GB2079273A - Preparation of 1-Hydropentadecafluoroadamantane and Perfluoroadamantane - Google Patents

Abstract

Perfluoroadamantane and 1- hydropentadecafluoro-adamantane are prepared by perfluorinating adamantane and/or bromoadamantane by contact with CoF3 at an elevated temperature. The fluoroadamantanes have utility as synthetic blood substitutes or perfusion media.

Description

SPECIFICATION Preparation of 1 Hydropentadecafluoroadamantane and Perfluoroadamantane Backgroumd of the Invention This invention relates to a process for preparing perfluoroadamantane and 1hydropentadecafluoroadamantane. More particularly, this invention relates to a process for converting adamantane or bromoadamantane to a mixture of perfluoroadamantane and 1hydropentadecafluoroadamantane. The mixture can have utility as a synthetic blood substitute and/or a perfusion medium.

N.J. Maraschin eft at in J.A.C.S. 97:3,513- 517 (Feb. 5, 1975) and G. Roberston et al in J.

Organic Chemistry, Vol 43, No. 26, 4981-4983 (1978) report the preparation of 1hydropentadecafluoroadamantane from adamantane using elemental fluorine (78OC to room temperature) and requiring many hours.

However, the use of fluorine and a low temperature is not a viable commercial method for preparing large quantities in a short period.

Other processes involving perfluorination of cyclic hydrocarbons using CoF3 are disclosed in U.S. Patents Nos. 4,143,079 and 4,105,798.

These patents also disclose the use of perfluorinated cyclic carbon compounds as synthetic blood substitutes or prefusion media.

U.S. Patents Nos. 4,110,474 and 4,187,252 disclose that perfluorinated methylpentanes are useful as synthetic blood substitutes and/or prefusion media. U.S. Patent No.3,911,138 discloses that certain perfluorinated cyclic carbon compounds, when emulsified, can be used as blood substitutes. The five aforementioned U.S.

patents ure incorporated herein by reference.

However, none of the foregoing art suggests that it would be possible to perfluorinate adamantane or bromoadamantane over CoF3 without experiencing ring openings, or that the resulting mixture of perfluoroadamantane and 1hydropentadecafluoroadamantane would transpire from mice at a rate substantially greater than when using, e.g., perfluorodecalin, a fluorocarbon considered by those skilled in the art as being a very good blood substitute.

Summary The process of this invention comprises contacting adamantane or bromoadamantane, or a mixture of the two, with CoF3 at an elevated temperature. The process can be represented by the following reaction schemes:

in which "F" designates perfluorination. In reaction II, the bromine atom can be located on the adamantane nucleus at positions other than shown in scheme 11 above. Perfluoroadamantane and 1 -hydropentadecafluoroadamantane are useful as a synthetic blood substitute or a perfusion medium.

Description of the Invention The process of this invention is for the preparation of a perfluoroadamantane, and comprises perfluorinating an adamantane selected from the group consisting of adamantane (C10H16), bromoadamantane (CrOHr5Br), and a mixture of the two. The perfluorinating involves contacting the adamantane with CoF3 at an elevated temperature. The products resulting from the perfluorination of the adamantane include perfluoroadamantane and 1hydropentadecafluoroadamantane.

One embodiment of a process for carrying out schemes I and 11 is as follows. The adamantane is charged into a preheater by means of a Harvard infusion syringe pump. Since the feed adamantanes are solid at ambient temperature, the feed is generally first dissolved in a suitable solvent such as hexane, for ease of handling; however, such solvents are not essential. The preheater is maintained at a temperature sufficiently high to vaporise the adamantane and the solvent if any, prior to entry into a reactor. The reactor itself is a horizontal 3.5'x3" I.D. monel tube containing 3500 gms of CoF3 which is stirred by a series of paddles connected to a central shaft. The reactor is divided into four separate heating zones to allow it to be thermally graduated More or fewer zones can work equally well.

Preferably, the material is passed through the reactor twice. The first pass is made with the reactor temperatures somewhat above the estimated boiling points of the materials being charged. As fluorination takes place, the boiling point of the product increases until 50% of the hydrogens have been replaced. Further fluorination causes a decrease in the boiling point of the product. The first pass is generally made at a moderate charge rate, desirably at a rate of 0.25 cc/min, with the reactor thermally graduated from just above the boiling point of the adamantane charge material, i.e., 2350C. to approximately 500C. above its boiling point. The second pass is made at considerably higher temperatures (approximately 1000C, greater across the reactor), to complete the perfluorination.

The product is removed from the reactor through traced lines into a series of traps varying in temperature from OOC. to -780C, which are designed not only to remove product but also HF and other gaseous products. A 3 to 4 hour nitrogen purge is required to remove all products from the reactor.

The CoF3 used in the reaction can be regenerated by the technique disclosed in the aforementioned U.S. Patent No. 4,143,079.

As indicated above, the perfluorination of the adamantane generally requires an elevated temperature which preferably exceeds the boiling point of the particular adamantane feed.

Generally, the perfluorination will be at atmospheric pressure; however, if a lower pressure is used then a lower elevated temperature can be used.

As indicated previously, the bromine atom can be located on the adamantane nucleus at positions other then that shown in the aforementioned scheme II. While the structure in scheme 11 indicates that the bromine atom is attached to a bridgehead carbon atom at position 1, other locations for the attachment will yield similar results. However, attachment of the bromine atom to a bridgehead carbon atom is preferred.

Both the perfluoroadamantane and the 1hydropentadecafluoroadamantane are solid at ambient temperature. Thus, the use of the aforementioned adamantanes as synthetic blood substitutes or prefusion media requires that the adamantanes be dissolved in a suitable liquid fluorocarbon, examples of which include F decalin. F-tricyclo[5.2.1 .02.6] decane, F-menthane (1-methyl, 4 isopropyl cyclohexane), F-1 - methyldecalin and F-alkyl adamantanes. The medical value of the aforementioned fluorocarbons lies in their ability to transport gases such as oxygen, carbon dioxide and carbon monoxide.

The following examples are provided by way of further illusiration: Example 1 Five grams of solid adamantane (melting point 2050C) were dissolved in 35 cc of liquid methylcyclohexane. Other suitable solvents include cyclohexane and dimethyl cyclohexane, for example. The resulting solution was pumped at 0.25 cc/min through the aforedescribed horizontal CoF3 bed, which was thermally graded from 2400C to 2750C between the inlet and outlet, respectively. The resulting product was water washed to remove hydrofluoric acid and then dried. The dried product was then passed through the same reactor at a rate of 0.25 cc/min for a second time at a temperature varying from 2500C to 3000C. The crude product weighed 259.Gas chromatographic analysis, IR, mass spec, and 19 9 FNMR showed this product to be a mixture of 1 -hydropentadecafluoroadamantane and perfluoroadamantane. Both are solids at ambient temperature.

Example 2 The procedure of Example 1 was repeated using 10 grams of bromoadamantane (melting point 11 60C) dissolved in 1 5 cc of n-hexane. The temperature of the reactor during the first pass was from 2400C to 2750C, while during the second pass it was from 2500C to 3250C. The crude product weighed 8.59. Analyses showed the product to be a mixture of 1 hydropentadecafluoroadamantane (90--92 wt.

%) and perfluoroadamantane (8-1 0 wt. %). The two materials were separated using a 300 ft.

capillary (3 wt.% hexadecane on Kel F polymer).

Example 3 The product mixture of 1-hydro pentadecafluoroadamantane and perfluoro adamantane, dissolved in, e.g. F-decalin and mixed with other suitable components, i.e., water and a surfactant, to form a suitable emulsion, was injected intraperitoneally into mice.

The fluoroadamantanes were found to transpire from the bodies of the mice at a rate substantially greater than that obtained using perfluorodecalin in an emulsion.

Claims (7)

Claims

1. A process for the preparation of a perfluoroadamanatane comprising: perfluorinating an adamantane selected from the group consisting of adamantane, bromoadamantane, and a mixture of the two, by contacting it with CoF3 at an elevated temperature.

2. A process according to Claim 1 , wherein the temperature is higher than 225 CC. -

3. A process according to Claim 1 , wherein the products are perfluoroadamantane and 1hydropentadecafluoroadamantane.

4. A process according to Claim 3, wherein the products are separated.

5. A liquid mixture, useful as a synthetic blood substitute or a perfusion medium, comprising a perfluoroadamantane selected from the group consisting of perfluoroadamantane, 1 hydropentadecafluoroadamantane, and a mixture of the two, and which perfluoroadamantane is dissolved in a suitable liquid perfluorocarbon.

6. A mixture comprising perfluoroadamantane and 1 -hydropentadecafluoroadamantane.

7. A process according to claim 1 substantially as herein described with reference to Examples 1 or2.