Highly efficient amination in neat water of benzyl chlorides with dialkylformamides catalysed by N-heterocyclic carbene-palladium(II)-1- methylimidazole complex

Article abstract of DOI:10.3184/174751913X13787959859344

Dialkylformamides are excellent N-sources in the amination of benzyl chlorides when catalysed by a NHC-Pd(II)-Im complex. In the presence of NaOH and the catalyst, variously substituted benzyl chlorides and five different dialkylformamides reacted smoothly to afford the corresponding N,N-dialkyl-benzylamines in good to almost quantitative yields in eco-friendly solvent water at 50 °C within 3 h.

Full text of DOI:10.3184/174751913X13787959859344

JOURNAL OF CHEMICAL RESEARCH 2013
OCTOBER, 611–614
RESEARCH PAPER 611
Highly efficient amination in neat water of benzyl chlorides with
dialkylformamides catalysed by N-heterocyclic carbene-palladium(II)-1-
methylimidazole complex
Wen-Xin Chen, Cai-Yun Zhang and Jian-Mei Lu
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou, Zhejiang Province 325035, P.R. China
Dialkylformamides are excellent N-sources in the amination of benzyl chlorides when catalysed by a NHC-Pd(II)-Im complex.
In the presence of NaOH and the catalyst, variously substituted benzyl chlorides and five different dialkylformamides reacted
smoothly to afford the corresponding N,N-dialkyl-benzylamines in good to almost quantitative yields in eco-friendly solvent
water at 50 °C within 3 h.
Keywords: N-heterocyclic carbene, palladium complex, benzyl chlorides, amination, water
During the past decade, N-heterocyclic carbenes (NHCs)-
metal complexes have shown efficient catalytic activity in
the formation of carbon–carbon and carbon–heteroatom
Table 1 Evaluation of the base and reaction time for the amination of
benzyl chloride with N-formylmorpholine by NHC-Pd(II)-Im
complex
H
O
1–3
Cl
bonds. In our continuing studies of the synthesis of novel
NHC–metal complexes and their applications in organic
synthesis, we have developed several new reactions for the
NHC-Pd(II)-Im 1
1.0 mol%)
N
(
N
+
base, H O
2
O
4
–6
formation of carbon–carbon and carbon–nitrogen bonds. For
instance, recently, we have found that amides can be excellent
N-sources in the catalysed amination of aryl chlorides by a
N-heterocyclic carbene-Pd(II)-1-methylimidazole [NHC-
Pd(II)-Im] complex 1; the corresponding anilines being formed
in moderate to almost quantitative yields at room temperature
O
3a
4a
2a
Entrya
1
2
3
Yield/%b
70
83
96
Base
KOH
NaOH
NaOH
Temp./°C
Time/h
25
25
50
12
12
3
6
aReaction conditions: 2a (0.8 mmol), 3a (2.0 equiv.), base (3.0 equiv.),
within 6 h (Scheme 1). These results prompted us to expand
its application to the reaction between benzyl chlorides and
amides for the synthesis of benzylamines.
NHC-Pd(II)-Im 1 (1.0 mol%), H O (1.0 mL).
2
b
Isolated yields.
Furthermore, compared to toxic, flammable and volatile
organic solvents, water, as a non-toxic, non-flammable and
the most eco-friendly solvent, has attracted much attention
base. As can be seen from Table 1, NaOH (83% yield) was
better than KOH (70%) as the base in the formation of the
corresponding aminated product 4a (Table 1, entries 1 and 2).
In the presence of the weaker bases K CO , Na CO , KHCO
3
7
in organic synthesis over the past 15 years. Considering our
2
3
2
3
experience in the reactions performed in neat water catalysed by
and NaHCO , no reaction occurred. Further study showed that
4
,5
3
NHC-metal complexes and to develop an alternative method
for the N-benzylation of benzyl halides, we investigated the
NHC-Pd(II)-Im-catalysed reactions between benzyl chlorides
when the reaction temperature was raised to 50 °C, product
4
a can be obtained in 96% yield within 3 h (Table 1, entry 3).
So the optimal reaction conditions were established as using
NHC-Pd(II)-Im complex 1 (1.0 mol%) as the catalyst, NaOH
8
–12
and amides in neat water.
detail.
We now report these results in
(3.0 equiv) as the base, with the temperature of 50 °C in neat
water (Table 1, entry 3). A similar complex such as NHC-Pd-Py
Results and discussion
12
developed by Organ’s group was also tested for the reaction
between benzyl chloride 2a and N-formylmorpholine 3a, and
an inferior result was obtained (80%).
With the optimal reaction conditions in hand, we then
investigated the reactions of a variety of benzyl chlorides
Initial investigations were carried out using benzyl chloride
a (0.8 mmol) and N-formylmorpholine 3a (2.0 equiv) as the
substrates in the presence of the NHC-Pd(II)-Im complex 1
1.0 mol%) in water (1.0 mL) at 25 °C for 12 h to find the best
2
(
2
b–n with N-formylmorpholine 3a to test the generality of the
Cl
O
NHC-Pd(II)-Im 1
1.0 mol%)
R2
reaction (Table 2). As can be seen from Table 2, regardless of
electron-donating or electron-withdrawing groups substituted
benzyl chlorides 2b–f and 2h–m as the substrates, all reactions
proceeded smoothly to give the desired products 4 in high to
almost quantitative yields in 3 h (Table 2, entries 1–5, 8–13).
R2
(
+
t
N
R
N
KO Bu, THF or DMF,
R3
1
R1
R3
rt, 6 h
R
Pri
1-Chloromethylnaphthalene 2n was also found to be a suitable
Pri Cl
Pd
substrate and 98% yield of product 4n was achieved (Table 2,
entry 14). Although 4-tert-butylbenzyl chloride 2g was not a
good substrate under the optimal conditions, the corresponding
product 4g could be obtained in 98% at elevated temperature
(80 °C) (Table 2, entries 6 and 7).
N
N
NHC-Pd(II)-Im 1:
N
N
Pri
Cl
Pri
Encouraged by these results, we also carried out the
amination reactions of various substitutes of benzyl
chlorides
formamides: N-formylpiperidine 3b, N,N-dimethylformamide
c, N,N-diethylformamide 3d, formanilide 3e and
2 under optical conditions with five other
Scheme 1.
Correspondent. E-mail: lujianmei1982@163.com
3
*
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612 JOURNAL OF CHEMICAL RESEARCH 2013
Table 2 Yields of the amination of a series of benzyl chlorides 2b–n with
N-formylmorpholine 3a catalysed by NHC-Pd(II)-Im complex
under optimal conditions
N-methylformanilide 3f. For the reactions of benzyl chlorides 2
with N-formylpiperidine 3b, N,N-dimethylformamide 3c, N,N-
diethylformamide 3d, and N-methylformanilide 3f, good to
almost quantitative yields of products 4o–4w, 4aa and 4ab were
achieved under the optimal reaction conditions (Table 3, entries
1–9, 13 and 14). The electronic effect of the substituents on the
benzyl chlorides 2 did not affect the reactions. For example,
whether electron-donating groups such as MeO- and Me- or
electron-withdrawing group such as F- and CN- were attached
on the benzyl chlorides, similar good to almost quantitative
yields were achieved. When formanilide 3e was used as the
substrate, products 4x–4z were also obtained in high yields
Cl
H
O
NHC-Pd(II)-Im 1
1.0 mol%)
N
O
(
N
+
NaOH, H O,
O
2
R1
o
R1
4
2
50 C, 3 h
3
a
Entrya
2 (R1)
Yield/%
4b, 98
4c, 99
4e, 99
4e, 99
4f, 99
4g, 61
4g, 94
4h, 98
4i, 98
1
2
3
4
5
6
2b (4-Me)
2c (3-MeO)
2d (4-MeO)
2e (2-Me)
2f (3-Me)
2g (4- Bu)
2g (4- Bu)
2h (4-Cl)
2i (2-CN)
2j (4-CN)
2k (4-F)
2l (4-NO2)
2m (2-Cl)
(
Table 3, entries 10–12).
All but one of the 25 N,N-dialkyl-benzylamines that were
t
synthesised were characterised by comparison of melting point
c
t
7
1
13
(
when a solid) and H and C NMR data with cited literature
8
9
data. The one new compound, 4i, was additionally characterised
by IR and HRMS.
10
4j, 98
4k, 95
4l, 97
1
1
In conclusion, we have found that formamides can be used as
N-sources in the NHC-Pd(II)-Im 1 complex-catalysed mono-
amination of benzyl chlorides. The reactions can tolerate a broad
scope of substrates. Under the optimal conditions, all reactions
performed very well to give the corresponding aminated
products in good to almost quantitative yields, providing a
convenient alternative method for the amination of benzyl
chlorides. It should be also pointed out that the reactions can be
performed in neat water under mild conditions, extending their
potential applications in industrial processes.
1
2
13
4m, 98
Cl
14
2n
4n, 98
aUnless otherwise specified, all reactions were carried out using 2
0.8 mmol), 3a (2.0 equiv.), NaOH (3.0 equiv.) in H O (1.0 mL) at 50 °C for
(
2
3
h.
b
Isolated yields.
c
Temperature was 80 °C.
Experimental
NMR spectra were obtained on a Bruker Avance-300 or -500 MHz
Table 3 Yields of the amination of a series of benzyl chlorides with a
series of dialkylformamides 3b–f catalysed by NHC-Pd(II)-Im
complex under optimal conditions
1
13
spectrometer ( H NMR at 300 or 500 Hz, C NMR at 75 or 125 Hz)
in CDCl3 with tetramethylsilane (TMS) as an internal standard;
J-values are in Hz. Commercially obtained reagents were used without
further purification. Flash column chromatography was carried out
using Huanghai 300–400 mesh silica gel at increased pressure. FT-
IR spectroscopy was performed using a NICOLET iS10 instrument.
HRMS was detected on a Bruker Esquire HCT spectrometer, and the
mass analyser type was an ion trap (ESI).
Cl
R3
NHC-Pd(II)-Im 1
R3
O
H
(
1.0 mol%)
N
+
N
NaOH, H O,
R2
2
R2
o
R1
4
R1
2
50 C, 3 h
3
Entry
2 (R1)
2a (H)
2b (4-Me)
2k (4-F)
2j (4-CN)
3
Yield/%
4o, 90
4p, 94
4q, 90
4r, 98
1
2
3
4
3b
3b
3b
3b
O
H
Amination of benzyl chlorides 2 with dialkylformamides 3 in neat water
catalysed by NHC-Pd(II)-Im complex 1; general procedure
N
Under a N atmosphere, NaOH (3.0 equiv), NHC-Pd(II)-Im complex
2
1
(1.0 mol%), water (1.0 mL), benzyl chloride 2a (0.8 mmol), and
O
H
N-formylmorpholine 3a (2.0 equiv) were successively added into a
Schlenk reaction tube. The mixture was stirred at 50 °C for 3 h. After
cooling to room temperature, the reaction mixture was extracted
with EtOAc, washed with brine, and dried over anhydrous Na SO .
N
5
2c (3-MeO)
3c
4s, 90
Cl
6
2n
2b
3c
4t, 95
4u, 93
2
4
Then the solvent was removed under reduced pressure and the residue
was purified by flash column chromatography on silica gel (eluent:
PE/EA=5:1) to give the pure products 4a.
7c
3d
O
H
N
13
1
8
9
2c
2n
2a
3d
3d
3e
4v, 98
4w, 99
4x, 90
4-Benzyl-morpholine (4a): Colourless liquid; H NMR (300 MHz): δ
7.31–7.23 (m, 5H), 3.68 (t, J=4.5 Hz, 4H), 3.47 (s, 2H), 2.42 (t, J=4.5 Hz,
O
Ph
H
13
10
4H); C NMR (75 MHz): δ 137.6, 129.0, 128.1, 127.0, 66.8, 63.3, 53.5.
N
14
4
-(4-Methyl-benzyl)-morpholine (4b): Yellow solid, m.p. 49–51 °C;
11
2c
3e
4y, 90
H
1
H NMR (300 MHz): δ 7.19 (d, J=8.1 Hz, 2H), 7.10 (d, J=8.1 Hz, 2H),
.68 (t, J=4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J=4.5 Hz, 4H), 2.32 (s, 3H);
1
2
2j
3e
3f
3f
O
4z
4aa, 98
4ab, 82
3
1
3
2d (4-MeO)
2j
N
1
3
C NMR (75 MHz): δ 136.5, 134.5, 129.0, 128.8, 66.8, 63.0, 53.4, 20.9.
14
H
Ph
15
1
a
4-(3-Methoxy-benzyl)-morpholine (4c): Yellow liquid; H NMR
300 MHz): δ 7.21 (t, J=7.8 Hz, 1H), 6.91–6.80 (m, 2H), 6.77 (dd, J= 0.9,
Unless otherwise specified, all reactions were carried out using 2
0.8 mmol), 3 (2.0 equiv.), NaOH (3.0 equiv.) in H O (1.0 mL) at 50 °C for
(
(
2
3
h.
2.4 Hz, 1H), 3.79 (s, 3H), 3.70 (t, J=4.5 Hz, 4H), 3.46 (s, 2H), 2.43 (t,
b
13
Isolated yields.
J=4.5 Hz, 4H); C NMR (75 MHz): δ 159.5, 139.4, 129.1, 121.3, 114.5,
c
Temperature was 80 °C.
112.4, 66.9, 63.2, 55.0, 53.5.
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JOURNAL OF CHEMICAL RESEARCH 2013 613
1
4
1
4
-(4-Methoxy-benzyl)-morpholine (4d): Colourless liquid; H NMR
J=7.8 Hz), 114.8 (d, J=21.0 Hz), 63.0, 54.3, 25.9, 24.3.
4-Piperidin-1-yl-methyl-benzonitrile (4r): Colourless liquid;
NMR (300 MHz): δ 7.59 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 3.50
(s, 2H), 2.37 (t, J=4.5 Hz, 4H), 1.61–1.54 (m, 4H), 1.48–1.44 (m, 2H); C
2
2
1
(
3
(
300 MHz): δ 7.22 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 3.78 (s,
H), 3.68 (t, J=4.5 Hz, 4H), 3.42 (s, 2H), 2.41 (t, J=4.5 Hz, 4H); C NMR
75 MHz): δ 158.7, 130.2, 129.6, 113.5, 66.8, 62.7, 55.1, 53.4.
-(2-Methyl-benzyl)-morpholine (4e): Colourless liquid; H NMR
300 MHz): δ 7.23 (d, J=6.6 Hz, 1H), 7.18–7.107 (m, 3H), 3.66 (t,
J=4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J=4.5 Hz, 4H), 2.36 (s, 3H);
H
13
13
16
1
4
NMR (75 MHz): δ 144.7, 131.9. 129.5, 119.0, 110.5, 63.2, 54.5, 25.9, 24.1.
2
3
1
(
3-Methoxy-benzyl)-dimethyl-amine (4s): Colourless liquid; H NMR
(500 MHz): δ 7.22 (t, J=7.5 Hz, 1H), 6.89 (d, J=7.5 Hz, 2H), 6.81–6.79
13
C
13
NMR (75 MHz): δ 137.4, 135.8, 130.2, 129.8, 127.0, 125.3, 67.0, 61.2, 53.6,
9.1.
-(3-Methyl-benzyl)-morpholine
(m, 1H), 3.80 (s, 3H), 3.43 (s, 2H), 2.26 (s, 6H); C NMR (125 MHz): δ
1
159.6, 139.9, 129.1, 121.4, 114.3, 112.8, 64.1, 55.1, 45.1.
2
4
1
4
4-(2-Methyl-benzyl)-morpholine
Dimethyl-naphthalen-1-yl-methyl-amine (4t): Colourless liquid; H
NMR (300 MHz): δ 8.24 (d, J=7.8 Hz, 1H), 7.83–7.75 (m, 2H), 7.51–7.36
17
1
(
(
4f): Colourless liquid; H NMR (300 MHz): δ 7.21–7.03 (m, 4H), 3.68
13
13
t, J=4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J=4.5 Hz, 4H), 2.33 (s, 3H);
NMR (75 MHz): δ 137.6, 137.5, 129.7, 128.0, 127.7, 126.1, 66.8, 63.3, 53.5,
1.2.
-(4-t-Butyl-benzyl)-morpholine (4g): Colourless liquid; H NMR
300 MHz): δ 7.32 (d, J=8.1 Hz, 2H), 7.23 (d, J=8.1 Hz, 2H), 3.68 (t,
C
(m, 4H), 3.79 (s, 2H), 2.27 (s, 6H); C NMR (75 MHz): δ 134.6, 133.8,
132.4, 128.4, 127.9, 127.4, 125.9, 125.5, 125.0, 124.4, 62.4, 45.6.
2
5
1
2
Diethyl-(4-methyl-benzyl)-amine (4u): Colourless liquid; H NMR
(500 MHz): δ 7.21 (d, J=8.0 Hz, 2H), 7.10 (d, J=8.0 Hz, 2H), 3.53 (s, 2H),
18
1
4
1
3
(
2.51 (q, J=7.0 Hz, 4H), 2.32 (s, 3H), 1.04 (t, J=7.0 Hz, 6H); C NMR
13
J=4.5 Hz, 4H), 3.45 (s, 2H), 2.42 (t, J=4.5 Hz, 4H), 1.31 (s, 9H); C NMR
75 MHz): δ 149.8, 134.5, 128.8, 125.0, 66.8, 63.0, 53.5, 34.3, 31.3.
(125 MHz): δ 136.6, 136.1, 128.84, 128.75, 57.1, 46.6, 21.0, 11.6.
2
6
1
(
Diethyl-(3-methoxy-benzyl)-amine (4v): colourless liquid; H NMR
(300 MHz): δ 7.20 (t, J=7.5 Hz, 1H), 6.92–6.89 (m, 2H), 6.78–6.75 (m,
1H), 3.78 (s, 3H), 3.53 (s, 2H), 2.51 (q, J=7.2 Hz, 4H), 1.03 (t, J=7.2 Hz,
1
6
1
4
-(4-Chloro-benzyl)-morpholine (4h): Colourless liquid; H NMR
(
(
6
300 MHz): δ 7.32–7.24 (m, 4H), 3.70 (t, J=4.5 Hz, 4H), 3.45 (s, 2H), 2.42
13
13
t, J=4.5 Hz, 4H); C NMR (125 MHz): δ 136.0, 132.8, 130.3, 128.3,
6.8, 62.5, 53.4.
-Morpholin-4-ylmethyl-benzonitrile (4i): Colourless liquid; IR (neat):
ν 2160, 1454, 1351, 1267, 1115, 1008, 913, 865, 763, 740, 701cm ; H
NMR (300 MHz): δ 7.65 (d, J=7.5 Hz, 1H), 7.57–7.53 (m, 2H), 7.39–7.28
6H); C NMR (75 MHz): δ 159.5, 141.6, 128.9, 121.1, 114.2, 112.1, 57.4,
55.0, 46.6, 11.6.
27
1
2
Diethyl-naphthalen-1-yl-methyl-amine (4w): Colourless liquid; H
–1
1
NMR (300 MHz): δ 8.46–8.42 (m, 1H), 7.94–7.83 (m, 2H), 7.60–7.48
(m, 4H), 4.07 (s, 2H), 2.69 (q, J=6.9 Hz, 4H), 1.17 (t, J=6.9 Hz, 6H);
NMR (75 MHz): δ 135.6, 133.8, 132.5, 128.3, 127.5, 127.0, 125.6, 125.4,
13
C
13
(
m, 1H), 3.71 (t, J=4.5 Hz, 4H), 3.69 (s, 2H), 2.51 (t, J=4.5 Hz, 4H);
C
NMR (75 MHz): δ 141.9, 132.9, 132.5, 130.0, 127.6, 117.7, 113.0, 66.8,
125.2, 124.6, 56.0, 46.9, 11.5.
Benzyl-phenylamine (4x): Colourless liquid; H NMR (500 MHz): δ
7.36-7.30 (m, 4H), 7.25 (t, J=7.0 Hz, 1H), 7.16 (dd, J=7.5, 8.5 Hz, 2H),
6.72 (t, J=7.5 Hz, 1H), 6.63 (d, J=8.0 Hz, 2H), 4.30 (s, 2H); C NMR
(125 MHz): δ 147.7, 139.1, 129.2, 128.6, 127.6, 127.2, 117.8, 113.1, 48.5.
3-Methoxy-benzyl)-phenylamine (4y): Colourless liquid; H NMR
(500 MHz): δ 7.24 (t, J=7.5 Hz, 1H), 7.17 (dd, J=7.0, 8.5 Hz, 2H), 6.95–
6.92 (m, 2H), 6.80 (dd, J=2.0, 8.5 Hz, 1H), 6.73 (t, J=7.0 Hz, 1H), 6.65 (d,
J=7.5 Hz, 2H), 4.29 (s, 2H), 3.78 (s, 3H); C NMR (125 MHz): δ 159.8,
147.6, 140.7, 129.6, 129.2, 119.8, 118.0, 113.2, 113.1, 112.7, 55.2, 48.5.
+
14
1
6
0.8, 53.3; MS (ESI): 203 [M+H] ; HRMS (ESI): calcd. for C H N O
12
15
2
+
[
M+H] : 203.1179; found: 203.1169.
19
13
4
-Morpholin-4-ylmethyl-benzonitrile (4j): Yellow solid, m.p. 78–
1
81 °C; H NMR (300 MHz): δ 7.51 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.1 Hz,
13
28
1
2H), 3.61 (t, J=4.5 Hz, 4H), 3.46 (s, 2H), 2.35 (t, J=4.5 Hz, 4H); C NMR
(
75 MHz): δ 143.6, 131.8, 129.2, 118.6, 110.6, 66.6, 62.4, 53.3.
16
1
4
-(4-Fluoro-benzyl)-morpholine (4k): Yellow liquid; H NMR
1
3
(
4
300 MHz): δ 7.30–7.25 (m, 2H), 7.02–6.96 (m, 2H), 3.69 (t, J=4.5 Hz,
H), 3.44 (s, 2H), 2.41 (t, J=4.5 Hz, 4H); C NMR (75 MHz): δ 161.6
13
2
9
1
(
d, J=243.8 Hz), 133.4 (d, J=3.2 Hz), 130.5 (d, J=7.9 Hz), 114.9 (d,
J=21.0 Hz), 66.8, 62.5, 53.4.
-(4-Nitro-benzyl)-morpholine (4l): Yellow solid, m.p. 76–78 °C;
H NMR (500 MHz): δ 8.17 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H),
2-Phenylaminomethyl-benzonitrile (4z): Colourless liquid; H NMR
(500 MHz): δ 7.56 (d, J=8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 7.15 (t,
J=7.5 Hz, 2H), 6.72 (t, J=7.5 Hz, 1H), 6.56 (d, J=7.5 Hz, 2H), 4.39 (s,
16
4
1
13
2H), 4.15 (br, 1H); C NMR (125 MHz): δ 147.3, 145.3, 132.3, 129.2,
13
3
.73 (t, J=4.5 Hz, 4H), 3.62 (s, 2H), 2.48 (t, J=4.5 Hz, 4H); C NMR
127.6, 118.8, 118.0, 112.8, 110.7, 47.6.
3
0
1
(
125 MHz): δ 147.0, 145.7, 129.4, 123.3, 66.7, 62.2, 53.4.
4
4-Methoxy-benzyl)-methyl-phenylamine (4aa): Colourless liquid; H
NMR (500 MHz): δ 7.18 (t, J=8.0 Hz, 2H), 7.11 (d, J=8.5 Hz, 2H), 6.81
(d, J=8.5 Hz, 2H), 6.73 (d, J=8.0 Hz, 2H), 6.68 (t, J=8.0 Hz, 1H), 4.41 (s,
2H), 3.71 (s, 3H), 2.92 (s, 3H); C NMR (125 MHz): δ 158.5, 149.7, 130.8,
129.1, 127.9, 116.5, 113.9, 112.5, 55.9, 55.1, 38.2.
2
0
1
-(2-Chloro-benzyl)-morpholine (4m): Yellow liquid; H NMR
500 MHz): δ 7.47 (dd, J=1.0, 7.5 Hz, 1H), 7.33 (dd, J=1.5, 8.0 Hz,
H), 7.22 (td, J=7.5, 1.5 Hz, 1H), 7.17 (td, J=7.5, 2.0 Hz, 1H), 3.71 (t,
(
1
13
13
J=4.5 Hz, 4H), 3.61 (s, 2H), 2.50 (t, J=4.5 Hz, 4H); C NMR (125 MHz):
31
δ 135.3, 134.3, 130.6, 129.3, 128.1, 126.4, 66.9, 59.5, 53.5.
4-[(Methyl-phenylamino)-methyl]-benzonitrile (4ab):
Colourless
18
1
1
4
-Naphthalen-1-yl-methyl-morpholine (4n): Colourless liquid;
H
liquid; H NMR (500 MHz): δ 7.59 (d, J=8.5 Hz, 2H), 7.34 (d, J=8.5 Hz,
2H), 7.23 (dd, J=7.5, 9.0 Hz, 2H), 6.76 (t, J=7.5 Hz, 1H), 6.71 (d,
NMR (300 MHz): δ 8.26 (d, J=7.8 Hz, 1H), 7.79–7.76 (m, 1H), 7.71 (dd,
J=2.7, 6.9 Hz, 1H), 7.47–7.33 (m, 4H), 3.81 (s, 2H), 3.62 (t, J=4.8 Hz,
1
3
J=9.0 Hz, 2H), 4.57 (s, 2H), 3.04 (s, 3H); C NMR (125 MHz): δ 148.9,
144.7, 132.4, 129.3, 127.4, 118.8, 117.6, 112.6, 110.8, 56.8, 39.0.
13
4
H), 2.42 (t, J=4.8 Hz, 4H); C NMR (75 MHz): δ 133.7, 133.4, 132.4,
1
28.2, 127.9, 127.3, 125.6, 125.5, 124.9, 124.6, 66.9, 61.4, 53.6.
15
1
1-Benzyl-piperidine (4o): Colourless liquid; H NMR (300 MHz):
Financial support from the National Natural Science Foundation
of China (No. 21002072) is greatly appreciated.
δ 7.31–7.21 (m, 5H), 3.47 (s, 2H), 2.35 (t, J=4.8 Hz, 4H), 1.57 (pent,
13
J=5.4 Hz, 4H), 1.46–1.40 (m, 2H); C NMR (75 MHz): δ 138.6, 129.2,
28.1, 126.8, 63.9, 54.5, 25.9, 24.4.
-(4-Methyl-benzyl)-piperidine (4p): Colourless liquid; H NMR
500 MHz): δ 7.19 (d, J=8.0 Hz, 2H), 7.10 (d, J=8.0 Hz, 2H), 3.43 (s, 2H),
.36 (t, J=4.8 Hz, 4H), 2.32 (s, 3H), 1.56 (pent, J=5.5 Hz, 4H), 1.42–1.41
1
Received 10 June 2013; accepted 27 July 2013
Paper 1302004 doi:10.3184/174751913X13787959859344
Published online: 7 October 2013
14
1
1
(
2
13
(
2
m, 2H); C NMR (125 MHz): δ 136.3, 135.3, 129.2, 128.7, 63.5, 54.3,
5.9, 24.3, 21.0.
-(4-Fluoro-benzyl)-piperidine (4q): Colourless liquid; H NMR
300 MHz): δ 7.27 (dd, J=5.7, 8.7 Hz, 2H), 6.98 (t, J=8.7 Hz, 2H), 3.42
References
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