Efficient synthesis of β-acetamido ketones and esters using aluminum chloride as an inexpensive and green catalyst

Article abstract of DOI:10.1002/cjoc.201180460

Aluminum chloride (AlCl₃) efficiently catalyzes one-pot multicomponent condensation of enolizable ketones or alkyl acetoacetates with aldehydes, acetonitrile and acetyl chloride to afford β-acetamido ketone or ester derivatives in high to excel

Full text of DOI:10.1002/cjoc.201180460

FULL PAPER
DOI: 10.1002/cjoc.201180460
Efficient Synthesis of β-Acetamido Ketones and Esters Using
Aluminum Chloride as an Inexpensive and Green Catalyst
Mohammad Ali, Zolfigol*,a
Ardeshir, Khazaei*,a
Maliheh, Safaieec Fatemeh, Derakhshan-Panaha
Ahmad, Ali Dehghani-Firouzabadia Maria, Merajoddinb
Mohammad, Mokhlesia
Abdolkarim, Zareb
Hassan, Keypoura
a Faculty of Chemistry, Bu-Ali Sina University, Hamedan, 6517838683, Iran
b Department of Chemistry, Payame Noor University, PO BOX 19395-3697 Tehran, Iran
c College of Science, Islamic Azad University, Hamedan Branch, Iran
Aluminum chloride (AlCl3) efficiently catalyzes one-pot multicomponent condensation of enolizable ketones or
alkyl acetoacetates with aldehydes, acetonitrile and acetyl chloride to afford β-acetamido ketone or ester derivatives
in high to excellent yields and in relatively short reaction times. Moreover, by this synthetic method, some novel
β-acetamido ketones and esters (i.e. one complex structure) are prepared.
Keywords β-acetamido ketone, β-acetamido ester, aluminum chloride, enolizable ketone, synthetic methods, mul-
ticomponent reactions
Introduction
use of large amount of catalyst, (iv) the use of toxic or
expensive catalysts, (v) tedious work-up procedure, and
(vi) performance of the reaction under certain special
conditions. Thus, search for an efficient, inexpensive,
simple and nonpolluting method for the synthesis of
β-acetamido carbonyl compounds is still of practical
importance.
In recent decades, the applications of eco-friendly
applicable industrial and green catalysts have received
considerable interest. In fact, green chemistry is the
utilization of a set of principles that reduces or elimi-
nates the use or generation of hazardous substances in
the design, manufacture and application of chemical
products. Along this line, using aluminum chloride
(AlCl3), which is green,[34] inexpensive and low in tox-
icity, has found more attention. It has been used as an
efficient acidic catalyst in organic synthesis, and found
several industrial applications.[34-38] For example, AlCl3
has been utilized as effective catalyst for Fries rear-
rangement,[38] Friedel-Crafts reactions (both acylations
and alkylations),[39] Gatterman-Koch reaction,[40]
esterification,[41] synthesis of 3,4-disubstituted dihydro-
coumarin derivatives,[42] synthesis of multi-walled car-
bon nanotubes,[43] and [3＋2] cycloadditions.[44]
Multicomponent reactions (MCRs) have drawn great
interest enjoying an outstanding status in modern or-
ganic synthesis and medicinal chemistry because they
are one-pot processes bringing together three or more
components and show high atom economy and high
selectivity.[1-12] MCRs have great contributions in con-
vergent synthesis of complex and important organic
molecules from simple and readily available starting
materials, and have emerged as powerful tools for drug
discovery.[2-12]
β-Acetamido ketone or ester derivatives are useful
building blocks for a number of biologically and phar-
maceutically valuable compounds.[13-17] They are pre-
cursors of molecules such as 1,3-amino alcohols,[13-17]
and structural scaffolds found in natural nucleoside pep-
tide antibiotics such as nikkomycins or neopolyoxins.
Moreover, recently, it is reported that β-acetamido ke-
tones can act as aglucosidase inhibitors.[18] The structural
and bioactive properties of β-acetamido carbonyl com-
pounds led to the generation of some processes em-
ploying some catalysts such as montmorillonite K10,[19]
CoCl2,[20-22]
H6P2W18O62,[23]
H3PW12O40,[24]
Zr(HSO4)4,[25] Mg(HSO4)2,[25] TMSCl,[26] BiCl3,[27] I2,[28]
silica sulfuric acid,[29] ZnO,[30] selectfluorTM [31]
sulfamic
,
Considering the above subjects, we describe here a
simple new procedure for the synthesis of β-acetamido
ketones and esters via the one-pot multicomponent
condensation reaction between enolizable ketones or
alkyl acetoacetates, aldehydes, acetonitrile and acetyl
acid,[32] and ZrOCl2•8H2O.[33] However, most of the
reported methods for the synthesis of these compounds
are associated with one or more of the following draw-
backs: (i) low yields, (ii) long reaction times, (iii) the
*
E-mail: mzolfigol@yahoo.com, Khazaei_1326@yahoo.com; Fax: ＋98(811)8272404, Fax: ＋98(811)8272404
Received May 20, 2011; accepted August 31, 2011; published online January 19, 2012.
Chin. J. Chem. 2012, 30, 345—352
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Mohammad Ali et al.
FULL PAPER
chloride in the presence of AlCl3 as an efficient, green
and very cheap catalyst at room temperature (Scheme 1).
Scheme 1 The synthesis of N-(3-(4-bromophenyl)-3-oxo-1-
phenylpropyl)acetamide (1l) via the condensation reaction be-
tween 4-bromoacetophenone, benzaldehyde, acetonitrile and
acetyl chloride
O
Me
CHO
AlCl3 (15 mol%)
CH3COCl, r.t.
+ CH3CN
+
Figure 2 The reaction of 4-bromoacetophenone with benzalde-
hyde, acetonitrile and acetyl using different amounts of AlCl3.
Br
O
solvents (6 mL) in the presence of different amounts of
acetyl chloride (Table 1). As Table 1 indicates, higher
yield and shorter reaction time were obtained when the
reaction was performed in acetonitrile as solvent in the
presence of 0.6 mL of acetyl chloride at room tempera-
ture (Table 1, Entry 6).
O
HN
Br
Results and Discussion
To optimize the reaction conditions for the synthesis
of β-acetamido carbonyl compounds, the condensation
of 4-bromoacetophenone with benzaldehyde, acetoni-
trile and acetyl chloride was selected as a model reaction
to provide compound 1l (Scheme 1). At first, the reac-
tion was examined in the presence of 15 mol% of some
metal salts and oxides such as AlCl3, MgCl2, Mn(OAc)2,
Ni(OAc)2, Cu(OAc)2, Zn(OAc)2, CuCl2, CuSO4 and
SiO2 at room temperature. The results are summarized
in Figure 1. As Figure 1 indicates, higher yield and
shorter reaction time were obtained when AlCl3 was
utilized as catalyst.
Table 1 Effect of solvent, amount of acetyl chloride and tem-
perature on the reaction of 4-bromoacetophenone with benzalde-
hyde, acetonitrile and acetyl chloride promoted by AlCl3
CH3COCl
amount/mL
Temperature/
℃
Entrya Solvent
Time/hYieldb/%
1
2
EtOH
MeOH
THF
0.6
0.6
0.6
0.6
0.6
0.6
0.4
0.8
0.6
0.6
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
45
70
5
5
28
34
79
37
45
93
46
87
41c
30c
3
5
4
EtOAc
CHCl3
MeCN
MeCN
MeCN
MeCN
MeCN
5
5
5
6
1.25
3
7
8
1.25
1.25
1.25
9
10
a The reaction conditions: 4-bromoacetophenone (2 mmol), ben-
zaldehyde (2 mmol), acetonitrile (3 mmol), acetyl chloride (0.4—
8 mL), AlCl3 (15 mol%), solvent (6 mL), temperature (30—70
b
℃). Isolated yield. c In this reaction, some by-products were
obtained besides the main product.
To assess the generality and efficacy of the method,
different enolizable carbonyl compounds were reacted
with structurally and electronically diverse aldehydes,
acetonitrile and acetyl chloride under the optimized re-
action conditions; the respective results are summarized
in Table 1. As it can be seen in Table 1, the protocol was
general and efficient; all reactions proceeded efficiently
and the desired products were obtained in good to ex-
cellent yields in relatively short reaction times. The in-
fluence of electron-releasing substituents, electron-
withdrawing substituents and halogens on the aromatic
ring of the aldehyde was also studied. As Table 2 shows,
electron-releasing groups increased the reaction yields
(Table 2, compounds 1b and 1e); electron-withdrawing
substituents slightly decreased the yields (Table 2,
Figure 1 The condensation of 4-bromoacetophenone with ben-
zaldehyde, acetonitrile and acetyl chloride using different cata-
lysts (15 mol%).
In the next step, the reaction of 4-bromoacetophen-
one with benzaldehyde, acetonitrile and acetyl chloride
was tested using different amounts of AlCl3 at room
temperature (Figure 2). As it can be seen in Figure 2, the
best amount of the catalyst was 15 mol%.
In another study, to choose the appropriate solvent,
amount of acetyl chloride and temperature for the reac-
tion, the condensation of 4-bromoacetophenone with
benzaldehyde, acetonitrile and acetyl chloride was ex-
amined using AlCl3 at range of 30—70 ℃ in various
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Efficient Synthesis of β-Acetamido Ketones and Esters
Table 2 The synthesis of β-acetamido ketones and esters via the condensation of enolizable ketones or alkyl acetoacetates with alde-
hydes, acetonitrile and acetyl chloride
Aldehyde
Producta
Time/h
1.25
Yieldb/%
m.p./℃ (lit.)
127—129
(130—132)[33]
94
1.25
1.25
96
96
124—127c
108—110c
3.5
85
138—140c
1
2
95
92
92
92
88
90
118—119c
130—132c
111—112
(112—114)[26]
1.25
2.5
3.5
3
75—77
(74—76)[33]
185—188
(187—188)[25]
114—116
(116—118)[26]
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Mohammad Ali et al.
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Continued
Aldehyde
Producta
Time/h
3
Yieldb/%
87
m.p./℃ (lit.)
165—166c
100—101
(98—100)[26]
1.25
2.5
2
93
88
86
162—163d
104—105c
1.5
90
138—140c
1.25
83
168—174c
3
86
166—167c
140—142
(140—141)[25]
1.75
88
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Efficient Synthesis of β-Acetamido Ketones and Esters
Continued
m.p./℃ (lit.)
Aldehyde
Producta
Time/h
1.75
Yieldb/%
89
138—139c
2.75
90
149—152c
a The reaction conditions: enolizable ketone or alkyl acetoacetate (2 mmol), aldehyde (2 mmol), acetonitrile (6 mL), acetyl chloride (0.6
c
mL), AlCl3 (15 mol%), room temperature. b Isolated yield. This compound is new. d The melting point of this compound has not been
reported.
Scheme 2 The synthesis of complex compound 2a
compounds 1i and 1m); and halogens had no significant
effect on the yields (Table 2, compounds 1f and 1j).
Moreover, the method was worked well when
2-naphthaldehyde and anthracene-10-carbaldehyde were
used instead of benzaldehydes (Table 2, compounds 1c,
1d, 1g, 1k, 1o—q, 1s and 1t). Various enolizable ke-
tones including acetophenones bearing electron-releas-
ing substituents, electron-withdrawing substituents and
halogens on the aromatic ring, as well as alkyl aceto-
acetates were also condensed with aldehydes, acetoni-
trile and acetyl chloride in the presence of AlCl3 to afford
the corresponding β-acetamido ketones and esters in high
yields within relatively short reaction times.
Interestingly, the condensation of p-bromoaceto-
phenone (3.2 equiv.) with a tris-aldehyde (1 equiv.),
acetonitrile (6 mL) and acetyl chloride (0.9 mL) in the
presence of AlCl3 (15 mol%) at room temperature af-
forded complex compound 2a in 79% yield within 2 h
(Scheme 2). This is the first report of the synthesis of
this class of β-acetamido ketones.
Based on the literature,[45,46] we suggest the follow-
ing mechanism for our reaction (Scheme 3).
Conclusions
Scheme 3 The proposed mechanism for the preparation of
β-acetamido carbonyl compounds using AlCl3 as catalyst.
In conclusion, we have developed a new method for
the preparation of β-acetamido ketone/ester derivatives
via one-pot multicomponent condensation of enolizable
ketones or alkyl acetoacetates with aldehydes, acetoni-
trile and acetyl chloride using AlCl3 as catalyst. The
promising points for the presented methodology are ef-
ficiency, generality, high yields, relatively short reaction
times, cleaner reaction profile and simplicity.
Experimental
All chemicals were purchased from Merck or Fluka
Chemical Companies. All known compounds were
identified by comparison of their melting points and
spectral data with those reported in the literature. Pro-
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Mohammad Ali et al.
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gress of the reactions was monitored by TLC using sil-
J＝7.0 Hz, 1H), 5.27 (s, 1H), 6.86 (d, J＝8.7 Hz, 2H),
7.13 (d, J＝6.3 Hz, 1H), 7.46 (t, J＝6.9 Hz, 2H), 7.56 (t,
J＝8.4 Hz, 2H), 7.91 (d, J＝8.7 Hz, 2H), 8.05 (d, J＝5.4
Hz, 2H), 8.42 (s, 1H), 8.52 (s, 2H); 13C NMR (CDCl3, 75
MHz) δ: 23.2, 29.7, 46.1, 55.4, 59.5, 113.7, 124.2, 124.9,
125.4, 126.5, 128.8, 129.1, 129.3, 129.7, 130.5, 131.9,
1
ica gel SIL G/UV 254 plates. The H NMR (300 MHz)
and 13C NMR (75 MHz) were run on a Bruker Avance
DPX-250, FT-NMR spectrometer. Microanalysis was
performed on a Perkin-Elmer 240-B microanalyzer.
Melting points were recorded on a Büchi B-545 appa-
ratus in open capillary tubes.
142.6, 163.5, 195.2; IR (KBr) ν: 1674, 3184, 3279 cm－1
;
MS m/z: 397 (M＋). Anal. calcd for C26H23NO3: C 78.57,
H 5.83, N 3.52; found C 78.77, H 5.94, N 3.59.
General procedure for the synthesis of β-acetamido
carbonyl compounds
N-(3-Oxo-1,3-dip-tolylpropyl)acetamide (1e) Pale
yellow solid; 1H NMR (CDCl3, 300 MHz) δ: 1.93 (s, 3H),
2.27 (s, 3H), 2.37 (s, 3H), 3.36 (q, J＝6.2 Hz, 1H), 3.64
(q, J＝5.8 Hz, 1H), 5.55 (q, J＝7.1 Hz, 1H), 7.09 (d, J＝
7.7 Hz, 2H), 7.22 (m, 2H), 7.41 (d, J＝7.7 Hz, 1H), 7.80
(d, J＝7.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ: 21.1,
21.7, 23.1, 43.6, 49.8, 126.5, 128.3, 129.2, 129.3, 134.1,
136.9, 138.4, 144.2, 169.8, 197.8; IR (KBr) ν: 1680,
3257 cm－1; MS m/z: 295 (M ＋ ). Anal. calcd for
C19H21NO2: C 77.26, H 7.17, N 4.74; found C 77.41, H
7.08, N 4.85.
To a mixture of compounds consisting of enolizable
ketone or alkyl acetoacetate (2 mmol), aldehyde (2
mmol), acetonitrile (6 mL) and acetyl chloride (0.6 mL,
8.4 mmol) in a 10 mL round-bottomed flask was added
AlCl3 (0.02 g, 0.3 mmol), and the resulting mixture was
stirred at room temperature. After completion of the
reaction, as monitored with TLC, crushed ice (20 mL)
was added to the reaction mixture and stirred thoroughly.
On solidification, the crude product was filtered, dried,
and purified by short column chromatography on silica
gel eluted with EtOAc/n-hexane (1/4).
N-(1-(4-Chlorophenyl)-3-oxo-3-p-tolylpropyl)acet-
1
amide (1f) Pale yellow solid; H NMR (CDCl3, 300
Some selected spectral data of the products
MHz) δ: 2.02 (s, 3H), 2.40 (s, 3H), 3.35 (dd, J＝3.8, 17.1
Hz, 1H), 3.68 (dd, J＝5.3, 17.1 Hz, 1H), 5.5 (q, J＝5.5
Hz, 1H), 7.26—7.32 (m, 5H), 7.37 (s, 1H), 7.77 (d, J＝
8.0 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ: 21.7, 23.1,
42.8, 49.3, 127.9, 128.2, 128.7, 129.4, 133.1, 133.8,
N-(3-(4-Methoxyphenyl)-3-oxo-1-phenylpropyl)-
1
acetamide (1a) Pale yellow solid; H NMR (CDCl3,
300 MHz) δ: 2.00 (s, 3H), 3.38 (dd, J＝5.9, 16.5 Hz, 1H),
3.66 (dd, J＝5.4, 16.6 Hz, 1H), 3.85 (s, 3H), 5.54 (q, J＝
7.5 Hz, 1H), 6.91 (d, J＝8.7 Hz, 2H), 7.21—7.35 (m, 6H),
7.88 (d, J＝9.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ:
23.3, 42.8, 50.1, 55.5, 113.8, 126.5, 127.3, 128.6, 129.7,
130.5, 141.1, 163.8, 169.6, 196.9; IR (KBr) ν: 1678,
3268 cm－1; MS m/z: 297 (M ＋ ). Anal. calcd for
C18H19NO3: C 72.71, H 6.44, N 4.71; found C 72.53, H
6.52, N 4.82.
139.6, 144.7, 170.1, 197.8; IR (KBr) ν: 1689, 3302 cm－1
MS m/z: 312 (M＋). Anal. calcd for C18H18ClNO2: C
68.46, H 5.75, N 4.44; found C 68.29, H 5.84; N 4.53.
;
N-(1-(Naphthalen-3-yl)-3-oxo-3-p-tolylpropyl)acet-
1
amide (1g) Pale yellow solid; H NMR (CDCl3, 300
MHz) δ: 1.96 (s, 3H), 2.39 (s, 3H), 3.46 (q, J＝8.7 Hz,
1H), 3.78 (q, J＝5.1 Hz, 1H), 5.73 (d, J＝6.8 Hz, 1H),
7.16—7.28 (m, 2H), 7.43—7.49 (m, 4H), 7.72—7.78 (m,
6H); 13C NMR (CDCl3, 75 MHz) δ: 21.7, 23.4, 43.1, 50.1,
124.7, 125.2, 125.9, 126.2, 127.9, 128.2, 128.4, 129.4,
129.6, 132.6, 133.2, 134.1, 138.4, 144.5, 169.7, 198.1; IR
(KBr) ν: 1676, 3280 cm－1; MS m/z: 331 (M＋). Anal.
calcd for C22H21NO2: C 79.73, H 6.39, N 4.23; found C
79.51, H 6.47, N, 4.11.
N-(3-(4-Nitrophenyl)-3-oxo-1-phenylpropyl)acet-
amide (1h) White solid; 1H NMR (CDCl3, 300 MHz) δ:
1.95 (s, 3H), 3.43 (dd, J＝3.5, 16.6 Hz, 1H), 3.78 (dd,
J＝3.5, 14.1 Hz, 1H), 5.53 (q, J＝3.9 Hz, 1H), 6.95 (d,
J＝6.3 Hz, 1H), 7.31 (s, 5H), 8.03 (d, J＝6.0 Hz, 2H),
8.23 (d, J＝5.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ:
23.1, 44.3, 50.1, 123.8, 126.5, 127.8, 129.2, 140.9, 150.3,
169.9, 196.6; IR (KBr) ν: 1689, 3302 cm－1; MS m/z: 312
(M＋). Anal. calcd for C17H16N2O4: C 65.38, H 5.16, N
8.97; found C 65.57, H 5.06, N 8.84.
N-(1,3-Bis(4-methoxyphenyl)-3-oxopropyl)acet-
1
amide (1b) Pale yellow solid; H NMR (CDCl3, 300
MHz) δ: 2.02 (s, 3H), 3.67 (s, 1H), 3.76 (s, 3H), 3.86 (s,
3H), 5.49 (s, 1H), 6.88 (q, J＝7.8 Hz, 5H), 7.26 (d, J＝
8.3 Hz, 2H), 7.90 (d, J＝8.0 Hz, 2H); 13C NMR (CDCl3,
75 MHz) δ: 23.4, 42.8, 49.7, 55.2, 55.5, 113.8, 113.9,
127.7, 129.6, 130.5, 133.1, 158.7, 163.7, 169.6, 197.2; IR
－
＋
1
(KBr) ν: 1678, 3273 cm ; MS m/z: 327 (M ). Anal.
calcd for C19H21NO4: C 69.71, H 6.47, N 4.28; found C
69.94, H 6.58, N 4.36.
N-(3-(4-Methoxyphenyl)-1-(naphthalen-3-yl)-3-
oxopropyl)acetamide (1c) Pale yellow solid; 1H NMR
(CDCl3, 300 MHz) δ: 2.03 (s, 3H), 3.43 (d, J＝6.6 Hz,
1H), 3.79 (s, 4H), 5.72 (s, 1H), 6.90 (q, J＝6.8 Hz, 2H),
7.42—7.53 (m, 4H), 7.75—8.10 (m, 5H), 8.23 (s, 1H);
13C NMR (CDCl3, 75 MHz) δ: 22.6, 43.1, 50.6, 55.5,
113.8, 124.8, 125.4, 126.0, 127.6, 127.9, 128.5, 129.5,
130.5, 132.6, 133.2, 138.4, 163.7, 170.9, 196.4; IR (KBr)
ν: 1671, 3276 cm－1; MS m/z: 347 (M＋). Anal. calcd for
C22H21NO3 C 76.06, H 6.09, N 4.03; found C 76.27, H
6.19, N 3.95.
N-(1,3-Bis(4-nitrophenyl)-3-oxopropyl)acetamide
(1i) White solid; 1H NMR (CDCl3, 300 MHz) δ: 2.10 (s,
3H), 3.61 (dd, J＝3.5, 14.1 Hz, 1H), 3.88 (dd, J＝3.8,
13.3 Hz, 1H), 5.69 (s, 1H), 6.73 (s, 1H), 7.27 (s, 1H),
7.54 (s, 1H), 8.09—8.32 (m, 5H); 13C NMR (CDCl3, 75
MHz) δ: 29.7, 49.1, 59.5, 124.1, 124.1, 124.4, 129.2,
140.3, 147.3, 147.7, 150.7, 169.8, 196.3; IR (KBr) ν:
N-(1-(Anthracen-10-yl)-3-(4-methoxyphenyl)-3-
1
oxopropyl)acetamide (1d) Deep red solid; H NMR
(CDCl3, 300 MHz) δ: 2.06 (s, 3H), 3.84 (s, 1H), 4.14 (q,
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Efficient Synthesis of β-Acetamido Ketones and Esters
－
1694, 3277 cm－1; MS m/z: 357 (M＋). Anal. calcd for
C17H15N3O6: C 57.14, H 4.23, N 11.76; found C 57.36,
H 4.11, N, 11.64.
138.2, 170.1, 197.1; IR (KBr) ν: 1682, 3276 cm ; MS
m/z : 395 (M＋). Anal. calcd for C21H18BrNO2: C 63.65,
H 4.58, N 3.53; found C 63.48, H 4.67, N 3.44.
1
N-(1-(4-Chlorophenyl)-3-(4-nitrophenyl)-3-oxo-
propyl)acetamide (1j) Pale yellow solid; H NMR
N-(4-(3-Acetamido-3-(naphthalen-2-yl)propanoyl)-
phenyl)acetamide (1p) Brown solid; 1H NMR (CDCl3,
300 MHz) δ: 1.89 (s, 3H), 2.06 (s, 3H), 3.84 (s, 1H), 4.14
(d, J＝7.2 Hz, 1H), 5.23 (s, 1H), 5.75 (s, 2H), 7.41—7.98
(m, 11H); 13C NMR (CDCl3, 75 MHz) δ: 26.5, 29.7, 42.1,
60.5, 118.8, 119.1, 123.6, 126.1, 127.8, 127.9, 128.6,
129.7, 132.6, 133.1, 142.6, 144.7, 170.1, 172.3, 189.2; IR
(KBr) ν: 1674, 3184, 3279 cm ; MS m/z: 374 (M ).
Anal. calcd for C23H22N2O3: C 73.78, H 5.92, N 7.48;
found C 73.94, H 6.04, N 7.39.
N-(4-(3-Acetamido-3-(anthracen-9-yl)propanoyl)-
phenyl)acetamide (1q) Brown solid; 1H NMR (CDCl3,
300 MHz) δ: 1.88 (s, 3H), 2.00 (s, 3H), 3.75 (dd, J＝7.2,
14.1 Hz, 1H), 3.94 (dd, J＝7.5, 15.9 Hz, 1H), 6.5 (s, 2H),
7.44—7.60 (m, 7H), 7.74—7.85 (m, 4H), 8.03 (d, J＝8.4,
2H); 13C NMR (CDCl3,75 MHz) δ: 23.2, 24.5, 45.4, 58.4,
118.8, 124.1, 124.9, 126.5, 128.8, 129.4, 129.8, 131.7,
142.7, 168.7, 170.2, 196.2; IR (KBr) ν: 1674, 3184, 3279
cm－1; MS m/z: 424 (M＋), 382 (M＋－CH3CO). Anal.
calcd for C27H24N2O3: C 76.39, H 5.70, N 6.60; found C
76.59, H 5.61, N 6.49.
1
(CDCl3, 300 MHz) δ: 1.99 (s, 3H), 3.46 (q, J＝6.9 Hz,
1H), 3.84 (s, 1H), 5.52 (s, 1H), 7.11—7.27 (m, 3H), 7.73
—7.78 (m, 1H), 8.05—8.31 (m, 5H); 13C NMR (CDCl3,
75 MHz) δ: 21.1, 22.7, 44.2, 44.4, 49.5, 50.1, 123.9,
126.5, 128.2, 128.9, 129.2, 129.5, 133.5, 137.1, 137.7,
140.8, 150.3, 170.7, 196.1; IR (KBr) ν: 1695, 3280
－
＋
1
－
＋
1
cm ; MS m/z: 347 (M ). Anal. calcd for C17H15ClN2O4:
C 58.88, H 4.36, N 8.08; found C 59.02, H 4.27, N 8.18.
N-(1-(Naphthalen-3-yl)-3-(4-nitrophenyl)-3-oxo-
1
propyl)acetamide (1k) Pale yellow solid; H NMR
(CDCl3, 300 MHz) δ: 2.08 (s, 3H), 2.85—3.05 (m, 2H),
5.50 (s, 1H), 7.47—8.50 (m, 12H); 13C NMR (CDCl3, 75
MHz) δ: 29.7, 49.8, 59.5, 124.7, 125.5, 126.4, 126.6,
126.8, 127.1, 127.5, 127.7, 128.1, 129.1, 129.4, 129.5,
－
1
130.5, 173.9, 194.1; IR (KBr) v: 1665, 3280 cm ; MS
m/z: 362 (M＋). Anal. calcd for C21H18N2O4: C 69.60, H
5.01, N 7.73; found C 69.39, H 5.12, N 7.65.
N-(3-(4-Bromophenyl)-3-oxo-1-phenylpropyl)ace-
1
tamide (1l) Pale yellow solid; H NMR (CDCl3, 300
MHz) δ: 2.04 (s, 3H), 3.37 (q, J＝5.4 Hz, 1H), 3.66 (q,
J＝5.4 Hz, 1H), 5.54 (q, J＝6.6 Hz, 1H), 6.99—7.75 (m,
9H); 13C NMR (CDCl3, 75 MHz) δ: 23.2, 29.6, 43.5, 50.0,
126.5, 127.5, 128.6, 129.6, 131.9, 135.3, 140.8, 169.7,
197.2; IR (KBr) ν: 1685, 3275 cm ; MS m/z: 345 (M ).
Anal. calcd for C17H16BrNO2: C 58.97, H 4.66, N 4.05;
found C 58.81, H 4.58, N 4.14.
Methyl 2-(acetamido(phenyl)methyl)-3-oxobut-
anoate (1r) Yellow solid; 1H NMR (CDCl3, 300 MHz)
δ: 1.95 (s, 3H), 2.16 (s, 3H), 3.64 (s, 3H), 4.10 (s, 1H),
5.75 (s, 1H), 7.29 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ:
23.2, 30.6, 52.3, 52.8, 62.8, 126.6, 127.8, 128.7, 139.1,
167.6, 169.8, 203.6; IR (KBr) ν: 1647, 1720, 1746, 3332
cm－1; MS m/z: 263 (M＋). Anal. calcd for C14H17NO4: C
63.87, H 6.51, N 5.32; found C 64.01, H 6.43, N 5.19.
Methyl 2-(acetamido(naphthalen-3-yl)methyl)-3-
oxobutanoate (1s) Yellow solid; 1H NMR (CDCl3, 300
MHz) δ: 2.01 (s, 3H), 2.19 (s, 3H), 3.65 (s, 3H), 4.26 (s,
1H), 5.96 (s, 1H), 7.46 (s, 3H), 7.77 (s, 5H); 13C NMR
(CDCl3, 75 MHz) δ: 23.3, 30.6, 52.6, 52.8, 62.7, 124.5,
125.7, 126.2, 127.6, 128.1, 128.6, 132.8, 133.1, 136.5,
－
＋
1
N-(3-(4-Bromophenyl)-1-(4-nitrophenyl)-3-oxo-
propyl)acetamide (1m) White solid; 1H NMR (CDCl3,
300 MHz) δ: 2.05 (s, 3H), 3.47 (q, J＝5.6 Hz, 1H), 3.79
(q, J＝5.19 Hz, 1H), 5.65 (q, J＝5.5 Hz, 1H), 7.02 (d,
J＝7.9 Hz, 1H), 7.58 (d, J＝8.7 Hz, 2H), 7.61 (d, J＝8.4
Hz, 2H), 7.76 (d, J＝8.4 Hz, 2H), 8.15 (d, J＝8.4 Hz, 2H);
13C NMR (CDCl3, 75 MHz) δ: 23.3, 42.7, 49.1, 113.8,
123.8, 127.4, 129.3, 129.5, 132.2, 134.8, 147.1, 148.4,
－
1
167.6, 169.8, 203.5; IR (KBr) ν: 1636, 1747, 3347 cm ;
MS m/z: 313 (M＋). Anal. calcd for C18H19NO4: C 68.99,
H 6.11, N 4.47; found C 69.81, H 6.23, N 4.56.
－
1
169.8, 196.8; IR (KBr) ν: 1687, 3261 cm ; MS m/z: 390
(M＋). Anal. calcd for C17H15BrN2O4: C 52.19, H 3.86, N
7.16; found C 52.01, H 3.98, N 7.05.
Ethyl
2-(acetamido(naphthalen-3-yl)methyl)-3-
Compound (1n) Pale yellow solid; 1H NMR
(CDCl3, 300 MHz) δ: 2.07 (s, 3H), 3.46 (d, J＝6.8 Hz,
1H), 3.81 (d, J＝7.8 Hz, 1H), 5.63 (s, 1H), 7.09 (s, 1H),
7.20—7.60 (m, 3H), 7.70—8.20 (m, 4H), 9.96 (s, 1H);
13C NMR (CDCl3, 75 MHz) δ: 23.3, 42.8, 49.5, 127.1,
129.2, 129.6, 130.1, 132.1, 134.9, 135.5, 147.6, 170.01,
oxobutanoate (1t) Yellow solid; 1H NMR (CDCl3, 300
MHz) δ: 1.11 (t, J＝5.0 Hz, 3H), 2.02 (s, 3H), 2.18 (s,
3H), 4.1 (q, J＝6.1 Hz, 2H), 4.17 (q, J＝6.3 Hz, 1H),
5.95 (s, 1H), 7.26—7.48 (m, 4H), 7.76 (t, J＝7.5 Hz, 4H);
13C NMR (CDCl3, 75 MHz) δ: 23.2, 30.6, 52.3, 52.8,
62.8, 126.6, 127.8, 128.7, 139.1, 167.6, 169.8, 203.6; IR
－
－
1
1
191.8, 197.1; IR (KBr) ν: 1689, 1736, 3286 cm ; MS
m/z: 373 (M＋). Anal. calcd for C18H16BrNO3: C 57.77,
H 4.31, N 3.74; found C 57.93, H 4.42, N 3.19.
(KBr) ν: 1647, 1720, 1746, 3332 cm ; MS m/z: 327
(M＋). Anal. calcd for C19H21NO4: C 69.71, H 6.47, N
4.28; found C 69.52, H 6.34, N 4.39.
1
N-(3-(4-Bromophenyl)-1-(naphthalen-3-yl)-3-oxo-
Compound (2a) Yellow solid; H NMR (CDCl3,
1
propyl)acetamide (1o) Pale yellow solid; H NMR
300 MHz) δ: 1.86 (s, 9H), 3.36—3.49 (m, 6H), 5.16 (s,
6H), 5.83 (s, 3H), 6.91—7.02 (m, 6H), 7.15—7.38 (m,
11H), 7.51—7.64 (m, 9H), 7.67—7.83 (m, 4H); 13C
NMR (CDCl3, 75 MHz) δ: 23.0, 43.1, 46.8, 69.8 112.3,
121.3, 126.2, 127.9, 128.4, 128.8, 129.7, 129.8, 131.8,
131.9, 135.2, 138.1, 155.4 168.2, 197.4; IR (KBr) ν:
(CDCl3, 300 MHz) δ: 1.98 (s, 3H), 3.41 (dd, J＝6.4, 12.7
Hz, 1H), 3.76 (dd, J＝6.6, 13.2 Hz, 1H), 5.70 (s, 1H),
7.27—7.59 (m, 6H), 7.69—7.92 (m, 6H); 13C NMR
(CDCl3, 75 MHz) δ: 23.2, 43.5, 50.1, 124.7, 125.3, 126.1,
126.3, 127.6, 128.6, 129.6, 131.9, 132.7, 133.1, 135.1,
Chin. J. Chem. 2012, 30, 345—352
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
351

Mohammad Ali et al.
FULL PAPER
1674, 3433 cm ; MS m/z: 1197 (M ). Anal. calcd for
C60H54Br3N3O9: C 60.01, H 4.53, N 3.50; found C 59.88,
H 4.65, N 3.42.
－
＋
1
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(Sun, H.)
352
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Chin. J. Chem. 2012, 30, 345—352