A reliable route to 1,2-diamino-4,5-phthalodinitrile

Article abstract of DOI:10.1055/s-2008-1042939

Starting from o-phenylenediamine, we have developed a new and reliable route to 1,2-diamino-4,5-phthalodinitrile that is based on the reductive desulfurisation of 5,6-dicyano-2,1,3-benzothiadiazole with sodium borohydride. The reaction sequence uses only

Full text of DOI:10.1055/s-2008-1042939

SHORT PAPER
1179
A Reliable Route to 1,2-Diamino-4,5-phthalodinitrile
A
C
R
eliable
R
oute
h
to 1,2-Dia
m
r
ino-4, 5-
i
phthalo
s
dinitrile tian Burmester, Rüdiger Faust*
Institute for Chemistry and CINSaT - Center for Interdisciplinary Nanostructure Science and Technology, University of Kassel,
Heinrich-Plett-Str. 40, 34132 Kassel, Germany
Fax +49(561)8044752; E-mail: r.faust@uni-kassel.de
Received 19 October 2007; revised 2 January 2008
H2N
H2N
CN
CN
Abstract: Starting from o-phenylenediamine, we have developed a
new and reliable route to 1,2-diamino-4,5-phthalodinitrile that is
based on the reductive desulfurisation of 5,6-dicyano-2,1,3-ben-
zothiadiazole with sodium borohydride. The reaction sequence uses
only cheap reagents and relies on simple recrystallisations for the
purification of all intermediates.
1
Figure 1
Key words: heterocycles, reduction, sulfur, boron, protecting
groups
routes5,6 for the synthesis of 1 are generally lengthy and
expensive, require tedious work-up procedures and are
notorious for their varying and often unsatisfactory low
The juxtaposition of electron-donating and accepting yields. Scheme 1 summarises two such syntheses and
5
a
groups across a delocalised organic framework is of con- serves to illustrate these points. Whereas route A starts
tinuing interest as this structural motif can be exploited to from 1,2-diaminobenzene (2), route B5 uses 1,2-dibro-
devise materials with unique electronic and/or optical mobenzene (4) as the starting material. In both cases, in-
b–d
1
properties. A prototypical representative of this class of troduction of the cyano groups is achieved by an exchange
compounds is 1,2-diamino-4,5-phthalodinitrile (1; of the vicinal bromine substituents in 3 and 5, respective-
Figure 1), which, as a consequence, has emerged as a ly, by Rosemund von Braun reactions with copper(I) cya-
valuable building block inter alia for the construction of nide. The yields of these reactions vary and range from 5–
2
organic light-emitting diodes and for chromophores with 25% (route A) to optimised 44% (route B). Difficulties in
3
non-linear optical properties. In addition, phthalodini- the work-up of these reactions result largely from the need
triles such as 1 serve as convenient starting materials for to remove residual copper salts from the chelating prod-
functionalised phthalocyanines and their nitrogen-rich ucts. These problems are augmented in route B, where a
congeners, the porphyrazines. Applications of these mac- subsequent reduction of the remaining nitro group in 6
rocyclic chromophores range from optical data storage, with tin chloride leads to similar (if not worse) problems.
signal processing and optical limiting, to biological sens- In addition, the nitration of 4 as well as the substitution of
ing and therapeutic applications.4
one of the nitro groups with gaseous ammonia is ham-
pered by low yields. Youngblood recently reported an al-
ternative procedure for the synthesis of 1, relying on the
The significance of 1 in organic materials chemistry is
contrasted by its synthetic availability. The reported
6
Route A
1
2
. TosCl, py, r.t.,
8 h, 90 %
. Br2, AcOH,
r.t., 2 h, 80%
1
CuCN,
DMF, PhNO2,
140 °C, 12 h
NH2
NH2
Br
Br
NH2
NH2
NC
NC
NH2
NH2
3. H2SO4, H2O,
5–25%
120 °C, 2 h, 98%
2
3
1
SnCl2, HCl,
0 °C, 20 min
95%
7
Route B
CuCN,
DMF, PhNO2,
190 °C, 4 h
1
. HNO3, H2SO4,
reflux, 12 h, 35%
Br
Br
Br
Br
NH2
NO2
NC
NC
NH2
NO2
2
. NH3, EtOH,
reflux, 3 h, 48%
44%
4
5
6
Scheme 1 Established routes to 1,2-diamino-4,5-phthalodinitrile
SYNTHESIS 2008, No. 8, pp 1179–1181
x
x
.
x
x
.2
0
0
8
Advanced online publication: 18.03.2008
DOI: 10.1055/s-2008-1042939; Art ID: T16407SS
Georg Thieme Verlag Stuttgart · New York
©

1
180
C. Burmester, R. Faust
SHORT PAPER
Br
NH2
NH2
Br
Br
SOCl2, Et3N, CH2Cl2,
reflux, 2 h, 66%
N
N
CuCN, DMF,
S
reflux, 3 h, 66%
Br
3
7
NC
NC
NC
NH2
NH2
N
S
N
NaBH4, EtOH,
r.t., 24 h, 53%
NC
1
8
Scheme 2 The 2,1,3-benzothiadiazole route to 1
diiodination of 1,2-dinitrobenzene followed by a reduc- combination of sodium borohydride and cobalt(II) chlo-
tion of the nitro groups with Fe/HCl and subsequent ha- ride,13 lithium aluminium hydride or tin(II) chloride.
14
15
lide exchange with copper(I) cyanide. Again, problems Lithium aluminium hydride can be readily discounted as
with tedious work-up and low yields remain.
For an extensive study of quinoxalino-porphyrazines,5a,7
a reducing agent in this particular case because of the re-
active nitrile groups present in 8. Consequently, an excess
of sodium borohydride in ethanol at room temperature
was used to furnish the desired target 1 in 53% yield. At
higher temperatures (>40 °C), the reaction failed com-
pletely and an excess of reducing agent was needed to
guarantee satisfactory yields. The use of alternative sol-
vents was possible (47% yield in THF) as long as condi-
tions were not strictly anhydrous. The reductive
desulfurisation of 8 with a combination of cobalt(II) chlo-
we needed to prepare larger amounts of 1,2-diamino-4,5-
phthalodinitrile (1) and were thus searching for a more re-
liable and more economical route to this valuable building
block. We present here the results of our efforts, which
capitalise on the successful reductive desulfurisation of a
dicyanobenzothiadiazole (Scheme 2).
Our route to the title compound starts from 4,5-dibro-
8
,9
mophenylene-1,2-diamine (3), whose synthesis could
13
ride and sodium borohydride only gave minute amounts
be significantly improved. Hence, o-phenylenediamine
15
of diamine 1. The capacity of tin chloride to effect this
(
2) was converted into N,N¢-di(p-toluenesulfonyl)-o-
transformation was also rather limited (27% yield).
phenylenediamine at room temperature according to
1
0
The overall yield for the synthesis of 1 via the benzothia-
diazole route is comparable to that of route A, but the re-
producibility is higher and the handling of intermediates
is more convenient. In comparison to route B, the ben-
zothiadiazole route gives higher overall yields.
Stetter in 90% yield. Conducting the reaction at higher
temperatures led to inferior yields, presumably due to the
formation of N,N,N¢-tri(p-toluenesulfonyl)-o-phenylene-
1
1
diamine. Conversion of this intermediate into 3 was ac-
complished by its treatment with bromine in glacial acetic
acid in the presence of anhydrous sodium acetate. Subse- In summary, we have devised a reliable route to 1,2-di-
quent protodetosylation with dilute sulphuric acid at amino-4,5-phthalodinitrile (1), using cheap reagents and
1
20 °C gave 1,2-diamino-4,5-dibromobenzene (3) in an obviating the need for chromatographic purifications of
8
overall yield of 78%.
intermediates. The synthesis delineated here is therefore
suitable for a preparation of 1 on a large scale.
Treatment of 3 with thionyl chloride in refluxing dichlo-
romethane smoothly converted 3 into 5,6-dibromo-2,1,3-
benzothiadiazole (7), which was obtained in 66% yield af- The H and 13C NMR spectra were recorded on a Varian Unity
1
9
ter recrystallisation from ethanol. As noted previously, 7 INOVA NMR spectrometer operating at 500 and 125 MHz, respec-
tively, using residual solvent peaks (CHCl at d = 7.26 ppm and
is electronically predisposed to act as an efficient sub-
strate in the Rosemund von Braun reaction with copper(I)
cyanide. Moreover, and in contrast to the diamino-func-
tionalised substrates 3 and 5, problems arising from the
3
1
DMSO at d = 2.50 ppm, for H spectra, CHCl at d = 77.0 ppm and
3
1
3
DMSO at d = 39.5 ppm for C spectra) as internal standards. IR
spectra were obtained on a Bruker Vector 22 instrument in the 400–
–1
4
000 cm range. Melting points were determined on a Stuart SMP
chelation of copper ions are not to be expected. Therefore, 10 hot-stage and are uncorrected. Reactions were monitored by an-
under slightly modified conditions to those originally re- alytical TLC on precoated plates (silica gel 60 F254). Compound 3
9
8,9
was prepared according to published procedures using the im-
provements described in the text.
ported by Moerkved et al. (omission of nitrobenzene,
shorter reaction times), phthalodinitrile 8 could be isolat-
ed in 66% yield after recrystallisation from ethanol. The
formation of 2,1,3-benzothiadiazole-5,6-dicarboximide, a
5
,6-Dibromo-2,1,3-benzothiadiazole (7)9
To a solution of 1,2-diamino-4,5-dibromobenzene (3; 5.52 g, 20.7
mmol) and Et N (12 mL, 83 mmol) in CH Cl (60 mL) was added,
under reflux, a solution of thionyl chloride (2.27 mL, 31 mmol) in
CH Cl (10 mL). After addition was complete, the reaction mixture
was stirred for 3 h under reflux. After cooling to r.t., H O (25 mL)
was added and the phases were separated. The organic phase was
washed with H O (2 × 25 mL), brine (25 mL) and dried (MgSO ).
9
side-product of the reaction, was not observed in our
3
2
2
case.
2
2
From 8, the title compound 1 could be accessed by a re-
2
ductive desulfurisation. Commonly used reagents for this
transformation in general are sodium borohydride,12
a
2
4
Synthesis 2008, No. 8, 1179–1181 © Thieme Stuttgart · New York

SHORT PAPER
A Reliable Route to 1,2-Diamino-4,5-phthalodinitrile
1181
The solvent was removed under vacuum and the benzothiadiazole 7 Acknowledgment
was recrystallised from EtOH.
We wish to thank Alexander Reimann for experimental assistance.
9
Yield: 4.00 g (66%); pale-yellow solid; mp 132–133 °C (Lit. 131–
35 °C)
1
References
IR (KBr): 3077, 3061, 1765, 1711, 1577, 1478, 1414, 1347, 1229,
–
1
1
062, 951, 887, 859, 823, 686, 532 cm .
(
1) (a) Tykwinski, R. R.; Schreiber, M.; Carlon, R. P.;
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H NMR (500 MHz, CDCl ): d = 8.38 (s, 2 H).
3
1
3
C NMR (125 MHz, CDCl ): d = 124.9, 127.2, 153.8.
3
,6-Dicyano-2,1,3-benzothiadiazole (8)9
5
2943.
A suspension of 5,6-dibromobenzo-2,1,3-thiadiazole (2.87 g, 9.8
mmol) and CuCN (2.84 g, 32 mmol) in DMF (40 mL) was heated
at reflux for 3 h under argon. After cooling to r.t., a solution of
iron(III) chloride hexahydrate (13 g) in concd HCl (3.5 mL) and
(
2) (a) Chen, S.; Xu, X.; Liu, Y.; Qiu, W.; Yu, G.; Wang, H.;
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H O (20 mL) was added and the mixture was stirred at 70 °C for 30
2
min. The solution was extracted with CH Cl (2 × 100 mL) and the
2
2
combined organic phases were extracted with HCl (6M, 3 × 50
(
(
mL), H O (50 mL), brine (50 mL) and dried (MgSO ). Solvent was
2
4
removed under vacuum and the benzothiadiazole 8 was recrystalli-
zation from EtOH.
9
Yield: 1.20 g (66%); pale-yellow solid; mp 201 °C (Lit. 205–
2
08 °C).
IR (KBr): 3091, 3015, 2237 (s), 1814 (m), 1492, 1452, 1351, 1149,
–
1
(5) (a) Mitzel, F.; FitzGerald, S.; Beeby, A.; Faust, R. Chem.
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9
11, 875, 829, 741 cm .
1
H NMR (500 MHz, DMSO-d ): d = 9.18 (s, 2 H).
6
1
3
C NMR (125 MHz, DMSO-d ): d = 112.5, 115.6, 130.4, 153.6.
6
1
,2-Diamino-4,5-dicyanobenzene (1)5a
To a solution of 5,6-dicyanobenzo-2,1,3-thiadiazole (8; 0.86 g, 4.6
mmol) in EtOH (80 mL) was added, portionwise, NaBH (0.70 g,
4
1
8.5 mmol) under argon and the purple solution was stirred for 12
h. Sat. aq NH Cl (10 mL) was added and, after 30 min, the reaction
4
mixture was extracted with CH Cl (4 × 20 mL). The combined or-
2
2
ganic phases were extracted with H O (20 mL), brine (20 mL) and
2
dried (MgSO ). After removal of the solvent under vacuum the res-
(11) Cheeseman, G. W. H. J. Chem. Soc. 1955, 3308.
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(b) Tsubata, Y.; Suzuki, T.; Miyashi, T. J. Org. Chem. 1992,
4
idue was purified by flash column chromatography on silica gel
(
CH Cl –EtOAc, 1:1) to give 1.
2 2
Yield: 387 mg (53%); off-white solid; mp 262–264 °C (Lit.5a 272–
75 °C).
57, 6749.
2
(
13) DaSilveira Neto, B. A.; Lopes, A. S.; Wüst, M.; Costa, V. E.
U.; Ebeling, G.; Dupont, J. Tetrahedron Lett. 2005, 46,
6843.
The product was pure enough to be used in further reactions, how-
ever, additional purification steps (recrystallisation from H O–
2
5a
EtOH mixtures ) can be undertaken if required. Conversion of
.3 g starting material furnished the product in 43% yield.
(
14) (a) Suzuki, T.; Okubo, T.; Okada, A.; Yamashita, Y.;
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Bangcuyo, C. G.; Smith, M. D.; Bunz, U. H. F. Angew.
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1
–
1
IR (KBr): 3444, 3334, 2218 cm .
1
H NMR (500 MHz, DMSO-d ): d = 5.86 (s, 4 H, NH), 6.86 (s,
6
(
15) Takahashi, K.; Eguchi, H.; Shiwaku, S.; Hatta, T.; Kyoya,
E.; Yonemitsu, T.; Mataka, S.; Tashiro, M. J. Chem. Soc.,
Perkin Trans. 1 1988, 1869.
2
H).
1
3
C NMR (125 MHz, DMSO-d ): d = 101.4, 115.5, 117.9, 139.1.
6
Synthesis 2008, No. 8, 1179–1181 © Thieme Stuttgart · New York