The Journal of Organic Chemistry
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dichloromethane (15 mL). Following removal of solvent, the product
was purified using column chromatography on silica (500:10:1 DCM/
MeOH/NH4OH) and isolated as a brown solid in 82% yield (104 mg,
(s, 3H, CH3), 2.29 (s, 6H, CH3), 2.07 (br s, 1H, NH). 13C{1H} NMR
(CDCl3): δ 143.8, 143.3, 141.4, 139.3, 129.6, 123.2, 120.8, 117.9,
116.5, 116.1, 56.1, 36.1, 21.7. HRMS (ESI/[M + H]+) calcd for
C16H21N2: 241.1699 Found: 241.1700.
1
0.41 mmol). H NMR (CDCl3): δ 7.22−7.19 (m, 2H, ArH), 7.05 (d,
2H, J = 9 Hz, ArH), 6.92 (d, 4H, J = 8 Hz, ArH), 6.82 (t, 1H, J = 7 Hz,
ArH), 5.48 (br s, 1H, NH), 3.10 (s, 4H, CH2), 1.76−1.71 (m, 4H,
CH2), 1.59−1.55 (m, 2H, CH2). 13C{1H} NMR (CDCl3): δ 148.5,
145.6, 135.2, 129.6, 122.1, 119.7, 118.4, 115.9, 51.9, 26.4, 24.6. HRMS
(ESI/[M + H]+) calcd for C17H21N2: 253.1699, found 253.1705.
Preparation of 3,5-Dimethyl-N-(4-(piperazin-1-yl)phenyl)-
aniline (4e). The general procedure was followed, with 1-(4-
chlorophenyl)piperazine (98 mg, 0.50 mmol) weighed out in the
glovebox and 3,5-Me-aniline (69 uL, 0.55 mmol) added via a
microlitre syringe. The reaction was allowed to proceed for 24 h, and
the reaction mixture was then cooled and filtered through a layer of
neutral alumina and washed with dichloromethane (15 mL).
Following removal of solvent, the product was purified using column
chromatography on silica (100:15:1.5 DCM/MeOH/NH4OH) and
isolated as an orange oil in 71% yield (100 mg, 0.36 mmol). 1H NMR
(CDCl3): δ 7.05 (m, 2H, ArH), 6.90 (m, 2H, ArH), 6.57 (s, 2H, ArH),
6.50 (s, 1H, ArH), 5.45 (br s, 1H, NH), 3.11−3.03 (m, 8H, CH2), 2.25
(s, 6H, CH3), 1.82 (br s, 1H, NH). 13C{1H} NMR (CDCl3): δ 147.6,
145.3, 139.2, 135.9, 121.9, 121.7, 117.8, 113.9, 51.6, 46.5, 21.7. HRMS
(ESI/[M + H]+) calcd for C18H24N3: 282.1965, found 282.1962.
Preparation of N-(4-(Piperazin-1-yl)phenyl)-3-
(trifluoromethyl)aniline (4f). The general procedure was followed,
with 1-(4-chlorophenyl)piperazine (98 mg, 0.50 mmol) weighed out
in the glovebox and 3-trifluoromethylaniline (68 uL, 0.55 mmol)
added via a microlitre syringe. The reaction was allowed to proceed for
24 h, and the reaction mixture was then cooled and filtered through a
layer of neutral alumina and washed with dichloromethane (15 mL).
Following removal of solvent, the product was purified using column
chromatography on silica (100:15:1.5 DCM/MeOH/NH4OH) and
Preparation of 3-((Methylamino)methyl)-N-(3-
(trifluoromethyl)phenyl)aniline (4i). The general procedure was
followed, with 3-chloro-N-methylbenzylamine (73 uL, 0.50 mmol) and
3-CF3-aniline (68 uL, 0.55 mmol) added via a microlitre syringe. The
reaction was allowed to proceed for 22 h, and the reaction mixture was
then cooled and filtered through a layer of neutral alumina and washed
with dichloromethane (15 mL). Following removal of solvent, the
product was purified using column chromatography on silica (50:10:1
DCM/MeOH/NH4OH) and isolated as an off-white solid in 67%
yield (94 mg, 0.34 mmol). 1H NMR (CDCl3): δ 7.34 (t, 1H, J = 8 Hz,
ArH), 7.28 (t, 2H, J = 8 Hz, ArH), 7.19 (m, 1H, ArH), 7.13 (d, 1H, J =
8 Hz, ArH), 7.07 (s, 1H, ArH), 7.04 (dd, 1H, J = 8 Hz, J = 1.5 Hz,
ArH), 6.97 (d, 1H, J = 8 Hz, ArH), 5.95 (br s, 1H, NH), 3.74 (s, 2H,
CH2), 2.48 (s, 3H, CH3), 2.02 (br s, 1H, NH). 13C{1H} NMR
(CDCl3): δ 144.3, 142.4, 141.8, 132.0 (quart., JCF = 32.7 Hz), 130.2,
129.9, 124.4 (quart., JCF = 276.8 Hz), 122.4, 120.2, 119.1, 117.7, 117.2
(m), 113.6 (m), 56.1, 36.2. HRMS (ESI/[M + H]+) calcd for
C15H16F3N2: 281.1260, found 281.1258.
Preparation of N1-Methyl-N3-phenylbenzene-1,3-diamine
(4j). The general procedure was followed, with 3-chloro-N-methylani-
line (61 uL, 0.50 mmol) and aniline (50 uL, 0.55 mmol) added via a
microlitre syringe. The reaction was allowed to proceed for 18 h, and
the reaction mixture was then cooled and filtered through a layer of
neutral alumina and washed with dichloromethane (15 mL).
Following removal of solvent, the product was purified using column
chromatography on silica (200:10:1 DCM/MeOH/NH4OH) and
1
isolated as an orange oil in 94% yield (93 mg, 0.47 mmol). H NMR
(CDCl3): δ 7.32−7.29 (m, 2H, ArH), 7.15−7.12 (m, 3H, ArH), 6.96
(t, 1H, J = 7 Hz, ArH), 6.50 (m, 1H, ArH), 6.39 (t, 1H, J = 2.5 Hz),
6.28 (m, 1H, ArH), 5.70 (br s, 1H, NH), 3.61 (br s, 1H, NH), 2.86 (s,
3H, CH3). 13C{1H} NMR (CDCl3): δ 150.7, 144.5, 143.6, 130.3,
129.6, 121.0, 118.3, 107.6, 106.1, 101.9, 31.1. HRMS (ESI/[M + H]+)
calcd for C13H15N2: 199.1230, found 199.1225.
1
isolated as a yellow solid in 60% yield (96 mg, 0.30 mmol. H NMR
(CDCl3): δ 7.27 (t, 1H, J = 8 Hz, ArH), 7.10−7.06 (m, 3H, ArH),
7.03−6.99 (m, 2H, ArH), 6.94−6.91 (m, 2H, ArH), 5.68 (br s, 1H,
NH), 3.13−3.04 (m, 8 H, CH2), 1.95 (br s, 1H, NH). 13C{1H} NMR
(CDCl3): 148.7, 146.3, 134.0, 131.9 (quart., JCF = 31 Hz), 130.0, 124.5
(quart., JCF = 273 Hz), 123.2, 118.2, 117.8, 115.7 (m), 111.5 (m), 51.2,
46.5. HRMS (ESI/[M + H]+) calcd for C17H19F3N3: 322.1526, found
322.1528.
Preparation of N1-(3,5-Dimethylphenyl)-N3-methylbenzene-
1,3-diamine (4k). The general procedure was followed, with 3-
chloro-N-methylaniline (61 uL, 0.50 mmol) and 3,5-Me-aniline (69
uL, 0.55 mmol) added via a microlitre syringe. The reaction was
allowed to proceed for 12 h, and the reaction mixture was then cooled
and filtered through a layer of neutral alumina and washed with
dichloromethane (15 mL). Following removal of solvent, the product
was purified using column chromatography on silica (1000:10:1
DCM/MeOH/NH4OH) and isolated as an orange oil in 95% yield
Preparation of 3-((Methylamino)methyl)-N-phenylaniline
(4g). The general procedure was followed, with 3-chloro-N-
methylbenzylamine (73 uL, 0.50 mmol) and aniline (50 uL, 0.55
mmol) added via a microlitre syringe. The reaction was allowed to
proceed for 36 h, and the reaction mixture was then cooled and filtered
through a layer of neutral alumina and washed with dichloromethane
(15 mL). Following removal of solvent, the product was purified using
column chromatography on silica (80:10:1 DCM/MeOH/NH4OH)
1
(107 mg, 0.48 mmol). H NMR (CDCl3): δ 7.11 (t, 1H, J = 8 Hz,
ArH), 6.75 (s, 2H, ArH), 6.61 (s, 1H, ArH), 6.47 (m, 1H, ArH), 6.36
(t, 1H, J = 2 Hz, ArH), 6.25 (m, 1H, ArH), 2.83 (s, 3H, CH3), 2.30 (s,
6H, CH3). 13C{1H} NMR (CDCl3): δ 150.6, 144.6, 143.5, 139.2,
130.3, 122.9, 116.1, 107.7, 105.9, 102.1, 31.1, 21.7. HRMS (ESI/[M +
H]+) calcd for C15H19N2: 227.1543, found 227.1541.
1
and isolated as a white solid in 82% yield (86 mg, 0.41 mmol). H
NMR (CDCl3): δ 7.29−7.25 (m, 2H, ArH), 7.22 (t, 1H, J = 8 Hz,
ArH), 7.09−7.07 (m, 2H, ArH), 7.02 (m, 1H, ArH), 6.99 (d of d of d,
1H, J = 8 Hz, J = 2.5 Hz, J = 1 Hz, ArH), 6.93 (t of t, 1H, J = 7.5 Hz, J
= 1 Hz, ArH), 6.88 (m, 1H, ArH), 5.77 (br s, 1H, NH), 3.71 (s, 2H,
CH2), 2.46 (s, 3H, CH3), 1.69 (br s, 1H, NH). 13C{1H} NMR
(CDCl3): δ 143.6, 143.4, 141.7, 129.7, 121.3, 121.1, 118.2, 117.8,
116.5, 56.3, 36.3. HRMS (ESI/[M + H]+) calcd for C14H17N2:
213.1386 Found: 213.1381.
Preparation of 3,5-Dimethyl-N-(3-((methylamino)methyl)-
phenyl)aniline (4h). The general procedure was followed, with 3-
chloro-N-methylbenzylamine (73 uL, 0.50 mmol) and 3,5-Me-aniline
(69 uL, 0.55 mmol) added via a microlitre syringe. The reaction was
allowed to proceed for 23 h, and the reaction mixture was then cooled
and filtered through a layer of neutral alumina and washed with
dichloromethane (15 mL). Following removal of solvent, the product
was purified using column chromatography on silica (50:10:1 DCM/
MeOH/NH4OH) and isolated as an off-white solid in 85% yield (102
mg, 0.43 mmol). 1H NMR (CDCl3): δ 7.23 (t, 1H, J = 7.5 Hz, ArH),
7.02−6.99 (m, 2H, ArH), 6.87 (d, 1H, J = 7.5 Hz, ArH), 6.72 (s, 2H,
ArH), 6.62 (s, 1H, ArH), 5.74 (br s, 1H, NH), 3.72 (s, 2H, CH2), 2.47
Preparation of N1-Methyl-N3-(3-(trifluoromethyl)phenyl)-
benzene-1,3-diamine (4l). The general procedure was followed,
with 3-chloro-N-methylaniline (61 uL, 0.50 mmol) and 3-CF3-aniline
(68 uL, 0.55 mmol) added via a microlitre syringe. The reaction was
allowed to proceed for 24 h, and the reaction mixture was then cooled
and filtered through a layer of neutral alumina and washed with
dichloromethane (15 mL). Following removal of solvent, the product
was purified using column chromatography on silica (DCM −
1000:10:1 DCM/MeOH/NH4OH) and isolated as a dark orange oil
in 88% yield (118 mg, 0.44 mmol). 1H NMR (CDCl3): δ 7.33 (t, 1H, J
= 8 Hz, ArH), 7.29 (s, 1H, ArH), 7.29 (dd, 1H, J = 8 Hz, J = 2 Hz,
ArH), 7.14−7.10 (m, 2H, ArH), 6.47 (ddd, 1H, J = 8 Hz, J = 2 Hz, J =
1 Hz, ArH), 6.37 (t, 1H, J = 2 Hz, ArH), 6.31 (ddd, 1H, J = 8 Hz, J = 2
Hz, J = 1 Hz, ArH), 5.78 (br s, 1H, NH), 2.83 (s, 3H, CH3). 13C{1H}
NMR (CDCl3): δ 150.7, 144.5, 143.2, 131.9 (quart., JCF = 32.7 Hz),
130.6, 130.1, 124.5 (quart., JCF = 272.9 Hz), 120.3, 116.9 (m), 113.7
(m), 108.6, 107.5, 103.0, 31.1. HRMS (ESI/[M + H]+) calcd for
C14H14F3N2: 267.1104, found 267.1120.
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dx.doi.org/10.1021/jo202358p | J. Org. Chem. 2012, 77, 1056−1071