Green, Efficient and Practical Michael Addition of Arylamines to α,

β–unsaturated Ketones
Ran Jiang, Dan-Hua Li, Jing Jiang, Xiao-Ping Xu*, Chen Tao, Shun-Jun Ji *
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123,
China
Fax: (+)86 512 65880307
E-mail: chemjsj@suda.edu.cn

Table of Contents
Page

1. General experimental methods 2

2. General procedure for preparation of β-amino and sulfido
carbonyl compounds
3. The table of optimizing conditions 2
4. Characterization of β-amino and sulfido carbonyl compounds 3
5. References 11
6. The 1H NMR and 13C NMR charts for β-amino and sulfide
carbonyl compounds 12

General experimental:

Melting points were recorded on an Electrothermal digital melting point apparatus. IR

spectra were recorded on a Varian FT-1000 spectrophotometer using KBr optics. 1H
NMR spectra were recorded on a Varian INOVA 400 and and 13C NMR were recorded
on a Varian INOVA 75 or 100 MHz spectrumeter using CDCl3 as solvent and TMS as
internal standard. High resolution mass spectra were obtained using Microma GCT-
TOF instrument.

Typical experimental procedure for the addition reaction of aromatic

amines to α, β unsaturated ketones:

Aromatic amines (1.0 mmol) and α, β-unsaturated ketones: (1.3 mmol or 2.0 mmol)
were added into a flask. Then the mixture was stirred at room temperature, until
amines were completely consumed (checked by TLC) or an appropriate time. For the
completion of reaction, the excess α, β unsaturated ketones were evaporated under the
reduced pressure to give purity adduct. For the uncompleted of reaction, the residue
was purified by flash column chromatography.

Table of screening of reaction conditionsa

Entry Ratio1 a/b Solvent Temp. Time/h Yield/%
1 1:1.3 H2 O r.t 10 87
2 1:1.3 CH3NO2 r.t 10 17
3 1:1.3 toluene r.t 10 23
4 1:1.3 THF r.t 10 19
5 1:1.3 Glycol r.t 10 75
6 1:1.3 DMF r.t 10 14
7 1:1.3 EtOH r.t 10 54
8 1:1.3 1,4-dioxane r.t 10 20
9 1:1.3 Glycerol r.t 10 57
10 1:1.3 PEG-300 r.t 10 74
11 1:1.3 CH3CN r.t 10 13
12 1:1 Solvent-free r.t 4 60
13 1:1.3 Solvent-free r.t 3 98
a: a = 4-chloroaniline, b = but-3-en-2-one, reaction conditions: a (0.5 mmol), solvent 2.0 mL.

Characterization of β-Amino and Sulfido Carbonyl Compounds

4-(phenylamino)butan-2-one (3aa)1
137 mg, 84%. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3H), 2.74 (t, J = 6.1 Hz, 2H),
3.41 (t, J = 6.1 Hz, 2H), 3.96 (s, 1H, NH), 6.60 (d, J = 7.9 Hz, 2H), 6.71 (t, J = 7.3
Hz, 1H), 7.17 (t, J = 7.9 Hz, 2H) ppm. HRMS (m/z): [M]+, calcd for C10H13NO:
163.0997, found: 163.0997.

4-(4-chlorophenylamino)butan-2-one (3ab)2
193 mg, 98%. 1H NMR (400 MHz, CDCl3): δ = 2.17 (s, 3H, CH3), 2.74 (t, J = 6.0 Hz,
2H), 3.38 (t, J = 6.0 Hz, 2H), 4.13 (s, 1H, NH), 6.53 (d, J = 8.8 Hz, 2H), 7.12 (d , J =
8.8 Hz , 2H) ppm. HRMS (m/z): [M]+, calcd for C10H1235ClNO: 197.0607, found:
197.0607.

4-(4-bromophenylamino)butan-2-one (3ac)
231 mg, 96%. 1H NMR (400 MHz, CDCl3): δ = 2.17 (s, 3H), 2.74 (t, J = 6.0Hz, 2H),
3.38 (t, J = 6.0 Hz, 2H), 4.04 (s, 1H, NH), 6.48(d, J = 8.6 Hz, 2H) ,7.24 (d , J = 8.7
Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3) δ = 208.1, 146.8, 132.1, 114.7, 109.2, 42.4,
38.5, 30.5 ppm. HRMS (m/z): [M]+, calcd for C10H1279BrNO: 241.0102, found:
241.0102
4-(4-iodophenylamino)butan-2-one (3ad)
282 mg, 98%. 1H NMR (400 MHz, CDCl3): δ = 2.16 (s, 3H), 2.73 (t, J = 6.0 Hz, 2H),
3.38 (t, J = 5.9 Hz, 2H), 4.06 (s, 1H, NH), 6.39 (d, J = 8.8 Hz, 2H), 7.41( d, J = 8.8
Hz ,2H) ppm. 13C NMR (75 MHz, CDCl3) δ = 208.1, 147.3, 137.8, 115.2, 78.1, 42.3,
38.2, 30.5 ppm. HRMS (m/z): [M]+, calcd for C10H12INO: 288.9964, found: 288.9964.

4-(2-iodophenylamino)butan-2-one (3ae)3
146 mg, 51%. 1H NMR (400 MHz, CDCl3): δ = 2.19 (s, 3H), 2.79 (t, J = 6.4 Hz , 2H),
3.47 (t, J = 6.4 Hz , 2H), 4.42 (s, 1H, NH), 6.45 (t, J = 7.5 Hz, 1H), 6.58 (d, J = 8.1
Hz, 1H), 7.21 (t, J = 7.1 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H) ppm. HRMS (m/z): [M]+,
calcd for C10H12INO: 288.9964, found: 288.9969.

4-(p-tolylamino)butan-2-one (3af)4
171 mg, 97%. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3H), 2.23 (s, 3H), 2.74 (t, J =
6.0 Hz, 2H) , 3.39 (t, J = 4.2 Hz, 2H), 653 (d, J = 9.2 Hz, 2H), 6.99 (d, J = 7.3 Hz ,
2H) ppm. HRMS (m/z): [M]+, calcd for C11H15NO: 177.1154, found: 177.1154.
4-(m-tolylamino)butan-2-one (3ag) 5
173 mg, 98%. 1H NMR (400 MHz, CDCl 3): δ = 2.16 (s, 3H), 2.27 (s, 3H), 2.74 (t, J =
5.9 Hz, 2H), 3.40 (t, J = 6.1 Hz, 2H), 6.42 (d, J = 7.6 Hz, 2H), 6.54 (d, J =7.5 Hz ,
1H) , 7.06 (t, J = 8.0 Hz ,1H) ppm. HRMS (m/z): [M]+, calcd for C11H15NO: 177.1154,
found: 177.1155.

4-(methyl(phenyl)amino)butan-2-one (3ah) 2
113 mg, 64%. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3H), 2.70 (t, J = 7.0 Hz, 2H),
2.92 (s, 3H), 3.63 (t, J = 7.0 Hz, 2H), 6.70-6.74 (m, 3H), 7.22-7.26 (m, 2H) ppm.
HRMS (m/z): [M]+, calcd for C11H15NO: 177.1154, found: 177.1155.

4-(pyridin-2-ylamino)butan-2-one (3ai)
159 mg ,97%. 1H NMR (400 MHz, CDCl3): δ = 2.16 (s, 3H, CH3), 2.77 (t, J = 6.0 Hz,
2H), 3.60 (t, J = 6.0 Hz, 2H), 4.82 (s, 1H, NH), 6.36 (d, J = 8.4Hz, 1H) , 6.54 (t , J =
5.8 Hz ,1H), 7.37 (t , J = 6.8 Hz , 1H) , 8.06 (d, J = 8.0 Hz, 1H) ppm. 13C NMR (75
MHz, CDCl3): δ = 208.6, 158.4, 147.9, 137.5, 112.9, 108.0, 43.2, 36.4, 30.5 ppm.
HRMS (m/z): [M]+, calcd for C9H12N2O: 164.0950, found: 164.0951

4-(thiazol-2-ylamino)butan-2-one (3aj)
154 mg, 91%. 1H NMR (400 MHz, CDCl3): δ = 2.18 (s, 3H), 2.83 (t, J = 5.8 Hz, 2H),
3.60 (t, J = 5.7 Hz, 2H), 5.57 (s, 1H, NH), 6.48 (d, J = 3.7 Hz, 1H) ,7 .10 (d, J = 3.0
Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ = 208.0, 170.1, 139.0, 106.5, 42.6, 40.2,
30.4 ppm. HRMS (m/z): [M]+, calcd for C7H10N2OS: 170.0514, found: 170.0514.

4-(naphthalen-1-ylamino)butan-2-one (3ak) 4
208 mg, 98%. 1H NMR (400 MHz, CDCl3): δ = 2.20 (s, 3H), 2.89 (t, J = 6.1 Hz, 2H),
3.60 (t, J = 6.1 Hz, 2H), 6.63 (d, J = 7.5 Hz, 1H), 7.25 (d, J = 7.7 Hz, 1H), 7.35 (t, J =
7.9 Hz, 1H), 7.42-7.45 (m, 2H), 7.77-7.79 (m, 2H) ppm. HRMS (m/z): [M]+, calcd for
C14H15NO: 213.1154, found: 213.1156.

4-((3-oxobutyl) amino) benzonitrile (3al)

120 mg, 64%. 1H NMR (400 MHz, CDCl3): δ = 2.19 (s, 3H, CH 3), 2.76 (t, J = 5.9 Hz,
2H), 3.45 ( t, J = 5.9 Hz, 2H), 6.55 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H)
ppm.13C NMR (75 MHz, CDCl3): δ = 207.8, 151.0, 134.0, 120.6, 112.4, 98.9, 42.3,
37.6, 30.5 ppm. HRMS (m/z): [M]+, calcd for C11H12N2O: 188.0950, found: 188.0949.

4-((3-oxobutyl)amino)benzoic acid (3am) 6

163 mg,79%. 1H NMR (400 MHz, DMSO-d6): δ = 2.11 (s, 3H), 2.71 (t, J = 6.6 Hz,
2H), 3.25 (t, J = 6.6 Hz, 2H), 6.38 (br s, 1H), 6.54 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.7
Hz, 2H) ppm. HRMS (m/z): [M]+, calcd for C11H13NO3: 207.0895 , found: 207.0896.
4-((4-acetylphenyl)amino)butan-2-one (3an)
150 mg, 73%. 1H NMR (400 MHz, CDCl 3): δ = 2.50 (s, 3H), 2.18 (s, 3H), 2.77 (t, J =
5.9, 2H), 3.49 (t, J = 5.9 Hz, 2H), 4.59 (s, 1H, NH), 6.55 ( d , J = 8.7 Hz, 2H), 7.82 (d,
J = 8.7 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ = 207.8, 196.5, 151.8, 131.0,
126.8, 111.5, 42.4, 37.7, 30.4, 26.1 ppm. HRMS (m/z): [M]+, calcd for C12H15NO2:
205.1103, found: 205.1103.

1-(phenylamino)pentan-3-one (3ba)7
143 mg,81%. 1H NMR (400 MHz, CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3H), 2.44 (q, J =
7.3 Hz, 2H), 2.72 (t, J = 6.1 Hz, 2H), 3.42 (t, J = 6.1 Hz, 2H), 6.61 (d, J = 7.2 Hz,
2H), 6.71 (t, J = 5.8 Hz, 1H), 7.17 (t, J = 7.9 Hz, 2H) ppm. HRMS (m/z): [M]+, calcd
for C11H15NO: 177.1154, found: 177.1154.

1-(m-tolylamino)pentan-3-one (3bg)
185 mg, 97%. 1H NMR (400 MHz, CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3H). 2.27 (s, 3H),
2.44 (q, J = 7.3 Hz, 2H), 2.71 (t, J = 6.1 Hz, 2H), 3.41 (t, J = 6.2 Hz, 2H), 6.41-6.43
(m, 2H), 6.54 (d, J = 7.4 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 210.9, 147.8, 139.0, 129.2, 118.5, 113.9, 110.2, 41.3, 38.5, 36.3, 21.6, 7.6
ppm. HRMS (m/z): [M]+, calcd for C12H17NO: 191.1310, found: 191.1309.
1-(p-tolylamino)pentan-3-one (3bf)
189 mg, 99%. 1H NMR (400 MHz, CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3H), 2.23 (s, 3H),
2.43 (q, J = 7.3 Hz, 2H), 2.71 (t, J = 6.1 Hz, 2H), 3.40 (t, J = 6.1 Hz, 2H), 6.54 (d, J =
8.4 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ = 211.2,
145.5, 129.9, 127.0, 113.4, 41.1, 39.0, 36.4, 20.5, 7.9 ppm. HRMS (m/z): [M]+, calcd
for C12H17NO: 191.1310, found: 191.1306.

1-(4-chlorophenylamino)pentan-3-one(3bb)
202 mg, 96%. 1H NMR (400 MHz, CDCl3): δ = 1.06 (t, J = 7.3 Hz, 3H), 2.42-2.47 (m,
2H), 2.72 (t, J = 6.1 Hz, 2H), 3.39 (t, J = 6.1 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 7.12
(d, J = 8.8 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ = 210.9, 146.4, 129.2, 122.2,
114.2, 41.1, 38.7, 36.5, 7.9 ppm. HRMS (m/z): [M]+, calcd for C11H14ClNO: 211.0764,
found: 211.0762.

1-(pyridin-2-ylamino)pentan-3-one(3bi)
174 mg, 98%. 1H NMR (400 MHz, CDCl3): δ = 1.06 (t, J = 7.3 Hz, 3H), 2.44 (q, J =
7.3 Hz, 2H), 2.75 (t, J = 6.0 Hz, 2H), 3.62 (q, J = 6.1 Hz, 2H), 4.83 (s, 1H, NH), 6.37
(d, J = 8.4 Hz, 1H), 6.54-6.57 (m, 1H), 7.36-7.40 (m, 1H), 8.07 (d, J = 5.0 Hz, 1H)
ppm. 1H NMR (75 MHz, CDCl3): δ = 211.2, 158.4, 148.0, 137.3, 112.8, 107.8, 41.8,
36.5, 36.4, 7.8 ppm. HRMS (m/z): [M]+, calcd for C10H14N2O: 178.1106, found:
178.1110.

3-(4-chlorophenylamino)cyclohexanone (3cb) 2
209 mg, 94%. 1H NMR (400 MHz, CDCl3): δ = 1.64-1.80 (m, 2H), 2.00-2.09 (m, 1H),
2.14-2.17 (m, 1H), 2.25-2.45 (m, 3H), 2.78-2.83 (m, 1H), 3.37 (s, 1H, NH), 3.70-3.77
(m, 1H), 6.51 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H). HRMS (m/z): [M]+, calcd
for C12H14ClNO: 223.0764, found: 223.0768.

4-(1H-benzo[d][1,2,3]triazol-1-yl)butan-2-one (4aa)
100 mg, 53%. 1H NMR (400 MHz, CDCl3): δ = 2.18 (s, 3H), 3.27 (t, J = 6.5 Hz, 2H),
4.84 (d, J = 6.5 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.63 (d, J =
8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.9,
127.8, 124.4, 120.2, 110.1, 43.0, 42.6, 30.6 ppm. HRMS (m/z): [M]+, calcd for
C10H11N3O: 189.0902, found: 189.0901.

4-(naphthalen-2-ylthio)butan-2-one (6aa)8
207 mg, 90%. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3H, CH 3), 2.81 (t, J = 7.3 Hz,
2H), 3.24 (t, J = 7.4 Hz, 2H), 7.41-7.50 (m, 3H), 7.74-7.81 (m, 4H) ppm. HRMS
(m/z): [M]+, calcd for C14H14OS: 230.0765, found: 230.0763.
1-(naphthalen-2-ylthio)pentan-3-one (6ba)
241 mg, 99%. 1H NMR (400 MHz, CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3H), 2.41 (q, J =
7.3 Hz, 2H), 2.78 (t, J = 7.3 Hz, 2H), 3.25 (t, J = 7.3 Hz, 2H), 7.40-7.50 (m, 3H),
7.74-7.80 (m, 4H) ppm. HRMS (m/z): [M]+, calcd for C15H16OS: 244.0922, found:
244.0921.

3-(naphthalen-2-ylthio)cyclohexanone (6ca) 9
187 mg, 73%. 1H NMR (400 MHz, CDCl3): δ = 1.70-1.83 (m, 2H), 2.14-2.21 (m, 2H),
2.31-2.46 (m, 3H), 2.71-2.75 (m, 1H), 3.52-3.57 (m, 1H), 7.48-7.50 (m, 3H), 7.78-
7.83 (m, 3H), 7.91 (s, 1H) ppm. HRMS (m/z): [M]+, calcd for C16H16OS: 256.0922,
found: 256.0924.

4-(p-tolylthio)butan-2-one (6ab) 8
170 mg, 88%. 1H NMR (400 MHz, CDCl 3): δ = 2.13 (s, 3H), 2.32 (s, 3H), 2.73 (t, J =
7.3 Hz, 2H), 3.08 (t, J = 7.3 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 2 Hz, 2H)
ppm. HRMS (m/z): [M]+, calcd for C11H14OS: 194.0765, found: 194.0764.
References
1. Wabnitz, T. C.; Spencer, J. B. Org. Lett. 2003, 5, 2141.
2. Firouzabadi, H.; Iranpoor, N.; Jafari, A. A. Adv. Synth. Catal. 2005, 347, 655.
3. Curran, D. P.; Yu, H.; Liu, H. Tetrahedron, 1994; 50, 7343.
4. Fetterly, B. M.; Jana, N. K.; Verkade, J. G. Tetrahedron, 2006, 62, 440.
5. De, K. ; Legros, J.; Crousse, B. ; Bonnet-Delpon, D. J. Org. Chem. 2009, 74, 6260.
6. Kim, Y.-H.; Mautner, H. G. J. Med. Chem. 1974, 17, 369.
7. Yang, L.; Xu, L.-W. ; Zhou, W. ; Li, L. ; Xia, C.-G. Tetrahedron Lett. 2006, 47,
7723.
8. Tilak, B. D. ; Desai, H. S. ; Deshpande, C. V. ; Jain, S. K.; Vaidya, V. M.
Tetrahedron, 1966, 22, 7.
9. Yadav, J. S.; Reddy, B. V. S.; Baishya, G. J. Org. Chem. 2003, 68, 7098.

The 1H NMR and 13

C NMR Charts for β-Amino and Sulfido
Carbonyl Compounds
4-(phenylamino)butan-2-one (3aa)
1
H NMR
4-(4-chlorophenylamino)butan-2-one (3ab)
1
H NMR

4-(4-bromophenylamino)butan-2-one (3ac)
1
H NMR
13
C NMR

4-(4-iodophenylamino)butan-2-one (3ad)
1
H NMR

13
C NMR

4-(2-iodophenylamino)butan-2-one (3ae)
1
H NMR
4-(p-tolylamino)butan-2-one (3af)
1
H NMR

4-(m-tolylamino)butan-2-one (3ag)
1
H NMR
4-(methyl(phenyl)amino)butan-2-one (3ah)
1
H NMR

4-(pyridin-2-ylamino)butan-2-one (3ai)
1
H NMR
13
C NMR

4-(thiazol-2-ylamino)butan-2-one (3aj)
1
H NMR
13
C NMR

4-(naphthalen-1-ylamino)butan-2-one (3ak)
1
H NMR
4-((3-oxobutyl) amino) benzonitrile (3al)
1
H NMR

4-((3-oxobutyl)amino)benzoic acid (3am)

1
H NMR
4-((4-acetylphenyl)amino)butan-2-one (3an)
1
H NMR

13
C NMR
1-(phenylamino)pentan-3-one (3ba)
1
H NMR
1-(m-tolylamino)pentan-3-one (3bg)
1
H NMR

13
C NMR
1-(phenylamino) pentan-3-one (3bf)
1
H NMR

13
C NMR
1-(4-chlorophenylamino)pentan-3-one (3bb)
1
H NMR

13
C NMR
1-(pyridin-2-ylamino)pentan-3-one (3bi)
1
H NMR

13
C NMR
3-(4-chlorophenylamino)cyclohexanone (3cb)
1
H NMR

4-(1H-benzo[d][1,2,3]triazol-1-yl)butan-2-one (4aa)
1
H NMR
13
C NMR

4-(naphthalen-2-ylthio)butan-2-one (6aa)
1
H NMR
1-(naphthalen-2-ylthio)pentan-3-one (6ba)
1
H NMR

3-(naphthalen-2-ylthio)cyclohexanone (6ca)
1
H NMR
4-(p-tolylthio)butan-2-one (6ab)
1
H NMR