Highly regioselective and efficient synthesis of aminoepoxides by ring closure of aminohalohydrins mediated by KF-Celite

Article abstract of DOI:10.1055/s-0030-1260961

The regioselective synthesis of several aminoepoxides has been achieved without observing any trace of azetidinols, which are usually reported as the exclusive reaction products when aminohalohydrins are treated with bases. The use of the mild supported base KF-Celite in refluxing acetonitrile is crucial for modulating the excellent regioselectivity observed. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0030-1260961

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SUPPORTING INFORMATION
Supporting Information
for DOI: 10.1055/s-0030-1260961
© Georg Thieme Verlag KG Stuttgart · New York 2011
Thieme

Supporting Information
For
Highly regioselective and efficient synthesis of aminoepoxides by ring
closure of aminohalohydrins in the presence of KF/Celite
Vittorio Pace,*a,b Pilar Hoyos,a José V. Sinisterra,a Andrés R. Alcántaraa and Wolfgang Holzerb
aOrganic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Universidad Complutense de Madrid,
Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.
bDepartment of Drug and Natural Products Symthesis, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
*Corresponding Author: Email: vpace@farm.ucm.es; Fax: +34 913941822; Tel: +34 913941820.
Materials and Instrumentation.
All 1H NMR and 13C NMR spectra were recorded on a Bruker AC-250 spectrometer at room temperature
at 250 MHz and at 62.5 MHz respectively, from CDCl3 solutions. The center of the solvent signal was
used as an internal standard which was related to TMS with δ 7.26 ppm (1H) and δ 77.0 ppm (13C).
1
Chemical shifts are reported in δ (ppm) referred to H (of residual protons) of the deuterated solvents.
Spin-spin coupling constants (J) are given in Hz. Carbon multiplicities were obtained from DEPT
experiments. Whenever necessary, 2D NMR experiments such as HMBC and HMQC were carried out.
Melting points were determined with a Buchi SMP-20 apparatus and are uncorrected. IR absorption
spectra were recorded on a Perkin-Elmer System 2000 FT-IR spectrophotomer. Elementary microanalyses
were carried out in the corresponding ‘Centro de Apoyo a la Investigación of the Complutense University,
Madrid, using a Leco® CHNS 932 equipment. Column chromatography purifications were conducted on
silica gel 60 (40-63 µm). TLC was carried out on aluminium sheets precoated with silica gel 60F254
(Macherey-Nagel, Merk); the spots were visualized under UV light (λ=254 nm) and/or I2 was used as
revealing system.

General procedure for the Preparation of starting N-aryl and N-benyzl aminohalohydrins 1 and 4a
4b, 4c, 4d, 4g, 4h, 4j and 4k.1,2
The mixture of arylamine (6 mmol) and epihalohydrin (6 mmol) in the presence of Zn(ClO4)6H2O2 (2
mol %) in chloroform (15 mL) at 50°C was stirred for 24 h. Then it was cooled to r.t., washed with water,
and extracted with dichloromethane (2 x 15 mL). The combined organic phases were dried with
anhydrous sodium sulfate, filtered and concentrated in vacuo. Whenever necessary the crude was purified
by column chromatography as indicated below.
1-chloro-3-(phenylamino)propan-2-ol (1)3
By using the aforementioned procedure, starting from aniline (559 mg, 6.00 mmol) and epichlorohydrin
(556 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the crude by LC
(silica gel, petroleum ether/ethyl acetate 8/2), compound 1 was recovered as a light yellow oil in 84%
yield (919 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 3.23 (dd, J = 7.3 Hz, J = 13.3 Hz, 1H), 3.39 (dd, J = 7.3 Hz, J
=13.3 Hz, 1H), 3.55 (bs, 1H), 3.62-3.72 (m, 2H), 3.98-4.11 (m, 1H), 6,64 (d, J = 7.8 Hz, 2H), 6.81 (t, J =
7.8 Hz, 1H), 7.25 (dd, J = 2.0 Hz, J = 7.8 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 47.5, 48.1, 70.2, 113.7, 118.7, 129.8, 148.1.
FT-IR (NaCl) (max/cm-1): 3366, 1603, 1504, 1101, 753.
Anal. Calcd for C9H12ClNO. Calcd.: C, 58.23; H, 6.52; N, 7.54. Found: C, 58.46; H, 6.66; N, 7.38.

1-chloro-3-(4-nitrophenylamino)propan-2-ol (4a)4
By using the aforementioned procedure, starting from 4-nitroaniline (829 mg, 6.00 mmol) and
epichlorohydrin (556 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the
crude by LC (silica gel, petroleum ether/ethyl acetate 9/1), compound 4a was recovered as a yellow oil in
71% yield (982 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 3.26 (dd, J = 7.3 Hz, J = 13.3 Hz, 1H), 3.35 (dd, J = 4.2 Hz, J =
13.3 Hz, 1H), 3.56 (dd, J = 6.1 Hz, J = 11.3 Hz, 1H), 3.64 (dd, J = 4.3 Hz, J = 11.3 Hz, 1H), 4.02-4.13 (m,
1H), 4.82 (bs, 1H), 6.52 (d, J = 8.6 Hz, 2H), 8.02 (d, J = 8.6 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 46.5, 47.7, 70.1, 111.9, 126.9, 138.9, 153.4.
FT-IR (NaCl) (max/cm-1): 3401, 3266, 1601, 1530, 1469, 1308, 1186, 1113, 833, 753.
Anal. Calcd for C9H11ClN2O3. Calcd.: C, 46.87; H, 4.81; N, 12.15. Found: C, 47.11; H, 4.60; N, 12.33.
1-chloro-3-(4-chlorophenylamino)propan-2-ol (4b)3
By using the aforementioned procedure, starting from 4-chloroaniline (765 mg, 6.00 mmol) and
epichlorohydrin (556 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the
crude by LC (silica gel, petroleum ether/ethyl acetate 9/1), compound 4b was recovered as a yellow solid
(mp 58°C, lit.3 56-60°C) in 77% yield (1017 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 3,11 (dd, J = 7.2 Hz, J = 13.2 Hz, 1H), 3.19 (bs, 1H), 3.28 (dd, J =
4.8 Hz, J = 13.3 Hz, 1H), 3.55 (dd, J = 6.9 Hz, J = 11.3 Hz, 1H), 3.71 (dd, J = 5.3 Hz, J = 11.3 Hz, 1H),
3.97-4.02 (m, 1H), 6.61 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 8.8 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 46.8, 47.4, 70.1, 113.6, 123.2, 128.8, 146.9.

FT-IR (NaCl) (max/cm-1): 3456, 3330, 1590, 1501, 1241, 1092, 815, 740.
Anal. Calcd for C9H11Cl2NO. Calcd.: C, 49.11; H, 5.04; N, 6.36. Found: C, 49.35; H, 4.84; N, 6.16.
1-chloro-3-(4-methoxyphenylamino)propan-2-ol (4c)3
A mixture of 4-methoxyaniline (739 mg, 6.00 mmol) and epichlorohydrin (278 mg, 3.00 mmol) was
refluxed in absolute ethanol during 24 h. After cooling, dichloromethane and water were added (15 + 10
mL) and the mixture was extracted. The combined organic phases were dried with anhydrous sodium
sulphate, filtered and concentrated in vacuo. Compound 4c was recovered in 78% yield (505 mg) as a light
yellow oil after LC (silica gel, petroleum ether/ethyl acetate 1/1).
1H NMR (250 MHz, CDCl3)  (ppm): 3.11 (bs, 1H), 3.19 (dd, J = 7.5 Hz, J = 13.0 Hz, 1H), 3.35 (dd, J =
4.2 Hz, J = 13.2 Hz, 1H), 3.55 (dd, J = 6.0 Hz, J = 11.2 Hz, 1H), 3.69 (dd, J = 4.8 Hz, J = 11.2 Hz, 1H),
3.78 (s, 3H), 3.98-4.05 (m, 1H), 6.58 (d, J = 8.8 Hz, 2H), 6.69 d, J = 8.7 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 46.9, 47.8, 55.5, 69.8, 115.0, 116.1, 142.1, 153.3.
FT-IR (NaCl) (max/cm-1): 3331, 2964, 2786, 1512, 1232, 1029, 818, 751.
Anal. Calcd for C10H14ClNO2. Calcd.: C, 55.69; H, 6.54; N, 6.49. Found: C, 55.48; H, 6.31; N, 6.71.
1-chloro-3-(2,6-dimethylphenylamino)propan-2-ol (4d)
By using the aforementioned procedure, starting from 2,6-dimethylaniline (727 mg, 6.00 mmol) and
epichlorohydrin (556 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the

crude by LC (silica gel, petroleum ether/ethyl acetate 9.5/0.5), compound 4d was recovered as a colorless
oil in 75% yield (1506 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 2.09 (s, 6H), 3.16 (dd, J = 6.5 Hz, J = 12.8 Hz, 1H), 3.22 (bs, 1H),
3.31 (dd, J = 4.6 Hz, J = 12.9 Hz, 1H), 3.58 (dd, J = 5.8 Hz, J = 11.1 Hz, 1H), 3.72 (dd, J = 5.0 Hz, J =
11.6 Hz, 1H), 3.91-3.99 (m, 1H), 6.65 (d, J = 7.8 Hz, 1H), 7.01 (dd, J = 2.0 Hz, J = 7.8 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 18.1, 45.8, 48.2, 70.2, 118.9, 127.9, 128.0, 149.9.
FT-IR (NaCl) (max/cm-1): 3391, 2964, 1613, 1521, 1261, 1086.
Anal. Calcd for C11H16ClNO. Calcd.: C, 61.82; H, 7.55; N, 6.55. Found: C, 61.60; H, 7.29; N, 6.72.
1-chloro-3-(methyl(phenyl)amino)propan-2-ol (4g)3
By using the aforementioned procedure, starting from N-methylaniline (643 mg, 6.00 mmol) and
epichlorohydrin (556 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the
crude by LC (silica gel, petroleum ether/ethyl acetate 8/2), compound 4g was recovered as a light yellow
oil in 93% yield (1114 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 2.51 (d, J = 4.5 Hz, 1H), 2.96 (s, 3H), 3.39 (d, J = 6.4 Hz, 1H), 3.55
(dd, J = 5.2 Hz, J = 10.9 Hz, 1H), 3.72 (dd, J = 4.5 Hz, J = 11.6 Hz, 1H), 4.08-4.13 (m, 1H), 6.75-6.85 (m,
3H), 7.26 (t, J = 8.0 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 38.9, 46.9, 56.5, 69.5, 113.0, 118.3, 130.5, 150.1.
FT-IR (NaCl) (max/cm-1): 3426, 2986, 1604, 1506, 1360, 1079, 995, 751, 689.
Anal. Calcd for C10H14ClNO. Calcd.: C, 60.15; H, 7.07; N, 7.01. Found: C, 60.36; H, 6.91; N, 7.24.
1-(benzylamino)-3-chloropropan-2-ol (4h)5

By using the aforementioned procedure, starting from benzylamine (536 mg, 5.00 mmol, 0.55 mL) and
epichlorohydrin (461 mg, 6.00 mmol) and Zn(ClO4)6H2O (18 mg, 2 mol %), after the purification of the
crude by LC (silica gel, petroleum ether/ethyl acetate 1/1), compound 4h was recovered as a white solid
(mp 73°C, lit.6 72-73°C) in 74% yield (739 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 2.75 (dd, J = 7.4 Hz, J = 11.9 Hz, 1H), 2.90 (dd, J = 4.5 Hz, J =
11.9 Hz, 1H), 3.48 (d, J = 6.0 Hz, 2H), 3.76 (d, J = 2.5 Hz, 2H), 3.82-3.91 (m, 1H), 7.22-7.42 (m, 5H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 46.8, 52.0, 54.3, 70.1, 128.0, 128.5, 127.9, 140.0.
FT-IR (NaCl) (max/cm-1): 3320, 3061, 2950, 1589, 1490, 1333, 1312, 1269, 1100, 1021, 745.
Anal. Calcd for C10H14ClNO. Calcd.: C, 60.15; H, 7.07; N, 7.01. Found: C, 60.01; H, 6.95; N, 6.79.
1-bromo-3-(phenylamino)propan-2-ol (4j)7
By using the aforementioned procedure, starting from aniline (559 mg, 6.00 mmol) and epibromohydrin
(822 mg, 6.00 mmol) and Zn(ClO4)6H2O (22 mg, 2 mol %), after the purification of the crude by LC
(silica gel, petroleum ether/ethyl acetate 7/3), compound 4j was recovered as a light yellow oil in 64%
yield (883 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 3.29 (dd, J = 6.9 Hz, J = 13.5 Hz, 1H), 3.42 (dd, J = 6.9 Hz, 13.6
Hz, 1H), 3.49 (bs, 1H), 3.56-3.68 (m, 2H), 4.03-4.12 (m, 1H), 6.74 (d, J = 8.0 Hz, 2H), 6.86 (t, J = 8.0 Hz,
1H), 7.21 (dd, J = 1.8 Hz, J = 7.9 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 40.5, 47.6, 69.8, 113.2, 118.0, 131.1, 148.6.
FT-IR (NaCl) (max/cm-1): 3485, 3351, 1610, 1497, 1111, 763.
Anal. Calcd for C9H12BrNO. Calcd.: C, 46.98; H, 5.26; N, 6.09. Found: C, 47.14; H, 5.45; N, 5.88.

2-hydroxy-3-(phenylamino)propyl 4-methylbenzenesulfonate (4k)
By using the aforementioned procedure, starting from aniline (559 mg, 6.00 mmol) and glycidyl tosylate
(1370 mg, 6.00 mmol) and Zn(ClO4)6H2O (66 mg, 6 mol %), after the purification of the crude by LC
(silica gel, petroleum ether/ethyl acetate 9/1), compound 4k was recovered as a white solid in 34% yield
(655 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 2.28 (s, 3H), 3.25 (dd, J = 6.6 Hz, J = 13.0 Hz, 1H), 3.38 (dd, J =
6.6 Hz, 12.9 Hz, 1H), 3.52 (bs, 1H), 3.60-3.71 (m, 2H), 4.00-4.08 (m, 1H), 6.64 (d, J = 7.5 Hz, 2H), 6.93
(t, J = 7.5 Hz, 1H), 7.19 (dd, J = 1.3 Hz, J = 7.5 Hz, 2H), 7.44 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.9 Hz,
2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 21.6, 47.5, 69.1, 71.4, 112.8, 119.5, 127.8, 128.2, 131.9, 139.6,
145.5, 148.6.
FT-IR (NaCl) (max/cm-1): 3468, 3361, 1615, 1505, 1120.
Anal. Calcd for C16H19NO4S. Calcd.: C, 59:79; H, 5:96; N, 4:36; S, 9.98. Found: C, 60.01; H, 5.75; N,
4.20; S, 9.75.
Synthesis of 3-N-acylamino-1-chloropropan-2-ols (4e and 4f)
tert-butyl 3-chloro-2-hydroxypropylcarbamate (4e)8
Compound 4e, has been prepared staring from 1-amino-3-chloropropan-2-ol hydrochloride, readily
available according the Barbachyn established procedure.9
1-amino-3-chloropropan-2-ol hydrochloride9 (6.85 mmol, 1000 mg) was dissolved in
THF/methanol/water solution (1/2/1, 15 mL) and sodium bicarbonate (7.00 mmol, 588 mg) was added at
a

r. t. The mixture was stirred for 30 min, then cooled to 0°C. Subsequently a solution of di-tert-
butyldicarbonate (7.19 mmol, 1569 mg) in THF (15 mL) was added drop-wise to the mixture for 2h.
Dichloromethane (20 mL) and water (10 mL) were added and the phases separated. The organic was dried
over anhydrous sodium sulfate and concentrated in vacuo. After LC (silica gel, petroleum ether/ethyl
acetate 7:.5/2.5), compound 4e was recovered as a white solid (mp 51°C, lit.9 48-52°C) in 86% yield
(1235 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 1.49 (s, 9H), 3.21-3.29 (m, 1H), 3.38-3.3.46 (m, 1H), 3.49-3.58 (m,
1H), 3.65-3.71 (m, 1H), 3.94 (bs, 1H), 5.19 (bs, 1H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 28.5, 44.0, 47.1, 71.3, 80.5, 156.8.
FT-IR (NaCl) (max/cm-1): 3448, 1696, 1590, 1416, 1357, 1230, 1074, 770.
Anal. Calcd for C8H16ClNO3. Calcd.: C, 45.83; H, 7.69; N, 6.68. Found: C, 46.11; H, 7.39; N, 6.86.
N-(3-chloro-2-hydroxypropyl)acetamide (4f)9
Compound 4f, has been prepared staring from 1-amino-3-chloropropan-2-ol hydrochloride, readily
available according the Barbachyn established procedure.9
To a mixture of 1-amino-3-chloropropan-2-ol hydrochloride9 (3.42 mmol, 500 mg) in THF at -30°C (5
mL), triethylamine (3.76 mmol, 381 mg, 0.52 mL) was slowly added. Subsequently a solution of acetic
anhydride (3.59 mmol, 367mg, 0.34 mL) in THF (3 mL) was added drop-wise, the mixture was allowed to
reach 0°C and then stirred for 1 h. Dichloromethane (10 mL) and water (5 mL) were added and the phases
separated. The organic was dried over anhydrous sodium sulfate and concentrated in vacuo. After LC
(silica gel, petroleum ether/ethyl acetate 9/1), compound 4f was recovered as a white solid in 70% yield
(364 mg).
1H NMR (250 MHz, CDCl3)  (ppm): 2.01 (s, 3H), 3.29-3.36 ( (m, 1H), 3.48-3.52 (m, 2H),3.90-3.96 (m,
1H), 4.66 (bs, 1H), 6.89 (bs, 1H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 21.8, 42.9, 47.5, 71.4, 173.0.

FT-IR (NaCl) (max/cm-1): 3421, 1678, 1597.
Anal. Calcd for C5H10ClNO3. Calcd.: C, 39.62; H, 6.65; N, 9.24. Found: C, 40.01; H, 6.76; N, 9.08.
Synthesis of 3-chloro-1-phthalimidopropan-2-ol (4i)10
To a solution of 2,3-epoxypropylphthalimide (2.0 mmol, 410 mg) in chloroform (10 mL) cooled at 0°C,
dropwise was added a concentrated solution (37%) of hydrochloric acid (3 mL). Mixture was allowed to
react during 30 min, therefore solution was washed with saturated aqueous NaCl (25 mL) and extracted
twice with dichloromethane. Organic phases were dried on anhydrous sodium sulphate and the removal of
the organic solvents in vacuo directly affords pure 3-chloro-1-phthalimidopropan-2-ol in quantitative yield
(479 mg) as a white solid (mp 95 °C; lit.10 92-96 ºC).
1H NMR (250 MHz, CDCl3)  (ppm): 3.01 (bs, 1H), 3.70 (dd, J = 5.2 Hz, J = 11.3 Hz, 2H), 4.04 (dd, J =
14.1 Hz, 23.3 Hz, 2H), 4.21-4.30 (m, 1H), 3.98-4.11 (m, 1H), 7.78 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H), 7.90
(dd, J = 3.0 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 41.6, 47.3, 69.8, 123.6, 131.9, 134.4, 168.7.
FT-IR (KBr) (max/cm-1): 3313, 1772.
Anal. Calcd. for C11H10ClNO3: C, 55.13; H, 4.21; N, 5.84. Found: C, 55.20; H, 4.26; N, 5.91.

General Procedure for the Epoxide Preparation through KF/Celte mediated ring closure of
aminohalohydrins
A mixture of aminohalohydrin (1, 4a-k) (1 equiv.) and potassium fluoride supported on Celite (2 equiv.,
50% w/w) was refluxed in acetonitrile for an appropriate time (10 min to 60 min) as reported in Table 3 of
the manuscript. After cooling to r.t. the mixture was filtered in vacuo and washed with dichloromethane.
Then, the organic solution was concentrated in vacuo to afford epoxides 2 and 5a-i and, whenever
necessary, followed by purification with liquid chromathography as reported below.
N-(oxiran-2-ylmethyl)aniline (2)3
Following the above mentioned procedure starting from compound 1 (464 mg, 2.50 mmol) and KF/Celite
(580 mg, 5.00 mmol, 50% w/w), compound 2 was obtained in 98% yield (365 mg), as a light brown solid
(mp 118°C, lit.3 115-120°C).
1H NMR (250 MHz, CDCl3)  (ppm): 2.61 (dd, J = 2.2 Hz, J = 5.3 Hz, 1H), 2.78 (t, J = 4.5 Hz, 1H), 3.21-
3.28 (m, 2H), 3.46-3.58 (m, 1H), 3.89 (bs, 1H), 6.72 (d, J = 7.5 Hz, 2H), 6.84 (t, J = 7.5 Hz, 1H), 7.19 (t, J
= 7.6 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 44.6, 45.3, 51.3, 113.0, 118.5, 130.1, 148.3.
FT-IR (KBr) (max/cm-1): 3381, 2865, 1601, 1498, 1346, 1220, 997, 698.
Anal. Calcd. for C9H11NO: C, 72.46; H, 7.43; N, 9.19. Found: C, 72.09 H, 7.59; N, 8.97.
4-nitro-N-(oxiran-2-ylmethyl)aniline (5a)
Following the above mentioned procedure starting from compound 4a (577 mg, 2.50 mmol) and
KF/Celite (580 mg, 5.00 mmol, 50% w/w), compound 5a was obtained in 95% yield (461 mg), as a
yellow solid (mp 127ºC).

1H NMR (250 MHz, CDCl3)  (ppm): 2.49 (dd, J = 2.6 Hz, J = 4.9 Hz, 1H), 2.79 (dd, J = 4.1 Hz, J = 4.7
Hz), 3.19-3.25 (m, 1H), 3.58 (dd, J = 5.7 Hz, J = 14.8 Hz, 1H), 3.86 (dd, J = 4.1 Hz, J = 14.8 Hz, 1H),
6.55 (d, J = 8.7 Hz, 2H), 8.07 (d, J = 8.7 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 46.3, 50.8, 53.4), 112.2, 127.3, 139.1, 153.9.
FT-IR (KBr) (max/cm-1): 3081, 1698, 1598, 1390, 1280, 1272, 870.
Anal. Calcd. for C9H10N2O3. Calcd.: C, 55.67; H, 5.19; N, 14.43. Found: C, 55.21; N, 5.36; N, 14.76.
4-chloro-N-(oxiran-2-ylmethyl)anilina (5b)3
Following the above mentioned procedure starting from compound 4b (550 mg, 2.50 mmol) and
KF/Celite (580 mg, 5.00 mmol, 50% w/w), compound 5b was obtained in 90% yield (413 mg), as a
yellow solid (mp. 106°C, lit.3 106-110°C) after purification with LC (silica gel, petroleum ether/ethyl
acetate 8/2).
1H NMR (250 MHz, CDCl3)  (ppm): 2.64 (dd, J = 2.3 Hz, J = 4.8 Hz, 1H), 2.82 (t, J = 4.8 Hz, 1H), 3.12-
3.19 (m, 2H), 3.40-3.49 (m, 1H), 3.80 (bs, 1H), 6.48 (d, J = 8.9 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 44.8, 45.9, 51.1, 113.6, 123.0, 129.7, 147.9.
FT-IR (KBr) (max/cm-1): 3391, 2985, 1605, 1502, 1369, 1245, 1185, 1100, 809.
Anal. Calcd. for C9H10ClNO. Calcd.: C, 58.86; H, 5.49; N, 7.63. Found: C, 59.14; N, 5.62; N, 7.36.
4-methoxy-N-(oxiran-2-ylmethyl)anilina (5c)3

Following the above mentioned procedure starting from compound 4c (539 mg, 2.50 mmol) and KF/Celite
(580 mg, 5.00 mmol, 50% w/w), compound 5c was obtained in 92% yield (412 mg), as a light yellow
solid (mp 52°C, lit.3 50-54°C) after purification with LC (silica gel, petroleum ether/ethyl acetate 3/2).
1H NMR (250 MHz, CDCl3)  (ppm): 2.70 (dd, J = 2.5 Hz, J = 4.9 Hz, 1H), 2.86 (dd, J = 4.1 Hz, J = 4.9
Hz 1H), 3.10-3.23 (m, 2H), 3.46-3.58 (m, 1H), 3.71 (bs, 1H), 3.76 (s, 3H), 6.68 (d, J = 9.1 Hz, 2H), 6.74
(d, J = 9.1 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 44.8, 46.6, 52.1, 58.4, 113.7, 142.0, 153.1.
FT-IR (KBr) (max/cm-1): 3426, 2950, 2794, 1605, 1502, 1453, 1240, 1148, 1003, 902.
Anal. Calcd. for C10H13NO2. Calcd.: C, 67.02; H, 7.31; N, 7.82. Found: C, 66.82; N, 7.53; N, 7.99.
2,6-dimethyl-N-(oxiran-2-ylmethyl)aniline (5d)11
Following the above mentioned procedure starting from compound 4d (534 mg, 2.50 mmol) and
KF/Celite (580 mg, 5.00 mmol, 50% w/w), compound 5d was obtained in 86% yield (381 mg), as a
colorless oil after purification with LC (silica gel, petroleum ether/ethyl acetate 9/1).
1H NMR (250 MHz, CDCl3)  (ppm): 2.11 (s, 6H), 2.53 (dd, J = 2.1 Hz, J = 5.2 Hz, 1H), 2.75 (dd, J = 3.8
Hz, J = 5.2 Hz), 3.13-3.18 (m, 1H), 3.68 (dd, J = 5.5 Hz, J = 13.9 Hz, 1H), 3.83 (dd, J = 3.9 Hz, J = 13.9
Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 1.6 Hz, J = 8.0 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 17.9, 44.6, 47.9, 119.3, 128.7, 128.9, 150.4.
FT-IR (KBr) (max/cm-1): 3391, 2968, 1612, 1523, 1264, 1089.
Anal. Calcd. for C11H15NO. Calcd.: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.96; N, 8.74; N, 7.49.
tert-butyl oxiran-2-ylmethylcarbamate (5e)9

Following the above mentioned procedure starting from compound 4e (524 mg, 2.50 mmol) and KF/Celite
(580 mg, 5.00 mmol, 50% w/w), compound 5e was obtained in 98% yield (424 mg), as a white solid (mp
48°C, lit.9 45-49°C).
1H NMR (250 MHz, CDCl3)  (ppm): 1.46 (s, 9H), 2.61 (s, 1H), 2.84 (t, J = 3.8 Hz, 1H), 3.11 (m, 1H),
3.25 (m, 1H), 3.61 (d, J = 13.9 Hz, 1H), 4.94 (s, 1H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 28.5, 42.0, 44.7, 51.2, 80.3, 156.5.
FT-IR (NaCl) (max/cm-1): 1703, 1587, 1410.
Anal. Calcd. for C8H15NO3. Calcd.: C, 55.47; H, 8.73; N, 8.09. Found: C, 55.84; N, 8.97; N, 7.79.
N-(oxiran-2-ylmethyl)acetamide (5f)9
Following the above mentioned procedure starting from compound 4f (379 mg, 2.50 mmol) and KF/Celite
(580 mg, 5.00 mmol, 50% w/w), compound 5f was obtained in 95% yield (273 mg), as a colorless oil.
1H NMR (250 MHz, CDCl3)  (ppm): 2.06 (s, 3H), 2.60 (dd, J = 2.8 Hz, J = 5.0 Hz, 1H), 2.81 (t, J = 5.0
Hz, 1H), 3.07 (m, 1H), 3.25 (dd, J = 5.1 Hz, J = 14.9 Hz, 1H),, 3.74 (dd, J = 5.0 Hz, J = 14.9 Hz, 1H),
6.51 (s, 1H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 22.8, 41.1, 45.9, 50.4, 171.2.
FT-IR (NaCl) (max/cm-1): 1669, 1602.
Anal. Calcd. for C5H9NO2. Calcd.: C, 52.16; H, 7.88; N, 12.17. Found: C, 52.47; N, 7.99; N, 11.86.
N-methyl-N-(oxiran-2-ylmethyl)aniline (5g)3

Following the above mentioned procedure starting from compound 4g (499 mg, 2.50 mmol) and
KF/Celite (580 mg, 5.00 mmol, 50% w/w), compound 5g was obtained in 88% yield (359 mg), as a light
yellow oil, after purification with LC (silica gel, petroleum ether/ethyl acetate 9/1).
1H NMR (250 MHz, CDCl3)  (ppm): 2.55 (dd, J = 2.8 Hz, J = 5.2 Hz, 1H), 2.81 (t, J = 4.8 Hz, 1H), 3.01
(s, 3H), 3.09-3.15 (m, 1H), 3.42 (dd, J = 4.9 Hz, J = 15.1 Hz, 1H), 3.60 (dd, J = 2.8 Hz, J = 15.1 Hz, 1H),
6.66-6.74 (m, 3H), 7.21 (d, J = 8.0 Hz, 2H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 39.3, 45.1, 50.4, 54.6, 111.7, 117.1, 130.0, 148.8.
FT-IR (NaCl) (max/cm-1): 3009, 2987, 2916, 1604, 1501, 697.
Anal. Calcd. for C10H13NO. Calcd.: C, 73.59; H, 8.03; N, 8.58. Found: C, 73.91; N, 7.84; N, 8.96.
N-benzyl-1-(oxiran-2-yl)methanamine (5h)
Following the above mentioned procedure starting from compound 4h (499 mg, 2.50 mmol) and
KF/Celite (580 mg, 5.00 mmol, 50% w/w), compound 5h was obtained in 93% yield (379 mg), as a
colorless oil after purification with LC (silica gel, petroleum ether/ethyl acetate 8/2).
1H NMR (250 MHz, CDCl3)  (ppm): 2.58 (dd, J = 3.0 Hz, J = 5.4 Hz, 1H), 2.77 (t, J = 5.0 Hz, 1H), 3.04-
3.10 (m, 1H), 3.37 (dd, J = 5.0 Hz, J = 14.6 Hz, 1H), 3.71 (dd, J = 3.0 Hz, J = 14.6 Hz, 1H), 3.87 (s, 2H),
7.18-7.33 (m, 5H).
13C NMR (62.5 MHz, CDCl3)  (ppm): 44.6, 51.7, 52.4, 55.0, 112.5, 115.8, 128.6, 149.5.
FT-IR (NaCl) (max/cm-1): 3281, 3082, 2946, 1601, 1494, 1274, 1098, 1017.
Anal. Calcd. for C10H13NO. Calcd.: C, 73.59; H, 8.03; N, 8.58. Found: C, 73.15; N, 8.26; N, 8.41.
2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (5i)12

Following the above mentioned procedure starting from compound 4i (599 mg, 2.50 mmol) and KF/Celite
(580 mg, 5.00 mmol, 50% w/w), compound 5h was obtained in 93% yield (498 mg), as a white solid (mp
99°C, lit.12 98-100°C).
1H NMR (250 MHz, CDCl3)  (ppm): 2.58 (dd, J = 2.6 Hz, J = 4.9 Hz, 1H), 2.66 (dd, J = 4.1 Hz, J
= 4.7 Hz, 1H), 3.19-3.25 (m, 1H), 3.78 (dd, J = 5.7 Hz, J = 4.7 Hz, 1H), 3.99 (dd, J = 5.7 Hz, J =
4.7 Hz, 1H), 7.78 (dd, J = 2.0 Hz, J = 8.3 Hz, 2H), 7.88 (dd, J = 2.0 Hz, J = 8.3 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ (ppm): 42.5, 68.8, 69.7, 122.8, 131.0, 134.2, 166.5.
FT-IR (KBr) (max /cm-1): 1718, 1687, 1615, 1357, 1224, 764, 745.
Anal. Calcd. for C11H9NO3: C, 65.02; H, 4.46; N, 6.89. Found: C, 65.33; H, 4.19; N, 6.70.
Spectral data for compound (3) 1-phenylazetidin-3-ol obtained by treating aminochlorohydrin 1
with different bases (see, Table 1). Viscous colorless oil.
1H NMR (250 MHz, CDCl3)  (ppm): 2.05 (bs, 1H), 2.91 (m, 2H), 3.45 (m, 2H), 4.41 (m, 1H), 7.14-7.31
(m, 5H).
13C NMR (62.5 MHz, CDCl3) δ (ppm): 61.9, 64.0, 113.9, 122.1, 128.5, 148.8.
FT-IR (KBr) (max /cm-1): 3424, 3081, 2860, 1601, 1501, 1454, 1353, 1170, 1054, 706.
Anal. Calcd. for C9H11NO: C, 72.46; H, 7.43; N, 9.39. Found: C, 72.10; H, 7.23; N, 9.58.
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