Synthesis of 1,4-diazabutadienes (=N,N′-ethane-1,2- diylidenebis[amines]) by grinding

Article abstract of DOI:10.1002/hlca.201000155

A simple and convenient method for the synthesis of 1,4-diazabutadienes (=N,N′-ethane-1,2-diylidenebis[amines]) by grinding glyoxal (=ethanedial) or an α-diketone and anilines (=benzenamines) in the presence of TsOH in a mortar with a pestle is described.

Full text of DOI:10.1002/hlca.201000155

Helvetica Chimica Acta – Vol. 94 (2011)
159
Synthesis of 1,4-Diazabutadienes (¼ N,N’-Ethane-1,2-diylidenebis[amines])
by Grinding
by Jingyu He, Hongxing Xin, Hong Yan*, Xiuqing Song, and Rugang Zhong
College of Life Science and Bio-engineering, Beijing University of Technology, Beijing 100124,
P. R. China (phone: þ 86-010-67396642; fax: þ 86-010-67392001; e-mail: hongyan@bjut.edu.cn)
A simple and convenient method for the synthesis of 1,4-diazabutadienes (¼ N,N’-ethane-1,2-
diylidenebis[amines]) by grinding glyoxal (¼ethanedial) or an a-diketone and anilines (¼ benzen-
amines) in the presence of TsOH in a mortar with a pestle is described. By this way, 1,4-diazabutadienes
were obtained in good to excellent yields.
Introduction. – The 1,4-diazabutadienes (¼ N,N’-ethane-1,2-diylidenebis[amines])
are versatile compounds in fine and pharmaceutical chemistry, especially in materials
science as liquid crystalline and mesoporous materials [1][2]. The traditional method
for the synthesis of 1,4-diazabutadienes is the condensation of a-diketones and anilines
(
¼ benzenamines) in organic solvents such as MeOH, i-PrOH, or CH Cl [3 – 5].
2
2
However, harsh reaction conditions, long reaction times, and the use of organic solvents
often present some disadvantages. Thus, the development of a simple and efficient
method for the synthesis of 1,4-diazabutadienes is still a rewarding challenge.
According to the literature, a large number of organic reactions can be carried out
in high yield under mild conditions simply by grinding [6]. We thought that this
observation warranted further investigation to better understand the influence of
grinding on the synthesis of 1,4-diazabutadienes 1 without solvent (Scheme).
Scheme
Results and Discussion. – A preliminary test was carried out to survey the requisite
conditions and establish modifications required for this methodology. Glyoxal trimer
dihydrate (instead of aqueous glyoxal solution) and anilines containing different
substituents were ground at room temperature (glyoxal ¼ ethanedial). The reaction
time and yields of 1 are summarized in Table 1 and compared with those of traditional
ꢀ
2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

1
60
Helvetica Chimica Acta – Vol. 94 (2011)
methods. The data in Table 1 showed that, in all cases, the reactions exhibited high
selectivity toward corresponding 1,4-diazabutadienes and short reaction times (30 to
90 min). The long reaction time (e.g., 24 and 96 h for 1g and 1h), which is one of the
main drawbacks of the traditional method, is substantially shortened by our method.
Moreover, the isolation of the products was simplified since the 1,4-diazabutadienes
were the main products which were purified by washing or recrystallization from
minimum amounts of EtOH. The conventional method gave the 1,4-diazabutadienes
with by-products such as 1,2-diamino-1,2-diols, or ethanetri- or ethanetetraamine
derivatives, requiring purification by column chromatography [3].
Table 1. Formation of 1,4-Diazabutadienes 1 by Different Methods
Ar
R
Grinding methoda)
Traditional methodb)
time [min]
yield [%]c)
time [h]
yield [%]d)
1
1
1
1
1
1
1
1
a
b
c
d
e
f
4-MeC H
H
Me
H
Me
H
Me
H
90
40
60
30
50
50
50
40
36
69
68
74
56
75
73
71
2
2.5
2
20
10
20
24
96
26 [3]
50 [4]
6
4
4
4
4
4-MeC H
6
2-MeC H
58 [3]
54 [5b]
37 [3]
60 [5c]
73 [5a]
26 [7a]
6
2-MeC H
6
4-ClC H
6
4
4-ClC H
6
4
g
h
3,5-(CF ) C H
3 2 6
3
3,5-(CF ) C H
Me
3
2
6
3
a) Glyoxal trimer dihydrate (1 mmol) or butane-2,3-dione (3 mmol), corresponding aniline (6 mmol),
b
and grinding. ) Glyoxal (40% aq. soln.; 1 mmol) or butane-2,3-dione (1 mmol), corresponding aniline
c
d
(
2 mmol), organic solvent. ) Yield of isolated product. ) Yield after purification by column
chromatography or recrystallization.
The catalytic activity of Lewis acid and TsOH was also studied. A blank reaction
was conducted with p-toluidine (¼4-methylbenzenamine) and glyoxal in the absence of
catalysts by grinding at room temperature, and 1,4-bis(4-methylphenyl)diazabutadiene
(
¼ N,N’-ethane-1,2-diylidenebis[4-methylbenzenamine]; 1a) was obtained in 36% yield
after 90 min. In the presence of a catalytic amount of TsOH (5 mol-%), 1a was
produced in 81% yield within 50 min. The effect of Lewis acids such as ZnCl , AlCl ,
2
3
FeCl , and SnCl are summarized in Table 2. The results show that Lewis acids can also
3
4
accelerate the formation of 1a, but TsOH was superior as catalyst for this reaction.
Table 2. Effects of Catalysts on the Synthesis of 1a by Grinding
Catalyst
Time [min]
Yield [%]a)
Catalyst
Time [min]
Yield [%]a)
no
TsOH
ZnCl2
90
50
80
36
81
74
AlCl3
80
70
70
70
75
76
FeCl · 6 H O
3
2
SnCl · 5 H O
4
2
a) Yield of isolated product.
The reaction outcome with increasing amounts of TsOH (1, 5, 10, 15, and 20 mol-
) resulted in an increase of yield (from 65 to 89%) and shortening of the reaction time
%

Helvetica Chimica Acta – Vol. 94 (2011)
161
(
from 60 to 30 min) as shown in Table 3. The use of 10 mol-% of TsOH was sufficient to
push the reaction forward, while a larger amount of the catalyst did not improve the
results greatly. Therefore, 10 mol-% of TsOH were chosen as the optimal catalyst
amount for all other syntheses of 1.
Table 3. Effects of the Amount of TsOH on the Synthesis of 1a by Grinding
TsOH [mol-%]
Time [min]
Yield [%]a)
TsOH [mol-%]
Time [min]
Yield [%]a)
1
5
0
60
50
30
65
81
86
15
20
30
30
87
89
1
a) Yield of isolated product.
The reactions generally gave high yields of products (Table 4). No obvious
electronic effect of the substituents of the anilines was observed in the reactions since
electron-donating as well as electron-withdrawing groups were well tolerated.
Compound 1a was previously prepared in 26% yield in i-PrOH as solvent, and 1c
and 1m in 58% yield in MeOH [3], whereas our procedure gave these 1,4-
diazabutadienes in 86, 88, and 93% yield, respectively. Compounds 1g and 1h were
previously prepared in 73 and 26% yield, respectively, catalyzed by HCOOH in MeOH
with reaction times of 24 and 96 h [5a][7a]. The present procedure gave 1g and 1h in 84
and 91% yield, respectively, within 30 min.
a
Table 4. Synthesis of 1,4-Diazabutadienes 1 ) by the Grinding Method
Ar
R
Time [min]
Yield [%]b)
foundc)
M.p. [8]
foundc)
reported
reported
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
g
h
i
j
k
l
m
n
4-MeC H
H
Me
H
Me
H
Me
H
Me
H
Me
H
Me
H
Me
30
30
30
30
50
45
30
30
35
45
50
30
45
30
86
82
88
81
86
85
84
91
88
80
84
76
93
89
26 [3]
50 [4]
58 [3]
54 [5b]
37 [3]
60 [5c]
73 [5a]
26 [7a]
78 [7b]
76 [5b]
85 [5b]
83 [5b]
58 [3]
131.8 – 132.7
110.2 – 111.6
123.2 – 125.0
70.8 – 71.6
107.5 – 108.9
172.4 – 173.8
223.4 – 224.6
198.2 – 199.6
102.2 – 103.5
95.5 – 97.3
132 – 133 [3]
112 [4]
123 – 124 [3]
73 [5b]
107 – 110 [3]
172 [9]
–
6
4
4
4
4
4-MeC H
6
2-MeC H
6
6
2-MeC H
4-ClC H
6
4
4-ClC H
6
4
3,5-(CF ) C H
3
2
6
3
3,5-(CF ) C H
–
3
2
6
3
2,6-(i-Pr) C H
3
104 [5b]
99 [5b]
151 [5b]
88 [5b]
153 – 154 [3]
186 – 187 [9]
2
6
2,6-(i-Pr) C H
3
2
6
2,6-Me C H
151.4 – 152.6
85.3 – 86.5
154.2 – 155.3
186.3 – 187.6
2
6
3
2,6-Me C H
2
6
3
4-MeOC H
6
4
4-MeOC H
35 [8]
6
4
a) All the isolated products were characterized by their physical properties, by H-NMR and IR spectra,
1
and by direct comparison with literature data [3 – 5][7 – 9]. ) Yield of isolated product. c) This work.
b
Conclusions. – We developed an efficient method for the synthesis of 1,4-
diazabutadienes via condensation of glyoxal or an a-diketone and anilines in the

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62
Helvetica Chimica Acta – Vol. 94 (2011)
presence of 10 mol-% of TsOH as catalyst by simple grinding at room temperature
without a solvent.
This work was financially supported by the National Natural Sciences Foundation (No. 20872009),
the Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan
Period (No. 2008ZX10001-015), and the Natural Sciences Foundation of Beijing (No. 200710005002).
Experimental Part
General. All chemicals and reagents were purchased from commercial sources and used without
further purification. Grinding was performed in a 100 ml mortar with a pestle. M.p.: X-5 melting-point
1
apparatus; uncorrected. IR Spectra: Vertex-70-FT-IR spectrophotometer; KBr pellets. H-NMR Spectra:
Bruker-Avance-II-400 instrument (400 MHz); in CDCl3.
General Procedure. Aniline (¼ benzenamine; 6 mmol), glyoxal trimer dihydrate (1 mmol, 210 mg)
or butane-2,3-dione (3 mmol, 258 mg), and TsOH (10 mol-%) were placed in a mortar. Then, the
mixture was ground with a pestle at r.t. The reactions were completed within 30 – 50 min. The product
was washed with EtOH or recrystallized from a minimum amount of EtOH to afford the 1,4-
1
diazabutadiene. All products were identified by their melting points, IR and H-NMR spectra, and
comparison with reported data [3 – 5][7 – 9] (see also Table 4).
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Received April 15, 2010