Reductive alkylation of perfluorocarboxylic acid esters with CCl 3F or CCl4 and synthesis of higher linear perfluoroketones

Article abstract of DOI:10.1016/j.jfluchem.2003.11.008

Barbier-type reductive alkylation of perfluorocarboxylic acid esters (I) with CFCl₃ and activated Al was successfully performed to give α,α-dichloroperfluoroketones (II). A similar reaction of CF ₃COOEt with CCl₄ and Al provided a convenient synthesis of CF₃COCCl₃. Ketones (II) were fluorinated further with SbF₅ to form higher linear perfluoroketones (IX). An alternative approach to the synthesis of ketones (IX) was proposed by reductive perfluoroalkylation of esters (I) under the action of R_FI and Al.

Full text of DOI:10.1016/j.jfluchem.2003.11.008

Journal of Fluorine Chemistry 125 (2004) 1815–1819
Reductive alkylation of perfluorocarboxylic acid esters with CCl3F
or CCl4 and synthesis of higher linear perfluoroketones
Yu.V. Zeifman*, S.A. Postovoi
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
Vavilov St., 28, 119991 Moscow, Russia
Received 1 September 2003; received in revised form 6 November 2003; accepted 7 November 2003
Available online 27 September 2004
Abstract
Barbier-type reductive alkylation of perfluorocarboxylic acid esters (I) with CFCl3 and activated Al was successfully performed to give a,a-
dichloroperfluoroketones (II). A similar reaction of CF3COOEt with CCl4 and Al provided a convenient synthesis of CF3COCCl3. Ketones
(II) were fluorinated further with SbF5 to form higher linear perfluoroketones (IX). An alternative approach to the synthesis of ketones (IX)
was proposed by reductive perfluoroalkylation of esters (I) under the action of RFI and Al.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Perfluorocarboxylic acid esters; Reductive alkylation; Higher linear perfluoroketones; Synthesis
1. Introduction
2. Results and discussion
Reductive addition of polyhaloalkanes to carbonyl com-
pounds is important for making carbon–carbon bonds in
organic syntheses, and various kinds of low-valent metals
have been employed for this purpose [1a–c]. Reductive
addition of CCl3X (X ¼ Cl, F) to aromatic aldehydes or
trifluoromethylketones under the action of activated Al in a
DMF medium, which is a convenient synthesis of carbinols
with CCl3 or CFCl2 groups, can serve as an example of
similar reactions [1–3].
This paper describes a new reaction of the same type,
namely, reductive polychlorofluoromethylation of perfluor-
ocarboxylic acid esters (I). This reaction makes it possible to
synthesize trichloromethyl- and a,a-dichloroperfluoroalk-
ylketones in high yields. The latter ketones can easily
exchange chlorine by fluorine by reaction with SbF5. Thus,
this succession of transformations comprising addition of
CFCl3 to esters I and substitution of the chlorine in ketones
II by fluorine, provides a new efficient method for the
synthesis of higher linear perfluoroketones. We studied also
an alternative approach to the synthesis of such perfluor-
oketones, namely, direct fluoroalkylation of esters (I) with
alkyl iodides (RFI) and Al.
It was found that perfluorocarboxylic acid ethyl esters (I)
reacted exothermally with CFCl3 and powdered Al, acti-
vated with either 5–7 mol.% HgCl2 or SnCl2 in DMF or N-
methylpyrrolidone (NMP), to give a,a-dichloroperfluoroke-
tones (II) in 60–85% yield (Scheme 1).
Attempts to perform this reaction using either Mg or Zn
failed.
Acids RFCOOH and monohydroketones RFCOCHFCl
(III) are formed as impurities in addition to the major
1
products (II), shown by GC–MS, H and 19F NMR.
To optimize the reaction conditions and to minimize the
formation of by-products, it would be reasonable to consider
a possible general scheme. At the first step, reductive
dechlorination of CFCl3 with a metal takes place to form
an intermediate anionoid species FCCl2À [4], which adds to
the carbonyl group of ester I to form hemiketal salt1 IV
and, finally, hydrolysis of this salt gives the corresponding
ketone II (Scheme 2).
The acid RFCOOH could be formed as a result of either
haloform reaction of hemiketal V (or its salt IV) or transfer-
ring the alkyl group from the starting ester I to anion
CFCl2À. The second assumption is supported by the fact
that, as a rule, the yield of chlorofluoroketones II is higher in
* Corresponding author. Tel.: þ7-95-135-9263.
E-mail address: isg@ineos.ac.ru (Yu.V. Zeifman).
1 L can be either Cl or the corresponding O-anion.
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2003.11.008

1816
Yu.V. Zeifman, S.A. Postovoi / Journal of Fluorine Chemistry 125 (2004) 1815–1819
Scheme 4.
Scheme 1.
the reactions of CFCl3 with ethyl esters I than in the
reactions with esters RFCOOCH3, which are known to be
the more active alkylating agents for nucleophiles.
The formation of monohydroketones III can be explained
by partial decomposition of hemiketal V under reaction
conditions yielding ketone II, which undergoes further
reduction to give enolate VI whose hydrolysis leads to
monohydroketone III (see Ref. [5]) (Scheme 3).
The relative instability of the intermediate hemiketals and
their salts is an important factor that determines the yields of
ketones II. The reaction temperature should not exceed 30–
35 8C, and the acid hydrolysis of the reaction mixture should
be carried out at temperature lower than 25 8C. It is espe-
cially important to follow these conditions for the higher
esters I, because the stability of the heminal derivatives V
decreases with increasing the length of the fluorocarbon
chain.
The synthesis of a,a-dichloroperfluoroketones II that we
report is much simpler and more efficient than the known
syntheses of ketones II both by reaction of internal olefin
oxides with AlCl3 [7] and reaction of Bu3P with CFCl3 and
RFCOCl [8].
The reaction of CCl4 with esters I gives trichloroketones
(VII) (Scheme 4).
The yields of ketones VIIa and b are lower than those of
the corresponding ketones with a CFCl2 group (II). This
may be explained by the intermediate geminal adducts of the
IVand V types with a CCl3 group being less stable than their
analogues with a CFCl2 group; the more electron-withdraw-
ing character of the latter makes compounds IV and V more
stable. Synthesis of ketone VIIa in 60% yield by the method
we report is much simpler than that described in the literature
reaction CF3COCF2Cl þ AlCl3 ! CF3COCCl3 [9].
According to the data reported in [10], ketones
RFCOCFCl2 can be easily transformed to RFCOCF3 when
they are heated with SbF5 (three-fold molar amount) in an
autoclave (60 8C, more than 12 h). An exothermic reaction
occurs when a,a-dichloroketones (IIc-e) are added to an
excess amount of SbF5 but it is necessary to heat the reaction
mixture additionally for a short period of time to achieve
It should be also noted that DMF is a more active reaction
medium (for the reaction presented by the Scheme 1) than N-
methylpyrrolidone (NMP), however, in this case, in addition
to by-products RFCOOH and III, aldehyde CFCl2CHO is
formed as a result of formylation of the anion CFCl2À with
DMF [6].
Scheme 2.
Scheme 3.

Yu.V. Zeifman, S.A. Postovoi / Journal of Fluorine Chemistry 125 (2004) 1815–1819
1817
ca. 20 8C for 1.5 h and poured into cooled dilute hydro-
chloric acid (1:5). The product was extracted with Et2O, the
extract was concentrated in vacuo and the residue was
distilled over conc. H2SO4 to give ketone IIa (8.7 g,
62%), bp 44–45 8C (Ref. [5]).
Scheme 5.
3.1.2. 1,1,3-Trichlorotrifluoropropan-2-one (IIb)
Ketone IIb was obtained similarly (in 69.5% yield) in
the form of a fraction with bp 82–85 8C, which contained
2.5% ClCF2COOH and 1.5% ClCF2COCHFCl as impurities
(Ref. [5]).
Scheme 6.
3.1.3. 1,1-Dichloroperfluorobutan-2-one (IIc)
complete transformation of the CFCl2 group to the CF3
group. Heating is carried out either in an autoclave (for IIc)
or in a flask fitted with a reflux condenser (for IId and e). The
yield of ketones IX was about 80% (Scheme 5).
Another method for the synthesis of perfluoroketones
consists of reductive perfluoroalkylation of perfluorocar-
boxylic acid esters (I) with RFI and metals (Scheme 6).
Ketones IXe and f were obtained by this method in ca.
40% yields.
When the reaction of ester Ia with C4F9I was carried out
in DMF, a mixture of ketone IXe and C4F9CHO (1:1) was
obtained. This type of process was described by Wakselman
and co-workers [11], who obtained (CF3)2CO and CF3CO-
COOEt using the reaction CF3Br and Zn in pyridine with
CF3COOEt and (COOEt)2, respectively. Reductive alkyla-
tion of perfluorocarboxylic acid esters by reaction with
either CFCl3 or RFI and activated Al opens new opportu-
nities for the syntheses of linear perfluoroketones [12,13].
Mercuric chloride (5 g, 0.02 mol) was added to powdered
Al (7 g, 0.26 mol) in NMP (200 ml) under Ar with stirring.
After an exothermic reaction was completed, ester Ic (49 g,
0.25 mol) and CFCl3 (39 g, 0.28 mol) were added and the
reaction mixture was stirred at 30–33 8C (with external
heating) for 50 min and then at the same temperature (after
an exothermic reaction started) with external cooling for 2 h.
The resulting mixture was poured into dilute hydrochloric
acid (1:5) (200 ml) on cooling to a temperature lower than
25 8C; the ester Ic (13 g) that did not react was distilled off in
vacuo at a temperature not higher than 25 8C. The resulting
solution was extracted with Et2O, Et2O was removed in
vacuo, and the residue (50 ml) was distilled over conc.
H2SO4 (120 ml) on heating to 120 8C to give a fraction
with bp 65–80 8C. Redistillation gave ketone IIc (bp 65–
68 8C) of 95% purity (GLC) in 77% yield at conversion of
ester Ic 73%. (Ref. [7]).
3.1.4. 1,1-Dichloroperfluoropentan-2-one (IId)
Trichlorofluoromethane (25 g, 0.18 mol) was added drop-
wise to a mixture of Al (4 g, 0.15 mol), SnCl2 (2.8 g,
0.015 mol), anhydrous NMP (120 ml), and ester Id (10 g,
0.15 mol) for 40 min at a temperature lower than 33 8C; the
resulting mixture was stirred for 30 min with cooling to 32–
34 8C. After an exothermic reaction was complete, the
reaction mixture was poured into an excess amount of
HCl (1:5) with stirring, while the temperature was main-
tained below 25 8C. The ester Id (5 g) that did not react was
distilled off in vacuo (20 mmHg), the residue was extracted
with Et2O; the extract was concentrated in vacuo and dis-
tilled over conc. H2SO4 to give ketone IId with bp 87–89 8C
(26.5 g, 86%) at conversion of ester Id 83% (Ref. [8]).
3. Experimental
The solvents were kept over KOH pellets and distilled
over CaH2 prior to their use. Powdered Al was stirred with a
aqueous NaOH solution (2–3%) for 2–3 min; after decant-
ing, the Al powder was filtered off and washed successively
with water, acetone and ether, and dried in vacuo. The 19F
NMR spectra were recorded using a Bruker WP-200 SY
(188.3 MHz) spectrometer. The mass-spectra were obtained
on a VG-7070E instrument (70 eV) at a temperature of the
ion source 140 8C. The boiling points and the 19F NMR
spectra of the compounds synthesized were identical with
those reported in literature.
3.1.5. 1,1-Dichloroperfluorohexan-2-one (IIe)
Ketone IIe was obtained similarly to ketone IIc in 75%
yield (at 69% conversion of ester IIe) in the form of a
fraction with bp 109–112 8C (Ref. [7]).
3.1. a,a-Dichloroperfluoroketones (II)
3.1.1. 1,1-Dichloro-1,3,3,3-tetrafluoropropan-2-one (IIa)
Mercuric chloride (1 g, 0.004 mol) was added to DMF
(60 ml) and Al (1.9 g, 0.07 mol) under Ar with stirring. After
an exothermic reaction was complete, a solution of ester Ia
(10 g, 0.07 mol) in CFCl3 (14.6 g, 0.11 mol) was added
dropwise while the temperature of the reaction mixture was
maintained below 35 8C. The reaction mixture was stirred at
3.2. 1,1,1-Trichloropolyfluoroketones (VII)
3.2.1. 1,1,1-Trichlorotrifluoropropan-2-one (VIIa)
Tetrachloromethane (18.5 g, 0.12 mol) was added drop-
wise to a mixture of Al (2.7 g, 0.1 mol), SnCl2 (1.9 g,

1818
Yu.V. Zeifman, S.A. Postovoi / Journal of Fluorine Chemistry 125 (2004) 1815–1819
0.01 mol), anhydrous NMP (80 ml), and ester Ia (14.2 g,
0.1 mol) with stirring for 30 min at a temperature lower than
34 8C; the resulting mixture was stirred for 1.5 h, a tem-
perature of 30–32 8C was maintained. After an exothermic
reaction was complete, the reaction mixture was poured into
an aqueous HCl solution (1:1), the temperature was main-
tained lower than 20 8C. Ester Ia (0.5 g) that did not react
was distilled off in vacuo, the residue was extracted with
Et2O, the extract was concentrated in vacuo (20 mmHg)
and distilled over conc. H2SO4 to give a fraction (15.8 g),
bp 72–84 8C that consisted of 90% ketone VIIa and 10%
CF3COOH. Redistillation gave ketone VIIa (13.7 g, 62.6%)
with bp 83–85 8C (Ref. [9]).
(100 ml) at a temperature lower than 25 8C; the C4F9I
and CF3COOEt that did not react were removed in
vacuo (at a temperature lower than 20 8C). The residue
was extracted with Et2O, the Et2O was evaporated in
vacuo. The crude ketone IXe hydrate that formed, was
added to conc. H2SO4 (40 ml) with stirring and
distilled upon heating to 110 8C. Ketone IXe (7 g,
38%) was distilled off and was identical to that
described above and contained ca. 2% CF3COOH
(GLC, 19F NMR).
3.3.4. Perfluoropentan-3-one (IXf)
Mercuric chloride (1 g, 0.0037 mol) was added to pow-
dered Al (2.5 g, 0.092 mol) in NMP (190 ml) under Ar with
stirring. After an exothermic reaction was complete, ester Ic
(18 g, 0.094 mol) and C2F5I (23.4 g, 0.095 mol) were added,
the reaction mixture was stirred at 30–32 8C for 25 min, and
after an exothermic reaction started, it was stirred at 30–
33 8C for 2 h. Then after acid hydrolysis was carried out,
ester Ic (5.5 g) was distilled off in vacuo, the residue was
extracted with Et2O, the extract was concentrated and dis-
tilled over conc. H2SO4 to give ketone IXf (9.6 g, bp 29–
31 8C), its yield was 38% (on the basis of C2F5I) and 55%
(on the basis of ester Ic that reacted) (cf. Ref. [12]).
The yield of ketone IXf in a similar experiment carried out
in dimethylacetamide was 22%. If Zn/CuCl was used
(instead of Al/HgCl2) in the reaction of C2F5I with ester
Ic, the yield of ketone IXf was 7%. In a similar experiment
with Al/SnCl2 used as a reducing agent (carried out in
NMP), the yield of ketone IXf was 33% at conversion ester
Ic 52%.
3.2.2. 1,1,1-Trichloropentafluorobutan-2-one (VIIb)
A fraction with bp 92–105 8C containing ketone VIIb,
C2F5COOH and C2F5COCHCl2 (NMR, GLC), was obtained
similarly from ester Ic, CCl4 and Al/HgCl2 in NMP. The
yield of ketone VIIb was 41.2% (according to 19F NMR
data). The 19F NMR spectrum of ketone VIIb was identical
to that reported in [7].
3.3. Perfluoroketones (IX)
3.3.1. Perfluorobutan-2-one (IXc)
Dichloroketone IIc (26 g, 0.1 mol) was added dropwise to
SbF5 (67 g, 0.31 mol) with stirring. After an exothermal
reaction was completed, the resulting mixture was trans-
ferred into a 100 ml autoclave and heated at 20–30 8C for 5 h
with stirring. Then ketone IXc (17.3 g, 77%) was condensed
in a trap (À78 8C), bp 0–2 8C (Ref. [10]).
3.3.2. Perfluoropentan-2-one (IXd)
Ketone IId (14.7 g, 0.072 mol) was added dropwise to
SbF5 (46 g, 0.21 mol) with stirring and the resulting mixture
was refluxed for 9 h. Then ketone IXd was distilled off (bp
28–30 8C). Yield 84%. (Refs. [10,12]).
Acknowledgements
The authors are grateful to DuPont Fluoroproducts for the
financial support to this research.
3.3.3. Perfluorohexan-2-one (IXe)
References
(A) Ketone IIe (15.6 g, 0.04 mol) (which contained 7%
C4F9COOEt Ie) was added dropwise to SbF5 (30 g,
0.14 mol). After an exothermic reaction was complete,
the resulting mixture was refluxed for 2 h with stirring;
the resulting ketone IXe (10.4 g, 78%) was distilled off
and redistilled over conc. H2SO4, bp 55–57 8C. (Ref.
[12]).
(B) Mercuric chloride (0.8 g, 0.003 mol) was added to
powdered Al (2.2 g, 0.08 mol) in NMP (70 ml) under
Ar with stirring. After an exothermic reaction was
complete, C4F9I (20 g, 0.057 mol) and ethyl ester Ia
(10 g, 0.07 mol) were added, and the reaction mixture
was stirred for 1 h at 30–33 8C (with external heating)
and then at the same temperature (after an exothermic
reaction started) with external cooling for 1.5 h. The
resulting mixture was poured into dilute HCl (1:1)
[1] (a) H. Tanaka, S. Yamashita, M. Yamanoue, S. Torii, J. Org. Chem.
54 (2) (1989) 444–450;
(b) C.-M. Hu, M.-H. Tu, J. Fluorine Chem. 67 (1994) 9–10;
(c) J. Groundin, H. Blankou, F. Commeyras, J. Fluorine Chem. 45
(1989) 349–354.
[2] Yu.V. Zeifman, Izv. Akad. Nauk, Ser. Khim. (1992) 464–467; Bull.
Russ. Akad. Sci., Div. Chem. Sci. (Engl. Transl.), 41 (2) (1992) 370–
373.
[3] S.A. Postovoi, E.M. Kagramanova, E.I. Mysov, Yu.V. Zeifman, Iv.
Akad. Nauk, Ser. Khim. (1996) 1496–1498; Russ. Chem. Bull. (Engl.
Transl.), 45 (6) (1996) 1425–1427.
[4] A. Moyano, M.A. Perikas, A. Rivera, S.L. Luche, Tetrahedron Lett.
31 (52) (1990) 7619–7621.
[5] Y.V. Zeifman, S.A. Postovoi, I.M. Vol’pin, L.S. German, Dokl. Akad.
Nauk. SSSR 307 (6) (1989) 1385–1390.
[6] J. Chang-Ming Hu, J. Chen, J. Fluorine Chem. 67 (1994) 189–192.
[7] L.A. Saloutina, A.Ya. Zapevalov, M.I. Kodes, I.P. Kolenko, L.S.

Yu.V. Zeifman, S.A. Postovoi / Journal of Fluorine Chemistry 125 (2004) 1815–1819
1819
German, Izv. Akad. Nauk SSSR, Ser. Khim. (1983) 1434–1437; Bull.
Russ. Akad. Sci., Div. Chem. Sci. (Engl. Transl.), 32 (6) (1983)
1303–1306.
[10] D.J. Burton, I.H. Jeong, J. Fluorine Chem. 65 (1993) 153–156.
[11] C. Francese, M. Tordeux, C. Wakselman, Tetrahedron Lett. 29 (1988)
1029–1030.
[8] I.H. Jeong, D.J. Burton, D.G. Cox, Tetrahedron Lett. 27 (1986)
3709–3712.
[12] A.Y. Zapevalov, I.P. Kolenko, V.S. Plashkin, P.G. Neyfel’d, Zh. Org.
Khim. 14 (1978) 259–282.
[9] Org. Synth. 56 (1977) 122–126.
[13] G.K. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786.