Boric acid catalyzed efficient synthesis of symmetrical N,N'-alkylidene bisamides

Article abstract of DOI:10.1007/bf03246228

Symmetrical N,N'-alkylidene bisamides were synthesized in excellent yield by condensation of aromatic aldehydes and amides in the presence of boric acid as a catalyst under thermal and neat microwave irradiation conditions. It is the first successful repo

Full text of DOI:10.1007/bf03246228

J. Iran. Chem. Soc., Vol. 8, No. 1, March 2011, pp. 298-305.
JOUIRrNaAnLiaOnF THE
Chemical Society
Boric acid Catalyzed Efficient Synthesis of Symmetrical N,N’-Alkylidene Bisamides
G. Harichandrana,*, S. David Amalraja and P. Shanmugamb,*
aDepartment of Polymer Science, University of Madras, Guindy Campus, Chennai-600 025, India
bOrganic Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai-600 020, India
(Received 24 January 2010, Accepted 30 August 2010)
Symmetrical N,N’-alkylidene bisamides were synthesized in excellent yield by condensation of aromatic aldehydes and
amides in the presence of boric acid as a catalyst under thermal and neat microwave irradiation conditions. It is the first successful
report of boric acid has been used as Lewis acid catalyst for the preparation of symmetrical N,N’-alkylidene bisamides. The
remarkable advantages offered by this method are green catalyst, mild reaction condition, simple procedure, fast reaction and
moderate to good yield of products.
Keywords: N,N’-Alkylidene bisamides, Amides, Aldehydes, Boric acid
INTRODUCTION
Recently, Perumal et al. have reported an alternative
approach to synthesis symmetrical N,N’-alkylidene bisamides
by the reaction of aldehydes with nitriles in the presence of
sulfamic acid, however the yields are moderate [8].
Milenkovic et al. have synthesized activated imines and
aminal derivatives as potential precursors for the synthesis of
β-amino acid using Dean-Stark water trap [9]. Zav'yalov et al.
have reported the condensation of amides with carbonyl
compounds in the presence of DMF-chlorotrimethylsilane as a
catalyst system [10]. Bhatnagar et al. have reported the
synthesis of benzylidene bisamides from direct condensation
of benzaldehyde and different amide derivatives [11].
Synthetic methodologies based on green chemistry
processes are of increasing interest in organic synthesis. In
recent years, boric acid have gained special attention as a
catalyst in organic synthesis for a number of synthetic
transformations, for example, aza Michael addition in water
[12], the thia Michael addition in water [13], Biginelli reaction
[14], transesterification of ethyl acetoacetate and
decarboxylation of cyclic β-enamino ketoesters [15],
condensation of imidazoles, amides and aldehydes to get
Amides and polyamides have been found as a key
component of many biologically active and pharmaceutical
compounds. In particular, symmetrical and unsymmetrical
N,N’-alkylidene bisamides and their derivatives are found as
key structural sub-units for the construction of peptidomimetic
frameworks [1,2]. Generally symmetrical alkylidene
bisamides are synthesized by the direct reaction of aldehydes
with the corresponding amides and similarly unsymmetrical
alkylidene bisamides are prepared from aldehydes with
different amides under suitable catalytic condition. Bronsted
acids such as acetic acid [3], hydrochloric acid [4] and sulfuric
acid [5] have been employed to catalyze the synthetic
transformation, although the results were not satisfying.
Trifluromethanesulfonic acid is a more efficient catalyst in the
formation of symmetrical bisamides [6]. Zhu et al. have
reported the synthesis of fluorine-containing N,N’-alkylidene
bisamides in the presence of fluoroalkanesulfonic acids [7].
*Corresponding author. E-mail: umhari@yahoo.co.in

Harichandran et al.
iminobenzamides are aroylated with acid chlorides to give N-
which was subjected to column chromatography on neutral
alumina using mixture of gradient hexane-ethyl acetate as
eluent to give pure products. The symmetrical N,N’-alkylidene
bisamides were further purified by recrystalization from
ethanol.
[alpha-(benzylidenamino)benzyl] benzamides and N,N'-
benzylidenebis(benzamides) [17,18]. The advantages of the
boric acid catalyst are excellent solubility in water,
uncomplicated handling, inexpensiveness and eco-friendly
nature. Recently, several synthetically useful organic
transformations using boric acid as a catalyst have also been
reported in the literature [19,20].
According to the literature, a general and green chemistry
method for the synthesis of symmetrical bisamides is still
demanded and there is no report on the formation of
symmetrical bisamides catalyzed by eco-friendly boric acid
catalyst. Hence, herein we report a convenient and efficient
method for the synthesis of symmetrical bisamides by
condensing aryl aldehydes and aryl amides using boric acid as
a catalyst.
General Procedure for the Preparation of N,N’-
Alkylidene Bisamides under Microwave Irradiation
A mixture of aldehyde (2 mmol) and amide (4 mmol) with
boric acid (0.3 mmol) in dichloromethane was made as slurry.
The slurry was irradiated in an Microwave oven (SAMSUNG,
650 W) for 0-40 min at 80% Power Level (PL). The progress
of the reaction was monitored by TLC analysis by taking a
small amount of compound under constant time interval
(eluent:n-hexane/ethyl acetate, 3:2). Further purification of the
compounds has been carried out as described in the
conventional heating.
EXPERIMENTAL
Spectral Data of Compounds
Chemicals and Apparatus
N,N’-(Phenylmethylene) dibenzamide (3a). White solid,
Melting points were determined in open capillaries and are
uncorrected. FT-IR spectra were recorded on a Thermo
Mattson Satellite FT-IR spectrophotometer by KBr pellet
method. 1H and 13C NMR (300.1 and 75.3 MHz) spectra were
recorded on a Bruker spectrometer in DMSO-d6 as a solvent
using tetramethylsilane (Me4Si) as internal standard. Chemical
shifts (δ) are reported in ppm. Mass spectra were recorded on
Q-TOF Micromass-UK spectrometer. Chromatography
purification was conducted by column chromatography using
neutral alumina. Solvents used for purification are of
commercial grade and purified before use [21].
m.p.: 235 °C (lit. 237-238 °C [6]); IR (KBr): ν
= 3276,
max
1
1649, 1539, 1484, 1342, 1271, 1046, 706 cm-1; H NMR
(300.1 MHz, DMSO-d6, Me4Si): δ (ppm): 7.08 (1H, t, J = 7.7
Hz, CH), 7.33-7.60 (11H, m, aroma), 7.93 (4H, d, J = 7.5 Hz,
CH), 9.07 (2H, d, J = 7.8 Hz, NH). 13C NMR (75.3 MHz,
DMSO-d6, Me4Si): δ (ppm): 165.6, 140.2, 133.8, 131.6, 128.3,
127.7, 127.4, 126.4, 58.6; FAB Mass calcd. for C21H18N2O2:
m/e 353 (M + Na); found: 353.
N,N’-(4-Methylphenylmethylene) dibenzamide (3c).
White solid, m.p.: 240 °C (lit. 242-243 °C [6]); IR (KBr): ν
max
= 3254, 2920, 2849, 1644, 1512, 1282, 1057, 701 cm-1. H
1
NMR (300.1 MHz, DMSO-d6, Me4Si): δ (ppm): 2.29 (3H, s,
CH3), 7.00 (1H, t, J = 7.5 Hz, CH), 7.19 (2H, d, J = 7.8 Hz,
CH), 7.35 (2H, d, J = 7.8 Hz, CH), 7.46-7.58 (6H, m, aroma),
7.89 (4H, d, J = 8.1 Hz, CH), 8.96 (2H, d, J = 7.5 Hz, NH).
13C NMR (75.3 MHz, DMSO-d6, Me4Si): δ (ppm): 165.5,
137.3, 136.8, 133.9, 131.6, 128.8, 128.3, 127.4, 126.3, 58.5,
20.6. FAB Mass calcd. for C22H20N2O2: m/e 367 (M + Na);
found: 367.
General Procedure for the Preparation of N,N’-
Alkylidene Bisamides under Conventional Heating
A mixture of aldehyde (2 mmol) and amide (4 mmol),
boric acid (0.3 mmol) was added in anhydrous toluene (10
ml). The mixture was stirred at 120 °C in an oil bath and the
reaction was followed by TLC analysis (eluent:n-hexane/ethyl
acetate, 3:2). After completion of the reaction, the mixture was
diluted with Et2O (20 ml) and the catalyst allowed to settle
down. The supernatant ethereal solution was decanted off, the
catalyst washed with Et2O (5 ml) and the combined ethereal
solution concentrated under vacuum to afford the product,
N,N’-(4-Cyanophenylmethylene) dibenzamide (3d).
White solid, m.p.: 230-234 °C; IR (KBr): ν = 3276, 1654,
max
1
1556, 1480, 1331, 1282, 1073, 706 cm-1. H NMR (300.1
MHz, DMSO-d6, Me4Si): δ (ppm): 7.05 (1H, t, J = 7.5 Hz,
299

Boric acid Catalyzed Efficient Synthesis of Symmetrical N,N’-Alkylidene Bisamides
CH), 7.48-7.61 (6H, m, aroma), 7.67 (2H, d, J = 8.1 Hz, CH),
m/e 354 (M + Na); found: 354.
7.88 (2H, d, J = 8.4 Hz, CH), 7.93 (4H, d, J = 7.8 Hz, CH),
9.19 (2H, d, J = 7.5 Hz, NH). 13C NMR (75.3 MHz, DMSO-
d6, Me4Si): δ (ppm): 165.9, 145.5, 133.5, 132.3, 131.7, 128.3,
128.2, 127.6, 127.5, 127.4, 118.7, 110.4, 58.6. FAB Mass
calcd. for C22H17N3O2: m/e 378 (M + Na); found: 378.
N,N’-(4-Methoxyphenylmethylene) dibenzamide (3j).
Yellowish solid, m.p.: 230-232 °C (lit. 232-234 °C [6]) °C; IR
(KBr): νmax = 3259, 3083, 2925, 2854, 1652, 1543, 1482, 1340,
1
1273, 1140, 1059, 909, 697 cm-1. H NMR (300.1 MHz,
DMSO-d6, Me4Si): δ (ppm): 3.74 (3H, s, OCH3), 6.93-7.02
(4H, m, CH), 7.38-7.56 (7H, m, aroma), 7.90 (4H, d, J = 8.1
Hz, CH), 8.99 (2H, d, J = 7.8 Hz, NH). 13C NMR (75.3 MHz,
DMSO-d6, Me4Si): δ (ppm): 165.5, 158.8, 133.8, 132.3, 131.6,
128.3, 127.7, 127.4, 113.6, 58.3. FAB Mass calcd. for
C22H20N2O3: m/e 383 (M + Na); found: 383.
N,N’-(4-Nitrophenylmethylene)
dibenzamide
(3e).
White solid, m.p.: 263-264 °C (lit. 265-267 °C [6]); IR (KBr):
1
ν
= 3265, 2926, 1643, 1512, 1347, 1276, 1073, 712. H
max
NMR (300.1 MHz, DMSO-d6): δ = 7.08 (1H, t, J = 7.5 Hz,
CH), 7.47-7.60 (6H, m, aroma), 7.74 (2H, d, J = 8.7 Hz, CH),
7.92 (4H, d, J = 7.2 Hz, CH), 8.25 (2H, d, J = 8.7 Hz, CH),
9.23 (2H, d, J = 7.5 Hz, NH). 13C NMR (75.3 MHz, DMSO-
D6, Me4Si): δ (ppm): 165.9, 147.5, 147, 133.4, 131.7, 128.3,
127.9, 127.5, 123.5, 58.4. FAB Mass calcd. for C21H17N3O4:
m/e 398 (M + Na); found: 398.
N,N’-(Thiophen-2-ylmethylene) dibenzamide (3k).
Yellowish solid, m.p.: 208-210 °C; IR (KBr): ν = 3264,
max
3062, 2925, 2852, 1645, 1550, 1506, 1342, 1249, 1140, 1056,
931, 804, 702 cm-1. 1H NMR (300.1 MHz, DMSO-d6, Me4Si):
δ (ppm): 7.00-7.035 (1H, m, CH), 7.121-7.131 (1H, m, CH),
7.27 (1H, t, J = 7.8 Hz, CH), 7.40-7.60 (7H, m, aroma), 7.88-
7.91 (4H, m, CH), 9.19 (2H, d, J = 7.8 Hz, NH). 13C NMR
(75.3 MHz, DMSO-d6, Me4Si): δ (ppm): 170.8, 149.5, 138.8,
137.0, 133.7, 133.6, 132.7, 132.2, 131.7, 130.7, 130.1, 60.4.
FAB Mass calcd. for C19H16N2O2S: m/e 359 (M + Na); found:
359.
N,N’-(4-Fluorophenylmethylene) dibenzamide (3f).
Yellowish solid, m.p.: 226-228 °C; IR (KBr): ν = 3271,
max
2915, 2855, 1644, 1507, 1348, 1271, 1222, 1052, 827, 707
cm-1. 1H NMR (300.1 MHz, DMSO-d6, Me4Si): δ (ppm): 7.06
(1H, t, J = 7.8 Hz, CH), 7.32-7.58 (10H, m, aroma), 7.88 (2H,
d, J = 8.1 Hz, CH), 7.91 (2H, d, 8.1 Hz, CH) 9.04 (2H, d, J =
7.8 Hz, NH). 13C NMR (75.3 MHz, DMSO-d6, Me4Si): δ
(ppm): 167.9, 165.6, 140.2, 134.1, 133.7, 131.6, 131.2, 128.3,
128.2, 127.7, 127.4, 127.4, 126.4, 58.6. FAB Mass calcd. for
C21H17FN2O2: m/e 371 (M + Na); found: 371.
N,N’-(Dimethylaminophenylmethylene) dibenzamide
(3l). Brown solid, m.p.: 210-212 °C; IR (KBr): νmax = 3279,
1
2923, 1650, 1533, 1273, 1139, 1051, 805, 705 cm-1. H NMR
(500.1 MHz, DMSO-d6, Me4Si): δ (ppm): 2.5 (6H, s, CH3),
7.01 (1H, t, J = 8.1 Hz, CH), 7.34-7.53 (10H, m, aroma), 7.87
(4H, d, J = 6.9 Hz, CH), 8.99 (2H, d, J = 8.4 Hz, NH). 13C
NMR (125.7 MHz, DMSO-d6, Me4Si): δ (ppm): 162.3, 145.4,
131.9, 130.7, 128.9, 128.0, 127.5, 119.2, 59.5. FAB Mass
calcd. for C23H23N3O2: m/e 396 (M + Na); found: 396.
N,N’-(4-Chlorophenylmethylene) dibenzamide (3g).
White solid, m.p.: 230-232 °C; IR (KBr): νmax = 3277, 2926,
2855, 1644, 1540, 1490, 1348, 1266, 1068, 800, 701 cm-1. 1H
NMR (300.1 MHz, DMSO-d6, Me4Si): δ (ppm): 7.05 (1H, t,
J = 7.5 Hz, CH), 7.46- 7.54 (10H, m, aroma), 7.90 (4H, d, J =
7.5 Hz, CH), 9.09 (2H, d, J = 7.8 Hz, NH). 13C NMR (75.3
MHz, DMSO-d6, Me4Si): δ (ppm): 165.7, 139.2, 133.6, 132.3,
131.7, 128.6, 128.4, 128.3, 128.2, 127.5, 58.3. FAB Mass
calcd. for C21H17ClN2O2: m/e 388 (M + Na); found: 388.
N,N’-(Pyridin-4-ylmethylene) dibenzamide (3h). Brown
solid, m.p.: 208-212 °C; IR (KBr): νmax = 3277, 2926, 2855,
N,N’-(3, 4-Dimethoxyphenylmethylene) dibenzamide
(3m). Yellowish solid, m.p.: 216-218 °C; IR (KBr): ν
=
max
3277, 3080, 2926, 2859, 1650, 1542, 1486, 1343, 1273, 1136,
1049, 801, 707 cm-1. 1H NMR (500.1 MHz, DMSO-d6,
Me4Si): δ (ppm): 3.49 (6H, s, OCH3), 7.02 (1H, t, J = 7.8 Hz,
CH), 7.27-7.57 (9H, m, aroma), 7.87 (4H, d, J = 9.2 Hz, CH),
9.02 (2H, d, J = 8.4 Hz, NH). 13C NMR (125.7 MHz, DMSO-
d6, Me4Si): δ (ppm): 165.9, 151.3, 141.5, 134.7, 132.2, 128.9,
128.0, 126.9, 100.1, 58.7. FAB Mass calcd. for C23H22N2O4:
m/e 413(M + Na); found: 413.
1
1647, 1540, 1460, 1320, 1276, 1075, 970, 719 cm-1. H NMR
(300.1 MHz, DMSO-d6, Me4Si): δ (ppm): 7.05 (1H, t, J = 7.8
Hz, CH), 7.34-7.68 (10H, m, aroma), 7.90 (4H, d, J = 7.2 Hz,
CH), 9.05 (2H, d, J = 7.8 Hz, NH). 13C NMR (75.3 MHz,
DMSO-d6, Me4Si): δ (ppm): 165.6, 140.2, 133.7, 131.6, 128.3,
127.7, 127.4, 126.4, 58.6. FAB Mass calcd. for C20H17N3O2:
N,N’-(Furan-2-ylmethylene)
dibenzamide
(3n).
Yellowish solid, m.p.: 206-208 °C; IR (KBr): ν = 3277,
max
300

Harichandran et al.
2928, 1650, 1489, 1340, 1273, 1137, 1051, 800, 706 cm-1. 1H
Table 1
O
O
O
Ph
O
NMR (500.1 MHz, DMSO-d6, Me4Si): δ (ppm): 7.03 (1H, t,
J = 8.2 Hz, CH), 7.27-7.51 (9H, m, aroma), 7.87 (4H, d, J =
7.7 Hz, CH), 8.97 (2H, d, J = 6.9 Hz, NH). 13C NMR (125.7
MHz, DMSO-d6, Me4Si): δ (ppm): 165.7, 152.7, 144.3, 140.7,
134.3, 130.1, 128.8, 127.9, 126.9, 119.2, 59.1. FAB Mass
calcd. for C19H16N2O3: m/e 343 (M + Na); found: 343.
Condition
+
Ph
NH2
Ph
H
Ph
N
N
Ph
B(OH)3
H
H
2a
1a
3a
Scheme 1. Optimization of N,N’-alkylidene bisamides
synthesis
RESULTS AND DISCUSSION
reaction was carried out under microwave irradiation
condition to afford the desired compound in 85% yield (Table
1, entry 8). The structure of the product 3a was assigned based
Initially the reaction of benzaldehyde 1a with benzamide
2a (2 equivalents) and catalytic amount of boric acid in
anhydrous toluene was refluxed. After completion of the
reaction followed by standard work-up and purification N,N’-
alkylidene bisamides 3a was obtained in 92% yield (Scheme
1). To understand the effect of solvent, the reaction has been
carried out with various solvents (Table 1, entries 1-6). No
product was observed in CH3CN and DCM as solvents (Table
1, entries 1 and 5). However, a considerable amount of desired
products were formed in EtOH, EtOAc and THF (Table 1,
entries 2, 3 and 6). Best yield was obtained when the reaction
was performed in refluxing toluene with lesser reaction time
and found as optimum condition (Table 1, entry 4).
The results indicated that reactions at elevated temperature
(120 ºC) afforded maximum yield with shorter reaction time.
It should be noted that in the absence of boric acid catalyst,
only a trace of desired product was obtained due to
equilibrium and the reaction takes longer time to complete
(Table 1, entries 7). In order to reduce the reaction time, the
on the analysis of spectroscopic data such as FTIR, 1H and 13
NMR and mass spectroscopy.
C
With the optimal conditions in hand and to show the
generality of the reaction, we examined the reaction of a series
of aromatic aldehydes 1a-m with benzamide 2a and acetamide
2b to afford symmetrical N,N’-alkylidene bisamides 3b-n in
moderate to good yields. The reaction is outlined in Scheme 2
and the results are summarized in Table 2.
Reactions are preceded well with various aromatic
aldehydes and benzamide to provide symmetrical N,N’-
alkylidene bisamides. However, the reaction of benzaldehyde
with acetamide did not occur and only starting material was
recovered in quantitative yield (Table 2, entry 2). In order to
synthesize unsymmetrical N,N’-alkylidene bisamides, the
reaction of benzaldehyde with one equivalent of benzamide
and one equivalent of acetamide was carried out. The reaction
provided only product of symmetrical N,N’-alkylidene
Table 1. Optimization Studies for the Synthesis of N,N’-Alkylidene Bisamides Using Boric Acida
Entry Solvent Temp (°C) Time(h)
Yield (%)b
CH3CN 80 24
1
0
2
3
4
5
EtOH
EtOAc
Toluene
Dichloromethane
80
80
115
45
20
25
30
24
35
45
92
0
6
7
THF
65
120
28
24
30
25
Toluene (absence of Boric acid)
8
Microwave irradiation
80% PL
0.20
85
301

Boric acid Catalyzed Efficient Synthesis of Symmetrical N,N’-Alkylidene Bisamides
O
Ar1
O
O
O
Ar2
N
H
N
Ar2
+
Boric acid
Ar2
NH2
toluene, reflux, 20-72 h
Ar1
H
H
2a,b
1a-m
3a-n
Scheme 2. Synthesis of various N,N’-alkylidene bisamides
Table 2. Synthesis of N,N’-Alkylidene Bisamides Using Boric Acid under Classical Heating Conditions or
Using Microwave Irradiation
Entry
Aldehyde
Amide
Product
Conventional
heating
Microwave
irradiation
Time Yield Time Yield
(h)
(%)
(min)
(%)
O
Ph
O
C6H5CHO
C6H5CONH2
16
92
20
85
1
2
3
Ph
N
H
N
H
Ph
CH3
Ph
1a
2a
3a
O
Ph
O
C6H5CHO
CH3CONH2
24
24
0
40
40
0
H3C
N
N
H
H
1a
2b
3b
O
Ph
O
C6H5CHO
C6H5CONH2 +
38
35
Ph
N
N
H
1a
2a
CH3CONH2
2b
H
3a
H3C
4-Methyl
C6H5CONH2
2a
60
30
80
68
25
35
75
64
4
5
O
O
O
C6H4 O
benzaldehyde
Ph
Ph
Ph
N
H
N
H
Ph
Ph
Ph
1b
3c
CN
4-Cyano
benzaldehyde
C6H5CONH2
C6H4 O
2a
N
H
N
H
1c
3d
NO2
C6H4 O
4-Nitro
benzaldehyde
C6H5CONH2
30
65
30
60
6
2a
N
H
N
H
1d
3e
302

Harichandran et al.
Table 2. Continued
F
4-Fluro benzaldehyde
C6H5CONH2
30
48
55
65
35
30
50
60
7
O
O
C6H4 O
1e
2a
Ph
Ph
N
H
N
H
Ph
Ph
3f
Cl
4-Chloro benzaldehyde
C6H5CONH2
8
C6H4 O
1f
2a
N
H
N
H
3g
O
O
Py
O
O
Pyridine-4-aldehyde
C6H5CONH2
45
40
70
65
35
40
64
58
9
Ph
Ph
N
H
N
H
Ph
Ph
1g
2a
3h
Fc
Ferrocenealdehyde
C6H5CONH2
10
N
H
N
H
1h
2a
3i
H3CO
O
C6H5CONH2
45
78
25
73
11
Anisaldehyde
C6H4 O
2a
1i
Ph
Ph
N
H
N
H
Ph
Ph
3j
O
Thc O
C6H5CONH2
32
70
80
38
25
35
77
32
12
13
Thiophene-2-
carboxyaldehyde
N
H
N
2a
H
1j
3k
(H3C)2N
C6H5CONH2
Dimethyl-
Aminobenzaldehyde
O
C6H4 O
2a
Ph
N
H
N
H
Ph
1k
3l
(H3CO)2
C6H5CONH2
65
40
45
60
25
35
40
54
14
15
3,4-Dimethoxy
benzaldehyde
O
C6H4 O
2a
Ph
N
H
N
H
Ph
Ph
1l
3m
3n
O
Fuc
O
C6H5CONH2
Furan-2-
carboxyaldehyde
1m
2a
Ph
N
H
N
H
303

Boric acid Catalyzed Efficient Synthesis of Symmetrical N,N’-Alkylidene Bisamides
. .
H2N
condition, simple procedure, lack of toxicity, low cost, the use
X
O
+
of a commercially available catalyst and simplicity of work-
up. Further work using the catalyst for the synthesis of novel
heterocycles is in progress in this laboratory.
B(OH)3
H
O
H
X
O
O
B(OH)3
OH
B(OH)3
N
+
H
O
H
. .
NH2
X
ACKNOWLEDGEMENTS
SDA thank University of Madras for providing Teaching
and Research Fellowship. GH thanks The Head, Department
Polymer Science, University of Madras for providing
infrastructure facilities. PS thanks Director, CLRI for
providing facilities. The authors thank Dr. P.T. Perumal,
Scientist-G, CLRI for useful discussion.
X
O
O
+
B(OH)3
N
H
N
H
Scheme 3. A plausible reaction mechanism for the synthesis of
symmetrical N,N’-alkylidene bisamides
REFERENCES
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
T. Yamazaki, K.I. Nunami, M. Goodman, Biopolymers
31 (1991) 1513.
M. Goodman, H. Shao, Pure & Appl. Chem. 68 (1996)
1303.
W.A. Noyes, D.B. Forman, J. Am. Chem. Soc. 55
(1933) 3493.
N.O. Brace, G.J. Mantell, J. Org. Chem. 26 (1961)
5176.
E.E. Magat, B.F. Faris, J.E. Reith, L.F. Salisbury, J.
Am. Chem. Soc. 73 (1951) 1028.
A.H. Fernandez, R.M. Alvarez, T.M. Abajo, Synthesis
(1996) 1299.
S. Zhu, G. Xu, Q. Chu, Y. Xu, C. Qui, J. Fluorine
Chem. 93 (1999) 69.
N.P. Selvam, S. Saranya, P.T. Perumal, Can. J. Chem.
85 (2008) 32.
A. Milenkovic, F. Fache, R. Faure, M. Lemaire, Synth.
Commun. 29 (1999) 1535.
bisamides in 38% yield with quantitative amount of unreacted
acetamide (Table 2, entry 3). The reaction of 4-
pyridylaldehyde under optimized condition afforded excellent
yield of pyridine substituted N,N’-alkylidene bisamides (Table
2, entry 9). It appears that substitution at the 4-position of
aromatic aldehyde produced no significant effects; aldehydes
possessing electron-donating groups or amide bearing
electron-withdrawing groups caused slightly lower yields.
Interestingly, the reaction of ferrocenealdehyde with
benzamide proceeds well and gave the desired product in good
yield (Table 2, entry 10). The reaction in Dean-Stark trap
apparatus has been carried out and found the reduction of
reaction time without altering the yield with lesser reaction
time (1.5 h). More to reduce the reaction time, all the reactions
reported in (Table 2) were also carried out under neat
microwave irradiation condition and found to afford almost
same yields of the products as that of thermal reaction within
15-40 min.
[10] S.I.
Zav'yalov,
L.B.
Kulikova,
Khimiko-
A plausible reaction mechanism for the synthesis of
symmetrical N,N’-alkylidene bisamides under boric acid as a
Lewis acid is shown in Scheme 3.
In conclusion, boric acid has been successfully used as
effective catalyst for the synthesis of symmetrical N,N’-
alkylidene bisamides for the first time. This procedure has
advantages in competition with the previously reported
methods, in terms of yield, green catalyst, mild reaction
Farmatsevticheskii Zhurnal 26 (1992) 88. CAN
117:150650.
[11] G.S. Bhatnagar, K.C. Pandya, Proceedings-Indian
Academy of Sciences, Section A 24 (1946) 487. CAN
41:18893; b) G.S. Bhatnagar, K.C. Pandya, Proceedings
-Indian Academy of Sciences, Section A 10A (1939)
285.
[12] M.K. Chaudhuri, S. Hussain, M. Lakshmi Kantam, B.
304

Harichandran et al.
Neelima, Tetrahedron Lett. 46 (2005) 8329.
(1982) 475.
[13] M.K. Chaudhuri, S. Hussain, J. Mol. Cat. A 269 (2007)
214.
[14] S.J. Tu, X.T. Zhu, F. Fang, X.J. Zhang, S.L. Zhu, T.J.
Li, D.Q. Shi, X.S. Wang, S.J. Ji, Tetrahedron Lett. 44
(2003) 6153.
[15] G.C.M. Kondaiah, L. Amarnath Reddy, K. Srihari
Babu, V.M. Gurav, K.G. Huge, R. Bandichhor, P.
Pratap Reddy, A. Bhattacharya, R. Vijaya Ananda,
Tetrahedron Lett. 49 (2008) 106.
[16] J. Pernak, B. Mrowczynski, J. Weglewski, Synthesis 12
(1994) 1415.
[18] L. Hazai, G. Deak, Acta Chim. Hung. 121 (1986) 237.
[19] a) A. Kumar, R.A. Maurya, Tetrahedron Lett. 49 (2008)
5471; b) T. Pingwah, Org. Synth. 81(2005) 262; c) K.F.
Shelke, S.B. Sapkal, S.S. Sonar, B.R. Madje, B.B.
Shingate, M.S. Shingare, Bull. Korean Chem. Soc. 30
(2009) 1057.
[20] P.V. Shinde, S.S. Sonar, B.B. Shingate, M.S. Shingare,
Tetrahedron Lett. 51 (2010) 1308.
[21] D.D. Perrin, W.F.L. Armearego, Purification of
Laboratory Chemicals, 3rd ed., Pergamon Press, New
York, 1988.
[17] S.S. Rawalay, C.F. Beam, J. Chem. Eng. Data 27
305