Methyl 3,3,3-trifluoropyruvate hemiaminals: Stability and transaminations

Article abstract of DOI:10.1016/j.jfluchem.2005.02.020

Hemiaminals of methyl 3,3,3-trifluoropyruvate with aromatic amines, benzylic monoamines and diamines were prepared and their interconversions studied using NMR spectrometry. In solution, benzylic hemiaminals were found to be stable in contrast to aromatic hemiaminals, which, in turn, were stable in the solid state.

Full text of DOI:10.1016/j.jfluchem.2005.02.020

Journal of Fluorine Chemistry 126 (2005) 745–751
www.elsevier.com/locate/fluor
Methyl 3,3,3-trifluoropyruvate hemiaminals:
Stability and transaminations
*
´
´ˇ ˇ
Bohumil Dolensky, Jaroslav Kvıcala, Oldrich Paleta
´
Department of Organic Chemistry, Institute of Chemical Technology, Technicka 5, 166 28 Prague 6, Czech Republic
Received 22 December 2004; received in revised form 14 February 2005; accepted 15 February 2005
Available online 19 April 2005
Abstract
Hemiaminals of methyl 3,3,3-trifluoropyruvate with aromatic amines, benzylic monoamines and diamines were prepared and their
interconversions studied using NMR spectrometry. In solution, benzylic hemiaminals were found to be stable in contrast to aromatic
hemiaminals, which, in turn, were stable in the solid state.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Methyl 3,3,3-trifluoropyruvate; Methyl 3,3,3-trifluoro-2-oxopropanoate; Hemiaminal equilibrium; Trifluoromethyl synthon
1. Introduction
enables MeTFP to form relatively stable hemiketals and/or
hemiaminals.
The building block strategy using simpler fluorinated
compounds, which are relatively easily accessible and
display appropriate reactivity, has been one of general ways
for the introduction of fluoro substituents in target
molecules. Methyl 3,3,3-trifluoropyruvate (1, MeTFP) can
be included in the pool of fluorinated building blocks. Two
reaction centers in MeTFP, i.e. the carbonyl and ester
groups, predetermine it for the syntheses of trifluoromethy-
lated heterocyclic compounds [1–3]. MeTFP has also been
used for the preparation of acyclic compounds as
trifluoromethylated amino acids and peptides [4,5].
MeTFP forms hemiaminal compounds 3 by a non-
catalysed nucleophilic addition of primary aliphatic amines
or amides to the carbonyl group [7–10]. However, the
adducts, hemiaminals 3, have been characterised or isolated
only in particular cases, viz. methylamine [7] and
benzylamine [8] hemiaminals. The hemiaminals prepared
from carboxamides [11–13] were applied in the syntheses of
trifluoromethylated amino acid analogues and peptides
[4,5]. Primary sulfonamides [14,15] and carbamates
[14,16,17] react in an analogous way (Scheme 2).
Aromatic amines react with MeTFP in a more complex
way to form four types of products (A–D, Scheme 3)
depending on amine structure and reaction conditions.
Hemiaminals A, i.e. the products of N-alkylations, are
formed only with primary aromatic amines. The hemiaminal
of aniline with MeTFP has been mentioned in several papers
[18–20], but was not completely characterised and has been
considered as unstable compound that slowly rearranged
[21] to the products of ortho- and/or para-C-hydroxyalk-
ylations (B and C). The mechanism of the formation of the
rearranged products of C-hydroxyalkylations has not been
established so far. A recent theoretical study [22] has also
not given a satisfactory explanation. On the other hand,
The reactivity of MeTFP and that of its non-fluorinated
analogue, methyl pyruvate, differ considerably. The reason
is, as characterised by the Taft sI constants [6], a strongly
electron-withdrawing trifluoromethyl group in MeTFP
molecule, which is in a sharp contrast to the electron-
donating methyl group [6] in methyl pyruvate (Scheme 1).
The trifluoromethyl group thus significantly increases the
electrophilicity of the oxo group in MeTFP. This property
* Corresponding author. Tel.: +420 22435 4284; fax: +420 22435 4288.
E-mail address: oldrich.paleta@vscht.cz (O. Paleta).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.02.020

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
746
Scheme 1. Comparison of inductive effects in MeTFP and methyl pyruvate
using Taft sI constants.
Scheme 2. Reactions of MeTFP (1) with nitrogen nucleophiles to form
hemiaminals 3.
hemiaminals of aromatic amines A possessing an electron-
withdrawing group, e.g. hemiaminal of 4-methyl-2-nitroani-
line [18], did not rearrange at all. Hemiaminals of amines
bearing alkylated ortho- and para-positions as 2,4,6-
trimethylaniline [20] did not rearrange either. In particular
cases, the products of the ortho-hydroxyalkylations C
underwent lactamisation to form indolinones D [18,19].
We have studied the formation and stability of particular
hemiaminals of MeTFP, including diamines, in the context
of their usage as potential building blocks. We report our
observations in this paper. Some of these hemiaminals have
been applied in the syntheses of trifluoromethylated
analogues of the alkaloid Peganine [23].
Scheme 4. Reactions of MeTFP (1) with primary aromatic and benzylic
amines.
prepared (Scheme 4) to obtain their NMR characteristics for
monitoring equilibration and competitive reactions (vide
infra). The hemiaminals 4–7 were formed immediately and
quantitatively after mixing the reagents. The compounds 4
and 5 are stable and can be purified by crystallization while
the compounds 6 and 7 are unstable in solution and
spontaneously undergo a rearrangement, which is probably
of electrophilic character, to afford the corresponding
products 8 [21] and 9 of C-hydroxyalkylation (Scheme
4). A special procedure for the preparation and isolation of
the hemiaminal 6 was applied to isolate it in a crystalline
form. In contrast to the literature information [21],
crystalline 6 appears to be stable under inert atmosphere.
Hemiaminal 7 rearranges much more rapidly in solution
than hemiaminal 6 and therefore we failed to isolate it. Its
presence in the reaction mixture was confirmed only by
NMR but the product 9 of its subsequent rearrangement was
completely characterised. Instability of hemiaminal 7 is
obviously caused by the presence of the methyl group at the
aromatic ring increasing its reactivity toward electrophiles.
This assumption of the probable electrophilic character of
the rearrangement has been supported by the recent
publication on the application of MeTFP as an electrophilic
reagent [24].
2. Results and discussion
2.1. Hemiaminals of anilines and benzylic monoamines
Hemiaminals of MeTFP with benzylamine (4), benzhy-
drylamine (5), aniline (6) and 2-methylaniline (7) were
Scheme 3. Types of the products formed by the reaction of MeTFP (1) with
arylamines.

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
747
2.2. Equilibria of the reactions of methyl 3,3,
3-trifluoropyruvate with monoamines
In the reaction of MeTFP with a diamine bearing two
amino groups of different nucleophilicity, e.g. 2-amino-
benzylamine, a hemiaminal can be formed potentially at
aromatic or benzylic amino groups. To estimate the
regioselectivity of the addition, some competitive reac-
tions were carried out. The reaction of the mixture of
benzylamine and aniline or 2-methylaniline led immedi-
ately to the hemiaminal of benzylamine (4). Analogously,
the mixture of benzhydrylamine and aniline or 2-
methylaniline afforded the hemiaminal of benzhydryla-
mine (5) immediately after mixing with MeTFP. The
formation of the products of both reactions was very
probably under kinetic control.
Scheme 6. Transamination reactions of aromatic hemiaminals 6 and 7 (1).
The question has arisen whether the products 4 and 5
can be formed also under thermodynamic control from the
less stable hemiaminals 6 and 7 formed from aromatic
amines, i.e. by
a nucleophilic substitution at the
hemiaminal carbon. In the experiments (Scheme 6),
benzylic amines were added in parts to the solutions
of hemiaminal 6 or 7. As a result, the products 4 or 5
1
were formed rapidly (the reactions were followed by H
Scheme 7. Equilibrium reaction of hemiaminal 4 with water.
and/or 19F NMR). The experiments depicted in Schemes 5
and 6 revealed that the more stable hemiaminals of
benzylic amines are formed under thermodynamic
control.
2.4. Reactions of methyl 3,3,3-trifluoropyruvate with
diamines
2.3. Equilibrium of the reactions of benzyl hemiaminal
4 with water
2.4.1. Reaction with propane-1,3-diamine
Propane-1,3-diamine forms the corresponding stable
mono-hemiaminal 11 (Scheme 8) together with a small
portion of bis-hemiaminal 12 (as a mixture of diastereoi-
somers 12a and 12b) immediately after mixing with MeTFP.
Bis-hemiaminal 12 is stable in diluted solution, but during
isolation while increasing its concentration in the solution, a
precipitate of 13 insoluble in common organic solvents, is
formed. The substance 13 is probably a polymer of a
polyamide type as indicated by its IR spectrum.
The stability of hemiaminal 4 towards water as a
nucleophile was tested under equilibrium conditions
(Scheme 7); water was portionwise added to the solution
of hemiaminal 4 in DMSO-d6 and the ratio of 4 and
trifluoropyruvate hydrate 10 was checked repeatedly
during 24 h to verify whether the equilibrium was
established. It usually occurred within several minutes.
The equilibrium constant was calculated on the basis of
these measurements as 3 ꢀ 10ꢁ4. The equilibrium data
have revealed that hemiaminal 4 is practically stable in an
aqueous solution.
Scheme 5. Competition of benzylic and aromatic primary amines for
Scheme 8. Reaction of propane-1,3-diamine with MeTFP (1) and probable
polymer 13.
MeTFP (1).

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
748
Scheme 10. Transformation of naphthalene-1,8-diamine to tetracyclic het-
erocycle 19 using MeTFP (1) and acetone.
CaCl2 and KOH and under argon atmosphere. The H, 19F
and 13C NMR spectra were recorded at frequencies of 300,
282 and 76 MHz, respectively, on Varian Gemini 300 HC.
Chemical shifts (d) are given in ppm relatively to TMS for
1H or 13C and to CFCl3 for 19F NMR. The interaction
constants (J) are given in Hz and if not mentioned otherwise
JHH is presented. CDCl3 was used as a solvent if not
mentioned otherwise. MS spectra were observed on a
Hewlett-Packard MSD 5971A instrument (1989, EI 70 eV).
Infrared spectra in KBr pellets were scanned on a NICOLET
740 USA apparatus. All reagents were purchased from
Sigma–Aldrich and used without additional purifications
with the exception of aniline. The solvents were purified and
dried according to standard procedures.
1
Scheme 9. Different reaction of MeTFP (1) and methyl pyruvate with
2-aminobenzylamine.
2.4.2. Reaction with 2-aminobenzylamine
2-Aminobenzylamine (14) affords the expected stable
hemiaminal 15 immediately after mixing with MeTFP
(Scheme 9). The reaction takes place at the more
nucleophilic benzylic amino group (see Section 2.1) with
complete regioselectivity. As depicted in Scheme 9, the
reactivity of the non-fluorinated analogue of MeTFP, methyl
pyruvate, differs from that of MeTFP: methyl pyruvate
affords cyclic aminal 16 when reacted with 2-aminobenzy-
lamine.
2.4.3. Reaction with naphthalene-1,8-diamine
Naphthalene-1,8-diamine affords unstable mono-hemi-
aminal 17 immediately after mixing with MeTFP
(Scheme 10). The compound 17 is much less stable than
the hemiaminal of 2-methylaniline (7, see Section 2.1),
therefore its presence in the mixture could be confirmed only
by 19F NMR spectroscopy in a mixture. It is converted by an
intramolecular reaction spontaneously into the product of
the ortho-C-alkylation (type C, Scheme 3), which subse-
quently forms the lactam ring to afford the indolinone
derivative 18 analogously to naphthalene-1-amine [18] (type
D, Scheme 3). Indolinone 18 absorbed carbon dioxide as
verified by elemental analysis. Therefore, it was reacted with
acetone to give stable tetracyclic aminal 19, which was
completely characterised.
3.1. Reaction of MeTFP with aniline: methyl 2-anilino-
3,3,3-trifluoro-2-hydroxypropanoate (6)
A flask immersed in an ice bath was charged with diethyl
ether (10 mL) and aniline (0.44 g, 4.7 mmol). MeTFP
(1.80 g, 11.5 mmol) was then distilled from another flask
into the reaction mixture, followed by stirring the mixture
for 1 h. MeTFP was then removed from the mixture by
distillation (oil bath, 140 8C) and the concentrated solution
of the product 6 was immediately evaporated to dryness in
vacuum on rotary evaporator to afford hemiaminal 6 (1.16 g,
100%) as a white solid, m.p. 66–68 8C. The compound was
immediately subjected to spectral measurements and
analyses and stored in a refrigerator.
1H NMR (CDCl3): d 7.23 (2H, dd, 7.5, 8.5), 6.97 (1H, tt,
1.0, 7.4), 6.88 (2H, dd, 1.0, 8.2), 4.64 (1H, bs, temp), 4.48
(1H, bs, temp), 3.85 (3H, s). 13C NMR (CDCl3): d 168.0,
141.0, 128.5 (2 ꢀ CH), 121.3 (CH), 121.2 (q, 1JCF = 288.5),
3. Experimental
2
General comments: The temperature data were not
corrected. All reactions were performed in a well-dried
distillation apparatus closed by a drying tube filled up with
117.1 (2 ꢀ CH), 83.7 (q, JCF = 31.6), 53.9. 19F NMR: d
ꢁ80.0 (s). LRMS (EI) (relative intensity, %): 249 (21, M+),
210 (2), 190 (66), 180 (5), 120 (70), 93 (84), 92 (20), 78 (3),

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
749
69 (100), 66 (20), 65 (20), 59 (98), 50 (11). Anal. calc. for
C10H10F3NO3: C, 48.2%; H, 4.05%; N, 5.6%; F, 22.9%.
Found: C, 47.7%; H, 4.15%; N, 5.65%; F, 23.5%.
MeTFP (0.61 g, 3.9 mmol) in dry Et2O (5 mL) was then
added dropwise while stirring. After 10 min, the mixture was
evaporated to dryness to obtain 0.84 g (70%) of pure
hemiaminal 5 (check by 1H NMR), m.p. 52–55 8C (hexane).
1H NMR: d 7.37–7.19 (10H, m), 5.21 (1H, d, 3.2, temp),
4.31 (1H, bs, temp), 3.32 (3H, s), 2.78 (1H, bd, 2.8, temp).
13C NMR: d 168.8, 143.5, 141.7, 128.7 (2 ꢀ CH), 128.3
(4 ꢀ CH), 127.5 (CH), 127.3 (CH), 127.2 (2 ꢀ CH), 122.2
3.2. Reaction of MeTFP with 2-methylaniline
(products 7 and 9)
Method A: The same procedure as that for 6—2-
methylaniline (0.30 g, 2.8 mmol), MeTFP (1.10 g, 7.0 mmol)
and diethyl ether (15 mL). After evaporation, an oily
compound was obtained. The NMR analysis showed that
the mixture contained 55% of hemiaminal 7 and 45% of the
product of the subsequent p-C-hydroxyalkylation, lactam 9.
Method B: A NMR tube was charged with CDCl3 (1 mL),
MeTFP (0.25 g, 1.6 mmol) and a solution of 2-methylaniline
(0.18 g, 1.7 mmol) in CDCl3 (1 mL) was added in three
1
2
(q, JCF = 286.8), 84.8 (q, JCF = 31.4), 59.3 (CH), 53.7
(CH3). 19F NMR: d ꢁ81.1 (s). Anal. calc. for C17H16F3NO3:
C, 60.2%; H, 4.75%; N, 4.15%; F, 16.8%. Found: C, 60.05%;
H, 4.7%; N, 4.2%; F, 17.1%.
3.4. Reaction of MeTFP with benzylamine: methyl 2-
(benzyl)amino-3,3,3-trifluoro-2-hydroxypropanoate (4)
1
portions. After each addition, the H, 19F and 13C NMR
The same procedure as that for 5: MeTFP (0.25 g,
1.6 mmol) and benzylamine (0.17 g, 1.5 mmol) afforded
spectra were recorded to obtain the NMR signals of
hemiaminal 7. The progress of the subsequent rearrangement
of 7, which was followed by 19F NMR, was completed in 13
days. The reaction mixture was then evaporated to dryness to
obtain 452 mg of a yellow solid, which was purified on
chromatographic column (silica gel, 2 g, chloroform) to
afford 0.27 g (63%) of 9 as white solid, m.p. 141.5–142 8C.
1
0.33 g (81%) of pure hemiaminal 4 (check by H NMR),
m.p. 54–57 8C.
1H NMR: d 7.22–7.37 (5H, m), 4.51 (1H, bs, temp), 3.95
(1H, d, 12.9), 3.81 (3H, s), 3.70 (1H, d, 12.9), 2.46 (1H, bs,
temp). 13C NMR: d 168.9, 138.5, 128.5 (2 ꢀ CH), 128.3
1
(2 ꢀ CH), 127.5 (CH), 122.2 (q, JCF = 287.6), 85.4 (q,
2JCF = 31.2), 54.3 (CH3), 45.9 (CH2). 19F NMR: d ꢁ80.5 (s).
LRMS (EI) (relative intensity, %): 204 (2, M+ ꢁ 59), 195
(1), 194 (1), 129 (3), 115 (4), 107 (66), 106 (88), 99 (8), 97
(7), 91 (35), 79 (33), 78 (18), 77 (19.5), 69 (100), 65 (7), 60
(5), 59 (92), 53 (6), 52 (6), 51 (17), 50 (17). Anal. calc. for
C11H12F3NO3: C, 50.2%; H, 4.6%. Found: C, 50.0%; H,
4.9%.
Methyl 3,3,3-trifluoro-2-hydroxy-2-[(2-methylphenyl)ami-
no]propanoate (7)
1H NMR: d 7.11 (1H, d, 7.7), 7.05 (1H, t, 7.7), 6.90 (1H,
d, 7.7), 6.86 (1H, t, 7.7), 4.66 (2H, bs), 3.97 (3H, s), 2.23
(3H, s). 13C NMR: d 168.7, 140.1, 130.6 (CH), 128.8 (CH),
125.9, 121.9 (quin, 1JCF = 288.6), 121.6 (CH), 115.8 (CH),
2
84.5 (q, JCF = 31.5), 54.5, 17.2. 19F NMR: d ꢁ81.1 (s).
3.5. Competitive reactions
Methyl 2-(4-aminophenyl)-3,3,3-trifluoro-2-hydroxypro-
panoate (9)
A flask (10 mL) was charged with dry Et2O (2 mL), 1 M
equivalent of aniline or 2-methylaniline (1.7 mmol) and 1 M
equivalent of benzylamine or benzhydrylamine (1.7 mmol).
A solution of MeTFP (0.5 M equivalent) was then added to
1H NMR: d 7.40 (1H, s), 7.38 (1H, d, 8.7), 6.65 (1H, d,
8.3), 3.93 (3H, s), 3.78 (3H, bs, temp), 2.17 (3H, s). 13C
NMR: d 169.9, 145.76, 128.7 (CH), 125.5 (CH), 123.2 (q,
1JCF = 285.5), 122.4, 121.9, 114.5 (CH), 77.7 (q,
2JCF = 32.8), 54.2 (CH3), 17.4 (CH3). 13C dec-off NMR:
169.9 (q, JCH = 4.0), 145.76 (m), 128.7 (dm, 1JCH = 157.8),
125.5 (dd, JCH = 6.8, 1JCH = 160.8), 123.2 (q, 1JCF = 285.5),
122.4 (d, JCH = 8.5), 121.9 (qui, JCH = 5.6), 114.5 (d,
1
the mixture in three portions while stirring. The H and/or
19F NMR spectra of the mixture were recorded immediately
after adding each portion of the MeTFP solution. After the
addition of the last portion of MeTFP, only the hemiaminal
of the more reactive amine was detected: benzylami-
ne ꢂ aniline, benzylamine ꢂ 2-methylaniline, benzhydry-
lamine ꢂ aniline and benzhydrylamine ꢂ 2-methylaniline.
1
1JCH = 156.5), 77.7 (m), 54.2 (q, JCH = 149.0), 17.4 (dq,
J
CH = 5.1, 1JCH = 126.5). 19F NMR: d ꢁ77.1 (s). IR (KBr):
1751 (s). LRMS: 263 (33, M+), 224 (2), 205 (12), 204 (100),
195 (1), 194 (9), 135 (9), 134 (90), 107 (48), 106 (26), 79
(10), 78 (6), 77 (11), 69 (2), 67 (7), 65 (2), 59 (6), 53 (7), 50
(2). Anal. calc. for C11H12F3NO3: N, 5.3%. Found: N, 5.2%.
3.6. Substitution reactions
(a) In a NMR tube, benzylamine (72 mg, 0.67 mmol) was
dissolved in CDCl3 (0.5 mL) and solid hemiaminal 6
(0.17 g, 0.69 mmol) was added in three portions. After
each addition, the 19F NMR was recorded and
immediate formation of hemiaminal 4 was detected.
(b) In a NMR tube, hemiaminal 7 was generated by mixing
the solution of MeTFP (0.10 g, 0.64 mmol) in CDCl3
(0.3 mL) and 2-methylaniline (68 mg, 0.64 mmol) in
3.3. Reaction of MeTFP with benzhydrylamine:
methyl 2-(diphenylmethyl)amino-3,3,
3-trifluoro-2-hydroxypropanoate (5)
A flask (25 mL) was charged with benzhydrylamine
(0.65 g, 3.5 mmol) and dry Et2O (5 mL). A solution of

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
750
CDCl3 (0.3 mL). A solution of benzhydrylamine
dryness to obtain 1.12 g (98%) of pure hemiaminal 15
(check by H NMR), m.p. 69.5–70.5 8C (cyclohexane).
1
(0.12 g, 0.64 mmol) in CDCl3 (0.3 mL) was then added
immediately in two equal portions. 1H NMR was
recorded after each addition, which confirmed immedi-
ate formation of hemiaminal 5.
Methyl 2-(2-aminobenzylamino)-3,3,3-trifluoro-
2-hydroxypropanoate (15)
(c) In a NMR tube, hemiaminal 4 (152 mmol) was
dissolved in CD3SOCD3 (0.5 mL) then water or
benzylamine were added and the ratio of hemiaminal
4 to hydrate of MeTFP (HTFP) 10 was determined by
19F NMR. Mixtures: (1) 40 mmol of benzylamine (in the
form of hemiaminal 4) and 5.5 mol of water, the
observed ratio of 4:10 was 87:13; (2) 40 mmol of 4 and
11.0 mol of H2O, the ratio was 14:86; (3) 40 mmol of 4
and 16.5 mol of H2O, the ratio was 13:87; (4)
243.3 mmol of 4 and 16.5 mol of H2O, the ratio was
71:29. The equilibrium constant of 3 ꢀ 10ꢁ4 was
calculated from these data.
1H NMR: d 7.11 (1H, td, 7.7, 1.4), 7.00 (1H, d, 7.2), 6.72–
6.66 (2H, m), 4.42 (3H, bs, temp), 3.91 (1H, dd, 12.1, 3.9,
temp), 3.84 (3H, s), 3.60 (1H, dd, 12.1, 8.2, temp), 2.37 (1H,
dd, 8.2, 3.9, temp). 13C NMR: d 168.5, 146.5, 130.3 (CH),
129.2 (CH), 122.0 (q, 287.4), 121.8, 118.1 (CH), 116.0
(CH), 85.3 (q, 31.3), 54.5 (CH3), 44.4 (CH2). 19F NMR: d
ꢁ81.0 (s). Anal. calc. for C11H13F3N2O3: C, 47.5%; H,
4.7%; N, 10.05%; F, 20.5%. Found: C, 47.8%; H, 4.9%; N,
9.9%; F, 20.45%.
3.9. Reaction of MeTFP with naphthalene-1,
8-diamine (products 17 and 18)
3.7. Reaction of MeTFP with propane-1,3-diamine
A solution of MeTFP (0.28 g, 1.8 mmol) in dry Et2O
(4 mL) was added dropwise to the stirred solution of
naphthalene-1,8-diamine (0.29 g, 1.8 mmol) in dry Et2O
(4 mL). Immediately recorded 19F NMR spectrum showed
the presence of hemiaminal 17 and indolinone 18. After 1 h,
the content of indolinone 18 was 55 mol% and after
additional 36 h, the complete conversion of hemiaminal 17
to indolinone 18 was observed. The mixture was then
evaporated to dryness to afford a solid residue (0.41 g),
which was purified by precipitation from methanol by
chloroform to obtain 0.23 g (44%) of light brown crude
indolinone 18, m.p. 191–194 8C. A part of the solid was
dried in vacuum (0.13 kPa) at 60 8C and subjected to all
analyses. The second part (112 mg) was dissolved in acetone
(15 mL) and dried over MgSO4. After 16 days, the solution
was filtered and evaporated to dryness to obtain 0.13 g of a
yellow solid, which was purified on a chromatographic
column (silica gel, 21 g, dichloromethane:acetone 95:5) to
afford 0.10 g (81%) of pure 19 as yellow crystals, m.p. 163–
165 8C (petroleum ether).
A flask (2 L) was charged with dry Et2O (900 mL),
propane-1,3-diamine (0.17 g, 2.3 mmol) and a solution of
MeTFP (0.36 g, 2.3 mmol) in dry Et2O (100 mL) was added
at room temperature while stirring. The immediate 19F NMR
analysis showed the presence of hemiaminal 11, and bis-
hemiaminal diastereoisomers 12a and 12b in a ratio of 6:2:2
in the reaction mixture. The same ratio was observed after 30
days keeping the mixture at room temperature. The mixture
was then evaporated to dryness under vacuum without bath
to afford polymeric 13 (0.39 g) as a white solid insoluble in
common organic solvents.
Methyl 2-(3-aminopropyl)amino-3,3,3-trifluoro-2-
hydroxypropanoate (11)
19F NMR: d ꢁ81.4 (s).
Dimethyl-3,3,3,30,30,30-hexafluoro-2,20-dihydroxy-
(1,3-propandiyldiamino)dipropanoate (13)
Diastereoisomer (12a)
19F NMR: d ꢁ80.8 (s).
Diastereoisomer (12b)
Methyl 2-[(8-aminonaphthalene-1-yl)amino]-3,3,
3-trifluoro-2-hydroxypropanoate (17)
19F NMR: d ꢁ80.9 (s).
Polymeric compound (13)
19F NMR: d ꢁ81.0 (s).
IR (KBr): 3324 m, 3280 m, 2967 w, 2945 w, 2907 w, 1675
s, 1550 m, 1491 w, 1443 w, 1384 w, 1306 w, 1273 m, 1252 m,
1209 s, 1180 s, 1122 s, 1067 w, 995 w, 840 w, 767 w, 711 w.
Anal. calc. for decamer C61H94F30N20O21: C, 36.4%; H,
4.7%; N, 13.9%; F, 28.3%. Found: C, 35.6%; H, 4.75%; N,
13.9%; F, 25.8%.
9-Amino-3-hydroxy-3-(trifluoromethyl)-1,
3-dihydrobenzo[g]indol-2-one (18)
19F NMR: d ꢁ79.6 (s). 1H NMR: d 7.51 (1H, d, 8.4), 7.45
(1H, dd, 8.4, 0.5), 7.33 (1H, dd, 8.2, 1.0), 7.28 (1H, dd, 8.2,
7.3), 6.91 (1H, dd, 7.2, 1.1). 13C APT NMR: d 175.2, 144.6,
1
140.6, 138.6, 129.0 (CH), 125.0 (q, JCF = 284.4), 124.0
(CH), 122.9 (CH), 121.9 (CH), 119.8, 116.3 (CH), 115.6,
some signals did not appear. IR: 3361 w, 3306 w, 3242 w,
1727 s, 1636 w, 1614 w, 1587 w, 1457 w, 1424 m, 1273 m,
1257 m, 1202 m, 1188 m, 1179 m, 1163 m, 1144 m, 994 w,
942 w, 886 w, 861 w, 835 w, 828 w, 791 w, 763 w, 730 w, 691
w, 654 w, broad bands in region 2400–3000 can be assigned
to absorbed CO2. Anal. calc. for crude C13H9F3N2O2 + CO2:
C, 51.55%; H, 2.8%; N, 8.6%; F, 20.5%. Found: C, 51.0%;
3.8. Reaction of MeTFP with 2-aminobenzylamine
(product 15)
A flask (50 mL) was charged with 2-ABA (0.51 g,
4.2 mmol) and dry Et2O (15 mL) and a solution of MeTFP
(0.64 g, 4.1 mmol) in dry Et2O (5 mL) was added dropwise
while stirring. After 15 min, the mixture was evaporated to

´
B. Dolensky et al. / Journal of Fluorine Chemistry 126 (2005) 745–751
751
[6] O. Exner, Correlation Equations in Organic Chemistry, SNTL/ALFA,
Praha, 1981 (Chapter 6) (in Czech).
H, 3.0%; N, 8.9%; F, 20.45%. Anal. calc. after drying for
C13H9F3N2O2: C, 55.35%; H, 3.2%; N, 9.95%. Found: C,
54.8%; H, 3.65%; N, 9.7%.
[7] V.I. Saloutin, I.A. Piterskikh, K.I. Pashkevich, Izv. Akad. Nauk SSSR
Ser. Khim. (1986) 625–634.
[8] V.A. Soloshonok, Y.L. Yagupolskii, V.P. Kukhar, Zh. Org. Khim. 24
(1988) 1638–1644.
4-Hydroxy-2,2-dimethyl-4-trifluoromethyl-1,2,3,4-tetrahy-
droindolo[1,7a,7,6-c,d,e]quinazolin-3-one (19)
[9] A.S. Golubiev, N.D. Tschkanikov, M.Y. Antipin, Y.T. Strushkov, A.F.
Kolomiets, A.V. Fokin, Izv. Akad. Nauk SSSR Ser. Khim. (1992)
1831–1836.
1H NMR: d 7.54 (1H, d, 8.3), 7.49 (1H, d, 8.2), 7.40 (1H,
dd, 8.3, 7.7), 7.29 (1H, d, 8.2), 6.64 (1H, d, 7.1), 3.94 (1H,
bs), 1.95 (3H, s), 1.67 (3H, s), 0.66 (1H, bs). 13C NMR: d
172.1, 137.7, 137.3, 136.6, 129,7 (CH), 122.5 (CH), 123.1
[10] (a) V.I. Dyatchenko, A.F. Kolomiets, A.V. Fokin, Zh. Org. Khim. 28
(1992) 1684–1692;
(b) V.I. Dyatchenko, A.F. Kolomiets, A.V. Fokin, Izv. Akad. Nauk
SSSR Ser. Khim. (1991) 1708–1713.
1
(q, JCF = 285.7), 121.3 (CH), 117.5 (CH), 112.2, 109.3,
106.9 (CH), 77.5 (q, 2JCF = 32.1), 70.2, 26.9, 26.3. IR: 3390
m, 1724 s, 1653 w, 1607 m, 1443 w, 1191 s, 1172 s, 1135 m.
Anal. calc. for C16H13F3N2O2: C, 59.6%; H, 4.1%; N, 8.7%.
Found: C, 59.3%; H, 4.4%; N, 8.7%.
[11] V.I. Saloutin, I.A. Piterskikh, K.I. Pashkevich, M.I. Kodess, Izv. Akad.
Nauk SSSR Ser. Khim. (1983) 2568–2575.
[12] N.D. Tchkanikov, V.D. Sviridov, A.E. Zelenin, V.Y. Tyutin, A.F.
Kolomiets, A.V. Fokin, Izv. Akad. Nauk SSSR Ser. Khim. (1992)
1820–1830.
[13] (a) K. Burger, K. Gaa, Chem.-Ztg. 114 (1990) 101–104;
(b) D. Matthies, S. Siewers, Liebigs Ann. Chem. (1992) 159–
161;
Acknowledgements
(c) N. Sewald, L.C. Seymour, K. Burger, S.N. Osipov, A.F. Kolomiets,
A.V. Fokin, Tetrahedron Asymmetry 5 (1994) 1051–1060.
[14] V.A. Soloshonok, I.I. Geruts, Y.L. Yagupolskii, V.P. Kukhar, Zh. Org.
Khim. 23 (1987) 2308–2313.
The research was supported by the Grant Agency of the
Czech Republic (Project 203/02/0306) and partly by the
Ministry of Education of the Czech Republic (Project MSM
223100001).
[15] (a) S.N. Osipov, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1989) 1648–1652;
(b) S.N. Osipov, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1986) 1384–1387.
[16] E. Dessipri, D.A. Tirrell, Macromolecules 27 (1994) 5463–5470.
References
¨
[17] (a) K. Burger, E. HoS, K. Gaa, Chem.-Ztg. 113 (1989) 243–249;
¨
(b) K. Burger, E. Hos, K. Gaa, N. Sewald, C. Schierlinger, Z.
[1] M.E.-S. Mustafa, A. Takaoka, N. Ishikawa, J. Fluorine Chem. 30
(1986) 463–468.
Naturforsch. B 46 (1991) 361–384.
[18] A.E. Zelenin, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1986) 2080–2085.
[2] (a) V.I. Dyatchenko, M.V. Galakhov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1988) 1196;
(b) V.I. Dyatchenko, M.V. Galakhov, A.F. Kolomiets, Khim. Geter-
otsykl. Soedin. (1989) 1429;
[19] A.E. Zelenin, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1985) 955–956.
[20] A.E. Zelenin, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1987) 231.
(c) M. Cushman, H.H. Patel, J. Scheuring, A. Bacher, J. Org. Chem.
57 (1992) 5630–5643.
[21] A.E. Zelenin, N.D. Tchkanikov, M.V. Galakhov, A.F. Kolomiets, A.V.
Fokin, Izv. Akad. Nauk SSSR Ser. Khim. (1985) 931–934.
[22] Y.A. Borisov, N.D. Tchkanikov, A.F. Kolomiets, A.V. Fokin, Izv.
Akad. Nauk SSSR Ser. Khim. (1993) 1883–1885.
[3] N. Katagiri, H. Watanabe, C. Kaneko, Chem. Pharm. Bull. 36 (1988)
3354–3372.
[4] S. Hoffmann, R. Frank, Ger. Offen. DE 4 431 317 (1996); Chem.
Abstr. 124 (1996) 344124.
¨
[5] E. Hoss, M. Rudolph, L. Seymour, C. Schierlinger, K. Burger, J.
ˇ
[23] B. Dolensky, J. Kvıcala, O. Paleta, J. Cejka, J. Ondracek, Tetrahedron
´
´ˇ
´ˇ
Lett. 37 (1996) 6939–6942.
¨ ¨
[24] G.K.S. Prakash, P. Yan, B. Torok, G.A. Olah, Synlett (2003) 527–531.
Fluorine Chem. 61 (1993) 163–170.