CA1156560A - Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantane - Google Patents
Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantaneInfo
- Publication number
- CA1156560A CA1156560A CA000378222A CA378222A CA1156560A CA 1156560 A CA1156560 A CA 1156560A CA 000378222 A CA000378222 A CA 000378222A CA 378222 A CA378222 A CA 378222A CA 1156560 A CA1156560 A CA 1156560A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- perfluoroadamantane
- solid component
- mixture
- hydropentadecafluoroadamantane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C23/00—Compounds containing at least one halogen atom bound to a ring other than a six-membered aromatic ring
- C07C23/18—Polycyclic halogenated hydrocarbons
- C07C23/20—Polycyclic halogenated hydrocarbons with condensed rings none of which is aromatic
- C07C23/38—Polycyclic halogenated hydrocarbons with condensed rings none of which is aromatic with three condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/20—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms
- C07C17/202—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction
- C07C17/208—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction the other compound being MX
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT
Perfluoroadamantane and l-hydropentadecafluoro-adamantane are prepared by perfluorinating adamantane and/or bromoadamantane by contacting CoF3 at an elevated temperature.
The fluoroadamantanes have utility as synthetic blood substitutes or perfusion media.
Perfluoroadamantane and l-hydropentadecafluoro-adamantane are prepared by perfluorinating adamantane and/or bromoadamantane by contacting CoF3 at an elevated temperature.
The fluoroadamantanes have utility as synthetic blood substitutes or perfusion media.
Description
BACKG~OUND OF THE INVENTION
, This invention relates to a process for preparing per1uoroadamantane and l-hydropentadecafluoroadamantane. More particularly, this invention relates to a process for converting adamantane or bromoadamantane to a mixture of perfluoroadaman-tane and l-hydropentadecafluoroadamantane. The mixture can have utility as a synthetic blood substitute and/or a perfusion medium.
N.J. Maraschin et al in J.A.C.S. 9?:3, 513-517 (Feb. 5, 1975) and G. Robertson et al in J. Organic Chemistry, Vol. 43, No. 26, 4981-4983 (1978) reports the preparation of l-hydropentadecafluoroadamantane from adamantane using elemental fluorine (-78C to room temperature) and requiring many hours.
However, 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 the 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 perfusion media. U.S. Patents Nos. 4,110,474 and 4,187,252 disclose that perfluorinated methylpentanes are useful as synthetic blood substitutes and/or perfusion media.
V.S. Patent 3,911,138 discloses that certain perfluorinated cyclic carbon compounds, when emulsified, can be used as blood substitutes.
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 l-hydropentadeca-fluoroadamantane would transpire from mice at a rate sub-11~6~60 stantially greater than when using e.g., perfluorodecalin, a fluorocarbon considered by those skilled in the art as being a very good blood suhstitute.
SUMMARY
The process of this invention comprises contacting adamantane, bromoadamantane or a mixture of the two with CoF3 at an elevated temperature. The process can be represented by the following reaction schemes:
H
CoF3 ~ ~ I
H
~ -Br 3 in which "F" designates perfluorination. In reaction II the bromide atom can be located on the adamantane nucleus at positions other than shown in scheme II above. Perfluoroad~ntane and l-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 fluorinating an adamantane selected from the group consisting of adamantane (CloH16)r bromoadamantane (C10H15Br), and a mixture of the two. The fluorinating involves contacting theadamantane with CoF3 at an elevated temperature. The products resulting from the fluorination of the adamantane include perfluoroadamantane and l-hydropentadecafluoroadamantane.
One embodiment of carrying out schemes I and II is as follows. The adamantane is charged into a preheater by means ofa Harvard infusion syringe pump. Since the feed adamantanes aresolid at ambient temperature the feed is first dissolved in 1156~60 a suitable solvent such as hexane, for ease of handling, however, such solvents are not required. The preheater is maintained at a temperature sufficiently high to vaporize the adamantane and solvent prior to entering a reactor. The reactor itself is a horizontal 3.5' x 3" 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 less zones can work equally well.
Preferably, the material is passed through the reactor two times. The first pass is made with the reactor temperatu~e 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., 235C to approximately 50C. above its boiling point. The second pass is made at considerably higher temperatures (approximately 100C. greater across the reactor) to complete the fluorination.
The product is removed from the reactor through traced lines into a series of traps varying in temperature from 0C to -78C 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 product 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 heretofore, the fluorination of the adamantane generally requires an elevated temperature which preferably exceeds the boiling point of the particular adamantane feed. Generally the fluorination 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 than that shown in aforementioned scheme II. While the structure in scheme II indicates the bromine atom is attached to a bridge-head 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 l-hydropenta-decafluoroadamantane are solid at ambient temperature. Thus the use of the aforementioned adamantanes as synthetic blood substitutes or perfusion media require 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 (l-methyl-4-isopropylcyclohexane), F-l-methyldecalin and F-alkyl adamantanes. The medical value of the afore-mentioned fluoroadamantanes lies in their ability to transport gases such as oxygen, carbon dioxide and carbon monoxide.
To further illustrate, the following examples are provided:
EXAMPLES
Five grams of solid adamantane (melting point 205C) were dissolved in 35 cc of liquid methylcyclohexane. Other suitable solvents include cyclohexane, dimethyl cyclohexane and the like. The resulting solution was pumped at 0.25 cc/min through the aforedescribed horizontal CoF3 bed whlch was thermally graded from 240C to 275C between the inlet and 1 15656o outlet respecti~ely. 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 250C to 300C.
The crude product weighed 25 g. Gas chromatographic analysis, IR, mass spec, and 19 FNMR showed this product to be a mixture of l-hydropentadecafluoroadamantane and perfluoroadamantane. Both are solids at ambient temperature.
The foregoing procedure was repeated using 10 grams of bromoadamantane ~melting point 116C) dissolved in 15 cc of n-hexane. The temperature of the reactor during the first pass was from 240C to 275C, while during the second pass it was from 250C to 325C. The crude product weighed 8.5 g. Analyses showed the product to be a mixture of l-hydropentadecafluoro-adamantane (90-92 wt. %) and perfluoroadamantane (8-10 wt. %).
The two materials were separated using a 300 ft. capillary (3 wt.
% hexadecane on Kel F polymer).
The resulting product mixture of l-hydropenta-decafluoroadamantane and perfluoroadamantane, 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.
, This invention relates to a process for preparing per1uoroadamantane and l-hydropentadecafluoroadamantane. More particularly, this invention relates to a process for converting adamantane or bromoadamantane to a mixture of perfluoroadaman-tane and l-hydropentadecafluoroadamantane. The mixture can have utility as a synthetic blood substitute and/or a perfusion medium.
N.J. Maraschin et al in J.A.C.S. 9?:3, 513-517 (Feb. 5, 1975) and G. Robertson et al in J. Organic Chemistry, Vol. 43, No. 26, 4981-4983 (1978) reports the preparation of l-hydropentadecafluoroadamantane from adamantane using elemental fluorine (-78C to room temperature) and requiring many hours.
However, 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 the 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 perfusion media. U.S. Patents Nos. 4,110,474 and 4,187,252 disclose that perfluorinated methylpentanes are useful as synthetic blood substitutes and/or perfusion media.
V.S. Patent 3,911,138 discloses that certain perfluorinated cyclic carbon compounds, when emulsified, can be used as blood substitutes.
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 l-hydropentadeca-fluoroadamantane would transpire from mice at a rate sub-11~6~60 stantially greater than when using e.g., perfluorodecalin, a fluorocarbon considered by those skilled in the art as being a very good blood suhstitute.
SUMMARY
The process of this invention comprises contacting adamantane, bromoadamantane or a mixture of the two with CoF3 at an elevated temperature. The process can be represented by the following reaction schemes:
H
CoF3 ~ ~ I
H
~ -Br 3 in which "F" designates perfluorination. In reaction II the bromide atom can be located on the adamantane nucleus at positions other than shown in scheme II above. Perfluoroad~ntane and l-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 fluorinating an adamantane selected from the group consisting of adamantane (CloH16)r bromoadamantane (C10H15Br), and a mixture of the two. The fluorinating involves contacting theadamantane with CoF3 at an elevated temperature. The products resulting from the fluorination of the adamantane include perfluoroadamantane and l-hydropentadecafluoroadamantane.
One embodiment of carrying out schemes I and II is as follows. The adamantane is charged into a preheater by means ofa Harvard infusion syringe pump. Since the feed adamantanes aresolid at ambient temperature the feed is first dissolved in 1156~60 a suitable solvent such as hexane, for ease of handling, however, such solvents are not required. The preheater is maintained at a temperature sufficiently high to vaporize the adamantane and solvent prior to entering a reactor. The reactor itself is a horizontal 3.5' x 3" 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 less zones can work equally well.
Preferably, the material is passed through the reactor two times. The first pass is made with the reactor temperatu~e 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., 235C to approximately 50C. above its boiling point. The second pass is made at considerably higher temperatures (approximately 100C. greater across the reactor) to complete the fluorination.
The product is removed from the reactor through traced lines into a series of traps varying in temperature from 0C to -78C 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 product 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 heretofore, the fluorination of the adamantane generally requires an elevated temperature which preferably exceeds the boiling point of the particular adamantane feed. Generally the fluorination 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 than that shown in aforementioned scheme II. While the structure in scheme II indicates the bromine atom is attached to a bridge-head 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 l-hydropenta-decafluoroadamantane are solid at ambient temperature. Thus the use of the aforementioned adamantanes as synthetic blood substitutes or perfusion media require 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 (l-methyl-4-isopropylcyclohexane), F-l-methyldecalin and F-alkyl adamantanes. The medical value of the afore-mentioned fluoroadamantanes lies in their ability to transport gases such as oxygen, carbon dioxide and carbon monoxide.
To further illustrate, the following examples are provided:
EXAMPLES
Five grams of solid adamantane (melting point 205C) were dissolved in 35 cc of liquid methylcyclohexane. Other suitable solvents include cyclohexane, dimethyl cyclohexane and the like. The resulting solution was pumped at 0.25 cc/min through the aforedescribed horizontal CoF3 bed whlch was thermally graded from 240C to 275C between the inlet and 1 15656o outlet respecti~ely. 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 250C to 300C.
The crude product weighed 25 g. Gas chromatographic analysis, IR, mass spec, and 19 FNMR showed this product to be a mixture of l-hydropentadecafluoroadamantane and perfluoroadamantane. Both are solids at ambient temperature.
The foregoing procedure was repeated using 10 grams of bromoadamantane ~melting point 116C) dissolved in 15 cc of n-hexane. The temperature of the reactor during the first pass was from 240C to 275C, while during the second pass it was from 250C to 325C. The crude product weighed 8.5 g. Analyses showed the product to be a mixture of l-hydropentadecafluoro-adamantane (90-92 wt. %) and perfluoroadamantane (8-10 wt. %).
The two materials were separated using a 300 ft. capillary (3 wt.
% hexadecane on Kel F polymer).
The resulting product mixture of l-hydropenta-decafluoroadamantane and perfluoroadamantane, 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 (9)
1. A liquid composition, useful as a synthetic blood substitute or a perfusion medium, comprising a normally solid component selected from the group consisting of perfluoro-adamantane, l-hydropentadecafluoroadamantane and a mixture of the two, and which solid component is dissolved in a suitable liquid perfluorocarbon.
2. The composition of Claim 1 wherein the solid component is said mixture of perfluoroadamantane and l-hydro-pentadecafluoroadamantane.
3. The composition of Claim 1 additionally containing water and a surfactant in amounts effective to emulsify said solid component and liquid perfluorocarbon.
4. The composition of Claim 3 wherein the solid component is a mixture of perfluoroadamantane and l-hydro-pentadecafluoroadamantane.
5. The composition of Claim 3 wherein the solid component is perfluoroadamantane.
6. The composition of Claim 3 wherein the solid component is l-hydropentadecafluoroadamantane.
7. The composition of Claim 1 wherein the liquid perfluorocarbon is selected from F-decalin, F-tricyclo[5.2.1.02,6]
decane, F-menthane, F-l-methyldecalin and F-alkyl adamantanes.
decane, F-menthane, F-l-methyldecalin and F-alkyl adamantanes.
8. The composition of Claim 3 wherein the solid component is a mixture of perfluoroadamantane and l-hydro-pentadecafluoroadamantane, and the liquid perfluorocarbon is selected from F-decalin, F-tricyclo [5.2.1.02,6] decane, F-menthane, F-l-methyldecalin and F-alkyl adamantanes.
9. The composition of Claim 4 wherein the mixture contains 8-10 wt. % perfluoroadamantane and 90-92 wt. % l-hydropentadecafluoroadamantane, and the liquid perfluorocarbon is F-decalin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16590280A | 1980-07-03 | 1980-07-03 | |
| US165,902 | 1980-07-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1156560A true CA1156560A (en) | 1983-11-08 |
Family
ID=22600948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000378222A Expired CA1156560A (en) | 1980-07-03 | 1981-05-25 | Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantane |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA1156560A (en) |
| GB (1) | GB2079273B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4402984A (en) * | 1980-07-03 | 1983-09-06 | Sun Tech, Inc. | Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantane |
| US4868318A (en) * | 1985-02-01 | 1989-09-19 | The Green Cross Corporation | Perfluoro chemicals and polyfluorinated compounds |
| US4686024A (en) * | 1985-02-01 | 1987-08-11 | The Green Cross Corporation | Novel perfluoro chemicals and polyfluorinated compounds and process for production of the same |
-
1981
- 1981-05-25 CA CA000378222A patent/CA1156560A/en not_active Expired
- 1981-06-05 GB GB8117244A patent/GB2079273B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2079273A (en) | 1982-01-20 |
| GB2079273B (en) | 1984-03-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3258500A (en) | Process for fluorinating halohydro-carbons | |
| AU634514B2 (en) | Processes using aluminum fluoride catalyst compositions for preparing 1,1-dichloro-1,2,2,2-tetrafluoroethane | |
| DE69400036T2 (en) | Purification of pentafluoroethane. | |
| US2992276A (en) | Process for preparing polyfluoro alkyl compounds | |
| US3480667A (en) | Method of producing fluorinated compounds | |
| EP0489773B1 (en) | Process for separating mixtures of partially fluorinated or perfluorinated hydrocarbon compounds | |
| US4402984A (en) | Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantane | |
| US5689019A (en) | Manufacturing method for 1,1,1,2,3,3,3-heptafluoropropane | |
| CA1156560A (en) | Preparation of 1-hydropentadecafluoroadamantane and perfluoroadamantane | |
| DE19654720C2 (en) | Process for the production of hexafluoroethane | |
| JPS625932A (en) | Fluorohalo ethers and manufacture | |
| Sato | Studies on l-Alkenyl Isocyanates and Their Derivatives1 | |
| Adcock et al. | Successful direct fluorination of oxygen-containing hydrocarbons | |
| US4769184A (en) | Process for producing carbonyl fluoride compound | |
| US2487820A (en) | Fluorination of fused-ring hydrocarbons with lead tetrafluoride | |
| US2493008A (en) | Fluorination of saturated halocarbons with cerium tetrafluoride | |
| US3226448A (en) | Preparation of fluorine compounds | |
| US3897478A (en) | Continuous process for the manufacture of alkyl chrysanthemate esters | |
| US3123571A (en) | Di-akene metal catalysts | |
| Durrell et al. | Polymers of fluorocarbon ethers and sulfides. I. Trifluoromethyl trifluorovinyl ether and sulfide | |
| CA2096898A1 (en) | Process for the preparation of hydrofluorocarbons | |
| US4225404A (en) | Perfluoroolefin and perfluoroparaffin mixture and process for making same | |
| US3235561A (en) | Method for preparing perfluoro-(n-methyl pyrrolidine) | |
| US3654369A (en) | Fluorination process for preparing certain difluoramino compounds | |
| US4220606A (en) | Cyclic hydrocarbon perfluorination process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |