Highly efficient synthesis of amides from ketoximes using trifluoromethanesulphonic anhydride

Article abstract of DOI:10.1039/c5ra07789c

Trifluoromethanesulphonic anhydride (triflic anhydride: TA) has been successfully used as a reagent for Beckmann rearrangement in the conversion of a variety of ketoximes into amides without any additive or base. This reagent works well for the synthesis of a library of amides with excellent yields.

Full text of DOI:10.1039/c5ra07789c

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Highly efficient synthesis of amides from ketoximes
using trifluoromethanesulphonic anhydride†
Cite this: RSC Adv., 2015, 5, 60106
*
Rajesh G. Kalkhambkar and Hemantkumar M. Savanur
Received 28th April 2015
Accepted 3rd July 2015
Trifluoromethanesulphonic anhydride (triflic anhydride: TA) has been successfully used as a reagent for
Beckmann rearrangement in the conversion of a variety of ketoximes into amides without any additive or
base. This reagent works well for the synthesis of a library of amides with excellent yields.
DOI: 10.1039/c5ra07789c
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their general applicability.27 In spite of all these still there is a
need for simpler and widely applicable method for the synthesis
Introduction
of amides.
Triuoromethanesulfonic anhydride has been an effective
Amides are highly signicant precursors for the synthesis of
various natural products and intermediates for a large number
of medicinally important compounds.1 Of a number of methods
reported for the synthesis of amides, Beckmann rearrangement
is quite effective since it avoids the use of corrosive acid chlo-
rides and has been employed in the industrial production of u-
caprolactam and laurolactam.2 In many cases, this reaction
requires strong Bronsted acids (which act as dehydrating
agents),3 thereby restricting its application to acid sensitive
substrates.
reagent in a number of reactions.28–31 We have demonstrated the
applications of this reagent for the conversion of aldoximes into
nitriles32 and formation of amides from nitriles by Ritter reac-
tion.33 In continuation of our work, the present paper illustrate
the utility of triic anhydride in Beckmann transformations.
Results and discussion
For optimization of reaction conditions benzophenone oxime
was selected as the model substrate to study the effect of
solvent, temperature and reaction time on the overall yield of
the reaction (Table 1). Reaction of equimolar quantities of
benzophenone oxime 12a and TA was attempted in methanol
under reux conditions. The yield of the product was very low in
this case (Table 1, entry 1). Solvents such as ethanol, acetonitrile
and acetone, were suitable for this reagent but to our disap-
pointment only 39–65% of product was isolated even aer 8 h
under reux conditions (Table 1, entries 2–4). Further, when we
used CCl4, reaction did not proceed even aer 12 h under reux
conditions (Table 1, entry 5) and very poor conversion of the
product was observed in THF and in dioxane (Table 2, entries 6
and 7). Reaction in dipolar aprotic solvents and high boiling
aromatic solvents were not effective which are reected in low
percentage of the transformation (Table 1, entries 8–10).
Serendipitously, excellent isolated yield (96%, Table 1, entry 11)
at a shorter reaction time (2.5 h) was realized when the reaction
was carried out at room temperature in DCM. On the other
hand, the same reaction was completed in 2 h at reux mode
with 98% of isolated yield. In order to evaluate the inuence of
other chlorinated solvent in this reaction, ethylene dichloride
(EDC) was tried. With EDC, 93% conversion and 81% isolated
yield are achieved in 3 h at rt while at reux mode, conversion
and isolated yield noticed are 98% and 87% respectively in 2.4 h
(Table 1, entry 12). On the grounds of obtained results and
carcinogenic nature (class 2) with EDC, we have demonstrated
A survey of literature reveals application of various tech-
niques and reagents for the synthesis of amides. Methods
involving vapour phase,4 solvent free conditions,5 supercritical
water,6 ionic liquids,7–9 liquid phase conditions,10–12 and
microwave irradiation on silica support have been reported.13
Heterogeneous reaction conditions that are facilitated by sup-
ported reagents on solid surfaces have also been developed to
bring about Beckmann rearrangement with certain
limitations.14
Metal salts like Ga(OTf)3,15 Sc(OTf)3,16 Cu(OAc)2,17 TiCl4,18 and
In/Zn couple19 have also been found to be effective in this
reaction. Organic acids or reagents capable of acting as better
leaving groups constitute a major group which includes sulfa-
mic acid,20 chlorosulfonic acid,21 anhydrous oxalic acids,22 O-
alkyl DMF salt,23 CF3COOH,24 triuoromethanesulfonic acid,25
and pivaloyl chloride-DMF complex.26 However, some of these
variants suffer from drawbacks such as toxicity, expensive
reagents, and production of considerable amounts of by-
products. In addition, these reactions also require longer reac-
tion times, high temperature and produce low yields. Though,
enzymatic methods are also available, their isolation costs and
application to limited substrates can present challenges for
Department of Chemistry, Karnatak, University's Karnatak Science College, Dharwad,
Karnatak 580001, India. E-mail: rgkalkhambkar@gmail.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra07789c
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the said Beckmann rearrangement in DCM as the only choice of This showed the nature of substituent (either electron with-
the solvent for rest of the substrates. drawing or electron donating) has no effect on the reactivity of
Further, the effect of the reaction temperature and time has TA for the Beckmann rearrangement. Furthermore, we were
also been investigated. Based on the observations it shows that, successful to convert oxime of 2-acetyl thiophene to thiophene-
increase in the reaction temperature and time is propitious to 2-yl acetamide in 4.5 h with 86% isolated yield (Table 2, entry
the increasing yield of product (Table 1, entries 11 and 12).
19) via Beckmann rearrangement. But to our disappointment,
The successful synthesis of N-benzylbenzamide in DCM reaction did not proceed with oxime of 3-acetyl coumarin even
prompted us to investigate the applicability of this procedure aer 12 h (Table 2, entry 20).
for the synthesis of other amides via Beckmann rearrangement
of variety of ketoximes (see Scheme 1).
Thus, the Beckmann rearrangement of wide range of struc-
turally varied ketoximes in the presence of TA was carried out
A similar trend of reaction was observed in the Beckmann under the optimized reaction conditions described above. The
rearrangement of acetoxime to the corresponding N-methyl- results (Table 2) show that a variety of structurally varied
acetamide (Table 2, entry 1). The reaction was completed in 2 h ketoximes rearranged smoothly in DCM to give the corre-
with 72% isolated yield. Further, we have also carried out the sponding amides in excellent yields (72–96%).
synthesis of piperidine-2-one in 78% isolated yield by the ring
However, under optimized reaction conditions, the reaction
enlargement of cyclopentanone oxime (Table 2, entry 2). In did not proceed when we subjected oximes of propiophenone,
addition, we were also successful in synthesizing 2-azepanone 2-methyl propiophenone, 1-(pyridine-2-yl)propanone, and 1-
(u-caprolactam) by the ring enlargement of cyclohexanone (pyridine-3-yl)propanone for Beckmann rearrangement even
oxime (Table 2, entry 3). Based on the qualitative analysis by GC aer 12 h under reux conditions (Table 2, entries 21–24).
and GC-MS (Table 1, optimization study), it could be known that
The plausible mechanism of formation of various amides is
their main by-products were the corresponding ketones and depicted in Fig. 1.
only trace amounts of dimeric oximes were observed (0.2–0.3%).
A plausible explanation for reaction mechanism is discussed
Much better results could be obtained if different substituted in Fig. 1. The hydroxyl group of the oxime 1 reacts with TA
aryl ketoximes were used as substrates in Beckmann results in the formation of O-trifyloxime 2 which undergoes
rearrangement.
intramolecular rearrangement leading to the formation of
To generalize the applicability of this method on the nature reactive intermediate nitrile 3. The conversion of 2–3 proceeds
of substitution, we also carried out the Beckmann rearrange- through a concerted 1,2 intramolecular shi. The subsequent
ment of substituted acetophenone oximes to the corresponding reaction of reactive intermediate 3 with O-Triate (OT) affords
amides (Table 2, entries 4–11). All the reactions were completed the formation of O-trifylimine 4 which upon hydrolysis losses
in 1.5 to 3.5 h with 92–96% isolated yield and 99% selectivity. triic acid leading to the formation of amide 5.
Table 1 Optimization of the reaction conditionsa
Entry
Solvent
Time (h)
Temp (ꢀ C)
Conversionb (%)
Yieldc (%)
1
2
3
4
5
6
7
8
MeOH
EtOH
MeCN
Acetone
CCl4
9
8
7
8
12
6
10
8
Reux
Reux
Reux
Reux
Reux
Reux
110
110
140
130
rt
38
55
62
70
Nil
54
34
28
35
27
39
54
65
None
43
26
THF
Dioxane
PhMe
DMF
DMSO
DCM
NIg
NIg
NIg
96, 98f
81, 87f
9
5
7
10
11
12
30
2.5, 2d
3, 2.4d
100
EDC
rt
93, 98e
a
Reaction carried out using compound 12a (2.0 mmol) and Triic anhydride (2.0 mmol) in 5 mL of solvent, unless otherwise stated. b Conversion
c
d
e
(%) of product based on GC analysis. Isolated yield of pure product. Reaction time in reux condition. Conversion (%) of product in reux
condition. f Isolated yield of pure product in reux condition. g Not isolated.
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Table 2 List of amides synthesized using TAd
Entry
1
Oximes
Product
Conversion (%)
74
Selectivity (%)
98
Time (h)
3
Yielda
72
2
3
80
86
98
99
3
4
78
82
4
99
99
99
99
99
98
99
98
2.5
2.5
1.5
2
96 (87b)
92 (81b)
96
5
100
100
99
6
7
94
8
99
3
94
9
99
3.5
2.5
95
10
99
90
11
12
99
98
99
3.5
2.5
92
96
100
13
14
100
100
99
99
3
3
88
90
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Table 2 (Contd.)
Entry
Oximes
Product
Conversion (%)
100
Selectivity (%)
99
Time (h)
Yielda
87
15
4
16
99
99
2.5
86
17
18
19
99
99
99
99
2
90
85
86
99
3
100
4.5
20
21
22
23
—
—
—
—
—
—
—
—
12
12
12
12
NRc
NRc
NRc
NRc
24
—
—
12
NRc
a
b
c
Isolated yield of pure product. The reaction was carried out in EDC. No reaction. d Note: (1) Identity of the products 4–11 was conrmed by
acetylation of corresponding amines except in the case of entry 7 which was conrmed by the nitration of acetanilide. (2) In the case of entry 13
and 14 migration of p-uorophenyl and p-bromophenyl moiety was conrmed by the IR carbonyl frequency and melting point with the
literature Reports.34–37
Under the optimized set of reaction conditions, different
ketoximes (1–19) having varying structural features were reacted
Experimental
with TA to afford corresponding amides in excellent yields via
Beckmann rearrangement.
In summary, we have identied new, convenient, and highly
efficient reagent which rearrange various ketoximes into amides
with good to excellent yields.
The reagents employed were of high purity commercial
samples which were used as received (Fischer, Merck and
Sigma Aldrich). Reactions were carried out in oven-dried RB
ask. Column chromatography was performed on silica gel
(200–400 mesh). TLC was performed on alumina silica gel
60F254 (Fischer) detected by UV light (254 nm) and iodine
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Characterization data of various amides
N-Methylacetamide (1).1–6 Yield: 170 mg (72%); colorless
liquid, MP ¼ 204–206 ꢀC; Rf: 0.48 (80 : 20 hexane : EtOAc,
1
Iodine vapors); IR (KBr): 3345, 1660, 1246, 1028, 822 cmꢃ1. H
NMR (300 MHz, DMSO-d6): d ¼ 2.18 (s, 3H, CH3), 2.83 (s, 3H,
CH3), 10.31 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 168.2,
28.7, 23.4 GC-MS: m/z 73 [M]+. Anal. calc. for C3H7NO: C, 49.30;
H, 9.65; N, 19.16% found: C, 49.28; H, 9.62; N, 19.15%.
Scheme 1 Synthesis of different substituted amides via Beckmann
rearrangement.
Piperidin-2-one (2).1–3,5 Yield: 190 mg (73%); colorless liquid,
MP ¼ 257–259 ꢀC; Rf: 0.37 (80 : 20 hexane : EtOAc, iodine
1
vapors); IR (KBr): 3342, 1672, 1541, 1308, 1132, 796 cmꢃ1. H
NMR (300 MHz, DMSO-d6): d ¼ 1.62 (m, 4H), 2.34 (m, 2H), 3.36
(m, 2H), 10.44 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼
169.1, 38.8, 36.2, 26.5, 24.2. GC-MS: m/z 99 [M]+. Anal. calc. for
C5H9NO: C, 60.58; H, 9.15; N, 14.13% found: C, 60.57; H, 9.14;
N, 14.13%.
u-Caprolactam (3).1–6 Yield: 230 mg; colorless solid, MP ¼
1
ꢀ
68–71 C; Rf: 0.51 (80 : 20, hexane : EtOAc, iodine vapors); H
NMR (300 MHz, DMSO-d6): d ¼ 1.2 (m, 2H, CH2), 1.55 (m, 2H,
CH2), 2.15 (m, 2H, CH2), 2.44 (m, 2H, CH2), 10.08 (s, 1H, NH).
13C NMR (75 MHz, DMSO-d6): d ¼ 179.2, 39.2, 35.8, 30.1, 29.6,
21.8. GC-MS: m/z 113 [M] +. Anal. calc. for C6H11NO: C, 63.68; H,
9.80; N, 12.38% found; C, 63.70; H, 9.78; N, 12.35%.
Fig. 1 Plausible mechanism of formation of amides using TA via
Beckmann rearrangement.
N-Phenylacetamide (4).1–6 Yield: 288 mg (96%); colorless
ꢀ
solid, MP ¼ 114–116 C; Rf: 0.47 (95 : 5, DCM : MeOH, UV); IR
vapors. The melting points were determined by open capil-
laries on a Buchi apparatus and are uncorrected. The IR spectra
were recorded on a Nicolet-Impact-410 FT-IR spectrometer,
using KBr pellets. 1H NMR and 13C NMR spectra were recorded
on a Bruker AC-300F, 300 MHz, spectrometer in DMSO-d6 using
(KBr): 3351, 3031, 1669, 1582, 1530, 1474, 1421, 1285, 1230, 698
cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 2.48 (s, 3H, CH3), 7.75
(m, 5H), 10.15 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼
167.1, 138.8, 128.3, 127.6, 124.1, 121.9, 121.6, 22.9. GC-MS: m/z
135 [M]+. Anal. calc. for C8H9NO: C, 71.09; H, 6.71; N, 10.36%
found: C, 71.07; H, 6.70; N, 10.34%.
1
TMS as an internal standard with H resonance frequency of
300 MHz, 13C resonance frequency of 75 MHz. GC analyses
were performed on Nucon 5700 series Gas chromatograph. GC-
MS analyses were performed on Shimadzu 2010 series mass
selective detector instrument. Elemental analysis was carried
out by using Heraus CHN rapid analyzer. All the compounds
gave C, H and N analysis within ꢁ0.4% of the theoretical
values. Dry DCM was obtained from commercial source by the
standard procedure.
N-p-Tolylacetamide (5).1–4 Yield: 245 mg (92%); colorless
ꢀ
solid, MP ¼ 145–148 C; Rf: 0.35 (98 : 2, DCM : MeOH, UV); IR
(KBr): 3331, 1665, 1573, 1394, 1310, 921, 719 cmꢃ1. 1H NMR (300
MHz, DMSO-d6): d ¼ 2.32 (s, 3H, CH3), 2.38 (s, 3H, CH3), 6.87 (d,
2H, J ¼ 8.5 Hz), 7.42 (d, 2H, J ¼ 8.5 Hz), 10.34 (s, 1H, NH). 13
C
NMR (75 MHz, DMSO-d6): d ¼ 168.4, 142.5, 135.2, 129.6, 122.1,
22.8, 24.6. GC-MS: m/z 149 [M]+. Anal. calc. for C9H11NO: C,
72.46; H, 7.43; N, 9.39% found: C, 72.45; H, 7.41; N, 9.40%.
N-(4-Methoxyphenyl)acetamide (6).1,3,4 Yield: 286 mg (96%);
colorless solid, MP ¼ 130–132 ꢀC; Rf: 0.48 (95 : 5 DCM : MeOH,
1
UV); IR (KBr): 3341, 1669, 1576, 1343, 1320, 887, 689 cmꢃ1. H
Typical procedure for the synthesis of amides using triic
NMR (400 MHz, DMSO-d6): d ¼ 2.37 (s, 3H, CH3), 3.86 (s, 3H,
OCH3), 6.89 (d, 2H, J ¼ 8.5 Hz), 7.46 (d, 2H, J ¼ 8.5 Hz), 9.97 (s,
1H, NH). 13C NMR (100 MHz, DMSO-d6): d ¼ 169.6, 154.5, 134.2,
130.2, 122.6, 56.4, 22.6. GC-MS: m/z 165 [M]+. Anal. calc. for
C9H11NO2: C, 65.44; H, 6.71; N, 8.48% found: C, 65.42; H, 6.70;
N, 8.47%.
anhydride
The desired ketoxime (2.0 mmol) in 5 mL dry DCM was taken in
an oven-dried RB ask. To the reaction mixture was added drop
wise triic anhydride (2.0 mmol) in DCM (5 mL) under nitrogen
for 10 to 15 minutes. The reaction mixture was stirred at RT and
the progress of the reaction was monitored by TLC and GC-MS
(Table 2). Aer completion of reaction, the contents were
poured to crushed ice (100 mL) and neutralized with 10%
NaHCO3 solution (20 mL) and extracted with DCM (15 mL ꢂ 3).
The pure products were obtained by column chromatography
with hexane–ethyl acetate and DCM–methanol mixture. All the
amides were characterized by IR, GC-MS, 1H NMR, 13C NMR
and by elemental analysis and the results are compared with
authentic samples.
N-(4-Nitrophenyl)acetamide (7).1–4 Yield: 266 mg (94%); pale
ꢀ
yellow solid, MP ¼ 215–218 C; Rf: 0.25 (95 : 5, DCM : MeOH,
1
UV); IR (KBr): 3320, 1667, 1565, 1380, 1302, 829, 834 cmꢃ1. H
NMR (400 MHz, DMSO-d6): d ¼ 2.30 (s, 3H, CH3), 7.84 (d, 2H, J ¼
9.0 Hz), 8.40 (d, 2H, J ¼ 9.0 Hz), 10.12 (s, 1H, NH). 13C NMR (100
MHz, DMSO-d6): d ¼ 169.1, 145.7, 142.8, 124.6, 122.1, 22.2. GC-
MS: m/z 180 [M]+. Anal. calc. For C8H8N2O3: C, 53.33; H, 4.48; N,
15.55% found: C, 53.32; H, 4.46; N, 15.54%.
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N-(4-Aminophenyl)acetamide (8).1,2,4,6 Yield: 285 mg (94%);
Hz), 7.58 (m, 2H), 7.72 (d, 2H, J ¼ 9.0 Hz), 8.16 (m, 3H), 10.28 (s,
1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 164.5, 159.4, 136.2,
132.6, 130.7, 129.8, 129.0, 128.5, 128.1, 127.2, 123.8, 123.2,
118.4. GC-MS: m/z 275 [M ꢃ 1]+, 277 [M + 1]+2 Anal. calc. for
colorless solid, MP ¼ 165–167 ꢀC; Rf: 0.34 (95 : 5, DCM : MeOH,
1
UV); IR (KBr): 3340, 1672, 1580, 1323, 1314, 857, 670 cmꢃ1. H
NMR (300 MHz, DMSO-d6): d ¼ 2.27 (s, 3H, CH3), 6.68 (d, 2H, J ¼
8.5 Hz), 7.42 (d, 2H, J ¼ 8.5 Hz), 10.18 (s, 1H, NH). 13C NMR (75
MHz, DMSO-d6): d ¼ 170.2, 142.5, 130.6, 122.8, 118.3, 22.8. GC-
MS: m/z 150 [M]+. Anal. calc. For C8H10N2O: C, 63.98; H, 6.71; N,
18.65% found: C, 63.97; H, 6.70; N, 18.66%.
C
13H10BrNO: C, 56.55; H, 3.65; N, 5.07% found: C, 56.53; H,
3.64; N, 5.05%.
N-(4-Nitrorophenyl)benzamide (15).1,2 Yield: 256 mg (87%);
pale yellow solid, MP
¼
202–204 ꢀC; Rf: 0.611 (98 : 2,
N-(4-Chlorophenyl)acetamide (9).1–3 Yield: 288 mg (95%);
colorless solid, MP ¼ 176–178 ꢀC; Rf: 0.33 (95 : 5, DCM : MeOH,
DCM : MeOH, UV); IR (KBr): 3333, 1650, 1563, 1325, 1312, 1280,
945, 780, 694 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 7.56 (m,
5H), 7.80 (d, 2H, J ¼ 8.5 Hz), 8.34 (d, 2H, J ¼ 8.5 Hz), 9.80 (s, 1H,
NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 164.6, 148.2, 142.2,
132.6, 131.1, 129.8, 129.3, 128.7, 128.1, 127.4, 124.6, 123.4,
121.2. GC-MS: m/z 242 [M]+. Anal. calc. for C13H10N2O3: C, 64.46;
H, 4.16; N, 11.56% found: C, 64.45; H, 4.16; N, 11.54%.
N-(2-Methoxyphenyl)acetamide (16).1,3,4 Yield: 248 mg (86%);
colorless solid, MP ¼ 87–90 ꢀC; Rf: 0.611 (98 : 2, DCM : MeOH,
UV); IR (KBr): 3340, 3331, 1674, 1580, 1520, 1466, 1411, 1280,
1230, 792 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 2.42 (s, 3H,
CH3), 3.86 (s, 3H, OCH3), 6.96 (m, 4H), 10.25 (s, 1H, NH). 13C
NMR (75 MHz, DMSO-d6): d ¼ 171.1, 153.2, 126.3, 124.1, 121.9,
121.6, 113.4, 56.8, 22.9. GC-MS: m/z 165 [M]+. Anal. calc. for
C8H9NO: C, 71.09; H, 6.71; N, 10.36% found: C, 71.08; H, 6.71;
N, 10.35%.
1
UV); IR (KBr): 3342, 1670, 1590, 1353, 1322, 890, 667 cmꢃ1. H
NMR (400 MHz, DMSO-d6): d ¼ 2.38 (s, 3H, CH3), 7.42 (d, 2H, J ¼
9.0 Hz), 7.60 (d, 2H, J ¼ 9.0 Hz), 10.28 (s, 1H, NH). 13C NMR (100
MHz, DMSO-d6): d ¼ 168.4, 138.8, 130.9, 129.4, 124.3, 23.4. GC-
MS: m/z 169 [M]+. Anal. calc. For C8H8ClNO: C, 56.65; H, 4.75; N,
8.26% found: C, 56.66; H, 4.74; N, 8.25%.
N-(4-Bromophenyl)acetamide (10).1,2 Yield: 268 mg (90%);
ꢀ
brown solid, MP ¼ 163–165 C; Rf: 0.34 (95 : 5, DCM : MeOH,
1
UV); IR (KBr): 3336, 1665, 1570, 1323, 1310, 812, 654 cmꢃ1. H
NMR (400 MHz, DMSO-d6): d ¼ 2.18 (s, 3H, CH3), 7.40 (d, 2H, J ¼
9.0 Hz), 7.68 (d, 2H, J ¼ 9.0 Hz), 9.98 (s, 1H, NH). 13C NMR (100
MHz, DMSO-d6): d ¼ 169.2, 138.8, 131.2, 125.4, 121.3, 23.8. GC-
MS: m/z 213 [M ꢃ 1]+, 215 [M + 1]+ Anal. calc. for C8H8BrNO: C,
44.89; H, 3.77; N, 6.54% found: C, 44.88; H, 3.75; N, 6.55%.
N-(4-Fluorophenyl)acetamide (11).1,2 Yield: 280 mg (92%);
colorless solid, MP ¼ 153–155 ꢀC; Rf: 0.38 (95 : 5, DCM : MeOH,
N-(3-Methoxyphenyl)acetamide (17).3,4 Yield: 265 mg (90%);
colorless solid, MP
¼
103–105 ꢀC; Rf: 0.514 (98 : 2,
1
UV); IR (KBr): 3330, 1668, 1530, 1345, 1312, 845, 656 cmꢃ1. H
DCM : MeOH, UV); IR (KBr): 3338, 1670, 1540, 1530, 1468, 1421,
1230, 1218, 754 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 2.36 (s,
3H, CH3), 3.92 (s, 3H, OCH3), 6.72 (d, 2H, J ¼ 8.5 Hz), 7.76 (m,
2H), 10.15 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 170.6,
161.5, 140.4, 131.6, 114.4, 110.3, 105.6, 55.4, 24.1. GC-MS: m/z
165 [M]+. Anal. calc. for C8H9NO: C, 71.09; H, 6.71; N, 10.36%
found: C, 71.07; H, 6.71; N, 10.34%.
NMR (400 MHz, DMSO-d6): d ¼ 2.10 (s, 3H, CH3), 7.12 (d, 2H, J ¼
9.0 Hz), 7.80 (d, 2H, J ¼ 9.0 Hz), 10.38 (s, 1H, NH). 13C NMR (100
MHz, DMSO-d6): d ¼ 169.2, 159.8 (C–F, J ¼ 245.20 Hz), 134.3,
124.3, 116.4, 22.8. GC-MS: m/z 153 [M]+. Anal. calc. for
C8H8FNO: C, 62.74; H, 5.26; N, 9.15% found: C, 62.75; H, 5.24;
N, 9.15%.
N-(Naphthalene-2-yl)acetamide (18).5 Yield: 230 mg (85%);
colorless solid, MP ¼ 176–178 ꢀC; Rf: 0.36 (80 : 20, hex-
ane : EtOAc, UV); IR (KBr): 3331, 3020, 1668, 1584, 1530, 1424,
1410, 1235, 1250, 658 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼
2.18 (s, 3H, CH3), 6.75 (m, 2H), 7.10 (m, 2H), 7.89 (m, 3H), 10.10
(s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 170.2, 136.4,
132.4, 127.8, 126.4, 125.8, 124.6, 124.1, 121.9, 118.6, 110.3, 23.2.
GC-MS: m/z 185 [M]+. Anal. calc. for C12H11NO: C, 77.81; H, 5.99;
N, 7.56% found: C, 77.80; H, 5.98; N, 7.54%.
N-Phenylbenzamide (12).1–6 Yield: 285 mg (96%); colorless
ꢀ
solid, MP ¼ 161–163 C; Rf: 0.52 (80 : 20, hexane : EtOAc, UV);
IR (KBr): 3359, 1660, 1580, 1530, 1478, 1420, 1320, 1285, 688
cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 7.35 (m, 2H), 7.62 (m,
3H), 7.86 (m, 2H), 8.10 (m, 3H), 10.32 (s, 1H, NH). 13C NMR (75
MHz, DMSO-d6): d ¼ 166.3, 136.8, 134.8, 132.3, 131.6, 129.1,
128.9, 128.4, 127.6, 122.9, 121.4, 120.6. GC-MS: m/z 197 [M]+.
Anal. calc. for C13H11NO: C, 79.16; H, 5.62; N, 7.10% found: C,
79.17; H, 5.60; N, 7.10%.
N-(4-Fluorophenyl)benzamide (13).1,2,4 Yield: 260 mg (88%);
colorless solid, MP ¼ 169–172 ꢀC; Rf: 0.55 (80 : 20, hex-
ane : EtOAc, UV); IR (KBr): 3341, 1652, 1535, 1325, 1312, 845,
650 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 7.05 (d, 2H, J ¼ 9.0
Hz), 7.54 (m, 2H), 7.68 (d, 2H, J ¼ 9.0 Hz), 7. 95 (m, 3H), 10.18 (s,
1H, NH). 13C NMR (75 MHz, DMSO-d6): d ¼ 166.6, 160.2, (C–F, J
¼ 246.12 Hz), 135.2, 131.6, 130.7, 129.8, 129.3, 128.5, 128.0,
127.4, 124.6, 123.4, 116.8. GC-MS: m/z 215 [M]+. Anal. calc. for
N-(Thiophen-2-yl)acetamide (19). Yield: 230 mg (85%);
colorless solid, MP ¼ 159–161 ꢀC; Rf: 0.36 (97 : 3, DCM : MeOH,
iodine vapors);1 1H NMR (300 MHz, DMSO-d6): d ¼ 2.08 (s, 3H,
CH3), 6.75 (m, 1H), 6.90 (m, 1H), 7.38 (m, 1H), 10.24 (s, 1H, NH).
13C NMR (75 MHz, DMSO-d6): d ¼ 171.3, 144.4, 126.6, 122.4,
112.8, 23.2. GC-MS: m/z 141 [M]+. Anal. calc. for C6H7NOS: C,
51.04; H, 5.00; N, 9.92% found; C, 51.01; H, 4.98; N, 9.90%.
C
13H10FNO: C, 72.55; H, 4.68; N, 6.51% found: C, 72.55; H, 4.66;
Conclusions
N, 6.50%.
N-(4-Bromophenyl)benzamide (14).1–3 Yield: 266 mg (90%);
pale yellow solid, MP ¼ 162–165 ꢀC; Rf: 0.67 (80 : 20, hex-
ane : EtOAc, UV); IR (KBr): 3334, 1656, 1540, 1320, 1332, 840,
760 cmꢃ1. 1H NMR (300 MHz, DMSO-d6): d ¼ 7.36 (d, 2H, J ¼ 9.0
In conclusion, we have successfully demonstrated the conve-
nient method for the synthesis of wide variety of amides from
various ketoximes using triic anhydride. Further work,
including the development of synthetic applications of aryl and
heteroaryl oximes and exploration of the enormous potential of
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triic anhydride as a triyl source in organic synthesis is
underway in our laboratory.
L. Ronchin and A. Vavasori, J. Mol. Catal. A: Chem., 2009,
313, 22.
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Acknowledgements
The authors thank the University Sophisticated Instrument
Center, KUD for IR, GC, GC-MS, 1H NMR and 13C NMR. Thanks
are also due to Department of Science and Technology, Science
and Engineering Research Board New Delhi (DST-SERB) Project
No SB/FT/CS-175/2013 for nancial assistance. Authors also
thank Prof. M. V. Kulkarni for his useful discussion.
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