Convenient method for reduction of C-N double bonds in oximes, imines, and hydrazones using sodium Borohydride-Raney ni system

Article abstract of DOI:10.1080/00397911.2011.562063

(Chemical Equation Presented) A practical method has been developed for reduction of C-N double bond in oximes, imines, and hydrazones with sodium borohydride catalyzed by Raney Ni. The reactions were carried out in basic aqueous solution, and the desired products were obtained in moderate yields after a simple procedure. This method can be applied to synthesize simpler aliphatic or aromatic amines and its analogs. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.562063

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Convenient Method for Reduction
of C-N Double Bonds in Oximes,
Imines, and Hydrazones Using Sodium
Borohydride–Raney Ni System
Yihua Yang a , Shouxin Liu a , Junzhang Li a , Xia Tian b , Xiaoli Zhen b
& Jianrong Han b
a College of Chemical and Pharmaceutical Engineering, Hebei
University of Science and Technology, Shijiazhuang, China
b College of Sciences, Hebei University of Science and Technology,
Shijiazhuang, China
Available online: 02 Jan 2012
To cite this article: Yihua Yang, Shouxin Liu, Junzhang Li, Xia Tian, Xiaoli Zhen & Jianrong Han
(2012): Convenient Method for Reduction of C-N Double Bonds in Oximes, Imines, and Hydrazones
Using Sodium Borohydride–Raney Ni System, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 42:17, 2540-2554
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Synthetic Communications1, 42: 2540–2554, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.562063
CONVENIENT METHOD FOR REDUCTION OF
C-N DOUBLE BONDS IN OXIMES, IMINES, AND
HYDRAZONES USING SODIUM BOROHYDRIDE–
RANEY Ni SYSTEM
Yihua Yang,1 Shouxin Liu,1 Junzhang Li,1 Xia Tian,2
Xiaoli Zhen,2 and Jianrong Han2
1College of Chemical and Pharmaceutical Engineering, Hebei University
of Science and Technology, Shijiazhuang, China
2College of Sciences, Hebei University of Science and Technology,
Shijiazhuang, China
GRAPHICAL ABSTRACT
Abstract A practical method has been developed for reduction of C-N double bond in oximes,
imines, and hydrazones with sodium borohydride catalyzed by Raney Ni. The reactions were
carried out in basic aqueous solution, and the desired products were obtained in moderate
yields after a simple procedure. This method can be applied to synthesize simpler aliphatic
or aromatic amines and its analogs.
Keywords C-N double bond; Raney Ni; reduction; sodium borohydride
INTRODUCTION
Reduction of compounds bearing C-N double bonds, such as oximes, imines,
and hydrazones, to amines is one of the most widely used and valuable functional
group transformations in organic synthesis.[1] Two approaches are commonly used
for this conversion. One is catalytic hydrogenation. The other one is hydride
reduction employing metal hydrides, such as lithium aluminum hydride or sodium
borohydride (Scheme 1).
Raney Ni has been used extensively as an effective catalyst in catalytic hydro-
genation of C-N double bonds. Certain hydroxyimino compounds may be trans-
formed into primary amines under these conditions.[2] However, high pressure is
frequently required for catalytic hydrogenation over Raney Ni. Lithium aluminum
hydride has been used extensively in this context. However, these reactions normally
Received December 20, 2010.
Address correspondence to Shouxin Liu, College of Chemical and Pharmaceutical Engineering,
Hebei University of Science and Technology, Shijiazhuang 050018, China. E-mail: chlsx@hebust.edu.cn
2540

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM
2541
Scheme 1. Reduction of C-N double bond.
have to be carried out in a dry organic solvent and under the protection of an inert
atmosphere.[3]
Sodium borohydride is a reducing reagent that is relatively safe to handle and
environmentally friendly. It has been frequently used for reduction of carbonyl
compounds in organic synthesis.[4] However, it is not always efficient in reduction
of C-N double bonds. A number of Lewis acid–mediated reduction systems, such as
NaBH4-LiCl,[5a] NaBH4-TiCl4,[5b] NaBH4-TiCl3,[5c] NaBH4-Ni2B,[5d] NaBH4-I2,[5e]
NaBH4-ZrCl4,[5f] and NaBH4-CoCl2,[5g] have been used for the reduction of C-N
double bonds to the corresponding amines and their derivatives. Tedious workup
procedures have been frequently reported for these conditions because of formation
of colloids during the process.
Although the system of sodium borohydride–Raney Ni has already been used
for reduction of aromatic nitro compounds[6] and aromatic N-oxides,[7] it has not
been reported for reduction of C-N double bonds. In this article, we report our
investigation of the reduction of oximes, imines, and hydrazones by a general and
convenient protocol, which employs commercially available Raney Ni to catalyze
such a reduction by excess of NaBH4 in basic aqueous methanol. After the reaction,
the nickel powder can be removed by filtering. This method not only avoids some
tedious workup but also is more convenient and effective.
RESULTS AND DISCUSSION
We previously reported[8] that some alkyl a-hydroxyiminoarylpropionate can
be reduced to a-acetylamino arylpropionate by Zn=AcOH in the presence of acetic
anhydride. As a part of our continued interest in the reduction of oximes, we initiated
an investigation to find a simple reagent for this functional group transformation.
The oxime 1 was selected as a model substrate to study its reduction behavior,
and we discovered that Raney Ni efficiently catalyzed reduction of this model
Scheme 2. Reduction of model substrate.

2542

2543

2544

2545

2546
Y. YANG ET AL.
substrate with NaBH4 to produce N-acylamino acid 2 in the presence of acetic
anhydride (Scheme 2). In comparison, NaBH4–Raney Ni reduction in the absence
of acetic anhydride led to a complex mixture that is difficult to purify. Further study
showed much improved activity of this binary NaBH4–Raney Ni reduction system
compared with single metal hydrides for C-N double bond reduction. Our results
are presented herein.
We tested the reduction system using several alkyl, aryl, carboxyl, and ester sub-
stituted oximes, which underwent C-N double bond reduction to give the correspond-
ing N-acetyl amines in 76–91% yields. The results are summarized in Table 1. As
shown in Table 1, the conjugated carboxyl group (Table 1, entry 2) remained intact,
whereas the conjugated ester was hydrolyzed under these conditions (Table 1, entries
3–11). Various halogen-substituted phenyl rings were well tolerated and gave the
reduction products with high efficiency (Table 1, entries 2, 4, 6, and 7). For example,
para-fluoro- and para-=chloro-substituted N-acetylphenylglycines were obtained in
90% and 78% yields, respectively (Table 1, entries 4 and 2). The para-chloro- and
para-bromo-substituted N-acetylphenylanaline were also obtained in more than
86–88% yields (Table 1, entries 6 and 7). To ascertain the role of Raney Ni, control
experiments were carried out for reduction of oximes in the absence of Raney Ni.
Only a little or hardly any of the desired C-N double-bond reduction products were
obtained from the oximes that were subjected to this reaction condition (Table 1,
entries 1–11). These results strongly support the role of Raney Ni in the binary
reduction system.
Because similar C-N double bonds are also present in imines and hydrazones,
reduction of these two series compounds by the binary reduction system was also
investigated. As shown in Table 2, a wide range of structurally varied imines under-
went clear and complete reduction to the corresponding saturated amino compounds
by this method. Alkyl-substituted imines gave moderate yields without any difficulty
(Table 2, entries 3 and 8), and conjugated imines gave better yields than nonconju-
gated imines (Table 2, entries 4–7). Under current conditions, reduction of arylimines
gave better yields than other imines (Table 2, entries 4–7). Not surprisingly, most imi-
nes gave better results than hydrazones (Table 2, entries 1 and 2) under current
reduction conditions. Control experiments with two imines (Table 2, entries 4 and
8) also demonstrated that Raney Ni was necessary for the reduction. No reduction
products were observed in these two cases when Raney Ni was absent.
CONCLUSIONS
In summary, a facile and efficient reducing system (i.e., NaBH4-Raney Ni=
MeOH-NaOH) was developed for reduction of C-N double bonds. The advantages
of this method include (a) a general and efficient process for reduction of oximes,
imines, and hydrazones to the corresponding amines; (b) easy purification; and
(c) good chemical selectivity with excellent yields.
EXPERIMENTAL
Melting points were determined with an electrothermal micromelting-point
apparatus and are uncorrected. 1H NMR spectra of samples were recorded on Bruker

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM
2547
Avance III 500 (500 MHz) and Varian Mecury Plus 300 spectrometers, using
tetramethylsilane (TMS) as an internal reference, and J values are given in hertz
(Hz). All reagents are commercially available and were used as purchased, without
further purification. Reactions were monitored by thin-layer chromatography
(TLC) on silica-gel plate (GF254). Column chromatography was performed with silica
gel, using petroleum ether and acetic acetate mixtures as eluent unless otherwise sta-
ted. All the starting materials were prepared according to literature procedures[8,19]
and characterized by comparison of their 1H NMR spectra with literature data. Mass
spectra were performed on a LC-MS2010EV spectrometer by electrospray ionization.
Elemental analyses were performed on a Perkin-Elmer PE 2400 instrument.
Reduction of Oxime: General Procedure (Table 1, Entries 1–11)
A solution of the substrate (25 mmol) in methanol (20 ml) was stirred at room
temperature with Raney Ni (27–55 mol%) of substrate. A solution of NaBH4
(79 mmol) in 50 ml aqueous sodium hydroxide solution (5.0 M) was slowly added
to the suspension at about 50–64 ꢀC with vigorous stirring. After addition, the sol-
ution was cooled to room temperature, and then acetic anhydride (5.0 ml, 53 mmol)
was added. The reaction was continued at room temperature and monitored by
thin-layer chromatography (TLC). After reaction, the solution was filtered to remove
Raney Ni. The filtrate was concentrated to a half of the volume in vacuum. The resi-
due was acidified with 1 M HCl to pH 2. Then the solution was extracted with ethyl
acetate (3 ꢁ 80 ml). The extracts were washed with water and brine and dried over
anhydrous sodium sulfate. After evaporation of the solvent under reduced pressure,
the residue was purified by recrystallization to give the product.
N-(1-Phenylethyl)acetamide (1b)
Synthesized from 1-(hydroxyimino)-1-phenylethane 1a (3.4 g, 25 mmol) accord-
ing to the general procedure, stirred for 2.5 h, and recrystallized in hexane. Yield: 78%
(3.2 g, 19.6 mmol), white solid, mp 101.5–103 ꢀC. dH (CDCl3, 500 MHz): 7.35 (m, 3H,
ArH), 7.26 (m, 2H, ArH), 5.16 (m, 1H, CH), 1.98 (s, 3H, COCH3), 1.66 (d, J ¼ 9.0,
3H, CH3). m=z (ESI) 164 (C10H13NO, [M þ H]þ). Found: C, 73.57; H, 8.05; N,
8.55. Calc. for C10H13NO: C, 73.59; H, 8.03; N, 8.58%.
N-Acetyl-4-chlorophenylglycine (2b)
Synthesized from 2-(4-chlorophenyl)-2-(hydroxyimino)acetic acid 2a (4.5 g,
22.6 mmol) according to the general procedure, stirred for 2.5 h, and purified by
recrystallization in water. Yield: 78% (4.0 g, 17.6 mmol), white solid, mp 195–
196.5 ꢀC. dH (CD3OD, 500 MHz): 8.56 (d, J ¼ 9.0, 1H, NH), 7.41 (d, J ¼ 7.5, 2H,
ArH), 7.33 (d, J ¼ 7.5, 2H, ArH), 5.22 (br, s, 1H, CH), 1.94 (s, 3H, CH3). m=z
(ESI) 228 (100%), 229 (10%), 230 (32%) (C10H10ClNO3 [M þ H]þ). Found: C,
52.79; H, 4.46; Cl, 15.54; N, 6.18. Calc. for C10H10ClNO3: C, 52.76; H, 4.43; Cl,
15.57; N, 6.15.

2548
Y. YANG ET AL.
N-Acetyl-phenylglycine (3b)
Synthesized from ethyl 2-(hydroxyimino)-2-phenylacetate 3a (4.5 g, 23 mmol)
according to the general procedure, stirred for 2.5 h, and purified by recrystallization
in water. Yield: 81% (3.6 g, 18.7 mmol), white solid, mp 197.5–199 ꢀC. dH (DMSO-d6,
500 MHz): 8.60 (d, J ¼ 9.0, 1H, NH), 7.51 (m, 2H, ArH), 7.41 (m, 3H, ArH), 5.26 (d,
J ¼ 9.0, 1H, CH), 1.92 (s, 3H, CH3). m=z (ESI) 216 (C10H11NO3, [M þ Na]þ).
Found: C, 62.20; H, 5.77; N, 7.23. Calc. for C10H11NO3: C, 62.17; H, 5.74; N, 7.25.
N-Acetyl-4-fluorophenylglycine[10] (4b)
Synthesized from ethyl 2-(4-fluorophenyl)-2-(hydroxyimino)acetate 4a (5.0 g,
23.7 mmol) according to the general procedure, stirred for 2.5 h, and purified by
recrystallization in water. Yield: 90% (4.5 g, 21.3 mmol), white solid, mp 187.5–
188.5 ꢀC. dH (DMSO-d6, 500 MHz): 7.30 (dd, J ¼ 6.0, J ¼ 8.5, 2H, ArH), 7.17 (dd,
J ¼ 8.5, J ¼ 8.5, 2H, ArH), 6.71 (br, s, 1H, NH), 4.24 (s, 1H, CH), 1.96 (s, 3H,
CH3). m=z (ESI) 234 (C10H10FNO3 [M þ Na]þ). Found: C, 56.90; H, 4.79; F, 8.98;
N, 6.65. Calc. for C10H10FNO3: C, 56.87; H, 4.77; F, 9.00; N, 6.63.
N-Acetyl-a -phenylalanine (5b)
Synthesized from ethyl 2-(hydroxyimino)-3-phenylpropanoate 5a (5.0 g,
24.2 mmol) according to the general procedure, stirred for 2.5 h, and purified by
recrystallization in water. Yield: 91% (4.6 g, 22.2 mmol), white solid, mp
170.5–172.5 ꢀC. dH (DMSO-d6, 500 MHz): 7.30 (m, 3H, ArH), 7.10 (m, 2H, ArH),
5.94 (br, s, 1H, NH), 4.90 (m, 1H, CH), 3.17 (m, 1H, CHH), 3.10 (m, 1H, CHH),
1.88 (s, 3H, CH3). m=z (ESI) 208 (C11H13NO3 [M þ H]þ). Found: C, 63.77; H,
6.35; N, 6.74. Calc. for C11H13NO3: C, 63.76; H, 6.32; N, 6.76.
N-Acetyl-4-chlorophenylalanine[19] (6b)
Synthesized from ethyl 3-(4-chlorophenyl)-2-(hydroxyimino)propionate 6a
(6.0 g, 25 mmol) according to the general procedure, stirred for 2.5 h, and purified
by recrystallization in water. Yield: 86% (5.1 g, 21 mmol), white solid, mp
148.5–150 ꢀC. dH (DMSO-d6, 500 MHz): 7.16 (d, J ¼ 8.5, 2H, ArH), 7.09 (d, J ¼ 8.5,
2H, ArH), 5.98 (br, s, 1H, NH), 4.21 (m, 1H, CH), 3.22 (m, 1H, CHH), 3.10 (m,
1H, CHH), 1.86 (s, 3H, CH3). m=z (ESI) 242, 243, 244 (C11H12ClNO3, [M þ H]þ).
Found: C, 54.64; H, 5.04; Cl, 14.69; N, 5.78. Calc. for C11H12ClNO3: C, 54.67; H,
5.00; Cl, 14.67; N, 5.80.
N-Acetyl-4-bromophenylalanine[20] (7b)
Synthesized from ethyl 3-(4-bromophenyl)-2-(hydroxyimino)propionate 7a
(5.0 g, 17.5 mmol) according to the general procedure, stirred for 2.5 h, and purified
by recrystallization in water. Yield: 88% (4.4 g, 15.4 mmol), white solid, mp
193–196 ꢀC. dH (D2O, 500 MHz): 7.51 (d, J ¼ 8.5, 2H, ArH), 7.18 (d, J ¼ 8.0, 2H,
ArH), 4.57–4.54 (dd, J ¼ 9.0, J ¼ 9.0, 1H, CH), 3.20–3.16 (dd, J ¼ 5.5, J ¼ 14.0,

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM
2549
1H, CHH), 2.96–2.91 (dd, J ¼ 9.0, J ¼ 14.0, 1H, CHH), 1.92 (s, 3H, CH3). m=z (ESI)
285, 286, 287 (C11H12BrNO3, [M þ H]þ). Found: C, 46.15; H, 4.27; Br, 27.97; N,
4.94. Calc. for C11H12ClNO3: C, 46.18; H, 4.23; Br, 27.93; N, 4.90.
N-Acetyl-2-naphthalenylalanine (8b)
Synthesized from ethyl 2-(hydroxyimino)-3-(naphthalen-3-yl)propanoate 8a
(6.5 g, 25 mmol) according to the general procedure, stirred for 2.5 h, and purified
by recrystallization in water. Yield: 85% (5.4 g, 21 mmol), yellowish solid, mp
181–182.5 ꢀC. dH (D2O, 500 MHz): 7.76–7.72 (m, 3H, ArH), 7.63 (s, 1H, ArH),
7.40–7.32 (m, 3H, ArH), 4.69 (m, J ¼ 5.0, J ¼ 4.5, 1H, CH), 3.31 (dd, J ¼ 14.0,
J ¼ 4.5, 1H, CHH), 3.05 (dd, J ¼ 9.0, J ¼ 5.0, 1H, CHH), 1.82 (s, 3H, CH3). m=z
(ESI) 258 (C15H15NO3, [M þ H]þ). Found: C, 70.06; H, 5.90; N, 5.45. Calc. for
C15H15NO3: C, 70.02; H, 5.88; N, 5.44.
N-Acetyl-2-quinolinylglycine[21] (9b)
Synthesized from ethyl 2-(hydroxyimino)-3-(quinolin-2-yl)propionate 9a (6.5 g,
25.2 mmol) according to the general procedure, stirred for 2.5 h, and purified by
recrystallization in ethanol. Yield: 82% (5.3 g, 20.5 mmol), yellowish solid, mp
183–185 ꢀC. dH (D2O, 500 MHz): 8.16 (d, J ¼ 8.5, 1H, ArH), 7.98 (d, J ¼ 8.0, 1H,
ArH), 7.85 (d, J ¼ 8.5, 1H, ArH), 7.72 (t, J ¼ 7.0, J ¼ 8.5, 1H, ArH), 7.55 (t,
J ¼ 7.0, J ¼ 7.0, 1H, ArH), 7.31 (d, J ¼ 8.5, 1H, ArH), 7.18 (d, J ¼ 7.0, 1H, ArH),
4.92 (m, 1H, CH), 3.59 (dd, J ¼ 5.0, J ¼ 5.5, 1H, CHH), 3.43 (dd, J ¼ 4.5, J ¼ 4.5,
1H, CHH), 1.90 (s, 3H, CH3). m=z (ESI) 259 (C14H14N2O3 [M þ H]þ). Found: C,
65.09; H, 5.48; N, 10.88. Calc. for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85.
2-Acetamidomalonic Acid (10b)
Synthesized from diethyl 2-(hydroxyimino)malonate 10a (4.7 g, 24.8 mmol)
according to the general procedure, stirred for 2.5 h, and purified by recrystallization
in mixture of solvent (water–acetone). Yield: 83% (3.3 g, 20.5 mmol), white solid, mp
122–124.5 ꢀC. dH (CDCl3, 500 MHz): 6.73 (d, J ¼ 8.0, 1H), 5.12 (d, J ¼ 8.0, 1H), 2.01
(s, 3H, CH3), MS (ESI): m=z ¼ 184 [M þ Na]þ. Anal. calcd. for C5H7NO5: C, 37.27;
H, 4.38; N, 8.69. Found: C, 37.25; H, 4.37; N, 8.71.
3-Acetamidobutanoic Acid[22] (11b)
Synthesized from ethyl 3-(hydroxyimino)butanoate 11a (3.5 g, 24.1 mmol)
according to the general procedure, stirred for 2.5 h, and purified by recrystallization
in water. Yield: 79% (2.8 g, 19.3 mmol), white solid, mp 121–124 ꢀC. dH (CDCl3,
300 MHz): 6.33 (br, s, 1H, NH), 4.05–4.01 (m, 1H, CH), 2.28–2.25 (m, 2H, CH2),
1.96 (s, 3H, CH3), 1.25–1.23 (d, J ¼ 6.0, 3H, CH3). m=z (ESI) 146 (C6H11NO3
[M þ H]þ). Found: C, 49.64; H, 7.65; N, 9.63. Calc. for C6H11NO3: C, 49.65; H,
7.64; N, 9.65.

2550
Y. YANG ET AL.
Reduction of Imines and Hydrazones: General Procedure (Table 2,
Entries 1–10)
A solution of the substrate (25 mmol) in methanol (20 ml) was stirred with
Raney Ni (27–55 mol%) of substrate at room temperature. A solution of NaBH4
(79 mmol) in 50 ml aqueous sodium hydroxide (5.0 M) was slowly added to the sus-
pension at about 40–60 ꢀC with vigorous stirring. The reaction was continued at the
same temperature and monitored by TLC. After reaction, the solution was cooled
and filtered to remove Raney Ni. The filtrate was concentrated to half of the volume
in vacuum. Then the solution was extracted with ethyl acetate (3 ꢁ 80 ml). The
extracts were washed with water and brine, dried over anhydrous sodium sulfate,
and concentrated under reduced pressure. The residue was purified by column
chromatography or distillation under reduced pressure to give the product.
1-(1-Phenylethyl)hydrazine[23] (1d)
Synthesized from 1-(1-phenylethylidene)hydrazine 1c (3.3 g, 24.6 mmol)
according to the general procedure, stirred for 100 min, and purified by distillation
under reduced pressure. Yield: 76% (2.5 g, 18.4 mmol), bp 74.5–76.5 ꢀC=1.5 mmHg.
dH (CDCl3, 300 MHz): 7.30–7.22 (m, 5H, ArH), 4.46 (m, 1H, CH), 4.03 (br, s, 2H,
NH2), 2.33 (br, s, 1H, NH), 1.36 (d, J ¼ 8.4, 3H, CH3). m=z (ESI) 137 (C8H12N2
[M þ H]þ). Found: C, 70.56; H, 8.90; N, 20.54. Calc. for C8H12N2: C, 70.55; H,
8.88; N, 20.57.
2-Phenyl-1-(1-phenylethyl)hydrazine[24] (2d)
Synthesized from 2-phenyl-1-(1-phenylethylidene)hydrazine 2c (5.2 g,
24.7 mmol) according to the general procedure, stirred for 100 min, and purified
by distillation under reduced pressure. Yield: 77% (4.0 g, 18.8 mmol), bp 188–
190 ꢀC=12 mmHg. dH (CDCl3, 300 MHz): 7.28–7.22 (m, 5H, ArH), 7.13 (m, 2H,
ArH), 6.76 (m, 1H, ArH), 6.72 (m, 2H, ArH), 4.58 (m, 1H, CH), 4.05 (br, s, 1H,
NH), 2.36 (br, s, 1H, NH), 1.35 (d, J ¼ 7.8, 3H, CH3). m=z (ESI) ¼ 213 (C14H16N2
[M þ H]þ). Found: C, 79.18; H, 7.62; N, 13.23. Calc. for C14H16N2: C, 79.21; H,
7.60; N, 13.20.
N-Isopropylcyclohexanamine (3d)
Synthesized from N-(propan-2-ylidene)cyclohexanamine 3c (3.4 g, 24.5 mmol)
according to the general procedure, stirred for 2 h, and purified by distillation under
reduced pressure. Yield: 80% (2.7 g, 19.6 mmol), bp 169–171 ꢀC. dH (CDCl3,
500 MHz): 2.99–2.94 (m, 1H, cyclohex, CH), 2.52–2.47 (m, 1H, NCH), 1.89–1.86
(m, 2H, cyclohex, CH2), 1.74–1.70 (m, 2H, cyclohex, CH2), 1.63–1.59 (m, 2H, cyclo-
hex, CH2), 1.28–1.00 (m, 4H, cyclohex, 2CH2), 1.05–1.03 (d, J ¼ 10.5, 6H, 2CH3).
m=z (ESI) 156 (C10H21N [M þ H]þ). Found: C, 77.36; H, 13.61; N, 9.03. Calc. for
C10H21N: C, 77.35; H, 13.63; N, 9.02.

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM
2551
N-Benzyl-1-phenylethanamine (4d)
Synthesized from phenyl-N-(1-phenylethylidene)methanamine 4c (5.2 g,
24.8 mmol) according to the general procedure, stirred for 2 h, and purified by distil-
lation under reduced pressure. Yield: 93% (4.9 g, 23.2 mmol), bp 170–171.5 ꢀC=
15 mmHg. dH (CDCl3, 300 MHz): 10.22 (br, s, 1H, NH), 7.48 (m, 3H, ArH), 7.32
(m, 5H, ArH), 7.18 (m, 2H, ArH), 4.06 (m, 1H, CH), 3.87 (m, 1H, CHH), 3.56 (m,
1H, CHH), 1.77 (d, J ¼ 7.2, 3H, CH3). m=z (ESI) 212 (C15H17N [M þ H]þ). Found:
C, 85.23; H, 8.12; N, 6.65. Calc. for C15H17N: C, 85.26; H, 8.11; N, 6.63.
N-Benzyl-4-methylbenzenamine (5d)
Synthesized from N-benzylidene-4-methylbenzenamine 5c (4.7 g, 24.1 mmol)
according to the general procedure, stirred for 2 h, and purified by flash chromato-
graphy on silica gel (petroleum ether–EtOAc, 8:1). Yield: 93% (4.4 g, 22.3 mmol),
bp 154–157 ꢀC=5 mmHg. dH (CDCl3, 300 MHz): 7.36–7.24 (m, 5H, ArH), 6.70 (d,
J ¼ 8.4, 2H, ArH), 6.58 (m, J ¼ 8.4, 2H, ArH), 4.31 (s, 2H, CH2), 3.88 (br, s, 1H,
NH), 2.23 (s, 3H, CH3). m=z (ESI) 198 (C14H15N [M þ H]þ). Found: C, 85.21; H,
7.68; N, 7.11. Calc. for C14H15N: C, 85.24; H, 7.66; N, 7.10.
N-(4-Chlorobenzyl)benzenamine (6d)
Synthesized from N-(4-chlorobenzylidene)benzenamine 6c (5.3 g, 24.7 mmol)
according to the general procedure, stirred for 2 h, and purified by flash chromato-
graphy on silica gel (petroleum ether–AcOEt, 7:1). Yield: 90% (4.8 g, 22.1 mmol). dH
(CDCl3, 500 MHz): 7.28–7.21 (m, 4H, ArH), 7.16–7.12 (m, 2H, ArH), 6.71–6.63 (m,
3H, ArH), 4.23 (s, 2H, CH2), 4.07 (br, s, 1H, NH). m=z (ESI) 218, 219, 230
(C13H12ClN [M þ H]þ). Found: C, 71.70; H, 5.58; Cl, 16.30; N, 6.40. Calc. for
C13H12ClN: C, 71.72; H, 5.56; Cl, 16.29; N, 6.43.
Dibenzylamine (7d)
Synthesized from N-benzylidene(phenyl)methanamine 7c (4.8 g, 24.6 mmol)
according to the general procedure, stirred for 2 h, and purified by distillation under
reduced pressure. Yield: 92% (4.5 g, 22.8 mmol), bp 159–161.5 ꢀC=10 mmHg. dH
(CDCl3, 500 MHz): 7.68–7.63 (m, 8H, ArH), 7.58–7.54 (m, 2H, ArH), 4.05 (s, 4H,
2CH2), 1.83 (s, 1H, NH). m=z (ESI) 198 (C14H15N [M þ H]þ). Found: C, 85.26;
H, 7.65; N, 7.09. Calc. for C14H15N: C, 85.24; H, 7.66; N, 7.10.
3,3-Dimethyl-N-(1-phenylethyl)butylan-2-amine[25] (8d)
Synthesized from N-(3,3-dimethylbutan-2-ylidene)-1-phenylethanamine 8c
(5.0 g, 24.6 mmol) according to the general procedure, stirred for 2 h, and purified
by flash chromatography on silica gel (petroleum ether–EtOAc, 6:1). Yield: 82%
(4.1 g, 20.0 mmol). dH (CDCl3, 500 MHz): 8.25 (br, s, 1H, NH), 7.28 (m, 2H, ArH),
7.18 (m, 3H, ArH), 4.01 (m, 1H, CH), 2.32 (m, 1H, CH), 1.37 (d, J ¼ 7.5, 3H, CH3),
1.17 (d, J ¼ 8.0, 3H, CH3), 1.05 (s, 9H, t-Bu). m=z (ESI) 206 (C14H23N [M þ H]þ).
Found: C, 81.91; H, 11.31; N, 6.80. Calc. for C14H23N: C, 81.89; H, 11.29; N, 6.82.

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2-(N-Methyl-N-phenethylamino)ethanol[26] (9d)
Synthesized from N-methyl-N-(2-phenylethylene)-2-hydroxyethylamonium
chloride 9c (4.5 g, 25.3 mmol) according to the general procedure, stirred for 2 h,
and purified by flash chromatography on silica gel (petroleum ether–EtOAc, 6:1).
Yield: 88% (3.9 g, 21.8 mmol), bp 106–110 ꢀC=1 mmHg. dH (CDCl3, 300 MHz):
7.38–7.20 (m, 5H, ArH), 3.56 (t, J ¼ 8.1, 2H, CH2), 2.83–2.80 (t, J ¼ 8.4, 2H,
CH2), 2.71–2.68 (t, J ¼ 8.4, 2H, CH2), 2.55 (t, J ¼ 8.1, 2H, CH2), 2.38 (s, 3H,
NCH3). m=z (ESI) 180 (C11H17NO [M þ H]þ). Found: C, 73.73; H, 9.54; N, 7.84.
Calc. for C11H17NO: C, 73.70; H, 9.56; N, 7.81.
N-[1-(4-Chlorophenyl)-2-propanyl]pyrrolidine[26] (10d)
Synthesized from 1-(4-Cl-phenyl)-2-propylene pyrrolidinylium chloride 10c
(5.5 g, 24.8 mmol) according to the general procedure, stirred for 2 h, and purified
by flash chromatography on silica gel (petroleum ether–EtOAc, 8:1). Yield 91%
(5.1 g, 22.9 mmol), beige solid, mp 175–176.5 ꢀC. dH (CDCl3, 500 MHz): 7.14 (d,
J ¼ 8.5, 2H, ArH), 7.02 (d, J ¼ 8.5, 2H, ArH), 3.17 (m, 1H, CH), 2.71 (m, 1H,
CHH), 2.50 (m, 1H, CHH), 2.26–2.24 (m, 4H, 2NCH2), 1.63–1.59 (m, 4H, 2CH2),
1.02 (d, J ¼ 8.0, 3H, CH3). m=z (ESI) 224, 225, 226 (C13H18ClN [M þ H]þ). Found:
C, 69.80; H, 8.10; Cl, 15.88; N, 6.24. Calc. for C13H18ClN: C, 69.79; H, 8.11; Cl,
15.85; N, 6.26.
ACKNOWLEDGMENTS
This work is supported by the National Natural Science Foundation of China
(Grant Nos. 30472074 and 30873139) and the Natural Science Foundation of Hebei
Province (Nos. B2006000302 and 10276406D6).
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