A novel, non-high-dilution method for preparation of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane

Article abstract of DOI:10.1021/ol005943f

(Formula presented) A novel synthesis of octafluoro[2.2]paracyclophane (AF4), one that remarkably does not require the use of high dilution methodology, is presented. Using this unprecedented methodology, AF4 is produced in 60% yield in a reaction of Zn with 0.35 M p-bis(chlorodifluoromethyl)-benzene in DMA at 100°C. The process comprises a convenient, inexpensive, and highly scaleable preparation of AF4 for both research and commercial purposes.

Full text of DOI:10.1021/ol005943f

ORGANIC
LETTERS
2000
Vol. 2, No. 13
1867-1869
A Novel, Non-High-Dilution Method for
Preparation of
1,1,2,2,9,9,10,10-Octafluoro[2.2]paracyclophane
William R. Dolbier, Jr.,* Jian-Xin Duan, and Alex J. Roche
Department of Chemistry, UniVersity of Florida, GainesVille, Florida 32611-7200
wrd@chem.ufl.edu
Received April 12, 2000
ABSTRACT
A novel synthesis of octafluoro[2.2]paracyclophane (AF4), one that remarkably does not require the use of high dilution methodology, is
presented. Using this unprecedented methodology, AF4 is produced in 60% yield in a reaction of Zn with 0.35 M p-bis(chlorodifluoromethyl)-
benzene in DMA at 100 °C. The process comprises a convenient, inexpensive, and highly scaleable preparation of AF4 for both research and
commercial purposes.
Since their first designed synthesis in 1951,1 [2.2]paracy-
clophanes have been considered valuable compounds for
testing theories of bonding, ring strain, and π-electron
interactions.2-4 A number of methods have been devised for
the relatively convenient synthesis of parent hydrocarbon 1,
all of which require the use of high dilution methodology.5-7
industry as “parylenes”.8 Such parylenes are ideally suited
for use as conformal coatings in a wide variety of applica-
tions, such as in the electronics, semiconductor, automotive,
and medical industries. Parylene coatings are inert and
transparent and have excellent barrier properties. Parylene
N, which is generated from the parent hydrocarbon 1, has
been found to be useful at temperatures up to 130 °C.
1,1,2,2,9,9,10,10-Octafluoro[2.2]paracyclophane, 2,9 the
bridge-fluorinated version of 1 (and known in the industry
as AF4), is the CVD precursor of Parylene-HT polymer,
In addition, it has been recognized since the mid-1960s
that [2.2]paracyclophanes are useful chemical vapor deposi-
tion (CVD) precursors of thin film polymers, known in the
poly(R,R,R′,R′-tetrafluoro-p-xylylene). The Parylene-HT poly-
mer combines a low dielectric constant (2.25)10 with high
thermal stability (<1 wt % loss/2 h at 450 °C), low moisture
absorption (<0.1%), and other advantageous properties.10,11
With such properties and because its in vacuo deposition
(1) Cram, D. J.; Steinberg, H. J. Am. Chem. Soc. 1951, 73, 5691.
(2) Boekelheide, V. Top. Curr. Chem. 1983, 113, 87.
(3) Cram, D. J. In Cyclophanes; Keehn, P. M., Rosenfeld, S. M., Eds.;
Academic Press: New York, 1983; Vol. 1, p 1.
(4) Cram, D. J.; Cram, J. M. Acc. Chem. Res. 1971, 4, 204-213.
(5) Winberg, H. E.; Fawcett, F. S. Organic Syntheses; Wiley: New York,
1973; Collect. Vol. V, pp 883-885.
(6) Vogtle, F.; Neumann, P. Synthesis 1973, 85-103.
(7) Ito, Y.; Miyata, S.; Nakatsuka, M.; Saegusa, T. J. Org. Chem. 1981,
46, 1044-1045.
(8) Gorham, W. F. J. Polym. Sci.: Part A-1 1966, 4, 3027.
(9) Chow, S. W.; Pilato, L. A.; Wheelwright, W. L. J. Org. Chem. 1970,
35, 20-22.
10.1021/ol005943f CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/01/2000

process ensures conformality to microcircuit features and
superior submicron gap-filling capability, Parylene-HT con-
tinues to show considerable promise as an interlayer dielectric
for on-chip high-speed semiconductor device interconnection.
Heretofore, a significant aspect of methods for synthesis
of virtually every [2.2]paracyclophane has been the necessity
to carry out such reactions using high dilution conditions.
The classic and still most commonly used method of
preparing [2.2]paracyclophanes involves generation of a
p-xylylene intermediate such as 2, which then dimerizes to
form the paracyclophane, as exemplified in Scheme 1 for
one to circumvent conventional high dilution technology with
the result that both high yield and scale-up were feasible.13
Nevertheless, use of this process has been inhibited by the
high costs of the required AF4 precursor, p-bis(bromodi-
fluoromethyl)benzene, 4, and the tinsilane reagent 5, as well
as by the lack of a good scale-up procedure for 4.
Scheme 1
Thus, work has continued to find a convenient, inexpen-
sive, and scaleable method for synthesis of AF4, a goal made
all the more important since methods have recently been
reported for mono- and multisubstituted ring derivatization
of AF4,14,15 which opens up a number other potential
applications of AF4 and its derivatives. In this Letter, we
are pleased to report an exciting new method for the synthesis
of AF4, one that moreover describes what we believe is the
first example of the synthesis of a [2.2]paracyclophane by a
method that does not require the use of high dilution
technology.
It has been found that heating a mixture of 4 equiv of
zinc dust and 0.35 M p-bis(chlorodifluoromethyl)benzene,
6, in dimethylacetamide, for 4 h at 100 °C produces AF4 in
a yield of ∼60%, with some apparent oligomeric side
products but little insoluble polymer being formed. A typical
small scale procedure is given in ref 18, but the reaction
can be scaled proportionally to virtually any magnitude.16
the general synthesis of AF4. Use of high dilution conditions
is generally required in such processes in order to provide
the optimal kinetic environment to allow unimolecular
cyclization of intermediate diradical 3 to compete effectively
with undesired bimolecular oligomerization.
In our initially reported Ti* process, although the use of
traditional high dilution methodology allowed preparation
of gram quantities of AF4 for the first time, it also essentially
precluded significant scale-up of the procedure.12
Significantly, when the reaction is carried out under typical
high dilution conditions, little or no AF4 is formed.
Moreover, use of dibromide precursor, 4 (which was essential
to the success of both the Ti* and tinsilane processes), in
place of dichloride 6 leads to a greatly diminished (∼10%)
yield of AF4. Numerous other metals, including Mg, were
examined, but zinc proved to be unique in giving good yields
in the reaction. The presence of O2 inhibits the reaction. It
should also be mentioned that the conditions of this reaction
unfortunately proved inappropriate for synthesis of parent
[2.2]paracyclophane 1 from p-bis(chloromethyl)benzene
(yield < 5%), although numerous ring-substituted derivatives
of 6 proved to be decent substrates for the reaction, albeit
none so efficacious as 6 itself.
Subsequently, we found that a process involving use of
(trimethylsilyl)tributyltin, 5, with cesium fluoride allowed
(13) Dolbier, W. R. J.; Rong, X. X.; Xu, Y.; Beach, W. F. J. Org. Chem.
1997, 62, 7500-7502.
(10) Majid, N.; Dabral, S.; McDonald, J. F. J. Electron. Mater. 1989,
18, 301-311.
(11) Williams, K. R. J. Thermal Anal. 1997, 49, 589-594.
(12) Dolbier, W. R.; Asghar, M. A.; Pan, H. Q.; Celewicz, L. J. Org.
Chem. 1993, 58, 1827-1830.
(14) Roche, A. J.; Dolbier, W. R., Jr. J. Org. Chem. 1999, 64, 9137-
9143.
(15) Roche, A. J.; Dolbier, W. R., Jr. Submitted for publication.
(16) Dolbier, W. R., Jr.; Duan, J.-X.; Roche, A. J. U.S. Pat. 5,841,005,
1998.
1868
Org. Lett., Vol. 2, No. 13, 2000

Note that small amounts of unusual bridge-unsaturated
compound 7 are formed in the reaction as it is run.17 If
desired, one can modify the reaction conditions to form larger
quantities of 7, at the expense of AF4. Thus, carrying out
the reaction in refluxing THF for 2 days gives 14% of 7 and
only 6% of AF4.
It is apparent that the mechanism of this [2.2]paracyclo-
phane-forming reaction cannot involve free R,R,R′R′-tet-
rafluoroxylylene, 2, undergoing its usual mechanism of
dimerization and cyclization as depicted in Scheme 1. Rather
we believe that the reaction is occurring on the surface of
the zinc metal and that dimerization is occurring without the
intermediacy of free 2. Further studies, presently underway,
should shed additional light on the mechanism of the
reaction.
(17) NMR (in CDCl3) characterization of 7: 1H, δ 7.06 and 7.15 (AB,
JAB ) 8.7 Hz); 19F, δ -115.98 (s, 4F), -118.68 (s, 2F).
(18) Experimental procedure: Into a 1 L three-necked round-bottomed
flask are added 600 mL of N,N-dimethylacetamide (DMA), p-bis(chlorodi-
fluoromethyl)benzene (6) (60 g, 0.24 mol), and zinc dust (61 g, 0.96 mol).
The mixture is heated over a period of 40 min to 100 °C under vigorous
stirring and an N2 atmosphere, and it was maintained at that temperature
for 4 h, after which no 6 remained and the solution had become yellow.
The reaction mixture was then cooled to room temperature and filtered,
washing the resulting oligomeric solids with two 50 mL portions of DMA
to extract small amounts of AF4. Combining these washings with the original
DMA filtrate, the impurities 7 (∼6% yield) and heptafluoro[2.2]para-
cyclophane (<1%) were removed by stirring the combined DMA solution
at room temperature with 5 g of KMnO4 overnight, followed by again
filtering the mixture to obtain a clear, colorless DMA solution. The crude
AF4 product was then obtained by evaporating the DMA filtrate at 100 °C
under full vacuum. After washing the resulting residue with water and cold
methanol, the crude product was extracted with benzene, the benzene was
evaporated, and the residue was recrystallized from hexane to give >99%
pure AF4 (25.6 g, 60.5%).
Combining the ease of the new AF4-forming process with
the fact that dichloro precursor 6 is much more readily
prepared (photolytically or thermally initiated chlorination
of R,R,R′R′-tetrafluoroxylene)9 than its dibromo analogue 4,
the current overall methodology for synthesis of AF4 should
enable convenient, inexpensive, and highly scaleable prepa-
ration of AF4 for both research and commercial purposes.
Acknowledgment. Support of this research in part by
AlphaMetals, Inc. is gratefully acknowledged.
OL005943F
Org. Lett., Vol. 2, No. 13, 2000
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