U.S. patent application number 09/812514 was filed with the patent office on 2002-02-28 for process for the preparation of derivatives of octafluoro-[2,2]paracylophan- e.
Invention is credited to Dolbier, William R. JR., Duan, Jian-Xin, Roche, Alex J..
Application Number | 20020026086 09/812514 |
Document ID | / |
Family ID | 26886435 |
Filed Date | 2002-02-28 |
United States Patent
Application |
20020026086 |
Kind Code |
A1 |
Dolbier, William R. JR. ; et
al. |
February 28, 2002 |
Process for the preparation of derivatives of
octafluoro-[2,2]paracylophan- e
Abstract
Processes for the preparation of parylene dimers, and more
particularly to processes for the preparation of derivatives of
octafluoro-[2,2] paracylophane, otherwise known as AF4.
Inventors: |
Dolbier, William R. JR.;
(Gainesville, FL) ; Duan, Jian-Xin; (Gainesville,
FL) ; Roche, Alex J.; (Haddonfield, NJ) |
Correspondence
Address: |
MINTZ, LEVIN, COHN, FERRIS,
GLOVSKY and POPEO, P.C.
One Financial Center
Boston
MA
02111
US
|
Family ID: |
26886435 |
Appl. No.: |
09/812514 |
Filed: |
March 20, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60190778 |
Mar 20, 2000 |
|
|
|
Current U.S.
Class: |
570/151 |
Current CPC
Class: |
C07C 209/365 20130101;
C07C 211/61 20130101; C07B 2200/07 20130101; C07C 17/263 20130101;
C07C 17/12 20130101; C07C 17/12 20130101; C07C 25/22 20130101; C07C
17/093 20130101; C07C 25/22 20130101; C07C 23/18 20130101; C07C
23/18 20130101; C07C 23/18 20130101; C07C 25/22 20130101; C07C
211/61 20130101; C07C 205/12 20130101; C07C 201/08 20130101; C07C
2603/92 20170501; C07C 209/365 20130101; C07C 17/23 20130101; C07C
17/23 20130101; C07C 201/08 20130101; C07C 17/093 20130101; C07C
17/263 20130101; C07C 17/32 20130101; C07C 17/32 20130101 |
Class at
Publication: |
570/151 |
International
Class: |
C07C 025/22 |
Claims
What is claimed is:
1. A process for the preparation of derivatives of octafluoro-[2,2]
paracyclophane, which comprises the steps of: reacting
octafluoro-[2,2] paracyclophane with a nitronium reagent to provide
dinitro octafluoro-[2,2] paracylophane isomers; reducing said
dinitro octafluoro-[2,2] paracylophane isomers by reacting the
dinitro octafluoro-[2,2] paracyclophane isomers with iron powder in
concentrated hydrochloric acid to provide pseudo-meta, pseudo-para
and pseudo ortho isomers of diamino octafluoro-[2,2] paracyclophane
in good yield; and reacting said diamino octafluoro-[2,2]
paracylophane isomers with an aqueous halogen solution to provide
pseudo-meta, pseudo-para and pseudo ortho isomers of hetero-annular
dihalo-octafluoro-[2,2] paracylophane in good yield.
2. The process as recited in claim 1, wherein the step of reacting
said dinitro octafluoro-[2,2] paracylophane isomers exist as
pseudo-meta, pseudo-para and pseudo-ortho isomers.
3. The process as recited in claim 2, wherein said dinitro
octafluoro-[2,2] paracylophane isomers are formed in a 1:1:1
ratio.
4. The process of claim 1, wherein the dihalo-octafluoro-[2,2]
paracylophane isomers formed in the second reacting step comprise
dibromo-octafluoro-[2,2] paracylophane and diiodo-octafluoro-[2,2]
paracylophane isomers.
5. The process of claim 1, wherein diamino octafluoro-[2,2]
paracylophane isomers were prepared in isolated yields of from
82-84%.
6. The process of claim 4, wherein the dibromo-octafluoro[2,2]
paracylophane and diiodo-octafluoro-[2,2] paracylophane isomers
were prepared in isolated yields of from 60-78%.
7. The process of claim 1, wherein said nitration agent consists of
5 equivalents of NO.sub.2PF.sub.4 in sulpholane at 80.degree.
C.
8. Isomeric derivatives of octafluoro-[2,2] paracyclophase, having
the structures: 20wherein X.dbd.NH.sub.2, Br, or I.
9. The isomeric derivatives according to claim 8, wherein X is
NH.sub.2.
10. The isomeric derivatives according to claim 8, wherein X is
Br.
11. The isomeric derivatives according to claim 8, wherein X is
I.
12. The isomeric derivatives according to claim 9, wherein said
isomeric derivatives are formed by reacting octafluoro-[2,2]
paracyclophane with a nitronium reagent to provide dinitro
octafluoro-[2,2] paracylophane isomers; reducing said mononitro
octafluoro-[2,2] paracylophane by reacting the dinitro
octafluoro-[2,2] paracyclophane with iron powder in concentrated
hydrochloric acid to provide hetero-annular isomeric diamino
octafluoro-[2,2] paracyclophane products.
13. The isomeric derivatives according to claim 12, wherein said
diamino octafluoro-[2,2] paracyclophane products are formed in a
1:1:1 ratio.
14. The isomeric derivatives according to claim 13, wherein said
diamino octafluoro-[2,2] paracyclophane products are reacted with
an aqueous halogen solution to provide homo-annular
dihalo-octafiluoro-[2,2] paracylophane isomers in high yields.
15. The isomeric derivatives according to claim 8, wherein said
derivatives exist as pseudo-meta, pseudo-para and pseudo-ortho
isomers.
16. The isomeric derivatives according to claim 8, for use as
versatile precursors for the production of novel homo- and
hetero-annular disubstituted octafluoro-[2,2] paracylcophane
derivatives.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to processes for the
preparation of parylene dimers, and more particularly to processes
for the preparation of derivatives of octafluoro-[2,2]
paracylophane, otherwise known as AF4.
BACKGROUND AND SUMMARY OF THE INVENTION
[0002] Parylene is a generic term used to describe a class of
poly-p-xylylenes which are derived from a dimer having the
structure: 1
[0003] wherein X is typically a hydrogen, or a halogen. The most
commonly used forms of parylene dimers include the following: 2
[0004] Parylene coatings are obtained from parylene dimers by means
of a well-known vapor deposition process in which the dimer is
vaporized, pyrolized, i.e. cleaved into a monomer vapor for, and
fed to a vacuum chamber wherein the monomer molecules polymerize,
and deposit onto a substrate disposed within the vacuum
chamber.
[0005] Due to their ability to provide thin films and conform to
substrates of varied geometric shapes, parylene materials are
ideally suited for use as a conformal coating in a wide variety of
fields, such as for example, in the electronics, automotive, and
medical industries.
[0006] Parylene polymers are usually formed by chemical vapor
deposition (CVD) processes. One such process is the Gorham process
in which a parylene dimer having the molecular structure: 3
[0007] is vaporized and the dimer bonds are then cleaved to yield
parylene monomers. The parylene monomers are deposited onto a
surface and subsequently polymerized. Because the dielectric
constant and melting temperature of parylene polymers usually
increases as the number of fluorine atoms within the polymer
increases, it is desirable to use octafluoro-[2,2] paracylcophane
(AF4).
[0008] Octafluoro- [2,2] paracyclophane, more precisely
1,1,2,2,9,9,10,10-Octafluoro-[2,2] paracyclophane, and more
commonly referred to in the industry as AF4, is a fluorine
substituted version of the above-noted dimers and has the
structure: 4
[0009] It is known that parylene coatings (Parylene AF.sub.4) which
are derived from the AF.sub.4 dimer by the vapor deposition process
have a very high melting temperature (about 540.degree. C.), and a
low dielectric constant (about 2.3). These characteristics make
Parylene AF.sub.4 ideally suited for many high temperature
applications, including electronic applications, and potentially as
an inter-layer dielectric material for the production of
semiconductor chips. However, up to the present time, AF4,which is
used as the dimer starting material for depositing Parylene F
coatings, has been commercially unavailable due to high costs of
production. Both OFP and AF4 are used interchangeably herein and
are intended to refer to the same compound.
[0010] One known method of producing AF4 is described in U.S. Pat.
No. 5,210,341 wherein the process of preparing AF4 utilizes a low
temperature in conjunction with a reduced form of titanium in order
to produce dimerization of dihalide monomers. One aspect of the
'341 patent provides a process for preparing octafluoro-[2,2]
paracyclophane, which comprises contacting a
dihalo-tetrafluoro-p-xylylene with an effective amount of a
reducing agent comprising a reduced form of titanium and an organic
solvent at conditions effective to promote the formation of a
reaction product comprising octafluoro-[2,2] paracyclophane.
[0011] While the process described in the '341 patent is effective
for its intended purpose, it has been found that the process is
still too expensive for commercial realization due to low yields,
that there are some impurities in the AF4 dimer, and furthermore
that it would be difficult to adapt to a large scale commercial
production.
[0012] TFPX-dichloride having the following structure: 5
[0013] is another preferred starting material for the preparation
of AF4. Heretofore, the only useful preparation of TFPX-dichloride
has been via a high yield, photo-induced chlorination of
.alpha.,.alpha.,.alpha.',.alpha- .'-tetrafluoro-p-xylene
(hereinafter "TFPX") having the molecular structure: 6
[0014] The conventional procedure for synthesizing TFPX involves
the fluorination of terephthaldehyde, which has the molecular
structure: 7
[0015] SF.sub.4 and MoF.sub.6 are the most commonly used reagents
for terephFthaldehyde fluorination. However, SF.sub.4 and MoF.sub.6
are expensive, reducing the industrial utility of this synthetic
scheme. In addition, SF.sub.4 and MoF.sub.6 are toxic materials, so
a large amount of hazardous waste is produced using these
reagents.
[0016] Russian patent 2,032,654 discloses an alternative method of
synthesizing TFPX in which
.alpha.,.alpha.,.alpha.',.alpha.'-tetrabromo-p- -xylene
(hereinafter "TBPX") having the molecular structure: 8
[0017] is reacted with SbF.sub.3 to produce TFPX. This method
employs the well established electrophilic catalyzed S.sub.N1
reaction mechanism for replacement of benzylic halogen atoms of the
TFPX with fluorine atoms. According to this method, the anitmony in
SbF.sub.3 acts as an elctrophile which removes bromine from TBPX to
form a carbocation. The carbocation subsequently reacts with
fluorine to form TFPX. While this reaction is reported to provide
good yield when carried out under comparatively mild reaction
conditions, antimony containing compounds are highly toxic and
explosive. Furthermore, the SbF.sub.3 is used in a stoichiometric
amount rather than a catalytic amount, resulting in large
quantities of hazardous waste materials. This method of
synthesizing TFPX thus has limited use for industrial
applications.
[0018] AF4 is a member of the class of paracyclopenones.
Paracyclophenone (PCP) chemistry has grown considerably since the
isolation of the parent compound in 1949. Braun et al., NATURE
(1949) 164, 915. Besides finding commercial application as monomers
for the parylene type polymers, these molecules have spawned an
unusual and unique chemistry. The close proximity of the
face-to-face aromatic rings, coupled with the rigid skeleton and
high strain energy translates into such effects as trans-annular
interactions, thermal racemization and isomerism, surprising
directing effects in multiple electrophilic substitution and
unusual spectroscopic phenomena. The use of ring-substituted [2,2]
PCP skeletons as chiral backbones is of considerable current
interest. Highly fluorinated cyclophanes on the other hand, have
received much less attention, even though these compounds have
desirable industrial properties and should at least display as
equally rich a chemistry as their hydrocarbon counterparts. This
imbalance is being redressed following the syntheses of the bridge
fluorinated cyle 1,1,2,2,9,9,10,10 octafluoro[2,2] paracyclophane
(abbreviated as OFP, and more commonly referred to in the industry
as AF4) that have been reported previously.
[0019] Two complementary synthetic methods for the introduction of
two substituents into the rings of octaflouroparayclophane have
thus been developed. Nitration gives three isomers with the nitro
functionalities in different rings, oriented pseudo meta, pseudo
para and pseudo ortho. Bromination on the other hand gives a
dibromide where both halogens are in the same ring, para to each
other. All such products serve as versatile starting materials for
the preparation of a variety of novel homo- and hetero-annular
disubstitututed OFP derivatives. The compounds synthesized have
also been found to be precursors of a variety of other
disubstituted OFP derivatives. The synthesis, characterization and
thermal isomerization of a variety of both homo- and
hetero-annularly disubstituted OFP derivatives has also been
developed and described.
[0020] The instant invention provides improved processes for the
preparation of octafluoro-[2,2] paracyclophane which involve
contacting a OFP with dry nitrogen, nitronium tetrafluoroborate
dissolved in sulphophane to provide pseudo meta-, pseudo para-, and
pseudo ortho- dinitro-1,1,2,2,9,9,10,10-octafluoroparacyclophanes.
Reduction of these three products using iron powder/concentrated
hydrochloric acid provided the corresponding diamino products in
good isolated yields. The three diamino products proved to be
versatile starting materials for further transformations by
reacting with an aqueous solution of copper (I) bromide and
hydrobromic acid or an aqueous solution of potassium iodide to
provide three isomeric dibromo and diiodo-OFP derivatives in good
yield.
[0021] Accordingly, among the objects of the instant invention are:
the provision of improved processes for the preparation of
octafluoro-[2,2] paracyclophane; and more specifically, the
provision of improved processes for the preparation of
octafluoro-[2,2] paracyclophane from novel OFP precursor
derivatives.
[0022] Other objects, features and advantages of the invention
shall become apparent as the detailed description thereof
proceeds.
DETAILED DESCRIPTION OF THE INVENTION
[0023] The present invention relates to highly thermally stable
derivatives and precursors of octafluoro[2,2] paracyclophenone
(AF4) and their preparation.
[0024] The nitration of AF4 gives a mononitro product in high
yield. However, when such nitration is carried out under the more
forcing conditions of five equivalents of NO.sub.2BF.sub.4 and a
temperature of 80.degree. C. (step i), the products generated are
observed to be a mixture of three isomeric dinitro derivatives in
over 80% combined isolated yield, with the ratio of the isomers
being 1:1:1.
[0025] One of the isomers could be separated from the other two by
column chromatography since it displayed a lower R.sub.f value than
the other two, which co-eluted. The quicker running mixture of the
two isomers could be enriched in one or the other isomer by
fractional crystallization or sublimation. The .sup.19F NMR
spectrum of each isomer showed only 2 AB patterns. The .sup.19F NMR
spectra of AF4 consists of a singlet, and that mononitro-AF4
appears as 4 AB patterns. The increase in the symmetry of these new
products relative to mono-nitro-AF4 indicated incorporation of at
least two nitro groups.
[0026] Mass spectrometry confirmed not only that the products did
indeed contain two nitro groups, but also that they were located on
different rings. The relative orientation of the nitro groups in
each of the three isomers was established through .sup.1H NMR, and
further confirmed by thermal isomerizations and correlation of
their physical properties with those already established for
hetero-annularly disubstituted [2,2] PCP derivatives. The products
were identified as pseudo-meta-, pseudo-para- and
pseudo-ortho-dinitrooctafluoroparacyclophanes 2a-c, as illustrated
in Scheme 1. No evidence of the pseudo-geminal isomer was observed,
although as little as 1% could have been detected. 9
[0027] The introduction of a nitro functionality into one ring
deactivates that ring to further electrophilic substitution and
guides subsequent reaction to the other unsbubstituted ring. The
lack of a pseudo geminal isomer is somewhat surprising since there
are many examples of complete (or predominant) pseudo geminal
electrophilic aromatic substitutions promoted by the substituents
bearing basic functionalities, through their participation as
intramolecular bases. Nitrations, however, are known to be less
susceptible to such kinetic effects, in comparison to brominations,
for example. The inventors have proposed that the lack of such a
dinitro isomer in this reaction is due to steric effect. The
nitration of the hydrocarbon [2,2] PCP using nitric acid at
75.degree. C. is reported to yield mononitro [2,2] PCP (26%), and
pseudo-meta (2%), pseudo-para (2%), pseudo-ortho (1.4%) and
pseudo-geminal (0.7%) dinitro isomers.
[0028] The inventors have previously demonstrated that nitro-AF4
provides a route to a variety of ring substituted AF4 derivatives
and similar synthetic methodologies can be applied here that allow
the generation of a number or inter-annularly disubstituted AF4.
See Roche et al., J. ORG. CHEM. 1999, 64, 9137.
[0029] The reactions in Scheme 1 were all performed on both single
isomers and mixtures of the three isomers. The pseudo ortho isomer
could always be separated from the pseudo meta/pseudo para mixture
by column chromatography, regardless of the substituents. The
pseudo meta/pseudo para isomers were, in general, unable to be
separated by column chromatography. All reaction yields were
essentially the same whether preformed on single or multiple
isomers, and are comparable to the corresponding reactions used to
make the monosubstituted AF4 analogues. The only difference in
reactivity for the three disubstituted isomers in the reactions in
Scheme 1 was observed in their trifluoromethylation reactions,
where pseudo ortho diiodo isomer gave lower conversions and slower
reactions. No isomerism or loss of integrity of the AF4 skeleton
was observed during any of these reactions, although deliberate
high temperature isomerization of selected examples of these
compounds was studied.
[0030] The reduction of 2a-c using iron powder/conc. hydrochloric
acid (step ii) gave the corresponding diamino products 3a-c in good
isolated yields (82-84%). Cyclophanes containing electron donating
substituents in one ring and electron acceptors in the other ring
are often reported to be colored, and the corresponding
inter-annular nitro-arnino systems for the hydrocarbon [2,2] PCP
vary from yellow to red, depending on the relative orientation of
the two substituents. In an attempt to generate 6 (Scheme 2) with
an amino group in one ring and a nitro group in the other, the
milder reducing agent of cyclohexene and Pd on carbon was used in
conjunction with 2c. Besides the corresponding diamino AF4 3c
(38%), the nitroamino derivative 6 (11%) was isolated, and the
hydroxyl-amino product 7 (15%). 10
[0031] Dissapointingly, 6 was a white solid, in contrast to the
orange/yellow color of the corresponding [2,2] PCP compound. This
difference can be attributed to the electron density from the
interacting .pi. systems by the electron withdrawing fluoroalkyl
bridging units, thus reducing charge transfer.
[0032] The diamino AF4 isomers 3a-c proved to be versatile starting
materials for further transformations, with the most
straightforward being the formation of the respective N-acetyl and
-triflouroacetyl-amides in high isolated yield (84-97%). These
compounds proved not only useful for characterization purposes, but
also as protecting groups which moderated the reactivity of the
diamino AF4 systems, and thus made appropriate materials for the
high temperature thermal isomserization studies described infra
herein.
[0033] The double diazotization of these diamino-systems proved as
successful diazotization of monoamino-AF4, and thus the three
isomeric dibromo (5a-c) and diiodo-AF4 (4a-c) derivatives were
prepared in good isolated yield (60-78%) via Sandmeyer type
chemistry (steps iii, iv, v in Scheme 1). The hetero-annular
dibromides proved useful for comparison purposes when a
homo-annular dibromide was later prepared. The hetero-annular
dibromides also served as useful intermediates for further
transformations, although the diiodes generally gave higher yields
in such reactions, and were therefore the more desirable starting
materials.
[0034] Triflouromethylation of the pseudo meta and pseudo para AF4
diiodides 4a,b gave moderate yields of corresponding
bis(triflouromethylated) products 8a,b (50%) (Scheme 3), along with
appreciable amounts of monotrifluoromethylated product 10 (30%)
(Scheme 4). It was also observed that the addition of palladium
dichloride provided vast improvements in the yields of
bis(triflouromethylated) products (80%), and a consequent decrease
in chemically reduced side products (Scheme 4). 11
[0035] When a typical uncatalyzed triflouromethylation was
performed on pseudo ortho AF4 diiodide 4c (Scheme 4), the only two
products obtained besides starting materials were identified as 10
(33%) and pseudo ortho iodo-triflouromethyl OFP 9 (21%). However,
the addition of PdCl.sub.2 promoted a superior reaction with the
pseudo ortho bis(trifluoromethyl) derivative, 8c, being isolated in
68% yield, along with a 10% yield of iodo-triflouromethyl
derivative, 9, which could itself be reduced by zinc in acetic acid
to form triflouromethyl-AF4 (91%). 12
[0036] The difference in reactivity displayed by the isomeric
diiodides can be best understood in terms of the iodides simply
being located either on the same or different sides of the
cyclophane. Although exchange of triflouromethyl for iodine should
make the iodo-triflouromethyl intermediate compounds more reactive
toward further substitution, clearly this is not the case for the
pseudo ortho isomer. It is likely that the two reaction centers in
the pseudo ortho isomers are so close that when one iodine is
replaced by a trifluoromethyl group, there is sufficient steric and
electronic shielding by the attached trifluoromethyl group to
inhibit further substitution. Having observed through space NMR
interaction between syn bridging flourines and a triflouromethyl
substituent on the ring, the inventors believe that these syn
bridge fluorines also provide steric and electrostatic shielding to
an attacking nucleophile. The use of a relatively large transition
metal catalyst like Pd(III) may serve to reduce such steric
constraints on the incoming nucleophile by coordinating the
substrate and the nucleophile before joining them through a
reductive elimination, thus resulting in the superior observed
yields of triflouromethylyated products in PdCl.sub.2 catalyzed
reactions.
[0037] The pseudo ortho diiodide 4c was also used to produce the
corresponding diphenyl derivative via reaction with phenyl
magnesium bromide and PdCl.sub.2, providing the diphenyl derivative
in 21% yield along with 20% monophenyl-AF4. Identical mono and
diphenylated products were also obtained via diazonium chemistry
and benzene.
[0038] Although the overall yields of the diiodides and dibromides
were acceptable for a three step procedure (40-53% isolated from
AF4) as in Scheme 1, a direct bromination procedure to dibrominate
OFP would be much more desirable. To this end, AF4 was subjected to
several known bromination methods. However, the only method that
was successful in generating more than a trace of dibromo-AF4 was a
method recently reported by the inventors for bromination of
deactivated aromatics. See Duan et al., SYNLETT (1999), 1245.
[0039] When triflouroacetic acid solution of AF4 was exposed to a
combination of four equivalents of NBS and sulfuric acid at
80.degree. C., a single major product was produced. The presence of
2AB patterns in the .sup.19F NMR of this compound led to the belief
that the product was a dibromide. The isolated yield of this
compound, after column chromatography, was 55% m and somewhat
surprisingly, the NMR of the product did not match any of those of
the three inter-annular dibromides that had been prepared via the
nitration/reduction/diazonium chemistry described hereinabove. Mass
spectrometry revealed that the product was indeed a dibromide
isomer, but that the bromines were both on the same ring. This
information, coupled with the .sup.1H and .sup.19F NMR patterns
(described infra.) indicated that this was para dibromo AF4,
5d.
[0040] A bromine susbtituent is normally viewed as a deactivating
and ortho/para directing substituent in electrophilic aromatic
substitution, and usually a deactivating substituent would guide
subsequent substitution into the other ring of a [2,2] PCP. This
was not, however, the case for this reaction, although the second
bromine did enter para to the first. 13
[0041] With p-dibromo AF4 (5d) in hand, it was then possible to
prepare the p-bis(triflouoromethyl) AF4 derivative, 8d, (Scheme 5)
albeit in lower yields than had been obtained for the
hetero-annular diiodides, 4c. As expected, the NMR spectra of 8d
were also distinctively different from those of 8a, 8b, and 8c.
[0042] Thermal Isomerizations
[0043] The [2,2] PCP skeleton is rigid, and under normal
conditions, maintains its integrity allowing, for example, the
application of [2,2] PCP derivatives as chiral ligands and
molecular scaffolds of known fixed geometry..sup.5 This holds true
for temperatures below 150-200.degree. C. Above these temperatures,
ring substituted [2,2] PCP derivatives exhibit a thermal
isomerization which is unique to this system. Typically, the
deliberate isomerizations have been performed without solvent at
200.degree. C. for 24 hours. It has been demonstrated that they
proceeded though a bibenzyl type diradical intermediate. Reich et
al., AM. CHEM. SOC. (1969) 91, 3517.
[0044] One might expect the longer C-C bridge length in OFP (1.577
.ANG.) relative to [2,2] PCP (1.569 .ANG.) to allow the
racemization of AF4 derivatives to occur at lower temperatures
since it is this bond that must break and reform. Conversely, since
replacement of hydrogen by fluorine in saturated systems usually
increases thermal and chemical stability, coupled with the lower
stability of difluorobenzyl radicals relative to benzyl radicals,
OFP derivatives might be predicted to require much higher
temperatures to undergo such isomerizations. The inventors were
therefore interested to determine whether OFP derivatives would
undergo such thermal isomenzations, and if so, what temperatures
would be required.
[0045] Initially the pseudo ortho dibromo-, pseudo ortho diamino-
and dinitro-OFP derivatives were examined, but these compounds
proved to be perfectly stable and unchanged when heated neat at
200.degree. C. for 12 hours. After 8 hours at 300.degree. C., the
diamino compound had fully decomposed, whilst the dibromo and
dinitro compounds showed no isomerization. When the temperature was
raised to 350.degree. C. the dinitro compound was extensively
charred, but showed traces of isomerization to its pseudo para
counterpart, whereas the dibromide was also charred but showed no
isomerizations. In contrast, heating the pseudo ortho
bis(trifluoroaceamido) AF4 led to no charring, and the sample
showed traces of isomerization to its pseudo para isomer. 14
[0046] Therefore, the pseudo ortho bis(trifluoroacetamido)-OFP was
heated to 381-390.degree. C. for 2 hours, and was shown by NMR
analysis to have converted to a 5:1 ratio of pseudo ortho and
pseudo para isomers. Encouraged by this result, this mixture was
further heated at 350-360.degree. C. for 24 hrs and the ratio of
isomers was found to have changed to 1:7 in favor of the less
sterically congested pseudo para isomer. The mass recovery was 75%,
with the balance presumably being insoluble polymeric material.
Therefore the bridging fluorine atoms in OFP appear to impart
150.degree. C. more kinetic thermal stability to a [2,2] PCP ring
system. This not only demonstrates the stabilizing effect of
exchanging fluorine for hydrogen, but has serious implications in
the use of these fluorinated phanes as chiral ligands, catalysts
and auxiliaries, since they display far superior resistance to
thermal isomerization than the hydrocarbon analogues, and could
therefore be employed at higher temperatures without losing their
chirality through thermal racemization.
[0047] Characterization
[0048] The introduction of a second substituent onto a ring in a
[2,2] PCP system can give rise to 7 possible isomers, of which 3
are racemic and 4 are meso (if the two substituents are
equivalent). There has been substantial work in this area, and
numerous strategies and techniques have evolved that allow
unambiguous isomer and structure determination in hydrocarbon [2,2]
PCP systems, with .sup.1H NMR and mass spectrometry comprising the
most powerful tools. Previously the inventors reported that not
only were these strategies and techniques equally applicable to the
characterization of mono substituted OFP derivatives, but that the
OFP derivatives also offered the added bonus of .sup.19F NMR to
distinguish between products. Roche et al., J. ORG. CHEM. (1999)
64, 9137. The inventors have demonstrated that the .sup.1H
Substituent Chemical Shift (SCS) values previously derived for the
amino-OFP system allow accurate prediction of the .sup.1H shifts of
the three new diamino-OFP products synthesized in accordance with
the present invention, and also that the .sup.19F NMR shifts of the
bis(trifluoromethylated) OFP compounds (both hetero- and
homo-annular) can also be predicted via the use of the .sup.19F SCS
values derived from monotrifluoromethylated OFP.
[0049] Heretobefore, the calculation of .sup.19F SCS values, and
the first demonstration that they may be used to predict the shifts
of the bridging fluorines in multiply-substituted OFP derivatives
has not been reported
[0050] .sup.1H NMR
[0051] Due to their symmetric nature, hetero-annularly identically
disubstituted [2,2] PCP's display a simple and characteristic
.sup.1H NMR pattern consisting of one singlet and one AB pattern.
All of the disubstituted OFP products described herein also display
this feature. The pseudo ortho disubstituted isomer is generally
the easiest to recognize since any "gem shift" operates upon the
resonance which is a singlet, forcing it downfield, normally clear
of the other resonances.
[0052] Since it has been demonstrated that amino substituted [2,2]
PCP's are the most convenient for NMR investigation, the inventors
earlier derived the SCS values for the amino-OFP system (Table 1).
Prior work in hydrocarbon [2,2] PCP systems has amply shown that
these SCS values are additive, and therefore may be used to
calculate proton shifts for multiply substituted systems. The
observed 1H shifts can be compared for the three diamino-OFP
isomers of the present invention, with those shifts calculated from
the SCS values previously dereived (Table 2).
1TABLE 1 Amino OFP SCS values o m p m' p' 0' gem -1.21 .0.36 -0.76
-0.20 0.01 -0.12 +0.69 (Where o = ortho, p = para, m = meta, m' =
pseudo meta, p' = pseudo para, 0' = pseudo ortho and gem = pseudo
geminal).
[0053]
2TABLE 2 Predicted 'H Chemical Shifts using Amino OFP SCS Values
Compound Peak Type SCS Effects Calculated/ppm Observed/ppm Pseudo
meta singlet o + p' 6.10 6.08 DiNH.sub.2 A m + gem 7.63 7.57 3a B p
+ o' 6.42 6.44 Pseudo para singlet o + m' 5.89 6.00 diNH.sub.2 A m
- o' 6.82 6.87 3b B p + gem 7.23 7.04 pseudo singlet o + gem 6.78
6.89 ortho diNH.sub.2 A m + p' 6.95 7.00 3c B p + m' 6.34 6.36
[0054] It is clear that there is good agreement between the
predicted and observed chemical shifts.
[0055] .sup.19F NMR
[0056] Mono-functionalised OFP derivatives exhibit a characteristic
four AB pattern in their .sup.19F NMR spectra, whereas
inter-annular identically disubstituted OFP derivatives contain
only four different bridging fluorine atoms, which manifest
themselves as two A-B patterns. (This is also true for para and
ortho oriented intra-annular substituted OFP derivatives). All of
the disubstituted OFP derivatives described herein display only two
AB patterns in their .sup.19F NIMR spectra. (Of course, OFP
derivatives bearing two different substituents have eight different
bridge fluorines that appear as four A-B's, similar to a mono OFP
product).
[0057] The problem previously described concerning the assignment
of fluorine resonances to specific fluorine atoms still exists for
the derivatives described here except for the four
bis(trifluoromethyl)-OFP derivatives. The "through space" coupling
that occurs between a trifluoromethyl ring substituent and the
proximate syn bridging fluorines.sup.10 allowed the instant
recognition of those bridge fluorines since they appear as
quartets. Their partners in the respective A-B patterns could be
located by line shape and coupling constant. Thus
F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a for trifluoromethyl-OFP could
be assigned, although the assignment of the remaining 4 fluorines
was ambiguous.
3 Chart 1. Assignment of bridge fluorine resonances in
trifluoromethyl substituted AF4s 10 and 8a-d 15 .sup.19F: 4AB
patterns (F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a, F.sub.3s/F.sub.3a,
F.sub.4s/F.sub.4a) F.sub.2s = q, 29.07 Hz F.sub.1s = q, 9.88 Hz 16
.sup.19F: 2AB patterns (F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a)
F.sub.1s = q, 29.07 Hz F.sub.1a = q, 14.68 Hz 17 .sup.19F: 2AB
patterns (F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a) F.sub.2s = q, 31.51
Hz F.sub.1s = q, 9.88 Hz 18 .sup.19F: 2AB patterns
(F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a) F.sub.2s = q, 29.07 Hz
F.sub.1s = q, 14.68 Hz 19 .sup.19F: 2AB patterns
(F.sub.1s/F.sub.1a, F.sub.2s/F.sub.2a) F.sub.2s = q, 29.07 Hz
F.sub.2a = q, 16.93 Hz
[0058] However, because of symmetry in the bis(trifluoromethyl)-OFP
derivatives 8a-d, we can use this coupling interaction to fully
assign, for the first time, the bridge fluorine resonances of these
systems (and further confirm the accuracy of our isomer
assignments). The strategy was to first identify the resonances
split in to the large and small quartets, and then find their AB
partners. Easiest to identify was the pseudo meta isomer, since
this is the only isomer to contain both quartet resonances within
the same AB. (This also has the unfortunate consequence that the
other two fluorines for this isomer cannot be assigned
unambiguously). For the other isomers, the resonances with the
larger and smaller quartets were assigned F.sub.2s and F.sub.1s
respectively. Identification of their AB partners via line shape
and coupling constant gave F.sub.2a and F.sub.1a. Thus, for the
first time, all the fluorine atoms could be assigned to their
fluorine resonances.
[0059] This presented a situation where there were .sup.19F
chemical shifts and assignments for four disubstituted OFP
derivatives, and assignments for half of the shifts for the
corresponding monosubstituted derivative. Since it has been
demonstrated that .sup.1H SCS values are additive for the OFP
system, it was projected that the .sup.19F SCS values should be
too, and therefore we should be able to work backwards and assign
the remaining four fluorine shifts for the mono derivative. Indeed,
one set of assignments for the remaining four fluorines gave much
better agreement than the others, as predicted from SCS values
taken from the disubstituted systems. These assignments were
therefore used in the calculation of the .sup.19F SCS values for
the monotrifluoromethyl OFP system 10.
4TABLE 3 .sup.19F SCS values for 10, in ppm F.sub.1a F.sub.1S
F.sub.2a F.sub.2S F.sub.3a F.sub.3S F.sub.4a F.sub.4S 3.18 4.19
9.77 4.72 3.32 -0.19 2.55 0.38
[0060] When these values were used to calculate the shifts for the
four bis(trifluoromethyl) derivatives, reasonable agreement was
found.
5TABLE 4 Calculated .sup.19F Chemical Shifts for 10, 8a-d. Isomer
Assignment Calculated Found Pseudo F.sub.2s -110.73 -112.90 Para
F.sub.2a -107.85 -108.28 8b F.sub.1s -110.49 -111.77 F.sub.1a
-115.01 -115.65 Pseudo F.sub.1s -110.10 -112.03 Meta F.sup.1a
-104.04 -105.86 8a F.sub.2s -115.64 -118.29 F.sub.2a -114.30
-113.56 pseudo F.sub.2s -112.90 -112.23 ortho F.sub.2a -105.68
-108.07 8c F.sub.1s -114.00 -114.75 F.sub.1a -111.50 -113.16 para
F.sub.2s -109.96 -112.85 8d F.sub.2a -108.42 -109.27 F.sub.1s
-111.26 -114.83 F.sub.1a -114.44 -113.47
[0061] Homo-annular Substitution
[0062] When a second identical substituent is introduced into the
same ring as the first in an OFP, there are only three possible
isomeric products, of which two are meso and one is racemic. The
three isomers can in principle be differentiated simply by
inspection of the format of the .sup.19 F and .sup.1H NMR spectra.
The para isomer will result in AB patterns in both the .sup.19F and
the .sup.1H spectra, whereas the ortho isomer will produce .sup.19F
AB's but singlets in the .sup.1H NMR spectrum. The para meta isomer
would also produce no AB patterns in the .sup.19F spectrum, but
would give an AB in the .sup.1H spectrum. The only isomer to give
rise to AB patterns in both fluorine and proton NMR spectra would
be the para isomer. This was observed for dibromo OFP, 5d, and
bis(trifluoromethyl) OFP, 8b.
[0063] Mass Spectrometry
[0064] It has been well documented that mass spectroscopic analysis
of [2,2] PCP derivatives provides an excellent method for
determination of the number of substituents on each ring. This has
also been demonstrated to be the case for mono substituted OFP
derivatives, and all the new OFP compounds described herein have
mass spectra appropriate to the general rules previously
established for both the hydrocarbon and fluorocarbon systems.
[0065] This technique provides the simplest way to discriminate
between homo- and hetero-annular disubstituted isomers. For
example, both the para and pseudo para bis(trifluoromethyl)-OFP'S
give the same molecular mass of parent ion of 488. The isomer with
a trifluoromethyl group in each ring fragments into two xylylene
units of mass 244, whereas the homo-annular isomer fragments into
unsubstituted and disubstituted xylylene fragments of mass 176 and
312.
[0066] Physical Properties
[0067] Reich et al., J. AM. CHEM. SOC. (1969) 91, 3534 derived many
correlations between physical properties and relative orientation
of disubstituted [2,2] PCP isomers. These general relationships
proved equally valid for the OFP systems, and indeed were
fundamental to our early characterization work. For example, during
column chromatography the disubstituted OFP derivatives always
eluted in the same order of pseudo meta/pseudo para, pseudo ortho,
pseudo gem. The pseudo meta and pseudo para isomers could never be
separated by column chromatography, although they could be
separated on a capillary GC (DB5) column. The pseudo paral pseudo
meta isomer mixture could be enriched in one isomer or the other by
fractional crystallization or sublimation, with the pseudo para
isomer being the least soluble and slowest to sublime. In certain
cases, analytical samples of pure pseudo para isomer could be
obtained by fractional crystallization. The pseudo para isomer was
also the isomer with highest melting point.
[0068] Characterization Summary
[0069] Both the previously established rules and strategies for
characterization of [2,2] PCP and mono OFP derivatives are equally
applicable to the identification of disubstituted OFP derivatives,
and furthermore allow the discrimination between disubstituted OFP
isomers. The use of previously derived .sup.1H SCS values allowed
the prediction of .sup.1H NMR spectra of disubstituted isomers, and
also that derived .sup.19F SCS values for trifluoromethyl OFP can
be used for the prediction of the .sup.19F NMR shifts of the bridge
fluonnes for bis(trifluoromethylated) OFP isomers. Mass
spectroscopy allows the easiest discrimination between homo- and
hetero-annular disubstituted isomers.
[0070] The following examples are provided for illustrative
purposes and are not intended to limit the scope of the claims
which follow.
EXAMPLES
[0071] Experimental
[0072] All NMR spectra were obtained at ambient temperatures in
deuterated acetone, and run on a Varian VXR-300 spectrometer with
.sup.1H at 299.949 MHz with TMS as reference, and at 282.202 MHz
for .sup.19F, using CFCl.sub.3 as reference. All reagents, unless
otherwise specified, were used as purchased from Aldrich,
Milwaukee, Wis. or are Fischer products obtainable from numerous
chemical suppliers. Column chromatography was performed using
Chromatographic Silica Gel 200-425 mesh as purchased from Fischer.
Melting points are uncorrected. Mass spectroscopic analyses were
performed on a Finnigan MAT95Q, with an ionizing potential of 70
eV.
[0073] Dinitration of OFP
[0074] Under a counter current of dry nitrogen, nitronium
tetrafluoroborate (22. 10 g, 166.17 mmol) was added to
octafluoroparacyclophane 1 (0.20 g, 28.98 mmol) dissolved in
sulpholane (100 mL), and the reaction was warmed to 80.degree. C.
and stirred at this temperature overnight. The reaction mixture was
then allowed to cool to room temperature and then added to ice
water (400 mL), and the white precipitate was filtered and
chromatographed (hexane/dicholormethane 7/3) to give (R.sub.f=0.32)
pseudo meta- and pseudo para-dinitro 1,1,2,2,9,9,10,10-octafluoro
[2,2] paracyclophanes 2a,b (6.92 g, 54% combined; 1:1 mixture): MS
m/z 442 (M+, 6%), 125 (100); Anal. Calcd for
C.sub.16H.sub.6F.sub.8N.sub.2O.sub.4: C, 43.44; H, 1.36; N, 6.33.
Found: C, 43.70; H, 1.23; N, 6.21; 2a .sup.1H NMR .delta. 8.009 (s,
1H); 8.009 (m, 1H); 7.783 (d, .sup.3J=8.10 Hz, 1H); .sup.19F NMR
.delta. -108.806 (d, .sup.2J=244.70 Hz, 1F); -111.989 (d,
.sup.2J=244.70 Hz, 1F); -115.321 (d, .sup.2J=239.90 Hz, 1F);
-117.317 (d, .sup.2J=239.90 Hz, 1F); 2b .sup.1H NMR .delta. 8.009
(s, 1H); 8.009 (m, 1H); 7.783 (d, .sup.3J=8.10 Hz, 1H); .sup.19F
NMR .delta. -109.829 (d, .sup.2J=246.95 Hz, 1F); -113.986 (d,
.sup.2J=246.95 Hz, 1F); -114.352 (d, .sup.2J=237.36 Hz, 1F);
-115.028 (d, .sup.2J=237.36 Hz, 1F); (R.sub.f=0.20) Pseudo
ortho-dinitro-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 2c
(3.46 g, 27%): mp 213-215.degree. C. .sup.1H NMR .delta. 8.075 (s,
1H); 7.827 (m, 2H); .sup.19F NMR .delta. -111.023 (d,
.sup.2J=244.70 Hz, 1F); -112.293 (d, .sup.2J=244,70 Hz, 1F);
-114.428 (d, .sup.2J=242.44 Hz, 1F); -115.582 (d, .sup.2J=242.44
Hz, 1F); MS m/z 442 (M+, 10%), 125 (100); Anal. Calcd for
C.sub.16H.sub.6F.sub.8N.sub.2O.sub.4: C, 43.44; H, 1.36; N, 6.33.
Found: C, 43.70; H, 1.29; N, 6.19. The combined yield of the three
dinitro isomers is 81%.
[0075] When only 4 equivalents of nitronium tetrafluoroborate was
used, the product mixture was subjected to chromatography and shown
to contain the mononitrated cyclophane (36%), the pseudo meta- 2a
(16%), pseudo para- 2b (16%) and pseudo ortho- 2c (16%)
dinitro-1,1,2,2,9,9,10,10-octaf- luoro [2,2] paracyclophanes.
[0076] Pseudo ortho-diamino-1,1,2,2,9,9,10,10-Octafluoro [2.21]
Paracyclophane, 3c
[0077] A suspension of pseudo
ortho-dinitro-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 2c
(1.30 g, 2.94 mmol) in ethanol/water (1/1 v/v, 50 mL) was stirred
for one hour at room temperature. Iron powder (2.00 g, 35.71 mmol)
was added, and the reaction mixture was heated to reflux.
Concentrated hydrochloric acid (7 mL) was added dropwise to the
mixture, and reflux was continued for 4 hours. After this time, the
reaction was cooled to room temperature, and was added to ice water
(200 mL). The solids thus produced were filtered, and redissolved
in chloroform. This chloroform solution was filtered, evaporated
and the solid residue was chromatographed (chloroform) to give
(R.sub.f=0.41) pseudo ortho-diamino-1,1,2,2,9,9,10,10-octafluoro
[2,2] paracyclophane 3c (0.91 g, 82%): mp 211.degree. C. (dec.).
.sup.1H NMR .delta. 6.999 (d,.sup.3J=8.40 Hz, 1H); 6.885 (s, 1H);
6.361 (d, .sup.3J=8.40 Hz, 1H); .sup.19F NMR .delta. -106.652 (dd,
.sup.2J=232.56, .sup.3J=9.60 Hz, 1F); -114.370 (d, .sup.2J=232.56
Hz, 1F); -106.873 (dd, .sup.2J=242.44, .sup.3J=9.60 Hz, 1F);
-111.223 (d, .sup.2J=242.44 Hz, 1F); MS m/z 382 (M+, 19%), 191
(100); Anal. Calcd for C.sub.16H.sub.10, F.sub.8N.sub.2: C, 50.26;
H, 2.62; N, 7.33. Found: C, 50.17; H, 2.41; N, 7.21.
[0078] An identical reaction with a 1:1 mixture of pseudo meta- and
pseudo para-dinitro-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 2a,b gave the corresponding pseudo meta- and pseudo
para-diamino-1,1,2,2,9,9,10,10-- octafluoro [2,2] paracyclophanes
3a,b in 84% yield. (hexane/chloroform 1/1, R.sub.f=0.46): Anal.
Calcd for C.sub.16H.sub.10F.sub.8N.sub.2: C, 50.26; H, 2.62; N,
7.33. Found: C, 49.98; H, 2.55; N, 7.07. MS m/z 382 (M+, 21%), 191
(100); 3a, .sup.1H NMR .delta. 7.566 (d, .sup.3J=8.40 Hz, 1H);
6.442 (d, .sup.3J=8.40 Hz, 1H); 6.084 (s, 1H); .sup.19F NMR .delta.
-100.315 (m, 2F); -112.440 (d, .sup.2J=234.25 Hz, 1F); -116.601 (d,
.sup.2J=234.25 Hz, 1F); 3b, .sup.1H NMR .delta. 7.038 (d,
.sup.3J=8.40 Hz, 1H) 6.874 (d, .sup.3J=8.40 Hz, 1H); 6.003 (s, 1H);
.sup.19F NMR .delta. -103.339 (d, .sup.2J=239.33 Hz, 1F); -109.085
(d, .sup.2J=239.33 Hz, 1F); -108.562 (d, .sup.2J=234.25 Hz, 1F);
-109.685 (d, .sup.2J=234.25 Hz, 1F).
[0079] An ethanol (10 ml) solution containing pseudo ortho
dinitro-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 2c (380
mg, 0.86 mmol), cyclohexene (420mg, 5.16 mmol) and 10% Pd on carbon
(0.2 g) was warmed to reflux, and after 15 minutes of observable
reflux, the reaction was evaporated under reduced pressure to a
solid residue which was subjected to chromatography
(chloroform/hexane 7/3, then chloroform) to give three compounds:
(R.sub.f=0.46) pseudo ortho
nitro-amino-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 6 (40
mg, 11%): .sup.1HNMR .delta. 8.267 (s, 1H); 7.692 (d, .sup.3J=8.40
Hz, 1H); 7.466 (d, .sup.3J=8.40 Hz, 1H); 7.107 (d, .sup.3J=8.40 Hz,
1H); 6.631 (d, .sup.3J=8.40 Hz, 1H); 6.453 (s, 1H); 5.818 (br s 2H,
NH.sub.2); .sup.19F NMR .delta. -105.172 (d, J=244.70 Hz, 1F);
-112.620 (d, 2J=244.70 Hz, 1F); -106.128 (d, .sup.2J=239.90 Hz,
1F); -110.660 (d, 2J=239.90 Hz, 1F); -109.339 (d, 2J=244.70 Hz,
1F); -112.615 (d, .sup.2J=244.70 Hz, 1F); -111.964 (d, 2J=234.82
Hz, 1F); -116.298 (d, .sup.2J=234.82 Hz, 1F); MS m/z 412 (M+, 25%),
191 (100). HRMS calcd. for C.sub.16H.sub.8F.sub.8N.sub- .2O.sub.2
412.0458, found 412.0481. (R.sub.f=0.20, chloroform) pseudo ortho
diamino-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 3c (126
mg, 38%), as above. (R.sub.f=0.11, chloroform) pseudo ortho
hydroxylamino-amino-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane 7 (51 mg, 15%): .sup.1H NMR .delta. 7.609 (s, 1H);
7.118 (d, .sup.3J=8.40 Hz, 1H); 6.958 (d, .sup.3J=8.40 Hz, 1H);
6.627 (d, .sup.3J=8.40 Hz, 1H); 6.373 (d, .sup.3J=8.40 Hz, 1H);
6.691 (s, 1H); 8.249 (br s, 1H NH); 7.952 (br s, 1H, OH); 5.337 (br
s 2H, NH.sub.2);.sup.19F NMR .delta. -104.796 (d, 2J=242.16 Hz,
IF); -111.062 (d, .sup.2J =242.16 Hz, 1F); -106.012 (d,
.sup.2J=244.70 Hz, 1F); -111.220 (d, .sup.2J=244.70 Hz, 1F);
-106.120 (d, .sup.2J=235.10 Hz, 1F); -113.514 (d, .sup.2J=235.10
Hz, 1F); -106.529 (d,.sup.2J=232.28 Hz, 1F); -114.462 (d,
.sup.2J=232.28 Hz, 1F); MS m/z 398 (M+, 23%), 207 (5), 191 (100);
HRMS calcd. for C.sub.16H.sub.10F.sub.8ON.sub.2 398.0665, found
398.0656.
[0080] Typical diazotization producedure
[0081] A solution of pseudo ortho-diamino-1,
1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 3c (2.00 g, 5.24
mmol) in acetic acid (4ml) was cooled to 0.degree. C. in an
ice/brine bath, ice (1.5 mL) and concentrated 98% sulfuric acid
(1.5 mL) were carefully added with stirring, and ensuring the
temperature was still below 0.degree. C., sodium nitrite (2.00 g,
28.99 mmol) was added in one batch. The reaction was stirred at
this temperature for 2 hours, and then used for the following
transformations:
[0082] Pseudo ortho-dibromo-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane, 5c
[0083] An aqueous solution (10 mL) of copper (I) bromide (4.00 g,
27.87 mmol) and 47% hydrobromic acid (10 mL) was warmed to
70.degree. C., and the diazotization solution previously prepared
was added in one batch with stirring. The mixture was kept at
70.degree. C. for 1 hour, and then left to cool overnight. The
precipitated product was filtered, and chromatographed
(hexane/ether 9/1) to give (R.sub.f=0.45) pseudo
ortho-dibromo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 5c
(1.60 g, 60%): mp 125-126.degree. C. .sup.1H NMR .delta. 7.845 (s,
1H); 7.520 (d, .sup.3J=8.10 Hz, 1H); 7.369 (d, .sup.3J=8.10 Hz,
1H); .sup.19F NMR .delta. -109.460 (d, .sup.2J=239.90 Hz, 1F);
-113.529 (d, 2J=239.90 Hz, 1F); -110.473 (d, .sup.2J=239.90 Hz,
1F); -110.620 (d, .sup.2J=239.90 Hz, 1F); MS m/z 510 (M+, 5%), 508
(2), 512 (2), 254 (100), 256 (94); Anal. Calcd for
C.sub.16H.sub.6F.sub.8Br.sub.2: C, 37.65; H, 1.18. Found: C, 37.69;
H, 1.15.
[0084] An identical reaction with a 1: 1 mixture of pseudo meta-
and pseudo para-diamino-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 3a,b gave the corresponding pseudo meta- and pseudo
para-dibromo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophanes
5a,b in 65% yield: (hexane/chloroform 9/1, R.sub.f=0.62); Anal.
Calcd for C.sub.16H.sub.6F.sub.8Br.sub.2: C, 37.65; H, 1.18. Found:
C, 37.44; H, 1.13. MS m/z 510 (M+, 4%), 508 (2), 512 (2), 254
(100), 256 (94). 5a .sup.1H NMR .delta. 7.428 (s, 1H): 7.799 (d,
.sup.3J=8.10 Hz, 1H); 7.486 (d, 3J=8.40 Hz, 1H); .sup.19F NMR
.delta. -103.640 (d, 2J=239.90 Hz, 1F); -113.529 (d, .sup.2J=239.90
Hz, 1F); -110.473 (d, .sup.2J=239.90 Hz, 1F); -110.620 (d,
.sup.2J=239.90 Hz, 1F); 5b .sup.1H NMR .delta. 7.165 (s, 1H); 7.895
(d, .sup.3J=8.40 Hz, 1H); 7.411 (d, .sup.3J=8.40 Hz, 1H); .sup.19F
NMR .delta. -108.141 (d, .sup.2J=239.62 Hz, 1F); -109.137 (d,
.sup.2J=239.62 Hz, 1F); -110.582 (m, 2F).
[0085] Pseudo ortho-diiodo-1,1,2,2,9,9,10,10-octafluoro [2,21 ]
paracyclophane, 4c
[0086] An aqueous solution (10 mL) of potassium iodide (5.11 g,
30.78 mmol) was warmed to 70.degree. C., and the diazotization
solution previously prepared was added in one batch with stirring.
The mixture was kept at 70.degree. C. for 1 hour, and then left to
cool overnight. The precipitated product was filtered, and
chromatographed (hexane/ether 9/1) to give (R.sub.f=0.42) pseudo
ortho-diiodo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 4c
(2.47 g, 78%): mp 132-133.degree. C. .sup.1H NMR .delta. 8.157 (s,
1H); 7.457 (d, .sup.3J=8.70 Hz, 1H); 7.403 (d, .sup.3J=8.70 Hz,
1H); .sup.19F NMR .delta. -107.330 (d, .sup.2J=237.36 Hz, 1F);
-112.570 (d, J=237.36 Hz, 1F); -109.323 (d, .sup.2J=239.90 Hz, 1F);
-110.319 (d, 2J=239.90 Hz, 1F); MS m/z 604 (M+, 3%), 302 (100);
Anal. Calcd for C.sub.16H.sub.6F.sub.8I.sub.2: C, 31.79; H, 0.99.
Found: C, 31.96; H, 0.92.
[0087] An identical reaction with a 1:1 mixture of pseudo meta- and
pseudo para-diamino-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 3a,b gave the corresponding pseudo meta- and pseudo
para-diiodo-1,1,2,2,9,9,10,10-o- ctafluoro [2,2] paracyclophanes
4a,b in 78% yield: (hexane/ether 9/1, R.sub.f=0.61); Anal. Calcd
for C.sub.16H.sub.6F.sub.8I.sub.2: C, 31.79; H, 0.99. Found: C,
31.86; H, 0.86. MS m/z 604 (M+, 3%), 302 (100). 4a .sup.1H NMR
.delta. 7.820 (s, 1H); 7.758 (d, .sup.3J=8.10 Hz, 1H); 7.450 (d,
.sup.3J=8.10 Hz, 1H); .sup.19F NMR .delta. -102.046 (d, 2J=241.03
Hz, 1F); -105.807 (d, 2J=241.03 Hz, 1F); -115.704 (d, 2J=239.90 Hz,
1F); -116.452 (d, .sup.2J=239.90 Hz, 1F). 4b .sup.1H NMR .delta.
7.573 (s, 1H); 7.994 (d, .sup.3J=8.40 Hz, 1H); 7.482 (d,
.sup.3J=8.40 Hz, 1H); .sup.19F NMR .delta. -107.109 (d,
.sup.2J=237.36 Hz, 1F); -109.445 (d, .sup.2J=237.36 Hz, 1F);
-108.734 (d, .sup.2J=237.36 Hz, 1F); -111.322 (d, .sup.2J=237.36
Hz, 1F).
[0088] Pseudo ortho-diphenyl-1,1,2,2,9,9,10,10-octafluoror [2,2]
paracyclophane
[0089] Benzene (10 mL) was added to the chilled diazotization
solution, and one minute later an aqueous (3 mL) solution of
soldium acetate (1.00 g, 12.20 mmol) was added. The bi-phasic
mixture was allowed to warm to room temperature overnight with
vigorous stirring. Ether was then added, and the bright orange
organic phase was separated, dried and evaporated. The crude
residue was chromatographed (hexane/dichloromethan 9/1) to give
(R.sub.f=0.27) 4-phenyl-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane.sup.10 (0.72 g, 32%) and (R.sub.f=0.20) pseudo
ortho-diphenyl-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane
(0.42 g, 16%): .sup.1H NMR .delta. 7.437 (s, 1H); 7.782 (d,
.sup.3J=8.10 Hz, 1H); 7.641-7.523 (m, 5H); 7.452 (d, .sup.3J=8.10
Hz, 1H); .sup.19F NMR .delta. -104.750 (d, 2J=239.62 Hz, 1F);
-113.413 (d, .sup.2.sup.2J=239.62 Hz, IF); -112.688 (d,
.sup.2J=244.70 Hz, 1F); -117.061 (d, .sup.2J=244.70 Hz, 1F); MS m/z
504 (M+, 8%), 251 (80), 232 (100). HRMS calcd. for
C.sub.28H.sub.16F.sub.8 504.1124, found 504.1157.
[0090] Pesudo ortho-bis(trifluoromethyl)-
1,1,2.2,9.9,10,10-octafluoro [2,21 ] paracyclophane, 8c
[0091] A degassed DMF (40 ml) solution containing pseudo
ortho-diiodo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 4c
(3.00 g, 4.97 mmol), methly 2-(fluorosulphonyl) difluoroacetate
(9.53 g, 49.67 mmol) and palladium dichloride (40 mg, 0.23 mmol)
was warmed to 80.degree. C. under a blanket of nitrogen. Copper (I)
bromide (5.33 g, 37.25 mmol) was added in one portion, and the
mixture was maintained at that temperature overnight. Then the
mixture was cooled to ambient temperature before adding ice water.
The mixture was stirred for 30 minutes and then the precipitates
were removed by filtration and were subjected to column
chromatography (hexane/diethyl ether 9/1) affording (R.sub.f=0.31)
pseudo ortho-iodo-trifluoromethyl-1,1,2,2,9,9,10,10-octafl- uoro
[2,2] paracyclophane 9 (0.27 g 10%): .sup.1H NMR .delta. 7.309 (s,
1H); 6.726 (s, 1H); 6.892 (d, .sup.3J=8.40 Hz, 1H); 6.757 (d,
.sup.3J=8.40 Hz, 1H); 6.705 (d, .sup.3J=8.70 Hz, 1H); 6.652 (d,
.sup.3J=8.70 Hz, 1H); .sup.19F NMR .delta. -107.182 (dd, 2J=242.16,
.sup.3J=7.20 Hz, 1F); -112.966 (dq, .sup.2J=242.16, .sup.5J=29.06
Hz, 1F); -107.635 (dd, .sup.2J=239.90, .sup.3J=12.10 Hz, 1F);
-110.960 (dd, .sup.2J =239.90, .sup.3J=7.30 Hz, 1F), -108.138 (dd,
.sup.2J=236.23, .sup.3J=12.10 Hz, 1F); -110.315 (dd,
.sup.2J=236.23, .sup.3J=7.30 Hz, 1F); -113.747 (dq, .sup.2J=234.82,
.sup.6J=14.54 Hz, 1F); -114.623(dd, .sup.2J=234.82, .sup.3J=7.20
Hz, 1F); -59.257 (dd, .sup.5J=29.07, .sup.6J=14.54 Hz, 3F); MS m/z
546 (M+, 5%), 302 (100), 244 (10). HRMS calcd. for
C.sub.17H.sub.6F.sub.11I 545.9339, found 545.9401; (R.sub.f=0.17)
Pseudo ortho-bis(trifluoromethyl)-1,1,2,2,9,9,10,1 0-octafluoro
[2,2] paracyclophane 8c (1.65 g, 68%): mp 154-155.degree. C.;
.sup.1H NMR .delta. 7.493 (s, 1H); 7.733 (m, 2H); .sup.19F NMR
.delta. -108.067 (dd, .sup.2J=242.16, .sup.3J=9.60 Hz, 1F);
-112.234 (dq, .sup.2J=242.16, .sup.5J=29.07 Hz, 1F); -113.163 (dd,
.sup.2J=237.36, .sup.3J=9.60 Hz, 1F); -114.751 (dq, .sup.2J=237.36,
6.sup.6J=14.68 Hz, 1F); -59.160 (dd, .sup.5J=29.07, .sup.6J=14.68
Hz, 3F); MS m/z 488 (M+, 5%), 244 (100); Anal. Calcd for
C.sub.18H.sub.6F.sub.14: C, 44.26; H, 1.24. Found: C, 44.24; H,
1.02.
[0092] An identical reaction with a 1:1 a mixture of pseudo meta-
and pseudo para-diiodo-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 4a,b gave the corresponding pseudo meta- and pseudo
para-bis(trifluoromethyl)-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 8a,b in 80% yield: (hexane/ether 9/1,
R.sub.f=0.67); Anal. Calcd for C.sub.18H.sub.16F.sub.14: C, 44.26;
H, 1.24. Found: C, 44.32; H, 1.15. MS m/z 488 (M+, 4%), 244
(100).
[0093] There was no evidence of any iodo-trifluoromethyl isomers in
this reaction. (It was possible to collect an analytic sample of
the more insoluble pseudo
para-bis(trifluoromethyl)-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane 8b by fractional crystallization, which had mp
199-200.degree. C.): 8a .sup.1H NMR .delta. 7.824 (s, 1H); 7.710
(d, .sup.3J=8.40 Hz, 1H); 7.543 (d, .sup.3J=8.40 Hz, 1H); .sup.19F
NMR .delta. -105.860 (dq, .sup.2J=242.16, .sup.6J=14.68 Hz, 1F);
-112.029 (dq, .sup.2J=242.16, .sup.5J=29.07 Hz, 1F); -113.562 (d,
.sup.2J=247.24 Hz, 1F); -118.289 (d, .sup.2J=247.24 Hz, 1F);
-58.633 (dd, .sup.5J=29.07, .sup.6J=14.68 Hz, 3F); 8b .sup.1H NMR
.delta. 7.850 (s, 1H); 7.693 (d, .sup.3J=8.40 Hz, 1H); 7.574 (d,
.sup.3J=8.40 Hz, 1H); .sup.19F NMR .delta. -107.280 (dd,
.sup.2J=242.16, .sup.3J=7.06 Hz, 1F); -112.902 (dq, .sup.2J=242.16,
.sup.5J=31.61 Hz, 1F); -111.769 (dq, .sup.2J=237.36, .sup.6J=9.88
Hz, 1F); -115.648 (dd, .sup.2J=237.36, .sup.3J=7.06 Hz, 1F);
-58.300 (dd, .sup.5J=31.61, .sup.6J=9.88 Hz, 3F).
[0094] 4-Trifluoromethyl-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane, 10
[0095] An acetic acid solution (30 mL) containing pseudo
ortho-iodo-trifluoromethyl-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane 9 (230 mg, 0.42mmol) and zinc (110 mg, 1.70 mmol)
was refluxed overnight. The mixture was cooled to ambient
temperatures and added to ice water (100 mL). The precipitates were
collected and subjected to column chromatography (hexane/diethyl
ether 8/2) producing (R.sub.f=0.56)
4-trifluoromethyl-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane
10 (160 mg, 91%), analytically identical to an authentic
sample..sup.10
[0096] Pseudo ortho-diacetamido-1,1,2,2,9,9,10.10-octafluoro [2,2]
paracyclophane
[0097] A dichloromethane (5 ml) solution of pseudo
ortho-diamino-1,1,2,2,9- ,9,10,10-octafluoro [2,2] paracyclophane
3c (200 mg, 0.52mmol) was warmed to reflux, and acetyl chloride (2
mL) was added dropwise, and the reaction was refluxed overnight.
Rotary evaporation afforded a pale brown residue, which after
chromatography (hexane/ether 1/9) gave R.sub.f=0.60) pseudo
ortho-diacetamido-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane
(0.24 g, 97%): mp 199-201.degree. C.; .sup.1H NMR .delta. 7.818 (s,
1H); 7.392 (d,.sup.3J=8.10 Hz, 1H); 7.074 (d, .sup.3J=8.40 Hz, 1H);
8.854 (br s, 1H, NH); 2.243 (s, 3H, CH.sub.3); .sup.19F NMR .delta.
-107.595 (d, .sup.2J=244.70 Hz, 1F); -111.870 (d, .sup.2J=244.70
Hz, 1F); -111.439 (d,.sup.2J=237.36 Hz, 1F); -114.882
(d,.sup.2J=237.36 Hz, 1F); MS m/z 466 (M+, 27%), 446 (40), 233
(12), 191 (100). Anal. Calcd for
C.sub.20H.sub.14F.sub.8N.sub.2O.sub.2: C, 51.50; H, 3.00; N, 6.01.
Found: C, 51.32; H, 3.05; N, 5.91.
[0098] An identical reaction with a 1; 1 mixture of pseudo meta-
and pseudo para-diamino-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 3a,b gave the corresponding pseudo meta- and pseudo
para-diacetamido-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophanes
in 84% yield: (hexane/ether 4/6, R.sub.f=0.44); Anal. Calcd for
C.sub.20H.sub.14F.sub.8N.sub.2O.sub.2: C, 51.50; H, 3.00; N, 6.01.
Found: C, 51.38; H, 2.91; N, 5.91. MS m/z 466 (M+, 5%), 446 (42),
233 (22), 191 (100); pseudo meta isomer: .sup.1H NMR .delta. 8.112
(s, 1H); 7.401 (d, .sup.3J=8.40 Hz, 1H); 7.013 (d, .sup.3J=8.40 Hz,
1H); 8.817 (br s, 1H, NH); 2.251 (s, 3H, CH.sub.3); .sup.19F NMR
.delta. -103.130 (d, .sup.2J=247.10 Hz, 1F); -104.959 (d,
.sup.2J=247.10 Hz, 1F); -115.615 (d, .sup.2J=237.36 Hz, 1F);
-115.911 (d, .sup.2J=237.36 Hz, 1F). pseudo para isomer .sup.1H NMR
.delta. 7.808 (s, 1H); 7.401 (d,.sup.3J=8.10 Hz, 1H); 7.082 (d,
.sup.3J=8.10 Hz, 1H); 8.942 (br s, 1H, NH); 2.251 (s, 3H,
CH.sub.3); .sup.19F NMR .delta. -107.616 (d, .sup.2J=244.70Hz, 1F);
-111.836 (d, .sup.2J=244.70Hz, 1F); -113.462 (d,.sup.2J=237.36 Hz,
1F); -114.314 (d, .sup.2J=237.36 Hz, 1F).
[0099] Pseudo
ortho-bis(trifluoroacetamido)-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane
[0100] A solution of pseudo
ortho-diamino-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 3c
(270 mg, 0.71 mmol) in trifluoroacetic anhydride (4 mL) was
refluxed overnight. After this time, rotary evaporation yielded a
solid residue that after chromatography (chloroform) afforded
(R.sub.f=0.64) pseudo
ortho-bis(trifluoroacetamido)-1,1,2,2,9,9,10,10-oct- afluoro [2,2]
paracyclophane (0.39 g, 95%): mp 123-124.degree. C.; .sup.1H NMR
.delta. 7.550 (s, 1H); 7.470 (d,.sup.3J=8.40 Hz, 1H); 7.237 (d,
.sup.3J=8.40 Hz, 1H); 9.801 (br s 1H, NH); .sup.19F NMR .delta.
-109.464 (d, .sup.2J=247.24, Hz, 1F); -112.265 (d, .sup.2J=247.24,
Hz, 1F); -113.333 (d, .sup.2J=239.90 Hz, 1F); -114.249 (d,
.sup.2J=239.90, Hz, 1F); -75.832 (s, 3F); MS m/z 574 (M+, 6%), 554
(32), 287 (22), 267 (100); Anal. Calcd for
C.sub.20H.sub.8F.sub.14N.sub.2O.sub.2: C, 41.81; H, 1.39; N, 4.88.
Found: C, 41.64; H, 1.29; N, 4.80.
[0101] An identical reaction with a 1:1 mixture of pseudo meta-and
pseudo para-diamino-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes 3a,b gave the corresponding pseudo meta- and pseudo
para-bis(trifluoroacetamido)-1,- 1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes in 97% yield: (hexane/ether 4/6, R.sub.f=0.44);
Anal. Calcd for C.sub.20H.sub.8F.sub.14- N.sub.2O.sub.2: C, 41.81;
H, 1.39; N, 4.88. Found: C, 41.77; H, 1.34; N, 4.81. MS m/z 574
(M+, 3%), 554 (32), 287 (82), 267 (100); pseudo meta isomer:
.sup.1H NMR .delta. 7.641 (s, 1H); 7.533 (d, .sup.3J=8.40 Hz, 1H);
7.252 (d, .sup.3J=8.40 Hz, 1H); 10.117 (br s, 1H, NH); .sup.19F NMR
.delta. -107.988 (d, .sup.2J=247.24 Hz, 1); -108.255 (d, 247.24 Hz,
1F); -116.278 (d, .sup.2J=239.90 Hz, 1F); -118.013 (d,
.sup.2J=239.90 Hz, 1F); -75.514 (s, 3F); pseudo para isomer:
.sup.1H NMR .delta. 7.765 (s, 1H); 7.406 (d, .sup.3J=8.40 Hz, 1H);
7.374 (d,.sup.3J=8.40 Hz, 1H); 10.117 (br s, 1H, NH); .sup.19F NMR
.delta. -111.130 (d, .sup.2J=246.95 Hz, 1F); -111.292 (d, 2J=246.95
Hz, 1F); -113.375 (d, .sup.2J=239.62 Hz, 1F); -115.955 (d,
.sup.2J=239.62 Hz, 1F); -75.574 (s, 3F).
[0102] Pseudo ortho-diphenyl-1,1,2,2,9,9,10,10-octafluoro [2,21]
paracyclophane
[0103] A degassed THF solution (5 mL) containing pseudo
ortho-dilodo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 4c
(300 mg, 0.50 mmol) and palladium dichloride (21 mg, 0.12 mmol) was
stirred and brought to reflux under a nitrogen atmosphere. A 1M THF
solution of phenyl magnesium bromide (3.0 mL, 3.00 mmol) was added
via syringe, and the black solution was refluxed overnight.
Evaporation of the solvent was followed by the addition ice water,
and the precipitated solids were chromatographed
(hexane/dichloromethane 9/1) to give (R.sub.f=0.44)
4-phenyl-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane.sup.10
(43 mg, 20%), and R.sub.f=0.37) pseudo
ortho-diphenyl-1,1,2,2,9,9,10,10-octafluor- o [2,2] paracyclophane
(53 mg, 21%): .sup.1H NMR .delta. 7.437 (s, 1H); 7.782 (d,
.sup.3J=8.10 Hz, 1H); 7.641-7.523 (m, 5H); 7.452 (d, .sup.3J=8.10
Hz, 1H); .sup.19F NMR .delta. -104.750 (d, .sup.2J=239.62 Hz, 1F);
-113.413 (d, .sup.2J=239.62 Hz, 1F); -112.688 (d, .sup.2J=244.70
Hz, 1F); -117.061 (d, .sup.2J=244.70 Hz, 1F); MS m/z 504 (M+, 8%),
251 (80), 232 (100). HRMS calcd. for C.sub.28H.sub.16F.sub.8
504.1124, found 504.1157.
[0104] Para dibromi-1,1,2,2,9,9,10,10-octafluoro [2,21]
paracyclophane, 5d
[0105] A trifluoroacetic acid solution (3 ml) containing
1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 1 (1.00 g, 2.84
mmol) and N-bromo-succinamide (2.02 g, 11.35 mmol) was stirred
magnetically in a flask protected by a silica drying tube. After 5
minutes, 98% sulfuric acid (1mL) was added, and left to stir for 16
hrs. After this time analysis by .sup.19F NMR and TLC showed the
presence of starting material, mono-bromo OFP and several dibromide
isomers, one of which seemed predominant. The reaction was warmed
to 80.degree. C. and left another 12 hrs. The mixture was cooled to
ambient temperatures, and added to 100 mL of ice water. The pale
yellow precipitate was subjected to column chromatography
(hexane/chloroform 50/1), and gave (R.sub.f=0.36) para
dibromo-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophane 5d (0.65
g, 55%): mp 159-161.degree. C.; .sup.1H NMR .delta. 7.416 (s, 1H);
7.970 (d, .sup.3J=8.40 Hz, 1H); 7.481 (d, .sup.3.sup.3J=8.40 Hz,
1H); .sup.19F NMR .delta. -110.194 (d, .sup.2J=237.36 Hz, 1F);
-112.642 (d, .sup.2J=237.36 Hz, 1F); -111.499 (m, 2F); MS m/z 508
(M+, 6%), 510 (13), 512 (6), 334 (5), 254 (53), 256 (49), 176
(100); Anal. Calcd for C.sub.16H.sub.6F.sub.8Br.sub.2: C, 37.65; H,
1.18. Found: C, 37.81; H, 1.19; (R.sub.f=0.20) A mixture of
monobromo-, dibromi- (2 isomers) and tribromo-(3 isomers)
-1,1,2,2,9,9,10,10-octafluoro [2,2] paracyclophanes (0.172 g).
GLCMS indicted that the dibromo isomers in the second fraction
showed one isomer each of hetero- and homo-annular disbtribution,
whilst the tribromides all contained 2 bromines on one ring and 1
in the other. This second fraction was not further analyzed.
[0106] Para bis(trifluoromethyl)-1,1,2,2,9,9,10,10-octafluoro [2.2]
paracyclophane, 8d
[0107] A degassed DMF (20 mL) solution containing
para-dibromo-1,1,2,2,9,9- ,10,10-octafluoro [2,2] paracyclophane 5d
(0.53 g, 1.04 mmol) and methyl 2-(fluorosulphonyl) difluoroacetate
(0.80 g, 4.16 mmol) was warmed to 100.degree. C. under a blanket of
nitrogen. Copper (I) bromide (0.59 g, 4.16 mmol) was added in one
portion, and the mixture was maintained at that temperature
overnight. Then the mixture was cooled to ambient temperature
before adding ice water. The mixture was stirred for 30 minutes and
then the precipitates were removed by filtration and were subjected
to column chromatography (hexane/diethyl ether 9/1) affording
(R.sub.f=0.72)
para-bis(trifluoromethyl)-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophane 8d (66 mg, 13%): mp 125-126.degree. C.; .sup.1H NMR
.delta. 7.810 (s, 1H); 7.427 (m, 2H); .sup.19F NMR .DELTA. -109.271
(dd, .sup.2J=244.67, .sup.3J=9.88 Hz, 1F); -112.848 (dq,
.sup.2J=244.67, .sup.5J=29.07 Hz, 1F); -113.468 (dd,
.sup.2J=232.54, .sup.3J=9.88 Hz, 1F); -114.830 (dq, .sup.2J=232.54,
.sup.6J=16.93 Hz, 1F); -59.187 (dd, .sup.5J=29.07, .sup.6J=16.93
Hz, 3F); MS m/z 488 (M+, 3%), 312 (3), 176 (100); Anal. Calcd for
C.sub.18H.sub.6F.sub.14: C, 44.26; H, 1.23. Found: C, 44.47; H,
1.19; (R.sub.f=0.40) 4-Trifluoromethyl-1,1,2,2,9,9,10,10-oct-
afluoro [2,2] paracyclophane 10 (74 mg, 17%), whose
characterization was identical to an authentic sample..sup.10
[0108] Thermal Isomerization
[0109] A tube containing pseudo
ortho-bis(trifluoroacetamido)-1,1,2,2,9,9,- 10,10-octafluoro [2,2]
paracyclophane (90 mg, mmol) was evacuated, sealed immersed in a
Woods metal heating bath at 381-390.degree. C. for 2 hours. After
this time, the tube was cooled, opened and shown by .sup.19F NMR to
contain both pseudo ortho- and pseudo
para-bis(trifluoroacetamido)-1,1,2,- 2,9,9,10,10-octafluoro [2,2]
paracyclophanes in a 5:1 ratio. This material was placed into
another identical tube, and again evacuated, sealed and immersed
into the Woods metal heating bath and heated at 350-363.degree. C.
for 24 hours. The resulting product mixture was shown by .sup.19F
NMR to now contain a 1:7 ratio of pseudo ortho- and pseudo
para-bis(trifluoroacetamido)-1,1,2,2,9,9,10,10-octafluoro [2,2]
paracyclophanes. Integration versus an internal standard of
trifluorotoluene showed the mass balance of the two isomers was
75%.
* * * * *