Pyrazinium di(hydrogen sulfate) as a novel, highly efficient and homogeneous catalyst for the condensation of enolizable ketones with aldehydes, acetonitrile and acetyl chloride

Article abstract of DOI:10.1002/jccs.201100383

A highly efficient protocol for the synthesis of β-acetamido ketone or ester derivatives in the presence of pyrazinium di(hydrogen sulfate) {Py(OSO₃H)₂} as a novel, green and homogeneous solid acid catalyst at room temperature is des

Full text of DOI:10.1002/jccs.201100383

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Pyrazinium Di(hydrogen sulfate) as a Novel, Highly Efficient and Homogeneous
Catalyst for the Condensation of Enolizable Ketones with Aldehydes, Acetonitrile and
Acetyl Chloride
Ardeshir Khazaei,a,* Mohammad Ali Zolfigol,a,* Mohammad Mokhlesi,a
Abdolkarim Zare,b Fatemeh Derakhshan-Panah,a Maria Merajoddin,b
Hassan Keypoura and Ahmad Ali Dehghani-Firouzabadic
aFaculty of Chemistry, Bu-Ali Sina University, Hamedan, 6517838683, Iran
bChemistry Department, Payame Noor University, 19395-4697 Tehran, I.R. of Iran
cDepartment of Chemistry, Yazd University, Yazd 89195741, Iran
(Received Jun. 20, 2011; Accepted Sept. 6, 2011; Published Online Oct. 3, 2011; DOI: 10.1002/jccs.201100383)
A highly efficient protocol for the synthesis of b-acetamido ketone or ester derivatives in the presence of
pyrazinium di(hydrogen sulfate) {Py(OSO3H)2} as a novel, green and homogeneous solid acid catalyst at
room temperature is described. One-pot multi-component condensation of enolizable ketones or alkyl
acetoacetates with aldehydes, acetonitrile and acetyl chloride affords the title compounds in high to excel-
lent yields and in relatively short reaction times. In this work, the efficiency of our recently reported solid
acid catalyst, saccharin sulfonic acid (Sa-SO3H), in the synthesis of b-acetamido ketones/esters is also
studied. Moreover, in this research, some new b-acetamido ketones and esters (i.e. one complex structure)
are prepared.
Keywords: Pyrazinium di(hydrogen sulfate) {Py(OSO3H)2}; Saccharin sulfonic acid (Sa-SO3H);
Enolizable ketone; b-Acetamido ketone; b-Acetamido ester; Solid acid.
INTRODUCTION
In recent decades, application of eco-friendly appli-
of pyrazine (1 eq.) with sulfuric acid (2 eq.) at room tem-
perature during an easy and clean procedure (Scheme I).
On the basis of the structure of Py(OSO3H)2, we anticipate
that it can act as an efficient catalyst in reactions which
need the use of acidic catalysts to speed up. Herein, we
have found that the synthesis of b-acetamido ketones and
esters from enolizable ketones/alkyl acetoacetates, alde-
hydes, acetonitrile and acetyl chloride can be efficiently
performed in the presence of Py(OSO3H)2.
cable industrial and green catalysts has received consider-
able interest. Thus, green chemistry has been defined as a
set of principles which reduces or eliminates the use or gen-
eration of hazardous substances and catalysts throughout
the entire life of chemical materials. Along this line, the use
solid acid catalysts such as hydrogen sulfate salts,1 saccha-
rin sulfonic acid,2 silica sulfuric acid,3 and boron sulfonic
acid,4 which are green, inexpensive and non-toxic, has re-
ceived increased attention for various types of organic
transformations due to their operational simplicity, effi-
cacy, and selectivity coupled with their green natures. For
example, they have been used as efficient catalyst for syn-
thesis of dihydropyrimidones,5 triarylmethanes,6 bis-N-
acylsulfonamides,7 gem-dihydroperoxides,8 spiro bipyr-
imidine,9 quinolines,10 homoallylic amines,11 xanthenes,12
1,1-diacetates,13 N-Boc Protection of Amines,14 Michael
additions,15 acetylation,16 trimethylsilylation of alcohols,17
and synthesis of 2-thiazolamines.18 Considering the high
importance of solid acid catalysts in organic synthesis, we
have synthesized pyrazinium di(hydrogen sulfate)
{Py(OSO3H)2} as a new solid acid catalyst, by the reaction
The synthesis of pyrazinium di(hydrogen
sulfate) {Py(OSO3H)2}
Scheme I
H
OSO3H
OSO3H
N
N
N
Solvent-free
r.t.
+
H2SO4
N
H
Py(OSO3H)2
Multi-component reactions (MCRs) involve three or
more compounds reacting in a single event to form a prod-
uct, which contains the essential parts of all the starting ma-
terials. MCRs are welcome too in terms of economic and
practical considerations.19 They contribute to the require-
ments of an environmentally friendly process by reducing
* Corresponding author. E-mail: Khazaei_1326@yahoo.com or mzolfigol@yahoo.com
J. Chin. Chem. Soc. 2012, 59, 199-207
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Khazaei et al.
the number of synthetic steps, energy consumption and
waste production.20 Therefore, in the last decade research
in academia and industry has increasingly emphasized the
use of MCRs as well as domino reaction sequences for a
broad range of products.19,20
enolizable ketones or alkyl acetoacetates, aldehydes, aceto-
nitrile and acetyl chloride in the presence of our new cata-
lyst pyrazinium di(hydrogen sulfate) {Py(OSO3H)2}, or
saccharin sulfonic acid (Sa-SO3H) at room temperature
(Scheme II). It should be mentioned that Py(OSO3H)2
melts at 80-81 °C; thus, it can be used as solid acid in reac-
tions which carry out at room temperature or at less than its
melting point; however, the pyrazinium salt can act as ionic
liquid in reactions which perform at higher than 80 °C.57
b-Acetamido ketone and ester derivatives are versa-
tile and valuable building blocks for a number of biologi-
cally and pharmaceutically compounds.21-27 They can be
converted into 3-amino alcohols, which may be applied for
the synthesis of various important antibiotics.28 Generally,
this type of compounds is prepared by Dakin-West reac-
tion.29-34 This reaction includes the one-pot multi-compo-
nent condensation of enolizable ketones with aldehydes,
acetonitrile and acetyl chloride.29-34 Some catalysts includ-
ing BiOCl,35 CeCl3·7H2O,36 ZrOCl2·8H2O,37 I2,38 TMSCl,39
selectfluor,40 sulfamic acid,41 CoCl2,42 H3PW12O40 43 have
been employed for this transformation. Although some cat-
alysts for the synthesis of b-acetamido carbonyl com-
pounds are known, newer catalysts continue to attract at-
tention for their difference with the others, novelty and ef-
fectiveness. Furthermore, most of the reported methods for
the synthesis of these compounds have one or more of the
following drawbacks: (i) low yields, (ii) long reaction
times, (iii) the use of large amount of catalyst, (iv) the use
of toxic or expensive catalysts, (v) tedious work-up proce-
dure, (vi) harsh reaction conditions, and (vii) performance
the reaction under certain special conditions.
RESULTS AND DISCUSSION
To obtain the optimized reaction conditions for the
synthesis of b-acetamido carbonyl compounds, the reac-
tion of 4-bromoacetophenone (1 mmol) with benzaldehyde
(1 mmol), acetonitrile (3 mL) and acetyl chloride (0.3 mL)
was selected as a model reaction to provide compound 1k,
and its behavior was studied in the presence of different
molar ratios of Py(OSO3H)2 as well as Sa-SO3H at room
temperature. The results are summarized in Table 1. As Ta-
ble 1 indicates, higher yields of the product and shorter re-
action times were obtained when the reaction was carried
our using 10 mol% of Py(OSO3H)2 or 15 mol% of Sa-
SO3H.
To recognize efficiency and importance of the cata-
lysts in the synthesis of b-acetamido carbonyl compounds,
the model reaction was also examined using H2SO4 (start-
ing material of Py(OSO3H)2) as well as ClSO3H (starting
material of Sa-SO3H), separately (Table 1, entries 9 and
10). As it can be seen in Table 1, H2SO4 and ClSO3H af-
forded the product in 39 and 27% yields within 3.5 h, re-
spectively. In these conditions, a large amounts of the start-
ing materials were remained, an also some by-products
were obtained. This observation confirmed that to increase
Along the line of our studies in design and application
of new solid acid catalysts in chemical transformations,44-50
and also synthesis of organic compounds by multi-compo-
nent reactions,51-56 we describe here a simple new proce-
dure for the synthesis of b-acetamido ketones/esters via the
one-pot multi-component condensation reaction between
The synthesis of b-acetamido ketones/esters from enolizable ketones/alkyl acetoacetates, aldehydes,
Scheme II
acetonitrile and acetyl chloride using Py(OSO3H)2 or Sa-SO3H
O
O
O
O
O
O
NH OR"
O
I or II
NH
O
or
+
CH3CN
R
H
+
OR"
or
R'
CH3
R
CH3COCl, r.t.
R
R'
O
R = Phenyl, Naphthyl, Aryl R' = Phenyl, Aryl R" = Me, Et
H
1a-n
1o-q
O
O
OSO3H
N
S
N
SO3H
OSO3H
N
H
O
I
II
Sa-SO3H
Py(OSO3H)2
200
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Efficient Synthesis of b-Acetamido Ketones/esters
Table 1. Effect of different amounts of the catalysts on the
reaction of 4-bromoacetophenone with benzaldehyde,
acetonitrile and acetyl chloride at room temperature
in Table 2. Moreover, the method was worked well when
2-naphthaldehyde was used instead of benzaldehydes (Ta-
ble 2, compounds 1c, 1f, 1j, 1n, 1p, 1q).
Catalyst
Interestingly, the reaction of 4-bromoacetophenone
(3.2 equiv.) with a tris-aldehyde (1 equiv.), acetonitrile (6
mL) and acetyl chloride (0.9 mL) in the presence of
Py(OSO3H)2 (I, 10 mol%) at room temperature afforded
complex compound 2a in 81% yield within 2.25 h (Scheme
III). Sac-SO3H (II) also gave compound 2a in 79% after
2.5 h. This is the first report of the synthesis of this class of
b-acetamido ketones.
Entry
Catalyst
Amount
(Mol%)
Time (h)
Yielda (%)
1
-
-
12
2.5
0.5
0.5
3
No reaction
2
Py(HSO4)2
Py(HSO4)2
Py(HSO4)2
Sa-SO3H
Sa-SO3H
Sa-SO3H
Sa-SO3H
H2SO4
5
65
93
88
60
79
87
82
39
27
3
10
15
5
4
5
6
10
15
20
10
15
2
7
0.75
1.25
3.5
3.5
8
In summary, we have introduced a new efficient solid
acid catalyst, pyrazinium di(hydrogen sulfate), for organic
synthesis. In this work, we have used our new catalyst (as
well as saccharin sulfonic acid) for the preparation of b-
acetamido ketones/esters from enolizable ketones or alkyl
acetoacetates, aldehydes, acetonitrile and acetyl chloride.
The promising points for the presented methodology are ef-
ficiency, generality, high yields, relatively short reaction
times, cleaner reaction profile and simplicity.
9
10
ClSO3H
a Isolated yields.
efficiency of H2SO4 and ClSO3H in the synthesis of b-
acetamido ketones/esters, it is necessary to combine them
to organic compounds (here, pyrazine and saccharin).
Under the optimal reaction conditions, various eno-
lizable ketones (including acetophenones bearing elec-
tron-releasing substituents, electron-withdrawing substitu-
ents and halogens on their aromatic ring, as well as alkyl
acetoacetates) were condensed with different aromatic al-
dehydes (containing electron-releasing substituents, elec-
tron-withdrawing substituents and halogens on their aro-
matic ring), acetonitrile and acetyl chloride in the presence
of Py(OSO3H)2 and Sa-SO3H to afford the corresponding
b-acetamido ketones and esters in high to excellent yields
within relatively short reaction times; the reactions were
carried out efficiently within 0.75-2.75 h, and the products
were produced in 85-96% yields. The results are displayed
EXPERIMENTAL
All chemicals were purchased from Merck or Fluka
Chemical Companies. Sulphuric acid 98% was used for the
preparation of pyrazinium di(hydrogen sulfate). Sac-SO3H
was prepared according to the reported procedure.2 All
known compounds were identified by comparison of their
melting points and spectral data with those reported in the
literature. Progress of the reactions was monitored by TLC
1
using silica 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 (d in ppm).
Scheme III The synthesis of complex compound 2a
O
HN
O
O
OHC
O
Br
O
O
HN
O
O
I or II
CH3COCl, rt
O
+
+
CH3CN
CHO
O
Br
O
O
Br
N
H
CHO
O
Br
2a
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Table 2. The preparation of b-acetamido ketones/esters using Py(OSO3H)2 (I) or Sa-SO3H (II)
Time (h)
Yielda (%)
Aldehyde
Product
M.p. °C (lit.)
I/II
I/II
O
NH
O
127-129
(130-132)33
CHO
0.75/0.75
1/0.75
1.25 /1
0.75/0.75
0.75/1
1/1.5
96/94
95/93
92/89
94/93
91/92
91/93
92/94
88/85
91/90
89/85
93/87
(1a)
OMe
O
O
O
O
NH
O
124-127b
108-110b
CHO
MeO
MeO
OMe
(1b)
CHO
NH
O
OMe
(1c)
NH
O
118-119
(-)58
Me
CHO
Me
Me
(1d)
NH
O
130-132
(-)58
CHO
CHO
Cl
Cl
Me
(1e)
O
111-112
(112-114)26
NH
O
Me
(1f)
O
NH
O
75-77
(74-76)33
CHO
1.5/2
NO2
(1g)
O
NH
O
185-188
(187-188)25
CHO
O2N
2/2.5
O2N
NO2
NO2
NO2
(1h)
O
NH
O
114-116
(116-118)26
CHO
CHO
Cl
2/2.5
Cl
(1i)
O
NH
O
2/2.25
0.5/0.75
165-166b
(1j)
O
NH
O
100-101
(98-100)26
CHO
Br
(1k)
202
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Efficient Synthesis of b-Acetamido Ketones/esters
O
O
O
NH
O
162-163
(-)28
CHO
O2N
2/2.25
1.25/1.5
1.5/2
91/91
88/90
90/87
O2N
Br
Br
Br
(1l)
NH
O
104-105b
138-140b
OHC
CHO
OHC
(1m)
NH
O
CHO
(1n)
O
NH
O
140-142
(140-141)25
CHO
1/1.5
1.5/2.5
90/86
89/86
88/91
O
O
(1o)
O
NH
O
O
CHO
138-139b
149-152b
O
(1p)
O
NH
O
O
CHO
2.25/2.75
O
(1q)
a Isolated yield. bThis compound is new.
Microanalysis was performed on a Perkin-Elmer 240-B
microanalyzer. Melting points were recorded on a Büchi
B-545 apparatus in open capillary tubes.
acetate (1 mmol), aldehyde (1 mmol), acetonitrile (3 mL)
and acetyl chloride (0.3 mL) in a 10 mL round-bottomed
flask, was added Py(OSO3H)2 (0.0276 g, 0.1 mmol) or
Sac-SO3H (0.039 g, 0.15 mmol), and the resulting mixture
was stirred at room temperature. After completion of the
reaction, as monitored with TLC, crushed ice (10 mL) was
added to the reaction mixture and stirred thoroughly. On
solidification, the crude product was filtered, dried, and pu-
rified by short column chromatography on silica gel eluted
with EtOAc/n-hexane (1/4).
General procedure for the preparation of pyrazinium
di(hydrogen sulfate)
A 25 mL flask charged with sulphuric acid 98% (2.50
g, containing 25 mmol of the acid) was put into an ice-bath,
and pyrazine (1.00 g, 12.5 mmol) was added to it in por-
tions over a period of 5 min. The resulting mixture was
stirred for 20 min, and then CHCl3 (30 mL) was added to it,
and stirred for 3 min. The resulting solid was filtered,
washed with CHCl3, and dried to give Py(OSO3H)2 (3.42 g,
99%) as a pale yellow solid.
Physical properties and spectral data
Note: Compounds 1b, 1c, 1j, 1m, 1n, 1p, 1q and 2a
are new.
Spectral data of Py(OSO3H)2
N-(3-(4-Methoxyphenyl)-3-oxo-1-phenylpropyl)acet-
M.p. 80-81 °C. 1H-NMR (DMSO-d6): d 8.22 (s, 4H),
10.70 (s, 4H). 13C NMR (DMSO-d6): d 141.6. MS (EI, 70
eV): m/z = 297.
amide 1a
IR (KBr): 1678, 3268 cm-1. 1H NMR (CDCl3): d 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): d 23.3, 42.8, 50.1, 55.5, 113.8,
General procedure for the synthesis of b-acetamido
carbonyl compounds
To a mixture of enolizable ketone or alkyl aceto-
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126.5, 127.3, 128.6, 129.7, 130.5, 141.1, 163.8, 169.6,
196.9. MS (EI, 70 eV): m/z = 297. Anal. Calcd. for
C18H19NO3: C, 72.71; H, 6.44; N, 4.71. Found: C, 72.55; H,
6.58; N, 4.59.
N-(1-(Naphthalen-3-yl)-3-oxo-3-p-tolylpropyl)acet-
amide 1f
IR (KBr): 1676, 3280 cm-1, 1H-NMR (CDCl3): d 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): d
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. MS (EI, 70 eV): m/z = 331. Anal.
Calcd. For C22H21NO2: C, 79.73; H, 6.39; N, 4.23; Found:
C, 79.55; H, 6.50; N, 4.35.
N-(1,3-Bis(4-methoxyphenyl)-3-oxopropyl)acetamide
1b
IR (KBr): 1678, 3273 cm-1. 1H NMR (CDCl3): d 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): d 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; MS (EI, 70 eV): m/z = 327. Anal.
Calcd. for C19H21NO4: C, 69.71; H, 6.47; N, 4.28. Found:
C, 69.58; H, 6.58; N, 4.36.
N-(3-(4-Nitrophenyl)-3-oxo-1-phenylpropyl)acetamide
1g
IR (KBr): 1689, 3302 cm-1, 1H NMR (CDCl3): d 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): d 23.1, 44.3, 50.1, 123.8,
126.5, 127.8, 129.2, 140.9, 150.3, 169.9, 196.6. MS (EI, 70
eV): m/z = 312. 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-nitrophenyl)-3-oxopropyl)acetamide 1h
IR (KBr): 1694, 3277 cm-1, 1H NMR (CDCl3): d 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): d 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. MS (EI, 70 eV): m/z = 357. Anal.
Calcd. For C17H15N3O6: C, 57.14; H, 4.23; N, 11.76;
Found: C, 57.36; H, 4.11; N, 11.64.
N-(3-(4-Methoxyphenyl)-1-(naphthalen-3-yl)-3-oxo-
propyl)acetamide 1c
IR (KBr): 1671, 3276 cm-1. 1H NMR (CDCl3): d 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): d 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.
MS (EI, 70 eV): m/z = 347. Anal. Calcd. for C22H21NO3:
C, 76.06; H, 6.09; N, 4.03. Found: C, 76.27; H, 6.19; N,
3.95.
N-(3-Oxo-1,3-dip-tolylpropyl)acetamide 1d
IR (KBr): 1680, 3257 cm-1, 1H-NMR (CDCl3): d 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): d 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. MS (EI, 70 eV): m/z = 295. Anal.
Calcd. For C19H21NO2: C, 77.26; H, 7.17; N, 4.74; Found:
C, 77.05; H, 7.30; N, 4.85.
N-(1-(4-Chlorophenyl)-3-(4-nitrophenyl)-3-oxopropyl)-
acetamide 1i
IR (KBr): 1695, 3280 cm-1, 1H-NMR (CDCl3): d 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): d 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, MS (EI, 70 eV): m/z =
347. 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-(4-Chlorophenyl)-3-oxo-3-p-tolylpropyl)acetamide
1e
IR (KBr): 1689, 3302 cm-1, 1H NMR (CDCl3): d 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 (m,
5H), 7.37 (s, 1H), 7.77 (d, J = 8.0 Hz, 3H); 13C NMR
(CDCl3): d 21.7, 23.1, 42.8, 49.3, 127.9, 128.2, 128.7,
129.4, 133.1, 133.8, 139.6, 144.7, 170.1, 197.8. MS (EI,
70 eV): m/z = 312. Anal. Calcd. For C18H18ClNO2: C,
68.46; H, 5.75; N, 4.44; Found: C, 68.65; H, 5.90; N,
4.35.
N-(1-(Naphthalen-3-yl)-3-(4-nitrophenyl)-3-oxopropyl)-
acetamide 1j
IR (KBr): 1665, 3280 cm-1, 1H NMR (CDCl3): d 2.08
(s, 3H), 2.85-3.05 (m, 2H), 5.50 (s, 1H), 7.47-8.5 (m, 12H);
13C NMR (CDCl3): d 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,
204
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Efficient Synthesis of b-Acetamido Ketones/esters
129.5, 130.5, 173.9, 194.1; MS (EI, 70 eV): m/z = 362.
Anal. Calcd. For C21H18N2O4: C, 69.60; H, 5.01; N, 7.73,
Found: C, 69.49; H, 5.12; N, 7.69.
1H), 5.748 (s, 1H), 7.29 (s, 6H). 13C NMR (CDCl3): d 23.2,
30.6, 52.3, 52.8, 62.8, 126.6, 127.8, 128.7, 139.1, 167.6,
169.8, 203.6. MS (EI, 70 eV): m/z = 263. Anal. Calcd. for
C14H17NO4: C, 63.87; H, 6.51; N, 5.32; Found: C, 64.01; H,
6.43; N, 5.19.
N-(3-(4-Bromophenyl)-3-oxo-1-phenylpropyl)acet-
amide 1k
IR (KBr): 1685, 3275 cm-1, 1H-NMR (CDCl3): d 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): d 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. MS (EI, 70 eV):
m/z = 345. Anal. Calcd. For C17H16BrNO2: C, 58.97; H,
4.66; N, 4.05; Found: C, 58.81; H, 4.58; N, 4.14.
N-(3-(4-Bromophenyl)-1-(4-nitrophenyl)-3-oxopropyl)-
acetamide 1l
IR (KBr): 1687, 3261 cm-1, 1H-NMR (CDCl3): d 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 = 7.86 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): d 23.3,
42.7, 49.1, 113.8, 123.8, 127.4, 129.3, 129.5, 132.2, 134.8,
147.1, 148.4, 169.8, 196.8. MS (EI, 70 eV): m/z = 390.
Anal. Calcd. For C17H15BrN2O4: C, 52.19; H, 3.86; N, 7.16;
Found: C, 52.35; H, 4.05; N, 7.05.
Methyl 2-(acetamido(naphthalen-3-yl)methyl)-3-oxo-
butanoate 1p
IR (KBr): 1636, 1747, 3347 cm-1, 1H-NMR (CDCl3):
d 2.01 (s, 3H), 2.19 (s, 3H), 3.65 (s, 3H), 4.26 (s, 1H), 5.96
(s, 1H), 7.46 (m, 3H), 7.77 (m, 5H). 13C NMR (CDCl3): d
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, 167.6, 169.8, 203.5.
MS (EI, 70 eV): m/z = 313. Anal. Calcd. for C18H19NO4:
C, 68.99; H, 6.11; N, 4.47, Found: C, 69.81; H, 6.23; N,
4.56.
Ethyl 2-(acetamido(naphthalen-3-yl)methyl)-3-oxo-
butanoate 1q
1
IR (KBr): 1647, 1720, 1746, 3332 cm-1, H-NMR
(CDCl3): d 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), 7.27 (m, 4H), 7.76 (t, J = 7.5 Hz, 4H). 13C NMR
(CDCl3): d 23.2, 30.6, 52.3, 52.8, 62.8, 126.6, 127.8, 128.7,
139.1, 167.6, 169.8, 203.6. MS (EI, 70 eV): m/z = 327.
Anal. Calcd. For C19H21NO4 C, 69.71; H, 6.47; N, 4.28.
Found: C, 69.52; H, 6.34; N, 4.39.
Compound 1m
IR (KBr): 1689, 1736, 3286 cm-1, 1H NMR (CDCl3):
d 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), 7.2-7.6 (m, 3H), 7.7-8.2 (m,
4H), 9.96 (s, 1H); 13C NMR (CDCl3): d 23.3, 42.8, 49.5,
127.1, 129.2, 129.6, 130.1, 132.1, 134.9, 135.5, 147.6,
170.01, 191.8, 197.1. MS (EI, 70 eV): m/z = 373. Anal.
Calcd. For C18H16BrNO3: C, 57.77; H, 4.31; N, 3.74.
Found: C, 57.93; H, 4.42; N, 3.19.
Compound 2a
IR (KBr): 1674, 3433 cm-1, 1H NMR (CDCl3): d 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): d 23.0, 43.1, 46.8,
69.8, 112.3, 121.3, 126.2, 127.9, 128.4, 128.8, 129.7,
129.9, 131.8, 135.2, 138.1, 155.4, 168.2, 197.4; MS (EI,
70 eV): 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.
N-(3-(4-Bromophenyl)-1-(naphthalen-3-yl)-3-oxopro-
pyl)acetamide 1n
IR (KBr): 1682, 3276 cm-1, 1H NMR (CDCl3): d 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): d 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, 138.2, 170.1, 197.1. MS (EI, 70 eV): m/z =
395. Anal. Calcd. for C21H18BrNO2: C, 63.65; H, 4.58; N,
3.53, Found: C, 63.48; H, 4.67; N, 3.44.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge partial support
of this work by the Research Affairs Office of Bu-Ali Sina
University (Grant number 32-1716 entitled development of
chemical methods, reagents and molecules), and Center of
Excellence in Development of Chemical Method (CEDCM),
Hamedan, I.R. Iran.
Methyl 2-(acetamido(phenyl)methyl)-3-oxobutanoate
1o
IR (KBr): 1647, 1720, 1746, 3332 cm-1, H-NMR
1
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