Selective reactions of 1,1-cycloalkanedicarboxylic acids with SF4. a route to 1,1-bis(trifluoromethyl)cycloalkanes, 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes and 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids

Article abstract of DOI:10.1016/S0022-1139(99)00233-X

Six-, five-, four- and three-membered 1,1-cycloalkanedicarboxylic acid (2a-d) were synthesized by alkaline hydrolysis of the corresponding diesters (1a-d) and the reactions of the formers with SF₄ were investigated. 1,1-Bis(trifluoromethyl)cycloalkanes (3a-d) were the products of the reactions conducted at 120-150°C while at 30°C 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes (4a-d) were exclusively formed. The latter were isolated as pure compounds or converted in situ into 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids (5a-d).

Full text of DOI:10.1016/S0022-1139(99)00233-X

Journal of Fluorine Chemistry 102 (2000) 141±146
Selective reactions of 1,1-cycloalkanedicarboxylic acids with SF4.
A route to 1,1-bis(tri¯uoromethyl)cycloalkanes,
1-¯uoroformyl-1-(tri¯uoromethyl)cycloalkanes and
1-(tri¯uoromethyl)-1-cycloalkanecarboxylic acids
Wojciech Dmowski*, Adam Wolniewicz
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
Received 22 June 1999; received in revised form 19 July 1999; accepted 27 August 1999
Dedicated to Professor Paul Tarrant on the occasion of his 85th birthday
Abstract
Six-, ®ve-, four- and three-membered 1,1-cycloalkanedicarboxylic acid (2a±d) were synthesized by alkaline hydrolysis of the
corresponding diesters (1a±d) and the reactions of the formers with SF4 were investigated. 1,1-Bis(tri¯uoromethyl)cycloalkanes (3a±d)
were the products of the reactions conducted at 120±1508C while at 308C 1-¯uoroformyl-1-(tri¯uoromethyl)cycloalkanes (4a±d) were
exclusively formed. The latter were isolated as pure compounds or converted in situ into 1-(tri¯uoromethyl)-1-cycloalkanecarboxylic acids
(5a±d). # 2000 Elsevier Science S.A. All rights reserved.
Keywords: 1,1-Cycloalkanedicarboxylic acids; Fluorination; Sulphur tetra¯uoride; 1,1-Bis(tri¯uoromethyl)-cycloalkanes; 1-Fluoroformyl-1-(tri¯uoro-
methyl)cycloalkanes; 1-(Tri¯uoromethyl)-1-cycloalkanecarboxylic acids
1. Introduction
¯uoromethyl)cyclohexanes were obtained by Haas and cow-
orkers [8] via cycloaddition reactions of (CF3)2C=C±CHO
with dienes and a condensation of the diene (CF3)2=CH±
C(CH3)=CH2 with ethylene under pressure provided 1-
methyl-3,3-bis(tri¯uoromethyl)-cyclohexene suitable as an
Speci®c properties of the tri¯uoromethyl group [1±4]
cause that its introduction into biologically important mole-
cules, especially in place of the methyl group, is of con-
siderable importance. 1,1-Dimethylcycloalkanes are
common fragments of natural compounds, particularly ter-
penes and their derivatives such as vitamins D, retinoids and
pyrethroids. Replacing of one or two CH3 groups by CF3
groups on a carbocyclic quarternary carbon atom remains,
however, challenging synthetic problem and only a few such
approaches have been reported till now. These approaches
involved hardly available tri¯uoromethyl-containing build-
ing blocks. Thus, total synthesis of 16,16,16-tri¯uororetinal
using 2-(tri¯uoromethyl)propenoic as the starting material
was reported by Kobayashi and coworkers [5,6]. Wakselman
and coworkers [7] described a four-steps synthesis of a 1-
(tri¯uoromethyl)cyclopentanoid aldehyde, intended to serve
as a ring D precursor of tri¯uoromethylated steroids, starting
from 2-(tri¯uoromethyl)cyclopentan-1,3-dione. 1,1-Bis-(tri-
intermediate
to
16,16,16,17,17,17-hexa¯uororetinals.
Diels±Alder and 1,3-dipolar cycloadditions with CF3-sub-
stituted alkenes, e.g. a-tri¯uoromethylstyrene, were studied
and resulted in a carbo and heterocyclic compounds posses-
sing tri¯uoromethylated quarternary carbon atoms [9].
Another approach to cyclohexanes bearing CH2F, CHF2
and CF3 groups on quarternary carbon atoms has been
presented by Burton and coworkers [10]; tetramethyl
1,1,4,4-cyclohexanetetracarboxylate
was
selectively
reduced to trans-1,4-bis(carbomethoxy)-1,4-dialdehyde,
¯uorination of which with DAST (diethylaminosulphur
tri¯uoride) gave trans-1,4-bis(carbomethoxy)-1,4-bis(di-
¯uoromethyl)cyclohexane. Further elaboration of the latter
lead to 1,1,4,4-tetrasubstituted cyclohexanes bearing gem-
inal CH2F and CHF2 groups. These same authors also
reported ¯uorination of 1,1,4,4-cyclohexane tetracarboxylic
acid with SF4 leading to mixtures of cyclohexanes substi-
tuted with CF3 and COF groups.
* Corresponding author. Fax: ‡4822-632-6681.
E-mail address: dmowski@ichf.edu.pl (W. Dmowski).
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 2 3 3 - X

142
W. Dmowski, A. Wolniewicz / Journal of Fluorine Chemistry 102 (2000) 141±146
The above mentioned work prompted us to undertake a
carboxylic group stopped at the stage of an acid ¯uoride.
This drastic difference in reactivity of both carboxylic
groups allowed preparation of 1-(tri¯uoromethyl)-1-
cycloalkanoyl ¯uorides 4 in good yields and of high purity.
Under these condition no trace of bis(tri¯uoromethyl)-
cycloalkanes were formed. It is well know that the ®rst
step of the reaction of carboxylic acids with SF4, leading to
acid ¯uorides, proceeds rapidly even as low temperature as
788C, independently of a structure of the reactant acid, but
the rate of further conversion of a COF group into CF3 is
strongly affected by both electronic and steric factors [14].
Our results have shown that the two COF groups on this
same carbon atom do not interfere mutually in the con-
secutive reaction of one of them with SF4 such that 1-
¯uorocarbonyl-1-(tri¯uoromethyl)- derivatives 4 are formed
under rather mild conditions. In contrast, the formed bulky
CF3 group strongly retards further ¯uorination of the
remaining COF group. This is rather fortunate case which
allows highly selective preparation of the required a-tri-
¯uoromethylated acid ¯uorides 4.
study towards developing a general method for the con-
struction of carbocyclic fragments of natural or potentially
bioactive compounds bearing two CF3 or one CF3 and one
CH3 or other groups on a quarternary carbon atom using SF4
as a ¯uorinating agent. Our methodology has been based on
selective ¯uorination of 1,1-cycloalkanedicarboxylic acids
with SF4 to give bis(tri¯uoromethyl)- or 1-¯uorocarbonyl-1-
(tri¯uoromethyl)cycloalkanes and, in the case of the latters,
conversion of the COF group into other group. The present
paper reports results of preliminary studies using easily
accessible six-, ®ve- four- and three-membered 1,1-dicar-
boxylic acids 2a±d as model compounds; a ring size Ð
selectivity (reactivity) relationship was the main aim of the
work.
2. Results and discussion
The model 1,1-cycloalkanedicarboxylic acids 2a±d were
obtained by basic hydrolysis of diethyl 1,1-cycloalkanedi-
carboxylates 1a±d which were synthesized straightforward
by condensation of diethyl malonate with terminal dibro-
moalkanes. Two procedures were applied: a conventional
method using sodium ethoxylate as a base [11] for the
preparation of esters 1a±c but in the case of 1,1-cyclopro-
panedicarboxylate 1d, much better yield was achieved in a
two-phase system with solid K2CO3 as a base [12]. Hydro-
lysis of esters 1 to acids 2, in order to prevent decarboxyla-
tion to monocarboxylic acid, were carried out at ambient
temperature for a prolonged time, as suggested in the
literature [13].
1-(Tri¯uoromethyl)-1-cyclohexanoyl ¯uoride (4a) was
found to be unexpectedly resistant to alkaline hydrolysis
thus allowing its puri®cation by steam distillation from
saturated aqueous NaHCO3 solution. Conversion of 4a
into 1-(tri¯uoromethyl)-1-cyclohexane-carboxylic acid
(5a) required 2 days stirring with 5% aqueous KOH in
the presence of a phase-transfer catalyst. In contrast,
smaller ring acid ¯uorides 4b±d readily hydrolyzed, even
in aqueous NaHCO3, and because of that they were
puri®ed by direct distillation from the crude reaction
mixtures after binding free HF on solid NaF. Treatment
of the crude products obtained by ¯uorination of acids 2b±d
with aqueous NaHCO3 followed by acidi®cation gave
directly 1-(tri¯uoromethyl)-1-cycloalkanecarboxylic acids
(5b±d).
It appears that cyclohexane derivative 4a is in general,
less reactive than its smaller ring analogues; this should be
attributed to a different steric shielding of the COF group on
the cyclohexane ring and on smaller rings; probably in a
preferential conformation of 4a, bulky CF3 group is equa-
torial while the COF group occupies more hindered axial
position.
Conversion of 1,1-cycloalkanedicarboxylic acids 2 to
1,1-bis(tri¯uoromethyl)-cycloalkanes 3 with SF4 required
rather drastic reaction conditions. Cyclohexanedicarboxylic
acid 2a appeared to be particularly resistant; total conver-
sion to 1,1-bis(tri¯uoromethyl)-cyclohexane 3a was
achieved after 4 days treatment at 1508C with 13-fold molar
excess of SF4 and in the presence of an additional amount of
HF over that evolved in the reaction. The smaller ring acids
2b±d are much more reactive towards SF4 such that 1208C
for 24 h, sixfold excess of SF4 and with no HF added were
satisfactory conditions to obtain 1,1-bis(tri¯uoromethyl)cy-
cloalkanes 3b±d in satisfactory yields and as the only
isolable products.
When acids 2 were reacted with SF4 at 308C for a short
time (3 h) only one of the geminal carboxylic groups was
converted into CF3 group but ¯uorination of the second
Conversion of the COF group of acid ¯uorides 4 into
other functional groups and into the CH3 group is currently
under investigation.

W. Dmowski, A. Wolniewicz / Journal of Fluorine Chemistry 102 (2000) 141±146
143
3. Experimental
ent temperature for 2 days until a homogenous solution was
formed. The solution was extracted with ether (2 Â 50 ml)
to remove traces of unreacted ester, the water phase was
acidi®ed with concentrated hydrochloric acid and a free acid
was extracted with ether (3 Â 100 ml). The combined
extracts were dried over MgSO4, the solvent was removed
on a rotary evaporator to give a crude acid which was
recrystallized from ether/n-hexane (1:2). Yields 91±94%.
1,1-Cyclohexanedicarboxylic acid (2a): m.p. 179±1818C
(decomp.) (Lit. m.p. 179.58C [13]). Analysis: Found: C,
55.8%; H, 7.2%. C8H12O4 (172.18) requires: C, 55.8%; H,
7.0%.
1,1-Cyclopentanedicarboxylic acid (2b): m.p. 183±
1848C (decomp.) (Lit. m.p. 1878C [13]). Analysis: Found:
C, 53.0%; H, 6.6%. C7H10O4 (158.14) requires: C, 53.2%;
H, 6.3%.
1,1-Cyclobutanedicarboxylic acid (2c): m.p. 151±1538C
(decomp.) (Lit. m.p. 1598C [13]). Analysis: Found: C,
50.0%; H, 5.7%. C6H8O4 (144.13) requires: C, 50.0%; H,
5.6%.
Melting points were determined in capillaries and boiling
points were measured during distillation; both are uncor-
rected. 1H, 13C and 19F NMR spectra were recorded with a
Varian Gemini 200 spectrometer at 200, 50 and 188 MHz,
respectively. Chemical shifts are quoted in ppm from inter-
1
nal TMS for H and 13C (positive down®eld) and from
internal CFCl3 (positive up®eld). Crude mixtures of pro-
ducts were analyzed with a Shimadzu GC-14A Chromato-
graph using a 3.5 m  2 mm column packed with 5%
silicone oil SE-52 on Chromosorb G. GC±MS analyses
were performed with a Hewlett-Packard 5890 apparatus
using a 30 m capillary column coated with a HP-5 oil.
Mass spectra of pure compounds were obtained with an
AMD-604 spectrometer and IR spectra with a Perkin-Elmer
Spectrum 2000 instrument.
3.1. Diethyl 1,1-cycloalkanedicarboxylates (1)
3.1.1. General procedure for esters 1a±c
1,1-Cyclopropanedicarboxylic acid (2d): m.p. 136±
1378C (from Et2O/CHCl3 ˆ 1:2) (decomp.) (Lit. m.p.
139±1408C [18]). Analysis: Found: C, 46.3%; H, 4.8%.
C5H16O4 (130.10) requires: C, 46.2%; H, 4.7%.
Equimolar amounts of diethyl malonate and terminal
dibromoalkane (0.2±0.5 mol) and two mole equivalents
of sodium ethanolate (0.4±1.0 mol) were reacted in etha-
nolic solution and worked up as described in the literature
[11]. Products were puri®ed by distillation.
Diethyl 1,1-cyclohexanedicarboxylate (1a): b.p. 98±
1008C/6 torr (Lit. b.p. 76±808C/0.1 torr [11]); 105±
1068C/5 torr [15]. Yield: 61%.
Diethyl 1,1-cyclopentanedicarboxylate (1b): b.p. 84±
868C/6 torr (Lit. b.p. 1158C/16 torr [13]); 838C/3 torr
[16]. Yield: 52%.
Diethyl 1,1-cyclobutanedicarboxylate (1c): b.p. 78±
808C/5 torr (Lit. b.p. 101.58C/11 torr [13]); 62±658C/2 torr
[12]. Yield: 46%.
3.3. Reactions of 1,1-cycloalkanedicarboxylic acids (2)
with sulphur tetrafluoride. General procedure
An acid was placed in a 30 ml capacity stainless steel
autoclave ®tted with a needle valve, the autoclave was
cooled in an acetone±dry ice bath, evacuated, then sulphur
tetra¯uoride was condensed into it. The autoclave was
heated and mechanically agitated for the required time.
After completion of the reaction, gaseous products were
let off (excess SF4, SOF2, HF) and the residue was worked
up as described below.
3.1.2. Diethyl 1,1-cyclopropanedicarboxylate (1d)
A modi®ed two-phase procedure [12] was applied.
Diethyl malonate (87 g, 0.543 mol), 1,2-dibromoethane
(188 g, 1.0 mol), potassium carbonate (522 g, 4.0 mol)
and catalytic amount of Bu4NHSO4 (1.5 g) were vigorously
stirred in dimethylsulfoxide (400 ml) at ambient tempera-
ture for 24 h after which the reaction mixture was poured
into water (1500 ml). The product was extracted with ether
(5 Â 100 ml), combined extracts were dried over MgSO4
then the solvent was removed on a rotary evaporator and the
residue was distilled under reduced pressure: b.p. 115±
1188C/15 torr (Lit. b.p. 130±1328C/65 torr [12]); 110±
1158C/18 torr [17]. Yield: 78.6 g (92%).
3.3.1. Preparation of 1,1-bis(trifluoromethyl)cyclohexane
(3a)
1,1-Cyclohexanedicarboxylic acid (2a) (5.2 g, 30 mmol),
water (0.6 g, 33 mmol, a source of HF) and SF4 (42 g,
0.38 mol) were reacted at 1508C for 4 days (96 h). The
crude reaction product was poured into saturated aqueous
NaHCO3 (150 ml) and subjected to steam distillation. An
organic layer in the distillate was separated, dried over
MgSO4 and redistilled under atmospheric pressure to give
3a as a colourless liquid. Yield: 4.2 g (63%). b.p. 124±
1268C. GLC purity: >98%. Analysis: Found: F, 51.8%.
1
Calculated for C8H10F6 (220.16): F, 51.8%. H NMR (in
CDCl3): d: 1.45±1.70 ppm (m, 6H); 1.85±1.90 ppm (m, 4H ).
13C NMR (in CDCl3): d: 125.9 (qm, 1JCF ˆ 285.5 Hz, CF3);
48.9 (sept, 2JCF ˆ 24.1 Hz, C-1); 24.3 (sept, 3JCF ˆ 1.5 Hz,
C-2); 23.9 (s, C-3); 20.5 ppm (s, C-4). 19F NMR (in CDCl3):
d: 70.7 ppm (s, CF3). MS (EI, 70 eV) m/z (rel. int., ion):
3.2. 1,1-Cycloalkanedicarboxylic acids (2). General
procedure [13]
An ester 1a±d (0.1±0.5 mol) was added to ca. 15%
aqueous solution containing 3 mol equivalents of sodium
hydroxide and a suspension was vigorously stirred at ambi-
‡
‡
‡
220 (4, M ); 201 [6, (M F) ]; 200 [56, (M HF) ];
‡
‡
185 [6, (M CH3±HF) ]; 181[14, (M HF2) ]; 180

144
W. Dmowski, A. Wolniewicz / Journal of Fluorine Chemistry 102 (2000) 141±146
‡
‡
[6, (M 2HF) ]; 151 [13, (M CF3) ]; 149 [23, (M
‡
3.3.3. Preparation of 1-(trifluoromethyl)-1-cyclohexanoyl
fluoride (4a)
‡
CF3±2H) ]; 145 [16, (M CH3±2HF) ]; 136 [56,
‡
‡
(M CF3±CH3) ]; 135 (10); 132 [5, (M F±CF3) ];
‡
1,1-Cyclohexanedicarboxylic acid (2a) (8.3 g, 48 mmol)
and SF4 (32 g, 0.3 mol) were reacted at 308C for 3 h. The
reaction mixture was poured into saturated aqueous
NaHCO3 solution and an organic product was steam dis-
tilled The organic layer in the distillate was separated, dried
over MgSO4 and redistilled to give acid ¯uoride 3a as a
colorless liquid. Yield: 5.4 g (56%). b.p. 140±1428C. GLC
purity >99%. Analysis: Found: C, 48.2%; H, 5.0%; F,
38.3%. Calculated for C8H10F4O (198.16): C 48.5%; H,
131 [64, (M HF±CF3) ]; 111 (31); 90 (22); 77 (14 );
‡
‡
‡
69 (9, CF3 ); 67 (18, C5H7 ); 56 (100, C4H8 ); 41 (68,
‡
‡
C3H5 ). HRMS: M 220.06862. Calculated for C8H10F6:
220.06866.
3.3.2. Preparation of 1,1-bis(trifluoromethyl)cycloalkanes
(3b±d)
Acids 2b±d (30 mmol) and SF4 (20 g, 180 mmol) were
reacted at 1208C for 24 h (6 h in the case of 2c). Compound
3b was isolated by steam distillation as described above.
Compounds 3c and 3d were distilled directly from the crude
reaction mixture to which NaF (0.5 g) was added as a HF
scavenger.
1
1
5.1%; F, 38.4%. IR (®lm) n: 1841.6 cm (vs, COF). H
NMR (in CDCl3): d: 1.5±1.1 ppm (m, 2H); 1.50±1.90 ppm
(m, 6H); 2.25±2.31 ppm (m, 1H); 2.32±2.38 ppm (m, 1H).
13C NMR (in CDCl3): d: 159.4 (d, 1JCF ˆ 375.4 Hz, COF);
1
3
124.9 (qd, JCF ˆ 283.8 Hz, JCF ˆ 2.7 Hz, CF3);54.3 (dq,
1,1-Bis(tri¯uoromethyl)cyclopentane (3b): Yield: 56%.
b.p. 90±928C. GLC purity: >99%. Analysis: Found: F,
55.6%. Calculated for C7H8F6 (206.13): F, 55.3%. 1H
NMR (in CDCl3): d: 1.70±1.81 ppm (m, 4H); 1.98±
2.10 ppm (m, 4H). 13C NMR (in CDCl3): d: 126.8 (qq,
1JCF ˆ 282.5 Hz, 3JCF ˆ 2.7 Hz, CF3); 54.3 (sept,
2JCF ˆ 43.0 Hz,
2JCF ˆ 25.5 Hz,
C-1);
27.4
(d,
3JCF ˆ 2.7 Hz, C-2); 24.5 (s, C-3); 21.9 ppm (s, C-4). 19F
NMR (in CDCl3): d: 38.95 (m, COF); 74.76 ppm (d,
4JFF ˆ 8.5 Hz, CF3). MS (EI, 70 eV) m/z (rel. int., ion):
‡
‡
‡
‡
198 (6, M ); 178 [8, (M HF) ]; 158 [8, (M 2HF) ];
‡
156 (10); 151 [8, (M COF) ]; 150 [80, (M CO±HF) ];
‡
2JCF ˆ 26.0 Hz, C-1); 29.9 (q, JCF ˆ 2.7 Hz, C-2);
136 (45); 131 [32, (M COF±HF) ]; 130 [50, (M CO±
‡
3
26.7 ppm (s, C-3). 19F NMR (in CDCl3): d: 72.05 ppm
(s, CF3). MS (EI, 70 eV) m/z (rel. int., ion): 186 [6,
2HF) or (M 2HF±C2H4) ]; 123 [43, (M COF±
‡
‡
‡
C2H4) ]; 117 (62); 111 [25, (M COF±2HF) ]; 107
‡ ‡
‡
‡
(M HF) ]; 167 [35, (M HF2) ]; 166 [35,
‡
(24); 101 [50, (M CF3±C2H4) ]; 81 (36, C6H9 ); 69
‡ ‡ ‡
(7, CF3 ); 68 (44, C5H8 ); 59 (10); 56 (100, C4H8 ); 55
‡
(M 2HF) ]; 145 (24) 117 [28, (M C2H4±HF2) or
‡
‡
‡
‡
‡
(M CF3±HF) ]; 97 [20, (M CF3±2HF) ]; 69 (5,
‡
(49, C4H7 ); 43 (22, C3H7 ); 42 (14, C3H6 ); 41 (58,
‡
‡
‡
CF3 ); 42 (100, C3H6 ); 41 (16, C3H5 ).
C3H5 ).
1,1-Bis(tri¯uoromethyl)cyclobutane (3c): Yield: 51%.
b.p. 66±688C (Lit. b.p. 688C [19]). GLC purity: >99%.
Analysis: Found: F, 59.1%. Calculated for C6H6F6
(192.10): F, 59.3%. 1H NMR (in CDCl3): d: 2.00±
2.19 ppm (m, 2H); 2.40±2.57 ppm (m, 4H). 13C NMR (in
3.3.4. Preparation of 1-(trifluoromethyl)-1-cyclopentanoyl
fluoride (4b)
1,1-Cyclopentanedicarboxylic acid (2b) (6.0 g, 38 mmol)
and SF4 (32 g, 0.3 mol) were reacted at 308C for 3 h.
The reaction mixture was dissolved in CH2Cl2 (20 ml),
stirred overnight with solid NaF (5 g) (removal of HF),
®ltered and distilled under atmospheric pressure to give 4b
as a colorless liquid: Yield: 3.1 g (44%). b.p. 108±1108C.
GLC purity: >96%. Analysis: Found: F, 41.5%. Calculated
for C7H8F4O (184.13): F, 41.3% (C and H were not deter-
1
3
CDCl3): d: 125.0 (qq, JCF ˆ 279.3 Hz, JCF ˆ 2.4 Hz,
2
CF3); 48.7 (sept, JCF ˆ 29.0 Hz, C-1); 22.1 (sept,
3JCF ˆ 2.5 Hz, C-2); 14.8 ppm (s, C-3). 19F NMR (in
CDCl3): d: 72.3 ppm (s, CF3). MS (EI, 70 eV) m/z (rel.
int., ion): 192 (11, M ); 172 [8, (M HF) ]; 153 (27,
‡
‡
‡
‡
‡
(M HF2) ]; 145 [100, (M C2H4±F) ]; 133 [12,
‡
(M 2HF±F) ]; 123 [28, (M CF3) ]; 103 [18,
‡
‡
(M CF3±HF) ]; 95 [33, (M C2H4±CF3) ]; 69 (29,
‡
mined due to a high volatility of 4b). IR (®lm) n:
1844.1 cm
CF3 ); 47 (36); 41 (20, C3H5 ).
(vs, COF). 1H NMR (in CDCl3): d:
‡
1
1,1-Bis(tri¯uoromethyl)cyclopropane (3d): Yield: 59%.
b.p. 44±468C (Lit. b.p. 458C [20]). GLC purity: >99%.
Analysis: Found: F, 63.3% (an error occurred due to high
volatility of 3d). Calculated for C5H4F6 (178.08): F, 64.0%.
1H NMR (in CDCl3): d: 1.25 ppm (m, 4H). 13C NMR (in
1.75 1.90 ppm (m, 2H); 2.00±2.35 ppm (m, 2H). 13C
1
NMR (in CDCl3): d: 160.7 (d, JCF ˆ 364.3 Hz, COF);
125.7 (q, 1JCF ˆ 280.5 Hz, CF3); 58.2 (dq, 2JCF ˆ 47.2 Hz,
2JCF ˆ 27.0 Hz, C-1); 32.3 (s, C-2); 26.3 ppm (s, C-3). 19
F
NMR (in CDCl3): d: 38.95 (m, COF); 74.76 ppm (d,
4JFF ˆ 8.5 Hz, CF3). MS (EI, 70 eV) m/z (rel. int., ion):
1
3
CDCl3): d: 124.3 (qm, JCF ˆ 273.9 Hz, JCF ˆ 1.8 Hz,
2
‡ ‡
165 [3, (M F) ]; 164 [2, (M HF) ]; 144 [6, (M
CF3); 26.2 (sept, JCF ˆ 34.9 Hz, C-1); 7.25 ppm (sept,
3JCF ˆ 1.9 Hz, C-2). 19F NMR (in CDCl3): d: 68.2 ppm
2HF) ]; 143 [17, (M H3F2) ]; 141(5); 136 [7,
‡ ‡
‡
‡ ‡
(M HF±CO) ]; 123 [35, (M H2F3) ]; 117 [40,
(s, CF3). MS (EI, 70 eV) m/z (rel. int., ion): 178 (9, M ); 163
[21, (M CH3) ]; 159 [31, (M F) ]; 158 [20,
‡
‡
‡ ‡
(M CO±HF2) ]; 116 [14, (M CO±2HF) ]; 115 [10,
‡ ‡
(M CF3) ]; 97 (26); 95 [11, (M CF3±HF) ]; 89 [6,
‡
‡
‡
(M HF) ]; 145 (100); 139 (53, (M HF2) ]; 109 [41,
‡
‡ ‡ ‡
(M CF3) ]; 95 [19, (M CF3 CH2) ]; 89 [29,
‡
(M C2H4±CO±HF2) ]; 69(12, C5H9 ); 67 (35, C5H7 );
‡ ‡
42 (100, C3H6 ); 41 (23, C3H5 ).
‡
(M CF3±HF) ]; 75 (4, C3HF2 ); 69 (21, CF3); 46 (25).

W. Dmowski, A. Wolniewicz / Journal of Fluorine Chemistry 102 (2000) 141±146
145
3.3.5. Preparation of 1-(trifluoromethyl)-1-cyclobutanoyl
fluoride (4c)
reaction mixture was stirred at 208C for 2 days, then
acidi®ed with concentrated hydrochloric acid and extracted
with ether (2 Â 50 ml). The extract was dried over MgSO4,
evaporated and a solid residue was recrystallized from
hexane to give white crystals. Yield: 2.44 g (88%). m.p.
60±628C. Analysis: Found: C, 49.0%; H, 5.8%; F, 29.3%.
Calculated for C8H11F3O2 (196.17): C, 50.0%; H, 5.7%; F,
29.1%. IR (CCl4) n: 1717.6 cm 1 (vs, COOH). 1H NMR (in
CDCl3): d: 1.10±1.68 (m, 6H); 1.71 and 2.34 (AB system,
JAB ˆ 12.0 Hz, 4H); 12.3 ppm (s, COOH). 13C NMR (in
1,1-Cyclobutanedicarboxylic acid (2c) (4.0 g, 28 mmol)
and SF4 (22 g, 0.2 mol) were reacted at 308C for 3 h. The
crude liquid product was kept over NaF (0.5 g) for a few
hours and distilled (without ®ltration) under atmospheric
pressure. Yield: 2.6 g (55%). b.p. 84±868C. GLC purity:
>98%. Analysis: Found: F, 45.0%. Calculated for C6H6F4O
(170.11): F, 44.7% (C and H were not determined due to a
1
high volatility of 4c). IR (®lm) n: 1844.1 cm (vs, COF).
1H NMR (in CDCl3): d: 2.08±2.27 ppm (m, 2H); 2.40±
2.72 ppm (m, 4H). 13C NMR (in CDCl3): d: 159.3 (d,
CDCl3): d: 176.0 (s, COOH);125.6 (q, JCF ˆ 283.7 Hz,
1
2
CF3); 53.2 (q, JCF ˆ 24.5 Hz, C-1); 27.4 (s, C-2); 24.8 (s,
1
1JCF ˆ 364.0 Hz, COF); 124.7 (q, JCF ˆ 279.0 Hz, CF3);
C-3); 22.2 ppm (s, C-4). 19F NMR (in CDCl3): d: 76.1 ppm
(s, CF3). MS (EI, 70 eV) m/z (rel. int., ion): 197 [5,
50.1 (dq, 2JCF ˆ 52.2 Hz, 2JCF ˆ 30.7 Hz, C-1); 25.4 (s, C-
2); 15.6 ppm (s, C-3). 19F NMR (in CDCl3): d: 32.5 (q,
‡
‡
‡
(M ‡ H) ]; 196 (9, M ); 179 [5,(M OH) ]; 178 [34,
4
‡ ‡
4JFF ˆ 10.3 Hz, COF), 75.5 ppm (d, JFF ˆ 9.5 Hz, CF3).
(M H2O) ]; 176 [16, (M HF) ]; 158 [8, (M H2O±
(M 2HF) ];
‡
‡
‡
MS (EI, 70 eV) m/z (rel. int., ion): 170 (2, M );153 (57);
152 (16); 151 [6, (M F) ]; 150 [37, (M HF) ]; 131 [17,
HF) ];
156
[71,
‡
141
‡
[100,
‡
‡
(M ‡ H 2C2H4) ]; 140 [3, (M 2C2H4) ]; 136 [26,
‡
‡
‡
‡
‡
(M HF±F) ]; 130 [8, (M 2HF) ]; 123 [100,
(M COF) ]; 108 (19); 104 (25); 103 [71, (M CO±
(M 3HF) ]; 134 (20); 131 [62, (M COOH±HF) ];
127 [14, (M CF3) ]; 121 (76); 111 [26, (M COOH±
‡
‡
‡
‡ ‡
H2F3) ]; 102 (18); 101 [26, (M CF3) ]; 95 [16,
‡
2HF) ]; 109 [15, (M H2O±CF3) ]; 101 (67); 92 (32); 81
‡
‡
‡
‡
(M COF±C2H4) ]; 82 (25); 77 (17); 73 [24,
‡
(23, C6H9 ); 69 (6, CF3 ); 68 (80, C5H8 ); 56 (92, C4H8 );
‡
‡
‡
(M CF3±C2H4) or C4H6F ]; 69 (13, CF3 ); 59 (17,
‡
41 (23, C3H5 ).
‡
‡
C3H4F ); 55 (29, C4H7 ); 54 [13, (M CF3±COF) ]; 53
‡
[17, (M CF3±C2H4±HF) ]; 44 (21); 43 (10); 41 (22,
‡
3.5. 1-(Trifluoromethyl)-1-cycloalkanecarboxylic acids
(5b±d)
C3H5 ).
3.3.6. Preparation of 1-(trifluoromethyl)-1-cyclopropanoyl
fluoride (4d)
1,1-Cycloalkanedicarboxylic acids 2b±d (20 mmol) and
SF4 (14 g, 120 mmol) were reacted at 308C for 3 h and the
crude reaction product was poured into saturated aqueous
NaHCO3 (150 ml) the mixture was brought to boiling for a
few minutes (removal of traces of volatile products), ®l-
tered, strongly acidi®ed with concentrated hydrochloric acid
and extracted with hexane (3 Â 50 ml). The combined
extracts were dried over MgSO4, the solvent was removed
on a rotary evaporator and the residue was recrystallized
from hexane or distilled.
Cyclopropanedicarboxylic acid (2d) (2.6 g, 20 mmol)
and SF4 (14 g, 0.12 mol) were reacted at 308C for 3 h.
To avoid a loss of volatile 4d, the autoclave was cooled
to 108C prior to releasing of gaseous products. The crude
product was worked up as above. Yield: 1.25 g (41%). b.p.
79±808C. GLC purity: >95%. Analysis: Found: F, 48.9%.
Calculated for C5H4F4O (156.08): F, 48.7% (C and H were
not determined due to a high volatility of 4d). IR (®lm) n:
1
1
1848.2 cm (vs, COF). H NMR (in CDCl3): d: 1.58±
1-(Tri¯uoromethyl)-1-cyclopentanecarboxylic acid (5b):
Yield: 71%. m.p. 29±308C (from n-hexane). Analysis:
Found: C, 46.0%; H, 5.8%; F, 31.3%. Calculated for
C7H9F3O2 (182.14): C, 46.1%;H, 6.0%; F, 31.3%. IR
(CCl4): n: 1716.9 cm 1 (vs, COOH). 1H NMR (in CDCl3):
d: 1.73±1.85 ppm (m, 4H); 2.00 and 2.35 (4H); 10.5 ppm (s,
COOH). 13C NMR (in CDCl3): d: 177.8 (q, 3JCF ˆ 1.6 Hz,
1.68 ppm (m, 4H). 13C NMR (in CDCl3): d: 158.6 (d,
1
1JCF ˆ 344.1 Hz, COF); 123.2 (qd, JCF ˆ 272.9 Hz,
3JCF ˆ 2.8 Hz, CF3); 25.4 (dq, 2JCF ˆ 66.1 Hz,
3
2JCF ˆ 36.1 Hz, C-1); 14.4 ppm (d, JCF ˆ 1.8 Hz, C-2).
4
19F NMR (in CDCl3): d:
26.18 (q, JFF ˆ 9.9 Hz,
4
COF), 68.94 ppm (d, JFF ˆ 10.1 Hz, CF3). MS (EI,
‡
‡
1
70 eV) m/z (rel. int., ion): 156 (4, M ); 155 [9, (M H) ];
141 [15, (M CH3) ]; 137 [13, (M F) ]; 136 [100,
COOH); 126.2 (q, JCF ˆ 280.6 Hz, CF3); 58.3 (q,
2JCF ˆ 25.9 Hz, C-1); 32.5 (d, JCF ˆ 2.7 Hz, C-2);
‡
‡
3
‡
‡
(M HF) ]; 109 [17, (M COF) ]; 108 [45, (M HF±
‡
26.2 ppm (s, C-3). 19F NMR (in CDCl3): d: 72.25 ppm
(s, CF3). MS (EI, 70 eV) m/z (rel. int., ion): 183 [3,
‡
‡
CO) or (M HF±C2H4) ]; 89 [38, (M COF±HF) ]; 69
‡
‡
‡
‡
(22, CF3 ); 59 (27); 42 (54).
(M ‡ H) ]; 182 (3, M ); 162 [2, (M HF) ]; 143 [5,
‡ ‡
(M HF2) ]; 142 [57, (M 2HF) ]; 141 (100); 121
[33, (M H4F3) ] 117 [78, (M COOH±HF) ]; 114
‡ ‡
3.4. 1-(Trifluoromethyl)-1-cyclohexanecarboxylic acid
(5a)
‡ ‡
[22, (M CO±2HF) or (M C2H4±2HF) ]; 113 (15,
‡ ‡
M
CF3 ); 101 (27); 97 [35, (M COOH±2HF) ]; 69
‡
‡
‡
‡
1-(Tri¯uoromethyl)-1-cyclohexanoyl ¯uoride (4a) (2.8 g,
14 mmol) and Bu4NHSO4 (0.1 g, 0.3 mmol) were added to a
solution of KOH (1.2 g, 21 mmol) in water (20 ml) and the
(3, CF3 ); 67 (23, C5H7 ); 42 (10, C3H6 ); 41 (9, C3H5 ).
1-(Tri¯uoromethyl)-1-cyclobutanecarboxylic acid (5c):
Yield: 31%. b.p. 74±768C/13 torr (liquid). Analysis: Found:

146
W. Dmowski, A. Wolniewicz / Journal of Fluorine Chemistry 102 (2000) 141±146
‡
C, 42.5%; H, 4.2%; F, 34.2%. Calculated for C6H7F3O2
(168.04): C 42.8%; H, 4.4%; F, 33.9%. IR (CCl4): n:
1717.3 cm
(35, CF3 ) 64 (48); 59 (42); 58 (14); 57 (17); 45 (49,
‡
‡
‡
‡
CO2H ); 41 (11, C3H5 ); 40 (14, C3H4 ); 39 (78, C3H3 ).
1
(vs, COOH). 1H NMR (in CDCl3): d:
2.05 2.25 ppm (m, 2H); 2.42 2.71 ppm (m, 4H);
11.56 ppm (s, COOH). 13C NMR (in CDCl3): d: 176.2
References
3
1
(q, JCF ˆ 2.2 Hz, COOH); 125.6 (q, JCF ˆ 277.5 Hz,
CF3); 50.5 (q, 2JCF ˆ 28.8 Hz, C-1); 25.7 (d, 3JCF ˆ 2.7 Hz,
C-2); 15.6 ppm (s, C-3). 19F NMR (in CDCl3): d: 72.2 ppm
(s, CF3). MS (EI, 70 eV) m/z (rel. int., ion): 169 [4,
[1] R. Filler, in: R.E. Banks (Ed.), Organofluorine Chemicals and Their
Industrial Applications, ch. 6, Ellis Harwood, Chichester, UK, 1979.
[2] M.A. McClinton, D.A. McClinton, Tetrahedron 48 (1992) 6555.
[3] M. Charton, J. Am. Chem. Soc. 91 (1969) 615.
[4] M. Schlosser, D. Michel, Tetrahedron 52 (1996) 99 and references
therein.
‡
‡
‡
(M ‡ H) ]; 168 (1, M ); 167 [5, (M H) ]; 151 [5,
‡
‡
‡
‡
‡
(M OH) ]; 150 [3, (M H2O) ]; 148 [25, (M HF) ];
141 (51); 140 [4, (M C2H4) ]; 128 [18, (M 2HF) ];
‡
[5] Y. Hanzawa, M. Suzuki, Y. Kobayashi, Tetrahedron Lett. 30 (1989)
571.
‡
123 [36, (M COOH) ]; 121 (45); 108 [84, (M 3HF) ];
‡
[6] Y. Hanzawa, M. Suzuki, Y. Kobayashi, T. Taguchi, J. Org. Chem. 56
(1991) 1718.
103 [36, (M COOH±HF) ]; 102 [14, (M H2O±HF±
‡
‡
C2H4) ]; 101 (81); 100 (100); 99 [39, (M CF3) ]; 95
‡
[7] J.C. Blazejewski, M. Haddad, C. Wakselman, J. Fluorine Chem. 52
(1991) 353.
‡
(14, C3H2O2F2 ); 84 (40); 83 [17, (M COOH±2HF) ];
‡
[8] H. Abele, A. Haas, M. Lieb, J. Zwingenberger, Chem. Ber. 127
(1994) 145.
 Â
[9] D. Bonnet-Delpo, J.P. Begue, T. Lequeux, M. Ourevitch, Tetrahedron
81 (14); 80 [70, (M 3HF±C2H4) ]; 77 (22); 76 (23); 75
‡
(17); 73 (23); 72 (19); 69 (33, CF3); 53 (27, C4F7 ).
1-(Tri¯uoromethyl)-1-cyclopropanecarboxylic acid (5d):
Yield: 36%. b.p. 182±1848C/760 torr. m.p. 84±868C (during
distillation solidi®es in a condenser). Analysis: Found: C,
38.6%; H, 3.2%; F, 36.9%. Calculated for C5H5F3O2
52 (1996) 59.
[10] C.R. Davis, D.C. Swenson, D.J. Burton, J. Org. Chem. 58 (1993)
6843.
È
[11] L.G. Bergson, A. Biezais, Arkiv for Kemi 22 (1964) 475.
[12] N.S. Zefirov, T.S. Kuznecova, S.I. Kozhushkov, L.S. Surmina, Z.L.
Rashchipkina, Zh. Org. Khim. 19 (1983) 541.
[13] A. Vogel, J. Chem. Soc. (1929) 1429.
(154.02): C, 38.9%; H, 3.3%; F, 37.0%. IR (CCl4): n:
1712.1 cm
1
(vs, COOH). 1H NMR (in CDCl3): d:
1.39 1.58 ppm (m, 4H); 9.85 ppm (s, COOH). 13C NMR
[14] W. Dmowski, Introduction of fluorine in organic compounds using
sulphur tetrafluoride, in: B. Baasher, H. Hagemann, J.C. Tatlow
(Ed.), Houben-Weyl, Methods in Organic Chemistry, Vol. E10a,
Georg Thieme Verlag Stuttgart, New York, 1999.
(in CDCl3): d: 175.0 (s, COOH); 124.1 (q, 1JCF ˆ 272.5 Hz,
CF3); 26.5 (q, 2JCF ˆ 34.6 Hz, C-1); 13.9 ppm (s, C-2). 19
F
NMR (in CDCl3): d: 68.2 ppm (s, CF3). MS (EI, 70 eV) m/z
‡
‡
‡
[15] A. Dox, L. Yoder, J. Am. Chem. Soc. 43 (1921) 1368.
[16] W.P. Golimov, Zh. Obshch. Chim. 22 (1952) 1944.
[17] G.T. Szabo, K. Aranyosi, M. Csiba, L. ToÈke, Synthesis 6 (1987) 565.
[18] R.K. Sigh, S. Danishefsky, Org. Synth. 60 (1981) 66.
[19] W.R. Hasek, W.C. Smith, V.A. Engerlhardt, J. Am. Chem. Soc. 82
(1960) 543.
(rel. int., ion): 155 [4, (M ‡ H) ]; 154 (30, M ); 153 [5,
‡
‡
(M H) ]; 139 [2, (M CH3) ]; 137 [17, (M OH) ];
136 [3, (M H2O) ]; 135 [5, (M F) ]; 134 [46,
‡
‡
‡
‡
(M HF) ]; 115 [32, (M HF2) ]; 114 [23,
‡
‡
(M 2HF) ]; 109 [10, (M CO2H) ]; 105 (25); 104
‡
‡
[20] J.M. Pustovit, P.I. Ogoiko, V.P. Nazaretian, L.B. Fariateva, J.
Fluorine Chem. 69 (1994) 225.
(76); 95 [17, (M H2F3) ]; 90 [32, (M CO2H±F) ];
89 (39); 87 (14); 86 (100); 85 (47); 76 (15); 75 (17); 69