JPS5892658A - Perfluoro compound - Google Patents

Abstract

NEW MATERIAL:A perfluoro compound shown by the formula (one or both of the ring A and ring B may be substituted with a lower perfluoroalkyl; l is 3 or 4; m+n is 2 or 3; R is lower perfluoroalkyl). EXAMPLE:Perfluoro-N-methylperhydroquinoline. USE:A blood substitute, an oxygen transporting component for oxygen transporting transfusion. PROCESS:Anhydrous hydrogen fluoride is blended with a perhydro compound in an electrolytic cell, dissolved, and electrolyzed (voltage of 3-9V, anodic electrolytic density of 1-100A/dcm<2>, at 4-10 deg.C, total electrolysis of 900-1,500Ahr), to give a compound shown by the formulaI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel perfluorinated compounds useful as blood substitutes, oxygen-carrying infusions, and oxygen-carrying infusions.

More specifically, the present invention relates to the general formula () (in which either or both rings A and B may be substituted with a lower perfluoroalkyl group, and jti3 or Fi4 'e% m 10 n refers to a perfluoro compound represented by 2 or 3, and R 0), which represents a lower perfluoroalkyl group.

Regarding general formula (I), tFis or a 4 t s g
r + n represents 2 or 3), therefore, ring A and ring B each represent a 5-membered ring or a 6-membered ring, and both form a fused ring.

Thus, the condensed ring formed by ring A and ring B is quinoline, isoquinoline, indole, isoindole, cyclopenta(b)virol, cyclopentaCC.
) Perfluoro tetramers such as pyrrole, pyringine, and isopyridine are mentioned. Regarding the general formula (I), the lower perfluoroalkyl group represented by R is a straight chain or branched one, such as a perfluoromethyl group, a perfluoromethyl group, Fluoroethyl group, perfluoro n-propyl group, perfluoro-1go flovyl group,
Examples include those having 1 to 4 carbon atoms, preferably those having 1 to 2 carbon atoms, such as the fluoro group, and the like. In addition to the substituents represented by R, one or more (preferably 1)
41t or 2) lower perfluoroalkyl groups. Examples of such substituents are the same as those exemplified for R as the lower perfluoroalkyl group in '.If two or more substituents are present, they may be different from each other.

The total number of carbon atoms in compound (I) is usually 8 to 12, preferably by fluorination. The fluorination method includes, for example, electrochemical fluorination method,
Examples include cobalt fluorination method and electrolytic fluorination method.

In order to produce the compound (I) of the present invention, it is preferable to carry out an electrolytic fluorination method, which involves, for example, mixing and dissolving anhydrous hydrogen fluoride and a perhydro compound as a raw material compound in an electrolytic bath, and then subjecting the mixture to electrolysis. 1 The voltage in the electrolysis is usually 3 to 9 V, and the anodic electrolysis density is usually 1
-100°C bath temperature is usually 4~10°C, and total electrolytic Fi9o.

~l 500 Ahr.

Since the compound (I) #i thus produced is insoluble in anhydrous hydrofluoric acid, it precipitates in the lower layer of the electrolytic cell.

For the isolation and purification of compound (I) from the mosquito sediment, for example, add an equal volume of an aqueous alkaline solution and an amine compound mixture to the collected sediment, reflux it, and then separate the compound (I) in the bottom layer. (When a partially fluorinated compound is separated into the amine layer), this is mixed with a suitable amount of potassium iodide-containing acetone,
? After washing with # solution to remove a compound in which 7 IJg atoms are bonded to a nitrogen atom, further fractional distillation is performed to obtain compound (I).
This is done by t-separation.

Compound (I) according to the present invention can be used in large amounts! I! For example, 5 to 50 w/v To% of compound (I) is preferably l, since it is able to dissolve S and is metabolically inert, and is rapidly excreted from the body.
It can be prepared as an aqueous emulsion containing 0 to 40 w/mSt.
It is used as a blood substitute for rats, guinea pigs, etc., and as an oxygen carrier for oxygen-carrying infusions.

In producing the above emulsion, a polymeric nonionic surfactant, phospholipid, etc. are used as the emulsifier.
The amount added varies from 1 to 5 v/m. In addition, a physiologically acceptable aqueous solution is used as the medium, and if necessary, an isotonizing amount of Grisecur's tonicity agent and colloid osmotic pressure. Plasma expanders such as HES, dextran, etc. may be added for adjustment.

The above-mentioned components are then processed, for example, by a high-pressure injection emulsifier to a particle size of 0.05 to 0.03μ, preferably 0.
．． An emulsion is prepared by homogenizing the emulsion to a particle size of 2μ or less.

The perhydro compound 'M corresponding to the starting material Compound (I) is actually a known compound.

Example 1 As an electrolytic cell, nickel (axiality 99.6 or more) electrode plates (anode The tank was equipped with a reflux condenser made of copper at the upper part of the tank, with highly effective anode surfaces; mlo and sam.

1.2 t of hydrogen heptadide was introduced into this electrolytic cell, and trace amounts of impurities (water and sulfuric acid) were removed by preliminary electrolysis. Next, 0.85 mol of N-methylperhydroquinoline (130
11) Helium gas dissolved in t-hydrogen fluoride at a flow rate of 1
The anode current density was 1.0 to 2.0 d/ml while passing from the bottom of the tank. OA/dlK", voltage 4°0~6.2
(ii) When the bath temperature is 4 to 10°C, the pP4 voltage is 9.
Next, perform l 051 Ahr electrolysis until reaching Ov.

Hydrogen fluoride company added 200d per 24 hours.

The gas generated during electrolysis was first passed through an iron pipe made of sodium fluoride pellets (1) to collect accompanying fluoride water (Xta), and then led to a trap cooled with dry ice and acetone where it was liquefied and collected.9.51 A colorless liquid was obtained. On the other hand, the bath solution in the electrolytic cell was divided into two layers, the upper layer was hydrogen heptadide and the lower layer was fluorocarbons, and when the lower layer was separated and weighed, it was found to be 2631.

Equal volumes of 70% KOH aqueous solution and diisobutylamine were added to the above-mentioned mixture of the cooled collection liquid of the generated gas and the lower liquid of the electrolytic cell, and reflux was performed for 7 days. After separating the perfluorinated substance with a separating funnel, it was washed with a 90% w/v acetone aqueous solution containing potassium iodide at 10 v/m, and then precision fractionation was performed using a precision fractionator equipped with a spinning band column. Perfluoro-N-methylperhydroquinoline 4
4II (yield 1oLs) (boiling point 150-155℃/76
0 wmHI)t-obtained. As a result of analysis of the compound by infrared absorption spectroscopy, F nuclear magnetic resonance spectroscopy, mass spectrometry, etc., it was confirmed that the target compound was perfluoro-N-methylperhydroquinoline.

Examples 2 to 97 Corresponding perfluoro compounds were obtained using perhydro compounds as raw materials in the same manner as in Example 1.

(Leaving space below) Procedural Amendment (Voluntary) January 11, 1980 1. Indication of the case 1988 Patent Application No. 191357 2. Name of the invention: Fluoro compound 3. Related Patent applicant 7, subject of amendment (1) General formula (2) on page 2 of the specification ``Perfluoron-n'' is written in the third line of page 3 of the Ministry 11 Corrected to ``r-barfluoro-n'' 0 ( 3) On page 3, line 4 of the same ministry, it says “r iao propyl”.
o-propyl”0 (4) All “groups, etc.” in the 5th line of page 3 of the same 4N
per-70 oro-180 butyl group, -(-fluoro-8e)
Correct it to "C-butyl group, per-70 oro-tert-butyl group, etc." 0 (5) In the 1st and 2nd lines from the bottom of page 3 of Houjo, it says "electrochemical fluorination method" [directly] □Tsu Correct to ``elimization method'' 0 (6) Correct to ``current'' on page 4, line 7 of the same ministry, which says ``l!Solution.''

(7) On page 4, line 7 of the Ministry of Finance, replace rloOJ with “300
” is corrected.

(8) On page 4, lines 8-9 of the same book, the text "is, and the total electrolysis is 900 to 1,500 Ahr." is corrected to "is." in purple.

(9) Purple "reflux" that says "reflux" on page 4, line 14 of the same book
Correct.

In the fourth line from the bottom of page 4 of the same book, the word ``chitsu cum'' is corrected to ``nitrogen''.

(11) The third line from the bottom of No. 5 of the same oath is rO, 03J, which is corrected to ro, 3J.

(2) On page 7, line 8 of the Ministry of Foreign Affairs, the word ``recirculation'' should be corrected to ``reflux''.゛U In the 4th line from the bottom of page 7 of the circular, the phrase ``mono de tsuku-'' is corrected to ``mono, par.''

Correct to 0 00 In the table on page 18 of the same book ``.

a certain meeting Correct to.

i4T correct 0

Claims (1)

[Claims] General formula (wherein, either or both of ring A and B11a may be substituted with a lower perfluoroalkyl group, L is 3 or 4t-1m+n is 2 or #13t -%R
Fi, a perfluoro compound represented by 0) representing a lower perfluoroalkyl group.