Thermocontrolled benzylimine-benzaldimine rearrangement over Nafion-H catalysts for efficient entry into α-trifluoromethylbenzylamines

Article abstract of DOI:10.1016/j.tetlet.2011.11.088

Nafion-H and Nafion SAC-13 are efficient solid Br?nsted acid catalysts for the preparation of trifluoromethyl ketimines from benzylamines and trifluoromethylated ketones in high yields. A finely tuned benzylimine- benzaldimine rearrangement by facile 1,3-hydrogen shift has been achieved for the formation of fluorinated benzaldimines in high yields by careful optimization of reaction conditions including attempts under microwave conditions and a flow system. These α-trifluoromethylated benzaldimines are efficient precursors for pharmaceutically important α- trifluoromethylated benzylamines, accessed through their direct acid hydrolysis.

Full text of DOI:10.1016/j.tetlet.2011.11.088

Tetrahedron Letters 53 (2012) 607–611
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Thermocontrolled benzylimine–benzaldimine rearrangement over Nafion-H
catalysts for efficient entry into a-trifluoromethylbenzylamines
⇑
G.K. Surya Prakash , Kevin E. Glinton, Chiradeep Panja, Laxman Gurung, Patrice T. Battamack,
⇑
Béla Török , Thomas Mathew , George A. Olah
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-1661, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Nafion-H and Nafion SAC-13 are efficient solid Brønsted acid catalysts for the preparation of trifluoro-
methyl ketimines from benzylamines and trifluoromethylated ketones in high yields. A finely tuned ben-
zylimine–benzaldimine rearrangement by facile 1,3-hydrogen shift has been achieved for the formation
of fluorinated benzaldimines in high yields by careful optimization of reaction conditions including
Received 21 October 2011
Revised 14 November 2011
Accepted 16 November 2011
Available online 2 December 2011
attempts under microwave conditions and a flow system. These
a-trifluoromethylated benzaldimines
are efficient precursors for pharmaceutically important
through their direct acid hydrolysis.
a
-trifluoromethylated benzylamines, accessed
Keywords:
Nafion-H
Nafion-H SAC13
Ó 2011 Elsevier Ltd. All rights reserved.
Biomimetic reductive amination
Trifluoromethylated amines
Benzaldimines
1. Introduction
nated 1,2-oxazolidines7 and nucleophilic additions of TMSCF3 to
nitrones and imines.8 Within the last decade however, much of
the synthetic work in this area has been focused on the base-cata-
lyzed isomerization of trifluoromethylated imines pioneered by
Soloshonok and co-workers.9 Since more C–H acidic imine product
is thermodynamically favored, the so called ‘biomimetic reductive
amination’ approach exploits the electron withdrawing nature of
Fluorinated bioactive molecules have garnered much attention
in recent years due to the unique properties imparted by fluorine
substitution.1 In particular,
a-trifluoromethylated amino com-
pounds have become popular and indispensable building blocks
in the synthesis and design of fungicides, pesticides, insecticides,
selective antibacterial agents, enzyme inhibitors, and enzyme
receptor antagonists or agonists.2 Much of the interest associated
the a-trifluoromethyl group that favors the irreversible formation
of substituted benzaldimines 4 instead of benzylimines 3 from
with these precursors derives from the fact that a-trifluoromethy-
benzylamines 1 (Scheme 1).10
lated amines may act as efficient isosteres to the carbonyl groups
of amide bonds.3 Trifluoromethyl substitution in bioactive amino
compounds is a popular strategy to lower the basicity of the neigh-
boring amino group and in turn, enhance the lipophilicity and met-
abolic stability of the parent C–H analog.4 It increases their
bioavailabilities by increasing their ability to cross membranes. It
comes as no surprise that there have been a number of reported
synthetic routes to these compounds.
The reaction leads to the formation of a more stable imine and
has even been shown to occur without the use of catalysts though
only at higher temperatures.11 The Schiff bases that result from
such reactions can later be hydrolyzed under mildly acidic condi-
tions to yield trifluoromethylated amines.3a,b However, while this
is an important and elegant discovery, the methodology still
One of the most commonly exploited methods is the reductive
amination of trifluoromethylated carbonyl compounds usually
through the use of chiral metal catalysts.5 Other well known meth-
ods however, include the nucleophilic alkylation of trifluoromethyl
imines,6 various reductions, or ring opening reactions of fluori-
Rf
R
O
H+
Ar
NH2
+
Ar
N
R
Rf
3
2
1
Base
1,3-Proton Shift
R = Alkyl, Rf = Fluoroalkyl, Ar = Aromatic
O
Rf
R
Rf
R
H+
+
Ar
H
⇑
NH3
Ar
N
Corresponding authors. Tel.: +1 273 740 5984; fax: +1 213 740 6679 (G.K.S.P.).
E-mail addresses: gprakash@usc.edu (G.K.S. Prakash), tmathew@usc.edu
(T. Mathew).
Hydrolysis
5
4
Present address: University of Massachusetts Boston, 100 Morrissey, MA, USA.
Scheme 1. Biomimetic reductive amination.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.088

608
G. K. S. Prakash et al. / Tetrahedron Letters 53 (2012) 607–611
NafionÒ is formed by the copolymerization of a perfluorinated
(CF2 CF2) x CF CF2
y
vinyl ether comonomer possessing a sulfonated terminus with tet-
rafluoroethylene (TFE). Within the polymer’s superstructure, the
sulfonate groups tend to form aggregates or clusters creating chan-
nels through which cations can freely travel and it is this character-
istic property that gives the polymer its high proton conductivity (
Fig. 1).17 These channels also play an important role in the remark-
able acidic characteristics of NafionÒ. In its acid form, the presence
of so many electron withdrawing fluorine atoms within the poly-
mer’s backbone makes the acidity of Nafion-H comparable to that
of concentrated sulfuric acid and in effect a solid superacid. At the
same time, because the acid sites lie buried within the superstruc-
ture, bulk acidification of the solvent can largely be avoided.
The broad range of reactions catalyzed by Nafion-H not only
demonstrates the efficacy and synthetic versatility of the polymer
as a catalyst, but its many environmental benefits as well. Products
of these reactions can simply be filtered from the polymer and iso-
lated without the excessive use of hazardous solvents while, be-
cause of its high stability, the used polymer can be recovered,
cleaned, and regenerated for recycling. Thus, instead of using a sol-
uble organic Brønsted acid catalyst such as p-toluenesulfonic acid
or trifluoromethanesulfonic acid, Nafion-H could be used as an
effective catalyst for many reactions including imine synthesis that
requires both strong acidities and higher temperatures.
SO3H
O
(CF2 CF
CF3
CF2 CF2
O) m
a.
Nafion-H (Solid Resin)
SO3-
SO3
-
-
SO3-
SO3
SO3
-
-
-
SO3
-
SO3
SO3
-
SO3-
SO3
-
4nm
1nm
SO3
SO3-
SO3-
SO3
-
-
-
SO3
SO3
-
SO3- SO3
SO3-
5nm
b. Cluster Network-Model
Figure 1. Structure of NafionÒ
.
suffers significantly from several drawbacks, the most serious of
which is its multi-step approach. Considerable improvement of
this process has been achieved by various modifications including
those with substrates and reaction conditions.12
During the course of our experiments toward the synthesis of
trifluoromethylated imines using Nafion-H, we found that reac-
tions between aniline derivatives and trifluoromethylated ketones
do in fact produce imines in quantitative yields. Surprisingly how-
ever, when the reaction was extended to benzylamines, the corre-
sponding fluorinated imines were obtained along with a small
amount of trifluoromethylated benzaldimines; the products identi-
cal to the ones obtained by the biomimetic 1,3-H shift mechanism.
Further investigation revealed that a simple elevation in reaction
temperature resulted in a significant enhancement in the yield of
benzylidene-1-phenyl-2,2,2-trifluoroethylamine (4, Scheme 2).
The reaction was carefully monitored at different conditions and
the most suitable one for maximum conversion to the rearranged
product with the least side reaction was found.
It is known that the presence of electron withdrawing groups in
ketones dramatically increases their electrophilicity. Thus, despite
the presence of a trifluoromethyl group in the substrate, the addi-
tion of another fluorine atom or a CF3 group in the aryl ring also
helps to significantly enhance the electrophilicity of the ketones
and ultimately the reaction yields as reported earlier18 (Table 1,
entries 2, 4 and 7). Though we generally found high boiling sol-
vents best suited to this methodology, the amount of solvent used
in each reaction initially proved crucial. An excess of the solvent
(toluene), led to a mixture of both the imines while a minimal
amount (1 mL of toluene per mmol of the substrate) predomi-
nantly led to the formation of benzaldimine as the major product.
The aggregate-cluster model of Nafion-H (Fig. 1b) ensures, as
mentioned, that acid sites are only found within the sub-structure
of the catalyst’s pockets and not throughout the solvent solution as
The synthesis of trifluoromethylated imines as starting materi-
als is not a trivial process and it was the focus of recent work in
developing noticeably improved conditions.13a Afterward, the use
of a base such as triethylamine during the second step requires
careful neutralization and purification.13b Therefore, a need for
cleaner and more efficient routes to these valuable products has
emerged. Our attempts to improve the practical application of
the biomimetic route to trifluoromethylated amines began by
attempting to improve the way in which trifluoromethylated imi-
nes are synthesized.
2. Results and discussion
Most trifluoromethylated imines, as previously indicated, are
synthesized through reactions catalyzed by acids such as p-tolu-
enesulfonic acid. Therefore, we attempted to improve this process
by instead choosing Nafion-H, a solid supported perfluoroalkane-
sulfonic acid resin as the Brønsted acid catalyst. NafionÒ resins
were first developed by Dupont and their remarkable properties
led to their vast application as electrolyte membranes for electro-
chemical cells.14 The acidic form, Nafion-H was prepared from its
potassium salt by proton exchange and its application as an effi-
cient solid acid catalyst in a wide range of organic reactions such
as alkylations, acylations, nitrations, sulfonations, and isomeriza-
tions has been studied extensively by Olah and co-workers.15 In
chemical reactions, Nafion-H remains thermally stable up to
210 °C, chemically inert to many side reactions and can be easily
recovered and recycled.15,16
R
H
H
H
H
CF3
R
164 °C
+
Ar
N
CF3
Ar
N
O
4 minor
3 major
H
H
Nafion-H
+
Ar
NH2
R
CF3
1
H
R
2
H
CF3
R
H H
185 °C
+
Ar
N
Ar
N
CF3
3
4 major
minor
Scheme 2. Thermocontrolled synthesis of trifluoromethylated benzylimines and benzaldimines from trifluoromethylketones and benzylamines.

G. K. S. Prakash et al. / Tetrahedron Letters 53 (2012) 607–611
609
Table 1
Table 2
Formation of trifluoromethylated benzylimines and their isomerization to benzaldi-
mines catalyzed by Nafion-H
Synthesis of trifluoromethylated benzylimines and their isomerization to benzaldi-
mines using Nafion-H SAC-13
O
H
H
O
H CF3
R
H CF3
Nafion-H
Nafion-H SAC-13
Toluene,185°C
NH2
CF3
N
NH2
+
F3C
R
N
+
R
R
Toluene,
185 °C, 24 h
1
4
2
2
4
1
Entry
R
Time (h) Product (4a–i)
Yield (%)
Entry
R
Product (4)
Yield (%)
H
H
CF3
CF3
H
H CF3
1
2
24
24
82
N
1
2
H
54
68
N
4a
4a
H
H
H
H CF3
H
H
N
4b
4-F
N
80
94
73
4b
F
F
F
H CF3
H
H
H
CF3
CF3
N
4c
3
4
5
4-Cl
36
62
55
N
3
4
24
24
Cl
4c
Cl
H
CF3
Cl
N
4-CF3
4-OMe
H
N
4d
CF3
H
H
H
H CF3
4d
CF
3
CF3
N
4e
H
H
H
N
CF3
CF3
OMe
H CF3
5
48
83
4e
OCH3
N
6
7
4-Br
58
64
OCH3
4f
Br
H
N
H CF3
CF3
6
7
24
24
66
92
3-CF3
N
4g
4f
Br
Br
H
H
CF3
CF3
H
N
CF3
with other acids (so called high dilution effect). The present reac-
tion therefore requires a higher concentration of the reaction mix-
ture so that dilution effects can be minimized as more reactants are
forced into the proximity of acid sites in the catalyst. Beyond the
issue of access to the acid sites, inconsistencies in Nafion-H cata-
lyzed reactions observed in some cases can be due to inconsisten-
cies in the distribution and arrangement of reactants in these
cluster pockets.
CF3
4g
H
N
8
9
48
48
71
50
4h
CH3
CH3
S
H
H
CF3
S
N
In order to have greater accessibility to more acid sites and fur-
ther improve and enhance the reaction conditions, we examined
Nafion-H SAC-13, a catalyst derived from Nafion-H with a varied
morphology and its synthetic potential in the present protocol
has also been explored. First reported by Harmer and coworkers
in 1996, Nafion-H SAC-13 is a silica supported form of the solid
Nafion-H.19,20 By immobilizing Nafion-H on a silica matrix, Harmer
and his group found that the surface area of the catalyst could be
improved almost tenfold. This provides for greater accessibility
to acidic sites and, in our experiments, further yield improvements
and even greater selectivity. We found in fact, that using Nafion-H
SAC-13 led to the formation of trifluoromethylated benzaldimines
cleanly and, in some cases, as the sole product making purification
rather easier. When the reaction has been expanded to a variety of
trifluoromethylated acetophenones, the corresponding trifluorom-
ethylated benzaldimines were obtained in good to excellent yields
(Table 2)21 further establishing the profound catalytic effect of
Nafion-H SAC-13 on this reaction. The reactions carried out using
both the unsubstituted and 4-fluoro substituted 1,1,1-trifluoro-
acetophenone in the absence of catalyst resulted in much lower
4i
H
O
H
CF3
H CF3
3N HCl
N
H
H3N
Cl
+
Et2O, RT
R
R
4a-e
R = H, F, Cl, CF3, OCH3
5a-e
(72-79%)
Scheme 3. Hydrolysis of trifluoromethylated benzaldimines (4a–e) to 1,1,1-
trifluoro-2-phenylethylamines (5a–e).
yields (47%, 56%, respectively) of the benzaldimine product further
manifesting the influence of the catalyst.
Nafion-H based acids promote thermocontrolled chemoselec-
tivity in these reactions. Interestingly, 1,3-proton shift was shown
to occur under simple thermal conditions and we were able to

610
G. K. S. Prakash et al. / Tetrahedron Letters 53 (2012) 607–611
Table 3
1,1,1-Trifluoro-2-phenylethylamines (5a–e) obtained by the hydrolysis of trifluoromethylated benzaldimines (4a–e)
Entry
Benzaldimines (4a–e)
1,1,1-Trifluoro-2-phenylethylamines (5a–e)
CF3
Yield (%)
77
H
H
H
H
H
CF3
CF3
CF3
CF3
CF3
H3N
Cl
N
1
5a
CF3
4a
4b
4c
H
H
H3N
Cl
N
2
3
74
79
F
F
5b
CF3
H
H
H3N
Cl
N
Cl
Cl
5c
CF3
H
H
H
H
H3N
Cl
N
4
5
77
72
CF3
OCH3
CF3
OCH3
5d
CF3
4d
4e
H
H
H3N
Cl
N
5e
detect the presence of benzaldimine products at temperatures well
below 185 °C. As the reaction mixtures were heated from room
temperature, we were able to observe the initial formation of the
imine 3 and its subsequent conversion to the rearranged isomer
by 19F NMR spectroscopy. After carefully monitoring the formation
of the ketimine and its rearrangement to the benzaldimine at var-
ious stages of the reaction, it became evident that the rate-deter-
mining step in the reaction is the initial imine formation.
Substituent-effects in these reactions could, once again, be
clearly observed as electron deficient acetophenones generally re-
acted faster than the electron rich ones. However, even in instances
where the use of longer reaction time was required, reactions still
went essentially to completion with good yields. Afterward, the
isolated products may be further converted into the synthetically
valuable, fluorinated benzylamines by previously established min-
eral acid hydrolysis (Scheme 3). This particular transformation was
carried out on a selected number of trifluoromethylated benzaldi-
mines and the corresponding benzylamine hydrochloride salts
were obtained in good yields (Table 3).
efficient synthons in the design of many fluorinated amino com-
pounds in the pharmaceutical and industrial arena.
Acknowledgment
Financial support by the Loker Hydrocarbon Research Institute
is gratefully acknowledged.
References and notes
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As observed from the enhancement of yield and selectivity of
the benzaldimines upon change in solid acid morphology (Naf-
ion-H to Nafion-H SAC 13), the role of the acid catalyst and acces-
sibility of more acidic sites is further manifested. Thus elevated
heating may serve to merely ensure reaction completion in a more
timely fashion.
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SAC 13) act as effective Brønsted acid catalysts in the one-pot
synthesis of trifluoromethylated benzaldimines from trifluorome-
thylated ketones and benzylamines. Easy separation of the cata-
lysts and purification of the products in good yields as well as
general applicability to a variety of ketones and benzylamines
are the main features of the reaction. The products are used as
important precursors for trifluoromethylated benzylamines and

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was removed by adding aqueous sodium hydroxide (3 N) till the solution
turned slightly basic. The solution was the concentrated under vacuum to
obtain the hydrochloride salt of 2,2,2-trifluoro-1-phenylethylamine 5a. All
products were characterized by spectral analysis and by comparing the
spectral data (for known compounds) with those of the authentic samples
products.5a,6b,10
Spectral data of benzylidene-1-(phenyl)-2,2,2-trifluoroethyl-amine (4a)
1H NMR (400 MHz, CDCl3): d 4.79 (q, 1H, J = 7.63 Hz), 7.349–7.47 (m, 6H), 7.56
(d, 2H, J = 7.50 Hz), 7.83 (dd, 2H, J1 = 1.70 Hz, J2 = 7.90 Hz), 8.37 (s, 1H); 13C
NMR (1 00 MHz, CDCl3): d 75.07 (q, J = 28.23 Hz), 124.67 (q, J = 280.76 Hz),
128.57, 128.65, 128.79, 128.91, 128.98, 131.66, 134.98, 135.31, 165.81; 19F
NMR (376.1 MHz, CFCl3): d À74.35 (d, 3F, J = 7.63 Hz).
Benzylidene-1-(4-fluorophenyl)-2,2,2-trifluoroethylamine (4b)
1H NMR (400 MHz, CDCl3): d 4.82 (q, 1H, J = 7.50 Hz), 7.12 (t, 2H, J = 8.70 Hz),
7.48 (m, 3H), 7.59 (dd, 2H, J = 5.60 Hz, J = 8.6 Hz), 7.88 (dd, 2H, J1 = 1.50 Hz,
J2 = 8.00 Hz), 8.41 (s, 1H); 13C NMR (100 MHz, CDCl3): d 74.37 (q, J = 28.60 Hz),
115.55 (d, J = 21.6 Hz), 124.50 (q, J = 280.60 Hz), 128.70, 128.81, 130.46 (d, 1H,
J = 8.2 Hz), 130.79, 131.79, 135.18, 163.00 (d, J = 247.70 Hz), 166.02; 19F NMR
(376.1 MHz, CFCl3): d À113.29 (d, 1F, J = 9.16 Hz), -74.63 (d, 3F, J = 7.63 Hz);
HRMS (EI) for: C15H11F4N calcd 281.0828, found 281.0813.
Benzylidene-1-(4-chlorophenyl)-2,2,2-trifluoroethylamine (4c)
13. (a) Ohkura, H.; Berbasov, D. O.; Soloshonok, V. A. Tetrahedron 2003, 59, 1647–
1656; (b) Nagy, P.; Ueki, H.; Berbasov, D. O.; Soloshonok, V. A. J. Fluorine Chem.
2008, 129, 409–415.
1H NMR (400 MHz, CDCl3): d 4.75 (q, 1H, J = 7.40 Hz), 7.41 (m, 7H), 7.82 (dd,
2H, J1 = 1.60 Hz, J2 = 8.00 Hz), 8.36 (s, 1H); 13C NMR (100 MHz, CDCl3): d 74.56
(q, J = 28.60 Hz), 124.51 (d, J = 281.20 Hz), 128.85, 128.94, 128.97, 130.22,
131.99, 133.55, 135.04, 135.25, 166.30; 19F NMR (376.1 MHz, CFCl3): d À74.51
14. Conolly, D. J.; Gresham, W. F. U.S. Patent 3282,875, 1966.
15. (a) Prakash, G. K. S.; Vaghoo, H.; Panja, C.; Molnár, A.; Mathew, T.; Olah, G. A.
Synthesis 2008, 897–902; (b) Prakash, G. K. S.; Mathew, T.; Mandal, M.; Farnia,
M.; Olah, G. A. ARKIVOC 2004, 103–110; (c) Olah, G. A.; Mathew, T.; Prakash, G.
K. S. Chem. Commun. 2001, 1696–1697; (d) Olah, G. A.; Mathew, T.; Farnia, M.;
Prakash, G. K. S. Synlett 1999, 1067–1068; (e) Prakash, G. K. S.; Mathew, T.;
Krishnaraj, S.; Marinez, E. R.; Olah, G. A. Appl. Catal. A: General 1999, 181, 283–
288; (f) Hachoumy, M.; Mathew, T.; Tongco, E. C.; Vankar, Y. D.; Prakash, G. K.
S.; Olah, G. A. Synlett 1999, 363–365; (g) Olah, G. A.; Shamma, T.; Prakash, G. K.
S. Catal. Lett. 1997, 46, 1–4; (h) Olah, G. A.; Torok, B.; Shamma, T.; Torok, M.;
Prakash, G. K. S. Catal. Lett. 1996, 42, 5–13; (i) Yamato, T.; Hideshima, C.;
Suehiro, K.; Tashiro, M.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 1991, 56,
6248–6250; (j) Yamato, T.; Hideshima, C.; Prakash, G. K. S.; Olah, G. A. J. Org.
Chem. 1991, 56, 3955–3957; (k) Yamato, T.; Hideshima, C.; Prakash, G. K. S.;
Olah, G. A. J. Org. Chem. 1991, 56, 3192–3194; (l) Yamato, T.; Hideshima, C.;
Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 1991, 56, 2089–2091; (m) Yamato, T.;
Hideshima, C.; Tashiro, M.; Prakash, G. K. S.; Olah, G. A. Catal. Lett. 1990, 6, 341–
344; (n) Olah, G. A.; Yamato, T.; Hashimoto, T.; Shih, J. G.; Trivedi, N.; Singh, B.
P.; Piteau, M.; Olah, J. A. J. Am. Chem. Soc. 1987, 109, 3708–3713; (o) Olah, G. A.;
Prakash, G. K. S.; Iyer, P. S.; Tashiro, M.; Yamato, T. J. Org. Chem. 1987, 52, 1881–
1884; (p) Olah, G. A.; Yamato, T.; Iyer, P. S.; Prakash, G. K. S. J. Org. Chem. 1986,
51, 2826–2828; (q) Olah, G. A.; Iyer, P. S.; Prakash, G. K. S. Synthesis 1986, 7,
513–531.
(d, 3F, J = 7.63 Hz); HRMS (EI) for: C15H11ClF3N calcd 297.0532, found
297.0520.
Benzylidene-1-(4-trifluoromethylphenyl)-2,2,2-trifluoroethyl-amine (4d)
1H NMR (400 MHz, CDCl3): d 4.84 (q, 1H, J = 7.40 Hz), 7.47 (m, 3H), 7.68 (dd,
4H, J1 = 8.30 Hz, J2 = 25.50 Hz), 7.84 (dd, 2H, J1 = 1.50 Hz, J2 = 8.00 Hz), 8.40 (s,
1H); 13C NMR (100 MHz, CDCl3):
d 74.71 (q, J = 28.80 Hz), 123.89 (q,
J = 272.30 Hz), 124.14 (q, J = 261.40 Hz), 125.48, 125.52, 128.74, 128.87,
129.21, 131.11 (q, J = 32.50 Hz), 131.97, 134.99, 138.77, 166.52; 19F NMR
(376.1 MHz, CFCl3): d À63.25 (s, 3F), À74.29 (d, 3F, J = 7.60 Hz).
Benzylidene-1-(4-methoxyphenyl)-2,2,2-trifluoroethylamine (4e)
1H NMR (400 MHz, CDCl3): d 3.81 (s, 3H), 4.75 (q, 1H, J = 7.70 Hz), 6.92 (d, 2H,
J = 8.90 Hz), 7.44 (m, 5H), 7.83 (dd, 2H, J1 = 1.60 Hz, J2 = 8.00 Hz), 8.37 (s, 1H);
13C NMR (100 MHz, CDCl3):d 55.29, 74.45 (q, J = 28.50 Hz), 113.98, 124.75 (q,
J = 280.80 Hz), 127.09, 128.66, 128.77, 129.91, 131.61, 135.39, 159.97, 165.54;
19F NMR (376.1 MHz, CFCl3): d À74.68 (d, 3F, J = 7.63 Hz); HRMS (EI) for:
C16H14F3NO calcd 293.1027, found 293.1034.
Benzylidene-1-(4-bromophenyl)-2,2,2-trifluoroethylamine (4f)
1H NMR (400 MHz, CDCl3): d 4.74 (q, 1H, J = 7.40 Hz), 7.46 (m, 7H), 7.82 (dd,
2H, J1 = 1.60 Hz, J2 = 8.10 Hz), 8.37 (s, 1H); 13C NMR (100 MHz, CDCl3): d 74.46
(q, J = 28.60 Hz), 123.11, 124.28 (q, J = 283.60 Hz), 128.70, 128.82, 130.38,
131.74, 131.84, 133.91, 135.08, 166.20; 19F NMR (376.1 MHz, CFCl3): d À74.51
(d, 3F, J = 7.63 Hz); HRMS (EI) for:
C15H11BrF3N calcd 341.0027, found
16. Mauritz, K. A.; Moore, R. B. Chem. Rev. 2004, 104, 4535–4585.
17. Hsu, W. Y.; Gierke, T. D. J. Membr. Sci. 1983, 13, 307–326.
18. Soloshonok, V. A.; Yasumoto, M. J. Fluorine Chem. 2006, 127, 889–893.
19. Harmer, M. A.; Farneth, W. E.; Sun, Q. J. Am. Chem. Soc. 1996, 118, 7708–7715.
20. Harmer, M. A.; Sun, Q.; Vega, A. J.; Farneth, W. E.; Heidekum, A.; Hoelderich, W.
F. Green Chem. 2000, 7–14.
21. Typical procedure for the synthesis of substituted imines: A solution of 2,2,2-
trifluoroacetophenone 2a (2 mmol, 0.348 g) in toluene (1 mL) was taken in a
pressure tube containing 0.10 g of Nafion-H SAC 13. To this mixture, a solution
of benzylamine (1a, 3 mmol, 0.321 g) in toluene (1 mL) was slowly added with
stirring. The mixture was supplemented with another 1 mL of toluene, closed
and heated slowly to 185 °C. The reaction was then monitored by 19F NMR and
GC–MS. Upon completion, the mixture was allowed to cool to room
temperature, 50 mL of dichloromethane was added and the mixture was
filtered. The filtrate was then concentrated under vacuum and purified by flash
column chromatography using a mixture of n-hexane and ethyl acetate (9:1).
The solvent was removed in a rotary evaporator and the product benzylidene-
341.0026.
Benzylidene-1-(p-tolyl)-2,2,2-trifluoroethylamine (4g)
1H NMR (400 MHz, CDCl3): d 2.32 (s, 3H), 4.74 (q, 1H, J = 7.60 Hz), 7.17 (d, 2H,
J = 7.90 Hz), 7.39 (m, 5H), 7.80 (dd, 2H, J1 = 1.60 Hz, J2 = 7.90 Hz), 8.32 (s, 1H);
13C NMR (100 MHz, CDCl3):
d 21.26, 74.77 (q, J = 28.40 Hz), 124.92 (q,
J = 280.80 Hz), 128.75, 128.87, 129.42, 131.71, 132.17, 135.50, 138.91,
165.76; 19F NMR (376.1 MHz, CFCl3): d À74.38 (d, 3F, J = 7.63 Hz); HRMS (EI)
for: C16H14F3N calcd 277.1078, found 277.1082.
Benzylidene-1-(3-trifluoromethylphenyl)-2,2,2-trifluoroethyl-amine (4h)
1H NMR (400 MHz, CDCl3): d 4.83 (q, 1H, J = 7.40 Hz), 7.46 (m, 4H), 7.62 (d, 1H,
J = 7.80 Hz), 7.78 (d, 1H, J = 7.70 Hz), 7.85 (m, 3H), 8.40 (s, 1H); 13C NMR
(100 MHz, CDCl3): d 74.96 (q, J = 28.70 Hz), 124.09 (q, J = 272.30 Hz), 124.38 (q,
J = 269.20 Hz), 125.80 (m), 125.97 (q, J = 3.70 Hz), 128.91, 129.07, 129.27,
131.16 (q, J = 32.51 Hz), 132.34, 132.49, 135.17, 136.09, 166.76; 19F NMR
(376.1 MHz, CFCl3): d À69.10 (s, 3F), -74.45 (d, 3F, J = 7.40 Hz); HRMS (EI) for:
C16H11F6N calcd 331.0796, found 331.0790.
Benzylidene-1-(2-thiophenyl)-2,2,2-trifluoroethylamine (4i)
1-phenyl-2,2,2-trifluoroethylamine 4a, was obtained as
(0.432 g, 82%).
a
pale yellow oil
1H NMR (400 MHz, CDCl3): d 5.11 (q, 1H, J = 7.20 Hz), 7.04 (dd, 1H, J1 =3.60 Hz,
J2 = 5.10 Hz), 7.19 (d, 1H, J = 3.60 Hz), 7.35 (dd, 1H, J1 = 1.20 Hz, J2 = 5.10 Hz),
7.45 (m, 3H), 7.83 (dd, 2H, J1 = 1.50 Hz, J2 = 8.10 Hz), 8.37 (s, 1H); 13C NMR
(100 MHz, CDCl3): d 70.59 (q, J = 30.00 Hz), 123.98 (q, J = 280.80 Hz), 126.66,
126.74, 126.93, 128.68, 128.89, 131.88, 134.98, 136.26, 166.34; 19F NMR
(376.1 MHz, CFCl3): d À74.95 (d, 3F, J = 7.63 Hz); HRMS (EI) for: C13H10F3NS
calcd 269.0486, found 269.0480.
Typical procedure for the hydrolysis of substituted imines: Benzylidene-1-phenyl-
2,2,2-trifluoroethylamine 4a (1 mmol, 0.2723 g) was first dissolved in 2 mL of
diethyl ether and placed in a small vial. Hydrochloric acid (3 N, 5 mL) was
slowly added after which the vial was closed and stirred for 24 h. Upon
completion (as determined by TLC) the reaction mixture was added to ice
water (10 mL) and then washed with diethyl ether (2 Â 30 mL). The excess acid