PAPER
Synthesis of 2-[(Arylmethylene)amino]cyclopropanecarbonitriles
1109
IR (NaCl): 2250, 1642 cm–1.
MS (ES, +): m/z (%) = no [M + H]+, 167 (100).
1H NMR (300 MHz, CDCl3): d = 2.40 (s, 3 H), 2.77 (dd, J = 16.8,
7.4 Hz, 1 H), 2.89 (dd, J = 16.8, 4.7 Hz, 1 H), 3.49 (dd, J = 10.5, 6.3
Hz, 1 H), 3.62 (dd, J = 10.5, 6.6 Hz, 1 H), 3.71–3.79 (m, 1 H), 7.24
(d, J = 8.3 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 8.34 (s, 1 H).
Anal. Calcd for C17H18BrClN2: C, 55.83; H, 4.96; N, 7.66. Found:
C, 56.16; H, 4.59; N, 7.66.
3-(Benzhydrylamino)-4-bromobutanenitrile (11)
To a suspension of hydrochloride 10 (44 mg, 0.12 mmol) in EtOAc
(2 mL) was added 2 N aq NaOH (0.5 mL). The reaction mixture was
stirred at r.t. for 5 min. After separation of the organic layer, drying
(MgSO4), filtration and concentration under reduced pressure,
benzhydrylamine 11 was obtained [yield: 40 mg (100%)], and was
not purified further.
13C NMR (75 MHz, CDCl3): d = 21.5, 23.8, 34.8, 67.1, 117.2,
128.7, 129.4, 132.4, 142.1, 164.0.
MS (EI, 70 eV): m/z (%) = 264/266 (5) [M+], 224/226 (100), 171
(72), 144 (63), 131 (90), 118 (50), 91 (27).
(E)-4-Bromo-3-{[(2-chlorophenyl)methylene]amino}butaneni-
trile (9d)
Yield: 95%; brown viscous oil.
Colorless viscous oil.
IR (neat): 3318, 2249 cm–1.
IR (NaCl): 2251, 1635 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.95 (br s, 1 H, NH), 2.58 (dd,
J = 6.9, 16.8 Hz, 1 H, CHHCN), 2.67 (dd, J = 6.3, 16.8 Hz, 1 H,
CHHCN), 3.10–3.16 (m, 1 H, CHN), 3.59 (dd, J = 3.2, 10.9 Hz, 1
H, CHHBr), 3.67 (dd, J = 5.2, 10.7 Hz, 1 H, CHHBr), 4.94 (s, 1 H,
CHPh2), 7.21–7.48 (m, 10 H, 10 × CHAr).
1H NMR (300 MHz, CDCl3): d = 2.82 (dd, J = 16.7, 7.0 Hz, 1 H),
2.89 (dd, J = 16.8, 5.0 Hz, 1 H), 3.51 (dd, J = 10.5, 6.6 Hz, 1 H),
3.64 (dd, J = 10.5, 6.3 Hz, 1 H), 3.81–3.89 (m, 1 H), 7.29–7.42 (m,
3 H), 8.07 (dt, J = 7.7, 1.1 Hz, 1 H), 8.82 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.6, 35.6, 51.6, 64.1, 117.3,
127.2, 127.3, 127.66, 127.69, 128.79, 128.85, 142.1, 143.0.
13C NMR (75 MHz, CDCl3): d = 23.8, 34.4, 67.0, 116.9, 127.1,
128.7, 129.8, 132.0, 132.5, 135.6, 161.0.
MS (ES, +): m/z (%) = no [M + H]+, 167 (100).
MS (EI, 70 eV): m/z (%) = 284/286/288 (8) [M+], 244/246/248
(100), 191/193 (60), 164/166 (50), 151/153 (70), 138/140 (42), 130
(36), 102 (31), 89 (26), 75 (22).
trans- and cis-2-[(Diphenylmethylene)amino]cyclopropanecar-
bonitrile (5); Typical Procedures
The following procedures for cyclopropane 5 are representative for
the synthesis of the cyclopropanes 4 and 5.
(E)-4-Bromo-3-{[(4-chlorophenyl)methylene]amino}butaneni-
trile (9e)
Yield: 71%; brown viscous oil.
Procedure A
IR (NaCl): 2251, 1643 cm–1.
To a soln of nitrile 9f (0.16 g, 0.5 mmol) in anhyd THF (2 mL) was
added KOt-Bu (84 mg, 0.75 mmol). The reaction mixture was heat-
ed under reflux for 0.5 h. The solvent was evaporated, the residue
was redissolved in Et2O (10 mL), and the resulting solution was fil-
tered over MgSO4 and concentrated under reduced pressure to af-
ford a mixture of cyclopropanes trans-5 and cis-5 (81% crude
yield), which was separated by column chromatography (silica gel;
cyclohexane–EtOAc, 4:1); yield of trans-5: 31%; yield of cis-5:
22%.
1H NMR (300 MHz, CDCl3): d = 2.78 (dd, J = 16.7, 7.6 Hz, 1 H),
2.89 (dd, J = 16.7, 4.5 Hz, 1 H), 3.49 (dd, J = 10.5, 6.6 Hz, 1 H),
3.62 (dd, J = 10.5, 6.3 Hz, 1 H), 3.73–3.81 (m, 1 H), 7.41 (d, J = 8.5
Hz, 2 H), 7.72 (d, J = 8.5 Hz, 2 H), 8.34 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 23.8, 34.5, 67.1, 117.0, 129.0,
129.9, 133.4, 137.6, 162.9.
MS (EI, 70 eV): m/z (%) = 284/286/288 (12) [M+], 244/246/248
(100), 191/193 (67), 164/166 (46), 151/153 (63), 138/140 (40), 130
(29), 102 (15), 89 (25), 75 (17).
Procedure B
To a soln of nitrile 9f (0.16 g, 0.5 mmol) in anhyd t-BuOH (10 mL)
was added KOt-Bu (84 mg, 0.75 mmol). An immediate purple-
brown coloring was observed and the reaction mixture was stirred
at 40 °C for 1.5 h. The solvent was evaporated, the residue was re-
dissolved in Et2O (10 mL), and the resulting solution was poured
into H2O (5 mL) and extracted with Et2O (3 × 5 mL). Washing of
the combined organic extracts with brine (5 mL), drying (MgSO4),
filtration and evaporation of the solvent under reduced pressure af-
forded a mixture of cyclopropanes trans-5 and cis-5 (92% crude
yield), which was separated by column chromatography (silica gel;
PE–EtOAc, 9:1); yield of trans-5: 21%; yield of cis-5: 31%.
3-(Benzhydrylamino)-4-bromobutanenitrile Hydrochloride
(10)
To a soln of aziridine 8f (0.124 g, 0.5 mmol) in anhyd CH2Cl2 (3
mL) was added NBS (0.093 g, 0.525 mmol) and BHT (0.116 g,
0.525 mmol). The reaction mixture was stirred under reflux for 5 h,
then was poured into 0.5 N aq NaOH (5 mL) and extracted with
CH2Cl2 (3 × 10 mL). After drying (MgSO4) of the combined organic
extracts, filtration and concentration under reduced pressure, the
residue was redissolved in anhyd Et2O (20 mL). At 0 °C, a saturated
soln of anhyd HCl in anhyd Et2O was added and the resulting pre-
cipitate was collected by filtration to afford hydrochloride 10; yield:
0.161 g (88%).
trans-2-[(Diphenylmethylene)amino]cyclopropanecarbonitrile
(trans-5)
White crystals; mp 72 °C; Rf = 0.14 (PE–EtOAc, 9:1).
White solid; mp 151.4–151.8 °C.
IR (KBr): 3006, 2944, 2911, 2690, 2644, 2478, 2360, 2256 (w),
1572, 1488, 1466, 1455 cm–1.
IR (KBr): 2237, 1617 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.48 (ddd, J = 7.5, 6.2, 5.2 Hz, 1
H, CHH), 1.62 (ddd, J = 9.6, 4.9, 4.9 Hz, 1 H, CHH), 1.94 (ddd,
J = 9.4, 6.2, 3.2 Hz, 1 H, CHCN), 3.43 (ddd, J = 7.6, 4.7, 3.0 Hz, 1
H, CHN), 7.25–7.57 (m, 10 H, 10 × CHAr).
1H NMR (300 MHz, CDCl3): d = 2.66 (dd, J = 4.7, 17.3 Hz, 1 H,
CHHCN), 2.80 (dd, J = 9.8, 17.2 Hz, 1 H, CHHCN), 3.32 (dd,
J = 4.4, 12.7 Hz, 1 H, CHHBr), 3.42–3.49 (m, 1 H, CHN), 3.66 (dd,
J = 2.6, 12.5 Hz, 1 H, CHHBr), 5.55 (s, 1 H, CHPh2), 7.41–7.52 (m,
6 H, 6 × CHAr), 7.59–7.61 (m, 2 H, 2 × CHAr), 7.75–7.77 (m, 2 H,
2 × CHAr), 10.36 and 10.96 (each br s, each 1 H, NH·HCl).
13C NMR (75 MHz, CDCl3): d = 8.0, 17.2, 43.3, 120.5, 128.2,
128.3, 128.5, 128.9, 129.3, 130.6, 136.0, 139.0, 170.8.
13C NMR (75 MHz, CDCl3): d = 19.2, 28.4, 52.7, 65.2, 115.8,
128.8, 129.2, 129.9, 130.1, 130.6, 132.2, 133.0.
MS (ES, +): m/z (%) = 247 (100) [M + H]+.
Synthesis 2009, No. 7, 1105–1112 © Thieme Stuttgart · New York