Toward the synthesis of the rare N-(trifluoromethyl)amides and the N-(difluoromethylene)-N-(trifluoromethyl)amines [RN(CF3)CF 2R′] using BrF3

Article abstract of DOI:10.1021/jo901560b

(Chemical Equation Presented) A synthesis of a wide range of different aliphatic, aromatic, and heterocyclic N-(trifluoromethyl)-amides along with aromatic N-(difluoromethylene)-N-(trifluoromethyl)amine derivatives has been developed. The starting materia

Full text of DOI:10.1021/jo901560b

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Toward the Synthesis of the Rare N-(Trifluoromethyl)amides and the
N-(Difluoromethylene)-N-(trifluoromethyl)amines [RN(CF3)CF2R0]
Using BrF3
Youlia Hagooly,† Julia Gatenyo,† Aviv Hagooly,‡,§ and Shlomo Rozen*,†
‡
†School of Chemistry, Tel-Aviv University, Tel-Aviv 69978, Israel, and Department of Radiology,
Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110.
§
Present address: Radiochemistry, Hadassah Hospital, School of Medicine, Hebrew University,
Jerusalem 91120, Israel
rozens@post.tau.ac.il
Received July 19, 2009
A synthesis of a wide range of different aliphatic, aromatic, and heterocyclic N-(trifluoromethyl)-
amides along with aromatic N-(difluoromethylene)-N-(trifluoromethyl)amine derivatives has been
developed. The starting materials are the easily available isothiocyanates, and the fluorinating
reagent is the commercially available bromine trifluoride. The reaction is performed under mild
conditions, and the fluorinated amides and amines are produced in moderate to high yields.
Introduction
Only a few tailor-made syntheses are reported for their
preparation, and they are centered around the reaction of
perfluoro N-alkylamines with oleum,5 on attaching the
F2CdNCF3 group to different acids,2,6 and the electro-
chemical fluorination of N,N-dimethylperfluoroacryla-
mides.7 We report here a general and facile route for
the preparation of N-(trifluoromethyl)amides based on
the use of BrF3 along with an option of constructing
the corresponding unknown pentafluoroamines (mainly
for aromatic derivatives) by changing the reaction condi-
tions.
Although commercial, bromine trifluoride is not a com-
mon reagent in every organic laboratory, and many chemists
do not feel at ease with it because of its high reactivity.
However, under the right conditions, it can be used as a
fluorinating agent for various heteroatoms,8 for forming
Fluoro-organic compounds, whose chemistry is being
continuously developed at an unparallel rapid pace, have
an important role in our daily life. Among the major
players on this subject are the trifluoromethyl (CF3) and
the difluoromethylene (CF2) groups. These moieties influ-
ence significantly the physiological, physical, and chemi-
cal properties of numerous compounds used, among
others, in material sciences and medicinal and agricultural
chemistry.1 Yet, N-(trifluoromethyl)amide derivatives are
rare despite the fact that some of them have high anti-
fungal properties,2 show potential activity for HIV ther-
apy,3 and are useful electrolyte additives for batteries.4
(1) (a) Leroux, F.; Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827–
856. (b) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881–1886.
(c) Kirsch, P. In Modern Fluoroorganic Chemistry; Wiley-VCH: Weinheim,
2004. (d) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214–231.
(2) Vuettner, G.; Klauke, E.; Oehlmann, L.; Kaspers, H. Fungicidal
3-(trifluoromethyl)benzopyrimidine-2,4-diones and similar compounds.
Ger. Offen. DE 2218362 19731108, November 8, 1973; Chem. Abstr.
1974, 80, 27280.
(3) Sahu, K. K.; Ravichandran, V.; Mourya, V. K.; Agrawal, R. K. Med.
Chem. Res. 2007, 15, 418–430.
(4) Yoon, S.; Cho, J.; Lee, H. Lactam-based additive for electrolyte for
secondary battery. PCT Int. Appl. WO 2008010665, January 4, 2008; Chem.
Abstr. 2008, 148, 195277.
(5) (a) Hayashi, E.; Abe, T.; Nagase, S. J. Fluorine Chem. 1988, 41, 213–
225. (b) Abe, T.; Hayashi, E. J. Fluorine Chem. 1989, 45, 293–311.
(6) Buettner, G.; Klauke, E. N-(Trifluoromethyl)carboxamides. Ger.
Offen. DE 2215955 19731004, October 4, 1973; Chem. Abstr. 1973, 79,
146253.
(7) Ignat’ev, N. V.; Schmidt, M.; Heider, U.; Kucherina, A.; Sartori, P.;
Helmy, F. M. J. Fluorine Chem. 2002, 113, 201–205.
(8) Michalak, R. S.; Wilson, S. R.; Martin, J. C. J. Am. Chem. Soc. 1984,
106, 7529–7539.
8578 J. Org. Chem. 2009, 74, 8578–8582
Published on Web 10/16/2009
DOI: 10.1021/jo901560b
r
2009 American Chemical Society

Hagooly et al.
JOCArticle
hexafluorocyclopentadiene,9 producing modern anesthetics
such as desflurane,10 for transforming carbonyls to the CF2
moiety,11 and for converting either alkyl halides or carbonyls
to the CHF2 group.12 It was also used for synthesizing the
novel OCF2Cl,13 OCF2H,14 and OCF2O15 moieties, for
achieving difficult to obtain aromatic brominations16 and
for other transformations.17
SCHEME 2. Formation of N-(Trifluoromethyl)amides with
-
(MeS)3CþBF4
The major reason for the highly reactive nature of bromine
trifluoride is its weak Br-F bonds encouraging indiscriminate
radical reactions.18 In order to avoid such pathways, a soft
base (usually a sulfur or a nitrogen atom) has to be present in
the target molecule in order to form a complex with the soft
acidic bromine atom and thus place its fluorides near the site
where a substitution is planned (Scheme 1).17 It should be
emphasized that this proximity and the fact that the fluorides
are nonsolvated are responsible for a very fast substitution
(usually less than a minute), which is quite uncharacteristic for
reactions involving a nucleophilic fluorination.
The synthesis of 1, however, is somewhat problematic since it
is very moisture sensitive, and what is more, many amides did
not give satisfactory results. We turned our attention therefore
to the family of isothiocyanates (6), which proved to be the best
general entry to the family of N-(trifluoromethyl)amides and, if
desired, also to the novel family of aromatic N-(difluoromethy-
lene)-N-(trifluoromethyl)amines. The isothiocyanate deriva-
tives (6) were reacted with ethanethiol to form ethyl alkyldithi-
carbamates (7) in almost quantitative yield (Scheme 3). The next
step involved treating compounds 7 with carboxylic acids 8
in the presence of N,N0-dicyclohexylcarbodiimide (DCC) and
4-(dimethylamino)pyridine (DMAP) forming a variety of res-
pective ethyl alkyl(alkanoyl)dithiocarbamate derivatives (9) in
good yields. These readily obtained compounds could then
complex the bromine atom of the BrF3 and as a result the
nearby fluorides efficiently substituted the sulfur atoms form-
ing the desired N-(trifluoromethyl) compounds (10) in good
yields (Scheme 3).
SCHEME 1. General Mechanism for Selective Reactions with
BrF3
Results and Discussion
Our initial strategy for the preparation of N-(trifluoro-
methyl)amides was to react amides with strong bases such as
butyllithium followed by addition of carbon disulfide and
methyl iodide1d,19 in order to obtain the N-trismethylthioa-
mides (RC(O)N(R)CSSMe) in hope that they would be sui-
table substrates for reaction with BrF3. However, whenwetried
this approach with phtalimide and other amides, very low
yields (<20%) of the dithiocarbamates were obtained. A more
promising approach was to react different imides or amides
with tris(methylthio)methyl tetrafluoroborate (1).20 Indeed,
when 1 was reacted with the anion of phtalimide (2) or
caprolactam (3) we obtained the corresponding NC(SMe)3
derivatives which, when treated with bromine trifluoride pro-
duced the N-(trifluoromethyl)phthalimide (4)21 and N-(trifluoro-
methyl)caprolactam (5)4 both in 60% yield (Scheme 2).
SCHEME 3. Aliphatic N-(Trifluoromethyl)amides (10)
(9) For example, it has been used to make hexafluorocyclopentadiene:
Soelch, R. R.; Mauer, G. W.; Lemal, D. M. J. Org. Chem. 1985, 50, 5845-
5852.
(10) Ramig, K. Synthesis 2002, 2627–2631.
(11) (a) Rozen, S.; Mishani, E.; Bar-Haim, A. J. Org. Chem. 1994, 59,
2918. (b) Rozen, S.; Brand, M J. Org. Chem. 1986, 51, 222.
(12) (a) Sasson, R.; Hagooly, A.; Rozen, S. Org. Lett. 2003, 5, 769–771.
(b) Cohen, O.; Hagooly, Y.; Rozen, S. Tetrahedron 2009, 65, 1361–1365.
(13) Hagooly, Y.; Sasson, R.; Welch, M. J.; Rozen, S. Eur. J. Org. Chem.
2008, 19, 2875–2880.
(14) Hagooly, Y.; Cohen, O.; Rozen, S. Tetrahedron Lett. 2009, 50, 392–
394.
(15) (a) Hagooly, Y.; Rozen, S. J. Org. Chem. 2008, 73, 6780–6783.
(b) Hagooly, A.; Rozen, S. J. Org. Chem. 2004, 69, 7241–7245.
(16) Rozen, S.; Lerman, O. J. Org. Chem. 1993, 58, 239–240.
(17) Rozen, S. Acc. Chem. Res. 2005, 38, 803–812.
(18) Sasson, R.; Rozen, S. Tetrahedron 2005, 61, 1083–1086.
(19) (a) Kanie, K.; Mizuno, K.; Kuroboshi, M.; Hiyama, T. Bull. Chem.
Soc. Jpn. 1998, 71, 1973–1991. (b) Kuroboshi, M.; Mizuno, K.; Kanie, K.;
Hiyama, T. Tetrahedron Lett. 1995, 36, 563–566. (c) Kuroboshi, M.; Hiyama,
T. Tetrahedron Lett. 1992, 33, 4177–4178.
Thus, when ethyl butyl(hexanoyl)dithiocarbamate (9a),
prepared from 7a,22 was treated with 3 mol/equiv of bromine
(20) Barbero, M.; Cadamuro, S.; Degany, I.; Fochi, R.; Gatty, A.;
Regondy, V. Synthesis 1988, 1, 22–25.
(21) Vidal, B. J. Nature 1996, 8, 12–16.
(22) Harisadhan, G.; Singh, C. B.; Siva, M.; Veerababurao, K.; Bhisma,
K. P. Tetrahedron Lett. 2008, 49, 2602–2606.
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trifluoride, the product, obtained in a few seconds, proved
to be the desirable N-butyl-N-(trifluoromethyl)hexanamide
(10a) accompanied by another somewhat surprising com-
pound found to be N-butyl-N-1,1-difluorohexyl-N-(tri-
fluoromethyl)amine (11a). However, 11a was hydrolytically
unstable and in the presence of moisture was fully hydro-
lyzed to the desired 10a for a total yield of 85% in a few
minutes.15,23
11 was made possible when centers susceptible to nucleophi-
lic attacks such as carbonyls are in close proximity to the
complexed reagent. One molecule of BrF3 could then offer
one fluoride to the sulfur bonded carbon and another to the
carbonyl resulting in molecules of type 11 (Scheme 4).
SCHEME 4. Stepwise Formation of 10 and 11
Similarly, ethyl butyl(dodecanoyl)dithiocarbamate (9b)
served as a starting material for N-butyl-N-(trifluoromethyl)-
dodecanamide (10b) obtained in 85% yield with parallel
formation of N-butyl-N-(1,1-difluorododecyl)-N-(trifluoro-
methyl)amine (11b), which again could be readily, and practi-
cally quantitatively, hydrolyzed back to 10b (Scheme 3).
The scope of this reaction is quite wide. While it is known
that BrF3 can substitute chlorine with fluorine,24 we found
that the reaction at the sulfur center is much faster so a
chlorine atom is not much affected. Ethyl butyl(5-chloro-
pentanoyl)dithiocarbamate (9c) was thus converted to the
desired N-butyl-5-chloro-N-(trifluoromethyl)pentanamide
(10c), although in 65% yield, somewhat lower than usual.
Branched aliphatic compounds were not susceptible to elim-
inations or substitutions at the tertiary center,25 and N-butyl-
2-methyl-N-(trifluoromethyl)butanamide (10d) was formed
in 85% yield by applying bromine trifluoride to ethyl butyl-
(2-methylbutanoyl)dithiocarbamate (9d). Another common
functionality, the ester group, also does not affect the out-
come of the reaction as evident from the case of methyl
5-(butyl(ethylthiocarbonothioyl)amino)5-oxopentanoate (9e).
The product, which was obtained in seconds, was identified
to be methyl 5-(butyl(trifluoromethyl)amino)-5-oxopentano-
ate (10e) in 85% yield. It should be noted that unlike the cases in
which the nearby ester’s carbonyl was located close to the
complexed BrF3 and converted to the CF2 group, the remote
ester with its hard basic oxygens cannot complex the reagent,
and therefore, no reaction around this region was noted.
The reaction goes well with an array of isothiocyanates.
Ethyl ethyl(2-propylpentanoyl)dithiocarbamate (9f) was
prepared in 90% yield from ethyl ethyldithiocarbamate
(7f),26 which in itself was made from ethyl isothiocyanate
(6f). When 9f was reacted with bromine trifluoride, the
result, after hydrolysis, was found to be N-ethyl-2-propyl-
N-(trifluoromethyl)pentanamide (10f) in high yield. An ad-
ditional secondary cyclic isothiocyanate 6g was smoothly
converted to ethyl cyclohexyldithiocarbamate (7g)27 and
again successfully transformed to 10g in 85% yield.
Unlike the aliphatic series the stability of 11 increases with
the presence of aromatic substituents (either R or R’). In
general, the presence of aromatic rings, especially ones
activated toward electrophilic attacks, can pose a problem
when reactions with BrF3 are involved, since the strongly
electrophilic bromine could lead to aromatic brominations
which are mostly avoided with deactivated aromatics.13,28
Ethyl butyl (4-nitrophenylcarbonyl)dithiocarbamate (9h)
prepared from ethyl butyldithiocarbamate (7a) and 4-nitro-
benzoic acid (8h), was reacted with 3 mol/equiv of BrF3 to
form the new N-butyl-N-(difluoro(4-nitrophenyl)methyl)-
N-(trifluoromethyl)amine (11h) in 65% yield along with
N-butyl-N-(trifluoromethyl)-4-nitro benzamide (10h) obta-
ined in 30% yield (Scheme 5). The aromatic derivative 11h
was hydrolytically stable and could be isolated and purified.
It should be noted that when 10h itself served as a substrate,
the carbonyl remained intact, emphasizing the necessity of
the sulfur complexation center for transforming the amide’s
carbonyl to the CF2 moiety.
SCHEME 5. Aromatic 10 and 11
For a full conversion and best yields for the construction
of the CF3 group, about 3 mol/equiv of bromine trifluoride
was used. If less of the reagent is employed the yields were
affected, but we were able to identify a major type of product
found to be alkyl(alkanoyl)thiocarbamoic fluoride (12) ob-
tained in about 50% yield. We believe that compounds 12 are
intermediates for both final products 10 and 11 where in the
aliphatic series the latter was eventually quantitatively hy-
drolyzed back to 10. The formation of the somewhat unusual
The instability of the CF2 group toward hydrolysis in the
aliphatic series as well as its stability in the aromatic one may
be explained by fluorine hyperconjugation. In the aliphatic
domain this phenomenon is encouraged both by the nitrogen
lone pair and the positive inductivity of the alkyl group,
which makes the difluoromethylene carbon susceptible to
attack by the water nucleophilic oxygen. In contrast to the
series containing aromatic rings 11h - 11k the electron
(23) Rozen, S.; Rechavi, D.; Hagooly, A. J. Fluorine Chem. 2001, 111,
161–169.
(24) Rozov, L. A.; Huang, C. G.; Halpern, D. F.; Vernice, G. G.; Ramig,
K. Tetrahedron: Asymmetry 1997, 8, 3023–3025.
(25) (a) Boguslavskaya, L. S.; Kartashov, A. V.; Chuvatkin, N. N. J. Org.
Chem. USSR 1989, 25, 1835. (b) Zh. Org. Khim. 1989, 25, 2029-2030.
(26) Blotny, G. Liebigs Ann. Chem. 1982, 10, 1927–1932.
(27) Azizi, N.; Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275–5277.
(28) Rozen, S.; Lerman, O. J. Org. Chem. 1993, 58, 239–240.
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Hagooly et al.
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accepting ability of the aromatic rings, discourages fluorine
hyperconjugation necessary for the hydrolysis of the difluor-
omethylene moiety (Scheme 6). In the past we have witnessed
somewhat similar behavior.15
SCHEME 7. Formation of 13l
SCHEME 6. Hydrolysis of N-(Difluoromethylene)-N- (trifluoro-
methyl)amine 11
In conclusion, bromine trifluoride should not be suspi-
ciously looked upon any longer. This work adds another
layer to its rich but relatively hidden synthetic potential as we
have demonstrated here its role in the preparation of a
wide variety of the rare or unknown N-(trifluoromethyl)amide
and N-(difluoromethylene)-N-(trifluoromethyl)amine deriva-
tives. The fluorination step is usually completed in seconds,
and the fluorinated products are obtained under remarkably
mild conditions.
Since the pyridine ring does not react readily with bromine
trifluoride, we hoped to widen the scope of the reaction to
compounds that possess this heterocyclic. When 3 mol/equiv
of BrF3 were reacted with ethyl butyl(pyridine-3-carbonyl)-
dithiocarbamoate (9i), obtained from 7a22 and nicotinic acid
(8i), both N-butyl-N-(trifluoromethyl)pyridine-3-carboxa-
mide (10i) and N-(difluoro(pyridin-3-yl)methyl)-N-(trifluoro-
methyl)butan-1-amine (11i) were formed in 40% and 55%
yields respectively (Scheme 5). Here too, when 10i itself was
reacted with BrF3 the carbonyl resisted any transformation
again supporting the notion that a presence of soft base such as
sulfur is essential.
In order to show that it is of no consequence on which side
of the molecule the aromatic ring is located, we reacted ethyl
4-nitrophenyldithiocarbamate (7j)29 with hexanoic acid (8a)
and subjected the product 9j to a reaction with BrF3 resulting
in N-(4-nitrophenyl)-N-(trifluoromethyl)hexanamide (10j)
and N-(1,1-difluorohexyl)-4-nitro-N-(trifluoromethyl)aniline
(11j) in 30% and 60% yields. As with the case of dialkyl
derivatives when less than 3 mol/equiv of BrF3 was applied,
the selectivity of the reaction was reduced and 10j was found to
be the major product.
When bis-aromatic precursor such as ethyl 4-nitrophenyl-
(4-nitrophenylcarbonyl)dithiocarbamate (9k) was reacted
with 3 mol/equiv of BrF3 the stable N-(difluoro(4-nitro-
phenyl)methyl)-4-nitro-N-(trifluoromethyl)aniline (11k) was
successfully produced in 75% yield with only traces of 10k
(Scheme 5). Using about 2 mol/equiv of the fluorinating agent
reversed the distribution and 10k was obtained in a 60% yield
with not much of the pentafluoro derivative 11k.
In order to increase the amount of the pentafluoroamine
derivatives, we have constructed molecules containing two
separate sulfur centers starting from the easily made O-2,4-
dichlorophenyl chloridothiocarbonate (8l)15 and ethyl 4-nitro-
phenyldithiocarbamate (7j). The desired product O-2,4-dichloro-
phenyl ethylthiocarbonothioyl(4-nitrophenyl)thiocarbamate (9l)
was obtained in 95% yield (Scheme 7). When this compound
was reacted with BrF3, the novel N-((2,4-dichlorophenoxy)-
difluoromethyl)-4-nitro-N-(trifluoromethyl)aniline (13l) was
successfully formed in 75% yield (the balance seems to be
brominated 13l). Although the location of the CF2 moiety is bet-
ween oxygen and nitrogen atoms, which usually encourage
hydrolysis, the presence of the aromatic rings decreases the hyper-
conjugation thus increases the stability toward hydrolysis.
Experimental Section
General Procedure for the Preparation of Ethyl Alkyl/Aryl
Dithiocarbamate Derivatives (7). A solution of the different
aliphatic isothiocyanates (6) (26.0 mmol) was reacted with
3.3 mL (39.0 mmol) of ethanethiol in the presence of Et3N
(0.3 mL, 26.0 mmol) in 40 mL of dry THF and was refluxed for
20 h to form 7 in about 95% yields. In the case of aromatic
dithiocarbamates the reaction was carried out under the same
conditions with toluene as a solvent and in the presence of
catalytic amount of dibutyltin dilaurate. In both cases, evapora-
tion of the solvent followed by flash chromatography yielded the
desired product. Some general procedures and description of
representative experiments may be found below. The rest of
the experimental procedures can be found in the Supporting
Information.
Ethyl butyldithiocarbamate (7a)22 was prepared as described
in the general procedure, in 95% yield (4.4 g, colorless oil). In
alkyl dithiocarbamate derivatives, some tautomerization of
hydrogen atom occurred, and it distribute on both nitrogen
and sulfur atoms. This fact was demonstrated in the NMR
spectrum, where two different types of molecules may be seen:
1H NMR 8.22 and 7.31 (1 H, s), 3.75-3.68 and 3.48-3.38 (2 H,
m), 3.34-3.20 (2 H, m), 1.65 (2 H, quint, J=7.7 Hz), 1.45-1.29
(5 H, m), 0.88 ppm (3 H, t, J = 7.7 Hz); 13C NMR 200.4 and
197.6, 46.8 and 46.1, 30.5 and 30.3, 29.5, 20.1, 14.2, 13.6 ppm.
General Procedure for the Preparation of Ethyl Bis-aliphatic,
Aliphatic/Aromatic, or Bis-aromatic Dithiocarbamate Deriva-
tives 9. When 11 mmol of alkyl or 4-nitrophenyl dithiocarba-
mate (7) was reacted with 11 mmol of different acids 8 in the
presence of 3.5 g (16.9 mmol) of N,N0-dicyclohexylcarbodiimide
(DCC) and 134 mg (1.1 mmol) of 4-(dimethylamino)pyridine
(DMAP) in 50 mL of dichloromethane, the corresponding
dithiocarbamate derivatives (9) were formed in 70-95% yields.
Evaporation of the solvent followed by flash chromatography
yielded the desired products that were used, without further
purification, as precursors for the next fluorination step.
Ethyl butyl(hexanoyl)dithiocarbamate (9a) was prepared from
ethyl butyldithiocarbamate (7a) (2.0 g) and hexanoic acid (8a)
(1.3 g) as described in the general procedure, in 75% yield: 2.3 g,
1
orange oil; H NMR 4.08 (2 H, t, J = 7.0 Hz), 3.14 (2 H, q,
J = 7.0 Hz), 2.70 (2 H, t, J = 7.0 Hz), 1.70-1.59 (4 H, m),
1.34-1.26 (9 H, m), 0.89-0.84 ppm (6 H, m); 13C NMR 208.3,
174.9, 50.9, 36.9, 32.4, 31.1, 30.2, 25.2, 22.3, 19.9, 13.7, 13.5,
11.9 ppm.
(29) Zsolnai, T. Arzneim.-Forsch. 1966, 16, 1092–1099.
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General Procedure for the Preparation of the N-(Trifluoro-
methyl)amide (10) and N-Difluoro-N-(trifluoromethyl)amine (11)
Derivatives with BrF3. A dithiocarbamate derivative (3 mmol)
was dissolved in 25 mL of CHCl3 or CFCl3 in a glass flask and
cooled to 0 °C. The best results were achieved when BrF3
(3 molar equiv, 9 mmol) was dissolved in a few milliliters of
CFCl3, cooled to 0 °C, and added dropwise to the reaction
mixture using a glass dropping funnel also at 0 °C. The reaction
mixture was then washed with aqueous Na2SO3 until colorless,
extracted with CH2Cl2, and dried over MgSO4. Evaporation of
the solvent followed by flash chromatography yielded the
desired fluorinated compounds.
m), 1.51-1.48 (2 H, m), 1.31-1.22 (6 H, m), 0.90-0.88 ppm
(6 H, m); 13C NMR 172.5, 122.1 (q, J=265 Hz), 43.3, 34.9, 31.3,
31.1, 24.5, 22.4, 19.8, 13.8, 13.5 ppm; 19F NMR -51.8 ppm (3 F,
s); IR 1703.2 cm-1; MS (CI) m/z 240.2 (MH)þ. Anal. Calcd for
C11H20F3NO: C, 55.22; H, 8.42; N, 5.85. Found: C, 54.92; H,
8.37; N, 5.76.
Acknowledgment. This work was supported by the USA-
Israel Binational Science Foundation (BSF), Jerusalem,
Israel.
Supporting Information Available: Additional experimental
details, NMR’s spectra of all N-(trifluoromethyl)amide and
N-(difluoromethylene)-N-(trifluoromethyl)amine derivatives and
their novel precursors described in this work. This material is
available free of charge via the Internet at http://pubs.acs.org.
N-Butyl-N-(trifluoromethyl)hexanamide (10a) was prepared
from 9a (830 mg) as described in the general procedure for the
reaction with BrF3, in 85% yield (610 mg): oil; 1H NMR
3.54-3.49 (2 H, m), 2.45 (2 H, t, J = 7.0 Hz), 1.67-1.59 (2 H,
8582 J. Org. Chem. Vol. 74, No. 22, 2009