12
KR100682807B1 (ko) 2007-02-15

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