Package for safe storage of electrophilic fluorinating agent

Details Package for safe storage of electrophilic fluorinating agent Package for safe storage of electrophilic fluorinating agent

1998-09-29

2002-04-02

Pyon, Harold (Department: 1772)

Stock material or miscellaneous articles

Hollow or container type article

Polymer or resin containing

C215S306000

Reexamination Certificate

active

06365246

ABSTRACT:

CROSS-REFERENCE TO RELATED APPLICATIONS
Not applicable.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
BACKGROUND OF THE INVENTION
There is a general need in the fluorination and pharmaceutical industry for a safe and efficient means of storing, transporting and delivering electrophilic fluorination agents primarily because of the sensitivity of these agents to thermal degradation and also due to slow loss of “F
+
” activity in the solid undiluted form at ambient conditions.
Presently, most if not all of these agents must be stored and transported under refrigerated conditions in order to avoid the serious complications that may arise if these materials would undergo self accelerating decomposition, i.e., a runaway self-propagating thermal decomposition, as well as to preserve both the quality of the “F
+
” component. Moreover, these materials are typically handled as solids, which is less preferable in the chemical processing industry than liquids handling.
There are a few literature citations wherein the thermal stability of electrophilic fluorination agents in solution is discussed. In R. E. Banks, M. K. Besheesh, S. N. Mohialdin-Khaffaf, and I. Sharif J. Chem. Soc., Perkin Tans. 1, 1996, 2069, it is noted that “a solution of F-TEDA-BF
4
(5.0 mmol) in boiling acetonitrile (50 cm
3
) loses less than 10% of its ‘F
+
’ transfer capability during 24 hours.” F-TEDA-BF
4
is 1-chloromethyl-4-fluoro-1,4-diazoniabicy,clo[2.2.2]octane bis(tetrafluoroborate) (also known as Selectfluor™ agent).
However, this is not unexpected since in G.S. Lal J. Org. Chem. 1993, 58, 2791, Lal describes numerous efficient fluorinations using F-TEDA-BF
4
in refluxing acetonitrile for 16 hour periods, producing very good yields of the expected fluorinated products.
In M. Zupan, J. Iskra, and S. Stavber Bull. Chem. Soc. Jpn. 1995, 68, 1655, Zupan et. al. make one general statement relating to this issue wherein they claim that they “studied the stability of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA, 1
a
) in methanol, water, and acetonitrile” and found “less than a three percent loss of activity occured after 24 h at room temperature.”
In a subsequent paper by Zupan et al., M. Zupan, M. Papez, and S. Stavber, J. Fluorine Chem. 1996, 78, 137, the reactions of three different N-F class fluorinating agents (including F-TEDA-BF
4
) with different solvents was studied, however incomplete or only partial data was given, and therefore, it is not possible to make quantitative conclusions based or this work. For F-TEDA-BF
4
they observed a loss of “F
+
” activity of 7% in methanol, 4% in water, acetonitrile, and ethanol, and 2% in isopropanol during a 24 hour period at room temperature.
If one assumes a constant rate of degradation or loss of “F
+
” activity of 4% per day, the data of Zupan et al. would suggest that the “F
+
” activity of an aqueous solution of Selectfluor™ agent would be depleted to 0.2% of its initial value in 154 days. Clearly, since in Example 1 we have shown that an aqueous solution of Selectfluor™ agent loses only 7-9.5% “F
+
” activity in a 154 day period, our results are unexpected.
According to the work of Zupan et. al. (second citation), at higher temperature (54° C.) the rate of loss of activity was significantly accelerated. While data at room temperature was reported for F-TEDA-BF
4
only, the stability of the two other compounds, 1-hydro(y-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (also known as Accufluor™ or NFTh) and N-fluorobis(phenylsulfonyl)amine (also known as NFSi) was only assessed at 54° C. and compared to F-TEDA-BF
4
under similar conditions. In protic solvents, water and alcohols, NFTh was found to be more stable than F-TEDA-BF
4
with respect to loss of “F
+
” activity. NFSi was reported to be “very stable” at 54° C.
The prior art has shown that electrophilic fluorinating agents have various stabilities in an array of solvent systems depending on the agent and the solvent. No general pattern regarding this stability or lack of stability has been suggested by the prior art regarding when such agents would be stable in a solvent and therefore desirable in a solvent. In contrast, in the present invention provides an economical means of safely “containing” or “packaging” these commercial electrophilic fluorination agents whereby these agents are readily stored, transported and delivered in a form which is readily and directly useable, i.e., in an appropriate amount of solution, in which the solution medium provides a tremendous safety margin for storage, transportation and delivery since the solution medium will be shown below to have an enormous ability to absorb heat (due to the latent heat of vaporization of the liquid) relative to the contained electrophilic fluorination agent across an array of agents and solvents, and in some instances such a package provides storage, transportation and delivery without loss of “F
+
” activity.
BRIEF SUMMARY OF THE INVENTION
The present invention is a package for the safe containment of a quaternary nitrogen electrophilic fluorination agent, comprising:
a) a container, having a least one sealable orifice, capable of containing the quaternary nitrogen electrophilic fluorination agent and a solvent in liquid phase under ambient conditions;
b) a quantity of the quaternary nitrogen electrophilic fluorination agent; and
c) a solvent, compatible with the quaternary nitrogen electrophilic fluorination agent, in sufficient quantity to absorb the heat of decomposition of the quantity of quaternary nitrogen electrophilic fluorination agent.
Preferably, the quaternary nitrogen electrophilic fluorination agent is selected from the group consisting of: 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate); 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane fluoride (tetrafluoroborate); 1-fluoro4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate); 1-fluoro-4-methyl-1,4-diazoniabicyclo[2-2-2]octane bis(tetrafluoroborate); 1-fluoro-quinuclidinium triflate; 1-fluoro-pyridinium pyridine heptafluorodiborate; 1-fluoro-pyridinium tetrafluoroborate; 1-fluoro-pyridinium triflate; 1-fluoro-2,6-dichloropyridiinium tetrafluoroborate; 1,1′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) and mixtures thereof.
Preferably, the solvent is water for non-pyridinium fluorinating agents. More preferably, the solvent includes an organic solvent. Still more preferably, the organic solvent is selected from the group consisting of: acetonitrile, propionitrile, methanol, ethanol, propanol, isopnrpanol, N,N-dimethylformamide, tetrahydrofuran, ethyl ether, aromatic hydrocarbon of C
u-v
, halogenated hydrocarbon of C
w-x
, and perfluorinated hydrocarbon of C
y-z
. For pyridinium based fluorinating agents the solvent is preferably an organic solvent.
Alternatively, the solvent is a mixture of acetonitrile and methanol.
In a preferred embodiment, the quaternary nitrogen electrophilic fluorination agent is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and the solvent is water. More preferably in this embodiment, the solvent is at least 30 wt. % water and an organic solvent selected from the group consisting of: acetonitrile; tetrahydrofuran; N,N-dimethylformamide and mixtures thereof.
Altematively, the quaternary nitrogen electrophilic fluorination agent is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and the solvent is acetonitrile and methanol.
In another alternative embodiment, the quaternary nitrogen electrophilic fluorination agent is 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and the solvent is water. More preferably, the solvent is at least 40 wt. % water, and an organic solvent selected from the group consisting of: acetonitrile; tetrahydrofuran; N,N-dirnethylformamide

Affiliated with

Also associated with

Rating

Package for safe storage of electrophilic fluorinating agent does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Package for safe storage of electrophilic fluorinating agent, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Package for safe storage of electrophilic fluorinating agent will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2827108