Mangelinckx et al.
K2CO3. Evaporation of the solvent in vacuo yielded 2.97 g (88%) of
crude 7a, which was purified by recrystallization (pentane/ether 1:1)
to afford 1.59 g (47%) of the pure substance.
Synthesis of cis-3,3-Dichloroazetidines 10. The synthesis of 3,3-
dichloro-1-isopropyl-2,4-diphenylazetidine (10a) is representative.16
To a solution of ꢀ,ꢀ-dichloro-γ-(mesyloxy) amine 9a (2.36 g, 5.67
mmol) in DMSO (30 mL) was added potassium carbonate (2.35 g,
17.01 mmol). The mixture was stirred for 86 h at 90 °C, poured
into H2O (90 mL), and extracted with CH2Cl2 (4 × 45 mL). The
combined organic extracts were washed with H2O (30 mL) and
brine (2 × 30 mL), dried (MgSO4), and evaporated to give crude
3,3-dichloroazetidine 10a as a solid material, which was purified
by column chromatography (petroleum ether/EtOAc 98:2) to afford
0.94 g (52%) of pure 10a (Rf ) 0.33).
N-[2,2-Dichloro-3-(4-chlorophenyl)-3-hydroxy-1-phenyl-1-
propylidene]-isopropylamine 7c. 1H NMR (CDCl3, 300 MHz) δ
1.13 and 1.14 (2 × d, 2 × 3H, J ) 6.33 Hz), 3.30 (septet, 1H, J
) 6.33 Hz), 5.58 (d, 1H, J ) 2.20 Hz), 6.16 (d, 1H, J ) 2.75 Hz),
7.28-7.46 (m, 7H), 7.57-7.62 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ 23.1, 23.3, 53.2, 78.9, 89.5, 127.5, 127.9, 129.0, 129.1,
131.4, 132.4, 134.4, 135.4, 167.9; IR (KBr, cm -1) ν 3401 (OH),
1642 (CdN); MS (ES, pos. mode) m/z (%) 370/72/74/76 (M + H
+, 100). Anal. Calcd for C18H18Cl3NO: C 58.32; H 4.89; N 3.78.
Found: C 58.07; H 4.82; N 3.61. Yield ) 48%. Mp ) 115.9-116.8
°C. Amorphous light brown solid.
Synthesis of ꢀ-(Mesyloxy) Imines 8. The synthesis of N-[2,2-
dichloro-3-(mesyloxy)-1,3-diphenyl-1-propylidene]-isopropy-
lamine (8a) is representative.16 To a solution of R,R-dichloro-ꢀ-
hydroxy imine 7a (4.10 g, 12.2 mmol) in pyridine (30 mL) was
added dropwise at room temperature mesyl chloride (2.09 g, 18.2
mmol). After 5 h of stirring at room temperature, the reaction
mixture was poured into an ice-cooled 0.5 N NaOH solution (90
mL) and extracted with CH2Cl2 (3 × 60 mL). The organic layer
was dried (MgSO4) and evaporated in vacuo to give 8a as a crude
solid product, which was purified by recrystallization (pentane/ether
4:1) to afford 3.98 g (79%) of pure white crystals.
trans-3,3-Dichloro-1-isopropyl-4-(4-methylphenyl)-2-pheny-
lazetidine 11b. This compound was isolated via column chroma-
tography from the reaction crude of the cyclization reaction of the
1
crude ꢀ, ꢀ-dichloro-γ-(mesyloxy)amine 9b to azetidine 10b. H
NMR (CDCl3, 300 MHz) δ 0.69 (d, 3H, J ) 6.05 Hz), 0.70 (d,
3H, J ) 6.33 Hz), 2.40 (s, 3H) 3.06 (septet, 1H, J ) 6.1 Hz), 5.23
and 5.25 (each s, each 1H), 7.22-7.25 and 7.36-7.46 and
7.51-7.56 (m, 9H); 13C NMR (CDCl3, 75 MHz) δ 21.3, 21.4, 22.0,
48.7, 82.3, 85.5, 127.9, 128.7, 129.6, 129.8, 133.4, 136.9, 138.6;
IR (KBr, cm -1) ν 1455, 1229, 1194, 1059, 699; MS (ES, pos.
mode) m/z (%) 334/36/38 (M + H +, 100). Anal. Calcd for
C19H21Cl2N: C 68.27; H 6.33; N 4.19. Found: C 67.98; H 6.39; N
4.13. Yield ) 19%. Rf ) 0.13 (petroleum ether/EtOAc 99:1). Mp
) 82.5-84.4 °C. White crystals.
cis-3,3-Dichloro-2-(4-chlorophenyl)-1-isopropyl-4-phenylaze-
N-[2,2-Dichloro-3-(4-chlorophenyl)-3-(mesyloxy)-1-phenyl-1-
1
tidine 10c. H NMR (CDCl3, 300 MHz) δ 0.83 (d, 3H, J ) 6.05
1
propylidene]-isopropylamine 8c. H NMR (CDCl3, 300 MHz) δ
Hz), 0.84 (d, 3H, J ) 6.33 Hz), 2.84 (septet, 1H, J ) 6.2 Hz), 4.69
and 4.72 (each s, each 1H), 7.34-7.44 (m, 5H), 7.52-7.61 (m, 4H);
13C NMR (CDCl3, 75 MHz) δ 21.5, 21.6, 59.2, 80.1, 80.7, 84.8, 128.0,
128.2, 128.5, 129.6, 134.3, 136.1, 137.3; IR (KBr, cm -1) ν 1489,
1248, 1087, 1016, 699; MS (ES, pos. mode) m/z (%) 354/56/58/60
(M + H +, 100). Anal. Calcd for C18H18Cl3N: C 60.95; H 5.11; N
3.95. Found: C 60.85; H 5.26; N 4.12. Yield ) 38%. Rf ) 0.25
(petroleum ether/EtOAc 99/1). Mp ) 83.7-84.5 °C. White crystals.
Synthesis of Alkynes 12 and 13. The synthesis of N-(1,3-
diphenylprop-2-yn-1-ylidene)propyl-2-amine (12a) is representative.
To sodium hydride (0.08 g, 2 mmol, 60% dispersion in oil) was
added DMSO (2 mL) and the mixture was stirred for 20 min at
room temperature to generate dimsylsodium. Subsequently, 3,3-
dichloro-1-isopropyl-2,4-diphenylazetidine 10a (0.32 g, 1 mmol),
dissolved in DMSO (3 mL), was added dropwise at room
temperature. After the addition was completed, the mixture was
kept at 55 °C for 3 h. After cooling, water (10 mL) was added,
and the aqueous phase was extracted with diethyl ether (3 × 15
mL). The combined organic phases were dried (MgSO4), and after
filtration and evaporation of the solvent, the crude N-(1,3-diphe-
nylprop-2-yn-1-ylidene)propyl-2-amine (12a) was obtained. Further
purification was performed by column chromatography to yield
1.08 and 1.15 (2 × d, 2 × 3H, J ) 6.33 Hz), 2.86 (s, 3H), 3.31 (septet,
1H, J ) 6.33 Hz), 6.83 (s, 1H), 7.00-7.46 (m, 7H), 7.65-7.70 (m,
2H); 13C NMR (CDCl3, 75 MHz) δ 23.17, 23.22, 40.0, 54.3, 84.0,
89.4, 128.0, 128.2, 128.3, 129.0, 131.9, 132.2, 133.7, 136.0, 164.1;
IR (KBr, cm -1) ν 1642 (CdN); MS (ES, pos. mode) m/z (%) 448/
50/52/54 (M + H +, 100). Anal. Calcd for C19H20Cl3NO3S: C 50.85;
H 4.49; N 3.12. Found: C 50.63; H 4.54; N 3.05. Yield ) 92%. Mp
) 93.0-96.9 °C. Amorphous brown solid.
Synthesis of ꢀ-(Mesyloxy) Amines 9. The synthesis of N-iso-
propyl-N-(2,2-dichloro-3-(mesyloxy)-1,3-diphenylpropyl)amine (9a)
is representative.16 To a solution of R,R-dichloro-ꢀ-(mesyloxy)
imine 8a (0.83 g, 2 mmol) in methanol (10 mL) was added
NaCNBH3 (0.31 g, 5 mmol), followed by acetic acid (0.15 g, 2.4
mmol). The mixture was stirred for 96 h at room temperature,
poured into a 0.5 N NaOH solution (35 mL), and extracted with
CH2Cl2 (3 × 20 mL). The combined organic extracts were dried
(MgSO 4) and evaporated in vacuo. The reaction mixture obtained
was purified by column chromatography (pentane/diethyl ether 9/1)
to afford 0.56 g (67%) of pure 9a (Rf ) 0.12) and 0.078 g (12%)
of pure trans-azetidine 11a (Rf ) 0.54).
trans-3,3-Dichloro-1-isopropyl-2,4-diphenylazetidine 11a. 1H
NMR (CDCl3, 300 MHz) δ 0.69 (d, 3H, J ) 6.05 Hz), 0.71 (d,
3H, J ) 6.60 Hz), 3.07 (septet, 1H, J ) 6.2 Hz), 5.27 (s, 2H),
7.36-7.57 (m, 10H); 13C NMR (CDCl3, 75 MHz) δ 21.1, 21.9,
48.6, 82.3, 85.2, 127.9, 128.6, 129.7, 136.5; IR (KBr, cm -1) ν
1453, 1230, 1200, 929, 698; MS (ES, pos. mode) m/z (%) 320/22/
24 (M + H +, 100). Anal. Calcd for C18H19Cl2N: C 67.51; H 5.98;
N 4.37. Found: C 67.44; H 6.03; N 4.28. Yield ) 12%. Rf ) 0.54
(pentane/diethyl ether 9:1). Mp ) 114.1-115.1 °C. White crystals.
1
0.27 g (76%) of the pure compound. 12a. H NMR (CDCl3, 300
MHz) δ 1.32 (d, 6H, J ) 6.33 Hz), 4.33 (septet, 1H, J ) 6.33 Hz),
7.37-7.44 (m, 6H), 7.56-7.61 (m, 2H), 8.04-8.09 (m, 2H); 13C
NMR (CDCl3, 75 MHz) δ 23.5, 56.3, 81.5, 97.5, 121.7, 127.5,
-1
128.2, 128.6, 129.5, 130.2, 132.1, 137.9, 148.3; IR (NaCl, cm
)
ν 2204 (Ct C), 1591 (CdN); MS (ES, pos. mode) m/z (%) 248
(M + H +, 100). Anal. Calcd for C18H17N: C 87.41; H 6.93; N
5.66. Found: C 87.29; H 6.95; N 5.62. Yield ) 76%. Rf ) 0.35
(petroleum ether/EtOAc 9:1). Colorless viscous oil.
N-Isopropyl-N-[2,2-dichloro-3-(4-chlorophenyl)-3-(mesyloxy)-
1
1-phenylpropyl]amine 9c. H NMR (CDCl3, 300 MHz) δ 0.97
Acknowledgment. The authors are indebted to the “Fund
for Scientific Research - Flanders (Belgium)” (FWO-Vlaan-
deren) and to Ghent University (GOA) for financial support.
and 1.09 (2 × d, 2 × 3H, J ) 6.33 Hz), 1.80 (broad s, 1H), 2.68
(s, 3H), 2.69 (septet, 1H, J ) 6.33 Hz), 4.51 (s, 1H), 6.65 (s, 1H),
7.32-7.47 (m, 7H), 7.61-7.66 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ 22.0, 24.5, 40.1, 46.6, 65.9, 82.5, 94.9, 127.8, 128.2, 128.3,
129.8, 131.8, 136.1, 137.3; IR (KBr, cm -1) ν 3349 (NH, weak),
1371, 1179, 945, 847; MS (ES, pos. mode) m/z (%) 450/52/54/56
(M + H +, 100). Anal. Calcd for C19H22Cl3NO3S: C 50.62; H 4.92;
N 3.11. Found: C 50.24; H 4.85; N 3.00. Yield (after washing of
the reaction crude with petroleum ether/EtOAc 9/1) ) 65%. Mp
) 118.7-120.3 °C. Amorphous yellow-brown solid.
Supporting Information Available: General information,
spectroscopic data of compounds 12b,c/13b,c and computational
details. This material is available free of charge via the Internet
JO800522B
5488 J. Org. Chem. Vol. 73, No. 14, 2008