The conversion of aryl and heteroaryl methylketones to the corresponding secondary or tertiary amides

Article abstract of DOI:10.3184/174751911X13053065216840

Secondary or tertiary amides have been prepared directly from aryl, heteroaryl methyl ketones using an iodineamine-NaOH system which afforded the expected products in good yields in an aqueous medium. The present method has the advantages of using inexpensive reagents, mild reaction condition and ease of manipulation.

Full text of DOI:10.3184/174751911X13053065216840

298 RESEARCH PAPER
MAY, 298–301
JOURNAL OF CHEMICAL RESEARCH 2011
The conversion of aryl and heteroaryl methylketones to the
corresponding secondary or tertiary amides
Jiaoyang Ding, Liping Cao, Jungang Wang, Weijian Xue, Yanping Zhu and Anxin Wu*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P. R. China
Secondary or tertiary amides have been prepared directly from aryl, heteroaryl methyl ketones using an iodine–
amine–NaOH system which afforded the expected products in good yields in an aqueous medium. The present
method has the advantages of using inexpensive reagents, mild reaction condition and ease of manipulation.
Keywords: iodine, amide, water, Lieben iodoform reaction
The formation of amides is an important topic in organic syn-
thesis. The amide unit is a biological activity structural com-
ponent of biomolecules and commercial drugs (Scheme 1).1
Traditionally, amides have been successfully prepared using
reactions such as the Beckmann rearrangement,2–4 Ritter reac-
tion,5–7 Chapman rearrangement,8,9 Haller–Bauer reaction,10–11
Passerini reaction,12,13 Wolff rearrangement,14 and Schmidt
reaction.15–17 Apart from these conventional methods for the
synthesis of amides, many alternative strategies have been
reported.18–25 Typically the direct amidation of activated car-
boxylic acid derivatives with amines is a convenient approach
to amides.18,19 The transition-metal-catalysed carbonylation of
aryl halides or alkenes in the presence of nucleophiles is an
important atom-economic reaction that can be applied to the
synthesis of amides.20,21 In addition, a recent conceptually eco-
nomical amidation from alcohols has been explored with
highly active transition-metal catalysts such as Ru-,22,23 Rh-,24
and Ag-25 producing two molecules of hydrogen as the only
stoichiometric byproduct. Although various methods for
preparations of amides are available, the development of an
efficient, economic and environmental friendly method is still
desirable. Recently, we reported direct transformation of
methyl ketones or carbinols to corresponding primary amides.26
We now report an efficient method for the preparation of
secondary and tertiary amides in the presence of iodine and
various amines in aqueous media.
ammonia (1 equivalent) in methanol (Scheme 2).27 Heating the
reaction mixture at 100°C in a sealed tube for 10h gave the
desired product in 46% yield. Meanwhile, α-iodoketone 228
was obtained in 16% yield together with the 4-methoxybenzo-
ate 429 in 10% yield (Table 1, Entry 1). It was interesting to find
that the unexpected product 4-methoxybenzamide 326 was
obtained in 5% yield. When t-butyl alcohol was used as the
solvent, the ester was not detected owing to steric hindrance
(Table 1, Entry 2).30 To our disappointment, changing metal
oxides did not reduce the amount of the byproducts (Table 1,
entries 3–6). It was notable, however, that this transformation
Table 1 Effect of the basicity on the amidationa
Entry Metal Temp/°C Slovent Conv/%
oxide
Yield/%c
2
3
4
5
1
2
3
4
5
6
7
8
9
CuO
100
100
100
100
100
100
100
90
MeOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
H2O
81
80
16
5
10 46
CuO
12 10
10 12
10 18
11 20
–
–
–
–
–
–
–
–
55
50
68
48
15
5
MgO
CrO3
ZnO
81
100
89
MnO2
CuO
70
8
–
38
80
80
83
88
Noneb
Noneb
H2O
82
–
60
H2O
86
–
a Reaction conducted with 1 mmol of acetophenone, 1 mmol of
metal oxide and 1 mmol of I2 in 10h.
bReaction conducted with 1 mmol of acetophenone, 3 mmol of
NH3.H2O and 3 mmol of I2 in 1h.
Initially, we expected to obtain intermediate 5 in one pot
from p-methoxyacetophenone 1 in the presence of copper (II)
oxide (1 equivalent), iodine (1 equivalent), and aqueous
c Isolated yields.
Scheme 1
Scheme 2
* Correspondent. E-mail: chwuax@mail.ccnu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2011 299
Table 3 Preparation of amides from acetophenone with
took place smoothly in H2O to give the amide in 80% yields
(Table 1, Entry 7). We also found that the transformation of
compound 1 to 3 could be achieved in good yield without a
metal oxide in aqueous ammonia at 90°C (Table 1, Entry 8). A
higher conversion was observed upon heating the reaction
mixture to 60°C for one hour (Table 1, Entry 9). Based on
these result, we proposed a tandem Lieben-Haller-Bauer reac-
tion mechanism for the direct transformation of methyl ketones
or carbinols to corresponding primary amides.26
various aminesa
Entry
Amine
Product
Yieldb/%
In the course of further work on preparing amides, we now
report the tandem Lieben–Haller–Bauer reaction using several
other amines in place of ammonia in an aqueous media. Aceto-
phenone (6a) was used as a model substrate in the presence
of molecular iodine and ethylamine in water for 4 hours to
investigate the best condition for the synthesis of amides.
Unfortunately, as shown in Table 2, a low conversion of methyl
ketone to the corresponding secondary amide was observed
(Table 2, Entry 1). We speculated that basicity of ethylamine
might be too weak to induce the Lieben-iodoform process
in aqueous media. Therefore, the screening reactions were
performed with respect to a variety of bases. The results are
summarised in Table 2 and show that NaOH was the best base
for performing the conversion. Several parallel reactions were
performed with the other bases such as K2CO3, Et3N, DMAP,
and pyridine (Table 2, entries 2–6). On the basis of the
above-described results, two possibilities should be taken into
consideration. (i) The inorganic base was more suitable
than the organic base for the Lieben-iodoform process under
aqueous conditions.31,32 (ii) Sodium hypoiodite formed from
NaOH could be important to promote the Lieben-iodoform
process.33–36
1
2
Ethanamine
Methanamine
n-Butylamine
t-Butylamine
n-Octadecylamine
Dimethylamine
Diethylamine
Piperidinec
7a
7b
7c
7d
7e
7f
87
88
60
NR
35
55
52
56
44
NR
3
4
5
6
7
7g
7h
7i
8
9
Morpholine
10
Aniline
7j
a Reaction conducted with 1 mmol of acetophenone, 3 mmol of
ethylamine, 3 mmol of I2 and 3mmol NaOH in 4h.
b Isolated yields.
c Reaction conducted in 6h.
Table 4 Preparation of secondary amides from ethylamine
with various methyl ketones
Encouraged by these results, a number of primary and
secondary amines were subjected to the optimised set of
conditions to examine the effectiveness of this procedure. As
shown in Table 3, it was obvious that moderate to good yields
were obtained for most amines. However, tert-butylamine
did not give the expect product because of steric hindrance
(Table 3, Entry 4). Meanwhile, aniline failed to give the cor-
responding secondary amide (Table 3, Entry 10). We ssuggest
that aniline is not a good nucleophilic reagent because the
conjugation of phenyl ring leads the N atom losing its nucleo-
philicity in the reaction.
Entry
R
Product
Yielda/%
1
2
3
4
5
6
7
8
9
3,4-Cl2C6H3
4-NO2C6H4
4-BrC6H4
8a
8b
8c
8d
8e
8f
8g
8h
8i
81
89
84
78
71
76
70
86
63
4-MeC6H4
Piperonyl
4-EtOC6H4
2-Thienyl
2-Furyl
2-Naphthyl
a Isolated yield.
To assess the generality of the method and to evaluate the
electronic influence of the aromatic ring substituent, various
other aromatic ketones (6) were examined under the optimised
conditions (Table 4). Acetophenone and its derivatives were
readily transformed into the corresponding secondary amides
with moderate to good yields (63–89%). It was obvious that an
electron withdrawing substituent (e.g. –NO2, –Br) on the ben-
zene ring gave a considerable increase in the yield (Table 4,
entries 1–3), and the corresponding products 8a–c were
obtained in good yield. In contrast, when the benzene rings
bear electron-donating groups (Table 4, entries 4–6), the cor-
responding products 8d–f were obtained in slight lower yields.
Encouraged by the results obtained with aryl methyl ketones,
we turned our attention to the heteroaryl methyl ketones. The
presence of heteroatoms, including oxygen (8g) and sulfur
(8h) in the substrate, did not affect the overall efficiency,
and the corresponding amides were obtained. An attempt to
perform the reaction with 2-naphthyl methyl ketone (8i) also
succeeded in moderate yield (Table 4, Entry 9).
Table 2 Effect of the basicity on the amidationa
A possible reaction mechanism is shown in Fig. 1. The ace-
tophenone undergoes the formation of enolate ion under basic
condition provided by NaOH, and three sequential α-haloge-
nations take place to afford the α,α,α-triiodomethyl ketone.
This is the mechanism of the Lieben iodoform reaction.31,32
However, α,α,α-triiodomethyl ketone does not undergo rapid
hydrolysis to afford the iodoform and a carboxylate in the
presence of primary or secondary amines. Instead, α,α,α-triio-
domethyl ketone, which is a nonenolizable ketone, is attacked
by the amine as a nucleophilic reagent, and this is accompa-
nied by the cleavage of a carbon–carbon bonds leading to
benzamide and iodoform. This process is a Haller–Bauer
reaction.37,38 Meanwhile, NaOH can act as a base to neutralise
the hydrogen iodide, formed in the process of Lieben iodoform
Entry
Base
Yield/%b
1
2
3
4
5
6
7
—
35
78
51
5
30
36
87
NaOH
K2CO3
Et3N
DMAP
Pyridine
NaOHc)
a Reaction conducted with 1 mmol of acetophenone, 3 mmol of
ethylamine (35%), 1 nmmol base and 3 mmol of I2 in 4h.
b Isolated yield.

300 JOURNAL OF CHEMICAL RESEARCH 2011
113.7, 55.5, 55.4. MS (EI, 70 ev) m/z: 309 (21%), 135 (100), 107 (5),
92 (7), 77 (13).
2-(Thiophen-3-yl-carbonyl)-5-(thiophen-3-yl)-oxazole (5b): M.p.
170–171 °C, IR (KBr): 3121, 1597, 1510, 1467, 1267, 1139, 1068,
952, 850, 817, 659cm−1. 1H NMR (400 MHz, CDCl3): δ = 9.05 (d, 1H,
J = 2.4 Hz), 7.95 (d, 1H, J = 5.6 Hz), 7.83 (t, 1H, J = 2.0 Hz), 7.45
(d, 3H, J = 1.6 Hz), 7.38 (m, 1H, J = 2.8 Hz). 13C NMR (100 MHz,
CDCl3): δ =137.0, 128.5, 127.3, 125.9, 124.8, 123.8, 123.5. MS (EI,
70 ev) m/z: 260 (86%), 232 (26), 176 (14), 111 (100), 83 (23), 77 (4).
HRMS (EI) m/z Calcd for C12H7NO2S2 (M+Na)+ 283.9810. Found
283.9811.
N-Ethylbenzamide (7a): M.p. 64–65 °C (lit.40 64–65 °C). IR (KBr):
3318, 3080, 2979, 2934, 2870, 1636, 1604, 1549, 1488, 1432, 1358,
1311, 1145, 868, 720, 695 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.77
(d, 2H, J = 7.2 Hz), 7.46 (t, 1H, J = 7.2 Hz), 7.38 (t, 2H, J = 7.2 Hz),
Fig. 1 The possible reaction mechanism.
6.56 (br s, 1H), 3.48 (m, 2H, J = 7.2 Hz), 1.22 (t, 3H, J = 7.2 Hz). 13
C
NMR (100 MHz, CDCl3): δ =167.5, 134.7, 131.2, 128.4, 126.8, 34.9,
14.8. MS (EI, 70 ev) m/z: 149 (26%), 148 (29), 105 (89), 82 (100),
77 (61).
reaction. In addition, water as a solvent is indispensable to
this reaction because the iodoform that is formed during the
reaction is insoluble in hot water and can further promote the
transformation.
In conclusion, an efficient approach to secondary and
tertiary amides in the presence of iodine and amines has
been developed in aqueous media. The reaction provides an
efficient method for the preparation of secondary and tertiary
amides. It further confirms the rationality of the tandem
Lieben–Haller–Bauer reaction mechanism. The advantages of
the present method in term of good yields, mild reaction condi-
tions, ease of manipulation, and inexpensive reagents, should
make it a valuable alternative to existing methods.
N-Methylbenzamide (7b): M.p. 78–79 °C. lit.41 79–80 °C). IR
(KBr): 3330, 3065, 2932, 2803, 1688, 1667, 1594, 1541, 1447, 1412,
1
1293, 1219, 1178, 1159, 1070, 925, 807, 749, 689, cm−1. H NMR
(600 MHz, CDCl3): 1H NMR (600 MHz, CDCl3): δ = 8.33 (d, 2H, J =
7.8 Hz), 7.62 (t, 1H, J = 7.2 Hz), 7.48 (t, 2H, J = 7.2 Hz), 7.17 (br s,
1H), 2.97 (d, 3H, J = 4.8 Hz). 13C NMR (150 MHz, CDCl3): δ =187.7,
162.4, 134.3, 133.2, 131.1, 128.4, 26.0. MS (EI, 70 ev) m/z: 135
(10%), 134 (16), 105 (70), 82 (100), 77 (60).
N-Butylbenzamide (7c): M.p. 72–73 °C (lit.42 72–73 °C). IR (KBr):
3313, 3065, 2959, 2931, 2872, 1639, 1541, 1491, 1513, 1407, 1465,
1
1377, 1309, 1225, 1185s, 1154, 1075, 1028, 947, 852, 803 cm−1. H
NMR (600 MHz, CDCl3): δ =7.77 (d, 2H, J = 7.2Hz), 7.46 (t, 1H, J =
7.2 Hz), 7.39 (t, 2H, J = 7.2 Hz), 6.53 (br s, 1H), 3.42 (q, 2H, J = 6.6
Hz), 1.58 (t, 2H, J = 7.2Hz), 1.39 (q, 2H, J = 7.2 Hz), 0.93 (t, 3H, J =
7.2 Hz). 13C NMR (CDCl3, 150 MHz): δ = 167.6, 134.7, 131.1, 128.3,
126.8, 39.7, 31.6, 20.1, 13.7. MS (EI, 70 ev) m/z: 177 (10%), 135 (34),
104 (100), 77 (55).
Experimental
Methyl ketones 8a–i, amines 7a–j and other reagents were obtained
from commercial suppliers and used without further purification.
TLC analysis was performed using pre-coated glass plates. Column
chromatography was performed using silica gel (200–300 mesh). IR
spectra were recorded on a PE-983 spectrophotometer as KBr pellets
and were reported in cm−1. 1H and 13C NMR spectra were recorded on
a Varian Mercury 600 or 400 spectrometer operating at 600 or 400
and 150 or 100 MHz. Chemical shifts are reported in ppm, relative to
the internal standard of tetramethylsilane (TMS). Electron impact (EI)
mass spectra were acquired using a Finnegan Trace MS spectrometer.
Melting points were determined using XT-4 apparatus and not cor-
rected. HRMS were obtained on a Bruker 7-tesla FT-ICR MS equipped
with an electrospray source (Billelica, MA,USA).
N-Octadecylbenzamide (7e): M.p. 76–77 °C (lit.43 82 °C). IR (KBr):
3344, 2919, 2847, 1632, 1577, 1533, 1488, 1463, 1296, 1075,
866 cm−1. 1H NMR (400 MHz, CDCl3): δ =7.76 (d, 2H, J = 7.6 Hz),
7.49–7.41 (m, 3H), 6.12 (br s, 1H), 3.45 (q, 2H, J = 6.8 Hz), 1.38–1.26
(m, 32H), 0.88 (t, 3H, J = 6.8 Hz). 13C NMR (100 MHz, CDCl3): δ =
167.5, 134.9, 131.3, 128.5, 126.8, 40.1, 31.9, 29.7, 29.3, 27.0, 22.7,
14.1. MS (EI, 70 ev) m/z: 373 (21%), 372 (7), 344 (5), 330 (9), 316
(5), 207 (8), 190 (11), 176 (37), 148 (24), 135 (44), 105 (100),
77 (12).
N,N-Dimethylbenzamide (7f): Colourless oil, IR (KBr): 3496, 3344,
2936, 1646, 1596, 1580, 1450, 1405, 1316, 1246, 1145, 1063, 994,
882, 807, 757, 725 cm−1. 1H NMR (600 MHz, CDCl3): δ = 7.95 (d, 2H,
J = 7.2 Hz), 7.65 (t, 1H), 7.51 (q, 2H, J = 7.8 Hz), 3.13 (s, 3H), 2.97
(s, 3H), 13C NMR (150 MHz, CDCl3): δ = 156.8, 134.7, 133.0, 129.7,
129.0, 37.1, 34.0. MS (EI, 70 ev) m/z: 149 (27%), 148 (32), 105 (100),
82 (22), 77 (63).
N,N-Diethylbenzamide (7g): Colourless oil, IR (KBr): 3478, 3064,
2972, 2936, 2927, 1725, 1681, 1643, 1597, 1448, 1383, 1289, 1233,
1180, 1145, 1075, 1021, 971, 941, 855, 721, 688 cm−1. 1H NMR (400
MHz, CDCl3): δ = 7.94 (d, 2H, J = 7.2 Hz), 7.64 (t, 1H, J = 7.2 Hz),
7.51 (t, 2H, J = 7.2 Hz), 3.57 (q, 2H, J = 7.2 Hz), 3.25 (q, 2H, J = 7.2
Hz), 1.28 (q, 3H, J = 7.2 Hz), 1.16 (t, 3H, J = 7.2 Hz). 13C NMR (100
MHz, CDCl3): δ = 166.7, 134.5, 133.2, 129.6, 128.9, 42.1, 38.8, 29.7,
14.1, 12.8. MS (EI, 70 ev) m/z: 177 (6 %), 135 (19), 105 (100),
84 (30), 82 (40).
Synthesis of amides (7); general procedure
Finely powdered NaOH (120 mg, 3.0 mmol) and iodine (762 m g,
3.0 mmol) were added to a well-stirred solution of methyl ketone
(1.0 mmol) and amine in water (20 mL). The mixture was stirred for
5 min and then heated to 60°C for about 4h. After disappearance of the
reactant (monitored by TLC), the mixture was extracted by EtOAc
(3×50 mL) and washed with saturated Na2S2O3 (3×50 mL). The
organic layer was dried over anhydrous sodium sulfate. The solvent
was evaporated and the residue was purified by column chromatogra-
phy (petroleum ether/ethyl acetate) to give the target products in good
yield.
Synthesis of oxazole (5); general procedure
Finely powdered CuO (80 mg, 1.0 mmol) and iodine (254 m g,
1.0 mmol) were added to a well-stirred solution of methyl ketone
(1.0 mmol) and aqueous ammonia (35%, 100mg, 1mmol) in t-butyl
alcohol (20 mL). The mixture was stirred for 5 min and then heated to
100°C for about 10h. After disappearance of the reactant (monitored
by TLC), the mixture was extracted by EtOAc (3×50 mL) and washed
with saturated Na2S2O3 (3×50 mL). The organic layer was dried over
anhydrous sodium sulfate. The solvent was evaporated and the residue
was purified by column chromatography (petroleum ether/ethyl
acetate) to give the target products.
Phenyl(piperidin-1-yl)methanone (7h): Colourless oil, IR (KBr):
3421, 2974, 2859, 1671, 1643, 1603, 1594, 1496, 1448, 1317, 1294,
1
1242, 1214, 1176, 1173, 1074, 1042, 973, 912 cm−1, H NMR (600
MHz, CDCl3): δ = 7.54 (d, 1H, J = 7.8 Hz), 7.64 (t, 1H, J = 7.8 Hz),
7.52 (t, 3H, J = 7.8 Hz), 3.71 (s, 2H), 3.30 (t, 3H, J = 6.3 Hz), 1.70
(t, 4H, J = 3.0 Hz), 1.55 (m, 2H). 13C NMR (150 MHz, CDCl3): δ =
165.4, 134.6, 133.2, 129.5, 128.9, 47.0, 42.1, 26.1, 25.4, 24.3. MS (EI,
70 ev) m/z: 189 (22%), 147 (48), 112 (100), 105 (48), 99 (21), 85 (57),
77 (17).
Morpholino(phenyl)methanone (7i): Colourless oil, IR (KBr):
3416, 2968, 2922, 2862, 1675, 1640, 1595, 1494, 1466, 1448, 1389,
1364, 1291, 1272, 1219, 1179, 1113, 1066, 982, 932, 870, 840, 802,
732 cm−1. 1H NMR (600 MHz, CDCl3): δ = 7.96 (d, 2H, J = 7.2 Hz),
7.66 (t, 2H, J = 7.2 Hz), 7.53 (t, 2H, J = 7.8 Hz), 3.80 (t, 4H, J = 7.8
Hz), 3.66 (t, 2H, J = 5.4Hz), 3.39 (t, 2H, J = 4.8 Hz). 13C NMR (150
MHz, CDCl3): δ = 191.1, 165.4, 134.9, 132.9, 129.6, 129.0, 66.7,
66.6, 46.2, 41.5. MS (EI, 70 ev) m/z: 191 (25%), 105 (100), 77 (35).
2-(4-Methoxyphenylcarbonyl)-5-(4-methoxyphenyl)-oxazole (5a):
M.p. 145–146 °C (lit.39 153–155 °C). IR (KBr): 3443, 3126, 2977,
2836, 1645, 1598, 1567, 1482, 1424, 1306, 1248, 1157, 1069, 952,
828, 772 cm−1. 1H NMR (400 MHz, CDCl3): δ = 8.53 (d, 2H, J = 8.8
Hz), 7.76 (d, 2H, J = 8.4 Hz), 7.48 (s, 1H), 7.00 (t, 4H, J = 8.4 Hz),
3.88 (d, 2H, J = 15.6 Hz). 13C NMR (100 MHz, CDCl3): δ = 177.0,
164.1, 160.9, 156.8, 154.0, 133.2, 128.3, 127.0, 122.3, 119.5, 114.5,

JOURNAL OF CHEMICAL RESEARCH 2011 301
3,4-Dichloro-N-ethylbenzamide (8a): M.p. 92–93 °C (lit.44 97–
98 °C). IR (KBr): 3319, 3076, 2972, 2934, 1635, 1596, 1550, 1467,
1437, 1320, 1241, 1169, 1145, 1128, 1030, 897 cm−1. 1H NMR (400
MHz, CDCl3): δ = 7.86 (d, 1H, J = 1.6 Hz), 7.6–7.58 (m, 1H), 7.47 (d,
1H, J = 8.4 Hz), 6.44 (br s, 1H), 3.47 (m, 2H), 1.25 (t, 3H, J = 7.2 Hz).
13C NMR (100 MHz, CDCl3): δ = 165.3, 135.6, 134.5, 132.9, 130.5,
129.1, 126.0, 35.1, 14.7. MS (EI, 70 ev) m/z: 219 (M+1, 19%), 218
(M, 27), 217 (M-1, 31), 216 (M-2, 39), 174 (61), 172 (100), 144 (32),
108 (18).
Received 23 February 2011; accepted 27 April 2011
Paper 1100589 doi: 10.3184/174751911X13053065216840
Published online: 1 June 2011
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908, 851 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.63 (d, 2H, J = 8.4
Hz), 7.55 (d, 2H, J = 8.4 Hz), 6.18 (br s, 1H), 3.48 (m, 2H, J = 6.8 Hz),
1.25 (t, 3H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): δ = 166.4,
133.6, 131.7, 128.4, 125.9, 35.0, 14.8. MS (EI, 70 ev) m/z: 229
(M+1,31%), 228 (M, 47), 227 (M-1, 33), 182 (100), 156 (34).
N-ethyl-4-methylbenzamide (8d): M.p. 90–91 °C (lit.47 96–98 °C).
IR (KBr): 3259, 3066, 2972, 2934, 2877, 1628, 1549, 1508, 1473,
1357, 1302, 1145, 1104, 962 cm−1. 1H NMR (400 MHz, CDCl3): δ =
7.67 (d, 2H, J = 8.4 Hz), 7.18 (d, 2H, J = 8.0 Hz), 6.49 (br s, 1H),
3.48–3.44 (m, 2H), 2.37 (s, 3H), 1.24–1.20 (m, 3H). 13C NMR
(100 MHz, CDCl3): δ = 167.4, 141.5, 131.8, 129.0, 126.8, 34.7, 21.3,
14.8. MS (EI, 70 ev) m/z: 163 (39%), 162 (39), 119 (100), 91 (46),
65 (15).
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N-ethylpiperonylamide (8e): M.p. 80–81 °C (lit.48 87–88 °C). IR
(KBr): 3311, 3077, 2971, 2934, 2905, 1639, 1605, 1550, 1508, 1488,
1436, 1359, 1309, 1251, 1172, 1146, 1122s, 1098s, 1083, 1040, 920,
1
916, 880 cm−1. H NMR (400 MHz, CDCl3): δ =7.31–7.28 (m, 2H),
6.79 (d, 1H, J = 8.0 Hz), 6.24 (br s, 1H), 3.49–3.42 (m, 2H), 1.22 (t,
3H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): δ = 166.8, 150.0, 147.8,
129.0, 121.3, 107.8, 107.5, 101.5, 34.9, 14.8. MS (EI, 70 ev) m/z: 193
(54%), 192 (37), 149 (100), 121 (29), 65 (11).
4-Ethoxy-N-ethylbenzamide (8f): M.p. 93–94 °C (lit.49 94–96 °C).
IR (KBr): 3309, 2976, 2934, 2892, 1631, 1612, 1575, 1540, 1506,
1
1477, 1452, 1393, 1256, 1183, 1147, 1116, 1046, 923, 853 cm−1. H
NMR (400 MHz, CDCl3): δ = 7.72 (d, 2H, J = 8.8 Hz), 6.90 (d, 2H,
J = 4.8 Hz), 6.09 (br s, 1H), 4.07 (q, 2H, J = 6.8 Hz), 3.51–3.44 (m,
2H), 1.43 (t, 3H, J = 7.2 Hz), 1.24 (t, 3H, J = 7.2 Hz). 13C NMR (100
MHz, CDCl3): δ = 167.0, 161.4, 128.5, 126.8, 114.1, 63.6, 34.8, 15.0,
14.7. MS (EI, 70 ev) m/z: 193 (59%), 192 (45), 149 (100), 121 (89),
93 (19).
N-Ethylthiophene-2-carboxamide (8g): M.p. 65–66 °C (lit.50 75–
77 °C. IR (KBr): 3291, 3072, 2980, 2883, 1611s 1522, 1471, 1418,
1295, 1247, 1150, 1085, 913, 860 cm−1. 1H NMR (400 MHz, CDCl3):
δ = 7.53 (br s, 1H), 7.45 (d, 1H, J = 4.8 Hz), 7.06 (t, 1H, J = 4.8 Hz),
6.30 (br s, 1H), 3.50–3.43 (m, 2H); 1.24 (t, 3H, J = 7.2 Hz). 13C NMR
(100 MHz, CDCl3): δ = 161.8, 139.2, 129.6, 127.8, 127.5, 34.8, 14.8.
MS (EI, 70 ev) m/z: 155 (48%), 122 (18), 110 (100).
N-Ethylfuran-2-carboxamide (8h): M.p. 40–41 °C (lit.51 34–35 °C).
IR (KBr): 3289, 3072, 2980, 2936, 2882, 1611, 1411, 1551, 1471,
1
1418, 1362, 1295, 1247, 1150, 1058, 913, 860 cm−1. H NMR (400
MHz, CDCl3): δ = 7.53 (t, 1H, J = 3.2 Hz), 7.44 (d, 1H, J = 5.2 Hz),
7.06–7.04 (m, 1H), 6.34 (br s, 1H), 3.50–3.43 (m, 2H), 1.23 (t, 1H,
J = 3.6 Hz). 13C NMR (100 MHz, CDCl3): δ = 161.8, 139.2, 129.6,
127.8, 127.5, 34.8, 14.8. MS (EI, 70 ev) m/z: 139 (18%), 110 (100),
83 (10).
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N-ethyl-2-naphthamide (8i): M.p. 120–121 °C (lit.52129–130 °C).
IR (KBr): 3260, 3057, 2976, 2933, 2875, 1622, 1553, 1502, 1453,
1
1431, 1358, 1341, 1203, 1149, 954, 915 cm−1. H NMR (400 MHz,
CDCl3): δ = 8.28 (s, 1H), 7.91–7.81 (m, 4H), 7.58–7.50 (m, 2H), 6.33
(br s,1H), 3.59–3.52 (m, 2H), 1.30 (t, 3H, J = 7.2 Hz). 13C NMR (100
MHz, CDCl3): δ = 167.5, 134.6, 132.6, 132.0, 128.8, 128.4, 127.7,
127.5, 127.2, 126.7, 123.5, 35.0, 14.9. MS (EI, 70 ev) m/z: 200 (M+1,
8%), 199 (M, 62), 198 (M-1, 51), 155 (100), 127 (86).
We thank the National Natural Science Foundation of China
(Grant No. 20872042 and 21032001) for founding and
the research was supported in part by the PCSIRT (No.
IRT0953).
51 K. Kiyoshi, S. Tsunetaka and I. Masamichi, Yakugaku Zasshi, 1960, 80,
58.
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1484.

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