G Model
FLUOR 8822 No. of Pages 7
A. Wzorek et al. / Journal of Fluorine Chemistry xxx (2016) xxx–xxx
5
preferable [55–57]. Incorporation of one or two fluorine atoms in
acetyl group does not change the mode of association, but affects
the stability of supramolecular structure and as a result, the
observed SDE is reduced.
column chromatography with hexane ꢀ ethyl acetate as an eluent.
The spectral data were coincided with those reported in literature
[55,58].
4.2.1. N-fluoroacetyl-1-phenylethylamine (2a)
HPLC: hexane/2-propanol (85/15); flow rate = 0.5 mL/min; (S)
t1 = 16.9 min, (R) t2 = 17.6 min;
3. Conclusions
In general, N-fluoroacyl-
a
-phenylethylamines showed lower
1H NMR (500 MHz, CDCl3):
d (ppm): 1.55 (d, J = 6.9 Hz, 3H,
magnitude of the SDE as compared to the model amide, N-acetyl-
1-phenylethylamine. Quite remarkably, the fluoro-amides showed
very unusual and promising chromatographic behaviour. The
amides with perfluroalkyl groups bonded to carbonyl showed two
opposite eluting order. It indicates that the stability of the homo/
hetero- chiral aggregates strongly depends on fluorine content and
the chromatographic conditions. The data reported here, under-
score an exciting potential of fluorine in the SDE research as
virtually all chromatographic experiments performed in this study
gave unpredictable results. Further research into the SDE of
perfluoroalkyl containing compounds is currently ongoing and will
be reported in due course. Finally, as suggested by one of the
referees, the SDE phenomenon is closely related to the more
general field of asymmetric amplification [65–69] and can serve as
one of the mechanisms for the formation of prebiotic homo-
chirality [70].
CH3ꢀꢀCHꢀꢀ), 4.74 (dd, J = 28.4,14.2 Hz,1H, one of CH2FC(O)ꢀꢀ), 4.84
(dd, J = 28.4, 14.2 Hz, 1H, one of CH2FC(O)ꢀꢀ), 5.21 (p, J = 7.3 Hz, 1H,
CH3ꢀꢀCHꢀꢀ), 6.53 (brs, 1H, NH), 7.27–7.38 (m, 5HAr); 13C NMR
(CDCl3):
d (ppm): 21.86, 48.47, 80.40 (d, J = 47.3 Hz), 126.28, 127.78,
128.92, 142.51, 166.71 (d, J = 17.0 Hz); 19F NMR (CDCl3):
ꢀ224.50 (t, J = 17.0 Hz).
d (ppm):
4.2.2. N-difluoroacetyl-1-phenylethylamine (2b)
HPLC: hexane/2-propanol (90/10); flow rate = 1.0 mL/min; (S)
t1 = 13.2 min, (R) t2 = 16.3 min;
1H NMR (500 MHz, CDCl3):
d (ppm): 1.57 (d, J = 6.9 Hz, 3H,
CH3ꢀꢀCHꢀꢀ), 5.16 (p, J = 7.0 Hz, 1H, CH3ꢀꢀCHꢀꢀ), 5.88 (t, J = 54.3 Hz,
1H, CHF2C(O)-), 6.53 (brs, 1H, NH), 7.28–7.39 (m, 5HAr); 13C NMR
(CDCl3):
d (ppm): 21.45, 49.10, 108.65 (t, J = 252.8 Hz), 126.30,
128.08, 129.05, 141.66, 161.80 (t, J = 24.7 Hz); 19F NMR (CDCl3):
(ppm): ꢀ126.20 (dd, J = 54.4, 7.7 Hz).
d
4. Experimental
4.2.3. N-trifluoroacetyl-1-phenylethylamine (2c)
HPLC: hexane/2-propanol (90/10); flow rate = 0.8 mL/min; (S)
t1 = 8.6 min, (R) t2 = 14.4 min;
4.1. Materials and methods
1H NMR (500 MHz, CDCl3):
d
(ppm): 1.59 (d, J = 6.9 Hz, 3H,
CH3ꢀꢀCHꢀꢀ), 5.15 (p, J = 7.0 Hz, 1H, CH3ꢀꢀCHꢀꢀ), 6.54 (brs, 1H, NH),
7.31–7.40 (m, 5HAr); 13C NMR (CDCl3):
(ppm): 21.17, 49.95, 115.95
(q, J = 288.1 Hz), 126.31, 128.33, 129.16, 141.0, 156.44 (q, J = 36.9 Hz);
19F NMR (CDCl3):
(ppm): ꢀ75.92.
All reagents used in this work were purchased from Aldrich or
Fluka. Solvents for column chromatography, including CH2Cl2, c-
hexane, ethyl acetate, hexane were purchased from Chempur
(Poland). MTBE was purchased from POCh (Poland). All solvents
were used without further purification. Solvents for HPLC analysis:
hexane and 2-propanol and silica gel for chromatography 230–
400 mesh were purchased from E. Merck.
Thin layer chromatography (TLC) was performed on precoated
aluminium sheets (TLC silica gel 60 F254. The solvents polarity for
column chromatography for each compounds were selected on the
base of TLC. HPLC chromatographic analysis was performed on a
Varian ProStar instrument with UV–vis detector using a Vertex
d
d
4.2.4. N-pentafluoropropionyl-1-phenylethylamine (2d)
HPLC: hexane/2-propanol (90/10); flow rate = 0.5 mL/min; (S)
t1 = 10.7 min, (R) t2 = 16.0 min;
1H NMR (500 MHz, CDCl3):
d
(ppm): 1.59 (d, J = 6.9 Hz, 3H,
CH3ꢀꢀCHꢀꢀ), 5.18 (p, J = 7.1 Hz, 1H, CH3ꢀꢀCHꢀꢀ), 6.61 (brs, 1H, NH),
7.26–7.44 (m, 5HAr); 13C NMR (CDCl3):
(ppm): 21.14, 50.01,106.98
d
(tq, J = 263.1, 38.9 Hz), 117.98 (qt, J = 286.6, 34.7 Hz), 126.24, 128.32,
Plus Eurocel 01 chiral column (5
Germany) with hexane/2-propanol as a mobile phase.
mm, 250 ꢂ 4.6 mm) (Knauer,
129.16, 140.96, 156.94 (t, J = 25.6 Hz); 19F NMR (CDCl3):
ꢀ82.85 (t, J = 1.5 Hz), ꢀ123.11 (brs).
d (ppm):
Gravity-driven column chromatography was performed using a
column of diameter 10 mm and height 450 mm. The samples of
amides 2a-e enriched in the R enantiomer of various enantiomeric
purity were prepared by mixing S and R enantiomers and loaded
onto the column as a solution in c-hexane/CH2Cl2.
4.2.5. N-heptafluorobutyryl-1-phenylethylamine (2e)
HPLC: hexane/2-propanol (90/10); flow rate = 0.5 mL/min; (S)
t1 = 9.9 min, (R) t2 = 15.7 min;
1H NMR (500 MHz, CDCl3):
d
(ppm): 1.59 (d, J = 6.9 Hz, 3H,
CH3ꢀꢀCHꢀꢀ), 5.18 (p, J = 7.1 Hz, 1H, CH3ꢀꢀCHꢀꢀ), 6.61 (brs, 1H, NH),
7.31–7.40 (m, 5HAr); 13C NMR (CDCl3):
(ppm): 21.03, 50.14,
4.2. Synthesis of N-acetylamides 2a–e
d
105.87–110.92 (m),108.60 (tt, J = 265.0, 31.2 Hz),117.56 (qt, J = 287.7,
The amides 2a–e were synthesised according to the literature
procedure [55] by reaction between 1-phenylethylamine with
appropriate acyl chlorides in the presence of Et3N as a base in
anhydrous THF. In the case of amide 2c acid anhydride were used.
Fluoroacetic chloride, difluoroacetic chloride and pentafluoropro-
pionyl chloride were synthesised in reaction of appropriate acids
with thionyl chloride.
Procedure: To a solution of (R)-1-phenylethylamine or (S)-1-
phenylethylamine (1 g, 8.2 mmol) in anhydrous THF were added
Et3N (1.7 mL, 12.4 mmol) and after cooling to 0ꢃC acyl chloride
(8.2 mmol). After 5 h of stirring at room temperature, the reaction
mixture was poured into an aqueous saturated NH4Cl solution and
extracted with ethyl acetate (3 ꢂ 20 mL). The combined organic
extracts were washed with brine, dried over MgSO4 and
evaporated to dryness. The crude products were purified by
33.5 Hz), 126.28, 128.33, 129.14, 140.92, 156.75 (t, J = 25.9 Hz); 19F
NMR (CDCl3):
d
(ppm): ꢀ127.07 (m), ꢀ120.87 (m), ꢀ80.58 (m).
Acknowledgements
The authors gratefully acknowledge financial support from
IKERBASQUE, Basque Foundation for Science (VAS), the Ministry of
Science and Higher Education–Grant No. 612 561 (AW).
Appendix A. Supplementary data
Supporting information available: 1H, 19F and 13C NMR spectra
of amides 2a–e and graphical representation and tabulation of
fractions of runs 1–14.
Please cite this article in press as: A. Wzorek, et al., Self-Disproportionation of Enantiomers (SDE) via achiral gravity-driven column