Palladium and copper catalyzed one-pot Sonogashira reaction of 2-nitroiodobenzenes with aryl acetylenes and subsequent regioselective hydration in water: Synthesis of 2-(2-nitrophenyl)-1-aryl ethanones

Article abstract of DOI:10.1016/j.tetlet.2013.05.021

An attempted Sonogashira reaction of 2-nitroiodobenzene and phenyl acetylene catalyzed by Pd(PPh₃)₄/Cu in water in the presence of pyrrolidine proceeds with simultaneous regioselective hydration of the Sonogashira alkyne leading to the corresponding aryl ketone. A series of functionalized 2-(2-nitrophenyl)-1-aryl ethanones are obtained in high yields by this procedure.

Full text of DOI:10.1016/j.tetlet.2013.05.021

Tetrahedron Letters 54 (2013) 3697–3701
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Palladium and copper catalyzed one-pot Sonogashira reaction
of 2-nitroiodobenzenes with aryl acetylenes and subsequent
regioselective hydration in water: synthesis of 2-(2-nitrophenyl)-1-
aryl ethanones
⇑
Sabir Ahammed, Raju Dey, Brindaban C. Ranu
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An attempted Sonogashira reaction of 2-nitroiodobenzene and phenyl acetylene catalyzed by Pd(PPh3)4/
Cu in water in the presence of pyrrolidine proceeds with simultaneous regioselective hydration of the
Sonogashira alkyne leading to the corresponding aryl ketone. A series of functionalized 2-(2-nitro-
phenyl)-1-aryl ethanones are obtained in high yields by this procedure.
Received 29 March 2013
Revised 2 May 2013
Accepted 5 May 2013
Available online 13 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Sonogashira reaction
Hydration
Benzyl aryl ketone
Reaction in water
Palladium
During the course of our investigation we sought to have an ac-
cess to selected Sonogashira products by the condensation of iod-
obenzenes and phenyl acetylenes. The reaction was performed
using Pd(PPh3)4/CuI following a reported procedure.1 Interestingly,
we observed that when the reaction of 2-nitroiodobenzene and
phenyl acetylene was continued for a longer period, the initially
formed Sonogashira alkyne underwent regioselective hydration
under the reaction conditions to produce the corresponding benzyl
aryl ketone (Scheme 1) while other iodobenzenes furnished al-
kynes which remained inert towards hydration under identical
reaction conditions. This prompted us to investigate this observa-
tion in more detail to find its general applicability and mechanism.
The hydration of alkynes to the corresponding carbonyl deriva-
tives is a useful process.2 Traditionally, this reaction was per-
formed using mercury salts in strong acidic medium.3 Later,
several metal based catalysts containing Au,4 Ru,5 Rh,6 Pt,7, and
Pd8 have been employed. Significantly, hydration during Sonogash-
ira reaction on the same pot was not observed in any of these reac-
tions. We found only one report9 where the alkynes formed by the
reaction of aryl bromide and 3-butyn-1-ol using Pd-catalyst under-
went partial hydration on treatment with 20% HCl. However, no
reaction with aryl alkynes was addressed here.9 Interestingly, in
our procedure hydration occurs in basic medium under the stan-
dard Sonogashira conditions using Pd(0)/Cu(I) for the reaction of
aryl iodides containing nitro functionality at the 2-position and
aryl acetylenes. Toward better understanding of the reaction a ser-
ies of experiments were carried out with a variation of substituents
in the 2- and 4-position of aryl iodides and variation of solvent,
time, and temperature for a typical Sonogashira reaction with phe-
nyl acetylene. It was found that combined Sonogashira-hydration
reaction was very much dependent on the substituent in the aryl
iodides and reaction medium. The results are summarized in Ta-
ble 1. The Sonogashira-hydration sequence leading to benzyl aryl
ketone is successful for the reaction of 2-nitroiodobenzene and
phenyl acetylene in water at 80 °C for 8 h (Table 1, entry 8, high-
lighted). Replacement of the nitro group by similar electron with-
drawing functionalities such as –CN, –CHO, –COMe, –COOMe
furnished the corresponding alkynes without further hydration.
Interestingly, even 4-nitro iodobenzene provided the alkyne with-
out any hydrated product under identical reaction conditions. The
Ar
I
Ar
Pd(PPh3)4 / CuI
R
R
O
Pyrrolidine, H2O
80 oC, 8 h
NO2
NO2
⇑
Corresponding author. Tel./fax: +91 33 24732805.
E-mail address: ocbcr@iacs.res.in (B.C. Ranu).
Scheme 1. Hydration reaction followed by Sonogashira coupling.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.021

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S. Ahammed et al. / Tetrahedron Letters 54 (2013) 3697–3701
Table 1
yields. The results were reported in Table 2. The hydration is al-
Standardization of reaction conditions
ways highly regioselective giving only one product. The heteroaryl
acetylenes (Table 2, entries 8 and 12) also underwent clean reac-
tions. The products are obtained pure after simple work-up and
several of these compounds are new being reported for the first
time. However, a strong electron withdrawing group like nitro-
substituted phenyl acetylenes did not undergo any hydration and
the reaction stopped at the Sonogashira stage (Table 2, entry 14).
In general, the reactions are clean and high yielding although a
small amount of (2–5%) dimers of the corresponding acetylenes
and usual Sonogashira alkynes were also associated. These side-
products were separated easily during purification and all the
products are obtained in high purity and were characterized by
spectroscopic data. Significantly, when an aliphatic acetylene (Ta-
ble 2, entry 13) was employed in this reaction only the Sonogashira
product was obtained and no hydrated ketone was formed even
after prolonged reaction. This is possibly due to the absence of con-
jugation of the aliphatic moiety with the acetylenic triple bond
favoring the hydration process. The hydration of alkynes in basic
reaction medium by this procedure, which usually requires acidic
conditions, is also of much interest.
Ar1
X
Pd(PPh3)4 (0.5 mol%)
Ph
+
Ar1
1a
Ar1
Ph
+
CuI (1 mol%), Pyrrolidine
Solvent, Time, Temp.
Ph
O
1b
Entry
Ar1
Solvent
Time (h)
Temp (°C)
Yielda (%)
1a
1b
1
2
3
4
5
6
7
8
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-NO2C6H4
o-CN C6H4
o-CHOC6H4
o-COMeC6H4
o-COOMeC6H4
p-NO2C6H4
p-CN C6H4
Toluene
DMF
DMSO
THF
Dioxane
NMP
H2O
H2O
H2O
H2O
H2O
12
12
12
12
12
12
12
8
8
8
8
8
110
110
100
70
110
110
100
80
—
—
—
—
—
—
81
81
—
—
—
—
—
—
—
19
78
72
56
66
71
8
5
9
rt
—
10
11
12
13
14
15
80
80
80
80
80
80
73
74
78
69
82
78
H2O
H2O
H2O
H2O
8
8
8
It is believed that the reaction proceeds through a usual Pd(0)-
catalyzed Sonogashira pathway9 to provide the alkyne I which
then undergoes hydration catalyzed by Pd(II), generated in situ
from Pd(0) by molecular oxygen.13 To check this hypothesis when
the reaction is performed under argon atmosphere the hydration
step is greatly arrested reducing the hydrated product to the range
of 30%. (It is likely that hydration proceeds to some extent because
of the presence of traces of air in the reaction medium.) As –NO2
group is vital for this reaction, its participation in controlling the
hydration step is most likely. Thus it is proposed that the oxygen
of –NO2 functionality interacts with the Pd(II) complex of the al-
kyne to form an intermediate II which undergoes hydration via
III to provide the aryl ketone in a regioselective manner (Scheme 2).
The involvement of Pd(II) in the hydration process is established by
an experiment where the alkyne I was subjected to hydration un-
der identical reaction conditions using Pd(PPh3)2Cl2 to give the
same aryl ketone in comparative yield.
a
Yields refer to those of pure products characterized by IR, 1H NMR, and 13C NMR
spectroscopic data.
use of aprotic solvents such as toluene, DMF, DMSO, THF, dioxane,
and NMP did not initiate hydration at all. Among all solvents, H2O
is most suitable for Sonogashira as well as hydration.
The substituted aryl benzyl ketones are of much importance in
organic synthesis and have been employed as precursors to a vari-
ety of useful molecules.10 Specifically, 2-(2-nitrophenyl)-1-aryleth-
anones are valuable intermediates in the synthesis of 2,3-N-
substituted indoles.11 Considering the importance of these com-
pounds we focused our attention to develop a general method
for their synthesis based on our observation of the Sonogashira
reaction with 2-nitroiodobenzene.
Thus, 2-nitroiodobenzene and substituted 2-nitroiodobenzenes
were reacted with diversely substituted phenyl acetylenes cata-
lyzed by Pd(PPh3)4/CuI in water under open atmosphere at 80 °C
in the presence of pyrrolidine by a simple procedure12 to provide
the corresponding nitro-substituted benzyl aryl ketones in high
In conclusion, we have developed a general procedure for the
synthesis of 2-(2-nitrophenyl)-1-aryl ethanones, useful precursors
to indoles,11 by a simple one-pot reaction of 2-nitroiodobenzene
Table 2
Palladium catalyzed Sonogashira coupling followed by hydration reaction
Pd(PPh3)4 , CuI
Ar2
Ar1-I
+
Ar2
Ar1
Pyrrolidine, H2O
reflux, 8 h
O
Entry
1
Ar1
Ar2
Time (h)
Product
Yield (%)a
Refs.
14
o-NO2C6H4
Ph
8
8
81
O
NO2
2
3
o-NO2C6H4
o-NO2C6H4
4Me-C6H4
84
83
15
O
NO2
2,4-DiMeC6H4
8
O
NO2

S. Ahammed et al. / Tetrahedron Letters 54 (2013) 3697–3701
3699
Table 2 (continued)
Entry
Ar1
Ar2
Time (h)
Product
Yield (%)a
Refs.
OMe
Cl
4
5
6
o-NO2C6H4
4-OMe-C6H4
8
86
15
15
O
NO2
o-NO2C6H4
4-ClC6H4
8
8
81
82
O
NO2
nPentyl
o-NO2C6H4
4-nPentylC6H4
O
NO2
7
8
9
o-NO2C6H4
3-FC6H4
3-Thiophenyl
Ph
10
8
78
85
82
F
O
NO2
S
o-NO2C6H4
O
NO2
2-NO2,5-MeC6H3
8
O
NO2
10
11
o-NO2C6H4
4-PhC6H4
10
76
86
O
NO2
2-NO2,5-MeC6H3
4Me-C6H4
8
O
NO2
S
12
13
2-NO2,5-MeC6H3
3-Thiophenyl
8
8
85
56
O
NO2
TMS
o-COOMeC6H4
TMS
16b
NO2
14
o-NO2C6H4
o-NO2C6H4
8
38
17c
NO2
NO2
a
Yields refer to those of purified products characterized by IR, 1H, and 13C NMR spectroscopic data.
Sonogashira product was formed together with acetylene dimer (23%).
Only Sonogashira product was formed.
b
c
and aryl acetylenes in water catalyzed by Pd(PPh3)4/CuI involving
the best of our knowledge, this is the first report of Sonogashira
coupling of 2-nitroiodobenzene and aryl alkynes in water involving
hydration of the triple bond in the basic reaction media which
leads to the formation of 2-(2-nitrophenyl)-1-aryl ethanones and
Sonogashira coupling followed by hydration in the same pot. The
significant features of this procedure are simplicity in operation,
excellent regioselectivity, reaction in water, and high yields. To

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S. Ahammed et al. / Tetrahedron Letters 54 (2013) 3697–3701
Ar
I
Pd(PPh3)4 , CuI
Ar
+
H2O, 80 oC, 3 h
O
NO2
Pd(0)
N
O
I
O2, C4H9N.HI
Pd(II)
H
Pd(II)
Ar
Ar
Ar
H2O
H2O
O
O
O
N
NO2
N
O
O
III
II
Scheme 2. Plausible mechanism.
(CDCl3, 500 MHz) d 4.70 (s, 3H), 7.30 (d, J = 7.5 Hz, 1H), 7.43–7.48 (m, 3H),
7.53–7.59 (m, 2H), 8.01 (d, J = 12.5 Hz, 2H), 8.10 (d, J = 14.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) d 44.2, 125.3 (2C), 128.3, 128.5, 128.8 (2C), 130.7, 133.6,
133.7, 133.8, 136.5, 149.1, 195.5. These data are in good agreement with those
of an authentic sample.14
This procedure was followed for the synthesis of all the products listed in
Table 2. The known compounds were identified by comparison of their IR, 1H
NMR, 13C NMR, and HRMS spectral data with those reported (see references in
Table 2). The unknown products (Table 2, entries 3, 6–13) were properly
characterized by their spectroscopic (IR, 1H NMR, 13C NMR, and HRMS) data
which are provided below.
we believe, this will make an important addition to organic
synthesis.
Acknowledgments
We are pleased to acknowledge the financial support from the
CSIR, New Delhi (Grant No. 01(2365)/10/EMR-II) for this investiga-
tion. S.A. and R.D. also thank CSIR for their fellowships.
1-(2,4-dimethylphenyl)-2-(2-nitrophenyl)ethanone (Table 2, entry 3): yellow
solid; mp 81 °C; IR (KBr): 2924, 2852, 1684, 1521, 1517, 1350, 1311, 1173,
Supplementary data
977 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 2.30 (s, 3H), 2.33 (s, 3H), 4.53 (s, 3H),
;
7.05 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.50 (t,
J = 7.5 Hz, 1H), 7.53 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d
20.8, 21.1, 46.9, 125.3, 128.4, 129.2, 131.0, 132.1, 132.5, 133.5, 133.8, 135.4,
135.7, 137.1, 149.1, 199.0; HRMS calcd for C16H15NO3 (M+Na+): 292.0950;
found: 292.0951.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.021.
2-(2-nitrophenyl)-1-(4-pentylphenyl)ethanone (Table 2, entry 6): yellow solid;
mp 85–87 °C; IR (KBr): 3343, 3119, 2953, 2852, 1678, 1604, 1524, 1338, 1221,
References and notes
1180 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 0.91 (t, J = 6.5 Hz, 3H), 1.31–1.39 (m,
;
4H), 1.62–1.68 (m, 2H), 2.68 (t, J = 7.5 Hz, 2H), 4.71 (s, 2H), 7.28–7.35 (m, 3H),
7.47 (t, J = 8.0 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.95 (d, J = 8.0 Hz, 2H), 8.14 (d,
J = 8.0 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 14.1, 22.6, 30.9, 31.5, 36.1, 44.1,
125.3, 128.4, 128.5, 128.9, 130.9, 133.5, 133.7, 134.3, 149.3, 149.4, 195.1;
HRMS calcd for C19H21NO3 (M+Na+): 312.1600; found: 312.1593.
1. Bhattacharya, S.; Sengupta, S. Tetrahedron Lett. 2004, 45, 8733–8736.
2. Hintermann, L.; Labonne, A. Synthesis 2007, 1121–1150.
3. (a) Sturtz, G.; Charrier, C.; Normant, H. Bull. Soc. Chim. Fr. 1966, 1707–1713; (b)
Poss, A. J.; Belter, R. K. J. Org. Chem. 1987, 52, 4810–4812.
4. (a) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729–3731; (b) Casado, R.;
Contel, M.; Laguna, M.; Romero, P.; Sanz, S. J. Am. Chem. Soc. 2003, 125, 11925–
11935; (c) Roembke, P.; Schmidbaur, H.; Cronje, S.; Raubenheimer, H. J. Mol.
Catal. A: Chem. 2004, 212, 35–42; (d) Marion, N.; Ramon, R. S.; Nolan, S. P. J. Am.
Chem. Soc. 2009, 131, 448–449.
5. (a) Tokunaga, M.; Suzuki, T.; Koga, N.; Fukushima, T.; Horiuchi, A.; Wakatsuki,
Y. J. Am. Chem. Soc. 2001, 123, 11917–11924; (b) Grotjahn, D. B.; Lev, D. A. J. Am.
Chem. Soc. 2004, 126, 12232–12233; (c) Chevallier, F.; Breit, B. Angew. Chem.,
Int. Ed. 2006, 45, 1599–1602.
6. Blum, J.; Huminer, H.; Alper, H. J. Mol. Catal. 1992, 75, 153–160.
7. (a) Hiscox, W.; Jennings, P. W. Organometallics 1990, 9, 1997–1999; (b)
Francisco, L. W.; Moreno, D. A.; Atwood, J. D. Organometallics 2001, 20, 4237–
4245.
8. (a) Imi, K.; Imai, K.; Utimoto, K. Tetrahedron Lett. 1987, 28, 3127–3130; (b) Li,
X.; Hu, G.; Luo, P.; Tang, G.; Gao, Y.; Xu, P.; Zhao, Y. Adv. Synth. Catal. 2012, 354,
2427–2432.
9. Pal, M.; Parasuraman, K.; Gupta, S.; Yeleswarapu, K. R. Synlett 2002, 1976–1982.
10. (a) Zheng, Y.; Xue, Z.; Liu, L.; Shu, C.; Yuan, W.; Zhang, X. Org. Biomol. Chem.
2013, 11, 412–415; (b) Suárez, A. G.; Oonishi, Y.; Meiries, S.; Nolan, S. P.
Organometallics 2013, 32, 1106–1111.
1-(3-fluorophenyl)-2-(2-nitrophenyl)ethanone (Table 2, entry 7): yellow solid;
mp 83 °C; IR (KBr): 3358, 3085, 1687, 1588, 1524, 1445, 1336, 1249,
1150 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 4.70 (s, 2H), 7.30–7.34 (m, 2H),
;
7.45–7.52 (m, 2H), 7.59–7.65 (m, 1H), 7.68–7.72 (m, 1H), 7.81–7.84 (m, 1H),
8.14–8.17 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 44.6, 115.3 (d, J = 21.7 Hz, 1C),
120.8 (d, J = 21 Hz, 1C), 124.3 (d, J = 3.0 Hz, 1C), 125.6, 128.9 (2C), 130.7 (t,
J = 7.5 Hz, 1C), 133.9 (d, J = 2.3 Hz, 1C), 138.8 (d, J = 6.0 Hz, 1C), 149.2, 163.2 (d,
J = 246.8 Hz, 1C), 194.5; HRMS calcd for C14H10FNO3 (M+H+): 260.0723; found:
260.0718.
2-(2-nitrophenyl)-1-(thiophen-3-yl)ethanone (Table 2, entry 8): dark grey
solid; mp 91–93 °C; IR (KBr): 3107, 2920, 2852, 1678, 1612, 1521, 1414, 1334,
1232, 1175 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 4.63 (s, 2H), 7.34–7.36 (m, 2H),
;
7.46–7.49 (m, 1H), 7.58–7.61 (m, 2H), 8.13 (d, J = 4.5 Hz, 1H), 8.17–8.18 (m,
1H); 13C NMR (CDCl3, 125 MHz) 45.1, 125.3, 126.7, 127.1, 128.5, 130.3, 132.5,
133.6, 133.7, 141.6, 149.2, 189.6; HRMS calcd for C12H9NO3S (M+H+):
248.0381; found: 248.0376.
2-(5-methyl-2-nitrophenyl)-1-phenylethanone (Table 2, entry 9): yellow solid;
mp 105–106 °C; IR (KBr): 3059, 2897, 1686, 1591, 1508, 1445, 1339, 1217,
1076 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 2.55 (s, 3H), 4.82 (s, 2H), 7.26 (s, 1H),
;
7.38 (d, J = 8.5 Hz, 1H), 7.62 (t, J = 8.0 Hz, 2H), 7.73 (t, J = 7.5 Hz, 1H), 8.16 (d,
J = 7.5 Hz, 2H), 8.20 (d, J = 8.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d 21.4, 44.3,
125.4, 128.2 (2C), 128.7 (2C), 129.0, 130.8, 133.4, 134.4, 136.6, 144.9, 146.7,
195.7; HRMS calcd for C15H13NO3 (M+Na+): 278.0793; found: 278.0792.
2-(2-nitrophenyl)-1-(1,10 biphenyl)phenylethanone (Table 2, entry 10): yellow
solid; mp 113–115 °C; IR (KBr): 3059, 1680, 1602, 1521, 1402, 1342, 1197,
11. Rutherford, J. L.; Rainka, M. P.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
15168–15169.
12. Representative experimental procedure for Sonogashira coupling and
hydration of 2-iodonitrobenzene with phenyl acetylene (Table 1, entry 1). To
a stirred mixture of 2-iodonitrobenzene (249 mg, 1.0 mmol), phenyl acetylene
(153 mg, 1.5 mmol), pyrrolidine (142 mg, 2 mmol), Pd(PPh3)4 (12 mg,
0.01 equiv) and CuI (2 mg, 1 mol %) were added followed by water (5 mL).
The reaction mixture was then stirred at 80 °C (oil bath temperature) for 8 h
(TLC) and extracted with ethyl acetate (3 ꢀ 20 mL). The combined organic
extract was washed with brine, dried over anhydrous Na2SO4, and evaporated
to leave the crude product which was purified by column chromatography over
silica gel with hexane–ethyl acetate (90:10) as eluent to furnish pure 2-(2-
nitrophenyl)-1-phenylethanone as a yellowish viscous liquid (195 mg, 81%); IR
997 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 4.70 (s, 2H), 7.30–7.36 (m, 2H), 7.40–
;
7.45 (m, 3H), 7.52–7.59 (m, 3H), 7.66 (t, J = 8.5 Hz, 1H), 8.04 (t, J = 8 Hz, 2H),
8.10 (t, J = 8.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d 44.2, 125.5, 127.5 (2C),
127.6 (2C), 128.4, 128.5, 129.0 (2C), 129.1 (2C), 130.8, 133.6, 133.8, 135.4,
140.0, 146.4, 149.2, 195.1; HRMS calcd for C20H15NO3 (M+Na+): 340.0950;
found: 340.0950.
2-(5-methyl-2-nitrophenyl)-1-p-tolylethanone (Table 2, entry 11): light
yellow solid; mp 110–111 °C; IR (KBr): 3051, 2913, 1681, 1606, 1588, 1514,
(neat) 3055, 2891, 2837, 1688, 1590, 1503, 1341, 1212, 834 cmꢁ1 1H NMR
,

S. Ahammed et al. / Tetrahedron Letters 54 (2013) 3697–3701
3701
1336, 1206, 1001 cmꢁ1
;
1H NMR (CDCl3, 500 MHz) d 2.56 (s, 3H), 4.80 (s, 2H),
141.7, 144.9, 146.7, 189.9; HRMS calcd for C13H11NO3S (M+H+): 262.0538;
found: 262.0534.
13. (a) Kataoka, H.; Watanabe, K.; Miyazaki, K.; Tahara, S.; Ogu, K.; Matsuoka, R.;
Goto, K. Chem. Lett. 1990, 1705–1708; (b) Kataoka, H.; Watanabe, K.; Goto, K.
Tetrahedron Lett. 1990, 31, 4181–4184.
7.26 (s, 1H), 7.38 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 8.06 (d, J = 8.0 Hz,
2H), 8.20 (d, J = 8.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d 21.4, 21.7, 44.2, 125.5,
128.4 (2C), 128.9, 129.4 (2C), 131.0, 134.4, 144.3, 144.8, 146.8, 195.3; HRMS
calcd for C16H15NO3 (M+H+): 270.1130; found: 270.1124.
2-(5-methyl-2-nitrophenyl)-1-(thiophen-3-yl)ethanone (Table 2, entry 12):
dark grey solid; mp 91–92 °C; IR (KBr): 3133, 3081, 1673, 1558, 1510, 1403,
14. Prasad, G.; Hanna, P. E. J. Org. Chem. 1991, 56, 7188–7190.
15. Martin, L. L.; Setescak, L. L.; Worm, M.; Crichlow, C. A.; Geyer, H. M., III; Wilker,
J. C. J. Med. Chem. 1982, 25, 346–351.
1336, 1244, 1178 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 2.44 (s, 3H), 4.61 (s, 2H),
;
7.15 (s, 1H), 7.26 (d, J = 8.5 Hz, 1H), 7.35–7.37 (m, 1H), 7.60 (d, J = 4.5 Hz, 1H),
8.07 (d, J = 8.5 Hz, 1H), 8.19 (t, J = 3.5 Hz, 1H), 8.19 (t, J = 3.5 Hz, 1H); 13C NMR
(CDCl3,125 MHz) d 21.5, 45.3, 125.5, 126.6, 127.1, 129.1, 130.4, 132.5, 134.4,
16. Bakherad, M.; Keivanloo, A.; Bahramian, B.; Mihanparast, S. Tetrahedron Lett.
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