Solvent- and catalyst-free direct reductive amination of aldehydes and ketones with Hantzsch ester: synthesis of secondary and tertiary amines

Tetrahedron 69 (2013) 4938e4943

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Solvent- and catalyst-free direct reductive amination of aldehydes and ketones with Hantzsch ester: synthesis of secondary and tertiary amines Quynh Pham Bao Nguyen, Taek Hyeon Kim * School of Applied Chemical Engineering and Center for Functional Nano Fine Chemicals, Chonnam National University, Gwangju 500-757, Republic of Korea

a r t i c l e i n f o

a b s t r a c t

Article history: Received 11 October 2012 Received in revised form 8 April 2013 Accepted 11 April 2013 Available online 16 April 2013

A facile and rapid method for the parallel synthesis of a series of secondary and tertiary amines by the direct reductive amination of aldehydes and ketones with Hantzsch ester under solvent- and catalystfree has been developed. The scope and limitation of this method are described. Ó 2013 Elsevier Ltd. All rights reserved.

Keywords: Free catalyst Free solvent Reductive amination Aldehydes Ketones

1. Introduction Amines are important in natural products, pharmaceuticals, and agrochemicals.1 Reductive amination is one of the oldest but most powerful used methods of accessing different kinds of amines. In particular, a one-pot reaction, in which a carbonyl compound and an amine is treated directly with a suitable reductant, is very attractive from the synthetic viewpoint since it avoids the isolation of unstable imine or iminium intermediate.2 Catalytic hydrogenation and metal hydride reduction are the two most commonly used direct reductive amination methods. However, catalytic hydrogenation can be incompatible with the polyfunctional substrates that contain olefins or alkynes, nitro, cyano, and furyl groups. Metal hydrides, such as cyanoborohydride (NaBH3CN) and various borohydride derivatives, are expensive, highly toxic and have some drawbacks, such as long reaction time, require acidic and inert conditions, produce toxic by-products, and low selectivity.3 Furthermore, in most of these reductive conditions, the complete removal of toxic metal impurities is often difficult but essential, especially in the production of pharmaceutical intermediates. This renders the development of metal-free reductive processes a very

* Corresponding author. Tel.: þ82 62 530 1891; fax: þ82 62 530 1889; e-mail addresses: [email protected], [email protected], [email protected] (T.H. Kim). 0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2013.04.046

important research goal. For this reason, Hantzsch ester (HEH), a biomimetic, inexpensive, stable, and safe reducing agent, is of great interest.4 The direct reductive amination of aldehydes and ketones using HEH has been extensively developed, together with effective catalysts, such as Sc(OTf)3,5 ZnCl2,6 ZrCl4,7 TMSCl,8 HCl,9 binol phosphoric acid,10 gold (I) complex,11 single nucleotide,12 thioureas,13 and most recently, S-benzyl-isothiouronium.14 But all of these methods suffer some limitations, such as the need for inert reaction conditions, hazardous solvents and catalysts, long reaction times, tedious workups, low yields, and lack of generality. Herein, we wish to introduce a facile and rapid method for the parallel synthesis of a series of secondary and tertiary amines by the direct reductive amination of aldehydes and ketones with HEH under solvent- and catalyst-free conditions (Scheme 1).

2. Results and discussion Initially, the direct reductive amination of aldehydes was performed with benzaldehyde (1 equiv), 4-methoxyaniline (1.2 equiv), HEH (1.2 equiv), and 5  A MS, which were mixed together in air and then heated at 100
C for 5 h without stirring to give the required product 4a in 59% yield (Table 1, entry 1). Heating up to 150
C dramatically shortened the reaction time to 15 min and afforded 4a in nearly quantitative yield (Table 1, entry 2). In addition, 5  A MS has commonly been introduced to remove water, which has

Q.P.B. Nguyen, T.H. Kim / Tetrahedron 69 (2013) 4938e4943

EtO2C

O R2 EtO2C O R1

R2

CO2Et

1

4

R

5

R

+

R

N R H

CO2Et

R2

N H

3

1

N

R

o

R4

5A MS, 150oC

N H

+ H2N R3

4939

R3 R5

R2

o

5A MS, 150oC 1

R

N R1

R3 R2

Scheme 1. Direct reductive amination of aldehydes and ketones.

Table 1 Optimization of the reaction conditions R2

R2: H, 4a NH

EtO2C O R2

+

H2N

OMe

R2: CH3, 5a

CO2Et N H

R2

neat R2: H, 1a

OMe

OMe R2: H, 6a

N

3a

R2

R2: CH3, 7a

R2: CH3, 2a

Entry

Carbonyl compound

Equiv of Carbonyl/Amine/HEH

1 2 3 4 5 6 7 8 9 10 11 12

Benzaldehyde 1a Benzaldehyde 1a Benzaldehyde 1a Benzaldehyde 1a Acetophenone 2a Acetophenone 2a Acetophenone 2a Acetophenone 2a Benzaldehyde 1a Benzaldehyde 1a Benzaldehyde 1a Acetophenone 2a

1/1.2/1.2 1/1.2/1.2 1/1.2/1.2 1/1.2/1.2 1/1.5/1.5 1/1.5/1.5 1/1.5/1.5 1/1.5/1.5 3/1/2.5 3/1/2.5 3/1/2.5 5/1/4

a b c d

Additive 5 A MSa 5 A MSa None Nonec 5 A MSa None 5 A MSb 5 A MSa,c 5 A MSa 5 A MSa None 5 A MSa

Temperature (
C)

Reaction time (h)

Product

Yield (%)

100 150 150 150 150 150 150 150 130 150 150 200

5 0.25 0.25 0.25 14 24 14 14 24 12 12 96

4a 4a 4a 4a 5a 5a 5a 5a 6a 6a 6a 7a

59 99 98 96 90 45 87 82 48 91 51 dd

Unactivated (SigmaeAldrich, 1.6 mm pellets, product number: 334316). Activated at 400
C for 24 h. NaHCO3 (50 mol %) was added. Only monoalkylated intermediate 5a was formed.

a deleterious impact on both iminium formation and the reduction step,10a however, it had no considerable effect whatsoever upon the direct heating of all three reactants at 150
C (Table 1, entry 3). Next, the direct reductive amination of ketones with acetophenone, 4methoxyaniline, and HEH was investigated (Table 1, entries 5e8). Unlike with benzaldehyde, this reaction proceeded much more difficultly due to the sterical hindrance of the methyl group. Longer reaction time, a slight excess of the amine and HEH (1.5 equiv) with respect to the ketone (1 equiv) and 5  A MS additive were found to be crucial to achieve the best yield of product 5a (Table 1, entry 5). It might be possible that the auto-oxidation of the aldehydes involved may produce sufficient quantities of acids that could catalyze the reactions in the direct reductive amination of aldehydes and also the acidity of the molecular sieves used or of the volatile components in the molecular sieves might catalyze the reactions in the direct reductive amination of ketones.13d However, upon addition A MS at high of excess base (50 mol % NaHCO3) or activation of 5  temperature to eliminate the above mentioned effects, the direct reductive amination of aldehydes and ketones proceeded well under desired condition (Table 1, entries 4, 7, and 8). Therefore these reactions may proceed through thermal effect and easy removal of water with 5  A MS. Mechanistically, at the elevated temperature, the direct reductive amination of aldehydes and ketones

may involve a single-step hydride transfer from HEH to imines or iminiums, as previously reported (Scheme 2).15 With the optimized reaction conditions in hand, we examined the scope and limitations of aldehydes, ketones, and amines using benzaldehyde, acetophenone, and 4-methoxyaniline as representative substrates. It should be noted that 4-methoxyaniline was chosen because the 4-methoxyphenyl group can be oxidatively removed from the resulting amine to produce a primary amine, which renders the whole protocol more versatile.16 As revealed in Table 2, entries 1e17, the direct reductive amination of aldehydes provided the secondary amines with high yields by the various combination of aromatic and aliphatic aldehydes with primary amines. In contrast, upon the direct reductive amination of ketones, the nature of the substrates had great influence compared to aldehydes (Table 3, entries 1e22). For example, the cyclic aliphatic ketone (Table 3, entry 7) was the most reactive, while the more sterically hindered ketone (Table 3, entry 11) furnished low yield. The nitro substituted aromatic amine (Table 3, entry 18) proceeded more difficultly, and the aliphatic amine (Table 3, entry 21) was completely unreactive. It was also found that the functional groups, such as OH, C]O, NO2, and C]C were tolerated very well under our conditions (Table 2, entries 4 and 6; and Table 3, entries 4 and 8, respectively). In addition, the chemoselective reductive amination

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O R1

+

R2

R3 H N R4

R1 R2 HO

R3 N R4

R1

R3 N R4

R2 H

H

EtO2C

R1

CO2Et

R2

R3 N R4

+

EtO2C

CO2Et N

N H

Pyridine by-product

HEH

of HEH

Scheme 2. Proposed mechanism of the direct reductive amination of aldehydes and ketones.

Table 2 Synthesis of secondary amines by the direct reductive amination of aldehydes (1.2 equiv.) EtO2C N H

O 1

R

CO2Et

H

+ H2N R3

(1 equiv.)

(1.2 equiv.)

1

3

150oC, neat

R1

N R3 H 4

Entry

Carbonyl compound

Amine

Time (h)

Product

Yield (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Benzaldehyde1a 4-Methylbenzaldehyde 1b 4-Methoxybenzaldehyde 1c 3-Hydroxybenzaldehyde 1d 2-Chlorobenzaldehyde 1e 3-Acetylbenzaldehyde 1f 2-Thienylaldehyde1g 2-Furylaldehyde1h Cyclohexylaldehyde1i Isobutylaldehyde1j Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a

4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a Aniline3b 4-Methylaniline 3c 3-Chloroaniline 3d 2-Pyridylamine 3e Benzylamine3f n-Octylamine3g 2-Aminoanthracene 3hb

0.25 0.25 1 2 0.25 1 1 2 1 1 0.25 0.25 0.25 0.25 1 1 1

4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m 4n 4o 4p 4q

98 94 96 97a 99 97a 95a 80 86 80 99 96 98 92 81 75 98

a b

Solid aldehyde, amine, and Hantzsch ester were used. The melting point of the amine was 238e241
C.

of the aldehyde in the presence of the ketone moiety was achieved (Table 2, entry 6). To extend the applicability of our method, we also focused on the synthesis of tertiary amines by increasing the molar ratios of aldehydes, ketones, and HEH with respect to amines (Table 1, entries 9e12). Pleasingly, the dialkylated product 6a was obtained in excellent yield after heating the reaction mixture of benzaldehyde (3 equiv), 4-methoxyaniline (1 equiv), and HEH (2.5 equiv) in the presence of 5  A MS additive at 150
C for 12 h (Table 1, entry 10).  Without 5 A MS, the reaction proceeded sluggishly and gave low yield (Table 1, entry 11). A complete conversion to the tertiary amine was observed without a trace of the secondary amine intermediate. However, we were unable to obtain the required tertiary amine from the excess acetophenone. Even in the severe conditions, this reaction led only to the monoalkylated amine intermediate 5a (Table 1, entry 12). After a successful formation of tertiary amine 6a from excess aldehydes (3 equiv), we further extended the scope of this transformation by attempting a series of reactions between various

aldehydes and amines. In Table 4, entries 1e17, all of the required tertiary amines products 6 were shown in moderate to excellent yields.17 In addition, the benzaldehyde with the ketone moiety also provided the required amine chemoselectively without any byproducts derived from the reaction of the ketone moiety with the amine (Table 4, entry 6). For the synthesis of the more sterically hindered tertiary amines, our initial effort for the reaction of acetophenone 2a with the a-branched secondary amine 5a was unsuccessful, and also with the simple secondary amine 4a, it did not give good results (Table 5, entries 1 and 2). Next, we tested whether tertiary amines could be formed from the reaction of aldehydes with the sterically hindered secondary amines derived from the ketones. To our delight, the treatment of the aldehydes 1a and 1j with the abranched secondary amine 5a allowed for the production of the tertiary amines 8a and 8b, respectively, in very good yields (Table 5, entries 3 and 4). Therefore, the compound 8a (Table 5, entry 1 vs entry 3) could be prepared using the proper order of the reductive amination steps, that is, first reductive amination with the ketone,

Q.P.B. Nguyen, T.H. Kim / Tetrahedron 69 (2013) 4938e4943

4941

Table 3 Synthesis of secondary amines by the direct reductive amination of ketones (1.5 equiv.) EtO2C

CO2Et R2

N H

O

1

3

R2 + H2N R

R1

(1 equiv.)

(1.5 equiv.)

2

3

N R3 H

R

o

5A MS, 150oC, neat

5

Entry

Carbonyl compound

Amine

Time (h)

Product

Yield (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Acetophenone2a m-Methylacetophenone 2b p-Chloroacetophenone 2c p-Nitroacetophenone2d 2-Furyl methyl ketone 2e 2-Thienyl methyl ketone 2f Cyclohexanone2g 3-Butenyl methyl ketone 2h 2-Naphthyl methyl ketone 2i Ethyl phenyl ketone2j Diphenylketone2k 2-Acetylanthracene2lb Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a Acetophenone2a

4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a 4-Methoxyaniline3a Aniline3b 4-Methylaniline3c 3-Chloroaniline3d 2-Pyridylamine3e 3-(Trifluoromethyl)aniline 3i 4-Nitroaniline3j 3-Hydroxyaniline3k Benzylamine3f n-Octylamine3g 2-Aminoanthracene3h

14 24 24 48 48 24 24 24 48 24 48 48 16 24 24 48 24 48 48 96 96 48

5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p 5q 5r 5s 5t 5u 5v

90 89 75a 56a 72a 82 97 80 87a 89a 46a dc 88 76 65 53 61 40 70 dc dc <5d

a b c d

Solid ketone, amine, and Hantzsch ester were used. The melting point of the ketone was 189e192
C. No reaction. It was hard to purify the product 5v from the reaction mixture.

Table 4 Synthesis of tertiary amines of the type: NR(R0 )2 (2.5 equiv.) EtO2C O H

+ H2N R3

(3 equiv.)

(1 equiv.)

1

3

2 R1

CO2Et N H

o

5A MS, 150oC, neat

R1

N

R3

R1 6

Entry

Aldehyde

Amine

Time (h)

Product

Yield (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Benzaldehyde1a 4-Methylbenzaldehyde 1b 4-Methoxybenzaldehyde 1c 3-Hydroxybenzaldehyde 1d 2-Chlorobenzaldehyde1e 3-Acetylbenzaldehyde1f 2-Thienylaldehyde1g 2-Furylaldehyde1h Cyclohexylaldehyde1i Isobutylaldehyde1j Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a Benzaldehyde1a

4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a 4-Methoxyaniline 3a Aniline3b 4-Methylaniline3c 3-Chloroaniline3d 2-Pyridylamine3e Benzylamine3f n-Octylamine3g 2-Aminoanthracene 3h

12 12 12 12 12 12 12 12 12 12 48 24 48 24 12 12 12

6a 6b 6c 6d 6e 6f 6g 6h 6i 6j 6k 6l 6m 6n 6o 6p 6q

91 74 81 61a 86 60a 76a 74 99 85 50 89 52 60 99 71 66

a

Solid aldehyde, amine, and Hantzsch ester were used.

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Q.P.B. Nguyen, T.H. Kim / Tetrahedron 69 (2013) 4938e4943

Table 5 Synthesis of particularly sterically demanding tertiary amines of the type: NRR0 R00 (1.5 equiv.) EtO2C R2

O 4

R

5

R

+

(1 equiv.)

1

R

(1.5 equiv)

R2

N H

3

N R H

CO2Et

R1

o

5A MS, 150oC, neat

N R4

R3 R5

Entry

Carbonyl compound

Amine

Time (h)

Product

Yield (%)

1 2 3 4

Acetophenone 2a Acetophenone 2a Benzaldehyde 1a Isobutylaldehyde 1j

N-Benzyl-4-methoxyaniline4a N-(1-Phenylethyl)-4-methoxyaniline 5a N-(1-Phenylethyl)-4-methoxyaniline 5a N-(1-Phenylethyl)-4-methoxyaniline 5a

48 48 24 24

8a 7a 8a 8b

<5 da 84 77

a

No reaction.

and then reductive amination with the aldehyde. In this reaction system, it can be inferred that ketones may not be reactive with both secondary amines 4 and 5, while aldehydes reacted well with both cases. Finally, to apply our reaction conditions to the high melting point amine and ketone, such as 2-aminoanthracene 3h (mp: 238e241
C) and 2-acetylanthracene 2l (mp: 189e192
C) were used (Tables 2 and 4, entry 17; and Table 3, entries 12 and 22). It was found that the liquid aldehyde reacted with 2-aminoanthracene 3h to form the required secondary amine and tertiary amine in good yields (Tables 2 and 4, entry 17), and the liquid ketone reacted very difficultly with 2-aminoanthracene 3h (Table 3, entry 22). In addition, 2acetylanthracene 2l showed no reaction (Table 3, entry 12). 3. Conclusion In summary, we have developed a facile and rapid method for the parallel synthesis of a series of secondary and tertiary amines by the direct reductive amination of aldehydes and ketones using Hantzsch ester under solvent- and catalyst-free as well as metaland acid-free conditions. 4. Experimental section 4.1. General All reagents were obtained from commercial suppliers and were used without further purification. The products were purified by using flash column chromatography. TLC was developed on Merck silica gel 60 F254 aluminum sheets. The 1H and 13C NMR spectra were recorded at 300 and 75 MHz, respectively, using CDCl3 as solvent. HRMS were measured on a Micromass Q-TOF instrument (ESþ ion mode). 4.2. Typical procedure for the direct reductive amination of aldehydes and ketones In a small capped-vial, aldehydes 1 or ketones 2, amines 3, and HEH were mixed together in air at different molar ratios as follows: method I: aldehydes (0.2 mmol), amines (0.24 mmol), and HEH (62 mg, 0.24 mmol); method II: aldehydes or ketones (0.27 mmol), amines (0.41 mmol), HEH (104 mg, 0.41 mmol), and 5  A MS (0.5 g); method III: aldehydes (0.48 mmol), amines (0.16 mmol), HEH (101 mg, 0.4 mmol), and 5  A MS (0.2 g). The reaction mixtures were heated at 150
C without stirring. After completion of the reactions, the crude products were cooled to room temperature, dissolved in a small amount of dichloromethane, and subjected directly to the flash column chromatography to afford different kinds of the pure desired amines products 4, 5, 6, and 8. All known amines

compounds were identified by comparison of their 1H NMR spectra with those in authentic samples. 4.2.1. Selected spectra data of unknown compounds 4.2.1.1. N,N-Bis(3-hydroxybenzyl)-4-methoxybenzenamine (6d). Colorless oil (33 mg, 61%); IR (neat): nmax¼3308, 1589, 1510, 1453, 1227, 1180 cm1; 1H NMR (300 MHz, CDCl3) d 3.69 (s, 3H), 4.42 (s, 4H), 6.60e7.25 (m, 12H); 13C NMR (75 MHz, CDCl3) d 55.1, 55.9, 113.8, 113.9, 114.7, 114.9, 119.3, 129.8, 141.1, 143.8, 151.7, 155.9; HRMS (ESIQToF) m/z calcd for C21H21NO3 [Mþ] 335.1521, found 335.1529. 4.2.1.2. Diethyl 2-(3-hydroxystyryl)-6-methylpyridine-3,5-dicarboxylate (60 d). White solid (17 mg, 10%); Mp 105e110
C; IR (neat): nmax¼3444, 1715, 1690, 1580, 1469, 1285, 1185 cm1; 1H NMR (300 MHz, CDCl3) d 1.42 (m, 6H), 2.91 (s, 3H), 4.42 (m, 4H), 5.67 (br s, 1H), 6.70e6.85 (m, 4H), 7.98 (d, J¼15.6 Hz, 1H), 8.13 (d, J¼15.6 Hz, 1H), 8.70 (s, 1H); 13C NMR (75 MHz, CDCl3) d 14.3, 25.3, 61.5, 61.7, 114.2, 116.3, 120.7, 121.5, 123.2, 124.8, 129.9, 138.1, 138.3, 141.6, 156.1, 156.7, 162.4, 165.9, 166.0; HRMS (ESI-QToF) m/z calcd for C20H20NO5 [MH] 354.1342, found 354.1341. 4.2.1.3. N,N-Bis((thiophen-2-yl)methyl)-4-methoxybenzenamine (6g). Yellow oil (38 mg, 76%); IR (neat): nmax¼1589, 1511, 1453, 1228, 1181 cm1; 1H NMR (300 MHz, CDCl3) d 3.76 (s, 3H), 4.58 (s, 4H), 6.807.30 (m, 10H); 13C NMR (75 MHz, CDCl3) d 50.6, 55.6, 114.6, 117.8, 124.6, 125.4, 126.6, 142.2, 143.0, 153.2; HRMS (ESI-QToF) m/z calcd for C17H16NOS2 [iminium ionþ] 314.0673, found 314.0698. 4.2.1.4. N,N-Bis(cyclohexylmethyl)-4-methoxybenzenamine (6i). White solid (50 mg, 99%); Mp 9495
C; IR (neat): nmax¼2918, 2850, 1508,1449,1241,1217 cm1; 1H NMR (300 MHz, CDCl3) d 0.92 (m, 4H), 1.17 (m, 8H), 1.70 (m, 10H), 3.06 (d, J¼6.7 Hz, 4H), 3.76 (s, 3H), 6.61 (d, J¼9.1 Hz, 2H), 6.82 (d, J¼9.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 26.1, 26.7, 31.4, 36.1, 55.8, 60.0, 114.3, 114.8, 143.7, 150.7; HRMS (ESI-QToF) m/z calcd for C21H34NO [MþHþ] 316.2640, found 316.2637. 4.2.1.5. N,N-Bis(benzyl)-2-anthraceneamine (6q). Yellow oil (38 mg, 66%); IR (neat): nmax¼2920, 2851, 1626, 1491, 1362, 1214 cm1; 1H NMR (300 MHz, CDCl3) d 4.79 (s, 4H), 7.05 (d, J¼1.8 Hz, 1H), 7.207.80 (m, 13H), 7.807.92 (m, 3H), 8.06 (s, 1H), 8.25 (s, 1H); 13 C NMR (75 MHz, CDCl3) d 54.2, 104.2, 117.9, 122.8, 123.5, 125.2, 128.8, 126.8, 127.0, 127.4, 128.2, 128.7, 129.5, 129.6,132.4, 133.4,138.3; HRMS (ESI-QToF) m/z calcd for C28H24N [MþHþ] 374.1909, found 374.1906. 4.2.1.6. N-Benzyl-4-methoxy-N-(1-phenylethyl)benzenamine (8a). Colorless oil (72 mg, 84%); IR (neat): nmax¼1508, 1450, 1240 cm1; 1H NMR (300 MHz, CDCl3) d 1.54 (d, J¼6.9 Hz, 3H), 3.74 (s, 3H), 4.26 (d, J¼16.6 Hz, 1H), 4.40 (d, J¼16.6 Hz, 1H), 5.02 (q, J¼6.9 Hz, 1H),

Q.P.B. Nguyen, T.H. Kim / Tetrahedron 69 (2013) 4938e4943

6.707.40 (m, 14H); 13C NMR (75 MHz, CDCl3) d 18.5, 51.5, 55.6, 59.2, 114.4, 118.3, 126.4, 126.8, 127.1, 127.2, 128.2, 128.4, 140.3, 143.3, 143.4, 152.7; HRMS (ESI-QToF) m/z calcd for C22H23NO [Mþ] 317.1780, found 317.1784. Acknowledgements Following are results of a study on the Leader Industryuniversity Cooperation Project, supported by the Ministry of Education, Science, and Technology (MEST). We wish to thank the Korean Basic Science Institute, Gwangju Center, for analysis of the LCMS/MS Spectrometry. Supplementary data 1 H NMR and 13C NMR spectra of all compounds. Supplementary data related to this article can be found at http://dx.doi.org/10.1016/ j.tet.2013.04.046.

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