Y.-B. Huang et al. / Journal of Fluorine Chemistry 131 (2010) 879–882
881
3. Conclusions
2H), 6.57–6.58 (d, J = 7.7 Hz, 2H), 6.73–6.76 (t, J = 7.8 Hz, 1H), 7.15–
7.20 (m, 6H). 13C-NMR (CDCl3 75 MHz)
d: 47.5, 112.8, 118.1, 123.8,
In summary, we have developed an efficient and facial method
for the direct reductive amination of aldehydes via the imine
activation of hydrogen bond of recoverable fluorous thiourea
catalyst. The protocol is mild and acid-free, together with the high
chemoselectivity, which make a useful process for the synthesis of
various kinds of amine.
127.6, 129.3, 147.3, 147.5, 157.3. MS (EI) m/z 228 (M+).
N-(4-methoxybenzyl)-aniline (compound 4d): mp 63–65 8C
[63–64 8C Ref. [11]]. 1H-NMR (CDCl3 300 MHz)
d: 3.80 (s, 3H), 3.94
(s, 1H), 4.25 (s, 2H), 6.22 (d, J = 7.7 Hz, 2H), 6.73 (t, J = 7.8 Hz, 1H),
6.90 (d, J = 7.7 Hz, 2H), 6.62–7.38 (m, 4H). 13C-NMR (CDCl3
75 MHz) d: 47.8, 55.3, 112.8, 114.2, 117.5, 128.8, 129.2, 130.5,
148.2, 155.6. MS (EI) m/z 214 (M+).
4. Experimental
N-(2-hydroxybenzyl)-aniline (compound 4e): mp 110–112 8C
[113–114 8C Ref. [11]]. 1H-NMR (CDCl3 300 MHz)
d
: 3.94 (s, 1H),
4.1. General
4.40–4.41 (d, J = 4.9 Hz, 2H), 6.83–7.27 (m, 9H), 8.42 (s, 1H). 13C-
NMR (CDCl3 75 MHz) d: 48.7, 115.9, 116.6, 120.0, 120.8, 122.9,
Reagents were obtained from commercial sources. 1H-NMR and
13C-NMR spectra were recorded on a Bruker Advance RX300
spectrometer using TMS as an internal standard, chemical shift
values were given in ppm. Mass spectra were obtained on a
Sectorfield-MS. Elemental analyses were conducted using a Yanaco
MT-3CHN elemental analyser. Melting points were uncorrected.
128.7, 129.2, 129.3, 147.2, 156.7. MS (EI) m/z 199 (M+).
N-benzyl-p-anisidine (compound 4f): mp 48–50 8C [48.6–
48.9 8C, Ref. [8]]. 1H-NMR (CDCl3 300 MHz)
d: 3.73 (s, 3H), 4.28 (s,
2H), 6.60 (dt, J = 9.0, 3.0 Hz, 2H), 6.77 (dt, J = 9.0, 2.9 Hz, 2H), 7.25
(tt, J = 6.9, 2.1 Hz, 1H), 7.30–7.37 (m, 4H); 13C-NMR (CDCl3
75 MHz) d: 49.2, 55.8, 114.0, 114.8, 127.0, 127.4, 128.4, 139.5,
142.2, 152.0. MS (EI) m/z 213 (M+).
4.2. General procedure for synthesis of fluorous thiourea
N-benzyl-4-hydroxy-aniline (compound 4g): mp 88–90 8C
organocatalyst II
[89–90 8C, Ref. [11]]. 1H-NMR (CDCl3 300 MHz)
d
: 1.75 (s, 1H), 2.14
(s, 1H), 4.23 (s, 2H), 6.55 (d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H),
Phenyl isothiocyanate (0.55 mmol) was added dropwise to a
solution of perfluorooctyl aniline (0.5 mmol) in THF (10 ml) at
40 8C. After addition, the mixture was strongly stirred at 40 8C
under nitrogen atmosphere for 24 h. The bulk of solvent was
removed in rotary evaporator under reduced pressure. The residue
was added to cool diethyl ether 4 ml, then the mixtures was
filtered at once. The filter was dried in vacuo at 40 8C for 12 h to
obtain product (90% yield). Melting point 145–147 8C, 1H-NMR
7.24–7.35 (m, 5H). 13C-NMR (CDCl3 75 MHz)
d: 49.3, 114.4, 116.2,
127.2, 127.6, 128.6, 139.5, 142.3, 147.8. MS (EI) m/z 199 (M+).
N-(4-nitrobenzyl)-p-anisidine (compound 4h): mp 97–99 8C
[97.7–97.9 8C, Ref. [8]]. 1H-NMR (CDCl3 300 MHz)
d: 3.73 (s, 3H),
4.42 (s, 2H), 6.55 (dt, J = 9.0, 2.3 Hz, 2H), 6.75 (dt, J = 9.0, 2.3 Hz, 2H),
7.53 (d, J = 8.8 Hz, 2H,), 8.18 (dt, J = 8.8, 2.0 Hz, 2H); 13C-NMR
(CDCl3 75 MHz) d: 48.4, 55.6, 114.0, 114.7, 123.6, 127.5, 140.9,
146.8, 147.3, 152.3. MS (EI) m/z 258 (M+).
(CD3OD, 300 MHz)
2H), 7.48–7.52 (m, 1H), 7.60–7.63 (d, J = 9.0 Hz, 2H), 7.78–7.80 (d,
J = 6.1 Hz, 2H), 13C-NMR (CD3OD, 75 MHz)
: 112.3–119.6 (m,
CF2CF3), 124.5, 125.3, 125.6, 125.9, 127.2, 128.9, 139.5, 142.8,
180.8. 19F-NMR (282.4 MHz, CD3OD)
d
: 7.26–7.28 (m, 2H), 7.40–7.43 (d, J = 9.0 Hz,
N-(4-methoxybenzyl)-p-anisidine (compound 4i): mp 92–
94 8C [91–93 8C, Ref. [10]], 1H-NMR (CDCl3 300 MHz)
d: 3.73 (s,
d
6H), 4.32 (s, 2H), 6.32 (d, J = 8.7 Hz, 2H), 6.55 (d, J = 8.8 Hz, 2H), 6.65
(d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H). 13C-NMR (CDCl3 75 MHz)
d
: ꢀ80.82 (m, 3F), ꢀ110.23
d: 48.7, 55.3, 55.8, 114.0, 114.1, 114.9, 128.8, 131.6, 142.5, 152.2,
(m, 2F), ꢀ121.33(m, 2F), ꢀ121.83 (m, 6F), ꢀ122.80 (m, 2F),
158.8. MS (EI) m/z 243 (M+).
ꢀ126.21 (m, 2F); MS (EI) m/z 647 (M+).
N-(4-methoxybenzyl)-4-nitro-aniline (compound 4j): mp
140–142 8C [140–141 8C, Ref. [10]], 1H-NMR (CDCl3 300 MHz)
d:
4.3. General procedure for the direct reductive amination of aldehyde
3.81 (s, 3H), 4.35–4.36 (d, J = 5.5 Hz, 2H), 4.75–4.78 (m, 1H), 6.56–
6.58 (d, J = 9.0 Hz, 2H), 6.89–6.91 (d, J = 8.6 Hz, 2H), 7.26 (d,
J = 8.6 Hz, 2H), 8.07–8.09 (d, J = 9.0 Hz, 2H). 13C-NMR (CDCl3
A mixture of aldehyde 1 (2.0 mmol), amine 2 (2.2 mmol), the
Hantzsch 1,4-dihydropydine
3
(2.4 mmol), fluorous thiourea
75 MHz) d: 47.2, 55.4, 111.3, 114.3, 126.4, 128.8, 129.3, 138.3,
153.0, 159.3. MS (EI) m/z 258 (M+).
˚
catalyst II (0.02 mmol) and MS 5 A (1.0 g) were added into CH2Cl2
(10 ml). The reaction mixture was stirred at room temperature
under nitrogen atmosphere. After 8 h, the crude product was
filtrated and solvent was removed by reduced pressure. The
residue was loaded onto a FluoroFlash1 silica gel cartridge (5 g),
then eluted by methanol:water (75:25) 8–10 ml in order to
separate non-fluorous organic components from the mixture. Then
the first elutant was evaporated to remove solvent. The remains
was purified by column chromatography on silica gel using
mixtures of petroleum ether and ethyl acetate as elutant to give the
product amines 4a–4k in pure form.
N-cyclohexylmethyl-p-anisidine (compound 4k): Ref. [8]. 1H-
NMR (CDCl3 300 MHz) d: 0.92–1.02 (m, 2H), 1.12–1.30 (m, 3H),
1.56 (m, 1H), 1.66–1.82 (m, 5H), 2.90 (d, J = 6.6 Hz, 2H), 3.40 (brs,
1H), 3.74(s, 3H), 6.56 (d, J = 9.0 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H). 13C-
NMR (CDCl3 75 MHz) d: 26.0, 26.6, 31.3, 37.6, 51.7, 55.9, 113.9,
114.9, 143.0, 151.8, MS (EI) m/z 219 (M+).
4.4. General procedure for recovery of fluorous thiourea
organocatalyst
N-benzyl-aniline (compound 4a): Ref. [10]. 1H-NMR (CDCl3,
After the residue was eluted by methanol: water (v/v = 75:25) at
first for non-fluorous component, pure methanol was then added
onto the fluorous gel column continuously for obtaining the elutant
of fluorous thiourea catalyst II. When the bulk of solvent was
removed and product was dried invacuo at50 8Cfor8 h, thefluorous
thiourea catalyst II could be recycled effectively. Furthermore, the
recoverable organocatalyst could be used directly for the next run.
300 MHz)
d: 4.20 (s, 2H), 6.50–6.52 (d, J = 8.7 Hz, 2H), 6.59–6.63 (t,
J = 7.4 Hz, 1H,), 7.04–7.09 (t, J = 7.4 Hz, 2H), 7.14–7.27 (m, 5H). 13C-
NMR (CDCl3 75 MHz) d: 48.2, 112.8, 117.5, 127.1, 127.4, 128.5,
129.2, 139.4, 148.1. MS (EI) m/z 183 (M+).
N-(4-chlorobenzyl)-aniline (compound 4b): mp 50–52 8C
[51–52 8C Ref. [11]]. 1H-NMR (CDCl3, 300 MHz)
d
: 4.03 (s, 1H),
4.29 (s, 2H), 6.57–6.59 (d, J = 7.7 Hz, 2H), 6.71–6.73 (t, J = 7.8 Hz,
1H), 7.13–7.29 (m, 6H). 13C-NMR (CDCl3 75 MHz)
d: 47.6, 112.8,
Acknowledgements
117.8, 128.7, 129.3, 133.0, 138.0, 147.8. MS (EI) m/z 218 (M+).
N-(4-nitrobenzyl)-aniline (compound 4c): mp 67–69 8C [67–
We thank the project of ‘‘Excellence Initiative’’ and ‘‘Zijin Star’’
in NJUST, ‘‘Doctoral Fund of Ministry of Education of China’’
69 8C Ref. [11]]. 1H-NMR (CDCl3 300 MHz)
d: 4.26 (s, 1H), 4.77 (s,