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Convenient Method for Reductionof C-N Double Bonds in Oximes,Imines, and Hydrazones Using SodiumBorohydride–Raney Ni SystemYihua Yang a , Shouxin Liu a , Junzhang Li a , Xia Tian b , Xiaoli Zhen b

& Jianrong Han ba College of Chemical and Pharmaceutical Engineering, HebeiUniversity of Science and Technology, Shijiazhuang, Chinab 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 HydrazonesUsing Sodium Borohydride–Raney Ni System, Synthetic Communications: An International Journal forRapid Communication of Synthetic Organic Chemistry, 42:17, 2540-2554

To link to this article: http://dx.doi.org/10.1080/00397911.2011.562063

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CONVENIENT METHOD FOR REDUCTION OFC-N DOUBLE BONDS IN OXIMES, IMINES, ANDHYDRAZONES USING SODIUM BOROHYDRIDE–RANEY Ni SYSTEM

Yihua Yang,1 Shouxin Liu,1 Junzhang Li,1 Xia Tian,2

Xiaoli Zhen,2 and Jianrong Han21College of Chemical and Pharmaceutical Engineering, Hebei Universityof Science and Technology, Shijiazhuang, China2College 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 functionalgroup transformations in organic synthesis.[1] Two approaches are commonly usedfor this conversion. One is catalytic hydrogenation. The other one is hydridereduction employing metal hydrides, such as lithium aluminum hydride or sodiumborohydride (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 isfrequently required for catalytic hydrogenation over Raney Ni. Lithium aluminumhydride 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

Synthetic Communications1, 42: 2540–2554, 2012

Copyright # Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397911.2011.562063

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have to be carried out in a dry organic solvent and under the protection of an inertatmosphere.[3]

Sodium borohydride is a reducing reagent that is relatively safe to handle andenvironmentally friendly. It has been frequently used for reduction of carbonylcompounds in organic synthesis.[4] However, it is not always efficient in reductionof C-N double bonds. A number of Lewis acid–mediated reduction systems, such asNaBH4-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-Ndouble bonds to the corresponding amines and their derivatives. Tedious workupprocedures have been frequently reported for these conditions because of formationof colloids during the process.

Although the system of sodium borohydride–Raney Ni has already been usedfor reduction of aromatic nitro compounds[6] and aromatic N-oxides,[7] it has notbeen reported for reduction of C-N double bonds. In this article, we report ourinvestigation of the reduction of oximes, imines, and hydrazones by a general andconvenient protocol, which employs commercially available Raney Ni to catalyzesuch 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 sometedious workup but also is more convenient and effective.

RESULTS AND DISCUSSION

We previously reported[8] that some alkyl a-hydroxyiminoarylpropionate canbe reduced to a-acetylamino arylpropionate by Zn=AcOH in the presence of aceticanhydride. As a part of our continued interest in the reduction of oximes, we initiatedan 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.

Scheme 1. Reduction of C-N double bond.

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM 2541

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Table

1.Reductionofoxim

eswithNaBH

4–Raney

Nisystem

inthepresence

ofaceticanhydridea

Entry

Substrate

aProduct

bYield

(%)b

Mp(�C)

Lit.mp(�C)[Ref.]

178(12)

101.5–103

175–180[9]

278(6)

195–196.5

196[10]

381(8)

197.5–199

199–201[11]

490(10)

187.5–188.5

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591(9)

170.5–172.5

142[12]

686(8)

148.5–150

788(11)

193–196

885(15)

181–182.5

208[13]

982(12)

183–185

10

83(17)

122–124.5

122[14]

11

79(trace)

121–124

aAllproductswerecharacterized

by

1H

NMR

andtheirphysicalproperties

werecomparedwiththereported

values.

bIsolatedyield.Thefigure

inbracketsistheyield

withoutRaney

Ni.

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Table

2.Reductionofim

ines

andhydrazones

withNaBH

4–Raney

Nisystem

a

Entry

Substrate

cProduct

dYield

(%)b

Bpormp(�C)

Lit.mp(�C)[Ref.]

176

74.5–76.5=1.5mmHg

277

188–190=12mmHg

380

Oil,169–171

60–65=12Torr

[15]

493

170–171.5=15mmHg

Oil[16]

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593

154–157=5mmHg

130=0.2Torr

[17]

690

110.1–112.3[18]

792

159–161.5=10mmHg

175=15Torr

[18]

882

988

106–110=1mmHg

10

91

Beigesolid,175–176.5

aAllproductswerecharacterized

by

1H

NMR,andtheirphysicalproperties

werecomparedwiththereported

values.

bIsolatedyield.

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substrate with NaBH4 to produce N-acylamino acid 2 in the presence of aceticanhydride (Scheme 2). In comparison, NaBH4–Raney Ni reduction in the absenceof acetic anhydride led to a complex mixture that is difficult to purify. Further studyshowed much improved activity of this binary NaBH4–Raney Ni reduction systemcompared with single metal hydrides for C-N double bond reduction. Our resultsare 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. Asshown in Table 1, the conjugated carboxyl group (Table 1, entry 2) remained intact,whereas the conjugated ester was hydrolyzed under these conditions (Table 1, entries3–11). Various halogen-substituted phenyl rings were well tolerated and gave thereduction products with high efficiency (Table 1, entries 2, 4, 6, and 7). For example,para-fluoro- and para-=chloro-substituted N-acetylphenylglycines were obtained in90% and 78% yields, respectively (Table 1, entries 4 and 2). The para-chloro- andpara-bromo-substituted N-acetylphenylanaline were also obtained in more than86–88% yields (Table 1, entries 6 and 7). To ascertain the role of Raney Ni, controlexperiments 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 wereobtained 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 binaryreduction 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 alsoinvestigated. As shown in Table 2, a wide range of structurally varied imines under-went clear and complete reduction to the corresponding saturated amino compoundsby 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 aryliminesgave 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 currentreduction conditions. Control experiments with two imines (Table 2, entries 4 and8) also demonstrated that Raney Ni was necessary for the reduction. No reductionproducts 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 advantagesof 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-pointapparatus and are uncorrected. 1H NMR spectra of samples were recorded on Bruker

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Avance III 500 (500MHz) and Varian Mecury Plus 300 spectrometers, usingtetramethylsilane (TMS) as an internal reference, and J values are given in hertz(Hz). All reagents are commercially available and were used as purchased, withoutfurther purification. Reactions were monitored by thin-layer chromatography(TLC) on silica-gel plate (GF254). Column chromatography was performed with silicagel, 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. Massspectra 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 (25mmol) in methanol (20ml) was stirred at roomtemperature with Raney Ni (27–55mol%) of substrate. A solution of NaBH4

(79mmol) in 50ml aqueous sodium hydroxide solution (5.0M) was slowly addedto the suspension at about 50–64 �C with vigorous stirring. After addition, the sol-ution was cooled to room temperature, and then acetic anhydride (5.0ml, 53mmol)was added. The reaction was continued at room temperature and monitored bythin-layer chromatography (TLC). After reaction, the solution was filtered to removeRaney Ni. The filtrate was concentrated to a half of the volume in vacuum. The resi-due was acidified with 1M HCl to pH 2. Then the solution was extracted with ethylacetate (3� 80ml). The extracts were washed with water and brine and dried overanhydrous 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, 25mmol) accord-ing to the general procedure, stirred for 2.5 h, and recrystallized in hexane. Yield: 78%(3.2 g, 19.6mmol), white solid, mp 101.5–103 �C. dH (CDCl3, 500MHz): 7.35 (m, 3H,ArH), 7.26 (m, 2H, ArH), 5.16 (m, 1H, CH), 1.98 (s, 3H, COCH3), 1.66 (d, J¼ 9.0,3H, CH3). m=z (ESI) 164 (C10H13NO, [MþH]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,22.6mmol) according to the general procedure, stirred for 2.5 h, and purified byrecrystallization in water. Yield: 78% (4.0 g, 17.6mmol), white solid, mp 195–196.5 �C. dH (CD3OD, 500MHz): 8.56 (d, J¼ 9.0, 1H, NH), 7.41 (d, J¼ 7.5, 2H,ArH), 7.33 (d, J¼ 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 [MþH]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.

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N-Acetyl-phenylglycine (3b)

Synthesized from ethyl 2-(hydroxyimino)-2-phenylacetate 3a (4.5 g, 23mmol)according to the general procedure, stirred for 2.5 h, and purified by recrystallizationin water. Yield: 81% (3.6 g, 18.7mmol), white solid, mp 197.5–199 �C. dH (DMSO-d6,500MHz): 8.60 (d, J¼ 9.0, 1H, NH), 7.51 (m, 2H, ArH), 7.41 (m, 3H, ArH), 5.26 (d,J¼ 9.0, 1H, CH), 1.92 (s, 3H, CH3). m=z (ESI) 216 (C10H11NO3, [MþNa]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,23.7mmol) according to the general procedure, stirred for 2.5 h, and purified byrecrystallization in water. Yield: 90% (4.5 g, 21.3mmol), white solid, mp 187.5–188.5 �C. dH (DMSO-d6, 500MHz): 7.30 (dd, J¼ 6.0, J¼ 8.5, 2H, ArH), 7.17 (dd,J¼ 8.5, J¼ 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 [MþNa]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,24.2mmol) according to the general procedure, stirred for 2.5 h, and purified byrecrystallization in water. Yield: 91% (4.6 g, 22.2mmol), white solid, mp170.5–172.5 �C. dH (DMSO-d6, 500MHz): 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 [MþH]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, 25mmol) according to the general procedure, stirred for 2.5 h, and purifiedby recrystallization in water. Yield: 86% (5.1 g, 21mmol), white solid, mp148.5–150 �C. dH (DMSO-d6, 500MHz): 7.16 (d, J¼ 8.5, 2H, ArH), 7.09 (d, J¼ 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, [MþH]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, 17.5mmol) according to the general procedure, stirred for 2.5 h, and purifiedby recrystallization in water. Yield: 88% (4.4 g, 15.4mmol), white solid, mp193–196 �C. dH (D2O, 500MHz): 7.51 (d, J¼ 8.5, 2H, ArH), 7.18 (d, J¼ 8.0, 2H,ArH), 4.57–4.54 (dd, J¼ 9.0, J¼ 9.0, 1H, CH), 3.20–3.16 (dd, J¼ 5.5, J¼ 14.0,

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1H, CHH), 2.96–2.91 (dd, J¼ 9.0, J¼ 14.0, 1H, CHH), 1.92 (s, 3H, CH3). m=z (ESI)285, 286, 287 (C11H12BrNO3, [MþH]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, 25mmol) according to the general procedure, stirred for 2.5 h, and purifiedby recrystallization in water. Yield: 85% (5.4 g, 21mmol), yellowish solid, mp181–182.5 �C. dH (D2O, 500MHz): 7.76–7.72 (m, 3H, ArH), 7.63 (s, 1H, ArH),7.40–7.32 (m, 3H, ArH), 4.69 (m, J¼ 5.0, J¼ 4.5, 1H, CH), 3.31 (dd, J¼ 14.0,J¼ 4.5, 1H, CHH), 3.05 (dd, J¼ 9.0, J¼ 5.0, 1H, CHH), 1.82 (s, 3H, CH3). m=z(ESI) 258 (C15H15NO3, [MþH]þ). Found: C, 70.06; H, 5.90; N, 5.45. Calc. forC15H15NO3: 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,25.2mmol) according to the general procedure, stirred for 2.5 h, and purified byrecrystallization in ethanol. Yield: 82% (5.3 g, 20.5mmol), yellowish solid, mp183–185 �C. dH (D2O, 500MHz): 8.16 (d, J¼ 8.5, 1H, ArH), 7.98 (d, J¼ 8.0, 1H,ArH), 7.85 (d, J¼ 8.5, 1H, ArH), 7.72 (t, J¼ 7.0, J¼ 8.5, 1H, ArH), 7.55 (t,J¼ 7.0, J¼ 7.0, 1H, ArH), 7.31 (d, J¼ 8.5, 1H, ArH), 7.18 (d, J¼ 7.0, 1H, ArH),4.92 (m, 1H, CH), 3.59 (dd, J¼ 5.0, J¼ 5.5, 1H, CHH), 3.43 (dd, J¼ 4.5, J¼ 4.5,1H, CHH), 1.90 (s, 3H, CH3). m=z (ESI) 259 (C14H14N2O3 [MþH]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, 24.8mmol)according to the general procedure, stirred for 2.5 h, and purified by recrystallizationin mixture of solvent (water–acetone). Yield: 83% (3.3 g, 20.5mmol), white solid, mp122–124.5 �C. dH (CDCl3, 500MHz): 6.73 (d, J¼ 8.0, 1H), 5.12 (d, J¼ 8.0, 1H), 2.01(s, 3H, CH3), MS (ESI): m=z¼ 184 [MþNa]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, 24.1mmol)according to the general procedure, stirred for 2.5 h, and purified by recrystallizationin water. Yield: 79% (2.8 g, 19.3mmol), white solid, mp 121–124 �C. dH (CDCl3,300MHz): 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, J¼ 6.0, 3H, CH3). m=z (ESI) 146 (C6H11NO3

[MþH]þ). Found: C, 49.64; H, 7.65; N, 9.63. Calc. for C6H11NO3: C, 49.65; H,7.64; N, 9.65.

SODIUM BOROHYDRIDE–RANEY NICKEL SYSTEM 2549

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Reduction of Imines and Hydrazones: General Procedure (Table 2,Entries 1–10)

A solution of the substrate (25mmol) in methanol (20ml) was stirred withRaney Ni (27–55mol%) of substrate at room temperature. A solution of NaBH4

(79mmol) in 50ml aqueous sodium hydroxide (5.0M) was slowly added to the sus-pension at about 40–60 �C with vigorous stirring. The reaction was continued at thesame temperature and monitored by TLC. After reaction, the solution was cooledand filtered to remove Raney Ni. The filtrate was concentrated to half of the volumein vacuum. Then the solution was extracted with ethyl acetate (3� 80ml). Theextracts were washed with water and brine, dried over anhydrous sodium sulfate,and concentrated under reduced pressure. The residue was purified by columnchromatography 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, 24.6mmol)according to the general procedure, stirred for 100min, and purified by distillationunder reduced pressure. Yield: 76% (2.5 g, 18.4mmol), bp 74.5–76.5 �C=1.5mmHg.dH (CDCl3, 300MHz): 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, J¼ 8.4, 3H, CH3). m=z (ESI) 137 (C8H12N2

[MþH]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,24.7mmol) according to the general procedure, stirred for 100min, and purifiedby distillation under reduced pressure. Yield: 77% (4.0 g, 18.8mmol), bp 188–190 �C=12mmHg. dH (CDCl3, 300MHz): 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, J¼ 7.8, 3H, CH3). m=z (ESI)¼ 213 (C14H16N2

[MþH]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, 24.5mmol)according to the general procedure, stirred for 2 h, and purified by distillation underreduced pressure. Yield: 80% (2.7 g, 19.6mmol), bp 169–171 �C. dH (CDCl3,500MHz): 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, J¼ 10.5, 6H, 2CH3).m=z (ESI) 156 (C10H21N [MþH]þ). Found: C, 77.36; H, 13.61; N, 9.03. Calc. forC10H21N: C, 77.35; H, 13.63; N, 9.02.

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N-Benzyl-1-phenylethanamine (4d)

Synthesized from phenyl-N-(1-phenylethylidene)methanamine 4c (5.2 g,24.8mmol) according to the general procedure, stirred for 2 h, and purified by distil-lation under reduced pressure. Yield: 93% (4.9 g, 23.2mmol), bp 170–171.5 �C=15mmHg. dH (CDCl3, 300MHz): 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, J¼ 7.2, 3H, CH3). m=z (ESI) 212 (C15H17N [MþH]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, 24.1mmol)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, 22.3mmol),bp 154–157 �C=5mmHg. dH (CDCl3, 300MHz): 7.36–7.24 (m, 5H, ArH), 6.70 (d,J¼ 8.4, 2H, ArH), 6.58 (m, J¼ 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 [MþH]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, 24.7mmol)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, 22.1mmol). dH(CDCl3, 500MHz): 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 [MþH]þ). Found: C, 71.70; H, 5.58; Cl, 16.30; N, 6.40. Calc. forC13H12ClN: C, 71.72; H, 5.56; Cl, 16.29; N, 6.43.

Dibenzylamine (7d)

Synthesized from N-benzylidene(phenyl)methanamine 7c (4.8 g, 24.6mmol)according to the general procedure, stirred for 2 h, and purified by distillation underreduced pressure. Yield: 92% (4.5 g, 22.8mmol), bp 159–161.5 �C=10mmHg. dH(CDCl3, 500MHz): 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 [MþH]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, 24.6mmol) according to the general procedure, stirred for 2 h, and purifiedby flash chromatography on silica gel (petroleum ether–EtOAc, 6:1). Yield: 82%(4.1 g, 20.0mmol). dH (CDCl3, 500MHz): 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, J¼ 7.5, 3H, CH3),1.17 (d, J¼ 8.0, 3H, CH3), 1.05 (s, 9H, t-Bu). m=z (ESI) 206 (C14H23N [MþH]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-hydroxyethylamoniumchloride 9c (4.5 g, 25.3mmol) 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, 21.8mmol), bp 106–110 �C=1mmHg. dH (CDCl3, 300MHz):7.38–7.20 (m, 5H, ArH), 3.56 (t, J¼ 8.1, 2H, CH2), 2.83–2.80 (t, J¼ 8.4, 2H,CH2), 2.71–2.68 (t, J¼ 8.4, 2H, CH2), 2.55 (t, J¼ 8.1, 2H, CH2), 2.38 (s, 3H,NCH3). m=z (ESI) 180 (C11H17NO [MþH]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, 24.8mmol) according to the general procedure, stirred for 2 h, and purifiedby flash chromatography on silica gel (petroleum ether–EtOAc, 8:1). Yield 91%(5.1 g, 22.9mmol), beige solid, mp 175–176.5 �C. dH (CDCl3, 500MHz): 7.14 (d,J¼ 8.5, 2H, ArH), 7.02 (d, J¼ 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, J¼ 8.0, 3H, CH3). m=z (ESI) 224, 225, 226 (C13H18ClN [MþH]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 HebeiProvince (Nos. B2006000302 and 10276406D6).

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