Efficient and mild synthesis of novel schiff bases via one-pot, three-component reaction under solvent-free conditions

Article abstract of DOI:10.1080/10426500802466767

A simple, efficient, and cost-effective method has been developed for the synthesis of N,N'-bis(2-hydroxybenzylidene)-1,1-diaminoalkanes through one-pot, three-component reaction of salicylaldehyde, aliphatic aldehydes, and ammonium nitrate in the presenc

Full text of DOI:10.1080/10426500802466767

This article was downloaded by: [University of Toronto Libraries]
On: 22 December 2014, At: 12:31
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Efficient and Mild Synthesis of
Novel Schiff Bases Via One-Pot,
Three-Component Reaction
Under Solvent-Free Conditions
Hossein Naeimi a , Khadijeh Rabiei a & Fariba Salimi
a
a Department of Chemistry, Faculty of Science ,
University of Kashan , Kashan, Iran
Published online: 04 Sep 2009.
To cite this article: Hossein Naeimi , Khadijeh Rabiei & Fariba Salimi (2009) Efficient
and Mild Synthesis of Novel Schiff Bases Via One-Pot, Three-Component Reaction
Under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:9, 2351-2357
To link to this article: http://dx.doi.org/10.1080/10426500802466767
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or

indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 184:2351–2357, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802466767
Efficient and Mild Synthesis of Novel Schiff Bases Via
One-Pot, Three-Component Reaction Under Solvent-Free
Conditions
Hossein Naeimi, Khadijeh Rabiei, and Fariba Salimi
Department of Chemistry, Faculty of Science, University of Kashan,
Kashan, Iran
A simple, efficient, and cost-effective method has been developed for the synthe-
sis of N,Nꢀ-bis(2-hydroxybenzylidene)-1,1-diaminoalkanes through one-pot, three-
component reaction of salicylaldehyde, aliphatic aldehydes, and ammonium nitrate
in the presence of a base under solvent-free conditions at room temperature.
Keywords Aldehydes; ammonium nitrate; Schiff base; solvent free; three component
INTRODUCTION
Over the past few years, significant research has been directed to-
ward the development of new technologies for environmentally benign
processes (green chemistry),1 which are both economically and techno-
logically feasible.2,3 An important area of green chemistry deals with
solvent minimization. In a solvent-free process, the cost of processing,
handling, and disposal of the solvent is completely eliminated, resulting
in improved process efficiency.1
Multicomponent reactions (MCRs) are of increasing importance in
organic and medicinal chemistry for various reasons.4 In times where
a premium is put on speed, diversity, and efficiency in the process,
MCR strategies offer significant advantages over conventional linear-
type synthesis5 MCR condensations involve three or more compounds
reacting consecutively in a single event, to form a new product, which
contains the essential parts of all the starting materials. The search
and discovery for new MCRs on the one hand and the full exploita-
tion of already known multicomponent reactions on the other hand are
Received 8 July 2008; accepted 10 September 2008.
We are grateful to the University of Kashan Research Council for the partial support
of this work.
Address correspondence to Hossein Naeimi, Department of Chemistry, Faculty of
Science, University of Kashan, Kashan, 87317, I.R. Iran. E-mail: naeimi@kashanu.ac.ir
2351

2352
H. Naeimi et al.
therefore of considerable current interest.6 Schiff bases, as a class of
compounds with an imine group, are very important compounds in or-
ganic chemistry. A great deal of effort has been made concerning the
synthesis of Schiff bases.7 Those are once again topical in connection
with a diverse range of applications in organic synthesis and bioor-
ganic and medicinal chemistry, such as catalysts in the synthesis of
chiral cyanohydrins,7 as liquid crystals,8 as catalysts in the ring open-
ing of epoxides,9 in the preparation of ion-selective electrodes,10–15 in-
hibition of cytosolic/tumor-associated carbonic anhydrase isozymes,16
and in solid extraction.17 Schiff bases have been usually produced by
a two-component reaction that involves one carbonyl compound with
primary amines or diamines in protic solvents. In order to increase the
environmental and economical concerns, it is essential for chemists to
search environmentally reactions as many as possible.
Because of these economical and environmental reasons, and in con-
junction with ongoing work in our laboratory on the preparation of
double Schiff bases and their complexes,18,19 here we decided to re-
port the synthesis of double Schiff bases by a one-pot, three-component
reaction under mild and solvent-free conditions at room temperature.
RESULTS AND DISCUSSION
In this reaction, two different aldehydes were reacted with am-
monium nitrate in the presence of a base to produce N, Nꢀ-bis(2-
hydroxybenzilidene)-1,1-diaminoalkanes as shown in Scheme 1.
SCHEME 1
As shown in Scheme 1, when 2 mol eq. of salicylaldehyde and 1 mol
eq. of propanal reacted with 2 eq. NH4NO3 in the presence of a base
at room temperature under solvent-free conditions, after a short time
the yellow oil product was obtained. In order to study the effect of the
base, this reaction was carried out in the presence of various bases.
The results of the reaction are indicated in Table I. As shown in this

Novel Schiff Bases
2353
TABLE I Reaction of Salicylaldehyde, Propanal, and
Ammonium Nitrate at Room Temperature
Entry
Base
Time (min)
Yield (%)
1
2
3
4
5
6
7
NaHCO3
NaOOCCH3
KOH
NaOH
Pyridine
NEt3
20
15
8
8
40
45
90
90
—
94
—
Overnight
8
Overnight
None
table, triethylamine, KOH, and NaOH were the most effective in the
reaction.
Then, by dissolving the oil product in methanol and cooling the so-
lution, the yellow crystalline product in excellent yield was purely ob-
tained. In order to study the generality of this process, several examples
of aldehydes with salicylaldehyde and ammonium nitrate in the pres-
ence of NEt3 have been studied. The results are summarized in Table II.
As shown in Table II, in these reactions, the Schiff bases 3a–3h were
formed in excellent yield and short reaction times at room temperature.
The structures of products have been assigned from spectroscopic
data. In the IR spectra, the characteristic Schiff base C N stretching
frequency is found in the region between 1600 and 1700 cm−1 as a signal
strong band. The OH stretching frequency is found at 3000 cm−1 with
particular width as a broad band. The stretching vibration of C-H in
the alkyl groups appears at region between 2700 and 2800 cm−1 with
1
sharp absorptions. In the H NMR spectra, the broad signal around
TABLE II Reaction of Salicylaldehyde, Ammonium Nitrate, and
Different Aldehydes in the Presence of NEt3 at Room Temperature
Entry
Substrate
Product
Mp (◦C)
Time (min)
Yielda (/%)
1
2
3
4
5
6
7
8
Methanal
Propanal
Butanal
Pentanal
Hexanal
Heptanal
Isobutanal
3-Phenylpropanal
3a
3b
3c
3d
3e
3f
116–118
92–94
72–74
82–84
72–74
82–84
74–76
oil
8
7
7
5
3
3
2
3
90
94
94
95
95
95
98
95
3g
3h
aIsolated yield based on salicylaldehyde.

2354
H. Naeimi et al.
with 12.00–13.00 ppm is assigned to the protons of the hydroxyl groups.
Two protons of CH N have the same chemical shifts in 8.30–8.46 ppm
and the signal around the 4.60–5.00 ppm is assigned to the protons of
the NCHN. The UV spectra show maximum absorptions between 200
and 400 nm dependent on the particular compound.
In summary, we have developed an economical environmentally
friendly procedure for synthesis of the Schiff bases with excellent yields
and short reaction times under free solvent conditions through one-pot,
three-component reaction.
EXPERIMENTAL
Materials and Apparatus
Chemicals were purchased from the Merck Chemical Company in high
purity. All the materials were of commercial reagent grade. The aldehy-
des were purified by standard procedures,20 The purity was determined
by thin-layer chromatography (TLC) and gas chromatography (GC).
IR spectra were recorded as KBr pellet on a Perkin-Elmer 781 Spec-
trophotometer and an Impact 400 Nicolet FTIR Spectrophotometer.
1H NMR spectra were recorded in CDCl3 using a spectrometer at 400
MHZ using TMS as an internal reference. Melting points obtained with
a Yanagimoto micro melting point apparatus are uncorrected. The pu-
rity determination of the substrates and the reactions monitoring were
accomplished by TLC on silica-gel polygram SILG/UV 254 plates.
Typical Procedure for Synthesis of N,Nꢀ-bis(2-
Hydroxybenzylidene)-1,1-diamino-propane
To a mixture of salicylaldehyde (0.4 g, 3.27 mmol) and propanal
(R=C2H5, 0.095 g, 1.64 mmol) was added NH4NO3 (0.25 g, 3.27 mmol)
in the presence of the NEt3 (1 mL) as a base by stirring in one portion.
The mixture was stirred for a further 7 min. The progress of the re-
action was monitored by TLC. After the completion of the reaction, a
yellow oily substance was obtained. Then, by dissolving the mixture in
2 mL MeOH and cooling overnight, a yellow solid precipitated. The solid
product was filtered off and washed with cold MeOH. The crude product
was purified by recrystallization in ethanol and the pure Schiff base,
N,Nꢀ-bis(2-hydroxybenzylidene)-1,1-diaminopropane, was obtained in
94% yield, mp = 92–94◦C. The Schiff base products were identified by
spectroscopic data.

Novel Schiff Bases
2355
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminomethane (3a)
mp 116–118◦C; IR (KBr)/υ (cm−1) 3150–3450 (br, OH); 2980 (C-H,
alkyl), 1620 (s, C N), 1587, 1501 (Ar); 1H NMR/CDCl3/δ ppm: 4.46
(s, 2H), 6.90–7.60 (m, 8H), 8.60 (s, 2H), 12.70 (s, 2H, 2OH); 13C
NMR/CDCl3/δ ppm: 85.0, 117.6, 119.9, 118.7, 133.0, 133.9, 155.0, 161.0;
MS: m/z = 255 (M++1, 7), 254 (M+, 8), 132 (14), 133 (100), 91 (17), 77
(44), 58 (60); UV (CHCl3)/λmax (nm) 320 (w), 260 (s); Anal. Calcd for C,
H, N: C, 70.87; H, 5.51; N, 11.02; Found: C, 71.01; H, 5.54; N, 11.10.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminopropane (3b)
mp 92–94◦C; IR (KBr)/υ (cm−1): 3150–3450 (br, OH), 2965 (C-H, alkyl),
1
1625 (s, C N), 1501, 1587 (Ar); H NMR/CDCl3/δ ppm: 4.80 (t, 1H,
NCHN), 0.90 (t, 3H, CH3), 1.99 (m, 2H, CH2), 6.90–7.60 (m, 8H), 8.70
(s, 2H, C N), 13.01 (s, 2H, 2OH); 13C NMR/CDCl3/δ ppm: 19.0, 20.2,
85.0, 116.4, 118.40, 119.6, 133.0, 133.7, 155.4, 161.3; MS: m/z = 283
(M++1, 6%), 282 (M+, 10), 162 (13), 161 (100), 91 (20), 77 (45), 58 (59);
UV(CHCl3)/λmax (nm); Anal. Calcd for C, H, N: C, 72.34; H, 6.38; N,
9.93; Found: C, 72.37; H, 6.41; N, 9.93.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminobutane (3c)
mp 72–74◦C; IR (KBr)/υ (cm−1) 3100–3440 (br, OH); 2960 (C-H, alkyl),
1625 (s, C N), 1502, 1576 (Ar); 1H NMR/CDCl3/δ ppm: 0.90 (t, 3H,CH3),
1.40 (m, 2H, CH2),1.90 (q, 2H, CH2), 4.99 (t, 1H, NCHN), 6.90–7.70 (m,
8H), 8.70 (s, 2H, C N), 13.00 (s, 2H, 2OH); 13C NMR/CDCl3/δ ppm:
15.3, 18.0, 20.0, 84.0, 117.4, 118.8, 119.0, 133.0, 133.7, 155.2, 161.0; UV
(CHCl3)/λmax (nm) 322 (w), 260 (s); MS: m/z = 297 (M++1, 6), 296 (M+,
7), 176 (15), 175 (100), 91 (17), 77 (45), 58 (55), 56 (30), 42 (15); Anal.
Calcd for C, H, N: C, 73.55; H, 7.09; N, 9.03; Found: C, 73.60; H, 7.12;
N, 9.05.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminopentane (3d)
mp 82–84◦C; IR (KBr)/υ (cm−1) 3250–3430 (br, OH); 2950 (C-H, alkyl),
1
1625 (s, C N), 1491, 1577 (Ar); H NMR/CDCl3/δ ppm: 0.90 (t, 3H,
CH3), 1.40 (m, 4H, 2CH2), 1.90 (q, 2H, CH2), 4.99 (t, 1H, NCHN), 6.90–
7.70 (m, 8H), 8.70 (s, 2H, C N), 12.93 (s, 2H, 2OH); 13C NMR/CDCl3/δ
ppm: 15.3, 17.2, 20.0, 82.0, 117.0, 118.0, 119.0, 133.0, 133.2, 158.0,
165.0; UV(CHCl3)/λmax (nm) 320 (w), 260 (s); MS: m/z = 311 (M++1,
5), 310 (M+, 9), 190 (12), 189 (100), 91 (20), 77 (40), 58 (55), 56 (25), 42
(14); Anal. Calcd for C, H, N: C, 73.55; H, 7.09; N, 9.03; Found: C, 73.57;
H, 7.10; N, 9.03.

2356
H. Naeimi et al.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminohexane (3e)
mp 72–74◦C; IR (KBr)/υ (cm−1) 3000–3350 (br, OH), 2970 (C-H, alkyl),
1
1629 (s, C N), 1486, 1573 (Ar); H NMR/CDCl3/δ ppm: 0.90 (t, 3H,
CH3), 1.40 (m, 6H, 3CH2), 1.90 (q, 2H, CH2), 4.99 (t, 1H, NCHN), 6.90–
7.70 (m, 8H), 8.50 (s, 2H, C N), 13.10 (s, 2H, 2OH); 13C NMR/CDCl3/δ
ppm: 12.3, 15.1, 17.0, 19.0, 21.0, 86.0, 118.0, 119.0, 120,5 133.0, 133.2,
158.0, 166.0; UV(CHCl3)/λmax (nm) 322 (w), 261 (s); Anal. Calcd for C,
H, N: C, 74.07; H, 7.41; N, 8.64; Found: C, 74.11; H, 7.42; N, 8.64.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminoheptane (3f)
mp 82–84◦C; IR (KBr)/υ (cm−1) 3250–3500 (br, OH), 2950 (C-H, alkyl),
1
1631 (s, C N), 1491, 1571 (Ar); H NMR/CDCl3/δ ppm: 0.80 (t, 3H,
CH3), 1.30 (m, 8H, 4CH2), 1.90 (q, 2H, CH2), 5.00 (t, 1H, NCHN), 6.90–
7.60 (m, 8H), 8.70 (s, 2H, C N), 13.20 (s, 2H, 2OH); 13C NMR/CDCl3/δ
ppm: 13.4, 16.0, 17.0, 18.0, 19.0, 22.0, 87.0, 117.0, 119.0, 120, 133.0,
134.1, 157.0, 165.0; MS: m/z = 339 (M++1, 10%), 338 (M+, 15), 220 (20),
220 (100), 91 (29), 77 (50), 58 (57), 56 (34), 42 (20); UV (CHCl3)/λmax
(nm) 320 (w), 262 (s); Anal. Calcd for C, H, N: C, 74.56; H, 7.69; N, 8.28;
Found: C, 74.58; H, 7.71; N, 8.28.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diaminoisobutane (3g)
mp 74–76◦C; IR (KBr)/υ (cm−1) 3250–3520 (br, OH), 2965 (C-H, alkyl),
1
1615 (s, C N), 1502, 1577 (Ar); H NMR/CDCl3/δ ppm: 0.80 (d, 6H,
CH3), 2.01 (m, 1H, CH), 4.40 (t, 1H, NCHN), 6.90–7.20 (m, 8H), 8.20 (s,
2H, C N), 12.90 (s, 2H, 2OH); 13C NMR/CDCl3/δ ppm: 18.4, 35.2, 92.0,
117.4, 119.4, 119.7, 133.0, 133.7, 161.3; UV (CHCl3)/λmax (nm) 323 (w),
242 (w), 262 (s); MS: m/z = 297 (M++1, 5), 296 (M+, 6), 177 (12), 176
(100), 133 (11), 132 (58), 91 (18), 77 (42), 58 (58); Anal. Calcd for C, H,
N: C, 72.97; H, 6.76; N, 9.46; Found: C, 72.99; H, 6.79; N, 9.46.
N,N ꢀ-bis(2-Hydroxybenzylidene)-1,1-diamino-3-phenylpropane
(3h)
Oil; IR (neat)/υ (cm−1) 3000–3300 (br, OH), 2955 (C-H, alkyl), 1625
1
(s, C N), 1490, 1576 (Ar); H NMR/CDCl3/δ ppm: 0.90 (d, 6H, CH3),
1.40 (m, 1H, CH2), 1.90 (q, 2H, CH2), 4.99 (t, 1H, NCHN), 6.90–7.70
(m, 13H), 8.70 (s, 2H, C N), 13.02 (s, 2H, 2OH); 13C NMR/CDCl3/δ
ppm: 32.1, 45.0, 91.0, 117.3, 119.2, 119.6, 133.0, 137.2, 158.0, 164.0;
UV(CHCl3)/λmax (nm) 323 (w), 262 (s). Anal. Calcd for C, H, N: C,
77.09; H, 6.14; N, 7.82; Found: C, 77.24; H, 6.17; N, 7.83.

Novel Schiff Bases
2357
REFERENCES
[1] A. Bhattacharya and V. C. Purohit, Org. Proc. Res. Dev., 7, 254 (2003).
[2] (a) T. Cablewski, F. Faux, and C. R. Strauss, J. Org. Chem., 59, 3408 (1994); (b) C. R.
Strauss and R. W. Trainor, Aust. J. Chem., 48, 1665 (1995).
[3] (a) N. Hall, Science, 32, 266 (1994); (b) D. L. IIman, Chem. Eng. News, 26, 3519
(1993).
[4] (a) H. Bienayme, C. Hulme, and P. Schmitt, Chem. Eur. J., 6, 3321 (2000); (b) A.
Domling and I. Ugi, Angew. Chem. Int. Ed., 39, 3168 (2000).
[5] R. E. Dolle and K. H. Nelson, J. Comb. Chem., 1, 235 (1999).
[6] L. Weber, K. Illgen, and M. Almstetter, Synlett, 3, 366 (1999).
[7] M. North, Tetrahedron: Asymmetry, 14, 147 (2003).
[8] N. Hoshino, Coord. Chem. Rev., 174, 77 (1998).
[9] H. Sharghi and H. Naeimi, Bull. Chem. Soc. Jpn., 72, 1525 (1999).
[10] N. Alizadeh, S. Ershad, H. Naeimi, and H. Sharghi, Fresen. J. Anal. Chem., 365,
511 (1999).
[11] M. Shamsipur, M. Yousefi, M. Hosseini, M. R. Ganjali, H. Sharghi, and H. Naeimi,
Anal. Chem., 73, 2869 (2001).
[12] M. Mazlum Ardekany, A. A. Ensafi, H. Naeimi, A. Dastanpour, and A. Shamelli,
Sensor. Actuator. B Chem., 96, 441 (2003).
[13] S. Sadeghi, M. Eslahi, M. A. Naseri, H. Naeimi, H. Sharghi, and A. Shamelli,
Electroanalysis, 15, 1327 (2003).
[14] A. R. Khorrami, H. Naeimi, and A. R. Fakhari, Talanta, 64, 13 (2004).
[15] L. Puccetti, G. Fasolis, D. Vullo, Z. H. Chohan, A. Scozzafava, and C. T. Supuran,
Bioorg. Med. Chem. Lett., 15, 3096 (2005).
[16] M. Shamsipour, A. R. Ghiasvand, H. Sharghi, and H. Naeimi, Anal. Chim. Acta,
408, 271 (2000).
[17] H. Naeimi, H. Sharghi, F. Salimi, and Kh. Rabiei, Heteroatom. Chem., 19, 43 (2008).
[18] H. Naeimi, F. Salimi, and Kh. Rabiei, J. Coord. Chem., 61, 3659 (2008).
[19] B. S. Furniss, A. J. Hannaford, P. W. G. Smith, and A. R. Tatchell, Vogels Textbook
of Practical Organic Chemistry, 5th ed. (Longman, Inc., New York, 1989), p. 181.