The Journal of Organic Chemistry
Note
(CH), 29.4 (CH), 60.9 (CH2), 63.0 (CH), 117.8 (C), the numbers of
attached hydrogen atoms were derived from additional gHSQC data.
2-(Diisopentylamino)-4-methylpentanenitrile (7g). Following
General Procedure A, triisopentylamine 6g (0.29 mL, 0.95 mmol)
reacted with KSCN and aq tBuOOH for 2 h. The crude product was
purified by column chromatography (SiO2, pentane/Et2O = 45:1) to
give 7g (170 mg, 71%) as a colorless viscous liquid. Known
compound: the NMR spectroscopic data agree with those given in
ref 5c. 1H NMR (CDCl3, 300 MHz): δ 0.89 (d, J = 2.9 Hz, 6 H), 0.91
(d, J = 3.0 Hz, 6 H), 0.93 (d, J = 6.6 Hz, 6 H), 1.25−1.36 (m, 4 H),
1.53−1.66 (m, 4 H), 1.83 (sept, J = 6.7 Hz, 1 H), 2.28−2.37 (m, 2 H),
2.56−2.66 (m, 2 H), 3.66 (t, J = 7.7 Hz, 1 H); 13C{1H} NMR (CDCl3,
75.5 MHz): δ 22.2, 22.45, 22.52, 23.2, 24.8, 26.2, 37.2, 40.8, 50.1, 52.9,
118.8.
(133 mg, 86%) as a colorless viscous liquid. Known compound: the
NMR spectroscopic data agree with those given in ref 5a. H NMR
1
(CDCl3, 300 MHz): δ 2.33 (s, 3 H), 2.97 (s, 3 H), 4.12 (s, 2 H),
6.80−6.85 (m, 2 H), 7.14−7.17 (m, 2 H); 13C{1H} NMR (CDCl3,
75.5 MHz): δ 20.4, 39.4, 42.7, 115.3, 115.6, 129.7, 130.0, 145.7.
2-((4-Bromophenyl)(methyl)amino)acetonitrile (5b). Following
General Procedure C, 4-bromo-N,N-dimethylaniline 1b (0.20 g, 1.0
mmol) reacted with KSCN and aq tBuOOH for 1 h. The crude
product was purified by column chromatography (SiO2, pentane/Et2O
= 20:1) to give 5b (182 mg, 81%) as a colorless solid. Known
compound: the NMR spectroscopic data agree with those given in ref
5a. 1H NMR (CDCl3, 300 MHz): δ 2.98 (s, 3 H), 4.14 (s, 2 H), 6.70−
6.75 (m, 2 H), 7.37−7.42 (m, 2 H); 13C{1H} NMR (CDCl3, 75.5
MHz): δ 39.4, 42.3, 112.7, 115.2, 116.5, 132.4, 146.9.
2-(Methyl(phenyl)amino)acetonitrile (5c) and N,N-dimethyl-4-
thiocyanatoaniline (8). Following General Procedure C, N,N-
dimethylaniline 1c (0.13 mL, 1.0 mmol) reacted with KSCN and aq
tBuOOH for 1 h. The product mixture was separated by column
chromatography (SiO2, pentane/Et2O = 15:1 → 15:2) to give 5c and
8.
2-(Dioctylamino)nonanenitrile (7h). Following General Procedure
A, tri-n-octylamine 6h (0.45 mL, 1.0 mmol) reacted with KSCN and
tBuOOH (4.9 M in CH2Cl2) for 1.5 h. The crude product was purified
by column chromatography (SiO2, pentane/Et2O = 110:1) to give 7h
(273 mg, 72%) as a colorless viscous liquid. Known compound: the
1
NMR spectroscopic data agree with those given in ref 5c. H NMR
2-(Methyl(phenyl)amino)acetonitrile (5c). 76 mg (52%), colorless
(CDCl3, 400 MHz): δ 0.86−0.90 (m, 9 H), 1.23−1.45 (m, 34 H),
1.66−1.73 (m, 2 H), 2.30−2.36 (m, 2 H), 2.51−2.58 (m, 2 H), 3.55 (t,
J = 7.8 Hz, 1 H); 13C{1H} NMR (CDCl3, 100.6 MHz): δ 14.20, 14.24,
22.76, 22.81, 26.2, 27.4, 28.2, 29.1, 29.2, 29.5, 29.6, 31.9, 32.0, 32.1,
51.9, 54.7, 118.8.
viscous liquid. Known compound: the NMR spectroscopic data agree
1
with those given in ref 5a. H NMR (CDCl3, 300 MHz): δ 3.01 (s, 3
H), 4.15 (s, 2 H), 6.87−6.98 (m, 3 H), 7.32−7.37 (m, 2 H); 13C{1H}
NMR (CDCl3, 75.5 MHz): δ 39.2, 42.2, 114.8, 115.6, 120.1, 129.5,
147.8.
2-((1R,5S)-8-Azabicyclo[3.2.1]octan-8-yl)acetonitrile (7i). Follow-
ing General Procedure B, tropane 6i (0.14 mL, 1.0 mmol) reacted with
KSCN and aq tBuOOH for 1 h. The crude product was purified by
column chromatography (SiO2, pentane/EtOAc = 5:4) to give 7i (96
N,N-Dimethyl-4-thiocyanatoaniline (8). 52 mg (29%), colorless
solid, mp 73−73.5 °C. Known compound: the NMR spectroscopic
data agree with those given in refs 14,25. 1H NMR (CDCl3, 300
MHz): δ 2.99 (s, 6 H), 6.66−6.69 (m, 2 H), 7.39−7.45 (m, 2 H);
13C{1H} NMR (CDCl3, 75.5 MHz): δ 40.3, 106.7, 112.7, 113.3, 134.6,
151.8.
1
mg, 61%) as a colorless viscous liquid. Known compound: ref 24. H
NMR (CDCl3, 300 MHz): δ 1.34−1.78 (m, 8 H), 1.93−1.97 (m, 2
H), 3.27−3.29 (m, 4 H); 13C{1H} NMR (CDCl3, 75.5 MHz): δ 16.2
(CH2), 26.1 (CH2), 31.0 (CH2), 41.0 (CH2), 60.5 (CH), 117.9 (C),
the numbers of attached hydrogen atoms were derived from additional
2-(Mesityl(methyl)amino)acetonitrile (5d). Following General
Procedure C, N,N,2,4,6-pentamethylaniline 1d (0.18 mL, 1.0 mmol)
reacted with KSCN and aq tBuOOH for 1 h. The crude product was
purified by column chromatography (SiO2, pentane/Et2O = 2:1) to
give 5d (158 mg, 84%) as a colorless viscous liquid. Known
compound: the NMR spectroscopic data agree with those given in
̃
gHSQC data; IR (neat/ATR probe): ν = 2929, 2871, 1476, 1456,
1431, 1341, 1331, 1313, 1255, 1219, 1168, 1134, 1111, 1069, 1057,
1038, 980, 942, 874, 849, 821, 768, 720 cm−1.
2-((1R,5S)-3-Oxo-8-azabicyclo[3.2.1]octan-8-yl)acetonitrile (7j)
from tropinone (6j). Potassium thiocyanate (4.0 g, 40 mmol) and
tropinone 6j (1.4 g, 10 mmol) were dissolved in acetonitrile (20 mL)
and heated at 50 °C. The reaction was started by slow injection of aq
tBuOOH (5.5 mL, 40 mmol, within ca. 5 min). The reaction mixture
was then stirred at 50 °C for another 2.5 h, during which the mixture
became more and more opaque. After allowing the reaction mixture to
cool at ambient temperature, the suspension was poured on brine (60
mL) and extracted with dichloromethane (3 × 50 mL). The combined
organic phases were dried (MgSO4), and the solvent was removed
under reduced pressure. The crude product was purified by column
chromatography (SiO2, pentane/EtOAc = 4:5) to give 7j (1.4 g, 85%)
as a colorless solid (mp. 64.5−65 °C). Crystals suitable for X-ray single
crystal analysis were obtained by slow evaporation of a dichloro-
methane solution of 7j.13 Known compound: ref 9a. 1H NMR (CDCl3,
300 MHz): δ 1.63−1.71 (m, 2 H), 2.09−2.13 (m, 2 H), 2.22−2.27 (m,
2 H), 2.61−2.68 (m, 2 H), 3.50 (s, 2 H), 3.59−3.60 (m, 2 H);
13C{1H} NMR (CDCl3, 75.5 MHz): δ 27.5 (CH2), 40.2 (CH2), 48.7
1
ref 5c. H NMR (CDCl3, 300 MHz): δ 2.27 (s, 3 H), 2.29 (s, 6 H),
2.95 (s, 3 H), 3.93 (s, 2 H), 6.86 (s, 2 H); 13C{1H} NMR (CDCl3,
75.5 MHz): δ 19.0, 20.8, 40.4, 44.1, 117.7, 129.8, 136.0, 137.0, 144.3.
2-((4-Methoxyphenyl)(methyl)amino)acetonitrile (5e). Following
General Procedure C, 4-methoxy-N,N-dimethylaniline 1e (0.15 g, 0.99
mmol) reacted with KSCN and aq tBuOOH for 1 h. The crude
product was purified by column chromatography (SiO2, pentane/Et2O
= 2:1) to give 5e (151 mg, 87%) as a colorless viscous liquid. Known
compound: the NMR spectroscopic data agree with those given in ref
1
5a. H NMR (CDCl3, 300 MHz): δ 2.92 (s, 3 H), 3.78 (s, 3 H), 4.07
(s, 2 H), 6.88 (s, 2 H); 13C{1H} NMR (CDCl3, 75.5 MHz): δ 40.0,
44.0, 55.7, 114.9, 115.5, 117.8, 142.3, 154.4.
2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-1-carboni-
trile (5f). Following General Procedure C, 2-(4-methoxyphenyl)-
1,2,3,4-tetrahydroisoquinoline 1f (0.24 g, 1.0 mmol) reacted with
KSCN and aq tBuOOH for 1 h. The crude product was purified by
column chromatography (SiO2, pentane/Et2O = 15:2) to give 5f (114
mg, 43%) as a colorless solid. Known compound: the NMR
spectroscopic data agree with those given in ref 5a. 1H NMR
(CDCl3, 300 MHz): δ 2.88−2.96 (m, 1 H), 3.10−3.22 (m, 1 H),
3.39−3.48 (m, 1 H), 3.54−3.61 (m, 1 H), 3.79 (s, 3 H), 5.36 (s, 1 H),
6.88−6.94 (m, 2 H), 7.06−7.11 (m, 2 H), 7.20−7.33 (m, 4 H);
13C{1H} NMR (CDCl3, 75.5 MHz): δ 28.8, 45.0, 55.66, 55.68, 114.9,
(CH2), 59.7 (CH), 117.3 (C, CN), 208.1 (C, CO), the numbers of
attached hydrogen atoms were derived from additional gHSQC data;
̃
IR (neat/ATR probe): ν = 2955, 2886, 1709, 1473, 1411, 1341, 1234,
1194, 1152, 1134, 1101, 1008, 905, 842, 776, 726 cm−1.
2-((1R,5S)-3-Oxo-8-azabicyclo[3.2.1]octan-8-yl)acetonitrile (7j)
from tropine (6k). Analogous to General Procedure B, tropine 6k
(0.14 mL, 0.99 mmol) reacted with KSCN and 5 equiv of aq tBuOOH
(0.69 mL, 5.00 mmol) for 2 h. The crude product was purified by
column chromatography (SiO2, pentane/EtOAc = 4:5) to give 7j (118
117.7, 121.1, 126.8, 127.2, 128.8, 129.6, 129.8, 134.5, 142.7, 155.8.
1-Methyl-1,2,3,4-tetrahydroquinoline-2-carbonitrile (5g). Follow-
ing General Procedure B, 1-methyl-1,2,3,4-tetrahydroquinoline 1g
(0.15 g, 1.0 mmol) reacted with KSCN and aq tBuOOH for 1 h. The
crude product was purified by column chromatography (SiO2,
pentane/Et2O = 7:1) to give 5g (125 mg, 73%) as a colorless viscous
1
mg, 72%) as colorless crystals. H and 13C NMR spectra agree with
those of 7j that was obtained from 6j.
2-(Methyl(p-tolyl)amino)acetonitrile (5a). Following General
Procedure C, N,N,4-trimethylaniline 1a (0.14 mL, 0.97 mmol) reacted
with KSCN and aq tBuOOH for 1 h. The crude product was purified
by column chromatography (SiO2, pentane/Et2O = 6:1) to give 5a
1
liquid. H NMR (CDCl3, 300 MHz): δ 2.24−2.34 (m, 2 H), 2.80−
2.88 (m, 1 H), 3.02 (s, 3 H), 3.11−3.24 (m, 1 H), 4.28−4.31 (m, 1 H),
6.73−6.85 (m, 2 H), 7.05−7.21 (m, 2 H); 13C{1H} NMR (CDCl3,
E
J. Org. Chem. XXXX, XXX, XXX−XXX