Systematic studies on mechanochemical synthesis: Schiff bases from solid aromatic primary amines and aldehydes

Article abstract of DOI:10.1002/jccs.201800486

A versatile and robust mechanochemical route to Aldehyde–Schiff base conversions has been established for a broad range of aldehydes via a simple cogrinding in mortar with a pestle under a solvent-free, as well as solvent-assisted, environment. The extent

Full text of DOI:10.1002/jccs.201800486

Received: 24 December 2018
DOI: 10.1002/jccs.201800486
Revised: 29 April 2019
Accepted: 1 May 2019
A R T I C L E
Systematic studies on mechanochemical synthesis: Schiff bases
from solid aromatic primary amines and aldehydes
Getinet Tamiru Tigineh1,2,3 | Ling-Kang Liu1,4
1Institute of Chemistry, Academia Sinica,
Taipei, Taiwan
A versatile and robust mechanochemical route to Aldehyde–Schiff base conver-
2Department of Chemical Engineering,
National Taiwan University of Science and
Technology, Taipei, Taiwan
3Department of Chemistry, Bahir Dar
University, Bahir Dar, Ethiopia
sions has been established for a broad range of aldehydes via a simple cogrinding
in mortar with a pestle under a solvent-free, as well as solvent-assisted, environ-
ment. The extent of amines reactivity under these conditions has also been
explored, along with an examination of the possible connection between reactivity
and electronic substituent effects. Results obtained demonstrated that the solvent-
free mechanochemical conversion of p-toluidine and aromatic aldehydes to the
corresponding Schiff bases proceeded more smoothly than the corresponding syn-
thesis with 4-aminobenzonitrile. The present approach not only provides good to
excellent yields but also eliminates the disadvantages of the traditional synthesis of
Schiff bases, such as the use of hazardous solvents, more or less demand of expen-
sive catalysts, and looking for optimization on reaction conditions.
4Department of Chemistry, National Taiwan
University, Taipei, Taiwan
Correspondence
Getinet Tamiru Tigineh, Department of
Chemistry, Bahir Dar University, Bahir Dar,
Ethiopia.
Email: getsh2007@gmail.com
Funding information
Academia Sinica
K E Y W O R D S
aromatic aldehydes, mechanochemistry, Schiff base, solvent-free reaction
clean and sustainable technology, ranging from “green” syn-
thesis to mineral manufacturing and nanoparticle synthe-
sis. [4,12]
1 | INTRODUCTION
An important incentive to study mechanochemical phenom-
ena is their potential usefulness for making new materials
and to make current or future technologies more efficient.[1]
As the demand for better recovery, higher efficiency, and
greener operation increases, interest in the use of mechanical
activation will grow.[2]
The growing interest in mechanochemical processes has,
in the past decade, provided exciting developments in the
areas of supramolecular (cocrystals, capsules, catenanes,
rotaxanes),[3] pharmaceuticals (screening new solid drug
forms, pharmaceutical cocrystals),[4] materials (porous
metal–organic frameworks, luminescent sensors),[5] and
organic (solvent-free synthesis, solid-state deracemization,
organic cages) chemistry[6–9] and catalysis (stereoselective
organocatalysts, metal organic solvent-free catalysis, cata-
lytic solid-state photoreactions).[10,11] These developments
indicate that mechanochemistry will play a key role in future
In a recent Faraday discussion-themed issue on “Mecha-
nochemistry: From Functional Solids to Single Molecules,”
the mechanochemistry of organic molecules, soft materials
and pharmaceuticals, the mechanochemistry of inorganic
compounds and coordination-based materials, sonication
and macromolecular mechanochemistry, current theoretical
models for mechanochemical reactions, the mechanistic and
kinetic understanding, catalysis, and scaling up of mechano-
chemistry were broadly discussed.[13–39]
However, mechanochemical methods are a very active
and promising research area, their use in organic and organ-
ometallic synthesis is relatively rare and in a very infant
stage compared with other synthesis protocols, and also they
are poorly communicated for the scientific society.
Furthermore, interest in Schiff base, attributed to their func-
tion as primary reagents in cycloaddition,[40] cyclization,[41,42]
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–9.
http://www.jccs.wiley-vch.de
1

2
TIGINEH AND LIU
enantioselective oxidation,[43] metal complex synthesis for ver-
satile application,[44,45] etc., have drastically increased. How-
ever, most current protocols for the synthesis of Schiff bases
are environmentally stressful and less economical because of
However, grinding equivalent molar quantities of the two
powders together results in a dark green-colored intermediate,
followed by the formation of a liquid melt that transforms in a
matter of seconds into a white solid product. Similar behavior
was noted for a number of analogous substrates, although the
duration of transformation of liquid melt to solid product var-
ies from one substrate to another. Overall, the solid Schiff
base product begins to separate in a matter of minutes, and
the entire reaction mixture turns into a wet crystalline mass
within a few minutes. Note that similar behavior was hinted
in a previous report of the analogous reaction of aromatic
amines (vanillin and 4-chlorobenzaldehyde).[50] On the other
hand, in the reaction of p-toluidine with 4-nitrobenzaldehyde,
as soon as the reactants were mixed, an immediate color
change was demonstrated. The mixtures displayed uniform
color without melting for 10 min of cogrinding. Unlike
the previous two situations, in the reactions such as 3, 5-
dibromobenzealdehyde with 4-aminobenzonitrile, the
reactants did not show melt or color change for >15 min of
cogrinding. However, some were able to show color change
without melting after a prolonged period of cogrinding, for
example, SBB9.
the extensive use of volatile organic solvents and looking for
[46,47]
optimization on reaction conditions.
To our knowledge,
many Schiff bases have been synthesized in solution, yet the
corresponding synthesis in solid state is much less widespread,
and no systematic investigations with detail characterization
have been conducted before to address the scope.[48–50] There-
fore, in this work, attempts have been made to synthesize
20 Schiff bases from 10 differently functional solid aromatic
aldehydes and two solid primary aromatic amines by cog-
rinding in mortar with a pestle under a solvent-free, and differ-
ently under solvent-assisted, environment at room temperature
in order to determine the scope of solvent-free mechanochemi-
cal synthesis of the Schiff base from systematically selected
aromatic aldehyde and primary aromatic amine.
2 | RESULTS AND DISCUSSION
2.1 | Solvent-free mechanochemical synthesis
For the investigation of solvent-free mechanochemical syn-
thesis of Schiff base, the solid primary aromatic amines used
were carrying either an electron-donating substituent (-CH3)
or an electron-withdrawing substituent (-CN) at p position,
whereas 10 solid aromatic aldehydes systematically selected
and used contained para substituted halides (p-Cl, para-Br,
para-I), isomeric NO2 derivatives (o-, meta-, p-NO2), di-
substituted functional 2-OH-5NO2, 3-Br-5Br derivatives, and
p-OH (Scheme 1). The cogrinding was performed with a mor-
tar and a pestle under a solvent-free environment at room
temperature. The broad spectrum of aromatic aldehydes and
two primary aromatic amines with different electronic natures
examined here was meant to provide sufficient data to deter-
mine limitation, if any, of the solvent-free mechanochemical
conversion of p-toluidine and 4-aminobenzonitrile with differ-
ently functionalized aromatic aldehydes to corresponding
Schiff bases. The 20 target Schiff bases, abbreviated as
SBA1–SBA10 and SBB1–SBB10, are shown in Table 1. The
results demonstrated that, for instance, in the reaction of p-
toluidine with 4-bromobenzaldehyde, grinding each reactant
separately does not lead to any changes in bulk physical char-
acteristics except particle size (both are white powders).
1
2.2 | H NMR (CDCl3) spectra
The Schiff base product mixtures were periodically monitored
by H NMR spectroscopy in order to achieve the complete
1
disappearance of the aldehyde and amine protons and the full
emergence of the azomethine proton (Supporting Information
Appendix S1). At 100% conversion, the product spectra
exhibited a singlet at δ 8.35–8.98 attributed to azomethine
proton (–CH=N–) and no signal at ca.δ10 attributed to alde-
hyde proton (–CH=O). The extra single sharp peak around
δ1.56 is due to the solvent residual peak of H2O in CDCl3.[51]
It is worth mentioning that, on Schiff base formation, the sig-
nal of the azomethine hydrogen is upfield relative to the origi-
nal signal of the aldehyde hydrogen (–CH=O). For Schiff
bases SBA9 and SBB9, the –OH proton signal of aldehyde
originally at ca.δ11.6 (Figure 4(b)) changed to that of the
Schiff base at δ14.65 (Figure 4(d)) and δ13.61, respectively,
…
the downfield shift being attributed to the O–H N intramo-
lecular H-bonding as a common feature of o-hydroxysalicy-
lidene systems.[52,53] Among the 10 examples of A series
Schiff base, seven reactions (SBA1, SBA2, SBA3, SBA5,
SBA6, SBA7, SBA10) demonstrated virtually no evidence of
aromatic aldehyde or p-toluidine in the crude product mixture
taken directly from the mortar, indicating the efficiency of the
1
conversion. The H NMR spectrum of the ground product
mixture for SBA6 is shown in Figure 1 as a typical example,
in which the dehydration reaction was completed without side
products. For the Schiff bases (SBA4 and SBA9) prepared
with mortar and pestle, a trace amount of the aldehyde proton
SCHEME 1 Solvent-free mechanochemical synthesis of
Schiff base

TIGINEH AND LIU
3

4
TIGINEH AND LIU
2.3 | Solvent-assisted mechanochemical
synthesis
Attempts have been made to enhance the kinetics and yield of
solvent-free mechanochemical synthesis of Schiff base using
small drops of solvent in which the starting aldehyde and
amine are soluble. The investigation surprisingly demon-
strated that, in the case of SBB4, the solvent-free mechano-
chemical synthesis, under the given reaction circumstance,
was better than the corresponding solvent-assisted grinding
(Figure 2). This probably suggests that SBB4 may not be
achieved with good yield in solvents such as methanol solu-
tion. In the other experiment, both SBB7 and SBB8 demon-
strated no significant difference in the yield via solvent-free
or solvent-assisted synthesis protocols, likely because metha-
nol has no significant effect on the kinetics and yield of such
reactions at a given reaction condition. Moreover, we were
also able to observe the effect, if any, (a) by looking at the 1H
NMR in CDCl3 and CD3OD of the freshly prepared samples
after a week of mechanosynthesis of the above Schiff bases
and (b) by leaving the solutions in the NMR tubes for a week
in CDCl3, as well as CD3OD, at room temperature before the
remeasurement. In both cases, there were no observable dif-
ferences in the yield after a prolonged period of time in the
solid state or in the solution phase for B series, obtained using
both solvent-free and solvent-assisted techniques (Figure 3).
Interestingly, 1H NMR and 13C NMR of SBA9 after
being maintained for 4 days in CDCl3 solution in the NMR
tube demonstrated the disappearance of 2-hydroxy-
5-nitrobenzaldehyde and p-toluidine, indicating that solvents
such as CHCl3 have significant influence on the conversion
of aldehyde and amine into the corresponding Schiff bases
(Figure 4).
FIGURE 1 1H NMR spectra (δ −3 to 16.5, CDCl3) of (a) SBA6
directly taken from the ground product mixtures; (b) expansion (δ
7.2–9.0) of (a)
signal was observed, which could be removed by extending
the grinding time or assisting with the solvent. Conversely,
SBA8, resulted from 1:1 cogrinding between p-toluidine and
4-hydroxybenzaldehyde and showed mixing signals of reac-
1
tants and product on both H NMR and 13C NMR spectra in
both CDCl3 and CD3OD, in agreement with the previous
report.[50] Remarkably, the positive mode of EI-MS used for
SBA8 after 10 days of synthesis demonstrated the molecular
ion peak with best accuracy at 100% intensity of m/z [M+]
(see Appendix S1).
Among the 10 examples of B series Schiff bases, four reac-
tions (SBB1, SBB2, SBB6, SBB7) demonstrated trace evi-
dence of aromatic aldehyde, but no evidence of
4-aminobenzonitrile, in the crude product mixture taken
directly from the mortar. The other three (SBB4, SBB5,
SBB9) showed a substantial amount of aldehyde on the crude
product mixture directly taken from the mortar. SBB3 and
SBB10 displayed comparable amount of both reactants and
product on the 1H NMR spectra of the crude Schiff base sam-
ples directly taken from ground mixture. Astonishingly, SBB8
2.4 | Mass spectra
In the HRMS-EI and HRMS-FAB mode mass spectra of
Schiff bases (see experimental section), the molecular ion
peaks were observed with best accuracy at m/z [M + H]+
1
did not show any azometine proton on the H NMR spectra
taken in CDCl3 and CD3OD. Its 1H NMR spectra was the sum
of those of starting materials, indicating that there is no reac-
tion between 4-hydroxybenzaldehyde and 4-aminobenzonitrile
under the given reaction condition (see Appendix S1).
Overall, the solvent-free mechanochemical synthesis
results of A and B series Schiff bases showed that better
yield was obtained with p-toluidine (A series) than with p-
aminobenzonitrile (B series), which is seemingly attributable
to the electron-donating group (-CH3) in p-toluidine playing
a significant role in increasing the electron density on the
nitrogen atom of -NH2 and, accordingly, the nucleophilicity.
FIGURE 2 1H NMR spectra (δ −3 to 16.5, CDCl3) of
(a) 4-aminobenzonitrile, (b) SBB4 obtained via solvent-free method,
and (c) SBB4 obtained via solvent-assisted method

TIGINEH AND LIU
5
A solvent-free mechanochemical reaction proceeding
through a melt transition state gave better yield and showed
fast kinetics compared with those proceeding without melt
during cogrinding in both A and B series Schiff bases.
For SBA8, a significant amount of azomethine proton
signal was observed for the product obtained via solvent-free
mechanochemical synthesis, but not for SBB8. The reaction
between 4-hydroxybenzaldehyde and 4-aminobenzonitrile,
expected to form SBB8, showed no azomethine proton sig-
nal, neither through solvent-free nor solvent-assisted mecha-
nochemical synthesis (see Appendix S1). This is most likely
due to the synergistic effect of both the electron-donating –
OH group on aldehyde and the electron-withdrawing –CN
group on amine.
The observation for SBB4, the solvent-free mechano-
chemical synthesis, under the given reaction circumstance
was found to be better than the corresponding solvent-
assisted grinding, suggesting that solvent-free mechano-
chemical synthesis is important for the isolation of species,
which cannot be obtained in solution.
FIGURE 3 1H NMR spectra (δ −3 to 16.5, CDCl3) of
(a) 4-aminobenzonitrile, (b) SBB4 freshly prepared from solid material
after 5 days of mechanosynthesis, (c) SBB4 solution after 2 days in
NMR tube, and (d) SBB4 freshly prepared solution from solid material
after 7 days of mechanosynthesis
and [M]+, which are in good agreement with the molecular
weight of the proposed structure of corresponding Schiff
bases.[54]
The observation in solvent-assisted cogrinding at room
temperature showed that solvents like chloroform and meth-
anol presumably have no significant effect on the reaction
kinetics, as well as yield of the B series Schiff bases reported
in this paper, unless an otherwise external energy is supplied
and/or grinding time is prolonged.
2.5 | Comparative outlook of solvent-free and
solvent-assisted syntheses of Schiff bases
Experimentally, the solvent-free mechanochemical conver-
sion of p-toluidine and aromatic aldehydes to the
corresponding Schiff bases proceeded more smoothly than
the corresponding synthesis with 4-aminobenzonitrile. As a
result, the yield and reaction kinetics of A series Schiff base
synthesis are better than those of the corresponding B series
Schiff base synthesis. This is because the presence of the
electron-withdrawing –CN group on the aromatic ring of
amine decreases the reactivity, and hence nucleophilicity, of
the –NH2.[55]
3 | EXPERIMENTAL
3.1 | General information
Starting chemicals used were from commercial sources, for
example, Aldrich, RDH, Fluka, Acros, Matrix scientific and
were used directly without further purification. 1H NMR and
13C NMR spectra were recorded using BRUKER 400 and
300 MHz machines, with chemical shifts in δ units, down-
field positive, and referenced to the residual peak of deuter-
ated solvents (CDCl3 δ 7.24, CDCl3 δ 77, correspondingly)
and CD3OD. EI + MS spectra were recorded with a JMS-
700 double-focusing mass spectrometer (JEOL, Tokyo,
Japan) with a resolution of 8000 (3000) (5% valley defini-
tion). Melting points were determined by using a PERKIN
ELMER differential scanning calorimeter DSC 7 modules in
sealed aluminum pans, heated in flowing nitrogen (20.0 mL/
min) at 10ꢀC/min.
3.2 | General procedure for solvent-free
mechanochemical synthesis of Schiff-base
FIGURE 4 1H NMR spectra (δ −3 to 16.5, CDCl3) of (a) p-
toluidine, (b) 2-hydroxy-5-nitrobenzaldehyde, (c) SBA9 fresh solution,
and (d) SBA9 after staying in CDCl3 solution for 4 days
The solid reactants p-toluidine (1.0 mmol) and aromatic
aldehyde (1.0 mmol) were ground individually until finely
divided solids were formed; they were then mixed at a 1:1

6
TIGINEH AND LIU
SCHEME 2 Solvent-assisted mechanochemical synthesis of
Schiff base
m/z calcd for C14H12ClN+: 229.0658 [M+]; found:
229.0654.
FIGURE 5 Photos of the 20 target Schiff bases, abbreviated as
SBA1–SBA10 and SBB1–SBB10, obtained from a solvent-free
mechanochemical reaction between 10 differently functionalized
aromatic aldehydes with p-toluidine and with 4-aminobenzonitrile
3.3.2 | SBA2 (E)-N-[4-bromobenzylidene]-
4-methylaniline
Yield: 0.2698 g (98.4%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.44 (s, 1H; CH=N),
7.80 (d, J[H,H] = 8 Hz, 2H). 7.63 (d, J[H,H] = 8 Hz, 2H),
7.24 (d, J[H,H] = 8 Hz, 2H), 7.18 (d, J[H,H] = 8 Hz, 2H),
stoichiometric molar ratio at room temperature for cog-
rinding. As soon as the reactants were mixed, some
exhibited immediate color change, whereas the others did
not. The mixtures that displayed immediate color change
also melted after few minutes of cogrinding. Then, the melt
was further mixed and ground to solidify or otherwise left in
open air for about half a day at room temperature for drying.
Finally, the dried products were ground for an extra 1–3 min
and weighed. The resultant crude products without further
13
2.40 ppm (s, 3H; CH3); C NMR (300 MHz; CDCl3, 27ꢀC,
TMS): δ = 158.0 (CH=N), 149.0, 136.2, 135.3, 132.0, 130.1,
129.8, 125.7, 120.8, 21.0 (CH3) ppm; HRMS (EI+): m/z calcd
for C14H12BrN+: 273.0153 [M+]; found: 273.0159.
1
purification were investigated directly by DSC, H NMR,
3.3.3 | SBA3 (E)-N-(4-iodobenzylidene)-
4-methylaniline
13C NMR, and EI + MS. The other set of mixes that did not
melt took 5–15 min more of cogrinding to show color
change, if any, without melting, and the obtained products
were treated in a similar fashion, without further purifica-
tion. The same procedure was used for 4-aminobenzonitrile
with aromatic aldehyde (Figure 5).
Yield: 0.3194 g (99.5%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.42 (s, 1H; CH=N),
7.85 (d, J[H,H] = 8 Hz, 2H). 7.65 (d, J[H,H] = 8 Hz, 2H),
7.24 (d, J[H,H] = 8 Hz, 2H), 7.17 (d, J[H,H] = 8 Hz, 2H),
2.40 ppm (s, 3H; CH3); 13C NMR (300 MHz; CDCl3, 27ꢀC,
TMS): δ = 158.2 (CH=N), 149.0, 138.0, 136.2, 135.8,
130.1, 129.8, 120.8, 97.9, 21.0 (CH3) ppm; HRMS (EI+):
m/z calcd for C14H12IN+: 321.0015 [M+]; found: 321.0012.
3.3 | General procedure for solvent-assisted
mechanochemical synthesis of Schiff base
The solid reactants 4-aminobenzonitrile (1.0 mmol) and aro-
matic aldehyde (1.0 mmol) were ground individually until
finely divided solids were formed; they were then mixed at a
1:1 stoichiometric molar ratio, and three drops of solvent
were added to the mixture at room temperature for cog-
rinding. The rest reaction progress and the obtained products
were treated in a fashion similar to the solvent-free mechano-
chemical synthesis of Schiff base (Scheme 2 and Figure 6).
3.3.4 | SBA4 (E)-4-methyl-N-[4-nitrobenzyli-
dene]aniline
Yield: 0.2392 g (99.6%); color: yellow solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.59 (s, 1H; CH=N),
3.3.1 | SBA1 (E)-N-[4-chlorobenzylidene]-
4-methylaniline
Yield: 0.2263 g (98.6%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.46 (s, 1H; CH=N),
7.87 (d, J[H,H] = 8 Hz, 2H). 7.48 (d, J[H,H] = 8 Hz, 2H),
7.24 (d, J[H,H] = 8 Hz, 2H), 7.17 (d, J[H,H] = 8 Hz, 2H),
2.40 ppm (s, 3H; CH3); 13C NMR (300 MHz; CDCl3, 27ꢀC,
TMS): δ = 158.0 (CH=N), 149.1, 137.2, 136.1, 134.9,
129.8, 129.5, 129.0, 120.8, 21.0 (CH3) ppm; HRMS (EI+):
FIGURE 6 Photos of three Schiff bases, SBB4, SBB7, and
SBB8, obtained from a solvent-assisted mechanochemical reaction
between 4-aminobenzonitrile with 4-nitrobenzaldehyde,
4-cyanobenzaldehyde, and 4-hydroxybenzaldehyde, respectively

TIGINEH AND LIU
7
8.35 (d, J[H,H] = 8 Hz, 2H). 8.10 (d, J[H,H] = 8 Hz, 2H),
7.27–7.23 (m, 4H), 2.42 ppm (s, 3H; CH3); 13C NMR
(300 MHz; CDCl3, 27ꢀC, TMS): δ = 156.3 (CH=N), 149.2,
148.3, 141.8, 137.3, 130.0, 129.3, 124.0, 121.0, 21.1 (CH3)
ppm; HRMS (EI+): m/z calcd for C14H12N2O2+: 240.0899
[M+]; found: 240.0896.
CH=N), 7.78 (d, J[H,H] = 8 Hz, 2H), 7.23 (d, J[H,H] = 8 Hz,
2H), 7.14 (d, J[H,H] = 8 Hz, 2H), 6.91 (d, J[H,H] = 8 Hz,
2H), 2.36 ppm (s, 3H; CH3); HRMS (EI+): m/z calcd for
C14H13ON+: 211.0997 [M+]; found: 211.0993. Note: nei-
ther reactants nor Schiff-base signals were observed on both
1H NMR and 13C NMR spectra in CD3OD. SBA8 is insolu-
ble in CDCl3.
3.3.5 | SBA5 (E)-4-methyl-N-[3-nitrobenzyli-
dene]aniline
3.3.9 | SBA9 (E)-4-nitro-2-([p-tolylimino]
methyl)phenol
Yield: 0.2378 g (99.0%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.75 (s, 1H; CH=N),
8.58 (s, 1H), 8.34 (d, J[H,H] = 8 Hz, 1H), 8.27 (d, J[H,-
H] = 8 Hz, 1H), 7.69 (t, J[H,H] = 8 Hz, 1H), 7.25–7.20 (m,
4H), 2.42 ppm (s, 3H; CH3); 13C NMR (300 MHz; CDCl3,
27ꢀC, TMS): δ = 156.2 (CH=N), 148.7, 148.2, 138.1,
137.0, 134.0, 130.0, 129.8, 125.4, 123.4, 121.0, 21.1 (CH3)
ppm; HRMS (EI+): m/z calcd for C14H12N2O2+: 240.0899
[M+]; found: 240.0896.
Yield: 0.2531 g (98.8%); color: yellow solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 14.65 (s, 1H; OH),
8.72 (s, 1H; CH=N), 8.40 (s, 1H), 8.28–8.25 (m, 1H),
7.30–7.25 (m, 4H), 7.11 (d, J[H,H] = 8 Hz, 1H), 2.43 ppm
13
(s, 3H; CH3); C NMR (300 MHz; CDCl3, 27ꢀC, TMS):
δ = 167.05, 159.5 (CH=N), 143.9, 139.9, 138.4, 130.3,
128.2, 128.1, 121.1, 118.3, 118.2, 21.1 (CH3) ppm; HRMS
(EI+): m/z calcd for C14H12O3N2+: 256.0848 [M+]; found:
256.0846.
3.3.6 | SBA6 (E)-4-methyl-N-(2-nitrobenzyli-
dene)aniline
3.3.10 | SBA10 (E)-N-[3,5-dibromobenzyli-
dene]-4-methylaniline
Yield:0.2389 g (99.4%); color: light yellow-brown solid;
1H NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.98 (s,
1H; CH=N), 8.35 (d, J[H,H] = 8 Hz, 1H), 8.10 (d, J[H,-
H] = 8 Hz, 1H), 7.77 (t, J[H,H] = 8 Hz, 1H), 7.65 (t, J
[H,H] = 8 Hz, 1H), 7.27–7.23 (m, 4H), 2.41 ppm (s, 3H;
CH3); 13C NMR (300 MHz; CDCl3, 27ꢀC, TMS):
δ = 154.8 (CH=N), 149.3, 148.5, 137.0, 133.5, 131.3,
131.0, 129.9, 129.7, 124.5, 121.2, 21.1 (CH3) ppm;
HRMS (EI+): m/z calcd for C14H12N2O2+: 240.0899 [M
+]; found: 240.0901.
Yield: 0.3494 g (99.0%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.37 (s, 1H; CH=N),
8.00 (s, 2H), 7.77 (s, 1H), 7.25 (d, J[H,H] = 8 Hz, 2H), 7.17
(d, J[H,H] = 8 Hz, 2H), 2.41 ppm (s, 3H; CH3); 13C NMR
(300 MHz; CDCl3, 27ꢀC, TMS): δ = 155.8 (CH=N), 148.3,
139.7, 136.8, 136.2, 131.2, 130.2, 129.9, 123.4, 120.9, 21.0
(CH3) ppm; HRMS (EI+): m/z calcd for C14H11(79)Br2N+:
350.9250 [M+]; found: 350.9258.
3.3.11 | SBB1 (E)-4-([4-chlorobenzylidene]
amino) benzonitrile
3.3.7 | SBA7 (E)-4-([p-tolylimino]methyl)
benzonitrile
Yield: 0.2380 g (98.9%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.39 (s, 1H; CH=N),
7.88 (d, J[H,H] = 8 Hz, 2H). 7.71 (d, J[H,H] = 8 Hz, 2H),
7.50 (d, J[H,H] = 8 Hz, 2H), 7.25 (d, J[H,H] = 8 Hz, 2H);
13C NMR (300 MHz; CDCl3, 27ꢀC, TMS): δ = 160.9,
155.6 (CH=N), 138.4, 134.0, 133.8, 133.4, 130.9,130.3,
129.5, 129.3, 121.5, 118.9, 114.5, 109.3 ppm; HRMS (FAB
+): m/z calcd for C14H9ClN2 + H+: 241.0533 [M + H]+;
found: 241.0527.
Yield: 0.2185 g (99.2%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.53 (s, 1H; CH=N),
8.03 (d, J[H,H] = 8 Hz, 2H), 7.78 (d, J[H,H] = 8 Hz, 2H),
7.26 (d, J[H,H] = 8 Hz, 2H), 7.21 (d, J[H,H] = 8 Hz, 2H),
2.41 ppm (s, 3H; CH3); 13C NMR (300 MHz; CDCl3, 27ꢀC,
TMS): δ = 156.8 (CH=N), 148.4, 140.2, 137.0, 132.5,
129.9, 129.0, 120.9, 118.5, 114.2, 21.1 (CH3) ppm; HRMS
(EI+): m/z calcd for C15H12N2+: 220.1000 [M+]; found:
220.0999.
3.3.12 | SBB2 (E)-4-([4-bromobenzylidene]
amino) benzonitrile
3.3.8 | SBA8 (E)-4-([p-tolylimino]methyl)
phenol
Yield: 0.27970 g (98.1%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.38 (s, 1H; CH=N),
7.80 (d, J[H,H] = 8 Hz, 2H). 7.71 (d, J[H,H] = 8 Hz, 2H),
Yield: 81% (1H NMR estimation); color: white solid; H
NMR (400 MHz, CD3OD, 27ꢀC, TMS): δ = 8.44 (s, 1H;
1

8
TIGINEH AND LIU
7.67 (d, J[H,H] = 8 Hz, 2H), 7.25 (d, J[H,H] = 8 Hz, 2H);
13C NMR (300 MHz; CDCl3, 27ꢀC, TMS): δ = 161.1, 155.6
(CH=N), 134.4, 133.8, 133.4, 132.5, 132.3,131.0, 130.5,
127.0, 121.5, 118.9, 114.5, 109.4 ppm; HRMS (FAB+): m/z
calcd for C14H9(79)BrN2 + H+: 285.0027 [M + H]+; found:
285.0033.
8.06 (d, J[H,H] = 8 Hz, 2H), 7.82 (d, J[H,H] = 8 Hz, 2H),
7.74 (d, J[H,H] = 8 Hz, 2H), 7.28 (d, J[H,H] = 8 Hz, 2H);
HRMS (FAB+): m/z calcd for C15H9N3 + H+: 232.0875
[M + H]+; found: 232.0878.
3.3.18 | SBB8 (E)-4-([4-hydroxybenzylidene]
amino) benzonitrile
3.3.13 | SBB3 (E)-4-([4-Iodobenzylidene]
amino) benzonitrile
No product.
Note: SBB8 did not show any azometine proton on the
1
Yield: 32% (1H NMR estimation); color: white solid; H
1H NMR spectra taken from CDCl3 and CD3OD.
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.35 (s, 1H;
CH=N), 7.88 (d, J[H,H] = 8 Hz, 2H). 7.71 (d, J[H,H] = 8 Hz,
2H), 7.65 (d, J[H,H] = 8 Hz, 2H), 7.25 (d, J[H,H] = 8 Hz,
2H); HRMS (FAB+): m/z calcd for C14H9N2I + H+:
332.9889 [M + H]+; found: 332.9885.
3.3.19 | SBB9 (E)-4-([2-hydroxy-
5-nitrobenzylidene]amino) benzonitrile
1
Yield: 64% (1H NMR estimation); color: yellow solid; H
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 13.61 (s, 1H;
OH), 8.74 (s, 1H; CH=N), 8.46 (s, 1H), 7.81 (d, J[H,-
H] = 8 Hz, 2H), 7.43 (d, J[H,H] = 8 Hz, 2H), 7.19–7.17 (m,
1H), 6.68 (d, J[H,H] = 8 Hz, 1H); HRMS (FAB+): HRMS
(FAB+): m/z calcd for C14H9O3N3 + H+: 268.0722 [M
+ H]+; found: 268.0715.
3.3.14 | SBB4 (E)-4-([4-nitrobenzylidene]
amino)benzonitrile
Yield: 72% (1H NMR estimation); color: yellow solid; H
1
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.53 (s, 1H;
CH=N), 8.38 (d, J[H,H] = 8 Hz, 2H). 8.13 (d, J[H,H] = 8 Hz,
2H), 7.75 (d, J[H,H] = 8 Hz, 2H), 7.31 (d, J[H,H] = 8 Hz,
2H); HRMS (FAB+): m/z calcd for C14H9N3O2 + H+:
252.0773 [M + H]+; found: 252.0778.
3.3.20 | SBB10 (E)-
4-([3,5-dibromobenzylidene]amino)
benzonitrile
3.3.15 | SBB5 (E)-4-([3-nitrobenzylidene]
amino)benzonitrile
1
Yield: 50% (1H NMR estimation); color: white solid; H
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.31 (s, 1H;
CH=N), 8.00 (s, 2H), 7.95 (s, 1H), 7.44 (d, J[H,H] = 8 Hz,
2H), 7.25 (d, J[H,H] = 8 Hz, 2H); HRMS (FAB+): m/z
calcd for C14H8(79)Br2N2 + H+: 362.9132 [M + H]+;
found: 362.9135.
Yield: 84% (1H NMR estimation); color: white solid; H
1
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.78 (s, 1H;
CH=N), 8.53 (s, 1H), 8.41 (d, J[H,H] = 8 Hz, 1H), 8.28 (d,
J[H,H] = 8 Hz, 1H), 7.75–7.21 (m, 3H), 7.30 (d, J[H,-
H]
= 8 Hz, 2H); HRMS (FAB+): m/z calcd for
C14H9N3O2 + H+: 252.0773 [M + H]+; found: 252.0769.
4 | CONCLUSIONS
3.3.16 | SBB6 (E)-4-methyl-N-
(2-nitrobenzylidene)aniline
In this work, attempts have been made to synthesize Schiff
bases mechanochemically under solvent-free and solvent-
assisted environments from systematically selected aromatic
amines and aldehydes. Among the 20 solvent-free mechano-
chemical reactions between solid aromatic primary amines
and aldehydes, 13 Schiff bases were produced with a greater
than 98% yield, four Schiff bases obtained with good yield
(60%–85%), and two Schiff bases were synthesized with less
than 60% yield. However, one among 20 did not give any
Schiff base product. Based on our previous study[8] and the
investigation thereon, solvent-free mechanochemical synthe-
sis is a powerful method for Schiff base synthesis; it is how-
ever, not the universal standard in Schiff base formation.
Yield: 0.2493 g (99.3%); color: light yellow-brown solid; 1H
NMR (400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.93 (s, 1H;
CH=N), 8.31 (d, J[H,H] = 8 Hz, 1H), 8.15 (d, J[H,H] = 8 Hz,
1H), 7.82 (t, J[H,H] = 8 Hz, 1H), 7.75–7.69 (m, 3H) 7.33
(d, J[H,H] = 8 Hz, 2H); HRMS (FAB+): m/z calcd for
C14H9N3O2 + H+: 252.0773 [M + H]+; found: 252.0778.
3.3.17 | SBB7 (E)-4-([4-cyanobenzylidene]
amino)benzonitrile
Yield: 0.2298 g (99.0%); color: white solid; 1H NMR
(400 MHz, CDCl3, 27ꢀC, TMS): δ = 8.47 (s, 1H; CH=N),

TIGINEH AND LIU
9
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ACKNOWLEDGMENTS
This research was supported by Academia Sinica, Institute
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the Structural Chemistry laboratory, Institute of Chemistry,
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Additional supporting information may be found online in
the Supporting Information section at the end of this article.
How to cite this article: Tigineh GT, Liu L-K.
Systematic studies on mechanochemical synthesis:
Schiff bases from solid aromatic primary amines and
aldehydes. J Chin Chem Soc. 2019;1–9. https://doi.
org/10.1002/jccs.201800486