Revisiting the reaction between diaminomaleonitrile and aromatic aldehydes: A green chemistry approach

Article abstract of DOI:10.3390/11110858

The reaction between diaminomaleonitrile (DAMN) and aldehydes and the resulting monoimines are well known. Since the standard reaction conditions involve the use of toxic solvents (typically methanol), we have sought to apply green chemistry principles to

Full text of DOI:10.3390/11110858

Molecules 2006, 11, 858-866
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Revisiting the Reaction Between Diaminomaleonitrile and
Aromatic Aldehydes: a Green Chemistry Approach
Augusto Rivera 1,*, Jaime Ríos-Motta 1 and Francisco León 2
1
Departamento de Química, Universidad Nacional de Colombia, Ciudad Universitaria, Carrera 30 #
45-03, Bogotá-D.C., Colombia. Tel.: (+57)-1-3165000; Fax: (+57)-1-3165220.
2
Instituto Universitario de Bio-Orgánica-Instituto de Productos Naturales y Agrobiología, Avenida
Astrofísico Francisco Sánchez, 2, 38206, La Laguna, Tenerife, Spain
* Author to whom correspondence should be addressed. E-mail: ariverau@unal.edu.co
Received: 13 September 2006; in revised form: 9 October 2006 / Accepted: 10 October 2006 /
Published: 11 November 2006
Abstract: The reaction between diaminomaleonitrile (DAMN) and aldehydes and the
resulting monoimines are well known. Since the standard reaction conditions involve the
use of toxic solvents (typically methanol), we have sought to apply green chemistry
principles to this reaction by either using water as the solvent without any catalysts or
employing “solvent-free” conditions. The monoimines derived from DAMN are of
interest as precursors for obtaining different heterocyclic systems and linear polymers.
The methodologies used have significant advantages with regards to cost and
environmental considerations.
Keywords: DAMN, monoimines, Green Chemistry, aromatic aldehydes.
Introduction
Tetrameric HCN (diaminomaleonitrile, DAMN) is one of the most versatile reagents in Organic
Chemistry. It has been used as a precursor for producing nucleotides and for synthesising a wide
variety of heterocyclic compounds [1] including purines [2,3], pyrimidines [4], pyrazines [5] (some
which are widely employed in the fluorescent dye industry [6]), imidazoles [7], biphenylenes [8],
porphyrazines (which have great potential in optical sensor technology [9]) and diimines that are used

Molecules 2006, 11
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as catalysts [10]. The reaction of DAMN with aromatic aldehydes is widely known to produce
monoimines [11]. These compounds are important as synthetic intermediates and they are also used in
pharmacology [12]. Their great potential has recently been demonstrated in the synthesis of conjugated
linear polymers [13] and in the thermostable optical material industry [14]. Most reaction methods
described to date involve the use methanol as a solvent without catalysts, but ethanol and acid catalysis
are required if the aldehyde bears a strong electron-withdrawing group [4,5,14].
Based on our investigations of the reaction between 1,2-diamines and formaldehyde generating
macrocyclic aminals [15] and on reactions reported in the literature for preparing imines and aminals
[16,17], we carried out the reaction between DAMN and various aromatic aldehydes employing either
water as solvent without catalysts or under “solvent-free” conditions, thus obtaining the respective
monoimines. The fact that water was used as solvent in this type of reaction makes this a cleaner, more
efficient and attractive method for preparing this type of substances. In addition the reactions carried
out in water were also shown to be chemoselective. The cyano groups could be identified and
differentiated and their 13C-NMR and IR signals were unambiguously assigned.
Results and Discussion
The reactions of DAMN with aromatic aldehydes in water as solvent or under “solvent-free”
conditions proceeded as usual to give the respective monoimines 2a-k in good to excellent yields
(Scheme 1).
Scheme 1.
(a) R1=R2=R3=H
R2
(b) R1=R2= H, R3= MeO
(c) R1=R2= H, R3= EtO
(d) R1=R2= H, R3= OH
(e) R2=R3= H, R1=OH
(f) R1= H, R2= EtO, R3=OH
(g) R1= Cl, R2=R3=H
R3
H
R1
H
N
H
N
N
N
H
H
(h) R1= NO2, R2=R3=H
(i) R1=R3= H, R2= NO2
2 a-i
NC
N
CN
H
N
H
H
H
O
N
NH2
N
N
H
N
NH2
CN
2j
NC
2k
Reaction yields fluctuated between 50-100%, with the lower values, which we attribute to pH
1
13
effects, corresponding to the reactions with hydroxybenzaldehydes. IR, H-NMR, C-NMR spectral

Molecules 2006, 11
860
analysis and 2-D experiments allowed us to establish the structures of the momoimines 2a-2k.
Compounds 2a,b,d-j have been previously described [3,7,11,18,19] and the physical properties
determined during this work are in complete agreement with those reported. It is noteworthy that no
complete spectroscopic data for compounds 2a and 2g were found in the literature, while compounds
2c and 2k have not been described previously, although preparation of 2k under acid catalysis and
using DMSO as solvent was claimed in a patent [20].
This article reports on the full assignment of NMR spectra for compounds 2a-2k deduced from the
correlations established in the 2-D (COSY, HSQC, HMBC) experiments, especially for the imine
hydrogen (Table 1). Despite the fact that these substances are well known (with the aforementioned
exceptions of 2c and 2k), to our knowledge this is the first time that these compounds have been
obtained using water as solvent.
Table 1. 13C-NMR and 1H-NMR Chemical Shift Data of 2a-k.
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
NH2
7.94 7.77 7.76 7.76 7.86 7.72 8,19 8.27 8.27 7.77 7.77
113.7 115.1 115.1 115.2 115.0 115.2 114.6 114.9 114.6 114.9 114.8
126.9 126.3 126.3 125.9 126.5 125.8 128.4 129.4 128.6 126.7 127.7
103.9 103.6 103.6 103.9 103,9 103.9 103.0 103.0 102.0 103.7 103.7.
112.9 114.3 114.3 114.4 114.4 114.4 114.0 114.5 114.1 114.1 114.3
156.1 155.2 155.2 155.6 153.4 155.8 150.4 150.9 153.2 143.5 153.6
8.31 8.21 8.20 8.16 8.59 8.13 8.56 8.61 8.39 8.08 8.85
135.7 128.9 128.7 127.4 121.7 127.8 133.3 130.2 137.7 151.9 134.8
128.5 131.4 131.5 131.7 158.6 112.7 135.1 149.9 123.3 --- 134.8
1
2
3
4
ArCHN
1´
2´
7.93 7.98 7.97 7.87 --- 7.65 ---
--- 8.87 ---
---
128.6 114.7 115.2 116.2 116.9 147.8 130.5 125.6 148.7 118.1 130.0
7.47 7.02 7.00 6.84 6.92 --- 7.55 8.08 --- 7.27 8.28
131.3 162.6 161.9 161.4 133.7 151.3 133.7 132.6 125.8 113.5 131.4
7.48 7.44 --- 6.97 7.33 --- 7.50 7.71 8.29 6.73 7.56
128.6 114.7 115.2 116.2 119.9 115.9 127.9 134.3 130.6 147.5 131.4
7.47 7.02 7.00 6.84 6.91 6.85 7.40 7.81 7.75 7.96 7.56
128.5 131.4 131.5 131.7 129.4 125.2 129.5 130.4 135.5 --- 130.0
3´
4´
5´
6´
7.93 7.98 7.97 7.87 8.03 7.35 8.44 8,53 8.44 ---
8.28
Spectroscopic analysis of the products thus obtained led us to establish that the respective
monoimine was always formed. Diimines could not be obtained in any of the cases, in agreement with
the results obtained by Rasshofer and Vogtle when using methanol as solvent [18], despite the fact that

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861
reactions were carried out using a small excess of the corresponding aldehydes. This led us to carry out
a series of experiments that allowed us to unequivocally establish that the chemoselectivity of these
reactions was not affected by the experimental conditions employed. When the reaction was carried
out using the “solvent-free” process, directly mixing the DAMN with the respective aryl aldehyde, the
expected monoimines were also always obtained. The chemoselectivity of this reaction appears to have
been governed by the structure of the monoimine itself, since all the attempts to prepare diimines
carried out using the monoimines and benzaldehyde were unsuccessful, proving that Schiff base
formation at one nitrogen deactivates the second one. This chemoselectivity was even more evident
when o-phthalaldehyde (OPA) reacted with DAMN in water, to give diimine 2k in a good yield, while
no cyclic structures such as the corresponding phthalimidines [21] were obtained.
1
The signals of both the amino (δ ≥ 8.20 ppm) and ArCHN (δ ≥ 8.30 ppm) groups in the H-NMR
spectra (Table 2) were shifted to low field when the aromatic ring bore electron-withdrawing groups
(Cl and NO2). On the other hand, when an electron-releasing group (OH, OR) was involved, signals
were observed at high field (δ ≤ 7.90 ppm). An unusual chemical shift value was observed for the
ArCHN group of compound 2e, in which although the ring bears an electron-releasing group (OH), the
hydrogen nucleus was found to be deshielded, resonating at low field (δ 8.59 ppm). This difference
was attributed to the presence of a hydrogen bond intramolecular interaction [14]. These experimental
facts also accounted for the chemoselectivity of the reaction − the conjugation of the lone pair on the
amino group with the conjugated system led to the partial charge density on nitrogen becoming
delocalised, rendering it a soft nucleophile. Bearing in mind that aldehydes are considered to be hard
electrophiles, the reactivity of the second amino group towards the aldehydes was very low, in turn
explaining the absence of disubstitution.
Table 2. 1H-NMR Chemical Shift Data of NH2 and ArCHN for 2a-k.
2a 2b 2d 2e 2f 2g 2h 2i
2j 2k
ArCHN 8.31 8.21 8.16 8.59 8.13 8.56 8.61 8.39 8.08 8.85
NH2 7.94 7.77 7.76 7.86 7.72 8.19 8.27 8.27 7.77 7.77
1
This mesomeric effect results in a differentiation between both cyano groups in the H-NMR and
IR spectra. Based on the frequencies and the difference in intensity observed for the two signals close
to the frequencies of the cyano groups (Table 3), we unequivocally assigned the two infrared
frequences corresponding to each cyano group.
Table 3 IR frequencies of cyano groups of 2a-k.
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
CN1 2240 2231 2237 2247 2235 2231 2245 2247 2237 2237 2237
CN4 2205 2207 2197 2200 2206 2212 2203 2204 2200 2200 2200
In order to avoid using water as solvent, we then decided to carry out several experiments to
establish a “solvent-free” methodology (Procedure B) and compare the yields obtained for some
benzaldehydes when using water as solvent (Procedure A). Table 4 shows the yields obtained using
each methodology. The explanation for the yield differences may reside in the hydrophobic activation

Molecules 2006, 11
862
undergone by some organic reactions, produced by the tendency of organic compounds to associate in
order to reduce interface area [22].
Table 4. Yields (%) obtained using procedures A and B.
Aldehyde
Product Procedure A Procedure B
Benzaldehyde
2a
2b
2f
78
93
53
49
62
38
p-Methoxybenzaldehyde
3-Ethoxy-4-
hydroxybenzaldehyde
o-Chlorobenzaldehyde
o-Nitrobenzaldehyde
2g
2h
79
76
14
12
Conclusions
In summary, to the best of our knowledge, the use of water in reactions involving DAMN as reagent
has been little explored. A literature search revealed only one example, in which an unsuccessful
attempt was made to condense DAMN with glyoxal to obtain pyrazines [23]. This is the first example
of the formation of Schiff bases via the condensation of DAMN with aromatic aldehydes in water,
without the use of catalysts. It would be worthwhile to explore the use of water at the subcritical
temperature [24], a method known to be highly advantageous and environmentally friendly. The
1
13
complete assignment of the H and C-NMR spectral data for this important type of compounds is
also reported herein for the first time.
Experimental
General
DAMN was obtained from Aldrich and used without further purification. The aromatic aldehydes:
benzaldehyde, anisaldehyde, p-ethoxybenzaldehyde, p-hydroxybenzaldehyde, o-salicylaldehyde, 3-
ethoxy-4-hydroxybenzaldehyde, o-chlorobenzaldehyde, o-nitrobenzaldehyde, m-nitrobenzaldehyde,
furfuraldehyde and o-phthalaldehyde were obtained from Merck. The reactions were carried out in
distilled water or by mixing the reagents directly from the bottle without a solvent. Infrared spectra
(KBr disks) were recorded on a Perkin-Elmer Paragon FT-IR instrument. NMR spectra were recorded
in DMSO-d6 at room temperature on a Bruker AMX 400 Avance operating at 400 (1H) and 100 MHz
(13C), respectively. Melting points were taken with an Electrothermal apparatus and are uncorrected.
HR-EIMS and HR-FABMS were taken on a Micromass model Autospec (70 eV) spectrometer.
General procedures for the synthesis of imines 2a-k
Procedure A (with solvent): Under vigorous stirring DAMN (0.34 mmol) was suspended in water (5
mL) and the respective aldehyde 1a-j (0.34 mmol; 0.17 mmol for 1k) was slowly added. Stirring was
continued for 2-3 h at room temperature until a precipitate appeared. The solid was filtered off, washed

Molecules 2006, 11
863
with water and dried under reduced pressure in an Abderhalden drying apparatus and, when necessary,
recrystallised from methanol.
Procedure B (solvent-free): In the case of liquid aryl aldehydes, DAMN (x mmol) was added slowly
with constant stirring to the corresponding aldehyde (0.25 mL, i.e. for benzaldehyde 0.261 g, 2.46
mmol were used) and the reaction flask was maintained at 60 °C using a water bath. A homogeneous
solution was formed after 5 min, and after another 10 min a solid began to precipitate. After 5 min at
60 °C, the solid was filtered and the crude product was washed with water and then with ethanol. The
solid thus obtained was dried under reduced pressure in an Abderhalden drying apparatus and, if
necessary, recrystallised from a suitable solvent, usually methanol. For solid aldehydes, DAMN (52
mg, 0.50 mmol) was thoroughly mixed with the respective aldehyde (0.50 mmol) and the reaction
mixture was stirred and gently heated to 80 °C. After 10 min, the viscous liquids thus obtained were
allowed to stand overnight, whereupon the reaction mixtures solidified. The crude products obtained
were washed with hot ethanol and recrystallised from methanol. The products, unless otherwise noted,
were yellow solids.
(2Z)-2-Amino-3-{[(1E)-(phenyl)methylene]-amino}but-2-enedinitrile (2a). Yield: 78%; mp 193.6–
194.8°C (from methanol, lit. [3,12]: 206–208°C, 191°C); IR: νmax/cm-1: 3419, 3302, 3162, 2240, 2205,
700; 1H-NMR: δ 8.31 (s, 1H), 7.94 (broad s, 2H), 7.93 (d, J = 7.9 Hz, 2H), 7.48 (m, 1H), 7.47 (m, 2H);
13C-NMR: δ 156.1, 135.7, 131.3, 128.6, 128.5, 126.9, 113.7, 112.9, 103.9. The spectral data were
consistent with literature values [3].
(2Z)-2-Amino-3-{[(1E)-(4-methoxyphenyl)methylene]-amino}but-2-enedinitrile (2b). Yield: 93.3%;
mp 231.5–231.8°C (from methanol, lit. [18] 227°C); IR: νmax/cm-1: 3462, 3419, 3309, 3172, 2231,
2207; 1H-NMR: δ 8.21 (s, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.77 (broad s, 2H), 7.02 (d, J = 8.8 Hz, 2H),
3.83 (s, 3H); 13C-NMR: δ 162.6, 155.2, 131.4, 128.9, 126.3, 115.1, 114.7, 114.3, 103.6, 55.9.
(2Z)-2-Amino-3-{[(1E)-(4-ethoxyphenyl)methylene]-amino}but-2-enedinitrile (2c). Yield: 84%; mp
223.2–224.0°C (from methanol); IR: νmax/cm-1: 3421, 3307, 3160, 2237, 2197, 1254; 1H-NMR: δ 8.20
(s, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.76 (broad s, 2H), 7.00 (d, J = 8.0 Hz,2H), 4.10 (q, J = 7.0 Hz, 2H),
13
1.38 (t, J = 7.0 Hz, 3H); C-NMR: δ 161.9, 155.2, 131.5, 128.7, 126.3, 115.2, 115.1, 114.3, 103.6,
63.9, 15.0; HRFABMS (%) 240.1007 [M+] (calcd. for C13H12N4O, 240.1011) (36), 219 (6), 154 (100),
137 (61), 136 (60), 124 (9), 120 (10), 107 (19); Anal. calc. for C13H12N4O: C, 65.03; H, 5.04; N, 23.33.
Found: C, 65.06; H, 4.99; N, 23.13.
(2Z)-2-Amino-3-{[(1E)-(4-hydroxyphenyl)methylene]-amino}but-2-enedinitrile (2d). Yield: 55%; mp
213.2–213.9°C (from methanol, lit. [11] 222.5–223.0°C); IR: νmax/cm-1: 3554, 3482, 3421, 3304, 3160,
2247, 2200, 1249; 1H-NMR: δ 10.20 (broad s, 1H), 8.16 (s, 1H), 7.87 (d, J = 8.5 Hz, 2H), 7.76 (broad
13
s, 2H), 6.84 (d, J = 8.5 Hz, 2H); C-NMR: δ 161.4, 155.6, 131.7, 127.4, 125.9, 116.2, 115.2, 114.4,
103.9.

Molecules 2006, 11
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(2Z)-2-Amino-3-{[(1E)-(2-hydroxyphenyl)methylene]-amino}but-2-enedinitrile (2e). Yield: 49.2%; mp
242.0–244.0°C (from ethanol, lit. [19] 234.0°C); IR: νmax/cm-1: 3554, 3418, 3309, 3195, 2235, 2206;
1H-NMR: δ 10.50 (broad s, 1H), 8.59 (s ,1H), 8.03 (d, J = 8.0 Hz, 1H), 7.86 (broad s, 2H), 7.33 (t, J =
7.9 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.91 (t, J = 7.9 Hz, 1H); 13C-NMR: δ 158.6, 153.4, 133.7, 129.4,
126.5, 121.7, 119.9, 116.9, 115.0, 114.4, 103.9.
(2Z)-2-Amino-3-{[(1E)-(3-ethoxy-4-hidroxyphenyl)methylene]-amino}but-2-enedinitrile (2f). Yield:
1
53%; mp 209.0–210.0°C (from methanol); IR: νmax/cm-1: 3461, 3333, 2231, 2212, 1613, 1275; H-
NMR: δ 9.70 (broad s, OH), 8.13 (s, 1H), 7.72 (broad s, 2H), 7.65 (d, J = 1.6 Hz, 1H), 7.35 (dd, J =
13
1.6, 8.2 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H), 4.10 (q, J = 9.0 Hz, 2H), 1.36 (t, J = 9.0 Hz, 3H); C-
NMR: δ 155.8, 151.3, 147.8, 127.8, 125.8, 125.2, 115.9, 115.2, 114.4, 112.7, 103.9, 64.4, 15.3;
HRFABMS (%) 256.0947 [M+] (calcd. for C13H12N4O2, 256.0960) (21), 219 (5), 165 (5), 154 (100),
138 (31), 136 (61), 120 (10), 107 (18).
(2Z)-2-Amino-3-{[(1E)-(2-chlorophenyl)methylene]amino}but-2-enedinitrile (2g). Yield: 79%; mp
201.4–202.4°C (from ethanol, lit. [7] 222.0–223.0°C); IR: νmax/cm-1: 3421, 3209, 3198, 2245, 2203,
1
1617, consistent with literature values [7]; H-NMR: δ 8.56 (s, 1H), 8.44 (dd, J = 1.3, 7.9 Hz, 1H),
8.19 (broad s, 2H), 7.55 (dd, J = 1.2, 8.0 Hz, 1H), 7.50 (dt, J = 1.6, 8.0 Hz, 1H), 7.40 (t, J = 7.9 Hz,
1H); 13C-NMR: δ 150.4, 135.1, 133.7, 133.3, 130.5, 129.5, 128.4, 127.9, 114.6, 114.0, 103.0.
(2Z)-2-Amino-3-{[(1E)-(2-nitrophenyl)methylene]amino}but-2-enedinitrile (2h). Yield: 76%; mp
1
224.0–225.0°C (from ethanol); IR: νmax/cm-1: 3420, 3298, 3200, 2247, 2204, 1616, 1574, 1521; H-
NMR: δ 8.61 (s, 1H), 8.53 (d, J = 7.9 Hz, 1H), 8.27 (broad s, 2H), 8.08 (d, J = 8.1 Hz, 1H), 7.81 (t, J
13
= 7.5 Hz, 1H), 7.71 (t, J = 7.7 Hz, 1H); C-NMR: δ 150.9, 149.9, 134.3, 132.6, 130.4, 130.2, 129.4,
125.6, 114.9, 114.5, 103.0; HRFABMS (%) 242.0691 [M +1]+ (calcd. for C11H8N5O2, 242.0678) (7),
219 (5), 166 (4), 154 (100), 138 (32), 136 (61), 124 (8), 120 (11), 107 (15).
(2Z)-2-Amino-3-{[(1E)-(3-nitrophenyl)methylene]-amino}but-2-enedinitrile (2i). Yield: 80%; mp
158.0–159.0°C (from methanol); IR: νmax/cm-1: 3465, 3425, 3348, 3294, 2237, 2200s, 1613, 1523,
1355; 1H-NMR: δ 8.87 (d, J = 1.5 Hz, 1H), 8.44 (d, J = 7.9 Hz, 1H), 8.39 (s, 1H), 8.29 (d, J = 7.8 Hz,
1H), 8.27 (broad s, 2H), 7.75 (t, J = 7.8 Hz, 1H); 13C-NMR: δ 153.2, 148.7, 137.7, 135.5, 130.6, 128.6,
125.8, 123.3, 114.6, 114.1, 102.0; HRFABMS (%) 241.0592 [M+] (calcd. for C11H7N5O2, 241.0600)
(3), 219 (5), 166 (4), 154 (100), 139 (12), 136 (64), 120 (11), 107 (19).
(2Z)-2-Amino-3-{[(1E)-(furfurylidyl)methylene]-amino}but-2-enedinitrile (2j). Yield: 96%; mp 158.0–
1
159.0°C (from methanol); IR: νmax/cm-1: 3465, 3425, 3348, 3294, 2237, 2200, 1613; H-NMR: δ 8.08
(s, 1H), 7.96 (d, J = 1.4 Hz, 1H), 7.77 (broad s, 2H), 7.27 (d, J = 3.5 Hz, 1H), 6.73 (dd, J = 1.5, 3.5
Hz, 1H); 13C-NMR: δ 151.9, 147.5, 143.5, 126.7, 118.1, 114.9, 114.1, 113.5, 103.7.
(2Z)-2-amino-3-({(1E)-[2-((E)-{[(Z)-2-amino-1,2--dicyanovinyl]imino}methyl)phenylmethylene}-
amino)but-2-enedinitrile (2k). A brown solid, yield: 83%; mp 158.0–159.0°C (from methanol); IR:
ν
max/cm-1: 3465, 3425, 3348, 3294, 2237, 2200, 1613; 1H-NMR: δ 8.85 (s, 1H), 8.28 (dd, J = 3.4, 5.8

Molecules 2006, 11
865
13
Hz, 1H), 7.77 (broad s, 2H), 7.56 (dd, J = 3.4, 5.8 Hz, 1H); C-NMR: δ 153.6, 134.8, 131.4, 130.0,
127.7, 114.8, 114.3, 103.7. HREIMS (%) 314.0998 [M+] (calcd. for C16H10N8, 314.1028) (26), 222
(20), 206 (100), 181 (24); Anal. calc. for C16H10N8: C, 61.14; H, 3.21; N, 35.65. Found: C, 61.18; H,
3.19; N, 35.63.
Acknowledgements
The authors gratefully acknowledge the Dirección Nacional de Investigación (DINAIN) and the
Departamento de Química, Universidad Nacional de Colombia.
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Sample Availability: Samples of the compounds 2c and 2k are available from the authors.
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