Green, efficient and practical Michael addition of arylamines to α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.tet.2011.03.082

The aza-Michael addition of aromatic amines to α,β-unsaturated ketones was carried out effectively at room temperature in good to excellent yields without any catalyst or solvent. It was significant that part of adducts could be collected in almost quanti

Full text of DOI:10.1016/j.tet.2011.03.082

Tetrahedron 67 (2011) 3631e3637
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Tetrahedron
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Green, efficient and practical Michael addition of arylamines to a,b-unsaturated
ketones
*
*
Ran Jiang, Dan-Hua Li, Jing Jiang, Xiao-Ping Xu , Tao Chen, Shun-Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 March 2011
Received in revised form 21 March 2011
Accepted 25 March 2011
Available online 31 March 2011
The aza-Michael addition of aromatic amines to a,b-unsaturated ketones was carried out effectively at
room temperature in good to excellent yields without any catalyst or solvent. It was significant that part
of adducts could be collected in almost quantitative yield without column chromatography. This pro-
cedure offered a green, efficient, and practical approach for the synthesis of b-amino ketones.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Michael addition
b
-Amino ketones
Solvent-free
Catalyst-free
1. Introduction
catalyst or solvent was required in these reactions, the aromatic
amines were demonstrated to be almost inert in the reaction pos-
sibly as a result of their weaker nucleophilicity.4,12,13,14b On the
other hand, the selectivity of mono-addition and di-addition was
challenge in catalytic systems. In our continuing efforts to develop
green procedures for the 1,4-conjugated addition,18 we herein
disclose an efficient approach for the mono-addition of aromatic
The
b-amino carbonyl moiety is always found in biological
products and pharmaceutically active substances.1 Over the past
decades, many approaches have been developed for the synthesis
of this skeleton. Among these methods, the aza-Michael addition is
preferable due to its atom economy, high selectivity, and simple
processes. A great deal of catalyst systems have been explored to
date for the transformation2 using Lewis acids (In,3 Yb,4 Cu,5 Bi,6
Fe,7 Sm,8 molecular Iodine,9 Pd,10 etc.), Brønsted acids,11 base,12
ionic liquid,13 and others.14 However, most of these catalyst sys-
tems suffer from limitations including harsh reaction conditions
with low yields, tedious workup procedures and the necessity of
column chromatography for purification. On the other hand, the
elimination or reduction of hazardous solvents in chemical pro-
cesses is becoming more and more desirable in pursuit of ‘Green
Chemistry’.15 Quite recently, practical procedures in absence of
solvents16 or catalysts17,22 have been accomplished. However, the
development of greener system for the aza-Michael addition in
both catalyst- and solvent-free conditions, to the best of our
knowledge, is still an ongoing challenge. Our previous work
showed that secondary aliphatic amines could react with chalcones
to achieve adducts in excellent yields with the promotion of ul-
trasound irradiations.18a Although it was remarkable that no
amines to
a,b-unsaturated ketones with high selectivity, which
performs at room temperature in absence of any catalyst or solvent
(Scheme 1). In addition, the most often-used purification methods
of column chromatography and recrystallization are not necessary
for many of our cases at all. Significantly, the neat product can be
obtained over 2 g in one relatively large-scaled experiment. It is
expected to be potentially applied in industrial processes.
R1
O
R
no catalyst
R
+
XH
X
R2
no solvent
R1
R2
Y
r.t.
Y
O
X = NH, S; Y = C, N; R = H, Me, I, Cl, Br, CN, NO2, Ac, etc.; R1, R2 = alkyl, H
Scheme 1.
2. Results and discussion
Initially, a template reaction using the 1:1.3 M ratio of 4-chlor-
oaniline and but-3-en-2-one was selected to optimize the solvent
condition at room temperature (Fig. 1, see the detailed data in
* Corresponding authors. Tel./fax: þ86 512 65880307; e-mail address: chemjsj@
suda.edu.cn (S.-J. Ji).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.082

3632
R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
common solvents including CH3NO2, DMF, toluene,1,4-dioxane, THF
O
no catalyst
r.t.
Cl
NH
and EtOH (Fig.1, aeg). It was surprising that only protic solvent EtOH
could offer a moderate yield. Consequently, other protic solvents,
such as H2O, glycol, glycerol, and PEG-300 were introduced to in-
crease the yield of the final product. As expected, an obvious im-
provement in yields was observed from 54% to 87% when the
reaction was carried out in these solvents, respectively (Fig. 1, hek).
Considering the fact that the template reaction runs better in protic
solvents than in aprotic solvents, the hydrogen bond between sub-
strate and solvent is supposed to play an important role. Therefore,
the neat reaction of 4-chloroaniline with but-3-en-2-one was ex-
amined, whichwas expected toworkevenbetter thanwas dispersed
by solvents. The reaction proceeded smoothly and specifically, just
as we supposed, to afford the desired product in almost quantitative
yield. When our case is compared with other workup procedures,
such as column chromatography or recrystallization, only a simple
operation for the removal of the excessive but-3-en-2-one in vacuo
would lead to neat product (Fig. 1, l).
Cl
NH2 +
O
100
80
60
40
20
0
a
b
c
d
e
f
g
h
i
j
k
l
solvent
a = CH3CN, b = CH3NO2, c = DMF, d = Toluene, e = 1,4-dioxane, f = THF,
g = EtOH, h = H2O, i = Glycol, j = Glycerol, k = PEG-300, l = Sol-free
With the optimal condition, we subsequently investigated the
scope of the aromatic amines (2aen). As seen from Table 1, the
Fig. 1.
Supplementary data). It was found that the reaction could proceed
successfully in the absence of a catalyst when MeCN was used as the
solvent, although the desired product was isolated in a very low
yield. Encouraged by this result, we subsequently screened other
reactions offered moderate to excellent yields for the b-amino
carbonyl compounds when the substituted anilines were in-
troduced. Among the anilines selected, those bearing the chloro-
(2b), bromo-(2c), iodo-(2d), and methyl (2f) substituent at the
Table 1
Aza-Michael addition of aromatic amines to a,b
-unsaturated ketonesa
Entry
1
a
,
b
-unsaturated ketones
AreNH2
Product
Time(h)
6
Yield(%)b
84
1a
2a
2b
2c
2d
3aa
3ab
3ac
3ad
2
3
4
3
4
4
98c
96c
98c
5
2e
3ae
4
51
6
7
2f
3af
4
6
97c
98c
2g
3ag
8
9
2h
2i
3ah
3ai
24
4
64
97c

R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
3633
Table 1 (continued )
Entry
a
,
b
-unsaturated ketones
AreNH2
Product
Time(h)
4
Yield(%)b
10
2j
3aj
91
11
2k
3ak
6
98c
12
13
14
15
16
2l
3al
10
24
24
5
64
79
73
81
97c
2m
2n
2a
2g
3am
3an
3ba
3bg
1b
10
17
18
2f
3bf
2
99c
96c
2b
3bb
10
19
20
2l
2i
ee
ee
24
8
ee
3bi
98c
21
22
1c
2b
3cb
48
94
1d
1e
2a
2a
ee
ee
ee
ee
24
24
ee
ee
23
a
Reaction conditions: amines (1.0 mmol), a,b-unsaturated ketones (1.3 mmol), room temperature.
Yield of isolated product after flash chromatography.
Yield of pure product without column chromatography.
b
c
para-position reacted with but-3-en-2-one (1a) to give the corre-
sponding pure products in almost quantitative yield without any
need of column chromatography or recrystallization (Table 1, en-
tries 2e4, 6). Similar result was obtained as well in the reaction of
meta-toluidine with 1a (Table 1, entry 7). The steric effect for ani-
lines with ortho-iodo (2e) and N-methyl (2h) substituents (Table 1,
entries 5, 8) was observed obviously, which was illustrated by their
lower reactivity than aniline (2a) (Table 1, entry 1). It should be
noted that the hetero-aromatic amines, pyridin-2-amine (2i) (Table
1, entry 9) and thiazol-2-amine (2j) (Table 1, entry 10), could also
react well to give the desired products 3ai and 3aj in 97% and 91%
yields, respectively. Meanwhile, 4-(naphthalen-1-ylamino)butan-
2-one (3ak) could be obtained in a 98% yield through the reaction of
naphthalen-1-amine (2k) and 1a. However, when the anilines

3634
R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
containing electron-withdrawing groups (Table 1, entries 12e14)
were utilized as nucleophiles, the corresponding adducts were
provided in lower yields even after prolonged reaction time. It may
be attributed to the poorer nucleophilicity of these amines.
In order to examine the generality of enones, pent-1-en-3-one
(1b) and cyclohex-2-enone (1c) were introduced as well. Fortu-
nately, the methyl-(2g, 2f) and chloro-(2b) substituted anilines as
well as hetero-aromatic amine (2i) reacted with 1b to give the
adducts quantitatively without an extra purification process. As to
the cyclic vinylketone 1c, less reactivity than 1b was observed,
which offered the desired product in 94% yield. Similarly, as a result
of the negative influence from the strong electron-withdrawing
group on the nucleophilicity of amino group, the reaction of
4-aminobenzonitrile (2l) and 1b didn’t occur under the same
conditions (Table 1, entry 19). Study on wider generality for enones
and amines were carried out. It was found that introduction of
phenyl group into enone molecules hampered the reaction greatly,
which was well demonstrated in the reactions of chalcone (1d) or
4-phenylbut-3-en-2-one (1e) with 2a. As to phenylvinylketone, an
analog of 1d, only poor reactivity was observed in the standard
reaction, no expected product was isolated after workup. Combi-
nation of benzylamine and but-3-en-2-one (1a) also led to the
similar result. Notably, the reaction between 1H-benzo[d][1,2,3]
triazole (4a) and 1a could also carry out smoothly to give the
N-alkylation product (4aa) in 53% yield under standard condition
(Scheme 2).
Since this mild and green protocol is of a relatively wide gen-
erality for the syntheses of
-arylamino ketones, it would be po-
b
tentially useful in industrial processes if the reactions could be
scaled up. Therefore, a large-scaled reaction of 4-bromoaniline (2c)
(10.0 mmol) with 1a (13.0 mmol) was carried out (Scheme 3). To
our delight, the reaction was completed in 5 h to give the neat
product of 3ac in 99% yield only after the removal of excessive 1a
under the reduced pressure.
O
no catalyst
Br
NH
+
NH2
Br
no solvent
O
r.t.
1.72 g
0.91 g
5 h, 2.42 g, > 99% yield
Scheme 3.
In an endeavor to expand the scope of the methodology, some
other nucleophiles were tested to give the data as listed in Table 2. It
is satisfying that naphthalene-2-thiol (5a) could react smoothly
with 1a, 1b, and 1c to produce the b-sulfido carbonyl compounds in
moderate to good yields (Table 2, entries 1e3). However, an analog
of 5a, 4-methylbenzenethiol (4b) showed less reactivity to give the
corresponding adduct (6ab) in an 88% yield after 24 h (Table 2,
entry 4).
3. Conclusion
In summary, we have disclosed an environmentally benign
N
O
N
procedure for the synthesis of the
aza-Michael addition of aromatic amines to
b
-arylamino ketones using the
-unsaturated ke-
no catalyst
N
O
N
a,b
+
no solvent
N
N
H
r.t., 24h, 53%
tones. Some obvious advantages of this transformation are dem-
onstrated: (1) the reactions could proceed successfully without any
catalyst and solvent, thus avoiding the use of expensive or sensitive
4aa
1a
4a
Scheme 2.
Table 2
Thia-Michael addition of thiophenol to a,b
-unsaturated ketonesa
Entry
Substrate
Product
Time(h)
Yield(%)b
1
5a
1a
1b
2
90
6aa
2
3
1
99c
6ba
1c
1a
10
24
73
88
6ca
4
5b
6ab
a
Reaction conditions: thiols (1.0 mmol), a,b-unsaturated ketones (1.3 mmol), room temperature.
Yield of isolated product after flash chromatography.
Yield of pure product without column chromatography.
b
c

R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
3635
catalysts and toxic organic solvents; (2) the workup is greatly
4.3.5. 4-(2-Iodophenylamino)butan-2-one (3ae)20
CDCl3):
(s, 1H, NH), 6.45 (t, J¼7.5 Hz, 1H), 6.58 (d, J¼8.1 Hz, 1H), 7.21
(t, J¼7.1 Hz, 1H), 7.66 (d, J¼7.8 Hz, 1H) ppm. HRMS (m/z): [M]þ, calcd
for C10H12INO: 288.9964, found: 288.9969.
.
1H NMR (400 MHz,
simplified for the neat products in almost quantitative yields
without need of column chromatography in most of cases; (3) there
was no decrease in yield when the reaction was extended to gram
scales.
d
¼2.19 (s, 3H), 2.79 (t, J¼6.4 Hz, 2H), 3.47 (t, J¼6.4 Hz, 2H), 4.42
4.3.6. 4-(p-Tolylamino)butan-2-one (3af)21
.
1H NMR (400 MHz,
4. Experimental section
4.1. General
CDCl3):
d
¼2.15 (s, 3H), 2.23 (s, 3H), 2.74 (t, J¼6.0 Hz, 2H), 3.39
(t, J¼4.2 Hz, 2H), 653 (d, J¼9.2 Hz, 2H), 6.99 (d, J¼7.3 Hz, 2H) ppm.
HRMS (m/z): [M]þ, calcd for C11H15NO: 177.1154, found: 177.1154.
1H NMR spectra were recorded on a Varian INOVA 400 and and
13C NMR were recorded on a Varian INOVA 75 or 100 MHz spec-
trometer using CDCl3 as solvent and TMS as internal standard. High
resolution mass spectra were obtained using Microma GCT-TOF
instrument.
4.3.7. 4-(m-Tolylamino)butan-2-one (3ag)17f
.
1H NMR (400 MHz,
CDCl3):
d¼2.16 (s, 3H), 2.27 (s, 3H), 2.74 (t, J¼5.9 Hz, 2H), 3.40
(t, J¼6.1 Hz, 2H), 6.42 (d, J¼7.6 Hz, 2H), 6.54 (d, J¼7.5 Hz, 1H), 7.06
(t, J¼8.0 Hz, 1H) ppm. HRMS (m/z): [M]þ, calcd for C11H15NO:
177.1154, found: 177.1155.
4.3.8. 4-(Methyl(phenyl)amino)butan-2-one (3ah)19. 1H NMR (400
4.2. Typical experimental procedure for the reaction of
aromatic amines to
a,
b-unsaturated ketones
MHz, CDCl3):
d
¼2.15 (s, 3H), 2.70 (t, J¼7.0 Hz, 2H), 2.92 (s, 3H), 3.63
(t, J¼7.0 Hz, 2H), 6.70e6.74 (m, 3H), 7.22e7.26 (m, 2H) ppm. HRMS (m/
z): [M]þ, calcd for C11H15NO: 177.1154, found: 177.1155.
Aromatic amines (1.0 mmol) and
a,b
-unsaturated ketones
(1.3 mmol) were added into a round-bottom flask. Then the mix-
ture was stirred at room temperature in air, until amines were
completely consumed (checked by TLC) or an appropriate time.
4.3.9. 4-(Pyridin-2-ylamino)butan-2-one (3ai). 1H NMR (400 MHz,
CDCl3):
d
¼2.16 (s, 3H, CH3), 2.77 (t, J¼6.0 Hz, 2H), 3.60 (t, J¼6.0 Hz,
Upon the completion of reaction, the excessive
a,b-unsaturated
2H), 4.82 (s, 1H, NH), 6.36 (d, J¼8.4Hz, 1H), 6.54 (t, J¼5.8 Hz, 1H),
7.37 (t, J¼6.8 Hz, 1H), 8.06 (d, J¼8.0 Hz, 1H) ppm. 13C NMR (75 MHz,
ketones were evaporated under the reduced pressure to give the
neat adducts. For the uncompleted reaction, the residue was puri-
fied by flash column chromatography.
CDCl3):
d
¼208.6, 158.4, 147.9, 137.5, 112.9, 108.0, 43.2, 36.4,
30.5 ppm. HRMS (m/z): [M]þ, calcd for C9H12N2O: 164.0950, found:
164.0951.
4.3. Typical experimental procedure for the reaction of
aromatic thiols to
a,
b-unsaturated ketones
4.3.10. 4-(Thiazol-2-ylamino)butan-2-one (3aj). 1H NMR (400 MHz,
CDCl3):
d
¼2.18 (s, 3H), 2.83 (t, J¼5.8 Hz, 2H), 3.60 (t, J¼5.7 Hz, 2H),
Aromatic thiols (1.0 mmol) and
a,b
-unsaturated ketones
5.57 (s, 1H, NH), 6.48 (d, J¼3.7 Hz, 1H), 7.10 (d, J¼3.0 Hz, 1H) ppm.
(1.3 mmol) were added into a round-bottom flask. Then the mix-
ture was stirred at room temperature in air, until thiols were
completely consumed (checked by TLC) or an appropriate time.
13C NMR (75 MHz, CDCl3):
d¼208.0, 170.1, 139.0, 106.5, 42.6, 40.2,
30.4 ppm. HRMS (m/z): [M]þ, calcd for C7H10N2OS: 170.0514, found:
170.0514.
Upon the completion of reaction, the excessive
a,b-unsaturated
ketones were evaporated under the reduced pressure to give the
neat adducts. For the uncompleted reaction, the residue was puri-
fied by flash column chromatography.
4.3.11. 4-(Naphthalen-1-ylamino)butan-2-one (3ak)21
.
1H NMR
(400 MHz, CDCl3):
d
¼2.20 (s, 3H), 2.89 (t, J¼6.1 Hz, 2H), 3.60
(t, J¼6.1 Hz, 2H), 6.63 (d, J¼7.5 Hz, 1H), 7.25 (d, J¼7.7 Hz, 1H), 7.35
(t, J¼7.9 Hz, 1H), 7.42e7.45 (m, 2H), 7.77e7.79 (m, 2H) ppm.
HRMS (m/z): [M]þ, calcd for C14H15NO: 213.1154, found: 213.1156.
.
4.3.1. 4-(Phenylamino)butan-2-one (3aa)11c 1H NMR (400 MHz,
CDCl3):
d
¼2.15 (s, 3H), 2.74 (t, J¼6.1 Hz, 2H), 3.41 (t, J¼6.1 Hz, 2H),
3.96 (s, 1H, NH), 6.60 (d, J¼7.9 Hz, 2H), 6.71 (t, J¼7.3 Hz, 1H), 7.17
(t, J¼7.9 Hz, 2H) ppm. HRMS (m/z): [M]þ, calcd for C10H13NO:
163.0997, found: 163.0997.
4.3.12. 4-((3-Oxobutyl) amino)benzonitrile (3al). 1H NMR (400
MHz, CDCl3):
d
¼2.19 (s, 3H), 2.76 (t, J¼5.9 Hz, 2H), 3.45 (t, J¼5.9 Hz,
2H), 6.55 (d, J¼8.7 Hz, 2H), 7.42 (d, J¼8.7 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3):
d¼207.8, 151.0, 134.0, 120.6, 112.4, 98.9, 42.3, 37.6,
4.3.2. 4-(4-Chlorophenylamino)butan-2-one (3ab)19. 1H NMR (400
30.5 ppm. HRMS (m/z): [M]þ, calcd for C11H12N2O: 188.0950, found:
MHz, CDCl3):
d
¼2.17 (s, 3H, CH3), 2.74 (t, J¼6.0 Hz, 2H), 3.38
188.0949.
(t, J¼6.0 Hz, 2H), 4.13 (s, 1H, NH), 6.53 (d, J¼8.8 Hz, 2H), 7.12 (d,
J¼8.8 Hz, 2H) ppm. HRMS (m/z): [M]þ, calcd for C10H1235ClNO:
197.0607, found: 197.0607.
4.3.13. 4-((3-Oxobutyl)amino)benzoic acid (3am)22
MHz, DMSO-d6):
(t, J¼6.6 Hz, 2H), 6.38 (br s, 1H), 6.54 (d, J¼8.7 Hz, 2H), 7.66
(d, J¼8.7 Hz, 2H) ppm. HRMS (m/z): [M]þ, calcd for C11H13NO3:
207.0895, found: 207.0896.
.
1H NMR (400
¼2.11 (s, 3H), 2.71 (t, J¼6.6 Hz, 2H), 3.25
d
4.3.3. 4-(4-Bromophenylamino)butan-2-one(3ac). 1H NMR (400 MHz,
CDCl3):
d
¼2.17 (s, 3H), 2.74 (t, J¼6.0 Hz, 2H), 3.38 (t, J¼6.0 Hz, 2H), 4.04
(s, 1H, NH), 6.48(d, J¼8.6 Hz, 2H), 7.24 (d, J¼8.7 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3)
d¼208.1, 146.8, 132.1, 114.7, 109.2, 42.4, 38.5,
4.3.14. 4-((4-Acetylphenyl)amino)butan-2-one (3an). 1H NMR (400
MHz, CDCl3):
30.5 ppm. HRMS (m/z): [M]þ, calcd for C10H1279BrNO: 241.0102,
d
¼2.50 (s, 3H), 2.18 (s, 3H), 2.77 (t, J¼5.9, 2H), 3.49
found: 241.0102.
(t, J¼5.9 Hz, 2H), 4.59 (s, 1H, NH), 6.55 (d, J¼8.7 Hz, 2H), 7.82
(d, J¼8.7 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
¼207.8, 196.5,
d
4.3.4. 4-(4-Iodophenylamino)butan-2-one (3ad). 1H NMR (400 MHz,
151.8, 131.0, 126.8, 111.5, 42.4, 37.7, 30.4, 26.1 ppm. HRMS (m/z):
CDCl3):
d
¼2.16 (s, 3H), 2.73 (t, J¼6.0 Hz, 2H), 3.38 (t, J¼5.9 Hz, 2H),
[M]þ, calcd for C12H15NO2: 205.1103, found: 205.1103.
4.06 (s, 1H, NH), 6.39 (d, J¼8.8 Hz, 2H), 7.41(d, J¼8.8 Hz, 2H) ppm.
13C NMR (75 MHz, CDCl3)
d¼208.1, 147.3, 137.8, 115.2, 78.1, 42.3, 38.2,
4.3.15. 1-(Phenylamino)pentan-3-one (3ba)23
CDCl3):
¼1.05 (t, J¼7.3 Hz, 3H), 2.44 (q, J¼7.3 Hz, 2H), 2.72
(t, J¼6.1 Hz, 2H), 3.42 (t, J¼6.1 Hz, 2H), 6.61 (d, J¼7.2 Hz, 2H), 6.71
.
1H NMR (400 MHz,
30.5 ppm. HRMS (m/z): [M]þ, calcd for C10H12INO: 288.9964, found:
d
288.9964.

3636
R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
(t, J¼5.8 Hz, 1H), 7.17 (t, J¼7.9 Hz, 2H) ppm. HRMS (m/z): [M]þ, calcd
J¼7.3 Hz, 2H), 7.11 (d, J¼8.2 Hz, 2H), 7.26 (d, J¼2 Hz, 2H) ppm. HRMS
(m/z): [M]þ, calcd for C11H14OS: 194.0765, found: 194.0764.
for C11H15NO: 177.1154, found: 177.1154.
4.3.16. 1-(m-Tolylamino)pentan-3-one (3bg). 1H NMR (400 MHz,
Acknowledgements
CDCl3):
d
¼1.05 (t, J¼7.3 Hz, 3H). 2.27 (s, 3H), 2.44 (q, J¼7.3 Hz, 2H),
2.71 (t, J¼6.1 Hz, 2H), 3.41 (t, J¼6.2 Hz, 2H), 6.41e6.43 (m, 2H), 6.54
The work was partially supported by the National Natural Sci-
ence Foundation of China (No. 20672079, 20910102041, 21042007),
Natural Science Basic Research of Jiangsu Province for Higher Ed-
ucation (No. 10KJB150016), a Research Grant from the Innovation
Project for Graduate Student of Jiangsu Province, and Key Project in
Science & Technology Innovation Cultivation Program of Soochow
University.
(d, J¼7.4 Hz, 1H), 7.06 (t, J¼7.5 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3):
d
¼210.9, 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]þ, calcd for C12H17NO: 191.1310,
found: 191.1309.
4.3.17. 1-(p-Tolylamino)pentan-3-one (3bf). 1H NMR (400 MHz,
CDCl3):
d
¼1.05 (t, J¼7.3 Hz, 3H), 2.23 (s, 3H), 2.43 (q, J¼7.3 Hz, 2H),
2.71 (t, J¼6.1 Hz, 2H), 3.40 (t, J¼6.1 Hz, 2H), 6.54 (d, J¼8.4 Hz, 2H),
Supplementary data
6.99 (d, J¼8.1 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
¼211.2,
d
145.5, 129.9, 127.0, 113.4, 41.1, 39.0, 36.4, 20.5, 7.9 ppm. HRMS (m/z):
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.03.082.
[M]þ, calcd for C12H17NO: 191.1310, found: 191.1306.
4.3.18. 1-(4-Chlorophenylamino)pentan-3-one(3bb). 1H NMR (400
References and notes
MHz, CDCl3):
d
¼1.06 (t, J¼7.3 Hz, 3H), 2.42e2.47 (m, 2H), 2.72
(t, J¼6.1 Hz, 2H), 3.39 (t, J¼6.1 Hz, 2H), 6.56 (d, J¼8.8 Hz, 2H), 7.12 (d,
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J¼8.8 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
¼210.9, 146.4, 129.2,
d
122.2, 114.2, 41.1, 38.7, 36.5, 7.9 ppm. HRMS (m/z): [M]þ, calcd for
C11H14ClNO: 211.0764, found: 211.0762.
4.3.19. 1-(Pyridin-2-ylamino)pentan-3-one(3bi). 1H NMR (400
MHz, CDCl3):
d
¼1.06 (t, J¼7.3 Hz, 3H), 2.44 (q, J¼7.3 Hz, 2H), 2.75
(t, J¼6.0 Hz, 2H), 3.62 (q, J¼6.1 Hz, 2H), 4.83 (s, 1H, NH), 6.37 (d,
J¼8.4 Hz, 1H), 6.54e6.57 (m, 1H), 7.36e7.40 (m, 1H), 8.07 (d,
J¼5.0 Hz, 1H) ppm. 1H NMR (75 MHz, CDCl3):
¼211.2, 158.4, 148.0,
d
2006, 71, 352.
137.3, 112.8, 107.8, 41.8, 36.5, 36.4, 7.8 ppm. HRMS (m/z): [M]þ, calcd
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for C10H14N2O: 178.1106, found: 178.1110.
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4.3.20. 3-(4-Chlorophenylamino)cyclohexanone (3cb)19
.
1H NMR
(400 MHz, CDCl3):
d
¼1.64e1.80 (m, 2H), 2.00e2.09 (m, 1H),
2.14e2.17 (m, 1H), 2.25e2.45 (m, 3H), 2.78e2.83 (m, 1H), 3.37 (s,
1H, NH), 3.70e3.77 (m, 1H), 6.51 (d, J¼8.8 Hz, 2H), 7.10 (d,
J¼8.8 Hz, 2H). HRMS (m/z): [M]þ, calcd for C12H14ClNO: 223.0764,
found: 223.0768.
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4.3.21. 4-(1H-Benzo[d][1,2,3]triazol-1-yl)butan-2-one (4aa). 1H NMR
(400 MHz, CDCl3):
d
¼2.18 (s, 3H), 3.27 (t, J¼6.5 Hz, 2H), 4.84 (d,
J¼6.5 Hz, 2H), 7.35 (t, J¼7.6 Hz, 1H), 7.49 (t, J¼7.6 Hz, 1H), 7.63 (d,
J¼8.4 Hz, 1H), 8.01 (d, J¼8.4 Hz, 1H) ppm. 13C NMR (100 MHz,
CDCl3):
d
¼169.9, 127.8, 124.4, 120.2, 110.1, 43.0, 42.6, 30.6 ppm.
HRMS (m/z): [M]þ, calcd for C10H11N3O: 189.0902, found:
189.0901.
4.3.22. 4-(Naphthalen-2-ylthio)butan-2-one (6aa)24
(400 MHz, CDCl3):
.
1H NMR
¼2.15 (s, 3H, CH3), 2.81 (t, J¼7.3 Hz, 2H), 3.24
d
(t, J¼7.4 Hz, 2H), 7.41e7.50 (m, 3H), 7.74e7.81 (m, 4H) ppm. HRMS
(m/z): [M]þ, calcd for C14H14OS: 230.0765, found: 230.0763.
4.3.23. 1-(Naphthalen-2-ylthio)pentan-3-one(6ab). 1H NMR (400 MHz,
CDCl3):
d
¼1.05 (t, J¼7.3 Hz, 3H), 2.41 (q, J¼7.3 Hz, 2H), 2.78 (t, J¼7.3 Hz,
2H), 3.25 (t, J¼7.3 Hz, 2H), 7.40e7.50 (m, 3H), 7.74e7.80 (m, 4H) ppm.
HRMS (m/z): [M]þ, calcd for C15H16OS: 244.0922, found: 244.0921.
4.3.24. 3-(Naphthalen-2-ylthio)cyclohexanone (6ca)13c
.
1H NMR
15. (a) Anastas, P. T.; Warner, J. C. Green Chemistry, Theory and Practice; Oxford
University: Oxford, UK, 1998; (b) Clark, J.; Macquarrie, D. Handbook of Green
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(400 MHz, CDCl3):
d
¼1.70e1.83 (m, 2H), 2.14e2.21 (m, 2H),
2.31e2.46 (m, 3H), 2.71e2.75 (m, 1H), 3.52e3.57 (m, 1H), 7.48e7.50
(m, 3H), 7.78e7.83 (m, 3H), 7.91 (s, 1H) ppm. HRMS (m/z): [M]þ,
calcd for C16H16OS: 256.0922, found: 256.0924.
4.3.25. 4-(p-Tolylthio)butan-2-one (6ab)24
.
1H NMR (400 MHz,
CDCl3):
d
¼2.13 (s, 3H), 2.32 (s, 3H), 2.73 (t, J¼7.3 Hz, 2H), 3.08 (t,

R. Jiang et al. / Tetrahedron 67 (2011) 3631e3637
3637
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