Scientific paper
Trifluoromethylation of Perfluorinated Diacylfluorides: Synthesis of the Diketone CF3C(O)CF2C(O)CF3 and of New Perfluorinated Diol (CF3)2C(OH)CF2C(OH)(CF3)2
Sandra Corti,1 William T. Pennington2 and Darryl D. DesMarteau2*
1 3420 Ashton Drive, Suwanee, GA 30024, USA
2 H. L. Hunter Chemistry Laboratory, Clemson University, P.O. Box 341905, Clemson, South Carolina 29634-1905, USA
* Corresponding author: E-mail: fluorin@clemson.edu Phone: 01-864-656-1251; Fax: 01-864-656-2545
Received: 14-08-2012
Dedicated to Prof.Dr. Boris Zemva on the occasion of receiving the Zois' award for lifetime achievements.
Abstract
Perfluoromalonyl difluoride reacts with TMS-CF3 (1:1) in the presence of KF to give the new diketone CF2(C(O)CF3)2. A large excess (5:1) of TMS-CF3 results in the presumed potassium dialkoxide [(CF3)2COK]2CF2 which yields the 1,3-ditertiarydiol [(CF3)2C(OH)]2CF2 on reaction with H2SO4.
Keywords: Perfluoromalonyl difluoride, trifluoromethylated diketone, 1,3-ditertiarydiol
1. Introduction
It has been previously reported that (CH3)3SiCF3 (TMS-CF3) can be employed to generate tertiary alkoxides and alcohols by nucleophilic trifluoromethylation of a variety of fluoroketones and acid fluorides in the presence of metal fluorides.1 As an extension of this chemistry this reaction has been investigated2 with some diacyl fluorides in an attempt to prepare fluorinated diols (CF3)2C(OH)(CF2)nC(OH)(CF3)2 of various chain lengths which would have useful solvent properties. In fact fluo-roalcohols and their derivatives are attaining increasing importance in dyestuffs, plastics, pharmaceuticals and surface coatings, as well as use in fluorine-containing polymers and in organometallic chemistry. However, the reaction with F(O)C(CF2)nC(O)F n = 2,3 resulted in novel cyclic diols via the facile cyclodimerization of the diketo-nes with water. For n=0, the reaction led to decomposition of the starting diacylfluoride. It became of interest to investigate this trifluoromethylation reaction with the less readily available malonyl fluoride (n = 1). Herein we report the successful preparation of the diketone and the desired 1,3-tertiarydiol, but the reactions are somewhat complex.
2. Experimental Section
Caution! Working with highly acidic alcohols is potentially hazardous since perfluoropinacol has been determined to be a highly toxic material, both from the standpoint of skin contact and inhalation, while other alcohols have been tested as fumigants.3 The compound synthesi-sed in this work is quite similar to perfluoropinacol and should be treated as potentially highly toxic material.
General Methods. Infrared spectra were recorded on Perkin Elmer 1600 FT/IR using a 10 cm glass cell fitted with KCl windows attached with Halocarbon 1500 wax. NMR spectra were acquired at 200.13 MHz for 1H and 188.31 MHz for 19F on a Bruker AC 200. Chemical shifts are reported relative to Si(CH3)4 or CFCl3 with upfield shifts designated as negative. Tetramethylsilane was usually omitted from 1H samples, and the reference was actually set on the residual 1H resonance of the deuterated solvent.
Gases and volatile compounds were handled in glass vacuum systems, equipped with glass-Teflon valves. Amounts of volatile compounds were determined by PVT measurements using a Wallace & Tiernan Series 1500 differential pressure gauge. All trap-to-trap fractionations were performed under static vacuum.
The reaction vessel for preparation of the diketone and the diol consisted of a 100 mL round bottom Pyrex flask with a glass-Teflon valve attached through an Ace-thread®, O-ring seal connector. The body of the flask was modified by addition of a side arm fitted with a Teflon-faced silicone septum. Liquids could be added via syringe, without compromising the ability of the system to hold vacuum after removal of the syringe needle. The reactor contained a Teflon-coated magnetic stirring bar.
Purity of new compounds was determined by 19F NMR and also by 1H NMR as appropriate. Known compounds were identified by NMR and comparison with literature values.
Starting Materials. Perfluoromalonyl difluoride4-6 (1) and (trifluoromethyl)trimethylsilane1 (TMS-CF3) were prepared by literature methods. Active KF was prepared by fusion in a Pt dish followed by pulverization under very dry nitrogen in a porcelain mortar. Dry solid materials were handled inside an efficient drybox. Benzonitrile and acetonitrile were dried over P4O10.
Preparation of CF3(O)CCF2C(O)CF3 (2) from F(O)CCF2C(O)F. Freshly fused potassium fluoride (740 mg, 12,7 mmol) was loaded into the reactor (see above), the reactor was partially evacuated and 3 mL of dry ben-zonitrile was added by syringe. The reactor was cooled to -196 °C and evacuated. Perfluoromalonyl difluoride (2.0 mmol) and TMS-CF3 (4.0 mmol) were condensed into the reactor by vacuum transfer. The reactor was placed in a 0 °C bath and stirring was begun as soon as the reaction mixture melted. After 16 hours the volatiles were removed at room temperature by vacuum pumping through a -196 °C trap for 2 hours. The content of this trap was fractionated through traps at -33, -86, -96 and -196 °C. The -196 °C trap contained 4.2 mmol of a mixture consisting mainly of TMS-F with some CF3H. Benzonitrile was retained in the -33 °C trap. The -96 °C trap gave 0.6 mmol of 2 (30 % yield). The -86 °C trap gave 0.7 mmol of compound 3 (see Discussion). Compound 2 was characterized as follows: IR (5 torr) 1806 (s), 1322 (s), 1250 (vs), 1192 (vs), 1155 (s), 1092 (m), 992 (s), 911 (s), 862 (s), 756 (m) cm-1; NMR (CF3A(O)C)2CF2B (CDCl3, 24 °C) 5(19F) A -75.2 (6 F, t), B -114.5 (2 F, sept) . Compound 3 was characterized as follows: IR (in solution CDCl3): 1843 (vs), 1356 (m), 1210 (vs), 971 (s), 935 (m),
o
838 (s) cm-1; NMR ^^^SVT (CDCl3, 24 °C) 5(19F) A
-79.3 (3 F, dd), B -112.2, C -121.5 (2 F, AB pattern), D -77.2 (3 F, m), E -107.5, F -112.5 (2 F, AB pattern) G -71.0 (6 F, m); JAB = 17, JAC = 4, JBC = 298, JEF = 298 Hz.
Preparation of (CF3)2C(OH)CF2C(OH)(CF3)2 (4). Activated KF (850 mg, 14.6 mmol) was loaded into the reactor (see above), the reactor was partially evacuated and 4 mL of dried acetonitrile was added by syringe. After the reactor was cooled to -196 °C and evacuated, perfluo-
romalonyl difluoride (2.0 mmol) and TMS-CF3 (10.5 mmol) were condensed into the reactor by vacuum transfer. The reaction mixture was stirred for 1 hour in a -50 °C bath followed by three days additional stirring at 20 °C, giving a brown solution. Volatiles were removed under dynamic vacuum at 20 °C and the remaining brown solid was extracted with three 10 mL portions of diethyl ether [19F NMR, Et2O; 5 -104.8 (2F, m); 5 -74.0 (12F, M)]. After evaporation of the solvent, 5 mL of concentrated H2SO4 was added to the 492 mg of the remaining brown powder. After 5 hours the crude product was collected by vacuum pumping at 20 °C through a trap cooled at -196 °C for 4 hours. Fractionation through traps at -20 and -196 °C gave in the -20 °C trap 206 mg (30% yield) of a white solid which crystallizes by melting and slowly cooling into long white needles. The -196 °C trap contains traces of the known compound (CF3)2C(OH)CF2C(O)CF37.
The new compound 4 was characterized as follows: mp 58-60 °C; IR (KBr pellet) 3448 (b), 1623 (w), 1264 (vs), 1177 (s), 1127 (m), 968 (m), 819 (m), 738 (m), 724 (m) cm1; NMR [(CF3A)2C(OH)]2CF2B (CDCl3 24 °C) 5 (19F) A -72.5 (12 F, t), B -103.6 (2 F, m), JAB = 13 Hz; 5 (1H) 5.58 (br, s);
Preparation of [(CF3)2C(ONa)]2CF2 5. In a 50 mL round bottom flask 45 mg (0.11 mmol) of product 4 were dissolved in 2 mL of distilled water. 0.1 M NaOH solution was added until pH 7.0. The solution was then evaporated and the salt was dried under dynamic vacuum at 100 °C, leaving 50 mg (100% yield) of a white solid. The salt was characterized as follows: NMR [(CF3A)2C(ONa)]2CF2B (D2O, 24 °C) 5 (19F) A -70.4 (12 F, t), B -105.0 (2 F, m) JAB = 13.0 Hz.
2. 1. X-ray Crystallographic Analysis of 4
General details for the data collection and structural solution and refinement are given in Table 1.
Intensity data were measured at -70(2) °C with grap-hite-monochromated Mo Ka radiation (^ = 0.71073 A) on a Nicolet R3mV serial detection system. Data were corrected for Lorentz and polarization effects and for absorption. The latter correction was based on empirical methods.
The structure was solved by direct methods and refined by using full-matrix least-squares techniques (on F2). All non-hydrogen atoms were refined anisotropically; hydrogen atoms were refined with isotropic displacement parameters.
Structure solution, refinement and the calculation of derived results were performed with the SHELXTL8 package of computer programs. Neutral atom scattering factors were those of Cromer and Waber,9a and the real and imaginary anomalous dispersion corrections were those of
Cromer.9b
Crystallographic data have been deposited with the Crystallographic Data Center CCDC 896618. Copies may
be obtained free of charge on application to the Director, CCDC, 12 Union Road, Cambridge CB21EZ, UK. (http: //www.ccdc.com.ac.uk/conts/retrieving)
Table 1. Crystal data
Compound 1
Formula
Mw
Crystal System Space Group
a,	A
b,	A
c,	A
P, (°) V, A3 Z
F(000)
^ g cm-3
||, mm 1
Transmission coefficients Crystal dimensions (mm) 0 range (°)
hklrange
Reflections collected Reflections unique (Rmrge) Reflections observed (I>2a)
R1a
wR•
C7H2O2F14
384.09
Monoclinic
P2/n (No. 14)
7.0991(19)
18.706(4)
9.2652(18)
110.476(17)
1152.6(4)
4
744 2.21 0.30
0.48-1.00 0.14 x 0.22 x 0.29 2.6-26.6
0, 8; 0, 23; -11, 10 2564
2370 (0.035) 1417
0.0362 (0.0739) 0.0807 (0.0895)
aR1 = E||Fo| - |Fc||/?E|Fo| for observed data (I>2c(/)); number in parentheses is for all data.
bwR2 = {X[w(Fo2 - Fc2)2]/E[w(Fo2)2]}1/2 for observed data (/>2c(7)); number in parentheses is for all data.
3. Results and Discussion
The diacylfluoride FC(O)(CF2)nC(O)F (n = 1) is more reactive than the homologues studied previously. Depending on the ratio of TMS-CF3/diacylfluoride used, different products are isolated. Using a ratio acylfluoride: TMS-CF3 = 1:2 we did not observe the formation of the four-membered ring cyclic dialkoxide analogous to the 5,6-membered rings observed previously for n = 2,3. However the yield of diketone 2 is only around 30%. The starting material seems to be very reactive with formation of different compounds like the proposed lactone 3. The reactions are summarized in Scheme 1.
In the reaction of FC(O)(CF2)nC(O)F (n=2,3) with excess of TMS-CF3 the corresponding dialkoxides are not observed due to the facile intramolecular cyclization of the intermediate diketone with fluoride. In this case the free diketone was obtained by thermal decomposition of the monoalkoxide under vacuum, but no available route to the diols (CF3)2C(OH)(CF2)nC(OH)(CF3)2 was possible. In the case of CF2[C(O)F]2, excess TMS-CF3 gives the te-tra(trifluoromethylated) dialkoxide along with an unidentified cyclic compound and probably some (CF3)2C(OK)CF2C(O)CF3 and other unidentified products.
4TMS-CF3+CF2(C(0)F)2^iL— [(CFj)2COK]2CF2 (1)
While the potassium dialkoxide was not unequivocally identified, its reaction with H2SO4 to give 4 and the 19F NMR makes the identity fairly certain. Also the reac-
Scheme 1. Reaction of 1 with TMS-CF3/KF and suggested route to 3.
tion of 4 with NaOH gives the pure disodium alkoxide 5 with nearly identical 19F NMR.
The new compound (CF3)2C(OH)CF2C(OH)(CF3)2 4 crystallizes in long white needles in the monoclinic space group, P21/n (No. 14). The molecule occupies a general position within the unit cell, and is shown as a thermal ellipsoid plot in Figure 1. The intramolecular bonding parameters are given in Table 2, and are all within normal ran-
Table 2. Geometric parameters
Bond Distances (A)	
O1 C1 1.394(3)	F10 C6 1.338(3)
O2 C3 1.391(3)	F11 C6 1.317(3)
F1 C2 1.346(3)	F12 C7 1.325(3)
F2 C2 1.341(3)	F13 C7 1.315(3)
F3 C4 1.321(3)	F14 C7 1.329(3)
F4 C4 1.323(3)	C1 C5 1.541(3)
F5 C4 1.331(3)	C1 C4 1.547(3)
F6 C5 1.315(3)	C1 C2 1.581(3)
F7 C5 1.336(3)	C2 C3 1.572(3)
F8 C5 1.317(3)	C3 C6 1.544(3)
F9 C6 1.312(3)	C3 C7 1.564(4)
C-Favg 1.326(11)	
C-Cavg 1.558(17)	
Bond Angles (°)
O1 C1 C5 109.03(19) O1 C1 C4 109.23(19) C5 C1 C4 109.91(19)
01	C1 C2 107.11(17) C5 C1 C2 110.77(19) C4 C1 C2 110.72(18) F2 C2 F1 105.22(18) F2 C2 C3 107.25(18) F1 C2 C3 109.28(18) F2 C2 C1 109.65(18) F1 C2 C1 106.98(18) C3 C2 C1 117.77(17)
02	C3 C6 104.52(19) O2 C3 C7 109.3(2) C6 C3 C7 108.48(19) O2 C3 C2 113.09(18) C6 C3 C2 109.81(18) C7 C3 C2 111.29(19) F3 C4 F4 108.8(2) F3 C4 F5 107.4(2) F4 C4 F5 107.7(2)
C_C_Cav
C-C-O
C-C-F
^ ^ 1 av
F-C-F„,
111(3) 109(3) 110(2) 108(1)
F3 C4 C1 110.8(2) F4 C4 C1 112.8(2) F5 C4 C1 109.1(2) F6 C5 F8 108.5(2) F6 C5 F7 107.1(2) F8 C5 F7 108.3(2) F6 C5 C1 110.8(2) F8 C5 C1 112.9(2) F7 C5 C1 109.1(2) F9 C6 F11 108.8(2) F9 C6 F10 106.9(2) F11 C6 F10 107.4(2) F9 C6 C3 111.1(2) F11 C6 C3 112.5(2) F10 C6 C3 109.9(2) F13 C7 F12 107.8(2) F13 C7 F14 107.4(2) F12 C7 F14 108.2(2) F13 C7 C3 110.3(2) F12 C7 C3 112.5(2) F14 C7 C3 110.4(2)
Figure 1. Thermal ellipsoid plot (50% probability) of compound 4. Hydrogen bonds are shown as dashed lines.
Figure 2. Crystal packing viewed down the a-axis for compound 4. Oxygen atoms are represented as red boundary ellipses, fluorine atoms as solid green spheres, and carbon atoms as black hollow spheres. Hydrogen atoms are not shown.
Hydrogen Bonds (A,°)			
01-H1	0.77(3) 02-H2	0.74(3)	H1-O2a 2.01(3) H2-O1 1.91(3)	01-O2a	2.740(2) 02-O1	2.561(3)	01-H1-O2a	158(3) 02-H2-O21	147(3)
a) Atom generated by symmetry operation: '/2+x, '/2-y, '/2+z
ges. The hydroxyl groups participate in both intramolecular and intermolecular hydrogen bonding (shown as dashed lines in Figure 1). The latter intermolecular hydrogen bonds link the molecules into infinite chains running perpendicular to {1 0 1}. The crystal packing is shown in Figure 2.
The melting point of 4 at atmospheric pressure is 58-60 °C; it has a low vapor pressure but it can be readily sublimed under dynamic vacuum. The compound is soluble in CHCl3, slightly soluble in ethyl ether and has low solubility in H2O (pH of water solution is acidic). Because of its low solubility in H2O, attempts to measure the p-Ka were unsuccessful. The corresponding potassium and sodium salt are very hygroscopic and they are very soluble in ether and water.
This new product could have the same importance in the preparation of six-membered rings as the corresponding (CF3)2C(OH)C(OH)(CF3)2 has for a variety of five-membered rings. The perfluoropinacol molecule is known to form the basis of a number of five-membered hete-rocycles of type -OC(CF3)2C(CF3)2OM where the element M is Si, Ge, Sn, B, S or I3.
4. Conclusions
The reaction of FC(O)(CF2)nC(O)F (n = 1) with TMS-CF3/KF is more complex than previous results with n = 2,3. Very facile cyclization of the latter diketones is probably the reason for the clean reactions. In contrast for n = 1, the unfavorable cyclization to a four-membered ring allows the open chain intermediates/products to undergo further reactions. However the 1,3 trifluoromethylated di-
ketone 2 could be isolated in modest yield and in contrast to n = 2,3, the 1,3 tetra(trifluoromethylated) diol 4 was isolated.
5. Acknowledgement
We gratefully acknowledge the financial support of this research by Solvay Solexis (formerly Ausimont).
6. Reference
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5.	F. S. Facwett, C. W. Tullock, D. D. Coffman J. Am. Chem. Soc. 1962, 84, 4275-4285.
6.	D. G. Anderson, D. C. England, A. S. Milan, Jr. USP 4,357,282 1982.
7.	S. A. Postovi, I. M. Vol'pin, E. I. Mysov, Y. V. Ziefman, L. S. German Izv. Akad. Nauk SSSR, Ser. Khim, 1989, 1173-1176.
8.	G. M. Sheldrick SHELXTL, Version 6.10, Crystallographic Computing System (2000), Bruker AXS, Madison, WI.
9.	International Tables for X-ray Crystallography, Vol. C (1992), Ed. A. J. C. Wilson, Kluwer Academic Publishers, Dordrecht: a) Table 6.1.1.4, pp. 500-502; b) Table 4.2.6.8, pp. 219-222.
Povzetek
Perfluoromalonil difluorid reagira s TMS-CF3 (1:1) v prisotnosti KF v nov diketon CF2(C(O)CF3)2. Večji presežek (5:1) TMS-CF3 predvidoma vodi do nastanka kalijevega dialkoksida [(CF3)2COK]2CF2, ki da po reakciji s H2SO4 1,3-diter-ciarni diol [(CF3)2C(OH)]2CF2.