From alkyl halides to alkyltrifluoromethyls using bromine trifluoride

Article abstract of DOI:10.1021/jo026128b

Under the right conditions, bromine trifluoride can be a useful tool for generating new types of reactions and compounds. Thus, tris(methylthio)alkyl derivatives, easily prepared from the corresponding alkyl bromides, were converted to the corresponding RCHBrCF₂SMe or RCHBrCF₃ compounds. The bromine atom, however, could be easily reduced forming eventually R′CF₂SMe or R′CF₃. If desired, the bromine atom can serve as an entry for constructing terminal difluoroolefins.

Full text of DOI:10.1021/jo026128b

F r om Alk yl Ha lid es to Alk yltr iflu or om eth yls Usin g Br om in e
Tr iflu or id e
Aviv Hagooly, Iris Ben-David, and Shlomo Rozen*
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University,
Tel-Aviv 69978, Israel
rozens@post.tau.ac.il
Received J uly 2, 2002
Under the right conditions, bromine trifluoride can be a useful tool for generating new types of
reactions and compounds. Thus, tris(methylthio)alkyl derivatives, easily prepared from the
corresponding alkyl bromides, were converted to the corresponding RCHBrCF2SMe or RCHBrCF3
compounds. The bromine atom, however, could be easily reduced forming eventually R′CF2SMe or
R′CF3. If desired, the bromine atom can serve as an entry for constructing terminal difluoroolefins.
In tr od u ction
anchor to the electrophilic bromine of the BrF3. This
provides an opportunity for the nucleophilic fluorine
atoms in the reagent to react almost exclusively with the
relatively electron depleted nearby carbon atom bonded
to the heteroatom(s). In this paper, we concentrate on
the sulfur atom as such an anchor. Tris(methylthio)-
methyl derivatives are easily made by reacting tris-
(methylthio)methane (1) with alkyl bromides under basic
conditions. The conversion of this sulfur-containing moi-
ety to the CF3 group is the subject of this study.10
The introduction of the trifluoromethyl group in or-
ganic substrates and its profound influence on biologically
active molecules are often associated with its ability to
increase the lipophilicity of the whole compound. Its high
electronegativity, relative small size, and the extra
stability it offers have contributed to its ever-rising
popularity. Several new and exciting methods for the
incorporation of this moiety have been described in the
past decade, especially the use of trimethyl(trifluorom-
ethyl)silane (Me3SiCF3). No wonder that several excellent
reviews have appeared lately summarizing these meth-
ods.1 We describe here a novel approach for the introduc-
tion of this group starting from readily accessible alkyl
halides and bromine trifluoride.
Although BrF3 has been used for the preparation of
modern anesthetics such as desflurane2 and sevoflurane,3
it is still rarely mentioned in other fields of chemistry.
In the past few years, however, we have started to unveil
its synthetic potential for bromination of deactivated
aromatic rings,4 transforming carbonyls to the CF2 group5
and nitriles to the corresponding CF3 group,6 oxidizing
alcohols to acyl fluorides,7 constructing trifluoromethyl
ethers,8 and more.9
Resu lts a n d Discu ssion
Reacting tris(methylthio)undecane (2), made from
bromodecane (3), with 3-fold excess of BrF3 resulted in
the 1-methylthio-2-bromo-1,1-difluoroundecane (4) in
70% yield, while with 10-fold excess one obtains 2-bromo-
1,1,1-trifluoroundecane (5) in 60% yield. The reaction
conditions are mild and consist of reaction temperatures
of 0 °C and reaction times of a few minutes. It should be
noted that, if desired, the difluorinated products can be
transformed to the trifluoro ones (e.g. 4 to 5) by applying
3 equiv of bromine trifluoride. This provides an indication
that the former are stable intermediates of the reaction
leading to the latter (Scheme 1). In all cases, the bromine
atom could be easily removed either by replacing it with
hydrogen or by elimination reactions (see below). The
reaction between BrF3 and the tris(methylthio) deriva-
tives can be applied to a number of aliphatic chains with
similar results. Thus, heptyl, dodecyl, and cyclohexanem-
ethyl bromides (6, 7, and 8) were all converted in good
yields to the corresponding tris(methylthio) derivatives
(9, 10, and 11) and then, depending on the reaction
conditions, further transformed to the either difluoro
The above transformations have one thing in common.
All substrates have a basic heteroatom serving as an
* Corresponding author. Fax: +972 3 6409293.
(1) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757. (b)
Singh, R. P.; Shreeve, J . M. Tetrahedron 2000, 56, 7613. (c) Lin, P.;
J iang, J . Tetrahedron 2000, 56, 3635.
(2) Rozov, L. A.; Huang, C.; Halpern, D. F.; Vernice, G. G. U. S.
Patent 1994, 5,283,372.
(3) Halpern, D. F.; Robin, M. L. U.S. Patent 4,996,371, 1991.
(4) Rozen, S.; Lerman, O. J . Org. Chem. 1993, 58, 239.
(5) Rozen, S.; Mishani, E.; Bar- Haim, A. J . Org. Chem. 1994, 59,
2918.
(6) Rozen, S.; Rechavi, D.; Hagooly, A. J . Fluorine Chem. 2001, 111,
161.
(7) Rozen, S.; Ben-David, I. J . Fluorine Chem. 1996, 76, 145.
(8) Ben-David, I.; Rechavi, D.; Mishani, E.; Rozen, S. J . Fluorine
Chem. 1999, 97, 75.
(10) Preliminary results have been presented by us at the 13th
European Symposium on Fluorine Chemistry, Bordeaux, France, p A8,
2001. Hiyama had described the fluorination of orthothioesters using
Bu4NH2F3 and 1,3-dibromo-5,5-dimethylhydantoin, resulting in
RCHBrCF2SMe derivatives: Furuta, S.; Kuroboshi, M.; Hiyama, T.
Bull. Chem. Soc. J pn. 1998, 71, 1939.
(9) Rozen, S.; Ben-David, I. J . Org. Chem. 2001, 66, 496.
10.1021/jo026128b CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/06/2002
8430
J . Org. Chem. 2002, 67, 8430-8434

Alkyltrifluoromethyls from Bromine Trifluoride
SCHEME 1
derivatives (12, 13,10 and 14) or the trifluoromethyl ones
(15,11 16, and 17).
yl)ethyl bromide (30). When 31 was reacted with 3 mol
equiv of bromine trifluoride, the expected difluoro sulfide
32 was obtained in 65% yield. Using 10-fold excess,
however, two compounds were formed, both with extra
fluorine atom(s) attached to the adamantane skeleton.
The major one was identified as 3-(3-fluoroadamant-1-
yl)-2-bromo-1,1,1-trifluoropropane (33) accompanied by
15% of 3-(3,5-difluoroadamant-1-yl)-2-bromo-1,1,1-tri-
fluoropropane (34) (Scheme 1).
It was documented that the fluorine atoms in bromine
trifluoride can in certain cases act as electrophiles12 and
substitute tertiary hydrogens similarly to F2.13 It was of
interest to see if the scope of this reaction includes
substrates possessing such tertiary centers. We found out
that the reaction around the sulfur atoms is by far the
dominant one. Thus, no tertiary fluorination was ob-
served with 2-ethylbromohexane (18). The reaction be-
haved as expected, producing the di- or trifluoro deriva-
tives 19 or 20 via the corresponding 3-ethyl-1,1,1-
tris(methylthio)heptane (21). Even when a second more
remote, and therefore more reactive, tertiary center was
present, as in 3,7-dimethyl bromooctane (22), the reaction
proceeded smoothly and only around the methylthio
moiety of 23. As in the previous cases, one was able to
obtain either the difluoro 24 or the trifluoro product 25
by varying the BrF3 excess used. Working with bicyclo
compounds such as 2-norbornaneethyl bromide (26) also
resulted in no surprises. Its tris(methylthio) derivative
27 reacted fast with 3 mol equiv of BrF3 to give 2-bromo-
1,1-difluoro-1-methylthio-3-norbornylpropane (28), while
the reaction with a larger excess of the reagent furnished
the expected 2-bromo-1,1,1-trifluoro-3-norbornylpropane
(29) in 50% yield. The only time we did notice a tertiary
fluorination was in the case of 3-(adamant-1-yl)-1,1,1-
tris(methylthio)propane (31) made from 2-(adamant-1-
The mechanism of the reaction seems to be of ionic
nature, since adding radical scavengers such as dinitro-
benzene or oxygen did not change its outcome. We have
noticed that the hydrogen atoms R to the tris(methylthio)-
methyl moiety are labile and can be eliminated on
heating along with one thiomethyl group, as exemplified
by 2, which was converted to 1,1-dimethylthioundec-1-
ene (35). This compound was reacted with BrF3 to
produce again the difluoro derivative 4, but unlike the
reaction with 2, it required less than 2 equiv of BrF3 for
completion. This indicates that at least 1 mol equiv of
the reagent is needed for the first step of the reaction,
which we believe forms the corresponding olefin. Since
the hydrogen atoms R to the tris(methylthio)methyl
group are somewhat acidic, they are capable of forming
a strong hydrogen bond with the fluoride, followed by an
eventual elimination of the elements of methanthiol.
Consequently, bromine fluoride, always found in BrF3 (a
well known equilibrium reaction), can add itself across
the resulting π center. A somewhat indirect evidence to
the formation of this adduct was found in the reaction of
21 when not enough BrF3 was employed. In this case,
an elimination of HF took place, producing the bromo
(11) Fuchigami, T.; Hagiwara, T. J apanese Patent 10,287,596, 1998
(Chem. Abstr. 1998, 129, 343269z).
(12) Boguslavskaya, L. S.; Kartashov, A. V.; Chuvatkin, N. N. Zh.
Org Khim. (Eng. Transl.) 1989, 25, 1835.
(13) Rozen, S.; Gal, C. J . Org. Chem. 1987, 52, 2769 and 4928.
J . Org. Chem, Vol. 67, No. 24, 2002 8431

Hagooly et al.
SCHEME 2
SCHEME 3
chemistry. About 20 years ago, F2 was also considered
as a reagent to avoid in organic chemistry, and today
numerous laboratories use it routinely. We believe that
BrF3 will find its right place in the arsenal of reagents
for synthetic purposes. Its present use for converting
alkyl halides into trifluoromethyl derivatives is one more
step toward this goal.
olefin 36, which was isolated and characterized. Under
the standard conditions (3-fold excess of BrF3), however,
the reagent is attracted by the sulfur atoms, resulting
eventually in the displacement of the methylthio group
by fluorides (Scheme 2).14
The bromine atom invariably found in the R position
to either difluoromethyl sulfide or the CF3 group can be
replaced with a hydrogen atom by treating these com-
pounds with NaBH4. The reduction proceeds with 70-
75% yield and does not affect the sulfide moiety when
present. A few examples are outlined in Scheme 3,
producing the bromine-free derivatives (37-43).
An elimination of [BrF] elements could also be achieved
by treating the bromine-containing derivatives with Mg
and 1,2-dibromoethane.15 Thus, for example, 2-bromo-
1,1,1-trifluoroundecane (5) was converted to 1,1-difluoro-
undeca-1-ene (44)16 in 80% yield, providing a new method
for the construction of the important terminal difluoro-
olefins17 (Scheme 3).
We have also tried to reduce the sulfide group in order
to obtain the desirable difluoromethyl moiety. However,
using various conditions based on reactions with Bu3SnH
and Ra/Ni resulted in poor yields of about 10-15%, and
we did not continue to pursue this line of research for
the construction of this group.
Exp er im en ta l Section
1H NMR spectra were recorded using a 200 MHz machine
with CDCl3 as a solvent and Me4Si as an internal standard.
Only the relevant and characteristic peaks are reported. The
19F NMR spectra were measured at 188.1 MHz and are
reported in parts per million upfield from CFCl3 serving as
an internal standard. The proton broad-band decoupled 13C
NMR spectra were recorded at 50.2 MHz. Here too, CDCl3
served as a solvent with TMS as an internal standard. MS
and GC-MS spectra were usually measured under CI condi-
tions. In extreme cases where the CI method could not detect
the molecular ion, we have successfully used the Amirav’s
supersonic GC-MS developed in our department. The main
feature of this method is to provide electron ionization while
the sample is vibrationally cooled in a supersonic molecular
beam. This considerably enhances the relative abundance of
the molecular ions.18 The spectral properties of all products
presented in this work are in excellent agreement with their
structure, and where relevant, also with the ones described
in the literature.
The term “worked up as usual” means termination by
adding water to the reaction mixture, separation of layers,
extraction of the the aqueous layer three times with ether, and
drying of the combine organic layers over MgSO4. Evaporation
of the solvent followed by purification by column chromatog-
raphy (Merck silica gel 60H), with petroleum ether and ethyl
acetate serving as an eluent, completes the procedure.
P r ep a r a tion a n d Ha n d lin g Br F 3. Although commercially
available, we prepare our own BrF3 by simply passing 0.58
mol of pure fluorine through 0.2 mol of bromine placed in a
copper reactor cooled to 0 ( 10 °C. At that temperature, the
higher oxidation statesBrF5swill not form in any appreciable
In conclusion, we hope that this work will encourage
chemists to think positively about BrF3 and not dismiss
it as an uncontrollable reagent unsuitable for organic
(14) One of the referees pointed that on one hand 3 mol equiv of
BrF3 were used for obtaining the CF2SMe group and three more for
converting it to the CF3 one. On the other hand, 10 mol equiv were
reacted with the starting alkyl bromide for that purpose. We do not
have a definite answer for this apparent contradiction, and probably
the reason is that in the two-steps reaction, work was conducted with
relatively pure CF2SMe derivatives, while in the one-step reaction,
some BrF3 was probably wasted on reactions with the resulting initial
tars.
(15) Gilman, H.; J ones, R. G. J . Am. Chem. Soc. 1943, 65, 2037.
(16) Clinton, J . P. U.S. patent 4,876,285, 1989 (Chem. Abstr. 1990,
112, 178057t).
(18) (a) Dagan, S.; Amirav, A. J . Am. Soc. Mass. Spectrom. 1995, 6,
120. (b) Amirav, A.; Gordin, A.; Tzanani, N. Rapid Commun. Mass
Spectrom. 2001, 15, 811.
(17) Kim, K, I.; McCarthy, J . R. Tetrahedron Lett. 1996, 37, 3223.
8432 J . Org. Chem., Vol. 67, No. 24, 2002

Alkyltrifluoromethyls from Bromine Trifluoride
amount,19 although, we always use a small excess of bromine,
thereby keeping the reagent from disproportionating to BrF5.
This is also responsible for the reddish coloration of the
reagent. It can be stored in Teflon containers indefinitely.
CAUTION: BrF3 is a strong oxidizer and tends to react very
exothermically with water and oxygenated organic solvents.
The work with it should be conducted in a well-ventilated area
and caution and common sense should be exercised.
Gen er a l P r oced u r e for P r ep a r in g th e Tr is(m eth yl-
th io) Der iva tives. To a cold (-78 °C) THF solution of 1.8
mL (13.6 mmol) of tris(methylthio)methane (1) was added 8.9
mL (14.24 mmol) of BuLi under nitrogen. After stirring for 2
h at this temperature, 12 mmol of neat alkyl bromide was
added, the reaction was left for additional 2 h at -78 °C, and
the mixture stirred for another hour at room temperature. The
usual workup provides the corresponding tris(methylthio)
derivatives pure enough for the next step. No attempts were
made to obtain analytically pure samples of these materials.
Gen er a l P r oced u r e for th e Rea ction of Tr is(m eth -
ylth io) Der iva tives w ith Br F 3. The tris(methylthio) deri-
vates (1 mmol) were dissolved in 10-15 mL of dry CFCl3 and
cooled to 0 °C. About 3 mmol (for the difluoromethylmethyl
sulfide products) or 10 mmols (for the trifluoromethyl com-
pounds) of BrF3 was dissolved in 10-15 mL of the same
solvent, cooled to 0 °C, and added dropwise to the tris-
(methylthio) solution, at the same temperature, over a period
of up to 3 min. The reaction mixture was then washed with
aqueous Na2SO3 till colorless and worked up as usual. The
same procedure applied when the difluoromethyl methyl
sulfide compounds (1 mmol) were reacted with 3 mmol of BrF3,
converting them to the corresponding trifluoromethyl deriva-
tives.
124.1 (q, J ) 277 Hz), 47.7 (q, J ) 32 Hz), 35.8, 32.6, 28.2,
27.3, 22.5, 14.0 ppm; 19F NMR -72.81 ppm (d, J ) 7 Hz).
1,1,1-Tr is(m eth ylth io)tr id eca n e (10) was prepared from
1-bromododecane (7) in 85% yield: oil; 1H NMR 2.10 (9 H, s),
1.91-1.83 ppm (2 H, m); 13C NMR 70.9, 43.9, 38.2, 31.9, 29.4,
29.3, 28.9, 25.6, 24.8, 22.6, 14.0, 13.0, 11.4 ppm.
2-Br om o-1,1-d iflu or o-1-m eth ylth iotr id eca n e (13)10 was
1
prepared from 10 in 70% yield: oil; H NMR 4.20-4.05 (1 H,
m), 2.34 ppm (3 H, s); 13C NMR 129.0 (t, J ) 279 Hz), 54.5 (t,
J ) 26 Hz), 32.8, 31.9, 29.6, 29.3, 29.1, 28.7, 27.2, 23.9, 22.7,
14.0, 10.4 ppm; 19F NMR -78.48 (1 F, dd, J 1 ) 204 Hz, J 2
)
8 Hz), -80.60 ppm (1 F, dd, J 1 ) 204 Hz, J 2 ) 11 Hz); MS m/z
345 and 347, both (M + 1)+. Anal. Calcd for C14H27BrF2S: C,
48.69; H, 7.88; Br, 23.14. Found: C, 48.59; H, 7.59; Br, 22.83.
2-Br om o-1,1,1-tr iflu or otr id eca n e (16) was prepared from
10 in 45% yield: oil; 1H NMR 4.14-4.00 ppm (1 H, m); 13C
NMR 124.0 (q, J ) 276 Hz), 47.9 (q, J ) 30 Hz), 32.5, 31.7,
31.5, 30.0, 29.5, 29.1, 28.9, 28.5, 22.6, 14.1 ppm; 19F NMR
-72.8 ppm (d, J ) 7 Hz). Anal. Calcd for C13H24BrF3: C, 49.22;
H, 7.63. Found: C, 49.51; H, 7.33.
1,1,1-(Tr ism eth ylth io)m eth ylcycloh exa n e (11) was pre-
pared from bromomethylcyclohexane (8) in 60% yield: oil; 1H
NMR 2.11 ppm (9 H, s); 13C NMR 71.1, 45.2, 35.2, 34.7, 32.8,
26.4, 13.3 ppm.
2-B r o m o -2-c y c lo h e x y l-1,1-d iflu o r o -1-m e t h y lt h io -
eth a n e (14) was prepared from 11 in 65% yield: oil; 1H NMR
4.20-4.00 (1 H, m), 2.35 ppm (3 H, s); 13C NMR 128.8 (t, J )
276 Hz), 61.5 (t, J ) 24 Hz), 32.1, 28.3, 26.2, 25.8, 10.6 ppm;
19F NMR -73.3 (1 F, dd, J 1 ) 204 Hz, J 2 ) 9 Hz), -76.72 ppm
(1 F, dd, J 1 ) 204 Hz, J 2 ) 14 Hz); MS m/z 273 and 275, both
(M + 1)+. Anal. Calcd for C9H15BrF2S: C, 39.57; H, 5.53.
Found: C, 39.31; H, 5.47.
Red u ction of th e Br om in e Atom . To 1 mmol of the bromo
compound (di- or trifluorinated) was added 6 mmol of NaBH4
dissolved in 15 mL of DMSO. The reaction mixture was stirred
at 110 °C for 1-2 h. It was then acidified with aqueous HCl
and worked up as usual.
1,1,1-Tr is(m eth ylth io)u n d eca n e (2) was prepared from
1-bromodecane (3) as described above in 85% yield: oil, 1H
NMR 2.10 (9 H, s), 1.91-1.83 ppm (2 H, m); 13C NMR 70.8,
37.9, 29.4, 29.2, 24.6, 22.5, 13.9, 12.9 ppm.
2-Br om o-1,1-d iflu or o-1-m eth ylth iou n d eca n e (4) was
prepared from 2 as described above in 70% yield: oil; 1H NMR
4.20-4.05 (1 H, m), 2.34 ppm (3 H, s); 13C NMR 129.3 (t, J )
278 Hz), 54.3 (t, J ) 26 Hz), 31.9, 31.6, 29.4, 29.2, 28.5, 22.5,
14.0, 10.1 ppm; 19F NMR -83.4 (1 F, dd, J 1 ) 204 Hz, J 2 ) 9
Hz), -85.6 ppm (1 F, dd, J 1 ) 204 Hz, J 2 ) 11 Hz); MS m/z
316 and 318, both (M + 1)+. Anal. Calcd for C12H23BrF2S: C,
45.43; H, 7.31; Br, 25.18. Found: C, 45.61; H, 6.97; Br, 25.40.
2-Br om o-2-cycloh exyl-1,1,1-tr iflu or oeth a n e (17) was
1
prepared from 11 in 50% yield: oil; H NMR 4.12-4.00 ppm
(1 H, m); 13C NMR 124.1 (q, J ) 277 Hz), 54.5 (q, J ) 30 Hz),
38.7, 31.2, 28.3, 26.6 ppm; 19F NMR -68.13 ppm (d, J ) 8
Hz). Anal. Calcd for C8H12BrF3: C, 39.21; H, 4.94; Br, 32.60.
Found: C, 39.23; H, 4.82; Br, 33.12.
3-Eth yl-1,1,1-tr is(m eth ylth io)h ep ta n e (21) was prepared
from 2-ethylhexyl bromide (18) in 50% yield: oil; 1H NMR 2.12
ppm (9 H, s); 13C NMR 71.4, 42.5, 35.7, 33.7, 28.6, 26.9, 23.1,
14.1, 13.4, 10.5 ppm.
2-Br om o-3-eth yl-1,1-d iflu or o-1-m eth ylth ioh ep ta n e (19)
was prepared from 21 (a mixture of two diastereoisomers) in
1
75% yield: oil; H NMR (for the two diastereoisomers) 4.35-
4.15 (1 H, m), 2.35 ppm (3 H, s); 13C NMR (for the two
diastereoisomers) 128.9 (t, J ) 279 Hz), 58.8 (q, J ) 24 Hz),
41.5 and 41.4, 30.9 and 30.5, 29.5 and 29.2, 25.0 and 23.7, 22.8
and 22.5, 14.0, 11.7 and 11.6, 10.5 ppm; 19F NMR (for the two
diastereoisomers) -73.05 and -73.15 (both 1 F, dd, J 1 ) 204
Hz, J 2 ) 14 Hz), -68.33 ppm (1 F, dd, J 1 ) 204 Hz, J 2 ) 8
Hz); MS m/z 289 and 291, both (M + 1)+. Anal. Calcd for
2-Br om o-1,1,1-tr iflu or ou n d eca n e (5) was prepared from
2 in 60% yield: oil; 1H NMR 4.12-4.00 ppm (1 H, m); 13C NMR
124.1 (q, J ) 275 Hz), 47.7 (q, J ) 30 Hz), 31.6, 31.4, 29.5,
29.3, 28.6, 22.7, 14.1 ppm; 19F NMR -72.6 ppm (d, J ) 7 Hz);
C
10H19BrF2S: C, 41.53; H, 6.62; Br, 27.63. Found: C, 41.34;
H, 6.59; Br, 27.77.
MS m/z 287 and 289, both (M - 1)+. Anal. Calcd for C11H20
BrF3: C, 45.69; H, 6.97. Found: C, 45.39; H, 6.71.
-
2-Br om o-3-eth yl-1,1,1-tr iflu or oh ep ta n e (20) was pre-
pared from 21 in 45% yield: oil; 1H NMR (for the two
diastereoisomers) 4.26-4.00 ppm (1 H, m); 13C NMR (for the
two diastereoisomers) 124.4 (q, J ) 275 Hz), 51.7 (m), 40.5,
30.6 and 30.2, 29.4 and 29.2, 24.5 and 23.6, 22.8 and 22.6, 13.9,
11.6 ppm; 19F NMR -68.2 ppm (m); MS m/z 259 and 261, both
(M - 1)+.
4,8-Dim eth yl-1,1,1-tr is(m eth ylth io)n on an e (23) was pre-
pared from 1-bromo-3,7-dimethyloctane (22) in 80% yield: oil;
1H NMR 2.09 ppm (9 H, s); 13C NMR 70.9, 38.9, 36.8, 35.1,
32.4, 31.4, 27.6, 24.5, 22.4, 22.3, 19.5, 12.7 ppm.
2-B r o m o -1,1-d iflu o r o -4,8-d im e t h y l-1-m e t h y lt h io -
n on a n e (24) was prepared from 23 in 70% yield: oil; 1H NMR
(for the two diastereoisomers) 4.31-4.11 (1 H, m), 2.33 ppm
(3 H, s); 13C NMR (for the two diastereoisomers) 128.8 (t, J )
279 Hz), 52.5 (q, J ) 24 Hz), 39.8 and 39.3, 38.8 and 37.3,
34.2, 30.1 and 30.0, 27.6, 24.3 and 23.6, 22.3, 22.2, 19.9, 17.7
ppm; 19F NMR (for the two diastereoisomers) -81.09 and
1,1,1-Tr is(m eth ylth io)octa n e (9) was prepared from 1-
bromoheptane (6) in 85% yield: oil; 1H NMR 2.10 (9 H, s),
1.91-1.83 ppm (2 H, m); 13C NMR 70.9, 38.1, 31.6, 29.4, 29.1,
24.7, 22.5, 13.9, 12.9 ppm.
2-Br om o-1,1-d iflu or o-1-m eth ylth ioocta n e (12) was pre-
1
pared from 9 in 75% yield: oil; H NMR 4.20-4.05 (1 H, m),
2.34 ppm (3 H, s); 13C NMR 129.0 (t, J ) 278 Hz), 54.5 (t, J )
26 Hz), 32.9, 31.5, 28.3, 27.2, 22.5, 14.0, 10.5 ppm; 19F NMR
-78.17 (1 F, dd, J 1 ) 204 Hz, J 2 ) 8 Hz), -80.57 ppm (1 F,
dd, J 1 ) 204 Hz, J 2 ) 11 Hz); MS m/z 275 and 277, both (M +
1)+. Anal. Calcd for C9H17BrF2S: C, 39.28; H, 6.23; Br, 29.04.
Found: C, 39.98; H, 6.02; Br, 29.16.
2-Br om o-1,1,1-tr iflu or oocta n e (15)11 was prepared from
9 in 50% yield: oil; 1H NMR 4.10-4.00 ppm (1 H, m); 13C NMR
(19) Stein, L. J . Am. Chem. Soc. 1959, 81, 1269.
J . Org. Chem, Vol. 67, No. 24, 2002 8433

Hagooly et al.
-80.90 (both 1 F, dd, J 1 ) 214 Hz, J 2 ) 12 Hz), -78.35 ppm
(1 F, wide d, J 1 ) 214 Hz). Anal. Calcd for C12H23BrF2S: C,
45.43; H, 7.31; Br, 25.18; S, 10.10. Found: C, 44.82; H, 7.21;
Br, 25.23; S, 10.25.
2-Br om o-1,1,1-tr iflu or o-4,8-d im eth yln on a n e (25) was
prepared from 23 in 45% yield: oil; 1H NMR (for the two
diastereoisomers) 4.25-4.00 ppm (1 H, m); 13C NMR (for the
two diastereoisomers) 124.1 (q, J ) 275 Hz), 45.9 (m), 38.9
and 38.6, 37.9 and 37.4, 34.5, 29.9 and 27.8, 24.4 and 23.9,
22.5, 22.3, 19.7, 17.8 ppm; 19F NMR (for the two diastereo-
isomers) -72.07 and -72.91 ppm (both d, J ) 7 Hz). Anal.
Calcd for C11H20BrF3: C, 45.69; H, 6.97; Br, 27.63. Found: C,
45.87; H, 6.85; Br, 27.51.
(3 H, s), 2.20-1.96 ppm (2 H, m); 13C NMR 130.8 (t, J ) 274
Hz), 38.9 (t, J ) 23 Hz), 31.9, 29.6, 29.5, 29.4, 29.3, 29.1, 23.2,
22.6, 14.0, 10.1 ppm; 19F NMR -76.74 (t, J ) 15 Hz). Anal.
Calcd for C12H24F2S: C, 60.46; H, 10.15. Found: C, 60.31; H,
10.20.
1,1,1-Tr iflu or ou n d eca n e (38)20 was obtained in 70% yield
1
by reducing 5 as described above: oil; H NMR 2.06-2.02 (2
H, m), 1.56-1.51 ppm (2 H, m); 13C NMR 127.3 (q, J ) 275
Hz), 33.8 (q, J ) 29 Hz), 31.9, 29.6, 29.5, 29.4, 29.3, 28.8, 22.7,
21.9, 14.0 ppm; 19F NMR -66.93 ppm (t, J ) 11 Hz). Anal.
Calcd for C11H21F3: C, 62.83; H, 10.07. Found: C, 62.85; H,
9.77.
1,1-Diflu or o-4,8-d im eth yl-1-m eth ylth ion on a n e (39) was
obtained in 75% yield by reducing 24 as described above: oil;
1H NMR 2.28 (3 H, s); 13C NMR 130.9 (t, J ) 273 Hz), 39.1,
36.7, 36.5 (t, J ) 23 Hz), 32.2, 29.8, 27.8, 24.5, 22.6, 22.5, 19.2,
9.8 ppm; 19F NMR -76.90 (t, J ) 15 Hz). Anal. Calcd for
3-Nor bor n a n e-1,1,1-tr is(m eth ylth io)p r op a n e (27) was
prepared from 2-norbornaneethyl bromide (26) in 70% yield:
1
oil; H NMR 2.11 ppm (9 H, s); 13C NMR 70.1, 12.9 ppm.
2-Br om o-1,1-d iflu or o-1-m et h ylt h io-3-n or b or n ylp r o-
1
p a n e (28) was prepared from 27 in 70% yield: oil; H NMR
C
12H24F2S: C, 60.46; H, 10.15. Found: C, 60.46; H, 9.94.
(for the two diastereoisomers) 4.27-4.07 (1 H, m), 2.34 ppm
(3 H, s); 13C NMR (for the two diastereoisomers) 128.85 and
128.83 (both t, J ) 280 Hz), 53.3 and 52.5 (both t, J ) 27 Hz),
41.7 and 40.7, 39.3 and 39.2, 39.0 and 38.0, 36.6 and 36.4, 36.1
and 35.6, 35.0 and 34.5, 29.7 and 29.4, 28.4 and 28.2, 10.2 ppm;
1,1,1-Tr iflu or o-4,8-d im eth yln on a n e (40) was obtained in
70% yield by reducing 25 as described above: oil; 1H NMR
2.20-1.80 ppm (2 H, m); 13C NMR 127.4 (q, J ) 274 Hz), 39.1,
36.0, 31.9, 31.4 (q, J ) 28 Hz), 28.5, 27.8, 24.5, 22.5, 22.4, 19.1
ppm; 19F NMR -66.93 ppm (t, J ) 11 Hz). Anal. Calcd for
19F NMR (for the two diastereoisomers) -80.72 (1 F, dd, J 1
)
204 Hz, J 2 ) 11 Hz), -78.53 and -78.42 ppm (both 1 F, dd, J 1
) 204 Hz, J 2 ) 8 Hz). Anal. Calcd for C11H17BrF2S: C, 44.16;
H, 5.73; Br, 26.70. Found: C, 44.60; H, 5.65; Br, 25.92.
2-Br om o-1,1,1-tr iflu or o-3-n or bor n ylp r op a n e (29) was
prepared from 27 in 50% yield: oil; 1H NMR (for the two
diastereoisomers) 4.18-3.98 ppm (1 H, m); 13C NMR (for the
two diastereoisomers) 123.89 and 123.87 (both q, J ) 270 Hz),
46.8 and 46.5 (both q, J ) 32 Hz), 41.5 and 39.1, 38.9 and
38.8, 37.8 and 37.7, 37.6 and 36.5, 36.3 and 36.1, 35.6 and 35.0,
29.7 and 29.4, 28.3 and 28.1 ppm; 19F NMR (for the two
diastereoisomers) -72.83 and -72.73 ppm (both d, J ) 7 Hz).
Anal. Calcd for C10H14BrF3: C, 44.30; H, 5.20; Br, 29.47.
Found: C, 44.20; H, 5.23; Br, 29.05.
C
11H21F3: C, 62.83; H, 10.07. Found: C, 61.90; H, 9.77.
1,1,1-Tr iflu or o-3-n or bor n a n ep r op a n e (41) was obtained
in 75% yield by reducing 29 as described above: oil; 13C NMR
129.2 (q, J ) 275 Hz), 43.3, 42.8, 39.8, 38.4, 37.1, 34.2 (q, J )
28 Hz), 31.9, 30.5 ppm; 19F NMR -66.83 ppm (t, J ) 12 Hz);
MS (super sonic molecular beam)18 m/z 192 (M)+.
3-(3-F lu or oa d a m a n t-1-yl)-1,1,1-tr iflu or op r op a n e (42)
a n d 3-(3,5-d iflu or oa d a m a n t-1-yl)-1,1,1-tr iflu or op r op a n e
(43) were obtained in combined yield of 75% by reducing the
mixture of 33 and 34 as described above. Compound 42 was
identified by HRMS calcd for C13H18F4 249.1272 (M)+, found
249.1266. Compound 43 was identified by GC-MS (EI mode)
m/z 249 (M - 19)+ and 171 (AdF2)+. 13C NMR (for 42 and 43)
127.3 (q, J ) 274 Hz), and 127.0 (q, J ) 274 Hz), 27.9 (q, J )
28 Hz), 27.6 (q, J ) 28 Hz), (for 42) 92.5 (d, J ) 183 Hz), 46.5
(d, J ) 17 Hz), 41.8 (d, J ) 17 Hz), 36.0 (d, J ) 10 Hz), 30.8
ppm (d, J ) 10 Hz), (for 43) 92.7 (dd, J 1 ) 187 Hz, J 2 ) 14
Hz), 47.2 (t, J ) 19 Hz), 37.3 (t, J ) 10 Hz), 30.2 ppm (t, J )
10 Hz); 19F NMR (for 42) -66.96 (t, J ) 10 Hz), -132.0 ppm
(m), (for 43) -63.93 (t, J ) 10 Hz), -137.1 ppm (m).
3-(Adam an t-1-yl)-1,1,1-tr is(m eth ylth io)pr opan e (31) was
prepared from 2-(adamant-1-yl)-ethylbromide (30) in 45%
yield: mp 96 °C (from methanol); 1H NMR 2.09 ppm (9 H, s);
13C NMR 71.5, 42.4, 38.7, 37.1, 31.9, 30.5, 28.6, 12.9 ppm.
3-(Ad a m a n t -1-yl)-2-b r om o-1,1-d iflu or o-1-m et h ylt h io-
p r op a n e (32) was prepared from 31 in 65% yield: mp 48 °C
1
(from methanol); H NMR 4.25-4.05 (1 H, m), 2.36 (3 H, s),
2.08 (1 H, dd, J 1 ) 16 Hz, J 2 ) 1 Hz), 1.89 ppm (1 H, dd, J 1
)
16 Hz, J 2 ) 8 Hz); 13C NMR 129.3 (t, J ) 280 Hz), 47.42, 47.1
P r ep a r a tion of 1,1-d iflu or ou n d eca -1-en e (44)16 was
obtained by adding a dry THF solution of 1.3 g (4.5 mmol) of
2-bromo-1,1,1,-trifluoroundecane (5) to 1 g of Mg, activated
with 1,2-dibromoethane in 10 mL of the same solvent, during
a period of 10 min, after which the reaction was refluxed for
an additional hour. The reaction was cooled to room temper-
ature, dilute HCl was added, and the reaction mixture was
worked up as usual: yield 80%; oil; 1H NMR 4.13 (1 H, dtd, J 1
) 25 Hz, J 2 ) 8 Hz, J 3 ) 3 Hz), 2.34-1.90 ppm (4 H, m); 13C
NMR 156.1 (t, J ) 285 Hz), 78.0 (t, J ) 21 Hz), 31.8, 29.6,
29.5, 29.3, 29.2, 28.8, 22.6, 22.1, 14.0 ppm; 19F NMR -90.2 (1
(t, J ) 26 Hz), 42.1, 36.5, 32.5, 28.2, 10.3 ppm; 19F NMR -79.62
(1 F, dd, J 1 ) 202 Hz, J 2 ) 8 Hz), -81.33 ppm (1 F, dd, J 1
)
202 Hz, J 2 ) 12 Hz). Anal. Calcd for C14H21BrF2S: C, 49.56;
H, 6.24. Found: C, 50.04; H, 6.32.
3-(3-F lu or oa d a m a n t -1-yl)-2-b r om o-1,1,1-t r iflu or op r o-
pan e (33) an d 3-(3,5-diflu or oadam an t-1-yl)-2-br om o-1,1,1-
tr iflu or op r op a n e (34) were obtained from 31 as a mixture
(35% by GC for 33 and 15% by GC for 34). The MS (EI) for 33
showed m/z 311, 309, both (M - 19)+, while 34 showed (M -
19)+ peaks at m/z 329, 327. 1H NMR (for 33 and 34) 4.16-
4.05 (1 H, m); 13C NMR (for 33 and 34, respectively) 124.0 and
123.8 (both q, J ) 277 Hz), 93.0 (m) and 91.2 (m) ppm; 19F
NMR (for 33 and 34, respectively) -73.50 and -73.60 (both
d, J ) 7 Hz), -132.2 and -137.3 ppm.
1,1-Dim eth ylth iou n d ec-1-en e (35) was obtained in 90%
yield by heating neat 1,1,1-Tris(methylthio)undecane (2) to 100
°C for 2 h: oil; 1H NMR 5.90 (1 H, t, J ) 7 Hz), 2.30 (2 H, m),
2.27 (3 H, s), 2.25 (3 H, s).
2-Br om o-1,1-d im eth ylth io-3-eth ylh ep t-1-en e (36) was
isolated in higher than 40% yield when 21 was reacted with
less than 2 mol equiv of BrF3: oil; 1H NMR 3.47 (1 H, m), 2.39
(3 H, s), 2.26 ppm (3 H, s); 13C NMR 139.5, 132.6, 48, 34.2,
29.3, 27.5, 22.6, 18.5, 16.9, 13.9, 11.7 ppm; MS (EI) m/z 296,
298, both (M)+.
F, wide d, J ) 49 Hz), -92.5 ppm (1 F, ddt, J 1 ) 49 Hz, J 2
)
25 Hz, J 3 ) 2 Hz); For MS, the usual methods such as EI and
CI found on commercial instruments fail to show any molec-
ular ion peak. However, using Amirav’s method provided the
answer and indeed a strong molecular ion peak for 44 at m/z
) 190 (M)+ was observed.18
Ack n ow led gm en t. This research was supported by
the USA-Israel Binational Science Foundation (BSF),
J erusalem, Israel.
J O026128B
1,1-Diflu or o-1-m eth ylth iou n d eca n e (37) was obtained in
(20) Kobayashi, Y.; Yamamoto, K.; Kumadaki, I. Tetrahedron Lett.
1979, 4071.
70% yield by reducing 4 as described above: oil; 1H NMR 2.28
8434 J . Org. Chem., Vol. 67, No. 24, 2002