Sodium dithionite initiated reactions of Halothane with enol ethers: Facile synthesis of 3-trifluoromethyl substituted vinyl carbonyl compounds

Article abstract of DOI:10.1016/S0022-1139(01)00459-6

A convenient and simple method has been found for the preparation of 5,5,5-trifluoro-3-penten-2-one (3) and 4,4,4-trifluorocrotonaldehyde (9) by a sodium dithionite initiated addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to 2-methoxypropene and ethyl vinyl ether, respectively. Reduction of 3 with aluminium isopropoxide afforded allyl alcohol, 5,5,5-trifluoro-3-penten-2-ol (5) and oxidation of 9 gave 4,4,4-trifluorocrotonic acid (11).

Full text of DOI:10.1016/S0022-1139(01)00459-6

Journal of Fluorine Chemistry 111 02001) 227±232
Sodium dithionite initiated reactions of Halothane1 with enol ethers
Facile synthesis of 3-tri¯uoromethyl substituted
vinyl carbonyl compounds
*
1
Â
Halina Plenkiewicz, Wojciech Dmowski , Miroslaw Lipõnski
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
Received 16 April 2001; accepted 15 June 2001
Abstract
A convenient and simple method has been found for the preparation of 5,5,5-tri¯uoro-3-penten-2-one 03) and 4,4,4-tri¯uorocrotonaldehyde
09) by a sodium dithionite initiated addition of 1-bromo-1-chloro-2,2,2-tri¯uoroethane to 2-methoxypropene and ethyl vinyl ether,
respectively. Reduction of 3 with aluminium isopropoxide afforded allyl alcohol, 5,5,5-tri¯uoro-3-penten-2-ol 05) and oxidation of 9 gave
4,4,4-tri¯uorocrotonic acid 011). # 2001 Elsevier Science B.V. All rights reserved.
Keywords: 5,5,5-Tri¯uoro-3-penten-2-one; 4,4,4-Tri¯uorocrotonaldehyde; 5,5,5-Tri¯uoro-3-penten-2-ol; 4,4,4-Tri¯uorocrotonic acid; 1-Bromo-1-chloro-
2,2,2-tri¯uoroethane; Sodium dithionite; Enol ethers
1. Introduction
2,2,2-tri¯uoroacetophenone with alkylidene phosphoranes
0prepared from a-haloketones or haloacetates and triphe-
nylphosphine) [12,13]. This methodology was successfuly
applied for the synthesis of bis0tri¯uoromethyl) ketones and
esters from hexa¯uoroacetone [14,15]. A modi®cation of the
Wittig reaction, using antimony or arsenium yields has also
been reported [3]. Numerous per¯uoroalkyl substituted
unsaturated esters, including CF3-substituted, were prepared
from chlorides or esters of per¯uoroalkyl carboxylic acids
and alkylidene phosphoranes in Horner±Wadsworth±
Emmons reactions [16,17]. Highly stereoselective synthesis
of either Z or E isomers were achieved by this method using,
respectively, phosphonium salts or phosphonates [18,19]. A
Knoevenagel condensation of tri¯uoromethyl ketones and
aldehydes with malonic acid or acetylacetone, followed by
dehydration [20,21], and an ultrasound promoted Refor-
matsky-type reaction between tri¯uoroacetaldehyde and
ethyl bromoacetate [22] were also used for the synthesis
of CF3-substituted a,b-unsaturated carbonyl compounds.
The reduction of 3-tri¯uoromethyl vinyl aldehydes and
esters with LiAlH4 [23], LiAlH4/AlCl3 [22] or NaBH4 [24]
provided the corresponding allylic alcohols. Enzymatic
reduction led to chiral tri¯uoromethyl allylic alcohols [25].
W.Y. Huang and co-workers have developed a new method
of the synthesis of 3-per¯uoroalkyl vinyl aldehydes and
ketones. This method is based on a general procedure, named
sulphinatodehalogenation, in which per¯uoroalkyl radicals
are generated from per¯uoroalkyl iodides or bromides in a
The a,b-unsaturated carbonyl compounds containing tri-
¯uoromethyl groups as well as allylic alcohols are of con-
siderable interest as building blocks for tri¯uoromethyl
analogs of natural and bioactive molecules. A number of
tri¯uoromethylated amino acids have been prepared via
4,4,4-tri¯uorocrotonic acid, 3-0tri¯uoromethyl)crotonates
and 4,4,4-tri¯uoro-3-0tri¯uoromethyl)crotonates [1]. Vinyl
ketones and unsaturated esters containing tri¯uoromethyl
groups are valuable intermediates to tri¯uoromethyl sub-
stituted carbocycles [2,3], heterocycles [4±8] and aromatics
[9]. Allylic alcohols, 3-tri¯uoromethyl-2-propanols, were
reported to be useful precursors of tri¯uoromethyl substi-
tuted cyclopropane lactones, which in turn, are potential
intermediates to tri¯uoromethyl-containing pyrethroids
[10,11].
The most general method of synthesis of 3-tri¯uoro-
methyl substituted a,b-unsaturated carbonyl compounds
consists of the Wittig-type condensation of phosphorus
yields with tri¯uoromethyl aldehydes and ketones. A
number of tri¯uoromethyl vinyl ketones and esters were
obtained from reactions of 1,1,1-tri¯uoroacetone and
* Corresponding author. Fax: ‡48-22-632-66-81.
E-mail address: dmowski@icho.edu.pl 0W. Dmowski).
1 A part of work for B.Sc. diploma of Akademia Podlaska, Siedlce,
Poland.
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 0 0 1 ) 0 0 4 5 9 - 6

228
H. Plenkiewicz et al. / Journal of Fluorine Chemistry 111 +2001) 227±232
series of SET processes initiated by sodium dithionite and
related reagents [26±28]. Addition of these radicals to
alkyl vinyl ethers gives 3-per¯uoroalkyl aldehydes or
ketones [29,30] which on dehydro¯uorination afford
3-¯uoro-3-0per¯uoroalkyl)-a,b-unsaturated carbonyl com-
pounds according to the general scheme [31,32]:
the presence of 4-chloro-5,5,5-tri¯uoro-2-pentanone 02) as
the main product together with small amount of unsaturated
ketone, 5,5,5-tri¯uoro-3-penten-2-one 03). In some experi-
ments, the presence of trace amounts of the primary adduct
0component of longest retention time), 2-bromo-2-ethoxy-4-
chloro-5,5,5-tri¯uoropentane 01) was also found 0Scheme 1).
Reduction of per¯uoroalkyl vinyl aldehydes and ketones
allowed preparation of the corresponding allylic alcohols
[32]. The Huang procedure has a number of advantages:
simplicity, aqueous reaction medium, very mild reaction
conditions and usually excellent yields. Furthermore, in this
procedure there is no need to use highly toxic phosphorus
compounds or drastic reaction conditions which are usually
necessary to generate free radicals.
The Huang procedure was successfully applied for the
synthesis of vinyl carbonyl compounds substituted with
rather long per¯uoroalkyl chains 0C4±C8) but no tri¯uoro-
methylation has been reported till now. In the present paper
we report an application of sulphinatodehalogenation meth-
odology to the synthesis of 3-tri¯uoromethyl substituted
a,b-unsaturated carbonyl compounds, namely, 5,5,5-tri-
¯uoro-3-penten-2-one 03) and 4,4,4-tri¯uoro-2-butenal 09),
from commercially available and inexpensive reagents:
1-bromo-1-chloro-2,2,2-tri¯uoroethane 0Halothane1), 2-
methoxypropene and ethyl vinyl ether. Reductions of com-
pound 3 to the corresponding allyl alcohol 5 and homoallyl
alcohol 6 and oxidation of 9 to 4,4,4-tri¯uorocrotonic acid
11 are also reported.
A composition of a mixture of the reaction products, even
when separated from alkaline reaction medium, changed in
time in favour of ketone 3 and at the expense of ketone 2;
after 1 day the contents of 3 increases from the initial 2±3 to
10±15% with the corresponding drop of the amount of
saturated ketone 2. This indicates the instability of 2 which
easily undergoes dehydrochlorination.
The attempted isolation of 2 by distillation failed; 3:1 to
1:1 mixtures of 2 and 3 were obtained. Agitating this
distillate with concentrated hydrochloric acid gave almost
pure compound 2 098%), a sample of which was separated
and identi®ed by elemental analysis and spectral data. With
the aim to determine a yield of the addition product 2,
freshly prepared mixture of products, containing ca. 98% of
2, was treated with 2,4-dinitrophenylhydrazine. Elemental
analysis of the resulting hydrazone, after recrystallisation
and drying over P4O10 under reduced pressure for a few
days, showed the absence of chlorine thus showing total
dehydrochlorination; the analytical data were fully consis-
tent with those calculated for unsaturated hydrazone 4. The
hydrazone 4 was obtained with over 70% yield 0after
recrystallisation) which gives evidence for high ef®ciency
of the reaction of CF3CHClBr with 2-methoxypropene.
Treatment of an ether solution of a crude mixture of
products with triethylamine gave unsaturated ketone 3 as
practically the only product which was isolated by fractional
distillation. The volatility of 3 makes its separation from
ether rather dif®cult and because of that not a very high yield
of pure product was obtained. The dehydrochlorination of 2
proceeded with full stereoselectivity. Ketone 3 was formed
exclusively as trans-isomer, as shown by the high value of
the coupling constant of vinylic protons across the double
bond in its 1H NMR spectrum. This is contrary to the
reported dehydro¯uorinations of 3-per¯uoroalkyl substi-
tuted ketones which usually resulted in mixtures of trans-
and cis-isomers [31,32]. Semiempirical structure modeling
0PC Model 3.0) have shown that a conformation of 2
which by trans-elimination of HCl should give trans-3 is
by ca. 3 Kcal/mol more favourable then a conformation
leading to the cis-isomer. Also, a very high rotational barrier
0ca. 12 Kcal/mol) was found for compound 2.
2. Results and discussion
Sodium dithionite was used as an initiator of an electron
transfer processes together with sodium hydrogen carbonate
as a base 0neutralisation of evolved HBr). In primary trials,
the reaction of CF3CHClBr with 2-methoxypropene was
investigated on a 20 mmol scale under a variety of condi-
tions, solvents compositions and reactant ratios. The best
results were obtained when approximately equimolar
amounts of Na2S2O4 and NaHCO3 suspended in an acet-
onitrile:water mixture 01:1 by volume) were used and the
organic reagents were added to this mixture pre-cooled to
108C and then allowed to warm up slowly, while stirring, to
ambient temperature when a noticeable exothermic effect
occurred. This procedure was then applied to preparative
scale experiments. When the reaction was quenched after
2 h 0by dilution with water), GC±MS investigations revealed

H. Plenkiewicz et al. / Journal of Fluorine Chemistry 111 +2001) 227±232
229
Scheme 1.
Selective reduction of pentenone 3 to allyl alcohol, trans-
5,5,5-tri¯uoro-3-penten-2-ol 05), was successfully carried
out with aluminium isopropoxide by classical Meerwein±
Ponndorf±Verley methodology [33,34]. Alcohol 5 was
obtained in good yield and purity. Reduction of 3 with
LiAlH4 proceeded in a rather unexpected way. After 2 h
at room temperature almost equimolar amounts of 5 and the
homoallylic alcohol, 5,5,-di¯uoro-4-penten-2-ol 06), were
formed and after a prolonged reaction time compound 6 was
the only product. The attempted isolation of pure 6, free of
ether, failed; the best fraction obtained by careful distillation
afforded a sample containing 81% of 6, nevertheless, spec-
troscopic investigations gave unequivocal evidence for its
structure. A reaction pathway leading to 6 must involve
attack of hydride ion on carbon atom C-3 in 5 followed by
elimination of ¯uoride ion from the CF3 group. Similar
behaviour was previously reported for LiAlH4 reduction of
3-0tri¯uoromethyl)crotonate [24].
Reactions of CF3CHClBr with ethyl vinyl ether were
conducted and proceeded the same way as those with 2-
methoxypropene. The 3-chloro-4,4,4-tri¯uorobutyralde-
hyde 08) was the main product together with a small amount
of dehydrochlorinated product, 4,4,4-tri¯uorocrotonalde-
hyde 09), and a trace amount of primary adduct, 1-bromo-
1-ethoxy-3-chloro-4,4,4-tri¯uorobutane 07) 0Scheme 2).
Instability of 8, similarly to 2, prevents its direct isolation.
Treatment of the crude mixture of products with triethyla-
mine or pyridine resulted in total conversion of 8 into
tri¯uorocrotonaldehyde 09) but, unfortunately, high volati-
lity did not allowed isolation of this compound in a pure
state; fractional distillation gave only fractions of variable
concentration of 9 in diethyl ether. 1H NMR spectrum
Scheme 2.

230
H. Plenkiewicz et al. / Journal of Fluorine Chemistry 111 +2001) 227±232
showed the trans-conformation of aldehyde 9. The 2,4-
dinitrohydrazone prepared from 8, similarly to that from
2, dehydrochlorinated during the drying procedure to give
unsaturated hydrazone 10 in over 63% yield.
vigorously stirred and cooled to 108C, then 2-methoxypro-
pene or ethyl vinyl ether 06.92 g, 96 mmol) and CF3CHClBr
015.8 g, 80 mmol) were added one by one. The cooling
bath was removed and the reaction mixture, while stirring,
was allowed to warm up slowly. At about 208C a noticea-
ble exothermic effect occurred, the temperature reached
28±308C and most inorganic salts dissolved. Stirring was
continued for 1 h 0altogether about 2 h from the beginning of
the reaction) during which time the temperature of the
reaction mixture returned to ambient. Water 0120 ml) was
added and the reaction mixture was extracted with diethyl
ether 0120 ml), the organic layer was separated and washed
with water 04 Â 60 ml, removal of CH3CN) and dried over
MgSO4. GLC and GC±MS analyses of the extract revealed
the presence of compounds 2 and 3 0from 2-methoxypro-
pene) or 8 and 9 0from ethyl vinyl ether) in a ratio varying
from 40:1 to 10:1; this ratio changed in favour of 3 or 9
on standing for several hours. Trace amounts of primary
adducts 1 or 7 were also detected by GC±MS.
The attempted reduction of ether solutions of 9, either
with aluminium isopropoxide or sodium borohydride, failed.
Only trace amounts of the expected 4,4,4-tri¯uoro-2-buten-
1-ol were detected by GC±MS analysis but a viscous
unidenti®ed oil remained after removal of the solvents.
However, aldehyde 9 was, successfully oxidised with chro-
mium0VI) oxide by following the procedure used by Huang
and LuÈ [30]; high purity, crystalline trans-4,4,4-tri¯uoro-
crotonic acid 011) was obtained albeit in only moderate yield
0ca. 22%). The yield of acid 11 was undoubtedly lowered by
its inef®cient extraction from aqueous solution with trichlor-
o¯uoromethane. This solvent was used instead of diethyl
ether because acid 11 strongly binds diethyl ether so that it
was not possible to remove the latter by distillation. On the
other hand, the partition coef®cient of 11 between water and
CCl3F is probably not satisfactory for ef®cient extraction.
In conclusion, sodium dithionite initiated reactions of
CF3CHClBr with 2-methoxypropane and ethyl vinyl ether
in a water±acetonitrile solutions provide an easy and envir-
onmentally friendly way to valuable, tri¯uoromethyl sub-
stituted a,b-unsaturated carbonyl compounds, ketone 3 and
aldehyde 9, and further, to the corresponding allylic alcohol
5 and acid 11.
3.1.1. 2-Bromo-2-methoxy-4-chloro-5,5,5-
trifluoropentane +1)
‡
GC±MS:m/z0rel.int.,ion):177,175[4,120M À CH2Br) ];
‡
‡
139 [10, 0M À CH2Br±HCl) ]; 77 010, C3H3F2 ); 69 020,
‡
‡
CF3 ); 59 0100, C3H7O ).
3.1.2. 4-Chloro-5,5,5-trifluoro-2-pentanone +2)
Distillation of a solution of compounds 2 and 3 prepared
as above resulted in increased dehydrochlorination. A
sample of the distillate 0bp 126±1288C) containing roughly
70% of 2 and 30% of 3 was stirred overnight with concen-
trated hydrochloric acid, separated and dried over CaCl2.
GLC analysis shown only 2. Analysis, found: C, 34.2; H,
3.5; Cl, 20.6; F, 32.6%. Calculated for C5H6ClFO 0174.55):
C, 34.4; H, 3.5; Cl, 20.3; F, 32.7%. 1H NMR d: 2.25 0s, CH3);
3.05 0centre of narrow AB system, JAB ˆ 17:9 Hz, CH2);
3. Experimental
Melting points were determined in capillaries and boiling
points were measured during distillation; both are uncor-
rected. 1H NMR spectra were recorded with a Brucker 500
instrument and 19F NMR spectra with a Varian Gemini 200
spectrometer 0at 188 MHz), both in CDCl3 solutions. Che-
1
3
3
3
mical shifts are quoted in ppm from internal TMS for H
4.68 0dqd, JHH ˆ 7:8 Hz, JHF ˆ 6:9 Hz, JHH ˆ 4:9 Hz,
0positive down®eld) and from internal CFCl3 0positive
up®eld) for 19F nuclei. Crude mixtures of products were
analysed with a Shimadzu GC-14A chromatograph using a
3:5 m  2 mm column packed with 5% silicone oil SE-52 on
chromosorb G or a 30 m capillary column coated with a
BPX-5 oil. GC±MS analyses were performed with a Hew-
lett-Packard 5890 apparatus 030 m capillary column, 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. The 1-bromo-1-chloro-2,2,2-
tri¯uoroethane, 2-methoxypropene and ethyl vinyl ether
were commercial reagents.
CHCl) ppm. 19F NMR d: 75.4 0d, 3JHF ˆ 6:9 Hz) ppm. GC±
‡
MS: m/z 0rel. int., ion): 176, 174 08, 24, M ); 161, 159 [8, 24,
0M À CH3) ]; 133, 131 [30, 90, 0M À CH3CO) ]; 123
‡
‡
‡
‡
[20, 0M À CH3±HCl) ]; 95 [30, 0M À CH3O±HCl) ]; 69
‡
‡
[100, CF3 and 0M À CF3±HCl) ].
3.1.3. Trans-5,5,5-trifluoro-3-penten-2-one +3)
Triethylamine 012 ml, 8.7 g, 86 mmol) was added to a
solution of compounds 2 and 3 in diethyl ether, prepared as
in Section 3.1. A precipitate of Et3NÁHCl began to form
almost immediately. The reaction mixture was left overnight
then washed water 0100 ml) then with dilute hydrochloric
acid 0ca. 1%, 100 ml) followed by water until a neutral,
organic layer was separated and dried over anhydrous
MgSO4. Careful distillation through a 10 cm Vigreux col-
umn gave compound 3 as colourless liquid possessing
a strong irritating smell. GLC purity: ca. 98%. Yield:
5.3 g 038.4 mmol, 48% related to CF3CHClBr). The bp
102±1048C 0in agreement with [21]). Analysis, found: F,
3.1. General procedure for the reactions of
CF3CHClBr with enol ethers
Sodium dithionite 016.0 g 085%), 80 mmol) and sodium
hydrogen carbonate 06.0 g, 72 mmol) were suspended in
aqueous acetonitrile 01:1, 120 ml). The suspension was

H. Plenkiewicz et al. / Journal of Fluorine Chemistry 111 +2001) 227±232
231
‡
‡
‡
41.5% 0no C and H were determined due to a high volatility
of 3). Calculated for C5H5F3O 0138.3): F, 41.3%. 1H NMR d:
033, C3H3F2 ); 69 09, CF3 ); 45 034, C2H5O ); 43
‡
0100, CH3CO ). IR 0neat): n 0cmÀ1): 3551 0br, OH);
1685.7 0m, C=C).
3
3
2.37 0s, CH3); 6.58 0dq, JHH ˆ 16:1 Hz, JHF ˆ 6:3 Hz,
3
4
1H); 6.69 0dq, JHH ˆ 16:1 Hz, JHF ˆ 1:8 Hz, 1H) ppm.
19F NMR d: 65.3 0d, broaden, JHF ˆ ca: 6 Hz, CF3) ppm.
3.1.6. 5,5,-Difluoro-4-penten-2-ol +6)
3
‡
MS 0EI, 70 eV): m/z 0rel. int., ion): 138 034, M ); 123 [100,
0M À CH3) ]; 95 [44, 0M À CH3CO)] ; 69 [40, CF3 and
Lithium aluminium hydride 00.76 g, 20 mmol) was added
portionwise to a stirred solution of pentenone 3 in Et2O,
prepared as in Section 3.1.3. from a half amount of reagents
used in Section 3.1. After 2 h GLC analysis revealed the
presence of compound 5 and a shorter retention time com-
ponent in ca. 1:1 ratio. The stirring was continued overnight
after which time compound 5 disappeared and only a new
compound remained. Inorganic solids were dissolved by
stirring overnight with ca. 12% sulphuric acid, the organic
layer was separated washed with water until neutral and
dried over MgSO4. Distillation gave a number of fraction; a
small fraction 0bp 116±1188C) contained 81% of a com-
pound which was identi®ed by spectral means as alcohol
6. 1H NMR d: 1.19 0d, 3JHH ˆ 6:2 Hz, CH3); 2.12 0centre of
AB system, JAB ˆ ca: 8 Hz, CH2); 3.1 0s, OH); 3.81 0sxt,
‡
‡
‡
0M À CF3) ]; 43 068, CH3CO ). IR 0neat): n 0cmÀ1): 1715.4
‡
‡
‡
and 1698.3 0vs, C=O); 1665.8 0m, C=C). HRMS: M
138.02885. Calculated for C5H5F3O: 138.02925.
3.1.4. 2,4-Dinitrophenylhydrazone 4
A freshly prepared ether solution of pentanone 2
0contaminated with ca. 2% of 3), prepared from a quarter
amount of reagents used in Section 3.1., was added to a
reagent prepared by dissolution of 2,4-dinitrophenylhydra-
zine 04 g, 20 mmol) in warm 85% phosphoric acid 048 ml)
and diluted 0after cooling to ambient temperature) with 96%
ethyl alcohol 032 ml). A yellow-orange precipitate was
immediately formed. After 1 h the precipitate was ®ltered
off, washed with ethanolic solution of 85% phosphoric acid
02:3) then with water until neutral. Removal of ether from
the eluent on a rotary evaporator gave an additional amount
of the precipitate which was worked up as above. The
combined precipitates 06.4 g) were recrystallised from
ethanol and dried over P4O10 under reduced pressure. Yield:
4.54 g 014.3 mmol, 71.4% related to CF3CHClBr). The mp
179±1808C. Analysis, found: C, 41.4; H, 2.7; N, 17.6; F,
17.9%; no Cl found. Calculated for C11H9F3N4O4 0318.21):
C, 41.5; H, 2.9; N, 17.6; F, 17.9%.
3JHH ˆ 6:2 Hz, 1H); 4.23 0dtd, 3JHFtrans ˆ 25:4 Hz, 3JHH
ˆ
8:0 Hz, JHFcis ˆ 2:5 Hz, 1H) ppm. 19F NMR d: 88.4 0d,
3
2JFF ˆ 45:5 Hz, 1F); 91.4 0dd, JFF ˆ 45:5 Hz, JHFtrans
ˆ
2
3
25:4 Hz, 1F) ppm. MS 0EI, 70 eV): m/z 0rel. int., ion): 107
[4, 0M À CH3) ]; 77 022, C3H3F2 ); 69 02, CF3 ); 59
‡
‡
‡
‡
‡
‡
015, C3H7O ); 51 09, CF2H ); 45 0100, C2H5O ). IR 0neat):
n 0cmÀ1): 3353 0br, OH); 1750.6 0s, C=C) 01730 cmÀ1
‡
was reported for CH2=CF2 [35]. HRMS: 0M À CH3) :
‡
107.02996. Calculated for C4H5F2O : 107.03085.
3.1.7. 1-Bromo-1-ethoxy-3-chloro-4,4,4-
trifluorobutane +7)
3.1.5. Trans-5,5,5-trifluoro-3-penten-2-ol +5)
‡
A solution of pentenone 3 in Et2O, prepared as in Section
3.1.3., dry isopropyl alcohol 0120 ml) and aluminium iso-
propoxide 016.5 g, 81 mmol) were placed in a distillation
apparatus ®tted with a magnetic stirring bar and a short
Vigreux column. The reaction mixture was slowly warmed
up while stirring. Ether together with acetone formed in the
reaction, were distilled off to ca. 608C followed by isopro-
panol 060 ml, bp 818C). Hydrochloric acid 010%) was added
until dissolution of a suspension of inorganic solids. The
reaction mixture was then extracted with ether 02 Â 40 ml),
the extract was washed with water 05 Â 30 ml, removal of
isopropanol) and dried over MgSO4. Distillation gave com-
pound 5 as a liquid possessing a strong, geranium-like smell.
The GLC purity: 98%, yield: 4.7 g 033.5 mmol, 42% related
to CF3CHClBr), bp 130±1328C 0Lit.: 130±1338C [25]).
Analysis, found: C, 42.9; H, 5.2; F, 40.6%, calculated for
GC±MS: m/z 0rel. int., ion): 191, 189 [30, 90, 0M À Br) ];
‡
163, 161 [33, 100 0M À C2H4Br) ]; 143, 141 [15, 45,
‡
‡
0M À C2H4Br±HF) ]; 103 050), 77 030, C3H3F2 ); 69
‡
015, CF3 ).
3.1.8. 3-Chloro-4,4,4-trifluorobutyraldehyde +8)
‡
GC±MS: m/z 0rel. int., ion):160, 162 02, 6, M ); 142, 140
‡
‡
‡
[3, 9, 0M À HF) ]; 114, 112 [5, 15, 0M À HF±CO) ]; 96
‡
[100, 0M À HCl±CO) ]; 95 [100, 0M À HCl±CHO) ]; 77
‡
‡
0100, C3H3F2 ); 69 080, CF3 ).
3.1.9. Trans-4,4,4-trifluorocrotonaldehyde +9)
A solution of compounds 8 and 9 in diethyl ether, pre-
pared from ethyl vinyl ether as in Section 3.1., was treated
with pyridine and worked up as described in Section 3.1.3.
GLC analysis of an ether layer showed total conversion of 8
into 9 0GLC peak overlaps with Et2O). Distillation gave a
number of fractions; a small fraction 0bp 62±648C) contain-
ing 60% of aldehyde 9 0the richest one) was subjected to
spectral investigations. 1H NMR d: 6.65 0centre of AB
system, JAB ˆ 16:0 Hz, 2H); 9.72 0complex m, CHO) ppm.
19F NMR d: 66.3 0narrow m) ppm. MS 0EI, 70 eV) m/z 0rel.
1
C5H7F3O 0140.11): C, 42.9; H, 5.0; F, 40.7%. H NMR d:
1.33 0d, 3JHH ˆ 6:6 Hz, CH3); 1.91 0s br, OH); 4.45 0m, 1H);
3
3
4
5.88 0dqd, JHH ˆ 15:7 Hz, JHF ˆ 6:5 Hz, JHH ˆ 1:8 Hz,
3
3
4
1H); 6.42 0ddq, JHH ˆ 15:7 Hz, JHH ˆ 4:4 Hz, JHF
ˆ
2:2 Hz, 1H) ppm. 19F NMR d: 64.6 0dt, JHF ˆ 6:5 Hz,
3
4JHF and 5JHF ˆ ca: 2 Hz, CF3) ppm. MS 0EI, 70 eV)): m/z
‡
‡
‡
‡
0rel. int., ion): 139 [2, 0M À H) ]; 125 [78, 0M À CH3) ];
int., ion): 125 [37, 0M ‡ H) ]; 124 0100, M ); 123 [77,
‡
‡
‡ ‡ ‡
120 [5, 0M À HF) ]; 105 [10, ꢀM À CH3±HF) ]; 91 012); 77
0M À H) ]; 96 [56, 0M À CO) ]; 95 [83, 0M À CHO) ]; 77

232
H. Plenkiewicz et al. / Journal of Fluorine Chemistry 111 +2001) 227±232
‡
‡
043, C3H3F2 ); 69 081, CF3 ). IR 0neat): n 0cmÀ1): 1710.5
0vs, C=O); 1667.4 0m, C=C). HRMS: M 124.01411,
Calculated for C4H3F3O: 124.01356.
References
‡
[1] J.T. Welch, S. Eswarakshnan, Fluorine in Bioorganic Chemistry,
Wiley, New York, 1991, p. 41, 98.
[2] H. Molines, C. Wakselman, J. Fluorine Chem. 16 01980) 97.
[3] H. Abele, A. Haas, M. Lieb, Z. Zwingenberger, J. Fluorine Chem. 62
01993) 25.
3.1.10. 2,4-Dinitrophenylhydrazone +10)
The hydrazone was prepared as described in Section
3.1.4. from an ether solution of aldehyde 8, yield: 3.95 g
013 mmol, 65%). The mp 208±2108C. Analysis, found: C,
39.2; H, 2.3; N, 18.4; F, 18.6; no Cl found. Calculated
for C10H7F3N4O4 0304.19): C, 39.5; H, 2.3; N, 18.4; F,
18.7%.
[4] I.I. Gerus, M.G. Gorbunowa, V.P. Kukhar, J. Fluorine Chem. 69
01994) 195.
[5] I.I. Gerus, M.G. Gorbunowa, V.P. Kukhar, R. Schmutzler, J. Fluorine
Chem. 90 01998) 1.
[6] H.P. Guan, C.H. Hu, J. Fluorine Chem. 78 01996) 97.
[7] H.G. Bonacorso, A.D. Wastowski, N. Zanatta, M.A.P. Martins, J.A.
Naue, J. Fluorine Chem. 92 01998) 23.
Â
Â
Â
[8] J.P. Begue, D. Bonnet-Delpon, A. Chennoufi, M. Ourevitch, K.S.
Ravikumar, M.H. Rock, J. Fluorine Chem. 107 02001) 275.
[9] H.P. Guan, C.M. Hu, J. Fluorine Chem. 78 01996) 101.
3.1.11. Trans-4,4,4-trifluorocrotonic acid +11)
A solution of aldehyde 9 in diethyl ether, prepared as in
Section 3.1.9. was added portionwise to a pre-cooled to 58C
and stirred solution composed of acetone 0100 ml), water
060 ml), concentrated sulphuric acid 016 ml) and chromium
trioxide 014.5 g, 0.145 mol). An exothermic reaction
occured and a gel-suspension of chromium salts began to
form. The reaction mixture was stirred overnight at ambient
temperature. The upper organic layer was separated, the
bottom layer was extracted with ether 020 ml). The com-
bined ether solutions were vigorously shaken with 20%
aqueous NaOH 02 Â 40 ml) and separated. The alkaline
water solution, after removal of residual solvents on a rotary
evaporator, was cooled to 58C and strongly acidi®ed with
concentrated sulphuric acid and extracted with CCl3F
05 Â 30 ml). The extract was dried over MgSO4 and the
solvent was distilled off. Vacuum distillation of the residue
gave acid 11 as a white crystalline substance 0crystallised
in the condenser) possessing a strong irritating smell.
Yield: 2.5 g 018 mmol, 22.5% related to CF3CHClBr).
The mp 408C, bp 78±808C/37 Torr 0Lit.: 68±698C/20 Torr
[36]. Analysis, found: C, 34.3; H, 2.3; F, 40.7%, Calculated
for C4H3F3O2 0140.06): C, 34.3; H, 2.2; F, 40.7%. 1H NMR
  Â
[10] F. Faigl, T. Devenyi, A. Lauko, L. Toke, Tetrahedron 53 01997) 13001.
È
È È
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2027.
[25] T. Kitazume, N. Ishikawa, J. Fluorine Chem. 29 01985) 431.
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[27] F.H. Wu, W.Y. Huang, Youji Huaxue 17 01997) 106 0in Chinese).
[28] W.Y. Huang, F.H. Wu, Israel J. Chem. 39 01999) 167.
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[33] A.L. Wilds, Org. React. 2 01944) 178.
3
4
d: 6.50 0dq, JHH ˆ 15:8 Hz, JHF ˆ 1:9 Hz, 1H); 6.86
0dq, 3JHH ˆ 15:8 Hz, 3JHF ˆ 6:4 Hz, 1H); 10.72 0s, COOH)
ppm. 19F NMR d: 66.4 0dd, JHF ˆ 6:4 Hz, JHF ˆ 1:9 Hz,
3
4
‡
CF3) ppm. MS 0EI, 70 eV): m/z 0rel. int., ion): 140 [35, M ];
123 [60, 0M À OH) ]; 120 [15, 0M À HF) ]; 95 040,
‡
‡
[34] C.F. De Graauw, J.A. Peters, H.V. Bekkum, J. Huskens, Synthesis
01994) 1007.
‡
‡
‡
C3H2F3 ); 77 040, C3H3F2 ); 76 050, C3H2F2 ); 69
‡
[35] R.G.J. Miller, H. Willis 0Eds.), IRSCOT, Heyden, London,.
[36] E.T. MacBee, O.R. Pierce, D.D. Smith, J. Am. Chem. Soc. 76 01954)
3722.
0100, CF3 ); 45 085, CO2H ). IR 0neat); n 0cmÀ1): ca.
3000 0vs, br, OH); 1717.0 0vs, C=O).
‡