DD293578A5 - LIGHT-FILTER FILTER SOLUTIONS FOR THE PHOTOISOMERATION OF 5.7-DIEN-STEROIDS - Google Patents

Abstract

The invention relates to light stable filter solutions for the photoisomerization of 5.7-diene steroids, which are important as provitamins or provitamin metabolites of the D series. The object of the invention is to find filter solutions which allow an effective light output in the spectral range of 290-305 and a larger 330 nm, ensure a high proportion of previtamin D or previtamin D metabolites in the irradiation mixture and are stable for a long time against UV light. The object is achieved according to the invention by the use of metallic or alcoholic / aqueous solutions of trimethycyanine salts of the formulas II or III and compounds of the formulas IV, V or VI in the spectral range 280-310 and 330-360 nm which are non-absorbing metal salts, for example copper, nickel , Cobalt sulfate, sodium bromide, calcium chloride, lead, mercuric nitrate, silver sulfate, or mixtures thereof, or these metal salt solutions as a protective filter between light source and a cut-off filter solution consisting of a mixture of compounds of formulas II or III and IV, V or VI are brought. Such filter solutions can be used in any photoreactor or in a simple irradiation apparatus, are stable for a long time and, even with repeated use, permit short irradiation times and a high proportion of previtamin D or previtamin D metabolites in the mixture of isomers. formulas

Description

2. Light-stable filter solutions according to item 1, characterized in that are used as metal salts of copper, nickel, cobalt sulfate, sodium bromide, calcium chloride, lead, mercury nitrite, silver sulfate or combinations thereof.

3. Light-stable filter solutions according to item 1 and 2, characterized in that is used as Metaüsalzkonzentration the range 0.05 to 500 g / l.

4. Light-stable filter solutions according to item 1 and 3, characterized in that the metal salt solution separated from the cut-off filter solution consisting of one or more cyanine salts of the formulas II or III and one or more compounds of the formulas IV, V or VI as a protective filter brought in front of the light source.

Field of application of the invention

The invention relates to light stable filter solutions for the photoisomerization of 5.7-diene steroids. 5.7-Diene steroids are of great importance as provitamins and provitamin metabolites of the D series, since they can be used to produce the biodegradable vitamins of the D series.

Characteristic of the known state of the art

The preparation of vitamins of the D series and their derivatives is carried out by thermal isomerization of the previtamin formed in UV radiation from the respective provitamin. In the Photoisornerisierung but other than the desired previtamin, not convertible into vitamin D or vitamin D metabolites by-products (tachysterol, lumisterol and so-called. Over-irradiation products) are formed. The size of the proportion of these unwanted by-products in the irradiation mixture depends on the selected irradiation conditions. Therefore, the effectiveness of the synthesis of vitamin D and its derivatives from the respective provitamin is determined mainly by the attainable in the irradiation Prozvamin yield.

The known irradiation using high-, medium- or low-pressure mercury lamps with and without the use of filter glasses or filter solutions of aqueous quinine or metal salt solutions generally only results in a yield of less than 50% of previtamin D or previtamin D -motabolites in the irradiation mixture.

In order to improve the product yield, the unreacted starting material may be re-supplied to the irradiation process, or the irradiation may be carried out in a two-step process in the presence of an additive (sensitizer) or subsequently two different irradiation wavelengths were used for the photoisomerization.

A disadvantage of these methods is that either no appreciably higher yield of the desired previtamin D or previtamin D metabolites is achieved, the overall process is much more complicated and is associated with product losses, or that a greater proportion of non-reusable by-products.

The simultaneous use of irradiation wavelengths in the range 290-305 and greater than 330 nm is advantageous, since in this way a very high proportion of the respective previtamin D in the reaction mixture can be achieved in a single irradiation step.

The disadvantage, however, is that the necessary generation of the required irradiation light by means of two monochromators allows the photoisomerization only in a simple irradiation apparatus, but not in a photoreactor.

For the photoisomerization of provitamin D or its derivatives in a photoreactor using a single radiation source, filter solutions are used to filter out the irradiation wavelengths which favor a high product conversion to the respective previtamin. As particularly favorable filter solutions for this Trimethincyaninsalzlösungen in combination with, for example, benzoic acid, phenol, acetanilide or anisole have proven as a cut-off filter. Such filter solutions have a sufficiently steep-edged transmission characteristic in the required wavelength ranges and therefore allow the generation of high light intensities at the reaction site. Disadvantageously, however, the hitherto known cut-off filters are not sufficiently stable to the hr chenergetische UV light and change due to pnotochemischer decompositions already after a short period of irradiation considerably their transmission characteristics. This leads to a drastic reduction of the light intensity in the desired wavelength ranges and to the transmission of wavelengths, which favor the photochemical formation of by-products. To circumvent the associated high yield losses of previtamin D or previtamin D metabolites and the longer irradiation times due to uneconomical use of the irradiation light is a constant renewal of the filter solution, combined with high material, energy and time required.

Object of the invention

It is the object of the invention to find light-stable filter solutions for the photoisomerization of 5.7-diene steroids, which allow an effective light output, ensure a high proportion of previtamin or previtamin metabolites and are stable against UV light for a long time, and Lack of previously known filter solutions avoid.

Explanation of the essence of the invention

It is the object of the invention to find filter solutions which are stable against UV light for the photoisomerization of 5.7-diene steroids, which allow a high light intensity in the spectral range 290-305 and greater 330 .mu.m, a high proportion of previtamin D or previtamin D- Ensuring metabolites in the irradiation mixture and practically do not change their transmission properties even with long-term operation of the irradiation apparatus.

The object is achieved in that for the photoisomerization of 5.7-diene steroids of the general formula I,

wherein R 'R ² R ³ R \ R ⁵

Hydrogen, alkyl, acyl, Si (alkyl) ₃ hydrogen, OH, O acyl, OAlkyl, OSi (alkyl) ₃ -CH = CH-CH, vJH ₃ ) -OH (CH ₃ ) 2-CH 2 -CH _z -CHR ⁴ -C (CH 3) 2 R ^{5 is} hydrogen, OH, O acyl, OAlkyl, OSi (alkyl) ₃

-0

mean,

a combination of an aqueous or alcoholic / aqueous solution of Trimethinsyaninsalzen of the general formulas II or III

R '

C I

NH

NH ⁺ X

/ RS NH NH ⁺ X "

(CH ₂ ) _n (CH ₂ ) _n aryl aryl

II

with one or more compounds of the formulas IV, V or VI,

III

COOH R ⁷ ·

0-R ⁹

wherein R ¹ , R ³ R ²

IV

may be the same or different and are hydrogen, alkyl, OAlkyl or aryl

May be the same or different hydrogen, alkyl or aryl and alkyl, aryl or alkylene is hydrogen or alkyl

Hydrogen or one or more branched or unbranched alkyl groups

Alkyl or aryl

Halide, CIO ₄ ", NO ₃ ", '/ 2 SO ₄ ² ", CH ₃ SO ₃ ", BF ₄ ", R ⁶ -C ₆ H ₄ -SOr, R ⁶ -C ₆ H ₄ -COCr

VI

and with non-absorbing in the spectral range 280-310 and 330-360 nm metal salts, for example, copper, nickel, cobalt sulfate, sodium bromide, calcium bromide, lead mercury nitrate, silver sulfate or combinations thereof, or that an aqueous or alcoholic / aqueous Solution of this metal salt is brought as a protective filter between the light source and a solution consisting of one or more Trimethincyaninsalzen of the formulas II or III and compounds of the formulas IV, V or Vl.

The concentration of each Trimethincyaninsalzes of the formulas II or III is in the range of 0.001 to 1 g / l, of the compounds represented by formulas IV, V or VI in the range of 1 to 75g / l, and the concentration of the metal salts may 0.05 to SOOg / l amount.

The metal salts are virtually unlimitedly stable against UV light and absorb most of the light in the high-energy spectral region which effects the photochemical decomposition of the cut-off filter materials forming the steep-edged transmission curves in the short-wave spectral region (compounds IV, V or VI). Such filter solutions show a steep-edged transmission characteristic in the desired spectral range, they change only slightly at long irradiation times, allow consistently high light intensities in the spectrums favoring a high proportion of previtamin D or previtamin D metabolites and therefore require only short irradiation times.

The solutions according to the invention can be used to generate optimal irradiation conditions for the photoisomerization of 5.7-diene steroids in any photoreactor or in a simple irradiation apparatus as lichtsta JiIe and long-term usable filter or simultaneously as a filter and cooling liquid. Advantageously, in a photoreactor, the metal salt solution and the cut-off filter solution, consisting of cyanine salts of the formulas II or IIIl and one or

several compounds of the formulas IV, V, or Vl, used in separate circuits, since in this way a longer shelf life of the filter solution is achieved and lower reaction temperatures and thus a lower proportion of irreversible by-products are possible without the intensity of the light source by hypothermia noticeable weakened

embodiments example 1

An argon-saturated solution of 7-dehydrocholesterol (7-DHC) in dry ethanol (c = 1 x 10 ~ ⁴ mol / l) is irradiated in a quartz cuvette at ⁰ ° C with a high pressure mercury lamp (TQ 150). The filter solution used is an alcoholic solution of 90 mg / l of dimethyldiaza-cycloheptadiene-tetrafluoroborate and 65 g / l of anisole. After an irradiation time of 30 minutes, a proportion of 72% of previtamin D _{3 is obtained} in the isomer mixture.

a second irradiation of 7-DHC using the same filter solution takes 75 minutes to reach the ototational state, and the proportion of previtamin D ₃ remains below 50%. For further irradiation, the filter solution is practically unusable.

Example 2 Under the same conditions as in Example 1, 7-DHC is irradiated using the same filter solution, wherein

an aqueous solution of 20 g / l copper sulfate is placed between the filter solution and the light source. The photostationary state is reached after about 35 minutes and the proportion of previtamin D ₃ is 73%. Even after five times using the same

Filter solution becomes the photostationary state with a previtamin D ₃ content between 70% and 75% in the same reaction time

reached.

Example 3 In a commercial circulating photoreactor with a high pressure mercury immersion lamp (TQ 150), 250mg of 7-DHC in

500 ml under argon distilled ethanol at ^{0 0} C irradiated. The actmic light is filtered with a solution consisting of 90mg / l

Dimethyldiazacycloheptadien-methanesulfonate and 14g / l acetanilide selected. After 20 minutes irradiation time, a proportion of 71% previtamin D _{3 is obtained} in the isomer mixture. Using the same filter solution, a new solution of 7-DHC is irradiated under the same conditions. To

The proportion of previtamin D _{3 is} 35% for 20 minutes and 45% after 100 minutes. The filter solution turned yellow, and the

Transmission at 296nm decreased from 20 to 5% during the course of irradiation. Example 4

In a circulating photoreactor, the dipping device is changed so that the high-pressure mercury lamp TQ150 is surrounded by 2 filter solutions in different circuits. The radiation solution immediately adjacent filter solution consists of an aqueous copper sulfate solution (20g / l), and the second filter solution of a solution of 90 mg / 1 Dimethyldiazycycloheptadien-methanesulfonate and 14g / l acetanilide. Under the same conditions as in Example 3, 250 mg of 7-DHC are irradiated in 500 ml of ethanol. After an irradiation time of 20 minutes, a proportion of 72% previtamin D _{3 is obtained} in the isomer mixture. The transmission characteristic remained stable during the reaction period and only decreased by 0.5% after a six-hour photoreactor operating time at 296 nm.

Claims (1)

1. Light-stable filter solutions for the photoisomerization of 5.7-diene steroids of the formula I, vV ³ f wherein R ¹ Wassei fabric. Alkyl, acyl, Si (alkyl) ₃ R ^{2 is} hydrogen, OH, O acyl, OAlkyl, OSi (alkyl) ₃ R ^{3 is} -CH = CH-CH (CH ₃ ) -CH (CH ₃ ) ₂ , -CH ₂ -CH ₂ -CHR ⁴ -C (CH ₃ ) ₂ R ⁵ R ⁴ , R ^{5 are} hydrogen, OH, O acyl, OAlkyl, OSi (alkyl) ₃ R4_R5 -O ^ mean, characterized in that a combination of an aqueous or alcoholic / aqueous solution of Trimethincyaninsalzen of the general formulas Ii or III 2 R ' C
NH  z ' NH ⁺ X NH NH ⁺ X R5 (CH ₂ ) _n (CH ₂ ) n II Aryl aryl III with one or more compounds of the formulas IV, V or VI P ⁷ O NH-CR ⁸ COOH IV R ¹ , R ^{3 may be the} same or different and are hydrogen, alkyl, OAIkyl or aryl R ² . Hydrogen, alkyl or aryl R ⁴ , R ^{5 may be the} same or different and alkyl, aryl, or alkylene R ^{6 is} hydrogen or alkyl R ^{7 is} hydrogen or one or more branched or unbranched alkyl groups R ⁸ , R ^{9 is} alkyl or aryl X "halide, CIO ₄ ". NO ₃ ", V2 SO ₄ ² ", CH ₃ SO ₃ ", BF ₄ ", R ⁶ -C ₆ H ₄ -SO ₃ ", R 1 -C ₆ H ₄ -COO" η 1-6 mean and with non-absorbing metal salts in the spectral range 280-310 and 330-360 nm