Reaction of 2,3-diaminomaleonitrile with diones

Article abstract of DOI:10.1016/j.tet.2009.01.053

2,3-Diaminomaleonitrile (DAMN) was allowed to react with 2,6-heptanedione to produce (2Z)-2-amino-3-[(1E)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile and (2Z)-2-amino-3-[(1Z)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile. The reaction of D

Full text of DOI:10.1016/j.tet.2009.01.053

Tetrahedron 65 (2009) 2506–2511
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reaction of 2,3-diaminomaleonitrile with diones
,
a
a
a
a
Yasuhiro Kubota a , Toshihiro Shibata , Emi Babamoto-Horiguchi , Jun Uehara , Kazumasa Funabiki ,
*
Shinya Matsumoto b, Masahiro Ebihara c, Masaki Matsui a
,
*
a Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
b Faculty of Education and Human Sciences, Yokohama National University, Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan
c Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
2,3-Diaminomaleonitrile (DAMN) was allowed to react with 2,6-heptanedione to produce (2Z)-2-amino-
3-[(1E)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile and (2Z)-2-amino-3-[(1Z)-3-methyl-
cyclohex-2-enylideneamino]but-2-enedinitrile. The reaction of DAMN with 2,7-octanedione yielded
trans-5,8a-dimethyl-1,5a,6,7,8,8a-hexahydrocyclopenta[e]-1,4-diazepine-2,3-dicarbonitrile. DAMN re-
acted with 2,8-nonanedione to afford trans- and cis-5,9a-dimethyl-5a,6,7,8,9,9a-hexahydro-1H-benzo[e]-
1,4-diazepine-2,3-dicarbonitrile. These compounds were characterized by X-ray crystallography, NMR
spectroscopy, and DFT calculations.
Received 5 November 2008
Received in revised form 14 January 2009
Accepted 14 January 2009
Available online 20 January 2009
Keywords:
DAMN
Diazepine
Ó 2009 Elsevier Ltd. All rights reserved.
Heterocycles
DFT calculations
Crystal structures
Reaction mechanism
1. Introduction
(Z)-1-amino-1,2-dicyano-2-(2,5-dimethylpyroro)ethane or tri-
azabicyclononene, depending on the reaction conditions.16 Thus,
2,3-Diaminomaleonitrile1 (DAMN), a tetramer of HCN, and its
derivatives have received considerable attention as one of the
versatile precursors of heterocycles. The synthesis of imidazoles,2
triazoles,2a porphyrazines,3 pyrimidines,4 pyrazines,5 diazepines,6
and purines7 has been reported. DAMN can also serve as a synthetic
precursor of fluorescent dyes,5e,g,j,6a–c,8 jet-printing inks,9 hair
dyes,10 and biologically active compounds such as insecticides11
and anticancer agents.12 Furthermore, it has been recently observed
that monoimine derivatives of DAMN have a great potential to re-
alize hyperbranched polymers by thermal polymerization via
a 1,4-conjugate addition.13 Recently, a three-component reaction14
using DAMN as well as a general two-component reaction and the
application of green chemistry to the reaction between DAMN and
aldehydes have also been reported.15
the expected diimino derivative is not always obtained from the
reaction between DAMN and diketones. To the best of our knowl-
edge, the reaction of DAMN with 2,6-diones (n¼3), 2,7-diones
NC
NC
N
N
Me
Me
n = 0
O
O
Me
Me
N
N
NC
NC
NH2
NH2
NC
NC
Me
Me
n = 1
n
DAMN
Me
NC
In addition, the reaction of DAMN with diketones has also been
reported. DAMN reacts with 2,3-butanedione5j,k (n¼0) and
2,4-pentanedione5j,6d (n¼1) to yield a pyrazine and 6H-1,4-dia-
zepine, respectively (Scheme 1). However, it is interesting to note
that DAMN reacts with 2,5-hexanedione (n¼2) to afford either
n = 2
N
Me
NC
NH2
Me
+
H
N
NC
NC
CN
N
CN
NH2
* Corresponding authors. Tel.: þ81 59 293 2596; fax: þ81 58 230 1893 (Y.K.); tel.:
þ81 59 293 2601; þ81 58 230 1893 (M.M.).
N
H
Me
E-mail addresses: kubota@gifu-u.ac.jp (Y. Kubota), matsui@apchem.gifu-u.ac.jp
(M. Matsui).
Scheme 1. Previously reported reaction of DAMN with diketones.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.053

Y. Kubota et al. / Tetrahedron 65 (2009) 2506–2511
2507
(n¼4), and 2,8-diones (n¼5) has not yet been investigated. We
Me
Me
Me
Me
report herein the reaction of DAMN with 2,6-heptanedione (1),
2,7-octanedione (6), and 2,8-nonanedione (10).
NC
N
NC
NC
N
NC
NC
N
NC
N
2. Results and discussion
H2N
CN
NH2
NH2
H2N
CN
2c
2d
2b
2a
2.1. Reaction of DAMN with 2,6-heptanedione (1)
0.00 kJ/mol
+ 3.33 kJ/mol + 10.5 kJ/mol + 15.1 kJ/mol
The reaction of DAMN with 117 was examined in the presence of
oxalic acid. From the 1H NMR spectrum in CDCl3, it was elucidated
that two isomers were produced in a 2.5:1 ratio (Scheme 2, Fig. S1).
Figure 2. Relative energies of possible isomers calculated at the B3LYP/6-31G(d,p)
level.
using the B3LYP19 and 6-31G(d,p) basis sets. The optimized struc-
tures and relative energies of the isomers are shown in Figure S2
and Figure 2, respectively. The calculated stability order of these
isomers is as follows: (most stable) 2a>2b>2c>2d (least stable). It
is considered that 2Z-isomers 2a and 2b are more stable than
2E-isomers 2c and 2d owing to an internal N–H/H hydrogen bond.
This calculated result indicates that 2a is isomerized to 2b.
The signal of the spectrum showed a series of large methylene (dH
:
1.88, 2.23, and 2.67), methyl (dH: 1.95), amino (dH: 4.70), and
methine (dH: 6.04) signals along with another series of small
methylene (dH: 1.94, 2.28, and 2.48), methyl (dH: 1.99), amino (dH
:
4.54), and methine (dH: 6.47) signals.
Me
+
Me
The complete assignment of the 1H and 13C NMR spectra of 2a
and 2b was performed by DEPT, HMQC,20 and HMBC21 NMR ex-
periments (Figs. S3 and S4). The observed 13C NMR chemical shift
values of C1 (122.5 and 121.4 ppm) and C2 (105.5 and 105.6 ppm)
O
O
Me
Me
3
NC
NC
NH2
NH2
NC
NC
N
NC
NC
N
1
and the IR band (nNH¼3407, 3289, 3180, 3148 cmꢀ1
,
nCN¼2235,
oxalic acid,
benzene, reflux
NH2
NH2
2201 cmꢀ1) in the two isomers are close to the previously reported
values of (2Z)-2-amino-3-[(arylmethylene)amino]but-2-enedini-
triles15 (Table 1). This provides additional evidence for the forma-
tion of 2Z-isomers 2a and 2b. In the 1H NMR spectrum, a significant
low-field shift of 2a methylene signal at dH¼2.67 and 2b methine
signal at dH¼6.47 is observed in comparison with 2b methylene
signal at dH¼2.48 and 2a methine signal at dH¼6.04, respectively.
This may be attributed to the anisotropic deshielding effect of the
adjacent cyano group.
DAMN
2b
2a
Y = 43%
(2a : 2b = 2.5 : 1)
Scheme 2. Reaction of DAMN with 2,6-heptanedione (1).
Efforts to separate the two isomers by using column chroma-
tography were unsuccessful. Therefore, we performed re-
crystallization using CH2Cl2 and hexane as solvents. X-ray
crystallography was performed on the obtained crystalline pre-
cipitate. As a result, only 2a was observed. The X-ray structure of
the precipitate is shown in Figure 1. Surprisingly, the 1H NMR
spectra of the crystalline precipitate showed two isomers present
in a ratio of 2.5:1 in CDCl3. An identical 1H NMR spectrum was
obtained from the measurement of the mother liquor. These results
suggest that a part of 2a is isomerized to another isomer in solution.
The three compounds shown in Figure 2 are considered to be iso-
mers of 2a.
In order to obtain further evidence for the formation of 2a and
2b, a GIAO 13C chemical shift calculation22 (B3LYP/6-311þG(2d,p))
that is based on the optimized geometry of 2a–2d was performed.
The experimental and calculated 13C NMR chemical shifts are listed
in Table 1. The calculated values agree with the experimental re-
sults. A comparison of the observed 13C chemical shift values of 2a
and 2b reveals a significant difference at C20 (2a: 126.8 ppm, 2b:
118.3 ppm) and C60 (2a: 29.3 ppm, 2b: 34.7 ppm). This result is
In order to demonstrate the isomerization of 2a, DFT calcula-
tions were performed on isomers 2a–2d using the Gaussian 03
program package.18 A density functional method was employed
Table 1
Experimentala 13C shifts (ppm) for 2a,b and calculatedb 13C shifts (ppm) for 2a–2d
4'
4'
4'
4'
Me
Me
Me
Me
5'
6'
5'
6'
5'
6'
5'
6'
3'
2'
3'
2'
3'
2'
3'
2'
1'
1'
1'
1'
2
2
NC
NC
N
NC
N
2
NC
NC
N
NC
2
N
1
1
1
1
NH2
H2N
CN
NH2
H2N
CN
2b
2c
2a
2d
Entry
2a
2b
2c
2d
Expt.
Calcd
Expt.
Calcd
Calcd
Calcd
C1
C2
122.5
105.5
170.5
126.8
156.3
30.4
22.2
29.3
24.6
114.1
115.2
132.2
113.1
173.8
135.2
165.5
34.1
27.1
33.1
26.5
119.8
120.8
121.4
105.6
170.1
118.3
159.5
31.4
22.4
34.7
25.0
114.1
115.4
133.1
112.1
170.9
124.3
168.3
35.4
27.4
40.1
26.9
120.2
121.2
137.8
113.2
169.7
136.2
161.3
33.7
26.7
30.7
26.3
122.0
119.3
139.1
119.3
168.5
122.2
168.3
35.4
27.5
39.7
26.4
120.2
122.2
C10
C20
C30
C40
C50
C60
Me
CN
CN
a
Spectra were taken in CDCl3.
b
Chemical shift values were obtained relative to isotropic shielding of TMS as
calculated at the same level.
Figure 1. ORTEP drawing of 2a.

2508
Y. Kubota et al. / Tetrahedron 65 (2009) 2506–2511
O
O
O
Me
Me
Me
Me
Me
NC
NC
NH2
NH2
O
O
NC
NC
N
NC
NC
N
NC
NC
N
Me
Me
3
-H2O
H
H
1
NH2
NH2
NH2
3b
3a
3c
-H2O
Me
Me
Me
Me
Me
Me
N
NC
NC
N
NC
NC
NC
NC
N
NC
NC
N
NC
NC
NH
N
NH2
OH
Me
H
5
NH2
NH2
2b
NH2
4
2a
not obtained
Scheme 3. A plausible mechanism for the formation of 2a and 2b.
reproduced by the calculations. The results suggest that the re-
action of DAMN with 1 produced 2a and 2b.
form a cyclopentyl ring. Then, protonation, dehydration, E1-elimi-
nation, and intramolecular ring closure occurred to yield in-
termediate 9. When the 1,3-hydrogen shift of 9 occurs on the
opposite side of the methyl group at 2-position of 9, 7 is produced.
On the other hand, when the 1,3-hydrogen shift occurs on the same
side of the methyl group, 8 is produced. It is considered that owing
to a steric repulsion between the adjacent methyl group on the
diazepine ring, the 1,3-hydrogen shift of 9 occurred on the opposite
side of the methyl group to produce only 7. The optimized structure
of 9, calculated at the B3LYP/6-31G(d,p) level, is shown in Figure S8.
In order to investigate the isomerization of 7 to a thermodynami-
cally stable product 8, refluxing a benzene solution of 7 was ex-
amined. However, 7 was decomposed on heating.
A plausible mechanism for the reaction of DAMN with 1 is
shown in Scheme 3. The amino group of DAMN reacts with the
carbonyl group of 1 to yield the monoimine intermediate 3a, fol-
lowed by tautomerization to yield the enamine intermediates 3b
and 3c. The internal cyclization of 3b produces 2a and 2b. However,
the internal cyclization of 3c that leads to the formation of the
unstable four-membered ring product 4 was not observed.
When a benzene solution of a product consisting of a mixture of
2a and 2b in the ratio of 2.5:1 was refluxed for 3 days, the ratio
remained constant. This indicates that the mixture had already
attained equilibrium. A plausible mechanism for the observed tau-
tomerization between 2a and 2b in solution is shown in Scheme 3.
2.3. Reaction of DAMN with 2,8-nonanedione (10)
2.2. Reaction of DAMN with 2,7-octanedione (6)
The benzene solution of DAMN and 10 was heated in the pres-
ence of oxalic acid at 80 ꢁC for 2 days to yield a mixture of 11 and 12
in a ratio of 1:2 (Scheme 6, Fig. S9). The ratio between 11 to 12 was
determined from the 1H NMR spectra of the crude products by the
integration of well-separated signals. The separation of di-
astereomers by column chromatography was unsuccessful. The
ratio was maintained after purification by column chromatography.
However, on heating a benzene solution of the diastereomeric
DAMN was allowed to react with 617 in the presence of oxalic
acid to produce 7 in a 67% yield (Scheme 4). The structure of 7 was
determined by X-ray crystallography. An ORTEP drawing of 7 is
shown in Figure 3. Four pairs of enantiomers were observed in
a unit cell (Fig. S5). Compound 7 yielded satisfactory analytical and
spectroscopic data. The complete 1H and 13C NMR spectral as-
signment was carried out using a combination of DEPT, COSY,
HMQC, and HMBC experiments (Fig. S6). Although trans-isomer 7
was confirmed by X-ray crystallographic analysis, cis-isomer 8 was
not observed.
To analyze the diastereoselective formation of 7, DFT calcula-
tions were performed at the B3LYP/6-31G(d,p) level. The calculated
results are shown in Figure S7. According to the results, 8 is more
stable than 7, suggesting that the reaction is kinetically controlled.
A plausible mechanism for the formation of 7 is shown in
Scheme 5. DAMN reacted with dione 6 to produce an enamine in-
termediate followed by an intramolecular nucleophilic attack to
O
O
Me
H
Me
Me
4
N
NC
NC
NH2
NH2
6
NC
oxalic acid, benzene,
reflux
N
NC
Me
H
7
DAMN
Y = 67%
Scheme 4. Reaction of DAMN with 2,7-octanedione (6).
Figure 3. ORTEP drawing of 7.

Y. Kubota et al. / Tetrahedron 65 (2009) 2506–2511
2509
Me
Me
Me
O
O
H
NC
NC
NH2
NH2
NC
NC
N
N
H+
NC
NC
N
NC
NC
+
Me
Me
4
-H2O
-H2O
NH2
NH2
NH2
OH
Me
6
Me
Me
O
O
Me
H
Me
Me
Me
H
Me
3
-
N
N
H
N
N
NC
NC
N
NC
NC
NC
NC
NC
1,3-H shift
NC
NC
+
-H+
2
+
N
Me
N
H
Me
NC
N
NH2
1
NH2
H
Me
Me
Me
H2
8
7
9
kinetically
controlled product
not obtained
Scheme 5. A plausible mechanism for the formation of 7.
mixtures at 80 ꢁC for 5 days, only 12 was obtained. This indicates
that 11 was isomerized to a thermodynamically stable 12. This is
supported by DFT calculation performed at the B3LYP/6-31G(d,p)
level (Fig. S10). The diastereoselective formation of 12 was also
confirmed by increasing the reaction time.
adjacent methyl group on the diazepine ring (Fig. S13). Therefore, it
is considered that 11 is a kinetically controlled product. On the
other hand, 12 can be assumed to be a product that is thermody-
namically stable. Therefore, the heating of 11 causes the imine–
enamine tautomerization, which yields the thermodynamically
stable 12.
O
O
Me
Me
3. Conclusions
H
N
Me
Me
H
5
N
NC
NC
NH2
NH2
NC
+
NC
NC
10
The reaction of DAMN with 1 yielded 2a and 2b. NMR spectro-
scopy revealed imine–enamine tautomerization between 2a and 2b
in solution. The reaction between DAMN and 6 resulted in the
diastereoselective formation of 7. On the other hand, DAMN reacted
with 10 to afford 11 and 12. The diastereoselective formation of 12
was achieved by increasing the reaction time, suggesting that
heating 11 results in an imine–enamine tautomerization, which
yields thermodynamically stable 12.
oxalic acid,
benzene, reflux
N
N
NC
H
12
H
11
Me
Me
DAMN
Y = 71%
(11 : 12 = 1: 2)
Scheme 6. Reaction of DAMN with 2,8-nonanedione (10).
The structure of 12 was confirmed by NMR, IR, MS, and X-ray
crystallography. The ORTEP drawing and packing motif of 12 are
shown in Figure 4 and Figure S11, respectively. Two pairs of enan-
tiomers were observed in a unit cell (Fig. S11). The complete as-
signment of 1H and 13C NMR spectra of 12 is shown in Figure S12.
A reaction, similar to Scheme 5 occurs, thereby producing in-
termediate 13 (Scheme 7). The 1,3-hydrogen shift of 13 to yield 12
does not occur readily due to the steric repulsion between the
4. Experimental
4.1. Instrument
NMR spectra were recorded on ECX400P or ECA-600 spec-
trometer. Chemical shifts are referred to the internal standard tet-
ramethylsilane, TMS. Infrared (IR) spectra were determined on
a Perkin–Elmer 2000 FT-IR spectrometer. Mass spectra were
recorded on a JEOL JMS-700 spectrometer. High Resolution Mass
Spectra (HRMS) were obtained from the above instruments. Ele-
mental analyses were performed on a Yanaco MT-6 CHN corder.
Melting points were measured on a Yanagimoto MP-S2 micro-
melting-point apparatus. Analytical thin-layer chromatography
(TLC) was performed on pre-coated plates (Merck, silica gel 60
F254). Silica gel (Wakogel C-200) was used for column chromato-
graphy. X-ray data were taken on a Rigaku AFC7R Mercury CCD. The
structures were solved by direct methods, SIR97.23 Geometry op-
timizations and energy evaluations were carried out with Gaussian
03, revision B.03 package.18
4.2. Materials
2,3-Diaminomaleonitrile (DAMN) was purchased from Sigma–
Aldrich and used after recrystallization from ethyl acetate. Oxalic
acid and benzene were purchased from Wako Pure Chemical In-
dustries and used without further purification. 2,6-heptanedione
(1), 2,7-octanedione (6), and 2,8-nonanedione (10) were prepared
according to the previously reported procedure.17
Figure 4. ORTEP drawing of 12.

2510
Y. Kubota et al. / Tetrahedron 65 (2009) 2506–2511
Me
Me
Me
Me
H
N
Me
NC
NC
O
O
NC
NC
N
NC
NC
NH2
NH2
NC
H+
N
Me
H
Me
+
5
-H2O
-H2O
Me
NH2
NH2
NC
NH2
10
OH
O
O
N
Me
Me
Me
Me
Me
-
H
N
H
N
NC
NC
NC
NC
N
N
NC
NC
NC
NC
NC
NC
+
-H+
+
+
N
Me
Me
N
N
NH2
H
12
NH2
Me
H2
13
H
11
Me
Me
thermodynamically
controlled product
kinetically
controlled product
H
Me
Me
N
NC
NC
N
H
14
Scheme 7. A plausible mechanism for the reaction of DAMN with 10.
4.3. Reaction of DAMN with diketones
4.3.2.1. trans-5,8a-Dimethyl-1,5a,6,7,8,8a-hexahydrocyclopenta[e]-1,
4-diazepine-2,3-dicarbonitrile (7). Mp 153–155 ꢁC; 1H NMR
4.3.1. Reaction of DAMN with 2,6-heptanedione (1)
(600 MHz, CDCl3) d 1.03 (s, 3H), 1.77–1.89 (m, 3H), 1.97–2.04 (m,
In a round-bottomed flask were placed 2,6-heptanedione (1)
(323 mg, 2.52 mmol) and benzene (13 mL). 2,3-Diaminomaleoni-
trile (DAMN) (270 mg, 2.50 mmol) and oxalic acid (70 mg,
0.77 mmol) were added to the solution and the mixture was
refluxed for 24 h. After cooling, the solvent was evaporated off.
Chromatographic treatment of the residue on silica gel (ethyl ace-
tate/dichloromethane¼1:10) yielded a mixture of (2Z)-2-amino-3-
[(1E)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile (2a)
and (2Z)-2-amino-3-[(1Z)-3-methylcyclohex-2-enylideneamino]-
but-2-enedinitrile (2b) in the ratio of 2.5:1 (216 mg, Y¼43%).
1H), 2.11 (ddd, J¼11.7, 7.6, 5.3 Hz, 1H), 2.17–2.21 (m, 1H), 2.20 (s,
3H), 2.51 (dd, J¼11.7, 7.6 Hz, 1H), 5.17 (br s, 1H); 13C NMR (150 MHz,
CDCl3)
d 22.1 (CH2), 26.0 (CH3), 26.9 (CH3), 28.1 (CH2), 42.5 (CH2),
59.4 (CH), 67.1 (C), 105.3 (C), 114.8 (C), 118.7 (C), 118.8 (C), 172.6 (C);
IR (KBr) 3253 (NH), 3053 (NH), 2213 (C^N) cmꢀ1; HRMS (EI, 70 eV)
m/z calculated for C12H14N4 [M]þ 214.1219, found 214.1203.
4.3.3. Reaction of DAMN with 2,8-nonanedione (10)
DAMN (366 mg, 3.39 mmol) and oxalic acid (70 mg, 0.77 mmol)
were added to a solution of 2,8-nonanedione (10) (445 mg,
2.85 mmol) in benzene (20 mL). The solutionwas refluxed for 2 days.
After removal of the solvent in vacuo, the residue was chromato-
graphed on silica with EtOAc/CH2Cl2 1:2, giving a mixture of
trans-5,9a-dimethyl-5a,6,7,8,9,9a-hexahydro-1H-benzo[e]-1,4-dia-
zepine-2,3-dicarbonitrile (11) and cis-5,9a-dimethyl-5a,6,7,8,9,9a-
hexahydro-1H-benzo[e]-1,4-diazepine-2,3-dicarbonitrile (12) in a
ratio of 1:2 (468 mg, Y¼71%). The reaction mixture could not be
separated by column chromatography. Heating the benzene solution
of the mixture at 80 ꢁC for 5 days produced only 12 (468 mg, Y¼71%).
4.3.1.1. (2Z)-2-Amino-3-[(1E)-3-methylcyclohex-2-enylideneamino]-
but-2-enedinitrile (2a). 1H NMR (400 MHz, CDCl3)
d
1.88 (tt, J¼6.4,
6.4 Hz, 2H), 1.95 (s, 3H), 2.23 (t, J¼6.4 Hz, 2H), 2.67 (t, J¼6.4 Hz, 2H),
4.70 (br s, 2H), 6.04 (s, 1H); 13C NMR (150 MHz, CDCl3)
22.2 (CH2),
d
24.6 (CH3), 29.3 (CH2), 30.4 (CH2), 105.5 (C), 114.1 (C), 115.2 (C),
122.5 (C), 126.8 (CH), 156.3 (C), 170.5 (C).
4.3.1.2. (2Z)-2-Amino-3-[(1Z)-3-methylcyclohex-2-enylideneamino]-
but-2-enedinitrile (2b). 1H NMR (400 MHz, CDCl3)
d
1.94 (tt, J¼6.4,
6.4 Hz, 2H), 1.99 (s, 3H), 2.28 (t, J¼6.4 Hz, 2H), 2.48 (t, J¼6.4 Hz, 2H),
4.54 (br s, 2H), 6.47 (s, 1H); 13C NMR (150 MHz, CDCl3)
22.4 (CH2),
4.3.3.1. trans-5,9a-Dimethyl-5a,6,7,8,9,9a-hexahydro-1H-benzo[e]-1,
d
4-diazepine-2,3-dicarbonitrile (11). 1H NMR (600 MHz, CDCl3)
d1.25–
25.0 (CH3), 31.4 (CH2), 34.7 (CH2), 105.6 (C), 114.1 (C), 115.4 (C), 118.3
(CH), 121.4 (C), 159.5 (C), 170.1 (C).
1.28(m,1H),1.31 (s,3H),1.33–1.37(m,1H),1.62–1.72(m, 3H),1.78–1.82
(m, 1H), 1.83–1.88 (m, 1H), 1.94–1.99 (m, 1H), 2.19 (s, 3H), 2.50 (dd,
J¼13.1, 4.1 Hz, 1H), 4.25 (br s, 1H); 13C NMR (150 MHz, CDCl3)
d 22.3
4.3.1.3. Mixtures of 2a and 2b in the ratio of 2.5:1. Mp 114–116 ꢁC;
IR (KBr) 3407 (NH), 3289 (NH), 3180 (NH), 3148 (NH), 2235 (C^N),
2201 (C^N) cmꢀ1; MS (EI, 70 eV) m/z (rel intensity) 200 (41, Mþ),
172 (100, [MꢀCH2N]þ). Found: C, 65.82; H, 6.03; N, 27.84%. Calcu-
lated for C11H12N4: C, 65.98; H, 6.04; N, 27.98%.
(CH2), 24.6 (CH2), 25.0 (CH2), 26.3 (CH3), 26.5 (CH3), 43.8 (CH2), 51.0
(CH), 70.5 (C), 105.6 (C), 114.8 (C), 117.8 (C), 118.5 (C), 179.0 (C).
4.3.3.2. cis-5,9a-Dimethyl-5a,6,7,8,9,9a-hexahydro-1H-benzo[e]-1,4-
diazepine-2,3-dicarbonitrile (12). 1H NMR (600 MHz, CDCl3)
d 1.17
(s, 3H), 1.25–1.34 (m, 2H), 1.39 (ddd, J¼14.1, 14.1, 4.6 Hz, 1H), 1.47–
1.55 (m, 1H), 1.57–1.65 (m, 2H), 1.83 (d, J¼14.1 Hz, 1H), 1.86–1.91 (m,
1H), 2.23 (s, 3H), 2.63 (d, J¼10.8 Hz, 1H), 5.29 (br s, 1H); 13C NMR
4.3.2. Reaction of DAMN with 2,7-octanedione (6)
To a solution of 2,7-octanedione (6) (850 mg, 5.98 mmol) in
benzene (20 mL) were added DAMN (667 mg, 6.17 mmol) and
oxalic acid (70 mg, 0.77 mmol), and the reaction mixture was held
at reflux overnight. The solvent was removed under vacuum
pressure and the residue was purified by column chromatography
(ethyl acetate/dichloromethane¼1:2) to give trans-5,8a-dimethyl-
1,5a,6,7,8,8a-hexahydrocyclopenta[e]-1,4-diazepine-2,3-dicarboni-
trile (7) (849 mg, Y¼67%).
(150 MHz, CDCl3)
d 21.2 (CH2), 24.8 (CH2), 26.1 (CH2), 30.1 (CH3),
30.9 (CH3), 39.7 (CH2), 57.0 (C), 59.3 (CH), 103.8 (C), 114.5 (C), 119.2
(C), 119.4 (C), 174.9 (C).
4.3.3.3. Mixtures of 11 and 12 in the ratio of 1:2. Mp 208–209 ꢁC; IR
(KBr) 3245 (NH), 3069 (NH), 2216 (C^N) cmꢀ1; MS (EI, 70 eV) m/z
(rel intensity) 228 (56, Mþ), 81 (100, [MꢀC7H7N4]þ). Found: C,

Y. Kubota et al. / Tetrahedron 65 (2009) 2506–2511
2511
5. (a) Barker, C. A.; Zeng, X.; Bettington, S.; Batsanov, A. S.; Bryce, M. R.; Beeby, A.
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68.08; H, 6.99; N, 24.53%. Calculated for C12H14N4: C, 68.39; H, 7.06;
N, 24.54%.
5. X-ray crystallography
The single crystals of 2a, 7, and 12 were given by the slow diffu-
sion of hexane to CH2Cl2 solution at room temperature. Crystal data
for 2a: C11H12N4, Mw¼200.25, monoclinic, P21/n, Z¼4, a¼12.142(6),
b¼7.083(3), c¼13.245(7) Å,
b
¼104.859(6)ꢁ, Dcalcd¼1.208 g/cm3,
8703 reflections were collected, 2505 unique (Rint¼0.0331), 2304
6. (a) Horiguchi, E.; Funabiki, K.; Matsui, M. Bull. Chem. Soc. Jpn. 2005, 78, 316; (b)
Horiguchi, E.; Matsumoto, S.; Funabiki, K.; Matsui, M. Bull. Chem. Soc. Jpn. 2005,
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Matsuoka, M. Dyes Pigments 2001, 50, 99.
observed (I>2
s
(I)), 145 parameters, R1¼0.0589, wR2¼0.118,
GOF¼1.177, refinement on F2. Crystal data for 7: C12H14N4,
Mw¼214.27, orthorhombic, Pbca, Z¼8, a¼6.714(5), b¼25.030(18),
c¼13.314(10) Å, Dcalcd¼1.272 g/cm3, 16,610 reflections were
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s(I)),
8. (a) Matsumoto, S.; Kobayashi, T.; Aoyama, T.; Wada, T. Chem. Commun. 2003,1910;
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K. JP Pat. 54076822, 1979.
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3925.
147 parameters, R1¼0.1225, wR2¼0.221, GOF¼1.365, refinement
on F2. Crystal data for 12: C13H16N4, Mw¼228.3, monoclinic, P21/n,
Z¼4, a¼6.903(4), b¼13.005(7), c¼14.325(8) Å,
b
¼103.977(7)ꢁ,
Dcalcd¼1.215 g/cm3, 9744 reflections were collected, 2836 unique
(Rint¼0.0322), 2640 observed (I>2 (I)), 202 parameters, R1¼0.0662,
s
wR2¼0.131, GOF¼1.203, refinement on F2. Crystallographic data have
been deposited at the CCDC,12 Union Road, Cambridge CB2 1EZ, UK
and copies can be obtained on request, free of charge, by quoting the
publication citation and the deposition numbers for 2a (CCDC
686760), 7 (CCDC 686789), and 12 (CCDC 686862), respectively.
15. Rivera, A.; Rios-Motta, J.; Leon, F. Molecules 2006, 11, 858.
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Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.01.053.
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