Citric acid catalysed Beckmann rearrangement, under solvent free conditions

Article abstract of DOI:10.3184/174751911X557296

Citric acid is reported to be a highly efficient and eco-friendly catalyst for the Beckmann rearrangement under solvent free conditions.

Full text of DOI:10.3184/174751911X557296

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124 RESEARCH PAPER
FEBRUARY, 124–125
JOURNAL OF CHEMICAL RESEARCH 2011
Citric acid catalysed Beckmann rearrangement, under solvent free
conditions
Shankar Ramchandra Thopate*, Santosh Rajaram Kote, Sandeep Vasantrao Rohokale and
Nitin Madhukar Thorat
Post Graduate School for Biological Studies, Department of Chemistry, Ahmednagar College, Ahmednagar, Maharashtra, 414001, India
Citric acid is reported to be a highly efficient and eco-friendly catalyst for the Beckmann rearrangement under solvent
free conditions.
Keywords: amides, Beckmann rearrangement, citric acid, eco-friendly catalyst, solvent free conditions
Table 1 Citric acid catalysed Beckmann rearrangement of
Green chemistry has attracted an increasing interest in recent
years1–4 due to the growing concern over environmental pollu-
tion; arising from the use of toxic solvents. The problem may
be addressed by recycling the solvents or using environmen-
tally benign solvents. However, the most promising approach
is to perform organic reactions under solvent-free conditions.
Solvent-free reactions have received considerable attention in
recent years, not only for ecological and economical reasons,
but also for simplicity in procedures, high yields of products
and short reaction times. A number of organic reactions require
acid catalyst which generate toxic waste that is harmful to the
environment. The development of cheap, naturally occurring,
green acid catalyst could change the traditional procedures
into green ones, thus minimising chemical waste further.
As a part of ongoing program related to the development of
a clean and eco-friendly acid catalyst, citric acid was consid-
ered as a possible candidate. It is widely distributed in nature,
and is readily and cheaply available. Beckmann rearrangement
is a powerful tool in organic synthesis5,6 and is also a topic of
current interest. Several acids such as trifluromethanesulfonic
acid,7 chlorosulfonic acid,8 sulfamic acid,9 anhydrous oxalic
acid,10 p-toluenesulfonic acid11 have been employed for this
reaction. However, these methods suffers from certain draw-
backs such as use of toxic/costly solvents, expensive reagents,
co-catalysts, production of considerable amount of by-
products, long reaction time and low yields. Therefore, the
development of a simple, inexpensive, highly efficient yet eco-
friendly catalyst for Beckmann rearrangement is worthwhile.
We report here a simple and highly efficient protocol for
Beckmann rearrangement using citric acid as a green catalyst
under solvent free conditions.
ketoximes under solvent free condition
Entry
R
R′
3 % yielda, b
1
2
Ph
Me
93
92
93
72
88
95
90
90
84
85
92
94
90
70
68
97
89
4-Me-C6H4
4-OMe-C6H4
4-Br-C6H4
2-OH-C6H4
2-OMe-C6H4
3-NH2-C6H4
3-NO2-C6H4
Ph
Me
3
Me
4
Me
5
Me
6
Me
7
Me
8
Me
9
Et
10
11
12
13
14
15
16
17
Ph
n-Propyl
n-Propyl
Me
4-OMe-C6H4
Naphth-1-yl
Naphth-2-yl
Thiophene-2-yl
t-Butyl
Me
Me
Me
Ph
4-Me-C6H4
Ph
4-Me-C6H4
a Isolated yield
1
b All the products were identified spectroscopically (IR, H, 13C
NMR and GCMS)
Conclusion
In conclusion, we have shown that citric acid can be used as an
environment-friendly acid catalyst. It efficiently catalyses the
Beckmann rearrangement of a variety of ketoximes into cor-
responding amides under solvent free condition in short time.
The operational simplicity, use of commercially available
natural catalyst, solvent free reaction condition, short reaction
time, easy work up and high yield makes this catalyst a more
convenient alternative to the reported catalysts. Further studies
are in progress to expand the scope of this catalyst in organic
synthesis.
Results and discussion
Initially, acetophenone oxime (1.00 g) (Table 1, Entry 1) and
anhydrous citric acid 2 (1.20 equiv.), were heated at 160 °C
in preheated oil bath for five minutes to afford acetanilide
(0.930 g, 93 % yield). In order to establish the optimum reac-
tion conditions, we examined the effect of the amount of citric
acid on the Beckmann rearrangement of acetophenone oxime.
It was found that 0.33 equivalent citric acid was sufficient to
afford similar results. However, the use of less than 0.33 equiv-
alents of citric acid resulted in low yield of the product along
with the recovery of the starting material. This result showed
that 0.33 equivalent of citric acid was enough for the complete
conversion of the starting material. To check the generality and
scope of this reaction, various ketoximes were subjected to the
Beckmann rearrangement under the above conditions. Result
showed that the Beckmann rearrangement of various ketox-
imes proceeded smoothly to completion within five minutes
to give the corresponding amides in good to excellent yield
(Table 1).
Experimental
Reactions were performed in oven-dried glassware under a N2 atmo-
sphere and were monitored by TLC silica gel plates (60 F254) which
were visualised by UV and KMnO4 solution. All solvents and reagents
were used as obtained from commercial source. The oximes were pre-
pared by standard methods and their purities were established before
1
utilisation by melting point. Standard H NMR and 13C NMR were
recorded on a Varian Mercury spectrometer at 300 and 75 MHz
respectively in CDCl3 solution and with TMS as an internal standard.
IR spectra were recorded on Perkin Elmer Model 1600 series FTIR
instrument. Low resolution mass spectra were recorded on Shimadzu
GC-MS - Q 5050A, connected to GC-17A, at an ionisation potential
70 eV and the fragmentation pattern is given after the corresponding
m/z value.
* Correspondent. E-mail: srthopate@gmail.com

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JOURNAL OF CHEMICAL RESEARCH 2011 125
General procedure: The mixture of ketoxime (1.00 g) and anhy-
drous citric acid (33 mol %) was heated in an oil bath, preheated at
160 °C under nitrogen atmosphere. The reaction commenced with
effervescence and was completed in 5 minutes (TLC check). The
brownish black molten mass was cooled to room temperature, water
(10.00 mL) and ethyl acetate (10.00 mL) were added. Reaction mix-
ture was neutralised by addition of solid NaHCO3. Organic layer was
separated and the aqueous layer was extracted in ethyl acetate (2 ×
10.00 mL). Combined organic extract was dried over anhydrous
sodium sulfate and concentrated in vacuo. The crude product was
purified by column chromatography on silica gel using hexane-ethyl
acetate solvent system to give the corresponding amide in high yield.
Acetanilide (entry 1): M.p. 113–114 °C (lit.12,13 m.p. 114 °C); IR ν˜:
3295, 2856, 1663, 1599, 1500, 909, 848, 757 cm−1; 1H NMR
(300 MHz, CDCl3): δ 2.14 (3H, s), 7.09 (1H, t, J = 7.5 Hz), 7.28 (2H,
m), 7.53 (2H, m), 8.34 (1H, s); 13C NMR (75 MHz, CDCl3): δ 24.2
(CH3), 120.1 (2 × CH), 124.1 (CH), 128.7 (2 x CH), 137.9 (C), 169.0
(–CONH–); GC-MS (%): 135 (M+, 28), 93 (100), 77 (5), 66 (20),
43 (24).
(CH3), 19.0 (CH2), 39.2 (CH2), 55.3 (O–CH3), 113.8 (2 x CH), 121.8
(2 x CH), 131.1 (C), 156.1 (C), 171.5 (–CONH–).
N-(1-Naphthyl)acetamide (entry 12): M.p. 162–163 °C (lit.12 m.p.
163 °C); IR ν˜: 3271, 3051, 1655, 1551, 1505, 1280, 792, 774, 721,
760 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.20 (3Η, s), 7.34–7.82 (7H,
m), 7.90 (1H, s ); 13C NMR (75 MHz, CDCl3): δ 23.9 (CH3), 121.0
(CH), 121.6 (CH), 125.5 (CH), 125.8 (CH), 125.9 (CH), 126.0 (CH),
127.5 (C), 128.5 (CH), 132.2 (C), 133.9 (C), 169.3 (–CONH–).
N-(2-Naphthyl)acetamide (entry 13): M.p. 170–171 °C (lit.12 m.p.
171 °C); IR ν˜: 3285, 3209, 1667, 1589, 1560, 1354, 1283, 885, 858,
817, 750 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.16 (3H, s), 7.39 (3H,
m), 7.70 (3H, m), 8.15 (1H, s), 8.24 (1H, s); 13C NMR (75 MHz,
CDCl3): δ 24.4 (CH3), 116.8 (CH), 120.0 (CH), 124.9 (CH), 126.3
(CH), 127.4 (CH), 127.5 (CH), 128.5 (CH), 130.5 (C), 133.6 (C),
135.3 (C), 169.1 (–CONH–).
N-(2-Thiophenyl)acetamide (entry 14): M.p. 150–152 °C. 1H NMR
(300 MHz, CDCl3 /DMSO): δ 2.14 (3H, s), 6.73 (1H, m), 6.79 (2H,
m), 10.69 (1H, s); 13C NMR (75 MHz, CDCl3/DMSO): δ 22.2 (CH3),
110.4 (CH), 116.1 (CH), 123.2 (CH), 139.4 (C), 166.4 (–CONH–).
2,2-Dimethyl-N-acetylethylamine (entry 15): M.p. 95–97 °C; IR ν˜:
N-(4-Methylphenyl)acetamide (entry 2): M.p. 145–146 °C (lit.14
m.p. 149–150 °C); IR ν˜: 3293, 3122, 2944, 1666, 1604, 1454, 821,
1
3285, 3208, 3082, 2966, 1639, 1557, 1225, 1038, 721, 611 cm−1; H
NMR (300 MHz, CDCl3): δ 1.34 (9H, s), 1.91(3H, s), 5.57 (1H, s); 13
C
1
753 cm−1; H NMR (300 MHz, CDCl3): δ 2.10 (3H, s), 2.28 (3H, s),
7.06 (2H, d, J = 8.4 Hz), 7.37 (2H, d, J = 8.4 Hz), 8.21 (1H, s); 13C
NMR (75 MHz, CDCl3): δ 20.7 (CH3), 24.2 (CH3), 120.1 (2 x CH),
129.3 (2 × CH), 133.7 (CH), 135.3 (CH), 168.7 (–CONH–); GC-MS
(%): 149 (M+, 40), 107 (100), 91 (6), 77 (22), 65 (5), 43 (24).
N-(4-Methoxyphenyl)acetamide (entry 3): M.p. 130 °C (lit.12 m.p.
130 °C); IR ν˜: 3243, 2836, 1648, 1514, 1369, 1247, 1031, 839, 768
cm−1; 1H NMR (300 MHz, CDCl3): δ 2.09 (3H, s), 3.75 (3H, s), 6.79
(2H, d, J = 6.8 Hz), 7.39 (2H, d, J = 6.8 Hz), 8.28 (1H, s); 13C NMR
(75MHz, CDCl3): δ 23.9 (CH3), 55.3 (O-CH3), 113.8 (2 x CH), 122.0
(2 x CH), 131.1 (C), 156.2 (C), 168.8 (–CONH–); GC-MS (%): 165
(M+, 45), 123 (58), 108 (100), 95 (10), 80 (15), 65 (5), 43 (24).
N-(4-Bromophenyl)acetamide (entry 4): M.p. 165–167 °C (lit.12 m.
p. 167 °C); IR ν˜: 3300, 3115, 1667, 1600, 1530, 831, 741, 504 cm−1;
1H NMR (300 MHz, CDCl3): δ 1.71 (1H, s), 2.17 (3H, s), 7.38–7.44
(4H, m); 13C NMR (75 MHz, CDCl3): δ 24.5 (CH3), 116.8 (C), 121.3
(2 x CH), 131.9 (2 x CH), 136.9 (C), 168.3 (–CONH–); GC-MS (%):
213, 215 (M+, M++2, 1:1, 29), 169, 171 (1:1, 100), 92 (55), 65 (35),
63 (24).
NMR (75 MHz, CDCl3): δ 24.3 (CH3), 28.6 (3 x CH3), 51.0 (C), 169.5
(–CONH–); GC-MS (%): 115 (M+, 10), 71 (15), 58 (100), 42 (20),
27 (10).
Benzanilide (entry 16): M.p. 161–162 °C (lit.12 m.p. 162 °C); IR: ν˜:
3344, 3051, 1656, 1600, 1529, 1524, 1442, 1323, 925, 790, 725, 717
1
cm−1; H NMR (300 MHz, CDCl3): δ 7.10–7.20 (1H, m), 7.32–7.40
(2H, m), 7.41–7.58 (3H, m), 7.60–7.70 (2H, m), 7.60–7.92 (2H, m),
7.97 (1H, s); 13C NMR (75 MHz, CDCl3): δ 120.2 (2 x CH3), 124.5
(CH), 126.9 (2 x CH), 128.7 (2 x CH3), 129.0 (2 x CH3), 131.7 (CH),
134.9 (C), 137.8 (C), 165.7 (–CONH–) ; GC-MS (%): 197 (M+, 25),
105 (100), 77 (80), 65 (10), 51 (15).
N-(4-Methylphenyl)p-methylbenzanilide (entry 17): M.p. 158–160
°C (lit.12 m.p. 160 °C); IR ν˜: 3349, 3038, 1649, 1599, 1522, 814, 750,
704, 667 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.30 (3H, s), 2.36 (3H,
s), 7.09 (2H, d, J = 7.6 Hz), 7.16 (2H, d, J = 7.6 Hz), 7.49 (2H, d, J =
7.6 Hz), 7.71 (2H, d, J = 7.6 Hz), 8.13 (1H, s); 13C NMR (75 MHz,
CDCl3): δ 20.8 (CH3), 21.3 (CH3), 120.3 (2 x CH), 127.0 (2 x CH),
129.1 (2 x CH), 129.3 (2 x CH), 132.0 (C), 133.8 (C), 135.4 (C), 141.9
(C), 165.8 (–CONH–).
N-(2-Hydroxyphenyl)acetamide (entry 5): M.p. 209–210 °C (lit.12,13
m.p. 209 °C); 1H NMR (300 MHz, DMSO): δ 2.10 (3H, s), 6.75 (1H,
m), 6.95 (2H, m), 7.67 (1H, d, J = 7.7 Hz), 9.33 (1H, s), 9.76 (1H, s);
13C NMR (75 MHz, DMSO): δ 23.5 (CH3), 115.9 (CH), 118.9 (CH),
122.4 (C), 124.6 (CH), 126.3 (C), 147.9 (CH), 169.0 (–CONH–).
N-(2-methoxyphenyl)acetamide.(entry 6): M.p. 87–88 °C (lit.12 m.
p. 88 °C); 1H NMR (300 MHz, CDCl3): δ 2.17 (3H, s), 3.84 (3H, s),
6.83–7.04 (3H, m), 7.81 (1H, s), 8.38 (1H, d, J = 7.5 Hz); 13C NMR
(75 MHz, CDCl3): δ 24.7 (CH3), 55.4 (O-CH3), 109.7 (CH), 119.6
(CH), 120.8 (CH), 123.4 (CH), 127.5 (C), 141.5 (C), 168.1
(–CONH–).
We wish to thank Professor Mukund G. Kulkarni (Department
of Chemistry, University of Pune) and Dr R. J. Barnabas
(Ahmednagar College, Ahmednagar) for helpful discussion
and suggestions.
Received 2 December 2010; accepted 1 January 2011
Paper 100457 doi: 10.3184/174751911X557296
Published online: 10 February 2011
Propionanilide (entry 9): M.p. 106–107 °C (lit.12 m.p. 106 °C);
IR ν˜: 3262, 2978, 2934, 1668, 1602, 1546, 1496, 1440, 927, 751,
691 cm−1; 1H NMR (300 MHz, CDCl3): δ 1.20 (3H, t, J = 7.5 Hz), 2.36
(2H, q, J = 7.5 Hz), 7.07 (1H, t, J = 7.5 Hz), 7.27 (2H, t, J = 8.2 Hz),
7.52 (2H, d, J = 7.5 Hz), 7.98 (1H, s); 13C NMR (75 MHz, CDCl3):
δ 9.6 (CH3), 30.4 (CH2), 119.9 (2 × CH), 124.0 (CH), 128.7 (2 × CH),
138.0 (C), 172.5 (–CONH–). GC-MS (%): 149 (M+, 20), 77 (8), 93
(100), 57 (12), 51 (5).
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1
3274, 2961, 2868, 1659, 1599, 1500, 900, 760, 691 cm−1; H NMR
(300 MHz, CDCl3): δ 0.96 (3H, t, J = 7.2 Hz), 1.75 (2H, m), 2.31 (2H,
t, J = 7.5 Hz), 7.07 (1H, m), 7.27 (2H, t, J = 7.2 Hz), 7.52 (2H, d, J =
7.2 Hz), 7.90 (1H, s); 13C NMR (75 MHz, CDCl3): δ 13.6 (CH3), 19.0
(CH2), 39.4 (CH2), 119.9 (2 x CH), 124.0 (CH), 128.7 (2 x CH), 138.0
(C), 171.8 (–CONH–); GC-MS (%): 163 (M+, 15), 93 (100), 77 (9),
65 (10), 43 (22).
N-(4-Methoxyphenyl)butyramide (entry 11): M.p. 78–80 °C; IR ν˜:
3283, 2965, 1647, 1606, 1537, 1522, 1242, 826, 781, 785, 719 cm−1;
1H NMR (300 MHz, CDCl3): δ 0.96 (3H, t, J = 7.5 Hz), 1.72 (2H, m),
2.28 (2H, t, J = 7.5 Hz), 3.75 (3H, s), 6.80 (2H, d, J = 8.1 Hz), 7.40
(2H, J = 8.1 Hz), 7.85 (1H, s); 13C NMR (75 MHz, CDCl3): δ 13.6
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