Cycloaddition of N-substituted imines of trifluoropyruvate with diazomethane: Efficient synthesis of 2-(trifluoromethyl)aziridine-2-carboxylates

Article abstract of DOI:10.1016/j.jfluchem.2013.01.019

A convenient synthesis for 2-trifluorometylaziridine-2-carboxylates and respective acids, based on reaction of N-substituted trifluoropyruvate imines 1 with diazomethane, was developed.

Full text of DOI:10.1016/j.jfluchem.2013.01.019

Journal of Fluorine Chemistry 148 (2013) 14–18
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Cycloaddition of N-substituted imines of trifluoropyruvate with diazomethane:
Efficient synthesis of 2-(trifluoromethyl)aziridine-2-carboxylates
*
Yuliya V. Rassukana , Ludmyla V. Bezgubenko, Petro P. Onys’ko, Anatoly D. Synytsya
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv 02660, 5 Murmans’ka St, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
A convenient synthesis for 2-trifluorometylaziridine-2-carboxylates and respective acids, based on
reaction of N-substituted trifluoropyruvate imines 1 with diazomethane, was developed.
ß 2013 Elsevier B.V. All rights reserved.
Received 26 December 2012
Received in revised form 11 January 2013
Accepted 15 January 2013
Available online 28 January 2013
Keywords:
Trifluoropyruvate imines
Aziridinecarboxylic acids
Diazomethane
Triazolinecarboxylates
Cycloaddition
1. Introduction
acids based on cycloaddition of N-substituted iminotrifluoropro-
pionates with diazomethane. It is worthwhile to note that
Fluorinated amino acids attracted much attention as potential
enzyme inhibitors, antibacterial and antitumor agents etc. [1].
Introduction of fluorine atoms leads to profound changes in their
physico-chemical and biological properties, such as high electro-
negativity, high lipophilicity, steric demand that increases with a
number of fluorine atoms, and pharmacokinetic profile [1,2a,b]. On
the other hand, aziridinocaboxylates, due to the strain associated
with three-membered ring, have been widely used as versatile
building blocks for the synthesis of a variety of pharmaceutically
and biologically important molecules [3]. Furthermore, they are
found among naturally occurring products [3]. At the same time
there are only few examples of fluorinated aziridinecarboxylates
[4], and free aziridinecarboxylic acids bearing trifluoromehyl
group, to the best of our knowledge, are unknown so far. Therefore,
the elaboration of efficient methods for the synthesis of
compounds combining in their structure fragments of aziridine
and fluorinated amino acid is a challenging task.
cycloaddition of imines with diazomethane was reported to
proceed by different routes depending on substituents at
azomethine bond. Thus, N-trifluoroacetylimine of trifluoropyr-
uvate undergoes cycloaddition to form respective aziridine [4a],
whereas N-benzoylimine of hexafluoroacetone gives [1 + 4]-
cycloadduct [5]. We studied cycloaddition with diazomethane
for a series of trifluoropyruvate imines 1a–g essentially differing in
polar and sterical characteristics of substituent at the nitrogen
atom. It was found that in all cases the reaction leads initially to a
mixture of [2 + 3] and [2 + 1] cycloaddition products, triazolines 3
and aziridines 4. The observed ratio 3/4 depends on substituent X
at nitrogen atom and is sensitive even to small impurities in staring
compounds. Thus, the use of freshly distilled imines 1 leads to
increase in 3–4 ratio. In case of N-phenyliminotrifluoropyruvate 1a
we managed to isolate triazolinecarboxylate 3a and fully
characterize it by spectral and analytical data. Triazolines 3 upon
heating or/and in the presence of acidic catalysts (CF3COOH, HCl)
readily eliminate nitrogen to afford respective aziridinecarbox-
ylates 4 in high yields (Scheme 1). Slow transformation 3 ! 4
occurs even at room temperature and is completed within several
months. It is to be noted that from experimental viewpoint the
preparation of aziridinecarboxylates 4 is convenient and very
simple: virtually pure aiziridines 4 are obtained merely upon
2. Results and discussion
Herein we wish to disclose a convenient method for the
preparation of novel a-trifluoromethylated aziridine-2-carboxylic
exposing the ethereal solution of respective imine
1 and
diazomethane 2 overnight at room temperature followed by
* Corresponding author. Tel.: +38 044 5732594; fax: +38 044 5732643.
E-mail address: juravi@rambler.ru (Y.V. Rassukana).
heating in an organic solvent in the presence of acidic catalyst.
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.01.019

Y.V. Rassukana et al. / Journal of Fluorine Chemistry 148 (2013) 14–18
15
Scheme 1. Reagents and conditions: (i) Et2O, r.t., overnight; (ii)
D, CF3COOH; (iii) THF, 1 M aq NaOH, 0 8C to r.t.; 10% aq citric acid, 0 8C to r.t.
The spectral and analytical data of compounds obtained are in
complete agreement with their structure. Triazoline- (3) and
aziridinecarboxylates 4 give clearly distinguishable 19F NMR
characteristics (dF ꢀ74.3 ꢁ ꢀ76.2 ppm and ꢀ72.9 ꢁ ꢀ73.6 ppm,
respectively) that allow easy monitoring of the process and
identification of the products in the reaction mixture. The
transformation 3 ! 4 is accompanied by a downfield shift of
fluorine signals of CF3 group and essential upfield displacement
of hydrogen and carbon NMR signals of endocyclic CH2 group.
Generation of a new chiral center upon formation of compounds
3, 4 is an additional evidence to the fact that ring closure involves
imine carbon atom. This is clearly revealed in magnetic non-
equivalence of diastereotopic hydrogen atoms of CH2 group in
the 1H NMR spectra of compounds 3, 4. In five member
heterocycles 3 NCH2 proton signals reveal themselves as two
representing the first examples of 2-(trifluoromethyl)aziridine-
2-carboxylic acids. In case of dimethyl 2-trifluoromethylaziridine-
1,2-dicarboxylate 3f we managed to carry out selective hydrolysis
of 2-COOMe group leading to respective aziridine-2-carboxylic
acid 5f.
3. Conclusions
In summary, based on cycloaddition of readily accessible
trifluoropyruvate imines with diazomethane, we have developed a
simple and efficient synthesis of N-substituted 2-(trifluoromethy-
l)aziridine-2-carboxylates and respective carboxylic acids.
4. Experimental
2
IR spectra were obtained with an UR-20 instrument. 1H NMR
and 13C NMR spectra were recorded on Bruker Avance DRX 500
(operating frequency 500.068 and 125.76 MHz respectively), 19F
NMR and 31P spectra – on Gemini 200 Varian instrument operating
at 188.14 and 80.95 MHz, respectively. Chemical shifts are
doublets of AB system (dA 4.8–4.9, dB 5.0–5.1 ppm, JAB 17.6–
18.3 Hz), whereas in three-member heterocycles 4 - as poorly
2
resolved separate multiplets (dA 2.6–3.1 ppm, JAB 0.6–2 Hz, dB
4
3.0–3.5 ppm, JHF 1–2 Hz). Moreover, spin-spin coupling of the
NCH2 group signals on magnetic nuclei (31P and 19F) situated on
both atoms of the C–N diad, revealed in 1H, 13C NMR spectra of
reported relative to internal TMS (1H) or CFCl3
(
19F) and external
3
85%-H3PO4
(
31P) standards. Melting points are uncorrected.
compound 4h [
d
(NCHA) 2.63 ppm, JHP = 11.4 Hz,
d
(NCHB)
3
4
2
2
3.02 ppm, JHP = 15.3 Hz, JHF 2 Hz, JAB 2 Hz; dC 32.9 ppm, JCP
6.3 Hz, JCF 2.5 Hz] unequivocally proves the formation of
Solvents were dried before use according to standard methods.
Atmospheric pressure chemical ionization mass spectra (APCI MS)
were recorded on Agilent 1100/LC/MSD spectrometer. Starting
compounds 1a [6], 1b [7], 1c [8], 1f [9], 1h [10] were prepared as
described in the literature.
2
aziridine cycle.
Upon treatment with aq NaOH in THF, aziridinecarboxylates 4
were converted into respective water soluble free acids
5
Table 1
Synthesis of compounds 3 and 4.
Compound
X
The ratio of
Solvent and reaction
time (h) for 3 ! 4
conversion
Yield
Molecular
MS (m/z)
Analysis of 4 found (calcd.)
3/4 (see exptl.)
of 4 (%)
formula of 4
of 4 (M+1)
a
>20
Toluene, 7
70
90
C11H10F3NO2 (245.2)
C10H9F3N2O2 (246.2)
245.8
246.8
C, 53.35 (53.88); H, 4.15 (4.11);
N, 5.65 (5.71)
b
10:1
Toluene, 4
C, 48.35 (48.79); H, 3.62 (3.68);
N, 11.30 (11.38)
N
N
c
10:1
Toluene; 31
67
C10H10F3N3O2 (261.2)
262.0
C, 45.75 (45.98); H, 3.89 (3.86);
N, 16.1 (16.09)
N
Me
Me
d
e
10:1
2:1
Toluene; 35
Benzene; 6
62
70
C9H9F3N2O3 (250.2)
251.0
303.0
C, 43.18 (43.21); H, 3.59 (3.63);
N, 11.15 (11.20)
O
N
C12H9F3N2O2S (302.3)
C, 47.63 (47.68); H, 2.98 (3.00);
N, 9.25 (9.27); S, 10.55 (10.61)
N
S
COOMe
f
COOMe
10:1
––a
CHCl3, 3
––
95
75
C7H8F3NO4 (227.1)
––
227.8
––
C, 36.89 (37.01); H, 3.59 (3.55);
N, 6.11 (6.17)
––
g
O
S
Me
O
P(O)(OEt)2
h
P(O)(OEt)2
>20
CHCl3, 5
77
C9H15F3NO5P (305.2)
306.2
C, 35.37 (35.42); H, 4.90 (4.95);
N, 4.54 (4.59)
a
3 g was not detected.

Table 2
Characteristics of compounds 3 and 4.
Compound
Melting
IR
n
(cmꢀ1
)
19F NMR
(CDCl3),
1H NMR (CDCl3), (ppm), J (Hz); 13C NMR (CDCl3),
d d (ppm), J (Hz)
point (8C)
(C5O)
d
(ppm)
3a
Oil
1760
ꢀ74.5
1H NMR: 3.75 (s, 3H, MeO), 4.93 (d, 2J=H =17.6 Hz, 1H, NCHA), 5.03 (d, 2J=H = 17.6 Hz, 1H, NCHB), 7.19 (t, 3J=H = 7.5 Hz, 1H, Ph), 7.27 (d, 3J=H = 7.5 Hz, 2H,
Ph), 7.36 (t, 3J=H = 7.5 Hz, 2H, Ph) 13C NMR: 53.77 (MeO), 68.00 (q, 2JCF = 30.2 Hz, CCF3), 76.52 (CH2), 119.68, 125.70, 129.28, 138.93 (Ph), 123.13 (q,
1JCF = 289 Hz, CF3), 166.08 (C5O)
3b
3c
––a
––a
1760
1765
ꢀ75.2
ꢀ75.2
1H NMR: 3.77 (s, 3H, MeO), 4.82 (d, 2J=H = 17.6 Hz, 1H, NCHA), 5.02 (d, 2J=H = 17.6 Hz, 1H, NCHB), 7.00 (m, 1H, Ht), 7.70 (m, 2H, Ht), 8.21 (m, 1H, Ht)
1H NMR: 2.50 (s, 3H, MeC), 3.78 (s, 3H, MeO), 4.89 (d, 2J=H = 17.8 Hz, 1H, NCHA), 5.1 (d, 2J=H = 17.8 Hz, 1H, NCHB), 6.91 (d, 3J=H = 4.9 Hz, 1H, Ht), 8.44 (d,
3J=H = 4.9 Hz, 1H, Ht)
2
2
3d
3e
––a
––a
––a
––a
1755
––
ꢀ74.4
ꢀ74.3
ꢀ76.2
ꢀ77.4
1H NMR: 2.41 (s, 3H, MeC), 3.85 (s, 3H, MeO), 4.94 (d, J=H = 18 Hz, 1H, NCHA), 5.08 (d, J=H = 18Hz, 1H, NCHB), 6.34 (s, 1H, Ht)
––
2
2
3f
3hb
1765
1765
1H NMR: 3.85 (s, 3H, MeO), 3.96 (s, 3H, MeO), 4.83 (d, J=H = 18.3 Hz, 1H, NCHA), 5.00 (d, J=H = 18.3 Hz, 1H, NCHB)
1H NMR: 1.37 (m, 6H, MeCH2), 3.87 (s, 3H, MeO), 4.24 (m, 4H, CH2O), 4.76 (dd, J=H = 18.0 Hz, JHP = 0.9 Hz, 1H, NCHA), 5.00 (dd, J=H = 18.0 Hz,
2
4
2
4JHP = 1.8 Hz, 1H, NCHB) 13C NMR: 15.85 (d, JCP = 6.3 Hz, MeCH2), 54.01 (MeO), 64.66 (d, JCP = 7.5 Hz, CH2O), 64.73 (d, JCP =5 Hz, CH2O), 65.76 (qd,
3
2
2
2JCF = 31.4 Hz, JCP = 7.5 Hz, CCF3), 76.39 (d, JCP = 7.5 Hz, CH2N), 122.87 (q, JCF =284 Hz, CF3), 166.37 (C5O)
2
2
1
2
4a
4b
Oil
Oil
1750
1750
ꢀ72.9
1H NMR: 2.87 (d, J=H = 1.3 Hz, 1H, NCHA), 3.03 (m, 1H, NCHB) 3.55 (s, 3H, CH3O), 6.9 (d, 3J=H = 7.5 Hz, 2H, Ph), 7.05 (t, 3J=H = 7.5 Hz, 1H, Ph), 7.26 (t,
3J=H = 7.5 Hz, 2H, Ph) 13C NMR: 35.01 (CH2), 45.98 (q, 2JCF = 36.5 Hz, CCF3), 52.82 (CH3O), 122.46 (q, 1JCF = 275 Hz, CF3), 119.58, 123.96, 129.11, 146.79
(Ph), 163.21 (C5O)
2
3
3
3
ꢀ72.9
1H NMR: 2.94 (d, J=H = 0.9 Hz, 1H, NCHA), 3.23 (m, 1H, NCHB), 3.60 (s, 3H, CH3O), 6.86 (d, J=H = 8 Hz, 1H, 3-HPy), 6.99 (m, J=-5,H-4 = 7.3 Hz, J=-5,H-
3
3
3
6 = 5 Hz, 1H, 5-HPy), 7.60 (m, J=-4,H-3 = 8 Hz, J=-4,H-5 = 7.3 Hz, 1H, 4-HPy), 8.27 (d, J=H = 5.0 Hz, 1H, 6-HPy
)
4c
4d
4e
70–72
30–31
80–83
1745
1750
1760
ꢀ73.1
ꢀ72.9
ꢀ73.0
1H NMR: 2.43 (s, 3H, MeC), 2.98 (d, 2J=H = 1 Hz 1H, NCHA), 3.21 (m, 1H, NCHB), 3.68 (s, 3H, MeO), 6.82 (d, 3J=H = 5 Hz, 1H, Ht), 8.34 (d, 3J=H = 5 Hz, 1H, Ht)
2.32(s, 3H, MeC), 2.89 (br, 1H, NCHA), 3.16 (m, 1H, NCHB), 3.71 (s, 3H, MeO), 5.71 (s, 1H, Ht)
1H NMR: 3.09 (d, 3J=H = 0.6 Hz, 1H, NCHA), 3.46 (m, 1H, NCHB), 3.70 (s, 3H, CH3O), 7.29 (t, 3J=H = 7.9 Hz, 1H, Ht), 7.40 (t, 3J=H = 7.9 Hz, 1H, Ht), 7.69 (d,
3J=H = 7.9 Hz, 1H, Ht), 7.79 (d, 3J=H = 7.9 Hz, 1H, Ht); 13C NMR: 37.20 (CH2), 46.88 (q, 2JCF = 37.7 Hz, CCF3), 53.60 (CH3O), 121.74 (q, 1JCF = 276 Hz, CF3),
121.44, 121.99, 124.55, 126.42, 133.42, 150.62, 167.82, (Ht), 162.40 (C5O)
4f
Liquid
1765
1755
1765
ꢀ73.6
1H NMR: 2.70 (2J=H =1.1 Hz 1H, NCHA), 2.99 (quintet, 2J=H
=
4J=F = 1.1 Hz 1H, NCHB), 3.77 (s, 3H, CH3O), 3.88 (s, 3H, CH3O); 13C NMR: 34.41 (CH2), 43.05
4
2
1
(d, JFH 1 Hz)
(q, JCF = 37.7 Hz, CCF3), 53.71 (CH3O), 54.02 (CH3O), 121.33 (q, JCF = 276 Hz, CF3), 158.55 (C5O), 163.64 (C5O)
1H NMR: 2.46 (s, 3H, CH3), 2.79 (s, 1H, NCHA), 3.54 (q, 4J=F =1.6 Hz, 1H, NCHB), 3.93 (s, 3H, CH3O), 7.37 (d, 3J=H = 8.2 Hz, 2H, Ar), 7.85 (d, 3J=H = 8.2 Hz, 2H,
4g
4hd
78–80c
ꢀ73.4
4
(petroleum ether)
Oil
(d, JFH =1.5 Hz)
Ar)
ꢀ74.3
1H NMR: 1.36 (m, 6H, MeCH2, 2.63 (dd, 3JHP =11.4 Hz, 2J=H 2 Hz, 1H, NCHA), 3.02 (m, 3JHP = 15.3 Hz, 2JHH
ꢂ
4JHF ꢂ 2 Hz, 1H, NCHB), 3.85 (s, 3H, MeO), 4.20
(m, 4H, CH2O); 13C NMR: 15.95 (d, JCP = 6 Hz, MeCH2), 16.04 (d, JCP = 7 MeCH2), 32.90 (dq, JCP = 6 Hz, JCF = 2 Hz, CH2N), 44.60 (qd, JCF = 37.7 Hz,
2JCP =6.3 Hz, CCF3), 53.51(CH3O), 64.22 (d, 2JCP = 7 Hz, CH2O), 64.35 (d, 2JPC = 6 Hz, CH2O), 121.78 (qd, 1JCF = 277Hz, 3JCP = 6 Hz, CF3), 163.22 (d, 3JCP = 7 Hz,
C5O)
3
3
2
3
2
a
Identified in mixture with respective aziridine 4 (see Table 1).
dP ꢀ6.4 ppm (CDCl3).
b
c
lit. 4b m.p. 80–82 8C.
d
dP 5.7 ppm (CDCl3).

Y.V. Rassukana et al. / Journal of Fluorine Chemistry 148 (2013) 14–18
17
Table 3
Characteristics of compounds 5.
Compound
Melting point
Yield
(%)
IR,
n
(cmꢀ1
)
19F NMR,
d (ppm)
Molecular formula
MS (m/z)
Analysis found (calcd.)
(8C)
(C5O)
5a
5b
5c
5d
5e
5f
122–125
133–135
168–170
70–73
65
60
63
90
78
75
67
1740
ꢀ73.0 (CDCl3)
C10H8F3NO2 (231.2)
C9H7F3N2O2 (232.2)
C9H8F3N3O2 (247.2)
C8H7F3N2O3 (236.1)
C11H7F3N2O2S(288.2)
C6H6F3NO4 (213.1)
C11H10F3NO4S(309.3)
232.2 (M+1)
233.0 (M+1)
248.2 (M+1)
235.0 (M-1)
289.2 (M+1)
214.1 (M+1)
310.3 (M+1)
C, 51.89 (51.96); H, 3.44 (3.49);
N, 6.01 (6.06)
1735
1735
1740
1725
1760
1770
ꢀ72.7 (D2O)
C, 46.49 (46.56); H, 3.07 (3.04);
N, 12.03 (12.07)
ꢀ72.3 (acetone5d6)
ꢀ72.9 (CDCl3)
C, 43.67 (43.73); H, 3.23 (3.26);
N, 16.97 (17.00)
C, 40.65 (40.69); H, 3.01 (2.99);
N, 11.83 (11.86)
180–182
213–215
100–113
ꢀ73.0 (acetone-d6)
ꢀ72.1 (acetone-d6)
ꢀ71.5 (DMSO-d6)
C, 45.77 (45.84); H, 2.41 (2.45);
N, 9.70 (9.72); S, 11.09 (11.12)
C, 33.73 (33.82); H, 2.81 (2.84);
N, 6.52 (6.57)
5g
C, 42.65 (42.72); H, 3.22 (3.26);
N, 4.51 (4.53); S, 10.32 (10.37)
Table 4
1H, 13C NMR spectra of compounds 5.
Compound
1H NMR, (ppm), J (Hz); 13C NMR,
d d (ppm), J (Hz)
3
3
5a
1H NMR (CDCl3): 2.89 (br, 1H, NCHA), 2.98 (br, 1H, NCHB), 6.89 (d, J=H =7.5 Hz, 2H, Ph), 7.05 (t, J=H = 7.5 Hz, 1H, Ph),
3
7.24 (t, J=H = 7.5 Hz, 2H, Ph)
3
5b
5c
1H NMR (D2O): 2.93 (br, 1H, NCHA), 3.02 (br, 1H, NCHB) 7.23 (d, J=H = 8.7 Hz, 1H, 3-HPy), 7.32 (m, 1H, 5-HPy), 8.1
(m, 2H, 4-HPy, 6-HPy
)
1H NMR (acetone-d6): 2.25 (s, 3H, Me), 2.81 (d, J=H = 0.6 Hz, 1H, NCHA), 3.16 (br m, 1H, NCHB), 6.84 (d, J=H = 5 Hz,
3
3
3
1H, Ht), 8.22 (d, J=H = 5 Hz, 1H, Ht)
5d
5e
1H NMR (CDCl3): 2.31 (s, 3H, Me), 2.86 br, 1H, NCHA), 3.06 br, 1H, NCHB), 5.77 (s, 1H, Ht)
1H NMR (DMSO-d6): 3.25 (d, J=H = 1.5 Hz, 1H, NCHA), 3.32 (br, 1H, NCHB), 7.32 (m, 1H, Ht), 7.43 (m, 1H, Ht), 7.77
3
(d, J=H = 7.9 Hz, 1H, Ht), 7.94 (d, J=H = 7.6 Hz, 1H, Ht); 13C NMR (DMSO-d6): 37.56 (CH2), 46.92 (q, JCF = 35.2 Hz, CCF3),
3
3
2
1
122.70 (q, JCF =276 Hz, CF3), 121.83, 122.58, 124.76, 126.85, 133.46, 150.94, 169.02 (Ht), 163.17 (C5O),
3
5f
1H NMR (acetone-d6): 2.27 (d, J=H = 0.9 Hz, 1H, NCHA), 2.67 (br m, 1H, NCHB), 3.51 (s, 3H, CH3O); 13C NMR (acetone-d6):
2
1
32.62 (CH2), 44.60 (q, JCF = 35.6 Hz, CCF3), 53.15 (CH3O), 123.31 (q, JCF = 276 Hz, CF3), 161.44 (C5O), 166.20 (C5O)
3
3
5g
1H NMR (DMSO-d6): 2.39 (s, 3H, Me), 2.58 (d, J=H =0.7 Hz, 1H, NCHA), 3.05 (br m, 1H, NCHB), 7.39 (d, J=H = 8 Hz, 2H, Ar),
3
7.82 (d, J=H = 8 Hz, 2H, Ar)
4.1. Compounds 1d, e, g: general procedure [8]
4.2. Methyl 1-X-5-trifluoromethyl-1H-4,5-dihydro-1,2,3-triazole-5-
carboxylates 3 and methyl 1-X-2-trifluoromethylaziridine-2-
carboxylates 4: general procedure
The methyl trifluoropyruvate (20 mmol) was added dropwise to
a stirred suspension of appropriate amine (20 mmol) in benzene
(20 ml) at r.t. The reaction mixture is spontaneously warmed and
became homogeneous. The mixture was left for 1 h at r.t., and then
thionyl chloride (20 mmol) was added. After 15 minutes pyridine
(40 mmol) was added dropwise to stirred and cooled to 0 8C mixture
and allowed to warm to room temperature. Pyridine hydrochloride
was filtered off, the solvent was evaporated under reduced pressure
and the residue was distilled to give iminotrifluoropropanoate 1.
A solution of diazomethane 2 (1.3 mmol) in diethyl ether
(15 ml) was added to imine 1 (0.13 mmol) at 5 8C and stirred at
room temperature overnight. The solvent was evaporated in
vacuum to give the mixture of triazoline 3 and aziridine 4, the ratio
is indicated in Table 1. The mixture was dissolved in respective
solvent (in case of compounds 3a, b, h 1–2 drops of CF3COOH were
added to the solution) and refluxed. The solvent and reaction time
are indicated in Table 1. After reaction was complete the solvent
was evaporated in vacuum and the residue was extracted with
petroleum ether (3ꢃ 5 mL). The combine extracts were evaporated
under reduced pressure to give target compound 4 (Tables 1 and 2).
4.1.1. Methyl 3,3,3-trifluoro-2-[(5-methylisoxazol-3-
yl)imino]propanoate 1d
Yield 88%, bp 53 8C (0.07 mm Hg), m.p. 35–37 8C. IR (KBr): 1640
(C55N), 1790 (C55O) cmꢀ1
.
1H NMR (CDCl3):
d
2.45 (s, 3H, CH3C),
3.89 (s, 3H, CH3O), 6.07 (s, 1H, Ht). 19F NMR (188 MHz, CDCl3):
d
4.3. Preparation of 1-X-2-trifluoromethylaziridine-2-carboxylic acids
ꢀ71.07. Anal. calcd. for C8H7F3N2O3: C, 40.69; H, 2.99; N, 11.86.
5: general procedure
Found: C, 40.65; H, 2.96; N, 11.85.
To
a stirred and cooled solution of respective ester 4
4.1.2. Methyl 3,3,3-trifluoro-2-[(1,3-benzothiazol-2-
yl)imino]propanoate 1e
(0.81 mmol) in THF (2 mL), 1 M aq NaOH (1 mL) was slowly added
dropwise at 0 8E. The resulting reaction mixture was left at 15–
20 8C overnight. The organic solvent was removed in vacuo,
resulting water solution was washed with chloroform (5 ml) and
acidified to pH 4 with 10% aq citric acid at 0 8C. Water was
evaporated in vacuo, the residue was extracted with ethyl acetate
(3ꢃ 10 ml). The solvent was removed in vacuo and the residue was
triturated with diethyl ether to give acid 5 (Tables 3 and 4).
In case of compound 5e, acidification is accompanied by
precipitation. The precipitate formed was separated and washed
with diethyl ether to afford pure acid 5e.
Yield 90%, bp 101 8C (0.07 mm Hg). 1H NMR data of compound
1e are in agreement with the literature data [11].
4.1.3. Methyl 3,3,3-trifluoro-2-(tosylimino)propanoate 1 g
Yield 80%, m.p. 47–48 8C. IR (KBr): 1690 (C55N), 1770
(C55O) cmꢀ1
.
1H NMR (CDCl3):
d
2.47 (s, 3H, CH3C), 4.04 (s, 3H,
CH3O), 7.40 (d, 2H, 3JHH 8.3 Hz, Ar), 7.88 (d, 2H, 3JHH 8.3 Hz, Ar). 19
NMR (CDCl3):
= ꢀ71.5. Anal. calcd for C11H10F3NO4S: C, 42.72; H,
3.26; N, 4.53, S, 10.37. Found: C, 42.39; H, 3.35; N, 4.41, S, 10.23.
F
d

18
Y.V. Rassukana et al. / Journal of Fluorine Chemistry 148 (2013) 14–18
[5] Y.V. Zeifman, N.P. Gambaryan, L.A. Simonyan, R.B. Minasyan, I.L. Knunyants,
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