Chemistry: analytical and immunological testing – Condition responsive control
Patent
1995-12-05
1997-10-21
Snay, Jeffrey
Chemistry: analytical and immunological testing
Condition responsive control
73 2335, 73 2339, 95 88, 436124, 436126, 436161, 568683, G01N 3002
Patent
active
056795769
DESCRIPTION:
BRIEF SUMMARY
TECHNOLOGICAL FIELD
The present invention relates to a gas chromatographic analysis of impurities in fluoromethyl-1,1,1,3,3,3-hexafluoroisopropyl ether (hereinafter referred to as "SEVOFLURANE") that is used as a pharmaceutical(s) and an agricultural chemical(s) or intermediates of these and to a monitoring of impurities by a gas chromatograph in the production process of SEVOFLURANE and a process control based thereon.
BACKGROUND TECHNOLOGY
SEVOFLURANE can be produced in accordance with a production method described in U.S. Pat. No. 4,250,334. If there is collected a gas that is generated when 1,1,1,3,3,3-hexafluoroisopropyl alcohol (hereinafter referred to as "HFIP") is added dropwise to a heated reaction mixture comprising concentrated sulfuric acid, hydrogen fluoride and paraformaldehyde, the aimed SEVOFLURANE is recovered along with the non-reacted alcohol and organic by-products such as formal, acetal and the like, which have been formed as by-products. As is frequently seen in case that such a plurality of reactions, that is, fluorination and a reaction of ether bond's formation are conducted in one pot, extremely many isomers, the reaction products of disproportionation, and the like of small amounts are formed in this reaction system, too. Of these, most of the by-products can be virtually completely removed by water washing, alkali washing, distillation and the like. However, some compounds have boiling points which are nearly the same as that of SEVOFLURANE, or behaviors of azeotropy and the like. Therefore, SEVOFLURANE as a final product may be contaminated therewith. Therefore, in view of that SEVOFLURANE is used as an inhalation anesthetic, it is necessary to strictly identify the materials and to determine their contents.
Hitherto, for the purpose of quantitating fluorine-containing compounds of relatively low boiling point, a gas chromatograph has been used with selection of various columns. For example, packed columns having chlorotrifluoroethylene oligomer as the liquid phase, such as DAIFLOIL#50 and the like, have been used at a low temperature, or there have been used columns having a porous polystyrene resin as the fixed phase, such as PORAPAK Q and the like. However, they were not sufficient as a means of microanalysis that is required for impurities of pharmaceuticals. From a viewpoint of microanalysis, the use of capillary column is effective. However, in case that capillary columns having methyl silicone, phenyl silicone and the like as the fixed phase were used, it was impossible to get a sufficient degree of separation, with respect to by-products of low boiling point which cause problems particularly to SEVOFLURANE.
Furthermore, in the process management of reaction process, purification process and the like, the objects of analysis are not necessarily only samples containing only by-products having nearly the same boiling points. It is necessary to analyze at the same time high boiling point compounds such as non-reacted raw material and the like, too. However, the above-mentioned columns were not able to meet such requirements.
Furthermore, in the production of fluorine-containing organic compounds, hydrogen fluoride (HF) is frequently used as a fluorination agent of organic compounds. For example, there is disclosed in the specification of U.S. Pat. No. 4,766,260 (1988) that tetrahaloethylene and hydrogen fluoride are reacted together in the presence of a fluorinated alumina catalyst carrying thereon nickel and the like, at a temperature from 300.degree. C. to 450.degree. C., thereby producing 1,1,1-trifluorodichloroethane and 1,1,1,2-tetrafluorochloroethane.
In such a case, fluorine-containing organic compounds that are un-purified or in the reaction process are intended to be analyzed by a gas chromatograph, the column and the detector are corroded by hydrogen fluoride contained in the sample. In case that hydrogen fluoride is generated by the reaction between a fluorine-containing organic compound(s) and another compound, a similar problem may be caused.
By the way, it
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Kamakura Manami
Kawai Toshikazu
Watanabe Mineo
Yoshimura Takaaki
Central Glass Co. Ltd.
Ludlow Jan M.
Snay Jeffrey
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